Thermodynamics of nucleosome breathing and positioning.

Nucleosomes are fundamental units of chromatin in which a length of genomic DNA is wrapped around a histone octamer spool in a left-handed superhelix. Large-scale nucleosome maps show a wide distribution of DNA wrapping lengths, which in some cases are tens of base pairs (bp) shorter than the 147 bp canonical wrapping length observed in nucleosome crystal structures. Here, we develop a thermodynamic model that assumes a constant free energy cost of unwrapping a nucleosomal bp.

Work-biased path-sampling calculations of chemical potentials: Principles and applications to uranium oxide.

We present the work-biased path-sampling scheme to calculate chemical potentials in atomic scale simulations. This scheme is based on a series of chained insertion and deletion paths from N to N + 1 to N atom systems, the sampling being performed on the paths themselves rather than on the final configurations. Equations for parallel path generations as well as geometrically biased insertions or deletions are presented.

What intensivists need to know about cytomegalovirus infection in immunocompromised ICU patients.

Purpose: Advances in therapeutic care are leading to an increase in the number of patients living with overt immunosuppression. These patients are at risk of cytomegalovirus (CMV) infection and disease that can lead to or develop during ICU admission. This manuscript aims to describe the clinical presentation, risk factors, and management of CMV infection and disease in this patient population.

Left ventricular diastolic dysfunction is prevalent but not associated with mortality in patients with septic shock.

Purpose: Prognostic impact of left ventricular diastolic dysfunction (LVDD) in septic shock patients has not been determined using current diagnostic guidelines. We assessed the relation between LVDD during the first 3 days following intensive care unit (ICU) admission for septic shock and Day-28 mortality.

Methods: This prospective, multicenter, observational study enrolled 402 patients (age: 63 ± 13 year; 59% male; SAPS II: 59 ± 20; SOFA: 9.

Best clinical model predicting extubation failure: a diagnostic accuracy post hoc analysis.

Purpose: Predicting extubation failure remains a clinical challenge. This study aimed to determine diagnostic accuracy of models used at the bed side.

Methods: Post hoc analysis of 2341 patients at all risk included in five multicenter randomized trials.

Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial.

Purpose: We hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and describe putative biological effects of vitamin C treatment.

Methods: We measured biomarkers of inflammation, at baseline and at 7 days post-randomisation, in 457/863 (53.

The spatial organization of cDC1 with CD8+ T cells is critical for the response to immune checkpoint inhibitors in melanoma patients.

Dendritic cells (DCs) are promising targets for cancer immunotherapies because of their central role in the initiation and control of immune responses. The rare cDC1 population is of particular interest because of its remarkable ability to cross-present antigens (Ag) to CD8+ T cells, to promote Th1 cell polarization and NK cell activation and recruitment. However, the spatial organization and specific functions of cDC1s in response to immunotherapy remain to be clearly characterized in human tumors.

Bathymetry of the Antarctic continental shelf and ice shelf cavities from circumpolar gravity anomalies and other data.

Bathymetry critically influences the intrusion of warm Circumpolar Deep Water onto the continental shelf and under ice shelf cavities in Antarctica, thereby forcing ice melting, grounding line retreat, and sea level rise. We present a novel and comprehensive bathymetry of Antarctica that includes all ice shelf cavities and previously unmeasured continental shelf areas. The new bathymetry is based on a 3D inversion of a circumpolar compilation of gravity anomalies constrained by measurements from the International Bathymetric Chart of the Southern Ocean, BedMachine Antarctica, and discrete seafloor measurements from seismic and ocean robotic probes.

Taxonomy of high pressure vibration spectra of zincblende semiconductor alloys based on the percolation model.

Due to their simple structure (two bond species randomly arranged on a cubic lattice), the zincblende ABC semiconductor alloys (zb-SCA) set a benchmark to explore how physical properties are impacted by disorder. A longstanding controversy was whether the lattice dynamics (phonons), governed by the bond force constant, i.e.

Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies.

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

Predicting fiber content in herbivore fecal samples using a multispecies NIRS model.

Fiber is essential for rumen health, microbial fermentation, and the energy supply of herbivores. Even though the study of fecal fiber contents (neutral detergent fiber NDF, acid detergent fiber ADF, and acid detergent lignin ADL) using near-infrared reflectance spectroscopy (NIRS) has allowed investigating nutritional ecology of different herbivore species, NIRS calibrations are species-specific and require a large number of samples for predictions. A multispecies calibration would be an advantage since samples from different herbivores could be used to calibrate a model capable of predicting the fecal fiber content of other herbivores.

Durable remission after ileocolic resection for Crohn's disease is achievable in selected patients. Long-term results of a prospective multicentric cohort study of the GETAID Chirurgie.

Background And Aims: Postoperative recurrence requiring medical treatment intensification or redo-surgery is common after ileocolic resection (ICR) for Crohn's disease (CD). This study aimed to identify a subgroup of CD patients for whom ICR could achieve durable remission.

Methods: This retrospective follow-up study analyzed 592 CD patients who underwent ICR (2013-2015) in a nationwide prospective cohort.

PDE11A is a phenotype modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: results of a 334 patients' series.

Purpose: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing's syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal and morphological levels. ARMC5 inactivating pathogenic variants are causative of PBMAH and rare variants of PDE11A have been associated with PBMAH.

Methods: Leukocyte DNA of 354 PBMAH index cases was sequenced for ARMC5 and PDE11A genes by Next generation sequencing (NGS).

The vertebrate small leucine-rich proteoglycans: amplification of a clustered gene family and evolution of their transcriptional profile in jawed vertebrates.

Small Leucine-Rich Proteoglycans (SLRPs) are a major family of vertebrate proteoglycans. In bony vertebrates, SLRPs have a variety of functions from structural to signaling and are found in extracellular matrices, notably in skeletal tissues. However, there is little or no data on the diversity, function and expression patterns of SLRPs in cartilaginous fishes, which hinders our understanding of how these genes evolved with the diversification of vertebrates, in particular regarding the early events of whole genome duplications that shaped gnathostome and cyclostome genomes.

Pharmacokinetic Boosting of Calcineurin Inhibitors in Transplantation: Pros, Cons, and Perspectives.

The concept of pharmacokinetic (PK) boosting of calcineurin inhibitors (CNI) emerged after the FDA approval of cyclosporine-A. Several studies followed, and the proof of concept was well established by the late 1990s. This also continued for the next blockbuster immunosuppressant, tacrolimus.

Cascading expression of ApiAP2 transcription factors controls daughter cell assembly in Toxoplasma gondii.

Pathogenesis of Toxoplasma gondii in the intermediate host is based on the tachyzoite ability to divide rapidly to produce significant amount of daughter cells in a reduce time frame. The regulation of the cell-cycle specific expression program is therefore key to their proliferation. Transcriptional regulation has a crucial role in establishing this expression program and transcription factors regulates many aspects of tachyzoite cell cycle.

Injectable biocompatible hydrogels with tunable strength based on crosslinked supramolecular polymer nanofibers.

Hydrogels based on supramolecular assemblies offer attractive features for biomedical applications including injectability or versatile combinations of various building blocks. We here investigate a system combining benzenetrispeptides (BTP), which forms supramolecular fibers, with polymer polyethylene oxide (PEO) forming a dense hydrophilic shell around the fibers. Hydrogels are created through the addition of a bifunctional crosslinker (CL).