352 research outputs found
Whole-genome sequencing and the clinician: a tale of two cities.
Clinicians are faced with unprecedented opportunities to identify the genetic aetiologies of hitherto molecularly uncharacterised conditions via the use of high-throughput sequencing. Access to genomic technology and resultant data is no longer limited to clinicians, geneticists and bioinformaticians, however; ongoing commercialisation gives patients themselves ever greater access to sequencing services. We report an increasingly common medical scenario by describing two neuromuscular patients-a mother and adult son-whose consumer access to whole-genome sequencing affected their diagnostic journey
Strong Ultraviolet Pulse From a Newborn Type Ia Supernova
Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs.
Although they are used empirically to measure cosmological distances, the
nature of their progenitors remains mysterious, One of the leading progenitor
models, called the single degenerate channel, hypothesizes that a white dwarf
accretes matter from a companion star and the resulting increase in its central
pressure and temperature ignites thermonuclear explosion. Here we report
observations of strong but declining ultraviolet emission from a Type Ia
supernova within four days of its explosion. This emission is consistent with
theoretical expectations of collision between material ejected by the supernova
and a companion star, and therefore provides evidence that some Type Ia
supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur
Growing old, yet staying young: The role of telomeres in bats' exceptional longevity
Understanding aging is a grand challenge in biology. Exceptionally long-lived animals have mechanisms that underpin extreme longevity. Telomeres are protective nucleotide repeats on chromosome tips that shorten with cell division, potentially limiting life span. Bats are the longest-lived mammals for their size, but it is unknown whether their telomeres shorten. Using >60 years of cumulative mark-recapture field data, we show that telomeres shorten with age inRhinolophus ferrumequinumandMiniopterus schreibersii, but not in the bat genus with greatest longevity,Myotis. As in humans, telomerase is not expressed inMyotis myotisblood or fibroblasts. Selection tests on telomere maintenance genes show thatATMandSETX, which repair and prevent DNA damage, potentially mediate telomere dynamics inMyotisbats. Twenty-one telomere maintenance genes are differentially expressed inMyotis, of which 14 are enriched for DNA repair, and 5 for alternative telomere-lengthening mechanisms. We demonstrate how telomeres, telomerase, and DNA repair genes have contributed to the evolution of exceptional longevity inMyotisbats, advancing our understanding of healthy aging
Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient
We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide
ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
<p>Abstract</p> <p>Background</p> <p>We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE<sup>-/-</sup>) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.</p> <p>Methods</p> <p>Thickening of the aortic valve leaflets in apoE<sup>-/- </sup>mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.</p> <p>Results</p> <p>Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).</p> <p>Conclusion</p> <p>Moderate uremia causes thickening of the aortic valves in apoE<sup>-/- </sup>mice, which can be attenuated by ACE inhibition. The nephrectomized apoE<sup>-/- </sup>mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.</p
Exploring haemodynamics of haemodialysis using extrema points analysis model
Background: Haemodialysis is a form of renal replacement therapy used to treat
patients with end stage renal failure. It is becoming more appreciated that
haemodialysis patients exhibit higher rates of multiple end organ damage
compared to the general population. There is also a strong emerging evidence that
haemodialysis itself causes circulatory stress. We aimed at examining
haemodynamic patterns during haemodialysis using a new model and test that
model against a normal control.
Methods: We hypothesised that blood pressures generated by each heart beat
constantly vary between local peaks and troughs (local extrema), the frequency and
amplitude of which is regulated to maintain optimal organ perfusion. We also
hypothesised that such model could reveal multiple haemodynamic aberrations
during HD. Using a non-invasive cardiac output monitoring device (Finometer®) we
compared various haemodynamic parameters using the above model between a
haemodialysis patient during a dialysis session and an exercised normal control after
comparison at rest.
Results: Measurements yielded 29,751 data points for each haemodynamic
parameter. Extrema points frequency of mean arterial blood pressure was higher in
the HD subject compared to the normal control (0.761Hz IQR 0.5-0.818 vs 0.468Hz
IQR 0.223-0.872, P < 0.0001). Similarly, extrema points frequency of systolic blood
pressure was significantly higher in haemodialysis compared to normal. In contrary,
the frequency of extrema points for TPR was higher in the normal control compared
to HD (0.947 IQR 0.520-1.512 vs 0.845 IQR 0.730-1.569, P < 0.0001) with significantly
higher amplitudes.
