Miracle-dz/UniFAR-FTUs huggingface dataset:
Cholesterol lipids of Borrelia burgdorferi form lipid rafts and are required for the bactericidal mechanism of a complement-independent antibody

SUMMARY Borrelia burgdorferi (the agent of Lyme disease) is unusual in that it contains free cholesterol and cholesterol glycolipids. It is also susceptible to complement-independent bactericidal antibodies, such as CB2, a monoclonal IgG1 against outer surface protein B (OspB). The bactericidal action of CB2 requires the presence of cholesterol glycolipids and cholesterol. Through ultrastructural, biochemical and biophysical approaches, we show that these cholesterol glycolipids exist as lipid raft-like microdomains in the outer membrane of cultured and mouse-derived B. burgdorferi , and in model membranes from B. burgdorferi lipids. The order and size of the microdomains of intact cells and model membranes are temperature sensitive and correlate with the bactericidal activity of CB2. Here we demonstrate the existence of cholesterol-containing lipid raft-like microdomains in a prokaryote. be due to the absence of cholesterol in all but a few bacteria, namely Helicobacter , Mycoplasma , Ehrlichia , Anaplasma , Brachyspira , and, of course, Borrelia . We now show that lipid rafts exist in
[Burnout syndrome in medical staff affiliated to a tertiary care hospital].

INTRODUCTION the burnout syndrome (BS) is common among physicians, affecting their behavior, personality and professional goals; thus deteriorating the quality of their performance. OBJECTIVE to determine the BS prevalence among physicians affiliated to a tertiary care hospital and its associated risk factors. MATERIAL AND METHODS The study was conducted through a cross-sectional design. The sampling was nonprobabilistic. Participating physicians were interviewed using the Maslach Burnout Inventory and the Beck's depression inventory. The analysis included ascertainment of the BS prevalence and use of chi(2) and logistic regression analysis. The local Internal Review Board and the Ethics Committee approved the project and all participants gave their informed consent. RESULTS 166 physicians participated; the average age was 42 years, most were men. The response rate was 87.4 %. The prevalence of depression with more than 10 points in the Beck inventory was 18.6 % (95 % CI: 12-24). Depression in the last two years was 38.6%; the prevalence of BS was 26%; 15. 2 % scored above 27 in emotional exhaustion and 19.3 % scored more than 10 points in depersonalization. The risk of being depressed due to BS was five times higher (OR 5.163; 95 % CI 2.130-12.5). Working in the night shift, living without a permanent couple and being depressed were the main risk factors for BS. CONCLUSIONS BS is common among physicians and is associated with organizational and personal variables.
Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior olive

Principal neurons of the lateral superior olive (LSO) detect interaural intensity differences by integration of excitatory projections from ipsilateral bushy cells and inhibitory inputs from the medial nucleus of the trapezoid body. The intrinsic membrane currents active around firing threshold will form an important component of this binaural computation. Whole cell patch recording in an in vitro brain slice preparation was employed to study conductances regulating action potential (AP) firing in principal neurons. Current‐clamp recordings from different neurons showed two types of firing pattern on depolarization, one group fired only a single initial AP and had low input resistance while the second group fired multiple APs and had a high input resistance. Under voltage‐clamp, single‐spiking neurons showed significantly higher levels of a dendrotoxin‐sensitive, low threshold potassium current (ILT). Block of ILT by dendrotoxin‐I allowed single‐spiking cells to fire multiple APs and indicated that this current was mediated by Kv1 channels. Both neuronal types were morphologically similar and possessed similar amounts of the hyperpolarization‐activated nonspecific cation conductance (Ih). However, single‐spiking cells predominated in the lateral limb of the LSO (receiving low frequency sound inputs) while multiple‐firing cells dominated the medial limb. This functional gradient was mirrored by a medio‐lateral distribution of Kv1.1 immunolabelling. We conclude that Kv1 channels underlie the gradient of LSO principal neuron firing properties. The properties of single‐spiking neurons would render them particularly suited to preserving timing information.
Anti-Infective Potential Of A Medicinal Plant Pimpenella Stewartii Used Traditionally In Hazara.

