Genetic variation in the Epacris tasmanica complex (Epacridaceae).

RAPD (random amplified polymorphic DNA) markers were used to delimit species in the Epacris tasmanica complex (Epacridaceae) collected from various locations in Tasmania, Australia. The RAPD analysis placed morphologically similar taxa located closely geographically into discrete clusters. However, geographically distant populations of morphometrically similar taxa, such as the southern and northern Tasmanian populations of E. virgata and E. tasmanica, were less closely related to each other than those taxa classified as different species. The most geographically remote population (E. glabella [Serpentine Hill]) shared the least genetic similarities with the other taxa. The genetic information obtained from this study reinforces some previous morphometric data used to delimit species in the E. tasmanica complex. Furthermore, the strong geographical structure of the genetic variation is consistent with a model in which gene flow between populations is limited

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus

A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules

Genetic parameters for growth, wood density and pulp yield in Eucalyptus globulus

Genetic variation and co-variation among the key pulpwood selection traits for Eucalyptus globulus were estimated for a range of sites in Portugal, with the aim of improving genetic parameters used to predict breeding values and correlated response to selection. The trials comprised clonally replicated full-sib families (eight trials) and unrelated clones (17 trials), and exhibited varying levels of pedigree connectivity. The traits studied were stem diameter at breast height, Pilodyn penetration (an indirect measure of wood basic density) and near infrared reflectance predicted pulp yield. Univariate and multivariate linear mixed models were fitted within and across sites, and estimates of additive genetic, total genetic, environmental and phenotypic variances and covariances were obtained. All traits studied exhibited significant levels of additive genetic variation. The average estimated within-site narrowsense heritability was 0.19±0.03 for diameter and 0.29± 0.03 for Pilodyn penetration, and the pooled estimate for predicted pulp yield was 0.42±0.14. When they could be tested, dominance and epistatic effects were generally not statistically significant, although broad-sense heritability estimates were slightly higher than narrow-sense heritability estimates. Averaged across trials, positive additive (0.64±0.08), total genetic (0.58±0.04), environmental (0.38±0.03) and phenotypic (0.43±0.02) correlation estimates were consistently obtained between diameter and Pilodyn penetration. This data argues for at least some form of pleiotropic relationship between these two traits and that selection for fast growth will adversely affect wood density in this population. Estimates of the across-site genetic correlations for diameter and Pilodyn penetration were high, indicating that the genotype by environment interaction is low across the range of sites tested. This result supports the use of single aggregated selection criteria for growth and wood density across planting environments in Portugal, as opposed to having to select for performance in different environment

Spiral and Interlocking Grain in Eucalyptus Dunnii

Spiral grain in 181 trees from a 9-year-old plantation-grown Eucalyptus dunnii was normally distributed with mean 0.33 degrees (to the left) and standard deviation 1.7 degrees, and was affected by family and by crown asymmetry. Interlocking grain was common, exhibiting a mean amplitude of 3.4 degrees (standard deviation 1.5 degrees) and a mean wavelength of 39 mm (standard deviation 12 mm). The relatively large amplitude of interlocking grain means that most trees will have spiral grain that alternates between left and right during each year. The wavelength of interlocking grain is influenced by tree size, but amplitude of interlocking is under genetic control. Both spiral grain and the amplitude of any interlocking were heritable (h2 = 0.99 and 0.63 respectively)

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches

Organ replacement regenerative therapy is purported to enable the replacement of organs damaged by disease, injury or aging in the foreseeable future. Here we demonstrate fully functional hair organ regeneration via the intracutaneous transplantation of a bioengineered pelage and vibrissa follicle germ. The pelage and vibrissae are reconstituted with embryonic skin-derived cells and adult vibrissa stem cell region-derived cells, respectively. The bioengineered hair follicle develops the correct structures and forms proper connections with surrounding host tissues such as the epidermis, arrector pili muscle and nerve fibres. The bioengineered follicles also show restored hair cycles and piloerection through the rearrangement of follicular stem cells and their niches. This study thus reveals the potential applications of adult tissue-derived follicular stem cells as a bioengineered organ replacement therapy

Lentiviral gene therapy for X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4–1.8 copies per neutrophil) and the persistence of 16–46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

An outbreak of cardiovascular syndromes requiring urgent medical treatment and its association with environmental factors: an ecological study

