Electron transport through dipyrimidinyl-diphenyl diblock molecular wire: protonation effect

Recently, rectifying direction inversion has been observed in dipyrimidinyl-diphenyl (PMPH) diblock molecular wire [J. Am. Chem. Soc. (2005) 127, 10456], and a protonation mechanism was suggested to explain this interesting phenomena. In this paper, we study the protonation effect on transport properties of PMPH molecule by first principles calculations. No significant rectification is found for the pristine diblock molecular wire. Protonation leads to conductance enhancement and rectification. However, for all considered junctions with rectifying effect, the preferential current directions are samely from dipyrimidinyl side to diphenyl side. Effect of molecule-electrode anchoring geometry is studied, and it is not responsible for the discrepancy between experiment and theory.Comment: 17 pages, 8 figure

Solitary waves in the Nonlinear Dirac Equation

In the present work, we consider the existence, stability, and dynamics of solitary waves in the nonlinear Dirac equation. We start by introducing the Soler model of self-interacting spinors, and discuss its localized waveforms in one, two, and three spatial dimensions and the equations they satisfy. We present the associated explicit solutions in one dimension and numerically obtain their analogues in higher dimensions. The stability is subsequently discussed from a theoretical perspective and then complemented with numerical computations. Finally, the dynamics of the solutions is explored and compared to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger equation. A few special topics are also explored, including the discrete variant of the nonlinear Dirac equation and its solitary wave properties, as well as the PT-symmetric variant of the model

Maximum parsimony analysis of gene expression profiles permits the reconstruction of developmental cell lineage trees

AbstractSpatiotemporal control of gene expression lies at the heart of generating several hundred distinct cell types required for the development of higher order animals. Different cell types within complex organs are often characterised by means of genome-wide gene expression profiling, but analogous information for early developmental as well as adult stem and progenitor cells is largely missing because their identity is commonly unknown or they are present in prohibitively small numbers. Here we show that maximum parsimony approaches previously used to reconstruct evolutionary trees from gene content of extant species can be adapted to reconstruct cellular hierarchies both during development and steady state homeostasis of complex mammalian tissues. Using haematopoiesis as a model, we show that developmental trees reconstructed from expression profiles of mature cells are not only consistent with current experimentally validated trees but also have predictive value in determining progenitor cell specific transcriptional programmes and lineage determining transcription factors. Subsequent analysis across diverse developmental systems such as neuronal development and endoderm organogenesis demonstrated that maximum parsimony-based reconstruction of developmental trees represents a widely applicable approach to infer developmental pathways as well as the transcriptional control mechanisms underlying cell fate specification

Exposure to mercury among 9-year-old children and neurobehavioural function

Mercury (Hg) is an environmental neurotoxicant whose main route of exposure in humans is the consumption of seafood. The aim of this study was to explore the relationship between Hg exposure at 9 years old and behaviour assessed at 9 and 11 years old. Study subjects were mother-child pairs participating in the INMA (Environment and Childhood) Project in Valencia (Spain). Total Hg (THg) was measured in hair samples from the children at 9 years old. Behaviour and emotions were assessed at 9 (n = 472) years and 11 (n = 385) years of age using the Child Behaviour Checklist test (CBCL) and the Conners Parents Rating Scale-Revised: Short Form (CPRS-R:S). Furthermore, the attention function was assessed by the Attention Network Test at 11 years old. Socio-demographic, lifestyle and dietary information was collected through questionnaires during pregnancy and childhood. Polymorphism in BDNF, APOE and GSTP1 were genotyped in cord blood DNA. Multivariable negative binomial regression models were built in order to study the association between THg concentrations and the scores obtained by the children at 9 and 11 years old. Effect modification by sex and genetic polymorphisms was assessed. The association between Hg levels and CBCL scores was positive (worse neurobehavioural development) for the CBCL internalizing and total problem scales (Incidence Rate Ratio [95% confidence interval] = 1.07 [1.01,1.13] and 1.05 [0.99, 1.11], respectively). The association between Hg and the externalizing and total problems CBCL scales and the Attention Deficit Hyperactivity Disorder (ADHD) index of the CPRS-R:S was different according to sex, with boys obtaining worse scores with increasing Hg, compared to girls. Statistically significant interactions were also observed for genetic polymorphisms affecting the association between early exposure to Hg and both CBCL and CPRS-R:S scores. In conclusion, postnatal Hg exposure is associated with poorer neurobehavioural development in 9- and 11-year-old children. Sex and the presence of certain genetic polymorphisms modified this association

