MAGNETOSTRATIGRAPHIC DATA ON THE FIRST COLONIZATION OF EUROPE BY EARLY HOMININS DURING THE LATE EARLY PLEISTOCENE.

It is generally accepted in the paleoanthropological literature that the colonization of Europe by early hominins, intended as Homo erectus derived forms such as Homo heidelbergensis, occurred before the last magnetic polarity reversal that is dated back to 0.78 Ma and marks the transition form the Matuyama reversal polarity chron to the actual normal polarity chron known as Brunhes. The still ongoing debate concerns the possibility for early hominins to have firmly settled in Europe before 1 Million years ago. All the European sites presenting proper chronologies put the first convincing evidence of human occupation during the latter part of the Matuyama reverse polarity chron spanning from the top of Jaramillo normal polarity subchron (0.99 Ma) to the base of the Brunhes normal polarity chron (0.78 Ma). It seems therefore plausible that the first stable human residents came to Europe during the latter part of the Matuyama reverse polarity chron. This relatively brief period of time coincided with a major reorganization of the changing environmental conditions in Europe and elsewhere known as the Early late Pleistocene climate Revolution (EPR). The EPR coincided with the onset of the major Pleistocene glaciation in the Northern hemisphere that triggered the modification of the drainage patterns and consequently brought the formation of the modern fluvial systems especially the Danube in Eastern Europe and the Po in Italy. These environmental changes brought to the formation of new habitats characterized by lowlands colonized by grasslands during glacial/interglacial transitions, while steppic loess environments characterized full glacial periods and closed temperate forests full interglacial periods. The EPR caused also a faunal turnover as a consequence to the environmental changes, species adapted to a closed forest environment belonging to the so-called Villafranchian faunal association were substituted with species more adapted to the newly formed environments belonging to the so-called Galerian faunal association. It seems probable that the opening of the Danube-Po getaway constituted a fundamental element for the migrations of these animals and of early hominins to take place from Africa/Levant across the Balkans into southern Europe since MIS 22. After providing an initial review of the chronology presented for the sites manifesting human occupation of the Mediterranean area we investigated five new sites in order to provide new evidences that will substantiate the hypothesis of the colonization of Europe by early hominins not antecedent the EPR following the Danube-Po migration pathway. The first site is the Arda river section in northern Italy that provides a continuous record of the transition from marine sedimentation typical of the Pliocene-Early Pleistocene to late Early Pleistocene-Holocene continental sedimentation. Even though no human evidences have yet be found in this locality the discovery mammal layer with a mixed Villafranchian-Galerian faunal assemblage just preceding the EPR proves the first contact that occurred between these two faunal associations. The second investigated site is Kostolac, in Serbia, that even thus not revealing any evidence of human occupation, strongly supports the \u201cfollow the herd\u201d hypothesis since it yields the first occurrence of the Mammuthus trogontherii in the Pannonian region just before the Brunhes-Matuyama boundary at the bottom of a loessic sequence. This suggests that the first income of this species in the investigated region occurred just after the EPR taking advantage of the Danube-Po gateway. The third presented site is the stratigraphic sequence from the cave of Kozarnika in Northern Bulgaria. Evidences of human occupation of the cave are known throughout the entire stratigraphic sequence as far down as the bottom of the loess deposit that is located between the Jaramillo normal magnetic polarity subchron and the Brunhes normal polarity. The acquired data strongly support the idea that the income of hominins in the investigated region started with MIS 22 along the Danube drainage system from the Black sea into Europe. The fourth investigated site it the Greek site of Megalopolis where an archeological site bearing a specimen of Elephas antiquus with slaughtering evidences lies in an alternation between lignite and sediment levels. The Brunhes-Matuyama boundary lies at the bottom of the sequence but there is no evidence yet of human occupation of the area during the critic time lapse for this study. Strong evidence of the connection between the variation in the deposited facies and the glacial-interglacial cycles was observed therefore we dated the archeological site back to 3c450 ky. The last investigated site is the deposit of the Prince\u2019s cave near Ventimiglia (Northern Italy), where a preneanderthalian human ilium was found in a complex stratigraphic context. Only normal magnetic polarity, interpreted as the Brunhes chron, was observed throughout the entire sequence that was therefore attributed to the middle Pleistocene. Evidences on the oldest units deposited in the cave jointly with the uplift rates for that region suggest that the cave was probably submerged during the EPR and therefore no human frequentation was possible in this site before MIS 7. Except for the Prince\u2019s cave deposit, whose age resulted being to young, all the other sites give evidences of the colonization of Europe by early hominins not antecedent MIS 22 following the Danube-Po migration pathway, therefore supporting the central role of the EPR in the first stable peopling of the European continent

