Homo erectus found still further west: Reconstruction of the Kocabaş cranium (Denizli,Turkey)

Few human fossils are known in Turkey and no Homo erectus has been discovered until now. In this respect, the newly discovered partial skull from Kocaba? is very important: (1) to assess the pattern of the first settlements throughout the Old World; and (2) to document the extension of the species H. erectus to the west of continental Asia. Using CT data and 3D imaging techniques, this specimen was reconstructed and a more detailed analysis was done, including the inner anatomical features. The preliminary results of this study highlight that the fossil hominid from Kocaba? is close to the H. erectus species regarding the following cranial patterns: presence of a clear post-orbital constriction, strong development of the frontal brow-ridge with a depressed supratoral area in the lateral part, as well as endocranial patterns such as the development and orientation of the middle meningeal artery and the presence of a frontal bec. The Kocaba? skull is morphologically very close to the fossils from Zhoukoudian L-C. The partial Kocaba? skull is the oldest H. erectus known in Turkey and the only one from this species to have settled so far west in Asia.     

Nf1 RasGAP Inhibition of LIMK2 Mediates a New Cross-Talk between Ras and Rho Pathways

Background

Ras GTPases mediate numerous biological processes through their ability to cycle between an inactive GDP-bound form and an active GTP-bound form. Guanine nucleotide exchange factors (GEFs) favor the formation of the active Ras-GTP, whereas GTPase activating proteins (GAPs) promote the formation of inactive Ras-GDP. Numerous studies have established complex signaling cross-talks between Ras GTPases and other members of the superfamily of small GTPases. GEFs were thought to play a major role in these cross-talks. However, recently GAPs were also shown to play crucial roles in these processes. Among RasGAPs, Nf1 is of special interest. Nf1 is responsible for the genetic disease Neurofibromatosis type I, and recent data strongly suggest that this RasGAP connects different signaling pathways.

Methodology/Principal Findings

In order to know if the RasGAP Nf1 might play a role in connecting Ras GTPases to other small GTPase pathways, we systematically looked for new partners of Nf1, by performing a yeast two-hybrid screening on its SecPH domain. LIMK2, a major kinase of the Rho/ROCK/LIMK2/cofilin pathway, was identified in this screening. We confirmed this interaction by co-immunoprecipitation experiments, and further characterized it. We also demonstrated its specificity: the close related homolog of LIMK2, LIMK1, does not interact with the SecPH domain of Nf1. We then showed that SecPH partially inhibits the kinase activity of LIMK2 on cofilin. Our results furthermore suggest a precise mechanism for this inhibition: in fact, SecPH would specifically prevent LIMK2 activation by ROCK, its upstream regulator.

Conclusions/Significance

Although previous data had already connected Nf1 to actin cytoskeleton dynamics, our study provides for the first time possible detailed molecular requirements of this involvement. Nf1/LIMK2 interaction and inhibition allows to directly connect neurofibromatosis type I to actin cytoskeleton remodeling, and provides evidence that the RasGAP Nf1 mediates a new cross-talk between Ras and Rho signaling pathways within the superfamily of small GTPases.     

A 5-formyltetrahydrofolate cycloligase paralog from all domains of life: comparative genomic and experimental evidence for a cryptic role in thiamin metabolism

A paralog (here termed COG0212) of the ATP-dependent folate salvage enzyme 5-formyltetrahydrofolate cycloligase (5-FCL) occurs in all domains of life and, although typically annotated as 5-FCL in pro- and eukaryotic genomes, is of unknown function. COG0212 is similar in overall structure to 5-FCL, particularly in the substrate binding region, and has distant similarity to other kinases. The Arabidopsis thaliana COG0212 protein was shown to be targeted to chloroplasts and to be required for embryo viability. Comparative genomic analysis revealed that a high proportion (19%) of archaeal and bacterial COG0212 genes are clustered on the chromosome with various genes implicated in thiamin metabolism or transport but showed no such association between COG0212 and folate metabolism. Consistent with the bioinformatic evidence for a role in thiamin metabolism, ablating COG0212 in the archaeon Haloferax volcanii caused accumulation of thiamin monophosphate. Biochemical and functional complementation tests of several known and hypothetical thiamin-related activities (involving thiamin, its breakdown products, and their phosphates) were, however, negative. Also consistent with the bioinformatic evidence, the COG0212 proteins from A. thaliana and prokaryote sources lacked 5-FCL activity in vitro and did not complement the growth defect or the characteristic 5-formyltetrahydrofolate accumulation of a 5-FCL-deficient (ΔygfA) Escherichia coli strain. We therefore propose (a) that COG0212 has an unrecognized yet sometimes crucial role in thiamin metabolism, most probably in salvage or detoxification, and (b) that is not a 5-FCL and should no longer be so annotated.     

