Translocation of NS3 from Hepatitis C Virus on RNA: Insights from Atomistic Molecular Simulations

Helicases are motor proteins that unwind double stranded nucleic acids and are important parts of the genetic apparatus. A notable member of this family of enzymes is the nun-structural protein NS3 from Hepatitis C Virus. NS3 helicase unwinds nucleic acids by translocating along a single strand. Single molecule experiments and X-ray crystallography suggest that NS3 follows an inchworm-like motion during the translocation mechanism, consuming one ATP molecule per cycle. In spite of the available experimental data, the mechanistic and chemical details of the translocation process are still unclear. The aim of this study is to model at atomistic detail the NS3h-RNA complex at the different stages of the translocation. For this purpose, atomistic molecular dynamics simulations were performed in explicit solvent in the presence and in the absence of ATP and ADP. Simulations were initialized based on existing crystallographic structures. All the stages of translocation were considered, and their relative stabilities were analyzed by computing electrostatic interactions, relative enthalpies, and hydrogen-bond patterns. Additionally, well-tempered metadynamics and Hamiltonian replica exchange simulations were performed to characterize the free-energy landscape associated to translocation and to describe the conformational transitions

Aplicación del modelo Koter en el sistema de gestión de calidad e inocuidad, con el fin de generar cultura

El método de Kotter ha sido reiterado para el desarrollo y sostenimiento de la cultura en las organizaciones, parte de los sistemas de gestión aplicados en las empresas agroindustriales exige cultura en las organizaciones en relación con la inocuidad y calidad alimentaria. Y ante el reto de la implementación este tipo de estrategias facilitan los procesos. Son siete los pasos cuya implementación puede lograr el propósito cultural de que las personas actúen de la forma correcta aún cuando nadie los observa. En la organización que se está desarrollando dicho proceso, se tiene un diagnóstico inicial, el cual demuestra que se cuenta con una percepción favorable de cultura de inocuidad y calidad en la organización , y permite identificar las mejoras para lograr y sostener en el tiempo la cultura que se espera para el sistema de gestión.Kotter's method has been reiterated for the development and maintenance of culture in organizations, management systems in agro-industrial companies require food safety and quality culture in organizations. In regards to the of the food safety and quality culture implementation challenge, this type of strategy helps the processes to do it. There are seven steps whose implementation can achieve the cultural purpose of people acting correctly in the same way even when no one is watching. In the organization which is developing this kotter method process, there is an initial diagnosis that was done, and the results showed that there is a favorable perception of a culture of safety and quality inside the organization, and allowed to identify the improvements to achieve the goals in relation to the culture that is expected for the safety and quality management system.Rionegr

Crystal structure, physicochemical properties, Hirshfeld surface analysis and antibacterial activity assays of transition metal complexes of 6-methoxyquinoline

Five monomeric complexes of Co(ii), Cu(ii), Ni(ii), Zn(ii) and Ag(i) with 6-methoxyquinoline (6-MeOQ) as ligand have been prepared, and their crystal structures have been determined by single X-ray diffractions. The Cu(ii), Ni(ii) and Zn(ii) complexes are formulated as M(6-MeOQ) 2 Cl 2 , completing MN 2 Cl 2 coordination spheres. On the other hand, Co(ii) and Ag(i) compounds are ionic with formulae [Ag(6-MeOQ) 2 ] + NO 3 - and H(6-MeOQ) + [Co(6-MeOQ)Cl 3 ] - (where H(6-MeOQ) + is the protonated ligand). Hirshfeld surface analysis was employed to study the intermolecular interactions in the crystal lattices and from these studies it was found that π-stacking contacts play an important role. Besides, the complexes have been characterized by FTIR, UV-visible and emission spectroscopies. The singlet oxygen production and fluorescence quantum yields were measured for all the complexes employing steady-state methodologies. Finally, the antibacterial activity of the complexes was screened against both Gram-positive and Gram-negative bacteria.Fil: Villa Perez, Cristian. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; ArgentinaFil: Ortega, I.C.. Universidad Nacional de Colombia; ColombiaFil: Vélez Macías, Andrea. Universidad Nacional de Colombia; ColombiaFil: Payán, A. M.. Universidad Nacional de Colombia; ColombiaFil: Echeverría, Gustavo Alberto. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; ArgentinaFil: Soria, Delia Beatriz. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; ArgentinaFil: Valencia Uribe, Gloria Cristina. Universidad Nacional de Colombia; Colombi

In-flight calibration and verification of the Planck-LFI instrument

In this paper we discuss the Planck-LFI in-flight calibration campaign. After a brief overview of the ground test campaigns, we describe in detail the calibration and performance verification (CPV) phase, carried out in space during and just after the cool-down of LFI. We discuss in detail the functionality verification, the tuning of the front-end and warm electronics, the preliminary performance assessment and the thermal susceptibility tests. The logic, sequence, goals and results of the in-flight tests are discussed. All the calibration activities were successfully carried out and the instrument response was comparable to the one observed on ground. For some channels the in-flight tuning activity allowed us to improve significantly the noise performance.Comment: Long technical paper on Planck LFI in flight calibration campaign: 109 pages in this (not final) version, 100 page in the final JINST versio

A new case report of severe mucopolysaccharidosis type VII: diagnosis, treatment with haematopoietic cell transplantation and prenatal diagnosis in a second pregnancy

A new patient with severe mucopolysaccharidosis (MPS) type VII is reported. Non-immune hydrops fetalis (NIHF) was diagnosed during pregnancy. At birth, he showed generalized hydrops and dysmorphic features typical of MPS. Many diagnoses were excluded before reaching the diagnosis of MPS VII at 8 months of life. During the first year of life he had frequent respiratory infections associated with restrictive and obstructive bronchopneumopathy and underwent three surgical interventions: decompression of the spinal cord at the craniocervical junction, bilateral inguinal hernia, and bilateral clubfoot. At 14 months of life he underwent successful haematopoietic cell transplantation (HCT). During the following 10 months, his bronchopneumopathy progressively worsened, needing chronic pharmacological treatment and O2 administration. The patient died of respiratory insufficiency during a respiratory syncytial virus infection at 25 months of age. Molecular analysis showed the homozygous variant c.1617C > T, leading to the synonymous mutation p.Ser539=. This caused aberrant splicing with partial skipping of exon 10 (r.1616_1653del38) and complete skipping of exon 9 (r.1392_1476del85; r.1616_1653del38). No transcript of normal size was evident. The parents were both confirmed to be carriers. In a subsequent pregnancy, a prenatal diagnosis showed an affected fetus. Ultrasound examination before abortion showed NIHF. The skin and placenta examination by electron microscopy showed foamy intracytoplasmic vacuoles with a weakly electron-dense substrate. MPS VII is a very rare disease but it is possible that some cases go undiagnosed for several reasons, including that MPS VII, and other lysosomal storage diseases, are not included in the work-up for NIHF in many institutions, and the presence of anasarca at birth may be confounding for the recognition of the typical facial characteristics of the disease. This is the eighth patient affected by MPS VII who has undergone HCT. It is not possible to draw conclusions about the efficacy of HCT in MPS VII. Treatment with enzyme replacement is now available and will probably be beneficial for the patients who have a milder form with no or little cognitive involvement. Increased awareness among clinicians is needed for prompt diagnosis and to offer the correct treatment as early as possible

The STRIP instrument of the Large Scale Polarization Explorer: microwave eyes to map the Galactic polarized foregrounds

In this paper we discuss the latest developments of the STRIP instrument of the "Large Scale Polarization Explorer" (LSPE) experiment. LSPE is a novel project that combines ground-based (STRIP) and balloon-borne (SWIPE) polarization measurements of the microwave sky on large angular scales to attempt a detection of the "B-modes" of the Cosmic Microwave Background polarization. STRIP will observe approximately 25% of the Northern sky from the "Observatorio del Teide" in Tenerife, using an array of forty-nine coherent polarimeters at 43 GHz, coupled to a 1.5 m fully rotating crossed-Dragone telescope. A second frequency channel with six-elements at 95 GHz will be exploited as an atmospheric monitor. At present, most of the hardware of the STRIP instrument has been developed and tested at sub-system level. System-level characterization, starting in July 2018, will lead STRIP to be shipped and installed at the observation site within the end of the year. The on-site verification and calibration of the whole instrument will prepare STRIP for a 2-years campaign for the observation of the CMB polarization.Comment: 17 pages, 15 figures, proceedings of the SPIE Astronomical Telescopes + Instrumentation conference "Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy IX", on June 15th, 2018, Austin (TX

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project

OBJECTIVES: To estimate the risk of AMI for individual NSAIDs.METHODS: A nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999-2011) match

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum TimeCourse

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.This research was partially funded by FOREUM—Foundation for Research in Rheumatolog