Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Wnt5a in Prostate Cancer

Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays important roles in organ development and tissue orientation. Previous studies have reported that Wnt5a was upregulated at both mRNA and protein levels in prostate cancer, but information regarding its role in predicting clinical outcome in patients after radical prostatectomy is limited. The aim of the present thesis is to define the role of Wnt5a protein expression in prostate cancer. We started by evaluating Wnt5a protein expression by immunohistochemistry in a large, well-defined and population-based cohort and found Wnt5a protein expression to be upregulated in prostate cancer cells compared to benign epithelium. Interestingly, it predicted a favorable outcome for patients after radical prostatectomy as patients with preserved overexpression of Wnt5a protein in tumor cells had longer biochemical recurrence free time compared to patients with low Wnt5a protein expression. We demonstrated that this effect may be explained by the ability of Wnt5a to impair invasion in prostate cancer cells as recombinant Wnt5a treatment decreased invasion in 22Rv1 and DU145 cells while Wnt5a knockdown resulted in increase in invasion in LNCaP and 22Rv1 cells. In the light of conflicting reports on the role of Wnt5a in prostate cancer outcome, we validated our findings in an external population-based cohort. Again, we showed that Wnt5a protein expression was predictive of recurrence after radical prostatectomy in patients with low-grade prostate cancer and this was further enhanced whenWnt5a was combined with prostate cancer tissue biomarkers of known predictive value. We also demonstrated a positive correlation between Wnt5a and ERG protein expressions and that high Wnt5a protein and presence of ERG expression predicted a more favorable outcome. Despite this we observed that rWnt5a treatment of VCaP cells significantly decreased their ERG protein expression. Therefore, the relation between Wnt5a and ERG clearly need further exploration to better understand their functional interplay. In conclusion, our study indicates a tumor suppressor function of Wnt5a protein in localized PCa and that it can be used as a predictive tissue biomarker. Further, we suggest a novel therapeutic approach for patients with localized PCa targeting Wnt5a signaling to impair progression of PCa in these patients by using a Wnt5a mimicking peptide (Foxy5). (Less)
Physiology and development of the M and S molecular forms of Anopheles gambiae in Burkina Faso (West Africa)

In West Africa, M and S molecular forms of Anopheles gambiae sensu stricto (Diptera: Culicidae) Giles, frequently occur together, although with different population bionomics. The S form typically breeds in rain‐dependant water collections and is present during the rainy season only whereas the M form can thrive all year long in areas with permanent breeding opportunities. In the present study, we explored physiological and developmental trade‐offs at play in laboratory colonies and field populations of the M and S forms that originated from an area of sympatry in Burkina Faso, where M and S larvae exhibit such habitat segregation. In the laboratory, larvae of the M form developed slower than the S form (mean values 9.51 and 8.85 days, respectively, Wilcoxon's test, P < 0.001).
Human Cytomegalovirus Is Protected from Inactivation by Reversible Binding to Villous Trophoblasts1

Human cytomegalovirus (HCMV) is the leading cause of congenital disease in the developed world. Transmission of HCMV to the fetus can occur through the villous placenta. Previously, we have shown that although syncytiotrophoblast (ST) can be productively infected, it is more likely that HCMV reaches the fetus through breaks in the ST than through basal release of progeny virus from infected ST. Progeny virus released on the maternal side could interact back with the ST and accumulate. In pregnancy, the organ distribution of disease burden is dramatically shifted, with the placenta reported as a reservoir for some pathogens. Thus, we propose that the ST layer functions as a viral reservoir, where HCMV is harbored and ultimately protected from degradation. Using primary cytotrophoblasts differentiated into an ST culture in vitro and challenged with HCMV, we have defined reversible binding between the virus and trophoblasts that protects the virus from degradation. This is blocked by treatment with low pH and neutralizing intravenous immunoglobulin. This reversible binding likely is to heparan sulfate proteoglycans, because heparin treatment blocks it. Importantly, we show that bound and released virus maintained in culture for at least 48 h results from inoculum and not progeny virus. Thus, the placenta has the potential to accumulate a relatively high steady-state level of virus within the intervillous space resulting from localized binding and release at the ST. A better understanding of the molecular interactions between HCMV and ST will provide insights regarding interventions to prevent or minimize congenital transmission.
Mutational Constraints on Local Unfolding Inhibit the Rheological Adaptation of von Willebrand Factor*

