Literatura académica sobre el tema "Tykit"

Abstract LPS, a bacterial endotoxin, induces the expression of many genes in macrophages. We report the cloning of a novel 3.3-kb cDNA that is a member of the thymidylate kinase family of genes. This clone, which we have designated TYKi, was obtained by screening a cDNA library prepared from RNA isolated from the murine cell line RAW264.7 after bacterial LPS treatment. TYKi is quite similar to all thymidylate kinases for which there are sequence data. It conserves two very important domains in these kinases, namely, the catalytic domain or P-loop and the nucleotide binding domain. After LPS exposure, the TYKi message appears at 2 h, peaks at 6 h, and declines at 8 h. LPS induction of TYKi is dependent on de novo protein synthesis. Increasing cytosolic cAMP with forskolin attenuates the LPS induction of TYKi. However, treatment with 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) or dibutyryl-cAMP did not affect the LPS induction of TYKi. In contrast, activation of protein kinase C with phorbol ester augmented the LPS response, whereas inhibiting protein kinase C with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) suppressed the LPS response. Removing extracellular Ca2+ with EGTA inhibited LPS induction of TYKi, whereas increasing intracellular calcium with the calcium ionophore A23187 had little effect on the levels of the TYKi transcript. Inhibiting tyrosine kinase with genistein suppressed the induction of TYKi by LPS.

Traditionally, the problem of children behavioural adjustment was linked to the factors of surrounding environment and biology. This universal phenomenon occurring all over the world is dubbed as endless and becoming even more complex up to recent. Behavioural adjustment problem faced during early childhood development period will influence the overall individual response towards social connection, personality, physical and mental health, numeracy and literacy skills, lingual ability, communicative skill, verbal ability, and academic success. This study intends to provide early exposure in relation to the level of children behavioural adjustment problem in Terengganu Islamic Foundation Kindergarten or Tadika Yayasan Islam Terengganu (TYIT). Children behavioural adjustment problems are assessed based on three categories which are hyperactive-distractible, hostile-aggressive, and anxious-fearful. A number of 380 TYIT children becomes the sample in this study. They are selected in a simple random manner from eight districts in the state of Terengganu. Overall finding of this study shows that the problem of behavioural adjustment amongst TYIT children is at low level. Hyperactivity, a form of children behavioural adjustment problem is at moderate level. Hostile-aggressive and anxious-fearful behavioural adjustment problems are at low level. Male children tend to show higher behavioural adjustment problems compared to female children. Itis suggested that teachers assess and prepares children‟s behavioural profiles so as to enable early intervention towards children whom are in need. Abstrak Secara tradisi masalah penyesuaian tingkah laku kanak-kanak dikaitkan dengan faktor persekitaran dan biologi. Fenomena universal yang berlaku di seluruh dunia ini bukan sahaja tiada bernoktah, malah semakin kompleks mutakhir ini. Masalah penyesuaian tingkah laku yang dialami semasa zaman awal perkembangan kanak-kanak mempengaruhi keseluruhan tindak balas individu terhadap hubungan sosial, personaliti, kesihatan mental dan fizikal, kemahiran literasi dan numerasi, kebolehan berbahasa, kemahiran komunikasi, motivasi. kesediaan belajar, kesediaan ke sekolah, kebolehan berbahasa dan kejayaan dalam akademik. Kajian ini bertujuan untuk memberi pendedahan awal berkaitan tahap masalah penyesuaian tingkah laku kanak-kanak Tadika Yayasan Islam Terengganu (TYIT). Masalah penyesuaian tingkah laku kanak-kanak dinilai berdasarkan tiga kategori masalah penyesuaian tingkah laku kanak-kanak iaitu hiperaktif-terganggu, permusuhan- agresif dan kebimbangan-ketakutan. Seramai 380 kanak-kanak TYIT menjadi sampel dalam kajian ini. Mereka dipilih secara rawak mudah dari lapan daerah di negeri Terengganu. Dapatan kajian menunjukkan keseluruhannya masalah penyesuaian tingkah laku kanak-kanak TYIT berada pada tahap yang rendah. Satu bentuk masalah penyesuaian tingkah laku kanak-kanak berada pada tahap sederhana iaitu hiperaktif-terganggu. Dua bentuk masalah penyesuaian tingkah laku kanak-kanak berada pada tahap rendah iaitu permusuhan-agresif dan kebimbangan-ketakutan. Kanak-kanak lelaki menunjukkan tahap masalah penyesuaian tingkah laku yang lebih tinggi berbanding kanak- kanak perempuan. Dicadangkan guru menilai dan menyediakan profil tingkah laku kanak-kanak agar intervensi awal dapat diberi kepada kanak-kanak yang memerlukan.

Pronematus ubiquitus (McGregor) is redescribed based on specimens collected at the type locality. Additionally, in a survey for natural enemies of Aculops lycopersici (Tryon), P. ubiquitus was found in most European countries where samples were gathered as well as in Morocco. Together with specimens available from museum collections and originating from Brazil, South Africa and Türkiye, the newly collected specimens were measured and morphologically compared with those from the type locality. Additionally, single female expansion lines were set-up with specimens from California (USA), Belgium, France, Italy, The Netherlands and Morocco, and molecular analysis were performed in order to construct a phylogenetic tree. The tree showed differences between origins, but this was assigned to intraspecific variation. A PCA analysis on morphological characters separated the Brazilian specimens from those of all other geographical origins. The Californian (USA) specimens grouped together, as did the Moroccan and all European specimens, but with overlap between the groups. The Brazilian specimens were described as a new species, P. brasiliensis n. sp. All other specimens were considered as P. ubiquitus. Furthermore, we searched for types of early described Pronematus species and studied P. rykei, P. karrooi and P. tenuisetosus types; the first two species were confirmed morphologically as a distinct Pronematus species while the latter belongs to the genus Pseudopronematulus. The morphological characteristics of specimens that were used for a recent redescription of P. rykei did not coincide with our redescription of the type. We transferred those specimens to the new species, P. juglandi sp. nov.

Artykuł stanowi próbę analizy i interpretacji powieści W ciemność Anny Bolavej. Postać głównej bohaterki Anny Bartakovej analizowana jest przez pryzmat intertekstualnych nawiązań do literatury czeskiego romantyzmu (twórczość K. H. Máchy i K. J. Erbena) oraz jej znaczeń symbolicznych generowanych przez związki z kontekstem biblijnym. Istotną część artykułu stanowi wreszcie opis afektywnego wymiaru działania i funkcjonowania bohaterki oraz charakterystyka szczególnej poe- tyki, które służy do wyrażenia tego aspektu.

Przedmiotem rozważań jest analiza podstawowych koncepcji biopolityki funkcjonujących we współczesnym dyskursie, kwestii krzyżowania dwóch wariantów biopolityczności, czyli biopoli-tyki tradycyjnej oraz biopolityki nowoczesnej, jak również próba odnalezienia właściwych ich prze-jawów w szeroko rozumianej działalności społecznej. W ogólnym ujęciu biopolityka oznacza formę zarządzania przez ośrodki władzy procesami życia biologicznego przy ustaleniu normatywnych kryteriów życia i śmierci. Przegląd dostępnej literatury pokazuje, że tematyka ta doczekała się dość szerokich rozważań teoretycznych (na przykład M. Foucaulta, G. Agambena). Podejmując się re-fleksji badawczej zagadnienia biopolityki, chciałbym przyjąć wielowymiarową optykę obejmującą globalne procesy ekonomiczne, kulturowe i polityczne, kładąc szczególny nacisk na płaszczyznę normatywną wskazanych procesów.

W racjonalizowaniu systemu zabezpieczenia społecznego, który ma zapewniać okre‑ślony standard bezpieczeństwa socjalnego, istotne znaczenie powinna mieć możliwośćzastosowania w nim rozwiązań finansowych o charakterze publicznych funduszy celo‑wych, związanych z danym ryzykiem społecznym. Takie podejście do realizacji jednejz socjalnych funkcji państwa umożliwiałoby dokładniejsze przyjrzenie się ważnemupodsystemowi transferów dochodów, który ma istotne znaczenie w realnym kształtowaniustosunków społecznych wynikających ze skali redystrybucji dochodów. Praktyka poli‑tyki społecznej oraz organizacji i funkcjonowania systemu zabezpieczenia społecznegopokazuje jednak, że jesteśmy dalecy od przestrzegania zasady paraubezpieczeniowejw tworzeniu publicznych funduszy celowych. W takiej sytuacji nie można liczyć na więk‑szą akceptację społeczną dla ukierunkowanych obciążeń fiskalnych oraz na osłabieniewpływu czynnika politycznego na gromadzenie i wydatkowanie środków publicznychzwiązanych z socjalną funkcją państwa. Nie powinno to jednak oznaczać przekreśleniamożliwości posługiwania się odpowiednio skonstruowanymi publicznymi funduszamisocjalnymi w racjonalizowaniu

Nieosiągalny wcześniej rozkwit badań genetycznych, zwłaszcza po finali- zacji Projektu Sekwencjonowania Genomu Ludzkiego, stawia współczesną naukę, ale i społeczeństwo przed nowymi wyzwaniami. Jednym z istotnych jest określenie statusu uzyskiwanych w ramach tych badań informacji genetycznych. Niniejsze badania do- tyczą formułowanego coraz częściej nakazu wymogu odpowiedzialności genetycznej w kontekście zadań rodzicielskich. Celem badań było wskazanie płaszczyzn takiej od- powiedzialności i konsekwencji wprowadzania jej w życie. W badaniach zastosowano metodę naukową desk research, a więc analizę danych zastanych, z uwzględnieniem dostępnych dokumentów, badań i publikacji, oraz ich konfrontację z normami bioe- tyki personalistycznej. Osiągnięte wyniki potwierdzają zarówno zmianę paradygmatu w podejściu do zdrowia, jak i poważne konsekwencje stosowania norm określanych jako odpowiedzialność genetyczna, jeśli zostaną one zaaplikowane do funkcjonowania rodziny w zakresie przekazywania życia, gospodarowania pozyskaną informacją genetyczną czy zarządzania ryzykiem genetycznym.

I 2003 udsendte møbelfabrikken Montana en firefarvet og firesproget brochure, »Being Montana«, - en 136 siders sag, trykt på tykt papir og med omslag af kraftig karton. En utraditionel brochure, som ikke blot præsenterer virksomhedens produkt – en funktionel reolserie med næsten uendelige kombinationsmuligheder – men som med avanceret billedsprog og tvetydig symbolik vil kommunikere en særlig identitet og position. Med brochuren vil virksomheden konstruere en oplevelse af Montana, som er vigtig for kundens oplevelse af produktets symbol- og signalværdi, men som bestemt også er vigtig for virksomheden og dens ansattes oplevelse af Montana som et unikt kulturelt fællesskab. Forfatterne anskuer »Being Montana« som et eksempel på en fremherskende tendens i virksomheders kommunikation – deres corporate branding – som anskues som identitetsprojekter, hvor immaterielle værdier skal skabe den oplevede forskel som ofte forskelsløse og trivielle produktegenskaber i sig selv ikke kan skabe. Forfatterne forholder sig kritisk virksomheders bestræbelser på corporate branding og advarer mod terapeutisk selvrefleksivitet på bekostning af kunden, som ikke involveres tilstrækkeligt i kommunikationen.

