HEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions.

A comprehensive, large-scale analysis of "terroir" cheese and milk microbiota reveals profiles strongly shaped by both geographical and human factors.

An exhaustive analysis was performed on more than 2000 microbiotas from French Protected Designation of Origin (PDO) cheeses, covering most cheese families produced throughout the world. Thanks to a complete and accurate set of associated metadata, we have carried out a deep analysis of the ecological drivers of microbial communities in milk and "terroir" cheeses. We show that bacterial and fungal microbiota from milk differed significantly across dairy species while sharing a core microbiome consisting of four microbial species.

Nutritional and microbial profiles of ripened plant-based cheese analogs collected from the European market.

Plant-based cheese analogs have emerged as a novel global market trend driven by sustainability concerns for our planet. This study examines eleven soft ripened plant-based cheese analogs produced in Europe, primarily with bloomy rinds and cashew nuts as the main ingredient. First, we focused on exploring the macronutrients and salt content stated on the labels, as well a detailed fatty acid analysis of the samples.

Charge density waves tuned by biaxial tensile stress.

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change.

sp. nov., sp. nov. and sp. nov., isolated from French cheese rinds.

Eight Gram-stain-negative bacterial strains were isolated from cheese rinds sampled in France. On the basis of 16S rRNA gene sequence analysis, all isolates were assigned to the genus s. Phylogenetic investigations, including 16S rRNA gene studies, multilocus sequence analysis, reconstruction of a pan-genome phylogenetic tree with the concatenated core-genome content and average nucleotide identity (ANI) calculations, revealed that they constituted three novel and well-supported clusters.

Lebanese fermented goat milk products: From tradition to meta-omics.

Ambriss, Serdaleh and Labneh El Darff are traditional Lebanese products made from fermented goat's milk. A questionnaire completed by 50 producers of these products showed that they are prepared by periodic percolation either by milk or by Laban in amphora or goat skins during the lactation season. Production is carried out on a small scale and in a limited number of production units, often by elderly people, resulting in a real risk of disappearance of these products and loss of the corresponding microbial resources.

compression of micropillars under coherent X-ray diffraction: a case study of experimental and data-analysis constraints.

Micropillar compression is a method of choice to understand mechanics at small scale. It is mainly studied with electron microscopy or white-beam micro-Laue X-ray diffraction. The aim of the present article is to show the possibilities of the use of diffraction with a coherent X-ray beam.

Correction to Influence of Generated Defects by Ar Implantation on the Thermoelectric Properties of ScN.

[This corrects the article DOI: 10.1021/acsaem.2c01672.

Allosteric binding cooperativity in a kinetic context.

Allosteric modulators are of prime interest in drug discovery. These drugs regulate the binding and function of endogenous ligands, with some advantages over orthosteric ligands. A typical pharmacological parameter in allosteric modulation is binding cooperativity.

Evaluating Allosteric Perturbations in Cannabinoid Receptor 1 by Single-Point Mutation.

Cannabinoid receptor 1 (CB1) is a promising drug target involved in many physiological processes. Using atomistic molecular dynamics (MD) simulations, we examined the structural effect of F237L mutation on CB1, a mutation that has qualitatively similar effects to allosteric ligand ORG27569 binding. This mutation showed a global effect on CB1 conformations.

Influence of Generated Defects by Ar Implantation on the Thermoelectric Properties of ScN.

Nowadays, making thermoelectric materials more efficient in energy conversion is still a challenge. In this work, to reduce the thermal conductivity and thus improve the overall thermoelectric performances, point and extended defects were generated in epitaxial 111-ScN thin films by implantation using argon ions. The films were investigated by structural, optical, electrical, and thermoelectric characterization methods.

In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites.

ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across species and its essential role in the life cycle of . Despite its importance, the exact mechanism of its action and regulation is still not fully understood. In this study we used coarse-grained molecular dynamics (CG-MD) to elucidate the lipid-protein interactions between a heterogeneous lipid membrane containing phosphatidylinositol and ATP2 (PcATP2), an ortholog of ATP2.

Revealing the microbial heritage of traditional Brazilian cheeses through metagenomics.

