272 research outputs found
The Expanding Fireball of Nova Delphini 2013
A classical nova occurs when material accreting onto the surface of a white
dwarf in a close binary system ignites in a thermonuclear runaway. Complex
structures observed in the ejecta at late stages could result from interactions
with the companion during the common envelope phase. Alternatively, the
explosion could be intrinsically bipolar, resulting from a localized ignition
on the surface of the white dwarf or as a consequence of rotational distortion.
Studying the structure of novae during the earliest phases is challenging
because of the high spatial resolution needed to measure their small sizes.
Here we report near-infrared interferometric measurements of the angular size
of Nova Delphini 2013, starting from one day after the explosion and continuing
with extensive time coverage during the first 43 days. Changes in the apparent
expansion rate can be explained by an explosion model consisting of an
optically thick core surrounded by a diffuse envelope. The optical depth of the
ejected material changes as it expands. We detect an ellipticity in the light
distribution, suggesting a prolate or bipolar structure that develops as early
as the second day. Combining the angular expansion rate with radial velocity
measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc
from the Sun.Comment: Published in Nature. 32 pages. Final version available at
http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm
Radio emission from Supernova Remnants
The explosion of a supernova releases almost instantaneously about 10^51 ergs
of mechanic energy, changing irreversibly the physical and chemical properties
of large regions in the galaxies. The stellar ejecta, the nebula resulting from
the powerful shock waves, and sometimes a compact stellar remnant, constitute a
supernova remnant (SNR). They can radiate their energy across the whole
electromagnetic spectrum, but the great majority are radio sources. Almost 70
years after the first detection of radio emission coming from a SNR, great
progress has been achieved in the comprehension of their physical
characteristics and evolution. We review the present knowledge of different
aspects of radio remnants, focusing on sources of the Milky Way and the
Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief
overview of theoretical background, analyze morphology and polarization
properties, and review and critical discuss different methods applied to
determine the radio spectrum and distances. The consequences of the interaction
between the SNR shocks and the surrounding medium are examined, including the
question of whether SNRs can trigger the formation of new stars. Cases of
multispectral comparison are presented. A section is devoted to reviewing
recent results of radio SNRs in the Magellanic Clouds, with particular emphasis
on the radio properties of SN 1987A, an ideal laboratory to investigate
dynamical evolution of an SNR in near real time. The review concludes with a
summary of issues on radio SNRs that deserve further study, and analyzing the
prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure
Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis
Background: The farnesoid-x-receptor (FXR) is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite
FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver
diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury
caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from
the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated
genes and biological functions.
Principal Findings: Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation
assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of
human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and
thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic
FXR agonists on FXR-regulated genes, including SHP, OSTa, BSEP and MRP4. A proof-of-concept study carried out to
investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model
of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by
assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in
bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a
basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed
to rescue from liver injury and downregulated the expression of MRP4.
Conclusions: FXR antagonism in vivo results in a positive modulation of MRP4 expression in the liver and is a feasible
strategy to target obstructive cholestasis
Intradermal Electroporation of Naked Replicon RNA Elicits Strong Immune Responses
RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient and clinically feasible delivery technologies. This study evaluates the immunogenic potential of naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally in combination with electroporation. Replicon-immunized mice showed a strong cellular and humoral response, contrary to mice immunized with regular mRNA. RREP-elicited induction of interferon-γ secreting CD8+ T cells and antibody responses were significantly increased by electroporation. CD8+ T cell responses remained substantial five weeks post vaccination, and antigen-specific CD8+ T cells with phenotypic characteristics of both effector and central memory cells were identified. The immune response during the contraction phase was further increased by a booster immunization, and the proportion of effector memory cells increased significantly. These results demonstrate that naked RREP delivered via intradermal electroporation constitute an immunogenic, safe and attractive alternative immunization strategy to DNA-based vaccines
Triclocarban Mediates Induction of Xenobiotic Metabolism through Activation of the Constitutive Androstane Receptor and the Estrogen Receptor Alpha
Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs). To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR) and estrogen receptor alpha (ERα) activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR) because no induction occurred in hUGT1Car−/− mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for potential human health effects from exposure to TCC
MLH1 mediates PARP-dependent cell death in response to the methylating agent N-methyl-N-nitrosourea
Background:Methylating agents such as N-methyl-N-nitrosourea (MNU) can cause cell cycle arrest and death either via caspase-dependent apoptosis or via a poly(ADP-ribose) polymerase (PARP)-dependent form of apoptosis. We wished to investigate the possible role of MLH1 in signalling cell death through PARP.Methods:Fibroblasts are particularly dependent on a PARP-mediated cell death response to methylating agents. We used hTERT-immortalised normal human fibroblasts (WT) to generate isogenic MLH1-depleted cells, confirmed by quantitative PCR and western blotting. Drug resistance was measured by clonogenic and cell viability assays and effects on the cell cycle by cell sorting. Damage signalling was additionally investigated using immunostaining.Results:MLH1-depleted cells were more resistant to MNU, as expected. Despite having an intact G2/M checkpoint, the WT cells did not initially undergo cell cycle arrest but instead triggered cell death directly by PARP overactivation and nuclear translocation of apoptosis-inducing factor (AIF). The MLH1-depleted cells showed defects in this pathway, with decreased staining for phosphorylated H2AX, altered PARP activity and reduced AIF translocation. Inhibitors of PARP, but not of caspases, blocked AIF translocation and greatly decreased short-term cell death in both WT and MLH1-depleted cells. This MLH1-dependent response to MNU was not blocked by inhibitors of ATM/ATR or p53.Conclusion:These novel data indicate an important role for MLH1 in signalling PARP-dependent cell death in response to the methylating agent MNU
Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates
A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration
Attentional Set-Shifting Deficit in Parkinson’s Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study
The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients
Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome
Study QuestionWhat is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary AnswerInternational evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What is Known AlreadyPrevious guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, DurationInternational evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, MethodsGovernance included a six continent international advisory and a project board, five guideline development groups (GDGs), and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of ChanceThe evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (a) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (b) reducing unnecessary testing; (c) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (d) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for CautionOverall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the FindingsThe international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.Peer reviewe
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