Unusually large von Willebrand factor (VWF), the first responder to vascular injury in primary hemostasis, is designed to capture platelets under the high shear stress of rheological blood flow. In type 2M von Willebrand disease, two rare mutations (G1324A and G1324S) within the platelet GPIbα binding interface of the VWF A1 domain impair the hemostatic function of VWF. We investigate structural and conformational effects of these mutations on the A1 domain's efficacy to bind collagen and adhere platelets under shear flow. These mutations enhance the thermodynamic stability, reduce the rate of unfolding, and enhance the A1 domain's resistance to limited proteolysis. Collagen binding affinity is not significantly affected indicating that the primary stabilizing effect of these mutations is to diminish the platelet binding efficiency under shear flow. The enhanced stability stems from the steric consequences of adding a side chain (G1324A) and additionally a hydrogen bond (G1324S) to His1322 across the β2-β3 hairpin in the GPIbα binding interface, which restrains the conformational degrees of freedom and the overall flexibility of the native state. These studies reveal a novel rheological strategy in which the incorporation of a single glycine within the GPIbα binding interface of normal VWF enhances the probability of local unfolding that enables the A1 domain to conformationally adapt to shear flow while maintaining its overall native structure.
Teachers' Conceptions of Assessment: A Global Phenomenon or a Global Localism

How teachers conceive of the nature and purpose of assessment matters to the implementation of classroom assessment and the preparation of students for high-stakes external examinations or qualifications. It is highly likely that teacher beliefs arise from the historical, cultural, social, and policy contexts within which teachers operate. Hence, it may be that there is not a globally homogeneous construct of teacher conceptions of assessment. Instead, it is possible that a statistical model of teacher conceptions of assessment will always be a local expression. Thus, the objective of this study was to determine whether any of the published models of teacher assessment conceptions could be generalised across data sets from multiple jurisdictions. Research originating in New Zealand with the Teacher Conceptions of Assessment self-report inventory has been replicated in multiple locations and languages (i.e., English in New Zealand, Queensland, Hong Kong, and India; Greek in Cyprus; Arabic in Egypt; Spanish in Spain, Ecuador) and at different levels of instructional contexts (Primary, Secondary, Senior Secondary, and Teacher Education). This study conducts secondary data analyses in which eight previously published models of teacher conceptions of assessment were systematically compared across 11 available data sets. Nested multi-group confirmatory factor analysis (using Amos v25) was carried out to establish sequentially configural, metric, and scalar equivalence between models. Results indicate that only one model (i.e., India) had configural invariance across all 11 data sets and this did not achieve metric equivalence. These results indicate that while the inventory can be used cross-culturally after localized adaptations, there is indeed no single global model. Context, culture, and local factors shape teacher conceptions of assessment.
Exploring the Systems Analyst Skill Set: Perceptions, Preferences, Age, and Gender

Information systems (IS) workers need an appropriate skill set to effectively exploit technology innovations. Social constructivist theory would indicate that some aspect of a systems analyst's job evolution is attributable to the nature of both their perceptions of importance for various job skills and preferences toward using their professional job skills. Self-report survey data gathered from 124 systems analysts reveal analysts collectively recognize all skill dimensions explored have some degree of importance to their role. Systems analysts seem to perceive their role as a socio-technical function and desire this functional duality as they rank interpersonal skills and system development skills significantly higher than political skills and knowledge, technology skills, and business task knowledge for both preferences to use and perceptions of importance. Results show differences exist in perceptions and preferences among the sexes and age groups studied. Findings will add to the existing body of IS human resources research, and provide job development and career planning.
Ubiquitin D Regulates IRE1α/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells*

Pro-inflammatory cytokines contribute to pancreatic beta cell apoptosis in type 1 diabetes at least in part by inducing endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). It remains to be determined what causes the transition from “physiological” to “apoptotic” UPR, but accumulating evidence indicates that signaling by the ER transmembrane protein IRE1α is critical for this transition. IRE1α activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1α-interacting protein ubiquitin D (UBD) on the regulation of IRE1α and its downstream targets. UBD was identified by use of a MAPPIT (mammalian protein-protein interaction trap)-based IRE1α interactome screen followed by comparison against functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines. Knockdown of UBD in human and rodent beta cells and detailed signal transduction studies indicated that UBD modulates cytokine-induced UPR/IRE1α activation and apoptosis. UBD expression is induced by the pro-inflammatory cytokines interleukin (IL)-1β and interferon (IFN)-γ in rat and human pancreatic beta cells, and it is also up-regulated in beta cells of inflamed islets from non-obese diabetic mice. UBD interacts with IRE1α in human and rodent beta cells, modulating IRE1α-dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that UBD provides a negative feedback on cytokine-induced activation of the IRE1α/JNK pro-apoptotic pathway in cytokine-exposed beta cells.
What is feedback in clinical education?

