Loss of Pluripotency in Human Embryonic Stem Cells Directly Correlates with an Increase in Nuclear Zinc

The pluripotency of human embryonic stem cells (hESCs) is important to investigations of early development and to cell replacement therapy, but the mechanism behind pluripotency is incompletely understood. Zinc has been shown to play a key role in differentiation of non-pluripotent cell types, but here its role in hESCs is directly examined. By mapping the distribution of metals in hESCs at high resolution by x-ray fluorescence microprobe (XFM) and by analyzing subcellular metal content, we have found evidence that loss of pluripotency is directly correlated with an increase in nuclear zinc. Zinc elevation not only redefines our understanding of the mechanisms that support pluripotency, but also may act as a biomarker and an intervention point for stem cell differentiation

Intra-molecular coupling as a mechanism for a liquid-liquid phase transition

We study a model for water with a tunable intra-molecular interaction $J_\sigma$, using mean field theory and off-lattice Monte Carlo simulations. For all $J_\sigma\geq 0$, the model displays a temperature of maximum density.For a finite intra-molecular interaction $J_\sigma > 0$,our calculations support the presence of a liquid-liquid phase transition with a possible liquid-liquid critical point for water, likely pre-empted by inevitable freezing. For J=0 the liquid-liquid critical point disappears at T=0.Comment: 8 pages, 4 figure

Propiedades psicométricas y baremos del Cuestionario de Burnout Granada en profesionales de Enfermería

Nurses are an occupational group with extremely high levels of burnout. The most accepted definition of the burnout syndrome was proposed by Maslach and Jackson, who characterized it in terms of three dimensions: (i) Emotional Exhaustion; (ii) Depersonalization; (iii) Personal Accomplishment. This definition was the basis for the Granada Burnout Questionnaire (GBQ). The objective of this research was to evaluate the psychometric properties of the GBQ and to elaborate an evaluation scale to measure burnout in nursing professionals in Spain. A total of 1,177 nurses participated in this study and successfully completed the GBQ. Evidence of construct validity was verified by cross-validation and convergent validity, and evidence of criteria validity was checked by concurrent validity. Cronbach's alpha was used to measure internal consistency. The results obtained in our study show satisfactory fit values in the confirmatory factor analysis and in the evidence of convergent and concurrent validity. All of the Cronbach alpha values were greater than .83. This signifies that the GBQ has good psychometric properties that are applicable to nurses. For this purpose a scale of T-scores and centiles was created that permitted the evaluation of burnout in Spanish nursing professionals.Los enfermeros son uno de los colectivos profesionales que presentan mayores niveles de burnout. La definición más aceptada de este trastorno fue propuesta por Maslach y Jackson, y se caracteriza por Cansancio Emocional, Despersonalización y Realización Personal. Esta definición operativa fue usada en la elaboración del Cuestionario de Burnout Granada (CBG). El objetivo de la presente investigación fue evaluar las propiedades psicométricas del CBG y elaborar un baremo para profesionales de enfermería españoles. El CBG era cumplimentado por 1177 enfermeros. Las evidencias de validez de constructo fueron examinadas usando estrategias de validez cruzada y validez convergente, y las evidencias de validez de criterio mediante la validez concurrente. El coeficiente alfa de Cronbach se utilizó para medir la consistencia interna. Los resultados indican índices de ajuste satisfactorio en el análisis factorial confirmatorio, y en las evidencias de validez convergente y concurrente. Todos los valores de alfa de Cronbach fueron superiores a 0,83. Los resultados muestran que el CBG tiene buenas propiedades psicométricas para ser usado en enfermeros. Se elaboró un baremo en puntuaciones T y centiles que permite evaluar burnout en enfermeros españoles.This work was funded by the Excellence Research Project P11HUM-7771 (Junta de Andalucía-Spain) and the Research Project mP_BS_6 (CEI BioTic Granada and Ministerio de Ciencia e Innovación-Spain).Open Access funded by Asociacion Espanola de Psicologia Conductua

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

Impacts of carbohydrate-restricted diets on micronutrient intakes and status: a systematic review

A systematic review of published evidence on micronutrient intake/status with carbohydrate‐restricted diets (CRD) was conducted in Web of Science, Medline, Embase, Scopus, CENTRAL, and ClinicalTrials.gov up to October 2018. We identified 10 studies: seven randomized controlled trials (RCTs) (“Atkins”‐style, n = 5; “Paleolithic” diets, n = 2), two Atkins‐style noncontrolled trials and one cross‐sectional study. Prescribed carbohydrate varied 4% to 34% of energy intake. Only one noncontrolled trial prescribed multivitamin supplements. Dietary intakes/status were reported over 2 to 104 weeks, with weight losses from 2 to 9 kg. No diagnoses of deficiency were reported. Intakes of thiamine, folate, magnesium, calcium, iron, and iodine all decreased significantly (−10% to −70% from baseline) with any CRD types. Atkins diet trials (n = 6; 4%‐34%E carbohydrate) showed inconsistent changes in vitamin A, E, and β‐carotene intakes, while a single “Paleolithic” diet trial (28%E carbohydrate) reported increases in these micronutrients. One other “Paleolithic” diet (30%E carbohydrate) reported a rise in moderate iodine deficiency from 15% to 73% after 6 months. In conclusion, few studies have assessed the impacts of CRD on micronutrients. Studies with different designs point towards reductions in several vitamins and minerals, with potential risk of micronutrient inadequacies. Trial reporting standards are expected to include analysis of micronutrient intake/status. Micronutrients in foods and/or supplements should be considered when designing, prescribing or following CRDs