Ecce Homo in Milan

Come ogni essere vivente anche l\u2019uomo ha colonizzato gli habitat solo nel momento in cui questi presentavano le condizioni favorevoli alla sua sopravvivenza. La colonizzazione del continente europeo \ue8 avvenuta molto probabilmente da Est verso Ovest e l\u2019ingresso in Italia pu\uf2 essere avvenuto solo dal punto pi\uf9 comodo in cui si poteva superare la catena Alpina, ossia passando dai Balcani (Figura 2). Dal record geologico si deduce il susseguirsi di periodi caldi a periodi freddi durante tutto il Pleistocene, tuttavia non ci sono evidenze di un passaggio ad un clima glaciale nel nostro paese prima del Pleistocene Superiore. Questo cambiamento ha come prima conseguenza l\u2019espansione delle calotte glaciali legata all\u2019intrappolamento dell\u2019acqua degli oceani e il conseguente abbassamento del livello del mare che provoca il passaggio di molte zone precedentemente sommerse prima ad un ambiente litorale e inne emerso. Questo \ue8 quanto si \ue8 vericato in Pianura Padana. Il cambiamento di ambiente ha provocato una variazione nel materiale che si stava depositando: prima si avevano limi e sabbie marine, poi ciottoli legati al trasporto uviale e materiale ne legato alle esondazioni dei umi. La dierenza nel materiale deposto \ue8 stata riconosciuta lungo tutta la Pianura Padana ed \ue8 stata nominata Discontinuit\ue0 R. La Discontinuit\ue0 R \ue8 quindi legata a un cambiamento nel clima, e all\u2019istaurarsi delle grandi glaciazioni nel continente europeo. Mediante lo studio di diverse carote prelevate in Pianura Padana \ue8 stato possibile creare un modello di et\ue0 che ha permesso di associare la Discontinuit\ue0 R al MIS22, datandola a circa 870.000 anni fa (Figura 1). Il MIS22 corrisponde inoltre alla ne della cosiddetta \u201cRivoluzione del Pleistocene Medio\u201d, un momento in cui si \ue8 assistito ad un cambiamento nella ora con la comparsa delle prime piante legate all\u2019ambiente glaciale, ma anche ad un cambiamento nella fauna legato all\u2019arrivo di specie come il mammuth (Mammuthus meridionalis), l\u2019elefante antico (Elephas antiquus), e il rinoceronte lanoso (Coelodonta antiquitatis). La nostra ipotesi \ue8 che l\u2019arrivo dell\u2019uomo in Europa e in Italia sia stato legato alla sua tendenza a seguire le onde migratorie degli animali che costituivano le sue principali prede (Figura 2), e che sia avvenuto in concomitanza con l\u2019instaurarsi delle grandi glaciazioni Pleistocenica, ossia attorno all\u2019et\ue0 del MIS22

Magnetostratigrafia della serie Pleistocenica di Castell’Arquato (PC)

Abbiamo presentato i risultati preliminari relativi all'indagine magnetostratigrafica della sezione affiorante nel torrente Arda (PC) da cui \ue8 poi stato ricavato l'articolo Monesi et al., (21016

Magnetostratigraphic and chronostratigraphic constraints on the Marathousa 1 Lower Palaeolithic site and the Middle Pleistocene deposits of the Megalopolis basin, Greece

We investigated the magnetostratigraphy of the Megalopolis basin in central Peloponnese, Greece, which encompasses a record of Pleistocene lacustrine and lignite-bearing sedimentation, where lithic tools stratigraphically associated with remnants of an almost complete skeleton of Palaeoloxodon antiquus were recently found at the Marathousa 1 site. A magnetic polarity reversal was observed within a 3c10 m-thick lignite seam at the base of the (exposed) stratigraphic sequence, and it was interpreted as a record of the Brunhes/Matuyama boundary (0.78 Ma). Assuming that lignite seams were deposited generally under warm and humid climate conditions, this finding is in agreement with data from the literature indicating that the Brunhes/Matuyama boundary occurs within warm Marine Isotope Stage (MIS) 19. We then attempted to correlate the remainder of the lacustrine and lignite-bearing intervals above the Brunhes/Matuyama boundary to a standard oxygen isotope record of Pleistocene climate variability. Two age models of sedimentation were generated: according to preferred option #1, the artifact-bearing stratigraphic units of the Marathousa 1 site should have an age between 3c0.48 Ma and 3c0.42 Ma, while according to alternative option #2, the archaeological layers would have an age between 3c0.56 Ma and 3c0.54 Ma. Option #1 is at present considered the preferred option as it is in closer agreement with preliminary post-IR IRSL and ESR dates from the Marathousa 1 site. This age model has been exported to other areas of the Megalopolis basin, where additional archaeological and/or palaeontological sites could be present, by means of correlations to lithostratigraphic logs derived from commercial drill cores taken in the 1960s and 1970s for lignite exploitation

All-cause mortality and estimated renal function in type 2 diabetes mellitus outpatients: is there a relationship with the equation used?

