Impact of the Multiple Sclerosis-Associated Genetic Variant Gly307Ser on Human CD8 T-Cell Functions.

Background And Objectives: The rs763361 nonsynonymous variant in the gene, which results in a glycine-to-serine substitution at position 307 of the CD226 protein, has been implicated as a risk factor of various immune-mediated diseases, including multiple sclerosis (MS). Compelling evidence suggests that this allele may play a significant role in predisposing individuals to MS by decreasing the immune-regulatory capacity of Treg cells and increasing the proinflammatory potential of effector CD4 T cells. However, the impact of this CD226 gene variant on CD8 T-cell functions, a population that also plays a key role in MS, remains to be determined.

NK cells with adhesion defects and reduced cytotoxic functions are associated with a poor prognosis in multiple myeloma.

The promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call for a better stratification of patients based on immune components. The most pressing being cytotoxic lymphocytes such as natural killer (NK) cells that are mandatory for MM surveillance and therapy. Here, we performed a single-cell RNA sequencing analysis of NK cells from 10 patients with MM and 10 age/sex-matched healthy donors that revealed important transcriptomic changes in the NK cell landscape affecting both the bone marrow (BM) and peripheral blood compartment.

RAS/RAF landscape in monoclonal plasma cell conditions.

Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The RAS/RAF pathway is the most frequently mutated, in ∼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event.

TCR-independent CD137 (4-1BB) signaling promotes CD8-exhausted T cell proliferation and terminal differentiation.

CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by CD137 and its role in cancer immune surveillance remain unresolved. Using T cell-specific deletion and agonist antibodies, we found that CD137 modulates tumor infiltration of CD8-exhausted T (Tex) cells expressing PD1, Lag-3, and Tim-3 inhibitory receptors.

Lunaemycins, New Cyclic Hexapeptide Antibiotics from the Cave Moonmilk-Dweller MM109.

strains have been isolated from moonmilk deposits, which are calcium carbonate speleothems used for centuries in traditional medicine for their antimicrobial properties. Genome mining revealed that these strains are a remarkable example of a species with huge heterogeneity regarding their content in biosynthetic gene clusters (BGCs) for specialized metabolite production. BGC 28a is one of the cryptic BGCs that is only carried by a subgroup of .

Making Drawings Speak Through Mathematical Metrics.

Figurative drawing is a skill that takes time to learn, and it evolves during different childhood phases that begin with scribbling and end with representational drawing. Between these phases, it is difficult to assess when and how children demonstrate intentions and representativeness in their drawings. The marks produced are increasingly goal-oriented and efficient as the child's skills progress from scribbles to figurative drawings.

Draw yourself: How culture influences drawings by children between the ages of two and fifteen.

The place children live strongly influence how they develop their behavior, this is also true for pictorial expression. This study is based on 958 self-portraits drawn by children aged 2-15 years old from 35 countries across 5 continents. A total of 13 variables were extracted of each drawing allowing us to investigate the differences of individuals and environment representations in these drawings.

Structure of New Ferroverdins Recruiting Unconventional Ferrous Iron Chelating Agents.

Ferroverdins are ferrous iron (Fe)-nitrosophenolato complexes produced by a few species as a response to iron overload. Previously, three ferroverdins were identified: ferroverdin A, in which three molecules of -vinylphenyl-3-nitroso-4-hydroxybenzoate (-vinylphenyl-3,4-NHBA) are recruited to bind Fe, and Ferroverdin B and Ferroverdin C, in which one molecule of -vinylphenyl-3,4-NHBA is substituted by hydroxy--vinylphenyl-3,4-NHBA, and by carboxy--vinylphenyl-3,4-NHBA, respectively. These molecules, especially ferroverdin B, are potent inhibitors of the human cholesteryl ester transfer protein (CETP) and therefore candidate hits for the development of drugs that increase the serum concentration of high-density lipoprotein cholesterol, thereby diminishing the risk of atherosclerotic cardiovascular disease.

SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma.

Anti-CD38 monoclonal antibodies (mAbs) represent a breakthrough in the treatment of multiple myeloma (MM), yet some patients fail to respond or progress quickly with this therapy, highlighting the need for novel approaches. In this study we compared the preclinical efficacy of SAR442085, a next-generation anti-CD38 mAb with enhanced affinity for activating Fcγ receptors (FcγR), with first-generation anti-CD38 mAb daratumumab and isatuximab. In surface plasmon resonance and cellular binding assays, we found that SAR442085 had higher binding affinity than daratumumab and isatuximab for FcγRIIa (CD32a) and FcγRIIIa (CD16a).

sp. nov., isolated from forest soil.

A bacterial strain, named For3, was isolated from forest soil sampled in Champenoux, France. Based on its 16S rRNA gene sequence, the strain was affiliated to the family and, more specifically, to the genus . The strain had 99.

New indices to characterize drawing behavior in humans (Homo sapiens) and chimpanzees (Pan troglodytes).

Techniques used in cave art suggest that drawing skills emerged long before the oldest known representative human productions (44,000 years BC). This study seeks to improve our knowledge of the evolutionary origins and the ontogenetic development of drawing behavior by studying drawings of humans (N = 178, 3- to 10-year-old children and adults) and chimpanzees (N = 5). Drawings were characterized with an innovative index based on spatial measures which provides the degree of efficiency for the lines that are drawn.

Drawing in nonhuman primates: What we know and what remains to be investigated.

For over a century now, a number of researchers have explored the evolutionary emergence of mark-making and drawing behaviors through studies in monkeys and apes, and particularly in chimpanzees. Their observations and results remain relevant to this day and underline the interest of this question and the questions that remain to be answered. The present review begins by retracing the historical timeline of this specific and challenging topic from the earliest anecdotal evidence to the first systematic studies in the 1930s.

Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8 T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy.

CD8 T cells within the tumor microenvironment (TME) are exposed to various signals that ultimately determine functional outcomes. Here, we examined the role of the co-activating receptor CD226 (DNAM-1) in CD8 T cell function. The absence of CD226 expression identified a subset of dysfunctional CD8 T cells present in peripheral blood of healthy individuals.

CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8 T Cells.

The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8 TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226 TILs were highly functional.

On the Risks of Phylogeny-Based Strain Prioritization for Drug Discovery: as a Case Study.

Strain prioritization for drug discovery aims at excluding redundant strains of a collection in order to limit the repetitive identification of the same molecules. In this work, we wanted to estimate what can be unexploited in terms of the amount, diversity, and novelty of compounds if the search is focused on only one single representative strain of a species, taking as a model. For this purpose, we selected 18 strains taxonomically clustered with the archetype strain MM109.

Seizure onset location shapes dynamics of initiation.

Objective: Ictal electrographic patterns are widely thought to reflect underlying neural mechanisms of seizures. Here we studied the degree to which seizure patterns are consistent in a given patient, relate to particular brain regions and if two candidate biomarkers (high-frequency oscillations, HFOs; infraslow activity, ISA) and network activity, as assessed with cross-frequency interactions, can discriminate between seizure types.

Methods: We analyzed temporal changes in low and high frequency oscillations recorded during seizures, as well as phase-amplitude coupling (PAC) to monitor the interactions between delta/theta and ripple/fast ripple frequency bands at seizure onset.

Robust dynamic community detection with applications to human brain functional networks.

While current technology permits inference of dynamic brain networks over long time periods at high temporal resolution, the detailed structure of dynamic network communities during human seizures remains poorly understood. We introduce a new methodology that addresses critical aspects unique to the analysis of dynamic functional networks inferred from noisy data. We propose a dynamic plex percolation method (DPPM) that is robust to edge noise, and yields well-defined spatiotemporal communities that span forward and backwards in time.

Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma.

Introduction: Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. The patients displayed a distinct transcriptome and were functionally different from healthy donors' (HD) MSC.

Author Correction: Measuring dynamic social contacts in a rehabilitation hospital: effect of wards, patient and staff characteristics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A statistical framework to assess cross-frequency coupling while accounting for confounding analysis effects.

Cross frequency coupling (CFC) is emerging as a fundamental feature of brain activity, correlated with brain function and dysfunction. Many different types of CFC have been identified through application of numerous data analysis methods, each developed to characterize a specific CFC type. Choosing an inappropriate method weakens statistical power and introduces opportunities for confounding effects.

A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators.

Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability.