500 research outputs found
A quick guide for student-driven community genome annotation
High quality gene models are necessary to expand the molecular and genetic
tools available for a target organism, but these are available for only a
handful of model organisms that have undergone extensive curation and
experimental validation over the course of many years. The majority of gene
models present in biological databases today have been identified in draft
genome assemblies using automated annotation pipelines that are frequently
based on orthologs from distantly related model organisms. Manual curation is
time consuming and often requires substantial expertise, but is instrumental in
improving gene model structure and identification. Manual annotation may seem
to be a daunting and cost-prohibitive task for small research communities but
involving undergraduates in community genome annotation consortiums can be
mutually beneficial for both education and improved genomic resources. We
outline a workflow for efficient manual annotation driven by a team of
primarily undergraduate annotators. This model can be scaled to large teams and
includes quality control processes through incremental evaluation. Moreover, it
gives students an opportunity to increase their understanding of genome biology
and to participate in scientific research in collaboration with peers and
senior researchers at multiple institutions
Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction
BACKGROUND: Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin angiotensin system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic minipump in mice. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI).
OBJECTIVES: To evaluate effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post infarction.
METHODS: C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular (LV) pressure-volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation–contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff perfused whole heart model.
RESULTS: Gene delivery of Ang-(1-9) significantly reduced sudden cardiac death post-MI. Pressure–volume measurements revealed complete restoration of end systolic pressure, ejection fraction, end systolic volume and the end diastolic pressure–volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and increasing contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism.
CONCLUSIONS: Our novel findings show that Ang-(1-9) gene therapy preserves LV systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) has a direct effect on cardiomyocyte
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calcium handling through a protein kinase A-dependent mechanism. These data highlight Ang-(1-9) gene therapy as a potential new strategy in the context of MI
The genomes of two key bumblebee species with primitive eusocial organization
Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation
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SCIPP: An Expanded Community of Practice - Community Publishing
SCIPP redefines and expands the existing notions about what makes for a vibrant and robust community of practice by partnering CSUSB students and professors with K-12 students, parents, and educators, along with committed community partners. SCIPP encourages curiosity in ways that leads to critical thinking, exploration, risk taking , confidence building, open-mindedness, and other personal traits that equip them with the softskills to be active, critical, and creative contributors to our communities. SCIPP pedagogy embraces our students\u27 collective wisdom and focuses on relational building where multi-directional communication is promoted and students are viewed as equal stakeholders in their own educations. SCIPP puts collaboration into action which in turn fosters community-based lifelong learning. SCIPP provides the open intellectual space for future university students (our K-12 students) to engage with existing university students in meaningful ways so as to sustain interconnected partnerships facilitating community engagement. It supports parents as experts in the education of their children and acknowledges parents as the first conduits to spark their children’s imagination while they actively participate in education enriching activities and programs. Everyone involved is committed to creating a secure and open atmosphere for dreaming, sharing, and learning. Together we explore the aspects of community publishing through collaborative learning in formal and informal settings relating to digital and printed medias
Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI : Results of the ISACS-STEMI COVID-19 Registry
Background: The constraints in the management of patients with ST-segment elevation
myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely
impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of
the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the
registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed
in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI
in March–June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main
outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon
longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients
undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in
PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825–0.861, p < 0.0001). We found a significant agerelated reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore,
we observed significantly higher 30-day mortality during the pandemic period, especially among the
elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24–1.93], p < 0.001) as compared to younger
patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05–1.49], p = 0.013), as a potential consequence
of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19
pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in
PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients,
which may have contributed to increase in-hospital and 30-day mortality during the pandemic
Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry
Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (= 75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic
Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry
Background Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. Methods In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. Results A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. Conclusion This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. Trial registration number: NCT 04412655 (2nd June 2020)
Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI : Insights from the ISACS–STEMI COVID-19 Registry
The so-called “smoking paradox”, conditioning lower mortality in smokers among STEMI
patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS–
STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality,
reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic.
Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization
(p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with nonsmokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders,
and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day
(p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after
adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in
our population, active smoking was significantly associated with improved epicardial recanalization
and lower in-hospital and 30-day mortality compared with previous and non-smoking histor
Improved annotation of the insect vector of citrus greening disease: Biocuration by a diverse genomics community
The Asian citrus psyllid (Diaphorina citri Kuwayama) is the insect vector of the bacterium Candidatus Liberibacter asiaticus (CLas), the pathogen associated with citrus Huanglongbing (HLB, citrus greening). HLB threatens citrus production worldwide. Suppression or reduction of the insect vector using chemical insecticides has been the primary method to inhibit the spread of citrus greening disease. Accurate structural and functional annotation of the Asian citrus psyllid genome, as well as a clear understanding of the interactions between the insect and CLas, are required for development of new molecular-based HLB control methods. A draft assembly of the D. citri genome has been generated and annotated with automated pipelines. However, knowledge transfer from well-curated reference genomes such as that of Drosophila melanogaster to newly sequenced ones is challenging due to the complexity and diversity of insect genomes. To identify and improve gene models as potential targets for pest control, we manually curated several gene families with a focus on genes that have key functional roles in D. citri biology and CLas interactions. This community effort produced 530 manually curated gene models across developmental, physiological, RNAi regulatory and immunity-related pathways. As previously shown in the pea aphid, RNAi machinery genes putatively involved in the microRNA pathway have been specifically duplicated. A comprehensive transcriptome enabled us to identify a number of gene families that are either missing or misassembled in the draft genome. In order to develop biocuration as a training experience, we included undergraduate and graduate students from multiple institutions, as well as experienced annotators from the insect genomics research community. The resulting gene set (OGS v1.0) combines both automatically predicted and manually curated gene models.Peer reviewedBiochemistry and Molecular BiologyEntomology and Plant Patholog
Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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