Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonal Analysis of Newborn Hippocampal Dentate Granule Cell Proliferation and Development in Temporal Lobe Epilepsy1,2,3

Abstract Hippocampal dentate granule cells are among the few neuronal cell types generated throughout adult life in mammals. In the normal brain, new granule cells are generated from progenitors in the subgranular zone and integrate in a typical fashion. During the development of epilepsy, granule cell integration is profoundly altered. The new cells migrate to ectopic locations and develop misoriented “basal” dendrites. Although it has been established that these abnormal cells are newly generated, it is not known whether they arise ubiquitously throughout the progenitor cell pool or are derived from a smaller number of “bad actor” progenitors. To explore this question, we conducted a clonal analysis study in mice expressing the Brainbow fluorescent protein reporter construct in dentate granule cell progenitors. Mice were examined 2 months after pilocarpine-induced status epilepticus, a treatment that leads to the development of epilepsy. Brain sections were rendered translucent so that entire hippocampi could be reconstructed and all fluorescently labeled cells identified. Our findings reveal that a small number of progenitors produce the majority of ectopic cells following status epilepticus, indicating that either the affected progenitors or their local microenvironments have become pathological. By contrast, granule cells with “basal” dendrites were equally distributed among clonal groups. This indicates that these progenitors can produce normal cells and suggests that global factors sporadically disrupt the dendritic development of some new cells. Together, these findings strongly predict that distinct mechanisms regulate different aspects of granule cell pathology in epilepsy.
Effects of Antibiotic Prophylaxis in Patients with Open Fracture of the Extremities: A Systematic Review of Randomized Controlled Trials

Background:The purpose of the present study was to perform a systematic review and meta-analysis of the use of alternative antibiotic regimens—including (A) antibiotic prophylaxis versus no prophylaxis, (B) longer versus shorter duration of antibiotic prophylaxis, and (C) alternative drugs—for patients with open fracture of the extremities. Methods:Data sources included CINAHL, EMBASE, MEDLINE, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane database of systematic reviews from 1965 to December 2013. All randomized controlled trials comparing the effectiveness of antibiotic prophylaxis in patients with open fracture of the extremities were eligible. Results:We identified 329 potentially eligible articles, of which seventeen proved to be eligible. In four randomized controlled trials involving 472 patients, we found a significantly lower infection rate in patients receiving antibiotic prophylaxis compared with those not receiving antibiotic prophylaxis (risk ratio = 0.37 [95% confidence interval, 0.21 to 0.66]; absolute risk reduction = 9.6% [95% confidence interval, 5.2% to 12.1%]). In three studies involving 1104 patients, we found no difference in the infection rate when a longer duration of antibiotics (three to five days) was compared with a shorter duration (one day) (risk ratio = 0.97; 95% confidence interval, 0.69 to 1.37). Confidence in the estimates for both questions was low to moderate. Individual comparisons of alternative drugs yielded estimates warranting only low to very low confidence. Conclusions:Results of randomized controlled trials performed to date provide evidence that antibiotic prophylaxis reduces subsequent infection and that courses as short as one day are as effective as courses of three to five days, although the evidence warrants only low to moderate confidence. Given current practice, a large, multicenter, low risk of bias, randomized controlled trial enrolling representative populations and addressing the duration of antibiotics may be the next optimum step in investigation. Level of Evidence:Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Are the Human Papillomavirus Genotypes Different in Cervical Cancer and Intraepithelial Neoplasia in Jewish Israeli Women, a Low-Risk Population?

Objectives Israel is traditionally considered to have the lowest prevalence of cervical cancer compared with that in other countries of the Western world. The aim of the present study was to establish the human papillomavirus (HPV) genotypes distribution among Israeli Jewish women with premalignant and cervical cancer. Methods Fifty-two specimens with invasive cervical cancer and 50 specimens with high-grade cervical intraepithelial neoplasia (CIN2/3) were identified. Human papillomavirus genotyping in paraffin-embedded specimens was performed by deparaffinization of the tissue sections and DNA extraction, followed by HPV genotype detection using a validated polymerase chain reaction (PCR)–based HPV GenoArray test kit, to simultaneously identify 21 HPV genotypes. Results Forty-eight (48/52; 92.3%) cervical cancer samples demonstrated PCR-amplifiable DNA (non-HPV DNA). Forty (83.3%) of 48 samples were high-risk (HR) HPV positive. Six (12.5%) of 48 patients showed multiple HR HPV infections. Human papillomavirus types 16 and 18 dominated covering 28 (58.3%) and 14 (29.16%) of 48 samples. Human papillomavirus types 16 and 18 coinfected all 6 cases of multiple HR HPV infections. In CIN2/3 samples, 37 (78.7%) of 47 samples demonstrated PCR-amplifiable DNA (non-HPV DNA), and 20 (54.0%) of these 37 samples were infected by HPV. Human papillomavirus type 16 was found in 19 (95.0%) of 20 cases. Human papillomavirus type 18 was found in 3 (15.0%) of 20 cases; hence, HPV16 and HPV18 contributed to 100% of the cases. Conclusions Human papillomavirus types 16 and 18 were responsible for the vast majority of invasive cervical cancer and CIN2/3 specimens (81.2% and 100%, respectively). Therefore, it is essential to include the HPV vaccine in the vaccine schedule of the Israeli population.
Neurons tend to stop migration and differentiate along the cortical internal plexiform zones in the Reelin signal‐deficient mice

The Reelin molecule plays a fundamental role in corticogenesis. After Reelin binds to its receptors, the Reelin signal is transduced through tyrosine phosphorylation of the intracellular adaptor protein disabled 1 (Dab1). The reelin‐gene‐deficient mouse, reeler, and Dab1‐deficient mouse, yotari, show disrupted positioning of neurons. Several molecules have been identified recently as being involved in Reelin signaling, however, the biological function of Reelin during cortical plate development was still unknown. We observed the migrating behavior of neurons during development in Reelin‐signal‐deficient mice. To visualize the migrating neurons directly, we introduced green fluorescent protein (GFP)‐expression vectors into the ventricular zone with an in utero electroporation system and allowed the embryos to develop in utero until they were analyzed. The result showed that the migrating cells in the mutants were morphologically indistinguishable from those of normal mice. At the stage when the GFP‐expressing cells reached the marginal zone near the pial surface and began dendrite formation in normal mice, the GFP‐positive cells were found at various deeper positions in the mutant cortex. They had the morphology of migrating cells extending leading processes toward the pial surface. By contrast, in the mutants these cells tended to stop migration along the borders of the internal plexiform zone, the irregular structure consisting mainly of dendrites in the mutant cortex. Postnatally, these neurons began to develop dendrites later than the cells in the normal cortex. During this process, some neurons above the internal plexiform zone extended and developed dendrites in the opposite direction into the internal plexiform zone. These results suggest that the abnormal positioning of neurons in the Reelin‐signal‐deficient mice is caused, at least in part, by abnormal formation of the internal plexiform zone in the mutant cortex. © 2002 Wiley‐Liss, Inc.
Effect of low mass dark matter particles on the Sun

We study the effect of dark matter (DM) particles in the Sun, focusing, in particular, on the possible reduction of the solar neutrinos flux due to the energy carried away by DM particles from the innermost regions of the Sun, and to the consequent reduction of the temperature of the solar core. We find that in the very low-mass range between 4 and 10 GeV, recently advocated to explain the findings of the DAMA and CoGent experiments, the effects on neutrino fluxes are detectable only for DM models with a very small, or vanishing, self-annihilation cross section, such as the so-called asymmetric DM models, and we study the combination of DM masses and spin-dependent cross sections which can be excluded with current solar neutrino data. Finally, we revisit the recent claim that DM models with large self-interacting cross sections can lead to a modification of the position of the convective zone, alleviating or solving the solar composition problem. We show that when the 'geometric' upper limit on the capture rate is correctly taken into account, the effects of DM are reduced by orders of magnitude, and the position of the convective zone remains unchanged.
Spatial memory: behavioral determinants of persistence in the watermaze delayed matching-to-place task

The watermaze delayed matching-to-place (DMP) task was modified to include probe trials, to quantify search preference for the correct place. Using a zone analysis of search preference, a gradual decay of one-trial memory in rats was observed over 24 h with weak memory consistently detected at a retention interval of 6 h, but unreliably at 24 h. This forgetting function in the watermaze was similar to that found using a search-preference measure in a food-reinforced dry-land DMP task in a previous study. In a search for strong and weak encoding conditions, essential for a later behavioral tagging study, three encoding trials gave strong 6-h and 24-h memory when trials were separated by 10 min (spaced training) but not 15 sec (massed training). The use of six encoding trials gave good 6-h memory with both spaced and massed training. With respect to weak encoding, placement on the escape platform, instead of the rat swimming to it, resulted in detectable memory at 30 min but this had faded to chance within 24 h. In contrast to the search-preference measure, latencies to cross the correct place revealed neither the gradual forgetting of place memory nor the benefit of spaced training.
Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the transcriptional logic underpinning this process remains poorly defined. Here, we examined IPC production using mice lacking the transcription factor nuclear factor I/X (Nfix). We show that Nfix deficiency delays IPC production and prolongs the neurogenic window, resulting in an increased number of neurons in the postnatal forebrain. Loss of additional Nfi alleles (Nfib) resulted in a severe delay in IPC generation while, conversely, overexpression of NFIX led to precocious IPC generation. Mechanistically, analyses of microarray and ChIP-seq datasets, coupled with the investigation of spindle orientation during radial glial cell division, revealed that NFIX promotes the generation of IPCs via the transcriptional upregulation of inscuteable (Insc). These data thereby provide novel insights into the mechanisms controlling the timely transition of radial glia into IPCs during forebrain development. Summary: The Nfix and Nfib transcription factors are required for the timely transition of radial glia into intermediate progenitor cells during mouse forebrain development.
What Do We Know about High Performance Teams in Software Engineering? Results from a Systematic Literature Review

A high performance team is one that exceeds all reasonable expectations and produces extraordinary results. In this work, we are interested in understanding contexts and conditions in which software engineering teams are likely to achieve this status. To this end, we are carrying out a systematic literature review to identify what are the known factors that booster or hinder the performance of software engineering teams, and what evidence is available to support such factors. In this preliminary effort, we selected 15 papers from SCOPUS, analyzed them following a qualitative meta-summary procedure. As a result, we present a summary of characteristics that positively and negatively influence different process of the teamwork, based on evidence available in the literature. This work constitutes a key preliminary result towards the design of more elaborate models and theories to predict and explain the performance of software engineering teams.
T2384, a Novel Antidiabetic Agent with Unique Peroxisome Proliferator-activated Receptor γ Binding Properties*

The nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) plays central roles in adipogenesis and glucose homeostasis and is the molecular target for the thiazolidinedione (TZD) class of antidiabetic drugs. Activation of PPARγ by TZDs improves insulin sensitivity; however, this is accompanied by the induction of several undesirable side effects. We have identified a novel synthetic PPARγ ligand, T2384, to explore the biological activities associated with occupying different regions of the receptor ligand-binding pocket. X-ray crystallography studies revealed that T2384 can adopt two distinct binding modes, which we have termed “U” and “S”, interacting with the ligand-binding pocket of PPARγ primarily via hydrophobic contacts that are distinct from full agonists. The different binding modes occupied by T2384 induced distinct patterns of coregulatory protein interaction with PPARγ in vitro and displayed unique receptor function in cell-based activity assays. We speculate that these unique biochemical and cellular activities may be responsible for the novel in vivo profile observed in animals treated systemically with T2384. When administered to diabetic KKAy mice, T2384 rapidly improved insulin sensitivity in the absence of weight gain, hemodilution, and anemia characteristics of treatment with rosiglitazone (a TZD). Moreover, upon coadministration with rosiglitazone, T2384 was able to antagonize the side effects induced by rosiglitazone treatment alone while retaining robust effects on glucose disposal. These results are consistent with the hypothesis that interactions between ligands and specific regions of the receptor ligand-binding pocket might selectively trigger a subset of receptor-mediated biological responses leading to the improvement of insulin sensitivity, without eliciting less desirable responses associated with full activation of the receptor. We suggest that T2384 may represent a prototype for a novel class of PPARγ ligand and, furthermore, that molecules sharing some of these properties would be useful for treatment of type 2 diabetes.
Sleep Patterns and Fatigue in New Mothers and Fathers

