A non-canonical role for the tyrosyl tRNA synthetase: YARS regulates senescence induction and escape and controls the transcription of LIN9.

Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53-p21 and p16-Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized.

Deficiency in hereditary hemorrhagic telangiectasia-associated Endoglin elicits hypoxia-driven heart failure in zebrafish.

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease caused by mutations affecting components of bone morphogenetic protein (BMP)/transforming growth factor-β (TGF-β) signaling in endothelial cells. This disorder is characterized by arteriovenous malformations that are prone to rupture, and the ensuing hemorrhages are responsible for iron-deficiency anemia. Along with activin receptor-like kinase (ALK1), mutations in endoglin are associated with the vast majority of HHT cases.

Sphingomyelin nanosystems decorated with TSP-1 derived peptide targeting senescent cells.

Senescent cells accumulation can contribute to the development of several age-related diseases, including cancer. Targeting and eliminating senescence cells, would allow the development of new therapeutic approaches for the treatment of different diseases. The 4N1Ks peptide, a 10 amino acid peptide derived from TSP1 protein, combines both features by targeting the CD47 receptor present in the surface of senescent cells and demonstrating senolytic activity, thereby representing a new strategy to take into account.

Anterior gradient protein 2 is a marker of tumor aggressiveness in breast cancer and favors chemotherapy‑induced senescence escape.

Among the different chemotherapies available, genotoxic drugs are widely used. In response to these drugs, particularly doxorubicin, tumor cells can enter into senescence. Chemotherapy‑induced senescence (CIS) is a complex response.

LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis.

Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression.

Methods: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells.

Characterization of a member of the CEACAM protein family as a novel marker of proton pump-rich ionocytes on the zebrafish epidermis.

In humans, several members of the CEACAM receptor family have been shown to interact with intestinal pathogens in an inflammatory context. While CEACAMs have long been thought to be only present in mammals, recent studies have identified ceacam genes in other vertebrates, including teleosts. The function of these related genes remains however largely unknown.

Protective role of the mitochondrial fusion protein OPA1 in hypertension.

Hypertension is associated with excessive reactive oxygen species (ROS) production in vascular cells. Mitochondria undergo fusion and fission, a process playing a role in mitochondrial function. OPA1 is essential for mitochondrial fusion.

The detrimental invasiveness of glioma cells controlled by gadolinium chelate-coated gold nanoparticles.

Glioblastoma are characterized by an invasive phenotype, which is thought to be responsible for recurrences and the short overall survival of patients. In the last decade, the promising potential of ultrasmall gadolinium chelate-coated gold nanoparticles (namely Au@DTDTPA(Gd)) was evidenced for image-guided radiotherapy in brain tumors. Considering the threat posed by invasiveness properties of glioma cells, we were interested in further investigating the biological effects of Au@DTDTPA(Gd) by examining their impact on GBM cell migration and invasion.

-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of during Colon Carcinogenesis.

While it is now accepted that nutrition can influence the epigenetic modifications occurring in colorectal cancer (CRC), the underlying mechanisms are not fully understood. Among the tumor suppressor genes frequently epigenetically downregulated in CRC, the four related genes of the family: , , and encode dependence receptors that regulate the apoptosis/survival balance. Herein, in a mouse model of CRC, we found that the expression of , and was diminished in tumors but only in mice subjected to a High Carbohydrate Diet (HCD) thus linking nutrition to their repression in CRC.

Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells.

Cancer cells are characterized by the Warburg effect, a shift from mitochondrial respiration to oxidative glycolysis. We report here the crucial role of cyclin D1 in promoting this effect in a cyclin-dependent kinase (CDK)4/6-independent manner in multiple myeloma (MM) cells. We show that the cyclin D1 oncoprotein targets hexokinase 2 (HK2), a major glycolysis regulator, through two original molecular mechanisms in the cytoplasmic and nuclear compartments.

Proteomics Approaches to Define Senescence Heterogeneity and Chemotherapy Response.

In primary cells, senescence induces a permanent proliferative arrest to prevent the propagation of malignant cells. However, the outcome of senescence is more complex in advanced cancer cells where senescent states are heterogeneous. Here, this heterogeneity is discussed and it is proposed that proteomic analysis should be used to identify specific signatures of cancer cells that use this pathway as an adaptive mechanism.

Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment.

Senescence is a tumor-suppressive mechanism induced by telomere shortening, oncogenes, or chemotherapy treatment. Although it is clear that this suppressive pathway leads to a permanent arrest in primary cells, this might not be the case in cancer cells that have inactivated their suppressive pathways. We have recently shown that subpopulations of cells can escape chemotherapy-mediated senescence and emerge as more transformed cells that induce tumor formation, resist anoikis, and are more invasive.

