Systems genetics identifies miRNA-mediated regulation of host response in COVID-19.

BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.

The genetic architecture of youth anxiety: a study protocol.

BACKGROUND: Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. METHODS: The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10-19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. DISCUSSION: Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world.

Hybrid lung lesions in children with segmental infantile hemangiomas, a new association?

Infantile hemangiomas (IHs) are the most common tumors of infancy and, in rare instances, can present in the setting of congenital structural anomalies or as part of syndromic disorders. In this study, we present three cases of children with segmental IHs born with concurrent pulmonary anomalies: congenital pulmonary airway malformations and bronchopulmonary sequestration. To date, no known association between these entities and hemangiomas has been described.

Electro-Osmotic Propulsion of Jeffrey Fluid in a Ciliated Channel Under the Effect of Nonlinear Radiation and Heat Source/Sink.

Mathematical modeling of mechanical system in microfluidics is an emerging area of interest in microscale engineering. Since microfluidic devices use the hair-like structure of artificial cilia for pumping, mixing, and sensing in different fields, electro-osmotic cilia-driven flow helps to generate the fluid velocity for the Newtonian and viscoelastic fluid. Due to the deployment of artificial ciliated walls, the present research reports the combined effect of an electro-osmotic flow and convective heat transfer on Jeffrey viscoelastic electrolytic fluid flow in a two-dimensional ciliated vertical channel. Heat generation/absorption and nonlinear radiation effects are included in the present mathematical model. After applying Debye-Huckel approximation and small Reynolds number approximation to momentum and energy equation, the system of nonlinear partial differential equation is reduced into nonhomogenous boundary value problem. The problem determines the velocity, pressure, and temperature profiles by the application of semi-analytical technique known as homotopy perturbation method (HPM) with the help of software Mathematica. The graphical results of the study suggest that HPM is a reliable methodology for thermo physical electro-osmotic rheological transport in microchannels.

Serotonin system genes and hoarding with and without other obsessive-compulsive traits in a population-based, pediatric sample: A genetic association study.

BACKGROUND: Hoarding, originally only considered a symptom of obsessive-compulsive disorder (OCD), is now categorized as a separate disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). We studied candidate serotonergic genes and the distinctness of hoarding in children and adolescents and hypothesized that unique gene variants would be associated with hoarding alone. METHODS: We examined obsessive-compulsive (OC) traits, including hoarding, in a total of 5,213 pediatric participants in the community. We genotyped candidate serotonin genes (5-HTTLPR polymorphism in SLC6A4 for 2,018 individuals and single nucleotide polymorphisms [SNPs] across genes SLC6A4, HTR2A, and HTR1B for 4,711 individuals). In a previous study conducted by our group in the same sample, we identified a significant association between 5-HTTLPR and hoarding in males. In this study, we examined hoarding more closely by testing the association between serotonin gene variants and hoarding traits with and without other accompanying OC traits. RESULTS: The [LG +S] variant in 5-HTTLPR was significantly associated with hoarding alone in males (p-value of 0.009). There were no significant findings for 5-HTTLPR in females. There were no significant findings after correction for multiple comparisons using SNP array data, but top SNP findings suggested that variation downstream of HTR1B may be implicated in hoarding alone in females. CONCLUSIONS: Our results suggest specific serotonin gene variants are associated with hoarding traits alone, differing between sexes. Top findings are in line with our former study, suggesting that individuals with hoarding alone were driving previous results. Our paper supports hoarding disorder's new designation.

Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study.

BACKGROUND: Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. METHODS: Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. RESULTS: The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). CONCLUSIONS: This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

SWAN scale for ADHD trait-based genetic research: a validity and polygenic risk study.

BACKGROUND: Population-based samples with valid, quantitative and genetically informative trait measures of psychopathology could be a powerful complement to case/control genetic designs. We report the convergent and predictive validity of the parent- and self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN). We tested if SWAN scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as traits and polygenic risk for disorders that co-occur with ADHD: anxiety and obsessive-compulsive disorder (OCD). METHODS: We collected parent- and self-report SWAN scores in a sample of 15,560 children and adolescents (6-17 years) recruited at a science museum (Spit for Science sample). We established age and sex norms for the SWAN. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with and without a reported ADHD diagnosis. These cut-points were validated in a clinic sample (266 ADHD cases; 36 controls). Convergent validity was established using the Conners' parent- and self-report scales. Using Spit for Science participants with genome-wide data (n = 5,154), we tested if low, medium and high SWAN scores were associated with polygenic risk for ADHD, OCD and anxiety disorders. RESULTS: Parent- and self-report SWAN scores showed high convergent validity with Conners' scales and distinguished ADHD participants with high sensitivity and specificity in the Spit for Science sample. In a clinic sample, the Spit for Science cut-points discriminated ADHD cases from controls with a sensitivity of 84% and specificity of 92%. High SWAN scores and scores above the Spit for Science cut-points were significantly associated with polygenic risk for ADHD. SWAN scores were not associated with polygenic risk for OCD or anxiety disorders. CONCLUSIONS: Our study supports the validity of the parent- and self-report SWAN scales and their potential in ADHD population-based genetic research.

Tetramethylpyrazine inhibited hypoxia-induced expression of calcium-sensing receptors in pulmonary artery smooth muscle cells in chickens.

Tetramethylpyrazine (TMP) is a biologically active ingredient, which is isolated from a popularChinese medicinal plant. It has been used effectively to treat ischemic heart problems, cerebrovascular and thrombotic vascular diseases. This study was designed to evaluate the effect of TMP on calciumsensing receptors in pulmonary artery smooth muscle in chickens. For this purpose forty day-old chicks were distributed into five groups: the control group, the hypoxia group (kept under low Oxygen treatment), and TMP groups (kept under low Oxygen treatment along with treatment of different concentrations of TMP). The pulmonary artery smooth muscle cells were also cultured on 6-well plates in high glucose culture medium and divided into the same five groups. We used in vivo and in vitro study models by applying immunohistochemistry, RT-qPCR assay and Western blotting analysis. Our results showed that pre-incubation with hypoxia markedly stimulated the activation of calcium-sensing receptor (CaSR) in pulmonary artery smooth muscle cells (PASMCs). The TMP decreased the mRNA and protein levels of CaSR. Treatment with TMP clearly inhibited the activation of all CaSR in a dose-dependent manner. Our data demonstrated that TMP can down-regulate the expression of CaSR. Therefore, these findings provide a new target to treat pulmonary arterial hypertension (PAH) under hypoxic conditions.

Haemoglobin concentrations in pregnancy and respiratory and allergic outcomes in childhood: Birth cohort study.

BACKGROUND: Limited epidemiological evidence suggests that low maternal iron status and anaemia in pregnancy may increase the risk of childhood respiratory and allergic outcomes. OBJECTIVES: To investigate the relation between maternal haemoglobin concentrations in pregnancy and childhood respiratory and allergic outcomes. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined associations of maternal haemoglobin concentrations (g/dL) in pregnancy with hayfever, eczema, wheezing, doctor-diagnosed asthma, allergic sensitisation and total IgE at 7 years, and with lung function at 8-9 years in the offspring, after controlling for potential confounders (N = 3234-5335). RESULTS: Maternal haemoglobin was not associated with offspring hayfever, eczema, wheezing or asthma. However, the first haemoglobin measurement in pregnancy (<18 weeks' gestation) and the last measurement (>28 weeks' gestation) were negatively associated with allergic sensitisation (adjusted odds ratio [95% CI] per g/dL 0.91 [0.83 to 0.99] and 0.90 [0.83 to 0.98], respectively). The last haemoglobin measurement was also negatively associated with total IgE (adjusted geometric mean ratio 0.94 [0.88 to 0.99]). Anaemia (haemoglobin <11 g/dL) in late pregnancy was negatively associated with forced vital capacity (difference in standard deviation score -0.07 [-0.13 to -0.01]). CONCLUSIONS AND CLINICAL RELEVANCE: Lower maternal haemoglobin in pregnancy may be a risk factor for allergic sensitisation, elevated IgE and lower FVC in childhood, which may reflect effects of lower prenatal iron status. However, maternal haemoglobin was not associated with risk of childhood asthma or other allergic disorders.

Genetic barcoding and phylogenetic analysis of dusky cotton bug (Oxycarenus hyalinipennis) using mitochondrial cytochrome c oxidase I gene.

