Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1–ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates.

Bruce B. Duncan
Jul 1, 2003; 52:1799-1805
Pathophysiology

The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets.

Many chemicals and cellular processes cause oxidative stress that can damage lipids, proteins, or DNA (1). To quickly sense and respond to this ubiquitous threat, organisms have evolved enzymes that neutralize harmful oxidants such as reactive oxygen species and electrophilic compounds (including xenobiotics and their breakdown products) in cells.These antioxidant enzymes include GSH S-transferase (GST),2 NADPH:quinone oxidoreductase 1, thioredoxin, hemeoxygenase-1, and others (2, 3). Many of these proteins are commonly expressed in cells exposed to oxidative stress.The antioxidant response element (ARE) is a major regulatory component of this cellular stress response. The ARE is a conserved, 11-nucleotide-long DNA motif present in the 5'-flanking regions of many genes encoding antioxidant proteins. The laboratory of Cecil Pickett (Fig. 1) at the Merck Frosst Centre for Therapeutic Research in Quebec discovered ARE, a finding reported in the early 1990s in two JBC papers recognized as Classics here (4, 5).jbc;295/12/3929/F1F1F1Figure 1.Cecil Pickett (pictured) and colleagues first described the ARE motif, present in the 5' regions of many genes whose expression is up-regulated by oxidative stress and xenobiotics. Photo courtesy of Cecil Pickett.ARE's discovery was spurred in large part by Pickett's career choice. After completing a PhD in biology and a 2-year postdoc at UCLA in the mid-1970s, he began to work in the pharmaceutical industry.Recruited to Merck in 1978 by its then head of research and development (and later CEO), Roy Vagelos, “I became interested in how drug-metabolizing enzymes were induced by various xenobiotics,” Pickett says.According to Pickett, Vagelos encouraged researchers at the company...

Invitation Only Research Event

Event participants

John Zogby, Founder and Senior Partner, John Zogby Strategies
Chair: Dr Lindsay Newman, Senior Research Fellow, US and Americas Programme, Chatham House

Appslure is the best iOS apps development company in Delhi, Gurgaon, Noida, Mumbai, India. Our iOS app developers are expert in responsive iphone and iPad app development services.

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Invitation Only Research Event

Event participants

Yang Cheng, Professor of International Relations, Assistant Dean, School of International Relations and Public Affairs, Shanghai International Studies University
Yu Jie, Senior Research Fellow, Asia-Pacific Programme, Chatham House
Marcin Kaczmarski, Lecturer in Security Studies, University of Glasgow
Natasha Kuhrt, Lecturer, Department of War Studies, King’s College London
Bobo Lo, Non-Resident Fellow, Lowy Institute
Alexey Maslov, Professor, School of Asian Studies, National Research University, Higher School of Economics, Moscow

We are leading Top mobile app development company in Mumbai, Delhi, Noida, India. We have award winning Android and iOS developers to build your mobile apps with long term support.

Sales Fundaa is a Dial N Search Pvt. Ltd. initiative, provides ERP software, CRM Software, Project Management Software, Manufacturing Software, AMC Software, Data Management Software, Real Estate CRM, Logistics Software and Human Resource Management Software.

7 September 2012 , Volume 88, Number 5

Women with endometriosis have significantly higher rates of depression than women in the general population. That’s according to psychiatrist Dr Kristen Robinson-Barrett. It’s the end of endometriosis month, so Flair spoke to the expert to explore...

Western Bureau: A number of swimming officials in western Jamaica say that the region’s struggles with underdevelopment will continue even if the COVID-19 pandemic is brought under control. They say this is because they still lack proper pools to...

Interviews from the Women deliver conference in Copenhagen. Catrin Schulte-Hillen, co-ordinator of reproductive health and sexual violence care at Medecins Sans Frontieres, explains why the development community shouldn't conflate sexual violence and access to abortion.

With the emergence of sofobuvir, a new direct acting antiviral, treatment for Hepatitis C infection is currently undergoing it's greatest change since the discovery of the virus 25 years ago. However Gilead, who manufacture the treatment, are under fire for the cost of the druge - around $90 000 for a course of treatment. Victor Roy, doctoral...

Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications

D Koya
Jun 1, 1998; 47:859-866
Articles

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article

John W Baynes
Apr 1, 1991; 40:405-412
Perspectives in Diabetes

At the outset, author Ivy Slater shares the existential crisis that spurred her to change careers. Slater’s psychosocial experience after the passing of her father and the stagnation she experienced at her printing business proved exhaustively...

2 July 2014 , Volume 90, Number 4

Research Event

Invitation Only Research Event

Event participants

Moïse Katumbi Chapwe, Governor, Katanga Province, Democratic Republic of the Congo

15 November 2016

Research Event

Event participants

Tom Butler, Chief Executive Officer, International Council for Mining and Metals (ICMM)
Evelyn Dietsche, Associate Fellow, Energy, Environment and Resources, Chatham House
Chair: Bernice Lee, Executive Director, Hoffman Centre, Chatham House 

The Armenian diaspora, which significantly exceeds the country's resident population, has played an instrumental role in Armenia's political and economic development since independence in 1991. Yet a picture emerges of divergent currents within the diaspora, often seen from above as a unified entity. Delve into differences in engagement among Armenia's "old" and "new" diasporas with this feature article.

For generations, migrants have emigrated from Senegal, particularly from in and around the Senegal River Valley. With France a key destination, French policy changes have had significant impact on Senegalese migrants and the hometown associations through which they support development in Senegal. This article explores how these policy shifts influence development and quality of life in the Senegal River Valley.

Migration and development are intimately linked, but they have not always shared the international policy stage. As UN Member States kick off negotiations for the Global Compact for Safe, Orderly, and Regular Migration—and with adoption planned for 2018—this brief examines the evolving relationship between these policy areas and considers what a global compact has to offer, if well designed.

Development assistance may be a blunt tool for reshaping migration patterns—and indeed one that could increase flows over the short term. Shifting the focus away from increasing individuals’ skills and assets toward investments in the broader economic or governance structures that are a prerequisite for growth and stability may offer more alternatives to emigration in the long run.

As policymakers look for ways to address the drivers of illegal immigration, many have called for migration aims to be incorporated into development work and development tools into migration partnerships. This policy brief analyzes the benefits and risks of heightened cooperation between actors in these fields, and identifies areas where joint initiatives may prove fruitful.

From ongoing emigration flows and a surge in asylum seekers, to more than 150,000 returnees, this country profile examines contemporary and historical migration trends in Albania. Driven by extreme poverty and unemployment, more than one-third of Albania's population has emigrated in the last 25 years. The government now seeks to capitalize on diaspora resources by linking migration and development policies.

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.

This report summarizes the economic and social development policy achievements of Central American countries over the past 20 years, as well as the notable obstacles to development that remain. The author identifies long-term challenges and outlines how they can be incorporated into a new development agenda.

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 partnerships to facilitate skilled migration have had mixed success in the past, the Global Compact for Migration is advancing a new approach that may change this. This policy brief compares this new partnership model with the traditional one, highlighting the questions policymakers will need to answer if they are to encourage mobility, sustain employer engagement, and see development benefits in countries of origin.

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.

American Diabetes Association
Feb 1, 1998; 21:310-314
Consensus Development Conference Report

American Diabetes Association
Sep 1, 1998; 21:1551-1559
Consensus Development Conference Report

The international group SNOMED International honored ADA member dentist Dr. Mark Jurkovich with the Award of Excellence for spearheading the important work the ADA has done on SNODENT, the group announced Jan. 16.

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.

Wisconsin dentists have answered the call for personal protective equipment by organizing drives and donating their surplus supplies to hospitals and urgent care facilities treating patients with COVID-19.

Bio-engineered models of the human brain infected with herpes simplex virus-1 develop many of the same characteristics found in Alzheimer's disease, according to a new analysis published by Science Advances.

OBJECTIVE

The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians.

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.

A timeline of key immigration laws and policy developments between 1986 and 2013.

Enactment of the Every Student Succeeds Act (ESSA) in 2015 introduced opportunities to use federal funds to strengthen the early childhood education and care (ECEC) workforce as a means of better meeting the needs of the growing and increasingly diverse young child population.

The Knowledge Sharing for the Development of Learning Resources tutorial provides a professional step forward, a learning experience that leads to recognition that your leadership is well founded as well as ensuring that participants in the development of learning resources recognize they are contributing to an exceptional achievement.