<p>Abstract</p> <p>Background</p> <p>In April 2005, syndromic surveillance based on statistical control chart methods in Sydney, Australia, signalled increasing incidence of urgent emergency department visits for cardiovascular and chest pain syndromes compared to the preceding twelve months. This paper aimed to determine whether environmental factors could have been responsible for this 'outbreak'.</p> <p>Methods</p> <p>The outcome studied was daily counts of emergency department visits for cardiovascular or chest pain syndromes that were considered immediately or imminently life threatening on arrival at hospital. The outbreak had a mean daily count of 5.7 visits sustained for eight weeks, compared with 4.0 in the same months in previous years. Poisson regression was used to systematically assess the emergency department visits in relation to available daily weather and pollution variables by first finding the best model that explained short-term variation in the outcome over the period 25 January 2002 to 31 May 2005, and then assessing interactions of all available variables with the 'outbreak' period, April-May 2005. Rate ratios were estimated for an interquartile increase in each variable meaning that the ratio measures the relative increase (or decrease) in the emergency department visits for an interquartile increase in the weather or pollution variable. The rate ratios for the outbreak period measure the relative increase (or decrease) in the emergency department visits for an interquartile increase in the weather or pollution variable during the outbreak period only.</p> <p>Results</p> <p>The best fitting model over the whole study period included minimum temperature with a rate ratio (RR) of 0.86 (95% confidence interval (CI), 0.77–0.96), maximum relative humidity of 1.09 (95% CI 1.05–1.14) and minimum daily particulate matter less than 10 microns (PM₁₀) of 1.05 (95% CI, 1.01–1.09). During the outbreak period, maximum temperature (RR 1.27, 95% CI 1.03–1.57), solar radiation (RR 1.44, 95% CI, 1.00–2.07) and ozone (RR 1.13, 95% CI 1.01–1.26) were associated with the outcome.</p> <p>Conclusion</p> <p>The increase may have been associated with photochemical pollution. Syndromic surveillance can identify outbreaks of non-communicable diseases associated with environmental factors.</p

Temporal transcriptome changes induced by MDV in marek's disease-resistant and -susceptible inbred chickens

<p>Abstract</p> <p>Background</p> <p>Marek's disease (MD) is a lymphoproliferative disease in chickens caused by Marek's disease virus (MDV) and characterized by T cell lymphoma and infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves and muscle. Resistance to MD and disease risk have long been thought to be influenced both by genetic and environmental factors, the combination of which contributes to the observed outcome in an individual. We hypothesize that after MDV infection, genes related to MD-resistance or -susceptibility may exhibit different trends in transcriptional activity in chicken lines having a varying degree of resistance to MD.</p> <p>Results</p> <p>In order to study the mechanisms of resistance and susceptibility to MD, we performed genome-wide temporal expression analysis in spleen tissues from MD-resistant line 6₃, susceptible line 7₂and recombinant congenic strain M (RCS-M) that has a phenotype intermediate between lines 6₃and 7₂after MDV infection. Three time points of the MDV life cycle in chicken were selected for study: 5 days post infection (dpi), 10dpi and 21dpi, representing the early cytolytic, latent and late cytolytic stages, respectively. We observed similar gene expression profiles at the three time points in line 6₃and RCS-M chickens that are both different from line 7₂. Pathway analysis using Ingenuity Pathway Analysis (IPA) showed that MDV can broadly influence the chickens irrespective of whether they are resistant or susceptible to MD. However, some pathways like cardiac arrhythmia and cardiovascular disease were found to be affected only in line 7₂; while some networks related to cell-mediated immune response and antigen presentation were enriched only in line 6₃and RCS-M. We identified 78 and 30 candidate genes associated with MD resistance, at 10 and 21dpi respectively, by considering genes having the same trend of expression change after MDV infection in lines 6₃and RCS-M. On the other hand, by considering genes with the same trend of expression change after MDV infection in lines 7₂and RCS-M, we identified 78 and 43 genes at 10 and 21dpi, respectively, which may be associated with MD-susceptibility.</p> <p>Conclusions</p> <p>By testing temporal transcriptome changes using three representative chicken lines with different resistance to MD, we identified 108 candidate genes for MD-resistance and 121 candidate genes for MD-susceptibility over the three time points. Genes included in our resistance or susceptibility genes lists that are also involved in more than 5 biofunctions, such as <it>CD8α</it>, <it>IL8</it>, <it>USP18</it>, and <it>CTLA4</it>, are considered to be important genes involved in MD-resistance or -susceptibility. We were also able to identify several biofunctions related with immune response that we believe play an important role in MD-resistance.</p

Access Rate to the Emergency Department for Venous Thromboembolism in Relationship with Coarse and Fine Particulate Matter Air Pollution

Particulate matter (PM) air pollution has been associated with cardiovascular and respiratory disease. Recent studies have proposed also a link with venous thromboembolism (VTE) risk. This study was aimed to evaluate the possible influence of air pollution-related changes on the daily flux of patients referring to the Emergency Department (ED) for VTE, dissecting the different effects of coarse and fine PM. From July 1st, 2007, to June 30th, 2009, data about ED accesses for VTE and about daily concentrations of PM air pollution in Verona district (Italy) were collected. Coarse PM (PM10-2.5) was calculated by subtracting the finest PM2.5 from the whole PM10. During the index period a total of 302 accesses for VTE were observed (135 males and 167 females; mean age 68.3±16.7 years). In multiple regression models adjusted for other atmospheric parameters PM10-2.5, but not PM2.5, concentrations were positively correlated with VTE (beta-coefficient = 0.237; P = 0.020). During the days with high levels of PM10-2.5 (≥75th percentile) there was an increased risk of ED accesses for VTE (OR 1.69 with 95%CI 1.13–2.53). By analysing days of exposure using distributed lag non-linear models, the increase of VTE risk was limited to PM10-2.5 peaks in the short-term period. Consistently with these results, in another cohort of subjects without active thrombosis (n = 102) an inverse correlation between PM10-2.5 and prothrombin time was found (R = −0.247; P = 0.012). Our results suggest that short-time exposure to high concentrations of PM10-2.5 may favour an increased rate of ED accesses for VTE through the induction of a prothrombotic state