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Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

Introduction The National Institute on Aging (NIA) provides funding to academic researchers and small businesses working in the Alzheimer's Disease (AD) and AD-related dementia (ADRD) fields to help commercialize their products. The NIA uses Small Business Innovation Research (SBIR) awards to bridge the funding gap in the diagnostic, therapeutic, and care interventions areas, enabling startups to reach key value inflection points to achieve scientific milestones. Methods Only publicly available information is reported. The National Institutes of Health Report Portfolio Online Reporting Tool database and the commercial database Global Data, were used to track the progress of companies that received SBIR or Small Business Technology Transfer (STTR) funding from the NIA. Results Since 2008, the NIA has awarded $280 million-including $207 million from fiscal year (FY) 2015 to FY 2019-in new small business program awards for AD/ADRD research. Discussion NIA seed capital and mentoring programs are critical resources to help small businesses reach key value inflection points and advance their research from concept to commercialization.

Since 2015, the National Institute on Aging (NIA), National Institutes of Health (NIH), has experienced significant increases in funding for Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). This analysis assesses the impact of these funds on expanding the AD/ADRD workforce. NIA administered 860 awards to 695 AD/ADRD R01 awardees during fiscal year 2015–2018. Twenty-nine percent of awardees were new or early-stage investigators, while 38% were new to the AD/ADRD research field (NTF). Among these NTFs, 59% were established investigators, that is, experts with NIH funding in another discipline but new to AD/ADRD research. Awards were further analyzed to determine the focus of their research based on International Alzheimer’s Disease Research Portfolio (IADRP) categories. Forty-six percent were focused on Molecular Pathogenesis and Physiology. Other IADRP categories, including Diagnosis, Assessment, and Disease Monitoring and Translational Research and Clinical Interventions, represented 5%–15% of awards. Significantly, NTF investigators received 50%, 42%, and 70% of the total grants awarded in Population Studies, Dementia Care, and Brain Aging, respectively, suggesting that NTF investigators are filling research gaps. While these results suggest that enhanced funding is associated with recruitment of new talent, opportunities for further growth remain, particularly related to care, caregiving, and health disparities.

A Psychrotrophic bacterium producing cold active lipase enzyme at low temperature was isolated from soil sample of Satopanth glacier. It was identified as Pseudomonas fluorescens based on colony morphology, biochemical characteristics. Out of the seven selected lipase producing isolates the best one SGPR-4 was showing activity maximum at 20oC temperature. The cold active lipase was purified to 6.44 fold by DEAE cellulose column chromatography. The bacterial strain SGPR-4 showed maximum activity at pH 8.0 and temperature 20°C and it showed thermostability up to 30oC. Therefore these properties of enzyme could be explored for industrial application and commercialization

Heavy metals are responsible to create toxicity in environment and these causes serious challenge worldwide. Arsenic is a heavy metal that is non-essential but toxic to all living beings. Arsenic has always been under emerging issue due to its toxicity in living beings including human and animals. Arsenic (As) is a toxic pollutant released into the environment either by natural phenomena or anthropogenic activities. Arsenic is known as carcinogenic element that can harm not only human health but, plant and bacteria as well. Pesticides are the major source for accumulation of As in the agricultural soils. Currently available bioremediation techniques have major disadvantages such as secondary environmental pollution and are less cost effective. Therefore, the present study was aimed to isolate arsenic resistant bacteria from terrestrial environment Bahraich, Uttar Pradesh, India for their potential applications in bioremediation strategies. Total thirty eight isolated arsenic-resistant bacteria were isolated, in which three bacterial isolates BBAU/LP3, BBAU/MMM1, and BBAU/MMM5 were taken for further studies due to their higher resistance ability to As and two isolates BBAU/LP3 and BBAU/MMM1 taken for molecular identification. The 16S rRNA gene sequence of the isolate BBAU/LP3 belongs to the genera Bacillus infantis and BBAU/MMM1 belongs to the genera Bacillus litoralis. The results revealed that our isolates BBAU/LP3 and BBAU/MMM1 encoded arsenite oxidizing gene and arsenate reducing gene respectively that will be useful for the development of efficient bioremediation strategies in the detoxification of arsenic from polluted environments., {"references":["1.\tAbernathy C O, Lui YP, Longfellow D, Aposhian HV, Beck B, Fowler B, Goyer R, Menzer R, Rossman T, Thompson C, Waalkes M (1999). Environ. Health Perspect. (107)593. 2.\tAronson J (1992). 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The progesterone receptor (PR) plays roles in normal mammary development and breast cancer formation, where it may exert both stimulatory and inhibitory actions. Previously, the breast cancer susceptibility gene product BRCA1 was found to interact with and inhibit the transcriptional activity of estrogen receptor-α. In this study, we found that exogenous wild-type BRCA1 inhibited the activity of the PR in transient transfection assays utilizing a mouse mammary tumor virus-Luc reporter. Wild-type BRCA1 inhibited the activity of endogenous PR in human breast cancer cells (T47D and MCF-7) and inhibited the activity of exogenous PR-A, PR-B, and [PR-A plus PR-B] isoforms. On the other hand, knockdown of endogenous BRCA1 using small interfering RNA enhanced the progesterone-stimulated activity of the PR by about 4-fold. We documented an in vivo association of the endogenous BRCA1 with PR isoforms A and B and a direct in vitro interaction between BRCA1 and PR, which was partially mapped. Whereas down-regulation of the coactivator p300 contributes to the BRCA1-mediated repression of estrogen receptor-α, this mechanism does not contribute to inhibition of PR activity, because exogenous p300 did not rescue the BRCA1 repression of PR activity. The BRCA1-PR interaction has functional consequences. Thus, we showed that BRCA1 inhibits the expression of various endogenous progesterone-responsive genes and inhibits progesterone-stimulated proliferation of T47D cells. Finally, exogenous progesterone caused an exaggerated proliferative response in the mammary glands of mice harboring a mammary-targeted conditional deletion of the full-length isoform of Brca1. These findings suggest that BRCA1 regulates the activity of progesterone, a major hormone of pregnancy that may also participate in mammary carcinogenesis.

Previously, we reported that BRCA1 inhibits progesterone receptor (PR) activity and blocks progesterone-stimulated gene expression and cell proliferation. In the present manuscript, we studied the mechanism of BRCA1 inhibition of PR activity, using c-Myc as a model progesterone-regulated promoter. Here, we found that BRCA1 has little or no effect on PR ligand-binding affinity. However, BRCA1 overexpression inhibited the R5020-induced recruitment of PR to the c-Myc and mouse mammary tumor virus progesterone response elements (PREs) and blocked R5020-stimulated c-Myc expression, whereas BRCA1 underexpression did the opposite. In EMSAs, BRCA1 overexpression blocked the R5020-induced complex formation between PR and several radiolabeled PRE-containing oligonucleotides, and in vitro-translated BRCA1 blocked the interaction of full-length PR-A or a fragment containing the DNA-binding domain of PR with a radiolabeled PRE oligonucleotide. In further studies, BRCA1 overexpression inhibited the recruitment of coactivators (steroid receptor coactivator 1 and amplified in breast cancer 1) and enhanced the recruitment of a corepressor (histone deacetylase 1) to the c-Myc PRE, whereas BRCA1 knockdown increased the abundance of AIB1 and decreased the abundance of HDAC1 at the c-Myc PRE. These findings suggest that BRCA1 inhibits progestin-stimulated PR activity, in part, by preventing PR from binding to the PRE and by promoting the formation of a corepressor complex rather than a coactivator complex.

Previously, we reported that BRCA1 strongly represses the transcriptional activity of estrogen receptor-alpha (ER-alpha) in human breast and prostate cancer cells but only weakly inhibits ER-alpha in cervical cancer cells. We now report that introduction of the human papillomavirus E7 or E6 oncogenes into human papillomavirus-negative cells rescues the BRCA1 repression of ER-alpha activity and that the E7 and E6 oncoproteins interact directly with BRCA1 in vitro and associate with BRCA1 in vivo in cultured cells. This interaction involves at least two contact points on BRCA1, one within an N-terminal site shown previously to interact with ER-alpha and the other in a C-terminal region of BRCA1 containing the first BRCA1 C-terminal domain. Point mutations within the zinc finger domains of E7 and E6 inactivated the binding to the N terminus of BRCA1 and reduced their ability to rescue BRCA1 inhibition of ER-alpha. E6 and E7 also antagonized the ability of BRCA1 to inhibit c-Myc E-box-mediated transactivation and human telomerase reverse transcriptase promoter activity, in a manner dependent upon the zinc finger domains. Finally, the ability of E6 and E7 to antagonize BRCA1 did not involve proteolytic degradation of BRCA1. These findings suggest functional interactions of BRCA1 with E7 and E6. The potential significance of these findings is discussed.