Vesta's surface is characterized by abundant impact craters, some with preserved ejecta blankets, large troughs extending around the equatorial region, enigmatic dark material, and widespread mass wasting, but as yet an absence of volcanic features. Abundant steep slopes indicate that impact-generated surface regolith is underlain by bedrock. Dawn observations confirm the large impact basin (Rheasilvia) at Vesta's south pole and reveal evidence for an earlier, underlying large basin (Veneneia). Vesta's geology displays morphological features characteristic of the Moon and terrestrial planets as well as those of other asteroids, underscoring Vesta's unique role as a transitional solar system body.

Causes of autosomal-recessive intellectual disability (ID) have, until very recently, been under researched because of the high degree of genetic heterogeneity. However, now that genome-wide approaches can be applied to single multiplex consanguineous families, the identification of genes harboring disease-causing mutations by autozygosity mapping is expanding rapidly. Here, we have mapped a disease locus in a consanguineous Pakistani family affected by ID and distal myopathy. We genotyped family members on genome-wide SNP microarrays and used the data to determine a single 2.5 Mb homozygosity-by-descent (HBD) locus in region 5p15.32-p15.31; we identified the missense change c.2035G>A (p.Gly679Arg) at a conserved residue within NSUN2. This gene encodes a methyltransferase that catalyzes formation of 5-methylcytosine at C34 of tRNA-leu(CAA) and plays a role in spindle assembly during mitosis as well as chromosome segregation. In mouse brains, we show that NSUN2 localizes to the nucleolus of Purkinje cells in the cerebellum. The effects of the mutation were confirmed by the transfection of wild-type and mutant constructs into cells and subsequent immunohistochemistry. We show that mutation to arginine at this residue causes NSUN2 to fail to localize within the nucleolus. The ID combined with a unique profile of comorbid features presented here makes this an important genetic discovery, and the involvement of NSUN2 highlights the role of RNA methyltransferase in human neurocognitive development.

The concept of a trade-off has long played a prominent role in understanding the evolution of organismal interactions such as mutualism, parasitism, and competition. Given the complexity inherent to interactions between different evolutionary entities, ecological factors may especially limit the power of trade-off models to predict evolutionary change. Here, we use four case studies to examine the importance of ecological context for the study of trade-offs in organismal interactions:(1) resource-based mutualisms,(2) parasite transmission and virulence,(3) plant biological invasions, and (4) host range evolution in parasites and parasitoids. In the first two case studies, mechanistic trade-off models have long provided a strong theoretical framework but face the challenge of testing assumptions under ecologically realistic conditions. Work under the second two case studies often has a strong ecological grounding, but faces challenges in identifying or quantifying the underlying genetic mechanism of the trade-off. Attention is given to recent studies that have bridged the gap between evolutionary mechanism and ecological realism. Finally, we explore the distinction between ecological factors that mask the underlying evolutionary trade-offs, and factors that actually change the trade-off relationship between fitness-related traits important to organismal interactions.

Cr(3+), similar to Fe(3+), is transported into cells primarily via endocytosis as the metal-transferrin complex. As Cr(3+) ions are not readily reduced under biological conditions, the ion cannot be transported from endosomes by the same mechanism as iron that utilized divalent metal ion transporters. Cr(3+) has been hypothesized to potentially be transported as small ligand complexes with a free carboxylate functionality by monocarboxylate transporters (MCT), in a similar fashion to that proposed for Al(3+). Consequently, mouse C2C12 muscle cells were utilized to determine if Cr(3+) is potentially transported by MCT by examining the effects of MCT inhibitors on Cr and Fe transport and subcellular distribution when the metals are added as their transferrin complexes. The results suggest that Cr is not primarily transported by MCT from the endosomes to the cytosol, and that another mechanism for this transport needs to be identified.

The overwhelming majority of Rett syndrome cases are caused by mutations in the gene MECP2. MECP2 has two isoforms, termed MECP2_e1 and MECP2_e2, which differ in their N-terminal amino acid sequences. A growing body of evidence has indicated that MECP2_e1 may be the etiologically relevant isoform in Rett Syndrome based on its expression profile in the brain and because, strikingly, no mutations have been discovered that affect MECP2_e2 exclusively. In this study we sought to characterize four classical Rett patients with mutations that putatively affect only the MECP2_e1 isoform. Our hypothesis was that the classical Rett phenotype seen here is the result of disrupted MECP2_e1 expression, but with MECP2_e2 expression unaltered. We used quantitative reverse transcriptase PCR to assay mRNA expression for each isoform independently, and used cytospinning methods to assay total MECP2 in peripheral blood lymphocytes (PBL). In the two Rett patients with identical 11 bp deletions within the coding portion of exon 1, MECP2_e2 levels were unaffected, whilst a significant reduction of MECP2_e1 levels was detected. In two Rett patients harboring mutations in the exon 1 start codon, MECP2_e1 and MECP2_e2 mRNA amounts were unaffected. In summary, we have shown that patients with exon 1 mutations transcribe normal levels of MECP2_e2 mRNA, and most PBL are positive for MeCP2 protein, despite them theoretically being unable to produce the MECP2_e1 isoform, and yet still exhibit the classical RTT phenotype. Altogether, our work further supports our hypothesis that MECP2_e1 is the predominant isoform involved in the neuropathology of Rett syndrome. © 2011 Wiley Periodicals, Inc.

Transition metal-polyalanine complexes were analyzed in a high-capacity quadrupole ion trap after electrospray ionization. Polyalanines have no polar amino acid side chains to coordinate metal ions, thus allowing the effects metal ion interaction with the peptide backbone to be explored. Positive mode mass spectra produced from peptides mixed with salts of the first row transition metals Cr(III), Fe(II), Fe(III), Co(II), Ni(II), Cu(I), and Cu(II) yield singly and doubly charged metallated ions. These precursor ions undergo collision-induced dissociation (CID) to give almost exclusively metallated N-terminal product ions whose types and relative abundances depend on the identity of the transition metal. For example, Cr(III)-cationized peptides yield CID spectra that are complex and have several neutral losses, whereas Fe(III)-cationized peptides dissociate to give intense non-metallated products. The addition of Cu(II) shows the most promise for sequencing. Spectra obtained from the CID of singly and doubly charged Cu-heptaalanine ions,[M + Cu - H](+) and [M + Cu](2+), are complimentary and together provide cleavage at every residue and no neutral losses.(This contrasts with [M + H](+) of heptaalanine, where CID does not provide backbone ions to sequence the first three residues.) Transition metal cationization produces abundant metallated a-ions by CID, unlike protonated peptides that produce primarily b- and y-ions. The prominence of metallated a-ions is interesting because they do not always form from b-ions. Tandem mass spectrometry on metallated (Met = metal) a- and b-ions indicate that [b(n)  + Met - H](2+) lose CO to form [a(n)  + Met - H](2+), mimicking protonated structures. In contrast,[a(n)  + Met - H](2+) eliminate an amino acid residue to form [a(n-1)  + Met - H](2+), which may be useful in sequencing. Copyright © 2011 John Wiley & Sons, Ltd.

One of the challenges for sequencing peptides by MS-MS is the interpretation of complex fragment ion patterns. Many approaches have been explored seeking to produce fragmentation patterns that are more predictable and thus easier to interpret. One of these involves the formation of a gas-phase adduct of peptide with a metal ion which acts to preferentially activate certain fragmentation pathways. In this month's Special Feature, Prof. Carolyn Cassady and co-workers at the University of Alabama (Tuscaloosa, AL) examine the fragmentation patterns produced from first-row transition metal adducts of some model peptides with the goal of gaining insight into the gas-phase chemistry of transition metal-cationized peptides and to increase the understanding of how specific transition metal ions affect dissociation of the peptide backbone.

Vincent AK, Noor A, Janson A, Minassian BA, Ayub M, Vincent JB, Morel CF. Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures. Recently, missense and truncating mutations in the gene PCDH19 have been reported to cause female-restricted epilepsy with mental retardation (EFMR). EFMR (MIM#300088) is an X-linked disorder characterized by early onset seizures and intellectual disability (ID). Interestingly, unlike typical X-linked mode of inheritance, the phenotype is restricted to females, and males are unaffected carriers. PCDH19 is highly expressed in brain, and the encoded protein belongs to the cadherin superfamily. Here we report two unrelated female patients with deletions spanning PCDH19 identified by copy number variation (CNV) analysis and validated by qPCR. In one, we have identified a 3 Mb interstitial deletion at Xq21.33-q22.1 which spans PCDH19, LOC442459 & TNMD. This patient had her first seizure at 8 months old, and also has ID and aggressive behavior. In another female patient we identified a de novo 603 kb heterozygous deletion in a female patient with fits (since 1 year of age), ID, hyperactivity and aggressive behavior. The deletion spans the entire PCDH19 gene (also TNMD, SRPX2, TSPAN6 and SYTL4). In conclusion, our results suggest that deletions at PCDH19 also cause EFMR.

Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.