In-cell NMR in E. coli to Monitor Maturation Steps of hSOD1

In-cell NMR allows characterizing the folding state of a protein as well as posttranslational events at molecular level, in the cellular context. Here, the initial maturation steps of human copper, zinc superoxide dismutase 1 are characterized in the E. coli cytoplasm by in-cell NMR: from the apo protein, which is partially unfolded, to the zinc binding which causes its final quaternary structure. The protein selectively binds only one zinc ion, whereas in vitro also the copper site binds a non-physiological zinc ion. However, no intramolecular disulfide bridge formation occurs, nor copper uptake, suggesting the need of a specific chaperone for those purposes

Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research

<p>Abstract</p> <p>Background</p> <p>There is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies.</p> <p>Methods</p> <p>Sixteen studies, all observational, were identified using a standard citation search. They fulfilled the following inclusion criteria: conducted in the HAART era; sample size > 10; treatment effect involved more than one antiretroviral and none had a retrospective design. The qualitative phase of review of these studies consisted of (i) a blind assessment rating studies on features such as sample size, statistical methods and definitions of neuroHAART, and (ii) a non-blind assessment of the sensitivity of the neuropsychological methods to HIV-associated neurocognitive disorder (HAND). During quantitative evaluation we assessed the statistical power of studies, which achieved a high rating in the qualitative analysis. The objective of the power analysis was to determine the studies ability to assess their proposed research aims.</p> <p>Results</p> <p>After studies with at least three limitations were excluded in the qualitative phase, six studies remained. All six found a positive effect of neuroHAART on neurocognitive function or CSF HIV suppression. Of these six studies, only two had statistical power of at least 80%.</p> <p>Conclusions</p> <p>Studies assessed as using more rigorous methods found that neuroHAART was effective in improving neurocognitive function and decreasing CSF viral load, but only two of those studies were adequately statistically powered. Because all of these studies were observational, they represent a less compelling evidence base than randomised control trials for assessing treatment effect. Therefore, large randomised trials are needed to determine the robustness of any neuroHAART effect. However, such trials must be longitudinal, include the full spectrum of HAND, ideally carefully control for co-morbidities, and be based on optimal neuropsychology methods.</p

Self-Regulation Questionnaire (SRQ) in Spanish Adolescents: Factor Structure and Rasch Analysis

The Self-Regulation Questionnaire (SRQ) is an instrument employed to measure the generalized ability to regulate behavior. Self-regulation is related to the management of risk behaviors, such as drug abuse or anti-social behaviors. The SRQ has been used in young adult samples. However, some risk behaviors are increasing among adolescents. The aim of this study is to examine the psychometric properties of the SRQ among Spanish adolescents. While controlling for method effects, the data showed goodness of fit with the four-factor solution and 17 items (Goal setting, Decision making, Learning from mistakes, and Perseverance), and the four sub-scales were unidimensional according to the Rasch analysis. The Rasch model itself was shown to be reliable, but not at the level of persons. This means that the instrument was not sensitive enough to discriminate people with different self-regulation levels. These results support the use of the Spanish Short SRQ in adolescent samples. Some suggestions are made to improve the instrument, particularly in its application as a diagnostic tool

The mechanism and control of DNA transfer by the conjugative relaxase of resistance plasmid pCU1

Bacteria expand their genetic diversity, spread antibiotic resistance genes, and obtain virulence factors through the highly coordinated process of conjugative plasmid transfer (CPT). A plasmid-encoded relaxase enzyme initiates and terminates CPT by nicking and religating the transferred plasmid in a sequence-specific manner. We solved the 2.3 Å crystal structure of the relaxase responsible for the spread of the resistance plasmid pCU1 and determined its DNA binding and nicking capabilities. The overall fold of the pCU1 relaxase is similar to that of the F plasmid and plasmid R388 relaxases. However, in the pCU1 structure, the conserved tyrosine residues (Y18,19,26,27) that are required for DNA nicking and religation were displaced up to 14 Å out of the relaxase active site, revealing a high degree of mobility in this region of the enzyme. In spite of this flexibility, the tyrosines still cleaved the nic site of the plasmid’s origin of transfer, and did so in a sequence-specific, metal-dependent manner. Unexpectedly, the pCU1 relaxase lacked the sequence-specific DNA binding previously reported for the homologous F and R388 relaxase enzymes, despite its high sequence and structural similarity with both proteins. In summary, our work outlines novel structural and functional aspects of the relaxase-mediated conjugative transfer of plasmid pCU1

How affective-motivational variables and approaches to learning predict mathematics achievement in upper elementary levels

The relationship between students' motivation and attitudes towards mathematics, the approaches to learning they use, and their achievement in mathematics has been widely documented in middle school and further academic levels. However, the empirical research in earlier educational stages remains scarce. This study analyzed the predictive value of affective-motivational variables and deep and surface approaches to learning on mathematics achievement in a sample of 524 upper elementary students. Multiple linear regression analysis was used to examine the predictors of mathematics achievement. Mathematics enjoyment positively predicted mathematics achievement and age and the use of the surface approach to learning negatively predicted mathematics achievement. The variables in the model explained 21.3% of the variance in mathematics achievement. Mean differences in the affective-motivational variables and approaches to learning occurred between students with very high and very low achievement in Mathematics, yielding further evidence of important differences between the achievement extremes