Efficient generation of human immune system rats using human CD34 cells.

Human immune system (HIS) mice generated using human CD34 hematopoietic stem cells serve as a pivotal model for the in vivo evaluation of immunotherapies for humans. Yet, HIS mice possess certain limitations. Rats, due to their size and comprehensive immune system, hold promise for translational experiments.

VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response.

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges.

Bi-specific autoantigen-T cell engagers as targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases.

Introduction: In autoimmune diseases, autoreactive B cells comprise only the 0.1-0.5% of total circulating B cells.

Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model.

Objectives: Despite their efficacy, some immunotherapies have been shown to induce immune-related adverse events, including the potentially life-threatening cytokine release syndrome (CRS), calling for reliable and translational preclinical models to predict potential safety issues and investigate their rescue. Here, we tested the reliability of humanized BRGSF mice for the assessment of therapeutics-induced CRS features in preclinical settings.

Methods: BRGSF mice reconstituted with human umbilical cord blood CD34 cells (BRGSF-CBC) were injected with anti-CD3 antibody (OKT3), anti-CD3/CD19 bispecific T-cell engager Blinatumomab, or VISTA-targeting antibody.

Two birds with one stone: human SIRPα nanobodies for functional modulation and imaging of myeloid cells.

Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the "don't eat me" ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both approaches, we developed a set of novel human SIRPα (hSIRPα)-specific nanobodies (Nbs). We identified high-affinity Nbs targeting the hSIRPα/hCD47 interface, thereby enhancing antibody-dependent cellular phagocytosis.

Cytotoxic and Pro-Apoptotic Effects of Leaves Extract of Engler ().

Engler leaves have been used in Senegalese folk medicine to treat breast cancer. The present study aimed to investigate the anticancer potential of Engler leaves using several human cancer cell lines. The leaves of Engler were extracted in parallel with water or 70% ethanol and each extract divided into three parts by successive liquid-liquid extraction with ethyl acetate and butanol.

An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension.

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available coronavirus disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. The application of soluble angiotensin converting enzyme 2 (ACE2) as a SARS-CoV-2 decoy that reduces cell bound ACE2-mediated virus entry is limited by a short plasma half-life. This work presents a recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the plasma half-life by an FcRn-driven cellular recycling mechanism, investigated using a wild type (WT) albumin sequence and sequence engineered with null FcRn binding (NB).

Phenotype of Mrps5-Associated Phylogenetic Polymorphisms Is Intimately Linked to Mitoribosomal Misreading.

We have recently identified point mutation V336Y in mitoribosomal protein Mrps5 (uS5m) as a mitoribosomal (ribosomal ambiguity) mutation conferring error-prone mitochondrial protein synthesis. In vivo in transgenic knock-in animals, homologous mutation V338Y was associated with a discrete phenotype including impaired mitochondrial function, anxiety-related behavioral alterations, enhanced susceptibility to noise-induced hearing damage, and accelerated metabolic aging in muscle. To challenge the postulated link between Mrps5 V338Y-mediated misreading and the in vivo phenotype, we introduced mutation G315R into the mouse Mrps5 gene as Mrps5 G315R is homologous to the established bacterial mutation RpsE (uS5) G104R.

Premature aging in mice with error-prone protein synthesis.

The main source of error in gene expression is messenger RNA decoding by the ribosome. Translational accuracy has been suggested on a purely correlative basis to positively coincide with maximum possible life span among different rodent species, but causal evidence that translation errors accelerate aging in vivo and limit life span is lacking. We have now addressed this question experimentally by creating heterozygous knock-in mice that express the ribosomal ambiguity mutation RPS9 D95N, resulting in genome-wide error-prone translation.

[Contribution of the Xpert MTB / Rif test in the diagnosis of tuberculosis of any form in Saint-Louis].

Introduction: The Xpert MTB / RIF assay has a dual advantage on the one hand, the rapid diagnosis of even difficult cases by the standard technique of direct microscopic examination and on the other hand by the detection of resistance to rifampicin. Our objective was to determine the contribution of the Xpert test in the diagnosis of tuberculosis of all forms.

Materials And Method: retrospective, descriptive and analytical study carried out in the Pneumophtisiology department of the CHRU of Saint-Louis.

Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice.

Random errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy.

Observed and Modeled Seasonal Air Quality and Respiratory Health in Senegal During 2015 and 2016.

In this work, we use existing particulate matter (PM) data from Dakar, Senegal, satellite aerosol optical depth (AOD) and the Weather Research and Forecasting (WRF) model to evaluate the role of dust transport from the Sahara and PM concentrations and exposure into other administrative districts of Senegal during 2015 and 2016. We also use data from the Ministry of Health to examine spatial and temporal patterns of acute respiratory infections, asthma, bronchitis, and tuberculosis across Senegal with an emphasis on Northern Hemisphere winter December-February, when air quality is poor, and June-August when there is an improvement in air quality. Measurements in Dakar, Senegal, suggest hazardous PM concentrations associated with Saharan dust storms but lower PM concentrations during the summer.

Sequelae of thoracic tuberculosis: manifestations and patients'quality of life.

For many patients, a history of tuberculosis is synonymous with disabling sequelae, impaired quality of life, and high morbidity and mortality. This retrospective study reviewed the files of patients hospitalized for sequelae of thoracic tuberculosis during 2017, to assess its various manifestations and their impact on quality of life. Of the 176 patients included, 75 % were aged from 35 to 65 years.

[Smoking in People Living with HIV (PLHA) and followed up in the Outpatient Department of the Hospital Fann of Dakar].

Introduction: PLHA who smoke have twice the never-smoker mortality rate and have an increased risk of developing non-AIDS diseases. The prevalence of tobacco smoking is higher among PLHA than in the general population. The purpose of this study was to assess the prevalence of smoking among PLHA, to describe the clinical and spirometric features of smokers and ex-smokers and to assess their knowledge and attitudes toward smoking.

Lateral decubitus chest radiography or chest ultrasound to predict pleural adhesions before medical thoracoscopy: a prospective study.

Background: Medical thoracoscopy (MT) is the gold-standard to investigate unexplained pleural exudates. However, the major prerequisite is an easy pleural access obtained by creating an artificial pneumothorax at the beginning of the procedure which can be a challenge in case of pleural adhesions and make the procedure unsafe. The detection of pleural adhesions prior to MT is necessary.

The necessity of a more aggressive initial surgical treatment in patients with mesothelioma of the testicular tunica vaginalis.

Mesothelioma of the tunica vaginalis of the testis (MTVM) is a rare tumor encountering for less than 1% of mesothelioma. Patients suffering from these tumors have poor survival due to local and distant metastasis despite treatment. Actually, no specific treatment recommendations exist for this tumor, yet radical orchidectomy is the gold standard in limited disease.

VISTA is an acidic pH-selective ligand for PSGL-1.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood.

Unexpected genomic rearrangements at targeted loci associated with CRISPR/Cas9-mediated knock-in.

The CRISPR/Cas9 gene editing tool enables accessible and efficient modifications which (re)ignited molecular research in certain species. However, targeted integration of large DNA fragments using CRISPR/Cas9 can still be challenging in numerous models. To systematically compare CRISPR/Cas9's efficiency to classical homologous recombination (cHR) for insertion of large DNA fragments, we thoroughly performed and analyzed 221 experiments targeting 128 loci in mouse ES cells.

[Epidemiological, Clinical And Radiological Profile Of Positive Microscopy Pulmonary Tuberculosis (PMPT) At The Regional University Hospital Of Saint-Louis].

Unlabelled: Pulmonary tuberculosis is still a global scourge, especially in developing countries, despite the control measures that have been in place for decades. The aim of this work was to describe the epidemiological, clinical radiological and evolutionary aspects of PMPT at the Saint-Louis Regional Hospital Center. This was a retrospective descriptive study on 191 PMPT files, hospitalized in the medical department from January 1, 2016 to December 31, 2017.

[Management of a tracheal adenoid cystic medico-surgical carcinoma].

Adenoid cystic carcinoma or cylindroma is a rare tumor of the trachea which arises from mucous secreting cells. Its evolution and growth are slow but it is often fatal in the absence of radical treatment. The latter relies on a surgical sleeve resection of the pathological area, with a tracheo-tracheal anastomosis.

[Epidemiology of primary lung cancer among non-smokers in Senegal].

Introduction: According to global data for 2002, one quarter of new cases of primary bronchopulmonary cancer were non-smokers. We undertook this study with the aim of describing the epidemiological characteristics of non-smokers with primary bronchopulmonary cancer in the Dakar region of Senegal.

Methods: A multicenter descriptive study that included all non-smokers who presented with primary bronchopulmonary cancer between January 1st 2014 and December 31st 2015.

[Trans-vocal cord prostheses - preliminary experience treating benign laryngotracheal stenosis in adults].

Introduction: Benign laryngotracheal stenosis is a rare pathology with multiple etiologies, the management of which is complex. This is because of the configuration and proximity of the larynx and the difficulty with surgical approaches, which are potentially mutilating, especially for the management of a benign disease. When surgery is challenging, iterative dilatations of the stricture or the fashioning of a definitive tracheotomy are therapeutic alternatives.

Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.

The 1555 A to G substitution in mitochondrial 12S A-site rRNA is associated with maternally transmitted deafness of variable penetrance in the absence of otherwise overt disease. Here, we recapitulate the suggested A1555G-mediated pathomechanism in an experimental model of mitoribosomal mistranslation by directed mutagenesis of mitoribosomal protein MRPS5. We first establish that the ratio of cysteine/methionine incorporation and read-through of mtDNA-encoded MT-CO1 protein constitute reliable measures of mitoribosomal misreading.