The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)–mediated β-cell destruction in type 1 diabetes (T1D). Among them, the 10-mer epitope located at the C-terminal end of the signal peptide was found to be the most prevalent in patients with recent-onset T1D. While the combined action of signal peptide peptidase and endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) is required for processing of the signal peptide, the mechanisms controlling signal peptide trimming and the contribution of the T1D inflammatory milieu on these mechanisms are unknown. Here, we show in human β-cells that ER stress regulates ERAP1 gene expression at posttranscriptional level via the IRE1α/miR-17-5p axis and demonstrate that inhibition of the IRE1α activity impairs processing of preproinsulin signal peptide antigen and its recognition by specific autoreactive CTLs during inflammation. These results underscore the impact of ER stress in the increased visibility of β-cells to the immune system and position the IRE1α/miR-17 pathway as a central component in β-cell destruction processes and as a potential target for the treatment of autoimmune T1D.

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

President Trump has made reshaping the U.S. immigration system a top priority. Yet the fragmented nature of policy-making in the United States—with power split between branches and levels of government—has made it difficult to pursue some of his most ambitious proposals. This report explores the evolution of migration policy under Trump, and what these changes may mean in the long run.

The Dallas Cowboys agreed to terms with free-agent offensive lineman Cameron Erving, the team announced Wednesday.

Joy Dugan
Oct 1, 2017; 35:232-238
Practical Pointers

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

OBJECTIVE

Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle.

OBJECTIVE

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

A Utah man who lost his high school class ring in Germany in 1982 was reunited with the ring thanks to a man who found it on a beach in the United States.

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

The U.S. Navy Flight Demonstration Squadron, also known as the Blue Angels, will fly over Dallas/Fort Worth, Houston and New Orleans Wednesday to honor frontline workers fighting the COVID-19 pandemic.

Navy leaders and private contractors broke ground this week on what will become the fleet's only dedicated facility to test, fire and evaluate complete laser weapon systems in a maritime environment.

Apr 1, 1994; 17:360-361
Syst[egrave]me International (SI) Units

Nov 1, 1995; 18:1524-1525
Syst[egrave]me International (SI) Units

Aug 1, 1995; 18:1223-1224
Syst[egrave]me International (SI) Units

The American Dental Association is asking Congress to pass the Ensuring Lasting Smiles Act — legislation that would require all private group and individual health plans to cover medically necessary services that repair or restore congenital anomalies.

The American Dental Association is asking Congress to pass the Ensuring Lasting Smiles Act — legislation that would require all private group and individual health plans to cover medically necessary services that repair or restore congenital anomalies.

The National Academies of Sciences, Engineering, and Medicine announced March 5 that it does not find that the National Toxicology Program adequately supported its conclusion that fluoride is “presumed” to be a cognitive neurodevelopmental hazard to humans.

Some 30 companies including Dow, Total and other big makers of plastic raised $1 billion to contribute to cleaner ocean waters.

Average fuel prices in the United States started the week at $2.26 per gallon, showing little change from the last month or last week, and may remain flat.

Johns Hopkins University will start two clinical trials of convalescent blood plasma for treatment of COVID-19, the disease caused by the new coronavirus.

OBJECTIVE

To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes.

OBJECTIVE

Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.

OBJECTIVE

To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation.

Classroom observations occur to document behaviors and to help provide insight to teachers. Teachers are teaching and are typically focused on the overall learning of the entire class. It is not possible for a teacher to catch all of the details of classroom while teaching. An outside observer, often a School Psychologist, can sit in the classroom and observe a student or the entire class. These insights can be used to help provide better instruction, create behavioral or academic interventions, or to document behaviors.

When do classroom observations occur?

- During a special education evaluation The classroom observation is a required component in a special education evaluation. It provides data and insight to the eligibility committee.

- Before a Behavior Intervention Plan or Functional Behavioral Assessment Classroom observations are important before implementing a Functional Behavioral Assessment or a Behavior Intervention Plan. It helps to clarify the current behaviors, identify possible triggers of the behavior, and determine the frequency of the behaviors.

- When a teacher is worried about a particular student Often a teacher will have a concern about a student and ask the School Psychologist to conduct an observation. After the observation the teacher and psychologist will meet to discuss and brainstorm strategies to assist in instruction.

Mars' ancient magnetic field emerged earlier and persisted for longer than scientists previously thought, according to a new study.

