Members Event Webinar

Event participants

Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House

Dr Sheri Berman, Professor of Political Science, Barnard College

Chair: Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House

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.

As federal and state governments ramp up efforts to implement the Workforce Innovation and Opportunity Act, these fact sheets compare key characteristics of the foreign born and the U.S. born that are relevant to understanding needs for adult education and workforce training services. The fact sheets cover the United States, the 20 states and 25 counties with the largest immigrant populations, and New York City.

As the share of U.S. children under age 8 who are Dual Language Learners (DLLs) increases, state policies have an important role to play in ensuring all young learners are able to get their education off to a good start. These fact sheets compare key characteristics of DLLs and their peers nationwide and in 30 states, and identify state policies that support equitable access to high-quality early childhood education and care programs.

States are in the midst of designing new policies to hold schools accountable for the education of English Learner (EL) students, as mandated by the federal Every Student Succeeds Act (ESSA). This series of fact sheets sketches the characteristics of immigrant and EL students in 25 states, the gaps between their educational outcomes and those of their peers, and the accountability policies each state is developing.

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.

With many countries in East Asia facing unfavorable demographic shifts in the form of aging populations, low fertility, and shrinking workforces, governments in 2016 continued to explore immigration as a potential policy solution. However, a tradition of cultural homogeneity and wariness among publics about increased immigration is leading policymakers to test the waters with very small steps.

In the Philippines, a pervasive culture of migration has led millions to seek opportunities abroad, particularly since an economic downturn in the 1970s. The government has long embraced exporting labor as official economic policy, but over time, the focus has shifted: first to protecting workers overseas and much more recently to linking migration and development. This article explores the evolution of Filipino migration policy and trends.

Nearly 50,000 asylum seekers have entered Canada irregularly via land crossing from the United States since spring 2017—contributing to a doubling in the overall number of asylum requests seen in 2016. Based on interviews with asylum claimants, this article analyzes their motivations for making the journey and the political implications of rising irregular migration to Canada.

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.

Joseph Tran
Oct 1, 2012; 30:173-178
Practical Pointers

Vanessa J. Briscoe
Jul 1, 2006; 24:115-121
Feature Articles

Andrew J.M. Boulton
Jan 1, 2005; 23:9-15
Feature Articles

Warren Clayton
Mar 1, 2009; 27:52-58
Features

OBJECTIVE

To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post–myocardial infarction (MI) patients.

OBJECTIVE

This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D).

OBJECTIVE

To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes.

OBJECTIVE

Self-management education and support are essential for improved diabetes control. A 1-year randomized telephonic diabetes self-management intervention (Bronx A1C) among a predominantly Latino and African American population in New York City was found effective in improving blood glucose control. To further those findings, this current study assessed the intervention’s impact in reducing health care utilization and costs over 4 years.

Indianapolis Colts quarterback Philip Rivers will become the head football coach at St. Michael Catholic High School, the school announced Friday.

A testosterone-lowering drug can reduce male pedophiles' risk of sexually abusing children, according to a new Swedish study.

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

TODAY Study Group
Jun 1, 2013; 36:1735-1741
TODAY Study

Henry N Ginsberg
Sep 1, 1991; 14:839-855
Diet and Diabetes

Pearl G. Lee
Apr 1, 2017; 40:444-452
Emerging Science and Concepts for Management of Diabetes and Aging

Matthew C. Riddle
May 1, 2018; 41:929-932
The Costs Of Diabetes

ADA News welcomes digital submissions from GKAS program participants.

The Food and Drug Administration has approved the first over-the-counter ibuprofen and acetaminophen combination drug for the U.S.

At least one American Dental Association member has reported receiving a phishing email appearing to come from an address containing ADA President Chad P. Gehani's name and including a link to "view member's details."

The Association is asking member dentists and their dental teams to increase their vigilance over phishing emails as a result of the coronavirus, known as COVID-19.
Attackers often use emergencies as an opportunity to send fake emails tailored to that situation, the association said.

Springfield, Virginia — The Drug Enforcement Administration announced that effective March 23, the DEA Call Center has temporarily suspended phone operations due to COVID-19 pandemic.

In a time when teledentistry is gaining more attention during the COVID-19 pandemic, the ADA will stream a free webinar in May that takes a close look at the different types of images needed for diagnosis, treatment planning and operative procedures.

The American College of Emergency Physicians has endorsed the American Dental Association's clinical practice guideline on the use of antibiotics for the management of pulpal- and periapical-related pain and swelling.

Gujarat university, second MBBS examination, pharmacology question papers (2010-2014)

Gujarat university, second MBBS examination, pharmacology question papers, January 2015

MD pharmacology examination, question papers, Gujarat university, April 2012

MD pharmacology examination, question papers, Gujarat university, October 2012

MD pharmacology examination, question papers, Gujarat university, April 2013

In honor of Mother's Day, May 10, 2020, here's a look at some celebrity moms who brought the kids along for a walk on the red carpet over the past few years.

I am torn, I know it is time to upgrade my phone, but I don't know whether to upgrade to just accept the larger phone size and go with the 2nd gen SE or go with an android. I'd be interested to know what the closest equivalent android device there is to the 1st gen SE. I am open to a bigger screen size, but not a bigger phone. So, if there was an andriod that was all screen on the front, but was similar size to the original SE, I would be open to that.

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

These fact sheets provide a sociodemographic sketch of parents with children ages 0 to 8 in the 30 states with the largest number of immigrant families, offering data and analysis of some of the key parental characteristics to help stakeholders identify populations that could be targets for early childhood and parent-focused programs working to improve child and parent outcomes.

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.

In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency.