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35 result(s) for "Calcagnile, Matteo"
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Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer’s Disease
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a gradual decline in cognitive abilities and a progressive loss of the neuronal system resulting from neuronal damage and death. The maintenance of neuronal homeostasis is intricately connected to the crosstalk and balance among organelles. Indeed, intracellular organelles are not just isolated compartments in the cell; instead, they are interdependent structures that can communicate through membrane contact sites (MCSs), forming physical connection points represented by proteinaceous tethers. Mitochondria and lysosomes have fundamental physiological functions within neurons, and accumulating evidence highlights their dysfunctions as AD features, strongly associated with the neurodegenerative process underlying the development and progression of AD. This review explores mitochondria-lysosome communication through MCSs, the tethering proteins and their functions in the cell, discussing the methodological challenges in measuring the structure and dynamics of contacts, and the potential role of altered mitochondria-lysosome communication in the context of organelle dysfunction related to neuron impairment in AD pathogenesis. The different abundance of the tethering proteins was considered in healthy physiological and in AD-related conditions to assess the possible organelle communication dysregulation and the subsequent cellular function alterations, and to evaluate the role of mitochondria-lysosome MCSs in the pathogenesis of this disorder.
Functional Assessment of Orphan Proteins in the Streptomyces Pan-Proteome Through Genome-Wide Synteny Analysis
Members of the genus Streptomyces possess large genomes, a vast and largely unexplored metabolic potential, and a distinctive life cycle characterized by pronounced morphological differentiation. However, despite extensive molecular, genomic, and microbiological research, the functions of many genes in this genus remain poorly characterized. In this study, 929 complete Streptomyces genomes were analyzed. From the predicted proteomes of these genomes, proteins conserved in at least 75% of strains and lacking annotation in the KEGG GENES database were identified and clustered. To expand the annotation, synteny and co-occurrence analyses were performed between these unannotated proteins and annotated genes. A total of 330 conserved clusters were identified; 284 out of 330 clusters contain proteins encoded by genes that are syntenic with those associated with transcriptional regulation, fatty acid metabolism, two-component signaling systems, and morphological development. Additional clusters included metalloproteins and enzymes such as dehydrogenases, suggesting a wide functional spectrum. The conserved yet uncharacterized proteins identified in this analysis represent promising targets for future research, both for elucidating the molecular biology of Streptomyces and for expanding the range of secondary metabolites produced by these ecologically and industrially significant microorganisms
Galleria mellonella (Greater Wax Moth) as a Reliable Animal Model to Study the Efficacy of Nanomaterials in Fighting Pathogens
The spread of multidrug-resistant microbes has made it necessary and urgent to develop new strategies to deal with the infections they cause. Some of these are based on nanotechnology, which has revolutionized many fields in medicine. Evaluating the safety and efficacy of these new antimicrobial strategies requires testing in animal models before being tested in clinical trials. In this context, Galleria mellonella could represent a valid alternative to traditional mammalian and non-mammalian animal models, due to its low cost, ease of handling, and valuable biological properties to investigate host–pathogen interactions. The purpose of this review is to provide an updated overview of the literature concerning the use of G. mellonella larvae as an animal model to evaluate safety and efficacy of nanoparticles and nanomaterials, particularly, of those that are used or are under investigation to combat microbial pathogens.
A Perspective on the Role of Mitochondrial Biomolecular Condensates (mtBCs) in Neurodegenerative Diseases and Evolutionary Links to Bacterial BCs
Biomolecular condensates (BCs), formed through liquid–liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies.
