Human papillomavirus is associated with monoclonal gammopathies of unknown significance

When monoclonal gammopathies arise in persons without evidence of plasma cell malignancy or lymphoproliferative disease, the term monoclonal gammopathy of unknown significance (MGUS) can be used. MGUS is believed to be the preneoplastic phase of lymphoproliferative diseases because many of these patients eventually develop malignant disease, mainly multiple myeloma. We have previously identified human papillomavirus (HPV) in a chronic benign plasma cell tumor of the cervix and in the bone marrow of multiple-myeloma patients. In the following study, we expanded upon our initial observation by analyzing 14 patients with MGUS. Bone marrow biopsies of the patients were analyzed for HPV sequences using polymerase chain reaction (PCR) and in situ hybridization. Normal controls included 26 bone marrow specimens, 24 analyzed by PCR and two by in situ hybridization. A significant association was found to exist between HPV and MGUS (p=0.001). Among 14 patients iwth MGUS, HPV sequences have been identified in 10 of the bone marrow biopsies. These results suggest that HPV can reside in the bone marrow of a premalignant lymphoproliferative disease.     

Micro and macro-habitat associations in saproxylic beetles: implications for biodiversity management

Restoration of habitats is critically important in preventing full realization of the extinction debt owed as a result of anthropogenic habitat destruction. Although much emphasis has been placed on macrohabitats, suitable microhabitats are also vital for the survival of most species. The aim of this large-scale field experiment was to evaluate the relative importance of manipulated microhabitats, i.e., dead wood substrates of spruce (snags, and logs that were burned, inoculated with wood fungi or shaded) and macrohabitats, i.e., stand types (clear-cuts, mature managed forests, and forest reserves) for species richness, abundance and assemblage composition of all saproxylic and red-listed saproxylic beetles. Beetles were collected in emergence traps in 30 forest stands in 2001, 2003, 2004 and 2006. More individuals emerged from snags and untreated logs than from burned and shaded logs, but species richness did not differ among substrates. Assemblage composition differed among substrates for both all saproxylics and red-listed saproxylic species, mainly attributed to different assemblage composition on snags. This suggests that the practise of leaving snags for conservation purposes should be complemented with log supplementation. Clear-cuts supported fewer species and different assemblages from mature managed forests and reserves. Neither abundance, nor species richness or assemblage composition differed between reserves and mature managed forests. This suggests that managed stands subjected to selective cutting, not clear-felling, maintain sufficient old growth characteristics and continuity to maintain more or less intact assemblages of saproxylic beetles. Thus, alternative management methods, e.g., continuity forestry should be considered for some of these stands to maintain continuity and conservation values. Furthermore, the significantly higher estimated abundance per ha of red-listed beetles in reserves underlines the importance of reserves for maintaining viable populations of rare red-listed species and as source areas for saproxylic species in boreal forest landscapes.     

Structural and genetical studies on the high-molecular-weight subunits of wheat glutenin

Summary The high-molecular-weight (HMW) subunits of glutenin from about 185 varieties were fractionated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). About 20 different, major subunits were distinguished by this technique although each variety contained, with only a few exceptions, between 3 and 5 subunits. Further inter-varietal substitution lines to those already described (Payne et al. 1980) were analysed and the results indicate that all the HMW subunits are controlled by the homoeologous group 1 chromosomes. All hexaploid varieties studied except ‘NapHal’ contained two major subunits controlled by chromosome 1D. Their genes were shown to be tightly linked genetically for only four different types of banding patterns were observed. The nominal molecular weights determined after fractionation in 10% polyacrylamide gels were between 110,000 and 115,000 for the larger of the two subunits and between 82,000 and 84,000 for the smaller. One quarter of the varieties contained only one major HMW subunit controlled by chromosome 1B whereas the rest had two. The chromosome 1B subunits were the most varied and nine different banding patterns were detected. All the subunits had mobilities which were intermediate between those of the two chromosome 1D-controlled subunits. Only two types of HMW subunit controlled by chromosome 1A were detected in all the varieties examined; a single variety never contained both of these subunits and 40% of varieties contained neither. The chromosome 1A-controlled subunits had slightly slower mobilities in 10% gels than the largest HMW subunit controlled by chromosome 1D. About 100 single grains were analysed from each of five different crosses of the type (F₁ of variety A × variety B) × variety C. The results indicate that the genes on chromosome 1B which control the synthesis of subunits 6, 7, 13, 14 and 17 are allelic, as are the genes of the chromosome 1A-controlled subunits, 1 and 2.     

A Regional Initiative to Reduce Skin Infections amongst Aboriginal Children Living in Remote Communities of the Northern Territory,Australia

Background

Linked to extreme rates of chronic heart and kidney disease, pyoderma is endemic amongst Aboriginal children in Australia''s Northern Territory (NT). Many of those with pyoderma will also have scabies. We report the results of a community-based collaboration within the East Arnhem Region, which aimed to reduce the prevalence of both skin infections in Aboriginal children.

Methodology/Principal Findings

Commencing September 2004, we conducted an ecological study that included active surveillance for skin infections amongst children aged <15 years in five remote East Arnhem communities over a three year period. Screening was undertaken by trained local community workers, usually accompanied by another project team member, using a standard data collection form. Skin infections were diagnosed clinically with the aid of a pictorial flip chart developed for the purpose. Topical 5% permethrin was provided for age-eligible children and all household contacts whenever scabies was diagnosed, whilst those with pyoderma were referred to the clinic for treatment in accordance with current guidelines. In addition, annual mass scabies treatment (5% permethrin cream) was offered to all community residents in accordance with current guidelines but was not directly observed. Pyoderma and scabies prevalence per month was determined from 6038 skin assessments conducted on 2329 children. Pyoderma prevalence dropped from 46.7% at baseline to a median of 32.4% (IQR 28.9%–41.0%) during the follow-up period – an absolute reduction of 14.7% (IQR 4.7%–16.8%). Compared to the first 18 months of observation, there was an absolute reduction in pyoderma prevalence of 18 cases per 100 children (95%CI −21.0, −16.1, p≤0.001) over the last 18 months. Treatment uptake increased over the same period (absolute difference 13.4%, 95%CI 3.3, 23.6). While scabies prevalence was unchanged, the prevalence of infected scabies (that is with superimposed pyoderma) decreased from 3.7% (95%CI 2.4, 4.9) to 1.5% (95%CI 0.7, 2.2), a relative reduction of 59%.

Conclusion

Although pyoderma prevalence remained unacceptably high, there was a substantial reduction overall with improvements in treatment uptake a critical factor. More acceptable alternatives, such as cotrimoxazole for pyoderma and ivermectin as a community-wide scabicide, warrant further investigation in these settings. We are encouraged by progress made through this work, where local action was led by local community members and primary health care providers with external training and support.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00884728","term_id":"NCT00884728"}}NCT00884728     

Descending vasa recta endothelium is an electrical syncytium

We examined gap junction coupling of descending vasa recta (DVR). DVR endothelial cells or pericytes were depolarized to record the associated capacitance transients. Virtually all endothelia and some pericytes exhibited prolonged transients lasting 10-30 ms. Carbenoxolone (100 microM) and 18beta-glycyrrhetinic acid (18betaGRA; 100 microM) markedly shortened the endothelial transients. Carbenoxolone and heptanol (2 mM) reduced the pericyte capacitance transients when they were prolonged. Lucifer yellow (LY; 2 mM) was dialyzed into the cytoplasm of endothelial cells and pericytes. LY spread diffusely along the endothelial monolayer, whereas in most pericytes, it was confined to a single cell. In some pericytes, complex patterns of LY spreading were observed. DVR cells were depolarized by voltage clamp as fluorescence of bis(1,3-dibarbituric acid)-trimethine oxanol [DiBAC(4)(3)] was monitored approximately 200 microm away. A 40-mV endothelial depolarization was accompanied by a 26.1 +/- 5.5-mV change in DiBAC(4)(3) fluorescence. DiBAC(4)(3) fluorescence did not change after 18betaGRA or when pericytes were depolarized. Similarly, propagated cytoplasmic Ca(2+) responses arising from mechanical perturbation of the DVR wall were attenuated by 18betaGRA or heptanol. Connexin (Cx) immunostaining showed predominant linear Cx40 and Cx43 in endothelia, whereas Cx37 stained smooth muscle actin-positive pericytes. We conclude that the DVR endothelium is an electrical syncytium and that gap junction coupling in DVR pericytes exists but is less pronounced.     

Early Proliferation Does Not Prevent the Loss of Oligodendrocyte Progenitor Cells during the Chronic Phase of Secondary Degeneration in a CNS White Matter Tract

Partial injury to the central nervous system (CNS) is exacerbated by additional loss of neurons and glia via toxic events known as secondary degeneration. Using partial transection of the rat optic nerve (ON) as a model, we have previously shown that myelin decompaction persists during secondary degeneration. Failure to repair myelin abnormalities during secondary degeneration may be attributed to insufficient OPC proliferation and/or differentiation to compensate for loss of oligodendrocyte lineage cells (oligodendroglia). Following partial ON transection, we found that sub-populations of oligodendroglia and other olig2+ glia were differentially influenced by injury. A high proportion of NG2+/olig2–, NG2+/olig2+ and CC1−/olig2+ cells proliferated (Ki67+) at 3 days, prior to the onset of death (TUNEL+) at 7 days, suggesting injury-related cues triggered proliferation rather than early loss of oligodendroglia. Despite this, a high proportion (20%) of the NG2+/olig2+ OPCs were TUNEL+ at 3 months, and numbers remained chronically lower, indicating that proliferation of these cells was insufficient to maintain population numbers. There was significant death of NG2+/olig2– and NG2−/olig2+ cells at 7 days, however population densities remained stable, suggesting proliferation was sufficient to sustain cell numbers. Relatively few TUNEL+/CC1+ cells were detected at 7 days, and no change in density indicated that mature CC1+ oligodendrocytes were resistant to secondary degeneration in vivo. Mature CC1+/olig2– oligodendrocyte density increased at 3 days, reflecting early oligogenesis, while the appearance of shortened myelin internodes at 3 months suggested remyelination. Taken together, chronic OPC decreases may contribute to the persistent myelin abnormalities and functional loss seen in ON during secondary degeneration.     

Prostaglandin E(2)-stimulated secretion of protein in the salivary glands of the lone star tick via a phosphoinositide signaling pathway

Previous studies identified a prostaglandin E(2) (PGE(2)) receptor in the salivary glands of partially fed female lone star ticks, Amblyomma americanum (L.). In the present studies, protein secretion from dispersed salivary gland acini was shown to be specific for PGE(2), as compared with PGF(2alpha) or the thromboxane analog U-46619, in accordance with their respective binding affinities for the PGE(2) receptor. Furthermore, the selective PGE(2) EP1 receptor agonist, 17-phenyl trinor PGE(2), was as effective as PGE(2) in stimulating secretion of anticoagulant protein. Calcium ionophore A-23187 (1 to 100 microM) stimulated secretion of anticoagulant protein in a dose-dependent manner but the voltage-gated Ca(2+)-channel blocker verapamil (1 to 1000 microM) and the receptor-mediated Ca(2+)-entry antagonist, SK&F 96365 (1 and 10 microM), and 5mM ethylene glycol bis(beta-aminoethyl ether)-N,NN', N'-tetraacetic acid (EGTA) had no appreciable effect on inhibiting PGE(2)-stimulated secretion of anticoagulant protein. PGE(2) (0.1 microM) and the non-hydrolyzable analog of guanosine triphosphate (GTP), GTPgammaS (10 microM), directly activated phospholipase C (PLC) in a membrane-enriched fraction of the salivary glands after PLC was first incubated with the PGE(2) EP1 receptor antagonist AH-6809, which presumably antagonized endogenous PGE(2) (0.3 microM) in the broken-cell-membrane-enriched fraction. TMB-8, an antagonist of intracellular inositol trisphosphate (IP(3)) receptors, inhibited PGE(2)-stimulated secretion. The results support the hypothesis that PGE(2) stimulates secretion of tick salivary gland protein via a phosphoinositide signaling pathway and mobilization of intracellular Ca(2+).     

Phylogenetic evidence for horizontal transfer of mutS alleles among naturally occurring Escherichia coli strains

mutS mutators accelerate the bacterial mutation rate 100- to 1,000-fold and relax the barriers that normally restrict homeologous recombination. These mutators thus afford the opportunity for horizontal exchange of DNA between disparate strains. While much is known regarding the mutS phenotype, the evolutionary structure of the mutS(+) gene in Escherichia coli remains unclear. The physical proximity of mutS to an adjacent polymorphic region of the chromosome suggests that this gene itself may be subject to horizontal transfer and recombination events. To test this notion, a phylogenetic approach was employed that compared gene phylogeny to strain phylogeny, making it possible to identify E. coli strains in which mutS alleles have recombined. Comparison of mutS phylogeny against predicted E. coli "whole-chromosome" phylogenies (derived from multilocus enzyme electrophoresis and mdh sequences) revealed striking levels of phylogenetic discordance among mutS alleles and their respective strains. We interpret these incongruences as signatures of horizontal exchange among mutS alleles. Examination of additional sites surrounding mutS also revealed incongruous distributions compared to E. coli strain phylogeny. This suggests that other regional sequences are equally subject to horizontal transfer, supporting the hypothesis that the 61.5-min mutS-rpoS region is a recombinational hot spot within the E. coli chromosome. Furthermore, these data are consistent with a mechanism for stabilizing adaptive changes promoted by mutS mutators through rescue of defective mutS alleles with wild-type sequences.     

Yield Results and Stability Analysis from the Sorghum Regional Biomass Feedstock Trial

Sorghum [Sorghum bicolor (L.) Moench] is one of four herbaceous dedicated bioenergy crops the U.S. Department of Energy identified as critical to annually produce one billion tons of dry biomass. Of these four crops, sorghum is unique as it is a drought-tolerant, annual crop established from seed that is readily tractable to genetic improvement. The purpose of this study was to assess the yield potential and stability of sorghums grown across diverse production environments in the USA. For this study, six sorghum genotypes (one cultivar, five hybrids) were grown in yield trials in seven locations in six states for 5 years (2008–2012). Variation in dry and fresh yield was attributable to not only genotypes, but also to the effects of year, location, and year × location. Even with the highest yielding genotype, environmental conditions were a major factor in determining the yield in a given year. This variability affects the consistency of the biomass supply for ethanol production. In general, the southeastern USA had the highest mean yields for fresh weight and dry weight, indicating that this area may be the most reliable for biomass production. A significant variation was detected among genotypes for fresh weight, dry weight, moisture content, and brix, revealing that sufficient variation within sorghum exists for continued improvement and that certain hybrids are more tractable for biomass/bioenergy production. With dedicated bioenergy sorghum germplasm and proper production environments, sorghum will be a valuable tool in the goal of the sustainable production of one billion tons of dry biomass each year in the USA.