Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Characterization of EscK (Orf4), a Sorting Platform Component of the Enteropathogenic Escherichia coli Injectisome

ABSTRACT The type III secretion system (T3SS) is a supramolecular machine used by many bacterial pathogens to translocate effector proteins directly into the eukaryotic host cell cytoplasm. Enteropathogenic Escherichia coli (EPEC) is an important cause of infantile diarrheal disease in underdeveloped countries. EPEC virulence relies on a T3SS encoded within a chromosomal pathogenicity island known as the locus of enterocyte effacement (LEE). In this work, we pursued the functional characterization of the LEE-encoded protein EscK (previously known as Orf4). We provide evidence indicating that EscK is crucial for efficient T3S and belongs to the SctK (OrgA/YscK/MxiK) protein family, whose members have been implicated in the formation of a sorting platform for secretion of T3S substrates. Bacterial fractionation studies showed that EscK localizes to the inner membrane independently of the presence of any other T3SS component. Combining yeast two-hybrid screening and pulldown assays, we identified an interaction between EscK and the C-ring/sorting platform component EscQ. Site-directed mutagenesis of conserved residues revealed amino acids that are critical for EscK function and for its interaction with EscQ. In addition, we found that T3S substrate overproduction is capable of compensating for the absence of EscK. Overall, our data suggest that EscK is a structural component of the EPEC T3SS sorting platform, playing a central role in the recruitment of T3S substrates for boosting the efficiency of the protein translocation process. IMPORTANCE The type III secretion system (T3SS) is an essential virulence determinant for enteropathogenic Escherichia coli (EPEC) colonization of intestinal epithelial cells. Multiple EPEC effector proteins are injected via the T3SS into enterocyte cells, leading to diarrheal disease. The T3SS is encoded within a genomic pathogenicity island termed the locus of enterocyte effacement (LEE). Here we unravel the function of EscK, a previously uncharacterized LEE-encoded protein. We show that EscK is central for T3SS biogenesis and function. EscK forms a protein complex with EscQ, the main component of the cytoplasmic sorting platform, serving as a docking site for T3S substrates. Our results provide a comprehensive functional analysis of an understudied component of T3SSs.
White matter alterations over the course of two consecutive high‐school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study

The cumulative effects of repetitive subclinical head impacts during sports may result in chronic white matter (WM) changes and possibly, neurodegenerative sequelae. In this pilot study, we investigated the longitudinal WM changes over the course of two consecutive high‐school football seasons and explored the long‐term effects of a jugular vein compression collar on these WM alterations. Diffusion tensor imaging data were prospectively collected both pre‐ and postseason in the two consecutive seasons. Participants were assigned into either collar or noncollar groups. Tract‐based spatial statistics (TBSS) approach and region of interest‐based approach were used to quantify changes in WM diffusion properties. Despite comparable exposure to repetitive head impacts, significant reductions in mean, axial, and/or radial diffusivity were identified in Season 1 in multiple WM regions in the noncollar group but not in the collar group. After an 8‐ to 9‐month long off‐season, these changes observed in the noncollar group partially and significantly reversed but also remained significantly different from the baseline. In Season 2, trend level WM alterations in the noncollar group were found but located in spatially different regions than Season 1. Last, the WM integrity in the collar group remained unchanged throughout the four time points. In conclusion, we quantitatively assessed the WM structural changes and partial reversal over the course of two consecutive high‐school football seasons. In addition, the mitigated WM alterations in athletes in the collar group might indicate potential effect of the collar in ameliorating the changes against repetitive head impacts. Hum Brain Mapp 39:491–508, 2018. © 2017 Wiley Periodicals, Inc.
Maternal serum 25-hydroxyvitamin D and placental vascular pathology in a multicenter US cohort.

BACKGROUND Maternal vitamin D deficiency has been linked to fetal growth restriction, but the underlying mechanisms are unclear. OBJECTIVE We tested the hypothesis that poor maternal 25-hydroxyvitamin D [25(OH)D] is associated with increased risk of placental vascular pathology. DESIGN Maternal serum 25(OH)D was measured at ≤26 wk of gestation in a random subcohort of term, singleton infants in the Collaborative Perinatal Project (1959-1966; n = 2048). A dichotomous vascular construct was created from the presence of any of 12 pathologies identified on placental examinations, including evidence of placental abruption, infarction, hypoxia, decidual vasculopathy, or thrombosis of fetal vessels (n = 240 cases). RESULTS The relation between 25(OH)D and vascular pathology was modified by infant sex (P = 0.003). A maternal 25(OH)D concentration ≥80 compared with <50 nmol/L was associated with 49% lower risk of pathology in boys [adjusted OR (95% CI): 0.27, 0.95] after conditioning on study site. No associations were observed between maternal 25(OH)D and pathology in mothers with female offspring. Subsequent analyses showed that, in pregnancies with a female fetus, vascular pathology was associated with a reduced birth-weight z score when the mother's 25(OH)D concentration was <30 nmol/L (β: -0.73; 95% CI: -1.17, -0.30). No association was observed between pathology and birth weight in mothers of female offspring with 25(OH)D concentrations ≥30 nmol/L or in boys, regardless of maternal 25(OH)D status. CONCLUSIONS Our findings suggest complex relations between vitamin D, placental vascular pathology, and birth weight that differ by infant sex. Maternal vitamin D status may be beneficial for male and female offspring through different mechanisms.
Auditory Affective Processing Requires Awareness

Recent work has challenged the previously widely accepted belief that affective processing does not require awareness and can be carried out with more limited resources than semantic processing. This debate has focused exclusively on visual perception, even though evidence from both human and animal studies suggests that existence for nonconscious affective processing would be physiologically more feasible in the auditory system. Here we contrast affective and semantic processing of nonverbal emotional vocalizations under different levels of awareness in three experiments, using explicit (two-alternative forced choice masked affective and semantic categorization tasks, Experiments 1 and 2) and implicit (masked affective and semantic priming, Experiment 3) measures. Identical stimuli and design were used in the semantic and affective tasks. Awareness was manipulated by altering stimulus-mask signal-to-noise ratio during continuous auditory masking. Stimulus awareness was measured on each trial using a four-point perceptual awareness scale. In explicit tasks, neither affective nor semantic categorization could be performed in the complete absence of awareness, while both tasks could be performed above chance level when stimuli were consciously perceived. Semantic categorization was faster than affective evaluation. When the stimuli were partially perceived, semantic categorization accuracy exceeded affective evaluation accuracy. In implicit tasks neither affective nor semantic priming occurred in the complete absence of awareness, whereas both affective and semantic priming emerged when participants were aware of the primes. We conclude that auditory semantic processing is faster than affective processing, and that both affective and semantic auditory processing are dependent on awareness.
Influence of Injury Characteristics and Payer Status on Burn Treatment Location in Washington State

The provision of optimal burn care is a resource-intensive endeavor. The American Burn Association has developed criteria to help guide the decision to refer a patient to a burn center for definitive injury care. The purpose of this study was to compare the patient and injury characteristics of patients admitted to the single verified burn center in Washington State with those treated at other facilities in the state. We performed a retrospective review of all patients admitted to a hospital with a burn injury in Washington State from 1987 to 2005 using the state’s discharge database (Comprehensive Hospital Abstract Reporting System). Patient and injury factors of patients admitted to the state’s single verified burn center or at other hospitals were compared. Multivariate poisson regression was used to calculate the relative risk of injury and patient factors that were significantly associated with admission to the verified burn center. From 1987 to 2005, a total of 16,531 patients were admitted to a Washington State hospital after burn injury. Of these patients, 8624 (52.2%) were treated definitively at the University of Washington Burn Center. Patients treated at this verified center had larger overall burn size (7.4% vs 4.5% TBSA, P < .001), higher percent full-thickness burn (4.3% vs 1.2%, P < .001), and higher rates of inhalation injury (2.3% vs 1.5%, P = .005). Uninsured status (relative risk = 1.46, 95% confidence interval = 1.4–1.5) was also significantly associated with treatment at the verified burn center. Injury severity and payer status were both found to be independent predictors of treatment at the single verified burn center in Washington.
A Systematic Review of Logging Practice in Software Engineering

Background: Logging practice is a critical activity in software development, which aims to offer significant information to understand the runtime behavior of software systems and support better software maintenance. There have been many relevant studies dedicated to logging practice in software engineering recently, yet it lacks a systematic understanding to the adoption state of logging practice in industry and research progress in academia. Objective: This study aims to synthesize relevant studies on the logging practice and portray a big picture of logging practice in software engineering so as to understand current adoption status and identify research opportunities. Method: We carried out a systematic review on the relevant studies on logging practice in software engineering. Results: Our study identified 41 primary studies relevant to logging practice. Typical findings are: (1) Logging practice attracts broad interests among researchers in many concrete research areas. (2) Logging practice occurred in many development types, among which the development of fault tolerance systems is the most adopted type. (3) Many challenges exist in current logging practice in software engineering, e.g., tradeoff between logging overhead and analysis cost, where and what to log, balance between enough logging and system performance, etc. Conclusion: Results show that logging practice plays a vital role in various applications for diverse purposes. However, there are many challenges and problems to be solved. Therefore, various novel techniques are necessary to guide developers conducting logging practice and improve the performance and efficiency of logging practice.
Social Environmental Correlates of Health Behaviors in a Faith-Based Policy and Environmental Change Intervention

