Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein.

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization.

Epitope-directed anti-SARS-CoV-2 scFv engineered against the key spike protein region could block membrane fusion.

The newly emerged SARS-CoV-2 causing coronavirus disease (COVID-19) resulted in >500 million infections. A great deal about the molecular processes of virus infection in the host is getting uncovered. Two sequential proteolytic cleavages of viral spike protein by host proteases are prerequisites for the entry of the virus into the host cell.

Antibody multispecificity: A necessary evil?

Antibodies represent key effectors of the adaptive immune system. The specificity of antibodies is an established hallmark of the immune response. However, a certain proportion of antibodies exhibit limited promiscuity or multireactivity.

Sensory Changes Related to Dental Implant Placement: A Scoping Review.

Aims: To perform a scoping review of the literature to elucidate the occurrence of nerve damage related to dental implant placement and the factors causing the sensory changes.

Methods: An extensive electronic search was conducted using the Cochrane Library, Medline via Ovid, PubMed, Wiley Online, Science Direct, CINAHL, and the Google Scholar databases from the year 1950 to 2020.

Results: The search resulted in 1,067 articles, out of which 76 were selected for this review.

Dynamics of lipid displacement inside the hydrophobic cavity of a nonspecific lipid transfer protein from .

Nonspecific lipid transfer proteins are multifunctional and multispecific seed proteins with a characteristic hydrophobic cavity that runs form N-terminal to the C-terminal end. They are capable of binding and transferring different lipid molecules by means of their hydrophobic cavity. Apart from the cavity, lipid molecules bind and interact at key positions on the nsLTP surface as well.

Immunoaffinity purification of endogenous proteins from for post-translational modification and protein interaction analysis.

Protein regulation by post-translational modifications and protein-protein interactions is critical to controlling molecular pathways. Here, we describe an immunoaffinity purification approach in . The protocol uses an endogenously-expressed epitope-tagged protein and can be applied to the identification of post-translational modifications or protein binding partners.

Set4 regulates stress response genes and coordinates histone deacetylases within yeast subtelomeres.

The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status identified a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions.

Function of the MYND Domain and C-Terminal Region in Regulating the Subcellular Localization and Catalytic Activity of the SMYD Family Lysine Methyltransferase Set5.

SMYD lysine methyltransferases target histones and nonhistone proteins for methylation and are critical regulators of muscle development and implicated in neoplastic transformation. They are characterized by a split catalytic SET domain and an intervening MYND zinc finger domain, as well as an extended C-terminal domain. contains two SMYD proteins, Set5 and Set6, which share structural elements with the mammalian SMYD enzymes.

Azoospermic infertility is associated with altered expression of DNA repair genes.

Compelling evidence suggest that germs cells are predominantly sensitive to DNA damaging agents in comparison to other cells. High fidelity DNA repair in testicular cells thus becomes indispensable to preserve the genomic integrity for passing on to the progeny. Compromised DNA repair machinery in the testicular cells may result in impaired spermatogenesis and infertility.

Set4 is a chromatin-associated protein, promotes survival during oxidative stress, and regulates stress response genes in yeast.

The Set4 protein in the yeast contains both a PHD finger and a SET domain, a common signature of chromatin-associated proteins, and shares sequence homology with the yeast protein Set3, the fly protein UpSET, and the human protein mixed-lineage leukemia 5 (MLL5). However, the biological role for Set4 and its potential function in chromatin regulation has not been well defined. Here, we analyzed yeast cell phenotypes associated with loss of Set4 or its overexpression, which revealed that Set4 protects against oxidative stress induced by hydrogen peroxide.

Chromatin Immunoprecipitation (ChIP) of Histone Modifications from Saccharomyces cerevisiae.

Histone post-translational modifications (PTMs), such as acetylation, methylation and phosphorylation, are dynamically regulated by a series of enzymes that add or remove these marks in response to signals received by the cell. These PTMS are key contributors to the regulation of processes such as gene expression control and DNA repair. Chromatin immunoprecipitation (chIP) has been an instrumental approach for dissecting the abundance and localization of many histone PTMs throughout the genome in response to diverse perturbations to the cell.

Repression of Middle Sporulation Genes in by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation.

The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark.

Choose Your Own Adventure: The Role of Histone Modifications in Yeast Cell Fate.

When yeast cells are challenged by a fluctuating environment, signaling networks activate differentiation programs that promote their individual or collective survival. These programs include the initiation of meiotic sporulation, the formation of filamentous growth structures, and the activation of programmed cell death pathways. The establishment and maintenance of these distinct cell fates are driven by massive gene expression programs that promote the necessary changes in morphology and physiology.

Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses.

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.

Dysregulation of apoptotic pathway candidate genes and proteins in infertile azoospermia patients.

Objective: To dissect the role of the apoptotic pathway and its regulation in the pathogenesis of male infertility in nonobstructive azoospermia.

Design: Prospective study.

Setting: University hospital.

Chromosome microarray analysis: a case report of infertile brothers with CATSPER gene deletion.

We present the case of two brothers who were referred to a male infertility clinic for infertility workup. Conventional chromosome analysis and Y chromosome microdeletions did not reveal any genetic alterations. We utilized the chromosome microarray analysis (CMA) to identify novel and common variations associated with this severely impaired spermatogenesis cases.

Association of interleukin-1beta C + 3953T gene polymorphism with human male infertility.

Cytokines are involved in the regulation of spermatogenesis likely mediating the crosstalk among Sertoli and germ cells to facilitate germ cell movement across the seminiferous epithelium during cellular events such as germ cell differentiation. Members of the Interleukin-1 (IL-1) family are pleiotropic cytokines that are involved in inflammation, immunoregulation, and other homeostatic functions. Interleukin-1 alpha (IL-1α), IL-1β, and the IL-1 antagonistic molecule (IL-1 Ra) are present in the testis under normal homeostasis and they further increase upon infection/inflammation.

Association of the IL1RN gene VNTR polymorphism with human male infertility.

Interleukin-1 (IL-1) is a regulatory cytokine that plays an important role in the maintenance of the immune environment of the testis, regulation of junction dynamics and cell differentiation during spermatogenesis. Members of the IL-1 family are pleiotropic cytokines that are involved in inflammation, immunoregulation and other homeostatic functions in the body. IL-1α, IL-1β, and the IL-1 receptor antagonistic molecule (IL-1 Ra) are expressed in the testis under normal homeostasis and they further increase upon infection/inflammation.

One-carbon metabolism, spermatogenesis, and male infertility.

Balanced diet is the natural source of micronutrients, such as folate and vitamins, vital for proper functioning of the body. One-carbon metabolic pathway along with folate and other vitamins plays an important role in DNA synthesis and in the establishment of epigenetic modifications like DNA/histone methylation. Spermatogenesis involves distinct cellular, genetic, and chromatin changes during the course of production of male gamete sperm.

Combined effect of GSTT1 and GSTM1 polymorphisms on human male infertility in north Indian population.

Genes of different pathways regulate spermatogenesis, and complexity of spermatogenic process indicates that polymorphisms or mutations in these genes could cause male infertility. Detoxification pathway is involved in the regulation of spermatogenesis by reducing oxidative stress and contributes to the maintenance of global methylation in concert with other pathways. Glutathione S-transferases (GSTs) belong to the family of phase II antioxidant enzymes involved in the cellular detoxification of various physiological substances.

Human male infertility: a complex multifactorial phenotype.

Infertility is a major reproductive health problem affecting 10% to 15% of couples, with approximately equal contributions. Spermatogenesis is a dynamic and multistep process of male germ cell proliferation and differentiation by which spermatozoa are produced from primordial germ cells. The causes of spermatogenic defects in infertile men are multifactorial and many environmental, nutritional, behavioral and genetic factors affect male infertility.