Vinculin Y822 phosphorylation regulates cardiomyocyte adhesion dynamics and adherens junction maturation in the heart.

In the heart, cell-matrix and cell-cell adhesions reorganize in response to increased cardiac demand and growth to promote cardiomyocyte maturation. Vinculin, a mechanosensitive adaptor protein, links filamentous actin to cell-matrix and cell-cell adhesions and is thus positioned to regulate adhesion reorganization. However, how the two adhesion systems are coordinated in the heart, and the role of vinculin in this process is poorly understood.

Development of a core outcome set for maternal and perinatal health research and surveillance in light of emerging and ongoing epidemic threats.

Background: Maternal and perinatal health is often directly and indirectly affected during infectious disease epidemics. Yet, a lack of evidence on epidemics' impact on women and their offspring delays informed decision-making for healthcare providers, pregnant women, women in the post-pregnancy period and policy-makers. To rapidly generate evidence in these circumstances, we aim to develop a Core Outcome Set (COS) for maternal and perinatal health research and surveillance in light of emerging and ongoing epidemic threats.

Cadherin-dependent adhesion is required for muscle stem cell niche anchorage and maintenance.

Adhesion between stem cells and their niche provides stable anchorage and signaling cues to sustain properties such as quiescence. Skeletal muscle stem cells (MuSCs) adhere to an adjacent myofiber via cadherin-catenin complexes. Previous studies on N- and M-cadherin in MuSCs revealed that although N-cadherin is required for quiescence, they are collectively dispensable for MuSC niche localization and regenerative activity.

Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia.

Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients' immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed.

Actomyosin-mediated cellular tension promotes Yap nuclear translocation and myocardial proliferation through α5 integrin signaling.

The cardiomyocyte phenotypic switch from a proliferative to terminally differentiated state results in the loss of regenerative potential of the mammalian heart shortly after birth. Nonmuscle myosin IIB (NM IIB)-mediated actomyosin contractility regulates cardiomyocyte cytokinesis in the embryonic heart, and NM IIB levels decline after birth, suggesting a role for cellular tension in the regulation of cardiomyocyte cell cycle activity in the postnatal heart. To investigate the role of actomyosin contractility in cardiomyocyte cell cycle arrest, we conditionally activated ROCK2 kinase domain (ROCK2:ER) in the murine postnatal heart.

Modified cued recall test in the French population with Down syndrome: A retrospective medical records analysis.

Background: Adults with Down syndrome (DS) are at increased risk of developing Alzheimer's disease (AD) due to genetic predisposition. Identification of patients with AD is difficult since intellectual disabilities (ID) may confound diagnosis. The objective of this study was to evaluate the ability of the French version of the modified cued recall test (mCRT) to distinguish between subjects with and without AD in the adult DS population.

The French translation of the dementia screening questionnaire for individuals with intellectual disabilities is a sensitive tool for screening for dementia in people with Down Syndrome.

Background: People with Down Syndrome (DS) are at an increased risk of developing Alzheimer's Disease (AD) relatively early in life. The dementia screening questionnaire for individuals with intellectual disabilities (DSQIID) has been developed for people with intellectual disabilities and was shown to have high discriminative power to distinguish between people with and without dementia. The objective of this study was to verify if the French version of the DSQIID (DSQIID-F) had a good diagnostic specificity and to determine the optimal cut-off for screening people with DS for dementia.

Cardiomyocyte orientation modulated by the Numb family proteins-N-cadherin axis is essential for ventricular wall morphogenesis.

The roles of cellular orientation during trabecular and ventricular wall morphogenesis are unknown, and so are the underlying mechanisms that regulate cellular orientation. Myocardial-specific and double-knockout (MDKO) hearts display a variety of defects, including in cellular orientation, patterns of mitotic spindle orientation, trabeculation, and ventricular compaction. Furthermore, - and -null cardiomyocytes exhibit cellular behaviors distinct from those of control cells during trabecular morphogenesis based on single-cell lineage tracing.

Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation.

