An approach to quantify natural durability of Eucalyptus bosistoana by near infrared spectroscopy for genetic selection

© 2020 Elsevier B.V. Natural durability within a timber species can be variable. Hence efficient assessments of natural durability are required to ensure quality either through tree breeding or segregation during production. In this study, first the relationship between extractive content and mass loss of Eucalyptus bosistoana heartwood caused by a white and a brown-rot fungus was validated. Then the ability of NIR spectroscopy as a high-throughput method to evaluate heartwood decay resistance was examined. Finally the NIR method was applied to a tree breeding trial. A correlation between extractive content and mass loss against the white-rot fungus (Perenniporia tephropora) and the brown-rot fungus (Coniophora olivacea) were found. Analysis of NIR spectra indicated that this relationship is causal with shared bands for mass loss and extractive content models at 6650, 6017, 5265 and 4659 cm−1. Partial least squares regression (PLSR), supplemented with spectra normalisation and variable selection, allowed prediction of mass loss with a residual mean square error (RMSE) of 7.48 % and 5.76 % for the white-rot and brown-rot, respectively. This level of precision allowed the characterisation of a E. bosistoana resource which showed a range of mass loss from 0 to 60 %. Genetic control was found for mass loss by the white-rot ( h2 = 0.70 and 0.24) and the brown-rot ( h2 = 0.15 and 0.13) at two sites in New Zealand. The rankings were correlated between sites, with genetic correlations (Rg2) of 0.69 and 0.63 for white-rot and brown-rot, respectively, as well as to the predicted extractive content (0.82 to 0.92). However, the study indicated a significant site effect on the decay resistance of the E. bosistoana heartwood. In summary, this study has shown that the decay resistance could be assessed rapidly and efficiently using NIR technology for genetic selection

Exploring what lies behind public preferences for avoiding health losses caused by lapses in healthcare safety and patient lifestyle choices

© 2013 Singh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Although many studies have identified public preferences for prioritising health care interventions based on characteristics of recipient or care, very few of them have examined the reasons for the stated preferences. We conducted an on-line person trade-off (PTO) study (N=1030) to investigate whether the public attach a premium to the avoidance of ill health associated with alternative types of responsibilities: lapses in healthcare safety, those caused by individual action or lifestyle choice; or genetic conditions. We found that the public gave higher priority to prevention of harm in a hospital setting such as preventing hospital associated infections than genetic disorder but drug administration errors were valued similar to genetic disorders. Prevention of staff injuries, lifestyle diseases and sports injuries, were given lower priority. In this paper we aim to understand the reasoning behind the responses by analysing comments provided by respondents to the PTO questions. Method: A majority of the respondents who participated in the survey provided brief comments explaining preferences in free text responses following PTO questions. This qualitative data was transformed into explicit codes conveying similar meanings. An overall coding framework was developed and a reliability test was carried out. Recurrent patterns were identified in each preference group. Comments which challenged the assumptions of hypothetical scenarios were also investigated. Results: NHS causation of illness and a duty of care were the most cited reasons to prioritise lapses in healthcare safety. Personal responsibility dominated responses for lifestyle related contexts, and many respondents mentioned that health loss was the result of the individual’s choice to engage in risky behaviour. A small proportion of responses questioned the assumptions underlying the PTO questions. However excluding these from the main analysis did not affect the conclusions. Conclusion: Although some responses indicated misunderstanding or rejection of assumptions we put forward, the results were still robust. The reasons put forward for responses differed between comparisons but responsibility was the most frequently cited. Most preference elicitation studies only focus on eliciting numerical valuations but allowing for qualitative data can augment understanding of preferences as well as verifying results.EPSRC through the MATCH programme(EP/F063822/1 and EP/G012393/1) and HERG within Brunel University

Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients

<br>Background:Prostate cancer cell growth is dependent upon androgen receptor (AR) activation, which is regulated by specific kinases. The aim of the current study is to establish if AR phosphorylation by Cdk1 or ERK1/2 is of prognostic significance.</br> <br>Methods: Scansite 2.0 was utilised to predict which AR sites are phosphorylated by Cdk1 and ERK1/2. Immunohistochemistry for these sites was then performed on 90 hormone-naive prostate cancer specimens. The interaction between Cdk1/ERK1/2 and AR phosphorylation was investigated in vitro using LNCaP cells.</br><br>Results:Phosphorylation of AR at serine 515 (pAR(S515)) and PSA at diagnosis were independently associated with decreased time to biochemical relapse. Cdk1 and pCdk1(161), but not ERK1/2, correlated with pAR(S515). High expression of pAR(S515) in patients with a PSA at diagnosis of ≤20 ng ml(-1) was associated with shorter time to biochemical relapse (P=0.019). This translated into a reduction in disease-specific survival (10-year survival, 38.1% vs 100%, P<0.001). In vitro studies demonstrated that treatment with Roscovitine (a Cdk inhibitor) caused a reduction in pCdk1(161) expression, pAR(S515)expression and cellular proliferation.</br> <br>Conclusion: In prostate cancer patients with PSA at diagnosis of ≤20 ng ml(-1), phosphorylation of AR at serine 515 by Cdk1 may be an independent prognostic marker.</br&gt

Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis

Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.

The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway MUC5AC and MUC5B concentrations during spontaneous and experimentally-induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with virus load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation as Muc5ac-deficient (Muc5ac-/-) mice had attenuated rhinovirus (RV)-induced airway inflammation and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of rhinovirus-induced inflammation in mice. Therapeutic suppression of mucin production using an epidermal growth factor receptor (EGFR) antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identifies a pro-inflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations

Prenatal Diagnosis of Oculocutaneous Albinism by Electron Microscopy of Fetal Skin

Oculocutaneous albinism was diagnosed prenatally by electron microscopic examination of fetal skin samples taken during fetoscopy at 20 weeks of gestation. Melanosome development in hair bulb melanocytes progressed no further than stage II, indicating a lack of melanin synthesis. In 4 age-matched control fetuses, numerous stage IV melanosomes, signifying active melanin synthesis, were identified. The diagnosis was confirmed after the pregnancy was terminated at 22 weeks. Examination of the fetal eye showed absence of pigment in the retinal epithelium and uvea at a stage when ocular melanogenesis would normally be active. This study shows that oculocutaneous albinism can be detected in the second trimester using similar techniques to those employed in the prenatal diagnosis of epidermolysis bullosa and ichthyosis

How robust are value judgements of health inequality aversion? Testing for framing and cognitive effects

Background: Empirical studies have found that members of the public are inequality averse and value health gains for disadvantaged groups with poor health many times more highly than gains for better off groups. However, these studies typically use abstract scenarios that involve unrealistically large reductions in health inequality, and face-to-face survey administration. It is not known how robust these findings are to more realistic scenarios or anonymous online survey administration. Methods: This study aimed to test the robustness of questionnaire estimates of inequality aversion by comparing the following: (1) small versus unrealistically large health inequality reductions; (2) population-level versus individual-level descriptions of health inequality reductions; (3) concrete versus abstract intervention scenarios; and (4) online versus face to face mode of administration. Fifty-two members of the public participated in face-to-face discussion groups, while 83 members of the public completed an online survey. Participants were given a questionnaire instrument with different scenario descriptions for eliciting aversion to social inequality in health. Results: The median respondent was inequality averse under all scenarios. Scenarios involving small rather than unrealistically large health gains made little difference in terms of inequality aversion, as did population-level rather than individual-level scenarios. However, the proportion expressing extreme inequality aversion fell 19 percentage points when considering a specific health intervention scenario rather than an abstract scenario, and was 11-21 percentage points lower among online public respondents compared to the discussion group. Conclusions: Our study suggests that both concrete scenarios and online administration reduce the proportion expressing extreme inequality aversion but still yield median responses implying substantial health inequality aversion

A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population

<p>Abstract</p> <p>Background</p> <p>Mutation in <it>SPINK5 </it>causes Netherton syndrome, a rare recessive skin disease that is accompanied by severe atopic manifestations including atopic dermatitis, allergic rhinitis, asthma, high serum IgE and hypereosinophilia. Recently, single nucleotide polymorphism (SNP) of the <it>SPINK5 </it>was shown to be significantly associated with atopy, atopic dermatitis, asthma, and total serum IgE. In order to determine the role of the <it>SPINK5 </it>in the development of asthma, a case-control study including 669 asthma patients and 711 healthy controls in Han Chinese was conducted.</p> <p>Methods</p> <p>Using PCR-RFLP assay, we genotyped one promoter SNP, -206G>A, and four nonsynonymous SNPs, 1103A>G (Asn368Ser), 1156G>A (Asp386Asn), 1258G>A (Glu420Lys), and 2475G>T (Glu825Asp). Also, we analyzed the functional significance of -206G>A using the luciferase reporter assay and electrophoresis mobility shift assay.</p> <p>Results</p> <p>we found that the G allele at SNP -206G>A was associated with increased asthma susceptibility in our study population (p = 0.002, odds ratio 1.34, 95% confidence interval 1.11–1.60). There was no significant association between any of four nonsynonymous SNPs and asthma. The A allele at -206G>A has a significantly higher transcriptional activity than the G allele. Electrophoresis mobility shift assay also showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the G allele.</p> <p>Conclusion</p> <p>Our findings indicate that the -206G>A polymorphism in the <it>SPINK5 </it>is associated with asthma susceptibility in a Chinese Han population.</p

Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85×10−20 and 7.08×10−19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78×10−4 and P = 1.95×10−3). The “top” SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28×10−7−4.46×10−8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels

Excess Circulating Alternatively Activated Myeloid (M2) Cells Accelerate ALS Progression While Inhibiting Experimental Autoimmune Encephalomyelitis

Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1) mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS), revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/Low)HLA-DR(-)CD33(+)) compared to controls.Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might represent a risk factor and a novel target for therapeutic intervention in ALS at least at the early stage