Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients

Background Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression patterns could reveal risk factors of severe COVID-19 illness. While the expression of ACE2 in healthy human tissues has been well characterized, it is not known which diseases and drugs might be associated with ACE2 expression. Results We develop GENEVA (GENe Expression Variance Analysis), a semi-automated framework for exploring massive amounts of RNA-seq datasets. We apply GENEVA to 286,650 publicly available RNA-seq samples to identify any previously studied experimental conditions that could be directly or indirectly associated with ACE2 expression. We identify multiple drugs, genetic perturbations, and diseases that are associated with the expression of ACE2, including cardiomyopathy, HNF1A overexpression, and drug treatments with RAD140 and itraconazole. Our joint analysis of seven datasets confirms ACE2 upregulation in all cardiomyopathy categories. Using electronic health records data from 3936 COVID-19 patients, we demonstrate that patients with pre-existing cardiomyopathy have an increased mortality risk than age-matched patients with other cardiovascular conditions. GENEVA is applicable to any genes of interest and is freely accessible at http://genevatool.org. Conclusions This study identifies multiple diseases and drugs that are associated with the expression of ACE2. The effect of these conditions should be carefully studied in COVID-19 patients. In particular, our analysis identifies cardiomyopathy patients as a high-risk group, with increased ACE2 expression in the heart and increased mortality after SARS-COV-2 infection.

Genome-Wide Identification and Characterization of HSP70 Gene Family in Aquilaria sinensis (Lour.) Gilg

The heat shock protein 70 (HSP70) gene family perform a fundamental role in protecting plants against biotic and abiotic stresses. Aquilaria sinensis is a classic stress-induced medicinal plant, producing a valuable dark resin in a wood matrix, known as agarwood, in response to environmental stresses. The HSP70 gene family has been systematic identified in many plants, but there is no comprehensive analysis at the genomic level in A. sinensis. In this study, 15 putative HSP70 genes were identified in A. sinensis through genome-wide bioinformatics analysis. Based on their phylogenetic relationships, the 15 AsHSP70 were grouped into six sub-families that with the conserved motifs and gene structures, and the genes were mapped onto six separate linkage groups. A qRT-PCR analysis showed that the relative expression levels of all the AsHSP70 genes were up-regulated by heat stress. Subcellular localization of all HSP70s was predicted, and three were verified by transiently expressed in Arabidopsis protoplasts. Based on the expression profiles in different tissues and different layers treated with Agar-Wit, we predict AsHSP70 genes are involved in different stages of agarwood formation. The systematic identification and expression analysis of HSP70s gene family imply some of them may play important roles in the formation of agarwood. Our findings not only provide a foundation for further study their biological function in the later research in A. sinensis, but also provides a reference for the analysis of HSPs in other species.

Short communication: A new tool to define multiscale bedform characteristics from bed elevation data

Systematic identification and characterization of bedforms from bathymetric data are crucial in many studies focused on fluvial processes. Automated and accurate processing of bed elevation data is challenging where dune fields are complex, irregular and, especially, where multiple scales co-exist. Here, we introduce a new tool to quantify dune properties from bathymetric data representing multiple dune scales. A first step in the procedure is to decompose the bathymetric data based on a LOESS algorithm. Steep dune lee side slopes are accounted for by implementing objective breaks in the algorithm, accounting for discontinuities in the bed level profiles, often occurring at the toe of the lee side slope of dunes. The steep lee slopes are then approximated by fitting a sigmoid function. Following the decomposition of the bathymetric data, bedforms are identified based on zero-crossing, and the relevant properties are calculated. The approach to decompose bedforms adopted in the presented tool is particularly applicable where secondary dunes are large and thus filtering could easily lead to undesired smoothing of the primary morphology. Application of the tool to two bathymetric maps demonstrates that the decomposition and identification are successful, as the lee side slopes are better preserved.

The phospho-docking protein 14-3-3 regulates microtubule-associated proteins in oocytes including the chromosomal passenger Borealin

Global regulation of spindle-associated proteins is crucial in oocytes due to the absence of centrosomes and their very large cytoplasmic volume, but little is known about how this is achieved beyond involvement of the Ran-importin pathway. We previously uncovered a novel regulatory mechanism in Drosophila oocytes, in which the phospho-docking protein 14-3-3 suppresses microtubule binding of Kinesin-14/Ncd away from chromosomes. Here we report systematic identification of microtubule-associated proteins regulated by 14-3-3 from Drosophila oocytes. Proteins from ovary extract were co-sedimented with microtubules in the presence or absence of a 14-3-3 inhibitor. Through quantitative mass-spectrometry, we identified proteins or complexes whose ability to binding microtubules is suppressed by 14-3-3, including the chromosomal passenger complex (CPC), the centralspindlin complex and Kinesin-14/Ncd. We showed that 14-3-3 binds to the disordered region of Borealin, and this binding is regulated differentially by two phosphorylations on Borealin. Mutations at these two phospho-sites compromised normal Borealin localisation and centromere bi-orientation in oocytes, showing that phospho-regulation of 14-3-3 binding is important for Borealin localisation and function. The mass spectrometry data are available from ProteomeXchange, identifier ID to be provided when available, PXD000xxx.

