The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor... more The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation
Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by b... more Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. Methodology/Principal Findings: Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1) specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. Conclusions/Significance: The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replicati...
Introduction: The article describes a post-discharge telephone Follow-Up pilot project that was a... more Introduction: The article describes a post-discharge telephone Follow-Up pilot project that was activated in 2018 in the city of Trieste. Methods: The pilot project, in addition to the interception of possible situations of discomfort to be reported to social services and to ensure informative support to guide people to an optimal use of services, aimed to investigate the conditions, 1 and 3 months after discharge, of people not followed by the community services, in particular: a) maintenance of functional capacity; b) self-assessment of the patient with respect to health conditions and level of engagement; c) state of the relationships network; d) use of public, private and/or third sector health or welfare resources. Results and Conclusions: The Telephone Follow-Up has made it possible to experiment a “light” way of taking care of people discharged from a hospital or rehabilitation facility, to intercept situations of discomfort, reporting them to the Local District and social se...
In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets... more In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets of TDP-43, a nuclear factor involved in neurodegeneration. A common outcome of all these studies is that changing the expression levels of this protein can alter the expression of several hundred RNAs within cells. What still remains to be clarified is which changes represent direct cellular targets of TDP-43 or just secondary variations due to the general role played by this protein in RNA metabolism. Using an HTS-based splicing junction analysis we identified at least six bona fide splicing events that are consistent with being controlled by TDP-43. Validation of the data, both in neuronal and non-neuronal cell lines demonstrated that TDP-43 substantially alters the levels of isoform expression in four genes potentially important for neuropathology: MADD/IG20, STAG2, FNIP1 and BRD8. For MADD/IG20 and STAG2, these changes could also be confirmed at the protein level. These alterations were also observed in a cellular model that successfully mimics TDP-43 loss of function effects following its aggregation. Most importantly, our study demonstrates that cell cycle alterations induced by TDP-43 knockdown can be recovered by restoring the STAG2, an important component of the cohesin complex, normal splicing profile.
The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor... more The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation
Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by b... more Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. Methodology/Principal Findings: Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1) specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. Conclusions/Significance: The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replicati...
Introduction: The article describes a post-discharge telephone Follow-Up pilot project that was a... more Introduction: The article describes a post-discharge telephone Follow-Up pilot project that was activated in 2018 in the city of Trieste. Methods: The pilot project, in addition to the interception of possible situations of discomfort to be reported to social services and to ensure informative support to guide people to an optimal use of services, aimed to investigate the conditions, 1 and 3 months after discharge, of people not followed by the community services, in particular: a) maintenance of functional capacity; b) self-assessment of the patient with respect to health conditions and level of engagement; c) state of the relationships network; d) use of public, private and/or third sector health or welfare resources. Results and Conclusions: The Telephone Follow-Up has made it possible to experiment a “light” way of taking care of people discharged from a hospital or rehabilitation facility, to intercept situations of discomfort, reporting them to the Local District and social se...
In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets... more In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets of TDP-43, a nuclear factor involved in neurodegeneration. A common outcome of all these studies is that changing the expression levels of this protein can alter the expression of several hundred RNAs within cells. What still remains to be clarified is which changes represent direct cellular targets of TDP-43 or just secondary variations due to the general role played by this protein in RNA metabolism. Using an HTS-based splicing junction analysis we identified at least six bona fide splicing events that are consistent with being controlled by TDP-43. Validation of the data, both in neuronal and non-neuronal cell lines demonstrated that TDP-43 substantially alters the levels of isoform expression in four genes potentially important for neuropathology: MADD/IG20, STAG2, FNIP1 and BRD8. For MADD/IG20 and STAG2, these changes could also be confirmed at the protein level. These alterations were also observed in a cellular model that successfully mimics TDP-43 loss of function effects following its aggregation. Most importantly, our study demonstrates that cell cycle alterations induced by TDP-43 knockdown can be recovered by restoring the STAG2, an important component of the cohesin complex, normal splicing profile.
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