Miracle-dz/UniFAR-FTUs huggingface dataset:
The Haemophilus ducreyi Cytolethal Distending Toxin Induces Cell Cycle Arrest and Apoptosis via the DNA Damage Checkpoint Pathways*

The cytolethal distending toxins (CDTs) induce cell cycle arrest by a mechanism still not well characterized. We demonstrate that the effect of the Haemophilus ducreyiCDT (HdCDT) is cell type-specific: B cell lines underwent apoptosis, epithelial cells and keratinocytes arrested exclusively in G2, whereas normal fibroblasts arrested both in G1 and G2. We studied normal keratinocytes and fibroblasts, which are relevant for understanding the pathogenicity ofH. ducreyi. The response to HdCDT resembles the checkpoint response activated by ionizing radiation. Both responses were characterized by an early induction of the p53 gene and the cyclin-dependent kinase inhibitor p21 in fibroblasts, and activation of the chk2 kinase in epithelial cells. In the Ataxia Telangiectasia-mutated gene (ATM)-deficient lymphoblastoid cell lines, intoxication was significantly delayed compared with ATM wild type cells, and was associated with a slower kinetic of p53 stabilization, suggesting that the early response to HdCDT is ATM-dependent. Activation of ATM-dependent pathways was further confirmed by the ability of caffeine to partially override the HdCDT-mediated cell cycle arrest. Our data shed new light on the mechanism of action of this novel family of bacterial toxins, limiting the target candidates to DNA or molecules directly involved in activation of checkpoint responses.
The scaling limits of the Minimal Spanning Tree and Invasion Percolation in the plane

We prove that the Minimal Spanning Tree and the Invasion Percolation Tree on a version of the triangular lattice in the complex plane have unique scaling limits, which are invariant under rotations, scalings, and, in the case of the MST, also under translations. However, they are not expected to be conformally invariant. We also prove some geometric properties of the limiting MST. The topology of convergence is the space of spanning trees introduced by Aizenman, Burchard, Newman & Wilson (1999), and the proof relies on the existence and conformal covariance of the scaling limit of the near-critical percolation ensemble, established in our earlier works.
Bullying behaviours among students in Pavia, Italy: prevalence and association with stress and cannabis use

Background. This study examined the prevalence of students’ reported experiences of bullying and victimization in primary and secondary schools and their association with levels of perceived stress and cannabis use. Methods. We consecutively enrolled 407 students attending three secondary schools in Pavia (Italy). Bullying and victimization were measured using the retrospective bullying questionnaire (RQB). The 10-item perceived stress scale (PSS-10) was used to assess the degree to which situations in life were perceived as stressful. Data on demographic characteristics and cannabis use in the previous 6 months were also collected. Results. There were 328 victims (80.6%) and 221 bullies (52.1%). The results of the stepwise regression analysis with bullying as the dependent variable were significant with either male sex (R2 = 0.030, p = 0.024) or PSS-10 scores (R2 = 0.056, p = 0.036) in the model. With victimization as the dependent variable, only the PSS-10 scores were retained in the model as an independent predictor variable (R2 = 0.048, p < 0.001). Conclusions. The results from this study indicate that the level of perceived stress has an independent association with both bullying and victimization. Further studies are needed to clarify the psychobiological links between stress, cannabis use and bullying behaviours.
Father's occupation and sex ratio of offspring

Aims: Ecological studies have demonstrated that when national economies contract the proportion of male live births is reduced. It has been suggested that the relative disadvantage this causes influences sex ratio among births. Here the authors use individual data to investigate whether there is a persistent association of father's occupation with the sex of offspring and if it varies by industry sector. Associations with season of birth are also investigated. Methods: All fathers with a first singleton live birth in Sweden between 1940 and 1949 were identified using population registers (n=523,671). Fathers' occupations from the 1960 Census was categorized into: manual workers; agricultural sector (divided into workers and owners/ managers); and office sector (divided into workers and managers). Results: Compared with manual workers, the routine workers in other sectors were not statistically significantly more likely to have a male first offspring. Agricultural owners/ managers and office managers were both statistically significantly more likely to have male offspring with adjusted odds ratios (and 95% confidence intervals) of 1.045 (1.024—1.066, p<0.001) and 1.021 (1.003—1.039, p=0.022), respectively. Compared with autumn births, spring births were less likely to be male: 0.983 (0.967—0.998, p=0.029). Conclusions: Fathers' occupation level, even 10—20 years after childbirth, but not labour market sector is associated with the sex ratio of offspring, indicating that material or social conditions are responsible. Spring births are less likely to be male, probably due to infections differentially reducing male foetal survival.
A Positive Stable Frailty Model for Clustered Failure Time Data with Covariate‐Dependent Frailty

Summary In this article, we propose a positive stable shared frailty Cox model for clustered failure time data where the frailty distribution varies with cluster‐level covariates. The proposed model accounts for covariate‐dependent intracluster correlation and permits both conditional and marginal inferences. We obtain marginal inference directly from a marginal model, then use a stratified Cox‐type pseudo‐partial likelihood approach to estimate the regression coefficient for the frailty parameter. The proposed estimators are consistent and asymptotically normal and a consistent estimator of the covariance matrix is provided. Simulation studies show that the proposed estimation procedure is appropriate for practical use with a realistic number of clusters. Finally, we present an application of the proposed method to kidney transplantation data from the Scientific Registry of Transplant Recipients.
Paternal Attachment Behavior as Related to Presence at Delivery and Preparenthood Classes: A Pilot Study

This pilot study explored father-infant attachment and its relationship to preparenthood classes, presence at delivery, and infant state. The sample consisted of 48 fathers and their infants who were observed in the mother's hospital room between 12 and 72 hours after delivery. The fathers were divided into three groups: those who took classes and were present at delivery, those who were present at delivery but did not take classes, and those who neither took classes nor were present at delivery. Fathers who were present at delivery demonstrated more social attachment behavior than fathers who were not present. Also, presence at delivery was significant in regard to total attachment scores. Sleeping infants elicited significantly less attachment behavior from fathers. Preparenthood classes were not significant in regard to fathers' attachment behavior. Results of this study support the theory of a sensitive period shortly after birth for the development of the parental-infant bond for fathers as well as mothers, and demonstrates, indirectly, that alert, awake infants may elicit certain attachment behaviors from fathers.
Longitudinal trajectories of post-concussive and depressive symptoms in adolescents with prolonged recovery from concussion

ABSTRACT Primary Objective: To investigate the symptom trajectories of depressive and post-concussive symptoms (PCS) in slow-to-recover adolescents to understand how the two sets of symptoms are related. Research Design: We used data from a randomized clinical trial of a collaborative care intervention for post-concussive symptoms to better understand how these two sets of symptoms change in parallel over 6 months. Methods and Procedure: PCS and depressive symptom scores for 49 adolescents (ages 11–17) were measured at enrolment and after 1, 3, and 6 months. Latent growth curve modelling for parallel processes was used to simultaneously examine change in PCS and depressive symptoms over time and to evaluate the influence of one change process on the other. Main Outcomes and Results: On average, patients enrolled 66 days following injury (Interquartile range (IQR) 43.5, 88.5). PCS and depressive symptoms were significantly associated at enrolment and over time, and both decreased over the course of 6 months. Higher PCS at enrolment predicted a greater decrease in depressive symptoms over time. Conclusions: Our results suggest that clinicians should screen for and treat depressive symptoms in patients with high post-concussive symptoms one month following injury.
A Physiologically Based Nonhomogeneous Poisson Counter Model of Visual Identification

A physiologically based nonhomogeneous Poisson counter model of visual identification is presented. The model was developed in the framework of a Theory of Visual Attention (Bundesen, 1990; Kyllingsbæk, Markussen, & Bundesen, 2012) and meant for modeling visual identification of objects that are mutually confusable and hard to see. The model assumes that the visual system’s initial sensory response consists in tentative visual categorizations, which are accumulated by leaky integration of both transient and sustained components comparable with those found in spike density patterns of early sensory neurons. The sensory response (tentative categorizations) feeds independent Poisson counters, each of which accumulates tentative object categorizations of a particular type to guide overt identification performance. We tested the model’s ability to predict the effect of stimulus duration on observed distributions of responses in a nonspeeded (pure accuracy) identification task with eight response alternatives. The time courses of correct and erroneous categorizations were well accounted for when the event-rates of competing Poisson counters were allowed to vary independently over time in a way that mimicked the dynamics of receptive field selectivity as found in neurophysiological studies. Furthermore, the initial sensory response yielded theoretical hazard rate functions that closely resembled empirically estimated ones. Finally, supplied with a Naka-Rushton type contrast gain control, the model provided an explanation for Bloch’s law.
Efficacy and Safety of Antiepileptic Drugs: A Review of Controlled Trials

Summary: Twenty randomized, double‐blind, controlled clinical trials of antiepileptic drugs (AEDs) in mostly adult patients with mostly partial onset and/or generalized tonic‐clonic seizures have been reported, with a total of 1,336 patients. None of these studies has demonstrated significant differences in antiepileptic efficacy between available antiepileptic drugs, but the results show that there are considerable individual differences between patients' responses to the same drug. While side effects are common with all of the antiepileptic drugs currently available, these are usually mild and reversible. Although some toxic effects may occur more frequently with certain drugs, there is sufficient overlap between the effects of various antiepileptic drugs that most side effects cannot be attributed with certainty to any one drug. Since side effects are generally dose‐related, they can frequently be avoided or minimized by careful dosage titration and individualization of therapy.
Pulmonary hemosiderin in deceased infants: baseline data for further study of infant mortality.

Infant lung samples were obtained prospectively at autopsy by medical examiner pathologists in five areas of the United States. Tissues were submitted regardless of the cause of death. Lung sections were stained with Prussian blue to detect deposits of hemosiderin. Fifty-nine cases were evaluated for the study. The four sections examined for each case were taken from the anterior and posterior aspects of the right and left upper lung. Three pathologists independently scanned the lung sections microscopically using a 10x objective lens (with 10x ocular lens) and indicated an "iron score" by indicating for each section if it showed no staining for iron-hemosiderin (Score 0), occasional staining with most fields negative (Score 1), focally abundant staining with most fields having no staining (Score 2), focally abundant staining with most fields showing positive staining (Score 3), or prominent staining throughout the section (Score 4). There was good agreement between pathologists on the iron score for each case. A total iron score was calculated by adding the scores based on each pathologist's observations. The mean total iron score was 6 (range, 1-44), with the range of possible total iron scores being 0 to 48. There was no significant difference between the four lung sections in a given case. Six cases had total iron scores that were at least twice the mean (i.e., total iron score > 12); in five of these cases death was caused by conditions other than sudden infant death syndrome, including one case in which asphyxia was the cause of death. These data are consistent with other reports that pulmonary hemosiderin in deceased infants is suggestive of a cause of death other than sudden infant death syndrome. The data may be useful as baseline data for further studies of infant mortality involving possible pathologic changes in the lungs.
A Multiscale Filtering Explanation of Gradient Induction and Remote Brightness Induction Effects: A Reply to Logvinenko (2003)

