45 results on '"Hay Mele, B."'
Search Results
2. Anatomy, photochemical activity, and DNA polymorphism in leaves of dwarf tomato irradiated with X-rays
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Arena, C., Turano, M., Hay Mele, B., Cataletto, P. R., Furia, M., Pugliese, M., and De Micco, V.
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- 2017
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3. Radioresistance of dwarf bean plants irradiated with C and Ti heavy ions
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Vitale E., De Micco V., Hay Mele B., Amitrano C., De Maio A., Carfagna S., Arena C., Società Italiana per le Ricerche sulle Radiazioni, Vitale, E., De Micco, V., Hay Mele, B., Amitrano, C., De Maio, A., Carfagna, S., and Arena, C.
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Space Biology, dwarf bean, high LET ionizing radiation, radio-resistance, antioxidants - Abstract
Plant cultivation in Space is a challenge for biology. In this context, preliminary studies with high energetic particles provide information about the capability of plants to withstand ionizing radiation in space. Non-lethal levels of high-LET ionizing radiation may stimulate physiological and morphological traits in plants, increasing their ability to be cultivated in extraterrestrial environments. In this study, we test the radioresistance of Dolichos melanophtalmus DC. (dwarf bean) irradiated at seed stage with low doses of heavy ions, namely C 1Gy, C 10 Gy, Ti 1 Gy and Ti 10 Gy. These doses, lethal for mammalian cells resulted not as dangerous for plants. After germination, alterations in growth were recorded by morphometric analysis; the photosynthetic efficiency was evaluated by chlorophyll a fluorescence emission measurements and determination of photosynthetic pigments’ content.The occurrence of oxidative stress and plant capability to withstand it were tested by measuring the intracellular H2O2 level, the ascorbic acid content and the poly(ADPribose) polymerase (PARP) activity. The irradiation of the seeds with different types of heavy ions and doses did not prevent either seed germination or the completion of plant life cycle; indeed irradiated plants were able to produce a new generation of seeds. Stimulatory effects on plant height were observed at Ti10 Gy, whereas C 10 Gy treatment determined a decrease in plant growth. The dose of C 10 Gy also reduced plant photochemistry and pigment content compared to other treatments, indicating the occurrence of damages at the photosystem level. However, in C 10 Gy treated plants the increase in intracellular H2O2 concentration, together with the rise in ascorbic acid and PARP activity, suggests the occurrence of a radio-induced oxidative stress mitigated by plant capability to activate the defense mechanisms successfully.
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- 2017
4. Can be Solanum lycopersicum L. cv ‘Micro-Tom’ a good candidate for growth in Space? Testing the effects of High-LET ionizing radiation on plant growth, photosynthesis and antioxidants
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Vitale E., De Micco V., Amitrano C., Turano M., Hay Mele B., Manti L., Arena C., European Radiation Research Society (ERRS), Vitale, E., De Micco, V., Amitrano, C., Turano, M., Hay Mele, B., Manti, L., and Arena, C.
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Space ecosystem, photosynthesis, heavy ions, photochemistry, micro-tom - Abstract
The possibility to cultivate plants in Space represents an ongoing challenge because in extraterrestrial environments, plant growth is controlled by factors, some of which are also acting on Earth (e.g. temperature, relative humidity, light) while others are peculiar such as altered gravity in addition to a profoundly different ionizing radiation (IR) field (De Micco et al., 2011). In particular, exposure to Space IR may determine several outcomes depending on the dose, radiation quality (high vs. low LET), exposure rate (acute vs. chronic), but also by the intrinsic characteristics of the organism, such as species, cultivars, developmental stage, structure of organs and tissues and genetic traits (De Micco et al., 2011). Generally, plant response to IR is manifestly dose-dependent with irreparable damage at high doses, sublethal consequences at intermediate levels and stimulatory effects at low dose (De Micco et al., 2011; Arena et al., 2014). In this study we explore the possibility that low doses of heavy ions, namely C ions at dose of 25 Gy delivered at seed stage, may exert beneficial effects on Solanum Lycopersicum L. cv ‘Micro-Tom’ on physiological, biochemical and anatomical traits, promoting the fruit ripening and quality. This would have important consequences in the view of its utilization on board of the Bioregenerative Life Support Systems (BLSSs) as food for crew. For this purpose, the plant life cycle from germination to fruit harvesting was monitored in terms of plant growth, photosynthetic efficiency, leaf anatomical traits and antioxidant production in leaf and fruits. The irradiation did not affect plant germination. Plants from irradiated seeds showed reduced height and a more compact size. The PSII quantum yield as well as the electron transport rate was promoted in irradiated compared to control plants. These data are consistent with a high level of D1 protein and photosynthetic pigment content in the leaves. As regards fruit, plants from irradiated seeds showed a significantly higher content of ascorbic acid, carotenoids and anthocyanins.
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- 2017
5. Suitability ofSolanum lycopersicumL. ‘Microtom’ for growth in Bioregenerative Life Support Systems: exploring the effect of high‐LETionising radiation on photosynthesis, leaf structure and fruit traits
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Arena, C., primary, Vitale, E., additional, Hay Mele, B., additional, Cataletto, P. R., additional, Turano, M., additional, Simoniello, P., additional, and De Micco, V., additional
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- 2019
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6. Suitability of Solanum lycopersicum L. 'Microtom' for growth in Bioregenerative Life Support Systems: exploring the effect of high‐LET ionising radiation on photosynthesis, leaf structure and fruit traits.
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Arena, C., Vitale, E., Hay Mele, B., Cataletto, P. R., Turano, M., Simoniello, P., De Micco, V., and Leegood, R.
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LIFE support systems in critical care ,TOMATOES ,BERRIES ,PLANT size ,FRUIT ripening ,PHOTOSYNTHESIS - Abstract
The realisation of manned space exploration requires the development of Bioregenerative Life Support Systems (BLSS). In such self‐sufficient closed habitats, higher plants have a fundamental role in air regeneration, water recovery, food production and waste recycling. In the space environment, ionising radiation represents one of the main constraints to plant growth.In this study, we explore whether low doses of heavy ions, namely Ca 25 Gy, delivered at the seed stage, may induce positive outcomes on growth and functional traits in plants of Solanum lycopersicum L. 'Microtom'. After irradiation of seed, plant growth was monitored during the whole plant life cycle, from germination to fruit ripening. Morphological parameters, photosynthetic efficiency, leaf anatomical functional traits and antioxidant production in leaves and fruits were analysed.Our data demonstrate that irradiation of seeds with 25 Gy Ca ions does not prevent achievement of the seed‐to‐seed cycle in 'Microtom', and induces a more compact plant size compared to the control. Plants germinated from irradiated seeds show better photochemical efficiency than controls, likely due to the higher amount of D1 protein and photosynthetic pigment content. Leaves of these plants also had smaller cells with a lower number of chloroplasts. The dose of 25 Gy Ca ions is also responsible for positive outcomes in fruits: although developing a lower number of berries, plants germinated from irradiated seeds produce larger berries, richer in carotenoids, ascorbic acid and anthocyanins than controls.These specific traits may be useful for 'Microtom' cultivation in BLSS in space, in so far as the crew members could benefit from fresh food richer in functional compounds that can be directly produced on board. [ABSTRACT FROM AUTHOR]
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- 2019
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7. ViDiMiGe as powerful, robust and innovative approach proposed for Genome-wide Comparative Phylogenetic analyses of Prokariotic Domains
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Hay Mele B., CHIUSANO, MARIA LUISA, DEL GAUDIO, ROSANNA, SIMGBM, Hay Mele, B., Chiusano, MARIA LUISA, and DEL GAUDIO, Rosanna
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- 2012
8. Co-Occurrence of Beckwith–Wiedemann Syndrome and Early-Onset Colorectal Cancer
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Francesco Cecere, Laura Pignata, Bruno Hay Mele, Abu Saadat, Emilia D’Angelo, Orazio Palumbo, Pietro Palumbo, Massimo Carella, Gioacchino Scarano, Giovanni Battista Rossi, Claudia Angelini, Angela Sparago, Flavia Cerrato, Andrea Riccio, Cecere, F., Pignata, L., Hay Mele, B., Saadat, A., D'Angelo, E., Palumbo, O., Palumbo, P., Carella, M., Scarano, G., Rossi, G. B., Angelini, C., Sparago, A., Cerrato, F., Riccio, A., Cecere, Francesco, Pignata, Laura, Hay Mele, Bruno, Saadat, Abu, D’Angelo, Emilia, Palumbo, Orazio, Palumbo, Pietro, Carella, Massimo, Scarano, Gioacchino, Rossi, Giovanni Battista, Angelini, Claudia, Sparago, Angela, Cerrato, Flavia, and Riccio, Andrea
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Cancer Research ,DNA methylation ,Oncology ,Beckwith–Wiedemann syndrome, colorectal cancer, DNA methylation, genomic imprinting, imprinting disorders, CFTR ,imprinting disorders ,colorectal cancer ,CFTR ,Beckwith–Wiedemann syndrome ,genomic imprinting - Abstract
CRC is an adult-onset carcinoma representing the third most common cancer and the second leading cause of cancer-related deaths in the world. EO-CRC (
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- 2023
9. Intersecting Ecosystem Services Across the Aquatic Continuum: From Global Change Impacts to Local, and Biologically Driven, Synergies and Trade-Offs
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Domenico D’Alelio, Luca Russo, Bruno Hay Mele, Francesco Pomati, D'Alelio, D., Russo, L., Hay Mele, B., and Pomati, F.
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0106 biological sciences ,010504 meteorology & atmospheric sciences ,sea ,river ,lcsh:Evolution ,Climate change ,Carbon sequestration ,01 natural sciences ,Ecosystem services ,Conceptual blending ,lcsh:QH540-549.5 ,lcsh:QH359-425 ,Systems thinking ,Ecosystem ,14. Life underwater ,lake ,ecosystem services ,ocean ,climate change ,trade-offs ,networks ,Ecology, Evolution, Behavior and Systematics ,0105 earth and related environmental sciences ,Continuum (measurement) ,Ecology ,business.industry ,010604 marine biology & hydrobiology ,Environmental resource management ,Global change ,15. Life on land ,6. Clean water ,ecosystem service ,Geography ,13. Climate action ,network ,lcsh:Ecology ,business - Abstract
The study of ecosystem services requires the integration of different observational points. This is particularly true in Water, as this element continuously cycles, increasing chances of interaction among services originating in different ecosystems. However, aquatic scientists historically approached the study of inland/freshwater and open/marine waters in different ways and this cultural division potentially hampers integrative approaches. Herein, we explored the literature pertaining to ecosystem services across the last 23 years, analysing 4,590 aquatic papers. By aggregating and intersecting topics included in this papers’ collection using text-mining and topical network approaches, we saw that the study of local environmental conditions (e.g., river estuary management) and synergies and trade-offs between services (e.g., carbon sequestration and water purification) can display several potential conceptual links between freshwater and marine sciences. Our analyses suggest that to intersect ecosystem services across the aquatic continuum, the conceptual integration between marine and freshwater science must be reinforced, especially at the interface between different “salinity realms.” Such integration should adopt a “system thinking” perspective, in which the focus is on multiple socio-ecological processes giving rise to interactions that are (i) biologically mediated, (ii) potentially conflicting, and (iii) entangled within networks.
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- 2021
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10. Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women
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Monticelli, M., Mele, B. H., Benetti, E., Fallerini, C., Baldassarri, M., Furini, S., Frullanti, E., Mari, F., Andreotti, G., Cubellis, M. V., Renieri, A., Daga, S., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Sarno, L. D., Tommasi, A., Palmieri, M., Carriero, M. L., Alaverdian, D., Beligni, G., Iuso, N., Inchingolo, G., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Pancrazi, A., Lorusso, M., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Miraglia, F. G., Mondelli, M. U., Bruno, R., Marco, V., Mantovani, S., Ludovisi, S., Girardi, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Emiliozzi, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiarol, E., Paciosi, F., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, E., Antoni, M. D., Zanella, I., Monica, M. D., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Squeo, G. M., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Biagio, A. D., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Parati, G. -F., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Bis-Carini, F., Stella, A., Rizzi, M., Maggiolo, F., Ripamonti, D., Suardi, C., Bachetti, T., Rovere, M. T. L., Sarzi-Braga, S., Bussotti, M., Bergomi, M., Capitani, K., Zguro, K., Dei, S., Monticelli, M., Hay Mele, B., Benetti, E., Fallerini, C., Baldassarri, M., Furini, S., Frullanti, E., Mari, F., Andreotti, G., Cubellis, M. V., Renieri, A., Monticelli, M, Mele, B, Benetti, E, Fallerini, C, Baldassarri, M, Furini, S, Frullanti, E, Mari, F, Andreotti, G, Cubellis, M, Renieri, A, Daga, S, Fava, F, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Pinto, A, Mencarelli, M, Rizzo, C, Montagnani, F, Sarno, L, Tommasi, A, Palmieri, M, Carriero, M, Alaverdian, D, Beligni, G, Iuso, N, Inchingolo, G, Fabbiani, M, Rossetti, B, Zanelli, G, Bargagli, E, Bergantini, L, D'Alessandro, M, Cameli, P, Bennet, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Caldarelli, G, Spagnesi, M, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Ognibene, A, Pancrazi, A, Lorusso, M, Vaghi, M, D'Arminio Monforte, A, Merlini, E, Miraglia, F, Mondelli, M, Bruno, R, Marco, V, Mantovani, S, Ludovisi, S, Girardi, M, Venturelli, S, Sita, M, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiarol, E, Paciosi, F, Scotton, P, Andretta, F, Panese, S, Scaggiante, R, Gatti, F, Parisi, S, Castelli, F, Quiros-Roldan, E, Antoni, M, Zanella, I, Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Merla, G, Squeo, G, Aucella, F, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Biagio, A, Sanguinetti, M, Masucci, L, Valente, S, Mandala, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Baratti, S, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Coviello, D, Mussini, C, Bosio, G, Martinelli, E, Mancarella, S, Tavecchia, L, Crotti, L, Parati, G, Picchiotti, N, Gori, M, Gabbi, C, Sanarico, M, Ceri, S, Pinoli, P, Raimondi, F, Bis-Carini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Rovere, M, Sarzi-Braga, S, Bussotti, M, Bergomi, M, Capitani, K, Zguro, K, and Dei, S
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0301 basic medicine ,Male ,COVID19 ,medicine.medical_treatment ,Disease ,V197M ,Comorbidity ,QH426-470 ,Pathogenesis ,0302 clinical medicine ,Gene Frequency ,Missense mutation ,COVID-19 ,TMPRSS2 ,Whole-Exome Sequencing (WES) ,Genetics (clinical) ,Communication ,Respiration ,Serine Endopeptidases ,Single Nucleotide ,Middle Aged ,3. Good health ,Hospitalization ,Serine Endopeptidase ,Treatment Outcome ,Italy ,030220 oncology & carcinogenesis ,Cohort ,Artificial ,Female ,Aged ,Humans ,Mutation ,Respiration, Artificial ,Polymorphism, Single Nucleotide ,Human ,V179M ,03 medical and health sciences ,medicine ,Genetics ,Polymorphism ,Allele frequency ,Protease ,business.industry ,medicine.disease ,030104 developmental biology ,Immunology ,business - Abstract
The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.
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- 2021
11. The Use of a Plant-Based Biostimulant Improves Plant Performances and Fruit Quality in Tomato Plants Grown at Elevated Temperatures
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Silvana Francesca, Patrizia Ambrosino, Maria Manuela Rigano, Carlo Schettini, Bruno Hay Mele, Amalia Barone, Carmen Arena, Francesca, S., Arena, C., Hay Mele, B., Schettini, C., Ambrosino, P., Barone, A., and Rigano, M. M.
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0106 biological sciences ,Antioxidant ,abiotic stress ,medicine.medical_treatment ,media_common.quotation_subject ,Nutritional quality ,Biology ,tomato ,01 natural sciences ,lcsh:Agriculture ,03 medical and health sciences ,medicine ,biostimulant ,030304 developmental biology ,media_common ,2. Zero hunger ,Abiotic component ,0303 health sciences ,Abiotic stress ,Crop yield ,fungi ,fruit quality ,lcsh:S ,food and beverages ,Plant based ,Ascorbic acid ,Horticulture ,antioxidants ,Reproduction ,Agronomy and Crop Science ,010606 plant biology & botany - Abstract
Abiotic stresses can cause a substantial decline in fruit quality due to negative impacts on plant growth, physiology and reproduction. The objective of this study was to verify if the use of a biostimulant based on plant and yeast extracts, rich in amino acids and that contains microelements (boron, zinc and manganese) can ensure good crop yield and quality in tomato plants grown at elevated temperatures (up to 42 °, C). We investigated physiological responses of four different tomato landraces that were cultivated under plastic tunnel and treated with the biostimulant CycoFlow. The application of the biostimulant stimulated growth (plants up to 48.5% taller) and number of fruits (up to 105.3%). In plants treated with the biostimulant, antioxidants contents were higher compared to non-treated plants, both in leaves and in fruits. In particular, the content of ascorbic acid increased after treatments with CycoFlow. For almost all the traits studied, the effect of the biostimulant depended on the genotype it was applied on. Altogether, the use of the biostimulant on tomato plants led to better plant performances at elevated temperatures, that could be attributed also to a stronger antioxidant defence system, and to a better fruit nutritional quality.
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- 2020
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12. THE ROLE OF MONOCHROMATIC RED AND BLUE LIGHT IN TOMATO EARLY PHOTOMORPHOGENESIS AND PHOTOSYNTHETIC TRAITS
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Luigi Gennaro Izzo, Luca Vitale, Carmen Arena, Bruno Hay Mele, Ermenegilda Vitale, Izzo, L. G., Hay Mele, B., Vitale, L., Vitale, E., and Arena, C.
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0106 biological sciences ,0301 basic medicine ,food.ingredient ,Rubisco ,Photochemistry ,Plant Science ,Photosynthesis ,7. Clean energy ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,food ,Solanum lycopersicum ,Chlorophyll fluorescence ,Chlorophyll content ,Ecology, Evolution, Behavior and Systematics ,2. Zero hunger ,biology ,Chemistry ,RuBisCO ,fungi ,food and beverages ,15. Life on land ,biology.organism_classification ,Photosynthetic capacity ,D1 Protein ,Horticulture ,030104 developmental biology ,Seedling ,Chlorophyll ,biology.protein ,Photomorphogenesis ,Agronomy and Crop Science ,Cotyledon ,hlorophyll content ,D1 protein ,Light quality ,010606 plant biology & botany - Abstract
Plant development and physiology are strongly influenced by the environmental light spectrum that triggers and controls several functional and structural response in plants. However, few studies investigated the effect of monochromatic light during plant photomorphogenesis from seed imbibition up to seedling development. The present research aimed to assess the mechanisms engaged by plants to optimize light harvesting and utilization of different wavelengths during the early photomorphogenesis in tomato, a high-value crop cultivated worldwide. Seeds were germinated in a growth chamber under four light treatments (100 % red light, R; 100 % blue light, B; 60 % red 40 % blue light, RB; white light, W) and seedlings were grown up to sixteen days. Hypocotyl and cotyledon development were measured during the early stages of growth. Chlorophyll fluorescence measurements, D1 and Rubisco protein expression, as well as chlorophyll and carotenoids content, were determined on the first true leaves to assess in the early growth stage the efficiency of photosynthetic apparatus. Tomato early photomorphogenesis was strongly influenced by light quality. The seedling growth under red-blue and white light determined comparable responses, enhancing both photosynthesis and biomass production compared to monochromatic treatments. The pure R light stimulated hypocotyl elongation, cotyledon expansion, plant height, and leaf area, but produced seedlings with reduced photosynthetic capacity as indicated by the lowest Rubisco content and photochemical efficiency, and the highest thermal dissipation. Monochromatic blue light induced in seedlings the highest Rubisco amount, more compact size and reduced biomass, but similar level of pigments and photochemical efficiency compared to other light treatments. Our data indicate that the lack of blue or red light negatively affects early tomato development, in term of morphology and physiology. However, blue wavelengths resulted more critical than red ones for the functionality of the photosynthetic apparatus.
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- 2020
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13. Large scale patterns of marine diatom richness: Drivers and trends in a changing ocean
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Francesco d'Ovidio, Roberta Piredda, Bruno Hay Mele, Daniele Iudicone, Colomban de Vargas, Adriana Zingone, Greta Busseni, Luigi Caputi, Lucia Campese, Chris Bowler, Paul Frémont, Maurizio Ribera d'Alcalà, Eleonora Scalco, Busseni, G., Caputi, L., Piredda, R., Fremont, P., Hay Mele, B., Campese, L., Scalco, E., de Vargas, C., Bowler, C., D'Ovidio, F., Zingone, A., Ribera d'Alcala, M., Iudicone, D., Stazione Zoologica Anton Dohrn (SZN), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Tara Oceans-GOSEE (FR2022), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Processus et interactions de fine échelle océanique (PROTEO), Laboratoire d'Océanographie et du Climat : Expérimentations et Approches Numériques (LOCEAN), Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), European Project: 654008,H2020,H2020-INFRADEV-1-2014-1,EMBRIC(2015), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Global Oceans Systems Ecology & Evolution - Tara Oceans (GOSEE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Aix Marseille Université (AMU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Université de Toulon (UTLN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche pour le Développement (IRD [France-Nord])-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-European Molecular Biology Laboratory (EMBL)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université australe du Chili, Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), d'Ovidio, Francesco, European Marine Biological Research Infrastructure Cluster to promote the Blue Bioeconomy - EMBRIC - - H20202015-06-01 - 2019-05-31 - 654008 - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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010504 meteorology & atmospheric sciences ,Scale (ratio) ,Tara Oceans ,richne ,01 natural sciences ,diversity ,03 medical and health sciences ,14. Life underwater ,Ecology, Evolution, Behavior and Systematics ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0105 earth and related environmental sciences ,[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere ,0303 health sciences ,Global and Planetary Change ,Ecology ,[SDU.OCEAN] Sciences of the Universe [physics]/Ocean, Atmosphere ,Marine diatom ,diatom ,[SDE.BE] Environmental Sciences/Biodiversity and Ecology ,Oceanography ,machine learning ,metabarcoding ,microscopy ,Environmental science ,Species richness ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology - Abstract
Aim: Plankton diversity is a pivotal element of marine ecosystem stability and functioning. A major obstacle in the assessment of diversity is the lack of consistency between patterns assessed by molecular and morphological data. This work aims to reconcile the two in a single richness measure, to investigate the environmental drivers affecting this measure, and finally to predict its spatio-temporal patterns. Location and time period: This is a global scale study, based on data collected within the 2009–2013 interval during the Tara Oceans expedition. Major taxa studied: The focus of this study is diatoms. They play an important role in several biogeochemical cycles and within marine food webs, and display high taxonomic and functional richness. Methods: We integrate measures of diatom richness across the global ocean using molecular and morphological approaches, giving particular attention to ‘the rare biosphere’. We then perform a machine-learning-based analysis of these reconciled patterns to extrapolate diatom richness at the global scale and to identify the main environmental processes governing it. Finally, we model the response of diatom richness to climate change. Results: By filtering out 0.3% of the rarest operational taxonomic units, molecular-based richness patterns show the best possible match with the morphological approach. Temperature, phosphate, chlorophyll a and the Lyapunov exponent are the major explainers of these reconciled patterns. Global scale predictions provide a first approximation of the global geography of diatom richness and of the possible impacts of climate change. Main conclusions: Our models suggest that diatom richness is controlled by different processes characteristic of distinct environmental scenarios: lateral mixing in highly dynamic regions, and both nutrient availability and temperature elsewhere. We present herein the effects of these processes on richness and how these same effects differ from other diversity indices because of the main component of richness: the rare biosphere.
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- 2020
14. Ecological assessment of anthropogenic impact in marine ecosystems: The case of Bagnoli Bay
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Francesco Paolo Patti, Michael Tangherlini, Bruno Hay Mele, Luca Russo, Domenico D'Alelio, Rosanna Guglielmo, Cristina Gambi, Maurizio Ribera d'Alcalà, Antonio Dell'Anno, Emilio Riginella, Fabio Crocetta, Luigi Musco, Roberto Danovaro, Hay Mele, B., Russo, L., Crocetta, F., Gambi, C., Dell'Anno, A., Danovaro, R., Guglielmo, R., Musco, L., Patti, F. P., Riginella, E., Tangherlini, M., Ribera d'Alcala, M., and D'Alelio, D.
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0106 biological sciences ,Aquatic Science ,Oceanography ,Coastal zone ,010603 evolutionary biology ,01 natural sciences ,Benthos ,Systems ecology ,Bagnoli Bay ,Animals ,Marine ecosystem ,14. Life underwater ,Ecosystem ,Ecology ,Animal ,010604 marine biology & hydrobiology ,Community structure ,Fishes ,Ecological assessment ,General Medicine ,15. Life on land ,Pollution ,Ecological network ,Benthic ecology ,Pollution indicator ,Fish ,Bays ,13. Climate action ,Benthic zone ,Bay ,Environmental science ,Environmental Pollutants ,Fishe ,Environmental Monitoring - Abstract
Pollutants alter marine systems, interfering with provisioning of ecosystem services; understanding their interaction with ecological communities is therefore critical to inform environmental management. Here we propose a joint compositional- and interaction-based analysis for ecological status assessment and apply it on the benthic communities of the Bagnoli Bay. We found that contamination differentially affects the communities’ composition in the bay, with prokaryotes influenced only by depth, and benthos not following the environmental gradient at all. This result is confirmed by analyses of the community structure, whose network structure suggest fast carbon flow and cycling, especially promoted by nematodes and polychaetes; the benthic prey/predator biomass ratio, adjusted for competition, successfully synthesise the status of predator taxa. We found demersal fish communities to separate into a deep, pelagic-like community, and two shallow communities where a shift from exclusive predators to omnivores occurs, moving from the most polluted to the least polluted sampling units. Finally, our study indicate that indices based on interspecific interactions are better indicators of environmental gradients than those defined based on species composition exclusively.
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- 2019
15. Why does SARS-CoV-2 hit in different ways? Host genetic factors can influence the acquisition or the course of COVID-19
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Guglielmo Riccio, Giuseppina Andreotti, Bruno Hay Mele, Maria Vittoria Cubellis, Maria Monticelli, Monticelli, M., Hay Mele, B., Andreotti, G., Cubellis, M. V., and Riccio, G.
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medicine.medical_specialty ,COVID19 ,Population ,SNP ,Single-nucleotide polymorphism ,Review ,Biology ,Mannose-Binding Lectin ,Polymorphism, Single Nucleotide ,TMPRSS2 ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Epidemiology ,Genetic variation ,Genetics ,medicine ,Data Mining ,Humans ,Genetic Predisposition to Disease ,education ,Gene ,Allele frequency ,CD27 ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Host Microbial Interactions ,SARS-CoV-2 ,Serine Endopeptidases ,COVID-19 ,Genetic Variation ,General Medicine ,Immunity, Innate ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,3. Good health ,MBL2 ,030220 oncology & carcinogenesis ,Identification (biology) ,SNPs - Abstract
The identification of high-risk factors for the infection by SARS-CoV-2 and the negative outcome of COVID-19 is crucial. The genetic background of the host might account for individual responses to SARS-CoV-2 infection besides age and comorbidities. A list of candidate polymorphisms is needed to drive targeted screens, given the existence of frequent polymorphisms in the general population. We carried out text mining in the scientific literature to draw up a list of genes referable to the term "SARS-CoV*". We looked for frequent mutations that are likely to affect protein function in these genes. Ten genes, mostly involved in innate immunity, and thirteen common variants were identified, for some of these the involvement in COVID-19 is supported by publicly available epidemiological data. We looked for available data on the population distribution of these variants and we demonstrated that the prevalence of five of them, Arg52Cys (rs5030737), Gly54Asp (rs1800450) and Gly57Glu (rs1800451) in MBL2, Ala59Thr (rs25680) in CD27, and Val197Met (rs12329760) in TMPRSS2, correlates with the number of cases and/or deaths of COVID-19 observed in different countries. The association of the TMPRSS2 variant provides epidemiological evidence of the usefulness of transmembrane protease serine 2 inhibitors for the cure of COVID-19. The identified genetic variants represent a basis for the design of a cost-effective assay for population screening of genetic risk factors in the COVID-19 pandemic.
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- 2021
16. Combining marine ecology and economy to roadmap the integrated coastal management: A systematic literature review
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Bruno Hay Mele, Luca Russo, Domenico D'Alelio, Hay Mele, B., Russo, L., and D'Alelio, D.
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0106 biological sciences ,Topic model ,Ecological economic ,Exploit ,Integrated coastal management ,lcsh:TJ807-830 ,Geography, Planning and Development ,Network science ,lcsh:Renewable energy sources ,010501 environmental sciences ,Management, Monitoring, Policy and Law ,ecological economics ,01 natural sciences ,Marine ecology ,socio-ecological systems ,Citizen science ,Systems ecology ,Environmental planning ,lcsh:Environmental sciences ,0105 earth and related environmental sciences ,lcsh:GE1-350 ,Marine/maritime economy ,Ecological economics ,Renewable Energy, Sustainability and the Environment ,lcsh:Environmental effects of industries and plants ,010604 marine biology & hydrobiology ,Economic sector ,Coastal resilience ,lcsh:TD194-195 ,Ecotourism ,Business ,Coastal management ,Socio-ecological system ,Topic modelling - Abstract
Integrated coastal management (ICM) relies on the inclusion of economic issues within marine ecology. To assess the progress of this integration, we applied topic modelling and network analysis to explore the pertinent literature (583 Isi-WoS, and 5459 Scopus papers). We classified the topics of interest (i.e., concepts, approaches, and sectors) that combined ecological and economic issues within marine science, we aggregated these topics in fields pertinent to ICM, and tracked the knowledge-exchange between these fields by using an information-flow network. Main findings were: (i) the high trans-disciplinary fashion of studies about marine protection and of those about commercial fisheries, (ii) the weak interaction between studies focusing on potential biohazards and those about environmental management, (iii) the isolation, in the overall information-flow, of studies about ecotourism and aquaculture. We included in a roadmap all the integration routes we detected within ICM, based on the combination of ecological and economic issues. We conclude that, to improve integration, ICM should: (i) Exploit marine protection as a bridge between ecological and economic concepts and approaches, and between maritime economy sectors, (ii) employ systems ecology to pursue trans-disciplinary investigations, (iii) complement systems ecology with citizen science by means of inclusive economic initiatives, such as ecotourism.
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- 2019
17. Rewiring and indirect effects underpin modularity reshuffling in a marine food web under environmental shifts
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Ferenc Jordán, Maurizio Ribera d'Alcalà, Simone Libralato, Domenico D'Alelio, Bruno Hay Mele, D'Alelio, D., Hay Mele, B., Libralato, S., Ribera d'Alcala, M., and Jordan, F.
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0106 biological sciences ,Ecology (disciplines) ,Biology ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,lcsh:QH540-549.5 ,ecological networks ,14. Life underwater ,Trophic cascade ,ecological network ,Ecology, Evolution, Behavior and Systematics ,modularity ,Original Research ,030304 developmental biology ,Nature and Landscape Conservation ,Trophic level ,0303 health sciences ,Modularity (networks) ,Ecology ,Community ,food web ,rewiring ,plankton ,Community structure ,15. Life on land ,Food web ,Ecological network ,13. Climate action ,food webs ,lcsh:Ecology ,roles - Abstract
Species are characterized by physiological and behavioral plasticity, which is part of their response to environmental shifts. Nonetheless, the collective response of ecological communities to environmental shifts cannot be predicted from the simple sum of individual species responses, since co‐existing species are deeply entangled in interaction networks, such as food webs. For these reasons, the relation between environmental forcing and the structure of food webs is an open problem in ecology. To this respect, one of the main problems in community ecology is defining the role each species plays in shaping community structure, such as by promoting the subdivision of food webs in modules—that is, aggregates composed of species that more frequently interact—which are reported as community stabilizers. In this study, we investigated the relationship between species roles and network modularity under environmental shifts in a highly resolved food web, that is, a “weighted” ecological network reproducing carbon flows among marine planktonic species. Measuring network properties and estimating weighted modularity, we show that species have distinct roles, which differentially affect modularity and mediate structural modifications, such as modules reconfiguration, induced by environmental shifts. Specifically, short‐term environmental changes impact the abundance of planktonic primary producers; this affects their consumers’ behavior and cascades into the overall rearrangement of trophic links. Food web re‐adjustments are both direct, through the rewiring of trophic‐interaction networks, and indirect, with the reconfiguration of trophic cascades. Through such “systemic behavior,” that is, the way the food web acts as a whole, defined by the interactions among its parts, the planktonic food web undergoes a substantial rewiring while keeping almost the same global flow to upper trophic levels, and energetic hierarchy is maintained despite environmental shifts. This behavior suggests the potentially high resilience of plankton networks, such as food webs, to dramatic environmental changes, such as those provoked by global change., We show, for the first time, the fine‐scale dynamics of structural re‐adjustment in a complex food web, under a regime of changing resources. Our observation is novel, since we investigated directed and weighted modularity in an ecological network, which provides a much sounder view of food web architecture, and therefore functioning; our results are exciting, since food web re‐adjustments shown herein are analogous to those “systemic behaviors” described for other complex systems, such as human brain networks, but an analogous behaviour was never shown in ecological studies with such detail; ultimately, our paper is of general interest in ecology, since it demonstrates that food webs compartmentalization overcomes physical barriers, because species can migrate, and is mainly driven by the aggregation of trophic pathways, more than species co‐occurrence.
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- 2019
18. Suitability of Solanum lycopersicum L. 'Microtom' for growth in Bioregenerative Life Support Systems: exploring the effect of high-{LET} ionising radiation on photosynthesis, leaf structure and fruit traits
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P. R. Cataletto, Carmen Arena, Mimmo Turano, B. Hay Mele, Ermenegilda Vitale, V. De Micco, Palma Simoniello, Arena, C., Vitale, E., Hay Mele, B., Cataletto, P. R., Turano, M., Simoniello, P., and De Micco, V.
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0106 biological sciences ,tomato fruits ,Blotting, Western ,Germination ,Ascorbic Acid ,Plant Science ,Photosynthetic pigment ,Photosynthetic efficiency ,Photosynthesis ,010603 evolutionary biology ,01 natural sciences ,Antioxidants ,chemistry.chemical_compound ,Solanum lycopersicum ,Heavy Ions ,Carotenoid ,Ecology, Evolution, Behavior and Systematics ,Plant Proteins ,chemistry.chemical_classification ,Catalepsy ,biology ,Superoxide Dismutase ,Chlorophyll A ,fungi ,food and beverages ,Ripening ,General Medicine ,biology.organism_classification ,Ascorbic acid ,heavy ion ,Plant Leaves ,Horticulture ,chemistry ,space ecosystem ,Fruit ,Seeds ,leaf anatomy ,Solanum ,Antioxidant ,Life Support Systems ,010606 plant biology & botany - Abstract
The realisation of manned space exploration requires the development of Bioregenerative Life Support Systems (BLSS). In such self-sufficient closed habitats, higher plants have a fundamental role in air regeneration, water recovery, food production and waste recycling. In the space environment, ionising radiation represents one of the main constraints to plant growth. In this study, we explore whether low doses of heavy ions, namely Ca 25 Gy, delivered at the seed stage, may induce positive outcomes on growth and functional traits in plants of Solanum lycopersicum L. 'Microtom'. After irradiation of seed, plant growth was monitored during the whole plant life cycle, from germination to fruit ripening. Morphological parameters, photosynthetic efficiency, leaf anatomical functional traits and antioxidant production in leaves and fruits were analysed. Our data demonstrate that irradiation of seeds with 25 Gy Ca ions does not prevent achievement of the seed-to-seed cycle in 'Microtom', and induces a more compact plant size compared to the control. Plants germinated from irradiated seeds show better photochemical efficiency than controls, likely due to the higher amount of D1 protein and photosynthetic pigment content. Leaves of these plants also had smaller cells with a lower number of chloroplasts. The dose of 25 Gy Ca ions is also responsible for positive outcomes in fruits: although developing a lower number of berries, plants germinated from irradiated seeds produce larger berries, richer in carotenoids, ascorbic acid and anthocyanins than controls. These specific traits may be useful for 'Microtom' cultivation in BLSS in space, in so far as the crew members could benefit from fresh food richer in functional compounds that can be directly produced on board.
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- 2019
19. Passenger mutations as a target for the personalized therapy of cancer
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Marcello Viscovo, Guglielmo Riccio, Giuseppina Andreotti, Maria Monticelli, Bruno Hay-Mele, Maria Vittoria Cubellis, Monticelli, M, Viscovo, M, Riccio, G, Andreotti, G, Hay Mele, B, and Cubellis, Mv
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Drug repositioning ,Text mining ,medical genetics ,business.industry ,oncology ,medicine ,computational science ,Cancer ,Personalized therapy ,business ,medicine.disease ,Bioinformatics - Abstract
The American FDA approved the first comprehensive NGS diagnostic assay for cancer at the end of 2017, leading the way to personalised therapy of cancer and the massive employ of bioinformatics (https://www.fda.gov/downloads/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ ucm584603.pdf ). In NGS-detected genes from cancer patients, driver and passenger mutations can be distinguished. The former provides a proliferative advantage to cancer cells and are commonly found, the latter do not provide proliferative fitness and are different in different patients. However, some passenger mutations might occur in genes involved in metabolism and could be mildly deleterious for cancer cells. Such deleteriousness could be increased using a specific inhibitor of the mutated protein product. A personalized therapy of cancer could address both driver and passenger mutations. To evaluate to which extent it is possible to address passenger mutations for the cure of cancers, we built a gene/ inhibitor list, crossing DrugBank, a database that combines detailed drug data with comprehensive drug target information, with COSMIC, the catalogue of somatic mutations in cancer. First, we obtained the approved drugs annotated as inhibitors from DrugBank, and the genes encoding their target proteins. We then looked for these genes in COSMIC, to check how many missense mutations have been detected in cancer patient genomes.
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- 2018
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20. Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase
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Giuseppina Andreotti, Bruno Hay Mele, Ludovica Liguori, Maria Vittoria Cubellis, Valentina Citro, Chiara Cimmaruta, Cimmaruta, Chiiara, Citro, V., Andreotti, G., Liguori, L., Cubellis, M. V., and Hay Mele, B.
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0301 basic medicine ,Bioinformatics ,In silico ,Mutation, Missense ,rare disease ,macromolecular substances ,Computational biology ,Disease ,Biology ,lcsh:Computer applications to medicine. Medical informatics ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Variant analysis ,Genetic variation ,Genotype ,medicine ,Humans ,clinical informatic ,Missense mutation ,lcsh:QH301-705.5 ,Molecular Biology ,Exome ,Bioinformatic ,Fabry disease ,Research ,Applied Mathematics ,Molecular Sequence Annotation ,medicine.disease ,Clinical informatics ,Variant analysi ,Lysosome ,Phenotype ,Computer Science Applications ,030104 developmental biology ,lcsh:Biology (General) ,alpha-Galactosidase ,lcsh:R858-859.7 ,Lysosomes ,030217 neurology & neurosurgery ,Human - Abstract
Background Severity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity. Results wANNOVAR, a popular tool that can generate several different types of deleteriousness-prediction scores, was tested on Fabry disease. This pathology, which is caused by a deficit of lysosomal alpha-galactosidase, has a very large genotypic and phenotypic spectrum and offers the possibility of associating a quantitative measure of the damage caused by mutations to the functioning of the enzyme in the cells. Some predictors, and in particular VEST3 and PolyPhen2 provide scores that correlate with the severity of lysosomal alpha-galactosidase mutations in a statistically significant way. Conclusions Sorting disease mutations by severity is possible and offers advantages over binary classification. Dataset for testing and training in silico predictors can be obtained by transient transfection and evaluation of residual activity of mutants in cell extracts. This approach consents to quantitative data for severe, mild and non pathological variants. Electronic supplementary material The online version of this article (10.1186/s12859-018-2416-7) contains supplementary material, which is available to authorized users.
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- 2018
21. Cell-Based Models in Plant Developmental Biology: Insights into Hybrid Approaches
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Fabrizio Cartenì, Christian E. Vincenot, Francesco Giannino, Bruno Hay Mele, Stefano Mazzoleni, Hay Mele, B, Giannino, F, Vincenot, C, Mazzoleni, S, and Carteni, Fabrizio
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lcsh:GE1-350 ,Plant growth ,Computer simulation ,Mathematical model ,differential equations ,individual-based modeling ,Context (language use) ,Biology ,Toolbox ,System dynamics ,pattern formation ,numerical simulation ,Environmental Science ,procambium differentiation ,Biophysics ,system dynamics ,Biochemical engineering ,primary vascular structure ,mathematical models ,Developmental biology ,lcsh:Environmental sciences ,General Environmental Science ,Cell based ,system dynamics, individual-based modeling, differential equations, mathematical models, numerical simulation, pattern formation, procambium differentiation, primary vascular structure - Abstract
Computer models are nowadays part of the biologist's toolbox for studying biological dynamics and processes. Tissue development and functioning results from extremely complicated dynamics, that usual analysis does not come very far in terms of understanding the processes underlying those dynamics. In this context, mathematical and numerical models can help to disentangle complex interactions and to analyze non-intuitive dynamics that drives tissue development and functioning.Since these are multi-scale processes, both in time and space, there is the need to develop an appropriate modelling approach.The most promising one is hybrid modelling, that is a synthesis of the differential equation based reaction-diffusion approach at molecular and chemical continuous scales, and the Individual-Based modelling approach for simulating the mechanical and behavioural interactions of the cell ensemble constituting the tissue. Such an approach has been often used in developmental biology, both for plants and animals. In this paper, a brief history of hybrid modelling approaches and tools will be reviewed, and a simple example of its application to a current problem in plant developmental biology (the appearance of vascular patterning during plant growth) will be illustrated, showing the intuitiveness and the strength of such an approach.
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- 2015
22. Tomato and ionizing radiation: the balance between detrimental and positive effects
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ARENA, CARMEN, TURANO, MIMMO, CATALETTO, PIA ROSA, ARONNE, GIOVANNA, DE MICCO, VERONICA, B. Hay Mele, Bulgarian Academy of Science, Arena, Carmen, Turano, Mimmo, Cataletto, PIA ROSA, Hay Mele, B., Aronne, Giovanna, and DE MICCO, Veronica
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Microtom ,x-ray ,DNA ,Photochemical efficiency - Published
- 2014
23. Effects of heavy ion irradiation on growth, anatomy and photosynthetic efficiency of mung bean plants
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ARENA, CARMEN, CATALETTO, PIA ROSA, DE MICCO, VERONICA, C. Romeo Di Tuosto, B. Hay Mele, FESPB/EPSO, FESPB/EPSO committee, Arena, Carmen, Romeo Di Tuosto, C., Hay Mele, B., Cataletto, PIA ROSA, and DE MICCO, Veronica
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BLSS ,Leaf anatomy ,ionizing radiation - Published
- 2014
24. Population bottlenecks and sexual recombination shape diatom microevolution.
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Hay Mele B, Ruggiero MV, and D'Alelio D
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Diatoms are single-celled organisms that contribute approximately 20% of the global primary production and play a crucial role in biogeochemical cycles and trophic chains. Despite their ecological importance, our knowledge of microevolution is limited. We developed a model using the SLiM evolutionary framework to address this knowledge gap. As a reference, we used the diatom Pseudo-nitzschia multistriata , which has been extensively studied in the Gulf of Naples. Our model recapitulates what we observe in natural populations, with microevolutionary processes that occur annually during a three-stage bloom phase. Interestingly, we found that non-bloom phases allow the population to maintain sex-generated diversity produced during blooms. This finding suggests that non-bloom phases are critical to counteract bloom-related pressures and mitigate genetic divergence at the species level. Moreover, our model showed that despite the consistent genetic differentiation during bloom phases, the population tends to return to pre-bloom states. While our model is limited to neutral dynamics, our study provides valuable insights into diatoms' microevolution, paving the way to explore the ecological implications of the life history dynamics of these organisms., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)
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- 2024
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25. Exploring ligand interactions with human phosphomannomutases using recombinant bacterial thermal shift assay and biochemical validation.
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Monticelli M, Hay Mele B, Wright DM, Guerriero S, Andreotti G, and Cubellis MV
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- Humans, Molecular Docking Simulation, Ligands, Recombinant Proteins metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Protein Binding, Congenital Disorders of Glycosylation genetics, Congenital Disorders of Glycosylation metabolism, Phosphotransferases (Phosphomutases) metabolism, Phosphotransferases (Phosphomutases) genetics, Phosphotransferases (Phosphomutases) chemistry
- Abstract
PMM2-CDG, a disease caused by mutations in phosphomannomutase-2, is the most common congenital disorder of glycosylation. Yet, it still lacks a cure. Targeting phosphomannomutase-2 with pharmacological chaperones or inhibiting the phosphatase activity of phosphomannomutase-1 to enhance intracellular glucose-1,6-bisphosphate have been proposed as therapeutical approaches. We used Recombinant Bacterial Thermal Shift Assay to assess the binding of a substrate analog to phosphomannomutase-2 and the specific binding to phosphomannomutase-1 of an FDA-approved drug - clodronate. We also deepened the clodronate binding by enzyme activity assays and in silico docking. Our results confirmed the selective binding of clodronate to phosphomannomutase-1 and shed light on such binding., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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26. A maternal-effect Padi6 variant causes nuclear and cytoplasmic abnormalities in oocytes, as well as failure of epigenetic reprogramming and zygotic genome activation in embryos.
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Giaccari C, Cecere F, Argenziano L, Pagano A, Galvao A, Acampora D, Rossi G, Hay Mele B, Acurzio B, Coonrod S, Cubellis MV, Cerrato F, Andrews S, Cecconi S, Kelsey G, and Riccio A
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- Animals, Child, Female, Humans, Mice, CCAAT-Enhancer-Binding Proteins genetics, Cytoplasm genetics, Cytoplasm metabolism, DNA Methylation genetics, Embryonic Development genetics, Genomic Imprinting genetics, Ubiquitin-Protein Ligases metabolism, Oocytes, Zygote
- Abstract
Maternal inactivation of genes encoding components of the subcortical maternal complex (SCMC) and its associated member, PADI6, generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multilocus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. We generated a mouse line carrying a Padi6 missense variant that was identified in a family with Beckwith-Wiedemann syndrome and MLID. If homozygous in female mice, this variant resulted in interruption of embryo development at the two-cell stage. Single-cell multiomic analyses demonstrated defective maturation of Padi6 mutant oocytes and incomplete DNA demethylation, down-regulation of zygotic genome activation (ZGA) genes, up-regulation of maternal decay genes, and developmental delay in two-cell embryos developing from Padi6 mutant oocytes but little effect on genomic imprinting. Western blotting and immunofluorescence analyses showed reduced levels of UHRF1 in oocytes and abnormal localization of DNMT1 and UHRF1 in both oocytes and zygotes. Treatment with 5-azacytidine reverted DNA hypermethylation but did not rescue the developmental arrest of mutant embryos. Taken together, this study demonstrates that PADI6 controls both nuclear and cytoplasmic oocyte processes that are necessary for preimplantation epigenetic reprogramming and ZGA., (© 2024 Giaccari et al.; Published by Cold Spring Harbor Laboratory Press.)
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- 2024
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27. Drug Repurposing and Lysosomal Storage Disorders: A Trick to Treat.
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Hay Mele B, Rossetti F, Cubellis MV, Monticelli M, and Andreotti G
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- Humans, Mutation, Lysosomes metabolism, Drug Repositioning, Lysosomal Storage Diseases drug therapy, Lysosomal Storage Diseases genetics
- Abstract
Rare diseases, or orphan diseases, are defined as diseases affecting a small number of people compared to the general population. Among these, we find lysosomal storage disorders (LSDs), a cluster of rare metabolic diseases characterized by enzyme mutations causing abnormal glycolipid storage. Drug repositioning involves repurposing existing approved drugs for new therapeutic applications, offering advantages in cost, time savings, and a lower risk of failure. We present a comprehensive analysis of existing drugs, their repurposing potential, and their clinical implications in the context of LSDs, highlighting the necessity of mutation-specific approaches. Our review systematically explores the landscape of drug repositioning as a means to enhance LSDs therapies. The findings advocate for the strategic repositioning of drugs, accentuating its role in expediting the discovery of effective treatments. We conclude that drug repurposing represents a viable pathway for accelerating therapeutic discovery for LSDs, emphasizing the need for the careful evaluation of drug efficacy and toxicity in disease-specific contexts.
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- 2024
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28. Oxidoreductases and metal cofactors in the functioning of the earth.
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Hay Mele B, Monticelli M, Leone S, Bastoni D, Barosa B, Cascone M, Migliaccio F, Montemagno F, Ricciardelli A, Tonietti L, Rotundi A, Cordone A, and Giovannelli D
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- Metals chemistry, Metals metabolism, Oxidation-Reduction, Catalytic Domain, Oxidoreductases chemistry, Oxidoreductases metabolism, Metalloproteins chemistry, Metalloproteins metabolism
- Abstract
Life sustains itself using energy generated by thermodynamic disequilibria, commonly existing as redox disequilibria. Metals are significant players in controlling redox reactions, as they are essential components of the engine that life uses to tap into the thermodynamic disequilibria necessary for metabolism. The number of proteins that evolved to catalyze redox reactions is extraordinary, as is the diversification level of metal cofactors and catalytic domain structures involved. Notwithstanding the importance of the topic, the relationship between metals and the redox reactions they are involved in has been poorly explored. This work reviews the structure and function of different prokaryotic organometallic-protein complexes, highlighting their pivotal role in controlling biogeochemistry. We focus on a specific subset of metal-containing oxidoreductases (EC1 or EC7.1), which are directly involved in biogeochemical cycles, i.e., at least one substrate or product is a small inorganic molecule that is or can be exchanged with the environment. Based on these inclusion criteria, we select and report 59 metalloenzymes, describing the organometallic structure of their active sites, the redox reactions in which they are involved, and their biogeochemical roles., (© 2023 The Author(s).)
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- 2023
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29. Female Sex Determination Factors in Ceratitis capitata : Molecular and Structural Basis of TRA and TRA2 Recognition.
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Perrotta MM, Lucibelli F, Mazzucchiello SM, Fucci N, Hay Mele B, Giordano E, Salvemini M, Ruggiero A, Vitagliano L, Aceto S, and Saccone G
- Abstract
In the model system for genetics, Drosophila melanogaster , sexual differentiation and male courtship behavior are controlled by sex-specific splicing of doublesex ( dsx ) and fruitless ( fru ). In vitro and in vivo studies showed that female-specific Transformer (TRA) and the non-sex-specific Transformer 2 (TRA2) splicing factors interact, forming a complex promoting dsx and fru female-specific splicing. TRA/TRA2 complex binds to 13 nt long sequence repeats in their pre-mRNAs. In the Mediterranean fruitfly Ceratitis capitata (Medfly), a major agricultural pest, which shares with Drosophila a ~120 million years old ancestor, Cctra and Cctra2 genes seem to promote female-specific splicing of Ccdsx and Ccfru , which contain conserved TRA/TRA2 binding repeats. Unlike Drosophila tra , Cctra autoregulates its female-specific splicing through these putative regulatory repeats. Here, a yeast two-hybrid assay shows that CcTRA interacts with CcTRA2, despite its high amino acid divergence compared to Drosophila TRA. Interestingly, CcTRA2 interacts with itself, as also observed for Drosophila TRA2. We also generated a three-dimensional model of the complex formed by CcTRA and CcTRA2 using predictive approaches based on Artificial Intelligence. This structure also identified an evolutionary and highly conserved putative TRA2 recognition motif in the TRA sequence. The Y2H approach, combined with powerful predictive tools of three-dimensional protein structures, could use helpful also in this and other insect species to understand the potential links between different upstream proteins acting as primary sex-determining signals and the conserved TRA and TRA2 transducers.
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- 2023
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30. Co-Occurrence of Beckwith-Wiedemann Syndrome and Early-Onset Colorectal Cancer.
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Cecere F, Pignata L, Hay Mele B, Saadat A, D'Angelo E, Palumbo O, Palumbo P, Carella M, Scarano G, Rossi GB, Angelini C, Sparago A, Cerrato F, and Riccio A
- Abstract
CRC is an adult-onset carcinoma representing the third most common cancer and the second leading cause of cancer-related deaths in the world. EO-CRC (<45 years of age) accounts for 5% of the CRC cases and is associated with cancer-predisposing genetic factors in half of them. Here, we describe the case of a woman affected by BWSp who developed EO-CRC at age 27. To look for a possible molecular link between BWSp and EO-CRC, we analysed her whole-genome genetic and epigenetic profiles in blood, and peri-neoplastic and neoplastic colon tissues. The results revealed a general instability of the tumor genome, including copy number and methylation changes affecting genes of the WNT signaling pathway, CRC biomarkers and imprinted loci. At the germline level, two missense mutations predicted to be likely pathogenic were found in compound heterozygosity affecting the Cystic Fibrosis (CF) gene CFTR that has been recently classified as a tumor suppressor gene, whose dysregulation represents a severe risk factor for developing CRC. We also detected constitutional loss of methylation of the KCNQ1OT1 :TSS-DMR that leads to bi-allelic expression of the lncRNA KCNQ1OT1 and BWSp. Our results support the hypothesis that the inherited CFTR mutations, together with constitutional loss of methylation of the KCNQ1OT1 :TSS-DMR, initiate the tumorigenesis process. Further somatic genetic and epigenetic changes enhancing the activation of the WNT/beta-catenin pathway likely contributed to increase the growth advantage of cancer cells. Although this study does not provide any conclusive cause-effect relationship between BWSp and CRC, it is tempting to speculate that the imprinting defect of BWSp might accelerate tumorigenesis in adult cancer in the presence of predisposing genetic variants.
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- 2023
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31. Computational modeling of cambium activity provides a regulatory framework for simulating radial plant growth.
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Lebovka I, Hay Mele B, Liu X, Zakieva A, Schlamp T, Gursanscky NR, Merks RMH, Großeholz R, and Greb T
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- Plants, Xylem, Computer Simulation, Gene Expression Regulation, Plant, Phloem, Cambium, Plant Development
- Abstract
Precise organization of growing structures is a fundamental process in developmental biology. In plants, radial growth is mediated by the cambium, a stem cell niche continuously producing wood (xylem) and bast (phloem) in a strictly bidirectional manner. While this process contributes large parts to terrestrial biomass, cambium dynamics eludes direct experimental access due to obstacles in live-cell imaging. Here, we present a cell-based computational model visualizing cambium activity and integrating the function of central cambium regulators. Performing iterative comparisons of plant and model anatomies, we conclude that the receptor-like kinase PXY and its ligand CLE41 are part of a minimal framework sufficient for instructing tissue organization. By integrating tissue-specific cell wall stiffness values, we moreover probe the influence of physical constraints on tissue geometry. Our model highlights the role of intercellular communication within the cambium and shows that a limited number of factors are sufficient to create radial growth by bidirectional tissue production., Competing Interests: IL, BH, XL, AZ, TS, NG, RM, RG, TG No competing interests declared, (© 2023, Lebovka et al.)
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- 2023
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32. Characterization of Linezolid-Analogue L3-Resistance Mutation in Staphylococcus aureus .
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Zanfardino A, Di Napoli M, Migliore F, Hay Mele B, Soriente A, De Rosa M, Notomista E, and Varcamonti M
- Abstract
In a previous study, a linezolid analogue, called 10f, was synthesized. The 10f molecule has an antimicrobial activity comparable to that of the parental compound. In this study, we isolated a Staphylococcus aureus ( S. aureus ) strain resistant to 10f. After sequencing the 23S rRNA and the ribosomal proteins L3 (rplC) and L4 (rplD) genes, we found that the resistant phenotype was associated with a single mutation G359U in rplC bearing to the missense mutation G120V in the L3 protein. The identified mutation is far from the peptidyl transferase center, the oxazolidinone antibiotics binding site, thus suggesting that we identified a new and interesting example of a long-range effect in the ribosome structure.
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- 2023
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33. Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy.
