911 research outputs found
A quantitative view of the transcriptome of Schistosoma mansoni adult-worms using SAGE
<p>Abstract</p> <p>Background</p> <p>Five species of the genus Schistosoma, a parasitic trematode flatworm, are causative agents of Schistosomiasis, a disease that is endemic in a large number of developing countries, affecting millions of patients around the world. By using SAGE (Serial Analysis of Gene Expression) we describe here the first large-scale quantitative analysis of the Schistosoma mansoni transcriptome, one of the most epidemiologically relevant species of this genus.</p> <p>Results</p> <p>After extracting mRNA from pooled male and female adult-worms, a SAGE library was constructed and sequenced, generating 68,238 tags that covered more than 6,000 genes expressed in this developmental stage. An analysis of the ordered tag-list shows the genes of F10 eggshell protein, pol-polyprotein, HSP86, 14-3-3 and a transcript yet to be identified to be the five top most abundant genes in pooled adult worms. Whereas only 8% of the 100 most abundant tags found in adult worms of S. mansoni could not be assigned to transcripts of this parasite, 46.9% of the total ditags could not be mapped, demonstrating that the 3 sequence of most of the rarest transcripts are still to be identified. Mapping of our SAGE tags to S. mansoni genes suggested the occurrence of alternative-polyadenylation in at least 13 gene transcripts. Most of these events seem to shorten the 3 UTR of the mRNAs, which may have consequences over their stability and regulation.</p> <p>Conclusion</p> <p>SAGE revealed the frequency of expression of the majority of the S. mansoni genes. Transcriptome data suggests that alternative polyadenylation is likely to be used in the control of mRNA stability in this organism. When transcriptome was compared with the proteomic data available, we observed a correlation of about 50%, suggesting that both transcriptional and post-transcriptional regulation are important for determining protein abundance in S. mansoni. The generation of SAGE tags from other life-cycle stages should contribute to reveal the dynamics of gene expression in this important parasite.</p
Genomic surveillance of Acinetobacter baumannii in the Philippines, 2013-2014
This work was supported by a Newton Fund award from the Medical Research Council (UK) MR/N019296/1 and the Philippine Council for Health Research and Development. This work was also partially supported by research grant U01CA207167 from the U.S. National Institutes of Health. S.A. and D.M.A. were additionally supported by the National Institute for Health Research (UK) Global Health Research Unit on genomic Surveillance of AMR (16_136_111) and by the Centre for Genomic Pathogen Surveillance.Objective: Acinetobacter baumannii is an opportunistic nosocomial pathogen that has increasingly become resistant to carbapenems worldwide. In the Philippines, rates of carbapenem resistance and multidrug resistance are above 50%. We undertook a genomic study of carbapenem-resistant A. baumannii in the Philippines to characterize the population diversity and antimicrobial resistance mechanisms. Methods: We sequenced the whole genomes of 117 A. baumannii isolates recovered by 16 hospitals in the Philippines between 2013 and 2014. From the genome sequences, we determined the multilocus sequence type, presence of acquired determinants of antimicrobial resistance and relatedness between isolates. We also compared the phenotypic and genotypic resistance results. Results: Carbapenem resistance was mainly explained by acquisition of the class-D beta-lactamase gene bla(OXA-23). The concordance between phenotypic and genotypic resistance to imipenem was 98.15%, and it was 94.97% overall for the seven antibiotics analysed. Twenty-two different sequence types were identified, including 7 novel types. The population was dominated by the high-risk international clone 2 (i.e. clonal complex 92), in particular by ST195 and ST208 and their single locus variants. Using whole-genome sequencing, we identified local clusters representing potentially undetected nosocomial outbreaks, as well as multi-hospital clusters that indicated interhospital dissemination. Comparison with global genomes suggested that the establishment of carbapenem-resistant international clone 2 in the Philippines is likely the result of clonal expansion and geographical dissemination, and at least partly explained by inadequate hospital infection control and prevention. Discussion: This is the first extensive genomic study of carbapenem-resistant A. baumannii in the Philippines, and it underscores the importance of hospital infection control and prevention measures to contain high-risk clones.Publisher PDFPeer reviewe
PhagoSight: an open-source MATLAB® package for the analysis of fluorescent neutrophil and macrophage migration in a zebrafish model
Neutrophil migration in zebrafish larvae is increasingly used as a model to study the response of these leukocytes to different determinants of the cellular inflammatory response. However, it remains challenging to extract comprehensive information describing the behaviour of neutrophils from the multi-dimensional data sets acquired with widefield or confocal microscopes. Here, we describe PhagoSight, an open-source software package for the segmentation, tracking and visualisation of migrating phagocytes in three dimensions. The algorithms in PhagoSight extract a large number of measurements that summarise the behaviour of neutrophils, but that could potentially be applied to any moving fluorescent cells. To derive a useful panel of variables quantifying aspects of neutrophil migratory behaviour, and to demonstrate the utility of PhagoSight, we evaluated changes in the volume of migrating neutrophils. Cell volume increased as neutrophils migrated towards the wound region of injured zebrafish. PhagoSight is openly available as MATLAB® m-files under the GNU General Public License. Synthetic data sets and a comprehensive user manual are available from http://www.phagosight.org
Prognostic value of discharge heart rate in acute heart failure patients: More relevant in atrial fibrillation?
Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results: The mean age of the study population was 72+/-12years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR)=1.182, confidence interval (CI) 95% 1.024-1.366, p=0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR=1.276, CI 95% 1.115-1.459, p</=0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients
Inhaled budesonide for adults with mild-to-moderate asthma: a randomized placebo-controlled, double-blind clinical trial
Estudo da influência do torque de inserção na resistência ao arrancamento dos parafusos pediculares
Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus
Coastal lagoons are semi-isolated ecosystems
exposed to wide fluctuations of environmental conditions
and showing habitat fragmentation. These features may
play an important role in separating species into different
populations, even at small spatial scales. In this study, we
evaluate the concordance between mitochondrial (previous
published data) and nuclear data analyzing the genetic
variability of Pomatoschistus marmoratus in five localities,
inside and outside the Mar Menor coastal lagoon (SE
Spain) using eight microsatellites. High genetic diversity
and similar levels of allele richness were observed across
all loci and localities, although significant genic and
genotypic differentiation was found between populations
inside and outside the lagoon. In contrast to the FST values
obtained from previous mitochondrial DNA analyses
(control region), the microsatellite data exhibited significant
differentiation among samples inside the Mar Menor
and between lagoonal and marine samples. This pattern
was corroborated using Cavalli-Sforza genetic distances.
The habitat fragmentation inside the coastal lagoon and
among lagoon and marine localities could be acting as a
barrier to gene flow and contributing to the observed
genetic structure. Our results from generalized additive
models point a significant link between extreme lagoonal
environmental conditions (mainly maximum salinity) and
P. marmoratus genetic composition. Thereby, these environmental
features could be also acting on genetic structure
of coastal lagoon populations of P. marmoratus favoring
their genetic divergence. The mating strategy of P. marmoratus
could be also influencing our results obtained from
mitochondrial and nuclear DNA. Therefore, a special
consideration must be done in the selection of the DNA
markers depending on the reproductive strategy of the
species
Shot noise in mesoscopic systems
This is a review of shot noise, the time-dependent fluctuations in the
electrical current due to the discreteness of the electron charge, in small
conductors. The shot-noise power can be smaller than that of a Poisson process
as a result of correlations in the electron transmission imposed by the Pauli
principle. This suppression takes on simple universal values in a symmetric
double-barrier junction (suppression factor 1/2), a disordered metal (factor
1/3), and a chaotic cavity (factor 1/4). Loss of phase coherence has no effect
on this shot-noise suppression, while thermalization of the electrons due to
electron-electron scattering increases the shot noise slightly. Sub-Poissonian
shot noise has been observed experimentally. So far unobserved phenomena
involve the interplay of shot noise with the Aharonov-Bohm effect, Andreev
reflection, and the fractional quantum Hall effect.Comment: 37 pages, Latex, 10 figures (eps). To be published in "Mesoscopic
Electron Transport," edited by L. P. Kouwenhoven, G. Schoen, and L. L. Sohn,
NATO ASI Series E (Kluwer Academic Publishing, Dordrecht
Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis
- …