In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

The action mechanisms revealed by the biochemical and structural analyses of replicative and translesion synthesis (TLS) DNA polymerases (Pols) are retained in their cellular roles. In this regard, DNA polymerase θ differs from other Pols in that whereas purified Polθ misincorporates an A opposite 1,N6-ethenodeoxyadenosine (ϵdA) using an abasic-like mode, Polθ performs predominantly error-free TLS in human cells. To test the hypothesis that Polθ adopts a different mechanism for replicating through ϵdA in human cells than in the purified Pol, here we analyze the effects of mutations in the two highly conserved tyrosine residues, Tyr-2387 and Tyr-2391, in the Polθ active site. Our findings that these residues are indispensable for TLS by the purified Pol but are not required in human cells, as well as other findings, provide strong evidence that the Polθ active site is reconfigured in human cells to stabilize ϵdA in the syn conformation for Hoogsteen base pairing with the correct nucleotide. The evidence that a DNA polymerase can configure its active site entirely differently in human cells than in the purified Pol establishes a new paradigm for DNA polymerase function.

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

Faced with a lack of employment opportunities and recurrent poverty, Albanian youth migrate to Italy alone in the hopes of improving their educational prospects or making money for their families. Yet upon arrival, they face many vulnerabilities. While some protections for unaccompanied minors exist in the Italy, the system is greatly fragmented and challenges, including how to return them to Albania, remain persistent.

This fact sheet uses U.S. and Mexican apprehensions data to trace the evolving trends in unaccompanied child and family migration from Central America through Mexico and to the United States, and discusses the push factors and pull factors responsible for the increase in flows seen in recent years, as well as the growing role of smuggling organizations.

A high school diploma has been a core requirement of proposed DREAM Act legislation and the Deferred Action for Childhood Arrivals (DACA) program. Yet a fresh estimate of the number of unauthorized immigrants graduating annually from U.S. high schools has long been missing from the debate. This fact sheet provides up-to-date estimates for the United States and top 15 states, estimating 98,000 such students graduate yearly.

This report analyzes the exploitation of migrants in three spheres: the domestic care sector, the labor market, and the sex industry. It details several obstacles governments face in their efforts to weaken the "bad actors" that profit from exploitation, and shows how one of the biggest challenges facing law enforcement is that serious criminals and lawbreakers often operate on the edge of legality and exploit legal routes wherever possible.

Having emerged from a long era of military rule, Myanmar's leaders and many citizens are looking outward. In particular, with Burmese labor migration abroad on the rise, policymakers are examining ways in which to harness remittances as a vehicle for economic development, particularly in impoverished rural areas. This article explores Burmese labor migration flows, financial reforms, and challenges on migration and development.

This event focuses on the changing face of Mexican migration to the United States, Mexican immigrants' contributions to U.S. society and political and economic power, as well as that of those who have returned to Mexico.

Colombia has more internally displaced persons (IDPs) than any other country in the world, the result of a 52-year civil war. Beyond improving the lives of its 7.3 million IDPs, the country faces a number of crucial migration issues as it works to achieve stability in the wake of an historic peace accord signed in late 2016. This country profile examines historical trends and current and future migration challenges in Colombia.

While emigration increased after Portugal plunged into an economically turbulent period amid the global financial crisis, the country's image as the poster child for post-crisis outmigration may be misplaced. This report explores the scale, drivers, and impact of emigration from Portugal since the turn of the millennium, and examines how the country can stem emigration and promote the return of emigrants.

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.

This event with UN High Commissioner for Refugees António Guterres includes a discussion on the state of citizen security in Central America and the resulting humanitarian impact, featuring findings from Children on the Run, a UNHCR report based on interviews with more than 400 unaccompanied children from the region.

Marking the release of an MPI report, speakers on this webinar present an overview of regional immigration enforcement trends, including U.S. and Mexican apprehensions and deportations of both children and adults, along with a demographic, socioeconomic, and criminal profile of child and adult deportees.

This report examines the rising numbers of apprehensions and deportations of Central American children and adults by the United States and Mexico, and provides a demographic, socioeconomic, and criminal profile of deportees to El Salvador, Guatemala, and Honduras. The report traces how rising Mexican enforcement is reshaping regional dynamics and perhaps ushering in changes to long-lasting trends in apprehensions.

This webinar includes an overview of regional immigration enforcement trends, including U.S. and Mexican apprehensions and deportations of Central American migrants, along with a demographic, socioeconomic, and criminal profile of child and adult deportees.

Authors of a year-long study of reception and reintegration services in Mexico and the Northern Triangle discuss the findings of their fieldwork, including the differing reintegration needs of individual migrant groups, promising reception and reintegration programs, ongoing challenges for origin communities, and policy recommendations to improve reintegration strategies. 

OBJECTIVE

Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects.

OBJECTIVE

Excessive iron intake has been linked to diabetes risk. However, the evidence is inconsistent. This study examined the association between dietary heme and nonheme iron intake and diabetes risk in the Chinese population.

OBJECTIVE

To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications.

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.

Firefighters in Arizona came to the rescue of a puppy that plunged into a 15-foot-deep hole at a construction site.

Police and public works employees in Wisconsin came to the rescue of a deer that found itself struggling to escape a soccer net.

Animal rescuers in California said they reached over the side of a freeway on-ramp to rescue a raccoon seen dangling from a metal beam under the ramp.

Animal rescuers in Britain said a fox was rescued from the narrow gap between the external walls of a house and its garage.

Migration and development policy discussions have edged closer to each other on the international stage. The adoption of the Global Compact for Migration in December 2018 marks an important milestone. As all eyes turn toward the compact’s implementation, this brief examines some of the key topics states have pledged to work more closely on—from labor migration and migrants’ rights, to returns and reintegration.

How did the U.S. border enforcement picture go in the span of two years from the lowest levels of illegal immigration since 1971 to a spiraling border security and humanitarian crisis? This report draws on enforcement and other data as well as analysis of changing migration trends and policies to tell this story. The authors outline key elements for a new strategy that can succeed over the long term.

A "Shoeless" Joe Jackson baseball card from 1910 sold at auction for $492,000 this week.

Tadej Battelino
Aug 1, 2019; 42:1593-1603
International Consensus Report

Itamar Raz
Jun 1, 2013; 36:1779-1788
Diabetes Care Expert Forum

Katherine M Flegal
Jul 1, 1991; 14:628-638
Supplement 3: Diabetes in Hispanic Americans

Caroline S. Fox
Sep 1, 2015; 38:1777-1803
Scientific Statement

William T. Cefalu
Jan 1, 2018; 41:14-31
Diabetes Care Expert Forum

Sarah D. de Ferranti
Oct 1, 2014; 37:2843-2863
Scientific Statement

Earl S. Ford
May 1, 2005; 28:1228-1230
BR Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes

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

Kellee M. Miller
Jun 1, 2015; 38:971-978
Type 1 Diabetes at a Crossroads

Sarah D. de Ferranti
Oct 1, 2014; 37:2843-2863
Scientific Statement

Christian Bommer
May 1, 2018; 41:963-970
The Costs Of Diabetes

Richard M. Bergenstal
Nov 1, 2018; 41:2275-2280
Perspectives in Care

William T. Cefalu
Jan 1, 2018; 41:14-31
Diabetes Care Expert Forum

Ofri Mosenzon
Aug 1, 2016; 39:S146-S153
II. Diabetes Treatment Options

Tadej Battelino
Aug 1, 2019; 42:1593-1603
International Consensus Report

OBJECTIVE

To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S.

The national origins of new arrivals to the United States are shifting, in ways not always fully appreciated. Recent newcomers are more likely to come from Asia, Central America, and Africa, and less likely to be from Mexico. This article offers key demographic information about the 15 immigrant groups that have experienced the largest growth since 2010, including Indians, Chinese, Colombians, Nigerians, and Bangladeshis.

From online petitions to organized walkouts, corporate America is facing increasing employee activism over its business involvement with agencies implementing the federal government's immigration policies. This "cubicle activism," seen at companies ranging from Amazon and Google to Bank of America and Wayfair, has garnered mixed success to date, forcing divestiture from private prison contractors but fewer results in other contexts, as this article explores.

Through a set of interlocking policies, the Trump administration has walled off the asylum system at the U.S.-Mexico border, guaranteeing that only a miniscule few can successfully gain protection. While the Migrant Protection Protocols, more commonly known as Remain in Mexico, have been a key part of throttling asylum applications, two newer, far less visible programs hold the potential to complete the job, as this article explores.

This MPI webinar focuses on reception and reintegration services for returning migrants, along with the heightened pressure policymakers in Mexico and Central America are facing to design systems and programs that support both returnees and the communities in which they settle. Authors of a year-long study of reception and reintegration services in Mexico and the Northern Triangle discuss the findings of their fieldwork.

Dr. Theressa Eliscar-Hewett began volunteering at the Nassau County Give Kids A Smile event in Long Island, New York, as a high school student. More than 10 years later, she continues to volunteer, only now as a dentist.

Nearly 49% of responding dental practices have experienced employee theft, and nearly 46% of those have experienced theft or embezzlement more than once, according to a survey conducted by the ADA Council on Dental Practice.