Locomotor anatomy and biomechanics of the Dmanisi hominins

The Dmanisi hominins inhabited a northern temperate habitat in the southern Caucasus, approximately 1.8 million years ago. This is the oldest population of hominins known outside of Africa. Understanding the set of anatomical and behavioral traits that equipped this population to exploit their seasonal habitat successfully may shed light on the selection pressures shaping early members of the genus Homo and the ecological strategies that permitted the expansion of their range outside of the African subtropics. The abundant stone tools at the site, as well as taphonomic evidence for butchery, suggest that the Dmanisi hominins were active hunters or scavengers. In this study, we examine the locomotor mechanics of the Dmanisi hind limb to test the hypothesis that the inclusion of meat in the diet is associated with an increase in walking and running economy and endurance. Using comparative data from modern humans, chimpanzees, and gorillas, as well as other fossil hominins, we show that the Dmanisi hind limb was functionally similar to modern humans, with a longitudinal plantar arch, increased limb length, and human-like ankle morphology. Other aspects of the foot, specifically metatarsal morphology and tibial torsion, are less derived and similar to earlier hominins. These results are consistent with hypotheses linking hunting and scavenging to improved walking and running performance in early Homo. Primitive retentions in the Dmanisi foot suggest that locomotor evolution continued through the early Pleistocene.     

Revisiting the Association of Cationic Groove-Binding Drugs to DNA Using a Poisson-Boltzmann Approach

Proper modeling of nonspecific salt-mediated electrostatic interactions is essential to understanding the binding of charged ligands to nucleic acids. Because the linear Poisson-Boltzmann equation (PBE) and the more approximate generalized Born approach are applied routinely to nucleic acids and their interactions with charged ligands, the reliability of these methods is examined vis-à-vis an efficient nonlinear PBE method. For moderate salt concentrations, the negative derivative, SK_pred, of the electrostatic binding free energy, ΔG_el, with respect to the logarithm of the 1:1 salt concentration, [M⁺], for 33 cationic minor groove drugs binding to AT-rich DNA sequences is shown to be consistently negative and virtually constant over the salt range considered (0.1-0.4 M NaCl). The magnitude of SK_pred is approximately equal to the charge on the drug, as predicted by counterion condensation theory (CCT) and observed in thermodynamic binding studies. The linear PBE is shown to overestimate the magnitude of SK_pred, whereas the nonlinear PBE closely matches the experimental results. The PBE predictions of SK_pred were not correlated with ΔG_el in the presence of a dielectric discontinuity, as would be expected from the CCT. Because this correlation does not hold, parameterizing the PBE predictions of ΔG_el against the reported experimental data is not possible. Moreover, the common practice of extracting the electrostatic and nonelectrostatic contributions to the binding of charged ligands to biopolyelectrolytes based on the simple relation between experimental SK values and the electrostatic binding free energy that is based on CCT is called into question by the results presented here. Although the rigid-docking nonlinear PB calculations provide reliable predictions of SK_pred, at least for the charged ligand-nucleic acid complexes studied here, accurate estimates of ΔG_el will require further development in theoretical and experimental approaches.     

Extramedullary hematopoiesis in a case of benign mixed mammary tumor in a female dog: cytological and histopathological assessment

Backgroud  

Extramedullary hematopoiesis (EMH) is defined as the presence of hematopoietic stem cells such as erythroid and myeloid lineage plus megakaryocytes in extramedullary sites like liver, spleen and lymph nodes and is usually associated with either bone marrow or hematological disorders. Mammary EMH is a rare condition either in human and veterinary medicine and can be associated with benign mixed mammary tumors, similarly to that described in this case.     

Structure of a classical MHC class I molecule that binds "non-classical" ligands

Chicken YF1 genes share a close sequence relationship with classical MHC class I loci but map outside of the core MHC region. To obtain insights into their function, we determined the structure of the YF1*7.1/β₂-microgloblin complex by X-ray crystallography at 1.3 Å resolution. It exhibits the architecture typical of classical MHC class I molecules but possesses a hydrophobic binding groove that contains a non-peptidic ligand. This finding prompted us to reconstitute YF1*7.1 also with various self-lipids. Seven additional YF1*7.1 structures were solved, but only polyethyleneglycol molecules could be modeled into the electron density within the binding groove. However, an assessment of YF1*7.1 by native isoelectric focusing indicated that the molecules were also able to bind nonself-lipids. The ability of YF1*7.1 to interact with hydrophobic ligands is unprecedented among classical MHC class I proteins and might aid the chicken immune system to recognize a diverse ligand repertoire with a minimal number of MHC class I molecules.     

HIV-1 Populations in Semen Arise through Multiple Mechanisms

HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus.     

PeroxiBase: the peroxidase database

Peroxidases (EC 1.11.1.x), which are encoded by small or large multigenic families, are involved in several important physiological and developmental processes. Analyzing their evolution and their distribution among various phyla could certainly help to elucidate the mystery of their extremely widespread and diversified presence in almost all living organisms. PeroxiBase was originally created for the exhaustive collection of class III peroxidase sequences from plants (Bakalovic, N., Passardi, F., et al., 2006. PeroxiBase: a class III plant peroxidase database. Phytochemistry 67, 534-539). The extension of the class III peroxidase database to all proteins capable to reduce peroxide molecules appears as a necessity. Our database contains haem and non-haem peroxidase sequences originated from annotated or not correctly annotated sequences deposited in the main repositories such as GenBank or UniProt KnowledgeBase. This new database will allow obtaining a global overview of the evolution the protein families and superfamilies capable of peroxidase reaction. In this rapidly growing field, there is a need for continual updates and corrections of the peroxidase protein sequences. Following the lack of unified nomenclature, we also introduced a unique abbreviation for each different family of peroxidases. This paper thus aims to report the evolution of the PeroxiBase database, which is freely accessible through a web server (http://peroxibase.isb-sib.ch). In addition to new categories of peroxidases, new specific tools have been created to facilitate query, classification and submission of peroxidase sequences.     

Detection of diarrheagenic Escherichia coli from children with and without diarrhea in Salvador, Bahia, Brazil

We identified different diarrheagenic (DEC) Escherichia coli pathotypes isolated from 1,207 children with and without acute endemic diarrhea in Salvador, Bahia, Brazil collected as part of a case-control study. Since the identification of DEC cannot be based on only biochemical and culture criteria, we used a multiplex polymerase chain reaction developed by combining five specific primer pairs for Enteropathogenic Escherichia coli (EPEC), Shiga toxin-producing E. coli/ Enterohaemorrhagic E. coli (STEC/EHEC), Enterotoxigenic E. coli (ETEC) and Enteroaggregative E. coli (EAEC) to detect these pathotypes simultaneously in a single-step reaction. In order to distinguish typical and atypical EPEC strains, these were tested for the presence of EAF plasmid. The prevalence of diarrheagenic E. coli in this sample of a global case-control study was 25.4% (259 patients) and 18.7% (35 patients) in the diarrhea group (1,020 patients) and the control group (187 patients), respectively. The most frequently isolated pathotype was EAEC (10.7%), followed by atypical EPEC (9.4%), ETEC (3.7%), and STEC (0.6%). Typical EPEC was detected only in one sample. The prevalence of the pathotypes studied in children with diarrhea was not significantly different from that in children without diarrhea.     

Gene inactivation mediated by <Emphasis Type="Italic">Agrobacterium tumefaciens</Emphasis> in the filamentous fungi <Emphasis Type="Italic">Metarhizium anisopliae</Emphasis>

The list of fungal species with known complete genome and/or expressed sequence tag collections is extending rapidly during the last couple of years. Postgenomic gene function assignment is an obvious follow-up and depends on methodologies to test gene function in vivo. One of such methods is the generation of null mutants via homologous recombination at the wild–type loci by using inactivation cassettes. In this paper, the ability of Agrobacterium tumefaciens to genetically transform filamentous fungi was exploited to drive homologous recombination at the trp1 locus of the enthomopathogenic fungus Metarhizium anisopliae. The trp1 disruptants exhibited a clearly distinguishable phenotype from wild-type cells and were recovered with high efficiency of homologous recombination (22%). The complementation of such mutants with the wild-type gene generates only transformants with homologous integration.     

C-terminal tail phosphorylation of N-formyl peptide receptor: differential recognition of two neutrophil chemoattractant receptors by monoclonal antibodies NFPR1 and NFPR2

The N-formyl peptide receptor (FPR), a G protein-coupled receptor that binds proinflammatory chemoattractant peptides, serves as a model receptor for leukocyte chemotaxis. Recombinant histidine-tagged FPR (rHis-FPR) was purified in lysophosphatidyl glycerol (LPG) by Ni(2+)-NTA agarose chromatography to >95% purity with high yield. MALDI-TOF mass analysis (>36% sequence coverage) and immunoblotting confirmed the identity as FPR. The rHis-FPR served as an immunogen for the production of 2 mAbs, NFPR1 and NFPR2, that epitope map to the FPR C-terminal tail sequences, 305-GQDFRERLI-313 and 337-NSTLPSAEVE-346, respectively. Both mAbs specifically immunoblotted rHis-FPR and recombinant FPR (rFPR) expressed in Chinese hamster ovary cells. NFPR1 also recognized recombinant FPRL1, specifically expressed in mouse L fibroblasts. In human neutrophil membranes, both Abs labeled a 45-75 kDa species (peak M(r) approximately 60 kDa) localized primarily in the plasma membrane with a minor component in the lactoferrin-enriched intracellular fractions, consistent with FPR size and localization. NFPR1 also recognized a band of M(r) approximately 40 kDa localized, in equal proportions to the plasma membrane and lactoferrin-enriched fractions, consistent with FPRL1 size and localization. Only NFPR2 was capable of immunoprecipitation of rFPR in detergent extracts. The recognition of rFPR by NFPR2 is lost after exposure of cellular rFPR to f-Met-Leu-Phe (fMLF) and regained after alkaline phosphatase treatment of rFPR-bearing membranes. In neutrophils, NFPR2 immunofluorescence was lost upon fMLF stimulation. Immunoblotting approximately 60 kDa species, after phosphatase treatment of fMLF-stimulated neutrophil membranes, was also enhanced. We conclude that the region 337-346 of FPR becomes phosphorylated after fMLF activation of rFPR-expressing Chinese hamster ovary cells and neutrophils.     

Extended gene map reveals tripartite motif, C-type lectin, and Ig superfamily type genes within a subregion of the chicken MHC-B affecting infectious disease

MHC haplotypes have a remarkable influence on whether tumors form following infection of chickens with oncogenic Marek's disease herpesvirus. Although resistance to tumor formation has been mapped to a subregion of the chicken MHC-B region, the gene or genes responsible have not been identified. A full gene map of the subregion has been lacking. We have expanded the MHC-B region gene map beyond the 92-kb core previously reported for another haplotype revealing the presence of 46 genes within 242 kb in the Red Jungle Fowl haplotype. Even though MHC-B is structured differently, many of the newly revealed genes are related to loci typical of the MHC in other species. Other MHC-B loci are homologs of genes found within MHC paralogous regions (regions thought to be derived from ancient duplications of a primordial immune defense complex where genes have undergone differential silencing over evolutionary time) on other chromosomes. Still others are similar to genes that define the NK complex in mammals. Many of the newly mapped genes display allelic variability and fall within the MHC-B subregion previously shown to affect the formation of Marek's disease tumors and hence are candidates for genes conferring resistance.