Abstract:

The focus of this special issue is to highlight the role of autophagy in cellular homeodynamics, cell differentiation, and development with an outlook to diseases. Autophagy is an evolutionarily conserved catabolic process where cytoplasmic components are sequestered into double-membrane vesicles called autophagosomes, which then fuse with lysosomes and their content is degraded. Despite the significant progress observed over recent years in our understanding of the molecular mechanisms of autophagy, the elucidation of its role in developmental processes still remains a challenge for the scientific community. Given the role of autophagy in pathophysiology and diseases, it is essential to uncover how the mechanisms of autophagy function during developmental processes in the context of tissue and organismal physiology. This special issue contains a collection of four original research papers, four review articles, and one methodology report, covering a broad range of topics.

Author affiliation: Nezis, Ioannis P.. University of Warwick; Reino Unido

Author affiliation: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina

Author affiliation: Devenish, Rodney J.. Monash University; Australia

Author affiliation: Juhász, Gábor. Eötvös University, Budapest; Argentina

Abstract:

Corticotropin-releasing hormone (CRH) is a key player of basal and stress activated responses in the hypothalamic-pituitary-adrenal axis (HPA) and in extrahypothalamic circuits, where it functions as a neuromodulator to orchestrate humoral and behavioral adaptive responses to stress. This review describes molecular components and cellular mechanisms involved in CRH signaling downstream of its G protein-coupled receptors (GPCRs) CRHR1 and CRHR2, and summarizes recent findings that challenge the classical view of GPCR signaling, and impact on our understanding of CRHRs function. Special emphasis is placed on recent studies of CRH signaling that revealed new mechanistic aspects of cAMP generation and ERK1/2 activation in physiologically relevant contexts of the neurohormone action. In addition, we present an overview of the pathophysiological role of the CRH system, which highlights the need for a precise definition of CRHRs signaling at molecular level to identify novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders.

Author affiliation: Inda, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina

Author affiliation: Armando, Natalia Giannina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina

Author affiliation: Dos Santos Claro, Paula Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina

Author affiliation: Silberstein Cuña, Susana Iris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina

Abstract:

Background: It has been hypothesized that ischemic stroke can cause atrial fibrillation. By elucidating the mechanisms of neurogenically mediated paroxysmal atrial fibrillation, novel therapeutic strategies could be developed to prevent atrial fibrillation occurrence and perpetuation after stroke. This could result in fewer recurrent strokes and deaths, a reduction or delay in dementia onset, and in the lessening of the functional, structural, and metabolic consequences of atrial fibrillation on the heart. Methods: The Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE) study is an investigator-driven, translational, integrated, and transdisciplinary initiative. It comprises 3 complementary research streams that focus on atrial fibrillation detected after stroke: experimental, clinical, and epidemiological. The experimental stream will assess pre- and poststroke electrocardiographic, autonomic, anatomic (brain and heart pathology), and inflammatory trajectories in an animal model of selective insular cortex ischemic stroke. The clinical stream will prospectively investigate autonomic, inflammatory, and neurocognitive changes among patients diagnosed with atrial fibrillation detected after stroke by employing comprehensive and validated instruments. The epidemiological stream will focus on the demographics, clinical characteristics, and outcomes of atrial fibrillation detected after stroke at the population level by means of the Ontario Stroke Registry, a prospective clinical database that comprises over 23,000 patients with ischemic stroke. Conclusions: PARADISE is a translational research initiative comprising experimental, clinical, and epidemiological research aimed at characterizing clinical features, the pathophysiology, and outcomes of neurogenic atrial fibrillation detected after stroke.

Author affiliation: Paquet, Maryse. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Cerasuolo, Joshua O.. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Thorburn, Victoria. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Fridman, Sebastian. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Alsubaie, Rasha. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Lopes, Renato D.. University of Duke; Estados Unidos

Author affiliation: Cipriano, Lauren E.. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Salamone, Paula Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina

Author affiliation: Melling, C. W. James. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Khan, Ali R.. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina

Author affiliation: Fang, Jiming. Institute for Clinical Evaluative Sciences; Canadá

Author affiliation: Drangova, Maria. Western University; Canadá

Author affiliation: Montero Odasso, Manuel. Western University; Canadá. Parkwood Institute and Lawson Health Research Institute; Canadá

