New resources for functional analysis of omics data for the genus Aspergillus

<p>Abstract</p> <p>Background</p> <p>Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus <it>Aspergillus </it>comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely <it>A. nidulans</it>.</p> <p>Results</p> <p>Based on protein homology, we mapped 97% of the 3,498 GO annotated <it>A. nidulans </it>genes to at least one of seven other <it>Aspergillus </it>species: <it>A. niger</it>, <it>A. fumigatus</it>, <it>A. flavus</it>, <it>A. clavatus</it>, <it>A. terreus</it>, <it>A. oryzae </it>and <it>Neosartorya fischeri</it>. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all <it>Aspergillus </it>species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (<url>http://www.broadinstitute.org/fetgoat/index.html</url>). To demonstrate the value of those new resources for functional analysis of omics data for the genus <it>Aspergillus</it>, we performed two case studies analyzing microarray data recently published for <it>A. nidulans</it>, <it>A. niger </it>and <it>A. oryzae</it>.</p> <p>Conclusions</p> <p>We mapped <it>A. nidulans </it>GO annotation to seven other <it>Aspergilli</it>. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus <it>Aspergillus</it>. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data.</p

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4-18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent

Health workforce development planning in the Sultanate of Oman: a case study

<p>Abstract</p> <p>Introduction</p> <p>Oman's recent experience in health workforce development may be viewed against the backdrop of the situation just three or four decades ago, when it had just a few physicians and nurses (mostly expatriate). All workforce categories in Oman have grown substantially over the last two decades. Increased self-reliance was achieved despite substantial growth in workforce stocks. Stocks of physicians and nurses grew significantly during 1985–2007. This development was the outcome of well-considered national policies and plans. This case outlines how Oman is continuing to turn around its excessive dependence on expatriate workforce through strategic workforce development planning.</p> <p>Case description</p> <p>The Sultanate's early development initiatives focused on building a strong health care infrastructure by importing workforce. However, the policy-makers stressed national workforce development for a sustainable future. Beginning with the formulation of a strategic health workforce development plan in 1991, the stage was set for adopting workforce planning as an essential strategy for sustainable health development and workforce self-reliance. Oman continued to develop its educational infrastructure, and began to produce as much workforce as possible, in order to meet health care demands and achieve workforce self-reliance.</p> <p>Other policy initiatives with a beneficial impact on Oman's workforce development scenario were: regionalization of nursing institutes, active collaboration with universities and overseas specialty boards, qualitative improvement of the education system, development of a strong continuing professional development system, efforts to improve workforce management, planned change management and needs-based micro/macro-level studies. Strong political will and bold policy initiatives, dedicated workforce planning and educational endeavours have all contributed to help Oman to develop its health workforce stocks and gain self-reliance.</p> <p>Discussion and evaluation</p> <p>Oman has successfully innovated workforce planning within a favorable policy environment. Its intensive and extensive workforce planning efforts, with the close involvement of policy-makers, educators and workforce managers, have ensured adequacy of suitable workforce in health institutions and its increased self-reliance in the health workforce.</p> <p>Conclusion</p> <p>Oman's experience in workforce planning and development presents an illustration of a country benefiting from successful application of workforce planning concepts and tools. Instead of being complacent about its achievements so far, every country needs to improve or sustain its planning efforts in this way, in order to circumvent the current workforce deficiencies and to further increase self-reliance and improve workforce efficiency and effectiveness.</p

A preliminary screening and characterization of suitable acids for sandstone matrix acidizing technique: a comprehensive review

Matrix acidizing is a broadly developed technique in sandstone stimulation to improve the permeability and porosity of a bottom-hole well. The most popular acid used is mud acid (HF–HCl). It is a mixture of hydrofluoric acid and hydrochloric acid. However, one of the conventional problems in sandstone acidizing is that mud acid faces significant issues at high temperature such as rapid rate of reaction, resulting in early acid consumption. This downside has given a negative impact to sandstone acidizing as it will result in not only permeability reduction, but can even extend to acid treatment failure. So, the aim of this study is to provide a preliminary screening and comparison of different acids based on the literature to optimize the acid selection, and targeting various temperatures of sandstone environment. This paper has comprehensively reviewed the experimental works using different acids to understand the chemical reactions and transport properties of acid in sandstone environment. The results obtained indicated that fluoroboric acid (HBF4) could be useful in enhancing the sandstone acidizing process, although more studies are still required to consolidate this conclusion. HBF4 is well known as a low damaging acid for sandstone acidizing due to its slow hydrolytic reaction to produce HF. This would allow deeper penetration of the acid into the sandstone formation at a slower rate, resulting in higher porosity and permeability enhancement. Nevertheless, little is known about the effective temperature working range for a successful treatment. Considering the pros and cons of different acids, particularly those which are associated with HF and HBF4, it is recommended to perform a comprehensive analysis to determine the optimum temperature range and effective working window for sandstone acidizing before treatment operation. Prior to sandstone acid stimulation, it is essential to predict the feasibility of acid selected by integrating the effects of temperature, acid concentration and injection rate. Therefore, this manuscript has thrown light into the research significance of further studies

High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism

HFE Gene Variants Modify the Association between Maternal Lead Burden and Infant Birthweight: A Prospective Birth Cohort Study in Mexico City, Mexico

<p>Abstract</p> <p>Background</p> <p>Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (<it>HFE</it>) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight.</p> <p>Methods</p> <p>We investigated the role of <it>HFE C282Y</it>, <it>HFE H63 D</it>, and transferrin <it>(TF) P570 S </it>gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant <it>HFE </it>or <it>TF </it>genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates.</p> <p>Results</p> <p>3.1%, 16.8% and 17.5% of infants (N = 390) and 1.9%, 14.5% and 18.9% of mothers (N = 533) carried the <it>HFE C282Y</it>, <it>HFE H63D</it>, and <it>TF P570 S </it>variants, respectively. The presence of infant <it>HFE H63 D </it>variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal <it>HFE H63 D </it>variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant <it>HFE H63 D </it>genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal <it>HFE H63 D </it>variant carriers had a negative association between tibia lead and birthweight.</p> <p>Conclusions</p> <p>These results suggest that the <it>HFE H63 D </it>genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.</p

Antischistosomal Activity of Trioxaquines: In Vivo Efficacy and Mechanism of Action on Schistosoma mansoni

Schistosomiasis is among the most neglected tropical diseases, since its mode of spreading tends to limit the contamination to people who are in contact with contaminated waters in endemic countries. Here we report the in vitro and in vivo anti-schistosomal activities of trioxaquines. These hybrid molecules are highly active on the larval forms of the worms and exhibit different modes of action, not only the alkylation of heme. The synergy observed with praziquantel on infected mice is in favor of the development of these trioxaquines as potential anti-schistosomal agents