A phase II double-blind multicentre, placebo-controlled trial to assess the efficacy and safety of alpelisib (BYL719) in paediatric and adult patients with Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP): the SESAM study protocol.

Introduction: The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3Kα-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS).

Plant response to intermittent heat stress involves modulation of mRNA translation efficiency.

Acquired thermotolerance (also known as priming) is the ability of cells or organisms to survive acute heat stress if preceded by a milder one. In plants, acquired thermotolerance has been studied mainly at the transcriptional level, including recent descriptions of sophisticated regulatory circuits that are essential for this learning capacity. Here, we tested the involvement of polysome-related processes (translation and cotranslational mRNA decay (CTRD)) in Arabidopsis (Arabidopsis thaliana) thermotolerance using two heat stress regimes with and without a priming event.

Three-Dimensional Laser Creation of a Near-IR Laser-Gain Medium Based on Hydride Donor/Acceptor Complexes Made of Coupled Laser-Induced Silver Nanoclusters with Ytterbium Ions.

Femtosecond laser inscription in a ytterbium-doped silver-containing phosphate glass is demonstrated by achieving 3D highly localized laser-induced silver photochemistry. The produced fluorescent silver nanoclusters lead to high optical contrast in the visible range, showing that the coinsertion of Yb ions is not detrimental to the silver-based photochemistry. We demonstrate efficient energy transfer from these silver nanoclusters to the rare-earth Yb ions, leading to near-IR background-free fluorescence emission.

Multi-transcriptomics identifies targets of the endoribonuclease DNE1 and highlights its coordination with decapping.

Decapping is a crucial step in mRNA degradation in eucaryotes and requires the formation of a holoenzyme complex between the decapping enzyme DECAPPING 2 (DCP2) and the decapping enhancer DCP1. In Arabidopsis (Arabidopsis thaliana), DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1) is a direct protein partner of DCP1. The function of both DNE1 and decapping is necessary to maintain phyllotaxis, the regularity of organ emergence in the apex.

Giant organelle vesicles to uncover intracellular membrane mechanics and plasticity.

Tools for accessing and studying organelles remain underdeveloped. Here, we present a method by which giant organelle vesicles (GOVs) are generated by submitting cells to a hypotonic medium followed by plasma membrane breakage. By this means, GOVs ranging from 3 to over 10 µm become available for micromanipulation.

Variants in and Associated with Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs.

(1) Background: Muscle hypertrophy, swallowing disorders, and gait abnormalities are clinical signs common to many muscle diseases, including muscular dystrophies, non-dystrophic myotonias, genetic myopathies associated with deficiency of myostatin, and acquired inflammatory myopathies. Here, we investigated underlying causes of this triad of clinical signs in four young French bulldogs via muscle histopathology coupled with whole genome and Sanger sequencing. (2) Methods: Dogs were evaluated by veterinary clinical internists and neurologists, and biopsies were obtained for histopathological diagnosis.

The unique dual targeting of AGO1 by two types of PRMT enzymes promotes phasiRNA loading in Arabidopsis thaliana.

Arginine/R methylation (R-met) of proteins is a widespread post-translational modification (PTM), deposited by a family of protein arginine/R methyl transferase enzymes (PRMT). Regulations by R-met are involved in key biological processes deeply studied in metazoan. Among those, post-transcriptional gene silencing (PTGS) can be regulated by R-met in animals and in plants.

Origins and Functional Significance of Eukaryotic Protein Folds.

Folds are the architecture and topology of a protein domain. Categories of folds are very few compared to the astronomical number of sequences. Eukaryotes have more protein folds than Archaea and Bacteria.

Cell-type-specific control of secondary cell wall formation by Musashi-type translational regulators in .

Deciphering the mechanism of secondary cell wall/SCW formation in plants is key to understanding their development and the molecular basis of biomass recalcitrance. Although transcriptional regulation is essential for SCW formation, little is known about the implication of post-transcriptional mechanisms in this process. Here we report that two RNA-binding proteins homologous to the animal translational regulator Musashi, MSIL2 and MSIL4, function redundantly to control SCW formation in .

Telehealth through the pandemic at a safety net hospital: observations and next steps for cancer care delivery.

The COVID-19 pandemic revolutionized cancer care delivery leading to rapid adoption of digital technology for telehealth in the United States. In this study, we describe telehealth utilization trends across the three largest waves of the pandemic at a safety net academic center. We also provide a perspective on lessons learnt and our vision for cancer care delivery using digital technology in the near future.

NICOTIANAMINE SYNTHASE activity affects nucleolar iron accumulation and impacts rDNA silencing and RNA methylation in Arabidopsis.

In plant cells, a large pool of iron (Fe) is contained in the nucleolus, as well as in chloroplasts and mitochondria. A central determinant for intracellular distribution of Fe is nicotianamine (NA) generated by NICOTIANAMINE SYNTHASE (NAS). Here, we used Arabidopsis thaliana plants with disrupted NAS genes to study the accumulation of nucleolar iron and understand its role in nucleolar functions and more specifically in rRNA gene expression.

Analyses of Mutation Displacements from Homology Models.

Evaluation of the structural perturbations introduced by a single amino acid mutation is the main issue for protein structural biology. We propose here to present some recent advances in methods, allowing the splitting of distortion between the actual substitution effect and the contribution of the local flexibility of the position where the mutation occurs. Its main drawback is the need of many structures with a single mutation in each of them.

Cholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols.

Cellular cholesterol can be metabolized to its fatty acid esters, cholesteryl esters (CEs), to be stored in lipid droplets (LDs). With triacylglycerols (TGs), CEs represent the main neutral lipids in LDs. However, while TG melts at ~4 °C, CE melts at ~44 °C, raising the question of how CE-rich LDs form in cells.

Complementary peptides represent a credible alternative to agrochemicals by activating translation of targeted proteins.

The current agriculture main challenge is to maintain food production while facing multiple threats such as increasing world population, temperature increase, lack of agrochemicals due to health issues and uprising of weeds resistant to herbicides. Developing novel, alternative, and safe methods is hence of paramount importance. Here, we show that complementary peptides (cPEPs) from any gene can be designed to target specifically plant coding genes.

Triglyceride lipolysis triggers liquid crystalline phases in lipid droplets and alters the LD proteome.

Lipid droplets (LDs) are reservoirs for triglycerides (TGs) and sterol-esters (SEs), but how these lipids are organized within LDs and influence their proteome remain unclear. Using in situ cryo-electron tomography, we show that glucose restriction triggers lipid phase transitions within LDs generating liquid crystalline lattices inside them. Mechanistically this requires TG lipolysis, which decreases the LD's TG:SE ratio, promoting SE transition to a liquid crystalline phase.

Assessment of a fully automated RPR assay (Mediace RPR) for serological diagnosis and follow-up of syphilis: a retrospective study.

Objectives: This study assessed the Mediace RPR assay, an automated RPR (aRPR), for syphilis diagnosis and serological follow-up.

Methods: Serums from patients positively screened for syphilis between January 2017 and December 2019 were retrospectively selected. A focus was performed on patients with a serological follow-up after treatment and/or a reinfection.

Protein folds as synapomorphies of the tree of life.

Several studies showed that folds (topology of protein secondary structures) distribution in proteomes may be a global proxy to build phylogeny. Then, some folds should be synapomorphies (derived characters exclusively shared among taxa). However, previous studies used methods that did not allow synapomorphy identification, which requires congruence analysis of folds as individual characters.

MOSPD2 is an endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis.

Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER-anchored proteins, such as MOSPD2, that function as major ER-organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain.

Characterization of the complete plastome of , a polyploid, endemic and endangered Pyrenean Larkspur.

DC. 1815, is an endangered larkspur endemic to the Eastern Pyrenees. For biogeographic and conservation purpose, a hybrid assembly approach based on long- and short-read genomic data allowed us to successfully assemble whole plastid genome of .

Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial.

Background: The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015.

Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.

Purpose: PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients.

Methods: Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day).

LARP6C orchestrates posttranscriptional reprogramming of gene expression during hydration to promote pollen tube guidance.

Increasing evidence suggests that posttranscriptional regulation is a key player in the transition between mature pollen and the progamic phase (from pollination to fertilization). Nonetheless, the actors in this messenger RNA (mRNA)-based gene expression reprogramming are poorly understood. We demonstrate that the evolutionarily conserved RNA-binding protein LARP6C is necessary for the transition from dry pollen to pollen tubes and the guided growth of pollen tubes towards the ovule in Arabidopsis thaliana.