Miracle-dz/UniFAR-FTUs huggingface dataset:
Essential Role of Mitochondrial Antiviral Signaling, IFN Regulatory Factor (IRF)3, and IRF7 in Chlamydophila pneumoniae-Mediated IFN-β Response and Control of Bacterial Replication in Human Endothelial Cells

Chlamydophila pneumoniae infection of the vascular wall as well as activation of the transcription factor IFN regulatory factor (IRF)3 have been linked to development of chronic vascular lesions and atherosclerosis. The innate immune system detects invading pathogens by use of pattern recognition receptors, some of which are able to stimulate IRF3/7 activation and subsequent type I IFN production (e. g., IFN-β). In this study, we show that infection of human endothelial cells with C. pneumoniae-induced production of IFN-β, a cytokine that so far has been mainly associated with antiviral immunity. Moreover, C. pneumoniae infection led to IRF3 and IRF7 nuclear translocation in HUVECs and RNA interference experiments showed that IRF3 and IRF7 as well as the mitochondrial antiviral signaling (MAVS) were essential for IFN-β induction. Finally, C. pneumoniae replication was enhanced in endothelial cells in which IRF3, IRF7, or MAVS expression was inhibited by small interfering RNA and attenuated by IFN-β treatment. In conclusion, C. pneumoniae infection of endothelial cells activates an MAVS-, IRF3-, and IRF7-dependent signaling, which controls bacterial growth and might modulate development of vascular lesions.
The combined impact of professional role identity and public service motivation on decision-making in dilemma situations

Working in the public sector implies the need to make decisions in the face of dilemmas. As consistent decision-making is highly desirable for organizational performance, the question arises: what do public service professionals base their decisions on? This study aims to increase our understanding of whether public service motivation and professional role identity are useful concepts by which to predict what decisions public service professionals will make in complex situations. Using survey data, this research investigates the impact of these two concepts on the decision-making of veterinary inspectors working at the Dutch Food and Consumer Product Safety Authority. The results support the hypothesis that decision-making is influenced by the way in which veterinary inspectors interpret their professional role. Public service motivation, in contrast, seems to have neither a direct nor a moderating effect on decision-making in the context of dilemma situations. Points for practitioners Two important conclusions of this study are of interest for managers working with professionals. Our findings should urge them to consider the different views that employees have about their job when teams are formed or when specific combinations of tasks are assigned. For example, attention should be paid to the question of which mixture of professional role identities is most suitable to accomplish organizational objectives. Second, the construct of public service motivation can be used by human resource managers to assess whether public professionals are motivated to provide public services. However, the results also indicate that the operationalization of public service motivation needs to be adapted to the professional context of public service providers.
Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4+ T Cells

ABSTRACT The Leishmania-derived recombinant polyprotein Leish-111f or its three component proteins, thiol-specific antioxidant (TSA), Leishmania major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF), have previously been demonstrated to be efficacious against cutaneous or mucosal leishmaniasis in mice, nonhuman primates, and humans. In this study we demonstrate that Leish-111f is also a vaccine antigen candidate against visceral leishmaniasis (VL) caused by Leishmania infantum. We evaluated the immune response and protection induced by Leish-111f formulated with monophosphoryl lipid A in a stable emulsion (Leish-111f+MPL-SE) and demonstrated that mice developed strong humoral and T-cell responses to the vaccine antigen. Analysis of the cellular immune responses of immunized, uninfected mice demonstrated that the vaccine induced a significant increase in CD4+ T cells producing gamma interferon, interleukin 2, and tumor necrosis factor cytokines, indicating a Th1-type immune response. Experimental infection of immunized mice and hamsters demonstrated that Leish-111f+MPL-SE induced significant protection against L. infantum infection, with reductions in parasite loads of 99.6%, a level of protection greater than that reported for other vaccine candidates in animal models of VL. Taken together, our results suggest that this vaccine represents a good candidate for use against several Leishmania species. The Leish-111f+MPL-SE product we report here is the first defined vaccine for leishmaniasis in human clinical trials and has completed phase 1 and 2 safety and immunogenicity testing in normal, healthy human subjects.
The variability of the photoplethysmographic signal - a potential method for the evaluation of the autonomic nervous system

The heart rate variability is composed of low- and high-frequency fluctuations, which are mediated by the sympathetic and the parasympathetic nervous systems. The baseline and the amplitude of the photoplethysmographic (PPG) signal also show fluctuations in the same frequencies. In the current study, PPG examinations were performed on the fingers of normal subjects and diabetic patients, and three parameters were derived from each PPG pulse: the baseline of the pulse, its amplitude and its period (which is equal to the heart period). The level of the variability of each PPG pulse parameter was measured by the ratio of the standard deviation of the parameter to its mean value. The level of the low-frequency fluctuations for the PPG amplitude and for the heart cycle period did not differ between males and females, but was lower for diabetic patients, indicating lower activity of the autonomic nervous system. The curves of the baseline and the amplitude of the PPG signal for the non-diabetic subjects showed high correlation between the left and the right hands. For most of the diabetic patients the right-left correlation coefficients were significantly lower than those for the non-diabetic subjects. Our initial results have shown that the variability of the PPG parameters shows promise for the assessment of the function of the autonomic nervous system. Keywords: spontaneous variability, photoplethysmography, autonomic neuropathy, diabetic patients
Increased Pulse Wave Velocity in Systemic Lupus Erythematosus: A Meta-Analysis

Systemic lupus erythematosus (SLE) is associated with increased cardiovascular risk. This study aims to derive a more precise estimation on pulse wave velocity (PWV) level in patients with SLE and related factors. A literature search was performed using PubMed, EMBASE, and The Cochrane Library databases, studies published up to February 28, 2017, in English. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I2 ; publication bias was evaluated using a funnel plot and Egger’s linear regression test. Of 156 studies found, 27 met eligibility criteria, and 14 studies were finally included in the meta-analysis. Meta-analysis revealed that the SLE group had significantly higher PWV levels than the control group; SMD = 0.56 and 95% CI (0.30-0.82). Subgroup analyses showed that body mass index (BMI), sample size, and disease duration were associated with PWV in patients with SLE. Overall, our study suggests that patients with SLE have a higher PWV level, and it is associated with BMI, sample size, and disease duration.
Open Source Software User Communities: A Study of Participation in Linux User Groups

We conceptualize participation in Linux user groups (LUGs) in terms of group-referent intentional actions and investigate cognitive (attitudes, perceived behavioral control, identification with the open source movement), affective (positive and negative anticipated emotions), and social (social identity) determinants of participation and its consequences on Linux-related behaviors of users. This survey-based study, conducted with 402 active LUG members representing 191 different LUGs from 23 countries and employing structural equation modeling methodology, supports the proposed model. Furthermore, we find that the Linux user's experience level moderates the extent of the LUG's social influence and its impact on the user's participation. We conclude with a consideration of the managerial and research implications of the study's findings.
Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis

The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis. However, the individual contribution of the lack of methionine and choline in liver steatosis, advanced pathology and impact on mitochondrial S-adenosyl-l-methionine (SAM) and glutathione (GSH), known regulators of disease progression, has not been specifically addressed. Here, we examined the regulation of mitochondrial SAM and GSH and signs of disease in mice fed a MCD, methionine-deficient (MD), or choline-deficient (CD) diet. The MD diet reproduced most of the deleterious effects of MCD feeding, including weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD feeding was mainly responsible for steatosis, characterized by triglycerides and free fatty acids accumulation. These findings were preceded by MCD- or MD-mediated SAM and GSH depletion in mitochondria due to decreased mitochondrial membrane fluidity associated with a lower phosphatidylcholine/phosphatidylethanolamine ratio. MCD and MD but not CD feeding resulted in increased ceramide levels by acid sphingomyelinase. Moreover, GSH ethyl ester or SAM therapy restored mitochondrial GSH and ameliorated hepatocellular injury in mice fed a MCD or MD diet. Thus, the depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine. Moreover, therapy using permeable GSH prodrugs may be of relevance in NASH.
Cosuppression of Eukaryotic Release Factor 1-1 in Arabidopsis Affects Cell Elongation and Radial Cell Division

The role of the eukaryotic release factor 1 (eRF1) in translation termination has previously been established in yeast; however, only limited characterization has been performed on any plant homologs. Here, we demonstrate that cosuppression of eRF1-1 in Arabidopsis (Arabidopsis thaliana) has a profound effect on plant morphology, resulting in what we term the broomhead phenotype. These plants primarily exhibit a reduction in internode elongation causing the formation of a broomhead-like cluster of malformed siliques at the top of the inflorescence stem. Histological analysis of broomhead stems revealed that cells are reduced in height and display ectopic lignification of the phloem cap cells, some phloem sieve cells, and regions of the fascicular cambium, as well as enhanced lignification of the interfascicular fibers. We also show that cell division in the fascicular cambial regions is altered, with the majority of vascular bundles containing cambial cells that are disorganized and possess enlarged nuclei. This is the first attempt at functional characterization of a release factor in vivo in plants and demonstrates the importance of eRF1-1 function in Arabidopsis.
Physical activity, sedentary time, and risk of colorectal cancer: the Singapore Chinese Health Study

Singapore has experienced a marked increase in colorectal cancer incidence over the past 40 years. Evidence from prospective studies in Western Europe and the USA suggests that low physical activity and high amounts of sedentary time are associated with increased colorectal cancer risk. The aim of this study is to evaluate these relationships in an Asian population. The Singapore Chinese Health Study enrolled 63 257 adults between 1993 and 1998. At enrollment, participants reported past year physical activity and time spent sitting. Incident colorectal cancers (n=1994) were identified through 31 December 2014. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. Any strenuous–vigorous or moderate physical activity was reported by 13.7 and 22.1% of the cohort, respectively. Strenuous–vigorous physical activity was associated with statistically significant reduced colorectal cancer risk (HR=0.85; 95% CI: 0.74–0.99 for ≥0.5 h/week vs. none), but moderate was not. In analysis stratified by time spent watching television, an inverse relationship between moderate physical activity and colorectal cancer risk (HR=0.86; 95% CI: 0.72–1.01 for ≥0.5 h/week vs. none) was observed for those who reported at least 3 h/day sitting watching television (Pinteraction=0.042). Participation in strenuous–vigorous physical activity, such as jogging, swimming, or heavy manual labor, was associated with reduced colorectal cancer risk among Singapore Chinese. Further research on physical activity and sedentary behaviors, independently and in combination, and colorectal cancer risk in Asian populations is needed.
Validation of predictive models for germline mutations in DNA mismatch repair genes in colorectal cancer

Lynch syndrome is defined by the presence of germline mutations in mismatch repair (MMR) genes. Several models have been recently devised that predict mutation carrier status (Myriad Genetics, Wijnen, Barnetson, PREMM and MMRpro models). Families at moderate‐high risk for harboring a Lynch‐associated mutation, referred to the BC Cancer Agency (BCCA) Hereditary Cancer Program (HCP), underwent mutation analysis, immunohistochemistry and/or microsatellite testing. Seventy‐two tested cases were included. Twenty‐five patients were mutation positive (34.7%) and 47 were mutation negative (65.3%). Nineteen of 43 patients who were both microsatellite stable and normal on immunohistochemistry for MLH1 and MSH2 were also genotyped for mutations in these genes; all 19 were negative for MMR gene mutations. Model‐derived probabilities of harboring a MMR gene mutation in the proband were calculated and compared to observed results. The area under the ROC curves were 0.75 (95%CI; 0.63–0.87), 0.86 (0.7–0.96), 0.89 (0.82–0.97), 0.89 (0.81–0.98) and 0.93 (0.86–0.99) for the Myriad, Barnetson, Wijnen, MMRpro and PREMM models, respectively. The Amsterdam II criteria had a sensitivity and specificity of 0.76 and 0.74, respectively, in this cohort. The PREMM model demonstrated the best performance for predicting carrier status based on the positive likelihood ratios at the >10%, >20% and >30% probability thresholds. In this referred cohort, the PREMM model had the most favorable concordance index and predictive performance for carrier status based on the positive LR. These prediction models (PREMM, MMRPro and Wijnen) may soon replace the Amsterdam II and revised Bethesda criteria as a prescreening tool for Lynch mutations.
Labor Market Signaling and Unemployment Duration: Evidence from Germany

The aim of the paper is to examine the consequences of displacement on unemployment duration. Due to ex-ante asymmetric information about the productivity of unemployed applicants, prospective employers use the type of displacement as a costless signal about the ability of the worker when making hiring decisions. While individual layoffs might be caused by workers low productivity, plant closures can be considered as exogenous. Consequently, individual layoffs might attach a negative productivity signal to the worker resulting in longer unemployment duration. To test this hypothesis we use administrative linked employer-employee data for Germany which not only contain daily information on unemployment duration but also allows us to control for the type of displacement. We show that workers displaced due to plant closures and downsizings find indeed significantly faster a new job. We also find the strengths of the signaling value to be proportional to the share of displaced workers.
Generation and Analysis of End Sequence Database for T-DNA Tagging Lines in Rice1