Grating induction is a brightness effect in which a counterphase spatial brightness variation (a grating) is induced in a homogeneous test strip that is surrounded by an inducing luminance grating (McCourt, 1982 Vision Research 22 119–134). Moulden and Kingdom (1991 Vision Research 31 1999–2008) introduced an interesting variant of grating induction (sometimes referred to as gradient induction) in which multiple strips of either a linear luminance ramp or a sine-wave grating were interlaced with strips of homogeneous luminance. We (Blakeslee and McCourt, 1999 Vision Research 39 4361–4377) demonstrated that a simple multiscale filtering explanation could account for grating induction. Recently, however, Logvinenko (2003 Perception 32 621–626) presented several arguments impugning the adequacy of spatial filtering approaches to understanding brightness induction in gradient induction stimuli. We propose that Logvinenko's arguments apply only to a limited class of filtering models, specifically those which employ only a single spatial filter. To test this hypothesis we modeled gradient induction stimuli as a function of inducing contrast, as well as Logvinenko's (2003) remote induction stimulus, using our multiscale oriented difference-of-Gaussians (ODOG) model (Blakeslee and McCourt 1999). The ODOG model successfully predicts the appearance of the inducing strips and the homogeneous test strips in the gradient induction stimuli and the appearance of the test patches in the remote induction stimuli. These results refute Logvinenko's (2003) claims, and we interpret them as providing strong evidence for a multiscale filtering approach to understanding both gradient induction and remote brightness induction effects.
Cognitive and psychomotor development of infants with orofacial clefts.

OBJECTIVE To compare at ages 3, 12, and 24 months the cognitive and psychomotor development of 29 infants with cleft lip and palate (CLP), 28 infants with cleft palate only (CPO), and a demographically matched comparison (COMP) group of 69 infants; to examine predictors of cognitive status at age 24 months in the cleft group. METHODS Infants were administered the Bayley Scales of Infant Development (BSID), mother-infant interactions were observed, and medical records were reviewed. RESULTS CLP and CPO groups scored lower than the COMP group on the BSID, but did not differ from one another. Cleft group infants scored lower than COMP group infants on BSID items assessing nonverbal and expressive language skills. Quality of maternal interaction predicted the 2-year Mental Development Index (MDI) scores of infants with clefts. CONCLUSIONS Infants with clefts show relative deficits in cognitive and psychomotor development. Cognitive deficits are apparent in nonverbal as well as verbal areas of performance.
Impaired integrin‐mediated adhesion contributes to reduced barrier properties in VASP‐deficient microvascular endothelium

Recent studies point to a significant role of vasodilator‐stimulated phosphoprotein (VASP) in the maintenance of endothelial barrier functions in vivo and in vitro. Moreover, it has been reported that VASP is required for activation of the small GTPase Rac 1. However, little is known whether VASP is involved in the regulation of cell adhesion molecules that are critical for maintenance of the endothelial barrier. Here we demonstrate that impaired barrier properties in VASP‐deficient (VASP−/−) microvascular myocardial endothelial cells (MyEnd) correlated with both impaired integrin‐mediated adhesion as revealed by laser tweezer trapping and reduced integrin‐dependent cell migration. This was paralleled by reduction of focal adhesions at the cell periphery as well as of β1‐integrin and VE‐cadherin cytoskeletal anchorage. Incubation of MyEnd VASP wt with RGD peptide to block interaction of integrins with extracellular matrix (ECM) reduced barrier properties and Rac 1 activity in wt endothelial monolayers mimicking the situation in VASP (−/−) cells under resting conditions. Moreover, cAMP‐mediated Rac 1 activation was reduced under conditions of impaired integrin‐mediated adhesion in wt cells and cAMP‐induced increase in VE‐cadherin cytoskeletal anchorage was abolished in VASP (−/−) endothelium. In summary, these data indicate that VASP is required for integrin‐mediated adhesion which stabilizes endothelial barrier properties at least in part by facilitating Rac 1 activation. J. Cell. Physiol. 220: 357–366, 2009. © 2009 Wiley‐Liss, Inc.
Mental disorders following war in the Balkans: a study in 5 countries.

