Carla Mooney lands role in spy thriller ‘Kickback’ opposite John Cusack, Stuart Townsend nabs multi-episode part in US TV show ‘Elementary’ and Jason Barry and Brian Robinson both to star in new feature ‘Murphy’ from Caspian Pictures.

(University of Massachusetts Lowell) UMass Medical School and UMass Lowell will perform a key role in a new National Institutes of Health initiative aimed at speeding innovation, development and commercialization of COVID-19 testing technologies via their Center for Advancing Point of Care Technologies collaboration.

(New Jersey Institute of Technology) A team of NJIT physicists has developed a novel test swab that can be 3D printed using inexpensive, widely available materials and speedily assembled in a range of fabrication settings. To augment the nation's testing capabilities, the inventors are making the swab's design publicly available, free of licensing fees, during the COVID-19 emergency.

(DOE/Lawrence Berkeley National Laboratory) A new study, led by researchers at Berkeley Lab and UC Berkeley, suggests new paths for catching the signals of dark matter particles that have their energy absorbed by atomic nuclei.

Chia-Feng Tsai
May 1, 2020; 19:828-838
Research

Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells.

David Price is in the host's chair this week, as the team talk about the latest hot tech topics. Tamlin Magee has got the drinks in - futuristic meal-replacement drinks called Soylent, which he forces everyone to try and which are apparently not people.

Then Dominic Preston talks us through the positive and extremely negative sides of Amazon's Black Friday activities, before Sean Bradley attempts to explain why Bitcoin is tanking and what the future holds for crypto currencies. Cheers!

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In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.

Lipid droplets (LDs) are energy-storage organelles that are coated with hundreds of proteins, including members of the perilipin (PLIN) family. PLIN5 is highly expressed in oxidative tissues, including the liver, and is thought to play a key role in uncoupling LD accumulation from lipotoxicity; however, the mechanisms behind this action are incompletely defined. We investigated the role of hepatic PLIN5 in inflammation and lipotoxicity in a murine model under both fasting and refeeding conditions and in hepatocyte cultures. PLIN5 ablation with antisense oligonucleotides triggered a pro-inflammatory response in livers from mice only under fasting conditions. Similarly, PLIN5 mitigated lipopolysaccharide- or palmitic acid-induced inflammatory responses in hepatocytes. During fasting, PLIN5 was also required for the induction of autophagy, which contributed to its anti-inflammatory effects. The ability of PLIN5 to promote autophagy and prevent inflammation were dependent upon signaling through sirtuin 1 (SIRT1), which is known to be activated in response to nuclear PLIN5 under fasting conditions. Taken together, these data show that PLIN5 signals via SIRT1 to promote autophagy and prevent FA-induced inflammation as a means to maintain hepatocyte homeostasis during periods of fasting and FA mobilization.

A greater decrease in 24-h energy expenditure (24EE) during 24h fasting defines a thriftier metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male, age: 36.6±11.4y, percentage body fat: 34.8±10.5%). Greater decrease in 24EE during fasting (thriftier phenotype) was associated with less increase in 24EE during COLD, i.e. less cold-induced thermogenesis. Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated and mediated by the liver-derived hormone FGF21. Thus, the 24EE response to COLD further identifies the thrifty versus spendthrift phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change.

Juli Bai
Jun 1, 2019; 68:1099-1108
Perspectives in Diabetes

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The BMJ publishes a lot of educational articles, and in an attempt to help you with your CPD, we have put together this round-up. Our authors and editors will reflect on the key learning points in the articles we discuss, and explain how they may change their practice in light of that new understanding. In this week's round up we're...

Helen talks about new research on prevention of recurrent VTE - and Carl things the evidence goes further, and we can extend prophylaxis for a year. 13.00 - CRP testing for antibiotic prescription in COPD exacerbations, should we start doing it in primary care settings - and what will that mean. We also hear from Chris Butler, one of the...

A TB infection can take two forms, active and latent. Active disease is transmissible, and causes the damage to the lungs which makes TB one of the biggest killers in the world. In the latent form, the bacteria Mycobacterium tuberculosis is quiescent and can stay that way for years until it becomes active and causes those clinical signs. Testing...

