Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV-1 Vpr Accelerates Viral Replication during Acute Infection by Exploitation of Proliferating CD4+ T Cells In Vivo

The precise role of viral protein R (Vpr), an HIV-1-encoded protein, during HIV-1 infection and its contribution to the development of AIDS remain unclear. Previous reports have shown that Vpr has the ability to cause G2 cell cycle arrest and apoptosis in HIV-1-infected cells in vitro. In addition, vpr is highly conserved in transmitted/founder HIV-1s and in all primate lentiviruses, which are evolutionarily related to HIV-1. Although these findings suggest an important role of Vpr in HIV-1 pathogenesis, its direct evidence in vivo has not been shown. Here, by using a human hematopoietic stem cell-transplanted humanized mouse model, we demonstrated that Vpr causes G2 cell cycle arrest and apoptosis predominantly in proliferating CCR5+ CD4+ T cells, which mainly consist of regulatory CD4+ T cells (Tregs), resulting in Treg depletion and enhanced virus production during acute infection. The Vpr-dependent enhancement of virus replication and Treg depletion is observed in CCR5-tropic but not CXCR4-tropic HIV-1-infected mice, suggesting that these effects are dependent on the coreceptor usage by HIV-1. Immune activation was observed in CCR5-tropic wild-type but not in vpr-deficient HIV-1-infected humanized mice. When humanized mice were treated with denileukin diftitox (DD), to deplete Tregs, DD-treated humanized mice showed massive activation/proliferation of memory T cells compared to the untreated group. This activation/proliferation enhanced CCR5 expression in memory CD4+ T cells and rendered them more susceptible to CCR5-tropic wild-type HIV-1 infection than to vpr-deficient virus. Taken together, these results suggest that Vpr takes advantage of proliferating CCR5+ CD4+ T cells for enhancing viremia of CCR5-tropic HIV-1. Because Tregs exist in a higher cycling state than other T cell subsets, Tregs appear to be more vulnerable to exploitation by Vpr during acute HIV-1 infection.
Perceived organizational support and affective commitment: the mediating role of organization‐based self‐esteem in the context of job insecurity

Research on the relationship between perceived organizational support (POS) and affective organizational commitment (AC) has primarily adopted a social exchange perspective. In this study we considered complementary socio-emotional explanations of the POS–AC relationship. We focused on the mediating role of organization-based self-esteem (OBSE) and tested competing models of the POS–OBSE-AC relationship separately on data from two Korean banks that experienced different levels of downsizing following the 1997 Korean financial crisis. We further extended the analysis by examining the extent to which the relationship between POS and OBSE and AC, respectively, was affected by employees' perceived sense of job insecurity in the two banks. The results showed that OBSE was a significant mediator of the POS–AC relationship in both organizations. POS, however, also retained a strong independent direct effect on commitment. Moreover, as expected, perceived job insecurity tended to attenuate the POS–OBSE relationship, but augmented the direct relationship between perceived organizational support and affective commitment. Copyright © 2006 John Wiley & Sons, Ltd.
Do Low‐Wage Workers React Less to Longer Unemployment Benefits? Quasi‐Experimental Evidence

The fact that unemployed workers have different abilities to smooth consumption entails heterogeneous responses to extended unemployment benefits. Our empirical exercise explores a quasi-experimental setting generated by an increase in the benefits entitlement period. The results point towards a hump-shape response of unemployment duration over the one-year pre-unemployment wage distribution; individuals at the bottom and at the top of the wage distribution reacted less than those in the interquartile range. This behavior of job searchers is consistent with labor supply models with unemployment insurance and savings. It questions the optimality of very long entitlement periods to target the unemployment experiences of low-wage workers.
Birth Spacing of Pregnant Women in Nepal: A Community-Based Study

Background Optimal birth spacing has health advantages for both mother and child. In developing countries, shorter birth intervals are common and associated with social, cultural, and economic factors, as well as a lack of family planning. This study investigated the first birth interval after marriage and preceding interbirth interval in Nepal. Methods A community-based prospective cohort study was conducted in the Kaski district of Nepal. Information on birth spacing, demographic, and obstetric characteristics was obtained from 701 pregnant women using a structured questionnaire. Logistic regression analyses were performed to ascertain factors associated with short birth spacing. Results About 39% of primiparous women gave their first child birth within 1 year of marriage and 23% of multiparous women had short preceding interbirth intervals (<24 months). The average birth spacing among the multiparous group was 44.9 (SD 21.8) months. Overall, short birth spacing appeared to be inversely associated with advancing maternal age. For the multiparous group, Janajati and lower caste women, and those whose newborn was female, were more likely to have short birth spacing. Conclusion The preceding interbirth interval was relatively long in the Kaski district of Nepal and tended to be associated with maternal age, caste, and sex of newborn infant. Optimal birth spacing programs should target Janajati and lower caste women, along with promotion of gender equality in society.
Identification and Expression Analysis of the Complete Family of Zebrafish pkd Genes

