L'uomo e il cosmo nella storia: paradigmi, miti, simboli

L’idea del convegno L’Uomo e il Cosmo nella storia. Paradigmi, miti, simboli, che ha visto riuniti attorno allo stesso tavolo studiosi di discipline che ai più possono sembrare molto distanti tra di loro, nasce dal desiderio di interscambio di prospettive, di saperi e metodologie di indagine tra il mondo delle scienze umane e quello delle cosiddette scienze dure e dalla convinzione che tale scambio possa essere propulsivo di una diffusa e non settoriale crescita culturale e sociale. Nella consapevolezza che la relazione dell’essere umano con lo spazio e il tempo e con le sue rappresentazioni sia talmente centrale che nessuna attività umana, dalla più pratica alla più astratta, può prescinderne, ci siamo voluti inter- rogare su quali fossero le relazioni e i rapporti che l’essere umano, nel corso del tempo, ma anche all’interno delle diverse culture, ha istaurato con la sua idea di cosmo e come questa idea abbia influenzato le società umane a diversi livelli, anche da un punto di vista sociale e politico. L’obiettivo non è semplicemente quello di fare storia della cultura, quanto piuttosto quello di finalizzare il dibattito verso la contemporaneità. Abbiamo infatti voluto comprendere come la cosmologia scientifica moderna, proponendo comunque un modello di mondo, descrivendone l’origine e prospettandone la fine, incida, interagendo con esso, sull’immaginario collettivo a diversi livelli

Caenorhabditis elegans Cyclin D/CDK4 and Cyclin E/CDK2 Induce Distinct Cell Cycle Re-Entry Programs in Differentiated Muscle Cells

Cell proliferation and differentiation are regulated in a highly coordinated and inverse manner during development and tissue homeostasis. Terminal differentiation usually coincides with cell cycle exit and is thought to engage stable transcriptional repression of cell cycle genes. Here, we examine the robustness of the post-mitotic state, using Caenorhabditis elegans muscle cells as a model. We found that expression of a G1 Cyclin and CDK initiates cell cycle re-entry in muscle cells without interfering with the differentiated state. Cyclin D/CDK4 (CYD-1/CDK-4) expression was sufficient to induce DNA synthesis in muscle cells, in contrast to Cyclin E/CDK2 (CYE-1/CDK-2), which triggered mitotic events. Tissue-specific gene-expression profiling and single molecule FISH experiments revealed that Cyclin D and E kinases activate an extensive and overlapping set of cell cycle genes in muscle, yet failed to induce some key activators of G1/S progression. Surprisingly, CYD-1/CDK-4 also induced an additional set of genes primarily associated with growth and metabolism, which were not activated by CYE-1/CDK-2. Moreover, CYD-1/CDK-4 expression also down-regulated a large number of genes enriched for catabolic functions. These results highlight distinct functions for the two G1 Cyclin/CDK complexes and reveal a previously unknown activity of Cyclin D/CDK-4 in regulating metabolic gene expression. Furthermore, our data demonstrate that many cell cycle genes can still be transcriptionally induced in post-mitotic muscle cells, while maintenance of the post-mitotic state might depend on stable repression of a limited number of critical cell cycle regulators

Ultra diffuse galaxies in the Hydra I cluster from the LEWIS Project: Phase-Space distribution and globular cluster richness

Although ultra diffuse galaxies (UDGs) are found in large numbers in clusters of galaxies, the role of the cluster environment in shaping their low surface brightness and large sizes is still uncertain. Here we examine a sample of UDGs in the Hydra I cluster (D = 51 Mpc) with new radial velocities obtained as part of the LEWIS (Looking into the faintest with MUSE) project using VLT/MUSE data. Using a phase-space, or infall diagnostic, diagram we compare the UDGs to other known galaxies in the Hydra I cluster and to UDGs in other clusters. The UDGs, along with the bulk of regular Hydra I galaxies, have low relative velocities and are located near the cluster core, and thus consistent with very early infall into the cluster. Combining with literature data, we do not find the expected trend of GC-rich UDGs associated with earlier infall times. This result suggests that quenching mechanisms other than cluster infall should be further considered, e.g. quenching by strong feedback or in cosmic sheets and filaments. Tidal stripping of GCs in the cluster environment also warrants further modelling.Comment: 6 pages, 2 figures, MNRAS, 525, 9

Context-Dependent Requirement for dE2F during Oncogenic Proliferation

The Hippo pathway negatively regulates the cell number in epithelial tissue. Upon its inactivation, an excess of cells is produced. These additional cells are generated from an increased rate of cell division, followed by inappropriate proliferation of cells that have failed to exit the cell cycle. We analyzed the consequence of inactivation of the entire E2F family of transcription factors in these two settings. In Drosophila, there is a single activator, dE2F1, and a single repressor, dE2F2, which act antagonistically to each other during development. While the loss of the activator dE2F1 results in a severe impairment in cell proliferation, this defect is rescued by the simultaneous loss of the repressor dE2F2, as cell proliferation occurs relatively normally in the absence of both dE2F proteins. We found that the combined inactivation of dE2F1 and dE2F2 had no significant effect on the increased rate of cell division of Hippo pathway mutant cells. In striking contrast, inappropriate proliferation of cells that failed to exit the cell cycle was efficiently blocked. Furthermore, our data suggest that such inappropriate proliferation was primarily dependent on the activator, de2f1, as loss of de2f2 was inconsequential. Consistently, Hippo pathway mutant cells had elevated E2F activity and induced dE2F1 expression at a point when wild-type cells normally exit the cell cycle. Thus, we uncovered a critical requirement for the dE2F family during inappropriate proliferation of Hippo pathway mutant cells

BRCA1/2 Molecular Assay for Ovarian Cancer Patients: A Survey through Italian Departments of Oncology and Molecular and Genomic Diagnostic Laboratories

In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for BRCA1/2. The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the intersociety survey coordinated by four different Clinical and Laboratory Italian Scientific Societies (AIOM, SIAPEC-IAP, SIBIOC, and SIGU). A multidisciplinary team belonging to the four scientific societies drew up two different questionnaires: One was targeted toward all Italian Departments of Medical Oncology, and the second toward laboratories of clinical molecular biology. This survey was implemented from September 2017 to March 2018. Seventy-seven out of 305 (25%) Departments of Medical Oncology filled our survey form. Indeed, 59 molecular laboratories were invited. A total of 41 laboratories (70%) filled in the questionnaire. From 2014 to 2017, 16 new molecular laboratories were activated. A total of 12,559 tests were performed in the year 2016, with a mean of 339 tests and a median of 254 tests per laboratory, showing a glimpse of an extreme low number of tests performed per year by some laboratories. In terms of the type and number of professionals involved in the pre- and post-test counseling, results among the onco-genetic team were heterogeneous. Our data show that the number of laboratories providing BRCA1/2 germline assays is significantly increased with further implementation of the somatic test coming soon. The harmonization of the complete laboratory diagnostic path should be encouraged, particularly in order to reduce the gap between laboratories with high and low throughput

Fly-FUCCI: A Versatile Tool for Studying Cell Proliferation in Complex Tissues

One promising approach for in vivo studies of cell proliferation is the FUCCI system (fluorescent ubiquitination-based cell cycle indicator). Here, we report the development of a Drosophila-specific FUCCI system (Fly-FUCCI) that allows one to distinguish G1, S, and G2 phases of interphase. Fly-FUCCI relies on fluorochrome-tagged degrons from the Cyclin B and E2F1 proteins, which are degraded by the ubiquitin E3-ligases APC/C and CRL4Cdt2, during mitosis or the onset of S phase, respectively. These probes can track cell-cycle patterns in cultured Drosophila cells, eye and wing imaginal discs, salivary glands, the adult midgut, and probably other tissues. To support a broad range of experimental applications, we have generated a toolkit of transgenic Drosophila lines that express the Fly-FUCCI probes under control of the UASt, UASp, QUAS, and ubiquitin promoters. The Fly-FUCCI system should be a valuable tool for visualizing cell-cycle activity during development, tissue homeostasis, and neoplastic growth. Note: Graphical abstract on articl

Looking into the faintEst WIth MUSE (LEWIS): on the nature of ultra-diffuse galaxies in the Hydra-I cluster.I. Project description and preliminary results

Looking into the faintEst WIth MUSE (LEWIS) is an ESO large observing programme aimed at obtaining the first homogeneous integral-field spectroscopic survey of 30 extremely low-surface brightness (LSB) galaxies in the Hydra I cluster of galaxies, with MUSE at ESO-VLT. The majority of LSB galaxies in the sample (22 in total) are ultra-diffuse galaxies (UDGs). The distribution of systemic velocities Vsys ranges between 2317 km/s and 5198 km/s and is centred on the mean velocity of Hydra I (Vsys = 3683 $\pm$ 46 km/s). Considering the mean velocity and the velocity dispersion of the cluster, 17 out of 20 targets are confirmed cluster members. To assess the quality of the data and demonstrate the feasibility of the science goals, we report the preliminary results obtained for one of the sample galaxies, UDG11. For this target, we derived the stellar kinematics, including the 2-dimensional maps of line-of-sight velocity and velocity dispersion, constrained age and metallicity, and studied the globular cluster (GC) population hosted by the UDG. Results are compared with the available measurements for UDGs and dwarf galaxies in literature. By fitting the stacked spectrum inside one effective radius, we find that UDG11 has a velocity dispersion $\sigma = 20 \pm 8$ km/s, it is old ($10\pm1$ Gyr), metal-poor ([M/H]=-1.17$\pm$0.11 dex) and has a total dynamical mass-to-light ratio M$/L_V\sim 14$, comparable to those observed for classical dwarf galaxies. The spatially resolved stellar kinematics maps suggest that UDG11 does not show a significant velocity gradient along either major or minor photometric axes. We find two GCs kinematically associated with UDG11. The estimated total number of GCs in UDG11, corrected for the spectroscopic completeness limit, is $N_{GC}= 5.9^{+2.2}_ {-1.8}$, which corresponds to a GC specific frequency of $S_N = 8.4^{+3.2}_{-2.7}$.Comment: Accepted for publication in Astronomy and Astrophysic

Notch and Prospero Repress Proliferation following Cyclin E Overexpression in the Drosophila Bristle Lineage

Understanding the mechanisms that coordinate cell proliferation, cell cycle arrest, and cell differentiation is essential to address the problem of how “normal” versus pathological developmental processes take place. In the bristle lineage of the adult fly, we have tested the capacity of post-mitotic cells to re-enter the cell cycle in response to the overexpression of cyclin E. We show that only terminal cells in which the identity is independent of Notch pathway undergo extra divisions after CycE overexpression. Our analysis shows that the responsiveness of cells to forced proliferation depends on both Prospero, a fate determinant, and on the level of Notch pathway activity. Our results demonstrate that the terminal quiescent state and differentiation are regulated by two parallel mechanisms acting simultaneously on fate acquisition and cell cycle progression

Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria

This work was supported by the Medical Research Council (MR/L002876/1), the Royal College of Surgeons of England, Fondazione Telethon Italy (GGP10058), and Associazione Italiana Malati di Alcaptonuria (AimAKU, ORPHA263402