MAGP-1 and fibronectin control EGFL7 functions by driving its deposition into distinct endothelial extracellular matrix locations.

The extracellular matrix (ECM) is essential to provide mechanical support to tissues but is also a bioactive edifice which controls cell behavior. Cell signaling generated by ECM components through integrin-mediated contacts, modulates cell biological activity. In addition, by sequestrating or releasing growth factors, the ECM is an active player of physiological and pathological processes such as vascular development.

How to use sequence analysis for life course epidemiology? An example on HIV-positive Sub-Saharan migrants in France.

Background: Life course epidemiology is now an established field in social epidemiology; in sociodemography, the quantitative analysis of biographies recently experienced significant trend from event history analysis to sequence analysis. The purpose of this article is to introduce and adapt this methodology to a social epidemiology question, taking the example of the impact of HIV diagnosis on Sub-Saharan migrants' residential trajectories in the Paris region.

Methods: The sample consists of 640 migrants born in Sub-Saharan Africa receiving HIV care.

Regulation of senescence escape by the cdk4-EZH2-AP2M1 pathway in response to chemotherapy.

Senescence is a tumor suppressive mechanism that induces a permanent proliferative arrest in response to an oncogenic insult or to the genotoxic stress induced by chemotherapy. We have recently described that some cells can escape this arrest, either because senescence was incomplete or as a consequence of a phenotypic adaptation. Malignant cells which resisted senescence emerged as more transformed cells that resist anoikis and rely on survival pathways activated by Akt and Mcl-1.

Understanding Settlement Pathways of African Immigrants in France Through a Capability Approach: Do Pre-migratory Characteristics Matter?

With the increase in asylum-related immigration since 2015, understanding how immigrants settle in a new country is at the centre of social and political debate in European countries. The objective of this study is to determine whether the necessary time to settle for Sub-Saharan Africa immigrants in France depends more on pre-migratory characteristics or on the structural features of the host society. Taking a capability approach, we define settlement as the acquisition of three basic resources: a personal dwelling, a legal permit of a least 1 year and paid work.

Associations between transition to retirement and changes in dietary intakes in French adults (NutriNet-Santé cohort study).

Background: Few studies have focused on the influence of retirement on dietary behaviors. Our study aimed at assessing the associations between transition to retirement and changes in dietary intake in French adults, particularly according to spousal retirement and baseline income.

Methods: This prospective study included 577 French participants from the NutriNet-Santé cohort who retired over a 5-year follow-up (2009-2014 or 2010-2015).

"Times Are Changing": The Impact of HIV Diagnosis on Sub-Saharan Migrants' Lives in France.

Background: Migrants account for 35% of HIV diagnoses in the European Union (ECDC/WHO 2014). Little is known about the impact of such a lifelong infection diagnosis on lives that are already disrupted by migration. In this paper, we assess the impact of HIV diagnosis on activity, union, well-being among African migrants living in France, the second group most affected by HIV after MSM.

Counting the Population or Describing Society? A Comparison of English and Welsh and French Censuses.

Data collected at household level in censuses are used for a wide range of purposes including practical planning and academic analysis of changing social conditions. Comparability is a core demographic value, and to understand the limits of the comparability of census data across time and space, it is important to recognise if, how and why, concepts and definitions change between censuses. This paper examines definitions of the household in censuses in England and Wales (E&W) and France from 1960 to 2012 in order to investigate how census definitions have changed and to examine the drivers of such changes.

The angiotensin II type 2 receptor activates flow-mediated outward remodelling through T cells-dependent interleukin-17 production.

Aims: The angiotensin II type 1 receptor (AT1R) through the activation of immune cells plays a key role in arterial inward remodelling and reduced blood flow in cardiovascular disorders. On the other side, flow (shear stress)-mediated outward remodelling (FMR), involved in collateral arteries growth in ischaemic diseases, allows revascularization. We hypothesized that the type 2 receptor (AT2R), described as opposing the effects of AT1R, could be involved in FMR.

Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only.

HIV-related stigma experiences: Understanding gender disparities in Thailand.

This paper assesses the relationship between gender and HIV-related stigma experiences among people living with HIV (PLHIV) - enacted and anticipated stigma - and PLHIV caregivers - courtesy stigma - in Northern Thailand, along with the underlying reasons for stigmatising attitudes towards PLHIV - instrumental and symbolic stigma - expressed in the general population. We used data from the Living With Antiretrovirals (LIWA) study conducted on all PLHIV receiving antiretroviral treatment in four district hospitals in Northern Thailand (n = 513) and on a community sample of adults from the general population (n = 500). Women living with HIV and female caregivers of PLHIV reported higher rates of HIV-related stigma experiences than men.

Primitive macrophages control HSPC mobilization and definitive haematopoiesis.

In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta-gonad-mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM.