Publications by authors named "Veena Mathew"

This review addresses plant interactions with HMs, emphasizing defence mechanisms and the role of chelating agents, antioxidants and various elicitor molecules in mitigating metal toxicity in plants. To combat soil contamination with HMs, chelate assisted phytoextraction using application of natural or synthetic aminopolycarboxylic acids is an effective strategy. Plants also employ diverse signaling pathways, including hormones, calcium, reactive oxygen species, nitric oxide, and Mitogen-Activated Protein Kinases influencing gene expression and defence mechanisms to counter HM stress.

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Spatial compartmentalization is a key facet of protein quality control that serves to store disassembled or non-native proteins until triage to the refolding or degradation machinery can occur in a regulated manner. Yeast cells sequester nuclear proteins at intranuclear quality control bodies (INQ) in response to various stresses, although the regulation of this process remains poorly understood. Here we reveal the SUMO modification of the small heat shock protein Btn2 under DNA damage and place Btn2 SUMOylation in a pathway promoting protein clearance from INQ structures.

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Photosynthesis, as one of the most important chemical reactions, has powered our planet for over four billion years on a massive scale. This review summarizes and highlights the major contributions of Govindjee from fundamentals to applications in photosynthesis. His research included primary photochemistry measurements, in the picosecond time scale, in both Photosystem I and II and electron transport leading to NADP reduction, using two light reactions.

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Background: There are limited studies on barriers to seeking treatment for Alcohol Use Disorders (AUD) among males in tertiary care centers in India and abroad. Identification of these factors can aid in addressing the barriers to seeking treatment for AUD in low-and-middle-income countries.

Objective: To investigate the barriers to seeking treatment for AUD among males in a tertiary care center in South India.

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The nucleus is a highly organized organelle with an intricate substructure of chromatin, RNAs, and proteins. This environment represents a challenge for maintaining protein quality control, since non-native proteins may interact inappropriately with other macromolecules and thus interfere with their function. Maintaining a healthy nuclear proteome becomes imperative during times of stress, such as upon DNA damage, heat shock, or starvation, when the proteome must be remodeled to effect cell survival.

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More than 2 billion people worldwide suffer from micronutrient malnutrition, sometimes known as hidden hunger. Zn malnutrition affects around a third of the world's population. The physicochemical features of soil, which limit the availability of Zn to plants, cause Zn deficiency.

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Cdc48 (known as VCP in mammals) is a highly conserved ATPase chaperone that plays an essential role in the assembly and disassembly of protein-DNA complexes and in degradation of misfolded proteins. We find that in budding yeast, Cdc48 accumulates during cellular stress at intranuclear protein quality control sites (INQ). We show that Cdc48 function is required to suppress INQ formation under non-stress conditions and to promote recovery following genotoxic stress.

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Article Synopsis
  • Many patients with generalized myasthenia gravis (gMG) experience significant disability and need better therapies that are well-tolerated to improve their quality of life.
  • A phase 2 clinical trial was conducted to assess the effects of zilucoplan, a self-administered injectable treatment, on patients with moderate to severe gMG.
  • The study included 44 participants and compared the effectiveness of zilucoplan against a placebo over 12 weeks, focusing on changes in their disease symptoms and daily functioning.
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Hereditary transthyretin amyloidosis is a fatal autosomal dominant disorder characterized by deposition of transthyretin amyloid into the peripheral nervous system, heart, kidney, and gastrointestinal tract. Previous treatments using liver transplantation and small molecule stabilizers were not effective in stopping disease progression. Inotersen, a 2'-O-methyoxyethyl-modified antisense oligonucleotide, which acts by reducing the production of transthyretin, was recently demonstrated to improve disease course and quality of life in early hereditary transthyretin amyloidosis polyneuropathy in a 15-month Phase III study.

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RNA processing mutants have been broadly implicated in genome stability, but mechanistic links are often unclear. Two predominant models have emerged: one involving changes in gene expression that perturb other genome maintenance factors and another in which genotoxic DNA:RNA hybrids, called R-loops, impair DNA replication. Here we characterize genome instability phenotypes in yeast splicing factor mutants and find that mitotic defects, and in some cases R-loop accumulation, are causes of genome instability.

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Article Synopsis
  • Telomerase is a crucial enzyme that helps maintain chromosome ends, impacting how cells divide by forming T-loops essential for cell-cycle progression.
  • Inhibition of telomerase activity through a chemical called imetelstat was found to alter cell cycle dynamics, causing more cells to remain in the G-phase, indicating delays at this checkpoint.
  • The study reveals that telomerase inhibition leads to DNA damage at telomeres, which disrupts cell cycle progression, and this effect can be linked to ATM signaling, a key player in DNA damage response.
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To tolerate and recover from genotoxic stress cells must coordinate a range of stress response activities including cell cycle arrest, DNA repair, and remodeling of the transcriptome and proteome. The suppression of ribosome production is a key feature of many stress responses in yeast, and much is known about the dynamics of this process at the transcriptional level. In our recent study, (J Cell Biol doi: 10.

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Article Synopsis
  • The study investigates how proteins involved in DNA repair and cellular stress responses change their location in the cell during genotoxic stress, focusing on the splicing factor Hsh155.
  • Hsh155 moves away from its usual partners and accumulates in specific protein quality control aggregates in both the nucleus and cytoplasm when exposed to alkylation stress, a process influenced by molecular chaperones and TORC1 signaling.
  • This relocalization of Hsh155 is linked to changes in gene expression, including increased intron retention and reduced splicing efficiency, ultimately aiding the cell's recovery from stress.
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Bisulfite, in the form of sodium bisulfite or metabisulfite, is used commercially as a food preservative. Bisulfite is used in the laboratory as a single-stranded DNA mutagen in epigenomic analyses of DNA methylation. Recently it has also been used on whole yeast cells to induce mutations in exposed single-stranded regions in vivo.

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G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition.

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Standard treatment for advanced non-small cell lung cancer (NSCLC) with no known driver mutation is platinum-based chemotherapy, which has a response rate of only 30-33%. Through an siRNA screen, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of sulfate PAPS, was identified as a novel platinum-sensitizing target in NSCLC cells. PAPSS1 knockdown in combination with low-dose (IC10) cisplatin reduces clonogenicity of NSCLC cells by 98.

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Chromatin reorganization and the incorporation of specific histone modifications during DNA damage response are essential steps for the successful repair of any DNA lesion. Here, we show that the histone-fold protein CHRAC14 plays an essential role in response to DNA damage in Drosophila. Chrac14 mutants are hypersensitive to genotoxic stress and do not activate the G2/M cell-cycle checkpoint after damage induction.

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Heterochromatin integrity is crucial for genome stability and regulation of gene expression, but the factors involved in mammalian heterochromatin biology are only incompletely understood. Here we identify the oncoprotein DEK, an abundant nuclear protein with a previously enigmatic in vivo function, as a Suppressor of Variegation [Su(var)] that is crucial to global heterochromatin integrity. We show that DEK interacts directly with Heterochromatin Protein 1 α (HP1α) and markedly enhances its binding to trimethylated H3K9 (H3K9me3), which is key for maintaining heterochromatic regions.

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