Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural basis for diversity in the SAM clan of riboswitches

Significance Riboswitches are a broadly distributed means of regulation of gene expression in bacteria that solely rely on RNA. Seven distinct families of riboswitches bind S-adenosylmethionine (SAM) as their effector, regulating genes involved in sulfur metabolism across a broad spectrum of bacterial species. Further, SAM riboswitches regulate expression of genes essential for survival and/or virulence in medically important pathogens, suggesting they might be important targets for the development of new antimicrobial agents. Our studies reveal the atomic-resolution structure of a unique peripheral architecture that supports a SAM-binding core shared among three families that make up the “SAM clan” and how this subdomain facilitates both ligand binding and gene regulation. In bacteria, sulfur metabolism is regulated in part by seven known families of riboswitches that bind S-adenosyl-l-methionine (SAM). Direct binding of SAM to these mRNA regulatory elements governs a downstream secondary structural switch that communicates with the transcriptional and/or translational expression machinery. The most widely distributed SAM-binding riboswitches belong to the SAM clan, comprising three families that share a common SAM-binding core but differ radically in their peripheral architecture. Although the structure of the SAM-I member of this clan has been extensively studied, how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown. We have therefore solved the X-ray structure of a member of the SAM-I/IV family containing the alternative “PK-2” subdomain shared with the SAM-IV family. This structure reveals that this subdomain forms extensive interactions with the helix housing the SAM-binding pocket, including a highly unusual mode of helix packing in which two helices pack in a perpendicular fashion. Biochemical and genetic analysis of this RNA reveals that SAM binding induces many of these interactions, including stabilization of a pseudoknot that is part of the regulatory switch. Despite strong structural similarity between the cores of SAM-I and SAM-I/IV members, a phylogenetic analysis of sequences does not indicate that they derive from a common ancestor.
Twenty-four – hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction 1 – 3

Background: Plasma tryptophan concentrations and the ratio of tryptophan to other large neutral amino acids (plasma tryptophan ratio) are reportedly low in obese subjects. The plasma tryptophan ratio predicts brain tryptophan uptake and serotonin production. If this ratio is low in obese subjects, serotonin function may also be low. Plasma tryptophan concentrations and ratios have been measured only at single time points in obese subjects; it is not known whether low values for these 2 variables persist throughout a 24-h period. Objective: Our objective was to determine whether plasma tryptophan concentrations and ratios in obese subjects are lower than those in normal-weight subjects throughout a 24-h period and whether they increase when body weight is reduced. Design: Plasma tryptophan concentrations and ratios were examined in obese subjects before and after weight loss and in nonobese control subjects. Blood samples were drawn frequently throughout the 24-h period. An insulin tolerance test was also used to determine whether weight loss altered the ability of insulin to modify plasma concentrations of tryptophan and of the other large neutral amino acids. Results: Plasma tryptophan concentrations and ratios in obese subjects were low at all times; these effects persisted after weight reduction. Plasma concentrations of all the large neutral amino acids decreased during insulin infusion in all the groups. Conclusions: The low 24-h plasma tryptophan ratios in obese and formerly obese subjects suggest that brain tryptophan uptake may be continuously diminished and may remain below normal despite weight reduction. Am J Clin Nutr 2003;77:1112–8.
Adaptation and validation of the Diabetes Management Self-Efficacy Scale to Brazilian Portuguese 1

Objective: to perform the cultural adaptation and validation of the Diabetes Management Self-efficacy Scale for Patients with Type 2 Diabetes Mellitus with a Brazilian population sample. Method: cross-sectional methodological study in which the adaptation and validation process included the stages recommended in the literature. Construct validity and reliability were assessed with 200 adults with type 2 diabetes mellitus. Results: the items indicated by the panel of judges and by the target population were adjusted in the cultural adaptation to improve clarity and understanding. The instrument's four factors remained in the confirmatory factor analysis with factor loadings of items greater than 0.30, except for factor 4; convergent validity, verified by the multitrait-multimethod analysis, presented inter-item correlations from 0.37 to 0.92, while for discriminant validity, 100% of the items presented greater correlation in their own factors. Cronbach's coefficient alpha for the total scale was 0.78, ranging from 0.57 to 0.86 among factors. Conclusion: semantic, cultural, conceptual and idiomatic equivalences were achieved and the instrument's Brazilian version also presented psychometric properties that showed evidence of reliability and validity. Thus, it can be applied both in clinical practice and research. Self-efficacy is useful for planning and assessing educational interventions, as well as predicting behavior modification in self-care.
Predictability of smoking in adolescence: between optimism and pessimism.