Inhibitors of Vascular Endothelial Growth Factor target both tumor vasculature and cancer cells that have hijacked VEGF Receptors (VEGFRs) signaling for tumor growth-promoting activities. It is important to get precise insight in the specificity of cell responses to these antiangiogenic drugs to maximize their efficiency and minimize off-target systemic toxicity. Here we report that Axitinib, an inhibitor of VEGFRs currently in use as a second line treatment for advanced renal cell carcinoma, promotes senescence of human endothelial cells in vitro.

α-Catenin-dependent cytoskeletal tension controls Yap activity in the heart.

Shortly after birth, muscle cells of the mammalian heart lose their ability to divide. At the same time, the N-cadherin/catenin cell adhesion complex accumulates at the cell termini, creating a specialized type of cell-cell contact called the intercalated disc (ICD). To investigate the relationship between ICD maturation and proliferation, αE-catenin () and αT-catenin () genes were deleted to generate cardiac-specific α-catenin double knockout (DKO) mice.

Niche Cadherins Control the Quiescence-to-Activation Transition in Muscle Stem Cells.

Many adult stem cells display prolonged quiescence, promoted by cues from their niche. Upon tissue damage, a coordinated transition to the activated state is required because non-physiological breaks in quiescence often lead to stem cell depletion and impaired regeneration. Here, we identify cadherin-mediated adhesion and signaling between muscle stem cells (satellite cells [SCs]) and their myofiber niche as a mechanism that orchestrates the quiescence-to-activation transition.

N-cadherin regulates signaling mechanisms required for lens fiber cell elongation and lens morphogenesis.

Tissue development and regeneration involve high-ordered morphogenetic processes that are governed by elements of the cytoskeleton in conjunction with cell adhesion molecules. Such processes are particularly important in the lens whose structure dictates its function. Studies of our lens-specific N-cadherin conditional knockout mouse (N-cadcKO) revealed an essential role for N-cadherin in the migration of the apical tips of differentiating lens fiber cells along the apical surfaces of the epithelium, a region termed the Epithelial Fiber Interface (EFI), that is necessary for normal fiber cell elongation and the morphogenesis.

Autonomous Pointing Control of a Large Satellite Antenna Subject to Parametric Uncertainty.

With the development of satellite mobile communications, large antennas are now widely used. The precise pointing of the antenna's optical axis is essential for many space missions. This paper addresses the challenging problem of high-precision autonomous pointing control of a large satellite antenna.

Study on stability and rotating speed stable region of magnetically suspended rigid rotors using extended Nyquist criterion and gain-stable region theory.

This paper presents a novel and simple method to analyze the absolute stability and the rotor speed stable region of a magnetically suspended rotor (MSR). At the beginning of the paper, a complex variable is introduced to describe the movement of the MSR and a complex coefficient transfer function is obtained accordingly. The equivalent stability relationship between this new variable and the two traditional deflection angles is also demonstrated in a simple way.

N-cadherin functions as a growth suppressor in a model of K-ras-induced PanIN.

Cadherin subtype switching from E-cadherin to N-cadherin is associated with the epithelial-to-mesenchymal transition (EMT), a process required for invasion and dissemination of carcinoma cells. We found that N-cadherin is expressed in human and mouse pancreatic intraepithelial neoplasia (PanIN), suggesting that N-cadherin may also have a role in early-stage pancreatic cancer. To investigate the role of N-cadherin in mouse PanIN (mPanIN), we simultaneously activated oncogenic K-ras(G12D) and deleted the N-cadherin (Cdh2) gene in the murine pancreas.

N-Cadherin Induction by ECM Stiffness and FAK Overrides the Spreading Requirement for Proliferation of Vascular Smooth Muscle Cells.

In contrast to the accepted pro-proliferative effect of cell-matrix adhesion, the proliferative effect of cadherin-mediated cell-cell adhesion remains unresolved. Here, we studied the effect of N-cadherin on cell proliferation in the vasculature. We show that N-cadherin is induced in smooth muscle cells (SMCs) in response to vascular injury, an in vivo model of tissue stiffening and proliferation.

New functions for alpha-catenins in health and disease: from cancer to heart regeneration.

Strong cell-cell adhesion mediated by adherens junctions is dependent on anchoring the transmembrane cadherin molecule to the underlying actin cytoskeleton. To do this, the cadherin cytoplasmic domain interacts with catenin proteins, which include α-catenin that binds directly to filamentous actin. Originally thought to be a static structure, the connection between the cadherin/catenin adhesion complex and the actin cytoskeleton is now considered to be dynamic and responsive to both intercellular and intracellular signals.

Alpha-catenins control cardiomyocyte proliferation by regulating Yap activity.

Rationale: Shortly after birth, muscle cells of the mammalian heart lose their ability to divide. Thus, they are unable to effectively replace dying cells in the injured heart. The recent discovery that the transcriptional coactivator Yes-associated protein (Yap) is necessary and sufficient for cardiomyocyte proliferation has gained considerable attention.

N-cadherin/catenin complex as a master regulator of intercalated disc function.

Intercellular adhesive junctions are essential for maintaining the physical integrity of tissues; this is particularly true for the heart that is under constant mechanical load. The correct functionality of the heart is dependent on the electrical and mechanical coordination of its constituent cardiomyocytes. The intercalated disc (ID) structure located at the termini of the rod-shaped adult cardiomyocyte contains various junctional proteins responsible for the integration of structural information and cell-cell communication.

Calorie restriction delays the progression of lesions to pancreatic cancer in the LSL-KrasG12D; Pdx-1/Cre mouse model of pancreatic cancer.

Since pancreatic cancer is a lethal disease, developing prevention strategies is an important goal. We determined whether calorie restriction would prevent the development and delay progression of pancreatic intraepithelial neoplasms to pancreatic ductal adenocarcinoma (PDA) in LSL-KrasG12D/+; Pdx-1/Cre mice that develop all the precursor lesions that progress to PDA. Eight-week-old LSL-KrasG12D; Pdx-1/Cre mice were assigned to three groups: (1) ad libitum (AL) fed the AIN93M diet or (2) intermittently calorie restricted (ICR) a modified AIN93M at 50% of AL intake followed by one week intervals at 100% of AL intake, or (3) chronically calorie restricted (CCR) an AIN93M diet at 75% of AL intake.

N-cadherin-mediated adhesion and signaling from development to disease: lessons from mice.

Of the 20 classical cadherin subtypes identified in mammals, the functions of the two initially identified family members E- (epithelial) and N- (neural) cadherin have been most extensively studied. E- and N-Cadherin have mostly mutually exclusive expression patterns, with E-cadherin expressed primarily in epithelial cells, whereas N-cadherin is found in a variety of cells, including neural, muscle, and mesenchymal cells. N-Cadherin function, in particular, appears to be cell context-dependent, as it can mediate strong cell-cell adhesion in the heart but induces changes in cell behavior in favor of a migratory phenotype in the context of epithelial-mesenchymal transition (EMT).

Beyond cell adhesion: the role of armadillo proteins in the heart.

Plakoglobin (PG, γ-Catenin, JUP), a member of the armadillo protein family and close homolog of β-catenin, functions to link cell surface cadherin molecules with the cytoskeleton. PG is the only junctional component found in both desmosomes and adherens junctions and thus plays a critical role in the regulation of cell-cell adhesion. Similar to β-catenin, PG is able to interact with components of the Wnt signaling pathway and directly affect gene expression by binding with LEF/TCF transcription factors.

Analysis of a Jup hypomorphic allele reveals a critical threshold for postnatal viability.

Mutations in the human Jup gene cause arrhythmogenic right ventricular cardiomyopathy (ARVC), a heart muscle disease that often leads to sudden cardiac death. Inactivation of the murine Jup gene (also known as plakoglobin) results in embryonic lethality due to cardiac rupture. In an effort to generate a conditional knockout allele, a neomycin cassette was introduced into the murine plakoglobin (PG) gene.