Alteración en las pruebas de función hepática en pacientes hospitalizados por COVID-19: un estudio multicéntrico en Perú

Introduction: COVID-19 affects the liver, causing alteration in liver biochemistry tests such as aspartate transferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin. Objective: To determine the prevalence of alteration in liver functions tests and associated factors for severity among Peruvian COVID-19 patients. Materials and methods: A descriptive, retrospective and cross-sectional study was performed in 4 public hospitals in Peru. Patients admitted to hospitalization wards and intensive care units with a diagnosis COVID-19 were enrolled. The evaluation of AST, ALT, ALP, total bilirubin and albumin was performed. Associations with demographic and medical data were assessed. Results: 1,100 patients were enrolled, of which 81.7% had altered liver function tests. Only 2.8% of the patients had cirrhosis and 2.1% hepatitis B/C virus. AST and ALT were altered at admission in 64.7% and 63.7%, of the patients respectively. Factors associated with liver injury were: being female OR=0.53 (95% CI: 0.39-0.73; p<0.01), dyslipidemia OR=1.72 (95% CI: 1.10-2.70; p=0.01), previous medication OR=1.56 (95% CI: 1.12 -2.16, p<0.01) and fever OR=1.43 (95% CI: 1.03-1.199, p=0.03). Disease severity was associated with levels of AST and ALT (p<0.01). Patients taking self-medication OR=1.56 (95% CI: 1.12-2.16; p<0.01) and paracetamol OR= 1.41 (95% CI:1.01-1.98; p=0.04) had higher risk of liver injury. Meanwhile, corticosteroids OR=0.55 (95% CI: 0.38-0.78; p<0.01) and enoxaparin OR=0.53 (95% CI: 0.35- 0.81; p<0.01) were protective factors. Conclusions: Peruvian patients with COVID- teration in liver function tests, high levels of AST and ALT were related to disease severity.Introducción: La COVID-19 afecta al hígado, provocando alteración en las pruebas de función hepática como aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), fosfatasa alcalina (FA), bilirrubina total y albúmina. Objetivo: Determinar la prevalencia de alteración en las pruebas de función hepática y su asociación con la severidad en pacientes peruanos con COVID-19. Materiales y métodos: Se realizó un estudio descriptivo, retrospectivo y transversal en 4 hospitales públicos del Perú. Se incluyeron pacientes admitidos en hospitalización y unidades de cuidados intensivos con diagnóstico de COVID-19. Se realizó la evaluación de AST, ALT, FA, bilirrubina total y albúmina. Se evaluaron las asociaciones con datos demográficos y médicos. Resultados: Se incluyeron 1,100 pacientes, de los cuales el 81,7% presentaba alteraciones en las pruebas de función hepática. Solo el 2,8% de los pacientes tenía cirrosis y el 2,1% infección por virus de la hepatitis B / C. Se encontraron niveles alterados de AST y ALT al ingreso en el 64,7% y 63,7% de los pacientes, respectivamente. Los factores asociados con alteración en pruebas de función hepáticas fueron: ser mujer OR = 0,53 (IC 95%: 0,39-0,73; p <0,01), dislipidemia OR=1,72 (IC 95%: 1,10-2,70; p=0,01), uso de medicación previa OR = 1,56 (IC del 95%: 1,12 -2,16, p <0,01) y fiebre OR = 1,43 (IC del 95%: 1,03-1,199, p = 0,03). La gravedad de la enfermedad se asoció con los niveles de AST y ALT (p <0,01). Los pacientes que se automedicaban OR = 1,56 (IC 95%: 1,12-2,16; p <0,01) y tomaban paracetamol OR = 1,41 (IC 95%: 1,01-1,98; p =0,04) tenían mayor riesgo de injuria hepática. Mientras tanto, los corticosteroides OR=0,55 (IC del 95%: 0,38-0,78; p <0,01) y la enoxaparina OR=0,53 (IC del 95%: 0,35-0,81; p <0,01) fueron factores protectores. Conclusiones: los pacientes peruanos con COVID-19 presentaron alta prevalencia de alte hepática, niveles elevados de AST y ALT se relacionaron con la gravedad de la enfermedad

