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Article ; Online: High glucose induces an activated state of partial epithelial-mesenchymal transition in human primary tubular cell cultures.

Barbara Torsello / Sofia De Marco / Silvia Bombelli / Ingrid Cifola / Ivana Morabito / Lara Invernizzi / Chiara Meregalli / Nicola Zucchini / Guido Strada / Roberto A Perego / Cristina Bianchi

PLoS ONE, Vol 18, Iss 2, p e

2023 Volume 0279655

Abstract: Tubulointerstitial fibrosis is observed in diabetic nephropathy. It is still debated whether tubular cells, undergoing epithelial-mesenchymal transition (EMT) in high glucose (HG) conditions, may contribute to interstitial fibrosis development. In this ... ...

Abstract	Tubulointerstitial fibrosis is observed in diabetic nephropathy. It is still debated whether tubular cells, undergoing epithelial-mesenchymal transition (EMT) in high glucose (HG) conditions, may contribute to interstitial fibrosis development. In this study, we investigated the phenotypic and molecular EMT-like changes and the alteration of inflammatory and fibrogenic secretome induced by HG in human primary tubular cell cultures. Taking advantage of this in vitro cell model composed of proximal and distal tubular cells, we showed that HG-treated tubular cells acquired a fibroblast-like morphology with increased cytoplasmic stress fibers, maintaining the expression of the epithelial markers specific of proximal and distal tubular cells. HG increased Snail1, miRNA210 and Vimentin mesenchymal markers, decreased N-cadherin expression and migration ability of primary tubular cells, while E-cadherin expression and focal adhesion distribution were not affected. Furthermore, HG treatment of tubular cells altered the inflammatory cytokine secretion creating a secretome able to enhance the proliferation and migration of fibroblasts. Our findings show that HG promotes an activated state of partial EMT in human tubular primary cells and induces a pro-inflammatory and pro-fibrogenic microenvironment, supporting the active role of tubular cells in diabetic nephropathy onset.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Barbara Torsello / Sofia De Marco / Silvia Bombelli / Elisa Chisci / Valeria Cassina / Roberta Corti / Davide Bernasconi / Roberto Giovannoni / Cristina Bianchi / Roberto A. Perego

Biology Open, Vol 10, Iss

The 1ALCTL and 1BLCTL isoforms of Arg/Abl2 induce fibroblast activation and extra cellular matrix remodelling differently

2021 Volume 5

Keywords	Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Mitochondrial DNA Landscape of Modern Mexico

Martin Bodner / Ugo A. Perego / J. Edgar Gomez / Ricardo M. Cerda-Flores / Nicola Rambaldi Migliore / Scott R. Woodward / Walther Parson / Alessandro Achilli

Genes, Vol 12, Iss 1453, p

2021 Volume 1453

Abstract: Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European ... ...

Abstract	Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European colonization, the population landscape has dramatically changed. Today, the majority of Mexicans do not identify themselves as Indigenous but as admixed, and appear to have very little in common with their pre-Columbian predecessors. However, when the maternally inherited mitochondrial (mt)DNA is investigated in the modern Mexican population, this is not the case. Control region sequences of 2021 samples deriving from all over the country revealed an overwhelming Indigenous American legacy, with almost 90% of mtDNAs belonging to the four major pan-American haplogroups A2, B2, C1, and D1. This finding supports a very low European contribution to the Mexican gene pool by female colonizers and confirms the effectiveness of employing uniparental markers as a tool to reconstruct a country’s history. In addition, the distinct frequency and dispersal patterns of Indigenous American and West Eurasian clades highlight the benefit such large and country-wide databases provide for studying the impact of colonialism from a female perspective and population stratification. The importance of geographical database subsets not only for forensic application is clearly demonstrated.
Keywords	forensic science ; haplogroups ; phylogeny ; phylogeography ; MtDNA database ; quality control ; Genetics ; QH426-470
Subject code	390
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The 1ALCTL and 1BLCTL isoforms of Arg/Abl2 induce fibroblast activation and extra cellular matrix remodelling differently

Barbara Torsello / Sofia De Marco / Silvia Bombelli / Elisa Chisci / Valeria Cassina / Roberta Corti / Davide Bernasconi / Roberto Giovannoni / Cristina Bianchi / Roberto A. Perego

Biology Open, Vol 8, Iss

2019 Volume 3

Abstract: The fibrotic tissue and the stroma adjacent to cancer cells are characterised by the presence of activated fibroblasts (myofibroblasts) which play a role in creating a supportive tissue characterised by abundant extracellular matrix (ECM) secretion. The ... ...

