THE MOLLUSCAN ASSEMBLAGES IN THE FLUVIO-LACUSTRINE SUCCESSION OF THE PLIO-PLEISTOCENE MUGELLO BASIN (TUSCANY, ITALY)

New geologic studies on the fluvio-lacustrine Mugello Basin (Florence, Italy) stimulated a revision of the continental molluscan assemblages known since the last century. The fluvio-lacustrine succession has been subdivided in four synthems composed of fluvio-lacustrine (Torrente Ensa synthem, STE) and alluvial deposits (Scarperia, Luco di Mugello and Sagginale synthems). Two progressive angular unconformities in the STE allowed to distinguish three depositional sequences (S1, S2 and S3) composed of fan-delta gravels and sands, lacustrine silty clays (S1 and S2) and alluvial-fan gravels and sands (S3). Molluscs have been collected in various localities where S1 and S2 fan-delta and lacustrine deposits are exposed. The paleoecologic analysis of the molluscan assemblages is in accordance with the fluvio-lacustrine environment inferred from facies analysis. Different types of humid habitats, ranging from swamps, ponds, to channel-related environments (banks, leeves etc.), and open woody habitats have been recognized. The presence of Villafranchian extinct taxa such as Prososthenia oblonga, Emmericia cf. umbra and Tournouerina belnensis is in general agreement with the vertebrate fauna collected in the fluvio-lacustrine deposits since the last century and referred to the Tasso and Farneta faunal units (Late Villafranchian). A detailed integrated analysis of a 15 m thick gravelly-silty facies section of the S2 sequence reveals alternating depositional conditions in the subaerial portion of the fan deltas. Following a relative rise of base-level (i.e the lake level) flood-channels were disactivated with the formation of a floodplain-like environment dominated by fine-grained deposition, where localized poorly-drained areas created favourable habitats for molluscan taxa loving humid conditions. The sourrounding zones were characterized by open forests inhabited by terrestrial taxa. Low-magnitude, overland flows mixed the molluscan faunas of the different biotopes. The cyclic arrangement of gravels and silty clays reflects high-frequency uplift/denudational cycles during which biotopes for the molluscan fauna were alternatively activated.   SHORT NOTE

La progettazione personalizzata nelle nuove misure di contrasto alla povert\ue0 (RES-REI) in Emilia-Romagna: Ottanta studi di caso

The paper deals with the implementation of the new measures of minimum income in a Northern Region in Italy (Emilia-Romagna). The Inclusion income (Rei) and the Solidarity income (Res) both provide a cash transfer conditioned to the agreement on a project to activate their recipients. Focusing on 80 case studies, this paper underscores interesting clues on the effects of these projects on work and social inclusion status of recipients

Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop.

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting

Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia.

Approximately 18% of acute myeloid leukemia (AML) cases express a fusion transcript. However, few fusions are recurrent across AML and the identification of these rare chimeras is of interest to characterize AML patients. Here, we studied the transcriptome of 8 adult AML patients with poorly described chromosomal translocation(s), with the aim of identifying novel and rare fusion transcripts. We integrated RNA-sequencing data with multiple approaches including computational analysis, Sanger sequencing, fluorescence in situ hybridization and in vitro studies to assess the oncogenic potential of the ZEB2-BCL11B chimera. We detected 7 different fusions with partner genes involving transcription factors (OAZ-MAFK, ZEB2-BCL11B), tumor suppressors (SAV1-GYPB, PUF60-TYW1, CNOT2-WT1) and rearrangements associated with the loss of NF1 (CPD-PXT1, UTP6-CRLF3). Notably, ZEB2-BCL11B rearrangements co-occurred with FLT3 mutations and were associated with a poorly differentiated or mixed phenotype leukemia. Although the fusion alone did not transform murine c-Kit+ bone marrow cells, 45.4% of 14q32 non-rearranged AML cases were also BCL11B-positive, suggesting a more general and complex mechanism of leukemogenesis associated with BCL11B expression. Overall, by combining different approaches, we described rare fusion events contributing to the complexity of AML and we linked the expression of some chimeras to genomic alterations hitting known genes in AML

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Architettura e forma urbana. Mirandola come città per parti.

Sostituzione di tessuto urbano nella città di Mirandola. Tentativo di ridefinizione dell'identità del viale di collegamento fra centro storico e stazione attraverso lo studio della teoria della città per parti

La progettazione personalizzata nelle nuove misure di contrasto alla povertà (RES-REI) in Emilia-Romagna. Ottanta studi di caso

The paper deals with the implementation of the new measures of minimum income in a Northern Region in Italy (Emilia-Romagna). The Inclusion income (Rei) and the Solidarity income (Res) both provide a cash transfer conditioned to the agreement on a project to activate their recipients. Focusing on 80 case studies, this paper underscores interesting clues on the effects of these projects on work and social inclusion status of recipients

Synergism Through WEE1 and CHK1 Inhibition in Acute Lymphoblastic Leukemia

Introduction: Screening for synthetic lethality markers has demonstrated that the inhibition of the cell cycle checkpoint kinases WEE1 together with CHK1 drastically affects stability of the cell cycle and induces cell death in rapidly proliferating cells. Exploiting this finding for a possible therapeutic approach has showed efficacy in various solid and hematologic tumors, though not specifically tested in acute lymphoblastic leukemia. Methods: The efficacy of the combination between WEE1 and CHK1 inhibitors in B and T cell precursor acute lymphoblastic leukemia (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the therapeutic strategy was tested in terms of cytotoxicity, induction of apoptosis, and changes in cell cycle profile and protein expression using B/T-ALL cell lines. In addition, the efficacy of the drug combination was studied in primary B-ALL blasts using clonogenic assays. Results: This study reports, for the first time, the efficacy of the concomitant inhibition of CHK1/CHK2 and WEE1 in ALL cell lines and primary leukemic B-ALL cells using two selective inhibitors: PF-0047736 (CHK1/CHK2 inhibitor) and AZD-1775 (WEE1 inhibitor). We showed strong synergism in the reduction of cell viability, proliferation and induction of apoptosis. The efficacy of the combination was related to the induction of early S-phase arrest and to the induction of DNA damage, ultimately triggering cell death. We reported evidence that the efficacy of the combination treatment is independent from the activation of the p53-p21 pathway. Moreover, gene expression analysis on B-ALL primary samples showed that Chek1 and Wee1 are significantly co-expressed in samples at diagnosis (Pearson r = 0.5770, p = 0.0001) and relapse (Pearson r= 0.8919; p = 0.0001). Finally, the efficacy of the combination was confirmed by the reduction in clonogenic survival of primary leukemic B-ALL cells. Conclusion: Our findings suggest that the combination of CHK1 and WEE1 inhibitors may be a promising therapeutic strategy to be tested in clinical trials for adult ALL