Tumor cells can spread to distant sites through their ability to switch between mesenchymal and amoeboid (bleb-based) migration. Because of this difference, inhibitors of metastasis must account for each migration mode. However, the role of vimentin in amoeboid migration has not been determined. Because amoeboid leader bleb–based migration (LBBM) occurs in confined spaces and vimentin is known to strongly influence cell-mechanical properties, we hypothesized that a flexible vimentin network is required for fast amoeboid migration. To this end, here we determined the precise role of the vimentin intermediate filament system in regulating the migration of amoeboid human cancer cells. Vimentin is a classic marker of epithelial-to-mesenchymal transition and is therefore an ideal target for a metastasis inhibitor. Using a previously developed polydimethylsiloxane slab–based approach to confine cells, RNAi-based vimentin silencing, vimentin overexpression, pharmacological treatments, and measurements of cell stiffness, we found that RNAi-mediated depletion of vimentin increases LBBM by ∼50% compared with control cells and that vimentin overexpression and simvastatin-induced vimentin bundling inhibit fast amoeboid migration and proliferation. Importantly, these effects were independent of changes in actomyosin contractility. Our results indicate that a flexible vimentin intermediate filament network promotes LBBM of amoeboid cancer cells in confined environments and that vimentin bundling perturbs cell-mechanical properties and inhibits the invasive properties of cancer cells.

Lena Eliasson
May 1, 2020; 69:804-812
Small Noncoding RNAs in Diabetes

Many chemicals and cellular processes cause oxidative stress that can damage lipids, proteins, or DNA (1). To quickly sense and respond to this ubiquitous threat, organisms have evolved enzymes that neutralize harmful oxidants such as reactive oxygen species and electrophilic compounds (including xenobiotics and their breakdown products) in cells.These antioxidant enzymes include GSH S-transferase (GST),2 NADPH:quinone oxidoreductase 1, thioredoxin, hemeoxygenase-1, and others (2, 3). Many of these proteins are commonly expressed in cells exposed to oxidative stress.The antioxidant response element (ARE) is a major regulatory component of this cellular stress response. The ARE is a conserved, 11-nucleotide-long DNA motif present in the 5'-flanking regions of many genes encoding antioxidant proteins. The laboratory of Cecil Pickett (Fig. 1) at the Merck Frosst Centre for Therapeutic Research in Quebec discovered ARE, a finding reported in the early 1990s in two JBC papers recognized as Classics here (4, 5).jbc;295/12/3929/F1F1F1Figure 1.Cecil Pickett (pictured) and colleagues first described the ARE motif, present in the 5' regions of many genes whose expression is up-regulated by oxidative stress and xenobiotics. Photo courtesy of Cecil Pickett.ARE's discovery was spurred in large part by Pickett's career choice. After completing a PhD in biology and a 2-year postdoc at UCLA in the mid-1970s, he began to work in the pharmaceutical industry.Recruited to Merck in 1978 by its then head of research and development (and later CEO), Roy Vagelos, “I became interested in how drug-metabolizing enzymes were induced by various xenobiotics,” Pickett says.According to Pickett, Vagelos encouraged researchers at the company...

2 May 2019 , Volume 95, Number 3

One of the two men killed in Swallowfield, along Old Hope Road in St Andrew, yesterday has now been identified.  The police say he is 40 year-old Clinton Jarrett, a welder of Cambridge district, St. Andrew. The other man is yet...

MANILA (AP): The Philippines’ largest TV and radio network, which was shutdown this week by a government regulator, asked the Supreme Court on Thursday to allow it to return to the air amid an uproar over its closure. ABS-CBN Corp said in its...

It’s been called “the universal panacea” - exercise has a positive effect on almost all health measures, and governments are actively campaigning for us to do more. But at the opposite end of the scale, the realisation that some people may be addicted to exercise is gaining traction. In this podcast we're joined by Heather Hausenblas - professor...

The NHS is about caring for people, free at the point of care, creating a safety net which catches the most vulnerable. Tech has been defined by the facebook maxim "move fast, break things" - looking to disrupt a sector, get investment and move on.  We want to be able to harness the potential utility of digital tech in the NHS - but how can those...

The sale of two Jewel properties will inject US$60 million into loss-making Playa Resorts while reducing the hotel rooms it operates in Jamaica by more 40 per cent. Playa announced the sale of Jewel Runaway Bay Beach Resort...

This report summarizes the economic and social development policy achievements of Central American countries over the past 20 years, as well as the notable obstacles to development that remain. The author identifies long-term challenges and outlines how they can be incorporated into a new development agenda.

Given diverging demographics, rising educational attainment and wide variation in economic opportunities, countries in the Association of Southeast Asian Nations are poised to see an expansion of both the demand for and supply of skilled migrants willing and able to move. The convergence of these megatrends represents unique opportunities for human-capital development and brain circulation, as this report explores.

A Florida sheriff's office said a driver reversing out of a bank parking lot accidentally ended up backing up onto two other cars.

Kalevi Pyörälä
Mar 1, 1979; 2:131-141
Proceedings of the Kroc Foundation International Conference on Epidemiology of Diabetes and its Macrovascular Complications

OBJECTIVE

Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone.

ADA Member Advantage announced Jan. 8 the end of its endorsement relationship with two companies.

The ADA is presenting two free webinars March 27, aiming to help dentists financially weather the economic downturn during the COVID-19 outbreak and illustrate how ADA advocacy has helped turn the tide.

The ADA Board of Trustees has authorized the searches for the next editor of The Journal of the American Dental Association and the founding editor of JADA Open, a new peer-reviewed, open-access journal spanning basic and clinical sciences to advance research in oral health.

In the face of economic challenges, the ADA has released two online guides relating to third-party payment programs available at ADA.org/virus that are intended to help smooth the path of reopening practices: Handling Contract Negotiations and Handling Eligibility Verification

U.S. retail fuel prices will drop this year and in 2020 from 2018, but in both cases higher than January levels due to mandated lower sulfur in marine fuel.

On this webinar, MPI researchers and Utah and Colorado refugee coordinators explore promising practices to better serve refugee families, including education services for refugee youth, innovative efforts to secure better jobs for adult refugees, and other services designed to aid integration over time. They also discuss the potential for implementing and supporting two-generation approaches to refugee integration at a time when the system’s funding and capacity are in peril.  

More than two months after Ahmaud Arbery was fatally shot while jogging near Brunswick, Georgia police arrested two men for the shooting, authorities said.

Hundreds attended a rally Friday in support of Ahmaud Arbery, and officials said they will investigate the man who recorded a video of his shooting.

He shouldn't have fought back when the guy pointed the shot gun at him

In the two years since President Trump entered office, U.S. immigration policy has changed in many ways. Some actions have received significant media attention and public scrutiny, and others have been implemented with little fanfare. This document chronicles these wide-reaching policy changes, covering immigration enforcement, the immigration courts, humanitarian admissions, visa processing, and more.

You could be forgiven for thinking the television images in the experiment were from 2006. They were really from 1982: Israeli forces were clashing with Arab militants in Lebanon. The world was watching, charges were flying, and the air was thick with grievance, hurt and outrage.

Marking the release of two research reports that highlight promising, effective approaches to teaching and learning for Dual Language Learners in multilingual, multicultural classrooms, report authors present their findings on this webinar and discuss key implications for policy and practice.

At a time when the U.S. refugee resettlement system is facing unprecedented challenges, innovative and cost-effective tools for supporting refugee integration are in demand. This report explores how a two-generation approach to service provision could help all members of refugee families—from young children to working-age adults and the elderly—find their footing.

Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis.

Teachers in North Carolina and Oregon plan to walk out of their classrooms in protest in May.

Students returning to schools in Virginia and New York this fall will be required to participate in mental-health education as part of their health and physical education courses.

All 46 schools in the Mesa County Valley School District closed last Thursday and Friday after students and staff at more than a dozen schools experienced norovirus-like symptoms.

Biden's campaign announced March 31 that the 2020 Democratic presidential candidate backs two local attempts to raise more tax revenue for schools.

Teachers in North Carolina and Oregon plan to walk out of their classrooms in protest in May.

Pentecostalism -- History -- 21st century.

Weinstein, Harvey, 1952-

[late 1930s]

As the state rolls out a new school accountability system and a separate federal accountability system, disputes have flared between the state department and school board over which underperforming schools should get extra federal money.

Leipzig : J. Naumann, 1862.

Berlin : C. Nohring, 1868.

Romae [Rome] (ad Pasquinum) : Venit ... apud Montagnani-Mirabili, [1805?]

London : Published by J.B. Virtue & Co. Ltd. : Jean Boussod Manzi Joyant & Co., [1897]