A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

Item does not contain fulltextBACKGROUND: Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype-phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. METHODS: Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. RESULTS: The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype-phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. CONCLUSION: A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.1 februari 201

Superconducting and Quantum-Effect Devices

Contains reports on nine research projects and a list of publications.National Science Foundation Fellowship MIP 88-58764Advanced Research Projects Agency/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Grant DMR 91-08748National Science Foundation Fellowship ProgramU.S. Air Force - Office of Scientific Research Grant F49620-92-J-0064National Science Foundation Grant DMR 94-0202

Common Features at the Start of the Neurodegeneration Cascade

A single-molecule study reveals that neurotoxic proteins share common structural features that may trigger neurodegeneration, thus identifying new targets for therapy and diagnosis

The N-Terminal residues 43 to 60 form the interface for dopamine mediated α-synuclein dimerisation

α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature in the brains of Parkinson's disease patients. The neurotransmitter dopamine (DA) inhibits the fibrillisation of α-syn into amyloid, and promotes α-syn aggregation into SDS-stable soluble oligomers. While this inhibition of amyloid formation requires the oxidation of both DA and the methionines in α-syn, the molecular basis for these processes is still unclear. This study sought to define the protein sequences required for the generation of oligomers. We tested N- (α-syn residues 43-140) and C-terminally (1-95) truncated α-syn, and found that similar to full-length protein both truncated species formed soluble DA: α-syn oligomers, albeit 1-95 had a different profile. Using nuclear magnetic resonance (NMR), and the N-terminally truncated α-syn 43-140 protein, we analysed the structural characteristics of the DA:α-syn 43-140 dimer and α-syn 43-140 monomer and found the dimerisation interface encompassed residues 43 to 60. Narrowing the interface to this small region will help define the mechanism by which DA mediates the formation of SDS-stable soluble DA:α-syn oligomers

Locally harvested foods support serum 25-hydroxyvitamin D sufficiency in an indigenous population of Western Alaska

Background: Low serum vitamin D is associated with higher latitude, age, body fat percentage and low intake of fatty fish. Little documentation of vitamin D concentrations is available for Alaska Native populations. Objective: This study was undertaken to investigate serum 25-hydroxyvitamin D (25(OH)D) concentrations of the Yup'ik people of southwestern Alaska in relation to demographic and lifestyle variables, particularly with the use of locally harvested (local) foods. Design: Cross-sectional study. Methods: We estimated 25(OH)D, dietary vitamin D and calcium, percent of energy from local foods and demographic variables in 497 Yup'ik people (43% males) aged 14–92 residing in southwestern Alaska. Sampling was approximately equally divided between synthesizing and non-synthesizing seasons, although the preponderance of samples were drawn during months of increasing daylight. Results: Mean vitamin D intake was 15.1±20.2 µg/d, while local foods accounted for 22.9±17.1% of energy intake. The leading sources of vitamin D were local fish (90.1%) followed by market foods. Mean 25(OH)D concentration was 95.6±40.7 nmol/L. Participants in the upper 50th percentile of 25(OH)D concentration tended to be older, male, of lower body mass index, sampled during the synthesizing season, and among the upper 50th percentile of local food use. Conclusions: A shift away from locally harvested foods will likely increase the risk for serum 25(OH)D insufficiency in this population

The crystal structure of the TetR family transcriptional repressor SimR bound to DNA and the role of a flexible N-terminal extension in minor groove binding

SimR, a TetR-family transcriptional regulator (TFR), controls the export of simocyclinone, a potent DNA gyrase inhibitor made by Streptomyces antibioticus. Simocyclinone is exported by a specific efflux pump, SimX and the transcription of simX is repressed by SimR, which binds to two operators in the simR-simX intergenic region. The DNA-binding domain of SimR has a classical helix-turn-helix motif, but it also carries an arginine-rich N-terminal extension. Previous structural studies showed that the N-terminal extension is disordered in the absence of DNA. Here, we show that the N-terminal extension is sensitive to protease cleavage, but becomes protease resistant upon binding DNA. We demonstrate by deletion analysis that the extension contributes to DNA binding, and describe the crystal structure of SimR bound to its operator sequence, revealing that the N-terminal extension binds in the minor groove. In addition, SimR makes a number of sequence-specific contacts to the major groove via its helix-turn-helix motif. Bioinformatic analysis shows that an N-terminal extension rich in positively charged residues is a feature of the majority of TFRs. Comparison of the SimR–DNA and SimR–simocyclinone complexes reveals that the conformational changes associated with ligand-mediated derepression result primarily from rigid-body rotation of the subunits about the dimer interface

Can an Integrated Approach Reduce Child Vulnerability to Anaemia? Evidence from Three African Countries.

Addressing the complex, multi-factorial causes of childhood anaemia is best done through integrated packages of interventions. We hypothesized that due to reduced child vulnerability, a "buffering" of risk associated with known causes of anaemia would be observed among children living in areas benefiting from a community-based health and nutrition program intervention. Cross-sectional data on the nutrition and health status of children 24-59 mo (N = 2405) were obtained in 2000 and 2004 from program evaluation surveys in Ghana, Malawi and Tanzania. Linear regression models estimated the association between haemoglobin and immediate, underlying and basic causes of child anaemia and variation in this association between years. Lower haemoglobin levels were observed in children assessed in 2000 compared to 2004 (difference -3.30 g/L), children from Tanzania (-9.15 g/L) and Malawi (-2.96 g/L) compared to Ghana, and the youngest (24-35 mo) compared to oldest age group (48-59 mo; -5.43 g/L). Children who were stunted, malaria positive and recently ill also had lower haemoglobin, independent of age, sex and other underlying and basic causes of anaemia. Despite ongoing morbidity, risk of lower haemoglobin decreased for children with malaria and recent illness, suggesting decreased vulnerability to their anaemia-producing effects. Stunting remained an independent and unbuffered risk factor. Reducing chronic undernutrition is required in order to further reduce child vulnerability and ensure maximum impact of anaemia control programs. Buffering the impact of child morbidity on haemoglobin levels, including malaria, may be achieved in certain settings