Conformations of Flanking Bases in HIV-1 RNA DIS Kissing Complexes Studied by Molecular Dynamics

Explicit solvent molecular dynamics simulations (in total almost 800 ns including locally enhanced sampling runs) were applied with different ion conditions and with two force fields (AMBER and CHARMM) to characterize typical geometries adopted by the flanking bases in the RNA kissing-loop complexes. We focus on flanking base positions in multiple x-ray and NMR structures of HIV-1 DIS kissing complexes and kissing complex from the large ribosomal subunit of Haloarcula marismortui. An initial x-ray open conformation of bulged-out bases in HIV-1 DIS complexes, affected by crystal packing, tends to convert to a closed conformation formed by consecutive stretch of four stacked purine bases. This is in agreement with those recent crystals where the packing is essentially avoided. We also observed variants of the closed conformation with three stacked bases, while nonnegligible populations of stacked geometries with bulged-in bases were detected, too. The simulation results reconcile differences in positions of the flanking bases observed in x-ray and NMR studies. Our results suggest that bulged-out geometries are somewhat more preferred, which is in accord with recent experiments showing that they may mediate tertiary contacts in biomolecular assemblies or allow binding of aminoglycoside antibiotics

Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Glioblastoma: Pathology and genetics

Glioblastomas are by far the most frequent and the most malignant tumors originating in the parenchyma of the central nervous system (CNS). In the revised 4th edition of the WHO classification of CNS tumors (published in 2016), classification of these gliomas has fundamentally changed as for the first time presence or absence of particular molecular aberrations is now part of their definition. This review discusses current insights in characteristics of the main molecular subgroups of glioblastoma and how the paradigm shift of a purely histologic towards a histomolecular classification of gliomas has impacted the clinical diagnosis of these tumors

Improvement of the ISO 10634 guidance document for the preparation and treatment of poorly water-soluble organic compounds for the evaluation of their biodegradability in aqueous media

Current regulations on chemicals in most regions of the world recommend or require the assessment of biodegradability. It is commonly agreed that the assessment of biodegradability starts with a ready biodegradability test. To perform these tests, the recommendations of the ISO standards or OECD guidelines should be followed. Nevertheless, relevant infomation is missing when the chemical under test is not soluble in water. Since 2011, L'Oréal has worked on the preparation techniques in order to incorporate this type of compound in the media before the test. The systematic review of ISO 10634 standard dealing exclusively with this subject, was found as a good opportunity to disseminate the work carried out in this context. The recast of this standard is based on the updating of the methods already described as well as the proposal of new adapted methods. These bioavailability improvement methods in ready biodegradability tests were discussed to AFNOR and ISO working groups in order to revise the document ISO 10634. The performed experimental work made it possible to propose new bioavailability improvement methods and an subsequent update of ISO 10634 standard. This revised standard will make available to CROs all the information needed to improve the assessment of the readily biodegradability of water-insoluble chemicals. If the modification of an existing standard may seem long (several years), this must be put into perspective given the necessary scientific and bibliographic work and discussion between experts within the ISO/TC 147/SC5/WG 1. A new version of the 10634 ISO standard is expected to be published in 2018