Next-generation sequencing for identifying new genes in rare genetic diseases: many challenges and a pinch of luck

A report on the European Society of Human Genetics conference, held in Paris, France, June 8-11, 2013.     

Expression of a new chimeric protein with a highly repeated sequence in tobacco cells

In wheat, the high-molecular weight (HMW) glutenin subunits are known to contribute to gluten viscoelasticity, and show some similarities to elastomeric animal proteins as elastin. When combining the sequence of a glutenin with that of elastin is a way to create new chimeric functional proteins, which could be expressed in plants. The sequence of a glutenin subunit was modified by the insertion of several hydrophobic and elastic motifs derived from elastin (elastin-like peptide, ELP) into the hydrophilic repetitive domain of the glutenin subunit to create a triblock protein, the objective being to improve the mechanical (elastomeric) properties of this wheat storage protein. In this study, we investigated an expression model system to analyze the expression and trafficking of the wild-type HMW glutenin subunit (GS_W) and an HMW glutenin subunit mutated by the insertion of elastin motifs (GS_M-ELP). For this purpose, a series of constructs was made to express wild-type subunits and subunits mutated by insertion of elastin motifs in fusion with green fluorescent protein (GFP) in tobacco BY-2 cells. Our results showed for the first time the expression of HMW glutenin fused with GFP in tobacco protoplasts. We also expressed and localized the chimeric protein composed of plant glutenin and animal elastin-like peptides (ELP) in BY-2 protoplasts, and demonstrated its presence in protein body-like structures in the endoplasmic reticulum. This work, therefore, provides a basis for heterologous production of the glutenin-ELP triblock protein to characterize its mechanical properties.     

Investigation of mercury concentrations in fur of phocid seals using stable isotopes as tracers of trophic levels and geographical regions

Recent studies have shown that the complementary analysis of mercury (Hg) concentrations and stable isotopic ratios of nitrogen (δ¹⁵N) and carbon (δ¹³C) can be useful for investigating the trophic influence on the Hg exposure and accumulation in marine top predators. In this study, we propose to evaluate the interspecies variability of Hg concentrations in phocids from polar areas and to compare Hg bioaccumulation between both hemispheres. Mercury concentrations, δ¹⁵N and δ¹³C were measured in fur from 85 individuals representing 7 phocidae species, a Ross seal (Ommatophoca rossii), Weddell seals (Leptonychotes weddellii), crabeater seals (Lobodon carcinophagus), harbour seals (Phoca vitulina), grey seals (Halichoerus grypus), ringed seals (Pusa hispida) and a bearded seal (Erignathus barbatus), from Greenland, Denmark and Antarctica. Our results showed a positive correlation between Hg concentrations and δ¹⁵N values among all individuals. Seals from the Northern ecosystems displayed greater Hg concentrations, δ¹⁵N and δ¹³C values than those from the Southern waters. Those geographical differences in Hg and stable isotopes values were likely due to higher environmental Hg concentrations and somewhat greater number of steps in Arctic food webs. Moreover, dissimilarities in feeding habits among species were shown through δ¹⁵N and δ¹³C analysis, resulting in an important interspecific variation in fur Hg concentrations. A trophic segregation was observed between crabeater seals and the other species, resulting from the very specific diet of krill of this species and leading to the lowest observed Hg concentrations.