POS0349 SEQUENCE COMPLEMENTARITY BETWEEN SARS-CoV-2 GENOME AND HUMAN NONCODING RNAS ASSOCIATED WITH IMMUNOLOGICAL DISORDERS: AN IN SILICO PIVOTAL STUDY

Background:Recent evidence shows that human cells may produce several noncoding (nc)RNAs in response to viral infections. Among them, a central role has been attributed to long noncoding (lnc)RNAs, more than 200 nucleotides in length, which are also crucially involved in cancer and autoimmunity. LncRNAs epigenetically control the transcription of genes presiding over cell proliferation, differentiation, migration and apoptosis, by directly or indirectly binding cellular or foreign nucleic acids, including viral genomes.Objectives:The objectives of this study were to evaluate in silico the presence of a nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human ncRNA genes and to analyze any associations between SARS-CoV-2 gene-matching ncRNAs and human diseases.Methods:The FASTA sequence of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes (ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, S, E, M, N) was retrieved from NCBI.nlm.nih.gov/gene (reference sequence NC_045512.2). The ensembl.org library for human ncRNA genes was interrogated for any base-pair match and detected human ncRNAs analyzed for their functional activity. Finally, the associations between ncRNAs and human diseases were searched on GWAS databases (https://www.ebi.ac.uk/gwas and https://www.genecards.org).Results:A total of 252 matches between SARS-CoV-2 genes and human ncRNAs were recorded (ORF1ab: 28; ORF3a: 9; ORF6: 50; ORF7a: 31; ORF7b: 16; ORF8: 23; ORF10: 5; S: 24; E: 17; M: 32; N: 17). With the exception of two small nuclear RNAs (RNVU1-4 and RNU4-74P corresponding to ORF6 and ORF10, respectively), all of them were lncRNAs, mostly expressed in testis and central nervous system under physiological conditions. Percentage of alignment ranged from 91.30% to 100%, with a mean nucleotide alignment length of 17.5±2.4. Polymorphic variants of these transcripts have mostly been reported in patients with neuropsychiatric disorders, cancer and dysmetabolism. Of note, we found 13 and 15 complementarities with lncRNAs associated with immune-mediated diseases Table 1. and immunological pathways (IL-2, IL-6, IL-12, IL-12R, IL-13, IL-17, M-CSF, CXCL-10, TRAIL-R2 and IgG glycosylation), respectively.Conclusion:This pivotal study shows that SARS-CoV-2 genes contain complementary sequences to human ncRNAs in turn associated with several diseases, including autoimmunity. The biological effects of this interaction remain to be elucidated.Table 1.SARS-CoV-2 complementary ncRNAs and associated immunological disordersSARS-CoV-2 geneLncRNAGenomic locationNucleotide alignment lengthAlignment percentageAssociated immunological disorderSXACTX:113705866-11370588318100%Crohn's diseaseNLINC013581:59082428-5908257417100%Acute Graft-versus-Host DiseaseECOX10-AS117:14029229-1402924517100%Systemic lupus erythematosusORF8AC093765.34:116752764-1167527842195.24%Ulcerative colitisORF6CDKN2B-AS19:22033529-2203354618100%Multiple sclerosisCHROMR2:178433948-1784339682195.24%Multiple sclerosisPsoriasisAtopic eczemaWAKMAR26:137857643-13785765715100%Atopic eczemaHay feverAllergic rhinitisMultiple sclerosisPsoriasisSystemic sclerosisSystemic lupus erythematosusRheumatoid arthritisAC008691.15:159362809-159362828(promoter flank)2095%SarcoidosisPsoriasisPsoriatic arthritisSclerosing cholangitisCeliac diseaseType I diabetes mellitusSystemic lupus erythematosusJuvenile idiopathic arthritisUlcerative colitisCrohn's diseaseTakayasu arteritisMultiple sclerosisLMCD1-AS13:7953602-7953616(enhancer)15100%Systemic sclerosisMLINC019342:181403969-18140398416100%Multiple sclerosisAnkylosing spondylitisCeliac diseaseRheumatoid arthritisORF7bXACTX:113959816-11395983116100%Crohn's diseaseLINC0262110:62289643-6230233515100%Rheumatoid arthritisLINC019913:187966255-18796626915100%IgA deficitAtopic asthmaAllergic rhinitisDisclosure of Interests:None declare

Individual phenotypic variation reduces interaction strengths in a consumer–resource system

Natural populations often show variation in traits that can affect the strength of interspecific interactions. Interaction strengths in turn influence the fate of pairwise interacting populations and the stability of food webs. Understanding the mechanisms relating individual phenotypic variation to interaction strengths is thus central to assess how trait variation affects population and community dynamics. We incorporated nonheritable variation in attack rates and handling times into a classical consumer–resource model to investigate how variation may alter interaction strengths, population dynamics, species persistence, and invasiveness. We found that individual variation influences species persistence through its effect on interaction strengths. In many scenarios, interaction strengths decrease with variation, which in turn affects species coexistence and stability. Because environmental change alters the direction and strength of selection acting upon phenotypic traits, our results have implications for species coexistence in a context of habitat fragmentation, climate change, and the arrival of exotic species to native ecosystems

Sparsity and Incoherence in Compressive Sampling

We consider the problem of reconstructing a sparse signal $x^0\in\R^n$ from a limited number of linear measurements. Given $m$ randomly selected samples of $U x^0$, where $U$ is an orthonormal matrix, we show that $\ell_1$ minimization recovers $x^0$ exactly when the number of measurements exceeds $$m\geq \mathrm{Const}\cdot\mu^2(U)\cdot S\cdot\log n,$$ where $S$ is the number of nonzero components in $x^0$, and $\mu$ is the largest entry in $U$ properly normalized: $\mu(U) = \sqrt{n} \cdot \max_{k,j} |U_{k,j}|$. The smaller $\mu$, the fewer samples needed. The result holds for ``most'' sparse signals $x^0$ supported on a fixed (but arbitrary) set $T$. Given $T$, if the sign of $x^0$ for each nonzero entry on $T$ and the observed values of $Ux^0$ are drawn at random, the signal is recovered with overwhelming probability. Moreover, there is a sense in which this is nearly optimal since any method succeeding with the same probability would require just about this many samples

Determination of Odor Detection Threshold in the Göttingen Minipig

The aim of the study was to examine the ability of Göttingen minipigs to acquire an olfaction-based operant conditioning task and to determine the detection threshold for ethyl acetate and ethanol. We used an automated olfactometer developed for rodents to train and test 14 pigs. Odor sampling and reliable responding were obtained after three to fifteen 160-trial sessions. Successful transfer of the task from ethyl acetate to ethanol was achieved in 1–4 sessions. Detection threshold for ethyl acetate varied between 10−2% and 10−6% v/v and for ethanol between 0.1% and 5 × 10−6% v/v. The results provide evidence that minipigs can successfully acquire 2-odorant discrimination using a food-rewarded instrumental conditioning paradigm for testing olfactory function. This olfactory discrimination paradigm provides reliable measures of olfactory sensitivity and thereby enables detection of changes in olfaction in a porcine model of Alzheimer's disease currently being developed

Quantization and Compressive Sensing

Quantization is an essential step in digitizing signals, and, therefore, an indispensable component of any modern acquisition system. This book chapter explores the interaction of quantization and compressive sensing and examines practical quantization strategies for compressive acquisition systems. Specifically, we first provide a brief overview of quantization and examine fundamental performance bounds applicable to any quantization approach. Next, we consider several forms of scalar quantizers, namely uniform, non-uniform, and 1-bit. We provide performance bounds and fundamental analysis, as well as practical quantizer designs and reconstruction algorithms that account for quantization. Furthermore, we provide an overview of Sigma-Delta ($\Sigma\Delta$) quantization in the compressed sensing context, and also discuss implementation issues, recovery algorithms and performance bounds. As we demonstrate, proper accounting for quantization and careful quantizer design has significant impact in the performance of a compressive acquisition system.Comment: 35 pages, 20 figures, to appear in Springer book "Compressed Sensing and Its Applications", 201

A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case–control approach. FINDINGS: DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology. We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset. CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including RA and SLE

Blending Geospatial Technology and Traditional Ecological Knowledge to Enhance Restoration Decision-Support Processes in Coastal Louisiana

More informed coastal restoration decisions have become increasingly important given limited resources available for restoration projects and the increasing magnitude of marsh degradation and loss across the Gulf Coast. This research investigated the feasibility and benefits of integrating geospatial technology with the traditional ecological knowledge (TEK) of an indigenous Louisiana coastal population to assess the impacts of current and historical ecosystem change on community viability. The primary goal was to provide coastal resource managers with a decision-support tool that allows for a more comprehensive method of assessing localized ecological change in the Gulf Coast region, which can also benefit human community sustainability. Using remote sensing (RS) and geographic information systems (GIS) mapping products, integrated with a coastal community’s TEK to achieve this goal, the research team determined a method for producing vulnerability/sustainability mapping products for an ecosystem-dependent livelihood base of a coastal population based on information derived from RS imagery prioritized with TEK. This study also demonstrates how such an approach can engage affected community residents who are interested in determining and addressing the causes and mitigating the decline of marsh habitat. Historical image data sets of the study area were acquired to understand evolution of land change to current conditions and project future vulnerability. Image-processing procedures were developed and applied to produce maps that detail land change in the study area at time intervals from 1968 to 2009. This information was combined in a GIS with acquired TEK and scientific data sets relating to marsh vegetation health and vulnerability characteristics to produce mapping products that provide new information for use in the coastal restoration decision-making process. This information includes: (1) marsh areas that are most vulnerable; and (2) the areas that are most significant to community sustainability

Understanding young adult physical activity, alcohol and tobacco use in community colleges and 4-year post-secondary institutions: A cross-sectional analysis of epidemiological surveillance data

<p>Abstract</p> <p>Background</p> <p>Young adults experience many adverse health behavior changes as they transition from adolescence into adulthood. A better understanding of the relationships between health promoting and risky health behaviors may aid in the development of health promotion interventions for various types of young adult post-secondary students. Therefore, the purpose of this study was to examine associations between alcohol and tobacco use and physical activity among 2-year and 4-year college students.</p> <p>Methods</p> <p>Cross-sectional analyses were conducted using 2007 survey data, collected as part of an on-going post-secondary health surveillance system in Minnesota. Students were randomly selected to participant from 14 Minnesota colleges and universities (six 2-year community and/or technical colleges, eight 4-year post-secondary institutions). The 2007 surveillance data included 9,931 respondents.</p> <p>Results</p> <p>The prevalence of demographic characteristics and health behaviors (e.g., physical activity, tobacco use) differed between young adults attending 2-year and 4-year post-secondary institutions; in general, those attending 2-year institutions are representative of more at-risk populations. Overall, higher levels of moderate, vigorous and strengthening physical activity were associated with higher levels of alcohol consumption and lower levels of smoking. In general, despite the disparities in the prevalence of these risk behaviors, the associations between the behaviors did not differ substantially between 2-year and 4-year post-secondary populations.</p> <p>Conclusions</p> <p>These findings illustrate links between leading risk behaviors. Interventions targeting multiple risk behaviors among young adults may warrant further consideration. Overall, future research is needed to support and inform young adult health promotion efforts that may be implemented in a wide array of post-secondary institutions.</p

Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis

BackgroundImatinib, a tyrosine kinase inhibitor, has been shown to restore bloodâ brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes.MethodsA phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS).ResultsFour serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400â mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800â mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0â 2) increased by 18% versus controls (61 vs. 79; P = 0.296).ConclusionThis phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/1/joim12576_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/2/joim12576.pd