Threat Ranking to Improve Conservation Planning: An Example from the Gediz Delta, Turkey

Mediterranean wetlands are among the most threatened natural areas. The needs and demands of an increasing human population are modifying land use and converting natural habitats into artificial areas. In order to combat these trends, effective conservation planning needs to provide clear, systematic identification of threats to find sustainable conservation strategies. In this case study, we evaluated current threats in the Gediz Delta (Turkey) using a multi-method approach. First, we did a comprehensive literature review and stakeholder interviews to identify existing threats. We then did a complete survey of the Delta through intensive fieldwork. The threats were coded and ranked using the conservation standards. We used the threat ranking and field survey to map the most vulnerable areas of the Delta. The most commonly observed threats in the field were pollution and agriculture and aquaculture activities. According to the threat ranking, the most important threats are climate change and residential and commercial development. The habitats that are most at risk are agricultural grassland habitats. The results indicate a need to extend conservation actions in the inner part of the Delta. In addition, the multi-method threat ranking approach could serve as a model to improve conservation planning in other sites worldwide.

Genome-wide identification and analyses of tomato (Solanum lycopersicum L.) high-affinity nitrate transporter 2 (NRT2) family genes and their responses to drought and salinity

High-affinity nitrate transporter 2 (NRT2) proteins have vital roles in nitrate (NO3-) uptake and translocation in plants. The gene families coding NRT2 proteins have been identified and functionally characterized in many plant species. However, no systematic identification of NRT2 family members have been reported in tomato (Solanum lycopersicum). There is also little known about their expression profiles under environmental stresses. Accordingly, the present study aimed to identify NRT2 gene family in the tomato genome; then, investigate them in detail through bioinformatics, physiological and expression analyses. As a result, four novel NRT2 genes were identified in the tomato genome, all of which contain the same domain belonging to the Major Facilitator Superfamily (PF07690). The co-expression network of SlNRT genes revealed that they were co-expressed with several other genes in many different molecular pathways including transport, photosynthesis, fatty acid metabolism and amino acid catabolism. Programming many crucial physiological and metabolic pathways, various numbers of phosphorylation sites were predicted in the NRT2 proteins.

A standardized process in the electronic health record to identify and recruit family and other unpaid caregivers of Veterans for a caregiver survey study (Preprint)

BACKGROUND Most efforts to identify caregivers for research use passive approaches like self-nomination. We describe an approach where the EHR can help identify, recruit, and increase diverse representation of caregivers. OBJECTIVE Few health systems have implemented systematic processes to identify caregivers. We aimed to evaluate an electronic health record (EHR) algorithm for identifying Veterans with caregivers. METHODS We identified initial cohorts of Veterans likely to need supportive care from friends or family based with pre-defined EHR referrals for home and community care. Veterans were contacted assess whether the Veteran had an unpaid caregivers; unpaid caregivers were then contacted and offered enrollment in a caregiver survey. We compared Veteran characteristics from the EHR across these referral, screening, and recruitment groups using descriptive statistics and logistic regression models. RESULTS Of 12,212 Veterans identified through EHR referrals, 2,134 (17.4%) were selected for screening and 1,367 (11.2%) answered phone screening; 813 (60%) of those screened had a caregiver, and 435 (53%) caregivers participated in a survey. Married veterans had increased odds of having a caregiver (adjusted OR 2.63 [95%CI 1.65-4.24]) or had an adult day health care referral (adjusted OR 3.06 [95%CI 1.38 – 7.76]) or a respite care referral (adjusted OR 2.21 [95%CI 1.45-3.44].) Caregivers of Veterans with dementia had increased odds of participating in the survey (adjusted OR 1.78 [95%CI 1.20-2.65]). CONCLUSIONS The EHR algorithm process is systematic, resource intensive, and imperfect. Sixty percent of successfully screened Veterans had an unpaid caregiver. Implementing discrete caregiver fields in the EHR would support more efficient systematic identification of caregivers. CLINICALTRIAL ClincalTrials.gov Identifier: NCT03474380.

Innovative Solutions for Disaster Early Warning and Alert Systems: A Literary Review

In different parts of the world, decision-makers and risk managers use specific and particularly complex disaster early warning and alert systems to protect people and their material goods from the harmful effects of various disasters in a timely, efficient and appropriate manner. However, concerning the level of scientific-technological and economic development of certain countries, such systems can differ in the many characteristics that make them more efficient in specific situations. Guided by this, the subject of the paper is reflected in the systematic identification, analysis, and classification of the best innovative solutions of early warning systems regarding their usability and efficiency. To find appropriate innovative solutions, it was performed a search of different electronic databases. The findings of this review showed that there is a huge potential for innovative solutions in the field of disaster early warning and alert systems.