Cotton dusky bug (Oxycarenus spp.) mostly attack on cash crops such as Gossypium, Cola and Hibiscus which affect the national economy therefore sustainable pest management is needed. Cytochrome c oxidase I (COI) gene is utilized as marker gene for DNA barcoding, genetic and ecological study of insects. In present study insect (cotton dusky bug) samples were collected from cotton fields in Faisalabad. COI gene was amplified from genomic DNA of bug and cloned into pTZ57R/T vector (Fermentas). The clone was sent to Macrogen (South Korea) for Sanger sequencing. The phylogenetic analysis and pairwise multiple sequence alignment showed that our cotton dusky bug grouped with two species of Oxycarenus genus and highest sequence identity was 91.1% with Oxycarenus hylinipennis. This is the first report of genetic barcode of Oxycarenus hylinipennis from cotton from Pakistan.

Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function.

BACKGROUND: It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. OBJECTIVE: To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. METHODS: Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652-4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728-3784). RESULTS: Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5-49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. CONCLUSIONS: We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes.

Purification, characterization and preparation immunomatrixes of S-layer proteins of Thermobifida fusca.

AIM: S-layer proteins are considered as a good nanocarrier due to their binding and self-assembled properties. These can be used to prepare the immunomatrixes for the removal of toxins from the samples. METHODS AND RESULTS: Two S-layer proteins 70 and 40 kDa of thermophilic Thermobifida fusca were extracted with guanidine hydrochloride and purified. Antibodies against S-layer proteins were developed, and their monospecificity was checked. Immunogold labelling indicated that these are surface proteins. Immunomatrixes (70-SLIM, 40 SLIM) were prepared by covalently immobilizing S-layer proteins in microwell and further conjugated with anti- Staphylococcus aureus enterotoxin B (SEB) antibodies. The binding of 70 and 40 kDa proteins was observed nearly 7·0 µg cm(-1) to binding area, and the conjugation with anti-SEB antibodies was found 1·22 µg µg(-1) of 70 kDa and 0·875 µg µg(-1) of 40 kDa. The average binding and elution of pure SEB toxin on 70-SLIM and 40-SLIM was 5·0 µg SEB toxin. The SEB toxin in milk samples was also removed on immunomatrixes successfully. CONCLUSION: It is the first report, and this study shows that the thermophilic S-layer proteins can be used to prepare the immunomatrixes. SIGNIFICANCE AND IMPACT OF STUDY: Information in this study can be used to design the strategies for the removal of biologically important materials or toxins from samples.

Modulated complexed stenosed region consequences under the electroosmotic stimulation.

The present study analyzes the theoretical consequences of slip effects in a complex stenosed region. The flow of blood in a stenosed region is incorporated with hybrid nanofluid features which are being prepared with copper and copper oxide nanoparticles. The flow is also intensified by applying an electric field in the axial direction. The governing equations for the proposed paradigm are solved and the corresponding closed-form solutions are obtained for the cases of mild stenosis. Parameters such as Electro-osmotic, velocity slip and Helmholtz-Smoluchowski are specially focused in this study. The heat transfer, hemodynamic velocity, wall shear stress and resistance impedance for the flow are precisely determined. The various parameters that influence the physical characteristics of flow are plotted, and their effects are discussed in detail. The present model has the potential application in medical pumps for drug delivery systems.

Significance of peripheral layer: the case of mucus flow through a ciliated tube using Rabinowitsch model.

Modern medicine has taken energy loss during cilia beating in the human stomach, which under some circumstances causes blood flow to become acidic, very seriously. In current report covering a whole advancement and results for the impact of Rabinowitsch model with cilia-driven flow analysis with the help of ciliary beating in a cylindrical tube. The fluid is incompressible, and layers of fluid do not mix. The fluid flow with heat and mass transfer is firstly modeled in wave and then transformed into fixed frame. Exact solutions for stresses, temperature velocity, and concentration profiles whereas numerical pressure rise is obtained subject to relevant boundary conditions. The behavior of incipient parameters is shown graphically (plotted in MATHEMATICA 13.0) in the results section. The key findings obtained from graphical results show that maximum magnitude for velocity and temperature is achieved in middle layer of fluid whereas in the outer layer concentration profile is maximum. The current study may help researchers to develop new treatments for diseases such as cystic fibrosis, in which impaired ciliary function leads to mucus accumulation in the lungs. The attained exact and numerical outcomes are novel and offered here for first time in literature.

Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype.

BACKGROUND: Pharmacologic and animal studies have strongly implicated the norepinephrine transporter (NET) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD. METHODS: Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT. RESULTS: A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2. LIMITATIONS: The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype. CONCLUSION: The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples.

