Adiponectin-induced activation of ERK1/2 drives fibrosis in retinal pigment epithelial cells.

Adiponectin (APN), a vasoactive cytokine produced by adipocytes, has emerged as a critical player in retinal diseases. Renowned for its antioxidant, anti-angiogenic, and anti-inflammatory properties, APN levels are closely linked to metabolic disorders, such as insulin resistance, obesity, and diabetic retinopathy (DR). Our previous work demonstrated that APN is similar in efficiency as Avastin in limiting neovascularization in retinal endothelial cells.

Human Antigen R -mediated modulation of Transforming Growth Factor Beta 1 expression in retinal pathological milieu.

The fate and stability of messenger RNA (mRNA), from transcription to degradation is regulated by a dynamic shuttle of epigenetic modifications and RNA binding proteins in maintaining healthy cellular homeostasis and disease development. While Transforming Growth Factor Beta 1 (TGFβ1) has been implicated as a key regulator for diabetic retinopathy, a microvascular complication of diabetes, the RNA binding proteins post-transcriptionally regulating its expression remain unreported in the ocular context. Further, dysfunction of TGFβ1 signalling is also strongly associated with angiogenesis, inflammatory responses and tissue fibrosis in many eye conditions leading to vision loss.

Virtual screening and multilevel precision-based prioritisation of natural inhibitors targeting the ATPase domain of human DNA topoisomerase II alpha.

Human DNA topoisomerase II alpha (hTopIIα) is a classic chemotherapeutic drug target. The existing hTopIIα poisons cause numerous side effects such as the development of cardiotoxicity, secondary malignancies, and multidrug resistance. The use of catalytic inhibitors targeting the ATP-binding cavity of the enzyme is considered a safer alternative due to the less deleterious mechanism of action.

Evaluating the impact of ocular UV exposure for the development for pseudoexfoliation syndrome in a South Indian population.

Clinical Relevance: Pathophysiology of pseudoexfoliation syndrome (XFS) can be influenced by environmental factors such as solar exposure/occupational factors and genetic factors.

Background: The study aims to assess the association of lifetime ocular UV exposure and its impact on the risk of development of XFS.

Methods: All eligible subjects underwent a comprehensive ocular examination.

Whole exome and targeted sequencing reveal novel mutations associated with inherited PCOS condition in an Indian cohort.

A cohort of polycystic ovary syndrome (PCOS) women presents themselves with persistent abnormal reproductive hormone levels and has a familial representation of characteristics. In our study, we have aimed to identify genetic variants which are inherited across such PCOS families and also validate them among Indian population. Independent discovery was done by whole exome sequencing in a three-generation family (Family P01).

Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.

Purpose: To elucidate the mechanism behind epigenetic alteration associated with dexamethasone (DEX) sodium phosphate treatment.

Methods: We performed enzyme-linked immunosorbent assay to quantify changes in global DNA methylation and hydroxymethylation, quantitative real-time PCR (qRT-PCR) of the DNA methylation- and hydroxymethylation-related gene, in vitro DNA methyltransferase (DNMT) enzymatic activity assays with purified DNMTs, and DNA hydroxymethylation pattern with super-resolution imaging.

Results: We identified global DNA hypomethylation and hyper-hydroxymethylation upon DEX treatment, associated with aberrant mRNA expression levels of DNMT and ten-eleven translocation (TET) proteins.

Assessment of single nucleotide polymorphisms associated with steroid-induced ocular hypertension.

Aim: To access the association of forty-eight single nucleotide polymorphisms (SNPs) identified from Caucasian population with steroid-induced ocular hypertension (OHT) in India population.

Methods: Fifty-four triamcinolone-acetonide (TA) and forty-seven dexamethasone (Dex) administered subjects were enrolled in the study after a written consent. Intraocular pressure (IOP) values were recorded for a period of 6-month post steroid injections and patients were grouped as steroid-responders (SR: IOP≥21 mm Hg) and non-responders (NR: IOP≤20 mm Hg).

Mechanism of activation of the BNLF2a immune evasion gene of Epstein-Barr virus by Zta.

The human gamma herpes virus Epstein-Barr virus (EBV) exploits multiple routes to evade the cellular immune response. During the EBV lytic replication cycle, viral proteins are expressed that provide excellent targets for recognition by cytotoxic T cells. This is countered by the viral BNLF2a gene.