Brazilian artisanal cheeses date from the first Portuguese settlers and evolved via local factors, resulting in unique products that are now part of the patrimony and identity of different Brazilian regions. In this study, we combined several culture-independent approaches, including 16S/ITS metagenetics, assembly- and deep profiling-metagenomics to characterize the originality of the microbiota of five varieties of Brazilian artisanal cheeses from the South and Southeast regions of Brazil. Their core microbiota contained mainly lactic acid bacteria (LAB), of which Lactococcus lactis subsp.

Easy and computer-time-saving implementation of the van der Pauw method including anisotropy and probe positioning correction factors using approximate closed-form analytical functions.

Measurements in a van der Pauw configuration often require the use of complicated mathematical expressions or implicit relations, which may be computer-time-consuming or tedious to implement in a given software. Thus, a closed-form expression is often desirable. We propose to approximate these relations by closed-form analytical functions using only basic operators that can be easily implemented.

Making Waves: Modeling bioturbation in soils - are we burrowing in the right direction?

The burrowing, feeding and foraging activities of terrestrial and benthic organisms induce displacements of soil and sediment materials, leading to a profound mixing of these media. Such particle movements, called "sediment reworking" in aquatic environments and "bioturbation" in soils, have been thoroughly studied and modeled in sediments, where they affect organic matter mineralization and contaminant fluxes. In comparison, studies characterizing the translocation, by soil burrowers, of mineral particles, organic matter and adsorbed contaminants are paradoxically fewer.

Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor.

There is increasing support for water molecules playing a role in signal propagation through G protein-coupled receptors (GPCRs). However, exploration of the hydration features of GPCRs is still in its infancy. Here, we combined site-specific labeling with unnatural amino acids to molecular dynamics to delineate how local hydration of the ghrelin receptor growth hormone secretagogue receptor (GHSR) is rearranged upon activation.

Unraveling the world of halophilic and halotolerant bacteria in cheese by combining cultural, genomic and metagenomic approaches.

Halophilic/halotolerant bacteria are generally assumed to live in natural environments, although they may also be found in foods such as cheese and seafood. These salt-loving bacteria have been occasionally characterized in cheese, and studies on their ecological and technological functions are still scarce. We therefore selected 13 traditional cheeses to systematically characterize these microorganisms in their rinds via cultural, genomic and metagenomic methods.

Dynamical Correlations Reveal Allosteric Sites in G Protein-Coupled Receptors.

G protein-coupled Receptors (GPCRs) play a central role in many physiological processes and, consequently, constitute important drug targets. In particular, the search for allosteric drugs has recently drawn attention, since they could be more selective and lead to fewer side effects. Accordingly, computational tools have been used to estimate the druggability of allosteric sites in these receptors.

Road Map to Safe and Well-Designed De-escalation Trials of Systemic Adjuvant Therapy for Solid Tumors.

An important challenge in the field of cancer is finding the balance between delivering effective treatments and avoiding adverse effects and financial toxicity caused by innovative, yet expensive, drugs. To address this, several treatment de-escalation trials have been conducted, but only a few of these have provided clear answers. A few trials had poor accrual or had design flaws that led to conflicting results.

Switch maintenance chemotherapy versus observation after carboplatin and weekly paclitaxel doublet chemotherapy in elderly patients with advanced non-small cell lung cancer: IFCT-1201 MODEL trial.

Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.

Patients And Methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m d1, 8, 22) in squamous cell carcinoma to simple observation.

Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial.

Background: Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer.

Methods: In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment.

Draft-genome sequence data and phylogenomic comparison of two marine-sourced bacterial strains . MIP2626 and . BI730.

Halophilic and psychrophilic marine bacteria are source of interesting bioactive molecules for biotechnology. We report here the whole-genome sequences of two of them, . MIP2626 isolated from tropical peeled shrimps and BI730 isolated from deep-sea hydrothermal vent.

Traditional milk transformation schemes in Côte d'Ivoire and their impact on the prevalence of Streptococcus bovis complex bacteria in dairy products.

The Streptococcus bovis/Streptococcus equinus complex (SBSEC) and possibly Streptococcus infantarius subsp. infantarius (Sii) are associated with human and animal diseases. Sii predominate in spontaneously fermented milk products with unknown public health effects.

Weekly paclitaxel plus bevacizumab versus docetaxel as second- or third-line treatment in advanced non-squamous non-small-cell lung cancer: Results of the IFCT-1103 ULTIMATE study.

Purpose: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer (nsNSCLC).

Methods: In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS).