New insights in cellular senescence: The pituitary model.

Pituitary tumors are characterized by slow proliferation rates and a high prevalence within the population. The pathogenesis of these tumors remains incompletely understood, although accumulating evidence suggests that the activation of the cellular senescence program, triggered by various stressors and functioning as a brake on cellular proliferation, may contribute to their typically benign nature. Multiple mediators of the senescence response are implicated in this process.

Role of canonical and non-canonical cAMP sources in CRHR2α-dependent signaling.

Hippocampal neurons exhibit activation of both the conventional transmembrane adenylyl cyclases (tmACs) and the non-canonical soluble adenylyl cyclase (sAC) as sources of cyclic AMP (cAMP). These two cAMP sources play crucial roles in mediating signaling pathways downstream of CRHR1 in neuronal and neuroendocrine contexts. In this study, we investigate the involvement of both cAMP sources in the molecular mechanisms triggered by CRHR2α.

The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway.

Senescent cells produce a Senescence-Associated Secretory Phenotype (SASP) that involves factors with diverse and sometimes contradictory activities. One key SASP factor, interleukin-6 (IL-6), has the potential to amplify cellular senescence in the SASP-producing cells in an autocrine action, while simultaneously inducing proliferation in the neighboring cells. The underlying mechanisms for the contrasting actions remain unclear.

The shape of Nature's stingers revealed.

Stinger-like structures in living organisms evolved convergently across taxa for both defensive and offensive purposes, with the main goal being penetration and damage. Our observations over a broad range of taxa and sizes, from microscopic radiolarians to narwhals, reveal a self-similar geometry of the stinger extremity: the diameter () increases along the distance from the tip () following a power law [Formula: see text] , with the tapering exponent varying universally between 2 and 3. We demonstrate, through analytical and experimental mechanics involving three-dimensional (3D) printing, that this geometry optimizes the stinger's performance; it represents a trade-off between the propensity to buckle, for smaller than 2, and increased penetration force, for greater than 3.

SUMO regulation of FKBP51 activity and the stress response.

Glucocorticoids (GCs) actions are mostly mediated by the GC receptor (GR), a member of the nuclear receptor superfamily. Alterations of the GR activity have been associated to different diseases including mood disorders. FKBP51 is a GR chaperone that has gained much attention because it is a strong inhibitor of GR activity.

Expression of RSUME is Associated With Poor Prognosis in Clear Cell Renal Carcinoma: Involvement of ROS Related Metabolism.

Introduction: RSUME (RWD domain-containing protein SUMO Enhancer), RWD domain containing 3 (RWDD3) gene product, is upregulated by hypoxia and expressed in organs prone to develop von Hippel-Lindau (VHL) syndrome tumors.

Materials And Methods: We evaluated RSUME prognostic value in clear cell renal cell carcinoma (ccRCC) based mainly on the dataset (KIRC) from patients in The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and one-way analysis of variance (ANOVA) followed by Tukey's test were used to evaluate relationships between clinicopathological features and RSUME expression and univariate and multivariate Cox regression analysis methods were used to evaluate prognostic factors.

A bioinspired snap-through metastructure for manipulating micro-objects.

Micro-objects stick tenaciously to each other-a well-known show-stopper in microtechnology and in handling micro-objects. Inspired by the trigger plant, we explore a mechanical metastructure for overcoming adhesion involving a snap-action mechanism. We analyze the nonlinear mechanical response of curved beam architectures clamped by a tunable spring, incorporating mono- and bistable states.

Film-Terminated Fibrillar Microstructures with Improved Adhesion on Skin-like Surfaces.

Adhesives for interaction with human skin and tissues are needed for multiple applications. Micropatterned dry adhesives are potential candidates, allowing for a conformal contact and glue-free adhesion based on van der Waals interactions. In this study, we investigate the superior adhesion of film-terminated fibrillar microstructures (fibril diameter, 60 μm; aspect ratio, 3) in contact with surfaces of skin-like roughness ( 50 μm).

Impact of RSUME Actions on Biomolecular Modifications in Physio-Pathological Processes.

The small RWD domain-containing protein called RSUME or RWDD3 was cloned from pituitary tumor cells with increasing tumorigenic and angiogenic proficiency. RSUME expression is induced under hypoxia or heat shock and is upregulated, at several pathophysiological stages, in tissues like pituitary, kidney, heart, pancreas, or adrenal gland. To date, several factors with essential roles in endocrine-related cancer appear to be modulated by RWDD3.

Attachment of bioinspired microfibrils in fluids: transition from a hydrodynamic to hydrostatic mechanism.

Reversible and switchable adhesion of elastomeric microstructures has attracted significant interest in the development of grippers for object manipulation. Their applications, however, have often been limited to dry conditions and adhesion of such deformable microfibrils in the fluid environment is less understood. In the present study, we performed adhesion tests in silicone oil using single cylindrical microfibrils of a flat-punch shape with a radius of 80 µm.

Water as a "glue": Elasticity-enhanced wet attachment of biomimetic microcup structures.