CONTEXT War experience may affect mental health. However, no community-based study has assessed mental disorders several years after war using consistent random sampling of war-affected people across several Western countries. OBJECTIVES To assess current prevalence rates of mental disorders in an adult population who were directly exposed to war in the Balkans and who still live in the area of conflict, and to identify factors associated with the occurrence of different types of mental disorders. DESIGN, SETTING, AND PARTICIPANTS War-affected community samples in Bosnia-Herzegovina, Croatia, Kosovo, the Republic of Macedonia, and Serbia were recruited through a random-walk technique. MAIN OUTCOME MEASURE Prevalence rates of mood, anxiety, and substance use disorders were assessed using the Mini-International Neuropsychiatric Interview. RESULTS Between 637 and 727 interviewees were assessed in each country (N = 3313). The prevalence rates were 15.6% to 41.8% for anxiety disorders, 12.1% to 47.6% for mood disorders, and 0.6% to 9.0% for substance use disorders. In multivariable analyses across countries, older age, female sex, having more potentially traumatic experiences during and after the war, and unemployment were associated with higher rates of mood and anxiety disorders. In addition, mood disorders were correlated with lower educational level and having more potentially traumatic experiences before the war. Male sex and not living with a partner were the only factors associated with higher rates of substance use disorders. Most of these associations did not significantly differ among countries. CONCLUSIONS Several years after the end of the war, the prevalence rates of mental disorders among war-affected people vary across countries but are generally high. War experiences appear to be linked to anxiety and mood disorders but not substance use disorders. Long-term policies to meet the mental health needs of war-affected populations are required.
Accelerated cell line development using two‐color fluorescence activated cell sorting to select highly expressing antibody‐producing clones

The success of engineered monoclonal antibodies as biopharmaceuticals has generated considerable interest in strategies designed to accelerate development of antibody expressing cell lines. Stable mammalian cell lines that express therapeutic antibodies at high levels typically take 6–12 months to develop. Here we describe a novel method to accelerate selection of cells expressing recombinant proteins (e.g., antibodies) using multiparameter fluorescence activated cell sorting (FACS) in association with dual intracellular autofluorescent reporter proteins. The method is co‐factor‐independent and does not require complex sample preparation. Chinese hamster ovary (CHO) clones expressing high levels of recombinant antibody were selected on the basis of a two‐color FACS sorting strategy using heavy and light chain‐specific fluorescent reporter proteins. We were able to establish within 12 weeks of transfection cell lines with greater than a 38‐fold increase in antibody production when compared to the pool from which they were isolated, following a single round of FACS. The method provides a robust strategy to accelerate selection and characterization of clones and builds a foundation for a predictive model of specific productivity based upon on two‐color fluorescence. Biotechnol. Bioeng. 2008;99: 578–587. © 2007 Wiley Periodicals, Inc.
Identification of Putative Precursor Genes for the Biosynthesis of Cannabinoid-Like Compound in Radula marginata

The liverwort Radula marginata belongs to the bryophyte division of land plants and is a prospective alternate source of cannabinoid-like compounds. However, mechanistic insights into the molecular pathways directing the synthesis of these cannabinoid-like compounds have been hindered due to the lack of genetic information. This prompted us to do deep sequencing, de novo assembly and annotation of R. marginata transcriptome, which resulted in the identification and validation of the genes for cannabinoid biosynthetic pathway. In total, we have identified 11,421 putative genes encoding 1,554 enzymes from 145 biosynthetic pathways. Interestingly, we have identified all the upstream genes of the central precursor of cannabinoid biosynthesis, cannabigerolic acid (CBGA), including its two first intermediates, stilbene acid (SA) and geranyl diphosphate (GPP). Expression of all these genes was validated using quantitative real-time PCR. We have characterized the protein structure of stilbene synthase (STS), which is considered as a homolog of olivetolic acid in R. marginata. Moreover, the metabolomics approach enabled us to identify CBGA-analogous compounds using electrospray ionization mass spectrometry (ESI-MS/MS) and gas chromatography mass spectrometry (GC-MS). Transcriptomic analysis revealed 1085 transcription factors (TF) from 39 families. Comparative analysis showed that six TF families have been uniquely predicted in R. marginata. In addition, the bioinformatics analysis predicted a large number of simple sequence repeats (SSRs) and non-coding RNAs (ncRNAs). Our results collectively provide mechanistic insights into the putative precursor genes for the biosynthesis of cannabinoid-like compounds and a novel transcriptomic resource for R. marginata. The large-scale transcriptomic resource generated in this study would further serve as a reference transcriptome to explore the Radulaceae family.