Heterochromatic gene silencing controls CD4 T cell susceptibility to regulatory T cell-mediated suppression in a murine allograft model.

Protective immune responses require close interactions between conventional (Tconv) and regulatory T cells (Treg). The extracellular mediators and signaling events that regulate the crosstalk between these CD4 T cell subsets have been extensively characterized. However, how Tconv translate Treg-dependent suppressive signals at the chromatin level remains largely unknown.

Interplay between the Xer recombination system and the dissemination of antibioresistance in Acinetobacter baumannii.

Antibiotic-resistant infections are a pressing clinical challenge. Plasmids are known to accelerate the emergence of resistance by facilitating horizontal gene transfer of antibiotic resistance genes between bacteria. We explore this question in Acinetobacter baumannii, a globally emerging nosocomial pathogen responsible for a wide range of infections with a worrying accumulation of resistance, particularly involving plasmids.

Deep-blur: Blind identification and deblurring with convolutional neural networks.

We propose a neural network architecture and a training procedure to estimate blurring operators and deblur images from a single degraded image. Our key assumption is that the forward operators can be parameterized by a low-dimensional vector. The models we consider include a description of the point spread function with Zernike polynomials in the pupil plane or product-convolution expansions, which incorporate space-varying operators.

Pivotal role of exogenous pyruvate in human natural killer cell metabolism.

Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.

E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development.

Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U).

Mechanical compressive forces increase PI3K output signaling in breast and pancreatic cancer cells.

Mechanical stresses, including compression, arise during cancer progression. In solid cancer, especially breast and pancreatic cancers, the rapid tumor growth and the environment remodeling explain their high intensity of compressive forces. However, the sensitivity of compressed cells to targeted therapies remains poorly known.

DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.

The enzyme dihydropyrimidine dehydrogenase (DPD) is the primary catabolic pathway of fluoropyrimidines including 5 fluorouracil (5FU) and capecitabine. Cases of lethal toxicity have been reported in cancer patients with complete DPD deficiency receiving standard dose of 5FU or capecitabine. DPD is encoded by the pharmacogene DPYD in which more than 200 variants have been identified.

The multi-faceted roles of MYC in the prognosis of chronic lymphocytic leukemia.

In this review, we focus on the pro-oncogene MYC, the modes of deregulation in mouse and human B-cells, its undisputable importance in the evaluation of biological prognostication of patients, but also how it impacts on response to modern therapeutics, and how it should be targeted to improve the overall survival of chronic lymphocytic lymphoma (CLL) patients. After an overview of the current understanding of the molecular dysregulation of c-MYC, we will show how CLL, both in its indolent and transformed phases, has developed among other B-cell lymphomas a tight regulation of its expression through the chronic activation of B-Cell Receptors (among others). This is particularly important if one desires to understand the mechanisms at stake in the over-expression of c-MYC especially in the lymph nodes compartment.

A stable combination of non-stable genes outperforms standard reference genes for RT-qPCR data normalization.

Gene expression profiling is of key importance in all domains of life sciences, as medicine, environment, and plants, for both basic and applied research. Despite the emergence of microarrays and high-throughput sequencing, qPCR remains a standard method for gene expression analyses, with its data normalization step being crucial for ensuring accuracy. Currently, the most widely used normalization method is based on the use of reference genes, assumed to be stably expressed across all experimental conditions.

Ecological and anthropogenic effects on the genomic diversity of lemurs in Madagascar.

Ecological variation and anthropogenic landscape modification have had key roles in the diversification and extinction of mammals in Madagascar. Lemurs represent a radiation with more than 100 species, constituting roughly one-fifth of the primate order. Almost all species of lemurs are threatened with extinction, but little is known about their genetic diversity and demographic history.

Cerebrotendinous xanthomatosis: a literature review and case study.

Cerebrotendinous xanthomatosis (CTX) is a rare but treatable inherited neurometabolic disorder that can lead to severe sequelae if left untreated. Chenodeoxycholic acid is a safe and effective treatment for CTX. Early diagnosis is essential to improve patient outcomes.

Size-fractionated carbonaceous and iron-rich particulate matter in urban environments of France and Senegal.

Road traffic is one of the main sources of particulate matter in the urban environment, emitting particulate organic and elemental carbon compounds and metal-rich particles through combustion and brakes and tires wear. In Western Africa, the carbon and metal composition of airborne particles is also influenced by additional sources linked to biomass combustion and recent industrialization. Here, we investigated the impact of combustion-related and non-combustion-related emissions on the distribution of carbonaceous fractions and iron-rich particles in two urban environments in France and Senegal.

Mass Spectrometry-Based Workflow for the Identification and Quantification of Alternative and Canonical Proteins in Pancreatic Cancer Cells.

The identification of small proteins and proteins produced from unannotated open reading frames (called alternative proteins or AltProts) has changed our vision of the proteome and has attracted more and more attention from the scientific community. Despite several studies investigating particular AltProts in diseases and demonstrating their importance in such context, we are still missing data on their expression and functions in many pathologies. Among these, pancreatic ductal adenocarcinoma (PDAC) is a particularly relevant case to study alternative proteins.

Real-world multicentre study of cefiderocol treatment of immunocompromised patients with infections caused by multidrug-resistant Gram-negative bacteria: CEFI-ID.

Introduction: The increase in the population of immunocompromised patients due to advances in management of end-stage diseases and transplants poses challenges in treating infections caused by multi-drug resistant (MDR) pathogens. Cefiderocol (FDC), a siderophore cephalosporin, has shown efficacy against carbapenem-resistant Gram-negative bacteria.

Methods: This retrospective multicentre study investigated the real-world use of FDC in 114 immunocompromised adults treated for MDR infections in 12 French hospitals (June 2020-November 2023).

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Shaping tomorrow: how the STEP training course pioneered noninvasive brain stimulation training for psychiatry in France.

Over the past three decades, non-invasive brain stimulation (NIBS) techniques have gained worldwide attention and demonstrated therapeutic potential in various medical fields, particularly psychiatry. The emergence of these novel techniques has led to an increased need for robust training programs to provide practitioners, whether clinicians or scientists, with the necessary skills and knowledge. In response, a comprehensive training curriculum for NIBS in psychiatry has been developed in France.

Disease-modifying treatment and disability progression in subclasses of patients with primary progressive MS: results from the Big MS Data Network.

Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.

Testing General Relativity through the E_{G} Statistic Using the Weyl Potential and Galaxy Velocities.

We combine measurements of galaxy velocities from galaxy surveys with measurements of the Weyl potential from the Dark Energy Survey to test the consistency of general relativity at cosmological scales. Taking the ratio of two model-independent observables-the growth rate of structure and the Weyl potential-we obtain new measurements of the E_{G} statistic with precision of 6.0-11.

Human colonic organoids for understanding early events of familial adenomatous polyposis pathogenesis.

Patients with familial adenomatous polyposis (FAP) harbor mutations in the APC gene and will develop adenoma and early colorectal cancer. There is no validated treatment, and animal models are not sufficient to study FAP. Our aim was to investigate the early events associated with FAP using the intestinal organoid model in a single-center study using biopsies from nonadenomatous and adenomatous colonic mucosa of FAP patients and from healthy controls (HCs).

MRI management of NMOSD and MOGAD: Proposals from the French Expert Group NOMADMUS.

Background: Currently, there are no available recommendations or guidelines on how to perform MRI monitoring in the management of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The issue is to determine a valuable MRI monitoring protocol to be applied in the management of NMOSD and MOGAD, as previously proposed for the monitoring of multiple sclerosis.

Objectives: The objectives of this work are to establish proposals for a standardized and feasible MRI acquisition protocol, and to propose control time points for systematic MRI monitoring in the management of NMOSD and MOGAD.

Association between education level and access to disease-modifying treatment in patients with multiple sclerosis in France.

Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS).

Objective: This study aimed to analyze the association between education level and DMT use in France.

Methods: All patients from OFSEP network with MS onset over 1996-2014 and aged ⩾ 25 years at onset were included.