2,181 research outputs found
Vigorous star formation hidden by dust in a galaxy at
Near-infrared surveys have revealed a substantial population of enigmatic
faint galaxies with extremely red optical-to-near-infrared colours and with a
sky surface density comparable to that of faint quasars. There are two
scenarios for these extreme colours: (i) these distant galaxies have formed
virtually all their stars at very high redshifts and, due to the absence of
recently formed stars, the colours are extremely red and (ii) these distant
galaxies contain large amounts of dust, severely reddening the rest-frame
UV--optical spectrum. HR10 () is considered the archetype of the
extremely red galaxies. Here we report the detection of the continuum emission
from HR10 at 850m and at 1250m, demonstrating that HR10 is a very
dusty galaxy undergoing a major episode of star formation. Our result provides
a clear example of a high-redshift galaxy where the star formation rate
inferred from the ultraviolet luminosity would be underestimated by a factor up
to 1000, and shows that great caution should be used to infer the global star
formation history of the Universe from optical observations only.Comment: 12 pages, 1 figure, Nature, in press (30 April 1998
Host-plasmid network structure in wastewater is linked to antimicrobial resistance genes
This is the final version. Available on open access from Springer Nature via the DOI in this record. Data availability:
Sequencing data are available in FASTQ format at SRA accession PRJNA506462. All data and code for both the ecological model and the Hi-C metagenome data are available at https://doi.org/10.17605/OSF.IO/K8PMF. Source data to reproduce figures is available as in the source data file. Source data are provided with this paper.Code availability:
All data and code for both the ecological model and the Hi-C metagenome data are available at https://doi.org/10.17605/OSF.IO/K8PMF.As mobile genetic elements, plasmids are central for our understanding of antimicrobial resistance spread in microbial communities. Plasmids can have varying fitness effects on their host bacteria, which will markedly impact their role as antimicrobial resistance vectors. Using a plasmid population model, we first show that beneficial plasmids interact with a higher number of hosts than costly plasmids when embedded in a community with multiple hosts and plasmids. We then analyse the network of a natural host-plasmid wastewater community from a Hi-C metagenomics dataset. As predicted by the model, we find that antimicrobial resistance encoding plasmids, which are likely to have positive fitness effects on their hosts in wastewater, interact with more bacterial taxa than non-antimicrobial resistance plasmids and are disproportionally important for connecting the entire network compared to non- antimicrobial resistance plasmids. This highlights the role of antimicrobials in restructuring host-plasmid networks by increasing the benefits of antimicrobial resistance carrying plasmids, which can have consequences for the spread of antimicrobial resistance genes through microbial networks. Furthermore, that antimicrobial resistance encoding plasmids are associated with a broader range of hosts implies that they will be more robust to turnover of bacterial strains.Natural Environment Research Council (NERC)Biotechnology and Biological Sciences Research Council (BBSRC)USDA National Institute of Food and AgricultureMedical Research Council (MRC)Royal Commission for the Exhibition of 1851 Research Fellowshi
Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol
<b>Background</b> Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.<p></p>
<b>Objectives</b> The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.<p></p>
<b>Methods</b> A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.<p></p>
<b>Discussion</b> The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices
Stress causes interspecific facilitation within a compost community
This is the final version. Available on open access from Wiley via the DOI in this record. Data availability: The data supporting the results are archived in Zenodo:
https://doi.org/10.5072/zenodo.835531Ecological theory predicts interactions between species to become more positive
under abiotic stress, while competition should prevail in more benign environments. However, experimental tests of this stress gradient hypothesis in natural
microbial communities are lacking. We test this hypothesis by measuring interactions between 10 different members of a bacterial community inhabiting potting
compost in the presence or absence of toxic copper stress. We found that copper
stress caused significant net changes in species interaction signs, shifting the net
balance towards more positive interactions. This pattern was at least in part driven
by copper-sensitive isolates – that produced relatively small amounts of metaldetoxifying siderophores – benefitting from the presence of other species that produce extracellular detoxifying agents. As well as providing support for the stress
gradient hypothesis, our results highlight the importance of community-wide public goods in shaping microbial community compositionNatural Environment Research Council (NERC)Biotechnology and Biological Sciences Research Council (BBSRC)University of ExeterAXA Research FundFP7 People: MarieCurie Action
Effect of urbanization on bone mineral density: A Thai epidemiological study
BACKGROUND: The incidence of fractures in rural populations is lower than in urban populations, although the reason for this difference is unclear. This cross-sectional study was designed to examine the difference in bone mineral density (BMD), a primary predictor of fracture risk, between urban and rural Thai populations. METHODS: Femoral neck and lumbar spine BMD was measured by dual-energy X-ray absorptiometry (GE Lunar, Madison, WI) in 411 urban and 436 rural subjects (340 men and 507 women), aged between 20 and 84 years. Body mass index (BMI) was calculated from weight and height. RESULTS: After adjusting for age and body weight in an analysis of covariance model, femoral neck BMD in rural men and women was significantly higher than those in urban men and women (P < 0.001), but the difference was not observed at the lumbar spine. After stratifying by sex, age group, and BMI category, the urban-rural difference in femoral neck BMD became more pronounced in men and women aged <50 years and with BMI ≥ 25 kg/m(2). CONCLUSIONS: These data suggest that femoral neck BMD in rural men and women was higher than their counterparts in urban areas. This difference could potentially explain part of the urban-rural difference in fracture incidence
Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent
Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1
Dosimetry during intramedullary nailing of the tibia: Patient and occupational exposure
Background Intramedullary nailing under fluoroscopic guidance is a common operation. We studied the intraoperative radiation dose received by both the patient and the personnel
Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.
One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis
The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis
<p><b>Background:</b> <i>Trypanosoma brucei gambiense</i> is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a <i>T. b. brucei</i> isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between <i>T. b. gambiense</i> and the reference genome. We sought to identify features that were uniquely associated with <i>T. b. gambiense</i> and its ability to infect humans.</p>
<p><b>Methods and findings:</b> An improved high-quality draft genome sequence for the group 1 <i>T. b. gambiense</i> DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with <i>T. b. brucei</i> showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in <i>T. b. gambiense</i> DAL 972. A comparison of the variant surface glycoproteins (VSG) in <i>T. b. brucei</i> with all <i>T. b. gambiense</i> sequence reads showed that the essential structural repertoire of VSG domains is conserved across <i>T. brucei</i>.</p>
<p><b>Conclusions:</b> This study provides the first estimate of intraspecific genomic variation within <i>T. brucei</i>, and so has important consequences for future population genomics studies. We have shown that the <i>T. b. gambiense</i> genome corresponds closely with the reference, which should therefore be an effective scaffold for any <i>T. brucei</i> genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in <i>T. b. brucei</i>, no <i>T. b. gambiense</i>-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.</p>
The Pioneer Anomaly
Radio-metric Doppler tracking data received from the Pioneer 10 and 11
spacecraft from heliocentric distances of 20-70 AU has consistently indicated
the presence of a small, anomalous, blue-shifted frequency drift uniformly
changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was
interpreted as a constant sunward deceleration of each particular spacecraft at
the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of
the Newton's gravitational inverse-square law has become known as the Pioneer
anomaly; the nature of this anomaly remains unexplained. In this review, we
summarize the current knowledge of the physical properties of the anomaly and
the conditions that led to its detection and characterization. We review
various mechanisms proposed to explain the anomaly and discuss the current
state of efforts to determine its nature. A comprehensive new investigation of
the anomalous behavior of the two Pioneers has begun recently. The new efforts
rely on the much-extended set of radio-metric Doppler data for both spacecraft
in conjunction with the newly available complete record of their telemetry
files and a large archive of original project documentation. As the new study
is yet to report its findings, this review provides the necessary background
for the new results to appear in the near future. In particular, we provide a
significant amount of information on the design, operations and behavior of the
two Pioneers during their entire missions, including descriptions of various
data formats and techniques used for their navigation and radio-science data
analysis. As most of this information was recovered relatively recently, it was
not used in the previous studies of the Pioneer anomaly, but it is critical for
the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living
Reviews in Relativit
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