AIMS The present study aimed to assess how far associations between possible explanatory variables and smoking onset depend on the use of cross-sectional versus prospective designs. DESIGN AND SUBJECTS Data were analysed from a three-wave 5-year longitudinal survey among 1063 secondary schoolchildren (12-18-year-olds) in The Netherlands. MEASUREMENTS The survey questionnaire contained items on smoking history, smoking-specific beliefs and attitudes, social influence variables and socio-demographic variables in each wave. FINDINGS AND CONCLUSIONS The cross-sectional analyses showed strong associations between explanatory variables and smoking behaviour (R2 varied from 0.50 to 0.71). However, only 8% of the variance in change of smoking status from non-smoking to regular smoking over a period of 5 years and 14% of the variance over a period of 3 years could be predicted by the model variables. Factors believed to lead to smoking may result from smoking or they may change quickly in ways that make them of low predictive value even though they may be important aetiologically.
Determination of Colorectal Cancer Risk Levels, Colorectal Cancer Screening Rates, and Factors Affecting Screening Participation of Individuals Working in Agriculture in Turkey

Background: Colorectal cancer (CRC) is the fourth ranked malignancy leading to death in Turkey. Agricultural workers with low socioeconomic level are particularly at risk due to the intense use of pesticides. Objective: The aim of this study was to determine CRC risk levels, status of participation in CRC screenings, and the factors affecting participation in screenings among individuals between 50 and 70 years old working in agriculture. Methods: Data in this cross-sectional study were collected from 244 agricultural workers in Turkey. Results: The rate of participation in CRC screenings among these workers at high risk was low. Their knowledge and health beliefs did not affect their participation in CRC screenings. Having a friend or neighbor with CRC and knowing which doctor to consult increased participation in CRC screenings 10 times, and having abdominal pain increased participation in CRC screenings 4 times. Conclusions: The rate of participation in CRC screenings is low in this group of workers, but rates may increase when these individuals are directed to be screened. Implications for Practice: Health professionals should advise agricultural workers to participate in CRC screenings and should inform workers about the locations where screenings are conducted.
Influence of prilled fat and calcium salt of palm oil fatty acids on ruminal fermentation and nutrient digestibility.

Four rumen cannulated Holstein cows were used in a Latin square design to examine the effect of supplemental calcium salt of palm oil fatty acids (.68 kg/d) or prilled fat (.68 or .91 kg/d) on DM intake, rumen fermentation, and nutrient digestibility. Basal diet contained 45% concentrate, 27.5% alfalfa silage, and 27.5% corn silage (DM basis), and treatments were balanced for calcium. Dry matter intake was similar among treatments. Ruminal pH, total VFA, and molar percentage acetate and propionate were not affected by fat supplementation. Feeding prilled fat decreased slightly ruminal molar percentage butyrate. Forage DM and neutral detergent fiber disappearance from ruminally suspended dacron bags did not differ due to treatment. For unknown reasons, total tract apparent digestibility of DM and NDF was lower when cows received the low amount but not the high amount of prilled fat. Milk yield and fat percentage were not significantly affected by treatment. Milk protein was maintained during prilled fat supplementation but decreased . 13% during calcium salt of palm oil fatty acid supplementation. Both fat supplements appeared inert in the rumen and did not markedly affect nutrient digestion when supplemented at 3.5% or less of the total ration DM.
Cerium oxide nanoparticles induce oxidative stress in the sediment-dwelling amphipod Corophium volutator

Abstract Cerium oxide nanoparticles (CeO2 NPs) exhibit fast valence exchange between Ce(IV) and Ce(III) associated with oxygen storage and both pro and antioxidant activities have been reported in laboratory models. The reactivity of CeO2 NPs once they are released into the aquatic environment is virtually unknown, but this is important to determine for assessing their environmental risk. Here, we show that amphipods (Corophium volutator) grown in marine sediments containing CeO2 NPs showed a significant increase in oxidative damage compared to those grown in sediments without NPs and those containing large-sized (bulk) CeO2 particles. There was no exposure effect on survival, but significant increases in single-strand DNA breaks, lipid peroxidation and superoxide dismutase activity were observed after a 10-day exposure to 12.5 mg L−1 CeO2. Characterisation of the CeO2 NPs dispersed in deionised or saline exposure waters revealed that more radicals were produced by CeO2 NPs compared with bulk CeO2. Electron energy loss spectroscopy (EELS) analysis revealed that both CeO2 NPs were predominantly Ce(III) in saline waters compared to deionised waters where they were predominantly Ce(IV). In both types of medium, the bulk CeO2 consisted mainly of Ce(IV). These results support a model whereby redox cycling of CeO2 NPs between Ce(III) and Ce(IV) is enhanced in saline waters, leading to sublethal oxidative damage to tissues in our test organism.
Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs

Bone marrow-derived mesenchymal stem cells (BM-MSCs) provide a large quantitative alternative source for regenerative medicine. this study was undertaken to determine the effect of BM-MSCs in the treatment of busulfan-induced azoospermia in guinea pigs. BM-MSCs were isolated from the femur bones of 6 adult guinea pigs as the donor group, and characterized by morphology, MSC markers and osteogenic and adipogenic differentiation. a dose of 40 mg/kg of busulfan was administered at a 21 day interval to induce azoospermia in 6 guinea pigs. Thirty-five days after the second injection of busulfan, transplantation of 1×106 BM-MSCs was performed into the seminiferous tubules of the left testes. the right testis was considered as the positive busulfan treated control. the testes of the donor group were applied as an intact normal control. then, 60 days after cell therapy, histopathological and histomorphometric evaluations of the testes were performed. the seminiferous tubules treated with BM-MSCs, similar to the intact group, showed a normal appearance of spermatogenesis in comparison to the busulfan-induced azoospermic testes. In conclusion, BM-MSCs were effective in the treatment of azoospermia in a guinea pig model where they restore the fertility of busulfaninduced azoospermic animals after transplantation of BM-MSCs. therefore, this report could open a window in future to the possibility of BM-MSCs transplantation in the treatment of azoospermia in humans, but more studies should be undertaken for further verification.
Influence of culture conditions on the DNA‐damaging effect of benzene and its metabolites in human peripheral blood mononuclear cells

The DNA‐damaging ability of benzene and its metabolites on peripheral blood mononuclear cells (PBMC) has been investigated by using the alkaline comet assay. The PBMC were incubated with different compounds in two different media for 2 and 24 hr at concentrations that did not affect cell viability and the DNA damage was quantified by a computerized image analysis system. Benzene and phenol (5 mM) did not show any genotoxic activity after 2 hr of incubation in the two media tested, phosphate‐buffered saline (PBS) and RPMI containing 5% of heat‐inactivated fetal calf serum (RPMI + 5% FCS), whereas phenol was genotoxic and cytotoxic at 10 mM after 24 hr of incubation in RPMI + 5% FCS. All other benzene metabolites were genotoxic at micromolar concentrations when incubated in PBS with the following decreasing order of potency: benzenetriol, catechol, hydroquinone, and benzoquinone. When the PBMC were incubated in RPMI + 5% FCS, the effect of catechol (200–600 μM) and benzenetriol (10 μM) was reduced, whereas the genotoxicity of benzenetriol at high concentrations (50–100 μM) and hydroquinone (150–2500 μM) was not affected. In contrast, the effect of benzoquinone at 5 and 10 μM was greatly enhanced when the cells were incubated in RPMI + 5% FCS. This effect resulted mainly from the presence of serum in the medium and it was almost completely inhibited by boiling the serum (100°C, 5 min) and was partially reduced by extensive dialysis. Benzoquinone was the most damaging compound when tested under more physiological conditions, thereby supporting the general observation that it is the most myelotoxic benzene metabolite. Environ. Mol. Mutagen. 37:1–6, 2001 © 2001 Wiley‐Liss, Inc.
Teachers' Informal Learning via Social Networking Technology

Discussion on teacher learning is often limited to a focus on formal professional development programmes. What and how teachers learn informally through their daily experiences is rarely explored. This research attempts to investigate how teachers engage in informal learning for their professional development when using Social Networking Site (SNS) technology. Data were generated using ethnographic approach whereby Facebook Timelines belonged to 22 English language teachers were observed for a period of six months. The analysis shows that the teachers frequently exchanged teaching related knowledge in their Timeline conversations and they received rich responses from both teaching and non-teaching Friends. This paper thus argues that social networking site, such as Facebook is a potential platform to engage teachers in informal learning for their professional development.
Alcoholism. I. Two types of alcoholism in women.

ALCOHOLISM may not be a single disease. 1 A recent study by Pitts and Winokur 2 points to the close relationship of alcoholism and affective disorder while other studies have shown the possible tie between alcoholism and schizophrenia, 3-5 psychoneurosis, 5 and sociopathy. 6 In addition, it has been suggested that alcoholism may not be the same disease in the two sexes. 4 A workable definition of alcoholism has emerged from Jellinek and the World Health Organization, 7,8 but such a definition allows assemblage of a heterogeneous group of alcoholics with other associated psychiatric illnesses. 5 An examination of alcoholism both as a primary disease entity and as a secondary complication of other psychiatric illnesses is lacking. The purpose of this paper is to describe an attempt to delineate alcoholism into nosologically homogeneous groups. We shall limit our present discussion to alcoholism in the female.
Receptor tyrosine kinase mutations in myeloid neoplasms

The receptor tyrosine kinases (RTKs) are transmembrane enzymes involved in ligand binding and signal transduction at the cell surface. They function in nearly all biological systems and have a broadly conserved molecular topology, which permits activation of intracellular protein kinase activity upon ligand binding. Mutations involving RTK genes occur in both acute and chronic myeloid leukaemias. In this review, we outline the phylogeny and biochemistry of RTKs with reference to myeloid ontogeny, classify the types of RTK mutation seen in myeloid malignancies, and discuss the prognostic and potential therapeutic significance of these acquired genetic changes.
Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus

In vitro evidence suggests that plasmacytoid dendritic cells (pDCs) are intimately involved in the pathogenesis of lupus. However, it remains to be determined whether these cells are required in vivo for disease development, and whether their contribution is restricted to hyperproduction of type I IFNs. To address these issues, we created lupus-predisposed mice lacking the IFN regulatory factor 8 (IRF8) or carrying a mutation that impairs the peptide/histidine transporter solute carrier family 15, member 4 (SLC15A4). IRF8-deficient NZB mice, lacking pDCs, showed almost complete absence of anti-nuclear, anti-chromatin, and anti-erythrocyte autoantibodies, along with reduced kidney disease. These effects were observed despite normal B-cell responses to Toll-like receptor (TLR) 7 and TLR9 stimuli and intact humoral responses to conventional T-dependent and -independent antigens. Moreover, Slc15a4 mutant C57BL/6-Faslpr mice, in which pDCs are present but unable to produce type I IFNs in response to endosomal TLR ligands, also showed an absence of autoantibodies, reduced lymphadenopathy and splenomegaly, and extended survival. Taken together, our results demonstrate that pDCs and the production of type I IFNs by these cells are critical contributors to the pathogenesis of lupus-like autoimmunity in these models. Thus, IRF8 and SLC15A4 may provide important targets for therapeutic intervention in human lupus.
Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis

Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community‐acquired and healthcare‐associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class‐definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de‐escalation or termination of antimicrobial therapy are now important parts of decision‐making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps. jp/modules/en/index.php? content_id=47. Related clinical questions and references are also included.
Estimation of Local Data-Insufficiency in Motion-Corrected Helical CT

Previously we have proposed a reconstruction algorithm which corrects for known rigid motion in helical CT. This paper describes a method to determine data-insufficiency of helical CT data affected by rigid object motion. We propose a local measure that quantifies the degree to which Tuy’s completeness condition is violated in each voxel. This measure identifies regions for which artifact-free reconstruction is not assured. For every voxel, a local data-insufficiency measure is computed. We call the resulting image the Tuy map. Its values range from 0 to 1, where high values indicate data-insufficiency. As shown by classic theory, exact reconstruction is not possible, where the Tuy map contains high values. The predictions based on this Tuy map were verified with simulated helical-CT data, where the object moved during the scan and the motion was correctly taken into account during reconstruction. We also analyzed the reconstruction from an actual motion-corrected CT-scan of a moving phantom. For motion-free helical scans, the Tuy map was close to zero everywhere and the reconstructions were artifact-free. Rigid motion induces an effective source trajectory (with respect to a stationary patient) which, combined with axial or even transaxial truncation, can cause incomplete sampling. In simulations with severe motion or transaxial detector truncation, the Tuy map contained high values and the reconstructions suffered from artifacts. In the phantom scan, the combination of a high pitch and severe motion created artifacts which the Tuy map successfully indicated. In all cases, the Tuy map indicated all regions with incomplete sampling which were prone to reconstruction artifacts. However, we also contrived a special case, where exact reconstruction was not assured although the local Tuy condition was satisfied. The proposed method provides a useful measure of data-incompleteness, which can be used to verify the validity of motion-corrected helical CT scans. The method is general and could also be useful for other tomographic problems for which no exact data sufficiency measures are available.
Perceptions of support-seeking in young people attending a Youth Offending Team: An interpretative phenomenological analysis

High levels of mental health problems have been identified in young people who have offended (committed/been convicted of a criminal offence). However, as with many young people, they tend not to seek support for their difficulties. This research aimed to explore support-seeking in this population by asking ‘What are the perceptions of support-seeking in young people attending a Youth Offending Team? ’ Semi-structured interviews were carried out with six males (aged 13–18) and the transcripts were analysed using interpretative phenomenological analysis. Four master themes were revealed: Youth Offending Team attendance prompting reflection, Damaged self, Complexity of relationships and Internal conflicts. Generally participants perceived support-seeking as beneficial, but various barriers meant that they did not tend to view it as a viable coping strategy for themselves. Interventions aimed at addressing these barriers may help young people who have offended to seek support.
Impacts of Universal Secondary Education Policy on Secondary School Enrollments in Uganda

While Sub-Saharan countries have improved primary school education significantly, secondary education is still far behind the rest of the world. Ugandan government introduced universal secondary education (USE) policy to improve secondary education in 2007.In this study we evaluate the impacts of USE policy on secondary school enrollments using household panel data. We find that USE policy has considerably increased public secondary school enrollments especially for girls from poor households. Still, Uganda may need further improvement in terms of quality of secondary school education.