Abstract	The fibrotic tissue and the stroma adjacent to cancer cells are characterised by the presence of activated fibroblasts (myofibroblasts) which play a role in creating a supportive tissue characterised by abundant extracellular matrix (ECM) secretion. The myofibroblasts remodel this tissue through secreted molecules and modulation of their cytoskeleton and specialized contractile structures. The non-receptor protein tyrosine kinase Arg (also called Abl2) has the unique ability to bind directly to the actin cytoskeleton, transducing diverse extracellular signals into cytoskeletal rearrangements. In this study we analysed the 1ALCTL and 1BLCTL Arg isoforms in Arg−/− murine embryonal fibroblasts (MEF) cell line, focusing on their capacity to activate fibroblasts and to remodel ECM. The results obtained showed that Arg isoform 1BLCTL has a major role in proliferation, migration/invasion of MEF and in inducing a milieu able to modulate tumour cell morphology, while 1ALCTL isoform has a role in MEF adhesion maintaining active focal adhesions. On the whole, the presence of Arg in MEF supports the proliferation, activation, adhesion, ECM contraction and stiffness, while the absence of Arg affected these myofibroblast features. This article has an associated First Person interview with the first author of the paper.
Keywords	Arg ; Abl2 ; Non-receptor tyrosine kinase ; Fibroblast ; Extra cellular matrix ; Stroma remodelling ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PKH high /CD133+/CD24− Renal Stem-Like Cells Isolated from Human Nephrospheres Exhibit In Vitro Multipotency

Silvia Bombelli / Chiara Meregalli / Chiara Grasselli / Maddalena M. Bolognesi / Antonino Bruno / Stefano Eriani / Barbara Torsello / Sofia De Marco / Davide P. Bernasconi / Nicola Zucchini / Paolo Mazzola / Cristina Bianchi / Marco Grasso / Adriana Albini / Giorgio Cattoretti / Roberto A. Perego

Cells, Vol 9, Iss 1805, p

2020 Volume 1805

Abstract: The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, ... ...

Abstract	The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, but it is difficult to argue whether these populations have the same capacities that have been described in mice. Using the nephrosphere (NS) model, we isolated the quiescent population of adult human renal stem-like PKH high /CD133+/CD24− cells (RSC). The aim of this study was to deepen the RSC in vitro multipotency capacity. RSC, not expressing endothelial markers, generated secondary nephrospheres containing CD31+/vWf+ cells and cytokeratin positive cells, indicating the coexistence of endothelial and epithelial commitment. RSC cultured on decellularized human renal scaffolds generated endothelial structures together with the proximal and distal tubular structures. CD31+ endothelial committed progenitors sorted from nephrospheres generated spheroids with endothelial-like sprouts in Matrigel. We also demonstrated the double commitment toward endothelial and epithelial lineages of single RSC. The ability of the plastic RSC population to recapitulate the development of tubular epithelial and endothelial renal lineages makes these cells a good tool for the creation of organoids with translational relevance for studying the parenchymal and endothelial cell interactions and developing new therapeutic strategies.
Keywords	human adult stem cell ; kidney ; endothelium ; scaffold ; nephrosphere ; multipotency ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas

Viola Grugni / Alessandro Raveane / Linda Ongaro / Vincenza Battaglia / Beniamino Trombetta / Giulia Colombo / Marco Rosario Capodiferro / Anna Olivieri / Alessandro Achilli / Ugo A. Perego / Jorge Motta / Maribel Tribaldos / Scott R. Woodward / Luca Ferretti / Fulvio Cruciani / Antonio Torroni / Ornella Semino

BMC Biology, Vol 17, Iss 1, Pp 1-

2019 Volume 14

Abstract: Abstract Background Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated ... ...

Abstract	Abstract Background Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America. Results Our analyses of 1.5 Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a “coastal and inland routes scenario” for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe. Conclusions We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples.
Keywords	Human Y-chromosome variation ; Haplogroup Q phylogeny ; Origin of Native Americans ; Origin of Eurasians ; Peopling of the Americas ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Multi-model simulation of soil temperature, soil water content and biomass in Euro-Mediterranean grasslands: Uncertainties and ensemble performance

Sándor, R / A. Perego / D. Hidy / E. Lellei-Kovács / F. Ruget / G. Bellocchi / G. Seddaiu / J. Minet / L. Doro / L. Wu / M. Acutis / M. Köchy / M. Sanna / S. Ma / S. Rolinski / Z. Barcza

European journal of agronomy. 2017 Aug., v. 88

2017

Abstract: This study presents results from a major grassland model intercomparison exercise, and highlights the main challenges faced in the implementation of a multi-model ensemble prediction system in grasslands. Nine, independently developed simulation models ... ...

Abstract	This study presents results from a major grassland model intercomparison exercise, and highlights the main challenges faced in the implementation of a multi-model ensemble prediction system in grasslands. Nine, independently developed simulation models linking climate, soil, vegetation and management to grassland biogeochemical cycles and production were compared in a simulation of soil water content (SWC) and soil temperature (ST) in the topsoil, and of biomass production. The results were assessed against SWC and ST data from five observational grassland sites representing a range of conditions – Grillenburg in Germany, Laqueuille in France with both extensive and intensive management, Monte Bondone in Italy and Oensingen in Switzerland – and against yield measurements from the same sites and other experimental grassland sites in Europe and Israel. We present a comparison of model estimates from individual models to the multi-model ensemble (represented by multi-model median: MMM). With calibration (seven out of nine models), the performances were acceptable for weekly-aggregated ST (R2>0.7 with individual models and >0.8–0.9 with MMM), but less satisfactory with SWC (R2<0.6 with individual models and <∼0.5 with MMM) and biomass (R2<∼0.3 with both individual models and MMM). With individual models, maximum biases of about −5°C for ST, −0.3m3m−3 for SWC and 360gDMm−2 for yield, as well as negative modelling efficiencies and some high relative root mean square errors indicate low model performance, especially for biomass. We also found substantial discrepancies across different models, indicating considerable uncertainties regarding the simulation of grassland processes. The multi-model approach allowed for improved performance, but further progress is strongly needed in the way models represent processes in managed grassland systems.
Keywords	biogeochemical cycles ; biomass production ; climate ; grasslands ; model validation ; prediction ; range management ; simulation models ; soil temperature ; soil water ; soil water content ; topsoil ; uncertainty ; France ; Germany ; Israel ; Italy ; Switzerland
Language	English
Dates of publication	2017-08
Size	p. 22-40.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1157136-6
ISSN	1873-7331 ; 1161-0301
ISSN (online)	1873-7331
ISSN	1161-0301
DOI	10.1016/j.eja.2016.06.006
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Molecular dissection of the basal clades in the human Y chromosome phylogenetic tree.

Rosaria Scozzari / Andrea Massaia / Eugenia D'Atanasio / Natalie M Myres / Ugo A Perego / Beniamino Trombetta / Fulvio Cruciani

PLoS ONE, Vol 7, Iss 11, p e

2012 Volume 49170

Abstract: One hundred and forty-six previously detected mutations were more precisely positioned in the human Y chromosome phylogeny by the analysis of 51 representative Y chromosome haplogroups and the use of 59 mutations from literature. Twenty-two new mutations ...

Abstract	One hundred and forty-six previously detected mutations were more precisely positioned in the human Y chromosome phylogeny by the analysis of 51 representative Y chromosome haplogroups and the use of 59 mutations from literature. Twenty-two new mutations were also described and incorporated in the revised phylogeny. This analysis made it possible to identify new haplogroups and to resolve a deep trifurcation within haplogroup B2. Our data provide a highly resolved branching in the African-specific portion of the Y tree and support the hypothesis of an origin in the north-western quadrant of the African continent for the human MSY diversity.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mitogenomes from two uncommon haplogroups mark late glacial/postglacial expansions from the near east and neolithic dispersals within Europe.