BACKGROUND: We investigated the relationship between serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), evaluated by different formulae, and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) outpatients. METHODS: This observational cohort study considered 1365 T2DM outpatients, who had been followed up for a period of up to 11 years. eGFR was estimated using several equations. RESULTS: Seventy subjects (5.1%) died after a follow-up of 9.8 ± 3 years. Univariate analysis showed that diagnosis of nephropathy (odds ratio (OR): 2.554, 95% confidence interval (CI): 1.616-4.038, p < 0.001) and microvascular complications (OR: 2.281, 95% CI: 1.449-3.593, p < 0.001) were associated with ACM. Receiving operating characteristic (ROC) curves showed that the areas under the curve for ACM were similar using the different eGFR equations. eGFR values were predictors of ACM, and the hazard ratios (HRs) of the different equations for eGFR estimation were similar. CONCLUSION: In our cohort of T2DM outpatients, different eGFR equations perform similarly in predicting ACM, whereas SCr did not

Meiotic silencing and fragmentation of the male germline restricted chromosome in zebra finch

During male meiotic prophase in mammals, X and Y are in a largely unsynapsed configuration, which is thought to trigger meiotic sex chromosome inactivation (MSCI). In avian species, females are ZW, and males ZZ. Although Z and W in chicken oocytes show complete, largely heterologous synapsis, they too undergo MSCI, albeit only transiently. The W chromosome is already inactive in early meiotic prophase, and inactive chromatin marks may spread on to the Z upon synapsis. Mammalian MSCI is considered as a specialised form of the general meiotic silencing mechanism, named meiotic silencing of unsynapsed chromatin (MSUC). Herein, we studied the avian form of MSUC, by analysing the behaviour of the peculiar germline restricted chromosome (GRC) that is present as a single copy in zebra finch spermatocytes. In the female germline, this chromosome is present in two copies, which normally synapse and recombine. In contrast, during male meiosis, the single GRC is always eliminated. We found that the GRC in the male germline is silenced from early leptotene onwards, similar to the W chromosome in avian oocytes. The GRC remains largely unsynapsed throughout meiotic prophase I, although patches of SYCP1 staining indicate that part of the GRC may self-synapse. In addition, the GRC is largely devoid of meiotic double strand breaks. We observed a lack of the inner centromere protein INCENP on the GRC and elimination of the GRC following metaphase I. Subsequently, the GRC forms a micronucleus in which the DNA is fragmented. We conclude that in contrast to MSUC in mammals, meiotic silencing of this single chromosome in the avian germline occurs prior to, and independent of DNA double strand breaks and chromosome pairing, hence we have named this phenomenon meiotic silencing prior to synapsis (MSPS)

A mathematical model for determining age-specific diabetes incidence and prevalence using body mass index

PurposeFew models have been developed specifically for the epidemiology of diabetes. Diabetes incidence is critical in predicting diabetes prevalence. However, reliable estimates of disease incidence rates are difficult to obtain. The aim of this study was to propose a mathematical framework for predicting diabetes prevalence using incidence rates estimated within the model using body mass index (BMI) data.MethodsA generic mechanistic model was proposed considering birth, death, migration, aging, and diabetes incidence dynamics. Diabetes incidence rates were determined within the model using their relationships with BMI represented by the Hill equation. The Hill equation parameters were estimated by fitting the model to National Health and Nutrition Examination Survey (NHANES) 1999-2010 data and used to predict diabetes prevalence pertaining to each NHANES survey year. The prevalences were also predicted using diabetes incidence rates calculated from the NHANES data themselves. The model was used to estimate death rate parameters and to quantify sensitivities of prevalence to each population dynamic.ResultsThe model using incidence rate estimates from the Hill equations successfully predicted diabetes prevalence of younger, middle-aged, and older adults (prediction error, 20.0%, 9.64%, and 7.58% respectively). Diabetes prevalence was positively associated with diabetes incidence in every age group, but the associations among younger adults were stronger. In contrast, diabetes prevalence was more sensitive to death rates in older adults than younger adults. Both diabetes incidence and prevalence were strongly sensitive to BMI at younger ages, but sensitivity gradually declined as age progressed. Younger and middle aged adults diagnosed with diabetes had at least a two-fold greater risk of death than their nondiabetic counterparts. Nondiabetic older adults were found to be under slightly higher death risk (0.079) than those diagnosed with diabetes (0.073).ConclusionsThe proposed model predicts diagnosed diabetes incidence and prevalence reasonably well using the link between BMI and diabetes development risk. Ethnic group and gender-specific model parameter estimates could further improve predictions. Model prediction accuracy and applicability need to be comprehensively evaluated with independent data sets

