Theoretical and experimental study of the vibrational spectra of 1.5-dimethylcytosine

The Raman spectra of the solid 1,5-dimethylcytosine and the FTIR spectra at room and low temperatures respectively have been registered. Quantum mechanical calculations of energies, geometries and vibrational wavenumbers were carried out by using ab initio (HF) and Density Functional Theory (DFT/BLYP and B3LYP) methods with different basis sets. The best level of theory in order to reproduce the experimental wavenumbers is the BLYP method with the 6-31G* basis set. The theoretical calculations indicate the presence of four stable tautomers of 1,5-dimethylcytosine: amino-oxo; imino-oxo (a and b) and imino-hidroxy. Their geometries were optimised by using the BLYP/6-31G* method, being the amino-oxo tautomer the most stable, followed by the imino-oxo tautomer, while the imino-hidroxy one is the most unstable. The complete assignment of the observed bands in the vibrational spectra of the amino-oxo tautomer is proposed in this work. © 2007 Elsevier B.V. All rights reserved.Fil: Brandán, S.A.. Universidad Nacional de Tucumán; ArgentinaFil: Benzal, María Graciela. Universidad Nacional de Tucumán; ArgentinaFil: García Ramos, J.V.. Csic - Instituto de Estructura de la Materia (iem);Fil: Otero, J.C.. Universidad de Málaga; EspañaFil: Ben Altabef, Aida. Universidad Nacional de Tucumán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentin

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype

The surface detector array of the Telescope Array experiment

The Telescope Array (TA) experiment, located in the western desert of Utah,USA, is designed for observation of extensive air showers from extremely high energy cosmic rays. The experiment has a surface detector array surrounded by three fluorescence detectors to enable simultaneous detection of shower particles at ground level and fluorescence photons along the shower track. The TA surface detectors and fluorescence detectors started full hybrid observation in March, 2008. In this article we describe the design and technical features of the TA surface detector.Comment: 32 pages, 17 figure

New air fluorescence detectors employed in the Telescope Array experiment

Since 2007, the Telescope Array (TA) experiment, based in Utah, USA, has been observing ultra high energy cosmic rays to understand their origins. The experiment involves a surface detector (SD) array and three fluorescence detector (FD) stations. FD stations, installed surrounding the SD array, measure the air fluorescence light emitted from extensive air showers (EASs) for precise determination of their energies and species. The detectors employed at one of the three FD stations were relocated from the High Resolution Fly's Eye experiment. At the other two stations, newly designed detectors were constructed for the TA experiment. An FD consists of a primary mirror and a camera equipped with photomultiplier tubes. To obtain the EAS parameters with high accuracies, understanding the FD optical characteristics is important. In this paper, we report the characteristics and installation of new FDs and the performances of the FD components. The results of the monitored mirror reflectance during the observation time are also described in this report.Comment: 44 pages, 23 figures, submitted to NIM-

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Validation of the Malay version of the multidimensional scale of perceived social support (MSPSS-M) among a group of medical students in Faculty of Medicine, University Malaya

Objective: The aim of this study was to validate the Malay version of the Multidimensional Scale of Perceived Social Support (MSPSS-M) among a group of medical students in Faculty of Medicine, University Malaya. Methods: 237 students participated in the study. They were given the Malay version of MSPSS, medical outcome study (MOS) social support survey, Malay version of General Health Questionnaire (GHQ), Malay version of Beck Depression Inventory (BDI) and English version of MSPSS. A week later, these students were again given the Malay version of MSPSS. Results: The instrument displayed good internal consistency (Cronbach's alpha = 0.89), parallel form reliability (0.94) and test�retest reliability (0.77) (Spearman's rho, p < 0.01). The negative correlation of the total and subscales of the instrument with the Malay version of GHQ and BDI confirmed its validity. Extraction method of the 12 items MSPSS using principle axis factoring with direct oblimin rotation converged into three factors of perceived social support (Family, Friends and Significant Others) with reliability coefficients of 0.88, 0.82 and 0.94, respectively. Conclusion: The Malay version of the MSPSS demonstrated good psychometric properties in measuring social support among a group of medical students from Faculty of Medicine, University Malaya and it could be used as a simple instrument on young educated Malaysian adolescents

Association of ADRA2A and MTHFR gene polymorphisms with weight loss following antipsychotic switching to aripiprazole or ziprasidone

ObjectivesVarious genetic polymorphisms have been reported to be associated with antipsychotic-induced weight gain. In this study, we aimed to determine whether risk polymorphisms in 12 candidate genes are associated with reduction in body mass index (BMI) of patients following switching of antipsychotics to aripiprazole or ziprasidone. MethodsWe recruited 115 schizophrenia patients with metabolic abnormalities and who have been on at least 1year treatment with other antipsychotics; they were then switched to either aripiprazole or ziprasidone. They were genotyped, and their BMI monitored for 6months. ResultsSignificant associations with reduction in BMI at 6months following switching were found in two of these genes: with rs1800544 of the ADRA2A gene (CC+CG -0.321.41kg/m(2) vs GG -1.04 +/- 1.63kg/m(2), p=0.013) and with rs1801131 of the MTHFR gene (AA -0.36 +/- 1.53 vs AC+CC -1.07 +/- 1.53, p=0.015). ConclusionThe study data indicated that carriage of the ADRA2A rs1800544 GG genotype and the MTHFR rs1801131 C allele are associated with BMI reduction in this population following switching of antipsychotics to aripiprazole and ziprasidone. Copyright (c) 2013 John Wiley & Sons, Ltd