Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs

Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer

Potential application of mesh-free SPH method in turbulent river flows

A comprehensive review has been completed on the simulation of turbulent flow over rough beds using mesh-free particle models. Based on the outcomes of this review, an improved Smoothed Particle Hydrodynamics (SPH) method has been developed for open channel flows over a rough bed, in which a mixing length model is used for modeling the 2D turbulence and a drag force equation is proposed for treating the boundary shear. The proposed model was applied to simulate a depth-limited open channel flow over a rough bed surface. The results of the velocity profile and shear stress distribution show a good agreement with the experimental data and existing analytical solutions. This work reveals that in order to correctly model turbulent open channel flow over a rough bed, the treatment of both flow turbulence and bed roughness effect is equally important

"Obesity" and "Clinical Obesity" Men's understandings of obesity and its relation to the risk of diabetes: A qualitative study

<p>Abstract</p> <p>Background</p> <p>The 2007 Wanless report highlights the ever increasing problem of obesity and the consequent health problems. Obesity is a significant cause of diabetes. An increasing evidence base suggests that in terms of reducing diabetes and CVD risk, it is better to be "fit and fat" than unfit and of normal weight. There has been very little previous research into the understandings that men in the general population hold about the issues of weight, exercise and health; we therefore undertook this study in order to inform the process of health promotion and diabetes prevention in this group.</p> <p>Methods</p> <p>A qualitative study in North East England General Practice using a purposive sample of men aged 25 and 45 years (selection process designed to include 'normal', 'overweight' and 'obese' men). One to one audio-recorded semi structured interviews focused on: overweight and obesity, diet, physical activity and diabetes. Transcripts were initially analysed using framework analysis. Emerging themes interlinked.</p> <p>Results</p> <p>The men in this study (n = 17) understand the word obesity differently from the clinical definition; "obesity" was used as a description of those with fat in a central distribution, and understandings of the term commonly take into account fitness as well as weight. Men in their late 30s and early 40s described becoming more aware of health issues. Knowledge of what constitutes a 'healthy lifestyle' was generally good, but men described difficulty acting upon this knowledge for various reasons e.g. increasing responsibilities at home and at work. Knowledge of diabetes and the link between obesity and diabetes was poor.</p> <p>Conclusion</p> <p>Men in this study had a complex understanding of the interlinked importance of weight and fitness in relation to health. Obesity is understood as a description of people with centrally distributed fat, in association with low fitness levels. There is a need to increase understanding of the causes and consequences of diabetes. Discussion of increased health awareness by men round the age of 40 may indicate a window of opportunity to intervene at this time.</p

The Arabidopsis protein phosphatase PP2C38 negatively regulates the central immune kinase BIK1

Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component

Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components

Antioxidant Defenses Predict Long-Term Survival in a Passerine Bird

Normal and pathological processes entail the production of oxidative substances that can damage biological molecules and harm physiological functions. Organisms have evolved complex mechanisms of antioxidant defense, and any imbalance between oxidative challenge and antioxidant protection can depress fitness components and accelerate senescence. While the role of oxidative stress in pathogenesis and aging has been studied intensively in humans and model animal species under laboratory conditions, there is a dearth of knowledge on its role in shaping life-histories of animals under natural selection regimes. Yet, given the pervasive nature and likely fitness consequences of oxidative damage, it can be expected that the need to secure efficient antioxidant protection is powerful in molding the evolutionary ecology of animals. Here, we test whether overall antioxidant defense varies with age and predicts long-term survival, using a wild population of a migratory passerine bird, the barn swallow (Hirundo rustica), as a model.Plasma antioxidant capacity (AOC) of breeding individuals was measured using standard protocols and annual survival was monitored over five years (2006-2010) on a large sample of selection episodes. AOC did not covary with age in longitudinal analyses after discounting the effect of selection. AOC positively predicted annual survival independently of sex. Individuals were highly consistent in their relative levels of AOC, implying the existence of additive genetic variance and/or environmental (including early maternal) components consistently acting through their lives.Using longitudinal data we showed that high levels of antioxidant protection positively predict long-term survival in a wild animal population. Present results are therefore novel in disclosing a role for antioxidant protection in determining survival under natural conditions, strongly demanding for more longitudinal eco-physiological studies of life-histories in relation to oxidative stress in wild populations

Flea Diversity as an Element for Persistence of Plague Bacteria in an East African Plague Focus

Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (∼725–1160 m) to higher elevation sites within the focus (∼1380–1630 m). Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence

Impacts of Parasites in Early Life: Contrasting Effects on Juvenile Growth for Different Family Members

Parasitism experienced early in ontogeny can have a major impact on host growth, development and future fitness, but whether siblings are affected equally by parasitism is poorly understood. In birds, hatching asynchrony induced by hormonal or behavioural mechanisms largely under parental control might predispose young to respond to infection in different ways. Here we show that parasites can have different consequences for offspring depending on their position in the family hierarchy. We experimentally treated European Shag (Phalacrocorax aristoteli) nestlings with the broad-spectrum anti-parasite drug ivermectin and compared their growth rates with nestlings from control broods. Average growth rates measured over the period of linear growth (10 days to 30 days of age) and survival did not differ for nestlings from treated and control broods. However, when considering individuals within broods, parasite treatment reversed the patterns of growth for individual family members: last-hatched nestlings grew significantly slower than their siblings in control nests but grew faster in treated nests. This was at the expense of their earlier-hatched brood-mates, who showed an overall growth rate reduction relative to last-hatched nestlings in treated nests. These results highlight the importance of exploring individual variation in the costs of infection and suggest that parasites could be a key factor modulating within-family dynamics, sibling competition and developmental trajectories from an early age