17 research outputs found
The genomics of heart failure: design and rationale of the HERMES consortium
AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01–0.05) at P < 5 × 10^{-8} under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction
The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis
<p>Abstract</p> <p>Background</p> <p>This is the second in a series of three articles documenting the geographical distribution of 41 dominant vector species (DVS) of human malaria. The first paper addressed the DVS of the Americas and the third will consider those of the Asian Pacific Region. Here, the DVS of Africa, Europe and the Middle East are discussed. The continent of Africa experiences the bulk of the global malaria burden due in part to the presence of the <it>An. gambiae </it>complex. <it>Anopheles gambiae </it>is one of four DVS within the <it>An. gambiae </it>complex, the others being <it>An. arabiensis </it>and the coastal <it>An. merus </it>and <it>An. melas</it>. There are a further three, highly anthropophilic DVS in Africa, <it>An. funestus</it>, <it>An. moucheti </it>and <it>An. nili</it>. Conversely, across Europe and the Middle East, malaria transmission is low and frequently absent, despite the presence of six DVS. To help control malaria in Africa and the Middle East, or to identify the risk of its re-emergence in Europe, the contemporary distribution and bionomics of the relevant DVS are needed.</p> <p>Results</p> <p>A contemporary database of occurrence data, compiled from the formal literature and other relevant resources, resulted in the collation of information for seven DVS from 44 countries in Africa containing 4234 geo-referenced, independent sites. In Europe and the Middle East, six DVS were identified from 2784 geo-referenced sites across 49 countries. These occurrence data were combined with expert opinion ranges and a suite of environmental and climatic variables of relevance to anopheline ecology to produce predictive distribution maps using the Boosted Regression Tree (BRT) method.</p> <p>Conclusions</p> <p>The predicted geographic extent for the following DVS (or species/suspected species complex*) is provided for Africa: <it>Anopheles </it>(<it>Cellia</it>) <it>arabiensis</it>, <it>An. </it>(<it>Cel.</it>) <it>funestus*</it>, <it>An. </it>(<it>Cel.</it>) <it>gambiae</it>, <it>An. </it>(<it>Cel.</it>) <it>melas</it>, <it>An. </it>(<it>Cel.</it>) <it>merus</it>, <it>An. </it>(<it>Cel.</it>) <it>moucheti </it>and <it>An. </it>(<it>Cel.</it>) <it>nili*</it>, and in the European and Middle Eastern Region: <it>An. </it>(<it>Anopheles</it>) <it>atroparvus</it>, <it>An. </it>(<it>Ano.</it>) <it>labranchiae</it>, <it>An. </it>(<it>Ano.</it>) <it>messeae</it>, <it>An. </it>(<it>Ano.</it>) <it>sacharovi</it>, <it>An. </it>(<it>Cel.</it>) <it>sergentii </it>and <it>An. </it>(<it>Cel.</it>) <it>superpictus*</it>. These maps are presented alongside a bionomics summary for each species relevant to its control.</p
The genomics of heart failure: design and rationale of the HERMES consortium
Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.Cardiolog
Telehealth in audiology: The need and potential to reach underserved communities
Permanent hearing loss is a leading global health care burden, with 1 in 10 people affected to a mild or greater degree. A shortage of trained healthcare professionals and associated infrastructure and resource limitations mean that hearing health services are unavailable to the majority of the world population. Utilizing information and communication technology in hearing health care, or tele-audiology, combined with automation offer unique opportunities for improved clinical care, widespread access to services, and more cost-effective and sustainable hearing health care. Tele-audiology demonstrates significant potential in areas such as education and training of hearing health care professionals, paraprofessionals, parents, and adults with hearing disorders; screening for auditory disorders; diagnosis of hearing loss; and intervention services. Global connectivity is rapidly growing with increasingly widespread distribution into underserved communities where audiological services may be facilitated through telehealth models. Although many questions related to aspects such as quality control, licensure, jurisdictional responsibility, certification and reimbursement still need to be addressed; no alternative strategy can currently offer the same potential reach for impacting the global burden of hearing loss in the near and foreseeable future. © British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.link_to_subscribed_fulltex
Mermithid nematodes found in adult <it>Anopheles</it> from southeastern Senegal