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Iacobucci I, Hay Mele B, Cozzolino F, Monaco V, Cimmaruta C, Monti M, Andreotti G, and Monticelli M
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- Humans, alpha-Galactosidase metabolism, Enzyme Replacement Therapy methods, Isoenzymes therapeutic use, Recombinant Proteins therapeutic use, Fabry Disease metabolism
- Abstract
Enzyme replacement therapy is the only therapeutic option for Fabry patients with completely absent AGAL activity. However, the treatment has side effects, is costly, and requires conspicuous amounts of recombinant human protein (rh-AGAL). Thus, its optimization would benefit patients and welfare/health services (i.e., society at large). In this brief report, we describe preliminary results paving the way for two possible approaches: i. the combination of enzyme replacement therapy with pharmacological chaperones; and ii. the identification of AGAL interactors as possible therapeutic targets on which to act. We first showed that galactose, a low-affinity pharmacological chaperone, can prolong AGAL half-life in patient-derived cells treated with rh-AGAL. Then, we analyzed the interactomes of intracellular AGAL on patient-derived AGAL-defective fibroblasts treated with the two rh-AGALs approved for therapeutic purposes and compared the obtained interactomes to the one associated with endogenously produced AGAL (data available as PXD039168 on ProteomeXchange). Common interactors were aggregated and screened for sensitivity to known drugs. Such an interactor-drug list represents a starting point to deeply screen approved drugs and identify those that can affect (positively or negatively) enzyme replacement therapy.
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- 2023
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34. Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease.
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Monticelli M, Hay Mele B, Allocca M, Liguori L, Lukas J, Monti MC, Morretta E, Cubellis MV, and Andreotti G
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- Humans, alpha-Galactosidase metabolism, Galactose metabolism, Mutation, Lysosomes metabolism, 1-Deoxynojirimycin pharmacology, 1-Deoxynojirimycin therapeutic use, Fabry Disease drug therapy, Fabry Disease genetics, Curcumin pharmacology, Curcumin therapeutic use, Curcumin metabolism
- Abstract
Fabry disease is a lysosomal storage disease caused by mutations in the GLA gene that encodes alpha-galactosidase (AGAL). The disease causes abnormal globotriaosylceramide (Gb3) storage in the lysosomes. Variants responsible for the genotypic spectrum of Fabry disease include mutations that abolish enzymatic activity and those that cause protein instability. The latter can be successfully treated with small molecules that either bind and stabilize AGAL or indirectly improve its cellular activity. This paper describes the first attempt to reposition curcumin, a nutraceutical, to treat Fabry disease. We tested the efficacy of curcumin in a cell model and found an improvement in AGAL activity for 80% of the tested mutant genotypes (four out of five tested). The fold-increase was dependent on the mutant and ranged from 1.4 to 2.2. We produced evidence that supports a co-chaperone role for curcumin when administered with AGAL pharmacological chaperones (1-deoxygalactonojirimycin and galactose). The combined treatment with curcumin and either pharmacological chaperone was beneficial for four out of five tested mutants and showed fold-increases ranging from 1.1 to 2.3 for DGJ and from 1.1 to 2.8 for galactose. Finally, we tested a long-term treatment on one mutant (L300F) and detected an improvement in Gb3 clearance and lysosomal markers (LAMP-1 and GAA). Altogether, our findings confirmed the necessity of personalized therapies for Fabry patients and paved the way to further studies and trials of treatments for Fabry disease.
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- 2023
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35. The mismatch-repair proteins MSH2 and MSH6 interact with the imprinting control regions through the ZFP57-KAP1 complex.
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Acurzio B, Cecere F, Giaccari C, Verma A, Russo R, Valletta M, Hay Mele B, Angelini C, Chambery A, and Riccio A
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- Animals, Chromatography, Liquid, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Female, Genomic Imprinting, Mammals metabolism, Mice, MutS Homolog 2 Protein genetics, MutS Homolog 2 Protein metabolism, Tandem Mass Spectrometry, DNA Methylation, Repressor Proteins metabolism
- Abstract
Background: Imprinting Control Regions (ICRs) are CpG-rich sequences acquiring differential methylation in the female and male germline and maintaining it in a parental origin-specific manner in somatic cells. Despite their expected high mutation rate due to spontaneous deamination of methylated cytosines, ICRs show conservation of CpG-richness and CpG-containing transcription factor binding sites in mammalian species. However, little is known about the mechanisms contributing to the maintenance of a high density of methyl CpGs at these loci., Results: To gain functional insights into the mechanisms for maintaining CpG methylation, we sought to identify the proteins binding the methylated allele of the ICRs by determining the interactors of ZFP57 that recognizes a methylated hexanucleotide motif of these DNA regions in mouse ESCs. By using a tagged approach coupled to LC-MS/MS analysis, we identified several proteins, including factors involved in mRNA processing/splicing, chromosome organization, transcription and DNA repair processes. The presence of the post-replicative mismatch-repair (MMR) complex components MSH2 and MSH6 among the identified ZFP57 interactors prompted us to investigate their DNA binding profile by chromatin immunoprecipitation and sequencing. We demonstrated that MSH2 was enriched at gene promoters overlapping unmethylated CpG islands and at repeats. We also found that both MSH2 and MSH6 interacted with the methylated allele of the ICRs, where their binding to DNA was mediated by the ZFP57/KAP1 complex., Conclusions: Our findings show that the MMR complex is concentrated on gene promoters and repeats in mouse ESCs, suggesting that maintaining the integrity of these regions is a primary function of highly proliferating cells. Furthermore, the demonstration that MSH2/MSH6 are recruited to the methylated allele of the ICRs through interaction with ZFP57/KAP1 suggests a role of the MMR complex in the maintenance of the integrity of these regulatory regions and evolution of genomic imprinting in mammalian species., (© 2022. The Author(s).)
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- 2022
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36. Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.
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Pignata L, Cecere F, Verma A, Hay Mele B, Monticelli M, Acurzio B, Giaccari C, Sparago A, Hernandez Mora JR, Monteagudo-Sánchez A, Esteller M, Pereda A, Tenorio-Castano J, Palumbo O, Carella M, Prontera P, Piscopo C, Accadia M, Lapunzina P, Cubellis MV, de Nanclares GP, Monk D, Riccio A, and Cerrato F
- Subjects
- DNA Methylation, Genomic Imprinting, Humans, Proteins genetics, Pseudohypoparathyroidism, Beckwith-Wiedemann Syndrome diagnosis, Beckwith-Wiedemann Syndrome genetics, Pseudohypoparathyroidism genetics
- Abstract
Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively. In both of these diseases a subset of the patients is affected by multi-locus imprinting disturbances (MLID). In several families, MLID is associated with damaging variants of maternal-effect genes encoding protein components of the subcortical maternal complex (SCMC). However, frequency, penetrance and recurrence risks of these variants are still undefined. In this study, we screened two cohorts of BWS patients and one cohort of PHP1B patients for the presence of MLID, and analysed the positive cases for the presence of maternal variants in the SCMC genes by whole exome-sequencing and in silico functional studies., Results: We identified 10 new cases of MLID associated with the clinical features of either BWS or PHP1B, in which segregate 13 maternal putatively damaging missense variants of the SCMC genes. The affected genes also included KHDC3L that has not been associated with MLID to date. Moreover, we highlight the possible relevance of relatively common variants in the aetiology of MLID., Conclusion: Our data further add to the list of the SCMC components and maternal variants that are involved in MLID, as well as of the associated clinical phenotypes. Also, we propose that in addition to rare variants, common variants may play a role in the aetiology of MLID and imprinting disorders by exerting an additive effect in combination with rarer putatively damaging variants. These findings provide useful information for the molecular diagnosis and recurrence risk evaluation of MLID-associated IDs in genetic counselling., (© 2022. The Author(s).)
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- 2022
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37. Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones.
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Monticelli M, Liguori L, Allocca M, Bosso A, Andreotti G, Lukas J, Monti MC, Morretta E, Cubellis MV, and Hay Mele B
- Subjects
- 1-Deoxynojirimycin pharmacology, 1-Deoxynojirimycin therapeutic use, Aspirin pharmacology, Aspirin therapeutic use, Drug Repositioning, Humans, Lysosomes, Molecular Chaperones genetics, Mutation, Fabry Disease drug therapy, Fabry Disease genetics, alpha-Galactosidase genetics, alpha-Galactosidase therapeutic use
- Abstract
Fabry disease is caused by a deficiency of lysosomal alpha galactosidase and has a very large genotypic and phenotypic spectrum. Some patients who carry hypomorphic mutations can benefit from oral therapy with a pharmacological chaperone. The drug requires a very precise regimen because it is a reversible inhibitor of alpha-galactosidase. We looked for molecules that can potentiate this pharmacological chaperone, among drugs that have already been approved for other diseases. We tested candidate molecules in fibroblasts derived from a patient carrying a large deletion in the gene GLA, which were stably transfected with a plasmid expressing hypomorphic mutants. In our cell model, three drugs were able to potentiate the action of the pharmacological chaperone. We focused our attention on one of them, acetylsalicylic acid. We expect that acetylsalicylic acid can be used in synergy with the Fabry disease pharmacological chaperone and prolong its stabilizing effect on alpha-galactosidase.
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- 2022
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38. Protective Role of a TMPRSS2 Variant on Severe COVID-19 Outcome in Young Males and Elderly Women.
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Monticelli M, Hay Mele B, Benetti E, Fallerini C, Baldassarri M, Furini S, Frullanti E, Mari F, Andreotti G, Cubellis MV, and Renieri A
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- Aged, COVID-19 epidemiology, COVID-19 genetics, COVID-19 therapy, Comorbidity, Female, Gene Frequency, Hospitalization, Humans, Italy epidemiology, Male, Middle Aged, Mutation, Respiration, Artificial, Serine Endopeptidases chemistry, Serine Endopeptidases metabolism, Treatment Outcome, COVID-19 etiology, Polymorphism, Single Nucleotide, Serine Endopeptidases genetics
- Abstract
The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients-young males and elderly women-and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.
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- 2021
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39. Bioinformatics tools for marine biotechnology: a practical tutorial with a metagenomic approach.
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Liguori L, Monticelli M, Allocca M, Cubellis MV, and Hay Mele B
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- Amino Acid Sequence, Bacterial Proteins chemistry, Base Sequence, Databases, Factual, Databases, Protein, Goals, Humans, Learning, User-Computer Interface, Biotechnology education, Computational Biology education, Marine Biology education, Metagenomics
- Abstract
Background: Bioinformatics has pervaded all fields of biology and has become an indispensable tool for almost all research projects. Although teaching bioinformatics has been incorporated in all traditional life science curricula, practical hands-on experiences in tight combination with wet-lab experiments are needed to motivate students., Results: We present a tutorial that starts from a practical problem: finding novel enzymes from marine environments. First, we introduce the idea of metagenomics, a recent approach that extends biotechnology to non-culturable microbes. We presuppose that a probe for the screening of metagenomic cosmid library is needed. The students start from the chemical structure of the substrate that should be acted on by the novel enzyme and end with the sequence of the probe. To attain their goal, they discover databases such as BRENDA and programs such as BLAST and Clustal Omega. Students' answers to a satisfaction questionnaire show that a multistep tutorial integrated into a research wet-lab project is preferable to conventional lectures illustrating bioinformatics tools., Conclusion: Experimental biologists can better operate basic bioinformatics if a problem-solving approach is chosen.
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- 2020
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40. Ecological assessment of anthropogenic impact in marine ecosystems: The case of Bagnoli Bay.
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Hay Mele B, Russo L, Crocetta F, Gambi C, Dell'Anno A, Danovaro R, Guglielmo R, Musco L, Patti FP, Riginella E, Tangherlini M, Ribera d'Alcalá M, and D'Alelio D
- Subjects
- Animals, Bays, Environmental Monitoring, Fishes, Ecosystem, Environmental Pollutants
- Abstract
Pollutants alter marine systems, interfering with provisioning of ecosystem services; understanding their interaction with ecological communities is therefore critical to inform environmental management. Here we propose a joint compositional- and interaction-based analysis for ecological status assessment and apply it on the benthic communities of the Bagnoli Bay. We found that contamination differentially affects the communities' composition in the bay, with prokaryotes influenced only by depth, and benthos not following the environmental gradient at all. This result is confirmed by analyses of the community structure, whose network structure suggest fast carbon flow and cycling, especially promoted by nematodes and polychaetes; the benthic prey/predator biomass ratio, adjusted for competition, successfully synthesise the status of predator taxa. We found demersal fish communities to separate into a deep, pelagic-like community, and two shallow communities where a shift from exclusive predators to omnivores occurs, moving from the most polluted to the least polluted sampling units. Finally, our study indicate that indices based on interspecific interactions are better indicators of environmental gradients than those defined based on species composition exclusively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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41. Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.
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Liguori L, Monticelli M, Allocca M, Hay Mele B, Lukas J, Cubellis MV, and Andreotti G
- Subjects
- Humans, Fabry Disease drug therapy, Fabry Disease enzymology, Fabry Disease genetics, Molecular Chaperones therapeutic use, Mutation, Missense, alpha-Galactosidase genetics, alpha-Galactosidase metabolism
- Abstract
The term "pharmacological chaperone" was introduced 20 years ago. Since then the approach with this type of drug has been proposed for several diseases, lysosomal storage disorders representing the most popular targets. The hallmark of a pharmacological chaperone is its ability to bind a protein specifically and stabilize it. This property can be beneficial for curing diseases that are associated with protein mutants that are intrinsically active but unstable. The total activity of the affected proteins in the cell is lower than normal because they are cleared by the quality control system. Although most pharmacological chaperones are reversible competitive inhibitors or antagonists of their target proteins, the inhibitory activity is neither required nor desirable. This issue is well documented by specific examples among which those concerning Fabry disease. Direct specific binding is not the only mechanism by which small molecules can rescue mutant proteins in the cell. These drugs and the properly defined pharmacological chaperones can work together with different and possibly synergistic modes of action to revert a disease phenotype caused by an unstable protein.
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- 2020
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42. Rewiring and indirect effects underpin modularity reshuffling in a marine food web under environmental shifts.
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D'Alelio D, Hay Mele B, Libralato S, Ribera d'Alcalà M, and Jordán F
- Abstract
Species are characterized by physiological and behavioral plasticity, which is part of their response to environmental shifts. Nonetheless, the collective response of ecological communities to environmental shifts cannot be predicted from the simple sum of individual species responses, since co-existing species are deeply entangled in interaction networks, such as food webs. For these reasons, the relation between environmental forcing and the structure of food webs is an open problem in ecology. To this respect, one of the main problems in community ecology is defining the role each species plays in shaping community structure, such as by promoting the subdivision of food webs in modules-that is, aggregates composed of species that more frequently interact-which are reported as community stabilizers. In this study, we investigated the relationship between species roles and network modularity under environmental shifts in a highly resolved food web, that is, a "weighted" ecological network reproducing carbon flows among marine planktonic species. Measuring network properties and estimating weighted modularity, we show that species have distinct roles, which differentially affect modularity and mediate structural modifications, such as modules reconfiguration, induced by environmental shifts. Specifically, short-term environmental changes impact the abundance of planktonic primary producers; this affects their consumers' behavior and cascades into the overall rearrangement of trophic links. Food web re-adjustments are both direct, through the rewiring of trophic-interaction networks, and indirect, with the reconfiguration of trophic cascades. Through such "systemic behavior," that is, the way the food web acts as a whole, defined by the interactions among its parts, the planktonic food web undergoes a substantial rewiring while keeping almost the same global flow to upper trophic levels, and energetic hierarchy is maintained despite environmental shifts. This behavior suggests the potentially high resilience of plankton networks, such as food webs, to dramatic environmental changes, such as those provoked by global change., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)
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- 2019
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43. Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.
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Cimmaruta C, Citro V, Andreotti G, Liguori L, Cubellis MV, and Hay Mele B
- Subjects
- Fabry Disease enzymology, Fabry Disease genetics, Humans, Phenotype, Lysosomes enzymology, Molecular Sequence Annotation methods, Mutation, Missense genetics, alpha-Galactosidase genetics
- Abstract
Background: Severity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity., Results: wANNOVAR, a popular tool that can generate several different types of deleteriousness-prediction scores, was tested on Fabry disease. This pathology, which is caused by a deficit of lysosomal alpha-galactosidase, has a very large genotypic and phenotypic spectrum and offers the possibility of associating a quantitative measure of the damage caused by mutations to the functioning of the enzyme in the cells. Some predictors, and in particular VEST3 and PolyPhen2 provide scores that correlate with the severity of lysosomal alpha-galactosidase mutations in a statistically significant way., Conclusions: Sorting disease mutations by severity is possible and offers advantages over binary classification. Dataset for testing and training in silico predictors can be obtained by transient transfection and evaluation of residual activity of mutants in cell extracts. This approach consents to quantitative data for severe, mild and non pathological variants.
- Published
- 2018
- Full Text
- View/download PDF
44. The Analysis of Variants in the General Population Reveals That PMM2 Is Extremely Tolerant to Missense Mutations and That Diagnosis of PMM2-CDG Can Benefit from the Identification of Modifiers.
- Author
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Citro V, Cimmaruta C, Monticelli M, Riccio G, Hay Mele B, Cubellis MV, and Andreotti G
- Subjects
- Genetic Association Studies, Glycosylation, Humans, Models, Molecular, Mutation, Missense, Phenotype, Phosphotransferases (Phosphomutases) chemistry, Protein Conformation, Congenital Disorders of Glycosylation diagnosis, Congenital Disorders of Glycosylation genetics, Mutation, Phosphotransferases (Phosphomutases) genetics
- Abstract
Type I disorders of glycosylation (CDG), the most frequent of which is phosphomannomutase 2 (PMM2-CDG), are a group of diseases causing the incomplete N -glycosylation of proteins. PMM2-CDG is an autosomal recessive disease with a large phenotypic spectrum, and is associated with mutations in the PMM2 gene. The biochemical analysis of mutants does not allow a precise genotype⁻phenotype correlation for PMM2-CDG. PMM2 is very tolerant to missense and loss of function mutations, suggesting that a partial deficiency of activity might be beneficial under certain circumstances. The patient phenotype might be influenced by variants in other genes associated with the type I disorders of glycosylation in the general population.
- Published
- 2018
- Full Text
- View/download PDF
45. Drug repositioning can accelerate discovery of pharmacological chaperones.
- Author
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Hay Mele B, Citro V, Andreotti G, and Cubellis MV
- Subjects
- Drug Approval, Humans, Drug Repositioning, Genetic Diseases, Inborn drug therapy
- Abstract
A promising strategy for the treatment of genetic diseases, pharmacological chaperone therapy, has been proposed recently. It exploits small molecules which can be administered orally, reach difficult tissues such as the brain and have low cost. This strategy has a vast field of application. In order to make drug development as fast as possible, it is important to exploit drug repositioning. We evaluated the impact and limitations of this approach for rare diseases and we provide a shortcut in finding drugs for off-target usage.
- Published
- 2015
- Full Text
- View/download PDF
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