Collagen concentration and biomechanical properties of samples from the lower uterine cervix in relation to age and parity in non-pregnant women

<p>Abstract</p> <p>Background</p> <p>During normal pregnancy the cervix has a load bearing function. The cervical tissue consists mainly of an extracellular matrix (ECM) rich in collagen; important for the biomechanical properties. The aim of the present study was to evaluate how the biomechanical strength of samples from the distal cervix is associated with collagen content in relation to age and parity. This study demonstrates a method to investigate cervical tissue from women who still have their uterus in situ.</p> <p>Methods</p> <p>Cervical punch biopsies (2 × 15 mm) were obtained from 57 healthy women (median age: 39 years, range: 29-49 years). Biomechanical tensile testing was performed, and collagen concentration (as % of dry defatted weight (DDW)) and content (mg of collagen per mm of specimen length) was determined. Histomorphometry was used to determine the volume densities of extracellular matrix and smooth muscle cells. Smooth muscle cells were identified by immunohistochemistry. Finally, orientation of collagen fibers was estimated. Data are given as mean +/- SD.</p> <p>Results</p> <p>The mean collagen concentration (62.2 +/- 6.6%) increased with age (0.5% per year, r = 0.45, p = 0.003) and decreased with parity (1.7% per birth, r = -0.45, p = 0.033). Maximum load was positively correlated with collagen content (mg of collagen per mm of specimen length) (r = 0.76, p < 0.001). Normalized maximum stiffness was increased with age (r = 0.32, p = 0.017), whereas no correlation was found with regard to parity. In tissue samples with a length of approximately one cm, volume density of smooth muscle cells increased gradually from 8.9% in the distal part near the epithelium, to 15.5% in the proximal part (p < 0.001).</p> <p>Conclusions</p> <p>The present study shows that cervical collagen concentration increases with age and decreases with parity in non-pregnant women. In addition, collagen stiffness increased with age, whereas no change in collagen tensile strength with respect to age and parity was found. These results show that collagen contributes to cervical tissue tensile strength and age and parity should be considered confounding factors.</p

Involving Citizen Scientists in Biodiversity Observation

The involvement of non-professionals in scientific research and environmental monitoring, termed Citizen Science (CS), has now become a mainstream approach for collecting data on earth processes, ecosystems and biodiversity. This chapter examines how CS might contribute to ongoing efforts in biodiversity monitoring, enhancing observation and recording of key species and systems in a standardised manner, thereby supporting data relevant to the Essential Biodiversity Variables (EBVs), as well as reaching key constituencies who would benefit Biodiversity Observation Networks (BONs). The design of successful monitoring or observation networks that rely on citizen observers requires a careful balancing of the two primary user groups, namely data users and data contributors (i.e., citizen scientists). To this end, this chapter identifies examples of successful CS programs as well as considering practical issues such as the reliability of the data, participant recruitment and motivation, and the use of emerging technologies

High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways

Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways

Children’s sedentary behaviour: descriptive epidemiology and associations with objectively-measured sedentary time

Background: Little is known regarding the patterning and socio-demographic distribution of multiple sedentary behaviours in children. The aims of this study were to: 1) describe the leisure-time sedentary behaviour of 9-10 year old British children, and 2) establish associations with objectively-measured sedentary time. Methods: Cross-sectional analysis in the SPEEDY study (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people) (N=1513, 44.3% boys). Twelve leisure-time sedentary behaviours were assessed by questionnaire. Objectively-measured leisure-time sedentary time (Actigraph GT1M, <100 counts/minute) was assessed over 7 days. Differences by sex and socioeconomic status (SES) in self-reported sedentary behaviours were tested using Kruskal-Wallis tests. The association between objectively-measured sedentary time and the separate sedentary behaviours (continuous (minutes) and categorised into 'none' 'low' or 'high' participation) was assessed using multi-level linear regression. Results: Sex differences were observed for time spent in most sedentary behaviours (all p ≤ 0.02), except computer use. Girls spent more time in combined non-screen sedentary behaviour (median, interquartile range: girls: 770.0 minutes, 390.0-1230.0; boys: 725.0, 365.0 - 1182.5; p = 0.003), whereas boys spent more time in screen-based behaviours (girls: 540.0, 273.0 - 1050.0; boys: 885.0, 502.5 - 1665.0; p < 0.001). Time spent in five non-screen behaviours differed by SES, with higher values in those of higher SES (all p ≤ 0.001). Regression analyses with continuous exposures indicated that reading (β = 0.1, p < 0.001) and watching television (β = 0.04, p < 0.01) were positively associated with objectively-measured sedentary time, whilst playing board games (β = -0.12, p < 0.05) was negatively associated. Analysed in categorical form, sitting and talking (vs. none: 'low' β = 26.1,ns; 'high' 30.9, p < 0.05), playing video games (vs. none: 'low' β = 49.1, p < 0.01; 'high' 60.2, p < 0.01) and watching television (vs. lowest tertile: middle β = 22.2,ns; highest β = 31.9, p < 0.05) were positively associated with objectively-measured sedentary time whereas talking on the phone (vs. none: 'low' β = -38.5, p < 0.01; 'high' -60.2, p < 0.01) and using a computer/internet (vs. none: 'low' β = -30.7, p < 0.05; 'high' -4.2,ns) were negatively associated. Conclusions: Boys and girls and children of different socioeconomic backgrounds engage in different leisure-time sedentary behaviours. Whilst a number of behaviours may be predictive of total sedentary time, collectively they explain little overall variance. Future studies should consider a wide range of sedentary behaviours and incorporate objective measures to quantify sedentary time where possible

Inclusive V0V^0 Production Cross Sections from 920 GeV Fixed Target Proton-Nucleus Collisions

Inclusive differential cross sections $d\sigma_{pA}/dx_F$ and $d\sigma_{pA}/dp_t^2$ for the production of \kzeros, \lambdazero, and \antilambda particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to $\sqrt {s} = 41.6$ GeV in the proton-nucleon system. The ratios of differential cross sections \rklpa and \rllpa are measured to be $6.2\pm 0.5$ and $0.66\pm 0.07$, respectively, for \xf $\approx-0.06$. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions $d\sigma_{pA}/dp_t^2$ also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections $\sigma_{pA}$ on the atomic mass $A$ of the target material is discussed, and the deduced cross sections per nucleon $\sigma_{pN}$ are compared with results obtained at other energies.Comment: 17 pages, 7 figures, 5 table

Predicting sulfotyrosine sites using the random forest algorithm with significantly improved prediction accuracy

addresses: School of Biosciences, University of Exeter, Exeter EX4 5DE, UK. [email protected]: PMCID: PMC2777180types: Journal Article; Research Support, Non-U.S. Gov't© 2009 Yang; 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.Tyrosine sulfation is one of the most important posttranslational modifications. Due to its relevance to various disease developments, tyrosine sulfation has become the target for drug design. In order to facilitate efficient drug design, accurate prediction of sulfotyrosine sites is desirable. A predictor published seven years ago has been very successful with claimed prediction accuracy of 98%. However, it has a particularly low sensitivity when predicting sulfotyrosine sites in some newly sequenced proteins

Jaguar Densities across Human-Dominated Landscapes in Colombia: The Contribution of Unprotected Areas to Long Term Conservation

Large carnivores such as jaguars (Panthera onca) are species of conservation concern because they are suffering population declines and are keystone species in their ecosystems. Their large area requirements imply that unprotected and ever-increasing agricultural regions can be important habitats as they allow connectivity and dispersal among core protected areas. Yet information on jaguar densities across unprotected landscapes it is still scarce and crucially needed to assist management and range-wide conservation strategies. Our study provides the first jaguar density estimates of Colombia in agricultural regions which included cattle ranching, the main land use in the country, and oil palm cultivation, an increasing land use across the Neotropics. We used camera trapping across two agricultural landscapes located in the Magdalena River valley and in the Colombian llanos (47–53 stations respectively; >2000 trap nights at both sites) and classic and spatially explicit capture-recapture models with the sex of individuals as a covariate. Density estimates were 2.52±0.46–3.15±1.08 adults/100 km2 in the Magdalena valley, whereas 1.12±0.13–2.19±0.99 adults/100 km2 in the Colombian llanos, depending on analysis used. We suggest that jaguars are able to live across unprotected human-use areas and co-exist with agricultural landscapes including oil-palm plantations if natural areas and riparian habitats persist in the landscape and hunting of both jaguar and prey is limited. In the face of an expanding agriculture across the tropics we recommend land-use planning, adequate incentives, regulations, and good agricultural practices for range-wide jaguar connectivity and survival

MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vβ-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses