Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (⩽50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (⩽10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients

Cholesterol-Dependent Anaplasma phagocytophilum Exploits the Low-Density Lipoprotein Uptake Pathway

In eukaryotes, intracellular cholesterol homeostasis and trafficking are tightly regulated. Certain bacteria, such as Anaplasma phagocytophilum, also require cholesterol; it is unknown, however, how this cholesterol-dependent obligatory intracellular bacterium of granulocytes interacts with the host cell cholesterol regulatory pathway to acquire cholesterol. Here, we report that total host cell cholesterol increased >2-fold during A. phagocytophilum infection in a human promyelocytic leukemia cell line. Cellular free cholesterol was enriched in A. phagocytophilum inclusions as detected by filipin staining. We determined that A. phagocytophilum requires cholesterol derived from low-density lipoprotein (LDL), because its replication was significantly inhibited by depleting the growth medium of cholesterol-containing lipoproteins, by blocking LDL uptake with a monoclonal antibody against LDL receptor (LDLR), or by treating the host cells with inhibitors that block LDL-derived cholesterol egress from late endosomes or lysosomes. However, de novo cholesterol biosynthesis is not required, since inhibition of the biosynthesis pathway did not inhibit A. phagocytophilum infection. The uptake of fluorescence-labeled LDL was enhanced in infected cells, and LDLR expression was up-regulated at both the mRNA and protein levels. A. phagocytophilum infection stabilized LDLR mRNA through the 3′ UTR region, but not through activation of the sterol regulatory element binding proteins. Extracellular signal–regulated kinase (ERK) was up-regulated by A. phagocytophilum infection, and inhibition of its upstream kinase, MEK, by a specific inhibitor or siRNA knockdown, reduced A. phagocytophilum infection. Up-regulation of LDLR mRNA by A. phagocytophilum was also inhibited by the MEK inhibitor; however, it was unclear whether ERK activation is required for LDLR mRNA up-regulation by A. phagocytophilum. These data reveal that A. phagocytophilum exploits the host LDL uptake pathway and LDLR mRNA regulatory system to accumulate cholesterol in inclusions to facilitate its replication

Signal transduction-related responses to phytohormones and environmental challenges in sugarcane

BACKGROUND: Sugarcane is an increasingly economically and environmentally important C4 grass, used for the production of sugar and bioethanol, a low-carbon emission fuel. Sugarcane originated from crosses of Saccharum species and is noted for its unique capacity to accumulate high amounts of sucrose in its stems. Environmental stresses limit enormously sugarcane productivity worldwide. To investigate transcriptome changes in response to environmental inputs that alter yield we used cDNA microarrays to profile expression of 1,545 genes in plants submitted to drought, phosphate starvation, herbivory and N(2)-fixing endophytic bacteria. We also investigated the response to phytohormones (abscisic acid and methyl jasmonate). The arrayed elements correspond mostly to genes involved in signal transduction, hormone biosynthesis, transcription factors, novel genes and genes corresponding to unknown proteins. RESULTS: Adopting an outliers searching method 179 genes with strikingly different expression levels were identified as differentially expressed in at least one of the treatments analysed. Self Organizing Maps were used to cluster the expression profiles of 695 genes that showed a highly correlated expression pattern among replicates. The expression data for 22 genes was evaluated for 36 experimental data points by quantitative RT-PCR indicating a validation rate of 80.5% using three biological experimental replicates. The SUCAST Database was created that provides public access to the data described in this work, linked to tissue expression profiling and the SUCAST gene category and sequence analysis. The SUCAST database also includes a categorization of the sugarcane kinome based on a phylogenetic grouping that included 182 undefined kinases. CONCLUSION: An extensive study on the sugarcane transcriptome was performed. Sugarcane genes responsive to phytohormones and to challenges sugarcane commonly deals with in the field were identified. Additionally, the protein kinases were annotated based on a phylogenetic approach. The experimental design and statistical analysis applied proved robust to unravel genes associated with a diverse array of conditions attributing novel functions to previously unknown or undefined genes. The data consolidated in the SUCAST database resource can guide further studies and be useful for the development of improved sugarcane varieties

Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms

Extent: 22p.Background: This study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB). Methods A random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults ([greater than or equal to]18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations. Results The prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 - 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12mL and 20mL in FEV1 and FVC respectively in men, and 4mL and 7mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women. Conclusions In this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may contribute up to one quarter of this association.Matthew T Haren, Gary Misan, Tracey-Jayne Paterson, Richard E Ruffin, Janet F Grant, Jonathan D Buckley, Peter RC Howe, Jonathan Newbury, Anne W Taylor and Robyn A McDermot

Does soil pyrogenic carbon determine plant functional traits in Amazon Basin forests?

Amazon forests are fire-sensitive ecosystems and consequently fires affect forest structure and composition. For instance, the legacy of past fire regimes may persist through some species and traits that are found due to past fires. In this study, we tested for relationships between functional traits that are classically presented as the main components of plant ecological strategies and environmental filters related to climate and historical fires among permanent mature forest plots across the range of local and regional environmental gradients that occur in Amazonia. We used percentage surface soil pyrogenic carbon (PyC), a recalcitrant form of carbon that can persist for millennia in soils, as a novel indicator of historical fire in old-growth forests. Five out of the nine functional traits evaluated across all 378 species were correlated with some environmental variables. Although there is more PyC in Amazonian soils than previously reported, the percentage soil PyC indicated no detectable legacy effect of past fires on contemporary functional composition. More species with dry diaspores were found in drier and hotter environments. We also found higher wood density in trees from higher temperature sites. If Amazon forest past burnings were local and without distinguishable attributes of a widespread fire regime, then impacts on biodiversity would have been small and heterogeneous. Alternatively, sufficient time may have passed since the last fire to allow for species replacement. Regardless, as we failed to detect any impact of past fire on present forest functional composition, if our plots are representative then it suggests that mature Amazon forests lack a compositional legacy of past fire

The pace of life for forest trees

This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this record Data availability statement: The plot-level input data and R code that are needed to replicate our analyses are available at https://github/Lalasia/pace_of_life.com and doi.org/10.5281/zenodo.11615767 (56). The tree-by-tree observations used to generate the plot-level input data are also published with this paper. However, this file does not include data from networks with sensitive species or a need for indigenous data sovereignty. These data are available upon request for research purposes by emailing the following networks: Alberta Agriculture and Forestry Division https://www.alberta.ca/permanent-sample-plots-program, email: [email protected], Saskatchewan Minister of Environment Forest Service Branch https://www.saskatchewan.ca/contact-us, ForestGeo https://forestgeo.si.edu/explore-data ((20–22), and ForestPlots https://forestplots.net/en/using-forestplots/in-the-field, email: [email protected] (18, 19).Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.3 to 3195 years) and show that the pace of life for trees can be accurately classified into four demographic functional types. We found emergent patterns in the strength of trade-offs between growth and longevity across a temperature gradient. Furthermore, we show that the diversity of life history traits varies predictably across forest biomes, giving rise to a positive relationship between trait diversity and productivity. Our pan-latitudinal assessment provides new insights into the demographic mechanisms that govern the carbon turnover rate across forest biomes.European Union Horizon 2020Royal SocietyNatural Environment Research Council (NERC

The embryo as moral work object: PGD/IVF staff views and experiences

Copyright @ 2008 the authors. This article is available in accordance with the Creative Commons Deed, Attribution 2.5, see http://creativecommons.org/licenses/by-nc-nd/2.5/deed.en_CA.We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of ‘affected’ or ‘spare’ embryos or using them for research. A variety of views were expressed on the ‘embryo question’ in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as ‘moral work objects’. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of ‘work objects’ and focusing on negotiation of the social order in a morally contested field.The Wellcome Trust Biomedical Ethics Programme, who funded the projects‘Facilitating choice, framing choice: the experience of staff working in pre-implantation genetic diagnosis’ (no: 074935), and ‘Ethical Frameworks for Embryo Donation:the views and practices of IVF/PGD staff’ (no: 081414)