The Use of Chromatin Precipitation Coupled to DNA Sequencing (ChIP-Seq) for the Analysis of Zta Binding to the Human and EBV Genome.

Determining which components of the transcription machinery associate with the viral and cellular genome, and how this changes at specific stages of the viral life cycle is paramount to understanding how the distinct transcriptional programs associated with primary infection, latency, and disease are established and how they are reprogrammed during initiation and execution of the viral lytic replication cycle. Chromatin precipitations linked to next generation DNA sequencing (ChIP-Seq) allow for the interactions of proteins with DNA to be mapped across both viral and cellular genomes. This can be applied to viral and cellular transcription factors, coactivators and corepressors, modified histones, and modulators of chromatin.

Identification of Epstein-Barr Virus Replication Proteins in Burkitt's Lymphoma Cells.

The working model to describe the mechanisms used to replicate the cancer-associated virus Epstein-Barr virus (EBV) is partly derived from comparisons with other members of the Herpes virus family. Many genes within the EBV genome are homologous across the herpes virus family. Published transcriptome data for the EBV genome during its lytic replication cycle show extensive transcription, but the identification of the proteins is limited.

Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression.

Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes.

Genome-wide analyses of Zta binding to the Epstein-Barr virus genome reveals interactions in both early and late lytic cycles and an epigenetic switch leading to an altered binding profile.

The Epstein-Barr virus (EBV) genome sustains substantial epigenetic modification involving chromatin remodelling and DNA methylation during lytic replication. Zta (ZEBRA, BZLF1), a key regulator of the EBV lytic cycle, is a transcription and replication factor, binding to Zta response elements (ZREs) in target promoters and EBV lytic origins of replication. In vitro, Zta binding is modulated by DNA methylation; a subset of CpG-containing Zta binding sites (CpG ZREs) is bound only in a DNA methylation-dependent manner.

Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome.

The ability of Epstein-Barr virus (EBV) to establish latency allows it to evade the immune system and to persist for the lifetime of its host; one distinguishing characteristic is the lack of transcription of the majority of viral genes. Entry into the lytic cycle is coordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, and EB1), and downstream effectors, while viral genome replication requires the concerted action of Zta and six other viral proteins at the origins of lytic replication. We explored the chromatin context at key EBV lytic cycle promoters (BZLF1, BRLF1, BMRF1, and BALF5) and the origins of lytic replication during latency and lytic replication.

Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor.

Epstein-Barr virus (EBV) encoded transcription factor Zta (BZLF1, ZEBRA, EB1) is the prototype of a class of transcription factor (including C/EBPalpha) that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication.

Rad8Rad5/Mms2-Ubc13 ubiquitin ligase complex controls translesion synthesis in fission yeast.

Many DNA lesions cause pausing of replication forks at lesion sites; thus, generating gaps in the daughter strands that are filled-in by post-replication repair (PRR) pathways. In Saccharomyces cerevisiae, PRR involves translesion synthesis (TLS) mediated by Poleta or Polzeta, or Rad5-dependent gap filling through a poorly characterized error-free mechanism. We have developed an assay to monitor error-free and mutagenic TLS across single DNA lesions in Schizosaccharomyces pombe.

Ubiquitin-PCNA fusion as a mimic for mono-ubiquitinated PCNA in Schizosaccharomyces pombe.

Translesion synthesis is a major mechanism with which eukaryotic cells deal with DNA damage during replication. Mono-ubiquitinated PCNA is a key regulator of this process. We have investigated whether a ubiquitin-PCNA fusion can mimic ubiquitinated PCNA, by transforming plasmids expressing this fusion protein into different mutants of Schizosaccharomyces pombe.

Australin: a chromosomal passenger protein required specifically for Drosophila melanogaster male meiosis.

The chromosomal passenger complex (CPC), which is composed of conserved proteins aurora B, inner centromere protein (INCENP), survivin, and Borealin/DASRA, localizes to chromatin, kinetochores, microtubules, and the cell cortex in a cell cycle-dependent manner. The CPC is required for multiple aspects of cell division. Here we find that Drosophila melanogaster encodes two Borealin paralogues, Borealin-related (Borr) and Australin (Aust).