Dissertations / Theses on the topic 'LGALS3'

Galectin-3 is involved in thyroid carcinogenesis. The single nucleotide polymorphism (SNP) rs4644 (c.191C>A, p.Pro64His) within its encoding gene, LGALS3, is completely conserved across phylogenetically distant organisms, and it was predicted to be damaging by analysis performed with Polyphen and SIFT. Thus, we hypothesized that this SNP could affect the risk to develop DTC. The hypothesis was corroborated by a case-control association study (1155 DTC cases and 1222 controls), showing a protective role for the carriers of the Histidine-64 (OR=0.66; IC 95% 0.46- 0.93) versus the Proline-64 allele. To better understand the role of this SNP, cell lines underwent gene editing for altering the specific LGALS3 genotype. The “generation” of the cell lines was performed with a Clustered Regularly Interspaced Short Palindromic Repeats-associated Endonuclease 9 (CRISPR/Cas9) system. Different vectors and approaches for DNA strand breaks induction, as well as alternative strategies of delivery, were employed and compared to each others in order to identify the most effective in terms of specificity, time, and costs. Isogenic cell lines were obtained following gene editing although with variable results, depending from the strategy employed. Further steps will include the identification of possible off targets and the evaluation of how global gene expression is affected by Pro to His variation. In the future these cells will be helpful to understand the biologic role of this aminoacid change within galectin-3.

Neste estudo, investigamos o envolvimento de galectina-3 na fisiologia e no câncer de tiróide usando vários modelos biológicos e metodologias. Observamos que o gene LGALS3 apresenta um SNP no códon 98, mas não observamos correlação entre os genótipos deste SNP e fenótipo de câncer de tiróide. Na linhagem de tiróide de rato PCCl3, mostramos que a indução da expressão do oncogene RET/PTC promove o aumento da expressão de galectina-3, no entanto, a expressão de galectina-3, por si só, não confere vantagem de proliferação à célula. Por outro lado, na linhagem de carcinoma papilífero de tiróide TPC-1, a galectina-3 contribui para a sobrevivência da célula tumoral e progressão do ciclo celular, aumentando a expressão de c-Myc, diminuindo a expressão de p21 e caspase-3, e favorecendo a ativação de importantes vias envolvidas no controle do ciclo celular. Além disto, em modelos in vivo e in vitro, a galectina-3 interferiu na função e diferenciação da célula folicular tiroidiana, exercendo um papel indireto na regulação da expressão da tireoglobulina e atividade de TTF-1.
In this study, we investigate the involvement of galectin-3 in thyroid physiology and cancer using several biological models and methodologies. We observed that LGALS3 gene presents a SNP in codon 98, but no correlation between the genotype and the phenotype of benign or malignant thyroid tumor was observed. In the rat thyroid cell line PCCl3, we showed that the conditional induction of RET/PTC oncogene expression promotes the increase of galectin-3 expression, however, galectin-3 expression itself did not confer a proliferative advantage to cell. On the other hand, in papillary thyroid carcinoma cell line TPC-1 the galectin-3 contributes to tumor cell survival and cell cycle progression, increasing c-Myc expression, decreasing p21 and caspase-3 expression and cooperating to activation of important signaling pathways which are involved in the cell cycle control. In addition, in vitro and in vivo models the galectin-3 interferes in the differentiation and function of thyroid follicular cell, playing an indirect role in the regulation of thyroglobulin expression and TTF-1 activity.

Thesis (MSc (Genetics))--University of Stellenbosch, 2009.
Pre-eclampsia is one of the most common hypertensive disorders of pregnancy in South Africa. Presently, the only cure for pre-eclampsia is delivery, which brings with it, additional complications. As an alternative, clinical management of this disorder relies on timely diagnosis. The predictive biomarker, Placental Protein 13 (PP13), is currently used for the early diagnosis of pre-eclampsia, in an ELISA-based diagnostic kit, developed by Diagnostic Technologies Limited (DTL)1. A decrease in serum PP13 levels has been reported during the first trimester of pregnancy in women who later develop pre-eclampsia. The function of PP13 has not been fully elucidated and it is also not known whether the reduction in PP13 levels is a cause or an effect of the disease. The use of PP13 as a predictive biomarker for pre-eclampsia therefore warrants a comprehensive study of this peptide and the encoding gene, LGALS13. The aim of this study was firstly to characterise LGALS13 using a range of in silico tools. PP13 was found to be most homologous to the predicted protein product of a neighbouring “putative” gene, LOC148003. A gene conversion event between these two genes most likely underlies the so-called “hotspot mutation” in LGALS13. Data also demonstrates that the DelT mutation disrupts functionally and structurally important features of the gene and peptide sequences. Through the analysis of the putative promoter region of LGALS13, the presence of a Stimulatory protein-1 (Sp1) binding sequence element was predicted, which has implications for regulation of LGALS13. Secondly, the study aimed to establish a study cohort for the investigation of the effect that the LGALS13 genotype has on the expression of its mRNA and protein products. Serum, plasma and whole blood samples were collected and prepared from 316 pregnant women. Placental tissue samples were obtained from a selected group of these subjects for RNA extraction. Once the sampling on the two remaining targeted deliveries has occurred, the collection of samples will be batched and sent to DTL in Israel, for PP13 measurement. DNA was extracted from the whole blood samples obtained, and all study participants were genotyped for seven sequence variants within the LGALS13 gene using (i) Multiphor Single Stranded Conformational Polymorphism and Heteroduplex (SSCP/HD) analysis, (ii) restriction enzyme analysis and (iii) DNA sequencing. The genotype data sets will be compared with PP13 levels when they become available, and also with clinical parameters, once the deliveries have all occurred and the database is complete. This study demonstrated the power of an in silico approach to direct the focus of future experimental work. The newly established study cohort will be used for prospective studies aiming at a better understanding of the role which LGALS13 and PP13 play in the early prediction of preeclampsia.

Thesis (MSc (Genetics))--University of Stellenbosch, 2009.
Abruptio placentae is the premature separation of the normally implanted placenta from the uterine wall, resulting in haemorrhage before delivery of the fetus. This has serious maternal and neonatal implications, and is one of the leading causes of perinatal and maternal mortality and morbidity in South Africa. Placental vasculopathies, such as abruptio placentae, are believed to result from faults occurring in early placental development. Placental protein 13 (PP13) is a member of the pregnancy-related protein family, and is believed to function in a number of important physiological processes such as trophoblast invasion, placentation and implantation. The aim of this study was to investigate whether DNA sequence variants in the LGALS13 gene (encoding PP13), underlie and/or confer susceptibility to abruptio placentae. The gene was screened and genotyped in a cohort of patients whose pregnancies were complicated by abruptio placentae, as well as an ethnically matched control cohort. Statistical and in silico analyses were performed in order to identify potential susceptibility factors in this South African cohort and to predict whether the identified variants may impact on gene expression or the structure and function of PP13. In addition, the luciferase reporter gene assay was employed to investigate the functionality of the -98A/C variant identified in the 5’ untranslated region of the LGALS13 gene. Statistically significant differences were observed between patient and control groups at the following loci in the Coloured population: -98A/C, IVS2 -36G/A, IVS2 -22A/G and the hotspot variant in exon 3 (p<0.05). These variants could represent a susceptibility profile of this population or alternatively have implications in the pathogenesis of abruptio placentae. The deletion of a single thymine in exon 3 was shown to result in truncation of PP13 and subsequent disruption of a number of cysteine residues and putative phosphorylation sites, which could impact on dimerization and ultimately, the function of the protein. The reporter gene assay revealed a significant reduction (p=0.004) in luciferase activity by the -98 C allele. iii In silico analysis suggests that this reduction could be due the disruption of a NF1 or GR transcription factor binding site. This study provides evidence that variants in the LGALS13 gene may underlie and/or confer susceptibility to abruptio placentae by impacting on gene regulation or resulting in the expression of an aberrant form of the PP13 which could affect functionality and thereby result in the disruption of normal implantation and placentation.

L'anticorps monoclonal po66 reconnait un antigene intracytoplasmique, po66-cbp, une galectine-8 exprimee par les carcinomes epidermoides bronchiques humains et qui possede deux isoformes. Chez des souris greffees avec des cellules de cancer bronchique, une chimiotherapie associee a une radioimmunotherapie avec l'anticorps po66 a permis une regression notable des tumeurs. Cependant, la toxicite liee a la forte quantite d'anticorps po66 radiomarque circulant etait trop importante. Afin d'optimiser ce traitement, nous avons synthetise un anticorps monoclonal bispecifique (anti-dtpa-in x po66) pour realiser une radioimmunotherapie en deux temps utilisant un haptene bivalent radiomarque (systeme aes). Puis nous avons etudie l'expression de la galectine-8, ainsi que la structure du gene lgals8. Une etude preliminaire de la biodistribution de l'anticorps bispecifique et du haptene bivalent, a permis de determiner les conditions optimales a utiliser lors de la radioimmunotherapie en deux temps : trois injections successives d'anticorps bispecifique en association avec une chimiotherapie et une injection de haptene bivalent radiomarque trois jours plus tard. De plus, nous avons mis en evidence qu'un traitement au butyrate de sodium pouvait augmenter in vitro la quantite d'antigene po66-cbp exprime par les cellules tumorales, ce qui semble etre confirme in vivo, sur des souris ou nous observons une fixation accrue de l'anticorps bispecifique. Nous avons egalement mis en evidence non pas trois isoformes de la galectine-8, mais cinq, codees par un unique gene lgals8 par le biais d'un epissage alternatif complexe. Ce gene est localise en position lq42. Les cinq proteines appartiennent a deux groupes de galectines : prototype et repetee

