Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load.

BACKGROUND: Increasing evidence suggests that neutrophils play a role in the host response to Mycobacterium tuberculosis. We determined whether neutrophil counts in peripheral blood are associated with tuberculosis (TB) and with mycobacterial load in sputum in HIV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Adults enrolling in an antiretroviral treatment (ART) clinic in a Cape Town township were screened for TB regardless of symptoms. Paired sputum samples were examined using liquid culture, fluorescence microscopy, and the Xpert MTB/RIF assay. Absolute neutrophil counts (ANC) were measured in blood samples. Of 602 HIV-infected patients screened, 523 produced one or more sputum samples and had complete results available for analysis. Among these 523 patients, the median CD4 count was 169×10(9)/L (IQR, 96-232) and median ANC was 2.6×10(9)/L (IQR, 1.9-3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients. Patients with TB had a median ANC of 3.4×10(9)/L (IQR, 2.4-5.1) compared to 2.5×10(9)/L (IQR, 1.8-3.4) among those who were culture negative (p7.5×10(9)/L; p = 0.0005). Patients were then classified into four mutually exclusive groups with increasing sputum mycobacterial load as defined by the results of culture, Xpert MTB/RIF and sputum smear microscopy. Multivariable analyses demonstrated that increasing sputum mycobacterial load was positively associated with blood ANC ≥2.6×10(9)/L and with neutrophilia. CONCLUSIONS/SIGNIFICANCE: Increased blood neutrophil counts were independently associated with pulmonary TB and sputum mycobacterial burden in this HIV-infected patient group. This observation supports the growing body of literature regarding the potential role for neutrophils in the host response to TB

Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?

BACKGROUND Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C- reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN Double-blind, randomized placebo-controlled trial. PATIENTS Fifty women with type 2 diabetes. MEASUREMENTS Classical and novel risk factors for vascular disease. RESULTS Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2.55 to - 0.29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P lt 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed

Geniculo-Cortical Projection Diversity Revealed within the Mouse Visual Thalamus.

The mouse dorsal lateral geniculate nucleus (dLGN) is an intermediary between retina and primary visual cortex (V1). Recent investigations are beginning to reveal regional complexity in mouse dLGN. Using local injections of retrograde tracers into V1 of adult and neonatal mice, we examined the developing organisation of geniculate projection columns: the population of dLGN-V1 projection neurons that converge in cortex. Serial sectioning of the dLGN enabled the distribution of labelled projection neurons to be reconstructed and collated within a common standardised space. This enabled us to determine: the organisation of cells within the dLGN-V1 projection columns; their internal organisation (topology); and their order relative to V1 (topography). Here, we report parameters of projection columns that are highly variable in young animals and refined in the adult, exhibiting profiles consistent with shell and core zones of the dLGN. Additionally, such profiles are disrupted in adult animals with reduced correlated spontaneous activity during development. Assessing the variability between groups with partial least squares regression suggests that 4-6 cryptic lamina may exist along the length of the projection column. Our findings further spotlight the diversity of the mouse dLGN--an increasingly important model system for understanding the pre-cortical organisation and processing of visual information. Furthermore, our approach of using standardised spaces and pooling information across many animals will enhance future functional studies of the dLGN.Funding was provided by a Wellcome Trust grant jointly awarded to IDT and SJE (083205, www.wellcome.ac.uk), and by MRC PhD Studentships awarded to MNL and ACH (http://www.mrc.ac.uk/).This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.pone.014484

Linkage maps of the Atlantic salmon (Salmo salar) genome derived from RAD sequencing

BACKGROUND: Genetic linkage maps are useful tools for mapping quantitative trait loci (QTL) influencing variation in traits of interest in a population. Genotyping-by-sequencing approaches such as Restriction-site Associated DNA sequencing (RAD-Seq) now enable the rapid discovery and genotyping of genome-wide SNP markers suitable for the development of dense SNP linkage maps, including in non-model organisms such as Atlantic salmon (Salmo salar). This paper describes the development and characterisation of a high density SNP linkage map based on SbfI RAD-Seq SNP markers from two Atlantic salmon reference families. RESULTS: Approximately 6,000 SNPs were assigned to 29 linkage groups, utilising markers from known genomic locations as anchors. Linkage maps were then constructed for the four mapping parents separately. Overall map lengths were comparable between male and female parents, but the distribution of the SNPs showed sex-specific patterns with a greater degree of clustering of sire-segregating SNPs to single chromosome regions. The maps were integrated with the Atlantic salmon draft reference genome contigs, allowing the unique assignment of ~4,000 contigs to a linkage group. 112 genome contigs mapped to two or more linkage groups, highlighting regions of putative homeology within the salmon genome. A comparative genomics analysis with the stickleback reference genome identified putative genes closely linked to approximately half of the ordered SNPs and demonstrated blocks of orthology between the Atlantic salmon and stickleback genomes. A subset of 47 RAD-Seq SNPs were successfully validated using a high-throughput genotyping assay, with a correspondence of 97% between the two assays. CONCLUSIONS: This Atlantic salmon RAD-Seq linkage map is a resource for salmonid genomics research as genotyping-by-sequencing becomes increasingly common. This is aided by the integration of the SbfI RAD-Seq SNPs with existing reference maps and the draft reference genome, as well as the identification of putative genes proximal to the SNPs. Differences in the distribution of recombination events between the sexes is evident, and regions of homeology have been identified which are reflective of the recent salmonid whole genome duplication

The San Antonio River Mammoth Site: Archaeological Testing Investigations for the Interstate 37 Bridge at the San Antonio River Improvement Project, Bexar County, Texas

On behalf of the Texas Department of Transportation (TxDOT), SWCA Environmental Consultants (SWCA) conducted test excavations on the San Antonio River Mammoth site (41BX1239) and 41BX1240 and surveys in the area of potential effects (APE) of the Interstate Highway (IH) 37 bridge project at the San Antonio River in southeastern Bexar County, Texas. Work was initiated to address the requirements of Section 106 of the National Historic Preservation Act (1966) as Amended and the Antiquities Code of Texas. The purpose of the investigations was to identify, delineate, and evaluate the significance of all archaeological and historic properties potentially affected by the undertaking and, if warranted, recommend the scope of additional work. Of particular concern, site 41BX1239 contains the remains of at least two mammoths with possible evidence of cultural association based on the initial investigations by Texas A&M in 1997. However, subsequent faunal analysis, conducted by Olga Potapova and Larry D. Agenbroad of the Mammoth Site in Hot Springs, North Dakota, found inconclusive evidence for definite or valid cultural modification to the specimens studied. The testing investigations on the San Antonio River Mammoth site included the re-exposure of the original Texas A&M 1997 site trench; limited hand-excavated units to further assess the prior interpretations of the deposits and recover a sample of bone; and a detailed geomorphological assessment. The work identified a bone bed consisting of the remains of at least two mammoths. Flotation of recovered sediments from these hand excavations identified flakes of siliceous material that are consistent with micro-debitage produced by the use and retouch of stone tools. Although at the highest thresholds of certainty, the cumulative evidence is likely yet insufficient to conclusively prove human interaction with the mammoth remains, the additional data gathered herein lend some credence to the prior interpretation of the site as archaeological rather than strictly paleontological. Concurring with the previous determination, the site is considered eligible for inclusion to the National Register of Historic Places (NRHP) and for listing as a State Archeological Landmark (SAL). However, the investigations determined the site deposits are located outside the APE of the current undertaking, and therefore the project will not affect deposits associated with the San Antonio River Mammoth site. The investigations of 41BX1240 identified only a very sparse scatter of primarily surficial materials in a heavily disturbed context with no associated features or diagnostic materials. Accordingly, the site is not recommended as eligible for listing on the NRHP or for designation as a SAL. The survey identified no new archaeological sites. Based on the avoidance of 41BX1239, it is SWCA’s recommendation that no archaeological properties will be affected by the IH 37 bridge rehabilitation

Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?☆

The objective of our study was to evaluate whether cognitively normal (CN) elderly participants showing elevated cortical beta-amyloid (Aβ) deposition have a consistent neuroanatomical signature of brain atrophy that may characterize preclinical Alzheimer's disease (AD). 115 CN participants who were Aβ-positive (CN +) by amyloid PET imaging; 115 CN participants who were Aβ-negative (CN −); and 88 Aβ-positive mild cognitive impairment or AD participants (MCI/AD +) were identified. Cortical thickness (FreeSurfer) and gray matter volume (SPM5) were measured for 28 regions-of-interest (ROIs) across the brain and compared across groups. ROIs that best discriminated CN − from CN + differed for FreeSurfer cortical thickness and SPM5 gray matter volume. Group-wise discrimination was poor with a high degree of uncertainty in terms of the rank ordering of ROIs. In contrast, both techniques showed strong and consistent findings comparing MCI/AD + to both CN − and CN + groups, with entorhinal cortex, middle and inferior temporal lobe, inferior parietal lobe, and hippocampus providing the best discrimination for both techniques. Concordance across techniques was higher for the CN − and CN + versus MCI/AD + comparisons, compared to the CN − versus CN + comparison. The weak and inconsistent nature of the findings across technique in this study cast doubt on the existence of a reliable neuroanatomical signature of preclinical AD in elderly PiB-positive CN participants

Sequencing and Characterisation of an Extensive Atlantic Salmon (Salmo salar L.) MicroRNA Repertoire

Atlantic salmon (Salmo salar L.), a member of the family Salmonidae, is a totemic species of ecological and cultural significance that is also economically important in terms of both sports fisheries and aquaculture. These factors have promoted the continuous development of genomic resources for this species, furthering both fundamental and applied research. MicroRNAs (miRNA) are small endogenous non-coding RNA molecules that control spatial and temporal expression of targeted genes through post-transcriptional regulation. While miRNA have been characterised in detail for many other species, this is not yet the case for Atlantic salmon. To identify miRNAs from Atlantic salmon, we constructed whole fish miRNA libraries for 18 individual juveniles (fry, four months post hatch) and characterised them by Illumina high-throughput sequencing (total of 354,505,167 paired-ended reads). We report an extensive and partly novel repertoire of miRNA sequences, comprising 888 miRNA genes (547 unique mature miRNA sequences), quantify their expression levels in basal conditions, examine their homology to miRNAs from other species and identify their predicted target genes. We also identify the location and putative copy number of the miRNA genes in the draft Atlantic salmon reference genome sequence. The Atlantic salmon miRNAs experimentally identified in this study provide a robust large-scale resource for functional genome research in salmonids. There is an opportunity to explore the evolution of salmonid miRNAs following the relatively recent whole genome duplication event in salmonid species and to investigate the role of miRNAs in the regulation of gene expression in particular their contribution to variation in economically and ecologically important traits

Impact of fresh fruit smoothie consumption on apparent health of Asian faces

Skin carotenoid coloration has been proposed as a valid cue to health in humans, reflecting fruit and vegetable intake, and enhancing apparent health. Supplementation with a carotenoid-rich fruit and vegetable smoothie affects skin colour, but it is not known if this skin color change enhances healthy appearance. In three experiments, we examine the effects of skin color change induced by supplementation with a carotenoid-rich fruit smoothie (25mg carotenoids/d) on the apparent health of Malaysian Chinese faces. In experiment 1, observers were asked to identify the healthier looking of pairs of photographs of the same subject taken pre- and post-supplementation (or pre- and post-placebo), choosing the pre-supplementation (or pre-placebo) images. When confounding due to facial expression was eliminated in experiment 2, observers showed no preference for unmodified pre-supplementation photograph or the same image with skin color manipulated to simulate a level of smoothie-induced color change associated with 4 weeks of supplementation. In experiment 3, observers manipulated the skin color of face photographs along the smoothie-induced color change axis to optimize healthy appearance. Observers chose to induce a color change approximately equivalent to one third of the change induced by daily consumption of our carotenoid rich smoothie. This suggests that the skin color change induced by the supplementation enhanced apparent facial health, however the dose and duration of the supplementation overshot the optimal healthy-looking color of Malaysian Chinese skin. This suggests that there is an optimal carotenoid color for healthy appearance, and that this optimal level may be constrained by preferences for averageness, by the association between very yellow skin and ill health, or by negative health impacts of very high doses of carotenoids