Polycystic kidney disease (PKD) proteins are trans-membrane proteins that have crucial roles in many aspects of vertebrate development and physiology, including the development of many organs as well as left–right patterning and taste. They can be divided into structurally-distinct PKD1-like and PKD2-like proteins and usually one PKD1-like protein forms a heteromeric polycystin complex with a PKD2-like protein. For example, PKD1 forms a complex with PKD2 and mutations in either of these proteins cause Autosomal Dominant Polycystic Kidney Disease (ADPKD), which is the most frequent potentially-lethal single-gene disorder in humans. Here, we identify the complete family of pkd genes in zebrafish and other teleosts. We describe the genomic locations and sequences of all seven genes: pkd1, pkd1b, pkd1l1, pkd1l2a, pkd1l2b, pkd2, and pkd2l1. pkd1l2a/pkd1l2b are likely to be ohnologs of pkd1l2, preserved from the whole genome duplication that occurred at the base of the teleosts. However, in contrast to mammals and cartilaginous and holostei fish, teleosts lack pkd2l2, and pkdrej genes, suggesting that these have been lost in the teleost lineage. In addition, teleost, and holostei fish have only a partial pkd1l3 sequence, suggesting that this gene may be in the process of being lost in the ray-finned fish lineage. We also provide the first comprehensive description of the expression of zebrafish pkd genes during development. In most structures we detect expression of one pkd1-like gene and one pkd2-like gene, consistent with these genes encoding a heteromeric protein complex. For example, we found that pkd2 and pkd1l1 are expressed in Kupffer's vesicle and pkd1 and pkd2 are expressed in the developing pronephros. In the spinal cord, we show that pkd1l2a and pkd2l1 are co-expressed in KA cells. We also identify potential co-expression of pkd1b and pkd2 in the floor-plate. Interestingly, and in contrast to mouse, we observe expression of all seven pkd genes in regions that may correspond to taste receptors. Taken together, these results provide a crucial catalog of pkd genes in an important model system for elucidating cell and developmental processes and modeling human diseases and the most comprehensive analysis of embryonic pkd gene expression in any vertebrate.
Acoustic analysis of speech prosody in Huntington's and Parkinson's disease: A preliminary report

Perceptual studies have indicated that basal ganglia dysfunctions such as Parkinson's disease (PD) and Huntington's disease (HD) may give rise to impaired prosodic speech modulation (dysprosodia, aprosodia). The available parametric data, however, are sparse. In the present study declarative, affectively neutral test sentences were used to investigate the production of sentence accent in PD and HD subjects. Reduced durational, pitch and loudness changes concomitant with accent realization could be disclosed in HD, whereas the PD group presented with slightly decreased durational stress contrast only. Both patient groups showed preserved categorical aspects of pitch accent signalling. Most presumably, speech motor deficits rather than disturbances of supramodal processing of prosody are responsible for the observed deviations of sentence accent production.
Leptosphaeria maculans Alters Glucosinolate Profiles in Blackleg Disease–Resistant and -Susceptible Cabbage Lines

Blackleg, a fungal disease caused by Leptosphaeria maculans, is one of the most devastating diseases of Brassica crops worldwide. Despite notable progress elucidating the roles of glucosinolates in pathogen defense, the complex interaction between B. oleracea (cabbage) and L. maculans infection that leads to the selective induction of genes involved in glucosinolate production and subsequent modulation of glucosinolate profiles remains to be fully understood. The current study was designed to identify glucosinolate-biosynthesis genes induced by L. maculans and any associated alterations in glucosinolate profiles to explore their roles in blackleg resistance in 3-month-old cabbage plants. The defense responses of four cabbage lines, two resistant and two susceptible, were investigated using two L. maculans isolates, 03–02 s and 00–100 s. A simultaneous increase in the aliphatic glucosinolates glucoiberverin (GIV) and glucoerucin (GER) and the indolic glucosinolates glucobrassicin (GBS) and neoglucobrassicin (NGBS) was associated with complete resistance. An increase in either aliphatic (GIV) or indolic (GBS and MGBS) glucosinolates was associated with moderate resistance. Indolic glucobrassicin (GBS) and neoglucobrassicin (NGBS) were increased in both resistant and susceptible interactions. Pearson correlation showed positive association between GER content with GSL-OH (Bol033373) expression. Expressions of MYB34 (Bol007760), ST5a (Bol026200), and CYP81F2 (Bol026044) were positively correlated with the contents of both GBS and MGBS. Our results confirm that L. maculans infection induces glucosinolate-biosynthesis genes in cabbage, with concomitant changes in individual glucosinolate contents. In resistant lines, both aliphatic and indolic glucosinolates are associated with resistance, with aliphatic GIV and GER and indolic MGBS glucosinolates particularly important. The association between the genes, the corresponding glucosinolates, and plant resistance broaden our molecular understanding of glucosinolate mediated defense against L. maculans in cabbage.
Two-Way Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Group 1 Animal CoVs Is Mediated through an Antigenic Site in the N-Terminal Region of the SARS-CoV Nucleoprotein

ABSTRACT In 2002, severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged in humans, causing a global epidemic. By phylogenetic analysis, SARS-CoV is distinct from known CoVs and most closely related to group 2 CoVs. However, no antigenic cross-reactivity between SARS-CoV and known CoVs was conclusively and consistently demonstrated except for group 1 animal CoVs. We analyzed this cross-reactivity by an enzyme-linked immunosorbent assay (ELISA) and Western blot analysis using specific antisera to animal CoVs and SARS-CoV and SARS patient convalescent-phase or negative sera. Moderate two-way cross-reactivity between SARS-CoV and porcine CoVs (transmissible gastroenteritis CoV [TGEV] and porcine respiratory CoV [PRCV]) was mediated through the N but not the spike protein, whereas weaker cross-reactivity occurred with feline (feline infectious peritonitis virus) and canine CoVs. Using Escherichia coli-expressed recombinant SARS-CoV N protein and fragments, the cross-reactive region was localized between amino acids (aa) 120 to 208. The N-protein fragments comprising aa 360 to 412 and aa 1 to 213 reacted specifically with SARS convalescent-phase sera but not with negative human sera in ELISA; the fragment comprising aa 1 to 213 cross-reacted with antisera to animal CoVs, whereas the fragment comprising aa 360 to 412 did not cross-react and could be a potential candidate for SARS diagnosis. Particularly noteworthy, a single substitution at aa 120 of PRCV N protein diminished the cross-reactivity. We also demonstrated that the cross-reactivity is not universal for all group 1 CoVs, because HCoV-NL63 did not cross-react with SARS-CoV. One-way cross-reactivity of HCoV-NL63 with group 1 CoVs was localized to aa 1 to 39 and at least one other antigenic site in the N-protein C terminus, differing from the cross-reactive region identified in SARS-CoV N protein. The observed cross-reactivity is not a consequence of a higher level of amino acid identity between SARS-CoV and porcine CoV nucleoproteins, because sequence comparisons indicated that SARS-CoV N protein has amino acid identity similar to that of infectious bronchitis virus N protein and shares a higher level of identity with bovine CoV N protein within the cross-reactive region. The TGEV and SARS-CoV N proteins are RNA chaperons with long disordered regions. We speculate that during natural infection, antibodies target similar short antigenic sites within the N proteins of SARS-CoV and porcine group 1 CoVs that are exposed to an immune response. Identification of the cross-reactive and non-cross-reactive N-protein regions allows development of SARS-CoV-specific antibody assays for screening animal and human sera.
Effects of phonological and musical training on the reading readiness of native- and foreign-Spanish-speaking children

The purpose of this study was to evaluate the effectiveness of a music training program on children’s phonological awareness and naming speed in Spanish. Participants were preschool children whose first language was either Spanish (n = 45) or Tamazight ( n = 52), a Berber dialect spoken in Morocco’s Rif area. The two-year pretest/posttest study showed that the children who received phonological training with or without music performed significantly better in a naming speed posttest and a series of phonological processing tasks than those who did not participate in specialized training. The phonological training that included music activities was particularly effective for the development of phonological awareness of ending sounds and naming speed. The benefits of the training on children’s phonological awareness and naming speed, two strong predictors of reading acquisition, were significant regardless of the native language of the children.
What is happening when we assess, and how can we use our understanding of this to improve assessment?

In an attempt to gain a fuller understanding of the basis of grading, ten assessors each assessed two portfolios drawn from the course archive which had been produced by participants on a course in teaching in higher education. Assessors gave a grade or judgement on each of a portfolio's 75 portfolio elements, reasons for each judgement they made, and recorded any alternative judgement they had considered. There were substantial differences between the judgements made during the study and those made when the portfolios were originally assessed. This article explores the differences between the original and experimental assessments, and then analyses reasons given by assessors for the judgements made. Beyond these particulars, the paper suggests some fundamental and problematic issues about the conduct and the reform of assessment, and offers a process which can be used to investigate and improve the quality, in particular the reliability, of any summative assessment.
De‐individuation and group polarization in computer‐mediated communication

A computer-mediated communication system (CMCS) was used to explore the effects of de-individuation on group polarization. Reicher (1984) argued that de-individuating members of a group should increase the salience of group identity and hence normative behaviour, while de-individuating subjects treated as individuals should have the reverse effect. We extended this idea to the group polarization paradigm and in addition independently manipulated group salience and de-individuation, which were confounded factors in Reicher's study. It was reasoned that the visual anonymity created by isolating discussants in separate rooms would be de-individuating compared to seating them together in the same room. At the same time either the subject's group or individual identity was made salient. A computer-mediated communication system provided text-based communication for discussants in all four conditions. Assuming that group polarization reflects conformity to a group norm (Turner, Hogg, Oakes, Reicher & Wetherell, 1987), we predicted an interaction between the de-individuation and group salience factors, such that greatest polarization in the direction of a pre-established group norm would be obtained in the de-individuated—group condition and least in the de-individuated—individual condition. This prediction was confirmed. Explanations of the findings in terms of Reicher's earlier study and in terms of self-attention processes are considered within the general framework of social identity theory. Finally, the relevance of this research to the realm of human communication via computer networks is evaluated.
Understanding of Affective False Beliefs, Perceptions of Parental Discipline, and Classroom Behavior in Children from Head Start

Fifty-five children (21 boys, 34 girls) between the ages of 3 years 6 months and 5 years 6 months from 3 Head Start classrooms were administered 5 affective false belief tasks and 5 hypothetical scenarios that measured their perceptions of parental discipline. A subset of 40 children were rated by their teachers for behavior problems in the classroom. Results indicated that children performed better on questions about their own false beliefs than on questions about others' false beliefs. Overall, children performed below average on the false belief measures. Children expected parents in the hypothetical scenarios to use power-assertive methods of discipline more often than induction or love withdrawal. As predicted, total false belief scores were negatively correlated with classroom behavior problems. Children who stated that they or the child in the scenario would feel sad after being disciplined were also less likely to experience behavior problems in the classroom. The results of this study, together with the results of previous research, suggest that children from Head Start populations are not performing as well on measures of false belief understanding as children from traditional preschool populations. The causes of this discrepancy and possible interventions should be explored in future research.
Heterosynaptic Plasticity Prevents Runaway Synaptic Dynamics

Spike timing-dependent plasticity (STDP) and other conventional Hebbian-type plasticity rules are prone to produce runaway dynamics of synaptic weights. Once potentiated, a synapse would have higher probability to lead to spikes and thus to be further potentiated, but once depressed, a synapse would tend to be further depressed. The runaway synaptic dynamics can be prevented by precisely balancing STDP rules for potentiation and depression; however, experimental evidence shows a great variety of potentiation and depression windows and magnitudes. Here we show that modifications of synapses to layer 2/3 pyramidal neurons from rat visual and auditory cortices in slices can be induced by intracellular tetanization: bursts of postsynaptic spikes without presynaptic stimulation. Induction of these heterosynaptic changes depended on the rise of intracellular calcium, and their direction and magnitude correlated with initial state of release mechanisms. We suggest that this type of plasticity serves as a mechanism that stabilizes the distribution of synaptic weights and prevents their runaway dynamics. To test this hypothesis, we develop a cortical neuron model implementing both homosynaptic (STDP) and heterosynaptic plasticity with properties matching the experimental data. We find that heterosynaptic plasticity effectively prevented runaway dynamics for the tested range of STDP and input parameters. Synaptic weights, although shifted from the original, remained normally distributed and nonsaturated. Our study presents a biophysically constrained model of how the interaction of different forms of plasticity—Hebbian and heterosynaptic—may prevent runaway synaptic dynamics and keep synaptic weights unsaturated and thus capable of further plastic changes and formation of new memories.
Event-related potentials and cue-reactivity in alcoholism.

BACKGROUND Relapse is a major problem in the treatment of addictive behaviors. Conditioning models of alcohol addiction suggest that stimuli associated with previous drug use (cues) may initiate relapse in a definite group of alcoholics. Event-related potentials (ERPs) might be useful to reveal the brain functional substrates of cue-reactivity. METHODS In a preliminary investigation, 11 alcohol-dependent patients who did not take part in the electrophysiological study completed a structured interview to rate 80 words as to the degree of relatedness to alcohol. Based on these results, cue-reactivity for 15 alcohol-related and 15 unrelated word cues, each repeated eight times, was investigated in 19 alcohol-dependent men (44.2 +/- 8.5 years) and 19 healthy control men (42.5 +/- 12.5 years). RESULTS A cue-reactivity that consisted of significantly higher amplitudes in the ERPs after alcohol-related words compared with unrelated words was found in alcohol-dependent patients, but not in controls, at the electrode location Pz [F(1,36) = 5.2,p < 0.05]. CONCLUSIONS Consistent with the hypothesis, only alcohol-dependent patients were characterized by signs of increased cerebral activity associated with alcohol-related compared with unrelated cues. Therefore, the results support the concept of cue-reactivity in alcoholism based on a neurobiological measurement. Future investigations will show whether this cue-reactivity can be applied to assess the risk of relapse in individual alcohol-dependent patients.