The purpose of this study was to describe the sleep patterns and fatigue of both mothers and fathers before and after childbirth. The authors used wrist actigraphy and questionnaires to estimate sleep and fatigue in 72 couples during their last month of pregnancy and 1st month postpartum. Both parents experienced more sleep disruption at night during the postpartum period as compared to the last month of pregnancy. Compared to fathers, with their stable 24-h sleep patterns over time, mothers had less sleep at night and more sleep during the day after the baby was born. Sleep patterns were also related to parents’work status and type of infant feeding. Both parents self-reported more sleep disturbance and fatigue during the 1st month postpartum than during pregnancy. Mothers reported more sleep disturbance than fathers, but there was no gender difference in ratings of fatigue. At both time points, fathers obtained less total sleep than mothers when sleep was objectively measured throughout the entire 24-h day. Further research is needed to determine the duration of sleep loss for both mothers and fathers, to evaluate the effect of disrupted sleep and sleep loss on psychosocial functioning and job performance, and to develop interventions for improving sleep patterns of new parents.
Nursing Students' First Placement: Peripherality and Marginality Within the Community of Practice.

BACKGROUND A nursing student's first placement is a significant and influential experience that can be a factor in attrition from nursing education programs. METHOD The first placement experiences of 17 nursing students at a Scottish university were collected through semistructured individual interviews or focus groups. The resultant transcripts were analyzed from the perspective of communities of practice using deductive content analysis. RESULTS Students' peripheral position within the communities of practice they encounter on placement can support learning. However, it can also leave them at risk of marginalization, which may have a detrimental effect on their emerging identity as nursing students. The central roles of mentors and liaison lecturers in supporting student participation within the community of practice are apparent. CONCLUSION Student experiences of peripherality and marginality highlight opportunities for practice settings and universities to better prepare and support students during their first placement. [J Nurs Educ. 2017;56(1):31-38. ].
TP 53 Polymorphism , HPV Infection , and Risk of Cervical Cancer

The role of a polymorphism at position 72 of the tumor suppressor gene TP53 in the development of cervical cancer is not well established. The arginine variant of the p53 protein could be more susceptible to degradation by human papillomavirus (HPV) E6 protein than the protein containing proline. Recent studies show controversial results. We investigated a possible association between TP53 polymorphism and cervical cancer in a Peruvian population with high prevalence of HPV infection. HPV status and TP53 polymorphism were determined for 119 cases of invasive cervical cancer and 127 control women from Peru. HPV infection was detected by PCR of cervical cells or tumor biopsies. For determination of TP53 polymorphism, exon 4 of the TP53 gene was amplified by PCR, and DNA was subsequently subjected to restriction enzyme digest. Associations between TP53 polymorphism, HPV infection, and cervical cancer were assessed using logistic regression. Women homozygotes for arginine had a 2.2-fold increased risk (95% confidence interval: 0.6–7.6) for cervical cancer. The odds ratio for women heterozygotes for Arg/Pro was 3.5 (95% confidence interval: 0.9–14). Similarly increased risks were found when restricting analysis to HPVpositive women only. The distribution of TP53 genotypes in this Peruvian population was comparable with that found in Caucasians. Our results cannot rule out an association between the TP53 polymorphism at codon 72, HPV infection, and the etiology of cervical cancer.
Mechanisms of eosinophil adherence to cultured vascular endothelial cells. Eosinophils bind to the cytokine-induced ligand vascular cell adhesion molecule-1 via the very late activation antigen-4 integrin receptor.

