Democracy in the Democratic Republic of Congo: Myth or Reality?

Democracy is a regime by which the people impose their veto by choosing their representatives for a defined time on the basis of a social program that adapts to the socio-political realities of the primary sovereign In the case of the DRC we are in fact proposing the foundation of the Congolese state which must start from democracy to impose a state with strong and enlightened leadership authoritarianism a bit like what happened in Russia with Putin and in Mao s China because for us not only does it correspond to a Western-type regime corresponding to the way of life the understanding of things and adaptations to Western realities and behavior but it is the result or the reflection of the States already mature developed which have already laid the foundations for development is where state institutions and entities are seated A State where the leaders and the people are well prepared educated in development and democratic values by defining its prerogatives its needs to love and protect national interest

Anti-IL5 Drugs in COVID-19 Patients: Role of Eosinophils in SARS-CoV-2-Induced Immunopathology

SARS-CoV-2 infection stimulates a complex activation of the immune system. Eosinophils belong to the host’s defense equipment against respiratory viruses. In the first phase of the infection, eosinophils contribution is probably appropriate and beneficial, as they facilitate the suppression of the viral replication. However, in severe COVID-19 patients, during the second and third phases of the disease, eosinophils may participate in a maladaptive immune response and directly contribute to immunopathology. In fact, in severe patients, the immune response is prevalently T helper 1 type, but T helper 2 is also present. Eosinophils’ expansion and activation are stimulated by Type 2 cytokines, especially IL-5. Moreover, bronchial asthma, in which eosinophils play a central role, seems not to be a major risk factor for severe COVID-19. Among possible explanations, asthmatic patients are often treated with corticosteroids, which have been demonstrated to reduce the progression to critical COVID-19 in hospitalized patients. In addition to steroids, severe asthmatic patients are currently treated with biological drugs that target Type 2 immune response. Because IL-5 is necessary for the growth, survival, and activation of eosinophils, IL-5 inhibitors, such as mepolizumab, decrease the peripheral blood count of eosinophils, but do not influence eosinophils activation in the airway. In severe COVID-19 patients, the blockade of eosinophils’ activation might contrast harmful immunity

Endocannabinoid Signaling in Midbrain Dopamine Neurons: More than Physiology?

Different classes of neurons in the CNS utilize endogenous cannabinoids as retrograde messengers to shape afferent activity in a short- and long-lasting fashion. Transient suppression of excitation and inhibition as well as long-term depression or potentiation in many brain regions require endocannabinoids to be released by the postsynaptic neurons and activate presynaptic CB1 receptors. Memory consolidation and/or extinction and habit forming have been suggested as the potential behavioral consequences of endocannabinoid-mediated synaptic modulation

SURFACE CHEMISTRY EVALUATION IN THE DESIGN AND FABRICATION OF MICRO-DEVICES FOR PROTEIN ANALYSIS

In this Ph.D. thesis, the problem of the coating and adhesion of polymers onto selected surfaces has been investigated with the aim of designing micro-devices and/or microarrays for protein analysis. In the first part of the thesis, the micro-fabrication of a device for isoelectric focusing has been studied. The development of this device has required the covalent attachment of hydrogel plugs functionalized with pH buffering monomers on an Indium Tin Oxide (ITO) flat surface. The two ITO-coated slides are separated by silicon frames (both 3mm thick) stuck on the surface and the whole device was named as Micro Parallel Isoelectric focusing Device (MPID). The problem of the adhesion of the hydrogel plugs onto the ITO anode under the high vacuum conditions of the MALDI-TOF/TOF analysis has been solved, by properly selecting the percentage of monomers and related polymerization conditions. The MPID fabricated in accord to previous observations did not afford a completely efficient isolectric separation of the model protein mixture (commercial carbonic anhydrase). Furthermore, the proteins were absorbed onto plugs too tightly for a satisfactory, direct analysis by MALDITOF/ TOF of the plugs. At this stage of the Ph.D. program, the MPID project has been abandoned and the second part of the Ph.D. thesis has been directed towards the study of a functional coating onto different surfaces using a polymer that is the result of the co-polymerization of N,N-dimethylacrylamide (DMA), 3- (trimethoxysilyl)-propylmethacrylate (MAPS) and acryloyloxysuccinimide (NAS) [ Copoly (DMANAS- MAPS)]. It has been shown that this copolymer is able to generate thin layer of nanometer size onto inorganic substrates like glass, silicon oxide, or gold, typically used for the development of microarrays or bio-sensors for immunoassays. Applications of silicon and gold surfaces coated by Copoly (DMA-NAS-MAPS) are presented and discussed

Rare variant genotype imputation with thousands of study-specific whole-genome sequences: implications for cost-effective study designs

The utility of genotype imputation in genome-wide association studies is increasing as progressively larger reference panels are expanded through whole-genome sequencing. Developing general guidelines for optimally cost-effective imputation, however, requires evaluation of performance issues that include the relative utility of study-specific compared with general reference panels; genotyping with various array scaffolds; and assessment of ranges of allele frequencies. Here we compared the effectiveness of study-specific reference panels to the commonly used 1000 Genomes Project (1000G) reference panels in the isolated Sardinian population and in cohorts of European ancestry including samples from Minnesota (USA). We examined different combinations of genome-wide and custom arrays for baseline genotypes. In Sardinians, the study-specific reference panel provided better coverage and genotype imputation accuracy than the 1000G panels and other large European panels. Gain in accuracy was also observed for Minnesotans using the study-specific reference panel, although the increase was smaller than in Sardinians, especially for rare variants. Finally, we found that when imputation is performed with a study-specific reference panel, cutoffs different from the standard thresholds of MACH-Rsq and IMPUTE-INFO metrics should be used to efficiently filter badly imputed rare variants. This study thus provides general guidelines for researchers planning large-scale genetic studies