Este artigo apresenta uma visão panorâmica sobre a semântica temporal e aspectual em Karitiana (Tupi). Apesar das investigações já existentes (STORTO, 2002; 2013 CARVALHO, 2009; ROCHA, 2018), esse sistema aspecto-temporal ainda não é bem compreendido e há questões que precisam ser respondidas. A língua possui sufixos verbais que distinguem futuro de não-futuro e auxiliares aspectuais que marcam os aspectos imperfeito-progressivo, perfeito e prospectivo. O objetivo geral deste artigo é aprofundar nosso entendimento em relação à semântica do sistema temporal e aspectual da língua Karitiana. Respondemos a duas questões que não foram enfocadas anteriormente pela literatura sobre a língua: (i) se a semântica da flexão de não-futuro seria ambígua ou subespecificada; (ii) qual seria o status da flexão de futuro - marca de tempo, de modo ou de aspecto?. Além disso, apontamos uma correlação tipologicamente desconhecida entre sentenças matrizes afirmativas e a ocorrência de flexão temporal. A relevância dessa descrição se dá na medida que ela ajuda a ampliar o nosso conhecimento de como as categorias de tempo e de aspecto funcionam em línguas pouco exploradas pela linguística formal. O artigo assume os pressupostos da semântica formal para a investigação do tempo e do aspecto. Nosso corpus é formado principalmente por sentenças coletadas com falantes nativos através de elicitação de dados contextualizada (MATTHEWSON, 2004; SANCHEZ-MENDES, 2014). Em nossa análise, argumentamos que a flexão de não-futuro é ambígua, ou seja, ela pode denotar o presente ou o passado, mas não ambos simultaneamente. Assumimos também que o sufixo de futuro é uma flexão temporal legítima, e não uma flexão modal ou aspectual (ABUSCH, 1998). Em relação à restrição do auxiliar progressivo tykat, que não pode coocorrer com a flexão de passado, argumentamos que este sufixo aspectual possui codificado lexicalmente em sua semântica a informação de que seu tempo do tópico deve ser posterior ou igual ao tempo da fala.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus is the causative agent of Japanese encephalitis (JE). The disease affects mostly children and around 30000– 50000 cases of JE and up to 15000 deaths are reported annually. No anti-viral drugs have been discovered against JE so far, but advances in our knowledge of the molecular biology of flaviviruses is propelling flaviviral drug research at an expeditious pace. Since JEV has a small genome which encodes for only ten proteins, there is dearth of potential drug targets. Researchers are now focusing on cellular interactomes, a complex and dynamic molecular biosystem which identifies host proteins which interact with either viral proteins or viral genomes, leading to the generation of an astronomical number of potential drug targets involving common cellular pathways that are required for the life cycle of different viruses. Such studies can pave way for the development of ‘broad-spectrum’, ‘silver-bullet’ anti-viral drugs for the treatment of multiple viral diseases. The cellular interactomes can be studied by Genomics tools such as microarray. Systematic profiling of genes involved in virus infection by RNAi, transcriptome sequencing, microRNA profiling and yeast two-hybrid system has allowed us to assess global gene expression changes providing an unprecedented view on the host-side of the virus–host interactions. Advent of these tools has led to identification of plethora anti-viral genes. For example, over expression of IFN-stimulated gene15 (ISG15) results in inhibition of JEV leading to significant reduction of viral titers. Chemokine profiling of JEV-infected cells by microarray can provide possible therapeutic modalities that can mitigate the morbidity associated with JEV infection. Functional classification of interferon-stimulated genes (ISG) identified using innovative methods have been the stepping stone for identification of many anti-viral genes, among them are few Broadly acting effectors like IRF1, C6orf150, HPSE, RIG-I, MDA5 and IFITM3 and some more targeted antiviral specific like DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT, OASL, RTP4, TREX1 and UNC84B. In this study, we have identified a B16F10 murine melanoma cell line that is resistant to JEV infection. DNA microarray analysis of JEV-susceptible and resistant B16F10 cell lines gave us interesting insights into JEV-induced host gene expression changes. Real time PCR validation of microarray data indicates that a number of virus and interferon inducible genes are expressed constitutively at high levels in this JEV-resistant cell line. Further, several of the mouse genes induced by JEV in B16F10 cell line were also upregulated in JEV-infected mouse brain. To understand the significance of these host gene expression