It’s not good for people to be alone. Quarantining has been difficult for many people who have gotten used to socializing daily, and because of that, some have found ways to follow the rules but feel a little less isolated. Some neighborhoods have decided to be social while maintaining the suggested distance apart, whether that’s…

The post ‘The Voice’ Contestant Alexa Cappelli Treats Neighbors to Weekly Performance in Her Cul-de-Sac appeared first on The Western Journal.

The genial young administrator with a burgeoning reputation chuckles when it's pointed out to him that he can't seem to shake off 'working' for some of South Africa's biggest businessmen.

The following article, BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO], was first published on 100PercentFedUp.com.

The Georgia Bureau of Investigations has arrested a father and son duo, 64-year-old ex-cop, Gregory McMichael, and his son, 34-year-old Travis McMichael for the February murder of  24-year-old Ahmaud Arbery, a black man who was jogging through their neighborhood when they jumped in their truck and pursued him. Yashar Ali shared the news of the […]

Continue reading: BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO] ...

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

Expert

The AMS is pleased to announce that Scott Hershberger has been chosen as the 2020 AMS Mass Media Fellow. Scott studied mathematics and physics at Washington University in St. Louis and will graduate in May 2020. He will be working at Scientific American this summer.

The Mass Media Science and Engineering Fellows program is organized by the American Association for the Advancement of Science (AAAS). This program is designed to improve public understanding of science and technology by placing advanced undergraduate, graduate and postgraduate science, mathematics and engineering students in media outlets nationwide. The fellows work for ten weeks over the summer as reporters, researchers, and production assistants alongside media professionals to sharpen their communication skills and increase their understanding of the editorial process by which events and ideas become news.

Now in its 45th year, this fellowship program has placed more than 700 fellows in media organizations nationwide as they research, write, and report today’s headlines. The program is designed to report science-related issues in the media in easy-to-understand ways so as to improve public understanding and appreciation for science and technology.

For more information on the AMS Mass Media Fellowship, visit the website.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

The PET radiotracer ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA-11) shows potential as an imaging biomarker for recurrent and metastatic prostate cancer. The purpose of this study was to determine repeatability of ⁶⁸Ga-PSMA-HBED-CC in a test-retest trial in subjects with metastatic prostate adenocarcinoma. Methods: Subjects with metastatic prostate cancer underwent two PET/CT scans with ⁶⁸Ga-PSMA-HBED-CC within 14 days (mean 6 ± 4 d). Lesions in bone, nodes, prostate/bed, and visceral organs as well as representative normal tissues (salivary glands and spleen) were segmented separately by two readers. Absolute and percent differences in SUV_max and SUVmean were calculated for all test-retest regions. Repeatability was assessed using percentage difference, within-subject coefficient of variation (wCV), repeatability coefficient (RC), and Bland-Altman analysis. Results: 18 subjects were evaluated, 16 of which demonstrated local or metastatic disease on ⁶⁸Ga-PSMA-HBED-CC PET/CT. A total of 136 lesions were segmented in bone (n = 99), nodes (n = 27), prostate/bed (n = 7), and viscera (n = 3). The wCV for SUV_max was 11.7% for bone lesions and 13.7% for nodes. The RC was ±32.5% SUV_max for bone lesions and ±37.9% SUV_max for nodal lesions, meaning 95% of the normal variability between two measurements will be within these numbers, so larger differences are likely attributable to true biological changes in tumor rather than normal physiologic or measurement variability. wCV in the salivary glands and spleen was 8.9% and 10.7% SUVmean, respectively. Conclusion: Repeatability measurements for PET/CT test-retest with ⁶⁸Ga-PSMA-HBED-CC show a wCV 12-14% SUV_max and RC ±33-38% SUV_max in bone and nodal lesions. These estimates are an important aspect of ⁶⁸Ga-PSMA-HBED-CC as a quantitative imaging biomarker. These estimates are similar to those reported for ¹⁸F-FDG, suggesting that ⁶⁸Ga-PSMA-HBED-CC PET/CT may be useful in monitoring response to therapy.

Shwetha K. Shetty
Apr 1, 2020; 61:546-559
Methods

Xia Meng
May 1, 2020; 61:591-591
Images in Lipid Research

Matt Egan is back in the hosting chair to chat with producer Chris about the Samsung Galaxy Note 7 and how we feel about phablets. Techworld.com editor Charlotte Jee comes in to explain what is going on at the GDS (government digital service) and why we should care (13:00). Then online editor at Techworld.com Scott Carey chats Instagram stories, why it is a blatant rip off of Snapchat stories and how the social media giant can get away with being so brazen (22:00).  

See acast.com/privacy for privacy and opt-out information.

4 December 2019

The hydrolysis of triglycerides in triglyceride-rich lipoproteins by LPL is critical for the delivery of triglyceride-derived fatty acids to tissues, including heart, skeletal muscle, and adipose tissues. Physiologically active LPL is normally bound to the endothelial cell protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), which transports LPL across endothelial cells, anchors LPL to the vascular wall, and stabilizes LPL activity. Disruption of LPL-GPIHBP1 binding significantly alters triglyceride metabolism and lipid partitioning. In this study, we modified the NanoLuc® Binary Technology split-luciferase system to develop a novel assay that monitors the binding of LPL to GPIHBP1 on endothelial cells in real time. We validated the specificity and sensitivity of the assay using endothelial lipase and a mutant version of LPL and found that this assay reliably and specifically detected the interaction between LPL and GPIHBP1. We then interrogated various endogenous and exogenous inhibitors of LPL-mediated lipolysis for their ability to disrupt the binding of LPL to GPIHBP1. We found that angiopoietin-like (ANGPTL)4 and ANGPTL3-ANGPTL8 complexes disrupted the interactions of LPL and GPIHBP1, whereas the exogenous LPL blockers we tested (tyloxapol, poloxamer-407, and tetrahydrolipstatin) did not. We also found that chylomicrons could dissociate LPL from GPIHBP1 and found evidence that this dissociation was mediated in part by the fatty acids produced by lipolysis. These results demonstrate the ability of this assay to monitor LPL-GPIHBP1 binding and to probe how various agents influence this important complex.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

4 December 2019

The molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on epidermal growth factor receptor (EGFR) signaling. The aim of this study was to determine the role of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) in the β-cell proliferative response to glucose, a β-cell mitogen and key regulator of β-cell mass in response to increased insulin demand. We show that exposure of isolated rat and human islets to HB-EGF stimulates β-cell proliferation. In rat islets, inhibition of EGFR or HB-EGF blocks the proliferative response not only to HB-EGF but also to glucose. Furthermore, knockdown of HB-EGF in rat islets blocks β-cell proliferation in response to glucose ex vivo and in vivo in transplanted glucose-infused rats. Mechanistically, we demonstrate that HB-EGF mRNA levels are increased in β-cells in response to glucose in a carbohydrate-response element–binding protein (ChREBP)–dependent manner. In addition, chromatin immunoprecipitation studies identified ChREBP binding sites in proximity to the HB-EGF gene. Finally, inhibition of Src family kinases, known to be involved in HB-EGF processing, abrogated glucose-induced β-cell proliferation. Our findings identify a novel glucose/HB-EGF/EGFR axis implicated in β-cell compensation to increased metabolic demand.

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article

The Trump administration has significantly cranked up the immigration enforcement machinery in the U.S. interior. Yet even as arrests and deportations are up in the early Trump months, they remain less than half their peaks. This report demonstrates how pushback from California and other "sanctuary" locations makes it quite unlikely that ICE will be able to match record enforcement levels.

OBJECTIVE

To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes.

OBJECTIVE

To improve outcomes of patients with adult type 2 diabetes by decreasing HbA_1c undertesting, reducing the proportion of patients with poor glycemic control, and lowering mean HbA_1c levels using a quality improvement (QI) program.

Roy W. Beck
Aug 1, 2017; 40:994-999
Perspectives in Care

Gina Agiostratidou
Dec 1, 2017; 40:1622-1630
Continuous Glucose Monitoring and Risk of Hypoglycemia

Lene R. Nielsen
May 1, 2004; 27:1200-1201
Brief Reports

Lene R. Nielsen
May 1, 2004; 27:1200-1201
Brief Reports

OBJECTIVE

To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA_1c, endogenous glucose production (EGP), and body weight versus each therapy alone.

OBJECTIVE

The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA_1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population.

"I May Destroy You," a new series from "Chewing Gum" creator Michaela Coel, will premiere on HBO in June.

HBO Max announced Friday that it has ordered "Santa Inc.," an adult-oriented animated series featuring the voices of Sarah Silverman and Seth Rogen.

After nearly two years of political jockeying for the presidency, hundreds of millions of dollars of advertising and wall-to-wall campaign coverage in the media, nearly half of all Americans eligible to cast ballots in the presidential election may not bother to vote. Turnout for primaries, as well...

Migration between Mexico and the United States has changed dramatically in recent years, but policies and political rhetoric in both countries have not always kept up. This report, which draws from discussions of a high-level Mexico-U.S. study group convened by MPI and El Colegio de México, explores this new migration reality and how the two governments could work more closely together to address shared policy challenges.

Monique Bowley, shared this recipe on Foodie Tuesday, a weekly segment on ABC Radio Melbourne's Drive program at 3.30pm.

OBJECTIVE

To investigate the association between visit-to-visit HbA_1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes.

The Spring 2020 issue of the Journal of the History of the Behavioral Sciences is now online. Full details about contributions to this issue follow below. “Practicing mind-body medicine before Freud: John G. Gehring, the “Wizard of the Androscoggin”” by. Ben Harris and Courtney J. Stevens. Abstract: This article describes the psychotherapy practice of physician … Continue reading New JHBS: Mind-Body Medicine Before Freud, Psychology and Biography, Jung and Einstein →

A number of articles now in press at the Journal of the History of the Behavioral Sciences will be of interest to AHP readers. Full details below. “Uncovering the metaphysics of psychological warfare: The social science behind the Psychological Strategy Board’s operations planning, 1951–1953,” Gabrielle Kemmis. Abstract: In April 1951 president Harry S. Truman established … Continue reading Forthcoming in JHBS: Quêtelet on Deviance, McClelland on Leadership, Psychological Warfare, and More →

New take on the traditional story of Hansel and Gretel, with the two children becoming world-famous food critics.

Berlin : Heuser, 1889.

London : Longmans, Green, 1889.

When Idaho education leaders pitched social-emotional learning training for teachers, some state lawmakers compared the plan to dystopian behavior control. Some walked out of the meeting.

When Idaho education leaders pitched social-emotional learning training for teachers, some state lawmakers compared the plan to dystopian behavior control. Some walked out of the meeting.

[Manchester] : [James Mudd], [between 1800 and 1899]

Nina Gantert, Markus Heydenreich, Timo Hirscher.

Source: Bernoulli, Volume 26, Number 2, 1269--1293.

Abstract:
We investigate a model for opinion dynamics, where individuals (modeled by vertices of a graph) hold certain abstract opinions. As time progresses, neighboring individuals interact with each other, and this interaction results in a realignment of opinions closer towards each other. This mechanism triggers formation of consensus among the individuals. Our main focus is on strong consensus (i.e., global agreement of all individuals) versus weak consensus (i.e., local agreement among neighbors). By extending a known model to a more general opinion space, which lacks a “central” opinion acting as a contraction point, we provide an example of an opinion formation process on the one-dimensional lattice $mathbb{Z}$ with weak consensus but no strong consensus.

The ongoing investigation of the fatal shooting in Brunswick, Georgia, will also look at a neighbor of suspects Gregory and Travis McMichael who recorded video of the incident, authorities said.

Benjamin E. Reese
Mar 2, 2005; 25:2167-2175
BehavioralSystemsCognitive