Miracle-dz/UniFAR-FTUs huggingface dataset:
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.
Lack of Association Between Prokineticin 2 Gene and Japanese Methamphetamine Dependence

Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor gene (PROKR2) and Japanese methamphetamine dependence patients. Also, prokineticin 2 (PK2) gene deficient mice showed reduced physiological and behavioral parameters, including circadian locomotor activity, circulating glucocorticoid, glucose levels and the expression of peripheral clock genes compared with WT mice. These evidences indicate that PK2 gene (PROK2) is a good candidate gene for the pathogenesis of methamphetamine dependence. To evaluate the association between PROK2 and methamphetamine dependence, we conducted a case-control study of Japanese samples (215 methamphetamine dependence and 232 controls) with four tagging SNPs selected by HapMap database. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. Written informed consent was obtained from each subject. This study was approved by the ethics committees at Fujita Health University, Nagoya University Graduate School of Medicine and each participating member of the Institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA). We did not detect an association between PROK2 and Japanese methamphetamine dependence patients in allele/genotype-wise analysis, or the haplotype analysis. Our findings suggest that PROK2 does not play a major role in the pathophysiology of methamphetamine dependence in the Japanese population.
A Transmembrane Amino Acid in the GABAA Receptor β2 Subunit Critical for the Actions of Alcohols and Anesthetics

Alcohols and inhaled anesthetics enhance the function of GABAA receptors containing α, β, and γ subunits. Molecular analysis has focused on the role of the α subunits; however, there is evidence that the β subunits may also be important. The goal of our study was to determine whether Asn265, which is homologous to the site implicated in the α subunit (Ser270), contributes to an alcohol and volatile anesthetic binding site in the GABAA receptor β2 subunit. We substituted cysteine for Asn265 and exposed the mutant to the sulfhydryl-specific reagent octyl methanethiosulfonate (OMTS). We used two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes and found that, after OMTS application, GABA-induced currents were irreversibly potentiated in mutant α1β2(N265C)γ2S receptors [but not α1β2(I264C)γ2S], presumably because of the covalent linking of octanethiol to the thiol group in the substituted cysteine. It is noteworthy that this effect was blocked when OMTS was applied in the presence of octanol. We found that potentiation by butanol, octanol, or isoflurane in the N265C mutant was nearly abolished after the application of OMTS, suggesting that an alcohol and volatile anesthetic binding site at position 265 of the β2 subunit was irreversibly occupied by octanethiol and consequently prevented butanol or isoflurane from binding and producing their effects. OMTS did not affect modulation or direct activation by pentobarbital, but there was a partial reduction of allosteric modulation by flunitrazepam and alphaxalone in mutant α1β2(N265C)γ2S receptors after OMTS was applied. Our findings provide evidence that Asn265 may contribute to an alcohol and anesthetic binding site.
Leadership and the Logic of Absurdity

Leaders are often thought to meaningfully influence the performance of the organizations they lead. However, considerable research suggests that their impact on organizational performance might actually be minimal. These claims of leader irrelevance pose a puzzle: If leaders are relatively insignificant, why would someone commit to leading? Applying decision-making theory, I first consider justifying the decision to lead according to the logics of consequence and appropriateness—the two principal decision-making logics underlying previous work on the motivation to lead. I then present the logic of absurdity—a decision-making logic in which decision makers knowingly choose to dedicate themselves to an irrational course of action. In terms of the decision to lead, a decision maker employing the logic of absurdity acknowledges the likely futility of leading but decides to commit to it nonetheless. I conclude by considering when leaders are most likely to decide to lead according to the logic of absurdity and.
Clinical, biochemical, and genetic spectrum of seven patients with NFU1 deficiency

Disorders of the mitochondrial energy metabolism are clinically and genetically heterogeneous. An increasingly recognized subgroup is caused by defective mitochondrial iron–sulfur (Fe–S) cluster biosynthesis, with defects in 13 genes being linked to human disease to date. Mutations in three of them, NFU1, BOLA3, and IBA57, affect the assembly of mitochondrial [4Fe–4S] proteins leading to an impairment of diverse mitochondrial metabolic pathways and ATP production. Patients with defects in these three genes present with lactic acidosis, hyperglycinemia, and reduced activities of respiratory chain complexes I and II, the four lipoic acid-dependent 2-oxoacid dehydrogenases and the glycine cleavage system (GCS). To date, five different NFU1 pathogenic variants have been reported in 15 patients from 12 families. We report on seven new patients from five families carrying compound heterozygous or homozygous pathogenic NFU1 mutations identified by candidate gene screening and exome sequencing. Six out of eight different disease alleles were novel and functional studies were performed to support the pathogenicity of five of them. Characteristic clinical features included fatal infantile encephalopathy and pulmonary hypertension leading to death within the first 6 months of life in six out of seven patients. Laboratory investigations revealed combined defects of pyruvate dehydrogenase complex (five out of five) and respiratory chain complexes I and II+III (four out of five) in skeletal muscle and/or cultured skin fibroblasts as well as increased lactate (five out of six) and glycine concentration (seven out of seven). Our study contributes to a better definition of the phenotypic spectrum associated with NFU1 mutations and to the diagnostic workup of future patients.
Identifying barriers in the South African Criminal Justice System : implications for individuals with severe communication disability

Individuals with severe communication disabilities and who are victims of crime, experience many access and opportunity barriers in the criminal justice system. The aim of this research was to identify the barriers experienced by this population in the South African Criminal Justice System as perceived by experts in the field. A qualitative research method, with 56 expert professionals in the criminal justice system divided into two different sequential data sources, was employed. The first data source included in-depth, semi-structured interviews (n=3), and these results informed the second data source, which was in the form of four focus groups (n=53). The results from both data sources (N=56) identified numerous barriers for individuals with a severe communication disability who had been victims of crime and needed access to the criminal justice system. The findings suggest that more support and resources need to be provided to individuals with severe communication disability. Additionally, disability training for all professionals working in the criminal justice system needs to be a top priority. Recommendations were made to develop an augmentative and alternative communication resource toolkit to assist these professionals, to ensure equal justice for one of the most vulnerable groups in society - those individuals with a severe communication disability who have been victims of crime.
Long-run performance analysis of a new sample of UK IPOs

36 month buy-and-hold returns are calculated for a recent sample of initial public offerings (IPOs) on UK stock markets in order to test the robustness of earlier results which suggest that IPOs deliver abnormally low long-run returns. A bootstrapped and skew-adjusted t statistic is employed. Overall, there is little evidence of significant abnormal long-run performance. Further tests reveal that the electronics and information technology IPOs experienced by far the highest initial returns but their long-run abnormal performance was poor. This may be the result of chance, or alternatively the sector may offer an isolated area of empirical support for theories of irrational stock market behaviour.
Digital Clock Drawing: Differentiating “Thinking” versus “Doing” in Younger and Older Adults with Depression

Abstract Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)—younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=−.46; p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=−.47; p=.03) and older euthymic groups (r=−.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics. (JINS, 2014, 20, 1–9)
Relationships of Contextual Factors and Personal Identity to Externalizing Problem Behavior Among Iranian Early Adolescents

ABSTRACT In the present study, we evaluated a model of relations among contextual factors (family, school, and peer group), personal identity (i.e., coherence and confusion), and problem behavior among Iranian adolescents. The sample consisted of 765 Iranian adolescents and 615 primary caregivers. Results indicated that family functioning (adolescent report) was related to adolescent problem behavior (a) directly and (b) indirectly through identity confusion. Peer support on the other hand was solely indirectly related to adolescent problem behavior through identity confusion. School functioning was also significantly and negatively related to adolescent problem behavior. The present findings suggest that identity and contextual factors play important roles in steering Iranian adolescents toward or away from behavior problems. Implications for further research are discussed.
Siblings, Teachers, and Spillovers on Academic Achievement

This study documents sibling spillover effects on child test score achievement using administrative school records from North Carolina. While teacher experience is a known determinant of student achievement, I show that teacher experience also affects the achievement of a child’s younger siblings. In contrast, teacher experience does not have an effect on the test scores of the child’s older siblings, suggesting that direct sibling effects rather than parental behavior responses are more important. These findings suggest that we are underestimating the importance of education inputs by ignoring the spillover effects on siblings.
Optimum Plasma Surface Treatment of Luffa Fibers

Luffa fiber is a renewable resource material with low cost and that contributes to a healthier ecosystem by its biodegradability. Its natural structure can be considered as a naturally occurring composite consisting mainly of cellulose fibrils imbedded in a lignin matrix. Surface pretreatment is necessary to maximize their potential use. In this work, plasma treatment at atmospheric pressure was carried out on the raw luffa fibers. The orthogonal method was used to optimize the plasma treatment condition. The optimal conditions were obtained at a discharge time of 10 s, power of 110 W, and electrode distance of 6 mm for the system used. The surface characterization of untreated and pretreated luffa fibers was investigated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermogravimetric (TGA) analysis. The results showed that plasma treatment did not cause significant harm to the fiber integrity and the inner cellulose fibrils were exposed from the lignin matrix. Plasma-treated luffa fibers also showed a slightly better thermal stability than the untreated fibers. Compared with chemical pretreatment, plasma treatment had a significantly shorter duration, no consumption of solvent, and improved the cellulose contents.
Age-related memory impairment associated with loss of parietal deactivation but preserved hippocampal activation

The neural underpinnings of age-related memory impairment remain to be fully elucidated. Using a subsequent memory face–name functional MRI (fMRI) paradigm, young and old adults showed a similar magnitude and extent of hippocampal activation during successful associative encoding. Young adults demonstrated greater deactivation (task-induced decrease in BOLD signal) in medial parietal regions during successful compared with failed encoding, whereas old adults as a group did not demonstrate a differential pattern of deactivation between trial types. The failure of deactivation was particularly evident in old adults who performed poorly on the memory task. These low-performing old adults demonstrated greater hippocampal and prefrontal activation to achieve successful encoding trials, possibly as a compensatory response. Findings suggest that successful encoding requires the coordination of neural activity in hippocampal, prefrontal, and parietal regions, and that age-related memory impairment may be primarily related to a loss of deactivation in medial parietal regions.
A Novel Partitivirus That Confers Hypovirulence on Plant Pathogenic Fungi

ABSTRACT Members of the family Partitiviridae have bisegmented double-stranded RNA (dsRNA) genomes and are not generally known to cause obvious symptoms in their natural hosts. An unusual partitivirus, Sclerotinia sclerotiorum partitivirus 1 (SsPV1/WF-1), conferred hypovirulence on its natural plant-pathogenic fungal host, Sclerotinia sclerotiorum strain WF-1. Cellular organelles, including mitochondria, were severely damaged. Hypovirulence and associated traits of strain WF-1 and SsPV1/WF-1 were readily cotransmitted horizontally via hyphal contact to different vegetative compatibility groups of S. sclerotiorum and interspecifically to Sclerotinia nivalis and Sclerotinia minor. S. sclerotiorum strain 1980 transfected with purified SsPV1/WF-1 virions also exhibited hypovirulence and associated traits similar to those of strain WF-1. Moreover, introduction of purified SsPV1/WF-1 virions into strain KY-1 of Botrytis cinerea also resulted in reductions in virulence and mycelial growth and, unexpectedly, enhanced conidial production. However, virus infection suppressed hyphal growth of most germinating conidia of B. cinerea and was eventually lethal to infected hyphae, since very few new colonies could develop following germ tube formation. Taken together, our results support the conclusion that SsPV1/WF-1 causes hypovirulence in Sclerotinia spp. and B. cinerea. Cryo-EM (cryo-electron microscopy) reconstruction of the SsPV1 particle shows that it has a distinct structure with similarity to the closely related partitiviruses Fusarium poae virus 1 and Penicillium stoloniferum virus F. These findings provide new insights into partitivirus biological activities and clues about molecular interactions between partitiviruses and their hosts. IMPORTANCE Members of the Partitiviridae are believed to occur commonly in their phytopathogenic fungal and plant hosts. However, most partitiviruses examined so far appear to be associated with latent infections. Here we report a partitivirus, SsPV1/WF-1, that was isolated from a hypovirulent strain of Sclerotinia sclerotiorum and describe its biological and molecular features. We have demonstrated that SsPV1 confers hypovirulence. Furthermore, SsPV1 can infect and cause hypovirulence in Botrytis cinerea. Our study also suggests that SsPV1 has a vigorous ability to proliferate and spread via hyphal contact. SsPV1 can overcome vegetative incompatibility barriers and can be transmitted horizontally among different vegetative compatibility groups of S. sclerotiorum, even interspecifically. Cryo-EM reconstruction of SsPV1 shows that it has a distinct structure with similarity to closely related partitiviruses. Our studies exploit a novel system, SsPV1 and its hosts, which can provide the means to explore the mechanisms by which partitiviruses interact with their hosts.
Dead beat controllability of polynomial systems: symbolic computation approaches

