Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment

There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a "proxy phenotype" for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion ("College," n = 95 427), and years of education ("EduYears," n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ.
Nurturing Supportive Learning Environments in Higher Education Through the Teaching of Study Skills: To Embed or Not to Embed?

The transnational widening of participation in higher education (HE) and the concomitant emphasis on promoting successful progression and high retention are focusing attention on how best to create supportive learning environments in HE. Using a phenomenographic approach, we explore variance in how first year undergraduate students experience the learning of generic, subject-related and metacognitive skills within a study skills module integrated into education programs. The findings suggest responses ranging from a lack of engagement in the module to evidence of increased confidence, criticality, self-reflection and change as a learner. The conclusion posits alternative ways of promoting the learning of study skills, which, whilst potentially including all learners, bring significant ramifications for the professional development of university lecturers. The renewed impetus for supporting the development of students’ learning in higher education (HE) comes as a result of the impact of a range of factors affecting the profile of undergraduate students. In the United Kingdom (UK) the widening participation agenda is a key driver that is predicated on the premise that “we cannot afford to waste talent simply because of a reluctance to foster it” (HEFCE, 2006, p. 9). In seeking to address the discrepancies in the participation rates between different social classes, universities in the UK are offering fair access to disabled students, mature students and men and women from all ethnic backgrounds, who wish to participate in HE. This, coupled with the exigencies of the information revolution and demands from employers for autonomous learners, requires greater flexibility and innovation in learning and teaching in order to maximize the retention and successful completion of those who progress into HE. As Hartley, Woods and Pill (2005, p. xiii) point out, recent HE initiatives in the UK have aimed at improving the quality of learning and teaching. At the sectoral level, the HE Academy, established in 2004, focuses on students and improving their learning. At the institutional level, the Higher Education Council for England (HEFCE) has invested £315 million to establish 74 Centres for Excellence in Teaching and Learning, “to recognise and reward specific areas of excellence in higher education institutions and to promote its further development to benefit students, teachers and universities and colleges (HEFCE, 2006, p. 18). At an individual level, the national teaching fellowship scheme was expanded in 2004 to provide rewards for excellence in promoting learning to 50 HE lecturers. This strong interventionist stance is serving to harness significant resources to enhance student learning and to promote and provide the opportunity for successful participation in HE to everyone who can benefit from it. This article reports on research designed to explore the efficacy of teaching study skills to students in a modern university which boasts a strong widening participation ethos.
Two-stage Genome-wide Methylation Profiling in Childhood-onset Crohn's Disease Implicates Epigenetic Alterations at the VMP1/MIR21 and HLA Loci

Background:As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onset disease. Methods:The Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. Data were corrected for differential leukocyte proportions. Targeted replication was performed in adults using pyrosequencing. Methylation changes were correlated with gene expression in blood and intestinal mucosa. Results:We identified 65 individual CpG sites with methylation alterations achieving epigenome-wide significance after Bonferroni correction (P < 1.1 × 10−7), and 19 differently methylated regions displaying unidirectional methylation change. There was a highly significant enrichment of methylation changes around GWAS single nucleotide polymorphisms (P = 3.7 × 10−7), notably the HLA region and MIR21. Two-locus discriminant analysis in the discovery cohort predicted disease in the pediatric replication cohort with high accuracy (area under the curve, 0.98). The findings strongly implicate the transcriptional start site of MIR21 as a region of extended epigenetic alteration, containing the most significant individual probes (P = 1.97 × 10−15) within a GWAS risk locus. In extension studies, we confirmed hypomethylation of MIR21 in adults (P = 6.6 × 10−5, n = 172) and show increased mRNA expression in leukocytes (P < 0.005, n = 66) and in the inflamed intestine (P = 1.4 × 10−6, n = 99). Conclusions:We demonstrate highly significant and replicable differences in DNA methylation in CD, defining the disease-associated epigenome. The data strongly implicate known GWAS loci, with compelling evidence implicating MIR21 and the HLA region.
Leadership by design: intentional organization development of physician leaders

Purpose – The purpose of this paper is: first, to present a qualitative descriptive case study of the Mayo Clinic leadership and organization development philosophy and approach; second, to summarize a strategy for using intentional organization design as a foundation for culturally aligned physician leadership development and third, to describe the Mayo Clinic Leadership Model. Design/methodology/approach – This manuscript is a qualitative descriptive case study of the Mayo Clinic leadership development philosophy and approach. The authors reviewed the organization design and leadership development programs of a leading healthcare institution. In the systematic appraisal, the authors sought to understand the key features and elements of team-based leadership development and the supporting organizational characteristics that guide development with the use of a customized institutional leadership model. Findings – The authors identified four intentional characteristics of the multi-specialty group practice.
Medial Temporal Lobe Projections to the Retrosplenial Cortex of the Macaque Monkey

The projections to the retrosplenial cortex (areas 29 and 30) from the hippocampal formation, the entorhinal cortex, perirhinal cortex, and amygdala were examined in two species of macaque monkey by tracking the anterograde transport of amino acids. Hippocampal projections arose from the subiculum and presubiculum to terminate principally in area 29. Label was found in layer I and layer III(IV), the former seemingly reflecting both fibers of passage and termination. While the rostral subiculum mainly projects to the ventral retrosplenial cortex, mid and caudal levels of the subiculum have denser projections to both the caudal and dorsal retrosplenial cortex. Appreciable projections to dorsal area 30 [layer III(IV)] were only seen following an extensive injection involving both the caudal subiculum and presubiculum. This same case provided the only example of a light projection from the hippocampal formation to posterior cingulate area 23 (layer III). Anterograde label from the entorhinal cortex injections was typically concentrated in layer I of 29a–c, though the very caudal entorhinal cortex appeared to provide more widespread retrosplenial projections. In this study, neither the amygdala nor the perirhinal cortex were found to have appreciable projections to the retrosplenial cortex, although injections in either medial temporal region revealed efferent fibers that pass very close or even within this cortical area. Finally, light projections to area 30V, which is adjacent to the calcarine sulcus, were seen in those cases with rostral subiculum and entorhinal injections. The results reveal a particular affinity between the hippocampal formation and the retrosplenial cortex, and so distinguish areas 29 and 30 from area 23 within the posterior cingulate region. The findings also suggest further functional differences within retrosplenial subregions as area 29 received the large majority of efferents from the subiculum. © 2012 Wiley Periodicals, Inc.
The Association of Recombination Events in the Founding and Emergence of Subgenogroup Evolutionary Lineages of Human Enterovirus 71

ABSTRACT Enterovirus 71 (EV71) is responsible for frequent large-scale outbreaks of hand, foot, and mouth disease worldwide and represent a major etiological agent of severe, sometimes fatal neurological disease. EV71 variants have been classified into three genogroups (GgA, GgB, and GgC), and the latter two are further subdivided into subgenogroups B1 to B5 and C1 to C5. To investigate the dual roles of recombination and evolution in the epidemiology and transmission of EV71 worldwide, we performed a large-scale genetic analysis of isolates (n = 308) collected from 19 countries worldwide over a 40-year period. A series of recombination events occurred over this period, which have been identified through incongruities in sequence grouping between the VP1 and 3Dpol regions. Eleven 3Dpol clades were identified, each specific to EV71 and associated with specific subgenogroups but interspersed phylogenetically with clades of coxsackievirus A16 and other EV species A serotypes. The likelihood of recombination increased with VP1 sequence divergence; mean half-lives for EV71 recombinant forms (RFs) of 6 and 9 years for GgB and GgC overlapped with those observed for the EV-B serotypes, echovirus 9 (E9), E30, and E11, respectively (1.3 to 9.8 years). Furthermore, within genogroups, sporadic recombination events occurred, such as the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization.
The FACT subunit TbSpt16 is involved in cell cycle specific control of VSG expression sites in Trypanosoma brucei

The African trypanosome Trypanosoma brucei monoallelically expresses one of more than 1000 Variant Surface Glycoprotein (VSG) genes. The active VSG is transcribed from one of about 15 telomeric VSG expression sites (ESs). It is unclear how monoallelic expression of VSG is controlled, and how inactive VSG ESs are silenced. Here, we show that blocking synthesis of the T. brucei FACT subunit TbSpt16 triggers a G2/early M phase cell cycle arrest in both bloodstream and insect form T. brucei. Segregation of T. brucei minichromosomes in these stalled cells is impaired, implicating FACT in maintenance of centromeres. Strikingly, knock‐down of TbSpt16 results in 20‐ to 23‐fold derepression of silent VSG ES promoters in bloodstream form T. brucei, with derepression specific to the G2/M cell cycle stage. In insect form T. brucei TbSpt16 knock‐down results in 16‐ to 25‐fold VSG ES derepression. Using chromatin immunoprecipitation (ChIP), TbSpt16 was found to be particularly enriched at the promoter region of silent but not active VSG ESs in bloodstream form T. brucei. The chromatin remodeler FACT is therefore implicated in maintenance of repressed chromatin present at silent VSG ES promoters, but is also essential for chromosome segregation presumably through maintenance of functional centromeres.
A defective cell surface collagen-binding protein in dermatosparactic sheep fibroblasts

Fibroblasts from dermatosparactic sheep fail to contract collagen gels and show a reduced attachment to collagenous substrates. By comparing collagen-binding membrane proteins of normal (+/+), homozygote (-/-), and heterozygote (+/-) fibroblasts, we present evidence that the interaction of normal fibroblasts with native type I collagen involves a protein of apparent Mr = 34,000 which is absent from dermatosparactic fibroblasts and seems to be related to anchorin CII. This conclusion was reached from the following experiments: (a) On a blot of membrane proteins from normal fibroblasts radioactively labeled type I collagen bound predominantly to a protein band of 34 kD; dermatosparactic membranes revealed only a small amount of binding to a component with a molecular mass of 47 kD. (b) After separation of normal fibroblast membrane proteins on type I collagen-Sepharose, a collagen-binding component of 34 kD was found which was absent from the corresponding fraction of dermatosparactic membranes. (c) Antibodies to anchorin CII stained the surface of normal (+/+), but not of dermatosparactic (-/-) fibroblasts and labeled a 34-kD component after immunoblotting of normal fibroblast membrane proteins. (d) After metabolic labeling of fibroblasts with [35S]methionine and immunoprecipitation with anti- anchorin CII, 40- and 34-kD components were precipitated from extracts of normal fibroblasts, while the latter component was absent from affected cells. Similar differences were found after immunoblotting of membranes from whole normal or affected skin. These data indicate that dermatosparaxis of sheep involves a molecular defect of a collagen- binding protein. Therefore this disease represents a model to study the complex interaction of cells with the extracellular matrix on a molecular level.
Disruption in the Balance Between Goal-Directed Behavior and Habit Learning in Obsessive-Compulsive Disorder

Objective: Obsessive-compulsive disorder (OCD) is characterized by repetitive, ritualistic behaviors and thought patterns. Although patients with OCD report that these compulsive behaviors are unproductive and often senseless, they are unable to desist. This study investigated whether the urge to perform compulsive acts is mediated by a disruption in the balance between flexible, goal-directed action control and habitual behavior. Method: A total of 21 patients with OCD and 30 healthy comparison subjects participated in a set of tasks designed to assess relative goal-directed versus habitual behavioral control. In the training stage, participants were asked to respond to different pictured stimuli in order to gain rewarding outcomes. In the subsequent (instructed) outcome devaluation test and in a novel “slips-of-action” test, the authors assessed whether participants were able to flexibly adjust their behavior to changes in the desirability of the outcomes. The authors also used a questionnaire to test explicit knowledge of the relationships between stimuli, responses, and outcomes. Results: Patients with OCD showed no deficit in their ability to use feedback to respond appropriately to stimuli in the training stage. However, their knowledge of the outcomes of these responses was impaired relative to healthy comparison subjects, and patients were more prone to slips of action, indicating a deficit in goal-directed control and an overreliance on habits. Conclusions: This study provides the first experimental evidence for selective impairment in flexible and goal-directed behavioral control in patients with OCD. The impairment forces patients with OCD to rely instead on habits that can be triggered by stimuli regardless of the desirability of the consequences. Goal-directed actions are supported by orbitofronto-striatal circuitry, and the study findings are thus in line with findings from research that implicate dysfunction in this circuitry in the neuropathology of OCD.
Insomnia and long sleep duration are risk factors for later work disability. The Hordaland Health Study

Both insomnia and sleep duration have previously been linked with a range of adverse outcomes, but no studies have explored their relative effect on subsequent work disability. The aim of the present study was to investigate the contribution of insomnia versus sleep duration to later long‐term work disability. Using a historical cohort design with 4‐year follow‐up, data on insomnia, sleep duration and potential confounders were gathered from 6599 working persons (40–45 years). The outcome was award of disability pension, as registered in the National Insurance Administration. After controlling for baseline exposure to disability and sick leave, insomnia was a strong predictor of permanent work disability [odds ratio (OR) = 4.56], and this effect remained significant after controlling for sleep duration, as well as for other possible confounders (OR = 1.88). Short sleep duration was not significantly associated with subsequent work disability, while long sleep duration (>8.5 h) did predict work disability (OR = 2.96), also in the fully adjusted model (OR = 2.14). The present study demonstrates that both insomnia and long sleep duration are strong and independent risk factors for subsequent work disability.
Lrig1 is a positive prognostic marker in hepatocellular carcinoma

Background The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide. As a consequence, there is an urgent need for identifying molecular markers of HCC development and progression. Recently, several studies have suggested that the Lrig1 may have prognostic implications in various cancer types, but its clinical value in HCC is not well evaluated. Materials and methods In this study, the expression level of Lrig1 was examined in 133 HCC tissues and adjacent normal tissues by immunohistochemistry. Furthermore, potential associations between Lrig1 expression and the carcinoma clinical parameters were investigated, including recurrence and survival rate. We silenced the Lrig1 in the normal liver cell line (LO2) and liver cancer cell line (Hep-G2) in vitro by the small interference RNA and detected its influence on proliferation, migration, and invasion. Results The expression of Lrig1 was significantly downregulated in liver cancer tissues and cell lines, and its expression levels were related to tumor size, tumor–node–metastasis staging and tumor recurrence. Furthermore, analysis of 6-year survival of 133 HCC patients showed that those with stronger Lrig1 expression had significantly longer overall survival time than those with weaker Lrig1 expression. In addition, decreased expression of Lrig1 in vitro promoted the growth, migration, or invasion of normal liver cells and cancer cells. Conclusion Our findings demonstrate that Lrig1 could serve as a potential marker in the prognosis of patients with HCC. We also revealed that Lrig1 might be involved in the metastatic progression of liver cancer. However, its clinical value should be further investigated in the future.
Lie to me: investigating the strategic regulation of fine-grain details in truth-tellers and liars

A metacognitive model of memory regulation was applied to information-gathering interviews with deceptive and truth-telling participants. Theoretically, differential strategies of the liars and truth-tellers would direct specific metacognitive processes and elicit veracity cues. 60 participants (40 female, 20 male) were interviewed and asked to lie or tell the truth about an event. Half the liars and half the truth-tellers were given 5 minutes preparation. It was found that, despite a majority of liars reported adopting an ‘embedding’ strategy (whereby lies are concealed within really experienced events), significantly more fine-grain precise details (e.g. ‘he was 6’ 3” tall’, ‘the chair was red’) were reported by truth-tellers than liars. Additionally, truth-tellers reports contained significantly more reminiscence (recalling details in follow up questions not originally remembered) than liars. This provides the first evidence suggesting that embedding is not an effective counter-strategy to reminiscence based veracity tools. However, no evidence was found for increased verbal-decline for liars. Furthermore, no effect of preparation was found for fine-grain details, reminiscence, or verbal-decline. It is concluded that although the current results with respect to reminiscence are encouraging, the boundary conditions associated with fine-grain detail reporting should be established before such models are integrated into cognitive based lie-detectors.
Immunolocalization of BK channels in hippocampal pyramidal neurons

Neurons are highly specialized cells in which the integration and processing of electrical signals critically depends on the precise localization of ion channels. For large‐conductance Ca2+‐ activated K+ (BK) channels, targeting to presynaptic membranes in hippocampal pyramidal cells was reported; however, functional evidence also suggests a somatodendritic localization. Therefore we re‐examined the subcellular distribution of BK channels in mouse hippocampus using a panel of independent antibodies in a combined approach of conventional immunocytochemistry on cultured neurons, pre‐ and postembedding electron microscopy and immunoprecipitation. In cultured murine hippocampal neurons, the colocalization of BK channels with both pre‐ and postsynaptic marker proteins was observed. Electron microscopy confirmed targeting of BK channels to axonal as well as dendritic membranes of glutamatergic synapses in hippocampus. A postsynaptic localization of BK channels was also supported by the finding that the channel coimmunoprecipitated with PSD95, a protein solely expressed in the postsynaptic compartment. These results thus demonstrate that BK channels reside in both post‐ and presynaptic compartments of hippocampal pyramidal neurons.
Automorphisms of hyperkähler manifolds in the view of topological entropy

First we show that any group of automorphisms of null-entropy of a projective hyperk\"ahler manifold $M$ is almost abelian of rank at most $\rho(M) - 2$. We then characterize automorphisms of a K3 surface with null-entropy and those with positive entropy in algebro-geometric terms. We also give an example of a group of automorphisms which is not almost abelian in each dimension.