Diet and physical activity are behavioral risk factors for many chronic diseases, which are among the most common health conditions in the United States. Yet most Americans fall short of meeting established dietary and physical activity guidelines. Faith-based organizations as settings for health promotion interventions can affect members at multiple levels of the social ecological model. The present study investigated whether change in the church social environment was associated with healthier behavior at church and in general at 1-year follow-up. Six churches received mini-grants and technical assistance for 1 year to support policy and environmental changes for healthy eating (HE) and physical activity (PA). Socioenvironmental (social support and social norms) and behavioral (HE and PA at church and in general) outcomes were derived from baseline and 1-year follow-up church member surveys (n = 258). Three of six churches demonstrated significant improvements in all three socioenvironmental aspects of HE. Two of five churches exhibited significant socioenvironmental improvements for PA at follow-up. Church social environmental changes were related to health behaviors at church and in general (p < .05). Change in social support for HE, social support for PA, and social norms for PA were each associated with three church-based and general behavioral outcomes. Social norms for healthy eating were related to two general behavior outcomes and social norms for unhealthy eating to one general behavioral outcome. Study findings demonstrate that socioenvironmental characteristics are essential to multilevel interventions and merit consideration in designing policy and environmental change interventions.
Coronary band autografting in donkeys: clinical and histological evaluation of healing quality of hoof wall defects.

Twelve healthy, adult donkeys of both sexes aged between 2 and 4 years were used to evaluate the feasibility of using coronary band autografts to aid in the healing of deep dermal hoof wall injuries. Wound healing and graft take were monitored visually and evaluated histologically at different time points. Epidermal cells of the coronary papillae survived the process of hoof wall stripping. Almost all areas of the basal membrane were intact and attached to the corium at the site of hoof wall stripping. Grafted basal cells were able to produce new generations of cells (keratinocytes or keratin producing cells) which matured and keratinised, resulting in the production of new stratum medium. Inspite of the fact that the new hoof wall was rough and irregular in shape, it was functional and donkeys were no longer lame at 28 days post surgery.
Conformational changes at cytoplasmic intersubunit interactions control Kir channel gating

The defining structural feature of inward-rectifier potassium (Kir) channels is the unique Kir cytoplasmic domain. Recently we showed that salt bridges located at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels control channel gating via stability of a novel inactivated closed state. The cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar conformational rearrangements to the common gating ligand, phosphatidylinositol bisphosphate (PIP2), although these exhibit opposite coupling to opening and closing transitions. In Kir2.1, mutation of one of these CD-I salt bridge residues (R204A) reduces apparent PIP2 sensitivity of channel activity, and here we show that Ala or Cys substitutions of the functionally equivalent residue (Arg-165) in the prokaryotic Kir channel KirBac1.1 also significantly decrease sensitivity of the channel to PIP2 (by 5–30-fold). To further understand the structural basis of CD-I control of Kir channel gating, we examined the effect of the R165A mutation on PIP2-induced changes in channel function and conformation. Single-channel analyses indicated that the R165A mutation disrupts the characteristic long interburst closed state of reconstituted KirBac1.1 in giant liposomes, resulting in a higher open probability due to more frequent opening bursts. Intramolecular FRET measurements indicate that, relative to wild-type channels, the R165A mutation results in splaying of the cytoplasmic domains away from the central axis and that PIP2 essentially induces opposite motions of the major β-sheet in this channel mutant. We conclude that the removal of stabilizing CD-I salt bridges results in a collapsed state of the Kir domain.
Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants

The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated Pepitope–a measure of antigenic diversity based on changes in the epitope regions–for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive.
Assessing the impact of cell phones on African societies: An investigation into the impact of cell phones on a community of practice of business women in Nigeria