Author affiliation: Mandzia, Jennifer. Western University; Canadá

Author affiliation: Khaw, Alexander V.. Western University; Canadá

Author affiliation: Racosta, Juan M.. Western University; Canadá

Author affiliation: Paturel, Justin. Western University; Canadá

Author affiliation: Samoilov, Lucy. Western University; Canadá

Author affiliation: Stirling, Devin. Western University; Canadá

Author affiliation: Balint, Brittany. Western University; Canadá

Author affiliation: Jaremek, Victoria. Western University; Canadá

Author affiliation: Koschinsky, Marlys L.. Western University; Canadá

Author affiliation: Boffa, Michael B.. Western University; Canadá

Author affiliation: Summers, Kelly. Western University; Canadá

Author affiliation: Ibáñez Barassi, Agustín Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina. Universidad Adolfo Ibañez; Chile. Universidad Autónoma del Caribe; Colombia. Australian Research Council; Australia

Author affiliation: Mrkobrada, Marko. Western University; Canadá

Author affiliation: Saposnik, Gustavo. University of Toronto; Canadá

Author affiliation: Kimpinski, Kurt. Western University; Canadá

Author affiliation: Whitehead, Shawn N.. Western University; Canadá

Author affiliation: Sposato, Luciano A.. Western University; Canadá

Abstract:

Vascular remodeling refers to alterations in the structure of resistance vessels contributing to elevated systemic vascular resistance in hypertension. We start with some historical aspects, underscoring the importance of Glagov’s contribution. We then move to some basic concepts on the biomechanics of blood vessels and explain the definitions proposed by Mulvany for specific forms of remodeling, especially inward eutrophic and inward hypertrophic. The available evidence for the existence of remodeled resistance vessels in hypertension comes next, with relatively more weight given to human, in comparison with animal data. Mechanisms are discussed. The impact of antihypertensive drug treatment on remodeling is described, again with emphasis on human data. Some details are given on the three mechanisms to date which point to remodeling resistance arteries as an independent predictor of cardiovascular risk in hypertensive patients. We terminate by considering the potential role of remodeling in the pathogenesis of endorgan damage and in the perpetuation of hypertension.

Author affiliation: Renna, Nicolas Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Author affiliation: de Las Heras, Maria Evangelina. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiologia; España;

Author affiliation: Miatello, Roberto Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;

Abstract:

Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms.

Author affiliation: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina

Author affiliation: Peralta, Cecilia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina

Author affiliation: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina

Abstract:

The gastrointestinal epithelium functions as a selective barrier to absorb nutrients, electrolytes and water, but at the same time restricts the passage into the systemic circulation of intraluminal potentially toxic compounds. This epithelium maintains its selective barrier function through the presence of very selective and complex intercellular junctions and the ability of the absorptive cells to reject those compounds. Accordingly, the enterocytes metabolize orally incorporated xenobiotics and secrete the hydrophilic metabolites back into the intestinal lumen through specific transporters localized apically. In the recent decades, there has been increasing recognition of the existence of the intestinal cellular barrier. In the present review we focus on the role of the multidrug resistance-associated protein 2 (MRP2, ABCC2) in the apical membrane of the enterocytes, as an important component of this intestinal barrier, as well as on its regulation. We provide a detailed compilation of significant contributions demonstrating that MRP2 expression and function vary under relevant physiological and pathophysiological conditions. Because MRP2 activity modulates the availability and pharmacokinetics of many therapeutic drugs administered orally, their therapeutic efficacy and safety may vary as well.

Author affiliation: Arana, Maite Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina

Author affiliation: Tocchetti, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina

Author affiliation: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. Ruprecht-Karls-Universität Heidelberg; Alemania

Author affiliation: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina

Author affiliation: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina

Abstract:

Upon the pathogen encounter, the host seeks to ensure an adequate inflammatory reaction to combat infection but at the same time tries to prevent collateral damage, through several regulatory mechanisms, like an endocrine response involving the production of adrenal steroid hormones. Our studies show that active tuberculosis (TB) patients present an immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro-inflammatory cytokines, and decreased amounts of dehydroepiandrosterone. Studies in patients undergoing specific treatment revealed that cortisol levels remained increased even after several months of initiating therapy. In addition to the well-known metabolic and immunological effects, glucocorticoids are involved in thymic cortical depletion with immature thymocytes being quite sensitive to such an effect. The thymus is a central lymphoid organ supporting thymocyte T-cell development, i.e., lineage commitment, selection events and thymic emigration. While thymic TB is an infrequent manifestation of the disease, several pieces of experimental and clinical evidence point out that the thymus can be infected by mycobacteria. Beyond this, the thymic microenvironment during TB may be also altered because of the immune-hormonal alterations. The thymus may be then an additional target of organ involvement further contributing to a deficient control of infection and disease immunopathology.

Author affiliation: D'Attilio, Luciano. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clínica y Experimental de Rosario, CONICET-UNR; Argentina

Author affiliation: Bottasso, Oscar. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clínica y Experimental de Rosario, CONICET-UNR; Argentina