Heterochromatin, synaptonemal complex, and NOR activity in the somatic and germ cells of a male domestic dog, Canis familiaris (Mammalia, Canidae)

C-banding and silver staining of the somatic and germ cells of the male domestic dog. Canis familiaris, have shown that: (1) the amount of C-banding is small compared to most other mammalian species, (2) three pairs of autosomes have nucleolus organizer regions (NORs) at the terminal ends of their long arms, whereas the Y chromosome has an NOR on the terminal end of the short arm, (3) the organization of the synaptonemal complex (SC) is similar to that of other mammalian species, (4) a distinct SC is formed between the long arm of the Y chromosome and probably the short arm of the X chromosome, and (5) the differential axes of both sex chromosomes do not demonstrate fusiform thickenings nor do they stain darkly with silver as do the XY bivalents in many other mammalian species.     

Nitrogen fixation by Cercocarpus ledifolius (Rosaceae) in pioneer habitats

Summary Soil properties of pioneer Pinus flexilis stands with similar topography and climate were investigated. Soils supporting this tree in association with Cercocarpus ledifolius were found to have higher percentages of total nitrogen than soils beneath similar stands lacking Cercocarpus.An excavated Cercocarpus ledifolius shrub in a Pinus flexilis stand in the San Bernardino Mountains of California was found to be nodulated and these nodules were found to be capable of fixing nitrogen. Other known nitrogen-fixing shrubs are frequent associates of Pinus flexilis in extreme sites.Implications of the phylogenetic relationship of some nitrogen-fixing species are briefly discussed, as well as their frequent occurrence in pioneer or extreme habitats.     

Health and Human Rights in Eastern Myanmar after the Political Transition: A Population-Based Assessment Using Multistaged Household Cluster Sampling

BackgroundMyanmar transitioned to a nominally civilian parliamentary government in March 2011. Qualitative reports suggest that exposure to violence and displacement has declined while international assistance for health services has increased. An assessment of the impact of these changes on the health and human rights situation has not been published.ConclusionThis large survey of health and human rights demonstrates that two years after political transition, vulnerable populations of eastern Myanmar are less likely to experience human rights violations compared to previous surveys. However, access to health services remains constrained, and risk of disease and death remains higher than the country as a whole. Efforts to address these poor health indicators should prioritize support for populations that remain outside the scope of most formal government and donor programs.     

Symbol nomenclature for representing glycan structures: Extension to cover different carbohydrate types

This Viewpoint article addresses comments made on our original article describing a symbolic system for the depiction of N- and O-linked carbohydrate structures and proposes a method for extending the symbol set to include monosaccharides commonly found in carbohydrates present in bacteria and plants. As before, basic monosaccharides are shown by shape with one or more additions such as solid fill or additions of lines, crosses or dots to represent functional groups. The use of colour to differentiate constituent monosaccharides is avoided, thus enabling the system to be used in a variety of formats. Linkage and anomericity are shown by the angle and type of line connecting the symbols. In this extended version, new symbols are proposed for additional hexoses and it is proposed that pyranose and furanose forms of the monosaccharides could be shown by solid or broken outlines to the symbols. Conventions for depicting the presence of multiple functional groups such as deoxy-(NH(2))(2) are also discussed. It is hoped that these proposals will stimulate discussion so that a consensus can be reached as to how the glycobiology community can best convey complex information in a simple manner.     

Structure and function of a cyanophage-encoded peptide deformylase

Bacteriophages encode auxiliary metabolic genes that support more efficient phage replication. For example, cyanophages carry several genes to maintain host photosynthesis throughout infection, shuttling the energy and reducing power generated away from carbon fixation and into anabolic pathways. Photodamage to the D1/D2 proteins at the core of photosystem II necessitates their continual replacement. Synthesis of functional proteins in bacteria requires co-translational removal of the N-terminal formyl group by a peptide deformylase (PDF). Analysis of marine metagenomes to identify phage-encoded homologs of known metabolic genes found that marine phages carry PDF genes, suggesting that their expression during infection might benefit phage replication. We identified a PDF homolog in the genome of Synechococcus cyanophage S-SSM7. Sequence analysis confirmed that it possesses the three absolutely conserved motifs that form the active site in PDF metalloproteases. Phylogenetic analysis placed it within the Type 1B subclass, most closely related to the Arabidopsis chloroplast PDF, but lacking the C-terminal α-helix characteristic of that group. PDF proteins from this phage and from Synechococcus elongatus were expressed and characterized. The phage PDF is the more active enzyme and deformylates the N-terminal tetrapeptides from D1 proteins more efficiently than those from ribosomal proteins. Solution of the X-ray/crystal structures of those two PDFs to 1.95 Å resolution revealed active sites identical to that of the Type 1B Arabidopsis chloroplast PDF. Taken together, these findings show that many cyanophages encode a PDF with a D1 substrate preference that adds to the repertoire of genes used by phages to maintain photosynthetic activities.     

Soluble androgen receptor oligomers underlie pathology in a mouse model of spinobulbar muscular atrophy

In polyglutamine diseases such as X-linked spinobulbar muscular atrophy (SBMA), it is unknown whether the toxic form of the protein is an insoluble or soluble aggregate or a monomer. We have addressed this question by studying a full-length androgen receptor (AR) mouse model of SBMA. We used biochemistry and atomic force microscopy to immunopurify oligomers soluble after ultracentrifugation that are comprised of a single approximately 50-kDa N-terminal polyglutamine-containing AR fragment. AR oligomers appeared several weeks prior to symptom onset, were distinct and temporally dissociated from intranuclear inclusions, and disappeared rapidly after castration, which halts disease. This is the first demonstration of soluble AR oligomers in vivo and suggests that they underlie neurodegeneration in SBMA.     

The heparanome--the enigma of encoding and decoding heparan sulfate sulfation

Heparan sulfate (HS) is a cell surface carbohydrate polymer modified with sulfate moieties whose highly ordered composition is central to directing specific cell signaling events. The ability of the cell to generate these information rich glycans with such specificity has opened up a new field of "heparanomics" which seeks to understand the systems involved in generating these cell type and developmental stage specific HS sulfation patterns. Unlike other instances where biological information is encrypted as linear sequences in molecules such as DNA, HS sulfation patterns are generated through a non-template driven process. Thus, deciphering the sulfation code and the dynamic nature of its generation has posed a new challenge to system biologists. The recent discovery of two sulfatases, Sulf1 and Sulf2, with the unique ability to edit sulfation patterns at the cell surface, has opened up a new dimension as to how we understand the regulation of HS sulfation patterning and pattern-dependent cell signaling events. This review will focus on the functional relationship between HS sulfation patterning and biological processes. Special attention will be given to Sulf1 and Sulf2 and how these key editing enzymes might act in concert with the HS biosynthetic enzymes to generate and regulate specific HS sulfation patterns in vivo. We will further explore the use of knock out mice as biological models for understanding the dynamic systems involved in generating HS sulfation patterns and their biological relevance. A brief overview of new technologies and innovations summarizes advances in the systems biology field for understanding non-template molecular networks and their influence on the "heparanome".     

ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor

Motor neuron degeneration resulting from the aggregation of the androgen receptor with an expanded polyglutamine tract (AR-polyQ) has been linked to the development of spinal and bulbar muscular atrophy (SBMA or Kennedy disease). Here we report that adding 5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one (ASC-J9) disrupts the interaction between AR and its coregulators, and also increases cell survival by decreasing AR-polyQ nuclear aggregation and increasing AR-polyQ degradation in cultured cells. Intraperitoneal injection of ASC-J9 into AR-polyQ transgenic SBMA mice markedly improved disease symptoms, as seen by a reduction in muscular atrophy. Notably, unlike previous approaches in which surgical or chemical castration was used to reduce SBMA symptoms, ASC-J9 treatment ameliorated SBMA symptoms by decreasing AR-97Q aggregation and increasing VEGF164 expression with little change of serum testosterone. Moreover, mice treated with ASC-J9 retained normal sexual function and fertility. Collectively, our results point to a better therapeutic and preventative approach to treating SBMA, by disrupting the interaction between AR and AR coregulators.     

The Potential effect of G915C polymorphism in regulating TGF-β1 transport into Endoplasmic Reticulum for cytokine production

The TGF-β1 cytokine concentration is known to be higher in nephritis with implied Lupus Nephritis severity. The production of TGF-β1 cytokine is associated with G915C polymorphism. Therefore, it is of interest to study G915C polymorphism. The G915C polymorphism changes codon 25 which encodes arginine into proline in the signal peptide of TGF-β1. The amino acid substitution affects signal peptide properties that may inhibit the transport of TGF-β1 into the endoplasmic reticulum and eventually decline the cytokine production. Hence, the effect of G915C polymorphism on the properties of the signal peptide, the ability of TGF-β1 transport into the endoplasmic reticulum and the concentrations of urinary TGF-β1 in Lupus Nephritis patients was studied. The arginine substitution into proline decreased the polarity of the signal peptide for TGF-β1. The increased hydrophobicity with increased binding energy of the signal peptide for TGF-β1 to Signal Recognition Particle (SRP) and translocon is shown. This implies decreased protein complex stability in potentially blocking the transport of TGF-β1 into the endoplasmic reticulum. This transport retention possibly hampers the synthesis and maturation of TGF-β1 leading to decreased cytokine production.     

Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB

Mucopolysaccharide diseases (MPS) are caused by deficiency of glycosaminoglycan (GAG) degrading enzymes, leading to GAG accumulation. Neurodegenerative MPS diseases exhibit cognitive decline, behavioural problems and shortened lifespan. We have characterised neuropathological changes in mouse models of MPSI, IIIA and IIIB to provide a better understanding of these events.Wild-type (WT), MPSI, IIIA and IIIB mouse brains were analysed at 4 and 9 months of age. Quantitative immunohistochemistry showed significantly increased lysosomal compartment, GM2 ganglioside storage, neuroinflammation, decreased and mislocalised synaptic vesicle associated membrane protein, (VAMP2), and decreased post-synaptic protein, Homer-1, in layers II/III-VI of the primary motor, somatosensory and parietal cortex. Total heparan sulphate (HS), was significantly elevated, and abnormally N-, 6-O and 2-O sulphated compared to WT, potentially altering HS-dependent cellular functions. Neuroinflammation was confirmed by significantly increased MCP-1, MIP-1α, IL-1α, using cytometric bead arrays. An overall genotype effect was seen in all parameters tested except for synaptophysin staining, neuronal cell number and cortical thickness which were not significantly different from WT. MPSIIIA and IIIB showed significantly more pronounced pathology than MPSI in lysosomal storage, astrocytosis, microgliosis and the percentage of 2-O sulphation of HS. We also observed significant time progression of all genotypes from 4-9 months in lysosomal storage, astrocytosis, microgliosis and synaptic disorganisation but not GM2 gangliosidosis. Individual genotype*time differences were disparate, with significant progression from 4 to 9 months only seen for MPSIIIB with lysosomal storage, MPSI with astrocytocis and MPSIIIA with microgliosis as well as neuronal loss. Transmission electron microscopy of MPS brains revealed dystrophic axons, axonal storage, and extensive lipid and lysosomal storage. These data lend novel insight to MPS neuropathology, suggesting that MPSIIIA and IIIB have more pronounced neuropathology than MPSI, yet all are still progressive, at least in some aspects of neuropathology, from 4-9 months.