Journal articles on the topic 'Other studies in human society, n.e.c'

Abstract BACKGROUND Gliomas are the most common brain cancer and survival is poor, with 11–15 months for high-grade glioblastoma patients, despite treatment. Gliomas are hypoxic tumours, which increases with tumour grade. Under hypoxia, the transcription factor hypoxia inducible factor-1 (HIF) accumulates and upregulates expression of genes involved in tumour development and progression. HIF-1 levels and activity are controlled by HIF hydroxylases which target HIF-1α for degradation and prevent co-activation. HIF hydroxylases are part of the 2-oxoglutarate (2-OG)-dependent dioxygenase enzyme family, that require 2-OG and oxygen as substrates and ascorbate and iron as co-factors. The role of ascorbate in regulating the hypoxic pathway in cancer is of interest, with previous research showing reduced HIF pathway activity with increasing tumour ascorbate levels. Brain tissue has one of the highest ascorbate levels in the body, and is one of the last to become depleted under deficiency, indicating an important role for ascorbate in this tissue. One previous study has analysed ascorbate levels in 11 human glioblastoma patients, and showed lower ascorbate in tumour tissue compared to normal brain tissue. There have been no studies investigating the relationship between ascorbate levels and the hypoxic pathway in human glioma tissues. MATERIAL AND METHODS Human glioma tissues (n = 39), obtained from the Cancer Society Tissue Bank Christchurch (ethics approval H19/163), were processed for ascorbate and hypoxic pathway proteins (HIF-1α, CA-IX, BNIP3, HKII, GLUT1 and VEGF). Ascorbate levels were quantified by HPLC-ED, and proteins were measured by Western blotting and ELISA. Spearman’s correlations were used to identify relationships between ascorbate and HIF pathway proteins. RESULTS Of the samples, 64% were GBM. Ascorbate was significantly lower in GBM compared to low-grade gliomas (p = 0.04). VEGF was significantly higher in GBM compared to astrocytomas (p = 0.01). Increased tumour ascorbate was associated with lower VEGF and CA-IX proteins. HIF-1α and BNIP3 protein were positively associated, and VEGF was positively associated with HKII and CA-IX. VEGF inversely associated with BNIP3, and CA-IX inversely associated with HKII. The hypoxic pathway score (calculated from protein levels of members of the hypoxic pathway) was reduced in tumours with higher ascorbate but this did not reach significance (p = 0.2). CONCLUSION This is the first study to show that ascorbate levels were reduced in high-grade gliomas compared to low-grade. Some members of the hypoxic pathway were associated with ascorbate levels. The overall hypoxic pathway score did not significantly correlate with ascorbate and increased numbers of samples are required to confirm any associations. Other variables, such as IDH-1 mutation status of the tumours may affect the correlation and will be analysed next.

ISCPES stands for International Society for Comparative Physical Education and Sports and it is going to celebrate its 40th anniversary in 2018. Since the beginning (Israel 1978) the main goals of the Society were established under a worldwide mind set considering five continents and no discrimination of any kind. The founders wanted to compare Physical Education and Sports across the world, searching for the best practices deserving consideration and applied on the purpose of improving citizen quality of life. The mission still stands for “Compare to learn and improve”.As all the organizations lasting for 39 years, ISCPES experienced several vicissitudes, usually correlated with world economic cycles, social and sports changes, which are in ISS journal articles - International Sport Studies.ISS journal is Scopus indexed, aiming to improve its quality (under evaluation) to reach more qualified students, experts, professionals and researchers; doing so it will raise its indexation, which we know it is nowadays a more difficult task. First, because there are more journals trying to compete on this academic fierce competitive market; secondly, because the basic requirements are getting more and more hard to gather in the publishing environment around Physical Education and Sports issues. However, we can promise this will be one of our main strategic goals.Another goal I would like to address on this Editorial is the language issue. We have this second strategic goal, which is to reach most of languages spoken in different continents; besides the English language, we will reach Chinese, Spanish and Portuguese speaking countries. For that reason, we already defined that all the abstracts in English will be translated into Chinese, Spanish and Portuguese words so people can find them on any search browser. That will expand the demand for our journal and articles, increasing the number of potential readers. Of course this opportunity, given by Motricidade, can be considered as a good example to multiply our scope.In June 2017 we organized a joint Conference in Borovets, Bulgaria, with our colleagues from the BCES – Bulgarian Society for Comparative Educational Studies. During those days, there was an election to appoint a new (Portuguese) president. This constitutes an important step for the Portuguese speaker countries, which, for a 4th year term, will have the opportunity to expand the influence of ISCPES Society diffusing the research results we have been achieving into a vast extended new public and inviting new research experts to innovative debates. This new president will be working with a wide geographical diverse team: the Vice President coming from a South American country (Venezuela), and the other several Executive Board members are coming from Brazil, China, Africa and North America. This constitutes a very favorable situation once, adding to this, we kept the previous editorial team from Australia and Europe. We are definitely committed to improve our influence through new incentives to organize several regional (continental) workshops, seminars and Conferences in the next future.The international research is crossing troubled times with exponential number of new indexed journals trying to get new influence and visibility. In order to do that, readers face new challenges because several studies present contradictory conclusions and outcome comparisons still lacking robust methodologies. Uncovering these issues is the focus of our Society.In the past, ISCPES started its activity collecting answers to the same questions asked to several experts in different countries and continents across the world. The starting studies developed some important insights on several issues concerning the way Physical Education professionals approached their challenges. In the very starting documents ISCPES activity focused in identifying certain games and indigenous activities that were not understood by people in other parts of the world, improving this international understanding and communication. This first attempt considered six groups of countries roughly comprehending 26 countries from all the continents.ISCPES has on its archives several seminal works, PhD proposals and program proposals, which constitutes the main theoretical framework considered in some textbooks printed at the end of the sixties in the XXth century.The methods used mostly sources’ country comparisons, historic development of comparative education systems, list of factors affecting those systems and a systematic analysis of case studies; additionally, international organizations for sports and physical education were also required to identify basic problems and unique features considered for the implementation of each own system. At the time, Lynn C. Vendien & John E. Nixon book “The World Today in Health, Physical Education and Recreation”, Englewood Cliffs, New Jersey: Prentice-Hall, Inc. 1968, together with two monographies from William Johnson “Physical Education around the World”, 1966, 1968, Indianapolis, Phi Epsilon Kappa editions, were the main textbook references.The main landscapes of interest were to study sports compared or the sport role in Nationalisms, Political subsidization, Religion, Race and volunteering versus professionalism. The goal was to state the true place of sports in societies.In March 1970, Ben W. Miller from the University of California compiled an interesting Exhibit n.1 about the main conclusions of a breakfast meeting occurred during the American Association for Health, Physical Education and Recreation. There, they identified thirty-one individuals, which had separate courses in “Comparative and/or International Physical Education, Recreation and Sports”; one month later, they collected eighteen responses with the bibliographic references they used. On this same Exhibit n.1 there is detailed information on the title, catalogue description, date of initial course (1948, the first), credit units, eligibility, number of year offer, type of graduation (from major to doctorate and professional). Concluding, the end of the sixties can be the mark of a well-established body of literature in comparative education and sports studies published in several scientific journals.What about the XXIst century? Is it still important to compare sports and education throughout the world? Only with qualitative methods? Mixed methods?We think so. That is why, after a certain decline and fuzzy goal definition in research motivations within ISCPES we decided to innovate and reorganize people from physical education and sports around this important theme of comparative studies. Important because we observe an increasing concern on the contradictions across different results in publications under the same subject. How can we infer? What about good research questions which get no statistically significant results? New times are coming, and we want to be on that frontline of this move as said by Elsevier “With RMR (results masked review) articles, you don’t need to worry about what editors or reviewers might think about your results. As long as you have asked an important question and performed a rigorous study, your paper will be treated the same as any other. You do not need to have null results to submit an RMR article; there are many reasons why it can be helpful to have the results blinded at initial review”.https://www.elsevier.com/connect/reviewers-update/results-masked-review-peer-review-without-publication-bias.This is a very different and challenging time. Our future strategy will comprehend more cooperation between researchers, institutions and scientific societies as an instrument to leverage our understanding of physical activity and sports through different continents and countries and be useful for policy designs.Next 2018, on the occasion of the UE initiative Sofia – European Capital of Sport 2018 we - Bulgarian Comparative Education Society (BCES) & the International Society for Comparative Physical Education and Sport (ISCPES) - will jointly organize an International Conference on Sport Governance around the World.Sports and Physical Education are facing complex problems worldwide, which need to be solved. For health reasons, a vast number of organizations are popularizing the belief that physical education and sports are ‘a must’ in order to promote human activity and movement. However, several studies show that modern lifestyles are the main cause for people's inactivity and sedentary lifestyles.Extensive funded programs used to promote healthy lifestyles; sports media advertising several athletes, turning them into global heroes, influencers in a new emerging industry around sports organizations. Therefore, there is a rise in the number of unethical cases and corruption that influence the image of physical education and sports roles.We, the people emotional and physically involved with sports and physical activity must be aware of this, studying, discussing and comparing global facts and events around the world.This Conference aims to offer an incentive to colleagues from all continents to participate and present their latest results on four specific topics: 1. Sport Governance Systems; 2. Ethics and Corruption in Physical Education and Sports Policies; 3. Physical Education and Sport Development; 4. Training Physical Educators and Coaches. Please consider your selves invited to attend. Details in http://bcesconvention.com/

The knowledge of the science of human body parts for early childhood is very important so that children have the ability to recognize and support the cleanliness and health of members of the body, as well as so that they recognize their identity. In addition, introducing environmentally friendly material for early childhood teachers to enrich learning media. This study aims to improve student learning outcomes in science using environmentally friendly media. The topic raised in this search was about recognizing body parts and their benefits and treatments. This type of research is action research. Respondents involved 19 early childhood students. The results showed that there was an increase in subjects' understanding of swallowing extremities and treatment 60% in the pre-cycle phase, 80% in the first cycle and 93% in the second cycle. The findings show that the use of happy body media has a positive effect on limb recognition. Further research is recommended on environmentally friendly media and ways of introducing limbs to early childhood through media or strategies suitable for the millennial era. Keywords: Media (Happy Body), Early Childhood Science, Human Body Parts References: Anagnou, E., & Fragoulis, I. (2014). The contribution of mentoring and action research to teachers’ professional development in the context of informal learning. Review of European Studies, 6(1), 133–142. Belsky, J., Steinberg, L., & Draper, P. (1991). Childhood experience, interpersonal development, and reproductive strategy: An evolutionary theory of socialization. Child Development, 62(4), 647. Black, M. M., & Hurley, K. M. (2016). Early child development programmes: further evidence for action. The Lancet Global Health, 4(8), e505–e506. Blok, H., Fukkink, R., Gebhardt, E., & Leseman, P. (2005). The relevance of delivery mode and other programme characteristics for the effectiveness of early childhood intervention. 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S., White, L. J., & Greenfield, D. B. (2018). Approaches to learning and science education in Head Start: Examining bidirectionality. Early Childhood Research Quarterly, 44, 34–42. https://doi.org/10.1016/j.ecresq.2018.02.013 Carr, W. (2006). Philosophy, methodology and action research. Journal of Philosophy of Education, 40(4), 421–435. Colker, L. J. (2008). Twelve characteristics of effective early childhood teachers. YC Young Children, 63(2). Cook, C., Goodman, N. D., & Schulz, L. E. (2011). Where science starts: Spontaneous experiments in preschoolers’ exploratory play. Cognition, 120(3), 341– 349. Dewi Kurnia, H. Z. (2017). Pentingnya Media Pembelajaran. Jurnal Pendidikan Anak Usia Dini, 1 No.1, 81–96. Gelman, R., & Brenneman, K. (2004). Science learning pathways for young children. Early Childhood Research Quarterly, 19(1), 150–158. Gersick, C. J. (1988). Time and transition in work teams: Toward a new model of group development. Academy of Management Journal, 31(1), 9–41. 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Young children’s understanding of pretense. Monographs of the Society for Research in Child Development, 58(1), 1–92. Hayati, H. S., Myrnawati, C. H., & Asmawi, M. (2017). Effect of Traditional Games, Learning Motivation And Learning Style On Childhoods Gross Motor Skills. International Journal of Education and Research, 5(7). Hedefalk, M., Almqvist, J., & Östman, L. (2015). Education for sustainable development in early childhood education: a review of the research literature. Environmental Education Research, 21(7), 975–990. https://doi.org/10.1080/13504622.2014.971716 Herakleioti, E., & Pantidos, P. (2016). The Contribution of the Human Body in Young Children’s Explanations About Shadow Formation. Research in Science Education, 46(1), 21–42. https://doi.org/10.1007/s11165-014-9458-2 İlin, G., Kutlu, Ö., & Kutluay, A. (2013). An Action Research: Using Videos for Teaching Grammar in an ESP Class. Procedia - Social and Behavioral Sciences. https://doi.org/https://doi.org/10.1016/j.sbspro.2013.01.065 Jennifer M. Zosh, Emily J. Hopkins, Hanne Jensen, Claire Liu, Dave Neale, Kathy Hirsh-Pasek, S. L. S. and D. W. (2017). Learning through play : a review of the evidence. Kagan, J., Reznick, J. S., & Snidman, N. (1987). The physiology and psychology of behavioral inhibition in children. Child Development, 1459–1473. Kemmis, S., & Taggart, M. (2002). The action research planner. Victoria: Dearcin University Press. Lebel, C., & Beaulieu, C. (2011). Longitudinal development of human brain wiring continues from childhood into adulthood. Journal of Neuroscience, 31(30), 10937–10947. Luna, B., Garver, K. E., Urban, T. A., Lazar, N. A., & Sweeney, J. A. (2004). Maturation of cognitive processes from late childhood to adulthood. Child Development, 75(5), 1357–1372. Nayfeld, I., Brenneman, K., & Gelman, R. (2011). 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The early age is a substantial period in human development. The long-term benefit from participating in the early childhood education programs is increasing opportunities for the children to complete their higher education in order to get the better welfare future. In Sumedang regency - the location of this study - the children’s participations in joining the early childhood education programs had not been optimized yet. Approximately 47% of the children aged 4-6 years had not participated in the early childhood education programs yet. Thus, it was significant to seek out the factors influencing the children’s accessibilities to participate in the early childhood education programs in Sumedang regency in order to find out the alternative policy to increase their accessibilities to participate in the early childhoodeducation programs. The research was conducted in 2017 using the quantitative method. The data were obtained from the “2015 Susenas” which involved 300 respondents. The data analysis was performed by using the logistic regression with the 12th version of STATA software. The findings showed that the children’s accessibilities to participate in the early childhood education programs in Sumedang regency was determined by the educational background of the head of family, the marital status of the parents, the head of the family’s income, the number of the family members, and the children’s domicile. Giving knowledge about the importance of early childhood education to the lower educational background parents and enlarging the early childhood schools’ facilities and infrastructures especially in rural areas of Sumedang regency still needed to be improved in order to have better human resources in the future. References Abdulhak, I. (2003). Memposisikan pendidikan anak usia dini dalam sistem pendidikan nasional. Buletin PADU Jurnal Ilmiah Anak Dini Usia. Jakarta: Dir. PAUD, Dirjend. PLSP, Depdiknas. Apriana, R. (2009). 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Society for Research in Child Development, (October), 1–24. https://www.fcd-us.org/assets/2013/10/20Base20on20Preschool20Education20FINAL.pdf Yusuf, A. A. (2017). Menyelesaikan darurat nutrisi anak sebagai prasyarat pertumbuhan inklusif. Diakses melalui http://sdgcenter.unpad.ac.id/menyelesaikan-darurat-nutrisi-anak-sebagaiprasyarat-pertumbuhan-inklusif/ pada tanggal 1 Maret 2018.

Background: Hepatic sinusoidal obstruction syndrome (SOS), which is also called veno-occlusive disease of the liver, remains a serious complication after hematopoietic stem cell transplantation (HSCT). Over the last years, some risk factors have already been identified to be associated with SOS. However, the cause of SOS is still not fully understood and the mortality remains high, especially for SOS leading to multi-organ failure with a mortality rate up to 84%. The aim of our study was to analyze several risk factors of SOS in pediatric patients undergoing allogeneic HSCT. In addition, we investigated new potential risk factors. Methods: We retrospectively analyzed 105 children who underwent allogeneic HSCT for the first time and did not receive a defibrotide prophylaxis. All transplantations were performed between January 2007 and December 2018 in a single center. The median age was 8.6 years and stem cell source was either bone marrow (n = 74) or peripheral blood (n = 31). Underlying diseases were acute lymphoblastic leukemia (n = 27), acute myeloid leukemia (n = 25), myelodysplastic syndrome (n = 14), lymphoma (n = 2), solid tumor (n = 12) and genetic disease (n = 25). All patients received a myeloablative conditioning regimen. We analyzed the transplantation-related factors graft source, donor-recipient human leukocyte antigen match, donor age, donor sex and conditioning regimen based on busulfan or total body irradiation. Furthermore, we investigated the patient-related factors patient age, patient sex, prior treatment with gemtuzumab ozogamicin as well as the following laboratory parameters: aspartate transaminase, alanine transaminase, cholinesterase, glutamyl transpeptidase, lactate dehydrogenase, alkaline phosphatase, ferritin, albumin, total bilirubin, C-reactive protein and international normalized ratio (INR). All laboratory parameters were measured before HSCT and cutoffs were determined by reference values and receiver operating characteristic (ROC) curves. SOS was defined by modified pediatric Seattle criteria up to day +30 after HSCT because nearly all transplantations were performed before the new pediatric criteria of the European Society for Blood and Marrow Transplantation have been published. In univariate analysis, chi-square test and Fisher's exact test were used. Additionally, the Mann-Whitney U-test was performed to compare the median values of continuous variables. Significant variables (P < .05) were entered in multivariate analysis, which was carried out by using backward stepwise logistic regression. Results: SOS occurred in 15 out of 105 transplantations (14.3%). The median time of SOS onset was 12 days after HSCT (range, 1 day - 26 days). Three patients died of multi-organ failure following SOS (20%). This mortality rate was very low compared to other studies because our patients were treated with defibrotide immediately after being diagnosed with SOS. In univariate analysis, we found a significant association between patient age <1 year and SOS (Odds Ratio (OR) = 7.25, P = .037). Furthermore, a prior treatment with gemtuzumab ozogamicin (OR = 11.00, P = .020) showed a significant correlation. Patients who developed SOS had a significantly higher median ferritin level (2816.9 ng/mL vs. 1554.0 ng/mL, P = .026). Based on this observation, different ferritin cutoffs were selected by ROC analysis. Ferritin >1500 ng/mL (OR = 4.00, P = .033), ferritin >2000 ng/mL (OR = 4.69, P = .016) as well as ferritin >2400 ng/mL (OR = 5.29, P = .005) revealed significant P values. Besides these results, INR ≥1.3 (OR = 5.91, P = .009) was significantly associated with SOS. In multivariate analysis, the following variables showed P values less than .05: treatment with gemtuzumab ozogamicin (OR = 9.24, P = .048), ferritin >2400 ng/mL (OR = 5.74, P = .023) and INR ≥1.3 (OR = 8.02, P = .007). Conclusions: Our data confirm the risk factors of young patient age (<1 year), prior treatment with gemtuzumab ozogamicin and high serum ferritin (>2400 ng/mL) in the pediatric population. Moreover, we report for the first time that there is a significant association between high INR (≥1.3) before HSCT and the occurrence of SOS. Especially this new finding could improve the risk stratification of SOS and should be evaluated in further trails. Disclosures No relevant conflicts of interest to declare.

Abstract SYNTHESIS OF THE FIRST INTERNATIONAL SYMPOSIUM FOR RESEARCH IN COMPARATIVE CRIMINOLOGY Introduction At the beginning of the development of the social sciences there was a considerable vogue for comparative research. A long period of empirical studies and almost total preoccupation with methodological problems followed. Once again, however, psychology, political science, sociology, and above all anthropology, have taken up the thread of this tradition, and the bibliography in these fields is becoming ever more abundant. The study of deviance, of various manifestations of criminality, and of social reaction against crime are, however, noticeably missing in the picture, even though there is nothing in the nature of criminology which precludes the development of comparative research. To many research workers in criminology, the time seemed ripe to take up the comparative tradition once again. Two imperatives were considered : the generalization of norms of deviance which are tied to the standard of living set by industrial civilization, thus putting the problem of criminality in a global light ; and, second, the development and standardization of methods of studying these phenomena, drawing on the experience of allied disciplines. The response of the participants in this Symposium and the results of their discussions were not unexpected. A consensus was arrived as to the problems it was thought important to study, and agreement was reached about the strategies of research to be undertaken. Priorities, however, were not established since too much depends on the availability of research teams, funds, etc. But the broad, overall look at the main problems in comparative criminology will, hopefully, open a new chapter in the history of crimino-logical research and in our continuing search for knowledge of man and society. The brief resume which follows should give the reader an idea of the extent of the problems tackled. The detailed proceedings of the Symposium will be published at a later date, in mimeographed form. Sectors of research proposed In a sense, this Symposium was prepared by all the participants. The organizers had requested that each person invited prepare a memorandum setting out the problems in comparative criminology which he considered to be most important. The compilation of their replies, reported to the plenary session at the opening of the Symposium, produced the following results : Summary of suggestions for research activities Note : In all that follows, it should be understood that all of these topics should be studied in a cross-cultural or international context. 1) Definitions and concepts : a) Social vs legal concept of deviance ; b) Distinction between political and criminal crimes ; c) The law : a moral imperative or a simple norm ; d) The concepts used in penal law : how adequate ? e.g. personality of criminal ; e) Who are the sinners in different cultures and at different times. 2) Procedures : a) Working concepts of criminal law and procedure ; b) Differentiating between factors relating to the liability-finding process and the sentencing process ; c) Behavioural manifestations of the administration of criminal justice ; d) Judicial decisions as related to the personality of the judges and of the accused ; e) Sentencing in the cross-national context (2 proposals) ; f) In developing countries, the gap between development of the legal apparatus and social behaviour ; g) Determination of liability ; h) The problem of definition and handling of dangerous offenders ; i) Decision-making by the sentencing judges, etc. (2 proposals) ; ;) Medical vs penal committals ; k) Law-enforcement, policing. 3) Personnel : a) Professionalization in career patterns ; b) Criteria for personnel selection ; c) Greater use of female personnel. 4) Causation. Situations related to criminality : a) How international relations and other external factors affect crime ; 6) Hierarchy of causes of crime ; c) Migrants. Minorities in general ; d) Relation to socio-economic development in different countries ; e) A biological approach to criminal subcultures, constitutional types, twin studies, etc. ; f) Cultural and social approach : norms of moral judgment, ideals presented to the young, etc. ; g) Effect of social change : crime in developing countries, etc. (6 proposals) ; h) Effects of mass media, rapid dissemination of patterns of deviant behaviour (2 proposals). 5) Varieties of crime and criminals : a) Traffic in drugs ; b) Prison riots ; c) Violence particularly in youth (7 proposals) ; d) Dangerousness ; e) Relation to the rights of man (including rights of deviants); f) Female crime (2 proposals) ; g) Prostitution ; i) The mentally ill offender ; ;) Cultural variations in types of crime ; k) Organized crime ; /) Use of firearms ; m) Gambling ; n) Victims and victimology. 6) Treatment : evaluation : a) Social re-adaptation of offenders ; b) Statistical research on corrections, with possible computerization of data ; c) Comparisons between prisons and other closed environments ; d) Extra-legal consequences of deprivation of liberty ; e) Rehabilitation in developing countries ; f ) Criteria for evaluation of programs of correction ; g) Biochemical treatment (2 proposals) ; i) Differential treatment of different types of offense. Evaluation ; /) Prisons as agencies of treatment ; k) Effects of different degrees of restriction of liberty ; /) Environments of correctional institutions ; m) Study of prison societies ; n) Crime as related to the total social system. 7) Research methodology : a) Publication of what is known regarding methodology ; b) Methods of research ; c) Culturally-comparable vs culturally-contrasting situations ; d) Development of a new clearer terminology to facilitate communication ; e) Actual social validity of the penal law. 8) Statistics : epidemiology : a) Need for comparable international statistics ; standardized criteria (3 proposals) ; b) Difficulties. Criminologists must collect the data themselves. 9) Training of research workers : Recruiting and training of « com-paratists ». 10) Machinery : Committee of co-ordination. Discussions The discussions at the Symposium were based on these suggestions, the main concentration falling on problems of manifestations of violence in the world today, the phenomenon of student contestation, and on human rights and the corresponding responsibilities attached thereto. Although the participants did not come to definite conclusions as to the respective merits of the problems submitted for consideration, they did discuss the conditions under which comparative studies of these problems should be approached, the techniques appropriate to obtaining valid results, and the limitations on this type or work. Four workshops were established and studied the various problems. The first tackled the problems of the definition of the criteria of « danger » represented by different type of criminals ; the problem of discovering whether the value system which underlies the Human Rights Declaration corresponds to the value system of today's youth; the problem of the treatment of criminals ; of female criminality ; and, finally, of violence in the form of individual and group manifestations. The second workshop devoted its main consideration to the revolt of youth and to organized crime, also proposing that an international instrument bank of documentation and information be established. The third workshop considered problems of theory : how the police and the public view the criminal ; the opportunity of making trans-cultural comparisons on such subjects as arrest, prison, etc. ; and the role of the media of information in the construction of value systems. The fourth workshop blazed a trail in the matter of methodology appropriate to research in comparative criminology. The period of discussions which followed the report of the four workshops gave rise to a confrontation between two schools of thought within the group of specialists. The question arose as to whether the problem of student contestation falls within the scope of the science of criminology. Several experts expressed the opinion that criminologists ought not to concern themselves with a question which really belongs in the realm of political science. On the other hand, the majority of the participants appeared to feel that the phenomenon of student contestation did indeed belong in the framework of criminological research. One of the experts in particular took it upon himself to be the spokesman of this school of thought. There are those, he said, who feel that criminology should confine itself and its research to known criminality, to hold-ups, rape, etc. However, one should not forget that penal law rests on political foundations, the legality of power, a certain moral consensus of the population. Today, it is exactly this « legitimate » authority that is being contested. Is it not to be expected, therefore, that criminology should show interest in all sociological phenomena which have legal and criminal implications ? Contestation and violence have consequences for the political foundations of penal law, and therefore are fit subjects for the research of the criminologist. International Centre {or Comparative Criminology The First International Symposium for Research in Comparative Criminology situated itself and its discussions within the framework and in the perspectives opened by the founding of the International Centre for Comparative Criminology. The Centre is sponsored jointly by the University of Montreal and the International Society for Criminology, with headquarters at the University of Montreal. As one of the participants emphasized, criminologists need a place to retreat from the daily struggle, to meditate, to seek out and propose instruments of research valid for the study of problems common to several societies. Viewing the facts as scientists, we are looking for operational concepts. Theoreticians and research workers will rough out the material and, hopefully, this will inspire conferences and symposiums of practitioners, jurists, sociologists, penologists, and other specialists. Above all, it will give common access to international experience, something which is lacking at present both at the level of documentation and of action. A bank of instruments of method- ology in the field of comparative criminology does not exist at the present time. The Centre will undertake to compile and analyse research methods used in scientific surveys, and it will establish such an instrument bank. It will also gather and analyse information pertaining to legislative reforms now in progress or being contemplated in the field of criminal justice. Through the use of computers, the Centre will be able to put these two projects into effect and make the results easily accessible to research workers, and to all those concerned in this field. The participants at the Symposium were given a view of the extent of the problems envisaged for research by the future Centre. It is hoped that this initiative will be of concrete use to research workers, private organizations, public services and governments at many levels, and in many countries.

Compared to men, women less often attain high-level positions and generally have lower status in society. In smaller groups, the relative influence of men and women depends on gender composition, but research is inconclusive regarding the relation between gender composition and female influence. Studies of nonhuman primates show that when females are in the minority they become more dominant over males, but only when conflict levels are high, because under these conditions men fight among each other. Similarly, here we show, in two studies with mixed gender groups ( N = 90 and N = 56), that women were more dominant in groups with a high percentage of men and high levels of conflict. This depends on gender differences in aggressive behavior, inducing more aggressive behavior in women eliminated this increase in female dominance. Our work reveals that status relations between the genders among nonhuman primates can generalize to humans.

Genotoxic Effects of Radiofrequency-Electromagnetic Fields. IntroductionRadiation is energy emission in the form of electromagnetic waves emitted from the solar system and natural resources on earth. The currents produced by the elementary particles formed by the electric current create the magnetic field. Earth's surface is under the influence of the geomagnetic field emanating from the sun. However, the outer liquid also has a magnetic field created as a result of heat transfer in the core. Therefore, all living organisms on earth live under the influence of electromagnetic fields (EMF). Today, besides these natural energy resources, rapidly developing technological developments provide most of the convenience in our lives and expose people to artificial electromagnetic fields. However, man's magnetic field is also under the influence of other natural and artificial magnetic fields around him. In particular, by ionizing radiation, which carries enough energy to break down the genetic material, die cells as a result of DNA damaging, and other diseases, especially cancer, can develop as a result of tissue damage. Electromagnetic Fields in Our LivesToday, apart from natural geomagnetic fields, radiation is emitted from many technological devices. The spectrum of these fields includes many different types of radiation, from subatomic radiation such as gamma and X-rays to radio waves, depending on their wavelengths. Though, as a result of the rapid increase of technological growth, the duration and amount of exposure to EMF is also steadily increasing. On the other hand, wireless gadgets such as computers, smartphones and medical radiological devices have become a necessity for humans. Almost everyone is exposed to radiofrequency electromagnetic fields (RF-EMF) from cell phone and base station antennas or other sources. Thus, the damage caused by the radiation to the environment affects living organisms even many kilometres away unlimitedly. All organisms in the world live under the influence of these negative environmental changes and a large part of the world population is exposed to radiofrequency (RF) radiation for a long time in their daily lives. So, though we are not aware of it, our organs and tissues are constantly exposed to radiation. Therefore, radiation adversely affects human, animal and plant health and disrupts the environment and ecological balance. An example of negative effects, radiation can cause genetic changes in the body (Figure 1). Radiation is divided into ionizing and non-ionizing. Ionizing radiations cause electron loss or gain in an atom or group of atoms in the medium they pass through. Thus, positively or negatively charged ions are formed. High energy X, gamma, ultraviolet and some visible rays in the ionized region of the electromagnetic spectrum can be counted. Since gamma rays, X rays and ultraviolet rays can ionize the molecules in living things more, they can easily disrupt the chemical structure of tissues, cells and DNA molecules in living organisms. Therefore, they can be very dangerous and deadly to living things. The energy of the waves in the non-ionizing region of the electromagnetic spectrum is low and the energy levels are insufficient for the ionization of molecules. Electricity, radio and TV waves, microwaves, and infrared rays are not ionizing because they have low energy. Waves emitted from electronic devices (cell phones, computers, microwave ovens, etc.) are absorbed by the human and animal body. The amount of energy absorbed by the unit biological tissue mass per unit time is called the specific absorption rate (SAR), and its unit is W/kg. Risks of Electromagnetic Fields on Living ThingsDepending on the structure of the tissues and organs, the radiation must reach a certain threshold dose for the effect to occur. Radiation levels below the threshold dose are not effective. Depending on the structure of the tissues and organs, the radiation must reach a certain threshold dose. The effects of small doses of waves are negligible. However, the clinical effects of waves above a certain threshold may increase. High dose waves can cause cell death in tissues. Damages in the cell may increase the risk of cancer and hereditary damage after a while, and somatic effects in people exposed to radiation may cause cancer to appear years later. There is much research on the effects of RF fields. In vitro and in vivo studies on rats, plants and different tissues of humans; suggests that the RF fields are not genotoxic and the fact that harmful effect is due to the heat effect. The contradictory results on this issue have brought about discussions. Therefore, there are still concerns about the potential adverse effects of RFR on human health. A good understanding of the biological effects of RF radiation will protect against potential damages. Due to these uncertainties, with the electromagnetic field project of the World Health Organization, experimental and modelling studies on the biological effects of RF radiation have been accelerated. In 2011, the International Agency for Research on Cancer decided that RF-EMR waves could be potentially carcinogenic to humans (2). Considering that almost everyone, including young children, uses mobile phones in addition to other technological devices, the danger of electromagnetic waves has increased social interest. Genotoxic Effects of EMFIn addition to stimulating apoptosis and changes in ion channels, RF-EMF waves also have a potential effect on genetic material. The radiation absorbed by organisms causes the ionization of target molecules. In particular, biological damage may occur as a result of stimulation/ionization of atoms and disruption of molecular structures while ionizing radiation passes through tissue. As a result of ionization in the cell, electron increases and free electrons cause damage, especially in macromolecules and DNA. Free electrons move directly or indirectly. Free electrons directly affect the phosphodiester or H-bonds of DNA. As a result, the phosphodiester bonds of DNA in the cell are broken, single or double-stranded breakages and chemical toxins increase. DNA double-strand breaks are the most relevant biologic damage induced by ionizing radiation (3,4). There are no cells that are resistant to radiation. The nucleus of the cell and especially the chromosomes in dividing cells are very sensitive to radiation. One of the most important effects of radiation on the cell is to suppress cell growth. In particular, growth is impaired in cells exposed to radiation during cell division (mitosis). Consequently, cells with a high division rate are more sensitive to radiation. DNA damage in somatic cells can lead to cancer development or cell death. Cell death can occur as a result of breaking down DNA because ionizing radiation has enough energy to break down the cell's genetic material. Thus, tissues are damaged and cancer development may be triggered. DNA damage caused by radiation in cells is repaired by metabolic repair processes. If the breaks in DNA as a result of DNA damage caused by radiation in cells are not too large, they can be repaired by metabolic repair processes. Still, errors may occur during this repair. Chromosomes containing different genetic codes and information may also occur. In the cell, the released electrons interact with water molecules, indirectly causing the water to be reactively divided into two parts. Free radicals carry an electron that is not electrically shared in their orbits. Free radicals can cause genetic damage in DNA such as nucleotide changes, double and single-strand breaks. Radiation can cause chromosomes to break, stick together and rearrange. All these changes can lead to mutations or even further, the death of the cell. However, in addition to ionizing radiation, extracellular genotoxic chemicals and intracellular oxidative metabolic residues can also create stress in cells during DNA replication and cell division. Damage may occur during DNA replication under such environmental stress conditions. To date, conflicting results have been reported regarding the genotoxic effects of RF-EMF waves on genetic material. It has been reported that the energy of low EM fields is not sufficient to break the chemical bonds of DNA, but the increase in exposure time is effective on the formation of oxygen radicals and the disruptions in the DNA repair process. The absorption of microwaves can cause significant local warming in cells. For example, an increase in temperature has been observed in cells in culture media exposed to waves of high SAR levels. However, there is evidence that reactive oxygen species are formed in cells indirectly and experimentally exposed to RF-EMF waves. Free oxygen radicals can create nucleotide entries in DNA as well as bind cellular components to DNA bases (5). The frequency of polymorphisms observed in DNA repair mechanism genes in children with acute leukaemia living close to high energy lines reveals the effect of this energy on the repair process. Significant evidence has been reported that genotoxic effects occur in various cell types when exposed to RF-EMF waves (6-10). Here, it has been reported that cells exposed to RF-EMF waves (1.800 MHz, SAR 2 W/kg) cause oxidative damage in mitochondrial DNA, DNA breaks in neurons and DNA breaks in amniotic cells (6,10). Similarly, the damage has been reported in lymphocytes exposed to various RF-EMF waves (8). However, exposure to RF-EMF waves is known to cause chromosome imbalance, changes in gene expression, and gene mutations. Such deleterious genetic effects have also been reported in neurons, blood lymphocytes, sperm, red blood cells, epithelial cells, hematopoietic tissue, lung cells, and bone marrow (1,11,12). It has been found that exposure to RF-EMF radiation also increases chromosome numerical aberrations (6,13). It has also been reported that increased chromosome separation in mouse oocytes exposed to EM and increased DNA fragmentation and apoptosis in fly egg cells (14,15). However, increased DNA breaks have been reported in the blastomeres of embryos of pregnant mice exposed to a frequency of 50 Hz, and a decrease in the number of blastocysts has been reported (16). Genetic damages to sex cells can lead to persistent genetic diseases in subsequent generations. Today, X-ray devices used for medical diagnosis have become one of the largest sources of radiation. These radiological procedures used for diagnosis constitute an important part of ionizing radiation. During these processes, the human body is visibly or invisibly affected by X-rays. As a matter of fact, X-rays have effects of disrupting the structure and biochemical activities of DNA, RNA, proteins and enzymes that are vital in the organism (17). Many studies on this subject have revealed that radiation has suppressive and mutational effects on DNA synthesis. These effects can cause serious damage to the cell as well as DNA and chromosome damage. In a recent study, chromosome damage was investigated in patients with X-ray angiography and personnel working in radiological procedures (18). Our findings showed that the beams used in interventional radiological procedures caused chromosomal damage and the rate of chromosomal abnormalities (CAs) increased significantly in patients after the procedure and this damage increased with the amount of radiation dose. Therefore, the radiation dose to be given to the patient should be chosen carefully. Besides, our findings showed that the frequency of CA is significantly higher in personnel working in radiological procedures. This reveals that interventional cardiologists are exposed to high radiation exposure. For this reason, we can say that the personnel working in radiological procedures (physician, health technician and nurse) are very likely to get diseases after years because they are exposed to low doses but long-term X-rays. Therefore, both the potential risks and safety of exposure to medical radiological devices must be continuously monitored. Furthermore, the fact that chromatid and chromosome breaks are very common among structural CAs in our findings suggests that they may be the cause of malignancy. Because, there are many cancer genes, tumour suppressor genes, enzyme genes involved in DNA repair and important genes or candidate genes responsible forapoptosis on these chromosomes. All this information shows that patients are more susceptible to DNA damage and inappropriate radiological examinations should be avoided. Therefore, X-ray and other diagnostic imaging techniques should not be applied unless necessary, and physicians and patients should be more careful in this regard. It has been reported that RF-EMR waves emitted from wireless communication device mobile phones have a genotoxic effect on human and mammalian cells (6,19). In a recent study; The effects of 900 and 1800 MHz cell phone frequencies on human chromosomes were investigated in amniotic cell cultures (6). Here, it has been reported that chromosome packing delays, damage and breaks occur in amniotic cells exposed to 900 and 1800 MHz every day at 3, 6 and 12 hours for twelve days. However, it was found that the frequency of 1800 MHz caused more CAs than 900 MHz, and the amount of damage increased with increasing usage time. These results confirm that GSM-like RF-EMR causes direct genotoxic effects in human in vitro cultures and has adverse effects on human chromosomes, and these effects increase in parallel with exposure time. This shows us that the mobile phone carries a risk for human health and these genetic damages can cause cancer. Therefore, necessary precautions should be taken for these harmful effects of mobile phones. Among these measures, the periods of mobile phone use should be kept short, especially the exposure of developing children and infants to mobile phones should be prevented, and avoiding excessive use of mobile phones may be one of the precautions against cancer. However, in order to evaluate it in more detail, the effects of mobile phones with environmental mutagens and/or carcinogens should be considered in subsequent researches. ConclusionToday, in parallel with the increasing technological developments, the demand of the society for electronic devices and phones and the frequency ranges of electronic devices are constantly increasing. Waves emitted from electronic devices are absorbed by human and animal bodies. Especially, the use of phones by contact with our body and the increase in usage time affects not only adults but also young children. Therefore, there is increasing concern in society about the negative biological effects of EM waves emitted from phones and other electronic devices. Results from all studies show that RF-EMF waves may be carcinogenic due to their genotoxic effect. Because cancer is a disease that occurs as a result of genetic damage. Considering these negative and harmful effects, regulations following international standards regarding the use of electronic devices should be made and society should be made aware of the risks.References Kim JH.; Lee K.; Kim HG.; Kim KB.; Kim HR. 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ABSTRACT: Character education in Islam has its own style, as well as the character values con- tained in various learning media for early childhood. This study is a follow-up study to find the effect of Movie Media with Islamic Character Values (M-ICV) in shaping "Ahlaqul Karimah" in early childhood. Using an experimental method with a control class, which involved 19 respondents of early childhood. Data shows that the ttest < t table (0.75 < 2.110), meaning that there is a significant difference in effect between the experimental class and the control class. The results conclude that M-ICV is able to form a child's "Ahlakul Karimah" slowly, because the child likes various movies with content interesting and easy to imitate. The implications of further research on movie content development for children are able to develop other aspects of children's development. Keywords: Early Childhood, Ahlakul karimah, Islamic Character Values Movie Media References: Al-Qardawi, Y. (1981). al-Khasais al-`ammah lil Islami [The general criteria of Islam]. Qaherah: Makatabah Wahbah. An-Nawawi, Y. ibn S. (2000). Imam Nawawi’s Forty Hadith Yahya ibn Sharaf an-Nawawi. Ethiopia: Gondar. Bae, B. (2012). Children and Teachers as Partners in Communication: Focus on Spacious and Narrow Interactional Patterns. International Journal of Early Childhood, 44(1), 53–69. https://doi.org/10.1007/s13158-012-0052-3 Balakrishnan, V. (2017). Making moral education work in a multicultural society with Islamic hegemony. Journal of Moral Education, 46(1), 79–87. https://doi.org/10.1080/03057240.2016.1268111 Budiningsih, C. A. (2004). Pembelajaran Moral: Berpijak pada Karakteristik Siswa dan Budayanya. Jakarta: Rineka Cipta. Chalik, L., & Dunham, Y. (2020). Beliefs About Moral Obligation Structure Children’s Social Category-Based Expectations. Child Development, 91(1), e108–e119. https://doi.org/10.1111/cdev.13165 Danby, Susan, & Farrell, A. (2005). Opening the Research Conversation. 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Pex7p is a WD40-containing protein involved in peroxisomal import of proteins containing an N-terminal peroxisome-targeting signal (PTS2). The interaction of human recombinant Pex7p expressed in different hosts/systems with its PTS2 ligand and other peroxins was analysed using various experimental approaches. Specific binding of human Pex7p to PTS2 could be demonstrated only when Pex7p was formed in vitro by a coupled transcription/translation system or synthesized in vivo in Chinese hamster ovary K1 cells transfected with a construct coding for a Pex7p-green fluorescent protein (GFP) fusion protein. Apparently, no cofactors are required and only monomeric Pex7p binds to PTS2. The interaction is reduced upon cysteine alkylation and is impaired upon truncation of the N-terminus of Pex7p. Interaction of Pex7p with other peroxins could not be demonstrated in bacterial or yeast two-hybrid screens, or in pull-down binding assays. The GFP fusion proteins, tagged at either the N- or C-terminus, were able to restore PTS2 import in rhizomelic chondrodysplasia punctata fibroblasts, and Pex7p-GFP was located both in the lumen of peroxisomes and in the cytosol.

ABSTRACT Human immunodeficiency virus (HIV) infects cells by fusing with cellular membranes. Fusion occurs when the envelope glycoprotein (Env) undergoes conformational changes while binding to cellular receptors. Fusogenic changes involve assembly of two heptad repeats in the ectodomain of the gp41 transmembrane subunit to form a six-helix bundle (6HB), consisting of a trimeric N heptad repeat (N-HR) coiled-coil core with three antiparallel C heptad repeats (C-HRs) that pack in the coiled-coil grooves. Peptides corresponding to the N-and C-HRs (N and C peptides, respectively) interfere with formation of the 6HB in a dominant-negative manner and are emerging as a new class of antiretroviral therapeutics for treating HIV infection. We generated an escape mutant virus with resistance to an N peptide and show that early resistance involved two mutations, one each in the N- and C-HRs. The mutations conferred resistance not only to the selecting N peptide but also to C peptides, as well as other types of N-peptide inhibitors. Moreover, the N-HR mutation altered sensitivity to soluble CD4. Biophysical studies suggest that the 6HB with the resistance mutations is more stable than the wild-type 6HB and the 6HB formed by inhibitor binding to either wild-type or mutant C-HR. These findings provide new insights into potential mechanisms of resistance to HIV peptide fusion inhibitors and dominant-negative inhibitors in general. The results are discussed in the context of current models of Env-mediated membrane fusion.

This article studies the perception of great powers in the eyes of students in Kyrgyzstan and Kazakhstan using data collected through an online survey. The research has compared the perceptions of China’s and other Great Powers’ economic, political, and military authority among the youth of Central Asian countries during the COVID-19 pandemic. To analyze these perceptions, young people from Kazakhstan and Kyrgyzstan (N = 262) took part in a survey in the spring of 2021. Responses were analyzed to reveal the differences in perception by applying descriptive and inferential statistical methods, i.e., one-sample t-test. An association of geodemographic factors with the perception towards global powers was discovered by applying the chi-square test statistical method. The early research revealed that the role of the other Great Powers was seen mainly in political terms, while China’s role was mostly economic, however, recent studies made it clear that China’s political influence is increasing in the region. Another finding from this research is that China’s position on human rights and environmental issues is more negatively perceived than that of the other Great powers.

Rapid urbanization rates impact significantly on the nature of Land Cover patterns of the environment, which has been evident in the depletion of vegetal reserves and in general modifying the human climatic systems (Henderson, et al., 2017; Kumar, Masago, Mishra, & Fukushi, 2018; Luo and Lau, 2017). This study explores remote sensing classification technique and other auxiliary data to determine LULCC for a period of 50 years (1967-2016). The LULCC types identified were quantitatively evaluated using the change detection approach from results of maximum likelihood classification algorithm in GIS. Accuracy assessment results were evaluated and found to be between 56 to 98 percent of the LULC classification. The change detection analysis revealed change in the LULC types in Minna from 1976 to 2016. Built-up area increases from 74.82ha in 1976 to 116.58ha in 2016. Farmlands increased from 2.23 ha to 46.45ha and bared surface increases from 120.00ha to 161.31ha between 1976 to 2016 resulting to decline in vegetation, water body, and wetlands. The Decade of rapid urbanization was found to coincide with the period of increased Public Private Partnership Agreement (PPPA). Increase in farmlands was due to the adoption of urban agriculture which has influence on food security and the environmental sustainability. The observed increase in built up areas, farmlands and bare surfaces has substantially led to reduction in vegetation and water bodies. The oscillatory nature of water bodies LULCC which was not particularly consistent with the rates of urbanization also suggests that beyond the urbanization process, other factors may influence the LULCC of water bodies in urban settlements. Keywords: Minna, Niger State, Remote Sensing, Land Surface Characteristics References Akinrinmade, A., Ibrahim, K., & Abdurrahman, A. (2012). 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N-acetylglucosamine (GlcNAc) is being increasingly recognized for its ability to stimulate cell signaling. This amino sugar is best known as a component of cell wall peptidoglycan in bacteria, cell wall chitin in fungi and parasites, exoskeletons of arthropods, and the extracellular matrix of animal cells. In addition to these structural roles, GlcNAc is now known to stimulate morphological and stress responses in a wide range of organisms. In fungi, the model organisms Saccharomyces cerevisiae and Schizosaccharomyces pombe lack the ability to respond to GlcNAc or catabolize it, so studies with the human pathogen Candida albicans have been providing new insights into the ability of GlcNAc to stimulate cellular responses. GlcNAc potently induces C. albicans to transition from budding to filamentous hyphal growth. It also promotes an epigenetic switch from White to Opaque cells, which differ in morphology, metabolism, and virulence properties. These studies have led to new discoveries, such as the identification of the first eukaryotic GlcNAc transporter. Other results have shown that GlcNAc can induce signaling in C. albicans in two ways. One is to act as a signaling molecule independent of its catabolism, and the other is that its catabolism can cause the alkalinization of the extracellular environment, which provides an additional stimulus to form hyphae. GlcNAc also induces the expression of virulence genes in the C. albicans, indicating it can influence pathogenesis. Therefore, this review will describe the recent advances in understanding the role of GlcNAc signaling pathways in regulating C. albicans morphogenesis and virulence.

Abstract Treatment of human myeloid leukemia cells with 1-beta-D- arabinofuranosylcytosine (ara-C) is associated with induction of protein kinase activity and early-response gene expression. The present studies in ara-C-treated U-937 cells extend these findings by demonstrating activation of a protein kinase that phosphorylates myelin basic protein (MBP). Purification by sequential ion-exchange chromatography and gel filtration supports the detection of a 40-kD MBP kinase. Substrate and inhibitor studies further support a pattern similar to that of protein kinase C (PKC) isozymes. Results of N- terminal amino acid sequencing and immunoblot analysis demonstrate detection of a 40-kD catalytic fragment of PKCdelta. The results also demonstrate the activation and cleavage of PKCdelta (1) is inhibited by expression of antiapoptotic proteins, and (2) is induced by camptothecin (CAM) and mitomycin C (MMC). These findings support proteolytic activation of PKCdelta in the cellular response to ara-C and other DNA-damaging agents.

Treatment of human myeloid leukemia cells with 1-beta-D- arabinofuranosylcytosine (ara-C) is associated with induction of protein kinase activity and early-response gene expression. The present studies in ara-C-treated U-937 cells extend these findings by demonstrating activation of a protein kinase that phosphorylates myelin basic protein (MBP). Purification by sequential ion-exchange chromatography and gel filtration supports the detection of a 40-kD MBP kinase. Substrate and inhibitor studies further support a pattern similar to that of protein kinase C (PKC) isozymes. Results of N- terminal amino acid sequencing and immunoblot analysis demonstrate detection of a 40-kD catalytic fragment of PKCdelta. The results also demonstrate the activation and cleavage of PKCdelta (1) is inhibited by expression of antiapoptotic proteins, and (2) is induced by camptothecin (CAM) and mitomycin C (MMC). These findings support proteolytic activation of PKCdelta in the cellular response to ara-C and other DNA-damaging agents.

Abstract Enzymatic (glucose oxidase) measurement of glucose concentration in the fluid compartment of Psammomys erythrocytes (Gfe) and of its concentration in the fluid compartment of blood plasma (Gfp) gives the ratio (mean +/- SD): Gfe/Gfp = 1.50 +/- 0.43 (n = 12, 23 degrees C). However, when we added 3H-labeled glucose (G*) in vitro to the whole blood, the ratio after 2 min was G*fe/G*fp = 0.90 (SD 0.11) and after 5 min G*fe/G*fp = 0.97 (SD 0.12). These calculations were based on previous determination of the fractional volumes of the fluid and non-fluid compartments in Psammomys blood. The results suggest that there is more than one compartment of measurable glucose in Psammomys erythrocytes. Glucose undergoes a fast free transfer between the plasma and the erythrocyte fluids, and a much slower transmission to another measurable compartment in the erythrocyte, where it is loosely bound to other molecules. This loosely bound glucose does not participate in the fast kinetic transmission across the erythrocyte membrane, but it is measurable by the glucose-oxidase-based method. Preliminary studies on human erythrocytes lead to similar conclusions.

Abstract ABSTRACT: The nucleophosmin-1 (NPM1) mutation represents the most common genetic lesion (30-35%) in adult acute myeloid leukemia (AML) with the mutation resulting in the cytoplasmic delocalization of the NPM protein (NPMc+, most commonly mutation type A, c.860_863dupTCTG). Outside of conventional chemotherapy, treatment options for those with relapsed disease are extremely limited. We have previously discovered that leukemic cells expressing NPMc+ are preferentially sensitive to the cytotoxic effects of the first generation proteasome inhibitor, bortezomib, as result of the induction of superoxide in these cells (Huang M, et al., Leukemia, 2013). However, bortezomib has demonstrated only modest anti-leukemic activity as a single agent in early phase clinical trials that have included primarily heavily pretreated patients not stratified according to mutational genotype. In addition, the high incidence of clinically significant peripheral neuropathy in these studies led to early discontinuation of treatment. MLN9708 (Ixazomib) is a novel second generation proteasome inhibitor that is orally bioavailable and has shown promising activity and improved tolerability in early phase clinical trials in lymphoma and in multiple myeloma, where it is currently in a Phase III clinical trial. The efficacy of MLN9708 in relapsed patients with AML has not yet been examined. We have investigated the in vitro effects of MLN9708 on the cytotoxicity, generation of reactive oxygen species (ROS), and cellular glutathione in both cultured NPMc+ AML cell lines and primary leukemic samples. Cultured OCI-AML3 cells (human AML cell line featuring the NPMc+ mutation) were approximately 50-fold more sensitive to MLN9708 with a mean half inhibitory concentrations (IC50 ± SD) of 67 nM ± 1.83 nM at 24 hours than were an AML cell line (THP-1) expressing wild type NPM1. Knockdown of both NPM1/NPMc+ by inducible NPM1 shRNA expression significantly attenuated the MLN9708-mediated cytotoxicity, as determined by MTS colorimetric and flow cytometric apoptosis assays. As with bortezomib, MLN9708 treatment at 75 nM induced a 2.1-fold (p < 0.002) increase in superoxide-specific DHE (PE)-derived fluorescence as compared to controls. Pre-incubation of cells with 25 mM N-acetylcysteine, a ROS scavenger, dramatically reduced cytotoxicity, strongly implicating the generation of ROS in the mechanism of MLN9708-induced cytotoxicity. Knockdown of NPM1/ NPMc+ expression resulted in an increase of glutathione levels of 2.6-fold (p < 0.04) in untreated cells, and 2.3-fold (p < 0.005) and 2.9-fold (p < 0.004) after a 22 hour incubation with MLN9708 at pharmacologically achievable doses of 75 nM and 150 nM, respectively (Figure 1). In addition, a concomitant 4-fold reduction (p < 0.04) in the NADP+/NADPH ratio was observed in the NPM1/NPMc+ depleted OCI-AML3 cells. In vitro apoptosis assays of primary leukemic blasts isolated from five patients with relapsed NPMc+ AML showed an IC50 for MLN9708 ranging from 49.963-467.487nM (183.8 nM ± 176.8 nM). Based on these promising in vitro studies, a Phase 2 clinical trial of single-agent oral MLN9708 (clinicaltrials.gov identifier: NCT02030405) has been initiated for patients with relapsed or refractory NPMc+ AML. We conclude that the expression of NPMc+ renders AML cells more susceptible to MLN9708 toxicity and that this effect results at least in part from the generation of superoxide. Lower glutathione levels in NPMc+ expressing cells suggests an underlying defect in the antioxidant defense pathway. Demonstration of the sensitivity of NPMc+ AML cells to MLN9708 as a single agent may serve as a platform for the development of novel combination strategies with this drug. Acknowledgments: Research was facilitated by the ASH Clinical Research Training Institute and AACR/ASCO Clinical Cancer Research training program. J.S.G is funded by the Leukemia & Lymphoma Society Career Development Award and ASCO YIA award through a grant supported by Mr. Aaron Sasson. J.S.G. is further supported by the Stanford Hematology Fellowship Program. Figure 1 Effect of NPM1/NPMc+ depletion in OCI-AML3 cells on intracellular glutathione levels Figure 1. Effect of NPM1/NPMc+ depletion in OCI-AML3 cells on intracellular glutathione levels Disclosures Off Label Use: MLN9708 is an investigational compound by Millennium Pharmaceuticals, Inc. (MPI). Through an MTA we have secured the compound for in vitro analysis. This data has led to a clinical trial and drug for that study is supplied by MPI.. Medeiros:Agios: Consulting - Ad board Other.

: Dyslipidemia is the major risk factor for atherosclerotic cardiovascular disease (ASCVD), cerebrovascular disease, and peripheral artery disease (PAD). It is characterized by higher plasma concentrations of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), apolipoprotein B (apoB), very low-density lipoprotein-cholesterol (VLDL-c), triglycerides (TGs) and low levels of high-density lipoprotein-cholesterol (HDL-c). Herbal medicines are preferred by many across the globe particularly to manage chronic conditions such as dyslipidemia, hypertension, type 2 diabetes, cancer, and plenty of others. Nigella sativa (black seeds or black cumin seeds) is a miracle herb employed within the management of many sicknesses for centuries. Hence, this review focuses on the ameliorative effects of N. sativa on the plasma lipid concentrations of human subjects. Numerous randomized controlled clinical trials (RCTs) and different clinical studies demonstrated that N. sativa possesses potential anti-dyslipidemic activity. The patients with dyslipidemia may well be benefited by using N. sativa along with healthy lifestyle changes and statin and other antihyperlipidemic medications as adjuvant therapy if needed.

Summary Background. The purpose of this study was to probe the pleiotrophic effects of Atorvastatin on intraplatelet-nitric oxide metabolism. Methods and Results. Hyperlipidemic subjects (n = 19) were treated for 1 month (following a 3-week washout) with either Atorvastatin or placebo in a double-blinded randomized (n = 2, crossover), placebo-controlled study. Changes in the levels of intraplatelet nitric oxide synthase, nitrotyrosine were correlated with cholesterol, LDL-C, HDL-C and triglyceride levels. These studies indicate that with atrovastatin ecNOS levels increased on average by ~1.7-fold (paired t-test p = 0.009). Interestingly, levels of nitrotyrosylated platelet proteins, an indication of peroxynitrite damage, decreased as ecNOS levels increased in presence of the drug (paired t-test p = 0.33). Atorvastatin, at 10 mg per day, lowered cholesterol and LDL-C levels in all patients with the average lowering of ~21% and ~17% respectively. The effect on HDL was not significant whilst triglyceride levels were lowered by an average of ~18%. Conclusions. This study adds to the volume of evidence that statins have beneficial effects other than lipid lowering. Here, Atorvastatin is shown to significanly elevate intraplatelet ecNOS levels in hyperlipidemic subjects without affecting iNOS expression. The net result of this would be the elevation of NO production which would promote platelet deaggregation and vasodilation.

Background: Public health policies in the area of food and diets tend to separate recommendations on food safety and nutrition. However, food products can simultaneously have risks and benefits. Risk-benefit assessment (RBA) seeks to integrate the assessment of both risks and benefits to aid complex decision-making using a multidisciplinary approach. In this study, a systematic literature review of recent RBA studies was performed, focusing on food consumption and human health following earlier reviews by Boué, et al. (2015) and Thomsen, et al. (2021). Results: A total of 50 new RBA studies were reviewed since 20 May 2014. Our current literature review shows that the majority of RBA studies conducted in recent years remain focused on seafood, with studies on fish alone comprising 34% of all studies; the focus being on the benefits of fish consumption versus contaminant exposure. Most of the studies have been conducted in Europe (n = 31) and Asia (n = 11). Conclusion: RBA has the potential to be applied more widely to other food choices such as alternative proteins, yet application remains limited to specific applications and contaminant/nutrient case studies. In recent years, a few RBA studies have been reported on less mainstream food sources and one specifically on novel foods. Novel foods offer a unique application space for RBA as their development is focused heavily on the benefits to the consumer, society, and environment, yet there remains uncertainty as to their safety.

The surfactant-associated protein A (SP-A) belongs to the collectin family, a group of C-type lectins encompassing also surfactant-associated protein D, mannan-binding protein (MBP) and conglutinin. These proteins all have carbohydrate-recognition domains joined to collagen stalks. It seems likely that SP-A, like MBP and conglutinin, may mediate anti-microbial activity through binding to carbohydrates on the microorganisms and collectin receptors on phagocytic cells. We have studied the influence of carbohydrates on the binding of SP-A, MBP and conglutinin to mannan in an enzyme-linked lectin-binding assay. All sugars were of D-configuration, except fucose of which both L- and D-configurations were tested. The order of inhibiting potency on the binding of SP-A was: N-acetylmannosamine > L-fucose, maltose > glucose > mannose. The following sugars were non-inhibitory: galactose, D-fucose, glucosamine, mannosamine, galactosamine, N-acetylglucosamine, and N-acetylgalactosamine. The best inhibitor of MBP was N-acetylglucosamine. Otherwise MBP showed a selectivity similar to that of SP-A. Conglutinin binding was inhibited by all the sugars examined except N-acetylgalactosamine. For conglutinin, as for MBP, the best inhibitor was N-acetylglucosamine. Normal human SP-A, alveolar-proteinosis SP-A purified by ion-exchange chromatography, and alveolar-proteinosis SP-A purified by n-butanol extraction showed no difference in sugar selectivity. The influence of pH and of the calcium concentration was also examined. Organic solvent-extracted SP-A from patients suffering from alveolar proteinosis and normal SP-A showed different sensitivity profiles.

N-Benzylphenethylamines are novel psychedelic substances increasingly used for research, diagnostic, or recreational purposes. To date, only a few metabolism studies have been conducted for N-2-methoxybenzylated compounds (NBOMes). Thus, the available 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe) metabolism data are limited. Herein, we investigated the metabolic profile of 25CN-NBOMe in vivo in rats and in vitro in Cunninghamella elegans (C. elegans) mycelium and human liver microsomes. Phase I and phase II metabolites were first detected in an untargeted screening, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of the most abundant metabolites by comparison with in-house synthesized reference materials. The major metabolic pathways described within this study (mono- and bis-O-demethylation, hydroxylation at different positions, and combinations thereof, followed by the glucuronidation, sulfation, and/or N-acetylation of primary metabolites) generally correspond to the results of previously reported metabolism of several other NBOMes. The cyano functional group was either hydrolyzed to the respective amide or carboxylic acid or remained untouched. Differences between species should be taken into account in studies of the metabolism of novel substances.

Abstract Previous studies indicate that factor H (fH) binds to a number of cell types and may have functions other than C regulation. We have examined for fH binding to PMN using flow cytometry and radiolabeled binding assays. Binding of fH was demonstrated to be specific and saturable with approximately 6 x 10(4) binding sites/polymorphonuclear leukocytes (PMN) and a Ka value of 3.3 x 10(8) L/M. Binding of fH to PMN was ionic strength dependent, required divalent cations, and was enhanced by PMN stimulation with FMLP and calcium ionophore, A23187. The 38-kDa N-terminal tryptic fragment of fH bound to PMN and blocking experiments with mAb suggested a receptor binding site was located within the fifth SCR of fH. fH binding was not due to associations with surface-bound C3 or to CR3. Binding of fH to U937 and Raji cells, but not to T cells was also demonstrated. These studies provide presumptive evidence for a fHR on PMN. Binding of fH by fHR could enhance recognition of opsonized targets, trigger secondary intracellular events or contribute to intrinsic protection of cells against C.

P450 oxidoreductase (POR) is a two-flavin protein that reduces microsomal P450 enzymes and some other proteins. Preparation of active bacterially expressed human POR for biochemical studies has been difficult because membrane-bound proteins tend to interact with column matrices. To reduce column-protein interactions and permit more vigorous washing, human POR lacking 27 N-terminal residues (N-27 POR) was modified to carry a C-terminal Gly3His6-tag (N-27 POR-G3H6). When expressed in Escherichia coli, N-27 POR-G3H6 could be purified to apparent homogeneity by a modified, single-step nickel-nitrilotriacetic acid affinity chromatography, yielding 31 mg POR per liter of culture, whereas standard purification of native N-27 POR required multiple steps, yielding 5 mg POR per liter. Both POR proteins had absorption maxima at 375 and 453 nm and both reduced cytochrome c with indistinguishable specific activities. Using progesterone as substrate for bacterially expressed purified human P450c17, the Michaelis constant for 17α-hydroxylase activity supported by N-27 POR or N-27 POR-G3H6 were 1.73 or 1.49 μm, and the maximal velocity was 0.029 or 0.026 pmol steroids per picomole P450 per minute, respectively. Using 17-hydroxypregnenolone as the P450c17 substrate, the Michaelis constant for 17,20 lyase activity using N-27 POR or N-27 POR-G3H6 was 1.92 or 1.89 μm and the maximal velocity was 0.041 or 0.042 pmol steroid per picomole P450 per minute, respectively. Thus, N-27 POR-G3H6 is equally active as native N-27 POR. This expression and purification system permits the rapid preparation of large amounts of highly pure, biologically active POR and may be generally applicable for the preparation of membrane-bound proteins.

Campylobacter is a major foodborne pathogen responsible for acute gastroenteritis characterized by diarrhea that is sometimes bloody, fever, cramps, and vomiting. Campylobacter species are carried in the intestinal tracts of mammals and birds, and sources of human infection include raw milk, contaminated water, direct contact with pets, and foods, particularly poultry. Campylobacter jejuni and C. coli are the species that account for the majority of human infections. The aim of this work was to determine the prevalence of Campylobacter in 190 poultry carcasses sampled at slaughter and to use a multiplex PCR assay to determine if the isolates were C. jejuni or C. coli. C. coli was not isolated, while C. jejuni was recovered from 52 (37.1%) of 140 carcasses for which pools of four sampling sites (neck, cloaca, breast, and back) were examined. In the remaining 50 carcasses, the four sites were analyzed separately, and C. jejuni was recovered from the samples in the following order: neck (n = 20), cloaca (n = 16), breast (n = 14), and back (n = 11). The results are in agreement with those of other studies, which showed that C. jejuni is more commonly associated with poultry than is C. coli. Control strategies for Campylobacter should include interventions to eliminate C. jejuni in poultry at various stages of production and processing, including at slaughter.

MUC1 is high-molecular-weight glycoprotein which is widely expressed on epithelial cell layers of various organs and is aberrantly overexpressed in most human carcinomas such as breast, ovarian or colon cancer. MUC1 contains three domains: short cytoplasmic and transmembrane domains, and a long extracellular domain. The protein is translated as a single polypeptide that undergoes auto-cleavage into two subunits: MUC1-N and MUC1-C, that form a stable noncovalent complex at the cell membrane. In normal epithelial cells, MUC1 expression is restricted to the apical side of the cells. During cancer transformation there is a loss of cell polarity and MUC1-C is found over the entire cell surface while MUC1-N is shed from the surface of carcinoma cells. As the result of depolarization, MUC1-C interacts with receptor tyrosine kinases (RTKs), such as EGFR and activates intracellular pathways which are important for cancer progression. Overexpression of MUC1 is also associated with the accumulation of MUC1-C in the cytoplasm and targeting of this subunit to the nucleus or mitochondria. Nuclear localization of MUC1-C is associated with activation of gene families involved in oncogenesis or cancer metabolism. Other results have shown that MUC1-C localizes to the mitochondrial outer membrane, where it blocks stress induced apoptosis. Recent studies have been directed at the MUC1-C subunit which reminds to be attractive target for the development of anti-cancer agents. In this review, the role of MUC1-C in cancer progression is discussed.

DNA MMR (mismatch repair) is an excision repair system that removes mismatched bases generated primarily by failure of the 3′–5′ proofreading activity associated with replicative DNA polymerases. MutL proteins homologous to human PMS2 are the endonucleases that introduce the entry point of the excision reaction. Deficiency in PMS2 function is one of the major etiologies of hereditary non-polyposis colorectal cancers in humans. Although recent studies revealed that the CTD (C-terminal domain) of MutL harbours weak endonuclease activity, the regulatory mechanism of this activity remains unknown. In this paper, we characterize in detail the CTD and NTD (N-terminal domain) of aqMutL (Aquifex aeolicus MutL). On the one hand, CTD existed as a dimer in solution and showed weak DNA-binding and Mn2+-dependent endonuclease activities. On the other hand, NTD was monomeric and exhibited a relatively strong DNA-binding activity. It was also clarified that NTD promotes the endonuclease activity of CTD. NTD-mediated activation of CTD was abolished by depletion of the zinc-ion from the reaction mixture or by the substitution of the zinc-binding cysteine residue in CTD with an alanine. On the basis of these results, we propose a model for the intramolecular regulatory mechanism of MutL endonuclease activity.

The publication presents an analysis of management specialist development problems arising in today's situation. Special attention is paid to management specialist development in the conditions of globalization, knowledge society development, European integration and the European Union enlargement. The publication provides an in‐depth analysis of management specialists development principles and practical experiences in the area of management specialist development. The absence of well‐founded general principles of management specialist development as well as specialprinciples of business and public management specialist development remains an important research problem.The absence of integrated and individualized university studies and of the practical realization of the life‐long learning principle in the area of management specialist development remains an important practical problem. The aim of the publication ‐ to formulate and ground the main principles of management specialist development as well as to describe an original management specialist development model based on the implementation of the idea of life ‐long learning. The research methodology is based on the concept of triangulation, combining the descriptive analysis, surveys and expert evaluation. The scientific novelty, theoretical and practical results are defined by the following:The following groups of principles are singled out: a) general development principles, applicable to specialists of all fields, including that of management; b) special principles of management specialist development, applicable exceptionally to management specialist development; c) specific principles of business management specialist development; d) specific principles of public management specialist development, applicable exceptionally to the development of specialists working in the public sector and public management. This model provides for combination of diverse forms of learning, university studies, independent researches, self‐development and in‐service training; long‐term individual programmers are designed to help people acquire different qualifications and develop their competences through studies in universities and other educational institutions and through participating in practical works, workshops and seminars. Introduction of long‐term individualized development programmers facilitates development of unique managerial skills and prepares every specialist for a unique position, a unique professional activity and individualized functions. The management specialist development model based on the implementation of the idea of life ‐ long learning as well as integrated and individualized university and non ‐ university studies is described. An important element of management specialist development process is development of human creativity. It also depicts specific characteristics of creativity and highlights new opportunities and possibilities for the development of the creative potential.

Hypoxia is a severe stress factor to which man and most other mammalian species are capable of adapting. However, the cellular mechanisms that enable cells to tolerate decreases in ambient oxygen tension are still unknown. We have previously shown that hypoxia induces the synthesis of unique proteins (molecular mass 38, 52, 74, 76 kDa) in human aortic endothelial cells and lymphocytes. In this study we investigated the specificity of hypoxia on the upregulation of these hypoxic stress proteins (HYP) in human peripheral blood lymphocytes and the role of calcium in this response. 35S-methionine pulse-labeling studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis and autoradiography demonstrated that normobaric hypoxia (4% O2–5% CO2–91% N2) enhanced synthesis of HYP, whereas heat-shock protein synthesis was not affected. Heat shock (42°C) and cold stress (4°C) did, however, induce synthesis of heat-shock protein but not HYP. The 38-kDa HYP is the major protein for which synthesis is upregulated by hypoxia. Its isoelectric point (pI) is 3.5–4.0, and it is localized in the cytosol. The 52-kDa HYP has a pI of >6.5, and it is also localized in the cytosol. The 74- and 76-kDa HYPs appear to be membrane bound. In addition to hypoxia, an increase in calcium concentration in the culture media (25–50 mM) enhanced synthesis of HYP. An ethylene glycol-bis(-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)/Ca2+ binding complex, when added to blood lymphocytes during exposure to hypoxia, significantly inhibited HYP synthesis. On the basis of the similarity of molecular masses, pI, localization in the cytosol, and Ca2+ dependence of HYP expression, we suggest that HYP 38 and 52 may be isoenzymes of inositol 1,4,5-triphosphate 3-kinase, an enzyme that regulates phosphoinositol turnover and intracellular calcium concentration in cells. calcium; internal localization; stress

Abstract Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc gene in normal adrenals was localized to the zona fasciculata and zona reticularis, with much lower expression in the zona glomerulosa and adrenal medulla. In hormonally active adrenocortical carcinomas (n=6) and in virilizing adenomas (n=4), c-myc mRNA levels were approximately 10% of those in normal adrenals (n=11). In contrast, adrenal adenomas from patients with Cushing's (n=4) and Conn's (n=9) syndrome, non-functional adenomas (n=2), adrenocortical hyperplasias (bilateral, n=5; nodular, n=4), and non-functional adrenocortical carcinomas (n=3) expressed c-myc mRNA to the same extent as normal adrenals. The c-myc mRNA abundance in benign adrenal pheochromocytomas (n=19) was similar to that in normal adrenal medulla. However, in malignant adrenal pheochromocytomas (n=6), the average c-myc mRNA levels were approximately threefold that in benign adrenal pheochromocytomas. There was a good correlation between c-myc mRNA expression and immunohistochemical reactivity in both normal and pathological adrenal tissues. Southern blot analysis revealed no amplification or rearrangement of the c-myc gene in any of the adrenal tumors. In conclusion, c-myc expression localized to zona fasciculata and reticularis in normal adrenals. Virilizing adenomas and hormonally active adrenocortical carcinomas expressed c-myc mRNA clearly less than the other adrenal neoplasms and normal adrenal tissue. On the other hand, malignant pheochromocytomas contained more c-myc mRNA than benign ones. Further studies are required to clarify the mechanisms and significance for the distinct expression pattern of the c-myc gene in different adrenal neoplasms. Journal of Endocrinology (1997) 152, 175–181

ABSTRACT The cadherin/catenin complex serves as an important structural component of adherens junctions in epithelial cells. Under certain conditions, β-catenin can be released from this complex and interact with transcription factors in the nucleus to stimulate the expression of genes that regulate apoptosis and cell cycle control. While studying the effects of the bacterial pathogen Chlamydia trachomatis on human cervical epithelial cells in culture, we observed that C. trachomatis caused the epithelial cells to separate from each other without detaching from their growing surface. The objective of the present study was to determine if this effect might involve the disruption of the cadherin/catenin complex. Primary cultures of human cervical epithelial cells or HeLa cells were infected with C. trachomatis serovar E. Cadherin-like immunoreactive materials and β-catenin were visualized by immunofluorescence. Preliminary studies showed that N-cadherin was the primary cadherin expressed in both the primary cultures and the HeLa cells. In noninfected cells, N-cadherin and β-catenin were colocalized at the intercellular junctional complexes. By contrast, the infected cells showed a marked loss of both N-cadherin and β-catenin labeling from the junctional complexes and the concomitant appearance of intense β-catenin labeling associated with the chlamydial inclusion. The results of Western blot analyses of extracts of C. trachomatis showed no evidence of cross-reactivity with the β-catenin antibody. These results indicate that C. trachomatis causes the breakdown of the N-cadherin/β-catenin complex and that the organism can sequester β-catenin within the chlamydial inclusion. This could represent an important mechanism by which C. trachomatis alters epithelial cell function.

Enteroviruses (EVs) are viruses of the family Picornaviridae that cause mild to severe infections in humans and in several animal species, including non-human primates (NHPs). We conducted a survey and characterization of enteroviruses circulating between humans and great apes in the Congo. Fecal samples (N = 24) of gorillas and chimpanzees living close to or distant from humans in three Congolese parks were collected, as well as from healthy humans (N = 38) living around and within these parks. Enteroviruses were detected in 29.4% of gorilla and 13.15% of human feces, including wild and human-habituated gorillas, local humans and eco-guards. Two identical strains were isolated from two humans coming from two remote regions. Their genomes were similar and all genes showed their close similarity to coxsackieviruses, except for the 3C, 3D and 5′-UTR regions, where they were most similar to poliovirus 1 and 2, suggesting recombination. Recombination events were found between these strains, poliovirus 1 and 2 and EV-C99. It is possible that the same EV-C species circulated in both humans and apes in different regions in the Congo, which must be confirmed in other investigations. In addition, other studies are needed to further investigate the circulation and genetic diversity of enteroviruses in the great ape population, to draw a definitive conclusion on the different species and types of enteroviruses circulating in the Republic of Congo.

Earth’s critical zone is defined as a plant–soil–water system, which covers a wide area and has a large vertical thickness, but the soil elemental stoichiometry characteristics of the critical zone at different depths are still unclear. In this study, the spatial distribution of soil carbon (C), nitrogen (N) and phosphorus (P) in the critical zone of a typical wetland in Dongting Lake, China, and their ecological chemometric characteristics were analyzed. The results indicated that: (1) the average C, N and P contents were 18.05, 0.86 and 0.52 g/kg, respectively, with a decreasing trend from the surface to the deeper layers. The soil is relatively rich in C and P, while N is the main element limiting plant growth and development. (2) The mean values of soil C/N, N/P and C/P were 21.1, 1.7 and 35.4 respectively, with the C/N ratio and C/P ratio showing a trend of increasing and then decreasing in the vertical direction and reaching a maximum at a depth of 2–5 m below ground. (3) According to the correlation results, C, N and P in soils are coupled and influenced by each other (p < 0.001), and pH, infiltration coefficient and human activities are closely related to the spatial distribution of C, N and P. (4) Stable Redfield ratios (1:1.6:35.4) may exist in lake wetland soils, and future studies should be conducted for complete systems of the same type of wetlands. The results of the study will provide a theoretical basis for the sustainable development and scientific management of lake wetlands.

Proliferating cell nuclear antigen (PCNA) plays essential roles in DNA replication, DNA repair, cell-cycle regulation and chromatin metabolism. The PCNA fromDrosophila melanogaster(DmPCNA) was purified and crystallized. The crystal of DmPCNA diffracted to 2.0 Å resolution and belonged to space groupH3, with unit-cell parametersa=b= 151.16,c= 38.28 Å. The structure of DmPCNA was determined by molecular replacement. DmPCNA forms a symmetric homotrimer in a head-to-tail manner. An interdomain connector loop (IDCL) links the N- and C-terminal domains. Additionally, the N-terminal and C-terminal domains contact each other through hydrophobic associations. Compared with human PCNA, the IDCL of DmPCNA has conformational changes, which may explain their difference in function. This work provides a structural basis for further functional and evolutionary studies of PCNA.

Brevin is a Ca2+-modulated actin-associated protein that will sever F-actin and cap barbed filament ends. Limited proteolysis with chymotrypsin or subtilisin cleaves the molecule approximately in half. Cleavage is approximately 10-fold more rapid in Ca2+ than in EGTA. The two fragments are readily separated from each other and from undigested brevin by high pressure liquid chromatography on a DEAE resin. A 40,000-mol-wt fragment from the N-terminal is not retained by DEAE, while a 45,000-mol-wt C-terminal fragment binds more tightly than brevin. The N-terminal fragment retains approximately 10% of the nucleation activity, caps barbed ends, and retains 50% of the total severing activity defined by dilution induced depolymerization of pyrenyl actin, but, in contrast to brevin, none of these functions are affected by Ca2+. Fluorescent actin binding studies and gel-filtration demonstrate that the 40,000-mol-wt fragment binds two actin monomers. The 45,000-mol-wt C-terminal fragment has no severing, nucleating, or capping activity. Cross-reaction with two monoclonal antibodies against two specific Ca2+-induced conformations of human platelet gelsolin suggest that both Ca2+ binding sites are located on the carboxyl half of the brevin molecule. One epitope, defined as the rapidly exchanging Ca2+ binding site in the gelsolin-actin complex, is lost when a 20,000-mol-wt fragment is cleaved from the carboxyl terminal. The second epitope, related to the poorly exchanging Ca2+ binding site in the complex, is nearer the middle of the brevin molecule.

Previous characterization of GLI, a gene found to be amplified and expressed in a subset of human brain tumors, revealed the presence of five tandem zinc fingers related to those of Krüppel (Kr), a Drosophila segmentation gene of the gap class. We have used the GLI cDNA as a molecular probe to isolate related sequences from the human genome. Partial characterization of six related loci, including sequence determination, expression studies, and chromosome localization, revealed that each locus could encode a separate finger protein. The predicted proteins all had similar H-C links, i.e., a conserved stretch of 9 amino acids connecting the C-terminal histidine of one finger to the N-terminal cysteine of the next. On the basis of amino acid sequence and intron-exon organization, the genes could be placed into one of two subgroups: the GLI subgroup (with the consensus finger amino acid sequence [Y/F]XCX3GCX3[F/Y]X5LX2HX3-4H[T/S]GEKP) or the Kr subgroup (with the consensus finger amino acid sequence [Y/F]XCX2CX3FX5LX2HXRXHTGEKP). Unlike GLI or Kr, most of the newly isolated genes were expressed in many adult tissues. The predicted proteins probably control the expression of other genes and, by analogy with Kr and GLI, may be important in human development, tissue-specific differentiation, or neoplasia.

Previous characterization of GLI, a gene found to be amplified and expressed in a subset of human brain tumors, revealed the presence of five tandem zinc fingers related to those of Krüppel (Kr), a Drosophila segmentation gene of the gap class. We have used the GLI cDNA as a molecular probe to isolate related sequences from the human genome. Partial characterization of six related loci, including sequence determination, expression studies, and chromosome localization, revealed that each locus could encode a separate finger protein. The predicted proteins all had similar H-C links, i.e., a conserved stretch of 9 amino acids connecting the C-terminal histidine of one finger to the N-terminal cysteine of the next. On the basis of amino acid sequence and intron-exon organization, the genes could be placed into one of two subgroups: the GLI subgroup (with the consensus finger amino acid sequence [Y/F]XCX3GCX3[F/Y]X5LX2HX3-4H[T/S]GEKP) or the Kr subgroup (with the consensus finger amino acid sequence [Y/F]XCX2CX3FX5LX2HXRXHTGEKP). Unlike GLI or Kr, most of the newly isolated genes were expressed in many adult tissues. The predicted proteins probably control the expression of other genes and, by analogy with Kr and GLI, may be important in human development, tissue-specific differentiation, or neoplasia.

In their current guidelines cardiac societies recommend the consumption of the twon-3 fatty acids EPA and DHA to prevent cardiovascular complications. Cardiovascular events are reduced by EPA and DHA, because they are antiarrhythmic, mitigate the course of atherosclerosis and stabilise plaque. As atherosclerosis is considered an inflammatory disorder a number of studies have investigated the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context in human dietary intervention studies. Pro-inflammatory cytokines, or cytokines reflecting inflammatory processes, e.g. IL-1β, IL-2, IL-6, TNFα, platelet-derived growth factor (PDGF)-A and -B and monocyte chemoattractant protein-1 (MCP-1), are reduced by ingestion of EPA and DHA by human subjects. Interestingly, C-reactive protein remains largely unaltered. However, inin vitroand animal models, but less so in human subjects, soluble cytokines reflecting interactions between blood cells and the vessel wall, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, are reduced. Moreover, in contrast to common expectations, oxidative stress seems to be reduced after ingestion of EPA and DHA, at least as indicated by measurement of urinary F2isoprostane excretion. Notably, for PDGF-A and -B and for MCP-1 the reduction has been demonstrated to occur at the gene expression level, which indicates that a deliberate change in diet can alter gene expression quantitatively. The precise underlying mechanism, however, remains to be clarified, but might involve PPAR, NF-κB and/or the eicosanoid system. The same holds true for the mechanisms by which levels of other cytokines are altered by EPA and DHA.

