G-quadruplexes (G4s) are nucleic acid secondary structures that form within guanine-rich DNA or RNA sequences. G4 formation can affect chromatin architecture and gene regulation and has been ...associated with genomic instability, genetic diseases and cancer progression. Here we present a high-resolution sequencing-based method to detect G4s in the human genome. We identified 716,310 distinct G4 structures, 451,646 of which were not predicted by computational methods. These included previously uncharacterized noncanonical long loop and bulged structures. We observed a high G4 density in functional regions, such as 5' untranslated regions and splicing sites, as well as in genes previously not predicted to contain these structures (such as BRCA2). G4 formation was significantly associated with oncogenes, tumor suppressors and somatic copy number alterations related to cancer development. The G4s identified in this study may therefore represent promising targets for cancer intervention.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
...the initial trials comparing COVID-19 vaccines versus placebo should seek reliable evidence not only of some efficacy but of worthwhile efficacy. ...although efficacy far greater than 50% would be ...better, efficacy of about 50% would represent substantial progress. Evaluation of multiple COVID-19 vaccines with standardised methodology will facilitate regulatory and deployment decisions.7 Unless such decisions are informed by reliable randomised evidence, the effect on public acceptance of COVID-19 vaccines could adversely affect COVID-19 control and the uptake of vaccines against other diseases.8 The WHO Solidarity Vaccines Trial9 (figure) aims to evaluate efficiently and rapidly (within 3–6 months of each vaccine's introduction into the study) the efficacy of multiple vaccines,10 helping to ensure that weakly effective vaccines are not deployed.
The response of cloud processes to an aerosol perturbation is one of the largest uncertainties in the anthropogenic forcing of the climate. It occurs at a variety of timescales, from the ...near-instantaneous Twomey effect to the longer timescales required for cloud adjustments. Understanding the temporal evolution of cloud properties following an aerosol perturbation is necessary to interpret the results of so-called "natural experiments" from a known aerosol source such as a ship or industrial site. This work uses reanalysis wind fields and ship emission information matched to observations of ship tracks to measure the timescales of cloud responses to aerosol in instantaneous (or"snapshot") images taken by polar-orbiting satellites.
Antimicrobial resistance in aquaculture Smith, P
Revue scientifique et technique (International Office of Epizootics),
04/2008, Letnik:
27, Številka:
1
Journal Article
Recenzirano
Appropriate antimicrobial therapy represents one of the most effective management responses to emergencies associated with infectious disease epizootics. The use of these agents, however, has the ...potential to increase the frequencies of bacterial resistance and this would have a negative impact on the subsequent use of these agents to control infectious disease in aquaculture. There is also a possibility that the enrichment of resistant bacteria or genes encoding resistance could have an adverse impact on the use of antimicrobial agents to control diseases in humans and other land-based animals. Attempts to apply formal risk analysis to this problem have been frustrated by the extreme diversity of aquaculture and by the general shortage of relevant data. A central argument made in this paper is, however, that not only do we lack the data this exercise would require; we also lack validated methods for collecting those data in the first place. At the most fundamental level we do not even possess validated methods for determining whether a bacterium isolated from an aquaculture site should or should not be classified as resistant. In the absence of any significant risk assessment, current attempts at risk management are centred on the development of lists of critically important antimicrobials for the various users of these agents. It is argued here that studies of gene ecology and models of gene flow in the environment are urgently required if we are to be able to evaluate this risk management approach, to predict its consequences or to generate more appropriate strategies.
Grasses and grasslands are of increasing interest to conservationists, biologists, and gardeners. There are more than 300 species of native California grasses and they are found in almost every ...climate—from cool, wet forests to hot, dry deserts. Native grasses are also important to land restoration as they improve soil quality, increase water infiltration, and recycle nutrients. Their deep roots can tap soil water, which allows them to stay green year-round and to act as fire buffers around residences. Native grasses also provide vital habitat for many species of insects, birds, reptiles, and mammals. Despite their importance, grasslands remain one of the most underprotected of California's vegetation types, and native grasslands have undergone the greatest percentage loss of any habitat type in the state. Grasses are also among the most difficult plants to identify. Organized alphabetically, Field Guide to Grasses of California covers common native and naturalized grasses and, to help identify them, also features over 180 color illustrations.
ObjectivesThis study examined patient adherence and persistence to oral bisphosphonates for the treatment of osteoporosis in real-world settings.MethodsA systematic review was completed according to ...the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) and National Health Service Economic Evaluation Database NHS EED) databases were searched for studies published in English language up to April 2018. Prospective and retrospective observational studies that used prescription claim databases or hospital medical records to examine patient adherence and persistence to oral bisphosphonate treatment among adults with osteoporosis were included. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of included studies.ResultsThe search yielded 540 published studies, of which 89 were deemed relevant and were included in this review. The mean age of patients included within the studies ranged between 53 to 80.8 years, and the follow-up varied from 3 months to 14 years. The mean persistence of oral bisphosphonates for 6 months, 1 year and 2 years ranged from 34.8% to 71.3%, 17.7% to 74.8% and 12.9% to 72.0%, respectively. The mean medication possession ratio ranged from 28.2% to 84.5%, 23% to 50%, 27.2% to 46% over 1 year, 2 years and 3 years, respectively. All studies included scored between 6 to 8 out of 9 on the NOS. The determinants of adherence and persistence to oral bisphosphonates included geographic residence, marital status, tobacco use, educational status, income, hospitalisation, medication type and dosing frequency.ConclusionsWhile a number of studies reported high levels of persistence and adherence, the findings of this review suggest that patient persistence and adherence with oral bisphosphonates medications was poor and reduced notably over time. Overall, adherence was suboptimal. To maximise adherence and persistence to oral bisphosphonates, it is important to consider possible determinants, including characteristics of the patients.
The type VI secretion system (T6SS) is a nanomachine used by many bacteria to drive a toxin-laden needle into other bacterial cells. Although the potential to influence bacterial competition is ...clear, the fitness impacts of wielding a T6SS are not well understood. Here we present a new agent-based model that enables detailed study of the evolutionary costs and benefits of T6SS weaponry during competition with other bacteria. Our model identifies a key problem with the T6SS. Because of its short range, T6SS activity becomes self-limiting, as dead cells accumulate in its way, forming "corpse barriers" that block further attacks. However, further exploration with the model presented a solution to this problem: if injected toxins can quickly lyse target cells in addition to killing them, the T6SS becomes a more effective weapon. We tested this prediction with single-cell analysis of combat between T6SS-wielding Acinetobacter baylyi and T6SS-sensitive Escherichia coli. As predicted, delivery of lytic toxins is highly effective, whereas nonlytic toxins leave large patches of E. coli alive. We then analyzed hundreds of bacterial species using published genomic data, which suggest that the great majority of T6SS-wielding species do indeed use lytic toxins, indicative of a general principle underlying weapon evolution. Our work suggests that, in the T6SS, bacteria have evolved a disintegration weapon whose effectiveness often rests upon the ability to break up competitors. Understanding the evolutionary function of bacterial weapons can help in the design of probiotics that can both establish well and eliminate problem species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Social Networks and Health Smith, Kirsten P.; Christakis, Nicholas A.
Annual review of sociology,
01/2008, Letnik:
34, Številka:
1
Journal Article
Recenzirano
People are interconnected, and so their health is interconnected. In recognition of this social fact, there has been growing conceptual and empirical attention over the past decade to the impact of ...social networks on health. This article reviews prominent findings from this literature. After drawing a distinction between social network studies and social support studies, we explore current research on dyadic and supradyadic network influences on health, highlighting findings from both egocentric and sociocentric analyses. We then discuss the policy implications of this body of work, as well as future research directions. We conclude that the existence of social networks means that people's health is interdependent and that health and health care can transcend the individual in ways that patients, doctors, policy makers, and researchers should care about.
Abstract
Motivated by the preponderance of so-called ‘heavy black holes’ in the binary black hole (BBH) gravitational wave (GW) detections to date, and the role that gravitational lensing continues ...to play in discovering new galaxy populations, we explore the possibility that the GWs are strongly lensed by massive galaxy clusters. For example, if one of the GW sources were actually located at z = 1, then the rest-frame mass of the associated BHs would be reduced by a factor of ∼2. Based on the known populations of BBH GW sources and strong-lensing clusters, we estimate a conservative lower limit on the number of BBH mergers detected per detector year at LIGO/Virgo’s current sensitivity that are multiply-imaged, of Rdetect ≃ 10−5 yr−1. This is equivalent to rejecting the hypothesis that one of the BBH GWs detected to date was multiply-imaged at ≲4σ. It is therefore unlikely, but not impossible, that one of the GWs is multiply-imaged. We identify three spectroscopically confirmed strong-lensing clusters with well-constrained mass models within the 90 per cent credible sky localizations of the BBH GWs from LIGO’s first observing run. In the event that one of these clusters multiply-imaged one of the BBH GWs, we predict that 20–60 per cent of the putative next appearances of the GWs would be detectable by LIGO, and that they would arrive at Earth within 3yr of first detection.
ABSTRACT
We present a rapid analytic framework for predicting kilonova light curves following neutron star (NS) mergers, where the main input parameters are binary-based properties measurable by ...gravitational wave detectors (chirp mass and mass ratio, orbital inclination) and properties dependent on the nuclear equation of state (tidal deformability, maximum NS mass). This enables synthesis of a kilonova sample for any NS source population, or determination of the observing depth needed to detect a live kilonova given gravitational wave source parameters in low latency. We validate this code, implemented in the public mosfit package, by fitting it to GW170817. A Bayes factor analysis overwhelmingly (B > 1010) favours the inclusion of an additional luminosity source in addition to lanthanide-poor dynamical ejecta during the first day. This is well fit by a shock-heated cocoon model, though differences in the ejecta structure, opacity or nuclear heating rate cannot be ruled out as alternatives. The emission thereafter is dominated by a lanthanide-rich viscous wind. We find the mass ratio of the binary is q = 0.92 ± 0.07 (90 per cent credible interval). We place tight constraints on the maximum stable NS mass, MTOV $=2.17^{+0.08}_{-0.11}$ M⊙. For a uniform prior in tidal deformability, the radius of a 1.4-M⊙ NS is R1.4 ∼ 10.7 km. Re-weighting with a prior based on equations of state that support our credible range in MTOV, we derive a final measurement R1.4 $=11.06^{+1.01}_{-0.98}$ km. Applying our code to the second gravitationally detected NS merger, GW190425, we estimate that an associated kilonova would have been fainter (by ∼0.7 mag at 1 d post-merger) and declined faster than GW170817, underlining the importance of tuning follow-up strategies individually for each GW-detected NS merger.
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