Identification of unannotated exons of low abundance transcripts in Drosophila melanogaster and cloning of a new serine protease gene upregulated upon injury

<p>Abstract</p> <p>Background</p> <p>The sequencing of the <it>D.melanogaster </it>genome revealed an unexpected small number of genes (~ 14,000) indicating that mechanisms acting on generation of transcript diversity must have played a major role in the evolution of complex metazoans. Among the most extensively used mechanisms that accounts for this diversity is alternative splicing. It is estimated that over 40% of <it>Drosophila </it>protein-coding genes contain one or more alternative exons. A recent transcription map of the <it>Drosophila </it>embryogenesis indicates that 30% of the transcribed regions are unannotated, and that 1/3 of this is estimated as missed or alternative exons of previously characterized protein-coding genes. Therefore, the identification of the variety of expressed transcripts depends on experimental data for its final validation and is continuously being performed using different approaches. We applied the Open Reading Frame Expressed Sequence Tags (ORESTES) methodology, which is capable of generating cDNA data from the central portion of rare transcripts, in order to investigate the presence of hitherto unnanotated regions of <it>Drosophila </it>transcriptome.</p> <p>Results</p> <p>Bioinformatic analysis of 1,303 <it>Drosophila </it>ORESTES clusters identified 68 sequences derived from unannotated regions in the current <it>Drosophila </it>genome version (4.3). Of these, a set of 38 was analysed by polyA⁺northern blot hybridization, validating 17 (50%) new exons of low abundance transcripts. For one of these ESTs, we obtained the cDNA encompassing the complete coding sequence of a new serine protease, named SP212. The <it>SP212 </it>gene is part of a serine protease gene cluster located in the chromosome region 88A12-B1. This cluster includes the predicted genes CG9631, CG9649 and CG31326, which were previously identified as up-regulated after immune challenges in genomic-scale microarray analysis. In agreement with the proposal that this <it>locus </it>is co-regulated in response to microorganisms infection, we show here that SP212 is also up-regulated upon injury.</p> <p>Conclusion</p> <p>Using the ORESTES methodology we identified 17 novel exons from low abundance <it>Drosophila </it>transcripts, and through a PCR approach the complete CDS of one of these transcripts was defined. Our results show that the computational identification and manual inspection are not sufficient to annotate a genome in the absence of experimentally derived data.</p

Blood component therapy and coagulopathy in trauma: A systematic review of the literature from the trauma update group

Background Traumatic coagulopathy is thought to increase mortality and its treatment to reduce preventable deaths. However, there is still uncertainty in this field, and available literature results may have been overestimated. Methods We searched the MEDLINE database using the PubMed platform. We formulated four queries investigating the prognostic weight of traumatic coagulopathy defined according to conventional laboratory testing, and the effectiveness in reducing mortality of three different treatments aimed at contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios, fibrinogen, and tranexamic acid administration). Randomized controlled trials were selected along with observational studies that used a multivariable approach to adjust for confounding. Strict criteria were adopted for quality assessment based on a two-step approach. First, we rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Then, this rating was downgraded if other three criteria were not met: high reporting quality according to shared standards, absence of internal methodological and statistical issues not detailed by the GRADE system, and absence of external validity issues. Results With few exceptions, the GRADE rating, reporting and methodological quality of observational studies was "very low", with frequent external validity issues. The only two randomized trials retrieved were, instead, of high quality. Only weak evidence was found for a relation between coagulopathy and mortality. Very weak evidence was found supporting the use of fibrinogen administration to reduce mortality in trauma. On the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality reduction. This does not exclude lower mortality rates, which have not been investigated. The use of tranexamic acid in trauma was supported by "high" quality evidence according to the GRADE classification but was downgraded to "moderate" for external validity issues. Conclusions Tranexamic acid is effective in reducing mortality in trauma. The other transfusion practices we investigated have been inadequately studied in the literature, as well as the independent association between mortality and coagulopathy measured with traditional laboratory testing. Overall, in this field of research literature quality is poor

Oligoasthenoteratozoospermia and Infertility in Mice Deficient for miR-34b/c and miR-449 Loci

Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation) are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA) gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449) that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility