Genetic variability in 3 co-occurring forms of the starfish genusOthilia (=Echinaster)

Summary High levels of genetic variability have been found in 3 (grey, brown, orange) co-occurring forms of the starfishOthilia. These high levels appear to correspond to the generalistic habit of this starfish. The biochemical data, coupled with morphological observations, indicate that the grey and orange forms are morphs of the same species and that the brown form is a species separate from the grey and orange forms.     

The dynamics of measles in sub-Saharan Africa

Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur.     

A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing

Messenger-RNA-directed protein synthesis is accomplished by the ribosome. In eubacteria, this complex process is initiated by a specialized transfer RNA charged with formylmethionine (tRNA(fMet)). The amino-terminal formylated methionine of all bacterial nascent polypeptides blocks the reactive amino group to prevent unfavourable side-reactions and to enhance the efficiency of translation initiation. The first enzymatic factor that processes nascent chains is peptide deformylase (PDF); it removes this formyl group as polypeptides emerge from the ribosomal tunnel and before the newly synthesized proteins can adopt their native fold, which may bury the N terminus. Next, the N-terminal methionine is excised by methionine aminopeptidase. Bacterial PDFs are metalloproteases sharing a conserved N-terminal catalytic domain. All Gram-negative bacteria, including Escherichia coli, possess class-1 PDFs characterized by a carboxy-terminal alpha-helical extension. Studies focusing on PDF as a target for antibacterial drugs have not revealed the mechanism of its co-translational mode of action despite indications in early work that it co-purifies with ribosomes. Here we provide biochemical evidence that E. coli PDF interacts directly with the ribosome via its C-terminal extension. Crystallographic analysis of the complex between the ribosome-interacting helix of PDF and the ribosome at 3.7 A resolution reveals that the enzyme orients its active site towards the ribosomal tunnel exit for efficient co-translational processing of emerging nascent chains. Furthermore, we have found that the interaction of PDF with the ribosome enhances cell viability. These results provide the structural basis for understanding the coupling between protein synthesis and enzymatic processing of nascent chains, and offer insights into the interplay of PDF with the ribosome-associated chaperone trigger factor.     

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10??). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.     

Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture

Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture. Genome-wide linkage analysis in two families identified a 7.5-Mb locus on chromosome 19q13.12 containing 148 genes. Targeted high throughput sequence analysis of linked genes in each family yielded > 4,000 DNA variants and implicated a single gene, WDR62, as harboring potentially deleterious changes. We subsequently identified additional WDR62 mutations in four other families. Magnetic resonance imaging and postmortem brain analysis supports important roles for WDR62 in the proliferation and migration of neuronal precursors. WDR62 is a WD40 repeat-containing protein expressed in neuronal precursors as well as in postmitotic neurons in the developing brain and localizes to the spindle poles of dividing cells. The diverse phenotypes of WDR62 suggest it has central roles in many aspects of cerebral cortical development.     

Synaptic integration by different dendritic compartments of hippocampal CA1 and CA2 pyramidal neurons

Pyramidal neurons have a complex dendritic arbor containing tens of thousands of synapses. In order for the somatic/axonal membrane potential to reach action potential threshold, concurrent activation of multiple excitatory synapses is required. Frequently, instead of a simple algebraic summation of synaptic potentials in the soma, different dendritic compartments contribute to the integration of multiple inputs, thus endowing the neuron with a powerful computational ability. Most pyramidal neurons share common functional properties. However, different and sometimes contrasting dendritic integration rules are also observed. In this review, we focus on the dendritic integration of two neighboring pyramidal neurons in the hippocampus: the well-characterized CA1 and the much less understood CA2. The available data reveal that the dendritic integration of these neurons is markedly different even though they are targeted by common inputs at similar locations along their dendrites. This contrasting dendritic integration results in different routing of information flow and generates different corticohippocampal loops.     

Effects of elevated [CO2] on stem and root lodging among rice cultivars

Studies showed that elevated [CO2] would improve photosynthetic rates and enhance yields of rice;however,few studies have focused on the response of rice lodging,which is a major cause of cereal yield loss and quality reduction,under elevated [CO2].In this study,we examined the effects of elevated [CO2] on stem and root lodging using 4 rice cultivars(86Y8,japonica hybrid;LYP9,2-line indica hybrid;variety 9311,type of indica inbred rice,and SY63,3-line indica hybrid) grown under two [CO2] levels:400 and 680 μmol mol-1.Our results indicated that under elevated [CO2],the stem-lodging risk(SLR) of 9311 decreased,while in SY63 the SLR increased,86Y8 and LYP9 were not significantly affected;the risk of root lodging was reduced for all cultivars,because root biomass(instead of root number) and bending strength were increased significantly,and then the increase of anti-lodging ability is far higher than that of self-weight mass moment for all cultivars.These findings suggested that higher [CO2] can enhance the risk of stem-lodging for cultivars with strong-[CO2]-responses,but may not aggravate the root lodging for all rice cultivars.     

Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability

Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.