Miracle-dz/UniFAR-FTUs huggingface dataset:
An alternative outer membrane secretion mechanism for an autotransporter protein lacking a C‐terminal stable core

Autotransporter (AT) proteins are a broad class of virulence factors from Gram‐negative pathogens. AT outer membrane (OM) secretion appears simple in many regards, yet the mechanism that enables transport of the central AT ‘passenger’ across the OM remains unclear. OM secretion efficiency for two AT passengers is enhanced by a ∼ 20 kDa stable core at the C‐terminus of the passenger, but studies on a broader range of AT proteins are needed in order to determine whether a stability difference between the passenger N‐ and C‐terminus represents a truly common mechanistic feature. Yersinia pestis YapV is homologous to Shigella flexneri IcsA, and like IcsA, YapV recruits mammalian neural Wiskott–Aldrich syndrome protein (N‐WASP). In vitro, the purified YapV passenger is functional and rich in β‐sheet structure, but lacks a ∼ 20 kDa C‐terminal stable core. However, the N‐terminal 49 residues of the YapV passenger globally destabilize the entire YapV passenger, enhancing its OM secretion efficiency. These results indicate that the contributions of AT passenger sequences to OM secretion efficiency extend beyond a C‐terminal stable core, and highlight a role of the passenger N‐terminus in reducing passenger stability in order to facilitate OM secretion of some AT proteins.
Motivation, self-efficacy and learning strategies of university students participating in work-integrated learning

ABSTRACT This study examined differences in the psychological constructs of motivation, academic self-efficacy, and learning strategies between higher education students who participated in a work-integrated learning (WIL) programme and those who did not. Undergraduate WIL (n = 1048) and non-WIL (n = 656) students in all years of study and from several academic faculties, completed the Motivated Strategies for Learning Questionnaire (MSLQ), which measures the constructs of motivation, academic self-efficacy and use of learning and study strategies. Results revealed that students who do not gain practical work experience while pursuing their studies have lower grade-point averages, are more likely to use shallow learning strategies, and are more extrinsically motivated compared to students who do gain work experience through a WIL programme. Differences in academic self-efficacy as a function of WIL were not found, however, significant relationships between self-efficacy, motivation, learning strategies, academic performance and anxiety did emerge. Implications and recommendation for future research are provided.
Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk

Background PET studies of verbal fluency in schizophrenia report a failure of ‘deactivation’ of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying ‘functional disconnectivity’. Aim To test whether these findings provide trait-markers for schizophrenia. Method We used H2 15O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. Results We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. Conclusions Failure of left STG ‘deactivation’ and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.
Predicting Win-Loss outcomes in MLB regular season games - A comparative study using data mining methods

Baseball is a statistically filled sport, and predicting the winner of a particular Major League Baseball (MLB) game is an interesting and challenging task. Up to now, there is no definitive formula for determining what factors will conduct a team to victory, but through the analysis of many years of historical records many trends could emerge. Recent studies concentrated on using and generating new statistics called sabermetrics in order to rank teams and players according to their perceived strengths and consequently applying these rankings to forecast specific games. In this paper, we employ sabermetrics statistics with the purpose of assessing the predictive capabilities of four data mining methods (classification and regression based) for predicting outcomes (win or loss) in MLB regular season games. Our model approach uses only past data when making a prediction, corresponding to ten years of publicly available data. We create a dataset with accumulative sabermetrics statistics for each MLB team during this period for which data contamination is not possible. The inherent difficulties of attempting this specific sports prediction are confirmed using two geometry or topology based measures of data complexity. Results reveal that the classification predictive scheme forecasts game outcomes better than regression scheme, and of the four data mining methods used, SVMs produce the best predictive results with a mean of nearly 60% prediction accuracy for each team. The evaluation of our model is performed using stratified 10-fold cross-validation.
Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression.

The mechanism by which prostaglandin E2 (PGE2) inhibits human T lymphocyte activation and proliferation was studied. We analyzed the effect of physiologic concentrations of PGE2 on interleukin 2 (IL 2) production, expression of IL 2 receptor (Tac antigen), and expression of the transferrin receptor after in vitro activation with phytohemagglutinin. PGE2 inhibited T lymphocyte proliferation by 80 to 90% of control values. This was associated with a similar degree of inhibition of IL 2 production while the expression of IL 2 receptor was not affected. This was in marked contrast to the expression of the transferrin receptor, which was inhibited 65% after 72 hr of in vitro activation. The addition of exogenous, purified IL 2 reconstituted lymphocyte proliferation to 50% of control values, but had no effect on transferrin receptor expression. Because PGE2 is known to increase the intracellular concentration of 3',5' cyclic adenosine monophosphate (cAMP), we investigated the effect of another adenylate cyclase activator, i.e., isoproterenol, as well as the effect of extracellular administration of the cAMP derivative dibutyryl cAMP (dBcAMP) on IL 2 production, Tac antigen expression, and transferrin receptor expression. It was demonstrated that isoproterenol, as well as dBcAMP, inhibited transferrin receptor expression on PHA-activated T lymphocytes to the same extent as PGE2, and exogenous IL 2 could not counteract the down-regulation of the receptor expression. In contrast, neither isoproterenol nor dBcAMP had any significant effect on IL 2 receptor expression. Prostaglandin F2 alpha (PGF2 alpha), which has been reported to elevate intracellular cyclic GMP levels, had no effect on lymphocyte activation and proliferation, and did not counteract the PGE2-induced depression in IL 2 production. In contrast to its effect on peripheral blood lymphocytes, PGE2 had no effect on transferrin receptor expression or cell proliferation by IL 2-dependent T cell clones and IL 2-independent T cell lines. These studies demonstrate that PGE2 exerts its inhibitory effects on T cell activation and proliferation via two distinct pathways: inhibition of IL 2 production and inhibition of transferrin receptor expression. The transferrin receptor inhibition is mediated via the cAMP pathway and is IL 2-independent.
Are adolescents receptive to current sales promotion practices of the tobacco industry?

BACKGROUND The tobacco industry increased the portion of its marketing budget for sales promotion to $2.5 billion in 1993. Although it claims not to target those under age 18 years, it is important to determine the extent to which adolescents are affected as participation may lead to smoking initiation. METHODS California population surveys, conducted in 1993 among youth ages 12-17 years (N = 5,531) and in 1994 among both youth (N = 1,735) and adults (N = 4,170), asked questions regarding possession and willingness to use promotional items. RESULTS In 1994, young adults (18-24 years) were the most likely to possess a promotional item (27.5 +/- 4.1, +/- 95% confidence limit). However, willingness to use an item was highest among those ages 15-17 years (35.4 +/- 3.4%) and was also high among those ages 12-14 years (24.4 +/- 2.7%). Among youth, ownership or willingness to use promotional items was more likely for boys, whites, those reporting below average school performance, and those smoking or susceptible to smoking. Youth ownership of promotional items increased from 1993 to 1994, as did the frequency of their obtaining items from coupons. CONCLUSIONS Promotional marketing undertaken by the tobacco industry was effective in capturing the interest of adolescents, although actual acquisition was highest among young adults. The rapidly increasing interest in tobacco promotional items from 1993 to 1994 may soon translate into increased adolescent smoking rates.
An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46

ABSTRACT Adenoviruses (Ads) are icosahedral, nonenveloped viruses with a double-stranded DNA genome. The 51 known Ad serotypes exhibit profound variations in cell tropism and disease types. The number of observed Ad infections is steadily increasing, sometimes leading to fatal outcomes even in healthy individuals. Species B Ads can cause kidney infections, hemorrhagic cystitis, and severe respiratory infections, and most of them use the membrane cofactor protein CD46 as a cellular receptor. The crystal structure of the human Ad type 11 (Ad11) knob complexed with CD46 is known; however, the determinants of CD46 binding in related species B Ads remain unclear. We report here a structural and functional analysis of the Ad11 knob, as well as the Ad7 and Ad14 knobs, which are closely related in sequence to the Ad11 knob but have altered CD46-binding properties. The comparison of the structures of the three knobs, which we determined at very high resolution, provides a platform for understanding these differences and allows us to propose a mechanism for productive high-affinity engagement of CD46. At the center of this mechanism is an Ad knob arginine that needs to switch its orientation in order to engage CD46 with high affinity. Quantum chemical calculations showed that the CD46-binding affinity of Ad11 is significantly higher than that of Ad7. Thus, while Ad7 and Ad14 also bind CD46, the affinity and kinetics of these interactions suggest that these Ads are unlikely to use CD46 productively. The proposed mechanism is likely to determine the receptor usage of all CD46-binding Ads.
Female Juvenile Sexual Offenders: Understanding Who They Are and Possible Steps That May Prevent Some Girls From Offending