Endocannabinoid-Like Lipid Neuromodulators in the Regulation of Dopamine Signaling: Relevance for Drug Addiction

The family of lipid neuromodulators has been rapidly growing, as the use of different -omics techniques led to the discovery of a large number of naturally occurring N-acylethanolamines (NAEs) and N-acyl amino acids belonging to the complex lipid signaling system termed endocannabinoidome. These molecules exert a variety of biological activities in the central nervous system, as they modulate physiological processes in neurons and glial cells and are involved in the pathophysiology of neurological and psychiatric disorders. Their effects on dopamine cells have attracted attention, as dysfunctions of dopamine systems characterize a range of psychiatric disorders, i.e., schizophrenia and substance use disorders (SUD). While canonical endocannabinoids are known to regulate excitatory and inhibitory synaptic inputs impinging on dopamine cells and modulate several dopamine-mediated behaviors, such as reward and addiction, the effects of other lipid neuromodulators are far less clear. Here, we review the emerging role of endocannabinoid-like neuromodulators in dopamine signaling, with a focus on non-cannabinoid N-acylethanolamines and their receptors. Mounting evidence suggests that these neuromodulators contribute to modulate synaptic transmission in dopamine regions and might represent a target for novel medications in alcohol and nicotine use disorder

Sex-specific tonic 2-arachidonoylglycerol signaling at inhibitory inputs onto dopamine neurons of Lister Hooded rats

Addiction as a psychiatric disorder involves interaction of inherited predispositions and environmental factors. Similarly to humans, laboratory animals self-administer addictive drugs, whose appetitive properties result from activation and suppression of brain reward and aversive pathways, respectively. The ventral tegmental area (VTA) where dopamine (DA) cells are located is a key component of brain reward circuitry, whereas the rostromedial tegmental nucleus (RMTg) critically regulates aversive behaviors. Reduced responses to either aversive intrinsic components of addictive drugs or to negative consequences of compulsive drug taking might contribute to vulnerability to addiction. In this regard, female Lister Hooded (LH) rats are more vulnerable than male counterparts to cannabinoid self-administration. We, therefore, took advantage of sex differences displayed by LH rats, and studied VTA DA neuronal properties to unveil functional differences. Electrophysiological properties of DA cells were examined performing either single cell extracellular recordings in anesthetized rats or whole-cell patch-clamp recordings in slices. In vivo, DA cell spontaneous activity was similar, though sex differences were observed in RMTg-induced inhibition of DA neurons. In vitro, DA cells showed similar intrinsic and synaptic properties. However, females displayed larger depolarization-induced suppression of inhibition (DSI) than male LH rats. DSI, an endocannabinoid-mediated form of short term plasticity, was mediated by 2-arachidonoylglycerol (2-AG) activating type 1-cannabinoid (CB1) receptors. We found that sex-dependent differences in DSI magnitude were not ascribed to CB1 number and/or function, but rather to a tonic 2-AG signaling. We suggest that sex specific tonic 2-AG signaling might contribute to regulate responses to aversive intrinsic properties to cannabinoids, thus resulting in faster acquisition/initiation of cannabinoid taking and, eventually, in progression to addiction

Crocodiles, sharks and turtles: the urban geo‑palaeontological heritage of Cagliari (Italy)

In this paper, we report on the first project on the promotion of urban geoheritage in Cagliari, the capital of the Autonomous Region of Sardinia (Italy). We briefly address the history of geo-palaeontological research in the city area and outline the main phases of development in the history of Cagliari’s geo-palaeontological museum. Geotourism is an efficient method of bringing geosciences to a wider audience. For this project, we compiled a geoitinerary of the main lithotypes and fossils present within the urban territory. Miocene lithotypes are the most important materials in the edification of the Cagliari’s old town, and in the past, the quarrying activity favoured the geology knowledge of the area. The presence of abandoned quarries and natural outcrops in parks, public gardens, on the nearby coastline, and also of fossils exposed in ashlars of historic buildings, made Cagliari an excellent example to valorise the geo-palaeontological heritage using geotourism. This project showcases the importance of knowledge transfer and non-technical communication methods by converting highly technical aspects into accessible and engaging information dissemination to a wide range of audience types, including non-specialised ones

Conjugated Linoleic Acid and Brain Metabolism: A Possible Anti-Neuroinflammatory Role Mediated by PPARα Activation

Fatty acids play a crucial role in the brain as specific receptor ligands and as precursors of bioactive metabolites. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid (LA, 18:2 n-6) present in meat and dairy products of ruminants and synthesized endogenously in non-ruminants and humans, has been shown to possess different nutritional properties associated with health benefits. Its ability to bind to peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor key regulator of fatty acid metabolism and inflammatory responses, partly mediates these beneficial effects. CLA is incorporated and metabolized into brain tissue where induces the biosynthesis of endogenous PPAR α ligands palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), likely through a positive feedback mechanism where PPAR α activation sustains its own cellular effects through ligand biosynthesis. In addition to PPAR α, PEA and OEA may as well bind to other receptors such as TRPV1, further extending CLA own anti-neuroinflammatory actions. Future studies are needed to investigate whether dietary CLA may exert antiinflammatory activity, particularly in the setting of neurodegenerative diseases and neuropsychiatric disorders with a neuroinflammatory basis