BAMBI is a novel HIF1-dependent modulator of TGF beta-mediated disruption of cell polarity during hypoxia

Hypoxia and loss of cell polarity are common features of malignant carcinomas. Hypoxia-inducible factor 1 (HIF1) is the major regulator of cellular hypoxia response and mediates the activation of similar to 300 genes. Increased HIF1 signaling is known to be associated with epithelial-mesenchymal transformation. Here, we report that hypoxia disrupts polarized epithelial morphogenesis of MDCK cells in a HIF1 alpha-dependent manner by modulating the transforming growth factor-beta (TGF beta) signaling pathway. Analysis of potential HIF1 targets in the TGF beta pathway identified the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transmembrane glycoprotein related to the type I receptors of the TGF beta family, whose expression was essentially lost in HIF1-depleted cells. Similar to what was observed in HIF1-deficient cells, BAMBI-depleted cells failed to efficiently activate TGF beta signaling and retained epithelial polarity during hypoxia. Taken together, we show that hypoxic conditions promote TGF beta signaling in a HIF1-dependent manner and BAMBI is identified in this pathway as a novel HIF1-regulated gene that contributes to hypoxia-induced loss of epithelial polarity.Peer reviewe

How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics

Subjective stress, objective heart rate variability-based stress, and recovery on workdays among overweight and psychologically distressed individuals : a cross-sectional study

Background: The present study aimed to investigate how subjective self-reported stress is associated with objective heart rate variability (HRV)-based stress and recovery on workdays. Another aim was to investigate how physical activity (PA), body composition, and age are associated with subjective stress, objective stress, and recovery. Methods: Working-age participants (n = 221; 185 women, 36 men) in this cross-sectional study were overweight (body mass index, 25.3-40.1 kg/m(2)) and psychologically distressed (>= 3/12 points on the General Health Questionnaire). Objective stress and recovery were based on HRV recordings over 1-3 workdays. Subjective stress was assessed by the Perceived Stress Scale. PA level was determined by questionnaire, and body fat percentage was assessed by bioelectrical impedance analysis. Results: Subjective stress was directly associated with objective stress (P = 0.047) and inversely with objective recovery (P = 0.046). These associations persisted after adjustments for sex, age, PA, and body fat percentage. Higher PA was associated with lower subjective stress (P = 0.037). Older age was associated with higher objective stress (P <0.001). After further adjustment for alcohol consumption and regular medication, older age was associated with lower subjective stress (P = 0.043). Conclusions: The present results suggest that subjective self-reported stress is associated with objective physiological stress, but they are also apparently affected by different factors. However, some of the found associations among these overweight and psychologically distressed participants with low inter-individual variation in PA are rather weak and the clinical value of the present findings should be studied further among participants with greater heterogeneity of stress, PA and body composition. However, these findings suggest that objective stress assessment provides an additional aspect to stress evaluation. Furthermore, the results provide valuable information for developing stress assessment methods.Peer reviewe

The effectiveness and applicability of different lifestyle interventions for enhancing wellbeing : the study design for a randomized controlled trial for persons with metabolic syndrome risk factors and psychological distress

Peer reviewe

Measurement of the Higgs boson width and evidence of its off-shell contributions to ZZ production

Since the discovery of the Higgs boson in 2012, detailed studies of its properties have been ongoing. Besides its mass, its width—related to its lifetime—is an important parameter. One way to determine this quantity is to measure its off-shell production, where the Higgs boson mass is far away from its nominal value, and relating it to its on-shell production, where the mass is close to the nominal value. Here we report evidence for such off-shell contributions to the production cross-section of two Z bosons with data from the CMS experiment at the CERN Large Hadron Collider. We constrain the total rate of the off-shell Higgs boson contribution beyond the Z boson pair production threshold, relative to its standard model expectation, to the interval [0.0061, 2.0] at the 95% confidence level. The scenario with no off-shell contribution is excluded at a p-value of 0.0003 (3.6 standard deviations). We measure the width of the Higgs boson as $\Gamma$$_H$=3.2$^{+2.4}_{−1.7}$MeV, in agreement with the standard model expectation of 4.1 MeV. In addition, we set constraints on anomalous Higgs boson couplings to W and Z boson pairs

Measurement of differential t(t)over-bar production cross sections in the full kinematic range using lepton plus jets events from proton-proton collisions at root s=13 TeV

Measurements of differential and double-differential cross sections of top-quark pair (t (t) over bar) production arc presented in the lepton + jets channels with a single electron or muon and jets in the final state. The analysis combines for the first time signatures of top quarks with low transverse momentum p(T), where the top-quark decay products can be identified as separated jets and isolated leptons, and with high p(T), where the decay products are collimated and overlap. The measurements arc based on proton-proton collision data at is - = 13 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross sections are presented at the parton and particle levels, where the latter minimizes extrapolations based on theoretical assumptions. Most of the measured differential cross sections are well described by standard model predictions with the exception of some double-differential distributions. The inclusive t (t) over bar production cross section is measured to be sigma(t (t) over bar) = 791 +/- 25 pb, which constitutes the most precise measurement in the lepton + jets channel to date.Peer reviewe

Search for new particles in an extended Higgs sector with four b quarks in the final state at √s = 13 TeV

A search for a massive resonance X decaying to a pair of spin-0 bosons ϕ that themselves decay to pairs of bottom quarks, is presented. The analysis is restricted to the mass ranges from 25 to 100 GeV and from 1 to 3 TeV. For these mass ranges, the decay products of each ϕ boson are expected to merge into a single large-radius jet. Jet substructure and flavor identification techniques are used to identify these jets. The search is based on CERN LHC proton-proton collision data at , collected with the CMS detector in 2016–2018, corresponding to an integrated luminosity of 138 . Model-specific limits, where the two new particles arise from an extended Higgs sector, are set on the product of the production cross section and branching fraction for as a function of the resonances' masses, where both the and branching fractions are assumed to be 100%. These limits are the first of their kind on this process, ranging between 30 and 1 fb at 95% confidence level for the considered mass ranges