The common 677C-->T mutation (+) in the 5,10-methylenetetrahydrofolate reductase gene, resulting in decreased activity of the enzyme, has been associated with spina bifida neural tube defects (NTD). We combined all known Dutch control groups, a total of 1273 individuals, and found a prevalence of the 677C-->T mutation of 8.4%. When compared with the frequencies in 55 SB patients and to mothers ...

In 2006 the U.S. Agency for International Development (USAID) established the Neglected Tropical Disease (NTD) Control Program to support national governments in developing successful, cost-efficient NTD programs that integrate disease-specific programs into coordinated national initiatives, in accord with the World Health Organization recommendations. A 3-stage "roll-out package" has been deve...

STUDY OBJECTIVES The aims were: (1) to compare the birth prevalence of malformations in different ethnic groups and (2) to explore the reasons for the ethnic variations found by examining birth prevalence in the offspring of matings between ethnic groups. DESIGN Analysis of data from a register of malformations and register of births. SETTING Birmingham, England. SUBJECTS A total of 432,7...

Translational GTPases (trGTPases) regulate all phases of protein synthesis. An early event in the interaction of a trGTPase with the ribosome is the contact of the G-domain with the C-terminal domain (CTD) of ribosomal protein L12 (L12-CTD) and subsequently interacts with the N-terminal domain of L11 (L11-NTD). However, the structural and functional relationships between L12-CTD and L11-NTD rem...

The authors examined whether maternal dieting behaviors were associated with increased neural tube defect (NTD) risk among offspring, using population-based, case-control data. The analysis included 538 cases and 539 nonmalformed controls delivered from 1989 to 1991 in selected California counties, and exposures were assessed by in-person maternal interview. Among four reported dieting behavior...

p97/VCP, a member of the AAA+ (ATPases associated with diverse cellular activities) family of proteins, is implicated in the etiology of a group of degenerative diseases affecting bone and muscle tissue as well as the central nervous system. Methyl-TROSY-based NMR studies have previously revealed how disease-causing mutations deregulate a subtle dynamic conformational equilibrium involving the ...

LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3beta-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 2...

Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline. Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine. The authors investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine inf...

The relationship between timing of closure of the posterior neuropore (PNP) and development of spinal neural tube defects (NTD) has been studied in individual mutant curly tail mouse embryos maintained in culture. Moderate delay in PNP closure results in development of tail flexion defects whereas extreme delay of PNP closure is associated with development of open NTD. Experimental enlargement ...

A protective effect of folate against the development of neural tube defects (NTDs), specifically, anencephaly and spina bifida, is now well recognized, having been established by a chain of clinical research studies over the past half century. This article summarizes the more important of these studies, which have led to the current situation in which all women capable of becoming pregnant are...