INTRODUÇÃO: A síndrome coronariana aguda (SCA) constitui uma síndrome clínica geralmente causada por doença arterial coronariana (DAC) aterosclerótica e está associada ao infarto agudo do miocárdio (IAM) que pode muitas vezes levar a óbito. Aterosclerose é uma doença progressiva, sistêmica e de inicio precoce caracterizada pelo acúmulo de lipides e elementos fibrosos nas grandes artérias e recentemente foi considerada como uma afecção de origem inflamatória. OBJETIVO: Avaliar a frequência genotípica de E-SELECTINA, MMP9, LIGHT, LTα, VCAM1, ICAM1, LGALS2 e NFκB em pacientes com infarto agudo do miocárdio (IAM), angina instável (AI) e indivíduos que foram submetidos á angiocoronariografia e que apresentaram ausência de processo ateromatoso significativo. Assim como analisar a associação dos polimorfismos com a concentração sérica das formas solúveis das proteínas com a expressão gênica em leucócitos do sangue periférico, procurando estabelecer modelo de analise menos invasiva da aterosclerose. CASUÍSTICA E MÉTODOS: O estudo foi realizado em um grupo de pacientes recrutados no Instituto Dante Pazzanese de Cardiologia (IDPC) com infarto agudo do miocárdio, angina instável e indivíduos que foram submetidos á angiocoronariografia e que apresentaram ausência de processo ateromatoso significativo. Foram incluídos no estudo 93 indivíduos sendo 47 com IAM com e sem supra ST compondo o grupo IAM e 46 com AI ou que foram submetidos á angiocoronariografia e que apresentaram ausência de processo ateromatoso significativo compondo o grupo SIAM, de ambos os sexos com idades entre 45 e 90 anos. Foi realizado o estudo dos polimorfismos dos genes LIGHT (rs344560 e rs2291668), MMP9 (rs17576), LTα (rs909253 e rs1041981), LGALS2 (rs7291467), VCAM1 (rs3176878), ICAM1 (rs281432), E-SELECTINA (rs5368) e NFκB (rs17032705) por pirosequenciamento, a análise da expressão dos genes LIGHT, MMP9, LTα, VCAM1, ICAM1 e NFκB por PCR em tempo real e a dosagem das formas solúveis de VCAM1, ICAM1, E-SELECTINA e MMP9 utilizando o sistema LUMINEX. RESULTADOS: A frequência alélica e genotípica dos polimorfismos estudados (LIGHT [rs344560 e rs2291668], MMP9 [rs17576)] LTα [rs909253 e rs1041981], LGALS2 [rs7291467], VCAM1 [rs3176878], ICAM1 [rs281432], E-SELECTINA [rs5368] e NFκB [rs17032705]) não apresentou relação com doença arterial coronariana. Foi encontrada associação da expressão de LTα com síndrome coronariana aguda (p<0,05) e relação de alguns dos polimorfismos estudados (6+3279C>T de LGALS2, 8+10029G>A de NFκB, 332-3499C>G de ICAM1, Lys178Glu de LIGHT e Asp693Asp de VCAM1) com alterações na expressão gênica, formas solúveis e parâmetros bioquímicos. CONCLUSÕES: Não houve associação dos polimorfismos estudados com síndrome coronariana aguda assim como não houve associação das formas solúveis. Em relação á expressão gênica, foi encontrada associação da expressão de LTα com síndrome coronariana aguda (p<0,05) e alguns dos polimorfismos estudados (6+3279C>T de LGALS2, 8+10029G>A de NFκB, 332-3499C>G de ICAM1, Lys178Glu de LIGHT e Asp693Asp de VCAM1)ocasionaram alterações da expressão gênica, formas solúveis e parâmetros bioquímicos.
BACKGROUND: : Acute coronary syndrome (ACS) is a clinical syndrome usually caused by atherosclerotic coronary artery disease (CAD) and is associates with acute myocardial infarction (AMI) and sometimes can take to death. Atherosclerosis is a progressive disease characterized by the accumulation of lipides and fibrous elements in arteries and recently was considered a disease of inflammatory origin. OBJECTIVE: : Evaluated the genotypic frequency of E-SELECTIN, MMP9, LIGHT, LTα, VCAM1, ICAM1, LGALS2 e NFκB in patients with acute myocardial infarction, unstable angina and individuals who were submitted to coronary angiography and had absence of significant atheromathous process. As well as analyze the polymorphism association with serum concentration of protein soluble forms with gene expression in peripheral blood leukocytes trying to establish a model less invasive to analyze atherosclerosis MATERIALS AND METHODS: : Study in a group of patients recruited in Dante Pazzanese of Cardiology Institute with acute myocardial infarction, unstable angina and in individuals who showed no significant atheromatous process. The study included 93 patients (47 with acute myocardial infarction and 46 with unstable angina or individuals who showed no significant atheromatous process) of both sexes with ages between 45 and 90 years. The genes polymorphisms study was by pyrosequencing, the gene expression was by PCR real time and soluble forms was dosage by LUMINEX. RESULTS: : The allelic and genotypic polymorphisms frequency studied (LIGHT [rs344560 e rs2291668], MMP9 [rs17576)] LTα [rs909253 e rs1041981], LGALS2 [rs7291467], VCAM1 [rs3176878], ICAM1 [rs281432], E-SELECTINA [rs5368] e NFκB [rs17032705]) don\'t presented relation with coronary arterial disease. Was found association with LTα gene expression and coronary acute syndrome (p<0,05) and relation of some polymorphism studied (6+3279C>T de LGALS2, 8+10029G>A de NFκB, 332-3499C>G de ICAM1, Lys178Glu de LIGHT e Asp693Asp de VCAM1) with changes in gene expression, serum soluble forms and biochemical parameters. CONCLUSION: : Do not have association between polymorphisms studied and serum soluble forms with acute coronary syndrome. Was found association with LTα gene expression and coronary acute syndrome (p<0,05) and relation of some polymorphism studied (6+3279C>T de LGALS2, 8+10029G>A de NFκB, 332-3499C>G de ICAM1, Lys178Glu de LIGHT e Asp693Asp de VCAM1) with changes in gene expression, serum soluble forms and biochemical parameters.

