ESTIMATING THE BIOGEOGRAPHICAL ORIGIN OF THE UNIDENTIFIED BODIES OF THE SHIPWRECK OF APRIL 18TH, 2015 IN THE MEDITERRANEAN: COMPARISON OF GENETIC AND ANTHROPOLOGICAL ASSESSMENTS

La crisi migratoria ha recentemente posto l’attenzione sulla necessità di identificare le vittime dei naufragi del Mediterraneo. Il presente studio fa parte del progetto del LABANOF (Laboratorio di Antropologia e Odontologia), Dipartimento di Scienze Biomediche dell’Università degli Studi di Milano, che ha come finalità quella di identificare le vittime del naufragio del 18 aprile 2015. Oltre ad occuparsi di tale aspetto identificativo, il presente lavoro di Tesi ha avuto come obiettivo il confronto tra metodiche genetiche e antropologiche al fine della stima dell’origine biogeografica di tali individui. A tal fine, i resti di 150 vittime sono stati sottoposti ad indagine genetica presso il laboratorio di genetica forense dell’Università degli Studi di Pavia, Torino, Brescia and Eurofins Genoma, a scopo identificativo con la tipizzazione dei marcatori autosomici STR. Sui 49 campioni che hanno restituito una qualità analitica ottimale, sono poi state effettuate analisi mirate alla valutazione dell’origine biogeografica: in particolare, sui casi si è proceduto alla tipizzazione dei marcatori autosomici sul cromosoma Y, oltre a marcatori SNP sia autosomici sia sul cromosoma Y. Essendosi altresì rilevate differenze in termini di resa e recupero dell’informazione genetica tra i diversi individui, utile al confronto con i profili dei presunti parenti, si è inoltre indagata l’eventuale sussistenza di una correlazione fra la qualità del materiale genetico risultante dall’analisi dei marcatori autosomici e le condizioni tafonomiche dei resti cadaverici studiati. L’unica variabile che ha mostrato di variare in modo significativo (p-value <0.05) è stato l’intervallo di tempo intercorso fra il naufragio e il momento dell’espletamento delle procedure autoptiche, nel corso delle quali si è provveduto al prelievo dei campioni ossei: i campioni con risultato analitico ottimale sono stati prelevati nella quasi totalità dei casi più precocemente (<200 giorni). Parallelamente i 49 campioni sono stati analizzati dal punto di vista antropologico applicando metodi morfologici sviluppati su popolazioni sovrapponibili a quelle di provenienza delle vittime. Per quanto riguarda l’ancestralità geografica, le predizioni dei due metodi valutati sui caratteri morfometrici del cranio (OSSA e hfeneR) appaiono coincidere tra loro se si considera il gruppo con percentuali di probabilità correlate alla stima. Tuttavia, la bassa numerosità delle risultanze del sistema OSSA non consente ulteriori considerazioni. Per quanto concerne i caratteri non metrici valutati sui denti, le analisi sono state effettuate mediante software rASUDAS. Le stime risultanti hanno rivelato una scarsa concordanza con le predizioni morfologiche craniche, in particolare con quelle del software hefneR, che è più paragonabile del sistema OSSA. Il confronto con le predizioni di origine biogeografica mediante polimorfismi Y-STR ha evidenziato un certo pattern di concordanza solamente con le stime ottenute mediante il metodo hefneR. L’opportunità di confermare quanto osservato su un campione maggiore rappresenterebbe un ambizioso obiettivo per ricerche future. In conclusione, il presente lavoro ha permesso di identificare i metodi potenzialmente più idonei per lo studio del campione in analisi, aprendo nuove prospettive nel processo identificativo delle vittime del Mediterraneo. La possibilità di avere metodi antropologici e odontologici accurati permetterebbe di circoscrivere il confrona sospetti di identità provenienti da una specifica area geografica, oltre a focalizzare la ricerca dei parenti in alcuni paesi e a consentire la selezione di dati di riferimento idonei per il confronto genetico. In aggiunta, il riscontro di come la qualità dei profili genetici venga significativamente influenzata dal tempo di sommersione sottolinea l’importanza di procedure precoci di recupero e identificazione delle vittime.The migratory crisis has recently drawn attention to the need to identify the victims of shipwrecks in the Mediterranean Sea. This study is part of a larger project carried out by the Forensic Laboratory of Anthropology and Odontology (LABANOF – Laboratorio di Antropologia e Odontologia Forense) of the University of Milan aimed at identifying the victims of the shipwreck of April 18, 2015. The present research had the objective of exploring the current methods of geographic origin estimation in forensic genetics and anthropology and contributing to the search in the field of identification. To this end, the remains of 150 victims were subjected to genetic investigation at the forensic genetics laboratory of the University of Brescia, Turin, Pavia and of the Eurofins Genoma for identification purposes. Also, on 49 cases with good quality profiles biogeographical ancestry estimation was performed using different techniques, according to the protocols used in the different laboratories involved (Brescia and Turin). Furthermore, having detected differences in terms of recovery of genetic information useful for comparison with the profiles of alleged relatives, the possible correlation between the quality of the results in the analysis of autosomal markers and the taphonomic condition of the cadaveric remains was investigated. The only variable that showed significant variation (p-value <0.01) was the time interval between the shipwreck and the autopsy procedures, during which sampling was performed. Bone samples with optimal analytical results were taken earlier (<200 days) in almost all cases. This finding underlines the importance of early victim recovery and identification procedures. The genetic samples used for biogeographical estimate were also analyzed by applying morphological methods developed on populations allegedly comparable to those of the origin of the victims. The estimates were then compared with the genetic results obtained. With regard to geographical ancestry, the predictions of the OSSA method appear to coincide with the group with probability percentages related to the higher estimate resulting from the hefneR software. However, the low number of OSSA findings does not allow for any additional considerations to be made. As far as the non-metric dental characters are concerned, the results of the analysis with the rASUDAS software show little agreement with the cranial morphological predictions, referring in this sense only to the hefneR method: the OSSA score, in fact, contrary to the first two, does not consider the Asian population among the reference population and is therefore less expendable in terms of comparison. The comparison with the predictions of biogeographical origin using Y-STR polymorphisms showed a certain pattern of agreement only with the estimates obtained by the hefneR method. The opportunity to confirm what was observed on a larger sample and when the identification process is completed would be an ambitious goal for future research. In conclusion, the present research made it possible to identify the potentially most suitable methods for geographical origin estimation, opening new perspectives in the identification process of the unknown victims of the Mediterranean. The availability of accurate anthropological and odontological methods can complement genetic analysis investigations. In this sense, the comparison of suspicious identities can be restricted to individuals from a specific geographical area, just as the search for relatives can be directed to certain African countries and thus suitable reference data can be selected for genetic comparison. In addition, knowing any links between the state of preservation of the remains and the quality of the genetic material stored in it may allow the selection of the most suitable portion of bone and/or protocols for subsequent genetic investigations

Sirtuins, aging, and cardiovascular risks

4noThe sirtuins comprise a highly conserved family proteins present in virtually all species from bacteria to mammals. Sirtuins are members of the highly conserved class III histone deacetylases, and seven sirtuin genes (sirtuins 1-7) have been identified and characterized in mammals. Sirtuin activity is linked to metabolic control, apoptosis, cell survival, development, inflammation, and healthy aging. In this review, we summarize and discuss the potential mutual relations between each sirtuin and cardiovascular health and the impact of sirtuins on oxidative stress and so age-related cardiovascular disorders, underlining the possibility that sirtuins will be novel targets to contrast cardiovascular risks induced by aging.openopenFavero, Gaia; Franceschetti, Lorenzo; Rodella, Luigi Fabrizio; Rezzani, RitaFavero, Gaia; Franceschetti, Lorenzo; Rodella, Luigi Fabrizio; Rezzani, Rit

Function computation via subspace coding

This paper considers function computation in a network where intermediate nodes perform randomized network coding, through appropriate choice of the subspace codebooks at the source nodes. Unlike traditional network coding for computing functions, that requires intermediate nodes to be aware of the function to be computed, our designs are transparent to the intermediate node operations

Metabolic syndrome and melatonin: a tool for prevent obesity-associated abnormalities

Obesity is a common and complex health problem, which impacts crucial organs; it is also considered an independent risk factor for chronic kidney disease [1]. Few studies have analyzed the consequence of obesity in the renal proximal convoluted tubules, the major section of the reabsorptive process. To best perform its functions, the kidney requires energy primarily provided by mitochondria. Melatonin, indoleamine and antioxidant, has been identified in mitochondria, and overwhelming evidence has documented its essential role in the prevention of oxidative mitochondrial damage [2]. Herein, we evaluated the mechanism(s) of mitochondrial alterations in an animal model of obesity (ob/ob mice) and describe the beneficial effects of melatonin treatment on mitochondria morphology and dynamics as influenced by mitofusin- 2 and the intrinsic apoptotic cascade. Melatonin was dissolved in 1% ethanol and added to the drinking water from postnatal week 5 to 13; the calculated dose of melatonin intake was 100 mg/kg body weight/day. Compared to control mice, obesity-induced morphological alterations were apparent in the proximal tubules; the tubules contained round mitochondria with irregular, short cristae and the lining cells excited and elevated apoptotic index. Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria- driven intrinsic apoptotic pathway. The results aid in reducing renal failure. The melatonin-mediated changes probably suggest the use of melatonin to protect against renal morphological damage and dysfunction during metabolic disease

Sirtuin 6 localization at cortical brain level of young diabetic mice

The metabolic syndrome, characterized by visceral obesity, dyslipidaemia, hyperglycaemia and hypertension, has become one of the major public-health challenges worldwide and it is strictly associated with the development of type II diabetes and neurodegenerative diseases (Alberti et al. 2005; Panza et al. 2010). Increased metabolic flux to the brain during overnutrition can orchestrate stress response, blood-brain barrier alteration, microglial cells activation and neuroinflammation (Nerurkar et al., 2011). The protein sirtuin family is a class of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that act on a variety of targets and so play a key role in central physiological regulation (Sebastian et al., 2012; Wang et al., 2012). To assess the physiopathological significance of sirtuin6 (SIRT6) at brain cortical level, we analysed its specific expression and subcellular localization in young db/db mice, animal model of type II diabetes mellitus, and respective control lean mice. In particular, we analysed the cytoarchitecture of the brain cortex, evaluated SIRT6 expression and its localization by immunohistochemistry comparing young db/db mice to lean control mice, distinguishing among the six cortical layers and between motor and somatosensory cortex. We observed that SIRT6 is mainly localized in the nucleus of both lean and db/db mice. Diabetic mice showed few SIRT6 positive cells respect to lean control mice in all cortical layers without significant differences between motor and somatosensory cortex. No morphological alteration have been find. In conclusion, our findings contribute to further understand SIRT6 protein expression in the early steps of type II diabetes mellitus and suggest its implication in the pathogenic processes of diabetes mellitus and diabetes–induced neurodegeneration