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).

Quantifying the topographical structure of rocky and coral seabeds.

Describing the structural complexity of seabeds is of primary importance for a number of geomorphological, hydrodynamical and ecological issues. Aiming to bring a decisive insight on the long-term development of a unified view, the present study reports on a comparative multi-site analysis of high resolution topography surveys in rough nearshore environments. The nine study sites have been selected to cover a wide variety of topographical features, including rocky and coral seabeds.

All taxa biodiversity inventory of the Bois de Bouis estate (Var, France): a 10-year public-private partnership.

Background: This data paper describes the results of a 10-year scientific investigation of a biodiversity-rich private golf estate in south-eastern France in partnership with PatriNat (Office français de la biodiversité/Centre national de la recherche scientifique/Muséum national d'Histoire naturelle, Institut de Recherche pour le Développement). In total, 3,160 species and subspecies, including 1,796 arthropods and 1,049 flora, were inventoried and 65 habitat types were surveyed and mapped. This project is the first All taxa biodiversity inventory (ATBI) in a private property in France with all information available in open data.

Functional specialization of short-lived and long-lived macrophage subsets in human tonsils.

Macrophages play a central role in tissue homeostasis and host defense. However, the properties of human macrophages in non-diseased tissues remain poorly understood. Here, we characterized human tonsil macrophages and identified three subsets with distinct phenotype, transcriptome, life cycle, and function.

A 31-plex panel for high-dimensional single-cell analysis of murine preclinical models of solid tumors by imaging mass cytometry.

Currently, the study of resistance mechanisms and disease progression in cancer relies on the capacity to analyze tumors as a complex ecosystem of healthy and malignant cells. Therefore, one of the current challenges is to decipher the intra-tumor heterogeneity and especially the spatial distribution and interactions of the different cellular actors within the tumor. Preclinical mouse models are widely used to extend our understanding of the tumor microenvironment (TME).

Single-cell high-dimensional imaging mass cytometry: one step beyond in oncology.

Solid tumors have a dynamic ecosystem in which malignant and non-malignant (endothelial, stromal, and immune) cell types constantly interact. Importantly, the abundance, localization, and functional orientation of each cell component within the tumor microenvironment vary significantly over time and in response to treatment. Such intratumoral heterogeneity influences the tumor course and its sensitivity to treatments.

IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4Foxp3 regulatory T lymphocytes.

Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results.

Continuous presence of proto-cereals in Anatolia since 2.3 Ma, and their possible co-evolution with large herbivores and hominins.

Cereals are a central resource for the human diet and are traditionally assumed to have evolved from wild grasses at the onset of the Neolithic under the pressure of agriculture. Here we demonstrate that cereals may have a significantly longer and more diverse lineage, based on the study of a 0-2.3 Ma, 601 m long sedimentary core from Lake Acıgöl (South-West Anatolia).

Identification of a regulatory Vδ1 gamma delta T cell subpopulation expressing CD73 in human breast cancer.

γδ T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poor prognosis in breast, colon, and pancreatic cancer, suggesting that γδ T cells may also display pro-tumor activities. Here, we identified in blood from healthy donors a subpopulation of Vδ1T cells that represents around 20% of the whole Vδ1 population, expresses CD73, and displays immunosuppressive phenotype and functions (i.

Higher Anti-Tumor Efficacy of the Dual HER3-EGFR Antibody MEHD7945a Combined with Ionizing Irradiation in Cervical Cancer Cells.

Purpose: The outcome of locally advanced cervical cancer (LACC) is dismal. Biomarkers are needed to individualize treatments and to improve patient outcomes. Here, we investigated whether coexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) could be an outcome prognostic biomarker, and whether targeting both EGFR and HER3 with a dual antibody (MEHD7945A) enhanced ionizing radiation (IR) efficacy.

[Predictive assays for responses of tumors and normal tissues in radiation oncology].

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments.

Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies.

Immune checkpoint inhibitors have revolutionized cancer treatment. However, many cancers are resistant to ICIs, and the targeting of additional inhibitory signals is crucial for limiting tumor evasion. The production of adenosine via the sequential activity of CD39 and CD73 ectoenzymes participates to the generation of an immunosuppressive tumor microenvironment.

Inhibition of Ataxia-Telangiectasia Mutated and RAD3-Related () Overcomes Oxaliplatin Resistance and Promotes Antitumor Immunity in Colorectal Cancer.

Although many patients with colorectal cancer initially respond to the chemotherapeutic agent oxaliplatin, acquired resistance to this treatment remains a major challenge to the long-term management of this disease. To identify molecular targets of oxaliplatin resistance in colorectal cancer, we performed an shRNA-based loss-of-function genetic screen using a kinome library. We found that silencing of ataxia-telangiectasia mutated and RAD3-related (ATR), a serine/threonine protein kinase involved in the response to DNA stress, restored oxaliplatin sensitivity in a cellular model of oxaliplatin resistance.

Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies.

Background: Triple-negative breast cancer (TNBC) treatment is currently restricted to chemotherapy. Hence, tumor-specific molecular targets and/or alternative therapeutic strategies for TNBC are urgently needed. Immunotherapy is emerging as an exciting treatment option for TNBC patients.

Harnessing the Rheological Properties of Liquid Metals To Shape Soft Electronic Conductors for Wearable Applications.

Emerging applications of the Internet of Things in healthcare, wellness, and gaming require continuous monitoring of the body and its environment, fueling the need for wearable devices able to maintain intimate, reliable, and unobtrusive contact with the human body. This translates in the necessity to develop soft and deformable electronics that match the body's mechanics and dynamics. In recent years, various strategies have been proposed to form stretchable circuits and more specifically elastic electrical conductors embedded in elastomeric substrate using either geometrical structuring of solid conductors or intrinsically stretchable materials.

The IL-17B-IL-17 receptor B pathway promotes resistance to paclitaxel in breast tumors through activation of the ERK1/2 pathway.

Interleukin 17B (IL-17B) is a pro-inflammatory cytokine that belongs to the IL-17 cytokines family and binds to IL-17 receptor B (IL-17RB). Here we found that high expression of IL-17B and IL-17RB is associated with poor prognosis in patients with breast cancer and that IL-17B expression upregulation is specifically associated with poorer survival in patients with basal-like breast cancer. We thus focused on IL-17B role in breast cancer by using luminal and triple negative (TN)/basal-like tumor cell lines.

PD-1 blockade at the time of tumor escape potentiates the immune-mediated antitumor effects of a melanoma-targeting monoclonal antibody.

Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy.

Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers.

Background: Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Aural Rehabilitation for Older Adults with Hearing Loss: Impacts on Quality of Life-A Systematic Review of Randomized Controlled Trials.

Background: Few systematic reviews have been conducted regarding aural rehabilitation for adults with hearing loss, with none specifically targeting the older adult population. With prevalence rates of hearing loss being highest in older adults, examining the effects of aural rehabilitation on this population is warranted.

Purpose: To evaluate the effects of aural rehabilitation on quality of life in an older adult population presenting with hearing loss.