Targeting Protein Kinase C-α Prolongs Survival and Restores Liver Function in Sepsis: Evidence from Preclinical Models.

Sepsis is a life-threatening organ failure resulting from a poorly regulated infection response. Organ dysfunction includes hepatic involvement, weakening the immune system due to excretory liver failure, and metabolic dysfunction, increasing the death risk. Although experimental studies correlated excretory liver functionality with immune performance and survival rates in sepsis, the proteins and pathways involved remain unclear.

Intrinsic and environmental drivers of pairwise cohesion in wild Canis social groups.

Animals within social groups respond to costs and benefits of sociality by adjusting the proportion of time they spend in close proximity to other individuals in the group (cohesion). Variation in cohesion between individuals, in turn, shapes important group-level processes such as subgroup formation and fission-fusion dynamics. Although critical to animal sociality, a comprehensive understanding of the factors influencing cohesion remains a gap in our knowledge of cooperative behavior in animals.

Engineered transcription-associated Cas9 targeting in eukaryotic cells.

DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they provide intrinsic spatial control over DNA targeting activities but naturally lack temporal control. Here we show that engineered Cas9 fusion proteins which bind to nascent RNAs near a protospacer can facilitate spatiotemporal coupling between transcription and DNA targeting at that protospacer: Transcription-associated Cas9 Targeting (TraCT).

CO-induced drastic decharging of dielectric surfaces in aqueous suspensions.

We study the influence of airborne CO on the charge state of carboxylate stabilized polymer latex particles suspended in aqueous electrolytes. We combine conductometric experiments interpreted in terms of Hessinger's conductivity model with Poisson-Boltzmann cell (PBC) model calculations with charge regulation boundary conditions. Without CO, a minority of the weakly acidic surface groups are dissociated and only a fraction of the total number of counter-ions actually contribute to conductivity.

Determination of the optimal time for planning SAVI brachytherapy for APBI.

Introduction: Accelerated partial breast irradiation with high dose rate brachytherapy treats early-stage carcinoma. Strut-adjusted volume implant applicators are inserted into the cavity post-lumpectomy. For an unstable applicator, changes in distance are seen each day between struts.

Unexpected Two-Stage Swelling of Weak Polyelectrolyte Brushes with Divalent Counterions.

We use particle-based, coarse-grained simulations to study the influence of divalent counterions on a weak polyelectrolyte brush. Our simulations show a profound influence of even small concentrations of divalent salt on the titration behavior of the brush, which is shown to be a combined effect of electrostatic interactions and the Donnan effect. Furthermore, we examine the partitioning of mono- and divalent counterions into the brush.

Development of radiofluorinated MLN-4760 derivatives for PET imaging of the SARS-CoV-2 entry receptor ACE2.

Purpose: The angiotensin converting enzyme 2 (ACE2) plays a regulatory role in the cardiovascular system and serves SARS-CoV-2 as an entry receptor. The aim of this study was to synthesize and evaluate radiofluorinated derivatives of the ACE2 inhibitor MLN-4760. [F]F-MLN-4760 and [F]F-Aza-MLN-4760 were demonstrated to be suitable for non-invasive imaging of ACE2, potentially enabling a better understanding of its expression dynamics.

pyMBE: The Python-based molecule builder for ESPResSo.

We present the Python-based Molecule Builder for ESPResSo (pyMBE), an open source software application to design custom coarse-grained (CG) models, as well as pre-defined models of polyelectrolytes, peptides, and globular proteins in the Extensible Simulation Package for Research on Soft Matter (ESPResSo). The Python interface of ESPResSo offers a flexible framework, capable of building custom CG models from scratch. As a downside, building CG models from scratch is prone to mistakes, especially for newcomers in the field of CG modeling, or for molecules with complex architectures.

Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space.

Fibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space.

[Development and implementation of primary nursing in the intensive care unit: evaluation in mixed-methods design.].

Development and implementation of primary nursing in the intensive care unit: evaluation in mixed-methods design. In a university hospital, the development and implementation of Primary Nursing (Prozessverantwortliche Pflege, PP) in a pilot intensive care unit was initiated. To develop the roles of nurses with and without process responsibility a working group PP was founded while taking into account the skill-grade mix.

Habitat selection of resident and non-resident gray wolves: implications for habitat connectivity.

Habitat selection studies facilitate assessing and predicting species distributions and habitat connectivity, but habitat selection can vary temporally and among individuals, which is often ignored. We used GPS telemetry data from 96 Gray wolves (Canis lupus) in the western Great Lakes region of the USA to assess differences in habitat selection while wolves exhibited resident (territorial) or non-resident (dispersing or floating) movements and discuss implications for habitat connectivity. We used a step-selection function (SSF) to assess habitat selection by wolves exhibiting resident or non-resident movements, and modeled circuit connectivity throughout the western Great Lakes region.

Explaining Giant Apparent pK_{a} Shifts in Weak Polyelectrolyte Brushes.

