Are Zinc-Finger Domains of Protein Kinase C Dynamic Structures That Unfold by Lipid or Redox Activation?

Protein kinase C (PKC) is activated by lipid second messengers or redox action, raising the question whether these activation modes involve the same or alternate mechanisms. Here we show that both lipid activators and oxidation target the zinc-finger domains of PKC, suggesting a unifying activation mechanism. We found that lipid agonist-binding or redox action leads to zinc release and disassembly of zinc fingers, thus triggering large-scale unfolding that underlies conversion to the active enzyme. These results suggest that PKC zinc fingers, originally considered purely structural devices, are in fact redox-sensitive flexible hinges, whose conformation is controlled both by redox conditions and lipid agonists. Antioxid. Redox Signal. 14, 757-766.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90473/1/ars-2E2010-2E3773.pd

Soilborne Diseases and their Control

Seed and seedling diseases, root rots, and wilts are caused by a number of soilborne fungi, all of which are facultative saprophytes and can survive in soil for long periods in the absence of a susceptible host. In general, these diseases are serious yield constraints where short rotations or monoculture of legume crops are the rule. Seedling diseases and root rots are enhanced by poor seed vigor, poor seedbed preparation, and other biotic and abiotic stresses which predispose the host plant. Control of these diseases requires an integrated approach of genetic resistance/tolerance, cultural practices, appropriate seed treatments, and high seed vigor. The most economical and durable control of Fusarium wilt is to grow resistant varieties. New races of a wilt pathogen have arisen due to increased selection pressure from growing resistant varieties in short rotations but have not outpaced the development of resistant cultivars

Adapting HIV prevention evidence-based interventions in practice settings: an interview study

<p>Abstract</p> <p>Background</p> <p>Evidence-based interventions that are being delivered in real-world settings are adapted to enhance the external validity of these interventions. The purpose of this study was to examine multiple intervention adaptations made during pre-implementation, implementation, maintenance, and evolution phases of human immunodeficiency virus HIV prevention technology transfer. We examined two important categories of adaptations -- modifications to key characteristics, such as activities or delivery methods of interventions and reinvention of the interventions including addition and deletion of core elements.</p> <p>Methods</p> <p>Study participants were thirty-four community-based organization staff who were implementing evidence-based interventions in Los Angeles, California. Participants were interviewed twice and interviews were professionally transcribed. Transcriptions were coded by two coders with good inter-rater reliability (kappa coefficient = 0.73). Sixty-two open-ended codes for adaptation activities, which were linked to 229 transcript segments, were categorized as modifications of key characteristics or reinvention.</p> <p>Results</p> <p>Participants described activities considered modifications to key characteristics and reinvention of evidence-based interventions during pre-implementation, implementation, and maintenance phases. None of the participants reported accessing technical assistance or guidance when reinventing their interventions. Staff executed many of the recommended steps for sound adaptation of these interventions for new populations and settings.</p> <p>Conclusion</p> <p>Staff reported modifying and reinventing interventions when translating HIV prevention programs into practice. Targeted technical assistance for formative evaluation should be focused on the pre-implementation phase during which frequent modifications occur. Continuous or repeated measurements of fidelity are recommended. Increased technical assistance and guidance are needed to ensure that reinventions are evaluated and consistent with the aims of the original interventions. Providing strategic technical assistance and written guidance can facilitate effective HIV prevention technology transfer of evidence-based interventions.</p

Regulation of the High Affinity IgE Receptor (FcεRI) in Human Neutrophils: Role of Seasonal Allergen Exposure and Th-2 Cytokines

The high affinity IgE receptor, FcεRI, plays a key role in the immunological pathways involved in allergic asthma. Previously we have demonstrated that human neutrophils isolated from allergic asthmatics express a functional FcεRI, and therefore it was of importance to examine the factors regulating its expression. In this study, we found that neutrophils from allergic asthmatics showed increased expression of FcεRI-α chain surface protein, total protein and mRNA compared with those from allergic non asthmatics and healthy donors (p<0.001). Interestingly, in neutrophils isolated from allergic asthmatics, FcεRI-α chain surface protein and mRNA expression were significantly greater during the pollen season than outside the pollen season (n = 9, P = 0.001), an effect which was not observed either in the allergic non asthmatic group or the healthy donors (p>0.05). Allergen exposure did not affect other surface markers of neutrophils such as CD16/FcγRIII or IL-17R. In contrast to stimulation with IgE, neutrophils incubated with TH2 cytokines IL-9, GM-CSF, and IL-4, showed enhanced FcεRI-α chain surface expression. In conclusion, these results suggest that enhanced FcεRI expression in human neutrophils from allergic asthmatics during the pollen season can make them more susceptible to the biological effects of IgE, providing a possible new mechanism by which neutrophils contribute to allergic asthma

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-μm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis

Phylogenetic Patterns of Colonization and Extinction in Experimentally Assembled Plant Communities

Evolutionary history has provided insights into the assembly and functioning of plant communities, yet patterns of phylogenetic community structure have largely been based on non-dynamic observations of natural communities. We examined phylogenetic patterns of natural colonization, extinction and biomass production in experimentally assembled communities.We used plant community phylogenetic patterns two years after experimental diversity treatments (1, 2, 4, 8 or 32 species) were discontinued. We constructed a 5-gene molecular phylogeny and statistically compared relatedness of species that colonized or went extinct to remaining community members and patterns of aboveground productivity. Phylogenetic relatedness converged as species-poor plots were colonized and speciose plots experienced extinctions, but plots maintained more differences in composition than in phylogenetic diversity. Successful colonists tended to either be closely or distantly related to community residents. Extinctions did not exhibit any strong relatedness patterns. Finally, plots that increased in phylogenetic diversity also increased in community productivity, though this effect was inseparable from legume colonization, since these colonists tended to be phylogenetically distantly related.We found that successful non-legume colonists were typically found where close relatives already existed in the sown community; in contrast, successful legume colonists (on their own long branch in the phylogeny) resulted in plots that were colonized by distant relatives. While extinctions exhibited no pattern with respect to relatedness to sown plotmates, extinction plus colonization resulted in communities that converged to similar phylogenetic diversity values, while maintaining differences in species composition

Genetic associations in diabetic nephropathy: a meta-analysis

Diabetes mellitus: pathophysiological changes and therap

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives