646 research outputs found
Dietary magnesium, not calcium, prevents vascular calcification in a mouse model for pseudoxanthoma elasticum
Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic calcification of connective tissue in skin, Bruch’s membrane of the eye, and walls of blood vessels. PXE is caused by mutations in the ABCC6 gene, but the exact etiology is still unknown. While observations on patients suggest that high calcium intake worsens the clinical symptoms, the patient organization PXE International has published the dietary advice to increase calcium intake in combination with increased magnesium intake. To obtain more data on this controversial issue, we examined the effect of dietary calcium and magnesium in the Abcc6−/− mouse, a PXE mouse model which mimics the clinical features of PXE. Abcc6−/− mice were placed on specific diets for 3, 7, and 12 months. Disease severity was measured by quantifying calcification of blood vessels in the kidney. Raising the calcium content in the diet from 0.5% to 2% did not change disease severity. In contrast, simultaneous increase of both calcium (from 0.5% to 2.0%) and magnesium (from 0.05% to 0.2%) slowed down the calcification significantly. Our present findings that increase in dietary magnesium reduces vascular calcification in a mouse model for PXE should stimulate further studies to establish a dietary intervention for PXE
The MSX1 allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts
Nonsyndromic orofacial clefts (OFC) are common birth defects caused by certain genes interacting with environmental factors. Mutations and association studies indicate that the homeobox gene MSX1 plays a role in human clefting. In a Dutch case-control triad study (mother, father, and child), we investigated interactions between MSX1 and the parents' periconceptional lifestyle in relation to the risk of OFC in their offspring. We s
Production and evolution of Li, Be and B isotopes in the Galaxy
We reassess the problem of the production and evolution of the light elements
Li, Be and B and of their isotopes in the Milky Way, in the light of new
observational and theoretical developments. The main novelty is the
introduction of a new scheme for the origin of Galactic cosmic rays (GCR),
which for the first time enables a self-consistent calculation of their
composition during galactic evolution. The scheme accounts for key features of
the present-day GCR source composition, it is based on the wind yields of the
Geneva models of rotating, mass losing stars and it is fully coupled to a
detailed galactic chemical evolution code. We find that the adopted GCR source
composition accounts naturally for the observations of primary Be and helps
understanding why Be follows closer Fe than O. We find that GCR produce ~70% of
the solar B11/B10 isotopic ratio; the remaining 30% of B11 presumably result
from neutrino-nucleosynthesis in massive star explosions. We find that GCR and
primordial nucleosynthesis can make at most 30% of solar Li. At least half of
solar Li has to originate in low-mass stellar sources (red giants, asymptotic
giant branch stars or novae), but the required average yields of those sources
are found to be much larger than obtained in current models of stellar
nucleosynthesis. We also present radial profiles of LiBeB elemental and
isotopic abundances in the Milky Way disc. We argue that the shape of those
profiles - and the late evolution of LiBeB in general - reveals important
features of the production of those light elements through primary and
secondary processes.Comment: Final version, matches the one to appear in Astronomy and
Astrophysics, typos corrected, references adde
Type Ia Supernova Explosion Models
Because calibrated light curves of Type Ia supernovae have become a major
tool to determine the local expansion rate of the Universe and also its
geometrical structure, considerable attention has been given to models of these
events over the past couple of years. There are good reasons to believe that
perhaps most Type Ia supernovae are the explosions of white dwarfs that have
approached the Chandrasekhar mass, M_ch ~ 1.39 M_sun, and are disrupted by
thermonuclear fusion of carbon and oxygen. However, the mechanism whereby such
accreting carbon-oxygen white dwarfs explode continues to be uncertain. Recent
progress in modeling Type Ia supernovae as well as several of the still open
questions are addressed in this review. Although the main emphasis will be on
studies of the explosion mechanism itself and on the related physical
processes, including the physics of turbulent nuclear combustion in degenerate
stars, we also discuss observational constraints.Comment: 38 pages, 4 figures, Annual Review of Astronomy and Astrophysics, in
pres
Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.
Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders
A Rapid Evidence Appraisal of influenza vaccination in health workers: an important policy in an area of imperfect evidence
IntroductionThe World Health Organization recommends vaccination of health workers (HWs) against influenza, but low uptake is intransigent.We conducted a Rapid Evidence Appraisal on: the risk of influenza in HWs, transmission risk from HWs to patients, the benefit of HW vaccination, and strategies for improving uptake. We aimed to capture a ‘whole-of-system’ perspective to consider possible benefits for HWs, employers and patients.MethodsWe executed a comprehensive search of the available literature published from 2006 to 2018 in the English language. We developed search terms for seven separate questions following the PICO framework (population, intervention, comparators, outcomes) and queried nine databases.ResultsOf 3784 publications identified, 52 met inclusion criteria. Seven addressed HW influenza risk, of which four found increased risk; 15 addressed influenza vaccine benefit to HWs or their employers, of which 10 found benefit; 11 addressed influenza transmission from HWs to patients, of which 6 found evidence for transmission; 12 unique studies addressed whether vaccinating HWs produced patient benefit, of which 9 concluded benefits accrued. Regarding the number of HWs needed to vaccinate (NNV) to deliver patient benefit, NNV estimates ranged from 3 to 36,000 but were in significant disagreement. Fourteen studies provided insights on strategies to improve uptake; the strongest evidence was for mandatory vaccination.ConclusionsThe evidence on most questions related to influenza vaccination in HWs is mixed and often of low-quality. Substantial heterogeneity exists in terms of study designs and settings, making comparison between studies difficult. Notwithstanding these limitations, a majority of studies suggests that influenza vaccination benefit HWs and their employers; and HWs are implicated in transmission events. The effects of vaccinating HWs on patient morbidity and mortality may include reductions in all-cause mortality and influenza-like illness (ILI). Taken together, the evidence suggests that HW vaccination is an important policy for HWs themselves, their employers, and their patients
Stellar Coronal and Wind Models: Impact on Exoplanets
Surface magnetism is believed to be the main driver of coronal heating and
stellar wind acceleration. Coronae are believed to be formed by plasma confined
in closed magnetic coronal loops of the stars, with winds mainly originating in
open magnetic field line regions. In this Chapter, we review some basic
properties of stellar coronae and winds and present some existing models. In
the last part of this Chapter, we discuss the effects of coronal winds on
exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief:
Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer
Reference Work
CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation and AP-1 Activation
Cyclin-dependent kinases (CDKs) and their targets have been primarily associated
with regulation of cell-cycle progression. Here we identify c-Jun, a
transcription factor involved in the regulation of a broad spectrum of cellular
functions, as a newly recognized CDK substrate. Using immune cells from mouse
and human, and several complementary in vitro and in
vivo approaches including dominant negative protein expression,
pharmacologic inhibitors, kinase assays and CDK4 deficient cells, we demonstrate
the ability of CDK4 to phosphorylate c-Jun. Additionally, the activity of AP-1,
a ubiquitous transcription factor containing phosphorylated c-Jun as a subunit,
was inhibited by abrogating CDK4. Surprisingly, the regulation of c-Jun
phosphorylation by CDK4 occurred in non-dividing cells, indicating that this
pathway is utilized for cell functions that are independent of proliferation.
Our studies identify a new substrate for CDK4 and suggest a mechanism by which
CDKs can regulate multiple cellular activation functions, not all of which are
directly associated with cell cycle progression. These findings point to
additional roles of CDKs in cell signaling and reveal potential implications for
therapeutic manipulations of this kinase pathway
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