Seven spot ladybird beetle, (Coccinella septempunctata) is a widely distributed natural enemy of soft-bodied insect pests especially aphids worldwide. Both the adult and larvae of this coccinellid beetle are voracious feeders and serve as a commercially available biological control agent around the globe. Different techniques are adopted to enhance the mass rearing and storage of this natural enemy by taking advantage of its natural ability to withstand under extremely low temperatures and entering diapause under unfavorable low temperature conditions. The key objective of this study was to develop a cost effective technique for enhancing the storage life and predatory potential of the larvae of C. septempunctata through cold storage in conjunction with the use of nuclear techniques, gamma radiations. Results showed that the host eating potential of larvae was enhanced as the cold storage duration was increased. Gamma irradiation further enhanced the feeding potential of larvae that were kept under cold storage. Different irradiation doses also affected the development time of C. septempuntata larvae significantly. Without cold storage, the lower radiation doses (10 and 25 GY) prolonged the developmental time as compared to un-irradiated larvae. Furthermore, the higher dose of radiation (50GY) increased the developmental time after removal from cold storage. This study first time paves the way to use radiation in conjunction with cold storage as an effective technique in implementation of different biological control approaches as a part of any IPM programs.Key wordGamma irradiations; cold storage, Coccinella septempunctata larvae; predatory potential; integrated pest management programme.INTRODUCTIONNuclear techniques such as gamma radiations have a vast application in different programmes of biological control including continuous supply of sterilized host and improved rearing techniques (Greany and Carpenter, 2000; Cai et al., 2017). Similarly irradiation can be used for sentinel-host eggs and larvae for monitoring survival and distribution of parasitoids (Jordão-paranhos et al., 2003; Hendrichs et al., 2009; Tunçbilek et al., 2009; Zapater et al., 2009; Van Lenteren, 2012). Also, at the production level, such technique may facilitate the management of host rearing, improve quality and expedite transport of product (Fatima et al., 2009; Hamed et al., 2009; Wang et al., 2009). Gamma irradiations can also be used to stop insect’s development to enhance host suitability for their use in different mass rearing programs (Celmer-Warda, 2004; Hendrichs et al., 2009; Seth et al., 2009). Development and survival of all insects have a direct connection with temperatures which in turn affect the physical, functional and behavioral adaptations (Ramløy, 2000). Many insects living in moderate regions can survive at low temperature by process of diapause. A temperature between 0 to 10oC may cause some insects to become sluggish and they only become active when the temperature is suitable. Such insects show greater adaptations to flexible temperature regimes for better survival. Many studies have reported this concept of cold-hardiness in insects in general (Bale, 2002; Danks, 2006) and specifically in coccinellid beetles over past years (Watanabe, 2002; Koch et al., 2004; Pervez and Omkar, 2006; Labrie et al., 2008; Berkvens et al., 2010). Using this cold hardiness phenomenon, many coccinellids have been studied for the effect of cold storage such as Coccinella undecimpunctata (Abdel‐Salam and Abdel‐Baky, 2000), Coleomegilla maculata (Gagné and Coderre, 2001) and Harmonia axyridis (Watanabe, 2002). This natural phenomenon, therefore, can be a helpful tool in developing low temperature stockpiling for improving mass-rearing procedures (Mousapour et al., 2014). It may provide a significant output in terms of providing natural enemies as and when required during pest infestation peaks (Venkatesan et al., 2000). Use of irradiation in conjunction with cold storage proves to be an effective technique in implementation of different biological control approaches as a part of any IPM programme. A study reported that the pupate of house fly, Musca domestica irradiated at dose of 500 Gy and can stored up to 2 months at 6°C for future use for a parasitoid wasp Spalangia endius rearing (Zapater et al., 2009). Similarly, when irradiated at 20 GY, parasitic wasps Cotesia flavipes were stored safely up to two months without deterioration of their parasitic potential (Fatima et al., 2009). Similarly, bio-control program of sugarcane shoot borer Chilo infescatellus proved successful through the use of irradiation combined with cold storage of its egg and larval parasitoids Trichogramma chilonis and C. flavipes (Fatima et al., 2009). Less mobile life stages such as larvae are of significance in any IPM strategy because they remain on target site for more time period as compared to adults. Therefore, use of predatory larvae is very promising in different biological control approaches because of their immediate attack on pests and more resistance to unfavorable environmental conditions than delicate egg stage. In addition, with their augmentation into fields, larval stage shows their presence for longer time than adult stage and their feeding potential is also satisfactory as that of adults. For the best utilization of these predators in the field and maximum impact of 3rd and 4th larval instars on prey, we should encourage late 2nd second instar larvae of predatory beetles in the fields as these instars have more feeding capacity due to increased size and ability to handle larger preys.In spite of higher significance, there is little information available about the effect of cold storage on the survival of larval instars of different ladybird beetles and its effect on their predatory potential. Very few studies report the use of cold storage for non-diapausing larval stage like for Semiadalia undecimnotata and only one study reported the short-term storage (up to two weeks) of 2nd and 3rd instar coccinellid, C. maculate, without any loss in feeding voracity of larvae after storage (Gagné and Coderre, 2001). The survival of 3rd and 4th larval instars of C. undecimpunctata for 7 days after storage at 5oC was reported in a study but the survival rate declined after 15-60 days of storage (Abdel‐Salam and Abdel‐Baky, 2000). As C. septempunctata is considered one of the voracious predators (Afroz, 2001; Jandial and Malik, 2006; Bilashini and Singh, 2009; Xia et al., 2018) and diapause is a prominent feature of this beetle and it may undergo facultative diapause under suitable laboratory conditions (Suleman, 2015). No information is available to date about the combined effect of cold storage and irradiation on the larval instars of this species.OBJECTIVES The objective of this study was to devise a cost effective technique for the cold storage and its effect on the subsequent predatory potential of the seven spotted ladybird beetle larvae in conjunction with the use of gamma radiations. Hypothesis of the study was that an optimum length of low temperature treatment for storage purpose would not affect the predation capacity of C. septempunctata larvae and their developmental parameters including survival and pupation will remain unaffected. Furthermore, use of gamma irradiation will have some additional effects on survival and feeding capacity of irradiated C. septempunctata larvae. Such techniques can be utilized in different biocontrol programs where short term storage is required. So these larvae can be successfully imparted in different IPM programs against sucking complex of insect pests as a component of biological control strategyMATERIALS AND METHODSPlant materials: Collection and rearing of C. septempunctata: Adult C. septempunctata were collected from the wheat crop (in NIAB vicinity and farm area) in the month of March during late winter and early in spring season 2016-2017. They were kept in plastic jars and were fed with brassica aphids. Under controlled laboratory conditions (25+2oC, 16h: 8h L:D and 65+5% R.H.), eggs of C. septempuctata were obtained and after hatching, larvae were also given brassica aphids as dietary source. Larvae of second instar were selected for this experiment (as the first instar is generally very weak and vulnerable to mortality under low temperatures). As the larvae approached second instar, they were separated for the experimentation. Irradiation of larvae at different doses: Irradiation of larvae was carried out by the irradiation source 137CS at Radiation laboratory, and the larvae were then brought back to the IPM laboratory, Plant Protection Division, Nuclear Institute for Agriculture and Biology (NIAB) Faisalabad. Radiation doses of 10 GY (Grey), 25 GY and 50 GY were used to treat the second instar larvae. There were three replicates for each treatment and five larvae per replicate were used. Control treatment was left un-irradiated.Cold storage of irradiated larvae: In present work, second instar C. septempunctata larvae were studied for storage at low temperature of 8oC. The larvae were kept at 8oC for 0, I and II weeks where week 0 depicts no cold treatment and this set of larvae was left under laboratory conditions for feeding and to complete their development. For larvae that were kept under cold storage for one week at 8°C, the term week I was devised. Similarly, week II denotes the larvae that remained under cold conditions (8°C) for two continuous weeks. Larvae were removed from cold storage in their respective week i.e., after week I and week II and were left under laboratory conditions to complete their development by feeding on aphids. Data collection: For recording the predatory potential of C. septempunctata larvae, 100 aphids were provided per larva per replicate on a daily basis until pupation as this number was more than their feeding capacity to make sure that they were not starved (personal observation). Observations were recorded for survival rate, developmental time and feeding potential. Data analysis: Data were statistically analysed by Statistical Software SPSS (Version 16.0). The data were subjected to normality check through the One-sample Kolmogorov-Smirnov test. Non normal data were transformed to normal data which were then used for all parametric variance tests. One-way and two-way analyses of variance were used. For comparison between variables, LSD test at α 0.05 was applied.RESULTSFeeding potential of irradiated larvae after removal from cold storage: Results showed an increase in the feeding potential of C. septempunctata larvae with increased cold storage duration. The feeding potential was significantly higher for the larvae that spent maximum length of time (week II) under cold storage conditions followed by week I and week 0. Gamma irradiations further enhanced the feeding potential of larvae that were kept under cold storage. When larvae were irradiated at 10 GY, the eating capacity of larvae increased significantly with the duration of cold storage. Similarly, larvae that were irradiated at 25 GY, showed increase in feeding potential on aphids as the time period of cold storage increased. The feeding potential of larvae that were irradiated at 50 GY, was again significantly increased with increase of cold storage duration. When different radiation doses were compared to week 0 of storage, there was a significant difference in feeding potential and larvae irradiated at 50 GY consumed the maximum numbers of aphids when no cold storage was done followed by larvae irradiated at 10 and 25 GY. With the other treatment, where larvae were kept under cold storage for one week (week I) the larvae irradiated at 50GY again showed the highest feeding potential. The feeding potential of irradiated larvae was again significantly higher than the un-irradiated larvae that were kept for two weeks (week II) under cold storage (table 1).Two-way ANOVA was performed to check the interaction between the different radiation doses and different lengths of storage durations for feeding potential of C. septempunctata larvae on aphids. The feeding potential of larvae irradiated at different doses and subjected to variable durations of cold storage were significantly different for both the radiation doses and cold storage intervals. Furthermore, the interaction between the radiation doses and storage duration was also significant meaning that the larvae irradiated at different doses with different length of cold storage were having significant variations in feeding levels (table 2).Developmental time of irradiated larvae after removal from cold storage: Significant difference was found in the development time of the larvae of C. septempunctata when irradiated at different doses at week 0 (without cold storage). The larvae irradiated at 10 GY took the maximum time for development and with the increase in irradiation dosage, from 25 to 50 GY, the time of development was shortened. The larvae irradiated at 50 GY had the same development time as the un-irradiated ones. When, the irradiated larvae were subjected to cold storage of one week duration (week I), their development time after removal from storage condition varied significantly. The larvae irradiated at 25 GY took the maximum time for development followed by larvae irradiated at 50 GY and 10 GY. There was an indication that the development time was extended for irradiated larvae as compared to un-irradiated larvae.Results also depicted a significant difference in the time taken by irradiated larvae to complete their development after taken out from cold storage of two weeks duration (week II). As the storage time of irradiated larvae increased, the development time was prolonged. Results showed that the larvae that were irradiated at 25 and 50 GY, took the maximum time to complete their development. With the prolonged duration of cold storage up to two weeks (week II), this difference of development time was less evident at lower doses (10 GY). The larvae irradiated at 10 GY showed a significant difference in their developmental duration after being taken out of cold storage conditions of the week 0, I and II. There was no difference in the developmental duration of larvae that were un-irradiated and subjected to different regimes of storage. Un-irradiated larvae were least affected by the duration of storage. With the increase in the storage time, a decrease in the developmental time was recorded. Larvae that were irradiated at 10 GY, took the maximum period to complete their development when no cold storage was done (week 0) followed by week I and II of cold storage. When the larvae irradiated at 25 GY were compared for their development time, there was again significant difference for week 0, I and II of storage duration. Maximum time was taken by the larvae for their complete development when removed from cold storage after one week (week I). With the increase in storage duration the time taken by larvae to complete their development after removal from cold storage reduced.When the larvae were removed after different lengths of cold storage duration i.e., week 0, week I and week II, there was a significant difference in the developmental time afterwards. Results have shown that the higher dose of radiation, increased the developmental time after removal from cold storage. The larvae irradiated at 50 GY took the longest time to complete their development after removal from cold storage (week I and week II) as compared the larvae that were not kept under cold storage conditions (week 0) (table 3).Interaction between the different radiation doses and different lengths of storage durations for development time of larvae were checked by two-way ANOVA. The development time of larvae irradiated at different doses and subjected to variable durations of cold storage were significantly different for both the doses and cold storage intervals. Furthermore, the interaction between the radiation doses and storage duration was also significant meaning that the larvae irradiated at different doses with different length of cold storage were having significant variations in development times (table 4). DISCUSSIONThe present research work indicates the possibility of keeping the larval instars of C. septempunctata under cold storage conditions of 8oC for a short duration of around 14 days without affecting its further development and feeding potential. Furthermore, irradiation can enhance the feeding potential and increase the development time of larval instars. This in turn could be a useful technique in mass rearing and field release programmes for biological control through larval instars. Usually temperature range of 8-10oC is an optimal selection of low temperature for storage as reported earlier for eggs two spotted ladybird beetle, Adalia bipunctata and the eggs of C. septempunctata (Hamalainen and Markkula, 1977), Trichogramma species (Jalali and Singh, 1992) and fairyfly, Gonatocerus ashmeadi (Hymenoptra; Mymaridae) (Leopold and Chen, 2007). However, a study reported more than 80% survival rate for the coccinellid beetle, Harmonia axyridis for up to 150 days at moderately low temperature of 3-6oC (Ruan et al., 2012). So there is great flexibility in coccinellid adults and larvae for tolerating low temperature conditions. After removal from cold storage, larvae showed better feeding potential with consumption of more aphids when compared to normal larvae that were not placed under low temperature conditions. This indicates that when the adult or immature insect stages are subjected to low temperature environment, they tend to reduce their metabolic activity for keeping them alive on the reserves of their body fats and sustain themselves for a substantial length of time under such cold environment. Hereafter, the larval instars that were in cold storage were behaving as if starved for a certain length of time and showed more hunger. This behavior of improved or higher feeding potential of stored larvae has been reported previously (Chapman, 1998). Hence, the feeding potential of C. septempunctata larvae significantly increased after cold storage. Gagné and Coderre (2001) reported higher predatory efficacy in larvae of C. maculata when stored at the same temperature as in the present study i.e., 8oC. Similarly, Ruan et al. (2012) showed that the multicolored Asian ladybug, H. axyridis, when stored under cold conditions, had more eating capacity towards aphids Aphis craccivora Koch than the individuals that were not stored. Such studies indicate that the higher feeding potential in insects after being subjected to low temperature environmental conditions could be due to the maintenance of their metabolism rate to a certain level while utilizing their energy reserves to the maximum extent (Watanabe, 2002).The individuals coming out from cold storage are therefore capable of consuming more pray as they were in a condition of starvation and they have to regain their energy loss through enhanced consumption. Furthermore, the starvation in C. septempunctata has previously been reported to affect their feeding potential (Suleman et al., 2017). In the present study, the larval development was delayed after returning to normal laboratory conditions. Cold storage affects the life cycle of many insects other than coccinellids. The cold storage of green bug aphid parasitoid, Lysiphlebus testaceipes Cresson (Hymenoptra; Braconidae) mummies increased the life cycle 3-4 times. Nevertheless, in current study the development process of stored larvae resumed quickly after taking them out and larvae completed their development up to adult stage. Similar kinds of results were reported for resumption of larval development after removal from cold storage conditions. Such studies only report satisfactory survival rates and development for a short duration of cold storage but as the length of storage is increased, it could become harmful to certain insects. Gagné and Coderre (2001) reported that cold storage for longer period (three weeks) proved fatal for almost 40% of larvae of C. maculata. Furthermore, in the same study, the feeding potential of C. maculata larvae was also affected beyond two weeks of cold storage due to the loss of mobility after a long storage period. Many studies have reported that longer durations of low temperature conditions can either damage the metabolic pathways of body cells or may increase the levels of toxins within the bodies of insects. Also, low temperature exposure for longer duration may cause specific interruptions in the insect body especially neuro-hormones responsible for insect development, which could be dangerous or even life threatening.Chen et al. (2004) also reported that the biological qualities of parasitized Bemisia tabaci pupae on population quality of Encarsia formosa were affected negatively with increase in cold storage duration. Similarly, the egg hatchability of green lacewing Chrysoperla carnea Stephen was lost completely beyond 18 days of cold storage (Sohail et al., 2019). However, in the present study the cold storage was done for maximum two weeks and it is to be regarded as a short term storage hence the survival rate was satisfactory. Longer periods of cold storage for larvae are not considered safe due to their vulnerable state as compared to adults which are hardier. Also 2nd instar larvae used in the present study for cold storage for being bigger in size and physical stronger than 1st instar. Abdel‐Salam and Abdel‐Baky (2000) reported that in C. undecimpunctata the cold storage of 3rd and 4th larval instars was higher and considered safer than early larval instars. The same study showed sharp decline in survival rate after two weeks and there was no survival beyond 30-60 days of cold storage. The present study showed that short term storage of the larvae of C. septempunctata could be done without any loss of their feeding potential or development so the quality of predator remained unaffected. Similar kind of work for many other insects had been reported previously where cold storage technique proved useful without deteriorating the fitness of stored insects. For example, the flight ability of reared codling moth Cydia pomonella Linnaeus remained unaffected after removal from cold storage (Matveev et al., 2017). Moreover, a sturdy reported that pupae of a parasitoid wasp Trichogramma nerudai (Hymenoptera; Trichogrammatidae) could be safely put in cold storage for above than 50 days (Tezze and Botto, 2004). Similarly, a technique of cold storage of non-diapausing eggs of black fly Simulium ornaturm Meigen was developed at 1oC. Another study reported safe storage of a predatory bug insidious flower bug Orius insidiosus for more than 10 days at 8°C (Bueno et al., 2014).In present study without cold storage, the lower doses of 10 and 25 GY prolonged the developmental time as compared to un-irradiated larvae and higher doses of irradiations in conjunction with cold storage again significantly prolonged the developmental time of larvae when returned to the laboratory conditions. Salem et al. (2014) also reported that Gamma irradiations significantly increased the duration of developmental stages (larvae and pupae) in cutworm, Agrotis ipsilon (Hufnagel). In another study, where endoparasitic wasps Glyptapanteles liparidis were evaluated with irradiated and non-irradiated gypsy moth Lymantria dispar larvae for oviposition, it was found that non-irradiated larvae had a shorter time to reach the adult stage as compared to irradiated larvae (Novotny et al., 2003). Both for higher doses with cold storage and lower doses without cold storage extended the larval duration of C. septempunctata. In another study when the parasitoid wasp Habrobracon hebetor was irradiated at the dose of 10 GY, it resulted in prolonged longevity (Genchev et al., 2008). In the same study, when another parasitoid Ventruria canescens was irradiated at lower doses of 4GY and 3 GY, it resulted in increased emergence from the host larvae, while gamma irradiations at the dose of 1 GY and 2 GY significantly stimulated the rate of parasitism (Genchev et al., 2008). The current study also indicated higher rates of predation in the form of increased feeding potential of larvae as a result of irradiations at lower doses.CONCLUSIONThe outcome of the current study shows that storage of 2nd instar C. septempunctata at low temperature of 8oC for a short duration of about 14 days is completely safe and could have broader application in different biocontrol programs. Such flexibility in storage duration can also assist in different mass rearing techniques and commercial uses. The combination of gamma radiation with low temperature cold storage could be a useful tool in developing different biological pest management programs against sucking insect pests. Incidence of periodic occurrence of both the target insect pests with their predatory ladybird beetles in synchrony is an important aspect that could be further strengthened by cold storage techniques. Therefore, short or long term bulk cold storage of useful commercial biocontrol agents and then reactivating them at appropriate time of pest infestation is a simple but an advantageous method in mass rearing programs. Increased feeding capacity of stored larvae is another edge and hence such larvae may prove more beneficial as compared to unstored larvae. Both cold storage and improved feeding of the C. septempuctata larvae can be utilized for implementation of IPM for many sucking insect pests of various crops, fruits and vegetables. Due to some constraints this study could not be continued beyond two weeks but for future directions, higher doses and longer duration periods could further elaborate the understanding and better application of such useful techniques in future IPM programmes on a wider scale. Also, some other predatory coccinellid beetle species can be tested with similar doses and cold storage treatments to see how effective this technique is on other species as well.ACKNOWLEDGMENTS We acknowledge the Sugarcane Research and Development Board for providing a research grant (No. SRDB/P/4/16) to carry out this research work. 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Previous studies of hypercapnic ventilatory responses (HCVR) in human heart-lung transplant recipients (HLTX) have yielded conflicting results. We compared the HCVR of restricted transplant recipients (HLTX-R) to recipients with normal pulmonary function (HLTX-N), and normal controls (C). HLTX-R exhibited limited tidal volume responses, whereas their frequency responses were essentially identical to those of other subjects. Accordingly, HCVR of HLTX-R (1.45 +/- 0.59 l.min-1.Torr CO2(-1)) were significantly depressed compared with both HLTX-N and C (2.90 +/- 0.55 vs 3.05 +/- 1.23, respectively) (P less than 0.02). Despite undoubtedly greater ventilatory impedances, airway (mouth) occlusion pressure responses (Pm0.1) during hypercarbia of HLTX-R (0.46 +/- 0.28 cmH2O) were similar to those of C (0.43 +/- 0.20) and paradoxically blunted compared with HLTX-N (0.83 +/- 0.36) (P less than 0.02). We conclude that pulmonary reflexes are superfluous for maintenance of HCVR in HLTX with normal respiratory mechanics, whereas the presence of moderate restriction results in profound depression of CO2 responses among these subjects.