State and output dead beat controllability tests for a very large class of polynomial systems with rational coefficients may be based on the quantifier elimination by partial cylindrical algebraic decomposition (QEPCAD) symbolic computation program. The method is unified for a very large class of systems and can handle one- or two-sided control constraints. Families of minimum time state/output dead beat controllers are obtained. The computational complexity of the test is prohibitive for general polynomial systems, but by constraining the structure of the system we may beat the curse of complexity. A computationally less expensive algebraic test for output dead beat controllability for a class of odd polynomial systems is presented. Necessary and sufficient conditions are given. They are still very difficult to check. Therefore, a number of easier-to-check sufficient conditions are also provided. The latter are based on the Grobner basis method and QEPCAD. It is shown on a subclass of odd polynomial systems how it is possible to further reduce the computational complexity by exploiting the structure of the system.
Sometimes It Just Feels Right: The Differential Weighting of Affect-Consistent and Affect- Inconsistent Product Information

An affect-confirmation process is proposed to explain the conditions in which information that is similar in valence (i.e., evaluatively consistent) with a person's mood is weighted more heavily in product judgments. Specifically, the affect that participants experience as a result of a transitory mood state may appear to either confirm or disconfirm their reactions to product information, leading them to give this information more or less weight when evaluating the product as a whole. This affective confirmation typically occurs when hedonic criteria are considered more important in evaluation than utilitarian criteria. Four experiments confirmed implications of this conceptualization.
Suburban Legend: School Cutoff Dates and the Timing of Births

Many states require children to reach age 5 by a specified date in the calendar year in order to begin kindergarten. We use birth certificate records from 1999 to 2004 to assess whether parents systematically time childbirth before these eligibility cutoff dates to capture the option value of sending their child to school at a relatively young age, thereby avoiding a year of child care costs. Testing for discontinuities in the distribution of births around cutoff dates, we find no evidence that the option value influences the timing of birth. Similarly, we find no systematic discontinuities in average mothers' characteristics or babies' health outcomes around cutoff dates. Timing in the neighborhood of eligibility cutoffs occurs only when the cutoffs coincide with weekends or holidays, which may have implications for recent research that assumes birth dates in the neighborhood of cutoffs are essentially randomly assigned.
Efficient teaching of digital design with automated assessment and feedback

A mechanism for the assessment and timely delivery of feedback on laboratory work undertaken with professional computer aided design (CAD) tools is proposed. The process has been applied to an established 1st year undergraduate course unit covering the fundamentals of computer engineering in the School of Computer Science, The University of Manchester. A concise discussion of the structure of the laboratory exercises is presented, followed by an overview of the traditional approach used (up to recently) for assessing submitted laboratory work. A new automated process is presented whereby students submit their work electronically. Professional CAD tools are used to test designs submitted by students to produce an assessment mark and generate detailed and consistent feedback to the students. The automated marking process evaluates designs using either simulation against a golden test bench, or via a logic equivalence test, depending on the type of design being assessed. The result of a student evaluation demonstrating the merits of the new assessment process is also presented.