The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the speed at which laboratories discover the viral composition and study health outcomes. The small ~30-kb ssRNA genome of coronaviruses makes them adept at cross-species spread, but also enable a robust understanding of all the proteins the viral genome encodes. We have employed protein modeling, molecular dynamic simulations, evolutionary mapping, and 3D printing to gain a full proteome- and dynamicome-level understanding of SARS-CoV-2. We established the Viral Integrated Structural Evolution Dynamic Database (VIStEDD at prokoplab.com/vistedd) to facilitate future discoveries and educational use. Here, we highlight the use of VIStEDD for nsp6, nucleocapsid (N), and spike (S) surface glycoprotein. For both nsp6 and N, we found highly conserved surface amino acids that likely drive protein–protein interactions. In characterizing viral S protein, we developed a quantitative dynamics cross-correlation matrix to gain insights into its interactions with the angiotensin I–converting enzyme 2 (ACE2)–solute carrier family 6 member 19 (SLC6A19) dimer. Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients. These variants had ultralow frequency but existed in males hemizygous for ACE2. Two ACE2 noncoding variants (rs4646118 and rs143185769) present in ~9% of individuals of African descent may regulate ACE2 expression and may be associated with increased susceptibility of African Americans to SARS-CoV-2. We propose that this SARS-CoV-2 database may aid research into the ongoing pandemic.
There is interest in expanding eastern wild turkey (Meleagris gallopavo silvestris) populations north of their current range. We hypothesized that winter survival and food availability are primary determinants in setting the northern extent of wild turkey distribution. To test our hypothesis, we translocated wild turkey females north of their present range into central Minnesota, USA, and compared survival in areas with supplemental food in the form of corn food plots versus areas with no supplemental food. During 2 winters with below‐average snow, winter survival was higher for females with supplemental food. In one winter with above‐average snow depths, survival was extremely low even with supplemental food. Supplemental food could augment survival during mild winters if wildlife managers arrange with farmers to, annually, retain standing corn near roosting habitat, but food plots may only partially offset effects of deep snow. Managers should critically evaluate northern habitats, long‐term costs of sustained feeding, and potential outcomes of concentrating animals and introducing wild animals into new ecosystems. Winter survival may delimit the northern range of wild turkeys, though annual survival rates may also be important and need further research.
The immune response to COVID-19 infection is variable. How COVID-19 influences clinical outcomes in hospitalized patients needs to be understood through readily obtainable biological materials, such as blood. We hypothesized that a high-density analysis of host (and pathogen) blood RNA in hospitalized patients with SARS-CoV-2 would provide mechanistic insights into the heterogeneity of response amongst COVID-19 patients when combined with advanced multidimensional bioinformatics for RNA. We enrolled 36 hospitalized COVID-19 patients (11 died) and 15 controls, collecting 74 blood PAXgene RNA tubes at multiple timepoints, one early and in 23 patients after treatment with various therapies. Total RNAseq was performed at high-density, with >160 million paired-end, 150 base pair reads per sample, representing the most sequenced bases per sample for any publicly deposited blood PAXgene tube study. There are 770 genes significantly altered in the blood of COVID-19 patients associated with antiviral defense, mitotic cell cycle, type I interferon signaling, and severe viral infections. Immune genes activated include those associated with neutrophil mechanisms, secretory granules, and neutrophil extracellular traps (NETs), along with decreased gene expression in lymphocytes and clonal expansion of the acquired immune response. Therapies such as convalescent serum and dexamethasone reduced many of the blood expression signatures of COVID-19. Severely ill or deceased patients are marked by various secondary infections, unique gene patterns, dysregulated innate response, and peripheral organ damage not otherwise found in the cohort. High-density transcriptomic data offers shared gene expression signatures, providing unique insights into the immune system and individualized signatures of patients that could be used to understand the patient’s clinical condition. Whole blood transcriptomics provides patient-level insights for immune activation, immune repertoire, and secondary infections that can further guide precision treatment.
During the years 1985 to 1987, 689 moose (Alces alces L.) collected throughout Sweden were necropsied at the National Veterinary Institute in Uppsala, Sweden. Sixty-eight of those investigated had catarrhal to hemorrhagic enteritis, atrophied lymphoid organs, and/or numerous erosive, uclerative, necrotizing lesions of the digestive mucosa. Histopathology of the mucous membranes revealed marked inter-and intracellular oedema, erosions, ulcers and intracytoplasmic inclusion bodies. Neither Bovine Virus Diarrhoea/Mucosal Disease (BVD/MD) or Infectious Bovine Rhinotracheitis (IBR) virus could be isolated from the diseased animals. It is suggested that the syndrome resembling BVD/MD complex, may have been caused by an yet unidentified virus.
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