<p>Abstract</p> <p>Background</p> <p>Over two dozen mermithid nematodes have been described parasitizing mosquitoes worldwide, however, only two species were found in Africa. Mermithid nematodes kill their mosquito host upon emergence, which suggests that they could be developed as biological control agents of mosquitoes. Both <it>Romanomermis culicivorax</it> and <it>Romanomermis iyengari</it> have been reared for mass release to control numerous <it>Anopheles</it> species vector populations, and in one instance this may have led to reduced malaria prevalence in a human population.</p> <p>Methods</p> <p><it>Anopheles</it> mosquitoes were collected during a malaria study in southeastern Senegal. Two different adult blood fed mosquitoes had a single mermithid nematode emerge from their anus while they were being held post-capture. Primers from the 18 S rDNA were developed to sequence nematode DNA and screen mosquitoes for mermithid DNA. 18 S rDNA from the Senegalese mermithid and other mermithid entries in GenBank were used to create a Maximum Parsimony tree of the Mermithidae family.</p> <p>Results</p> <p>The mermithid was present in 1.8% (10/551) of the sampled adult <it>Anopheles</it> species in our study area. The mermithid was found in <it>An. gambiae</it> s.s., <it>An. funestus</it>, and <it>An. rufipes</it> from the villages of Ndebou, Boundoucondi, and Damboucoye. Maximum parsimony analysis confirmed that the nematode parasites found in <it>Anopheles</it> were indeed mermithid parasites, and of the mermithid sequences available in GenBank, they are most closely related to <it>Strelkovimermis spiculatus</it>.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report of mermithids from adult <it>Anopheles</it> mosquitoes in Senegal. The mermithid appears to infect <it>Anopheles</it> mosquitoes that develop in diverse larval habitats. Although maximum parsimony analysis determined the mermithid was closely related to <it>Strelkovimermis spiculatus</it>, several characteristics of the mermithid were more similar to the <it>Empidomermis</it> genus. Future mermithid isolations will hopefully allow: formal taxonomic identification, laboratory colonization, determination of life history traits and species specificity, and characterize its usefulness as a biological control agent.</p
STARS (striated muscle activator of rho signalling) is essential to maintain cardiac development and function in vivo via a SRF pathway
Background
STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro.
Methodology and Principal Findings
Expression of zebrafish STARS (zSTARS) first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf)]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy), with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77%) of morpholino-injected embryos vs. 0/152 (0%) of control morpholino embryos]. Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells.
Conclusions/Significance
This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function
Sero-epidemioloical survey on African horse sickness virus among horses in Khartoum State, Central Sudan
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The Physical Conditions of Emission-line Galaxies at Cosmic Dawn from JWST/NIRSpec Spectroscopy in the SMACS 0723 Early Release Observations
Abstract
We present rest-frame optical emission-line flux ratio measurements for five z > 5 galaxies observed by the James Webb Space Telescope Near-Infared Spectrograph (NIRSpec) in the SMACS 0723 Early Release Observations. We add several quality-control and post-processing steps to the NIRSpec pipeline reduction products in order to ensure reliable relative flux calibration of emission lines that are closely separated in wavelength, despite the uncertain absolute spectrophotometry of the current version of the reductions. Compared to z ∼ 3 galaxies in the literature, the z > 5 galaxies have similar [O iii]λ5008/Hβ ratios, similar [O iii]λ4364/Hγ ratios, and higher (∼0.5 dex) [Ne III]λ3870/[O II]λ3728 ratios. We compare the observations to MAPPINGS V photoionization models and find that the measured [Ne III]λ3870/[O II]λ3728, [O iii]λ4364/Hγ, and [O iii]λ5008/Hβ emission-line ratios are consistent with an interstellar medium (ISM) that has very high ionization (
log
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−
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, units of cm s−1), low metallicity (Z/Z
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)
≃
8
−
9
, units of cm−3). The combination of [O iii]λ4364/Hγ and [O iii]λ(4960 + 5008)/Hβ line ratios indicate very high electron temperatures of
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log
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, further implying metallicities of Z/Z
⊙ ≲ 0.2 with the application of low-redshift calibrations for “T
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-based” metallicities. These observations represent a tantalizing new view of the physical conditions of the ISM in galaxies at cosmic dawn.</jats:p