Miracle-dz/UniFAR-FTUs huggingface dataset:
NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

ABSTRACT Bacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs against Escherichia coli, the individual roles of NOD1 and NOD2 in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen, E. coli. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2−/− mice following E. coli infection. Furthermore, we observed reduced activation of NF-κB and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2−/− mice upon E. coli challenge. Moreover, NOD2−/− neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2−/− mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2−/− mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2−/− mice demonstrate a reduction in activation of NF-κB and MAPKs similar to that seen with NOD2−/− mice in response to E. coli. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation.
A Proteolytic Pathway That Recognizes Ubiquitin as a Degradation Signal (*)

Previous work has shown that a fusion protein bearing a “nonremovable” N-terminal ubiquitin (Ub) moiety is short-lived in vivo, the fusion's Ub functioning as a degradation signal. The proteolytic system involved, termed the UFD pathway (Ub fusion degradation), was dissected in the yeast Saccharomyces cerevisiae by analyzing mutations that perturb the pathway. Two of the five genes thus identified, UFD1 and UFD5, function at post-ubiquitination steps in the UFD pathway. UFD3 plays a role in controlling the concentration of Ub in a cell: ufd3 mutants have greatly reduced levels of free Ub, and the degradation of Ub fusions in these mutants can be restored by overexpressing Ub. UFD2 and UFD4 appear to influence the formation and topology of a multi-Ub chain linked to the fusion's Ub moiety. UFD1, UFD2, and UFD4 encode previously undescribed proteins of 40, 110, and 170 kDa, respectively. The sequence of the last 280 residues of Ufd4p is similar to that of E6AP, a human protein that binds to both the E6 protein of oncogenic papilloma viruses and the tumor suppressor protein p53, whose Ub-dependent degradation involves E6AP. UFD5 is identical to the previously identified SON1, isolated as an extragenic suppressor of sec63 alleles that impair the transport of proteins into the nucleus. UFD5 is essential for activity of both the UFD and N-end rule pathways (the latter system degrades proteins that bear certain N-terminal residues). We also show that a Lys Arg conversion at either position 29 or position 48 in the fusion's Ub moiety greatly reduces ubiquitination and degradation of Ub fusions to β-galactosidase. By contrast, the ubiquitination and degradation of Ub fusions to dihydrofolate reductase are inhibited by the Ub but not by the Ub moiety. ufd4 mutants are unable to ubiquitinate the fusion's Ub moiety at Lys, whereas ufd2 mutants are impaired in the ubiquitination at Lys. These and related findings suggest that Ub-Ub isopeptide bonds in substrate-linked multi-Ub chains involve not only the previously identified Lys but also Lys of Ub, and that structurally different multi-Ub chains have distinct functions in Ub-dependent protein degradation.
Decreased levels of plasma adiponectin in prediabetes, Type 2 diabetes and coronary artery disease.

BACKGROUND Adiponectin, an adipocyte-derived hormone is implicated in insulin resistance and atherosclerosis. The aim of our study is to compare the levels of adiponectin in subjects with prediabetes and diabetes with subjects with normal glucose. MATERIAL/METHODS In a cross sectional study, we measured adiponectin and insulin in addition to fasting lipid panel and glucose in 28 subjects with prediabetes, 28 subjects with normal fasting glucose and 33 subjects with type 2 diabetes. RESULTS Adiponectin levels negatively correlate with insulin resistance index (r = -32.7). There is a significant difference in the levels of adiponectin between subjects with prediabetes and normal fasting glucose. There is a significant difference in adiponectin levels in subjects with prediabetes with Coronary artery disease (CAD) compared to those without CAD (10.24+/-1.02 vs. 7.02+/-0.92 with p<0.01). There is a significant difference in adiponectin levels in subjects with CAD compared to those without coronary artery disease (9.94+/-1.02 vs. 5.02+/-0.82 with p<0.01). CONCLUSIONS We conclude that decreased plasma adiponectin and insulin resistance coexist in subjects with prediabetes, diabetes and atherosclerosis. Adiponectin concentration is an independent correlate of insulin resistance and atherosclerosis.
Endogenous Circannual Cycles of Ovarian Activity and Changes in Prolactin and Melatonin Secretion in Wild and Domestic Female Sheep Maintained under a Long-Day Photoperiod1