This edition of talk evidence was recorded before the big increase in covid-19 infections in the UK, and then delayed by some self isolation. We'll be back with more evidence on the pandemic very soon. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you...

Director of the Pan American Health Organization (PAHO), Dr Carissa F. Etienne, today called for accelerated and expanded testing for COVID-19 in countries of the Americas. “We need a clearer view of where the virus is circulating and how...

Invitation Only Research Event

OP-ED CONTRIBUTION: COVID-19 AND THE ECONOMY FOR MOST countries in the Caribbean, the current testing for COVID-19 has not reached levels suitable for ascertaining an accurate picture of the state of outbreak and spread of the infection. This...

Invitation Only Research Event

Event participants

Professor Tim Benton, Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme, Chatham House
Professor Paul Stevens, Distinguished Fellow, Energy, Environment and Resources Programme, Chatham House
Antony Froggatt, Senior Research Fellow, Energy, Environment and Resources Programme, Chatham House
Chair: Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Programme

President Trump has made reshaping the U.S. immigration system a top priority. Yet the fragmented nature of policy-making in the United States—with power split between branches and levels of government—has made it difficult to pursue some of his most ambitious proposals. This report explores the evolution of migration policy under Trump, and what these changes may mean in the long run.

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.

John J O'Sullivan
Aug 1, 1991; 14:758-760
Short Report

Robert A. Ritzel
Mar 1, 2006; 29:717-718
BR Pathophysiology/Complications

Rob M. van Dam
Dec 1, 2004; 27:2990-2992
Brief Reports

The American Dental Association is asking Congress to pass the Ensuring Lasting Smiles Act — legislation that would require all private group and individual health plans to cover medically necessary services that repair or restore congenital anomalies.

The American Dental Association is asking Congress to pass the Ensuring Lasting Smiles Act — legislation that would require all private group and individual health plans to cover medically necessary services that repair or restore congenital anomalies.

The ADA is urging dentists to be cautious about using novel coronavirus diagnostic tests before they have been properly evaluated and made available for dentists.

OBJECTIVE

Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.

Whenever the United States goes to war, pro-war and antiwar advocates immediately reach for different history books. Hawks always equate the situation to a Hitler-Chamberlain standoff to show why hesitation can be fatal. Doves invariably pull the Vietnam War off the shelf to argue that plunging...

Since the 2015–16 refugee crisis, European policymakers have eagerly sought cooperation with origin and transit countries in the hopes of stemming unauthorized migration to Europe. This approach is neither new, nor without its limitations. By examining the evolution of two longstanding Mediterranean partnerships—between Spain and Morocco, and Italy and Tunisia—this report offers insights on what has and has not worked.

Fostering the social and economic inclusion of refugees has long been the domain of governments and NGOs. In the wake of the 2015–16 European migration and refugee crisis, however, new actors have emerged and taken on important roles in integrating newcomers. This report describes key discussions and takeaways from an MPI Europe conference on these developments.

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.

First report examines Canadian challenges & solutions in housing Syrian refugees

WASHINGTON — Four years after the peak of the 2015–16 migration and refugee crisis in Europe and amid swelling arrivals at the U.S.-Mexico border and elsewhere, new evidence sheds light on how well countries have responded to an unprecedented surge in mixed flows of humanitarian, economic and family migrants.

OBJECTIVE

To determine the effect of fitness on the association between BMI and mortality among patients with diabetes.

OBJECTIVE

Previous studies suggested that childhood prediabetes may develop prior to obesity and be associated with relative insulin deficiency. We proposed that the insulin-deficient phenotype is genetically determined and tested this hypothesis by longitudinal modeling of insulin and glucose traits with diabetes risk genotypes in the EarlyBird cohort.

As millions of U.S. workers lose jobs and the health insurance associated with them, Medicaid and similar programs are increasingly important for people seeking COVID-19 testing and treatment. Yet many low-income uninsured noncitizens, including green-card holders, are excluded from such programs because of their immigration status, as this fact sheet explores.