Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases

We define phosphovariants as genetic variations that change phosphorylation sites or their interacting kinases. Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions and may constitute a proportion of the mechanisms by which genetic variations cause individual differences or diseases. We categorized phosphovariants into three subtypes and developed a system that predicts them. Our method can be used to screen important polymorphisms and help to identify the mechanisms of genetic diseases

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of <it>LEPR </it>gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the <it>LEPR </it>gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the <it>LEPR </it>gene locus in DNA copy number analyses.</p> <p>Results</p> <p>We identified DNA copy number variations at the <it>LEPR </it>gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between <it>LEPR </it>and <it>LEPROT </it>genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (<it>p </it>= 1.24 × 10^-7) and women (<it>p </it>= 9.45 × 10^-5), as well as higher total cholesterol levels in men (<it>p </it>= 9.96 × 10^-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.</p> <p>Conclusions</p> <p>This work suggests that a structural variation at the <it>LEPR </it>gene locus is functionally associated with complex metabolic traits and the risk of T2DM.</p

In-situ fabrication of cobalt-doped SrFe2As2 thin films by using pulsed laser deposition with excimer laser

The remarkably high superconducting transition temperature and upper critical field of iron(Fe)-based layered superconductors, despite ferromagnetic material base, open the prospect for superconducting electronics. However, success in superconducting electronics has been limited because of difficulties in fabricating high-quality thin films. We report the growth of high-quality c-axis-oriented cobalt(Co)-doped SrFe2As2 thin films with bulk superconductivity by using an in-situ pulsed laser deposition technique with a 248-nm-wavelength KrF excimer laser and an arsenic(As)-rich phase target. The temperature and field dependences of the magnetization showing strong diamagnetism and transport critical current density with superior Jc-H performance are reported. These results provide necessary information for practical applications of Fe-based superconductors.Comment: 8 pages, 3figures. to be published at Appl. Phys. Let

Fabrication of FeSe1-x superconducting films with bulk properties

We have fabricated high-quality FeSe1-x superconducting films with a bulk Tc of 11-12 K on different substrates, Al2O3(0001), SrTiO3(100), MgO(100), and LaAlO3(100), by using a pulsed laser deposition technique. All the films were grown at a high substrate temperature of 610 oC, and were preferentially oriented along the (101) direction, the latter being to be a key to fabricating of FeSe1-x superconducting thin films with high Tc. According to the energy dispersive spectroscopy data, the Fe:Se composition ratio was 1:0.90+-0.02. The FeSe1-x film grown on a SrTiO3 substrate showed the best quality with a high upper critical magnetic field [Hc2(0)] of 56 T

Inhibition of HIF-1 alpha by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Folliculosebaceous Cystic Hamartoma in a Patient with Neurofibromatosis Type I

Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma composed of dilated folliculosebaceous units and mesenchymal elements. It presents as a papule or nodule usually on the face and scalp, rarely on the genital or trunk area. Histologically, FSCH shares several similar features to sebaceous trichofolliculoma. We report one case of FSCH misdiagnosed as a neurofibroma. He was a 38-year-old man with a neurofibromatosis type I and a nodule on his left earlobe was excised under the impression of neurofibroma. Pathological examination revealed FSCH. Although FSCH is clinically not distinctive, awareness of the lesion is important to differentiate papulonodular or cyst-like cutaneous lesions

Rapid diagnostic tests for molecular surveillance of Plasmodium falciparum malaria -assessment of DNA extraction methods and field applicability

Background: The need for new malaria surveillance tools and strategies is critical, given improved global malaria control and regional elimination efforts. High quality Plasmodium falciparum DNA can reliably be extracted from malaria rapid diagnostic tests (RDTs). Together with highly sensitive molecular assays, wide scale collection of used RDTs may serve as a modern tool for improved malaria case detection and drug resistance surveillance. However, comparative studies of DNA extraction efficiency from RDTs and the field applicability are lacking. The aim of this study was to compare and evaluate different methods of DNA extraction from RDTs and to test the field applicability for the purpose of molecular epidemiological investigations. Methods: DNA was extracted from two RDT devices (Paracheck-PfW and SD Bioline Malaria Pf/Pan (R)), seeded in vitro with 10-fold dilutions of cultured 3D7 P. falciparum parasites diluted in malaria negative whole blood. The level of P. falciparum detection was determined for each extraction method and RDT device with multiple nested-PCR and real-time PCR assays. The field applicability was tested on 855 paired RDT (Paracheck-Pf) and filter paper (Whatman (R) 3MM) blood samples (734 RDT negative and 121 RDT positive samples) collected from febrile patients in Zanzibar 2010. RDT positive samples were genotyped at four key single nucleotide polymorphisms (SNPs) in pfmdr1 and pfcrt as well as for pfmdr1 copy number, all associated with anti-malarial drug resistance. Results: The P. falciparum DNA detection limit varied with RDT device and extraction method. Chelex-100 extraction performed best for all extraction matrixes. There was no statistically significant difference in PCR detection rates in DNA extracted from RDTs and filter paper field samples. Similarly there were no significant differences in the PCR success rates and genotyping outcomes for the respective SNPs in the 121 RDT positive samples. Conclusions: The results support RDTs as a valuable source of parasite DNA and provide evidence for RDT-DNA extraction for improved malaria case detection, molecular drug resistance surveillance, and RDT quality control.ACT Consortium through Bill and Melinda Gates Foundation; Swedish International Development Agency (SIDA) [SWE 2009-193]; Swedish Civil Contingencies Agency (MSB) [2010-7991]; Swedish Medical Research Council (VR) [2009-3785]; Goljes Foundationinfo:eu-repo/semantics/publishedVersio

Levels of noise in a public hospital laundry

PURPOSE: to measure the noise levels in different shifts of Hospital São Paulo's (HSP) laundry and provide information on health and hearing conservation to the employees and supervisors of the sector. METHODS: this is a descriptive transversal study. The noise levels were checked using a Sound Pressure Meter in the Clean Area of the laundry, in three periods of the day: morning (between 7am and 8am), afternoon (between 12pm and 1pm) and night (between 5pm and 6pm), in three different days and each measurement lasted five minutes. The examiners also checked the use of Personal Protection Equipment (PPE) by the employees. RESULTS: we observed 11 machines (skylarks, dryers and washers) in the sector, which contribute to an important variation of noise levels in the laundry (70 to 101 dB) in the checked periods. The use of PPE by employees was rare, observing the use by only six employees (12.76%). CONCLUSIONS: regardless of the shift, Hospital São Paulo laundry's employees, who do not effectively use PPEs, are daily exposed to high levels of sound pressure and as the number of machines in operation increased, the noise levels were also higher.OBJETIVO: mensurar os níveis de ruído em diferentes turnos da lavanderia do Hospital São Paulo (HSP) e prestar esclarecimentos sobre a saúde e a conservação auditivas aos funcionários e supervisores do setor. MÉTODOS: trata-se de um estudo transversal descritivo. O ruído foi aferido por meio do medidor de pressão sonora na Área Limpa da lavanderia do HSP, em três períodos do dia: manhã (entre 7h e 8h), tarde (entre 12h e 13h) e noite (entre 17h e 18h), por três dias e cada medição durou cinco minutos. Observou-se o uso de Equipamento de Proteção Individual (EPI) pelos funcionários em cada ambiente do hospital. RESULTADOS: observou-se 11 máquinas (calandras, secadoras e lavadoras) no setor, que contribuiu para uma variação importante dos níveis de ruído na lavanderia (70 a 101 dB) nos períodos aferidos. O uso de EPI pelos funcionários foi raro, tendo sido observada sua utilização por seis funcionários (12,76%). CONCLUSÃO: independente do turno, os funcionários da lavanderia do Hospital São Paulo, os quais não fazem uso efetivo de EPIs, estão expostos diariamente a elevados níveis de pressão sonora, e que quanto maior o número de máquinas em funcionamento, maior foi o nível de ruído aferido.FESPUNIFESPUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Industrial validation of a predictive model of the nutritional quality of tomato-based products during processes

Opti’Tom aims to develop and confirm, at pilot and industrial scale, stoichio-kinetic models describing changes in micronutrients contents in tomato-based products during processing. Two kinds of processes were studied such as production of tomato paste from fresh tomatoes and sauces from tomato paste. Several pilot trials were conducted and the data (amounts of microconstituents, schedules of the processes) were exploited to develop a software in order to optimize the current manufacturing processes