BACKGROUND Medicinal plants have been used since long as folk medicines and also in Ayuvedic and Unani systems of treatment. They have importance to save human and animal lives because of their utilization in the herbal medicines. In all over the word plants are in constant use for curing of various kinds of diseases. The herbal medicines are effective due to presence of bioactive compounds along with vitamins and minerals in them. Moreover, plants produce photo-chemicals mainly secondary metabolites which have significant pharmaceutical activities like antioxidant, antimicrobial, pesticidal and anti-tumour activity. They are very effective and have little or no side effects. METHODS Five microbial strains including three fungal and two bacterial species were tested for the efficacy of plant materials by Agar diffusion method. The fungal species were Aspergilus flavus, Aspergilus niger and Alternaria alternata while bacterial species included Arvenia caratovora and Xanthomans spp. RESULTS Results obtained for methanolic extracts of Pimpenella stewartii against Aspergilus flavus, Aspergilus niger and Alternaria alternata showed significant antifungal activity. The antibacterial screening of Methanolic extracts of Pimpenella stewartii were evaluated against Arvenia caratovora and Xanthomans spp. The best zone of inhibition was found against Xanthomans spp (97.33±2 mm) at 250 ppm concentration followed by Arvenia caratovora (49.7±14 mm) at same concentration.
Differential cardiovascular and hypothalamic pituitary response to amphetamine in male pathological gamblers versus healthy controls

Cardiovascular and hypothalamic pituitary axis (HPA) disturbances have been observed in individuals who are pathological gamblers (PGs). These may partly derive from chronic exposure to gambling. Response to amphetamine (AMPH) may reveal such disturbances while controlling for differential conditioned responses to gambling in PGs vs healthy controls (HCs). This study assessed heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) and plasma cortisol following oral AMPH (0.4 mg/kg) in male PGs (n=12) and HCs (n=11) who underwent a positron emission tomography (PET) scan. The Stop Signal Task enabled assessment of the link between physiological and behavioral dysregulation. Trait moderating effects were explored. The responses of PGs to AMPH differed from those of HCs on every index. PGs displayed persistent elevation in DBP and concomitant reduction in HR (i.e. baroreflex) compared to HCs beyond 90 min post-dose. PGs displayed deficits in cortisol compared to HCs that were partially reversed by AMPH. Impairment on the Stop Signal Task correlated positively with HR in controls, but negatively with HR in PGs, suggesting that strong initial and compensatory cardiac responses to a stimulant may each predict disinhibition. Extraversion predicted greater disinhibition in PGs. Noradrenergic disturbances may contribute to sensitized responses to stimulant challenge and disinhibition in PGs.
Improvement of Perfusion and Function of Ischaemic Porcine Myocardium after Reduction of Heart Rate by Alinidine

Summary We studied the effect of alinidine on myocardial perfusion and function in 10 open-chest pigs with left anterior descending coronary artery (LAD) stenosis. Following LAD stenosis the systolic myocardial wall thickening (ultrasound) was reduced to 30% of the base-line value and the trans-mural blood flow and the endocardial/epicardial (endo/epi) ratio (microsphere method) in the affected segment of myocardium decreased from 1.42 ± 0.15 to 0.68 ±0.11 ml/min/g and from 1.05 ± 0.08 to 0.59 ± 0.10, respectively. Alinidine, in a dose (0.4–0.9 mg/kg) that decreased the heart rate by about 25%, caused a marked redistribution of ischaemic flow in favour of the endocardium: the endo/epi ratio increased to 1.08 ± 0.12. Concomitantly, systolic myocardial wall thickening of the hypokinetic myocardial segment returned to half its base-line value. The flow to the control area was decreased transmurally by about 30%, so that despite the presence of the stenosis, the whole heart was nearly homogenously perfused after alinidine. Right atrial pacing to the predrug heart rate only partially reduced the effects of alinidine on the endo/epi ratio (0.86 ± 0.09) of the ischaemic myocardium; wall thickness variables did not change. It is concluded that alinidine ameliorates the imbalance between oxygen supply and demand in the post-stenotic segment of the myocardium. Prolongation of the diastolic perfusion period through heart rate reduction plays an important role in the favourable redistribution of myocardial blood flow, but other factors, such as negative inotropic effects of alinidine, may also be involved.
Cardiovascular consequences of completing a 160-km ultramarathon.

PURPOSES To comprehensively investigate the cardiovascular consequences of a 160-km ultramarathon using traditional echocardiography, speckle tracking imaging, cardiac biomarkers, and heart rate variability (HRV) and to examine the relationship between the changes in these variables. METHODS We examined athletes before an ultramarathon and reassessed all finishers immediately after the race. Left ventricular (LV) systolic (ejection fraction [EF], systolic blood pressure/end-systolic volume [SBP/ESV] ratio) and diastolic (ratio of early [E] to late [A], filling E:A) measurements were assessed using traditional echocardiography, whereas myocardial peak strain and strain rate were analyzed using speckle tracking. Cardiac biomarkers measured were cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). HRV indices were assessed using standard frequency and time domain measures. RESULTS Twenty-five athletes successfully completed the race (25.5 +/- 3.2 h). Significant pre- to postrace changes in EF (66.8 +/- 3.8 to 61.2 +/- 4.0 %, P < 0.05) and E:A ratio (1.62 +/- 0.37 to 1.35 +/- 0.33, P < 0.05) were reported. Peak strain was significantly decreased in all planes, with the largest reduction occurring circumferentially. NT-pro-BNP concentrations increased significantly (28 +/- 17.1 vs 795 +/- 823 ng x L, P < 0.05), whereas postrace cTnT were elevated in just five athletes (20%). No significant alterations in HRV were noted postrace. Reductions in LV function were not significantly associated with changes in cardiac biomarkers and/or HRV. CONCLUSIONS Although the stress of an ultramarathon resulted in a mild reduction in LV function and biomarker release, the mechanisms behind such consequences remain unknown. It is likely that factors other than myocardial damage or strong vagal reactivation contributed to postexercise decreases in LV function after an ultramarathon.
Pediatric bone sarcoma: diagnostic performance of ¹⁸F-FDG PET/CT versus conventional imaging for initial staging and follow-up.

OBJECTIVE The purpose of this study was to compare the diagnostic performance of (18)F-FDG PET/CT and conventional imaging for staging and follow-up of pediatric osteosarcoma and skeletal Ewing sarcoma. MATERIALS AND METHODS We calculated sensitivity, specificity, and accuracy of PET/CT and conventional imaging (CT, MRI, bone scanning) for sites of disease and number of lesions. Diagnostic benefit, defined as better characterization of lesions, was evaluated on a per-scan basis, comparing PET/CT and conventional imaging. RESULTS A total of 412 lesions were characterized by imaging in 64 patients (20, osteosarcoma; 44, Ewing sarcoma). For osteosarcoma patients PET/CT was available only at follow-up, where it proved more accurate than conventional imaging for the detection of bone lesions (accuracy, 95% vs 67% for CT and 86% for MRI) and complementary to CT in evaluating lung nodules (sensitivity, 84% vs 94%; specificity, 79% vs 71%) with diagnostic benefit in 18% of examinations. In patients with Ewing sarcoma, PET/CT tended to perform better during follow-up than at initial staging (accuracy, 85% vs 69%). For lung findings, PET/CT was more specific than CT but was less sensitive. The diagnostic benefit of PET/CT was greater at staging (28%) than during followup (9%). On a per-patient basis, PET/CT provided diagnostic benefit in 21 of 44 patients with Ewing sarcoma and nine of 20 patients with osteosarcoma at least once during clinical management. CONCLUSION FDG PET/CT provides diagnostic benefit in Ewing sarcoma and osteosarcoma, with the exception of small lung nodules. Prospective studies are needed to define the best imaging algorithm and combination of tests in the staging and follow-up of patients with pediatric bone sarcoma.
De Novo Sirolimus-Based Immunosuppression After Liver Transplantation for Hepatocellular Carcinoma: Long-Term Outcomes and Side Effects

