15 April 2020

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.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

This MPI Europe webinar examines innovative ways to better design and implement predeparture orientation programs for resetttling refugees. The discussion features observations from a refugee who went through an orientation program before being resettled in the Netherlands, and a resettlement agency official in Norway.

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.

What President Trump calls a border crisis is in fact a crisis in the asylum system—one worsened at every turn by his administration’s harsh policies and rhetoric. Rather than spend $5.7 billion on a wall, it would be far more effective to use the money to retool an overwhelmed asylum system, adapt outmatched border enforcement infrastructure to respond to the changing composition of arrivals, and work cooperatively with Mexico to tackle the factors propelling Central Americans to flee.

Even as the 1.8 million number swirls in the discussion of how many DREAMers would be placed on a path to citizenship, proposals debated in the Senate in February 2018 would have resulted in the legalization of smaller numbers, as this commentary explains. It offers estimates of potential beneficiaries of several Senate proposals, including one backed by the White House, and analysis of key criteria.

More than 1 million international students were in the United States in 2015-16, a significant share of them in science, technology, engineering, or math (STEM) fields. While countries increasingly are vying for this population, these individuals face a complex choice upon graduation: to stay or leave? This article examines international STEM students in the United States and the motivations underlying their postgraduation plans.

Award winners were honored at the second annual awards ceremony in Washington, DC, on May 18, 2010.

Winners of the 2nd annual E Pluribus Unum Prizes awarded to exceptional immigrant integration initiatives by MPI's National Center on Immigrant Integration Policy are the Illinois New Americans Integration Initiative; the Latino Community Credit Union in Durham, NC; Tacoma Community House in Tacoma, WA; and Upwardly Global in San Francisco, CA. McDonald's Corp. of Oak Brook, IL, received the sole honorable mention. The Prizes seek to reward exemplary efforts that uphold and update the ideal of "out of many, one" and inspire others to take on the important work of helping immigrants and their children join the mainstream of U.S. society as well as build stronger ties between immigrants and the native-born. Award winners were honored at the second annual awards ceremony in Washington, DC, on May 18, 2010. Watch highlights of the ceremony here.

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.

Experts on this Spanish language webinar examine the operation of today’s interior immigration enforcement system and how state and local governments, civil society, and consulates are responding.    

The third Social Innovation for Refugee Inclusion conference in Brussels, co-organized by MPI Europe with the U.S. and Canadian Missions to the European Union and the European Economic and Social Committee, explored how innovations in living situations for refugees can promote community-driven inclusion, overcome divisions, facilitate economic opportunities, and foster a sense of "home."

Noncitizens have long served in the U.S. military, often encouraged by the promise of a fast track to U.S. citizenship. In recent years, however, Congress and the Defense Department have made it more difficult for noncitizens to enlist. This brief give context to these policy changes and explores ways the military could better balance concerns about national security and the need for recruits with key cultural and professional skills.

A Spanish language webinar examining the operation of today’s interior enforcement system and how state and local governments, civil society, and consulates are responding.    

Convocamos un seminario en línea (webinar) en español en la ocasión del lanzamiento del informe, Creatividad dentro de la crisis: opciones legales para inmigrantes venezolanos en América Latina, que describe donde se han radicado los migrantes venezolanos; las medidas que han utilizado los gobiernos latinoamericanos para regularizar el estatus legal de los migrantes venezolanos; y los esfuerzos por integrar a los recién llegados en sus nuevas comunidades de residencia.

In his first public address on his inaugural official visit to Washington, DC, IOM Director General António Vitorino discusses his vision for IOM; reforms in the UN system; coordination with other organizations in addressing humanitarian protection; and the operational steps IOM is taking to respond to forced migration and displacement.

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Environmental change is likely to affect global migration flows in a number of ways. Both long-term trends such as increased flooding and the increasing scarcity of resources as well as shorter term trends like severe weather are likely to contribute to displacement and increased migration for individuals already in vulnerable situations. While often viewed as a negative outcome of climate change, planned migration can also serve as a strategy for mitigating its impact.  

This policy brief, which concludes a nine-brief series examining what is known about the linkages between migration and development, suggests that the policy framework on migration and development remains relatively weak, and few development agencies have made it a priority to promote the positive impact of international migration.

While media and academic discussions of "climate refugees" paint a picture of mass displacement of millions, in reality many communities vulnerable to climate change may choose to stay as a result of strong cultural, historical, and spiritual attachments to place. This article explores this "voluntary immobility" and its implications in the Pacific Islands.

In his first public address during his inaugural formal visit to Washington, DC. International Organization for Migration (IOM) Director General António Vitorino discussed his vision for the agency; reforms in the UN system designed to address migration matters better; the coordination of efforts between IOM, the UN High Commissioner for Refugees, and other international partners in addressing humanitarian protection; and the operational steps IOM is taking to respond to forced migration and displacement in hotspots around the world, including Venezuela, Bangladesh, and Libya.

This report by MPI and the Asian Development Bank lays out a realistic roadmap toward freer movement among skilled professionals within the ASEAN Economic Community (AEC), encouraging cooperation among ASEAN Member States in recognizing foreign qualifications and making government investments in training and educations systems that prepare workers in accordance with common standards.

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.

Amid aging populations and the growth of chronic diseases, the demand for skilled health-care professionals is on the rise in the United States, Canada, and Mexico. This report explores the policy implications, benefits, and challenges of harmonizing nursing qualifications in the region, suggesting that a more collaborative approach could result in greater supply and quality of nurses.

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.

A discussion, including the former United Nations Deputy High Commissioner for Refugees, examining the huge strains on the global protection system and how it can better respond to protracted refugee situations and other long-term displacement, focusing on the conclusions of the Transatlantic Council on Migration's recent meeting, Beyond Asylum: Rethinking Protection Policies to Meet Sharply Escalating Needs.

La migración centroamericana a los Estados Unidos comenzó en gran números en los años ochenta, impulsada por la inestabilidad política, los desastres naturales y las dificultades económicas. Aproximadamente 3,4 millones de centroamericanos vivieron en los Estados Unidos en 2015, principalmente de El Salvador, Guatemala y Honduras. Dónde viven en los Estados Unidos, su competencia en inglés, su estado legal, las vías de inmigración, y más, están cubiertos en este artículo.

Una llamada en español que analiza las dinámicas cambiantes y las cuestiones políticas relacionadas con la migración a través de México a los Estados Unidos.

Durante este seminario, ponentes presentaron hallazgos de un reciente informe que utiliza datos de agencias gubernamentales mexicanas, entrevistas con funcionarios clave y relatos de la sociedad civil para examinar el marco legal para la protección de menores no acompañados y su aplicación, al igual que las brechas entre este marco y su aplicación durante los procesos de detención, interrogación y alojamiento. El presidente de MPI, Andrew Selee, también expuso cómo el cambio en la dinámica política en Estados Unidos puede afectar las cuestiones migratorias con México, así como los efectos en la relación bilateral en medio de tensiones sobre el muro fronterizo, la renegociación del acuerdo del TLCAN y una cifra significativa de repatriaciones de migrantes mexicanos.

Economy (date: 5/9/2020 - Rank: 3)

OBJECTIVE

To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

PGA Tour star Brooks Koepka said he'll no longer smack talk Michael Jordan on the golf course after he lost a round to the basketball legend.

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