In addition to their physiological and metabolic roles, anthocyanin (Antho) levels in lettuce contribute to visual and nutritional value-based assessments of crop quality. Although 7 genes are now thought to help regulate Antho synthesis, deposition and/or degradation in lettuce, the genetic and abiotic controls of Antho levels remain less well characterized in lettuce than other plants. Previous greenhouse studies demonstrated that Antho levels in diverse lettuce varieties are a function of temperature and lighting regimen. Here, three strongly related Lolla Rossa-type varieties (`Lotto', `Valeria', and `Impuls') varying in the number of genes controlling intensity of anthocyanins were subjected to differential temperature conditions in growth chambers to better discern the independent and interactive effects of temperature (T) and variety (V) on Antho levels. Fifteen day-old seedlings were placed into one of three chambers maintained at 20 °C day/night (D/N), 30 °C/20 °C D/N or 30 °C D/N. Antho levels were measured in leaf tissue collected 30 d after transplanting. The entire experiment was replicated twice. Although significant, the T x V interaction resulted from differences in the magnitude, not direction, of the change in Antho concentrations among varieties with changes in T. This suggests that T was a main driver of Antho levels in this study. Regardless of V, Antho concentrations were highest, moderate and lowest after growth at 20 °C D/N, 30 °C/20 °C D/N and 30 °C D/N, respectively. Likewise, regardless of T, Antho levels followed the pattern `Impuls' (three genes) > `Valeria' (two genes) > `Lotto' (one gene). Correlations among instrumented and human eye-based evaluations of color are also being tested in samples from both studies.

Human society has undergone many shifts and changes at structural and functional levels. The hierarchical structure which exists in the society is the root cause of discrimination among different groups and communities. Groups who are at the lower end are powerless and face discrimination in almost every domain of society. Such marginalization can occur due to gender, ethnicity, disability, caste, class and many more such constructs. The struggle of Girls with Disabilities (GwD) to access and participate in the educational domain remains an issue of great concern for disability activists and researchers. The purpose of this study was a) to explore and understand the lived experiences of GwD in their struggle for education through the lens of the Social Model of Disability (SMD) and b) to identify the issues, concerns, and challenges that GwD face due to their doubly marginalized identities-one based on disability and other on gender, by using the ‘case study’ research method. Themes emerging from the study are (a) socio-cultural issues and disability identity, (b) peer interaction in an educational setting, (c) access and participation in formal educational institutions, (d) gateways of empowerment, and e) structural access and assistive facilities. The findings indicate how policymakers can enhance access and the quality of participation of GwD in educational institutions.

ABSTRACT Ribavirin in combination with alpha 2 interferon is the consensus treatment for chronic hepatitis C. However, recent preliminary pharmacological studies have suggested that the bioavailability of ribavirin displays great interindividual variability. In order to monitor serum ribavirin levels during combination treatment, we developed and validated a quantitative assay using an approach adaptable for routine hospital laboratories. The method involved solid-phase extraction on phenyl boronic acid cartridges followed by high-performance liquid chromatography with a C18-bonded silica column and a mobile phase containing 10 mM ammonium phosphate buffer (with the pH adjusted to 2.5) and UV detection (207 nm). The sensitivity, recovery, linearity of the calibration curve, intra- and interassay accuracies, precision, and stability at 4°C were consistent with its use in the laboratory routine. In addition, other nucleoside analogues sometimes used with ribavirin in patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus did not interfere with the quantification of ribavirin levels. The ribavirin concentration was quantified in 24 serum samples from patients with chronic hepatitis C treated with a combination of ribavirin and alpha 2 interferon. The mean serum ribavirin concentration was 2.67 ± 1.06 μg/ml (n = 24) at week 12 of treatment (W12) and 3.24 ± 1.35 μg/ml (n = 24) at week 24 of treatment (W24). In addition, ribavirin concentrations displayed high interindividual variabilities: the coefficients of variation of the serum ribavirin concentrations adjusted to the administered dose were 44 and 48% at W12 and W24, respectively. Moreover, the ribavirin concentration was higher in patients with a sustained virological response (n = 11) than in patients with treatment failure (n = 13), with significant intergroup differences at W12 (P = 0.030) and W24 (P = 0.049). The present study describes a simple analytical method for the quantification of ribavirin in human serum that could be a useful tool for the monitoring of ribavirin concentrations in HCV-infected patients in order to improve the efficacy and safety of therapy with ribavirin plus interferon.

MSX1 is one of the homeoproteins with the homeodomain (HD) sequence, which regulates proliferation and differentiation of mesenchymal cells. In this study, we investigated the nuclear localization signal (NLS) in the MSX1 HD by deletion and amino acid substitution analyses. The web-based tool NLStradamus predicted 2 putative basic motifs in the N- and C-termini of the MSX1 HD. Green fluorescent protein (GFP) chimera studies revealed that NLS1 (161RKHKTNRKPR170) and NLS2 (216NRRAKAKR223) were independently insufficient for robust nuclear localization. However, they can work cooperatively to promote nuclear localization of MSX1, as was shown by the 2 tandem NLS motifs partially restoring functional NLS, leading to a significant nuclear accumulation of the GFP chimera. These results demonstrate a unique NLS motif in MSX1, which consists of an essential single core motif in helix-I, with weak potency, and an auxiliary subdomain in helix-III, which alone does not have nuclear localization potency. Additionally, other peptide sequences, other than predicted 2 motifs in the spacer, may be necessary for complete nuclear localization in MSX1 HD.

ABSTRACT The phosphoproteins (P proteins) of paramyxoviruses play a central role in transcription and replication of the viruses by forming the RNA polymerase complex L-P and encapsidation complex (N-P) with nucleocapsid protein (N) and binding to N protein-encapsidated genome RNA template (N-RNA template). We have analyzed the human parainfluenza virus type 3 (HPIV3) P protein and deletion mutants thereof in an in vitro transcription and in vivo replication system. The in vitro system utilizes purified N-RNA template and cell extract containing L and P proteins coexpressed via plasmids using a recombinant vaccinia virus expression system. The in vivo system takes advantage of minigenome replication, which measures luciferase reporter gene expression from HPIV3 minigenomes by viral proteins in a recombinant vaccinia virus expression system. These studies revealed that the C-terminal 20-amino-acid region of P is absolutely required for transcription in vitro and luciferase expression in vivo, suggesting its critical role in viral RNA synthesis. The N-terminal 40-amino-acid region, on the other hand, is essential for luciferase expression but dispensable for transcription in vitro. Consistent with these findings, the C-terminal domain is required for binding of P protein to the N-RNA template involved in both transcription and replication, whereas the N-terminal domain is required for the formation of soluble N-P complex involved in encapsidation of nascent RNA chains during replication. Coimmunoprecipitation analysis showed that the P protein forms a stable homooligomer (perhaps a trimer) that is present in L-P and N-P complexes in the higher oligomeric forms (at least a pentamer). Interestingly, coexpression of a large excess of N- or C-terminally deleted P with wild-type P had no effect on minigenome replication in vivo, notwithstanding the formation of heterooligomeric complexes. These data indicate that P protein with a deleted terminal domain can function normally within the P heterooligomeric complex to carry out transcription and replication in vivo.

SummaryActivated protein C (APC) is an antithrombotic serine proteinase having anticoagulant, profibrinolytic and anti-inflammatory activities. Despite its potential clinical utility, relatively little is known about its clearance mechanisms. In the present study we have characterized the interaction of APC and its active site blocked forms with human umbilical vein endothelial cells (HUVEC). At 4° C 125I-APC bound to HUVEC in a specific, time dependent, saturable and reversible manner. Scatchard analysis of the binding isotherm demonstrated a Kd value of 6.8 nM and total number of binding sites per cell of 359,000. Similar binding isotherms were obtained using radiolabeled protein C (PC) zymogen as well as D-phe-pro-arg-chloromethylketone (PPACK) inhibited APC indicating that a functional active site was not required. Competition studies showed that the binding of APC, PPACK-APC and PC were mutually exclusive suggesting that they bound to the same site(s). Proteolytic removal of the N-terminal γ-carboxyglutamic acid (gla) domain of PC abolished its ability to compete indicating that the gla-domain was essential for cell binding. Surprisingly, APC binding to these cells appeared to be independent of protein S, a cofactor of APC generally thought to be required for its high affinity binding to cell surfaces. The identity of the cell binding site(s), for the most part, appeared to be distinct from other known APC ligands which are associated with cell membranes or extracellular matrix including phospholipid, thrombomodulin, factor V, plasminogen activator inhibitor type 1 (PAI-1) and heparin. Pretreatment of HUVEC with antifactor VIII antibody caused partial inhibition of 125I-APC binding indicating that factor VIII or a homolog accounted for ∼30% of APC binding. Studies of the properties of surface bound 125I-APC or 125I-PC and their fate at 4°C compared to 37 °C were consistent with association of ∼25% of the initially bound radioligand with an endocytic receptor. However, most of the radioligand appeared not to be bound to an endocytic receptor and dissociated rapidly at 37° C in an intact and functional state. These data indicate the presence of specific, high affinity binding sites for APC and PC on the surface of HUVEC. While a minor proportion of binding sites may be involved in endocytosis, the identity and function of the major proportion is presently unknown. It is speculated that this putative receptor may be a further mechanisms of localizing the PC antithrombotic system to the vascular endothelium.

Abstract An in vitro gut-immune co-culture model with apical and basal accessibility, designed to more closely resemble a human intestinal microenvironment, was employed to study the role of the N-linked protein glycosylation pathway in Campylobacter jejuni pathogenicity. The gut-immune co-culture (GIC) was developed to model important aspects of the human small intestine by the inclusion of mucin-producing goblet cells, human enterocytes and dendritic cells, bringing together a mucus-containing epithelial monolayer with elements of the innate immune system. The utility of the system was demonstrated by characterizing host–pathogen interactions facilitated by N-linked glycosylation, such as host epithelial barrier functions, bacterial invasion and immunogenicity. Changes in human intestinal barrier functions in the presence of 11168 C. jejuni (wildtype) strains were quantified using GICs. The glycosylation-impaired strain 11168 ΔpglE was 100-fold less capable of adhering to and invading this intestinal model in cell infectivity assays. Quantification of inflammatory signaling revealed that 11168ΔpglE differentially modulated inflammatory responses in different intestinal microenvironments, suppressive in some but activating in others. Virulence-associated outer membrane vesicles produced by wildtype and 11168ΔpglE C. jejuni were shown to have differential composition and function, with both leading to immune system activation when provided to the gut-immune co-culture model. This analysis of aspects of C. jejuni infectivity in the presence and absence of its N-linked glycome is enabled by application of the gut-immune model, and we anticipate that this system will be applicable to further studies of C. jejuni and other enteropathogens of interest.

The relevance of the study is due, on the one hand, to the growing infl uence of society on nature, often leading to environmental problems, and, on the other hand, to insuffi cient understanding of the role of the natural foundations of human social behavior. The purpose of the article is to analyze the main methodological approaches to the study of the “nature – society” system and their potential for obtaining new knowledge. The article uses a historical approach: the well-known methodologies for studying this system are analyzed as they are introduced into scientifi c circulation, as well as a comparative approach: similarities and differences between the analyzed methodologies and the degree of their heuristicity are revealed. The article analyzes the methodological schemes by E. V. Girusov, V. A. Kobylyansky, N. D. Subbotina, E. Yu. Zakharova and others. The foreign authors K. Fuchs, R. Rees and R. Hambleton were selected, as their views, on the one hand, are very close to the theories of domestic specialists on this issue, on the other hand, they complement them. The authors conclude that almost all of the above methodological approaches are heuristic, they can be used to obtain new knowledge in this area of research. We suggest that these methodologies can be used to study a new phenomenon ‒ a digital system. The study is also of practical importance, as it argues that it is necessary to use these methodologies in the appraisal of social and technical projects.

Language makes human communication possible. Apart from everyday applications, language can provide insights into individuals’ thinking and reasoning. Machine-based analyses of text are becoming widespread in business applications, but their utility in learning contexts are a neglected area of research. Therefore, the goal of the present work is to explore machine-assisted approaches to aid in the analysis of students’ written compositions. A method for extracting common topics from written text is applied to 78 student papers on technology and ethics. The primary tool for analysis is the Latent Dirichlet Allocation algorithm. The results suggest that this machine-based topic extraction method is effective and supports a promising prospect for enhancing classroom learning and instruction. The method may also prove beneficial in other applied applications, like those in clinical and counseling practice. References Blei, D. M., Ng, A. Y., & Jordan, M. I. (2003). Latent Dirichlet Allocation. Journal of Machine Learning Research 3, 993-1022. Bruner, J. (1990). Acts of meaning. Cambridge, MA: Harvard University Press. Chen, K. Y. M., & Wang, Y. (2007). Latent dirichlet allocation. http://acsweb.ucsd.edu/~yuw176/ report/lda.pdf. Chung, C. K., & Pennebaker, J. W. (2008). Revealing dimensions of thinking in open-ended self-descriptions: An automated meaning extraction method for natural language. Journal of research in personality, 42(1), 96-132. Feldman, S. (1999). NLP meets the Jabberwocky: Natural language processing in information retrieval. Online Magazine, 23, 62-73. Retrieved from: http://www.onlinemag.net/OL1999/ feldmann5.html Mishlove, J. (2010). https://www.youtube.com/watch?v=0XTDLq34M18 (Accessed June 12, 2018). Ostrowski, D. A. (2015). Using latent dirichlet allocation for topic modelling in twitter. In Semantic Computing (ICSC), 2015 IEEE International Conference (pp. 493-497). IEEE. Pennebaker, J. W. (2004). Theories, therapies, and taxpayers: On the complexities of the expressive writing paradigm. Clinical Psychology: Science and Practice, 11(2), 138-142. Pennebaker, J.W., Boyd, R.L., Jordan, K., & Blackburn, K. (2015). The development and psychometric properties of LIWC 2015. Austin, TX: University of Texas at Austin. Pennebaker, J. W., Chung, C. K., Frazee, J., Lavergne, G. M., & Beaver, D. I. (2014). When small words foretell academic success: The case of college admissions essays. PLoS ONE, 9(12), e115844. Pennebaker, J. W., & King, L. A. (1999). Linguistic styles: Language use as an individual difference. Journal of Personality and Social Psychology, 77(6), 1296-1312. Recchia, G., Sahlgren, M., Kanerva, P., & Jones, M. N. (2015). Encoding sequential information in semantic space models: Comparing holographic reduced representation and random permutation. Computational intelligence and neuroscience, 2015, 1-18. Salzmann, Z. (2004). Language, Culture, and Society: An Introduction to Linguistic Anthropology (3rd ed). Westview Press. Schank, R. C., Goldman, N. M., Rieger III, C. J., & Riesbeck, C. (1973). MARGIE: Memory analysis response generation, and inference on English. In IJCAI, 3, 255-261. Taraban, R., Marcy, W. M., LaCour Jr., M. S., & Burgess II, R. A. (2017). Developing machine-assisted analysis of engineering students’ ethics course assignments. Proceedings of the American Society of Engineering Education (ASEE) Annual Conference, Columbus, OH. https://www.asee.org/public/conferences/78/papers/19234/view. Taraban, R., Marcy, W. M., LaCour, M. S., Pashley, D., & Keim, K. (2018). Do engineering students learn ethics from an ethics course? Proceedings of the American Society of Engineering Education – Gulf Southwest (ASEE-GSW) Annual Conference, Austin, TX. http://www.aseegsw18.com/papers.html. Taraban, R., & Marshall, P. H. (2017). Deep learning and competition in psycholinguistic research. East European Journal of Psycholinguistics, 4(2), 67-74. Weizenbaum, J. (1966). ELIZA—a computer program for the study of natural language communication between man and machine. Communications of the ACM, 9(1), 36-45. Winograd, T. (1972). Understanding natural language. New York: Academic Press.