This thesis focuses on investigating Enterprise Application Integration (EAI) adoption in the Local Government Authorities (LGAs). EAI has emerged to support organisations to integrate their Information Technology (IT) infrastructures and deliver high quality of services. Despite the fact that several private and public organisations have adopted EAI, its application in LGAs is limited. This may illustrate that LGAs develop EAI solutions at a slower pace and they can be characterised as a laggard comparing to other sectors. The small number of EAI applications in LGAs has resulted in limited research in this area with many issues, like its adoption requiring further investigation. Literature indicates various models that analyse various factors influencing EAI adoption in the private and public domain. However, the applicability and validity of these models is arguable and under research in LGAs, as these were proposed to support the decision-making process in other sectors and not in LGAs. To the best of the researcher's knowledge, none of the existing EAI adoption models explored the importance of factors during different phases of the adoption lifecycle. Notwithstanding, the implications of EAI have yet to be assessed, leaving scope for timeliness and novel research. Thus, the researcher demonstrates that it is of high importance to investigate this area within LGAs and result in research that contributes towards successful EAI adoption. This thesis makes a step forward and contributes to the body of knowledge as it: investigates factors influencing the decision making process for EAI adoption in LGAs (Figure 3.2), analyses and proposes the adoption lifecycle phases (Figure 3.3), maps and prioritises the importance of EAI adoption factors on different phases of the adoption lifecycle (Chapter 5 for empirical results) and in doing so, to propose a model for EAI adoption in LGAs (Figure 3.7). The researcher claims that such an EAI adoption process in LGAs is significant and novel as: it extends established norms for EAI adoption, by including Analytical Hierarchy Process (AHP) technique for prioritising the importance of factors, thus, enabling LGAs to produce more robust proposals for EAI adoption. The researcher discusses on EAI adoption by using a qualitative, interpretive, multiple case study research strategy. Findings from three case organisations exhibit that such an approach contributes towards more robust decisions for EAI adoption and indicates that it is acceptable by the case organisations. Despite these results cannot be generalised, yet they can allow others to relate their views with the ones reported in this thesis. This thesis proposes, tests and presents a novel model for EAI adoption in LGAs and contributes to the body of knowledge by extending the literature.

This thesis focuses on investigating inter-departmental Electronic Information Sharing (EIS) through Inter-organisational Systems (IOS) in the context of Local Government Authorities (LGAs) in England and Wales. There is an increasing demand to involve LGA departments in sharing information electronically in order to reduce the cost of storing and managing data, increase the level of data accuracy and timeliness and improve the accountability of the authority. During the last decades, several LGAs in the United Kingdom have started to employ IOSs to support information sharing and networked collaboration within their departments in order to meet a diverse range of citizen needs including housing services, social care services and education services. However, reaching a great level of crossdepartmental collaboration is not easy and requires additional time and effort. Normative literature proposed various models and frameworks that examine various issues and factors influencing the effort of EIS in the private and public domain. However, the applicability and validity of those models in the context of LGAs is arguable. Therefore, this research proposes and validates a novel conceptual framework that can be used as a tool for decision-making while sharing information electronically. The framework consists of four main levels: (a) investigation and presentation of factors influencing Electronic Information Sharing in LGAs based on external environment, organisational capacity, technology environment, EIS characteristics and inter-departmental environment, (b) investigation and presentation of the phases that departments adopt while participating in the EIS effort, (c) mapping of the influential factors onto the participation phases and (d) prioritisation of the factors influencing EIS in LGAs in relation to different phases. By validating the conceptual framework through using a qualitative, interpretive, multiple case study research strategy, this thesis attempts to contribute to the theoretical, methodological and practical aspects of inter-departmental EIS. Despite the results of the cases cannot be generalised, yetthey can allow others to relate their views with the onesreported in this thesis.

This research investigates accounting practices in four Tanzanian Local Government Authorities (LGAs). It seeks to understand how accounting is practiced and the situations which sustain its undertaking. The peculiar role of local governments in the delivery of public services and the influence of accounting on the same has motivated this study (Lapsley & Mussari, 2008). It has also been driven by the inadequacy of interpretive theoretically based informed studies into public sector entities, and the limited accounting research in the emerging economies (Goddard, 2010). The study applies an interpretive approach to investigate accounting in the organisations in which it operates (Ahrens & Mollona, 2007), and executes a grounded theory method to develop a theory systematically from the raw data (Glaser & Strauss, 1967). In order to ensure the general application of the emergent theory beyond the case studies, the development of a formal grounded theory was sought. This research revealed that the operations of the Tanzanian LGAs were constrained by factors such as deficient regulatory systems, political interference, donors’ influences, and funding uncertainties. These conditions forced the technocrats to use important accounting practices, such as budgeting, auditing, financial reporting, and performance measurement to manipulate the organisational legitimacy. The process of legitimacy manipulation ensured the availability of resources for the LGAs and the attainment of the individual interests of the Councils’ officials. This study contributes to the interpretive approach in emerging economies. Also, meta-coding, intra-relationships of categories, and development of formal grounded theory, add new insights to the grounded theory analysis. It is also worth noting that the study integrates the emergent theory within the New Institutional Sociology (NIS) framework. It was not intended to test NIS, but rather, to adopt it as a theoretical lens that assisted interpretation of the research findings. In the NIS framework, the study establishes the simultaneous achievement of legitimacy and efficiency, recognises multiple sources of loose coupling, and the influence of performance management on shaping accounting practices in the public sector organisations. It also offers the micro reactions of the Councils’ officials, and recognises the different patterns of the officials’ responses across Councils and service deliveries. The study argues that in emerging economies considerations of a country’s local contexts has the potential to minimise any counter-productivity of reform programs. Moreover, this research appeals for a holistic approach to the reform programs, harmonization of laws and regulations, the institution of efficient financial management and reporting mechanisms, and the improvement of employee welfare in the Tanzanian Councils.

Since the 1980s, public sector entities have been exposed to accounting reforms under an umbrella of New Public Management (NPM). The main purpose of adoption of accounting reforms is to increase efficiency in decision-making by producing useful accounting information. However, it is argued that the adoption of accounting reforms by public sector entities in developing countries is attributed to the seeking of financial legitimacy, rather than increasing organisational efficiency (Mzenzi, 2013; Mkasiwa, 2011; Adhikari and Mellemvik, 2011; Tambulasi, 2007; Sarker, 2006). Therefore, it is the interest of this study to research the use of accounting information by public sector entities in developing countries. This study is based on an interpretative approach and employs an exploratory case study strategy with two cases (LGAs) in order to accomplish four specific objectives. The roles and responsibilities of LGAs and their multiple actors in delivering public services to the citizens, and their roles in budgetary decision-making attributed by the adopted accounting practices, represent the major motivation of this study. Institutional theory and its three branches, which are Old Institutional Economics (OIE), New Institutional Sociology (NIS) and New Institutional Economics (NIE), were used in the process of developing the initial model, and the overall interpretation of findings. The findings of this study revealed three dimensions of instrumental-conceptual use, which included conceptual use, decision relevant, and recommendations use of accounting information in decisions related to estimations and collections of own source revenue. Furthermore, the study’s findings showed that legitimating use was the main dimension of the symbolic use of accounting information in the budget approval, as well as in the decision about estimating and collecting revenue from external sources. It further identified 22 factors influencing the use of accounting information in the budget decision-making processes. The study findings also revealed that instrumental-conceptual use of accounting information increases both an organisation’s budget efficiency as well as its external financial legitimacy. On the other hand, the symbolic use of accounting information decreases the organisation’s budget efficiency and the actual external financial legitimacy but increases the promised external financial legitimacy. This is attributed, mainly, by external institutional pressures that result in decoupling behavior in the use of accounting information in budgetary decision-making processes. In addition, the findings revealed that budget efficiency and acquired financial legitimacy are interdependent. This means that the high financial legitimacy acquired can indicate high budget efficiency in the situation the instrumental-conceptual use exists than the symbolic legitimating use of accounting information. The study proposes a model of the determinants of the use of accounting information in budget decision-making processes for budget efficiency and external financial legitimacy. It informs reformers, practitioners, policy-makers and researchers about the necessary measures to undertake to make sure that NPM reforms, especially accounting reforms, enhance both efficiency and financial legitimacy in the public sector organisations through the use of accounting information.

This essay examines sanitation workers who work with solid waste management and analyses their ability to create a sustainable livelihood based on livelihood assets and strategies. The study was undertaken in Babati, Tanzania and a qualitative method was applied, consisting of interviews and observations. The main findings were that sanitation workers employed four livelihood strategies, however, only two of these were sustainable and contributed towards a positive livelihood outcome. Multiple stresses were identified, such as low wages, inability to save money, unsafe work conditions, exposure to bacteria and other contaminants and no access to social services. Shocks were identified as work-related injuries resulting in extended time off work, wages being paid out late and sudden illness. This made the sanitation workers terms of employment in Babati almost equivalent to that of waste workers and waste pickers in the informal sector, despite being employed by the local government authorities. As a result, the workers were not able to attain a sustainable livelihood and the livelihood outcome appear to be a vicious cycle of debt and vulnerability. A key characteristic for this study is its examination of Tanzania’s political context and institutional framework as important factors that affect the sanitation workers’ resource base and strategies as well as their exposure to vulnerabilities.

Galectins are a family of secreted animal lectins with a high affinity to betagalactosides commonly involved in cellular functions such as apoptosis, adhesion and migration. Galectin 15 (LGALS15), a newest member of the galectin superfamily, has a unique C-terminal RGD sequence and participates in integrin-mediated ovine trophectoderm cell attachment and migration. In the ovine uterus, LGALS15 is expressed only by the endometrial luminal (LE) and superficial glandular (sGE) epithelia, induced by progesterone between Days 10 and 12 of the cycle and pregnancy, and then stimulated by interferon tau (IFNT) from the conceptus after Day 14 of pregnancy. During early pregnancy, the canonical janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is not active in the endometrial LE/sGE. Therefore, IFNT may utilizes a non-canonical signaling pathway to increase transcription of genes, including CST3, CTSL, HIF2A, LGALS15, and WNT7A, specifically in the endometrial LE/sGE. Alternatively, IFNT and progesterone could indirectly affect epithelial gene expression by influencing gene expression in the stroma, which then communicates with the epithelium. Although the LGALS15 gene is present in ovine, caprine and bovine species, it is only expressed in uteri of sheep and goats. Available data shows a tissue- and speciesspecific expression pattern for LGALS15, likely involving multiple layers of transcription regulation in the ruminant endometrium. Further analysis of the LGALS15 5? promoter/enhancer region revealed similar predicted transcription factor binding sites in all three species, including; PU.1, Ets-1, AP1, Sp1, and GRE or PRE sites. Interestingly, the proximal promoter region of the LGALS15 gene in all three species exhibited a conserved Sp1 binding site upstream of an AP1 binding site on both sense and antisense strands, and with similar spacing between binding sites. Sequence analysis revealed key differences in LGALS15 gene structure between ruminant species including the proximity of repetitive DNA sequences to the transcription start site (+1). Bovine LGALS15 has repetitive DNA sequences start at - 145 whereas in ovine or caprine LGALS15 it starts at about -300. The length of the repetitive DNA sequence is similar (~1.2 kb) in the 5' promoter/enhancer region of LGALS15 in all three species. Transient transfection analyses found that repetitive DNA sequences reduced basal promoter activity and responsiveness to treatments. None of the promoter construct showed responsiveness to interferon tau (IFNT). The bovine LGALS15 gene promoter showed no activity under any experimental conditions. The current studies indicate that uterine LGALS15 is expressed in ovine and caprine but not bovine species. Additionally, repetitive DNA sequences found in the promoter region may contribute to modulating the LGALS15 gene expression. Therefore, the ruminant LGALS15 gene, like other galectins, is under tight transcriptional control involving hormones, requisite transcription factors and potentially chromatin remodeling complexes working synergistically for LGALS15 promoter transactivation.

Yes
Second generation web-based technologies (Web 2.0) such as social media and networking sites are increasingly being used by governments for activities ranging from open policy making to communication campaigns and customer service. However, this in turn has brought about additional challenges. By its very nature, Web 2.0 technologies are more interactive than the traditional models of information provision or creation of digital services. Such technologies open up a new set of benefits, costs and risks to those government authorities who make use of these social and digital media to enhance their work. This study draws on the extant literature together with an in-depth qualitative case enquiry to propose an emergent framework for evaluating the intra-organisational use of Web 2.0 technologies and its impact on local government. The study findings identified additional four factors (i.e. benefits: intra-marketing, informal engagement, costs: workload constraints and risk: integration with other systems) as part of the evaluation criteria which have not previously been discussed in the existing literature surrounding the context of Web 2.0 use in local government. The study concludes that a combined analysis of the evaluation and impact assessment factors, rather than one particular approach would better assist decision makers when implementing Web 2.0 technologies for use by public administration employees.