1,120 research outputs found
Target search on a dynamic DNA molecule
We study a protein-DNA target search model with explicit DNA dynamics
applicable to in vitro experiments. We show that the DNA dynamics plays a
crucial role for the effectiveness of protein "jumps" between sites distant
along the DNA contour but close in 3D space. A strongly binding protein that
searches by 1D sliding and jumping alone, explores the search space less
redundantly when the DNA dynamics is fast on the timescale of protein jumps
than in the opposite "frozen DNA" limit. We characterize the crossover between
these limits using simulations and scaling theory. We also rationalize the slow
exploration in the frozen limit as a subtle interplay between long jumps and
long trapping times of the protein in "islands" within random DNA
configurations in solution.Comment: manuscript and supplementary material combined into a single documen
Reduced tillage, but not organic matter input, increased nematode diversity and food web stability in European longâterm field experiments
Soil nematode communities and food web indices can inform about the complexity, nutrient flows and decomposition pathways of soil food webs, reflecting soil quality. Relative abundance of nematode feeding and lifeâhistory groups are used for calculating food web indices, i.e., maturity index (MI), enrichment index (EI), structure index (SI) and channel index (CI). Molecular methods to study nematode communities potentially offer advantages compared to traditional methods in terms of resolution, throughput, cost and time. In spite of such advantages, molecular data have not often been adopted so far to assess the effects of soil management on nematode communities and to calculate these food web indices. Here, we used highâthroughput amplicon sequencing to investigate the effects of tillage (conventional vs. reduced) and organic matter addition (low vs. high) on nematode communities and food web indices in 10 European longâterm field experiments and we assessed the relationship between nematode communities and soil parameters. We found that nematode communities were more strongly affected by tillage than by organic matter addition. Compared to conventional tillage, reduced tillage increased nematode diversity (23% higher Shannon diversity index), nematode community stability (12% higher MI), structure (24% higher SI), and the fungal decomposition channel (59% higher CI), and also the number of herbivorous nematodes (70% higher). Total and labile organic carbon, available K and microbial parameters explained nematode community structure. Our findings show that nematode communities are sensitive indicators of soil quality and that molecular profiling of nematode communities has the potential to reveal the effects of soil management on soil quality
On the action potential as a propagating density pulse and the role of anesthetics
The Hodgkin-Huxley model of nerve pulse propagation relies on ion currents
through specific resistors called ion channels. We discuss a number of
classical thermodynamic findings on nerves that are not contained in this
classical theory. Particularly striking is the finding of reversible heat
changes, thickness and phase changes of the membrane during the action
potential. Data on various nerves rather suggest that a reversible density
pulse accompanies the action potential of nerves. Here, we attempted to explain
these phenomena by propagating solitons that depend on the presence of
cooperative phase transitions in the nerve membrane. These transitions are,
however, strongly influenced by the presence of anesthetics. Therefore, the
thermodynamic theory of nerve pulses suggests a explanation for the famous
Meyer-Overton rule that states that the critical anesthetic dose is linearly
related to the solubility of the drug in the membranes.Comment: 13 pages, 8 figure
Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects
During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pHi), we propose a direct mechanistic link between complement activation and neutrophil pHi In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis
Development of Readout Interconnections for the Si-W Calorimeter of SiD
The SiD collaboration is developing a Si-W sampling electromagnetic
calorimeter, with anticipated application for the International Linear
Collider. Assembling the modules for such a detector will involve special
bonding technologies for the interconnections, especially for attaching a
silicon detector wafer to a flex cable readout bus. We review the interconnect
technologies involved, including oxidation removal processes, pad surface
preparation, solder ball selection and placement, and bond quality assurance.
Our results show that solder ball bonding is a promising technique for the Si-W
ECAL, and unresolved issues are being addressed.Comment: 8 pages + title, 6 figure
Recombination rate and selection strength in HIV intra-patient evolution
The evolutionary dynamics of HIV during the chronic phase of infection is
driven by the host immune response and by selective pressures exerted through
drug treatment. To understand and model the evolution of HIV quantitatively,
the parameters governing genetic diversification and the strength of selection
need to be known. While mutation rates can be measured in single replication
cycles, the relevant effective recombination rate depends on the probability of
coinfection of a cell with more than one virus and can only be inferred from
population data. However, most population genetic estimators for recombination
rates assume absence of selection and are hence of limited applicability to
HIV, since positive and purifying selection are important in HIV evolution.
Here, we estimate the rate of recombination and the distribution of selection
coefficients from time-resolved sequence data tracking the evolution of HIV
within single patients. By examining temporal changes in the genetic
composition of the population, we estimate the effective recombination to be
r=1.4e-5 recombinations per site and generation. Furthermore, we provide
evidence that selection coefficients of at least 15% of the observed
non-synonymous polymorphisms exceed 0.8% per generation. These results provide
a basis for a more detailed understanding of the evolution of HIV. A
particularly interesting case is evolution in response to drug treatment, where
recombination can facilitate the rapid acquisition of multiple resistance
mutations. With the methods developed here, more precise and more detailed
studies will be possible, as soon as data with higher time resolution and
greater sample sizes is available.Comment: to appear in PLoS Computational Biolog
Managing phase purities and crystal orientation for high-performance and photostable cesium lead halide perovskite solar cells
Inorganic perovskites with cesium (Cs+) as the cation have great potential as photovoltaic materials if their phase purity and stability can be addressed. Herein, a series of inorganic perovskites is studied, and it is found that the power conversion efficiency of solar cells with compositions CsPbI1.8Br1.2, CsPbI2.0Br1.0, and CsPbI2.2Br0.8 exhibits a high dependence on the initial annealing step that is found to significantly affect the crystallization and texture behavior of the final perovskite film. At its optimized annealing temperature, CsPbI1.8Br1.2 exhibits a pure orthorhombic phase and only one crystal orientation of the (110) plane. Consequently, this allows for the best efficiency of up to 14.6% and the longest operational lifetime, T S80, of â300âh, averaged of over six solar cells, during the maximum power point tracking measurement under continuous light illumination and nitrogen atmosphere. This work provides essential progress on the enhancement of photovoltaic performance and stability of CsPbI3âââx Brx perovskite solar cells
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