Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermal denaturation pathway of starch phosphorylase from Corynebacterium callunae: Oxyanion binding provides the glue that efficiently stabilizes the dimer structure of the protein

Starch phosphorylase from Corynebacterium callunae is a dimeric protein in which each mol of 90 kDa subunit contains 1 mol pyridoxal 5′‐phosphate as an active‐site cofactor. To determine the mechanism by which phosphate or sulfate ions bring about a greater than 500‐fold stabilization against irreversible inactivation at elevated temperatures (≥50°C), enzyme/oxyanion interactions and their role during thermal denaturation of phosphorylase have been studied. By binding to a protein site distinguishable from the catalytic site with dissociation constants of Ksulfate = 4.5 mM and Kphosphate≈︁16 mM, dianionic oxyanions induce formation of a more compact structure of phosphorylase, manifested by (a) an increase by about 5% in the relative composition of the α‐helical secondary structure, (b) reduced 1H/2H exchange, and (c) protection of a cofactor fluorescence against quenching by iodide. Irreversible loss of enzyme activity is triggered by the release into solution of pyridoxal 5′‐phosphate, and results from subsequent intermolecular aggregation driven by hydrophobic interactions between phosphorylase subunits that display a temperature‐dependent degree of melting of secondary structure. By specifically increasing the stability of the dimer structure of phosphorylase (probably due to tightened intersubunit contacts), phosphate, and sulfate, this indirectly (1) preserves a functional active site up to≈︁ 50°C, and (2) stabilizes the covalent protein cofactor linkage up to ≈︁ 70°C. The effect on thermostability shows a sigmoidal and saturatable dependence on the concentration of phosphate, with an apparent binding constant at 50°C of ≈︁ 25 mM. The extra stability conferred by oxyanion‐ligand binding to starch phosphorylase is expressed as a dramatic shift of the entire denaturation pathway to a ≈︁ 20°C higher value on the temperature scale.
Long-term outcomes of acute myeloid leukemia in adults in Pakistan.

OBJECTIVE To describe the long-term outcomes of Acute Myeloid Leukemia (AML) and to study clinicopathological features at presentation, morphological subtypes and remission rates. METHODS Demographic information, response to therapy and survival of patients (>14 years of age) admitted between January 1988 to August 1996 with acute myeloid leukaemia was retrieved and analysed. RESULTS Seventy-four patients were admitted with a diagnosis of AML during the study period. There were 43 males and 31 females. Age ranged between 15 and 70 years with a mean age of 38 years. The most common presenting feature was fever (67.5%) and the morphological subtype according to French-American-British Group (FAB) criteria was M4. Fifty-five patients received treatment and were evaluable for response and outcomes. Thirty-six (65.4%) patients had complete remission. Sixteen (29.1%) died during the first 28 days after starting induction chemotherapy. The median survival was 11 months. Six (11%) patients (4 females, 2 males) are surviving beyond 4 years (long-term survivors). CONCLUSION Our study suggests that the long-term outcomes of adults with AML are comparable to what has been reported in the literature for patients who do not receive bone marrow transplants.
Assessment and characterisation of yeast-based products intended to mitigate ochratoxin exposure using in vitro and in vivo models

The aim of this paper was to evaluate the capacity of several yeast-based products, derived from baker’s and brewer’s yeasts, to sequester the mycotoxin ochratoxin A (OTA) and to decrease its rate of absorption and DNA adduct formation in vivo. The experimental protocol included in vitro binding studies using isotherm models, in vivo chicken experiments, in which the serum and tissue concentrations of OTA were analysed in the absence and presence of the test compounds, and the profile of OTA-derived metabolites and their associated DNA adducts were determined. Additionally in vitro cell culture studies (HK2 cells) were applied to assess further the effects for yeast cell product enriched with glutathione (GSH) or selenium. Results of the in vitro binding assay in a buffer system indicated the ability of the yeast-based products, as sequester of OTA, albeit at a different level. In the in vitro experiments in chickens, decreased serum and tissue concentrations of treated animals confirmed that yeast-based products are able to prevent the absorption of OTA. A comparison of the binding affinity in a standard in vitro binding assay with the results obtained in an in vivo chicken experiment, however, showed a poor correlation and resulted in a different ranking of the products. More importantly, we could show that yeast-based products actively modulate the biotransformation of OTA in vivo as well as in vitro in a cell culture model. This effect seems to be attributable to residual enzymatic activities in the yeast-based products. An enrichment of yeast cell wall products with GSH or selenium further modulated the profile of the generated OTA metabolites and the associated pattern of OTA-induced DNA adducts by increasing the conversion of OTA into less toxic metabolites such as OTA, OTB and 4-OH-OTA. A reduced absorption and DNA adduct formation was particularly observed with GSH-enriched yeast, whereas selenium-enriched yeasts could counteract the OTA-induced decrease in cell viability, but at the same time increased the OTA–DNA adducts formation. These findings indicate the need for an in-depth characterisation of yeast-based products used as mycotoxin-mitigating feed additives, in in vivo models with target animal species taking into account not only their ability to sequester toxins in the gastrointestinal tract but also their potential effects on the biotransformation of mycotoxins. Graphical Abstract
P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria

A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP) accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1) cell differentiation to the detriment of follicular T helper (Tfh) cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.
Association between Helicobacter pylori seropositivity and digestive tract cancers.

AIM To explore the role of Helicobacter pylori (H pylori) infection on the risk of digestive tract cancers. METHODS In total, 199 oral squamous-cell carcinoma (SCC), 317 esophageal SCC, 196 gastric cardia and non-cardia adenocarcinoma and 240 colon adenocarcinoma patients were recruited for serum tests of H pylori infection. Two hospital- and one community-based control groups were used for the comparisons. H pylori seropositivity was determined by an enzyme linked immunosorbent assay method against H pylori IgG. RESULTS Presence of H pylori infection was significantly inversely associated with esophageal SCC [adjusted odds ratio (AOR): 0.315-0.472, all P-value < 0.05] but positively associated with gastric adenocarcinoma (both cardia and non-cardia) (AOR: 1.636-3.060, all P-value < 0.05) in comparison to the three control groups. Similar results were not found in cancers of the oral cavity and colon. CONCLUSION Our findings support the finding that H pylori seropositivity is inversely associated with esophageal SCC risk, but increases the risk of gastric cardia adenocarcinoma.
Effect of Fv-1 gene product on proviral DNA formation and integration in cells infected with murine leukemia viruses.

The amounts of unintegrated murine leukemia virus-specific DNA detected by molecular hybridization in extracts of Fv-ln/n (strains NIH/3T3, SIM) or Fv-lb/b (strains JLS-V9, SIM.R) mouse cells after infection with N- or B-tropic viruses were found to be the same in both permissive and resistant cells. Therefore, formation of DNA products from the viral RNA template does not appear to be grossly affected by the Fv-l gene product. Integration of virus-specific DNA into chromosomal cellular DNA was assayed by hybridization of radioactive complementary DNA to DNA from infected cells. With either NIH/3T3 or SIM.R cells infected with N- or B-tropic viruses, integration of proviral DNA could be detected in permissive cells but not in nonpermissive cells. The Fv-l gene product therefore appears to prevent integration of proviral DNA.
Treatment Practices and Barriers for Depression and Anxiety by Primary Care Advanced Practice Nurses in Wyoming

Purpose The aim of this study was to investigate barriers to treatment and screening related to depression and anxiety and the diagnostic and treatment practices of primary care advanced practice nurses (APNs) in the state of Wyoming. Data sources Every primary care APN in Wyoming received a mailed questionnaire asking them about treatment barriers, screening and treatment practices, and attitudes toward depression and anxiety. Conclusions Wyoming APNs in primary care routinely identify, evaluate, and treat patients with both depression and anxiety. APNs generally felt positive about treating these patients, although they reported that their patients encounter a number of financial barriers in accessing treatment. Routine screening practices for depression and anxiety were relatively low among the APNs, and they used a wide variety of interventions for these patients. Implications for practice The findings identify a lack of standardized approaches to assessment, referral, and treatment, especially pharmacologic intervention, and may indicate the need for alterations in the educational preparation of primary providers in order to improve clinical outcomes of treatment for depression and anxiety.
Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of L‐arginine in regenerated endothelial cells

1 We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium‐dependent relaxation (EDR) and changes in the contents of L‐arginine, NG–monomethyl‐L‐arginine (l‐NMMA), asymmetrical NG, NG–dimethylarginine (ADMA) and symmetrical NG, NG–dimethylarginine (SDMA) in the regnerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery. 2 Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed. 3 L‐NMMA and ADMA contents in the regenerated ECs (23.5 ± 4.3 and 21.2 ± 2.0 pmol mg−1 DNA, respectively) were significantly (P<0.05 and P<0.01) higher than those in the control ECs (8.8 ± 3.0 and 7.4plusmn;1.9 pmol mg−1 DNA, respectively), whereas L‐arginine was significantly (P< 0.005) decreased in the regenerated ECs (31,470±1,050 pmol mg−1 DNA) as compared to that in the control ECs (47,870±1,890 pmol mg−1 DNA). SDMA content was below the assay limits. 4 L‐NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration‐dependent manner. The inhibition with L‐NMMA and ADMA was prevented by an addition of L‐arginine, but not by D‐arginine. 5 These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L‐arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.
Dietary intake of fibers: differential effects in men and women on perceived general health and immune functioning

ABSTRACT Background: It has been reported previously that dietary fiber intake provides health benefits. Nevertheless, only a limited number of human studies have investigated whether gender differences exist in the relationship between fiber intake and perceived health and immune status. Objective: To investigate potential gender differences in the effects of dietary fiber intake on perceived health and immune status of healthy young adults. Design: A survey was conducted among university students in Utrecht, the Netherlands. Data were collected on perceived general health status and perceived immune functioning. Dietary intake of fibers was assessed using a food frequency questionnaire. Perceived general health status and immune functioning were associated with daily intake of fibers using nonparametric (Spearman) correlations. Statistical analyses were conducted for the group as a whole, and for men and women separately. Results: N = 509 subjects completed the survey. Mean (SD) age was 20.8 (2.6) years old. 71.9% of the samples were females. Mean daily dietary fiber intake was 15.5 (6.9) g. Daily dietary fiber intake correlated significantly with general health rate (r = 0.171, p = 0.0001) and perceived immune functioning (r = 0.124, p = 0.008). After controlling for total caloric intake, the partial correlation between fiber intake and general health remained significant (r = 0.151, p = 0.002). In men, dietary fiber intake correlated significantly with perceived general health status (r = 0.320, p = 0.0001) and immune functioning (r = 0.281, p = 0.002). After controlling for caloric intake, the association between dietary fiber intake and perceived general health (r = 0.261, p = 0.005) remained significant. Remarkably, no significant correlations were observed in women. Conclusion: A significant association between daily dietary fiber intake and perceived general health status and immune rate was found in men, but not in women. Future studies should further address the nature and causes of the observed gender differences, including validated biomarkers for immune responsiveness. Abbreviations: FFQ: Food frequency questionnaire; GIT: Gastrointestinal tract; NCDs: Non-communicable diseases; SCFA: Short-chain fatty acid
Personality and drug preferences in normal volunteers.

This study examined the relationship between drug preferences as measured in a laboratory-based choice procedure and measures of personality and attitudes toward drugs. Healthy volunteers participated in laboratory-based double-blind studies measuring preference for ethanol or diazepam vs placebo. Frequency of drug choice was examined in relation to subjects' scores on personality questionnaires. Drug choice was not related to any of the personality measures examined. Personality scores were, however, related to both gender and habitual drug use. These data suggest that personality does not strongly influence responses to single doses of drugs as assessed under controlled conditions. Personality may, nevertheless, affect drug use in natural settings via other mechanisms (e.g., interacting with psychosocial variables).
GeOI pMOSFETs Scaled Down to 30-nm Gate Length With Record Off-State Current

We present in this letter the most aggressive dimensions reported to date in Ge-channel transistors: pMOSFETs with 30-nm gate length on ultrathin germanium-on-insulator substrates (TGe = 25 nm). By improving both the Ge-enrichment technique and the transistor fabrication process, we demonstrate devices with controlled threshold voltage (Vth) and excellent short-channel effects. Moreover, the low defectivity and the very low thickness of the Ge film lead to a record drain OFF-state leakage for Ge-channel devices (< 1 nA/¿m at VDS = -1 V) and thus, to the best ON-state to OFF-state current ratio (ION/IOFF ~5 × 105), even at Lg = 55 nm.
Monotherapy with peginterferon alpha-2b {12 kDa} for chronic hepatitis C infection in patients undergoing haemodialysis.

BACKGROUND A combination of Peginterferon and Ribavirin is the standard treatment for patients with chronic hepatitis C viral infection (HCV). Ribavirin is contraindicated in patients with chronic renal failure (CRF). Conventional Interferon monotherapy is effective in around 30% of such patients. There is scanty data on the use of Peginterferon monotherapy in them. METHODS We describe our preliminary experience of monotherapy with Peginterferon alpha- 2b {12 kDa} (Peg-IFN) for HCV patients undergoing haemodialysis for CRF. They were treated with Peg-IFN 1 microg/kg body weight subcutaneously once a week for 24 weeks. In all patients, clinical (age, sex, mode of acquiring HCV, pattern of haemodialysis) and virological (HCV RNA quantitative-PCR and genotype) profile was noted at baseline. Early virological response at 12 weeks (EVR), end-of-treatment virological response at 24 weeks (ETVR) and sustained virological response after 6 months of stopping treatment (SVR) were noted during the follow-up period. RESULTS The clinical and virological characteristics of patients were as follows: Of a total number of 6 patients, 5 were male and 1 was female with an age range of 35 to 62 years. The duration of haemodialysis was from between 5 and 12 months before the start of treatment and its frequency lay between 1 and 3 times a week. The mode of acquiring HCV was blood transfusion (100%). All 6 cases suffered from chronic hepatitis. The genotype distribution was genotype 3 in 3 (50%), genotype 1 in 1 (16.7%) and genotype none of 6 in 2 (33.3%) patients. All the patients (100%) completed treatment. EVR was seen in all 6 patients (100%). ETVR was seen in 5 of 6 patients (83.3%). A follow-up period of more than 1 year was available in 4 patients. 3 of these 4 patients (75%) had SVR. A virological response was maintained in all 3 (100%) patients with SVR even after 6 months of renal transplantation. CONCLUSION Peg-IFN monotherapy is safe and effective in patients with HCV who are on haemodialysis for CRF.
SMOOTH POTENTIALS WITH PRESCRIBED BOUNDARY BEHAVIOUR

This paper examines when it is possible to find a smooth potential on a C1 domain D with prescribed normal derivatives at the boundary. It is shown that this is always possible when D is a Liapunov-Dini domain, and this restriction on D is essential. An application concerning C1 superharmonic extension is given.
Propagation of the virus of porcine epidemic diarrhea in cell culture

Porcine epidemic diarrhea virus (PEDV) was adapted to serial propagation in Vero cell cultures by adding trypsin to the medium. PEDV-infected cells showed a distinct cytoplasmic fluorescence when examined by a fluorescent-antibody-staining technique. Cytopathic effects, such as vacuolation, formation of syncytia, and fusion of cells, were detected even at passage 1 of the PEDV in Vero cells. Once adapted, the virus induced numerous syncytia containing over 100 nuclei. From virus passage 5 on, all cells forming the monolayer were fused and totally destroyed within 24 h after inoculation. Cell culture-grown PEDV had typical coronavirus morphology when viewed by electron microscopy. Attempts to propagate PEDV in several primary and secondary fetal porcine cell cultures in the presence or absence of trypsin were unsuccessful.
Application of Molecular Techniques To Elucidate the Influence of Cellulosic Waste on the Bacterial Community Structure at a Simulated Low-Level-Radioactive-Waste Site

ABSTRACT Low-level-radioactive-waste (low-level-waste) sites, including those at various U.S. Department of Energy sites, frequently contain cellulosic waste in the form of paper towels, cardboard boxes, or wood contaminated with heavy metals and radionuclides such as chromium and uranium. To understand how the soil microbial community is influenced by the presence of cellulosic waste products, multiple soil samples were obtained from a nonradioactive model low-level-waste test pit at the Idaho National Laboratory. Samples were analyzed using 16S rRNA gene clone libraries and 16S rRNA gene microarray (PhyloChip) analyses. Both methods revealed changes in the bacterial community structure with depth. In all samples, the PhyloChip detected significantly more operational taxonomic units, and therefore relative diversity, than the clone libraries. Diversity indices suggest that diversity is lowest in the fill and fill-waste interface (FW) layers and greater in the wood waste and waste-clay interface layers. Principal-coordinate analysis and lineage-specific analysis determined that the Bacteroidetes and Actinobacteria phyla account for most of the significant differences observed between the layers. The decreased diversity in the FW layer and increased members of families containing known cellulose-degrading microorganisms suggest that the FW layer is an enrichment environment for these organisms. These results suggest that the presence of the cellulosic material significantly influences the bacterial community structure in a stratified soil system.
Chimpanzee intellect: personality, performance and motivation with touchscreen tasks

Human intellect is characterized by intercorrelated psychological domains, including intelligence, academic performance and personality. Higher openness is associated with higher intelligence and better academic performance, yet high performance among individuals is itself attributable to intelligence, not openness. High conscientiousness individuals, although not necessarily more intelligent, are better performers. Work with other species is not as extensive, yet animals display similar relationships between exploration- and persistence-related personality traits and performance on cognitive tasks. However, previous studies linking cognition and personality have not tracked learning, performance and dropout over time—three crucial elements of cognitive performance. We conducted three participatory experiments with touchscreen cognitive tasks among 19 zoo-housed chimpanzees, whose personalities were assessed 3 years prior to the study. Performance and participation were recorded across experiments. High conscientiousness chimpanzees participated more, dropped out less and performed better, but their performance could be explained by their experience with the task. High openness chimpanzees tended to be more interested, perform better and continue to participate when not rewarded with food. Our results demonstrate that chimpanzees, like humans, possess broad intellectual capacities that are affected by their personalities.