Octopus, clingfish, and larva use soft cups to attach to surfaces under water. Recently, various bioinspired cups have been engineered. However, the mechanisms of their attachment and detachment remain elusive.

Tricyclic antidepressants target FKBP51 SUMOylation to restore glucocorticoid receptor activity.

FKBP51 is an important inhibitor of the glucocorticoid receptor (GR) signaling. High FKBP51 levels are associated to stress-related disorders, which are linked to GR resistance. SUMO conjugation to FKBP51 is necessary for FKBP51's inhibitory action on GR.

Optoacoustically induced auditory brainstem responses in the mouse model enhanced through an absorbing film.

Significance: Optoacoustic stimulation offers an alternative stimulation strategy for the hearing organ. To serve as the base for a novel auditory prosthesis, the optoacoustic stimulation must be biocompatible and energy-saving.

Aim: Enhancing the efficiency of optoacoustic stimulation while reducing the energy input in a suited animal model.

Stress-Related Brain Neuroinflammation Impact in Depression: Role of the Corticotropin-Releasing Hormone System and P2X7 Receptor.

Depression and other psychiatric stress-related disorders are leading causes of disability worldwide. Up to date, treatments of mood disorders have limited success, most likely due to the multifactorial etiology of these conditions. Alterations in inflammatory processes have been identified as possible pathophysiological mechanisms in psychiatric conditions.

Mass Spectrometry-Based Metabolic Fingerprinting Contributes to Unveil the Role of RSUME in Renal Cell Carcinoma Cell Metabolism.

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. RSUME (RWD domain (termed after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases)-containing protein small ubiquitin-related modifier (SUMO) enhancer) acts as a negative regulator of VHL function in normoxia. A discovery-based metabolomics approach was developed by means of ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (MS) for fingerprinting the endometabolome of a human ccRCC cell line 786-O and three other transformed cell systems ( = 102) with different expressions of RSUME and VHL.

Enhancing Dry Adhesion of Polymeric Micropatterns by Electric Fields.

Micropatterned dry adhesives rely mainly on van der Waals interactions. In this paper, we explore the adhesion strength increase that can be achieved by superimposing an electrostatic field through interdigitated subsurface electrodes. Micropatterns were produced by replica molding in silicone.

Modifications in the cellular proteome and their clinical application.

Post-translational modifications (PTMs) are covalent modifications in proteins during or after their synthesis. Among them, the best known are phosphorylation, methylation, acetylation, and also cleavage or binding of small peptides (ubiquitination, SUMOylation and NEDDylation). Often the protein is modified in multiple sites and these modifications are coordinated generating a PTMs crosstalk.

GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours.

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease.

SUMO conjugation as regulator of the glucocorticoid receptor-FKBP51 cellular response to stress.

In order to adequately respond to stressful stimuli, glucocorticoids (GCs) target almost every tissue of the body. By exerting a negative feedback loop in the hypothalamic-pituitary-adrenal (HPA) axis GCs inhibit their own synthesis and restore homeostasis. GCs actions are mostly mediated by the GC receptor (GR), a member of the nuclear receptor superfamily.

Crosstalk of BMP-4 and RA signaling pathways on Pomc gene regulation in corticotrophs.

Retinoic acid (RA), an active metabolite of Vitamin A, and bone morphogenetic protein 4 (BMP-4) pathways control the transcription of pro-opiomelanocortin (Pomc), the precursor of ACTH. We describe a novel mechanism by which RA and BMP-4 act together in the context of pituitary corticotroph tumoral cells to regulate Pomc transcription. BMP-4 and RA exert a potentiated inhibition on Pomc gene expression.

Statistical properties of defect-dependent detachment strength in bioinspired dry adhesives.

Dry adhesives using surface microstructures inspired by climbing animals have been recognized for their potentially novel capabilities, with relevance to a range of applications including pick-and-place handling. Past work has suggested that performance may be strongly dependent on variability in the critical defect size among fibrillar sub-contacts. However, it has not been directly verified that the resulting adhesive strength distribution is well described by the statistical theory of fracture used.

Strong Wet and Dry Adhesion by Cupped Microstructures.

Recent advances in bio-inspired microfibrillar adhesives have resulted in technologies that allow reliable attachment to a variety of surfaces. Because capillary and van der Waals forces are considerably weakened underwater, fibrillar adhesives are however far less effective in wet environments. Although various strategies have been proposed to achieve strong reversible underwater adhesion, strong adhesives that work both in air and underwater without additional surface treatments have yet to be developed.

A Self-Adhesive Elastomeric Wound Scaffold for Sensitive Adhesion to Tissue.

Pressure sensitive adhesives based on silicone materials are used particularly for skin adhesion, e.g., the fixation of electrocardiogram (ECG) electrodes or wound dressings.

von Hippel-Lindau mutants in renal cell carcinoma are regulated by increased expression of RSUME.

Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Resistance to therapies targeting tumor angiogenesis opens the question about the underlying mechanisms. Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice.