126 research outputs found
Origin and Epidemiological History of HIV-1 CRF14_BG
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. Users must also make clear the license terms under which the work was published. CC BY Licence: http://creativecommons.org/licenses/by/4.0/Background: CRF14_BG isolates, originally found in Spain, are characterized by CXCR4 tropism and rapid disease
progression. This study aimed to identify the origin of CRF14_BG and reconstruct its epidemiological history based on new
isolates from Portugal.Methodology/Principal Findings: C2V3C3 env gene sequences were obtained from 62 samples collected in 1993–1998
from Portuguese HIV-1 patients. Full-length genomic sequences were obtained from three patients. Viral subtypes, diversity,
divergence rate and positive selection were investigated by phylogenetic analysis. The molecular structure of the genomes
was determined by bootscanning. A relaxed molecular clock model was used to date the origin of CRF14_BG. Geno2pheno
was used to predict viral tropism. Subtype B was the most prevalent subtype (45 sequences; 73%) followed by CRF14_BG (8;
13%), G (4; 6%), F1 (2; 3%), C (2; 3%) and CRF02_AG (1; 2%). Three CRF14_BG sequences were derived from 1993 samples.
Near full-length genomic sequences were strongly related to the CRF14_BG isolates from Spain. Genetic diversity of the
Portuguese isolates was significantly higher than the Spanish isolates (0.044 vs 0.014, P,0.0001). The mean date of origin of
the CRF14_BG cluster was estimated to be 1992 (range, 1989 and 1996) based on the subtype G genomic region and 1989
(range, 1984–1993) based on the subtype B genomic region. Most CRF14_BG strains (78.9%) were predicted to be CXCR4.
Finally, up to five amino acids were under selective pressure in subtype B V3 loop whereas only one was found in the
CRF14_BG cluster.Conclusions: CRF14_BG emerged in Portugal in the early 1990 s soon after the beginning of the HIV-1 epidemics, spread to
Spain in late 1990 s as a consequence of IVDUs migration and then to the rest of Europe. CXCR4 tropism is a general
characteristic of this CRF that may have been selected for by escape from neutralizing antibody response
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK
Cancer Research UK
ERC
H2020
Wellcome Trus
Progress along developmental tracks for electronic health records implementation in the United States
The development and implementation of electronic health records (EHR) have occurred slowly in the United States. To date, these approaches have, for the most part, followed four developmental tracks: (a) Enhancement of immunization registries and linkage with other health records to produce Child Health Profiles (CHP), (b) Regional Health Information Organization (RHIO) demonstration projects to link together patient medical records, (c) Insurance company projects linked to ICD-9 codes and patient records for cost-benefit assessments, and (d) Consortia of EHR developers collaborating to model systems requirements and standards for data linkage. Until recently, these separate efforts have been conducted in the very silos that they had intended to eliminate, and there is still considerable debate concerning health professionals access to as well as commitment to using EHR if these systems are provided. This paper will describe these four developmental tracks, patient rights and the legal environment for EHR, international comparisons, and future projections for EHR expansion across health networks in the United States
Moving beyond Marcuse: gentrification, displacement and the violence of un-homing
Displacement has become one of the most prominent themes in contemporary geographical debates, used to describe processes of dispossession and forced eviction at a diverse range of scales. Given its frequent deployment in studies describing the consequences of gentrification, this paper seeks to better define and conceptualise displacement as a process of un-homing, noting that while gentrification can prompt processes of eviction, expulsion and exclusion operating at different scales and speeds, it always ruptures the connection between people and place. On this basis – and recognising displacement as a form of violence – this paper concludes that the diverse scales and temporalities of displacement need to be better elucidated so that their negative emotional, psychosocial and material impacts can be more fully documented, and resisted
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients
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