Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.

The vascular endothelium, a specialized monolayer of endothelial cells (ECs), is crucial for maintaining vascular homeostasis by controlling the passage of substances and cells. In the tumor microenvironment, Vascular Endothelial Growth Factor A (VEGF-A) drives tumor angiogenesis, leading to endothelial anergy and vascular immunosuppression-a state where ECs resist cytotoxic CD8 T cell infiltration, hindering immune surveillance. Immunotherapies have shown clinical promise.

Rap1A Modulates Store-Operated Calcium Entry in the Lung Endothelium: A Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability.

Background: Store-operated calcium entry mediated by STIM (stromal interaction molecule)-1-Orai1 (calcium release-activated calcium modulator 1) is essential in endothelial cell (EC) functions, affecting signaling, NFAT (nuclear factor for activated T cells)-induced transcription, and metabolic programs. While the small GTPase Rap1 (Ras-proximate-1) isoforms, including the predominant Rap1B, are known for their role in cadherin-mediated adhesion, EC deletion of Rap1A after birth uniquely disrupts lung endothelial barrier function. Here, we elucidate the specific mechanisms by which Rap1A modulates lung vascular integrity and inflammation.

Rap1b-loss increases neutrophil lactate dehydrogenase activity to enhance neutrophil migration and acute inflammation .

Introduction: Neutrophils are critical for host immune defense; yet, aberrant neutrophil tissue infiltration triggers tissue damage. Neutrophils are heterogeneous functionally, and adopt 'normal' or 'pathogenic' effector function responses. Understanding neutrophil heterogeneity could provide specificity in targeting inflammation.

Mechano-growth factor E-domain modulates cardiac contractile function through 14-3-3 protein interactomes.

In the heart, alternative splicing of the gene produces two isoforms: IGF-IEa and IGF-IEc, (Mechano-growth factor, MGF). The sequence divergence between their E-domain regions suggests differential isoform function. To define the biological actions of MGF's E-domain, we performed analysis of the unique C-terminal sequence and identified a phosphorylation consensus site residing within a putative 14-3-3 binding motif.

Endothelial Rap1B mediates T-cell exclusion to promote tumor growth: a novel mechanism underlying vascular immunosuppression.

Overcoming vascular immunosuppression: lack of endothelial cell (EC) responsiveness to inflammatory stimuli in the proangiogenic environment of tumors, is essential for successful cancer immunotherapy. The mechanisms through which Vascular Endothelial Growth Factor A(VEGF-A) modulates tumor EC response to exclude T-cells are not well understood. Here, we demonstrate that EC-specific deletion of small GTPase Rap1B, previously implicated in normal angiogenesis, restricts tumor growth in endothelial-specific Rap1B-knockout (Rap1B) mice.

Corrigendum: Distinct Signaling Functions of Rap1 Isoforms in NO Release From Endothelium.

[This corrects the article DOI: 10.3389/fcell.2021.

Distinct Signaling Functions of Rap1 Isoforms in NO Release From Endothelium.

Small GTPase Rap1 plays a prominent role in endothelial cell (EC) homeostasis by promoting NO release. Endothelial deletion of the two highly homologous Rap1 isoforms, Rap1A and Rap1B, leads to endothelial dysfunction and hypertension . Mechanistically, we showed that Rap1B promotes NO release in response to shear flow by promoting mechanosensing complex formation involving VEGFR2 and Akt activation.

Clinical Spectrum and Outcomes of Neonatal Necrotizing Enterocolitis.

Background/aim: The objective of the study was analysis of risk factors associated with outcome of necrotizing enterocolitis (NEC) in infants in a single-center study.

Patients And Methods: All consecutive infants hospitalized for NEC over a period of 6 years were retrospectively analyzed for clinical course, infections, treatment and outcome.

Results: Out of 76 patients, surgical management was applied in 56 (53 exploratory laparotomy, three initial peritoneal drain placement) and in 20 there was only a conservative approach.

Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis.

Objective: Small GTPase Rap1 (Ras-association proximate 1) is a novel, positive regulator of NO release and endothelial function with a potentially key role in mechanosensing of atheroprotective, laminar flow. Our objective was to delineate the role of Rap1 in the progression of atherosclerosis and its specific functions in the presence and absence of laminar flow, to better define its role in endothelial mechanisms contributing to plaque formation and atherogenesis. Approach and Results: In a mouse atherosclerosis model, endothelial Rap1B deletion exacerbates atherosclerotic plaque formation.

Integration of Rap1 and Calcium Signaling.

Ca is a universal intracellular signal. The modulation of cytoplasmic Ca concentration regulates a plethora of cellular processes, such as: synaptic plasticity, neuronal survival, chemotaxis of immune cells, platelet aggregation, vasodilation, and cardiac excitation-contraction coupling. Rap1 GTPases are ubiquitously expressed binary switches that alternate between active and inactive states and are regulated by diverse families of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).

[Iatrogenic pleuropneumonia as a complication of nutritional treatment of preterm-delivery newborn].

Our study presents a case of pleuropneumonia caused by a leak of nutritional formula to pleural cavity, which was caused by perforation of the oesophagus. The child was born in 28 hbd with 1400 g birth weight and was fed with mother's milk by a nasogastric tube. From day 11 of life general state of the neonate worsened and on chest X-ray the contrast showed leaking into the right pleural cavity and the end of gastric tube was seen in the right lung area.

[Iatrogenic pleuropneumonia complicating central venous cannulation in a very low birth weight infant].

Background: Central venous cannulation is necessary for long-term parenteral nutrition in premature infants. Peripherally inserted long catheters are commonly used in these patients but even this relatively simple technique can end in serious complications. We present a case in which perforation of the vena cava and migration of the catheter to the intrapleural space resulted in multiple organ failure and death.