We have examined the mechanisms involved in the adherence of normal peripheral blood eosinophils to cultured human umbilical vein endothelial cells (HEC) under three conditions: (a) adherence in the absence of treatment of HEC or eosinophils with activating agents (basal adherence); (b) adherence induced by stimulation of eosinophils with phorbol ester (eosinophil-dependent adherence); and (c) adherence induced by pretreatment of HEC with LPS, tumor necrosis factor (TNF), or IL-1 (endothelial-dependent adherence). A mechanism was identified that was equally active in basal, eosinophil-dependent, and endothelial-dependent adherence. This mechanism was optimally active in the presence of both Ca++ and Mg++, and reduced in the presence of Ca++ only or Mg++ only. Furthermore, like the other mechanisms of eosinophil adherence, it was active at 37 degrees C but not at 4 degrees C. A second mechanism of adherence was involved in eosinophil- and in endothelial-dependent adherence. This mechanism was dependent on the CD11/CD18 adhesion complex of eosinophils (i.e., inhibited by anti-CD18 MAb) and it was active in the presence of Ca++ and Mg++ or Mg++ only, but not Ca++ only. The third mechanism of adherence was specific for endothelial-dependent adherence. It involved the endothelial ligand vascular cell adhesion molecule-1 (VCAM-1) and the eosinophil receptor very late activation antigen-4 (VLA-4, CD49d/CD29, i.e., inhibited by anti-VCAM-1 MAb or anti-VLA-4 MAb). This mechanism was active in the presence of Ca++ and Mg++ but not of Ca++ only or Mg++ only, and was not up- or downregulated when eosinophils were stimulated with phorbol ester. In contrast, the endothelial leukocyte adhesion molecule-1 (ELAM-1), that binds neutrophils and monocytes, was not involved in eosinophil adherence to LPS-, TNF-, or IL-1-stimulated HEC (i.e., not inhibited by anti-ELAM-1 MAb). We conclude that eosinophils, like monocytes and lymphocytes, bind to the cytokine-induced endothelial ligand VCAM-1 via the integrin receptor VLA-4.
Marathons for the Masses: Exploring the Role of Negotiation-Efficacy and Involvement on Running Commitment

Abstract Marathon running is a leisure behavior that has seen tremendous growth during the past decade. The purpose of this study was to gain a better understanding of factors associated with commitment to running for marathon participants. This study was designed to investigate the relationships among negotiation-efficacy, leisure involvement, and psychological commitment for individuals who had participated in a marathon event. A three-facet involvement measure was confirmed and then combined with negotiation-efficacy to predict commitment to running. The results revealed that two involvement dimensions and negotiation-efficacy explained 72% of the variance in commitment. A discussion of findings from the study as well as practical implications and suggestions for future research are presented.
Transposon‐dependent induction of Vincent van Gogh's sunflowers: Exceptions revealed

The radiate sunflower inflorescence is composed by zygomorphic ray flowers and actinomorphic disk flowers. Studies performed on mutants identify HaCYC2c, a CYCLOIDEA (CYC)‐like gene, as one of the key players controlling flower symmetry in sunflower. turf and tub mutants are characterized by a shift from zygomorphic to actinomorphic ray flowers, caused by insertion of transposable elements (TEs) in HaCYC2c gene. In dbl or Chry mutants, an insertion upstream the coding region of HaCYC2c causes the ectopic expression of the gene and the shift from actinomorphic to zygomorphic disk flowers. We focused on Chry2 mutant: a 1034 bp insertion placed 558 bp before the start codon of HaCYC2c was identified. The insertion is a truncated version of a CACTA TE. Unexpectedly, phenotypic and genetic co‐segregation analysis in F2 and F3 progenies derived from the crosses Chry2 × turf and turf × Chry2 demonstrated that CACTA insertion is not always sufficient to alter the expression of HaCYC2c gene and generate Chry2 phenotype. F3 plants homozygous for the CACTA insertion displayed either HaCYC2c transcription pattern identical to wild‐type plants or a normal heterogamous inflorescence. Stated these results, we conclude that a much more complex regulatory system stays behind the Chry2 phenotype. genesis 52:315–327, 2014. © 2014 Wiley Periodicals, Inc.