Objective Feedback is important in clinical education. However, the medical education literature provides no consensual definition of feedback. The aim of this study is to propose a consensual, research‐based, operational definition of feedback in clinical education. An operational definition is needed for educational practice and teacher training, and for research into the effectiveness of different types of feedback.
RNA Sequencing Reveals Novel Gene Clusters in Bovine Conceptuses Associated with Maternal Recognition of Pregnancy and Implantation1

ABSTRACT Successful establishment and maintenance of pregnancy can be attained only through optimum conceptus-maternal cross talk. Despite significant progress in our understanding of the temporal changes in the transcriptome of the uterine endometrium, we have only a rudimentary knowledge of the genes and pathways governing growth and development of the bovine conceptus. In particular, very little information exists for the posthatching embryo and elongating conceptus. This period of development is arguably the most important, as approximately 40% of all embryonic loss occurs between Days 8 and 17 of pregnancy in cattle. Here, we describe the global transcriptome profile of the bovine conceptus at five key stages of its pre- and peri-implantation growth (Days 7, 10, 13, 16, and 19) using state-of-the-art RNA sequencing techniques. More than 287 million reads were generated at the five stages, and more than 22 700 unique transcripts were detected. Analysis of variance followed by self-organizing maps identified differentially regulated (P < 0.05) genes organized in nine gene clusters forming a sequential transcript dynamics across these developmental stages. Of particular interest, genes in clusters 3 (n = 236) and 6 (n = 1409) were significantly up-regulated on Days 16 and 19, suggesting a role in maternal recognition and initiation of implantation. This transcriptome analysis of the bovine conceptus will provide a blueprint of the dynamic changes in gene expression occurring during maternal recognition and implantation and will complement existing knowledge of the temporal changes in the endometrial transcriptome, thus facilitating a better understanding of conceptus-maternal cross talk during the peri-implantation period of pregnancy.
Use of a Groupware Product: A Test of Three Theoretical Perspectives

This study is a survey of the acceptance of a groupware product in three Fortune 500 companies. It examines three theoretical perspectives related to the use of a groupware product: the theory of media richness, the theory of social influence, and the theory of critical mass. These three theoretical perspectives are combined to establish a pluralistic view of communication technology use behavior and permit the investigation of the research question: what factors, suggested by these theories, explain organizational members' use of groupware. Only social influence has a significant, although moderate, positive relationship with use. On the other hand, media richness explains little of an individual's media use behavior. In addition, critical mass, while intuitively appealing, fails to explain actual use behavior.
User Roles in Online Communities and Their Moderating Effect on Online Community Usage Intention: An Integrated Approach

ABSTRACT Recently, it has been evident that the analysis of user data and content in online environments allows practitioners to understand how to motivate online community members and keep them frequently involved in the community, and so to manage these communities successfully. In this sense, practitioners should comprehend community members’ usage intentions to give a better service and to motivate them. However, different user types engage in such communities, so understanding their diverse needs is also essential for practitioners. In parallel, this article addresses the problem of the different user types existing in online communities, and each of them requires different strategies to be motivated and involved in the community. Thus, unlike previous studies, this study firstly identifies user roles in an online community based on the structural role theory, social network analysis, and community members’ contribution behavior. After that, it investigates members’ usage intentions based on the technology acceptance model and examines the moderating effect of identified user roles on their usage intentions. The study also guides practitioners to develop motivational strategies to keep each type of member continually satisfied.
Carbohydrate-Carbohydrate Interactions Mediated by Sulfate Esters and Calcium Provide the Cell Adhesion Required for the Emergence of Early Metazoans*

Early metazoans had to evolve the first cell adhesion mechanism addressed to maintain a distinctive multicellular morphology. As the oldest extant animals, sponges are good candidates for possessing remnants of the molecules responsible for this crucial evolutionary innovation. Cell adhesion in sponges is mediated by the calcium-dependent multivalent self-interactions of sulfated polysaccharides components of extracellular membrane-bound proteoglycans, namely aggregation factors. Here, we used atomic force microscopy to demonstrate that the aggregation factor of the sponge Desmapsamma anchorata has a circular supramolecular structure and that it thus belongs to the spongican family. Its sulfated polysaccharide units, which were characterized via nuclear magnetic resonance analysis, consist preponderantly of a central backbone composed of 3-α-Glc1 units partially sulfated at 2- and 4-positions and branches of Pyr(4,6)α-Gal1→3-α-Fuc2(SO3)1→3-α-Glc4(SO3)1→3-α-Glc→4-linked to the central α-Glc units. Single-molecule force measurements of self-binding forces of this sulfated polysaccharide and their chemically desulfated and carboxyl-reduced derivatives revealed that the sulfate epitopes and extracellular calcium are essential for providing the strength and stability necessary to sustain cell adhesion in sponges. We further discuss these findings within the framework of the role of molecular structures in the early evolution of metazoans.
Exploring Knowledge Management Using Network Theories: Questions, Paradoxes and Prospects

This paper investigates knowledge management (KM) activities in communities and networks of practice and information and communication technologies' role and use in these knowledge networks. We develop five research questions based on network models and the existing literature. We then investigate these research questions using a case study of a university information technology (IT) department. While our findings confirm extant KM understandings, we also develop several new insights and contradictions. Our study reveals several KM research and practice paradoxes and proposes a pluralistic/paradoxical view of KM and its related concepts such as networks, knowledge sharing, learning, and information and communication technologies. We suggest that recognizing simultaneous opposites and contradictions can improve an organization's KM efforts and can explain conflicting research findings.
Ovarian Expression and Regulation of the Stromelysins During the Periovulatory Period in the Human and the Rat1

ABSTRACT The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after human chorionic gonadotropin (hCG). Intact rat ovaries, granulosa cells, and residual tissue (tissue remaining after granulosa cell collection) were isolated from equine CG (eCG)-hCG-primed animals. Mmp10 mRNA was highly induced in human granulosa and theca cells and intact rat ovaries, granulosa cells, and residual tissue. Localization of MMP10 to granulosa and theca cells in both human and rat ovarian follicles was confirmed by immunohistochemistry. Mmp3 mRNA was unchanged in human cells and rat granulosa cells, but increased in intact rat ovaries and residual tissue. Mmp11 mRNA decreased following hCG treatment in human granulosa and theca cells as well as rat granulosa cells. Regulation of Mmp10 in cultured rat granulosa cells revealed that the EGF inhibitor AG1478 and the progesterone receptor antagonist RU486 suppressed the induction of Mmp10 mRNA, whereas the prostaglandin inhibitor NS398 had no effect. Studies on the Mmp10 promoter demonstrated that forskolin plus PMA stimulated promoter activity, which was dependent upon a proximal AP1 site. In conclusion, there are divergent patterns of stromelysin expression associated with ovulation, with a marked induction of Mmp10 mRNA and a decrease in Mmp11 mRNA, yet a species-dependent pattern on Mmp3 mRNA expression. The induction of Mmp10 expression suggests an important role for this MMP in the follicular changes associated with ovulation and subsequent luteinization.
Food-Pics_Extended—An Image Database for Experimental Research on Eating and Appetite: Additional Images, Normative Ratings and an Updated Review

Our current environment is characterized by the omnipresence of food cues. The taste and smell of real foods—but also graphical depictions of appetizing foods—can guide our eating behavior, for example, by eliciting food craving and anticipatory cephalic phase responses. To facilitate research into this so-called cue reactivity, several groups have compiled standardized food image sets. Yet, selecting the best subset of images for a specific research question can be difficult as images and image sets vary along several dimensions. In the present report, we review the strengths and weaknesses of popular food image sets to guide researchers during stimulus selection. Furthermore, we present a recent extension of our previously published database food-pics, which comprises an additional 328 food images from different countries to increase cross-cultural applicability. This food-pics_extended stimulus database, thus, encompasses and replaces food-pics. Normative data from a predominantly German-speaking sample are again presented as well as updated calculations of image characteristics.
Rab8b Regulates Transport of West Nile Virus Particles from Recycling Endosomes*

West Nile virus (WNV) particles assemble at and bud into the endoplasmic reticulum (ER) and are secreted from infected cells through the secretory pathway. However, the host factor related to these steps is not fully understood. Rab proteins, belonging to the Ras superfamily, play essential roles in regulating many aspects of vesicular trafficking. In this study, we sought to determine which Rab proteins are involved in intracellular trafficking of nascent WNV particles. RNAi analysis revealed that Rab8b plays a role in WNV particle release. We found that Rab8 and WNV antigen were colocalized in WNV-infected human neuroblastoma cells, and that WNV infection enhanced Rab8 expression in the cells. In addition, the amount of WNV particles in the supernatant of Rab8b-deficient cells was significantly decreased compared with that of wild-type cells. We also demonstrated that WNV particles accumulated in the recycling endosomes in WNV-infected cells. In summary, these results suggest that Rab8b is involved in trafficking of WNV particles from recycling endosomes to the plasma membrane.