Isolation and molecular characterization of an enteric isolate of the genotype-Ia bovine coronavirus with notable mutations in the receptor binding domain of the spike glycoprotein.

BCoV new isolate was plaque purified, isolated, and propagated in vitro using MDBK and HRT-18. The full-length genome sequencing of this new BCoV isolate (31 Kbs) was drafted and deported in the GenBank. The genome organization is (5'-UTR-Gene-1-32kDa-HE-S-4.

The dual actions of miRNA16a in restricting Bovine Coronavirus replication through downregulation of Furin and enhancing the host immune response.

The roles of host cell miRNAs have not been well studied in the context of BCoV replication and immune regulation. This study aimed to identify miRNA candidates that regulate essential host genes involved in BCoV replication, tissue tropism, and immune regulation. To achieve these goals, we used two isolates of BCoV (enteric and respiratory) to infect bovine endothelial cells (BECs) and Madine Darby Bovine Kidney (MDBK) cells.

The ex vivo infection model of the peripheral bovine mononuclear cells (PBMCs) and the bovine spleen cells with the bovine coronavirus (BCoV) induced a differential expression of the host cytokine genes profiles and modulates the virus replication.

The adaptive immune response during BCoV infection of peripheral blood mononuclear cells (PBMCs), the bovine spleen cells, and their isolated T lymphocytes was not studied well. Our study confirmed successful BCoV infection in PBMCs and spleen T cells. The BCoV replication was evidenced by measuring genome copy numbers using real-time PCR and expression levels of BCoV spike and nucleocapsid proteins via western blot and immunofluorescence assays.

Machine learning tools used for mapping some immunogenic epitopes within the major structural proteins of the bovine coronavirus (BCoV) and for the design of the multiepitope-based vaccines.

Introduction: BCoV is one of the significant causes of enteritis in young calves; it may also be responsible for many respiratory outbreaks in young calves. BCoV participates in the development of bovine respiratory disease complex in association with other bacterial pathogens. Our study aimed (1) to map the immunogenic epitopes (B and T cells) within the major BCoV structural proteins.

The Potential Roles of Host Cell miRNAs in Fine-Tuning Bovine Coronavirus (BCoV) Molecular Pathogenesis, Tissue Tropism, and Immune Regulation.

Bovine coronavirus (BCoV) infection causes significant economic loss to the dairy and beef industries worldwide. BCoV exhibits dual tropism, infecting the respiratory and enteric tracts of cattle. The enteric BCoV isolates could also induce respiratory manifestations under certain circumstances.

Cost Associated with Geriatric Traumatic Brain Injury in Developing Countries: An Observational Study.

Background: Traumatic brain injury (TBI) in the geriatric population is a serious public health problem and has a huge impact on mortality and morbidity.

Methods: A retrospective cohort study including patients aged above 65 admitted to a tertiary specialized trauma center, in the period from January 2016 to 31 December 2019. The data collected include patients' demographics, diagnosis, Glasgow Coma Scale (GCS) on arrival, length of stay, investigations, and type of surgery done.

Truncated DNM1 variant underlines developmental delay and epileptic encephalopathy.

Background: Developmental and epileptic encephalopathies (DEEs) signify a group of heterogeneous neurodevelopmental disorder associated with early-onset seizures accompanied by developmental delay, hypotonia, mild to severe intellectual disability, and developmental regression. Variants in the gene have been associated with autosomal dominant DEE type 31A and autosomal recessive DEE type 31B.

Methods: In the current study, a consanguineous Pakistani family consisting of a proband (IV-2) was clinically evaluated and genetically analyzed manifesting in severe neurodevelopmental phenotypes.

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia.

Background: Anophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non-syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non-genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy.

Structural and dynamics insights into the GBA variants associated with Parkinson's disease.

The gene encodes for the lysosomal enzyme glucocerebrosidase (GCase), which maintains glycosphingolipid homeostasis and regulates the autophagy process. Genomic variants of are associated with Goucher disease; however, several heterozygous variants of GBA (E326K, T369M, N370S, L444P) are frequent high-risk factors for Parkinson's disease (PD). The underlying mechanism of these variants has been revealed through functional and patient-centered research, but the structural and dynamical aspects of these variants have not yet been thoroughly investigated.

The deleterious variants of N-acetylgalactosamine-6-sulfatase (GalN6S) enzyme trigger Morquio a syndrome by disrupting protein foldings.

Lysosomal enzymes degrade cellular macromolecules, while their inactivation causes human hereditary metabolic disorders. Mucopolysaccharidosis IVA (MPS IVA; Moquio A syndrome) is one of the lysosomal storage disorders caused by a defective Galactosamine-6-sulfatase (GalN6S) enzyme. In several populations, disease incidence is elevated due to missense mutations brought on by non-synonymous allelic variation in the GalN6S enzyme.

Pharmacoepidemiological evaluation of off label and unlicensed prescription in pediatric intensive care units at tertiary care hospitals of Peshawar, Pakistan.

Population of pediatric intensive care units are at high risk of receiving off label and unlicensed drug use. Little is known about the characteristics and prevalence of unlicensed and off label prescriptions in pediatric intensive care units (PICUs) at tertiary care settings of Pakistan. Case notes of 420 children were reviewed for unlicensed and off label prescriptions during the one year.

Molecular Dynamic Simulation Analysis of a Novel Missense Variant in Gene in Patients with Methemoglobinemia.

: Mutations in the gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM exists as RCM type I (RCM1) and RCM type II (RCM2). RCM1 leads to higher methemoglobin levels causing only cyanosis, while in RCM2, neurological complications are also present along with cyanosis.