changes, we attempted to generate stable murine cell lines constitutively expressing select JEV-inducible genes and study the JEV infection pattern in these cell lines. One of the JEV-inducible genes encoding thymidylate kinase (Tyki), a mitochondrial protein involved in the sysnthesis of nucleoside diphosphates, when overexpressed in NIH3T3 cells confers resistance to JEV infection as evident from reduced JEV-induced cytopathic effects and significant reduction in viral titer. Since TYKI has two distinct domains: the N-terminal domain with unknown function and the C-terminal domain with the nucleoside monophosphate kinase function, suggest that TYKI may be a bifunctional protein with other biological functions in addition to its UMP-CMP kinase activity. In order to examine whether N-terminal domain is responsible for antiviral activity of the protein, a stable cell line constitutively expressing N-terminal domain of gene was made, but the overexpression of N-terminal domain didn't confer any antiviral immunity. Thus signifying importance of kinase activity in confering antiviral immunity. Our studies indicate for the first time that Tyki may have a role in host resistance to JEV and understanding the mechanism of action Tyki may pave way for novel anti-JEV therapy. Stable cell lines constitutively expressing other JEV-inducible genes (Atf3, Gimap3, Rtp4, Glipr2, Tmem140 and Garg49) couldn't be generated. Therefore, to study the effect of overexpression of these genes on JEV infection, expression vectors encoding these genes were transfected individually to human 293T cells by nucleofection, then infected with JEV and viral titres were examined by plaque assay. Nucleofection was opted as a method of choice since it is the only non-viral method, which transfects DNA directly enter the nucleus. In contrast, other commonly used non-viral transfection methods rely on cell division for the transfer of DNA into the nucleus. Nucleofection of vectors encoding different JEV-inducible genes followed by JEV infection and assay of viral titer led to identification of one more anti-viral gene and three pro-viral genes. Garg49, an interferon and JEV inducible mitochondrial gene was identified as antiviral gene. Further studies led to the identification of GARG49 as a mitochondrial protein. Three genes, Atf3, encoding a cAMP responsive element binding protein family transcription factor, Glipr2, encoding a Glioma related pathogenesis protein and Gimap3, encoding an outer mitochondrial membrane GTPase were identified as pro viral genes. Overexpression of Tmem140, encoding a transmembrane protein and Rtp4, encoding a golgi chaperone did not significantly affect JEV titer. Conclusions: . A JEV-resistant B16F10 murine melanoma cell line was identified and several JEV-inducible genes were found to be expressed constitutively at high levels in this cell line. .We demonstrate for the first time that Tyki/Ump-Cmpk2 encoding a mitochondrial nucleoside monophosphate kinase has an anti-JEV function and the C-terminal domain is essential for anti-viral activity. .Garg49/Ifit3 encodes an interferon and JEV-inducible mitochondrial protein and it has an anti-JEV function. . Activating transcription factor 3 (ATF3), GTPase, IMAP family member 3 (GIMAP3) and GLI pathogenesis-related 2 (GLIPR2) are pro-viral proteins which facilitate virus multiplication resulting in enhanced JEV titer.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus is the causative agent of Japanese encephalitis (JE). The disease affects mostly children and around 30000– 50000 cases of JE and up to 15000 deaths are reported annually. No anti-viral drugs have been discovered against JE so far, but advances in our knowledge of the molecular biology of flaviviruses is propelling flaviviral drug research at an expeditious pace. Since JEV has a small genome which encodes for only ten proteins, there is dearth of potential drug targets. Researchers are now focusing on cellular interactomes, a complex and dynamic molecular biosystem which identifies host proteins which interact with either viral proteins or viral genomes, leading to the generation of an astronomical number of potential drug targets involving common cellular pathways that are required for the life cycle of different viruses. Such studies can pave way for the development of ‘broad-spectrum’, ‘silver-bullet’ anti-viral drugs for the treatment of multiple viral diseases. The cellular interactomes can be studied by Genomics tools such as microarray. Systematic profiling of genes involved in virus infection by RNAi, transcriptome sequencing, microRNA profiling and yeast two-hybrid system has allowed us to assess global gene expression changes providing an unprecedented view on the host-side of the virus–host interactions. Advent of these tools has led to identification of plethora anti-viral genes. For example, over expression of IFN-stimulated gene15 (ISG15) results in inhibition of JEV leading to significant reduction of viral titers. Chemokine profiling of JEV-infected cells by microarray can provide possible therapeutic modalities that can mitigate the morbidity associated with JEV infection. Functional classification of interferon-stimulated genes (ISG) identified using innovative methods have been the stepping stone for identification of many anti-viral genes, among them are few Broadly acting effectors like IRF1, C6orf150, HPSE, RIG-I, MDA5 and IFITM3 and some more targeted antiviral specific like DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT, OASL, RTP4, TREX1 and UNC84B. In this study, we have identified a B16F10 murine melanoma cell line that is resistant to JEV infection. DNA microarray analysis of JEV-susceptible and resistant B16F10 cell lines gave us interesting insights into JEV-induced host gene expression changes. Real time PCR validation of microarray data indicates that a number of virus and interferon inducible genes are expressed constitutively at high levels in this JEV-resistant cell line. Further, several of the mouse genes induced by JEV in B16F10 cell line were also upregulated in JEV-infected mouse brain. To understand the significance of these host gene expression changes, we attempted to generate stable murine cell lines constitutively expressing select JEV-inducible genes and study the JEV infection pattern in these cell lines. One of the JEV-inducible genes encoding thymidylate kinase (Tyki), a mitochondrial protein involved in the sysnthesis of nucleoside diphosphates, when overexpressed in NIH3T3 cells confers resistance to JEV infection as evident from reduced JEV-induced cytopathic effects and significant reduction in viral titer. Since TYKI has two distinct domains: the N-terminal domain with unknown function and the C-terminal domain with the nucleoside monophosphate kinase function, suggest that TYKI may be a bifunctional protein with other biological functions in addition to its UMP-CMP kinase activity. In order to examine whether N-terminal domain is responsible for antiviral activity of the protein, a stable cell line constitutively expressing N-terminal domain of gene was made, but the overexpression of N-terminal domain didn't confer any antiviral immunity. Thus signifying importance of kinase activity in confering antiviral immunity. Our studies indicate for the first time that Tyki may have a role in host resistance to JEV and understanding the mechanism of action Tyki may pave way for novel anti-JEV therapy. Stable cell lines constitutively expressing other JEV-inducible genes (Atf3, Gimap3, Rtp4, Glipr2, Tmem140 and Garg49) couldn't be generated. Therefore, to study the effect of overexpression of these genes on JEV infection, expression vectors encoding these genes were transfected individually to human 293T cells by nucleofection, then infected with JEV and viral titres were examined by plaque assay. Nucleofection was opted as a method of choice since it is the only non-viral method, which transfects DNA directly enter the nucleus. In contrast, other commonly used non-viral transfection methods rely on cell division for the transfer of DNA into the nucleus. Nucleofection of vectors encoding different JEV-inducible genes followed by JEV infection and assay of viral titer led to identification of one more anti-viral gene and three pro-viral genes. Garg49, an interferon and JEV inducible mitochondrial gene was identified as antiviral gene. Further studies led to the identification of GARG49 as a mitochondrial protein. Three genes, Atf3, encoding a cAMP responsive element binding protein family transcription factor, Glipr2, encoding a Glioma related pathogenesis protein and Gimap3, encoding an outer mitochondrial membrane GTPase were identified as pro viral genes. Overexpression of Tmem140, encoding a transmembrane protein and Rtp4, encoding a golgi chaperone did not significantly affect JEV titer. Conclusions: . A JEV-resistant B16F10 murine melanoma cell line was identified and several JEV-inducible genes were found to be expressed constitutively at high levels in this cell line. .We demonstrate for the first time that Tyki/Ump-Cmpk2 encoding a mitochondrial nucleoside monophosphate kinase has an anti-JEV function and the C-terminal domain is essential for anti-viral activity. .Garg49/Ifit3 encodes an interferon and JEV-inducible mitochondrial protein and it has an anti-JEV function. . Activating transcription factor 3 (ATF3), GTPase, IMAP family member 3 (GIMAP3) and GLI pathogenesis-related 2 (GLIPR2) are pro-viral proteins which facilitate virus multiplication resulting in enhanced JEV titer.