Conclusion: Haemodialysis patients potentially exhibit an aberrant haemodynamic
behaviour characterised by higher extrema frequencies of mean arterial blood
pressure and lower extrema frequencies of total peripheral resistance. This, in
theory, could lead to higher variation in organ perfusion and may be detrimental to vulnerable vascular beds
The role of temperature and frequency on fretting wear of a like-on-like stainless steel contact
The influences of environmental temperature and fretting frequency on the mechanisms and rates of wear in a like-on-like 304 stainless steel contact were examined, and mainly attributed to changes in the mechanical response of the bulk material and to changes in the behaviour of the oxide debris formed in the fretting process. At low temperatures, wear proceeds by continual oxide formation and egress from the contact, whilst at high temperatures, the rate of wear is much reduced, associated with the development of oxide formed into a protective bed within the contact. The temperature at which the change between these two behaviours took place was dependent upon the fretting frequency, with evidence that, at this transition temperature, changes in behaviour can occur as the fretting test proceeds under a fixed set of conditions. An interaction diagram has been developed which provides a coherent framework by which the complex effects of these two parameters can be rationalised in terms of widely accepted physical principles
Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes
Resting memory CD4+ T-cells harboring latent HIV proviruses represent a critical barrier to viral eradication. Histone deacetylase inhibitors (HDACis), such as suberanilohydroxamic acid (SAHA), romidepsin, and panobinostat have been shown to induce HIV expression in these resting cells. Recently, it has been demonstrated that the low levels of viral gene expression induced by a candidate HDACi may be insufficient to cause the death of infected cells by viral cytopathic effects, necessitating their elimination by immune effectors, such as cytotoxic T-lymphocytes (CTL). Here, we study the impact of three HDACis in clinical development on T-cell effector functions. We report two modes of HDACi-induced functional impairment: i) the rapid suppression of cytokine production from viable T-cells induced by all three HDACis ii) the selective death of activated T-cells occurring at later time-points following transient exposures to romidepsin or, to a lesser extent, panobinostat. As a net result of these factors, HDACis impaired CTL-mediated IFN-γ production, as well as the elimination of HIV-infected or peptide-pulsed target cells, both in liquid culture and in collagen matrices. Romidepsin exerted greater inhibition of antiviral function than SAHA or panobinostat over the dose ranges tested. These data suggest that treatment with HDACis to mobilize the latent reservoir could have unintended negative impacts on the effector functions of CTL. This could influence the effectiveness of HDACi-based eradication strategies, by impairing elimination of infected cells, and is a critical consideration for trials where therapeutic interruptions are being contemplated, given the importance of CTL in containing rebound viremia
Attitudes towards treatment among patients suffering from sleep disorders. A Latin American survey
BACKGROUND: Although sleep disorders are common, they frequently remain unnoticed by the general practitioner. Few data are available about the willingness and reasons of patients with sleep disturbances to seek for medical assistance. METHODS: The results of a cross-sectional community-based multinational survey in three major Latin American urban areas, i.e. Buenos Aires, Mexico City and Sao Paulo, are reported. Two-hundred subjects suffering sleep disturbances and 100 non-sufferers were selected from the general population in each city (total number: 600 sufferers vs. 300 non-sufferers). A structured interview was conducted, sleep characteristics, feelings about sleep disturbances and strategies to cope with those problems being recorded. Data were analyzed by employing either t-test or analysis of variance (ANOVA) to the Z-transformed proportions. RESULTS: 22.7 ± 3.5 % (mean ± SEM) of subjects reported to suffer from sleep disturbances every night. About 3 out of 4 (74.2 ± 2.0 %) considered their disorder as mild and were not very concerned about it. Only 31 ± 2 % of sufferers reported to have sought for medical help. Although 45 ± 2 % of sufferers reported frequent daily sleepiness, trouble to remember things, irritability and headaches, they did not seek for medical assistance. Among those patients who saw a physician with complaints different from sleep difficulties only 1 out of 3 (33 ± 2 % of patients) were asked about quality of their sleep by the incumbent practitioner. Strategies of patients to cope with sleep problems included specific behaviors (taking a warm bath, reading or watching TV) (44 ± 1.6 %), taking herbal beverages (17 ± 1.2 %) or taking sleeping pills (10 ± 1.1 %). Benzodiazepines were consumed by 3 ± 0.6 % of sufferers. CONCLUSION: Public educational campaigns on the consequences of sleep disorders and an adequate training of physicians in sleep medicine are needed to educate both the public and the general practitioners about sleep disorders
Measuring the impact of cancer: a comparison of non-Hodgkin lymphoma and breast cancer survivors
Introduction Self-report instruments such as the Impact of Cancer (IOC) are designed to measure quality of life (QOL) impacts that cancer survivors attribute to their cancer experience. Generalizability of QOL findings across dis-tinct diagnostic categories of survivors is untested. W
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