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

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

The use of Open Reading frame ESTs (ORESTES) for analysis of the honey bee transcriptome

BACKGROUND: The ongoing efforts to sequence the honey bee genome require additional initiatives to define its transcriptome. Towards this end, we employed the Open Reading frame ESTs (ORESTES) strategy to generate profiles for the life cycle of Apis mellifera workers. RESULTS: Of the 5,021 ORESTES, 35.2% matched with previously deposited Apis ESTs. The analysis of the remaining sequences defined a set of putative orthologs whose majority had their best-match hits with Anopheles and Drosophila genes. CAP3 assembly of the Apis ORESTES with the already existing 15,500 Apis ESTs generated 3,408 contigs. BLASTX comparison of these contigs with protein sets of organisms representing distinct phylogenetic clades revealed a total of 1,629 contigs that Apis mellifera shares with different taxa. Most (41%) represent genes that are in common to all taxa, another 21% are shared between metazoans (Bilateria), and 16% are shared only within the Insecta clade. A set of 23 putative genes presented a best match with human genes, many of which encode factors related to cell signaling/signal transduction. 1,779 contigs (52%) did not match any known sequence. Applying a correction factor deduced from a parallel analysis performed with Drosophila melanogaster ORESTES, we estimate that approximately half of these no-match ESTs contigs (22%) should represent Apis-specific genes. CONCLUSIONS: The versatile and cost-efficient ORESTES approach produced minilibraries for honey bee life cycle stages. Such information on central gene regions contributes to genome annotation and also lends itself to cross-transcriptome comparisons to reveal evolutionary trends in insect genomes

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

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

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)

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Temporally Regulated Traffic of HuR and Its Associated ARE-Containing mRNAs from the Chromatoid Body to Polysomes during Mouse Spermatogenesis

International audienceBACKGROUND: In mammals, a temporal disconnection between mRNA transcription and protein synthesis occurs during late steps of germ cell differentiation, in contrast to most somatic tissues where transcription and translation are closely linked. Indeed, during late stages of spermatogenesis, protein synthesis relies on the appropriate storage of translationally inactive mRNAs in transcriptionally silent spermatids. The factors and cellular compartments regulating mRNA storage and the timing of their translation are still poorly understood. The chromatoid body (CB), that shares components with the P. bodies found in somatic cells, has recently been proposed to be a site of mRNA processing. Here, we describe a new component of the CB, the RNA binding protein HuR, known in somatic cells to control the stability/translation of AU-rich containing mRNAs (ARE-mRNAs). METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of cell imagery and sucrose gradient fractionation, we show that HuR localization is highly dynamic during spermatid differentiation. First, in early round spermatids, HuR colocalizes with the Mouse Vasa Homolog, MVH, a marker of the CB. As spermatids differentiate, HuR exits the CB and concomitantly associates with polysomes. Using computational analyses, we identified two testis ARE-containing mRNAs, Brd2 and GCNF that are bound by HuR and MVH. We show that these target ARE-mRNAs follow HuR trafficking, accumulating successively in the CB, where they are translationally silent, and in polysomes during spermatid differentiation. CONCLUSIONS/SIGNIFICANCE: Our results reveal a temporal regulation of HuR trafficking together with its target mRNAs from the CB to polysomes as spermatids differentiate. They strongly suggest that through the transport of ARE-mRNAs from the CB to polysomes, HuR controls the appropriate timing of ARE-mRNA translation. HuR might represent a major post-transcriptional regulator, by promoting mRNA storage and then translation, during male germ cell differentiation