Background. We report long-term outcomes and side effects after transplantation for hepatocellular carcinoma (HCC) using de novo, sirolimus-based immunosuppression (IS). Methods. A total of 70 patients with HCC (mean age: 54.4±7 years, female/male: 12/58) were transplanted and included in the study. Immunosuppression included de novo sirolimus, low-dose calcineurin inhibitor for 6 to 12 months, with short-course (3 months) or no steroids. Results. After 49 months-median follow-up, eight patients have experienced an HCC recurrence, 2 of 34 when Milan criteria were respected (6%) and 6 of 36 when beyond Milan criteria (17%). One- and 4-year tumor-free survivals were 85 and 73%, when Milan criteria were respected and 82% and 75% when they were not, respectively. (P=0.9). After recurrence, mean survival was 23±28 months. Half (35 of 70) of the patients experienced a rejection. Incisional hernia (24 of 70, 34%), wound infection (12 of 70, 17%), anemia (39 of 70, 56%), leucopenia (39 of 70, 56%), high triglyceride (43 of 70, 61%), and cholesterol (28 of 70, 40%) levels and mouth ulcers (20 of 70, 29%) were among the most frequent complications. No hepatic artery thrombosis was observed. Conclusions. These data suggest that de novo sirolimus-based immunosuppression is associated with satisfactory outcomes after transplantation, even in selected patients beyond Milan criteria. The protocol has proven safe, with an acceptable side-effect profile. This study supports the conduct of larger randomized trials investigating sirolimus after transplantation for HCC.
The close relatives of people who have had a traumatic brain injury and their special needs

Primary objective: This study aims to paint a picture of the needs of people close to individuals with a TBI and the services offered to answer these needs, from the point of view of the individuals with a TBI and health professionals. Research design: This study has a qualitative design and a reflexive group was used to collect data. The démarche réflexive d’analyse en partenariat, DRAP (developing reflexive analysis for partnership) was used as a data collection method. The sample comprised Montreal family members (n = 4), Outaouais family members (n = 8), Abitibi family members (n = 7); Montreal care providers (n = 9), Outaouais care providers (n = 11) and Abitibi care providers (n = 9). Main outcomes and results: The results show that people close to individuals with a TBI need information on the health problem, specifically with regard to the diagnostic, the prognostic, and the factors that influence it, as well as the steps towards rehabilitation, and care and services. The results show that close ones need specific, quality services and continuity of services. Conclusion: In conclusion, the pertinence of this study lies in the desire of close ones and health professionals to ease the adaptation process imposed by a TBI, and to promote the well-being of informal caregivers.
The Anaerobic Regulatory Network Required for Pseudomonas aeruginosa Nitrate Respiration

ABSTRACT In Pseudomonas aeruginosa, the narK 1 K 2 GHJI operon encodes two nitrate/nitrite transporters and the dissimilatory nitrate reductase. The narK 1 promoter is anaerobically induced in the presence of nitrate by the dual activity of the oxygen regulator Anr and the N-oxide regulator Dnr in cooperation with the nitrate-responsive two-component regulatory system NarXL. The DNA bending protein IHF is essential for this process. Similarly, narXL gene transcription is enhanced under anaerobic conditions by Anr and Dnr. Furthermore, Anr and NarXL induce expression of the N-oxide regulator gene dnr. Finally, NarXL in cooperation with Dnr is required for anaerobic nitrite reductase regulatory gene nirQ transcription. A cascade regulatory model for the fine-tuned genetic response of P. aeruginosa to anaerobic growth conditions in the presence of nitrate was deduced.
Adenovirus type 5 fiber knob binds to MHC class I α2 domain at the surface of human epithelial and B lymphoblastoid cells

Adenovirus serotype 5 (Ad5) fiber receptor was investigated using reverse antibody biopanning of a phage‐displayed hexapeptide library, and virus‐neutralizing monoclonal antibodies (mAbs 1D6.3 and 7A2.7) raised against recombinant Ad5 fiber knob. Both mAbs inhibited attachment of Ad5 to HeLa cells. Mimotopes of 1D6.3 showed homology with the C‐terminal segment of the α2 domain of the heavy chain of human MHC class I molecules (MHC‐I α2), and mimotopes of 7A2.7 were consensus to human fibronectin type III (FNIII) modules. In vitro, GST‐fused MHC‐I α2‐ and FNIII‐derived oligopeptides interacted with recombinant fibers in a subgroup‐specific manner. In vivo, the MHC–I α2 synthetic icosapeptide RAIVGFRVQWLRRYFVNGSR showed a net neutralization effect on Ad5 in HeLa cells, whereas the FNIII icosapeptide RHILWTPANTPAMGYLARVS significantly increased Ad5 binding to HeLa cells. Daudi cells, which lack surface expression of HLA class I molecules, showed a weak capacity for Ad5 binding. In β2‐microglobulin‐transfected Daudi cells, Ad5 attachment and permissivity were restored to HeLa cell levels, with 4000 receptors per cell and a binding constant of 1.4×1010/M. The results suggested that the conserved region of MHC‐I α2‐domain including Trp167 represents a high affinity receptor for Ad5 fiber knob, whereas ubiquitous FNIII modules would serve as auxiliary receptors.
Transcriptional regulation of lignin biosynthesis

Lignin is the second most abundant plant biopolymer mainly present in the secondary walls of tracheary elements and fibers in wood. Understanding how lignin is biosynthesized has long been an interest to plant biologists and will have a significant impact on tree biotechnology. Lignin is polymerized from monolignols that are synthesized through the lignin biosynthetic pathway. To make lignin, all the genes in the lignin biosynthetic pathway need to be coordinately turned on. It has been shown that a common cis-element, namely the AC element, is present in the majority of the lignin biosynthetic genes and required for their expression in lignifying cells. Important progress has been made in the identification of transcription factors that bind to the AC elements and are potentially involved in the coordinated regulation of lignin biosynthesis. The Arabidopsis MYB58 and MYB63 together with their poplar ortholog PtrMYB28 are transcriptional activators of the lignin biosynthetic pathway, whereas the eucalyptus EgMYB2 and pine PtMYB4 transcription factors are likely Arabidopsis MYB46 orthologs involved in the regulation of the entire secondary wall biosynthetic program. It was found that the transcriptional regulation of lignin biosynthesis is under the control of the same transcriptional network regulating the biosynthesis of other secondary wall components, including cellulose and xylan. The identification of transcription factors directly activating lignin biosynthetic genes provides unprecedented tools to potentially manipulate the amount of lignin in wood and other plants products based on our needs.
The CHD3 Remodeler PICKLE Promotes Trimethylation of Histone H3 Lysine 27*

CHD3 proteins are ATP-dependent chromatin remodelers that contribute to repression of developmentally regulated genes in both animal and plant systems. In animals, this repression has been linked to a multiple subunit complex, Mi-2/NuRD, whose constituents include a CHD3 protein, a histone deacetylase, and a methyl-CpG-binding domain protein. In Arabidopsis, PICKLE (PKL) codes for a CHD3 protein that acts during germination to repress expression of seed-associated genes. Repression of seed-associated traits is promoted in pkl seedlings by the plant growth regulator gibberellin (GA). We undertook a microarray analysis to determine how PKL and GA act to promote the transition from seed to seedling. We found that PKL and GA act in separate pathways to repress expression of seed-specific genes. Comparison of genomic datasets revealed that PKL-dependent genes are enriched for trimethylation of histone H3 lysine 27 (H3K27me3), a repressive epigenetic mark. Chromatin immunoprecipitation studies demonstrate that PKL promotes H3K27me3 in both germinating seedlings and in adult plants but do not identify a connection between PKL-dependent expression and acetylation levels. Taken together, our analyses illuminate a new pathway by which CHD3 remodelers contribute to repression in eukaryotes.