Ghrelin in Central Neurons

Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, is released in the bloodstream in response to a negative energetic status. Since discovery, the hypothalamus was identified as the main source of ghrelin in the CNS, and effects of the peptide have been mainly observed in this area of the brain. In recent years, an increasing number of studies have reported ghrelin synthesis and effects in specific populations of neurons also outside the hypothalamus. Thus, ghrelin activity has been described in midbrain, hindbrain, hippocampus, and spinal cord. The spectrum of functions and biological effects produced by the peptide on central neurons is remarkably wide and complex. It ranges from modulation of membrane excitability, to control of neurotransmitter release, neuronal gene expression, and neuronal survival and proliferation. There is not at present a general consensus concerning the source of ghrelin acting on central neurons. Whereas it is widely accepted that the hypothalamus represents the most important endogenous source of the hormone in CNS, the existence of extra-hypothalamic ghrelin-synthesizing neurons is still controversial. In addition, circulating ghrelin can theoretically be another natural ligand for central ghrelin receptors. This paper gives an overview on the distribution of ghrelin and its receptor across the CNS and critically analyses the data available so far as regarding the effects of ghrelin on central neurotransmission

CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens

Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of secreting high levels of type I interferon (IFN) in response to viruses and bacterial stimuli. In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed. We report that CpG-matured murine PDCs are capable of eliciting in naive mice antigen-specific CTLs against endogenous antigens as well as exogenous peptides, but not against an exogenous antigen. Type I IFN is not required for priming, as injection of CpG-matured PDCs into type I IFN receptor–deficient mice elicits functional CTL responses. Mature PDCs prime CTLs that secrete IFN-γ and protect mice from a tumor challenge. In contrast, immature PDCs are unable to prime antigen-specific CTLs. However, mice injected with immature PDCs are fully responsive to secondary antigenic challenges, suggesting that PDCs have not induced long-lasting tolerance via anergic or regulatory T cells. Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN

Evaluation of mesoscale convective systems in South America using multiple satellite products and an object‐based approach

In this study, an object-based verification method was used to reveal the existence of systematic errors in three satellite precipitation products: Tropical Rainfall Measurement Mission (TRMM), Climate Prediction Center Morphing Technique (CMORPH), and Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN). Mesoscale convective systems (MCSs) for the austral summer 2002–2003 in the La Plata river basin, southeastern South America, were analyzed with the Contiguous Rain Area (CRA) method. Errors in storms intensity, volume, and spatial location were evaluated. A macroscale hydrological model was used to assess the impact of spatially shifted precipitation on streamflows simulations. PERSIANN underestimated the observed average rainfall rate and maximum rainfall consistent with the detection of storm areas systematically larger than observed. CMORPH overestimated the average rainfall rate while the maximum rainfall was slightly underestimated. TRMM average rainfall rate and rainfall volume correlated extremely well with ground observations whereas the maximum rainfall was systematically overestimated suggesting deficiencies in the bias correction procedure to filter noisy measurements. The preferential direction of error displacement in satellite-estimated MCSs was in the east-west direction for CMORPH and TRMM. Discrepancies in the fine structure of the storms dominated the error decomposition of all satellite products. Errors in the spatial location of the systems influenced the magnitude of simulated peaks but did not have a significant impact on the timing indicating that the system's response to precipitation was mitigating the effect of the errors.Fil: Demaria, E. M. C.. University Of Arizona; Estados UnidosFil: Rodriguez, D. A.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Ebert, E. E.. Centre for Australian Weather and Climate Research; AustraliaFil: Salio, Paola Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmosfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmosfera; ArgentinaFil: Su, F.. University of Washington; Estados UnidosFil: Valdes, J. B.. University Of Arizona; Estados Unido

Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis

Abstract Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We found that highly sensitive MPM lines display lower proteasome activity than more bortezomib-resistant clones, suggesting that reduced proteasomal capacity might contribute to the intrinsic susceptibility of mesothelioma cells to proteasome inhibitors-induced apoptosis. Moreover, MPM equipped with fewer active proteasomes accumulated polyubiquitinated proteins, at the expense of free ubiquitin, a condition known as proteasome stress, which lowers the cellular apoptotic threshold and sensitizes mesothelioma cells to bortezomib-induced toxicity as shown herein. Taken together, our data suggest that an unfavorable load-versus-capacity balance represents a critical determinant of primary apoptotic sensitivity to bortezomib in MPM

Increased Placental Anti‐Oxidant Response in Asymptomatic and Symptomatic COVID‐19 Third‐Trimester Pregnancies

Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-CoV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae of women testing positive for SARS-CoV-2 during the third trimester of pregnancy showed redox-related alterations involving Catalase (CAT) and Superoxide Dismutase (SOD) antioxidant enzymes as well as placenta morphological anomalies relative to a cohort of healthy pregnant women. Next, we evaluated if placental redox-related alterations and mitochondria pathological changes were correlated with the presence of maternal symptoms. We observed ultrastructural alterations of placental mitochondria accompanied by increased levels of oxidative stress markers Thiobarbituric Acid Reactive Substances (TBARS) and Hypoxia Inducible Factor-1 α (HIF-1α) in SARS-CoV-2 women during the third trimester of pregnancy. Importantly, we found an increase in placental CAT and SOD antioxidant enzymes accompanied by physiological neonatal outcomes. Our findings strongly suggest a placenta-mediated OxS inhibition in response to SARS-CoV-2 infection, thus contrasting the cytotoxic profile caused by Coronavirus Disease 2019 (COVID-19)

Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization

Inhibition in spinal nociceptive pathways is weaker and more labile in lamina I —where thermal input is primarily processed— than in lamina II that encodes predominantly high threshold mechanical input. This explains why noxious thermal input makes spinal circuits prone to catastrophic sensitization

Training and practice in bronchoscopy: A national survey in Italy

Training and practice in bronchoscopy. A national survey in Italy. N. Facciolongo, R. Piro, F. Menzella, M. Lusuardi, M. Salio, L. Lazzari Agli, M. Patelli. Background and Aim. Bronchoscopy is performed in a variety of different settings in Italy. The surveys conducted so far have highlighted the heterogeneity of the procedures and the frequent inability to adhere to the guidelines. The aim of this survey was to analyse procedures, training, and opinions of Italian respiratory physicians performing interventional bronchology in the clinical practice. Methods. The study was conducted retrospectively on 300 pulmonologists. From January to June 2008, these were invited to participate in an email survey to be sent out monthly to each participant for four consecutive months. Results. Two hundred and one respiratory physicians took part in the study, most of whom (83.5%) work in either Pulmonology or Interventional Pulmonology Units. The year before the survey, 21.2% of the participants had performed fewer than 100 examinations, 42.3% 100 to 300, and 36.6% more than 300 bronchoscopies; 53.9% were familiar with the international guidelines on the topic. Among the responders, 34.1% had received less than 6 months training, 55.3% considered further training in rigid bronchoscopy, laser procedures and thoracoscopy, invaluable for their professional activity. Adequate training for transbronchial needle aspirates, was reported by 49.6% of respondents. Conclusions. Our data show that interventional bronchoscopy procedures are regularly performed according to current recommendations by over half of the Italian Pulmonologists participating in our survey. The need for more comprehensive basic education and training was put forward by the majority of physicians

Global Precipitation Measurement: Methods, Datasets and Applications

This paper reviews the many aspects of precipitation measurement that are relevant to providing an accurate global assessment of this important environmental parameter. Methods discussed include ground data, satellite estimates and numerical models. First, the methods for measuring, estimating, and modeling precipitation are discussed. Then, the most relevant datasets gathering precipitation information from those three sources are presented. The third part of the paper illustrates a number of the many applications of those measurements and databases. The aim of the paper is to organize the many links and feedbacks between precipitation measurement, estimation and modeling, indicating the uncertainties and limitations of each technique in order to identify areas requiring further attention, and to show the limits within which datasets can be used