Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

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Protein disulphide isomerase-mediated grafting of cysteine-containing peptides onto over-bleached hair

The ability of Protein disulphide isomerase (PDI) to promote the grafting of two cysteine-containing peptides onto hair was investigated in order to develop an alternative treatment for over-bleached hair. The studied peptides were designed based on human keratin and human lung surfactant proteins and were linked to a fluorescent dye to facilitate visualisation of the grafting process and to assess hair penetration. The ability of the peptides to restore mechanical and thermal properties lost by repeated bleaching treatments was also studied. After eight bleaching treatments, hair samples displayed 42% less mechanical resistance, coupled with a decrease in α-helix denaturation enthalpies and temperatures. Hair surface damage following bleaching was visualized by scanning electron microscopy. Addition of PDI to the treatment formulations promoted peptide attachment to the hair via disulphide bonds, facilitating their penetration into the hair cortex, as observed by fluorescence microscopy. The proposed peptide treatment resulted in an increase in α-helix denaturation enthalpy in over-bleached hair, as well as an increase in both Young's modulus and tensile strength. Thus, mechanical and thermal properties were improved after the peptide treatment in the presence of PDI; suggesting that the formulations presented in this work are promising candidates for hair-care applications

The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.

Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk

Lineage Plasticity in SCLC Generates Non-Neuroendocrine Cells Primed for Vasculogenic Mimicry

Introduction: Vasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In genetically engineered mouse models (GEMMs) of SCLC, NOTCH, and MYC co-operate to drive a neuroendocrine (NE) to non-NE phenotypic switch, and co-operation between NE and non-NE cells is required for metastasis. Here, we define the phenotype of VM-competent cells and molecular mechanisms underpinning SCLC VM using circulating tumor cell–derived explant (CDX) models and GEMMs. Methods: We analyzed perfusion within VM vessels and their association with NE and non-NE phenotypes using multiplex immunohistochemistry in CDX, GEMMs, and patient biopsies. We evaluated their three-dimensional structure and defined collagen-integrin interactions. Results: We found that VM vessels are present in 23/25 CDX models, 2 GEMMs, and in 20 patient biopsies of SCLC. Perfused VM vessels support tumor growth and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures. On Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin β1–dependent process. Conclusions: We identified VM as an exemplar of functional heterogeneity and plasticity in SCLC and these findings take considerable steps toward understanding the molecular events that enable VM. These results support therapeutic co-targeting of both NE and non-NE cells to curtail SCLC progression and to improve the outcomes of patients with SCLC in the future

Chemical and Physical Environmental Conditions Underneath Mat- and Canopy-Forming Macroalgae, and Their Effects on Understorey Corals

Disturbed coral reefs are often dominated by dense mat- or canopy-forming assemblages of macroalgae. This study investigated how such dense macroalgal assemblages change the chemical and physical microenvironment for understorey corals, and how the altered environmental conditions affect the physiological performance of corals. Field measurements were conducted on macroalgal-dominated inshore reefs in the Great Barrier Reef in quadrats with macroalgal biomass ranging from 235 to 1029 g DW m−2 dry weight. Underneath mat-forming assemblages, the mean concentration of dissolved oxygen was reduced by 26% and irradiance by 96% compared with conditions above the mat, while concentrations of dissolved organic carbon and soluble reactive phosphorous increased by 26% and 267%, respectively. The difference was significant but less pronounced under canopy-forming assemblages. Dissolved oxygen declined and dissolved inorganic carbon and alkalinity increased with increasing algal biomass underneath mat-forming but not under canopy-forming assemblages. The responses of corals to conditions similar to those found underneath algal assemblages were investigated in an aquarium experiment. Coral nubbins of the species Acropora millepora showed reduced photosynthetic yields and increased RNA/DNA ratios when exposed to conditions simulating those underneath assemblages (pre-incubating seawater with macroalgae, and shading). The magnitude of these stress responses increased with increasing proportion of pre-incubated algal water. Our study shows that mat-forming and, to a lesser extent, canopy-forming macroalgal assemblages alter the physical and chemical microenvironment sufficiently to directly and detrimentally affect the metabolism of corals, potentially impeding reef recovery from algal to coral-dominated states after disturbance. Macroalgal dominance on coral reefs therefore simultaneously represents a consequence and cause of coral reef degradation

Quantifying the Ocean, Freshwater and Human Effects on Year-to-Year Variability of One-Sea-Winter Atlantic Salmon Angled in Multiple Norwegian Rivers

Many Atlantic salmon, Salmo salar, populations are decreasing throughout the species' distributional range probably due to several factors acting in concert. A number of studies have documented the influence of freshwater and ocean conditions, climate variability and human impacts resulting from impoundment and aquaculture. However, most previous research has focused on analyzing single or only a few populations, and quantified isolated effects rather than handling multiple factors in conjunction. By using a multi-river mixed-effects model we estimated the effects of oceanic and river conditions, as well as human impacts, on year-to-year and between-river variability across 60 time series of recreational catch of one-sea-winter salmon (grilse) from Norwegian rivers over 29 years (1979–2007). Warm coastal temperatures at the time of smolt entrance into the sea and increased water discharge during upstream migration of mature fish were associated with higher rod catches of grilse. When hydropower stations were present in the course of the river systems the strength of the relationship with runoff was reduced. Catches of grilse in the river increased significantly following the reduction of the harvesting of this life-stage at sea. However, an average decreasing temporal trend was still detected and appeared to be stronger in the presence of salmon farms on the migration route of smolts in coastal/fjord areas. These results suggest that both ocean and freshwater conditions in conjunction with various human impacts contribute to shape interannual fluctuations and between-river variability of wild Atlantic salmon in Norwegian rivers. Current global change altering coastal temperature and water flow patterns might have implications for future grilse catches, moreover, positioning of aquaculture facilities as well as the implementation of hydropower schemes or other encroachments should be made with care when implementing management actions and searching for solutions to conserve this species

Multi-Level Interactions between the Nuclear Receptor TRα1 and the WNT Effectors β-Catenin/Tcf4 in the Intestinal Epithelium

Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor

Data enhancement for co-morbidity measurement among patients referred for sleep diagnostic testing: an observational study

<p>Abstract</p> <p>Background</p> <p>Observational outcome studies of patients with obstructive sleep apnea (OSA) require adjustment for co-morbidity to produce valid results. The aim of this study was to evaluate whether the combination of administrative data and self-reported data provided a more complete estimate of co-morbidity among patients referred for sleep diagnostic testing.</p> <p>Methods</p> <p>A retrospective observational study of 2149 patients referred for sleep diagnostic testing in Calgary, Canada. Self-reported co-morbidity was obtained with a questionnaire; administrative data and validated algorithms (when available) were also used to define the presence of these co-morbid conditions within a two-year period prior to sleep testing.</p> <p>Results</p> <p>Patient self-report of co-morbid conditions had varying levels of agreement with those derived from administrative data, ranging from substantial agreement for diabetes (κ = 0.79) to poor agreement for cardiac arrhythmia (κ = 0.14). The enhanced measure of co-morbidity using either self-report or administrative data had face validity, and provided clinically meaningful trends in the prevalence of co-morbidity among this population.</p> <p>Conclusion</p> <p>An enhanced measure of co-morbidity using self-report and administrative data can provide a more complete measure of the co-morbidity among patients with OSA when agreement between the two sources is poor. This methodology will aid in the adjustment of these coexisting conditions in observational studies in this area.</p

Modeling the Spatial Distribution and Fruiting Pattern of a Key Tree Species in a Neotropical Forest: Methodology and Potential Applications

Damien Caillaud is with UT Austin and Max Planck Institute for Evolutionary Anthropology; Margaret C. Crofoot is with the Smithsonian Tropical Research Institute, Max Planck Institute for Ornithology, and Princeton University; Samuel V. Scarpino is with UT Austin; Patrick A. Jansen is with the Smithsonian Tropical Research Institute, Wageningen University, and University of Groningen; Carol X. Garzon-Lopez is with University of Groningen; Annemarie J. S. Winkelhagen is with Wageningen University; Stephanie A. Bohlman is with Princeton University; Peter D. Walsh is with VaccinApe.Background -- The movement patterns of wild animals depend crucially on the spatial and temporal availability of resources in their habitat. To date, most attempts to model this relationship were forced to rely on simplified assumptions about the spatiotemporal distribution of food resources. Here we demonstrate how advances in statistics permit the combination of sparse ground sampling with remote sensing imagery to generate biological relevant, spatially and temporally explicit distributions of food resources. We illustrate our procedure by creating a detailed simulation model of fruit production patterns for Dipteryx oleifera, a keystone tree species, on Barro Colorado Island (BCI), Panama. Methodology and Principal Findings -- Aerial photographs providing GPS positions for large, canopy trees, the complete census of a 50-ha and 25-ha area, diameter at breast height data from haphazardly sampled trees and long-term phenology data from six trees were used to fit 1) a point process model of tree spatial distribution and 2) a generalized linear mixed-effect model of temporal variation of fruit production. The fitted parameters from these models are then used to create a stochastic simulation model which incorporates spatio-temporal variations of D. oleifera fruit availability on BCI. Conclusions and Significance -- We present a framework that can provide a statistical characterization of the habitat that can be included in agent-based models of animal movements. When environmental heterogeneity cannot be exhaustively mapped, this approach can be a powerful alternative. The results of our model on the spatio-temporal variation in D. oleifera fruit availability will be used to understand behavioral and movement patterns of several species on BCI.The National Center For Ecological Analysis is supported by NSF Grant DEB-0553768, the University of California Santa Barbara and the State of California. The Forest Dynamics Plots were funded by NSF Grants to Stephen Hubbell DEB-0640386, DEB-0425651, DEB-0346488, DEB-0129874, DEB-00753102, DEB-9909347, DEB-9615226, DEB-9615226, DEB-9405933, DEB-9221033, DEB-9100058, DEB-8906869, DEB-8605042, DEB-8206992, DEB-7922197, and by the Center for Tropical Forest Science, the Smithsonian Tropical Forest Research Institute, The John D. and Catherine T. MacArthur Foundation, the Mellon Foundation and the Celera Foundation. DC is supported by NSF grant DEB-0749097 to L.A. Meyers. SS is supported by an NSF Graduate Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o