Recent experiments on weak polyelectrolyte brushes found marked shifts in the effective pK_{a} that are linear in the logarithm of the salt concentration. Comparing explicit-particle simulations with mean-field calculations we show that for high grafting densities the salt concentration effect can be explained using the ideal Donnan theory, but for low grafting densities the full shift is due to a combination of the Donnan effect and the polyelectrolyte effect. The latter originates from electrostatic correlations that are neglected in the Donnan picture and that are only approximately included in the mean-field theory.

Engineered transcription-associated Cas9 targeting in eukaryotic cells.

DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they provide intrinsic spatial control over DNA targeting activities but naturally lack temporal control. Here we show that engineered Cas9 fusion proteins which bind to nascent RNAs near a protospacer can facilitate spatiotemporal coupling between transcription and DNA targeting at that protospacer: Transcription-associated Cas9 Targeting (TraCT).

A generalized grand-reaction method for modeling the exchange of weak (polyprotic) acids between a solution and a weak polyelectrolyte phase.

We introduce a Monte-Carlo method that allows for the simulation of a polymeric phase containing a weak polyelectrolyte, which is coupled to a reservoir at a fixed pH, salt concentration, and total concentration of a weak polyprotic acid. The method generalizes the established grand-reaction method by Landsgesell et al. [Macromolecules 53, 3007-3020 (2020)] and, thus, allows for the simulation of polyelectrolyte systems coupled to reservoirs with a more complex chemical composition.

Assessing the Validity of NMR Relaxation Rates Obtained from Coarse-Grained Simulations of PEG-Water Mixtures.

NMR relaxometry is a powerful and well-established experimental approach for characterizing dynamic processes in soft matter systems. All-atom (AA) resolved simulations are typically employed to gain further microscopic insights while reproducing the relaxation rates . However, such approaches are limited to time and length scales that prevent to model systems such as long polymer chains or hydrogels.

Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial.

Purpose: To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer.

Methods: Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd).

Behavioral responses of terrestrial mammals to COVID-19 lockdowns.

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions.

Formation and Polymorphism of Semiconducting KSiH and Strategy for Metallization.

KSiH, crystallizing in the cubic KPtCl structure type (3̅), features unusual hypervalent SiH complexes. Here, the formation of KSiH at high pressures is revisited by in situ synchrotron diffraction experiments, considering KSiH as a precursor. At the investigated pressures, 8 and 13 GPa, KSiH adopts the trigonal (NH)SiF structure type (3̅1) upon formation.

Reply to the 'Comment on "Simulations of ionization equilibria in weak polyelectrolyte solutions and gels"' by J. Landsgesell, L. Nová, O. Rud, F. Uhlík, D. Sean, P. Hebbeker, C. Holm and P. Košovan, , 2019, , 1155-1185.

Levin and Bakhshandeh suggested in their comment that (1), we stated in our recent review that pH-p is a universal parameter for titrating systems, that (2), we omitted to mention in our review the broken symmetry of the constant pH algorithm, and that (3), a constant pH simulation must include a grand-canonical exchange of ions with the reservoir. As a reply to (1), we point out that Levin and Bakhshandeh misquoted and hence invalidated our original statement. We therefore explain in detail under which circumstances pH-p can be a universal parameter, and also demonstrate why their numerical example is not in contradiction to our statement.

A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides.

Purpose: The angiotensin converting enzyme-2 (ACE2)-entry receptor of SARS-CoV-2-and its homologue, the angiotensin-converting enzyme (ACE), play a pivotal role in maintaining cardiovascular homeostasis. Potential changes in ACE2 expression levels and dynamics after SARS-CoV-2 infection have been barely investigated. The aim of this study was to develop an ACE2-targeting imaging agent as a noninvasive imaging tool to determine ACE2 regulation.

IFITM3 blocks influenza virus entry by sorting lipids and stabilizing hemifusion.

Interferon-induced transmembrane protein 3 (IFITM3) inhibits the entry of numerous viruses through undefined molecular mechanisms. IFITM3 localizes in the endosomal-lysosomal system and specifically affects virus fusion with target cell membranes. We found that IFITM3 induces local lipid sorting, resulting in an increased concentration of lipids disfavoring viral fusion at the hemifusion site.

Distribution of Pb, Sr, and U isotopic signature and multielement composition of sediment in Lake Balaton (Hungary) at a sediment trap deep dredged 40 years ago near Balatongyörök-search for routes of recent pollution.

We studied the Pb, Sr, and U isotopic composition and the concentration of toxic metal elements in sediment core samples collected in Lake Balaton at a sediment trap that was deep dredged in 1979, to analyze their changes in the last 40 years. Pb isotopic composition profiles of cores taken from the sediment trap showed different Pb/Pb ratios ranging from 1.206 ± 0.

Genetic architecture and evolution of color variation in American black bears.

Color variation is a frequent evolutionary substrate for camouflage in small mammals, but the underlying genetics and evolutionary forces that drive color variation in natural populations of large mammals are mostly unexplained. The American black bear, Ursus americanus (U. americanus), exhibits a range of colors including the cinnamon morph, which has a similar color to the brown bear, U.