Abstract The present study examines the ovulatory activity of wild and domesticated ewes subjected to either a constant photoperiod of long days (16L:8D) or natural changes in daily photoperiod for 16 mo. The aim was to determine whether an endogenous reproductive rhythm controls seasonal reproductive activity in these sheep, and how the photoperiod might affect this. The effects of long-day photoperiods on long-term changes in prolactin and melatonin secretion were also evaluated. The two species showed changes in reproductive activity under the constant photoperiod conditions, suggesting the existence of an endogenous rhythm of reproduction. This rhythm was differently expressed in the two types of ewe (P < 0.05), with the domestic animals exhibiting much greater sensitivity to the effects of long days. A circannual rhythm of plasma prolactin concentration was also seen in both species and under both photoperiod conditions, although in both species the amplitude was always lower in the long-day animals (P < 0.01). The duration of the nocturnal melatonin plasma concentrations reflected the duration of darkness in both species and treatments. The peak melatonin concentration did not differ between seasons either under natural or long-day photoperiods.
Dynamics of event‐related causality in brain electrical activity

A new method (Event‐Related Causality, ERC) is proposed for the investigation of functional interactions between brain regions during cognitive processing. ERC estimates the direction, intensity, spectral content, and temporal course of brain activity propagation within a cortical network. ERC is based upon the short‐time directed transfer function (SDTF), which is measured in short EEG epochs during multiple trials of a cognitive task, as well as the direct directed transfer function (dDTF), which distinguishes direct interactions between brain regions from indirect interactions via brain regions. ERC uses new statistical methods for comparing estimates of causal interactions during prestimulus “baseline” epochs and during poststimulus “activated” epochs in order to estimate event‐related increases and decreases in the functional interactions between cortical network components during cognitive tasks. The utility of the ERC approach is demonstrated through its application to human electrocorticographic recordings (ECoG) of a simple language task. ERC analyses of these ECoG recordings reveal frequency‐dependent interactions, particularly in high gamma (>60 Hz) frequencies, between brain regions known to participate in the recorded language task, and the temporal evolution of these interactions is consistent with the putative processing stages of this task. The method may be a useful tool for investigating the dynamics of causal interactions between various brain regions during cognitive task performance. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Cardiac auscultatory skills of internal medicine and family practice trainees. A comparison of diagnostic proficiency.

CONTEXT Medical educators have had a growing sense that proficiency in physical diagnostic skills is waning, but few data have examined the question critically. OBJECTIVE, DESIGN, AND SETTING To compare the cardiac auscultatory proficiency of medical students and physicians in training. A multicenter cross-sectional assessment of students and house staff. A total of 8 internal medicine and 23 family practice programs of the mid-Atlantic area. PARTICIPANTS A total of 453 physicians in training and 88 medical students. INTERVENTIONS All participants listened to 12 cardiac events directly recorded from patients, which they identified by completing a multiple-choice questionnaire. MAIN OUTCOME MEASURES scores were expressed as the percentage of participants, for year and type of training, who correctly identified each event. Cumulative scores were expressed as the total number of events correctly recognized. An adjusted score was calculated whenever participants selected not only the correct finding but also findings that are acoustically similar and yet absent. RESULTS Trainees' cumulative scores ranged between 0 and 7 for both internal medicine and family practice residents (median, 2.5 and 2.0, respectively). Internal medicine residents had the highest cumulative adjusted scores for the 6 extra sounds and for all 12 cardiac events tested (P=.01 and .02, respectively). On average, internal medicine and family practice residents recognized 20% of all cardiac events; the number of correct identifications improved little with year of training and was not significantly higher than the number identified by medical students. CONCLUSIONS Both internal medicine and family practice trainees had a disturbingly low identification rate for 12 important and commonly encountered cardiac events. This study suggests a need to improve the teaching and assessment of cardiac auscultation during generalists' training, particularly with the advent of managed care and its search for more cost-effective uses of technology.
The Changing Religious Cleavage in Canadians' Voting Behaviour

