Actin cytoskeleton assembly regulates collagen production via TGF‐β type II receptor in human skin fibroblasts

The dermal compartment of skin is primarily composed of collagen‐rich extracellular matrix (ECM), which is produced by dermal fibroblasts. In Young skin, fibroblasts attach to the ECM through integrins. During ageing, fragmentation of the dermal ECM limits fibroblast attachment. This reduced attachment is associated with decreased collagen production, a major cause of skin thinning and fragility, in the elderly. Fibroblast attachment promotes assembly of the cellular actin cytoskeleton, which generates mechanical forces needed for structural support. The mechanism(s) linking reduced assembly of the actin cytoskeleton to decreased collagen production remains unclear. Here, we report that disassembly of the actin cytoskeleton results in impairment of TGF‐β pathway, which controls collagen production, in dermal fibroblasts. Cytoskeleton disassembly rapidly down‐regulates TGF‐β type II receptor (TβRII) levels. This down‐regulation leads to reduced activation of downstream effectors Smad2/Smad3 and CCN2, resulting in decreased collagen production. These responses are fully reversible; restoration of actin cytoskeleton assembly up‐regulates TβRII, Smad2/Smad3, CCN2 and collagen expression. Finally, actin cytoskeleton‐dependent reduction of TβRII is mediated by induction of microRNA 21, a potent inhibitor of TβRII protein expression. Our findings reveal a novel mechanism that links actin cytoskeleton assembly and collagen expression in dermal fibroblasts. This mechanism likely contributes to loss of TβRII and collagen production, which are observed in aged human skin.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145494/1/jcmm13685_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145494/2/jcmm13685-sup-0001-FigS1-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145494/3/jcmm13685.pd

Bone versus breast density

The common link with oestrogen levels suggests that bone mineral density and mammographic density might also be linked. One study found weak support for this, but another study failed to provide confirmation. Overall, the relationship is very weak, if it exists at all. Other factors such as weight-bearing exercise, which have opposing impacts on these variables, may have a more dominant effect

Evolution of cooperation driven by zealots

Recent experimental results with humans involved in social dilemma games suggest that cooperation may be a contagious phenomenon and that the selection pressure operating on evolutionary dynamics (i.e., mimicry) is relatively weak. I propose an evolutionary dynamics model that links these experimental findings and evolution of cooperation. By assuming a small fraction of (imperfect) zealous cooperators, I show that a large fraction of cooperation emerges in evolutionary dynamics of social dilemma games. Even if defection is more lucrative than cooperation for most individuals, they often mimic cooperation of fellows unless the selection pressure is very strong. Then, zealous cooperators can transform the population to be even fully cooperative under standard evolutionary dynamics.Comment: 5 figure

How to increase the potential policy impact of environmental science research

This article highlights eight common issues that limit the policy impact of environmental science research. The article also discusses what environmental scientists can do to resolve these issues, including (1) optimising the directness of their study so that it examines similar processes/populations/environments/ecosystems to that of policy interest; (2) using the most powerful study design possible, to increase confidence in the identified causal mechanisms; (3) selecting a sufficient sample size, to reduce the chance of false positives/negatives and increase policy-makers’ confidence in extrapolation of the findings; (4) minimizing the risk of bias through randomization of study units to treatment and control groups (reducing the risk of selection bias), blinding of study units and investigators (reducing the risk of performance and detection bias), following-up study units from enrolment to study completion (reducing the risk of attrition bias) and prospectively registering the study on a publically-available platform (reducing the risk of reporting and publication bias); (5) proving that statistical analyses meet test assumptions by reporting the results of statistical assumption checks, ideally publishing full datasets online in an open-access format; (6) publishing the research whether statistically significant or not, policy-makers are just as interested in the negative or insignificant results as they are in the positive results; (7) making the study easy to find and use, the title and abstract of an article are of high importance in determining whether articles are examined in detail or not and used to inform policy; (8) contributing towards systematic reviews on environmental topics, to provide policy-makers with comprehensive, reproducible and updateable syntheses of all the evidence on a given topic.</p

Genetic variation in the estrogen metabolic pathway and mammographic density as an intermediate phenotype of breast cancer

Introduction: Several studies have examined the effect of genetic variants in genes involved in the estrogen metabolic pathway on mammographic density, but the number of loci studied and the sample sizes evaluated have been small and pathways have not been evaluated comprehensively. In this study, we evaluate the association between mammographic density and genetic variants of the estrogen metabolic pathway. Methods: A total of 239 SNPs in 34 estrogen metabolic genes were studied in 1,731 Swedish women who participated in a breast cancer case-control study, of which 891 were cases and 840 were controls. Film mammograms of the medio-lateral oblique view were digitalized and the software Cumulus was used for computer-assisted semi-automated thresholding of mammographic density. Generalized linear models controlling for possible confounders were used to evaluate the effects of SNPs on mammographic density. Results found to be nominally significant were examined in two independent populations. The admixture maximum likelihood-based global test was performed to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three subpathways for androgen synthesis, androgen-to-estrogen conversion and estrogen removal. Results: Genetic variants of genes involved in estrogen metabolism exhibited no appreciable effect on mammographic density. None of the nominally significant findings were validated. In addition, global analyses on the overall estrogen metabolic pathway and its subpathways did not yield statistically significant results. Conclusions: Overall, there is no conclusive evidence that genetic variants in genes involved in the estrogen metabolic pathway are associated with mammographic density in postmenopausal women

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Thermodynamics of deformed AdS5_5 model with a positive/negative quadratic correction in graviton-dilaton system

By solving the Einstein equations of the graviton coupling with a real scalar dilaton field, we establish a general framework to self-consistently solve the geometric background with black-hole for any given phenomenological holographic models. In this framwork, we solve the black-hole background, the corresponding dilaon field and the dilaton potential for the deformed AdS$_5$ model with a positive/negative quadratic correction. We systematically investigate the thermodynamical properties of the deformed AdS$_5$ model with a positive and negative quadratic correction, respectively, and compare with lattice QCD on the results of the equation of state, the heavy quark potential, the Polyakov loop and the spatial Wilson loop. We find that the bulk thermodynamical properties are not sensitive to the sign of the quadratic correction, and the results of both deformed holographic QCD models agree well with lattice QCD result for pure SU(3) gauge theory. However, the results from loop operators favor a positive quadratic correction, which agree well with lattice QCD result. Especially, the result from the Polyakov loop excludes the model with a negative quadratic correction in the warp factor of ${\rm AdS}_5$.Comment: 26 figures,36 pages,V.3: an appendix,more equations and references added,figures corrected,published versio

Coherent optical spectroscopy in a biological semiconductor quantum dot-DNA hybrid system

We theoretically investigate coherent optical spectroscopy of a biological semiconductor quantum dot (QD) coupled to DNA molecules. Coupling with DNAs, the linear optical responses of the peptide QDs will be enhanced significantly in the simultaneous presence of two optical fields. Based on this technique, we propose a scheme to measure the vibrational frequency of DNA and the coupling strength between peptide QD and DNA in all-optical domain. Distinct with metallic quantum dot, biological QD is non-toxic and pollution-free to environment, which will contribute to clinical medicine experiments. This article leads people to know more about the optical behaviors of DNAs-quantum dot system, with the currently popular pump-probe technique

Atomic super-resolution tomography

We consider the problem of reconstructing a nanocrystal at atomic resolution from electron microscopy images taken at a few tilt angles. A popular reconstruction approach called discrete tomography confines the atom locations to a coarse spatial grid, which is inspired by the physical a priori knowledge that atoms in a crystalline solid tend to form regular lattices. Although this constraint has proven to be powerful for solving this very under-determined inverse problem in many cases, its key limitation is that, in practice, defects may occur that cause atoms to deviate from regular lattice positions. Here we propose a grid-free discrete tomography algorithm that allows for continuous deviations of the atom locations similar to super-resolution approaches for microscopy. The new formulation allows us to define atomic interaction potentials explicitly, which results in a both meaningful and powerful incorporation of the available physical a priori knowledge about the crystal's properties. In computational experiments, we compare the proposed grid-free method to established grid-based approaches and show that our approach can indeed recover the atom positions more accurately for common lattice defects