Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

Compression use during an exercise intervention and associated changes in breast cancer-related lymphoedema

Aim This study assessed the association between compression use and changes in lymphoedema observed in women with breast cancer-related lymphoedema who completed a 12 week exercise intervention. Methods This work uses data collected from a 12 week exercise trial, whereby women were randomly allocated into either aerobic-based only (n=21) or resistance-based only (n=20) exercise. Compression use during the trial was at the participant’s discretion. Differences in lymphoedema (measured by L-Dex score and inter-limb circumference difference [%]) and associated symptoms between those who wore, and did not wear compression during the 12 week intervention were assessed. We also explored participants’ reasons surrounding compression during exercise. Results No significant interaction effect between time and compression use for lymphoedema was observed. There was no difference between groups over time in the number or severity of lymphoedema symptoms. Irrespective of compression use, there were trends for reductions in the proportion of women reporting severe symptoms, but lymphoedema status did not change. Individual reasons for the use of compression, or lack thereof, varied markedly. Conclusion Our findings demonstrated an absence of a positive or negative effect from compression use during exercise on lymphoedema. Current and previous findings suggest the clinical recommendation that garments must be worn during exercise is questionable, and its application requires an individualised approach.

Efficient surface modification of biomaterial to prevent biofilm formation and the attachment of microorganisms

Biomaterials play a fundamental role in disease management and the improvement of health care. In recent years, there has been a significant growth in the diversity, function, and number of biomaterials used worldwide. Yet, attachment of pathogenic microorganisms onto biomaterial surfaces remains a significant challenge that substantially undermines their clinical applicability, limiting the advancement of these systems. The emergence and escalating pervasiveness of antibiotic-resistant bacterial strains makes the management of biomaterial-associated nosocomial infections increasingly difficult. The conventional post-operative treatment of implant-caused infections using systemic antibiotics is often marginally effective, further accelerating the extent of antimicrobial resistance. Methods by which the initial stages of bacterial attachment and biofilm formation can be restricted or prevented are therefore sought. The surface modification of biomaterials has the potential to alleviate pathogenic biofouling, therefore preventing the need for conventional antibiotics to be applied.

QTL for nodal root angle in sorghum (Sorghum bicolor L. Moench) co-locate with QTL for traits associated with drought adaptation.

Nodal root angle in sorghum influences vertical and horizontal root distribution in the soil profile and is thus relevant to drought adaptation. In this study, we report for the first time on the mapping of four QTL for nodal root angle (qRA) in sorghum, in addition to three QTL for root dry weight, two for shoot dry weight, and three for plant leaf area. Phenotyping was done at the six leaf stage for a mapping population (n = 141) developed by crossing two inbred sorghum lines with contrasting root angle. Nodal root angle QTL explained 58.2% of the phenotypic variance and were validated across a range of diverse inbred lines. Three of the four nodal root angle QTL showed homology to previously identified root angle QTL in rice and maize, whereas all four QTL co-located with previously identified QTL for stay-green in sorghum. A putative association between nodal root angle QTL and grain yield was identified through single marker analysis on field testing data from a subset of the mapping population grown in hybrid combination with three different tester lines. Furthermore, a putative association between nodal root angle QTL and stay-green was identified using data sets from selected sorghum nested association mapping populations segregating for root angle. The identification of nodal root angle QTL presents new opportunities for improving drought adaptation mechanisms via molecular breeding to manipulate a trait for which selection has previously been very difficult.

Surface Modification of Biomaterials for Biofilm Control

Amongst various methods to attain sound antibacterial and antifouling properties, surface modification of biomaterials combines efficiency, processing flexibility, and most importantly, the ability to preserve favourable bulk properties, such as mechanical strength and chemical inertness. This chapter will first briefly discuss key parameters by which the biomaterial surface can be described, namely surface chemistry and morphology, and their individual and combined contributions to cell-surface interactions. More emphasis will be placed on surface morphology as the area of much debate. The chapter will then describe a range of available methodologies for surface modification, with plasma-assisted modification as one of the foci.

Genetic variation in tumour necrosis factor and lymphotoxin is not associated with endometriosis in an Australian sample

BACKGROUND Tumour necrosis factor (TNF) is a pleiotropic cytokine with a wide range of immunoregulatory effects. Variation in the promoter region of TNF and the neighbouring lymphotoxin alpha (LTA) gene might be associated with endometriosis. METHODS We examined the association between endometriosis and common single-nucleotide polymorphisms (SNPs) or haplotypes in the TNF/LTA region in an Australian sample by analysing 26 SNPs in 958 endometriosis cases and 959 unrelated controls. We selected functional SNPs in the coding and the promoter region of the TNF gene and HapMap tagging SNPs and typed them on a Sequenom MassARRAY platform. A key SNP (rs1800630) in the promoter region typed in previous studies did not give reliable results. Therefore, we also examined a statistically identical (r(2) = 1) SNP (siSNP) (rs2844482), identified using the web based program ssSNPer. RESULTS Genotype completion rate was 99.5% for SNPs spanning a region of 15.5 kb across the TNF/LTA locus. There was no evidence for association between endometriosis and TNF/LTA SNPs or SNP haplotypes in our case-control study. CONCLUSIONS Our data suggest both TNF and LTA genes are not major susceptibility genes for endometriosis.

Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia

Several lines of evidence have implicated the catechol-O-methyltransferase (COMT) gene as a candidate for schizophrenia (SZ) susceptibility, not only because it encodes a key dopamine catabolic enzyme but also because it maps to the velocardiofacial syndrome region of chromosome 22q11 which has long been associated with SZ predisposition. The interest in COMT as a candidate SZ risk factor has led to numerous case-control and family-based studies, with the majority placing emphasis on examining a functional Val/Met polymorphism within this enzyme. Unfortunately, these studies have continually produced conflicting results. To assess the genetic contribution of other COMT variants to SZ susceptibility, we investigated three single-nucleotide polymorphisms (SNPs) (rs737865, rs4633, rs165599) in addition to the Val/Met variant (rs4680) in a highly selected sample of Australian Caucasian families containing 107 patients with SZ. The Val/Met and rs4633 variants showed nominally significant associations with SZ (P<0.05), although neither of the individual SNPs remained significant after adjusting for multiple testing (most significant P=0.1174). However, haplotype analyses showed strong evidence of an association; the most significant being the three-marker haplotype rs737865-rs4680-rs165599 (global P=0.0022), which spans more than 26 kb. Importantly, conditional analyses indicated the presence of two separate and interacting effects within this haplotype, irrespective of gender. In addition, our results indicate the Val/Met polymorphism is not disease-causing and is simply in strong linkage disequilibrium with a causative effect, which interacts with another as yet unidentified variant approximately 20 kb away. These results may help explain the inconsistent results reported on the Val/Met polymorphism and have important implications for future investigations into the role of COMT in SZ susceptibility.

Risk factors associated with corneal nerve alteration in type 1 diabetes in the absence of neuropathy: A longitudinal in vivo corneal confocal microscopy study

Purpose The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over four years using in vivo corneal confocal microscopy (IVCM) in participants with type 1 diabetes and to identify significant risk factors associated with these alterations. Methods A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning IVCM, ocular screening, and health and metabolic assessment at baseline and the examinations continued for four subsequent annual visits. At each annual visit, eight central corneal images of the SNP were selected and analyzed to quantify corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL). Linear mixed model approaches were fitted to examine the relationship between risk factors and corneal nerve parameters. Results A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between corneal nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure or BMI. However, CNFD was negatively associated with HbA1c (β=-0.76, P<0.01) and age (β=-0.13, P<0.01) and positively related to high density lipids (HDL) (β=2.01, P=0.03). Higher HbA1c (β=-1.58, P=0.04) and age (β=-0.23, P<0.01) also negatively impacted CNBD. CNFL was only affected by higher age (β=-0.06, P<0.01). Conclusions Glycemic control, HDL and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent corneal nerve damage as well as the capability of IVCM for monitoring subclinical alterations in the corneal SNP in diabetes.

Nausea associated with migraines

Migraines are particularly common in young adults, with the prevalence reducing after the late 40s and early 50s years of age.1,2 Migraines are headaches that can have a throbbing or pulsating feeling, and often occur with nausea, vomiting, and sensitivity to light and sound. These headaches can last between a few hours to three days.1,3 They place a significant burden of disease on quality of life, and have a socio-economic impact through loss of productiveness and sick days.4 Most people report experiencing at least one migraine attack each month, with many reporting that migraine attacks interfered with their daily activities.2 Migraines have been ranked as the third most prevalent and seventh highest specific cause of disability around the world...

Possible involvement of a calcium-stimulated ATP-hydrolyzing activity associated with mycobacteriophage I3 in the DNA injection process.

Ca2+ ions are necessary for the successful propagation of mycobacteriophage I3. An assay for the phage DNA release in the presence of an isolated cell wall preparation from the host was established, and in this system Ca2+ ions also stimulated the release of DNA. The inhibition of phage DNA injection caused by Tween 80 (polyoxyethylene sorbitan monooleate), a nonionic detergent routinely used in mycobacterial cultures, was reversed by Ca2+. The presence of a phage-associated ATP-hydrolyzing activity was demonstrated. This enzyme was stimulated by Ca2+ ions and inhibited by Tween 80. From this and the behavior of the two agents at the level of DNA injection, as well as the fact that phage I3 has a contractile tail structure, we conclude that the phage-associated ATPase is involved in the DNA injection process.

Diversity and abundance of fungivorous thrips (Thysanoptera) associated with leaf-litter and bark across forest types and two tree genera in subtropical Australia

Leaf-litter thrips were much more common and diverse in dry sclerophyll forest than in wetter forest types in subtropical southeast Queensland, Australia. In dry sclerophyll forest, the species composition of thrips in leaf-litter was strongly differentiated from the thrips fauna associated with bark of the trees Eucalyptus major and Acacia melanoxylon (4 of 34 species in common). The species composition of bark-dwelling thrips was similar across the two tree species and also across two eucalypts with different bark types, Eucalyptus major (flaky) and Eucalyptus siderophloia (rough). The diversity of thrips from the leaf-litter was not differentiated across all of these tree species. Virtually all thrips collected were Phlaeothripidae, subfamilies Idolothripinae and Phlaeothripinae. Idolothripinae were associated almost exclusively with leaf-litter, but Phlaeothripinae were in leaf-litter and bark. The association of fungal-feeding thrips with dry sclerophyll forest raises questions about their ecological requirements and the role they play in nutrient cycling. © 2012 Copyright Taylor and Francis Group, LLC.

Short-range resource location by Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) demonstrates a strong preference for fungi associated with cotton seed

Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) is a common stored grain pest for which a wide range of suitable resources has been recorded. These beetles are facultatively fungivorous and their resource range may extend to fungi associated with non-grain resources (e.g. cotton seed) and other decaying plant matter. Little is known with respect to fungi in terms of resource location by these beetles in the field. We, therefore, conducted a series of experiments in laboratory arenas, glasshouse cages and the field to determine how beetles respond to grain resources in relation to cotton seed (together with its lint stubble and associated fungal flora). Results from the tests conducted in relatively small arenas and cages in the laboratory and glasshouse reveal that the responses of T. castaneum adults to food resources were twice as strong when walking as when flying (as measured by the proportion of the released beetles that were trapped). Also, a clear preference for linted cotton seeds was evident in walking T. castaneum, especially in small-scale arenas in the laboratory, where at least 60% of beetles released preferred linted cotton seeds over wheat and sorghum. Similarly, in cages (1 m3) they responded five times more strongly to linted cotton seed than to conventional grain resources. However, this pattern was not consistent with those obtained from field trapping over 20 m and the beetles did not show any particular preference to any of the resources tested above. Our results suggest a focus on walking beetles in trapping studies for population estimations and, for developing effective food-based trapping lures, the potential use of active volatiles from the fungi associated with linted cotton seed. © 2012 Elsevier Ltd.

Responses of tribolium castaneum to olfactory cues from cotton seeds, the fungi associated with cotton seeds, and cereals

We tested, in an olfactometer, whether or not Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) responds preferentially to the volatiles that emanate from the fungi associated with cotton [Gossypium hirsutum L. (Malvaceae)] seed over those that emanate from cereals, because cereals are usually portrayed as the primary resources of these beetles. Pairwise comparisons were conducted between cotton seed, wheat (Triticum aestivum L.), and sorghum [Sorghum bicolor (L.) Moench] (both Poaceae); volatiles were tested from intact seeds and from both water and ethanol extracts. The results demonstrate that T. castaneum is attracted more strongly to cotton seeds with its lint contaminated with fungi, than to the conventional resources of this species (i.e., wheat and sorghum). Further tests prove that it is the fungus on the lint that produces the active volatiles, because the beetles did not respond to sterilized cotton lint (i.e., without the fungi typically associated with it when cotton seed is stored). Tests with five fungal cultures (each representing an unidentified species that was isolated from the field-collected cotton lint) were variable across the cultures, with only one of them being significantly attractive to the beetles. The others were not attractive and one may even have repulsed the beetles. The results are consistent with the beetles having a strong ecological association with fungi and suggest it would be worth investigating the ecology of T. castaneum from this perspective. © 2012 The Netherlands Entomological Society.

Identification of a new Polerovirus (family Luteoviridae) associated with cotton bunchy top disease in Australia

Cotton bunchy top (CBT) disease has caused significant yield losses in Australia and is now managed by control of its vector, the cotton aphid (Aphis gossypii). Its mode of transmission and similarities in symptoms to cotton Blue Disease suggested it may also be caused by a luteovirus or related virus. Degenerate primers to conserved regions of the genomes of the family Luteoviridae were used to amplify viral cDNAs from CBT-affected cotton leaf tissue that were not present in healthy plants. Partial genome sequence of a new virus (Cotton bunchy top virus, CBTV) was obtained spanning part of the RNA-dependent-RNA-polymerase (RdRP), all of the coat protein and part of the aphid-transmission protein. CBTV sequences could be detected in viruliferous aphids able to transmit CBT, but not aphids from non-symptomatic plants, indicating that it is associated with the disease and may be the causal agent. All CBTV open-reading frames had their closest similarity to viruses of the genus Polerovirus. The partial RdRP had 90 % amino acid identity to the RdRP of Cotton leafroll dwarf virus (CLRDV) that causes cotton blue disease, while other parts of the genome were more similar to other poleroviruses. The sequence similarity and genome organization of CBTV suggest that it should be considered a new member of the genus Polerovirus. This partial genome sequence of CBTV opens up the possibility for developing diagnostic tests for detection of the virus in cotton plants, aphids and weeds as well as alternative strategies for engineering CBT resistance in cotton plants through biotechnology. © 2012 Australasian Plant Pathology Society Inc.