Abstract Past studies have shown that religion plays an important role in voting behaviour in Canada. Yet, little is known about the changes this religious vote has undergone over the past few decades. Using Canadian Election Studies data, we analyze the evolving impact of religious affiliation and level of religiosity on vote choice in federal elections between 1965 and 2011. We find that, as the marginal impact of Catholic and mainline Protestant traditions has declined, the effect of level of religiosity has gained in importance. In 2011, religious citizens were overall more likely to vote Conservative and secular individuals were more likely to vote NDP both in Quebec and in the rest of Canada. Some distinct voting patterns also remain for non-mainline Protestant groups in the ROC and religious nones in Quebec. Résumé Des études antérieures montrent à voir l'importance de la religion dans les comportements électoraux des Canadiens. Toutefois, nous savons peu quant aux mutations qu'a connues le vote religieux dans les dernières décennies. Employant des données de l’Étude électorale canadienne, nous analysons l’évolution de l'impact de l'affiliation religieuse et du niveau de religiosité sur le choix de vote fédéral entre 1965 et 2011. Nos résultats indiquent une disparition de l'effet distinct des affiliations catholique et protestante libérale au cours des années, jumelée avec une prise d'importance de l'effet du niveau de religiosité. En 2011, les individus religieux détenaient en moyenne une plus grande probabilité de voter pour le Parti Conservateur, et les individus séculiers pour le Parti NDP— au Québec et dans le reste du Canada. Quelques comportements électoraux distincts subsistent également pour les protestants des traditions non libérales dans le ROC ainsi que pour les sans religion au Québec.
Efficacy of aspirin (325 mg) + omeprazole (40 mg) in treating coronary artery disease

ABSTRACT Introduction: Aspirin is indicated for primary and secondary prevention of cardiovascular diseases (CVD) by major guidelines. However, its use may be associated with gastrointestinal (GI) toxicities, including, but not limited to, GI bleeding. This may lead to increased morbidity and mortality, as well as diminished compliance, which again leads to increased risk of major cardiovascular events. Modified formulations of aspirin often have comparable risks of GI toxicity despite their dose or formulation and have had limited success to prevent GI toxicities. Simultaneous treatment with Proton pump inhibitors (PPIs) has been used successfully to prevent GI toxicities from aspirin. However, addition of an extra medication may lead to lower compliance and hence ineffective or less than optimal treatment. Areas covered: After a selective literature search, a brief review of the available evidence regarding GI toxicity of aspirin and the protective effects of PPIs was conducted. The concept of combination tablets, and the available data about Aralez Pharmaceuticals’ YOSPRALA (aspirin (81 mg or 325 mg) and omeprazole (40 mg) fixed dose combination tablet being evaluated for secondary prevention of cardiovascular and cerebrovascular events in patients at risk for GI complications of aspirin therapy) is also presented. Expert opinion: The available evidence suggests that PPIs are the best option to prevent aspirin-related GI toxicities, but compliance is low in people who are prescribed both aspirin and PPI. Combination tablets containing both aspirin and a PPI may be a good option for providing protection against GI toxicities in people who require aspirin for secondary prevention of cardiovascular diseases.
Thermal and electrical characterization of nanocomposites for thermoelectrics

Nanostructures have been shown theoretically, and to a certain extent experimentally, to exhibit enhanced thermoelectric properties. While the use of thermoelectric devices is not widespread today, even marginal improvements in performance could lead to a revolution in small-scale energy conversion and generation and heat removal applications. The potential integration of nanostructures into actual thermoelectric devices has not been fully realized since these devices generally require larger scale materials for the thermoelectric elements. Therefore, a focused investigation into thermal, electrical and thermoelectric characteristics of nanocomposites comprised of nanostructures that, in their bulk form, exhibit good thermoelectric characteristics, was conducted. The presented research explores the thermal and electrical properties of nanocomposites comprised of bismuth nanoparticles that were embedded in a conducting polymer matrix. The thermal and electrical conductivities as well as the thermopower of thin films of polyaniline (the conducting polymer) with different volume fractions of nanoparticles were measured. Results demonstrate that the thermal and electrical properties of polyaniline may be significantly influenced by the presence of the nanoparticles
Results of Strontium-89 Therapy in Patients With Prostate Cancer Resistant to Chemotherapy

Purpose: Strontium-89 (Sr-89) chloride is an effective palliative treatment of the bone metastases of prostate cancer. Chemotherapy has also been shown to have a palliative benefit in this disease. We aimed to determine the benefits and complications of Sr-89 therapy in patients with prostate cancer who had become refractory to chemotherapy. We conducted a retrospective review of 14 treatments administered to 13 patients with chemotherapy-resistant and hormone-resistant prostate cancer. Results: Of the 14 administered treatments, 8 (57%) resulted in improved pain control, with 2 patients able to stop analgesia. The median duration of response was 56 days. No prostate-specific antigen response was seen in the 8 patients tested. There was significant and prolonged bone marrow toxicity, with 6 patients requiring red blood cell transfusion. Prolonged thrombocytopenia was seen, with platelet counts remaining below baseline levels after treatment in all but one patient. Leukopenia was generally mild and not associated with infection. Conclusions: Sr-89 is an effective treatment of patients with chemotherapy-refractory prostate cancer, but careful and prolonged monitoring of hematologic parameters after therapy is required.
Reproduction of Meloidogyne incognita and M. graminis on Several Grain Sorghum Hybrids

Abstract A total of 27 grain sorghum hybrids were evaluated in a series of greenhouse experiments to determine their susceptibility to Meloidogyne incognita race 3 and M. graminis. Each hybrid was inoculated with 2,000 nematode eggs/pot. Reproduction by M. incognita was numerically greater than M. graminis on 93% of the hybrids tested, indicating that grain sorghum is a better host for M. incognita than M. graminis. A wide variation in host suitability was observed on these hybrids in a second experiment as reproduction by M. incognita ranged from 395 to 3,818 eggs/g of root. Only two hybrids, Terral RV9782 and RV9823, consistently supported ,20% reproduction by M. incognita compared to the most susceptible hybrid, Golden Acres 5556. Reproduction of four isolates of M. incognita was evaluated on six selected hybrids in a third greenhouse experiment. Hybrid susceptibility was similar to that observed in the previous experiment for all isolates. A difference in isolate aggressiveness was observed between two of the four isolates across all hybrids. In fields where damaging populations of M. incognita are present, most grain sorghum hybrids will likely maintain or increase the nematode population for the subsequent crop.
Efficacy of oral dexamethasone in outpatients with acute bronchiolitis.

OBJECTIVE To examine the efficacy of oral dexamethasone in acute bronchiolitis. STUDY DESIGN A double-blind randomized, placebo-controlled trial involving 70 children < 24 months old in the emergency department with Respiratory Disease Assessment Instrument > or = 6. Each patient received either 1 dose of 1 mg/kg of oral dexamethasone or placebo and was assessed hourly for a 4-hour period. Repeated measures regression analysis evaluated a change in the Respiratory Assessment Change Score (RACS). RESULTS The 2 groups had similar baseline characteristics with Respiratory Disease Assessment Inventory of 9.4 +/- 2.3 in the dexamethasone group (n = 36) and 10.0 +/- 2.7 in the placebo group (n = 34). The RACS was -5.0 +/- 3.1 in the dexamethasone group and -3.2 +/- 3.7 in the placebo group (P =.029). Poor RACS occurred in 41% and 17% of the placebo and dexamethasone groups, respectively (P =.034). Of the children treated with dexamethasone, 19% were hospitalized compared with 44% in the placebo group (P =.039). There was no difference in RACS between the groups on day 7 (P =.75). CONCLUSION Outpatients with moderate-to-severe acute bronchiolitis derive significant clinical and hospitalization benefit from oral dexamethasone treatment in the initial 4 hours of therapy.
Oligodendroglia are limited in type I interferon induction and responsiveness in vivo

Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism for oligodendroglia and microglia to probe innate antiviral responses during acute encephalomyelitis. Expression of genes associated with the IFNα/β pathways was monitored in microglia and oligodendroglia purified from naïve and infected mice by fluorescent activated cell sorting. Compared with microglia, oligodendroglia were characterized by low basal expression of mRNA encoding viral RNA sensing pattern recognition receptors (PRRs), IFNα/β receptor chains, interferon sensitive genes (ISG), as well as kinases and transcription factors critical in IFNα/β signaling. Although PRRs and ISGs were upregulated by infection in both cell types, the repertoire and absolute mRNA levels were more limited in oligodendroglia. Furthermore, although oligodendroglia harbored higher levels of viral RNA compared with microglia, Ifnα/β was only induced in microglia. Stimulation with the double stranded RNA analogue poly I:C also failed to induce Ifnα/β in oligodendroglia, and resulted in reduced and delayed induction of ISGs compared with microglia. The limited antiviral response by oligodendroglia was associated with a high threshold for upregulation of Ikkε and Irf7 transcripts, both central to amplifying IFNα/β responses. Overall, these data reveal that oligodendroglia from the adult CNS are poor sensors of viral infection and suggest they require exogenous IFNα/β to establish an antiviral state. © 2012 Wiley Periodicals, Inc.
Peer-Group Detection of Banks and Resilience to Distress

The paper looks at the importance of the true business model in shaping the risk profile of financial institutions. We adopt a novel indirect clustering approach to enrich the classic bank business model classification on a global data set including about 11,000 banks, both listed and non-listed representing more than 180 countries over the period 2005-2014. A comprehensive list of global distress events, which combines bankruptcies, liquidations, defaults, distressed mergers, and public bailouts, is regressed against financial statement ratios (i.e. proxies for CAMELS) and controlling for macro and sectoral effects using a rare-event logit model. Our findings suggest that individual characteristics along with macro and sectoral factors contribute differently, sometimes with opposite sign, to the likelihood of distress and to the volatility of business models with the exception of liquidity whose contribution appears exogenous to business model choice. By capturing the switching behaviour across groups, we find that business model volatility exacerbates vulnerability and distress, especially if moving from wholesale-oriented to deposit oriented groups.
Advancing Understanding of Knowledge's Role in Lay Risk Perception

Emphasizing how knowledge affects lay Risk perception, summarizing studies and suggesting further research, the author differentiates between knowledge production, knowledge dissemination and information processing as affected by, e.g., heuristics and Risk aversion. He also suggests that better understanding of lay knowledge can also illuminate experts' hazard knowledge.
Entry into Working Life: Internal Migration and the Job Match Quality of Higher‐Educated Graduates

We estimate the impact of internal migration on job-match quality for recent Dutch university and college graduates. We find positive yet modest wage returns. After controlling for the self-selection of migrants with an IV approach, this effect is no longer significant for university graduates and all graduates from peripheral areas. We also find that, for our alternative job-match measures, where there is evidence of migrant self-selection, controlling for self-selection strongly reduces the effect of internal migration on job-match quality. In some cases, the returns on internal migration are found to be negative, which may signal forced migration.