In recent years, there has been accumulating evidence that sexual abuse committed by females is not rare and can be just as traumatic as sexual abuse committed by males. Despite the increased recognition given to sex offending by adult women, however, very little attention has been given to sex offenses committed by juvenile females. There has further been very little published material that has focused specifically on intervening with female children and adolescents before they offend. In an attempt to fill this gap, this article describes common characteristics of juvenile female sex offenders, ways in which juvenile female sex offenders are similar to and different from juvenile male sex offenders, and the limitations that exist related to our knowledge about these offenders. Based on this information, suggestions are given for possible ways to intervene in the lives of at-risk female youth before they offend.
Cryo‐Injury and Biopreservation

Abstract: Mammalian cells appear to be naturally tolerant to cold temperatures, but the formation of ice when cells are cooled leads to a variety of damaging effects. The study of cryo‐injury, therefore, becomes the study of when and how ice is formed both inside and outside the cell during cooling. Protectant chemicals are used to control or prevent ice formation in many preservation protocols, but these chemical themselves tend to be damaging. Cooling and warming rates also strongly affect the amount and location of ice that is formed. Through careful modification of these parameters successful cold preservation techniques for many cell types have been developed, but there are many more cell types that have defied preservation techniques, and the extension of cell‐based techniques to tissues and whole organs has been very limited. There are many aspects to the damaging effects of ice in cells that are still poorly understood. In this brief article we review our current understanding of cellular injury and highlight the aspects of cellular injury during cryopreservation that are still poorly understood.
Traditional/restrictive vs patient-centered intensive care unit visitation: perceptions of patients' family members, physicians, and nurses.

BACKGROUND Patient-centered intensive care units (ICUs) are advocated by professional organizations for critical care nursing and medicine. The patient-centered ICU paradigm recognizes the patient-family unit as inseparable and supports visitation designed to meet the needs of patients and patients' families. OBJECTIVES To understand perceptions about patient-centered ICUs among patients' family members, physicians, and nurses from 5 ICUs that had restrictive visitation and to guide development of a patient-centered, open visitation paradigm. METHODS Patients' family members, nurses, and physicians from 5 ICUs with a traditional/restrictive visitation policy at a southeastern academic, tertiary care hospital were invited to participate in focus group meetings to understand perceptions about patient-centered care. All qualitative work was taped, transcribed, reviewed, and corrected after each session. Corrected transcripts and observer notes were integrated and coded. RESULTS Patients' families identified facilitators of patient-centeredness as nurses' and physicians' communication, concern, compassion, closeness, and flexibility. However, competing roles of control over the patient's health care served as barriers to a patient-centered paradigm. CONCLUSIONS Patient-centered care is an expectation among patients, patients' families, and health quality advocates. These exploratory methods increased understanding of the powerful perceptions of family members, physicians, and nurses involved with patient care and provided direction to plan interventions to implement patient-centered, family-supportive ICU services.
Reducing Symptoms of Trauma Among Carers of People With Psychosis: Pilot Study Examining the Impact of Writing About Caregiving Experiences

Objectives: To establish whether writing about experiences of the first episode of psychosis may alleviate trauma-like symptoms among carers of people with psychosis. Method: A total of 37 people caring for someone with early psychosis were randomized to two conditions: either writing about the first psychotic episode, or writing about time management. Data were collected before and after intervention, and 8 weeks later. Results: Those in the writing group were significantly less likely to avoid reminders and feelings associated with their relative's episode at follow up. Furthermore, carers in this group who exhibited trauma-like symptoms had significantly greater reductions in trauma severity. Conclusions: Written emotional disclosure can help carers who are experiencing trauma symptoms following a relative's first episode of psychosis. If writing about emotional events is beneficial through mechanisms of exposure then screening participants for trauma symptoms may eliminate previous research inconsistencies. These results, however, need to be replicated in a larger study.
INHIBITION OF THE ACCESSORY FUNCTION OF MURINE MACROPHAGES IN VITRO BY CYCLOSPORINE

The accessory function of macrophages, which is strictly related to the induction of T cell activation, has been studied to determine whether it is affected by cyclosporine (CsA). Irradiated spleen cells, used as a source of macrophages, were pulsed overnight with β-galactosidase (GZ) in the presence of CsA. After washing of the pulsed macrophages, cells from a GZ-specific T cell line were added to cultures and 3H-thymidine incorporation was measured 72 hr later. We found that 500 ng/ml CsA present during macrophage pulsing with GZ reduced T cell proliferation to 5%. On the other hand, 100 ng/ml CsA almost completely abrogated the proliferative response when present for the duration of the culture. Similar results were also obtained using antigen-pulsed peritoneal-adherent macrophages to stimulate the T cell line to proliferate, or a T hybridoma clone to produce interleukin-2 (IL-2). The possibility that CsA actually affects interleukin-1 (IL-1) production by macrophages by inhibiting uninvolved T cells could be ruled out. We conclude that CsA-induced inhibition of T cell functions (proliferation and IL-2 production) is partially due to the effect of the drug on the accessory function of macrophages. This immunosuppressive mechanism of action of CsA on macrophages has not been previously described.
Functional regulation of thyroid hormone receptor variant TR alpha 2 by phosphorylation

The thyroid hormone (T3) receptor (TR) variant TR alpha 2 is abundant in brain but does not bind T3 because of its unique C terminus. The only known function of TR alpha 2, inhibition of TR-dependent transactivation, involves competition for T3 response elements. Paradoxically, in vitro-translated TR alpha 2 bound poorly to these sites. We report here that dephosphorylation of TR alpha 2 restored its DNA binding. Mutation of C-terminal serine residues to alanine (TR alpha 2-SA) was equally effective. The C terminus of TR alpha 2 was phosphorylated in a human cell line, whereas that of TR alpha 2-SA was not. Conversely, TR alpha 2-SA was a much better inhibitor of T3 action than was wild-type TR alpha 2. The dominant negative activity of TR alpha 2-SA was less than stoichiometric with TR concentration, possibly because it was unable to heterodimerize with retinoid X receptor, which enhances the binding of other TRs. Purified casein kinase II as well as a reticulocyte casein kinase II-like activity phosphorylated TR alpha 2 on serines 474 and 475. Mutation of these two residues to alanine was sufficient to restore DNA binding. Thus, DNA binding by TR alpha 2 is regulated by phosphorylation at a site distant from the DNA-binding domain. The increased dominant negative activity of a nonphosphorylatable form of TR alpha 2 suggests that phosphorylation may provide a rapid, T3-independent mechanism for cell-specific modulation of the expression of T3-responsive genes.
Elevated plasma levels of high mobility group box protein 1 in patients with HIV-1 infection

High mobility group box protein 1 (HMGB1) is a potent proinflammatory mediator. It has a dichotomic effect on HIV-1 replication in vitro but its role in vivo is unknown. Here we report the novel finding that plasma HMGB1 levels are elevated in HIV-1-infected patients, with the highest concentrations in patients with clinical complications. HMGB1 is likely to contribute to immunoactivation in HIV-1 infection in vivo.
Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties

Background There is a substantial variation in life expectancy across US counties, primarily owing to differentials in chronic diseases. The authors' aim was to examine the association of life expectancy and mortality from selected diseases with altitude. Methods The authors used data from the National Elevation Dataset, National Center for Heath Statistics and US Census. The authors analysed the crude association of mean county altitude with life expectancy and mortality from ischaemic heart disease (IHD), stroke, chronic obstructive pulmonary disease (COPD) and cancers, and adjusted the associations for socio-demographic factors, migration, average annual solar radiation and cumulative exposure to smoking in multivariable regressions. Results Counties above 1500 m had longer life expectancies than those within 100 m of sea level by 1.2–3.6 years for men and 0.5–2.5 years for women. The association between altitude and life expectancy became non-significant for women and non-significant or negative for men in multivariate analysis. After adjustment, altitude had a beneficial association with IHD mortality and harmful association with COPD, with a dose–response relationship. IHD mortality above 1000 m was 4–14 per 10 000 people lower than within 100 m of sea level; COPD mortality was higher by 3–4 per 10 000. The adjusted associations for stroke and cancers were not statistically significant. Conclusions Living at higher altitude may have a protective effect on IHD and a harmful effect on COPD. At least in part due to these two opposing effects, living at higher altitude appears to have no net effect on life expectancy.
Experimental infection of rock pigeons (Columba livia) with three West Nile virus lineage 1 strains isolated in Italy between 2009 and 2012

SUMMARY West Nile virus (WNV) circulation dynamics in the context of the urban environment is not yet elucidated. In this perspective, three groups of eight rock pigeons (Columbia livia) were inoculated with three WNV lineage 1 strains isolated in Italy between 2009 and 2012. The pigeons did not develop any clinical signs consistent with WNV acute infection. All animals seroconverted and shed virus up to 15 days post-infection by the oral or cloacal routes. In all infected groups viraemia lasted for 4 days post-infection. No WNV-specific gross or histological lesions were found in infected birds compared to control birds and immunohistochemistry remained constantly negative from all tissues. The reservoir competence index was also assessed and it ranged between 0·11 and 0·14. This study demonstrates that pigeons are competent reservoir hosts for Italian WNV lineage 1 circulating strains thus potentially posing a risk to the public health system.