1,186 research outputs found
Disordered actomyosin networks are sufficient to produce cooperative and telescopic contractility
While the molecular interactions between individual myosin motors and F-actin are well
established, the relationship between F-actin organization and actomyosin forces remains
poorly understood. Here we explore the accumulation of myosin-induced stresses within a
two-dimensional biomimetic model of the disordered actomyosin cytoskeleton, where myosin
activity is controlled spatiotemporally using light. By controlling the geometry and the
duration of myosin activation, we show that contraction of disordered actin networks is
highly cooperative, telescopic with the activation size, and capable of generating non-uniform
patterns of mechanical stress. We quantitatively reproduce these collective biomimetic
properties using an isotropic active gel model of the actomyosin cytoskeleton, and explore
the physical origins of telescopic contractility in disordered networks using agent-based
simulations
Extended Huckel theory for bandstructure, chemistry, and transport. II. Silicon
In this second paper, we develop transferable semi-empirical parameters for
the technologically important material, silicon, using Extended Huckel Theory
(EHT) to calculate its electronic structure. The EHT-parameters areoptimized to
experimental target values of the band dispersion of bulk-silicon. We obtain a
very good quantitative match to the bandstructure characteristics such as
bandedges and effective masses, which are competitive with the values obtained
within an orthogonal-tight binding model for silicon. The
transferability of the parameters is investigated applying them to different
physical and chemical environments by calculating the bandstructure of two
reconstructed surfaces with different orientations: Si(100) (2x1) and Si(111)
(2x1). The reproduced - and -surface bands agree in part
quantitatively with DFT-GW calculations and PES/IPES experiments demonstrating
their robustness to environmental changes. We further apply the silicon
parameters to describe the 1D band dispersion of a unrelaxed rectangular
silicon nanowire (SiNW) and demonstrate the EHT-approach of surface passivation
using hydrogen. Our EHT-parameters thus provide a quantitative model of
bulk-silicon and silicon-based materials such as contacts and surfaces, which
are essential ingredients towards a quantitative quantum transport simulation
through silicon-based heterostructures.Comment: 9 pages, 9 figure
The effects of land use disturbance vary with trophic position in littoral cichlid fish communities from Lake Tanganyika
1. Impacts of anthropogenic disturbance are especially severe in freshwater ecosystems. In particular, land use disturbance can lead to increased levels of pollution, including elevated nutrient and sediment loads whose negative impacts range from the community to the individual level. However, few studies have investigated if these impacts are uniform across species represented by multiple trophic levels. To address this knowledge gap, we focused on Lake Tanganyika cichlid fishes, which comprise hundreds of species representing a wide range of feeding strategies. Cichlids are at their most diverse within the nearâshore environment; however, land use disturbance of this environment has led to decreasing diversity, particularly in herbivores. We therefore tested if there is a uniform effect of pollution across species and trophic groups within the hyperâdiverse rocky shore cichlid fish community.
2. We selected three sites with differing levels of human impact along the Tanzanian coastline and 10 cichlid species, comprising varying taxonomic and trophic groups, common to these sites. Nitrogen and carbon stable isotope values for 528 samples were generated and analysed using generalised linear mixed models. We also estimated stomach contents including sediment proportions.
3. Our study highlights that multiple sources of pollution are having differing effects across species within a diverse fish community. We found that nitrogen stable isotope values were significantly higher at the most disturbed (urbanised) site for benthic feeding species, whereas there was no difference in these isotopes between sites for the water column feeding trophic group. Stomach contents revealed that the elevated ÎŽ15N values were unlikely to have been caused by differences in diet between sites. However, at the most disturbed site, higher proportions of sediment were present in most herbivores, irrespective of foraging behaviour.
4. It is likely that anthropogenic nitrogen loading is the cause of higher nitrogen stable isotope values since there was no evidence of species shifting trophic levels between sites. Results support our previous study showing herbivore species to be most affected by human disturbance and make the link to pollution much more explicit. As lower diversity of consumers can negatively affect ecosystem processes such as stability, alleviating environmental impact through sewage treatment and afforestation programmes should continue to be a global priority for the conservation of aquatic ecosystems, as well as human health
Regulation of the apoptotic genes in breast cancer cells by the transcription factor CTCF
CTCF is a highly conserved and ubiquitous transcription factor with versatile functions. We previously demonstrated that elevated protein levels of CTCF in breast cancer cells were associated with the specific anti-apoptotic function of CTCF. We used proteomics and microarray approaches to identify regulatory targets of CTCF specific for breast cancer cells. Among the CTCF identified targets were proteins involved in the control of apoptosis. A proapoptotic protein, Bax, negatively regulated by CTCF, was chosen for further investigation. Repression of the human Bax gene at the transcriptional level by CTCF in breast cancer cells was confirmed by real-time PCR. Two CTCF binding sites within the Bax promoter were identified by electrophoretic mobility shift assay and footprinting. In reporter assays, the Bax-luciferase reporter construct, containing CTCF-binding sites, was negatively regulated by CTCF. In vivo, CTCF occupied its binding sites in breast cancer cells and tissues, as confirmed by chromatin immunoprecipitation assay. Our findings suggest a possible mechanism of the specific CTCF anti-apoptotic function in breast cancer cells whereby CTCF is bound to the Bax promoter, resulting in repression of Bax and inhibition of apoptosis; depletion of CTCF leads to activation of Bax and apoptotic death. CTCF binding sites in the Bax promoter are unmethylated in all cells and tissues inspected. Therefore, specific CTCF interaction with the Bax promoter in breast cancer cells, and the functional outcome, may depend on a combination of epigenetic factors characteristic for these cells. Interestingly, CTCF appears to be a negative regulator of other proapoptotic genes (for example, Fas, Apaf-1, TP531NP1). Conversely, stimulating effects of CTCF on the anti-apoptotic genes (Bcl-2, Bag-3) have been observed. Taken together, these findings suggest that specific mechanisms have evolved in breast cancer cells to protect them from apoptosis; regulation of apoptotic genes by CTCF appears to be one of the resistance strategies
Symbiotic partnerships and their chemical interactions in the leafcutter ants (Hymenoptera: Formicidae)
Full configuration interaction calculation of BeH adiabatic states
An all-electron full configuration interaction (FCI) calculation of the adiabatic potential energy curves of some of the lower states of BeH molecule is presented. A moderately large ANO basis set of atomic natural orbitals (ANO) augmented with Rydberg functions has been used in order to describe the valence and Rydberg states and their interactions. The Rydberg set of ANOs has been placed on the Be at all bond distances. So, the basis set can be described as 4s3p2d1f/3s2p1d(Be/H)+4s4p2d(Be). The dipole moments of several states and transition dipole strengths from the ground state are also reported as a function of the RBeâH distance. The position and the number of states involved in several avoided crossings present in this system have been discussed. Spectroscopic parameters have been calculated from a number of the vibrational states that result from the adiabatic curves except for some states in which this would be completely nonsense, as it is the case for the very distorted curves of the 3s and 3pâmath states or the double-well potential of the 4pâmath state. The so-called âD complexâ at 54â050âcmâ1 (185.0ânm) is resolved into the three 3d substates (math,math,math). A diexcited valence state is calculated as the lowest state of math symmetry and its spectroscopic parameters are reported, as well as those of the 2âmath (4d) state The adiabatic curve of the 4âmath state shows a swallow well at large distances (around 4.1âĂ
) as a result of an avoided crossing with the 3âmath state. The probability that some vibrational levels of this well could be populated is discussed within an approached LandauâZerner model and is found to be high. No evidence is found of the E(4sÏ) math state in the region of the âD complexâ. Instead, the spectroscopic properties obtained from the (4sÏ) 6âmath adiabatic curve of the present work seem to agree with those of the experimental F(4pÏ) math state. The FCI calculations provide benchmark results for other correlation models for the open-shell BeH system and evidence both the limitations and capabilities of the basis [email protected] [email protected]
Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus
Background: Nemolizumab targets the IL-31 receptor a subunit
involved in atopic dermatitis (AD) pathogenesis.
Objective: We sought to evaluate a new dosing strategy of
nemolizumab in patients with AD.
Methods: We performed a 24-week, randomized, double-blind,
multicenter study of nemolizumab (10, 30, and 90 mg)
subcutaneous injections every 4 weeks versus placebo, with
topical corticosteroids in adults with moderate-to-severe AD,
severe pruritus, and inadequate control with topical treatment
(n 5 226). The Eczema Area and Severity Index (EASI), the
peak pruritus (PP) numeric rating scale (NRS), and the
Investigatorâs Global Assessment (IGA) were assessed. Standard
safety assessments were performed.
Results: Nemolizumab improved EASI, IGA, and/or NRS-itch
scores, with the 30-mg dose being most effective.
Nemolizumab (30 mg) reduced EASI scores versus placebo at
week 24 (268.8% vs 252.1%, P 5 .016); significant
differences were observed by week 8 (P <_ .01). With significant
improvement (P 5 .028) as early as week 4, IGA 0/1 rates
were higher for 30 mg of nemolizumab versus placebo at week
16 (33.3% vs 12.3%, P 5 .008) but not week 24 because of an
increased placebo/topical corticosteroid effect (36.8% vs
21.1%, P 5 .06). PP-NRS scores were improved for 30 mg of
nemolizumab versus placebo at week 16 (268.6% vs 234.3%,
P <.0001) and week 24 (267.3% vs 235.8%, P <.0001), with a
difference by week 1 (P _4-point
decrease) were greater for 30 mg of nemolizumab versus
placebo at week 16 (P <_ .001) and week 24 (P <_ .01).
Nemolizumab was safe and well tolerated. The most common
adverse events were nasopharyngitis and upper respiratory
tract infection.
Conclusions: Nemolizumab resulted in rapid and sustained
improvements in cutaneous signs of inflammation and pruritus
in patients with AD, with maximal efficacy observed at 30 mg.
Nemolizumab had an acceptable safety profile. (J Allergy Clin
Immunol 2020;145:173-82.
Equation-Free Multiscale Computational Analysis of Individual-Based Epidemic Dynamics on Networks
The surveillance, analysis and ultimately the efficient long-term prediction
and control of epidemic dynamics appear to be one of the major challenges
nowadays. Detailed atomistic mathematical models play an important role towards
this aim. In this work it is shown how one can exploit the Equation Free
approach and optimization methods such as Simulated Annealing to bridge
detailed individual-based epidemic simulation with coarse-grained,
systems-level, analysis. The methodology provides a systematic approach for
analyzing the parametric behavior of complex/ multi-scale epidemic simulators
much more efficiently than simply simulating forward in time. It is shown how
steady state and (if required) time-dependent computations, stability
computations, as well as continuation and numerical bifurcation analysis can be
performed in a straightforward manner. The approach is illustrated through a
simple individual-based epidemic model deploying on a random regular connected
graph. Using the individual-based microscopic simulator as a black box
coarse-grained timestepper and with the aid of Simulated Annealing I compute
the coarse-grained equilibrium bifurcation diagram and analyze the stability of
the stationary states sidestepping the necessity of obtaining explicit closures
at the macroscopic level under a pairwise representation perspective
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