ATR expands embryonic stem cell fate potential in response to replication stress

Fondazione Italiana per la Ricerca sul Cancro FIRC 18112 Sina Atashpaz.Fondazione Umberto Veronesi Sina Atashpaz Associazione Italiana per la Ricerca sul Cancro AIRC 5xmille METAMECH program Vincenzo Costanzo Giovanni Armenise-Harvard Foundation Vincenzo Costanzo European Research Council Consolidator grant 614541 Vincenzo Costanzo Associazione Italiana per la Ricerca sul Cancro Fellowship 23961 Negar ArghavanifarDanish Cancer Society KBVU-2014 Andres Joaquin Lopez-Contreras Danish Council for Independent Research Sapere Aude, DFF Starting Grant 2014 Andres Joaquin Lopez-Contreras European Research Council ERC-2015-STG-679068 Andres Joaquin Lopez-Contreras Danish National Research Foundation DNRF115 Andres Joaquin Lopez-Contreras The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.Unrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response to replication stress (RS) in mouse embryonic stem cells (ESCs) that induces genes expressed in totipotent two-cell (2C) stage embryos and 2C-like cells. This response is mediated by Dux, a multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals. In response to RS, DUX triggers the transcription of 2C-like markers such as murine endogenous retrovirus-like elements (MERVL) and Zscan4. This response can also be elicited by ETAA1-mediated ATR activation in the absence of RS. ATR-mediated activation of DUX requires GRSF1-dependent post-transcriptional regulation of Dux mRNA. Strikingly, activation of ATR expands ESCs fate potential by extending their contribution to both embryonic and extra-embryonic tissues. These findings define a novel ATR dependent pathway involved in maintaining genome stability in developing embryos by controlling ESCs fate in response to RS.S

Integration of energy and electron transfer processes in the photosynthetic membrane of Rhodobacter sphaeroides

Photosynthesis converts absorbed solar energy to a protonmotive force, which drives ATP synthesis. The membrane network of chlorophyll–protein complexes responsible for light absorption, photochemistry and quinol (QH2) production has been mapped in the purple phototrophic bacterium Rhodobacter (Rba.) sphaeroides using atomic force microscopy (AFM), but the membrane location of the cytochrome bc1 (cytbc1) complexes that oxidise QH2 to quinone (Q) to generate a protonmotive force is unknown. We labelled cytbc1 complexes with gold nanobeads, each attached by a Histidine10 (His10)-tag to the C-terminus of cytc1. Electron microscopy (EM) of negatively stained chromatophore vesicles showed that the majority of the cytbc1 complexes occur as dimers in the membrane. The cytbc1 complexes appeared to be adjacent to reaction centre light-harvesting 1-PufX (RC–LH1–PufX) complexes, consistent with AFM topographs of a gold-labelled membrane. His-tagged cytbc1 complexes were retrieved from chromatophores partially solubilised by detergent; RC–LH1–PufX complexes tended to co-purify with cytbc1 whereas LH2 complexes became detached, consistent with clusters of cytbc1 complexes close to RC–LH1–PufX arrays, but not with a fixed, stoichiometric cytbc1–RC–LH1–PufX supercomplex. This information was combined with a quantitative mass spectrometry (MS) analysis of the RC, cytbc1, ATP synthase, cytaa3 and cytcbb3 membrane protein complexes, to construct an atomic-level model of a chromatophore vesicle comprising 67 LH2 complexes, 11 LH1–RC–PufX dimers & 2 RC–LH1–PufX monomers, 4 cytbc1 dimers and 2 ATP synthases. Simulation of the interconnected energy, electron and proton transfer processes showed a half-maximal ATP turnover rate for a light intensity equivalent to only 1% of bright sunlight. Thus, the photosystem architecture of the chromatophore is optimised for growth at low light intensities

Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the single nucleotide polymorphism 309 (SNP309, T -> G) in the promoter region of the MDM2 gene is important for tumor development; however, with regards to breast cancer, inconsistent associations have been reported worldwide. It is speculated that these conflicting results may have arisen due to different patient subgroups and ethnicities studied. For the first time, this study explores the effect of the MDM2 SNP309 genotype on Taiwanese breast cancer patients.</p> <p>Methods</p> <p>Genomic DNA was obtained from the whole blood of 124 breast cancer patients and 97 cancer-free healthy women living in Taiwan. MDM2 SNP309 genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. The multivariate logistic regression and the Kaplan-Meier method were used for analyzing the risk association and significance of age at diagnosis among different MDM2 SNP309 genotypes, respectively.</p> <p>Results</p> <p>Compared to the TT genotype, an increased risk association with breast cancer was apparent for the GG genotype (OR = 3.05, 95% CI = 1.04 to 8.95), and for the TG genotype (OR = 2.12, 95% CI = 0.90 to 5.00) after adjusting for age, cardiovascular disease/diabetes, oral contraceptive usage, and body mass index, which exhibits significant difference between cases and controls. Furthermore, the average ages at diagnosis for breast cancer patients were 53.6, 52 and 47 years for those harboring TT, TG and GG genotypes, respectively. A significant difference in median age of onset for breast cancer between GG and TT+TG genotypes was obtained by the log-rank test (p = 0.0067).</p> <p>Conclusion</p> <p>Findings based on the current sample size suggest that the MDM2 SNP309 GG genotype may be associated with both the risk of breast cancer and an earlier age of onset in Taiwanese women.</p