Mitochondrial Neurodegenerative Diseases: Three Mitochondrial Ribosomal Proteins as Intermediate Stage in the Pathway That Associates Damaged Genes with Alzheimer’s and Parkinson’s
Currently, numerous research endeavors are dedicated to unraveling the intricate nature of neurodegenerative diseases. These conditions are characterized by the gradual and progressive impairment of specific neuronal systems that exhibit anatomical or physiological connections. In particular, in the last twenty years, remarkable efforts have been made to elucidate neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. However, despite extensive research endeavors, no cure or effective treatment has been discovered thus far. With the emergence of studies shedding light on the contribution of mitochondria to the onset and advancement of mitochondrial neurodegenerative disorders, researchers are now directing their investigations toward the development of therapies. These therapies include molecules designed to protect mitochondria and neurons from the detrimental effects of aging, as well as mutant proteins. Our objective is to discuss and evaluate the recent discovery of three mitochondrial ribosomal proteins linked to Alzheimer's and Parkinson's diseases. These proteins represent an intermediate stage in the pathway connecting damaged genes to the two mitochondrial neurological pathologies. This discovery potentially could open new avenues for the production of medicinal substances with curative potential for the treatment of these diseases.
Neisseria meningitidis: a traditional extracellular pathogen with an intense intracellular lifestyle
Neisseria meningitidis (meningococcus) is a transitory colonizer of the human nasopharynx that occasionally, for largely unknown reasons, reaches the bloodstream, translocating across the nasopharyngeal mucosa, causing septicemia. The bloodstream spread of bacteria to the meninges can cause meningitis after crossing the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). Thus, the meningococcus must cross several epithelial and endothelial barriers to cause invasive meningococcal disease (IMD). While meningococcal interactions on the surface of epithelial and endothelial cells have been intensively investigated, leading to the identification of key determinants of virulence of this bacterium, relatively little is known about the crossing of the nasopharyngeal epithelial barrier (NEB), the BBB, and BCSFB by the meningococcus. Several mechanisms (transcellular and paracellular) have been proposed, including transcellular crossing and paracellular crossing that might be favored by an epicellular lifestyle of this bacterium. Little is also known about the prevalent (vacuolar or cytoplasmic) localization of N. meningitidis in infected epithelial and endothelial cells and the mechanisms adopted by this microorganism to survive and multiply in the intracellular environment. The purpose of this article is to collect and review what is actually known about the intracellular lifestyle of these microorganisms. The picture that emerges is that although it is traditionally considered an extracellular pathogen (despite its original name, Diplococcus intracellularis meningitidis [Weichseilbaum, 1887]), N. meningitidis engages in complex interactions with host cells in the intracellular microenvironment, involving signal transduction, membrane trafficking, cytoskeleton, metabolic cross-talk, and programmed cell death.
The Microbiome of the Maculinea-Myrmica Host-Parasite Interaction
Maculinea (= Phengaris ) are endangered butterflies that are characterized by a very complex biological cycle. Maculinea larvae behave as obligate parasites whose survival is strictly dependent on both particular food plants and species-specific Myrmica ants. In this interaction, Maculinea caterpillars induce Myrmica workers to retrieve and rear them in the nest by chemical and acoustic deception. Social insect symbiotic microorganisms play a key role in intraspecific and interspecific communication; therefore, it is possible that the Maculinea caterpillar microbiome might be involved in the chemical cross-talk by producing deceptive semiochemicals for host ants. To address this point, the microbiota of Maculinea alcon at different larval stages (phytophagous early larvae, intermediate larvae, carnivorous late larvae) was analyzed by using 16S rRNA-guided metabarcoding approach and compared to that of the host ant Myrmica scabrinodis . Structural and deduced functional profiles of the microbial communities were recorded, which were used to identify specific groups of microorganisms that may be involved in the chemical cross-talk. One of the most notable features was the presence in all larval stages and in the ants of two bacteria, Serratia marcescens and S . entomophila , which are involved in the chemical cross-talk between the microbes and their hosts.
Aquatic Moss Mats Are Alternative Biofilter Media for Aquaculture and Aquaponic Effluents Treating
Inert media such as plastic, ceramic or zeolite are conventionally used for wastewater biofiltration. They all need microbial activation and are essentially chosen for their surface/mass ratio, since biofiltration is entirely performed within the surface biofilm. Using biodegradable media may enhance the sustainability of the system, but it should not produce decomposition-related pollutants. Due to their surface extension, peculiar microbiota and structural resistance, aquatic moss appears to be a very good support for biofilters. Thus, in this study, we evaluated aquatic moss mats as an alternative medium for biofiltration of aquaculture or aquaponic effluents. Two moss species, Taxiphyllum barbieri and Leptodictyum riparium, were tested, also for their contribution on nitrogen metabolism and potential negative effects on hydroponic plants cultivation, due to competition for nutrients. Our proof-of-concept research demonstrates equivalence in real conditions, as inert and moss media exhibited comparable rates; however, the amount of moss required can be several times lower than that of any competing media. Preliminary results suggest the possibility to integrate moss-based biofilters in aquaculture and aquaponics technologies.
HrpA anchors meningococci to the dynein motor and affects the balance between apoptosis and pyroptosis
Background In Neisseria meningitidis the HrpA/HrpB two-partner secretion system (TPS) was implicated in diverse functions including meningococcal competition, biofilm formation, adherence to epithelial cells, intracellular survival and vacuolar escape. These diverse functions could be attributed to distinct domains of secreted HrpA. Methods A yeast two-hybrid screening, in vitro pull-down assay and immunofluorescence microscopy experiments were used to investigate the interaction between HrpA and the dynein light-chain, Tctex-type 1 (DYNLT1). In silico modeling was used to analyze HrpA structure. Western blot analysis was used to investigate apoptotic and pyroptotic markers. Results The HrpA carboxy-terminal region acts as a manganese-dependent cell lysin, while the results of a yeast two-hybrid screening demonstrated that the HrpA middle region has the ability to bind the dynein light-chain, Tctex-type 1 (DYNLT1). This interaction was confirmed by in vitro pull-down assay and immunofluorescence microscopy experiments showing co-localization of N. meningitidis with DYNLT1 in infected epithelial cells. In silico modeling revealed that the HrpA-M interface interacting with the DYNLT1 has similarity with capsid proteins of neurotropic viruses that interact with the DYNLT1. Indeed, we found that HrpA plays a key role in infection of and meningococcal trafficking within neuronal cells, and is implicated in the modulation of the balance between apoptosis and pyroptosis. Conclusions Our findings revealed that N. meningitidis is able to effectively infect and survive in neuronal cells, and that this ability is dependent on HrpA, which establishes a direct protein–protein interaction with DYNLTI in these cells, suggesting that the HrpA interaction with dynein could be fundamental for N. meningitidis spreading inside the neurons. Moreover, we found that the balance between apoptotic and pyroptotic pathways is heavily affected by HrpA.
Chemical Composition, Fatty Acid and Mineral Content of Food-Grade White, Red and Black Sorghum Varieties Grown in the Mediterranean Environment
Grain sorghum (Sorghum bicolor) is a gluten-free cereal grown around the world and is a food staple in semi-arid and subtropical regions. Sorghum is a diverse crop with a range of pericarp colour including white, various shades of red, and black, all of which show health-promoting properties as they are rich sources of antioxidants such as polyphenols, carotenoids, as well as micro- and macro-nutrients. This work examined the grain composition of three sorghum varieties possessing a range of pericarp colours (white, red, and black) grown in the Mediterranean region. To determine the nutritional quality independent of the contributions of phenolics, mineral and fatty acid content and composition were measured. Minor differences in both protein and carbohydrate were observed among varieties, and a higher fibre content was found in both the red and black varieties. A higher amount of total saturated fats was found in the white variety, while the black variety had a lower amount of total unsaturated and polyunsaturated fats than either the white or red varieties. Oleic, linoleic, and palmitic were the primary fatty acids in all three analysed sorghum varieties. Significant differences in mineral content were found among the samples with a greater amount of Mg, K, Al, Mn, Fe, Ni, Zn, Pb and U in both red and black than the white sorghum variety. The results show that sorghum whole grain flour made from grain with varying pericarp colours contains unique nutritional properties.