Reversible ADP-ribosylation of the 78 kDa glucose-regulated protein

AbstractStarvation of Mouse hepatoma cells for essential amino acids or glucose results in the mono-ADP-ribosylation of the 78 kDa glucose-regulated protein, GRP78. Here we show that the ADP-ribosylated and non-ADP-ribosylated forms of GRP78 are interconvertible during tryptophan starvation and refeeding. In addition, the ADP-ribosylation of GRP78 was shown to be reversible even during nutritional stress. The overexpressed pool of non-ADP-ribosylated GRP78 synthesized during tunicamycin treatment was available for ADP-ribosylation during subsequent amino acid starvation, especially in the absence of tunicamycin. The reversible ADP-ribosylation of GRP78 could be part of a metabolic control mechanism in operation during nutritional stress

Dynamic Environmental Control in Microfluidic Single‐Cell Cultivations: From Concepts to Applications

Täuber S, Lieres E, Grünberger A. Dynamic Environmental Control in Microfluidic Single‐Cell Cultivations: From Concepts to Applications. Small. 2020;16(16): 1906670.Microfluidic single‐cell cultivation (MSCC) is an emerging field within fundamental as well as applied biology. During the last years, most MSCCs were performed at constant environmental conditions. Recently, MSCC at oscillating and dynamic environmental conditions has started to gain significant interest in the research community for the investigation of cellular behavior. Herein, an overview of this topic is given and microfluidic concepts that enable oscillating and dynamic control of environmental conditions with a focus on medium conditions are discussed, and their application in single‐cell research for the cultivation of both mammalian and microbial cell systems is demonstrated. Furthermore, perspectives for performing MSCC at complex dynamic environmental profiles of single parameters and multiparameters (e.g., pH and O2) in amplitude and time are discussed. The technical progress in this field provides completely new experimental approaches and lays the foundation for systematic analysis of cellular metabolism at fluctuating environments

Intermediate Tail Dependence: A Review and Some New Results

The concept of intermediate tail dependence is useful if one wants to quantify the degree of positive dependence in the tails when there is no strong evidence of presence of the usual tail dependence. We first review existing studies on intermediate tail dependence, and then we report new results to supplement the review. Intermediate tail dependence for elliptical, extreme value and Archimedean copulas are reviewed and further studied, respectively. For Archimedean copulas, we not only consider the frailty model but also the recently studied scale mixture model; for the latter, conditions leading to upper intermediate tail dependence are presented, and it provides a useful way to simulate copulas with desirable intermediate tail dependence structures.Comment: 25 pages, 1 figur

Cooperativity of Kv7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells.

The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency. Here, we report ultrafast electromechanical gating of clustered Kv7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-Kv7.4 were revealed, using optogenetics strategies. Upon clustering, the half-activation voltage shifted negative, and the speed of activation increased relative to solitary channels. Clustering also rendered Kv7.4 channels mechanically sensitive, confirmed in consolidated Kv7.4 channels at the base of OHCs. Kv7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast Kv7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies

Allergen immunotherapy on the way to product-based evaluation - a WAO statement

Allergen immunotherapy (AIT) is widely used in clinical practice for patients with moderate to severe allergic rhinitis due to inhalant allergens and may be delivered via subcutaneous (SCIT) and sublingual routes (SLIT). However, the quality of evidence for individual AIT products is very heterogeneous, and extensions of overall conclusions ("class effects") on the efficacy and disease-modifying effects to all AIT products are unjustified. In contrast, each product needs to be evaluated individually, based on available study results, to justify efficacy and specific claims on sustained and disease modifying effects per allergen and targeted patient group (children vs. adults, allergic rhinitis vs. asthma). WAO intends to support the current development to evidence-based AIT, which ultimately will lead to a more efficacious treatment of allergic patients and the appropriate recognition of AIT

Open access and open source in chemistry

Scientific data are being generated and shared at ever-increasing rates. Two new mechanisms for doing this have developed: open access publishing and open source research. We discuss both, with recent examples, highlighting the differences between the two, and the strengths of both

RICE Limits on the Diffuse Ultra-High Energy Neutrino Flux

We present new limits on ultra-high energy neutrino fluxes above 100 PeV based on data collected by the Radio Ice Cherenkov Experiment (RICE) at the South Pole from 1999-2005. We discuss estimation of backgrounds, calibration and data analysis algorithms (both on-line and off-line), procedures used for the dedicated neutrino search, and refinements in our Monte Carlo (MC) simulation, including recent in situ measurements of the complex ice dielectric constant. An enlarged data set and a more detailed study of hadronic showers results in a sensitivity improvement of more than one order of magnitude compared to our previously published results. Examination of the full RICE data set yields zero acceptable neutrino candidates, resulting in 95% confidence-level model dependent limits on the flux (E_\nu)^2(d\phi/dE_\nu)<10^{-6} GeV/(cm^2s~sr}) in the energy range 10^{17}< E_\nu< 10^{20} eV. The new RICE results rule out the most intense flux model projections at 95% confidence level.Comment: Submitted to Astropart. Phy

ONZIN deficiency attenuates contact hypersensitivity responses in mice

ONZIN is abundantly expressed in immune cells of both the myeloid and lymphoid lineage. Expression by lymphoid cells has been reported to further increase after cutaneous exposure of mice to antigens and haptens capable of inducing contact hypersensitivity, suggesting that ONZIN plays a critical role in this response. Here, we report that indeed ONZIN-deficient mice develop attenuated CHS to a number of different haptens. Dampened CHS responses correlated with a significant reduction in pro-inflammatory IL-6 at the challenge site in ONZIN-deficient animals compared to wild type controls. Together the study of these animals indicates that loss of ONZIN impacts the effector phase of the CHS response through the regulation of pro-inflammatory factors

Legacy of COVID‐19 – the opportunity to enhance surgical services for patients with colorectal disease

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