Functional roles and cancer variants of the bifunctional glycosylase NEIL2.

Over 70,000 DNA lesions occur in the cell every day, and the inability to properly repair them can lead to mutations and destabilize the genome, resulting in carcinogenesis. The base excision repair (BER) pathway is critical for maintaining genomic integrity by repairing small base lesions, abasic sites and single-stranded breaks. Monofunctional and bifunctional glycosylases initiate the first step of BER by recognizing and excising specific base lesions, followed by DNA end processing, gap filling, and finally nick sealing.

Topical hypochlorous acid (HOCl) blocks inflammatory gene expression and tumorigenic progression in UV-exposed SKH-1 high risk mouse skin.

Hypochlorous acid (HOCl) is the active oxidizing principle underlying drinking water disinfection, also delivered by numerous skin disinfectants and released by standard swimming pool chemicals used on a global scale, a topic of particular relevance in the context of the ongoing COVID-19 pandemic. However, the cutaneous consequences of human exposure to HOCl remain largely unknown, posing a major public health concern. Here, for the first time, we have profiled the HOCl-induced stress response in reconstructed human epidermis and SKH-1 hairless mouse skin.

Deuterium Oxide (DO) Induces Early Stress Response Gene Expression and Impairs Growth and Metastasis of Experimental Malignant Melanoma.

There are two stable isotopes of hydrogen, protium (H) and deuterium (H; D). Cellular stress response dysregulation in cancer represents both a major pathological driving force and a promising therapeutic target, but the molecular consequences and potential therapeutic impact of deuterium (H)-stress on cancer cells remain largely unexplored. We have examined the anti-proliferative and apoptogenic effects of deuterium oxide (DO; 'heavy water') together with stress response gene expression profiling in panels of malignant melanoma (A375, A375, G361, LOX-IMVI), and pancreatic ductal adenocarcinoma (PANC-1, Capan-2, or MIA PaCa-2) cells with inclusion of human diploid Hs27 skin fibroblasts.

The Endogenous Tryptophan-derived Photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) is a Nanomolar Photosensitizer that Can be Harnessed for the Photodynamic Elimination of Skin Cancer Cells in Vitro and in Vivo.

UV-chromophores contained in human skin may act as endogenous sensitizers of photooxidative stress and can be employed therapeutically for the photodynamic elimination of malignant cells. Here, we report that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan-derived photoproduct and endogenous aryl hydrocarbon receptor agonist, displays activity as a nanomolar sensitizer of photooxidative stress, causing the photodynamic elimination of human melanoma and nonmelanoma skin cancer cells in vitro and in vivo. FICZ is an efficient UVA/Visible photosensitizer having absorbance maximum at 390 nm (ε = 9180 L mol  cm ), and fluorescence and singlet oxygen quantum yields of 0.

The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis.

Sunless (chemical) tanning is widely regarded as a safe alternative to solar UV-induced skin tanning known to be associated with epidermal genotoxic stress, but the cutaneous biology impacted by chemical tanning remains largely unexplored. Chemical tanning is based on the formation of melanin-mimetic cutaneous pigments ('melanoidins') from spontaneous amino-carbonyl ('glycation') reactions between epidermal amino acid/protein components and reactive sugars including the glycolytic ketose dihydroxyacetone (DHA). Here, we have examined the cutaneous effects of acute DHA-exposure on cultured human HaCaT keratinocytes and epidermal reconstructs, profiled by gene expression array analysis and immunodetection.

Genetic Target Modulation Employing CRISPR/Cas9 Identifies Glyoxalase 1 as a Novel Molecular Determinant of Invasion and Metastasis in A375 Human Malignant Melanoma Cells In Vitro and In Vivo.

Metabolic reprogramming is a molecular hallmark of cancer. Recently, we have reported the overexpression of glyoxalase 1 (encoded by ), a glutathione-dependent enzyme involved in detoxification of the reactive glycolytic byproduct methylglyoxal, in human malignant melanoma cell culture models and clinical samples. However, the specific role of in melanomagenesis remains largely unexplored.

Repurposing the Electron Transfer Reactant Phenazine Methosulfate (PMS) for the Apoptotic Elimination of Malignant Melanoma Cells through Induction of Lethal Oxidative and Mitochondriotoxic Stress.

Redox-directed pharmacophores have shown potential for the apoptotic elimination of cancer cells through chemotherapeutic induction of oxidative stress. Phenazine methosulfate (PMS), a N-alkylphenazinium cation-based redox cycler, is used widely as an electron transfer reactant coupling NAD(P)H generation to the reduction of tetrazolium salts in biochemical cell viability assays. Here, we have explored feasibility of repurposing the redox cycler PMS as a superoxide generating chemotherapeutic for the pro-oxidant induction of cancer cell apoptosis.

Assessment of teaching to predict gains in student achievement in urban schools.

We examined the degree to which assessment of teachers' instructional and behavior management practices, as measured by the Classroom Strategies Assessment System (CSAS; Reddy & Dudek, 2014), relates to gains in student achievement as measured by the Measures of Academic Progress (Northwest Evaluation Association [NWEA], 2011). Two-level hierarchical linear modeling was applied to achievement scores from 2,771 students in 130 kindergarten through 8-grade classrooms in 13 urban schools serving students in communities with high concentrations of poverty. Results suggest that teachers' use of evidence-based instructional and behavior management strategies, as measured by the CSAS, were associated with reading and mathematics gains.

Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review.

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses.

Lessons learnt in recruiting disadvantaged families to a birth cohort study.

Background: Dental decay in early childhood can be prevented by a model based on shared care utilising members of primary care team such as Child and Family Health Nurses (CFHNs) in health promotion and early intervention. The aims of this study were to identify the facilitators and barriers faced by CFHNs in recruiting research participants from disadvantaged backgrounds to a birth cohort study in South Western Sydney, Australia.

Methods: Child and Family Health Nurses recruited mothers-infants dyads ( = 1036) at the first post-natal home visit as part of Healthy Smiles Healthy Kids Study, an ongoing birth cohort study in South Western Sydney.

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis.

Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified.

The B -vitamer Pyridoxal is a Sensitizer of UVA-induced Genotoxic Stress in Human Primary Keratinocytes and Reconstructed Epidermis.

UVA-driven photooxidative stress in human skin may originate from excitation of specific endogenous chromophores acting as photosensitizers. Previously, we have demonstrated that 3-hydroxypyridine-derived chromophores including B -vitamers (pyridoxine, pyridoxamine and pyridoxal) are endogenous photosensitizers that enhance UVA-induced photooxidative stress in human skin cells. Here, we report that the B -vitamer pyridoxal is a sensitizer of genotoxic stress in human adult primary keratinocytes (HEKa) and reconstructed epidermis.

Issues in Identifying Poor Comprehenders.

Studies of poor comprehenders vary in the selection criteria and tests that they use to define poor comprehension. Could these differences play a role in determining findings about poor comprehension? This study assessed the extent to which differences in selection methods affect who gets identified as poor comprehenders, and examined how their cognitive profiles differ. Over 1,500 children, ages 8 - 19, took multiple tests of reading comprehension, listening comprehension, single word reading and nonword reading.

The Role of Text Memory in Inferencing and in Comprehension Deficits.

Comprehension tests often compare accuracy on inferential versus literal questions and find inferential harder than literal, and poor comprehenders performing worse than controls. Difficulties in integration are assumed to be the reason. This research explores another reason - differences in memory for the passage information underlying the questions.