Sub-Saharan Africa is one of the regions with the fastest penetration of mobile phones globally, but still in some parts of the region faces extreme poverty. The mobile phone is ubiquitous technology that has the potential of transforming the lives of millions in the Sub-Saharan African Region especially in Nigeria with over 93 million connected cell phone lines. This paper provides an empirical assessment of the impact that cell phones have on the lives of Business Women in Nigeria through the organic social structure of Communities of Practice (COP). COPs are part of the fiber of the social structure in Africa. They exist informally and formally and have historically been known to be causative factors for socio-economic growth. The empirical assessment of technological impact in Sub-Saharan Africa is often challenging. This paper therefore also presents a novel tool for the assessment of technology impact in SSA through “Wegner's Value Creation Assessment Framework”. The value created through the use of cell phones in the lives of a Community of Practice of Business Women in Nigeria is assessed through “Value Creation Stories” recommended by Wegner's Assessment Framework. Findings presented in this paper can be used in the design and development of mobile applications or Mobile Value Added Services (MVAS) for the Empowerment of Business Women in Sub-Saharan Africa. A more Qualitative (Ethnography) approach is in this study.
Social support and religiosity as coping strategies for anxiety in hospitalized cardiac patients

Background: Prospective studies have demonstrated that anxiety is associated with an increased risk of mortality and sudden cardiac death. There is therefore a need to understand what factors contribute to anxiety in patients with coronary heart disease (CHD). Purpose: This study examined whether social support and religiosity are individually or jointly associated with lower anxiety in cardiac patients.Methods: Anxiety, perceived social support, and religiosity were assessed in 228 (71% male, 29% female) hospitalized CHD patients aged 62 ± 11 years.Results: Higher levels of social support were related to lower levels of state and trait anxiety (state anxiety, r = −.26, p < .01; trait anxiety, r = −.30, p < .01;). Religiosity was related to lower state anxiety (r = −.27, p < .01) but only modestly related to lower trait anxiety (trait anxiety, r = −.18, p < .01). The relationship between religiosity and trait anxiety was no longer significant after controlling for social support (p = .26). Conclusions: These findings suggest that religiosity and social support provide a buffer against anxiety in CHD patients and that higher levels of social support may account for the relationship between religiosity and trait anxiety. These findings underscore the importance of social support and religiosity as buffers against distress, with possible implications for prognosis in a patient group where high levels of anxiety appear to confer increased risk of mortality.
Takotsubo-Like Myocardial Dysfunction in Ischemic Stroke: A Hospital-Based Registry and Systematic Literature Review

Background and Purpose— We investigated clinical and radiological characteristics of ischemic stroke patients with Takotsubo-like myocardial dysfunction. Methods— From multicenter stroke registry database, ischemic stroke patients who underwent transthoracic echocardiography were found. Among these, patients were classified if they had specific ventricular regional wall motion abnormalities discording with coronary artery distribution, such as apical (typical pattern) or nonapical ballooning (atypical pattern), considered as echocardiographic findings of Takotsubo cardiomyopathy. Patients with ischemic heart disease history, myocarditis, or pheochromocytoma were excluded. We compared patients with Takotsubo-like myocardial dysfunction with those without and further performed systematic literature review on those with Takotsubo cardiomyopathy. Results— This study included 23 patients (0.42%). The mean age was 70.7±13.9 years, with predominance of women (73.9%) and typical pattern of Takotsubo-like myocardial dysfunction (91.3%). They were associated with short-term poor functional outcomes, including high mortality, neurological deterioration, and functional status at discharge, compared with those without (39.1% versus 2.4%, 47.8% versus 7.4%; and median [interquartile range], 5 [5–6] versus 3 [2–4]; all P<0.001). They had a higher inflammatory marker level and lower triglyceride level. Ischemic lesions were more commonly found in the right anterior circulation with specific dominant regions being the insula and peri-insular areas. In addition, a trend toward a remarkable mortality rate and higher prevalence of insular involvement was observed in the propensity-score matching, subgroup fulfilling the strict Takotsubo cardiomyopath criteria, and was as reported in literature review. Conclusion— Stroke patients with Takotsubo-like myocardial dysfunction may differ from those without in clinical outcomes, laboratory findings, and radiological features.
Stress-induced cortisol hampers memory generalization

Integrative encoding and generalization across past experiences depends largely on the hippocampus, an area known to be particularly sensitive to stress. Yet, whether stress influences the ability to generalize memories is unknown. We exposed volunteers to a stressor or a control manipulation before they completed an acquired equivalence task probing memory generalization. While stress left learning performance intact, it reduced participants’ ability to generalize and this deficit was directly linked to the cortisol response to the stressor. These findings show that stress, presumably through the action of glucocorticoids, creates rather rigid memories that are difficult to transfer to novel situations.