Validation of the Spanish version of the Multidimensional State Boredom Scale (MSBS)

BACKGROUND: Boredom, which is a common problem in the general population, has been associated with several psychiatric disorders. The Multidimensional State Boredom Scale (MSBS) was developed, based on a theoretically and empirically grounded definition of boredom, to assess this construct. The aim of the present study was to assess the psychometric properties of the Spanish validated version of the MSBS in a multi-age sample recruited from the general population. METHODS: The patients (N = 303) were recruited from primary care settings. In addition to the sociodemographic variables and the MSBS, the General Health Questionnaire 28 items (GHQ-28), Positive and Negative Affect Scale (PANAS), Negative subscale and the Mindful Attention Awareness Scale (MAAS) were administered. We used confirmatory factor analysis (CFA) to analyse the dimensionality of the MSBS. Cronbach’s α coefficient was used to analyse the internal consistency of the scale. The consistency of the MSBS over time (test-retest reliability) was assessed using the intra-class correlation coefficient. The construct validity was examined by calculating Pearson’s r correlations between the MSBS with theoretically related and unrelated constructs. Cronbach’s α for MSBS was 0.89 (95 % CI, 0.87–0.92), ranging from 0.75 to 0.83 for the 5 subscales. RESULTS: The characteristics of the final sample (N = 303) were that the participants were primarily female (66.77 %) with a mean age of 49.32 years (SD, 11.46) and primarily European (94.71 %). The CFA of the MSBS confirmed that the original five-factor model showed good fit indices: CFI = .96; GFI = .94; SRMR = .05; and RMSEA = .06 [.05–.08]. Cronbach’s α for MSBS was 0.89 (95 % CI, 0.87–0.92), ranging from 0.75 to 0.83 for the 5 subscales. The MSBS showed a test-retest coefficient measured with an ICC of 0.90 (95 % CI, 0.88–0.92). The ICC for the 5 subscales ranged from 0.81 to 0.89. The MSBS showed a significant negative correlation with MAAS and a significant positive correlation with the GHQ (total score and subscales) and PANAS-Negative Affect. CONCLUSIONS: The Spanish version of the MSBS has been validated as a reliable instrument for measuring boredom in the general population. This study will facilitate the assessment of boredom for clinical and research purposes in Spanish-speaking populations

Generation of the first BAC-based physical map of the common carp genome

<p>Abstract</p> <p>Background</p> <p>Common carp (<it>Cyprinus carpio</it>), a member of Cyprinidae, is the third most important aquaculture species in the world with an annual global production of 3.4 million metric tons, accounting for nearly 14% of the all freshwater aquaculture production in the world. Apparently genomic resources are needed for this species in order to study its performance and production traits. In spite of much progress, no physical maps have been available for common carp. The objective of this project was to generate a BAC-based physical map using fluorescent restriction fingerprinting.</p> <p>Result</p> <p>The first generation of common carp physical map was constructed using four- color High Information Content Fingerprinting (HICF). A total of 72,158 BAC clones were analyzed that generated 67,493 valid fingerprints (5.5 × genome coverage). These BAC clones were assembled into 3,696 contigs with the average length of 476 kb and a N50 length of 688 kb, representing approximately 1.76 Gb of the common carp genome. The largest contig contained 171 BAC clones with the physical length of 3.12 Mb. There are 761 contigs longer than the N50, and these contigs should be the most useful resource for future integrations with linkage map and whole genome sequence assembly. The common carp physical map is available at <url>http://genomics.cafs.ac.cn/fpc/WebAGCoL/Carp/WebFPC/</url>.</p> <p>Conclusion</p> <p>The reported common carp physical map is the first physical map of the common carp genome. It should be a valuable genome resource facilitating whole genome sequence assembly and characterization of position-based genes important for aquaculture traits.</p