Anna Olivieri / Maria Pala / Francesca Gandini / Baharak Hooshiar Kashani / Ugo A Perego / Scott R Woodward / Viola Grugni / Vincenza Battaglia / Ornella Semino / Alessandro Achilli / Martin B Richards / Antonio Torroni

PLoS ONE, Vol 8, Iss 7, p e

2013 Volume 70492

Abstract: The current human mitochondrial (mtDNA) phylogeny does not equally represent all human populations but is biased in favour of representatives originally from north and central Europe. This especially affects the phylogeny of some uncommon West Eurasian ... ...

Abstract	The current human mitochondrial (mtDNA) phylogeny does not equally represent all human populations but is biased in favour of representatives originally from north and central Europe. This especially affects the phylogeny of some uncommon West Eurasian haplogroups, including I and W, whose southern European and Near Eastern components are very poorly represented, suggesting that extensive hidden phylogenetic substructure remains to be uncovered. This study expanded and re-analysed the available datasets of I and W complete mtDNA genomes, reaching a comprehensive 419 mitogenomes, and searched for precise correlations between the ages and geographical distributions of their numerous newly identified subclades with events of human dispersal which contributed to the genetic formation of modern Europeans. Our results showed that haplogroups I (within N1a1b) and W originated in the Near East during the Last Glacial Maximum or pre-warming period (the period of gradual warming between the end of the LGM, ∼19 ky ago, and the beginning of the first main warming phase, ∼15 ky ago) and, like the much more common haplogroups J and T, may have been involved in Late Glacial expansions starting from the Near East. Thus our data contribute to a better definition of the Late and postglacial re-peopling of Europe, providing further evidence for the scenario that major population expansions started after the Last Glacial Maximum but before Neolithic times, but also evidencing traces of diffusion events in several I and W subclades dating to the European Neolithic and restricted to Europe.
Keywords	Medicine ; R ; Science ; Q
Subject code	930
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phylogenetic relationships of three Italian merino-derived sheep breeds evaluated through a complete mitogenome analysis.

Hovirag Lancioni / Piera Di Lorenzo / Simone Ceccobelli / Ugo A Perego / Arianna Miglio / Vincenzo Landi / Maria T Antognoni / Francesca M Sarti / Emiliano Lasagna / Alessandro Achilli

PLoS ONE, Vol 8, Iss 9, p e

2013 Volume 73712

Abstract: In Italy, the crisis of the wool industry triggered the necessity to reconvert the two traditional Merino-derived breeds, Gentile di Puglia and Sopravissana, to meat production, by creating the Merinizzata Italiana. The aim of the present study was to ... ...

Abstract	In Italy, the crisis of the wool industry triggered the necessity to reconvert the two traditional Merino-derived breeds, Gentile di Puglia and Sopravissana, to meat production, by creating the Merinizzata Italiana. The aim of the present study was to assess the genetic diversity of these three Italian Merino-derived (IMd) breeds by examining the molecular information encoded in the maternally-inherited mitochondrial DNA (mtDNA). A parallel molecular investigation was performed on the putative paternal and maternal breeds, the Merino from Spain and the Appenninica from Italy, respectively, as well as on three unrelated dairy breeds (Sarda and Comisana from Italy, and Lacaune from France). Firstly, the mtDNA control region of 291 samples was analyzed. When comparing the overall genetic distances among the eight stocks, the three IMd breeds clustered together close to the Appenninica, thus confirming its parental role. Among the 90 IMd samples, 82 different haplotypes were observed, almost all belonging to haplogroup B, and only one to A. For 23 mtDNAs, including nine IMd, the analysis was then brought to the level of entire mitogenomes. Three distinct sub-haplogroups within B were found to encompass the IMd samples, with one clade (B1a2a1) apparently restricted to those sheep. Thus, despite experiencing a drastic reduction in number (mainly due to changes in breeding practices driven by the economy), the IMd breeds still represent a reservoir of distinctive mitochondrial variants, which could potentially contribute to the development of conservation and management programs of Italian sheep breeds.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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