An extremely rare complete bilateral duplication of inferior vena cava in a male cadaver: anatomy, embryology and clinical relevance.

The study presented an extremely rare case of real complete bilateral duplication of inferior vena cava (IVC) in a male cadaver which has never been reported before. Both IVC had approximately the same diameter. The right IVC drained into the right atrium; the left IVC continued as hemiazygos vein and drained into the superior vena cava. Three anastomotic venous channels, a cranial preaortic, a middle and a caudal retroaortic, joined both vessels. Multiple variations in the way of drainage of posterior intercostal veins, on both sides, were also present. The present report invalidates an old classification defining the two vessels when joined at the level of the renal veins as complete bilateral duplication of IVC. Although the presence of combination of venous variations is extremely rare, awareness of such variations is essential for clinical and surgical procedures to avoid misdiagnosis and surgical complications.

Mesenchymal tumor cells drive adaptive resistance of Trp53-/- breast tumor cells to inactivated mutant Kras.

As precision medicine increases the response rate of treatment, tumors frequently bypass inhibition, and reoccur. In order for treatment to be effective long term, the mechanisms enabling treatment adaptation need to be understood. Here, we report a mouse model that, in the absence of p53 and the presence of oncogenic KrasG12D , develops breast tumors. Upon inactivation of KrasG12D , tumors initially regress and enter remission. Subsequently, the majority of tumors adapt to the withdrawal of KrasG12D expression and return. KrasG12D -independent tumor cells show a strong mesenchymal profile with active RAS-RAF-MEK-ERK (MAPK/ERK) signaling. Both KrasG12D -dependent and KrasG12D -independent tumors display a high level of genomic instability, and KrasG12D -independent tumors harbor numerous amplified genes that can activate the MAPK/ERK signaling pathway. Our study identifies both epithelial-mesenchymal transition (EMT) and active MAPK/ERK signaling in tumors that adapt to oncogenic KrasG12D withdrawal in a novel Trp53-/- breast cancer mouse model. To achieve long-lasting responses in the clinic to RAS-fueled cancer, treatment will need to focus in parallel on obstructing tumors from adapting to oncogene inhibition.

Hypoglycemic and Hyperglycemic Crises Among U.S. Adults With Diabetes and End-stage Kidney Disease: Population-Based Study, 2013-2017.

OBJECTIVE: We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (ESKD). RESEARCH DESIGN AND METHODS: This was a nationwide, retrospective study of adults (≥18 years old) with diabetes/ESKD, from the United States Renal Data System registry, between 2013 and 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1,000 person-years. Event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen, and U.S. region. RESULTS: Among 521,789 adults with diabetes/ESKD (median age 65 years [interquartile range 57-73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1,000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, respectively, the risks decreased with age and were lowest in older patients (≥75 vs. 18-44 years old: incidence rate ratio 0.35, 95% CI 0.33-0.37, and 0.03, 0.02-0.03), women (1.09, 1.06-1.12, and 1.44, 1.35-1.54), and those with smoking (1.36, 1.28-1.43, and 1.71, 1.53-1.91), substance abuse (1.27, 1.15-1.42, and 1.53, 1.23-1.9), retinopathy (1.10, 1.06-1.15, and 1.36, 1.26-1.47), and insulin therapy (vs. no therapy; 0.60, 0.59-0.63, and 0.44, 0.39-0.48). For hypoglycemia, specifically, additional risk was conferred by Black race (1.11, 1.08-1.15) and amputation history (1.20, 1.13-1.27). CONCLUSIONS: In this nationwide study of patients with diabetes/ESKD, hypoglycemic crises were threefold more common than hyperglycemic crises, greatly exceeding national reports in nondialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected.

Identification of a minority population of LMO2+ breast cancer cells that integrate into the vasculature and initiate metastasis.

Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1+/VEGFA+ tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher abundance of LMO2+ basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. Using MMTV-PyMT/Lmo2CreERT2 mice, we demonstrated that Lmo2 lineage-traced cells integrate into the vasculature and have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by tumor necrosis factor-α and interleukin-6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis.

Current understanding of an Emerging Coronavirus using in silico approach: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2).

Novel coronavirus (nCoV) namely "SARS-CoV-2" is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the "SARS-CoV-2" although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among "SARS-CoV-2" and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that "SARS-CoV-2" has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.