Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid

The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA

Chronic irradiation of human cells reduces histone levels and deregulates gene expression

Abstract: Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6–20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology

Chronic irradiation of human cells reduces histone levels and deregulates gene expression

Abstract: Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6–20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology

Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer

Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a subset of regulatory transposable elements shared with pluripotent/stem cells, including Tigger3a. Using chromatin editing technology, we show how such elements promote prostate cancer growth by regulating AR transcriptional activity. Collectively, our results suggest that oncogenesis arises from lineage-specific transcription factors hijacking pluripotent/stem cell regulatory transposable elements.</p

Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer

Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a subset of regulatory transposable elements shared with pluripotent/stem cells, including Tigger3a. Using chromatin editing technology, we show how such elements promote prostate cancer growth by regulating AR transcriptional activity. Collectively, our results suggest that oncogenesis arises from lineage-specific transcription factors hijacking pluripotent/stem cell regulatory transposable elements.</p

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Reversing age: Dual species measurement of epigenetic age with a single clock

Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.Fil: Horvath, Steve. University of California at Los Angeles; Estados UnidosFil: Singh, Kavita. NMIMS University; IndiaFil: Raj, Ken. Public Health England; Reino UnidoFil: Khairnar, Shraddha. NMIMS University; IndiaFil: Sanghav, Akshay. Nugenics Research Pvt Ltd; IndiaFil: Shrivastava, Agnivesh. Nugenics Research Pvt Ltd; IndiaFil: Zoller, Joseph A.. University of California at Los Angeles; Estados UnidosFil: Li, Caesar Z.. University of California at Los Angeles; Estados UnidosFil: Hereñú, Claudia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Canatelli Mallat, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Lehmann, Marianne. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Solberg Woods, Leah C.. Wake Forest University School of Medicine; Estados UnidosFil: Garcia Martinez, Angel. University of Tennessee; Estados UnidosFil: Wang, Tengfei. University of Tennessee; Estados UnidosFil: Chiavellini, Priscila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Levine, Andrew J.. University of California at Los Angeles; Estados UnidosFil: Chen, Hao. University of Tennessee; Estados UnidosFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Katcher, Harold L.. Nugenics Research Pvt Ltd; Indi

Crop Updates 2011 - Farming Systems

This session covers twelve papers from different authors: 1. Fallowing 50% of the farm each year – does it pay? Janette Drew and Rob Grima Department of Agriculture and Food 2. How crop sequences affect the productivity and resilience of cropping systems in two Western Australian environments, Bob French, Raj Malik, Mark Seymour, Department of Agriculture and Food 3. When is continuous wheat or barley sustainable? Christine Zaicou-Kunesch and Rob Grima Department of Agriculture and Food 4. Identifying constraints to bridging the yield gap, Glenn McDonald, Department of Agriculture and Food 5. Land constraints limiting wheat yields in the Bridging the Yield Gap project area, Brendan Nicholas and Dennis van Gool, Department of Agriculture and Food 6. Can livestock have a long-term role in no-till cropping systems? James Fisher1, Peter Tozer2, and Doug Abrecht3, 1Désirée Futures, York, WA, 2PRT Consulting, West Wyalong, NSW and 3Department of Agriculture and Food 7. Pros and cons of dry seeding to counter variable seasonal breaks, Michael Robertson1, Cameron Weeks2, Michael O’Connor1, Doug Abrecht3, Rob Grima3, Peter Newman3, 1CSIRO, 2PlanFarm, 3Department of Agriculture and Food 8. Defining economic optimum plant densities of open pollinated and hybrid canola in WA, Mark Seymour, Department of Agriculture and Food 9. Alternative uses for unproductive soils examined in the North Eastern Agricultural Region (NEAR), Mike Clarke and Andrew Blake, Department of Agriculture and Food MARKETS 10. What the world wants from Australian wheat, Gordon MacAulay, Principal Economist, BRI Australia, Emeritus Professor of Agricultural Economics, University of Sydney 11. Effect of lupin flour incorporation on the physical and sensory quality of pasta, Vijay Jayasena1,2 and Syed M. Nasar-Abbas1,2, 1Food Science and Technology, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, 2Centre for Food and Genomic Medicine 12. Wheat quality requirements for Saudi Arabia: baking quality and blending potential of some Australian exporting grades, Larisa Cato1, Robert Loughman1 and Ken Quail2, 1Department of Agriculture and Food, 2BRI Australi

Positive Psychology in Sales: Integrating Psychological Capital

As positive psychology moves into the workplace, researchers have been able to demonstrate the desirable impact of positive organizational behavior. Specifically, psychological capital (PsyCap) improves employee attitudes, behaviors, and performance. Advancing PsyCap in sales research is important given the need for a comprehensive positive approach to drive sales performance, offset the high cost of salesperson turnover, improve cross-functional sales interfaces, and enrich customer relationships. The authors provide an integrative review of PsyCap, discuss its application in sales, and advance an agenda for future research. Research prescriptions are organized according to individual-level, intra-organizational, and extra-organizational outcomes pertinent to the sales field