Haemophilus somnus possesses two systems for acquisition of transferrin-bound iron

Haemophilus somnus strain 649 was found to acquire iron from ovine, bovine, and goat transferrins (Tfs). Expression of Tf receptors, as evaluated by solid-phase binding assays, required the organisms to be grown under iron-restricted conditions in the presence of Tf. Competition binding assays revealed the presence of two distinct Tf-binding receptor systems, one specific for bovine Tf and the other capable of binding all three ruminant Tfs. Affinity isolation procedures using total membranes yielded three putative bovine Tf-binding polypeptides and one putative ovine and goat Tf-binding polypeptide. PCR amplification followed by DNA sequence analyses revealed that H. somnus strain 649 possesses genes that encode a bipartite TbpA-TbpB receptor along with a homolog of the Histophilus ovis single-component TbpA receptor. Expression of TbpB and the single-component TbpA would appear to be subject to a form of phase variation involving homopolymeric nucleotide tracts within the structural genes.     

Indicators of hippocampal neurogenesis are altered by 56Fe-particle irradiation in a dose-dependent manner

The health risks to astronauts exposed to high-LET radiation include possible cognitive deficits. The pathogenesis of radiation-induced cognitive injury is unknown but may involve loss of neural precursor cells from the subgranular zone (SGZ) of the hippocampal dentate gyrus. To address this hypothesis, adult female C57BL/6 mice received whole-body irradiation with a 1 GeV/nucleon iron-particle beam in a single fraction of 0, 1, 2 and 3 Gy. Two months later mice were given BrdU injections to label proliferating cells. Subsequently, hippocampal tissue was assessed using immunohistochemistry for detection of proliferating cells and immature neurons. Routine histopathological methods were used to qualitatively assess tissue/cell morphology in the hippocampal formation and adjacent areas. When compared to controls, irradiated mice showed progressively fewer BrdU-positive cells as a function of dose. This observation was confirmed by Ki-67 immunostaining in the SGZ showing reductions in a dose-dependent fashion. The progeny of the proliferating SGZ cells, i.e. immature neurons, were visualized by doublecortin staining and were significantly reduced by irradiation, with the decreases ranging from 34% after 1 Gy to 71% after 3 Gy. Histopathology showed that in addition to cell changes in the SGZ, (56)Fe particles induced a chronic and diffuse astrocytosis and changes in pyramidal neurons in and around the hippocampal formation. The present data provide the first evidence that high-LET radiation has deleterious effects on cells associated with hippocampal neurogenesis.     

Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid receptor TGR5

Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes.     

Bacterial Communities of Two Ubiquitous Great Barrier Reef Corals Reveals Both Site- and Species-Specificity of Common Bacterial Associates

Background

Coral-associated bacteria are increasingly considered to be important in coral health, and altered bacterial community structures have been linked to both coral disease and bleaching. Despite this, assessments of bacterial communities on corals rarely apply sufficient replication to adequately describe the natural variability. Replicated data such as these are crucial in determining potential roles of bacteria on coral.

Methodology/Principal Findings

Denaturing Gradient Gel Electrophoresis (DGGE) of the V3 region of the 16S ribosomal DNA was used in a highly replicated approach to analyse bacterial communities on both healthy and diseased corals. Although site-specific variations in the bacterial communities of healthy corals were present, host species-specific bacterial associates within a distinct cluster of gamma-proteobacteria could be identified, which are potentially linked to coral health. Corals affected by “White Syndrome” (WS) underwent pronounced changes in their bacterial communities in comparison to healthy colonies. However, the community structure and bacterial ribotypes identified in diseased corals did not support the previously suggested theory of a bacterial pathogen as the causative agent of the syndrome.

Conclusions/Significance

This is the first study to employ large numbers of replicated samples to assess the bacterial communities of healthy and diseased corals, and the first culture-independent assessment of bacterial communities on WS affected Acroporid corals on the GBR. Results indicate that a minimum of 6 replicate samples are required in order to draw inferences on species, spatial or health-related changes in community composition, as a set of clearly distinct bacterial community profiles exist in healthy corals. Coral bacterial communities may be both site and species specific. Furthermore, a cluster of gamma-proteobacterial ribotypes may represent a group of specific common coral and marine invertebrate associates. Finally, the results did not support the contention that a single bacterial pathogen may be the causative agent of WS Acroporids on the GBR.     

Structure Determination and Improved Model of Plant Photosystem I

Photosystem I functions as a sunlight energy converter, catalyzing one of the initial steps in driving oxygenic photosynthesis in cyanobacteria, algae, and higher plants. Functionally, Photosystem I captures sunlight and transfers the excitation energy through an intricate and precisely organized antenna system, consisting of a pigment network, to the center of the molecule, where it is used in the transmembrane electron transfer reaction. Our current understanding of the sophisticated mechanisms underlying these processes has profited greatly from elucidation of the crystal structures of the Photosystem I complex. In this report, we describe the developments that ultimately led to enhanced structural information of plant Photosystem I. In addition, we report an improved crystallographic model at 3.3-Å resolution, which allows analysis of the structure in more detail. An improved electron density map yielded identification and tracing of subunit PsaK. The location of an additional ten β-carotenes as well as five chlorophylls and several loop regions, which were previously uninterpretable, are now modeled. This represents the most complete plant Photosystem I structure obtained thus far, revealing the locations of and interactions among 17 protein subunits and 193 non-covalently bound photochemical cofactors. Using the new crystal structure, we examine the network of contacts among the protein subunits from the structural perspective, which provide the basis for elucidating the functional organization of the complex.     

Genomic and epigenomic instability, fragile sites, schizophrenia and autism

Increasing evidence links genomic and epigenomic instability, including multiple fragile sites regions to neuropsychiatric diseases including schizophrenia and autism. Cancer is the only other disease associated with multiple fragile site regions, and genome and epigenomic instability is a characteristic of cancer. Research on cancer is far more advanced than research on neuropsychiatric disease; hence, insight into neuropsychiatric disease may be derived from cancer research results. Towards this end, this article will review the evidence linking schizophrenia and other neuropsychiatric diseases (especially autism) to genomic and epigenomic instability, and fragile sites. The results of studies on genetic, epigenetic and environmental components of schizophrenia and autism point to the importance of the folate-methionine-transulfuration metabolic hub that is diseases also perturbed in cancer. The idea that the folate-methionine-transulfuration hub is important in neuropsychiatric is exciting because this hub present novel targets for drug development, suggests some drugs used in cancer may be useful in neuropsychiatric disease, and raises the possibility that nutrition interventions may influence the severity, presentation, or dynamics of disease.     

Testing Putative African Tropical Forest Refugia Using Chloroplast and Nuclear DNA Phylogeography

The location and definition of Pleistocene refugia for tropical forest assemblages remains controversial. Phylogeographic methods have been used successfully in temperate ecosystems to locate past forest refugia using genetic data that coincide with pollen core evidence, and in some cases provide the sole basis for their location. Here we present molecular phylogeographic data from nuclear and chloroplast loci for the forest tree Irvingia gabonensis, across the majority of its natural range, in Nigeria, Cameroon and Gabon. It is the first detailed phylogeographic study to posit the location of tropical forest refugia across this region of Africa. Using the same method of restriction fragment length polymorphism screening, 17 alleles were identified across five anonymous nuclear loci and two haplotypes at a single chloroplast locus. Analysis based on nuclear variation identified two genetically diverse, differentiated allelic clusters within the species range, one in southern Nigeria/western Cameroon and the other in southwestern Cameroon. Molecular data are consistent with a historical genetic contraction and bottleneck into these regions in the Pleistocene and/or Holocene, which has been followed by subsequent expansion. Both genetic refugia are located within areas previously suggested as forest refugia from biogeographic studies, supported by available pollen core data, and occur either side of the Sanaga River, a notable biogeographic divide for mammals (particularly primates). Other putative refugia in Gabon do not appear to have acted as genetic refugia for I. gabonensis, and Gabon was most likely recolonised from the SW Cameroon refugial source. In this study, nuclear loci were able to highlight significant phylogeographic structure across the range of a tropical African tree, whereas chloroplast analysis gave a much more limited picture. With the increased availability of sequence data for non-model species, the de novo development and further application of nuclear loci is strongly recommended for phylogeographic studies of plants.     

Relationship between patient-reported disease severity in osteoarthritis and self-reported pain, function and work productivity

Introduction

The purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA).

Methods

Systemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105.

Results

At baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3).

Conclusions

Synovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.