We analyzed 6,749 lines tagged by the gene trap vector pGA2707. This resulted in the isolation of 3,793 genomic sequences flanking the T-DNA. Among the insertions, 1,846 T-DNAs were integrated into genic regions, and 1,864 were located in intergenic regions. Frequencies were also higher at the beginning and end of the coding regions and upstream near the ATG start codon. The overall GC content at the insertion sites was close to that measured from the entire rice (Oryza sativa) genome. Functional classification of these 1,846 tagged genes showed a distribution similar to that observed for all the genes in the rice chromosomes. This indicates that T-DNA insertion is not biased toward a particular class of genes. There were 764, 327, and 346 T-DNA insertions in chromosomes 1, 4 and 10, respectively. Insertions were not evenly distributed; frequencies were higher at the ends of the chromosomes and lower near the centromere. At certain sites, the frequency was higher than in the surrounding regions. This sequence database will be valuable in identifying knockout mutants for elucidating gene function in rice. This resource is available to the scientific community at http://www.postech. ac.kr/life/pfg/risd.
Handout on ‘ Risky Habits ’ and the Relationship Between Saving and Growth 1 Theory

Assume that each infinitely-lived consumer in the economy is endowed with one unit of labor which is supplied inelastically in an aggregate labor market, and that the individual consumer’s labor income is subject to multiplicative idiosyncratic transitory shocks i,t+1 such that Et[̃i,t+1] = 1. 1 Idiosyncratic ‘permanent labor income’ is defined as the level of labor income that would obtain for individual i if the transitory shock to labor income took on its mean value of one. Permanent labor income Pi,t is also subject to lognormally distributed shocks Ni,t+1 (again such that Et[Ñi,t+1] = 1) in each period; the marginal propensity to consume out of permanent income will be determined by examining the response of consumption to these shocks. Denoting by Hi,t the habit stock inherited from past consumption behavior, and designating total resources available for consumption (the sum of undepreciated past capital, current capital income, and current labor income) as Xi,t, the consumer’s optimization problem for a finite horizon beginning at the current period t and ending at period T (and dropping the i subscripts to reduce clutter) is given by
Twinning on the brain: The effect on neurodevelopmental outcomes

Twinning is currently considered a complex multifactorial trait. Few studies have explored how the unique genetic and environmental influences that create twinning affect phenotypes and outcomes. Previous data has shown that twins account for a significant proportion of preterm and low‐birth‐weight infants, who are at risk for long‐term neurodevelopmental disabilities such as cerebral palsy and cognitive impairment. More recently, it has been postulated that even without these co‐morbidities, twinning in and of itself may incur a neurodevelopmental disadvantage even among term newborns. The purpose of this review is to report primarily on neuromotor outcomes of twins compared to singletons. In addition, we describe specific environmental risk factors among twins which are associated with poorer outcomes. Several putative neurodevelopmental modulators are explored, including death of a co‐twin, chorionicity, birth weight discordance, and twin‐twin transfusion. By teasing out environmental influences that potentially influence neurocognitive outcomes, families can receive more specific counseling and developmental services can be provided to those twins at especially high risk. © 2009 Wiley‐Liss, Inc.
Immunological and virological responses to combined antiretroviral therapy in HIV/hepatitis B virus-coinfected patients from a multicenter cohort

Objective:To evaluate the influence of hepatitis B virus (HBV) coinfection on immunological, virological and clinical responses to lamivudine (3TC)-based combined antiretroviral therapy (cART) in Chinese patients. Design and methods:This prospective, multicenter cohort study recruited 529 antiretroviral-naive participants (aged 18–65 years, both sexes) between 2008 and 2010. They were grouped by HBV serostatus. Virological and immunological responses were monitored at baseline and week 4, 8, 12, 24, 36 and 48. cART for all patients was nevirapine, 3TC with either zidovudine or stavudine. Results:First, HIV/HBV coinfection rate in our cohort was 14.6%. Second, among 508 patients with complete baseline information, median CD4 level was significantly lower in the chronic HBV-infected (CHB) group and isolated core group. In the CHB group, hepatitis B e antigen positivity rather than HBV DNA level was associated with lower CD4 cell count. Third, in the isolated core group, occult infection rate was 9.5%. Fourth, at week 48, rate of HIV suppression below 40 copies/ml was 74.2%. Median increase in the CD4 cell count at week 48 was 127 cells/&mgr;l. Of note, HBV serostatus did not influence virological and immunological response to cART at each follow-up time point. Although HBV serostatus was associated with different alanine aminotransferase levels during follow-up, hepatitis and hyperbilirubinemia rates were not significantly different. Fifth, the 3TC-based regimen was efficacious against HBV replication, with median decrease in HBV DNA of 2.87 log copies/ml. However, hepatitis B e antigen positivity was associated with poorer HBV DNA suppression. Conclusion:In our cohort, CHB infection and isolated hepatitis B core antibody positivity were related to faster HIV progression. Despite of this, virological and immunological responses were not affected by HBV serostatus. (ClinicalTrials.gov identifier: NCT00872417)