Insights into the human cDNA: A descriptive study using library screening in yeast.

The utilization of human cDNA libraries in yeast genetic screens is an approach that has been used to identify novel gene functions and/or genetic and physical interaction partners through forward genetics using yeast two-hybrid (Y2H) and classical cDNA library screens. Here, we summarize several challenges that have been observed during the implementation of human cDNA library screens in Saccharomyces cerevisiae (budding yeast). Upon the utilization of DNA repair deficient-yeast strains to identify novel genes that rescue the toxic effect of DNA-damage inducing drugs, we have observed a wide range of transcripts that could rescue the strains.

Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility.

An alternative theoretical approach to develop a new conception about pain in people with dementia.

The theoretical approach presented in this paper describes a novel experimental-theoretical methodology to conceptualise pain in people with dementia. Existing procedures for assessment of pain rely on subjective self-report using pain questionnaires and rating scales that have proven to be highly problematic where a person has dementia. Consequently, pain in people with dementia can be undetected and/or undertreated.

High Glucose Increases DNA Damage and Elevates the Expression of Multiple DDR Genes.

The DNA Damage Response (DDR) pathways sense DNA damage and coordinate robust DNA repair and bypass mechanisms. A series of repair proteins are recruited depending on the type of breaks and lesions to ensure overall survival. An increase in glucose levels was shown to induce genome instability, yet the links between DDR and glucose are still not well investigated.

Aging, Parkinson's Disease, and Models: What Are the Challenges?

Parkinson's disease (PD) is a chronic, neurodegenerative condition characterized by motor symptoms such as bradykinesia, rigidity, and tremor, alongside multiple nonmotor symptoms. The appearance of motor symptoms is linked to progressive dopaminergic neuron loss within the substantia nigra. PD incidence increases sharply with age, suggesting a strong association between mechanisms driving biological aging and the development and progression of PD.

Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls.

Long-Term Health Associated with Small and Large for Gestational Age Births among Young Thai Adults.

We examined the long-term health outcomes associated with being born small for gestational age (SGA) or large for gestational age (LGA). A total of 632 young adults aged ≈20.6 years were recruited from a longitudinal study (Chiang Mai, Thailand) in 2010: 473 born appropriate for gestational age (AGA), 142 SGA, and 17 LGA.

SMN-deficient cells exhibit increased ribosomal DNA damage.

Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity.

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661-PTPN11 mRNA Axis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of -miR-661-PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis.

USP11 controls R-loops by regulating senataxin proteostasis.

R-loops are by-products of transcription that must be tightly regulated to maintain genomic stability and gene expression. Here, we describe a mechanism for the regulation of the R-loop-specific helicase, senataxin (SETX), and identify the ubiquitin specific peptidase 11 (USP11) as an R-loop regulator. USP11 de-ubiquitinates SETX and its depletion increases SETX K48-ubiquitination and protein turnover.

A role for Rad5 in ribonucleoside monophosphate (rNMP) tolerance.

Ribonucleoside monophosphate (rNMP) incorporation in genomic DNA poses a significant threat to genomic integrity. In addition to repair, DNA damage tolerance mechanisms ensure replication progression upon encountering unrepaired lesions. One player in the tolerance mechanism is Rad5, which is an E3 ubiquitin ligase and helicase.

DNA Homeostasis and Senescence: Lessons from the Naked Mole Rat.

As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration.

Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies.

Cellular senescence is a key component of human aging that can be induced by a range of stimuli, including DNA damage, cellular stress, telomere shortening, and the activation of oncogenes. Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response.

TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts.

Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient DNA replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate-a covalent TOP1-DNA adduct known as a TOP1 cleavage complex (TOP1cc)-is stabilised. TOP1ccs are highly cytotoxic and a failure to resolve them underlies the pathology of neurological disorders but is also exploited in cancer therapy where TOP1ccs are the target of widely used frontline anti-cancer drugs.