TDP-43 regulates the Microprocessor complex activity during in vitro neuronal differentiation

TDP-43 is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events. In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression. Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate-specificity of the microprocessor complex and provide new insights onto TDP-43 as a key player in neuronal differentiation

The Building Information Model and the IFC standard: analysis of the characteristics necessary for the acoustic and energy simulation of buildings

The new European Directive 2014/24 / EU requires for all member States the use of BIM procedures in the construction of public buildings. The countries belonging to the European Union shall be obliged to transpose the Directive and adapt their procedures to that effect. The paper analyzes the IFC format, the only recognized by the European Directive Standards for BIM procedures, in order to assess its use for simulations of buildings. IFC, described by the ISO 16739 (2013), is today a standard that describes the topology of the constructive elements of the building and what belongs to it overall. The format includes geometrical information on the room and on all building components, including details of the type for performance (transmittance, fire resistance, sound insulation), in other words it is an independent object file for the software producers to which, according to the European Directive, it will be compulsory to refer in the near future, during the different stages of the life of a building from the design phase, to management and possible demolition at the end of life. The IFC initiative began in 1994, when an industry consortium invested in the development of a set of C ++ classes that can support the development of integrated applications. Twelve US companies joined the consortium: these companies that were included initially are called the consortium "Industry Alliance for Interoperability". In September 1995 the Alliance opened up membership to all interested parties, and in 1997 changed its name to "International Alliance for Interoperability". The new alliance was reconstituted as a non-profit organization, with the aim of developing and promoting the '' Industry Foundation Class "(IFC) as a neutral data model for the building product that were useful to gather information throughout the life cycle of a building facility. Since 2005 the Alliance has been carrying out its activities through its national chapters called SMART building. The present study aims at evaluating the IFC, comparing the information and data contained in it, with other formats already used for energy simulations of buildings such as the gbXML (Green Building XML), highlighting the missing required information and proposing the inclusion of new ones to issue the energy and acoustic simulation. More generally the attention is focused to building physics simulation software devoted to exploit the BIM model potential enabling interoperability

Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration

Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes. We previously identified the founding member of the Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication. Here we report the discovery of the CG3303 gene product, which we named DendoU, as a novel family member in Drosophila. Functional characterisation revealed that DendoU is essential for Drosophila viability and nervous system activity. Pan-neuronal silencing of dendoU resulted in fly immature phenotypes, highly reduced lifespan and dramatic motor performance defects. Neuron-subtype selective silencing showed that DendoU is particularly important in cholinergic circuits. At the molecular level, we unveiled that DendoU is a positive regulator of the neurodegeneration-associated protein dTDP-43, whose downregulation recapitulates the ensemble of dendoU-dependent phenotypes. This interdisciplinary work, which comprehends in silico, in vitro and in vivo studies, unveils a relevant role for DendoU in Drosophila nervous system physio-pathology and highlights that DendoU-mediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function

Perioperative care in elderly patients undergoing thyroid surgery

AbstractThe features of western world population are rapidly changing. The increment geriatric population obliges clinicians to implement specific recommendations and guidelines to manage these patients.In the field of thyroid surgery, when indications are represented by benign conditions, surgeons and endocrinologists tent to avoid surgery for the increased perioperative risks in the over 70 year old population.We reviewed our experience in thyroid surgery in geriatric patients within the environment of a “week surgery unit”. This unit was conceived to offer a highly specialized setting for thyroid patients needing short stay after surgery.Results showed that the surgical outcomes were comparable to the ones from third surgery in young patients.The week surgery approach is the best and safest formula to offer to the geriatric population needing thyroid surgery

Ct-Guided Pancreatic Percutaneous Fine-needle Biopsy in Differential Diagnosis Between Pancreatic Cancer and Chronic Pancreatitis

Differential diagnosis between pancreatic cancer and chronic pancreatitis is still difficult to establish. In 63 patients with suspected pancreatic neoplasm we performed: serum CA 19-9 assessment, abdominal ultrasound, CT scan and CT-guided pancreatic percutaneous fine-needle biopsy. The conclusive diagnosis was pancreatic cancer in 40 patients and chronic pancreatitis in 23 patients. With regard to the differential diagnosis, sensitivity and specificity were respectively 80% and 78% for serum CA 19-9, 75% and 65% for abdominal US, 85% and 70% for CT scan, 00% and 87% for percutaneous fine-needle biopsy. We conclude that CT-guided percutaneous fine-needle biopsy is the most reliable method for differential diagnosis between pancreatic cancer and chronic pancreatitis

The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity

Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA-induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p, miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de-repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic expression in the aggressive Group 3 MB cells attenuates their proliferation, migration and invasion. This study unveils the first lncRNA-based ceRNA network in central nervous system tumours and provides a novel molecular circuit underlying the enigmatic Group 4 medulloblastoma