Genetic Diagnosis Of Vexas Syndrome: A New Rare And Deadly Autoinflammatory Disorder In Adults

VEXAS (Vacuoles, E1 enzyme, X linked, autoinflammatory, somatic syndrome) syndrome is a rare autoimmune condition that can be fatal in adult persons. VEXAS syndrome is classified as an autoinflammatory disease. This syndrome typically affects older adults, primarily males, with signs and symptoms of the condition developing in a person's fifties, sixties, or seventies. About 1 in every 13,591 adults may have the condition. Mutations affecting methionine-41 (p. Met41) in UBA1 of blood cells, the major E1 enzyme that initiates ubiquitylation is responsible for VEXAS. The peripheral-blood exome sequence data was analysed, independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9-edited zebrafish were used as an in vivo model to assess the gene function. In such patient, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristics vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Patients can also have a shortage of blood cells called platelets. Treatments include corticosteroids, immunosuppressants and sometimes a bone marrow transplant. In the future, VEXAS syndrome along with other related autoinflammatory conditions, and maybe other hemato-inflammatory diseases, in adulthood may change our perception of the already supposedly known rheumatic or systemic autoimmune diseases, and genetic diagnosis may become a routine clinical practice for physicians in experienced referral centres

Immunity Risk Associated With Cytomegalovirus Infection After Organ Transplantation

Cytomegalovirus (CMV), a member of the Herpesviridae family, is frequently seen in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) patients and is a major cause of morbidity and mortality in absence of antiviral prophylaxis in the transplant patients. CMV infection can cause serious problems in organ transplant patients following transplantation, in which the virus could reactivate or could contract a new infection, both result in signs of an active CMV infection consequently leading to organ rejection. CMV generates a robust and diverse innate and adaptive immune response and infects epithelial cells, macrophages, and T lymphocytes. During a three tier infective reaction cycle, it   establishes lifetime latency within its host. Ganciclovir , Valganciclovir and Foscarnet though remain successful as treatment strategies against CMV infection, they suffer from some major side effects like leukopenia, drug toxicity and some resistance development. So more recent medicines like letermovir and maribavir have provided new insights as therapy of drug resistant CMV infection. The demand for efficient and well-tolerated medicines still remains a challenge. Early clinical trials have shown potential for adoptive immunotherapy, which involves the virus specific T-cells (VSTs) as drug regime for highly resistant viral infections. With a focus on the clinical strategy for the challenge of CMV infection, this review encompasses positive findings and problems of the widespread use of VSTs to treat immunocompromised patients

Not Available

Not AvailableThe discovery and subsequent repurposing of the CRISPR (clustered regularly interspaced short palindromic repeats) and Cas proteins (CRISPR-associated proteins) has revolutionized our ability to manipulate DNA and RNA sequences in vitro, ex vivo, and in vivo. In this introductory chapter, we present a brief overview of basics of CRISPR-Cas-mediated genome editing and different orthologues and engineered versions of Cas protein with altered specificity and expanded targetability. More importantly, we comprehensively portray the advances made by developing diverse CRISPR-Cas-based genome modification tools and their application in basic biology, agriculture, and medicine.Not Availabl

Development of pod borer-resistant transgenic chickpea using a pod-specific and a constitutive promoter-driven fused cry1Ab/Ac gene

Crystal (Cry) proteins derived from the soil bacterium Bacillus thuringiensis (Bt) play an important role in controlling infestation of Helicoverpa armigera, which has been considered a serious problem in chickpea productivity. This study was undertaken to overcome the problem by introducing fused cry1Ab/Ac insecticidal gene under the control of pod-specific soybean msg promoter as well as rice actin1 promoter into chickpea var. DCP 92-3 by Agrobacterium-mediated transformation. Transgenic chickpea lines were characterized by real-time PCR, ELISA and insect bioassay. Expression of fused cry gene under constitutive and pod-specific promoter results in increase of 77- and 110-fold, respectively, compared to non-transgenic control plants. Levels of Cry toxins produced under the control of actin1 and soybean msg promoter were also estimated by ELISA in the leaves and pods, respectively. The higher expression of fused cry gene caused a lethal effect in larvae. The results of insect bioassay study revealed significant reduction in the survival rate of H. armigera reared on transgenic chickpea twigs as well as on pods. Pod-specific promoter-driven fused cry gene provides better and significant management strategy of pest control of chickpea without phenotypic cost

Kinetic and Mechanistic Studies on the Interaction of Glycyl-L-alanine, Glycyl-L-asparagine, and Glycyl-L-tyrosine with Hydroxopentaaquarhodium(III) Ion

The kinetics of the interaction of three glycine-containing dipeptides, namely, glycyl-L-alanine (L1-L′H), glycyl-L-asparagine (L2-L′H), and glycyl-L-tyrosine (L3-L′H) with has been studied spectrophotometrically in aqueous medium as a function of the molar concentration of , [dipeptide], pH, and temperature at constant ionic strength. Reactions were studied at pH 4.3, where the substrate complex exists predominantly as the hydroxopentaaqua species and dipeptides as the zwitterion. The reaction has been found to proceed via two parallel paths: both processes are ligand dependent. The rate constant for the processes are and . The activation parameters for both the steps were evaluated using Eyring’s equation. The low and large negative value of as well as and indicate an associative mode of activation for both the aqua ligand substitution processes for both the parallel paths. The product of the reaction has been characterized by IR and ESI-mass spectroscopic analyses

Kinetic and Mechanistic Studies on the Interaction of Glycyl-L-alanine, Glycyl-L-asparagine, and Glycyl-L-tyrosine with Hydroxopentaaquarhodium(III) Ion

The kinetics of the interaction of three glycine-containing dipeptides, namely, glycyl-L-alanine ( , pH, and temperature at constant ionic strength. Reactions were studied at pH 4.3, where the substrate complex exists predominantly as the hydroxopentaaqua species and dipeptides as the zwitterion. The reaction has been found to proceed via two parallel paths: both processes are ligand dependent. The rate constant for the processes are 1 ∼ 10 −3 s −1 and 2 ∼ 10 −5 s −1 . The activation parameters for both the steps were evaluated using Eyring's equation 2 indicate an associative mode of activation for both the aqua ligand substitution processes for both the parallel paths. The product of the reaction has been characterized by IR and ESI-mass spectroscopic analyses

Not Available

Not AvailableRice sheath blight disease, caused by the basidiomycetous necrotroph Rhizoctonia solani,became one of the major threats to the rice cultivation worldwide, especially after the adoptionof high-yielding varieties. The pathogen is challenging to manage because of its extensivelybroad host range and high genetic variability and also due to the inability to find any satisfactorylevel of natural resistance from the available rice germplasm. It is high time to find remedies tocombat the pathogen for reducing rice yield losses and subsequently to minimize the threat toglobal food security. The development of genetic resistance is one of the alternative means toavoid the use of hazardous chemical fungicides. This review mainly focuses on the effort ofbetter understanding the host–pathogen relationship, finding the gene loci/markers impartingresistance response and modifying the host genome through transgenic development. The latestdevelopment and trend in the R. solani–rice pathosystem research with gap analysis areprovide

Green tissue-specific co-expression of chitinase and oxalate oxidase 4 genes in rice for enhanced resistance against sheath blight

Overexpressing two defense-related genes (OsOXO4 and OsCHI11) cloned from rice is effective at enhancing resistance against sheath blight caused by Rhizoctonia solani. These genes were expressed under the control of two different green tissue-specific promoters, viz. maize phosphoenolpyruvate carboxylase gene promoter, PEPC, and rice cis-acting 544-bp DNA element, immediately upstream of the D54O translational start site, PD54O–544. Putative T0 transgenic rice plants were screened by PCR and integration of genes was confirmed by Southern hybridization of progeny (T1) rice plants. Successful expression of OsOXO4 and OsCHI11 in all tested plants was confirmed. Expression of PR genes increased significantly following pathogen infection in overexpressing transgenic plants. Following infection, transgenic plants exhibited elevated hydrogen peroxide levels, significant changes in activity of ROS scavenging enzymes and reduced membrane damage when compared to their wild-type counterpart. In a Rhizoctonia solani toxin assay, a detached leaf inoculation test and an in vivo plant bioassay, transgenic plants showed a significant reduction in disease symptoms in comparison to non-transgenic control plants. This is the first report of overexpression of two different PR genes driven by two green tissue-specific promoters providing enhanced sheath blight resistance in transgenic rice