A Hybrid Sequencing Approach Completes the Genome Sequence of Thermoanaerobacter ethanolicus JW 200

This is the final version. Available on open access from American Society for Microbiology via the DOI in this recordData availability.The complete genome sequence of T. ethanolicus JW 200 is deposited in GenBank under the accession number CP033580. Illumina and Oxford Nanopore DNA sequence reads have been deposited in the NCBI Sequence Read Archive (accession numbers SRR8113455 and SRR8113456).Thermoanaerobacter ethanolicus JW 200 has been identified as a potential sustainable biofuel producer due to its ability to readily ferment carbohydrates to ethanol. A hybrid sequencing approach, combining Oxford Nanopore and Illumina DNA sequence reads, was applied to produce a single contiguous genome sequence of 2,911,280 bp.Shell Research Ltd

Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule.

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling. Mitophagy was found to be mediated by PINK1/Parkin-dependent pathway involving p62 as a selective autophagy receptor (SAR). Importantly, this pathway was suppressed upon the induction of cellular senescence and in naturally aged cells, leading to a robust shutdown of mitophagy. Inhibition of mitophagy in proliferating cells was sufficient to trigger the senescence program, while reactivation of mitophagy was necessary for the anti-senescence effects of NAD precursors or rapamycin. Furthermore, reactivation of mitophagy by a p62-targeting small molecule rescued markers of cellular aging, which establishes mitochondrial quality control as a promising target for anti-aging interventions. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

A qualitative exploration of the health needs and goals of urban women to inform the tailoring and adaptation of Strong Hearts Healthy Communities: a community-based cardiovascular disease prevention intervention

Abstract Background In the United States, cardiovascular diseases (CVD) are the leading cause of death and disability in women. CVD-modifiable risk factors, including poor diet quality and inadequate physical activity, can be addressed through evidence-based interventions (EBIs). Strong Hearts Healthy Communities (SHHC) is an EBI that has demonstrated effectiveness in reducing CVD risk and improving health outcomes among rural white women. The aims of this study were to understand the general health, diet, and physical activity-related needs and goals of women living in an urban community, to inform the tailoring and adaptation of the SHHC EBI to an urban setting and more diverse population. Methods Focus groups (FGs) were conducted with African American/Black and Hispanic/Latinx women in the Dallas metropolitan area who had a BMI ≥ 25 kg/m2 and engaged in ≤ 150 min per week of moderate physical activity. The data were coded using a team-based, deductive, and thematic analysis approach, that included multiple coders and in-depth discussions. Results Four FGs with a total of 18 participants (79% Black and 21% Latinx) were conducted, and three themes were developed: (1) participants had adequate knowledge and positive attitudes towards healthy living but faced many barriers to practicing healthy behaviors; (2) culturally-based beliefs and community practices exerted a strong influence on behaviors related to food and stress, revealing barriers to healthy eating and generational differences in stress and stress management; (3) participants desired a more individualized approach to nutrition and physical activity interventions that included familiar and enjoyable activities and social support centered around shared health goals. Conclusions The SHHC intervention and similar health programs for Black/African American and Hispanic/Latinx women in urban settings should emphasize individualized nutrition and practical skills for healthy eating with accessible, familiar, and enjoyable exercises. Additionally, stress management strategies should be culturally and generationally sensitive and social support, whether through family, friends, or other program participants, should be based on shared health goals

Additional file 1 of A qualitative exploration of the health needs and goals of urban women to inform the tailoring and adaptation of Strong Hearts Healthy Communities: a community-based cardiovascular disease prevention intervention

Supplementary Material

Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC50 0.62 µM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons

Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling. Mitophagy was found to be mediated by PINK1/Parkin-dependent pathway involving p62 as a selective autophagy receptor (SAR). Importantly, this pathway was suppressed upon the induction of cellular senescence and in naturally aged cells, leading to a robust shutdown of mitophagy. Inhibition of mitophagy in proliferating cells was sufficient to trigger the senescence program, while reactivation of mitophagy was necessary for the anti-senescence effects of NAD precursors or rapamycin. Furthermore, reactivation of mitophagy by a p62-targeting small molecule rescued markers of cellular aging, which establishes mitochondrial quality control as a promising target for anti-aging interventions.</p