Loss of tolerance to dietary proteins: From mouse models to human model diseases.

The critical importance of the immunoregulatory mechanisms, which prevent adverse responses to dietary proteins is demonstrated by the consequences of their failure in two common but distinct human pathological conditions, food allergy and celiac disease. The mechanisms of tolerance to dietary proteins have been extensively studied in mouse models but the extent to which the results in mice can be extrapolated to humans remains unclear. Here, after summarizing the mechanisms known to control oral tolerance in mouse models, we discuss how the monogenic immune disorders associated with food allergy on the one hand, and celiac disease, on the other hand, represent model diseases to gain insight into the key immunoregulatory pathways that control immune responses to food antigens in humans.

Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects.

Erythrocyte membrane protein band 4.1 like 3 (EPB41L3: NM_012307.5), also known as DAL1, encodes the ubiquitously expressed, neuronally enriched 4.

Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials.

Recent studies highlighted genetic aberrations associated with prognosis in Mantle Cell lymphoma (MCL), yet comprehensive testing is not implemented in clinical routine. We conducted a comprehensive genomic characterization of 180 patients from the European MCL network trials by targeted sequencing of peripheral blood DNA using the EuroClonality(EC)-NDC assay. The IGH::CCND1 fusion was identified in 94% of patients, clonal IGH-V-(D)-J rearrangements in all, and 79% had ≥1 somatic gene mutation.

Biological functions of extracellular vesicles from mammalian cells.

Extracellular vesicles (EVs) are enclosed by a phospholipid bilayer and can be secreted by most types of cells. EVs deliver cargo from the secreting cell into the cytoplasm of recipient cells, influencing the function of the recipient cells. EVs are attracting increasing attention from a broad range of clinicians and scientists due to their ability to promote or inhibit various physiological pathways or pathological conditions.

A U-shaped association between selenium intake and cancer risk.

While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case-control study of 3758 incident cancer cases (i.

Molecular programs guiding arealization of descending cortical pathways.

Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets. Two cardinal subtypes exist: (1) Slco2a1-expressing neurons (ET), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ET), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ET and ET emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis.

Treating Sickle Cell Disease: Gene Therapy Approaches.

Sickle cell disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin molecules and thus distortion (sickling) of the red blood cells. SCD causes chronic pain and organ damage and shortens life expectancy. Gene therapy emerges as a potentially curative approach for people with SCD who lack a matched sibling donor for hematopoietic stem cell transplantation.

Osteogenesis Imperfecta: A study of the patient journey in 13 European countries.

Introduction: Osteogenesis imperfecta (OI) is a heritable skeletal disorder and comprises various subtypes that differ in clinical presentation, with Type I considered the least severe and Types III/IV the most severe forms. The study aim was to understand the OI patient diagnostic and treatment journey across Europe.

Methods: We conducted a qualitative, descriptive study to understand the OI patient journey.

[Preventing relapse of acute leukemias and myelodysplastic syndromes in post-allograft transplantation: Prophylactic and preemptive strategies (SFGM-TC)].

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute myeloid and lymphoid leukemia (AML and ALL) and for myelodysplastic syndroms (MDS). More and more patients are eligible for allo-HCT over the years and for many of them, only reduced intensity conditioning is possible, which is associated with a higher risk of relapse. Knowledge and biotechnology allow us to better identify diseases at very high risk of relapse and to measure residual disease before allo-HCT.

Long-term assessment of haematological recovery following somatic genetic rescue in a MYSM1-deficient patient: Implications for in vivo gene therapy.

MYSM1 deficiency causes inherited bone marrow failure syndrome (IBMFS). We have previously identified an IBMFS patient with a homozygous pathogenic variant in MYSM1 who recovered from cytopenia due to spontaneous correction of one MYSM1 variant in the haematopoietic compartment, an event called somatic genetic rescue (SGR). The study of the genetic and biological aspects of the patient's haematopoietic/lymphopoietic system over a decade after SGR shows that one genetically corrected haematopoietic stem cell (HSC) can restore a healthy and stable haematopoietic system.

Heterozygous variant as a novel genetic cause of telomere biology disorders.

Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in Although the replication protein A2 (RPA2) mutant did not affect ssDNA binding and G-quadruplex-unfolding properties of RPA, the mutation reduced the affinity of RPA2 with the ubiquitin ligase RFWD3 and reduced RPA ubiquitination.