The last supermoon of 2020, May's so-called "Flower Moon," will be visible in the night skies this week, and its brightness will likely obscure the yearly Eta Aquarids meteor shower, according to NASA.

Engineers in China have developed a fossil fuel-free jet propulsion prototype design that uses microwave air plasmas.

Director Rachel Lee Goldenberg discusses how her "Valley Girl" musical remake puts a twist on the hit music of the '80s.

Since the 2015–16 refugee crisis, European policymakers have eagerly sought cooperation with origin and transit countries in the hopes of stemming unauthorized migration to Europe. This approach is neither new, nor without its limitations. By examining the evolution of two longstanding Mediterranean partnerships—between Spain and Morocco, and Italy and Tunisia—this report offers insights on what has and has not worked.

Fostering the social and economic inclusion of refugees has long been the domain of governments and NGOs. In the wake of the 2015–16 European migration and refugee crisis, however, new actors have emerged and taken on important roles in integrating newcomers. This report describes key discussions and takeaways from an MPI Europe conference on these developments.

As the number and share of Dual Language Learners (DLLs) continues to grow across the United States, diversity within this population is also increasing. This webinar marks the release of a report providing analysis of the diversity within the DLL population nationwide and at the state and local levels. Speakers discuss data on the three rapidly growing subgroups within the DLL population: Black and Asian American and Pacific Islander DLLs and young children of refugees, and the implications for the early education and care field and K-12 education systems. 

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.

First report examines Canadian challenges & solutions in housing Syrian refugees

WASHINGTON — Four years after the peak of the 2015–16 migration and refugee crisis in Europe and amid swelling arrivals at the U.S.-Mexico border and elsewhere, new evidence sheds light on how well countries have responded to an unprecedented surge in mixed flows of humanitarian, economic and family migrants.

WASHINGTON – A pesar de que los gobiernos de América Latina y el Caribe han tomado medidas generosas e innovadoras para lidiar con el desplazamiento forzado desde Venezuela y más recientemente desde Nicaragua, la cálida bienvenida se ha enfriado en algunos lugares a medida que el número de entradas, la presión sobre los servicios públicos y la preocupación del público aumenta.

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, courtesy of Justine Schofield. Justine's latest book is "Dinner With Justine".

1.2kg butternut pumpkin, peeled, cut into 2cm pieces 2 tablespoons olive oil 1 tablespoon chopped fresh sage, plus 12 whole leaves to serve 1/4 teaspoon freshly grated nutmeg 350g ricotta 1 egg 1 cup grated parmesan, plus extra to serve 8 fresh lasagne sheets 100g unsalted butter 2 tablespoons chopped walnuts

Responsables de políticos principales y partes interesadas de América Latina, así como representantes de instituciones internacionales claves, ofrecen sus puntos de vista sobre los desafíos futuros mientras gobiernos latinoamericanos buscan establecer las estrategias para responder a flujos migratorios forzados a gran escala, como los de Venezuela y Nicaragua.

MPI llevó a cabo un seminario en línea para marcar el lanzamiento de: Un portal sobre Migración en América Latina y el Caribe; y un informe que examina los efectos de las políticas migratorias y de integración en 11 países en América Latina y el Caribe ante el aumento de la migración venezolana y nicaragüense.

OBJECTIVE

Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke).

Responsables de políticos principales y partes interesadas de América Latina, así como representantes de instituciones internacionales claves, ofrecen sus puntos de vista sobre los desafíos futuros mientras gobiernos latinoamericanos buscan establecer las estrategias para responder a flujos migratorios forzados a gran escala, como los de Venezuela y Nicaragua.

MPI llevó a cabo un seminario en línea para marcar el lanzamiento de: Un portal sobre Migración en América Latina y el Caribe; y un informe que examina los efectos de las políticas migratorias y de integración en 11 países en América Latina y el Caribe ante el aumento de la migración venezolana y nicaragüense.

As long-simmering passions related to federal immigration policies have come to a full boil, less noted but no less important debates are taking place at state and local levels with regards to policies affecting immigrants and their children. As states are increasingly diverging in their responses, this report examines how some of the key policies and programs that support long-term integration success are faring in this volatile era.

A sea of red swept the capitals of North and South Carolina on Wednesday, as thousands of teachers turned out to demand higher pay and more school funding.

“Detracking” math teachers is tough because many educators resist upending their routines or challenging informal hierarchies, and PD initiatives to make it happen are limited.