The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.

Monthly apprehension statistics at the Southwest border have become a preoccupation for the Trump administration, which compares the 2018 numbers to 2017 and declares a crisis. Yet it was 2017, when the "Trump effect" temporarily paused illegal crossings, that was the outlier. Recent trends have reverted to the pattern seen in 2016, a result notable at a time of very low U.S. unemployment, as this commentary explores.

During his first 100 days in office, President Trump has taken a sweeping set of actions on immigration, ranging from imposing a travel ban to cutting refugee admissions, "extreme" vetting, and fortifying immigration enforcement at the border and in the U.S. interior. This fact sheet examines the major immigration actions taken to date, legal challenges, and related policy and personnel developments.

One of the least developed countries in sub-Saharan Africa, the Democratic Republic of the Congo has experienced significant migration outflows and inflows tied to political and economic crises in recent decades. While most Congolese migrants head to neighboring countries, destinations have diversified, with an uptick in those leaving for opportunities in Europe and beyond. This country profile explores historical and contemporary patterns of migration to and from DR Congo.

Climate-related displacement is not hypothetical: An average of 21.5 million people per year have been displaced since 2008 by natural disasters, and thousands more have fled slow-onset environmental hazards. While migration can serve as a safety valve to adapt to changing conditions, few orderly, legal channels exist for climate migrants (also known as environmental migrants), as this article explores.

An Australian man who scored a lottery jackpot of nearly $800,000 said he bought his ticket by mistake while attempting to play a different drawing.

Police in Britain said a surprised jogger tipped officers off to the location of a wallaby that escaped from a zoo and went hopping through the countryside.

Police and firefighters in Michigan came to the rescue of a family of baby geese that wandered out onto a busy highway and fell into a storm sewer.

Pratik Choudhary
Jun 1, 2015; 38:1016-1029
Type 1 Diabetes at a Crossroads

Bernhard J. Hering
Jul 1, 2016; 39:1230-1240
Emerging Technologies and Therapeutics

Ricardo V. Cohen
Jul 1, 2012; 35:1420-1428
Diabetes Care Symposium

Saila B. Koivusalo
Jan 1, 2016; 39:24-30
Considerations in the Management of Gestational Diabetes Mellitus

Francesco Rubino
Jun 1, 2016; 39:861-877
Metabolic Surgery and the Changing Landscape for Diabetes Care

U.S. Navy ships on Monday entered the Barents Sea between Norway and Russia, for the first time since the 1980s, "to assert freedom of navigation and demonstrate seamless integration among allies," the U.S. Navy said.

Francesco Rubino
Jun 1, 2016; 39:861-877
Metabolic Surgery and the Changing Landscape for Diabetes Care

John B. Buse
Feb 1, 2020; 43:487-493
Consensus Report Update

OBJECTIVE

To determine if the International Hypoglycaemia Study Group (IHSG) level 2 low glucose definition can identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials.

The American Dental Association Standards Committee on Dental Informatics has approved two documents for circulation and comment.

The ADA Standards Committee on Dental Informatics has approved the technical report for circulation and comment.

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.

Dentists can find regulations, recommendations and mandates regarding the practice of dentistry in their state during the COVID-19 pandemic on the ADA Center for Professional Success.

Oil prices fell early Thursday despite an OPEC report confirming a sizable cut due to bearishness related to rising United States production and inventories.

A face-aging app could encourage young people to protect their skin from harmful UV rays and lessen their risk for skin cancer, a study published Wednesday by JAMA Dermatology has found.

Communities across the U.S. still need to expand hospital capacity to manage new COVID-19 cases, even as some states loosen social distancing restrictions, a study published Wednesday by JAMA Network Open says.

Anakinra, a drug developed to treat rheumatoid arthritis might help patients who have developed acute respiratory distress syndrome caused by COVID-19, a small study published by The Lancet Rheumatology has found.

OBJECTIVE

We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study.

OBJECTIVE

To examine differences in myocardial blood flow (MBF) at rest and during stress between patients with type 2 diabetes and controls, and to identify potential predictors of changes in MBF at rest and during stress.

An average of 915 DACA recipients every day will lose their work authorization and protection from deportation once the phaseout of the program moves into full force in spring 2018, MPI estimates. This fact sheet also offers U.S. and state estimates of the school enrollment and educational attainment, workforce participation, and industries and occupations of employment for the nearly 690,000 current DACA holders.

Asian baseball, Grimes' baby, scary invasive insects -- how well did you follow the news this week? Take the UPI News Quiz for May 8, 2020.

This fact sheet compares key components of immigration reform outlined in the 2013 Senate immigration bill against provisions included in bills considered by the Senate in 2006 and 2007: border security, detention, and enforcement; worksite enforcement; visa reforms; earned legalization of unauthorized immigrants; strengthening the U.S. economy and workforce; and integration of new Americans.

MPI has completed an analysis of the major provisions in the 2013 framework, comparing them to provisions of the legislation the Senate considered in 2006 and 2007. 

This fact sheet is formatted as a chart comparing the framework of comprehensive immigration reform outlined in the 2013 Senate immigration bill against provisions included in bills considered by the Senate in 2006 and 2007.

This fact sheet offers a detailed review of the comprehensive immigration reform legislation approved by the U.S. Senate in June 2013 and compares its major provisions with those of the five targeted immigration bills approved by the House Judiciary Committee and the House Homeland Security Committee.

Netflix shared a premiere date and teaser trailer for its "Baby-Sitters Club" series, based on the Ann M. Martin book series.

Rapper YoungBoy Never Broke Again's "38 Baby 2" is No. 1 on the U.S. album chart.

  All good things must come to an end. And today is one of those days. In this episode of The Not Crazy Podcast, we say a sad farewell to...

i even got this from pro trans page that say they have laws banning men from women's room & trans aka GD was put into mad house, & even then there been alot of time where rapists &perverted freaks been using other Gender's bath room too doesn't make it right, they go to prison if they find out

For Stephen we'd  use the nickname "Stevie" and for Thomas we'd use the nickname "Tommy" if that helps.

Swedish asylum policy has taken a restrictionist turn since the country received a record-breaking number of asylum seekers in 2015 and after electoral gains by the nationalist, anti-immigration Sweden Democrats pushed the governing coalition to a harder line. Still, other aspects of the country’s migration policy remain welcoming, as this country profile explores.

As European asylum systems are tested again by the COVID-19 pandemic, which has injected the need for social distancing during processing and in reception centers, it appears lessons learned during the 2015-16 migration and refugee crisis may be fading. Chief among them: A number of Member States have phased out their buffer capacity. This MPI Europe commentary explores the diametrically different approaches taken to asylum during the pandemic.

My first exposure to Robert Macfarlane happened a year ago when I picked up a battered copy of The Wild Places in order to shelve it. Instead, I checked it out from my branch and stayed up past midnight to read it. Thanks to Macfarlane, I was exposed to Roger Deakin's Wild Wood and Notes from Walnut Tree Farm. I found photos of Walnut Tree Farm, the late Deakin's house, much visited by Macfarlane, while searching for more information about both of them online.

I am from probably the last generation of American children to be raised on English children's books. I know that there is a generation of Quidditch-playing adults that were weaned on the Harry Potter books of British-born J. K. Rowling. While the Harry Potter books are gripping, they lack an essential British characteristic shared by many successful authors of British children's books:

• Rudyard Kipling - the two Puck of Pook's Hill books
• Rosemary Sucliff - all of her books
• Elizabeth Goudge - Rowling helped get Linnets & Valerians and The Little White Horse republished
• L. M. Boston - the Greene Knowe series
• William Mayne
• Robert Westall
• Diana Wynne Jones - the British landscape of an alternative Britain
• J. R. R. Tolkein -The Hobbit
• Kenneth Graham - The Wind in the Willows
• T. H. White - The Once and Future King
• Susan Cooper - The Dark is Rising series