Comprehensive in-silico analysis of deleterious SNPs in APOC2 and APOA5 and their differential expression in cancer and cardiovascular diseases conditions.

Genetic variations in APOC2 and APOA5 genes involve activating lipoprotein lipase (LPL), responsible for the hydrolysis of triglycerides (TG) in blood and whose impaired functions affect the TG metabolism and are associated with metabolic diseases. In this study, we investigate the biological significance of genetic variations at the DNA sequence and structural level using various computational tools. Subsequently, 8 (APOC2) and 17 (APOA5) non-synonymous SNPs (nsSNPs) were identified as high-confidence deleterious SNPs based on the effects of the mutations on protein conservation, stability, and solvent accessibility.

Proteomics approaches: A review regarding an importance of proteome analyses in understanding the pathogens and diseases.

Proteomics is playing an increasingly important role in identifying pathogens, emerging and re-emerging infectious agents, understanding pathogenesis, and diagnosis of diseases. Recently, more advanced and sophisticated proteomics technologies have transformed disease diagnostics and vaccines development. The detection of pathogens is made possible by more accurate and time-constrained technologies, resulting in an early diagnosis.

Effectiveness of Autoinoculation in Patients with Multiple Warts Presenting at a Tertiary Care Hospital.

Objective: To determine the effectiveness of autoinoculation in patients with multiple skin warts.

Study Design: A Quasi-experimental study.

Place And Duration Of Study: Dermatology department of PNS Shifa Hospital, from April to October 2021.

Corrigendum: Disease specific symptoms indices in patients with celiac disease-A hardly recognised entity.

[This corrects the article DOI: 10.3389/fnut.2022.

Clinical and genetic characterization of patients segregating variants in KPTN, MINPP1, NGLY1, AP4B1, and SON underlying neurodevelopmental disorders: Genetic and phenotypic expansion.

Neurodevelopmental disorders (NDDs) are heterogeneous genetic conditions of the central nervous system (CNS). Primary phenotypes of NDDs include epilepsy, loss of developmental skills, abnormal movements, muscle weakness, ocular anomalies, hearing problems, and macro- or microcephaly. NDDs occur due to variants in genes encoding proteins involved in the structure and function of CNS, thus interrupting its normal physiological role.

Disease specific symptoms indices in patients with celiac disease-A hardly recognised entity.

Background: Celiac disease (CD) was considered a rare disease before and was perceivably only limited to children but now affects almost 1-2% of the global population. This abrupt increase in prevalence is due to advancements in diagnostic criteria and medical facilities but still many countries lack the basic data that can assess the severity of this health issue. The present study was conducted with the aim to assess the common but rarely diagnosed condition with the identification of its underlying secondary ailments.

A novel biallelic variant in the Popeye domain-containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25.

POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb-girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio-whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features.

Construction of a Novel Infectious Clone of Recombinant Herpesvirus of Turkey Fc-126 Expressing VP2 of IBDV.

The increased virulence of infectious bursal disease virus (IBDV) is a threat to the chicken industry. The construction of novel herpesvirus of turkey-vectored (HVT) vaccines expressing VP2 of virulent IBDV may be a promising vaccine candidate for controlling this serious disease in chickens. We generated a novel infectious clone of HVT Fc-126 by inserting mini-F sequences in lieu of the glycoprotein C (gC) gene.

Molecular Insights into the Role of Pathogenic nsSNPs in Gene Provoking Neurodevelopmental Disorders.

The GluN2B subunit of N-methyl-D-aspartate receptors plays an important role in the physiology of different neurodevelopmental diseases. Genetic variations in the GluN2B coding gene () have consistently been linked to West syndrome, intellectual impairment with focal epilepsy, developmental delay, macrocephaly, corticogenesis, brain plasticity, as well as infantile spasms and Lennox-Gastaut syndrome. It is unknown, however, how genetic variation impacts protein function.

Nrf2 Activation and NF-Kb & caspase/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells.

Mastitis, an inflammation of the mammary gland, is a complex disease that affects the health of dairy cows worldwide. Sodium butyrate (SB) is a short-chain fatty acid that has recently been shown to have antioxidant, anti-inflammatory and anti-apoptotic potential in various cells types, although its role in bovine mammary epithelial cells (bMECs) has not been comprehensively reported. Therefore, the aim of this study was to assess the protective effect of sodium butyrate on Lipopolysaccharide (LPS)-induced mastitis model in vitro and to elucidate the possible underlying molecular mechanisms.

Inhibition of the antigen-presenting ability of dendritic cells by non-structural protein 2 of influenza A virus.

Influenza A viruses (IAV), including human IAV and avian IAV (H9N2 subtype), are recurring of influenza outbreaks worldwide in a wide range of mammalian and avian species. Dendritic cells (DCs) are specialised antigen presenting cells. Although DCs can take up IAV and transmit it to other cells, it still unclear why DCs do not effectively present IAV antigens.

From nasal to basal: single-cell sequencing of the bursa of Fabricius highlights the IBDV infection mechanism in chickens.

Background: Chickens, important food animals and model organisms, are susceptible to many RNA viruses that invade via the nasal cavity. To determine the nasal entry site of the virus and clarify why avians are susceptible to RNA viruses, infectious bursal disease virus (IBDV) was selected because it is a typical avian RNA virus that infects chickens mainly via the nasal route.

Results: First, we found that IBDV infected the posterior part of the nasal cavity in chickens, which is rich in lymphoid tissue and allows the virus to be easily transferred to the blood.