LINKING NMDA RECEPTOR-DEPENDENT PLASTICITY AND NEURONAL ARCHITECTURE: THE ROLE OF RING FINGER PROTEIN 10

An active synapse-to-nucleus communication is essential for long-term changes in neurons, like the regulation of neuronal plasticity and shaping neuronal morphology. Next to the fast electrochemical signaling, neurons employ a slower mechanism that involves a recently discovered class of proteins, the synaptonuclear messengers. Different studies showed the pivotal role of synaptonuclear messengers in the modulation of synaptic transmission at excitatory synapses. On the other hand, alterations of synaptonuclear messengers\u2019 activity have been correlated to synaptic failure as observed in different synaptopathies, including both neurodevelopmental disorders and neurodegenerative diseases. Ring Finger Protein 10 (RNF10) has been recently identified as a novel synapse-to-nucleus signaling protein that specifically links the activation of synaptic GluN2A-containing NMDA receptors (NMDARs) to gene expression. RNF10 synaptonuclear trafficking is responsible for the remodeling of dendritic spines that substance the postsynaptic modifications required for long-term potentiation (LTP). However, the molecular mechanisms leading to NMDAR/RNF10 complex disruption and for initiating the importin-mediated trafficking of RNF10 to the nucleus remain unclear. In this PhD project we investigated the molecular mechanisms that underlie RNF10 activation and in this matter we discovered a protein kinase C (PKC)-dependent phosphorylation event on RNF10-Ser31, which drives RNF10 synaptonuclear trafficking. Moreover, we show that pSer31-RNF10 plays a role both in synaptonuclear signaling and in neuronal morphology. In particular, the prevention of Ser31 RNF10 phosphorylation induces a decrease in spine density, neuronal branching, and CREB signaling, while opposite effects are obtained by mimicking a stable RNF10 phosphorylation at Ser31.Based on these results, we investigated the role of RNF10 in vivo, in the RNF10-/- mouse model. In particular we studied the putative involvement of the synaptonuclear protein in neurodevelopment, focusing our attention on the first three weeks of postnatal life, which represents the critical period for neuronal differentiation and synaptogenesis in rodents. We found that RNF10-/- mice have an alteration in brain morphology, in particular in the hippocampal area, and impaired cognition. At a microscopic level, RNF10-/- deficiency alters the molecular composition and the morphology of the glutamatergic synapse. In the CA1 region of the Hippocampus, dendritic arborization of RNF10-/- neurons is severely reduced and LTP induction is compromised. Overall, these results add novel information about the functional and structural role of synaptonuclear protein messengers in shaping dendritic architecture and regulating synaptic plasticity in hippocampal neurons. \u200

Siderophilin Metal Coordination. 1. Complexation of Thorium by Transferrin: Structure-Function Implications

As part of a program to develop actinide-specific sequestering agents, the coordination of actinide ions by human transferrin is being investigated. Therapeutically useful synthetic ligands must be able to compete with this iron-transport protein for the bound actinide ion. As in the Fe(III) complex of the native protein, two Th(IV) ions bind at pH 7. This coordination has been monitored at several pH values by using difference ultraviolet spectroscopy. The corresponding coordination of a phenolic ligand, ethylene-bis-(o-hydroxyphenylglycine) [EHPG], has been used to determine {Delta}{epsilon} for a tyrosyl group coordinated to Th(IV), in contrast to the common practice of assuming the {Delta}{epsilon} for protons and all metal ions is the same. This in turn is used to determine, from the observed {Delta}{epsilon} upon protein coordination, the number of transferrin tyrosine residues that coordinate. Maxima in the Th(IV) + EHPG difference UV spectra occur at 292 and 238 nm, with corresponding {Delta}{epsilon} values per phenolic group of 2330 and 8680 cm{sup -1} M{sup -1}, respectively. At pH 7.2, the Th(IV) transferrin spectrum is closely similar to the TH(IV) EHPG spectrum, with maxima at 292 and 240 nm. The {Delta}{epsilon} at 240 nm reaches a maximum of 24700 cm{sup -1} M{sup -1}, which corresponds to coordination of three tyrosine residues in the dithorium-transferrin complex; the stronger binding site (“A” or C-terminal) coordinates via two tyrosines and the weaker (“B” or N-terminal) via one. There is evidence suggesting that the N-terminal site is slightly smaller than the C-terminal site; while Th(IV) easily fits into the C-terminal site, the large ionic radius of Th(IV) makes this ion of borderline size to fit into the N-terminal site. This may be an important biological difference between Th(IV) and the slightly smaller Pu(IV), which should easily fit into both sites. At pH values below 7, the complexation of Th(IV) by transferrin decreases rapidly. At pH 6 and a Th(IV)/transferrin ratio of 2, only ~0.3 Th(IV) are bound per protein ([Th] = 10{sup -5}M). The N-terminal site is more rapidly affected by lowering the pH, so that coordination is entirely at the C-terminal site at low pH. Above pH 9, the conformation at the C-terminal site (two tyrosines) changes such that only one tyrosine is bound, the same that pertains at the N-terminal site at neutral pH. In addition to the three protons released by the coordinating tyrosine residues, the complexation of two Th(IV) ions releases two more protons at pH 8.6, which are ascribed to hydrolysis, so that the metal is bound as a monohydroxo species. It is suggested that diferric transferrin undergoes a similar reaction, and the other implications of these results for the structure and function of the native ferric transferrin are discussed

Hydrodynamics and Nonlocal Conductivities in Vortex States of Type II Superconductors

A hydrodynamical description for vortex states in type II superconductors is presented based on the time-dependent Ginzburg-Landau equation (TDGL). In contrast to the familiar extension of a single vortex dynamics based on the force balance, our description is consistent with the known hydrodynamics of a rotating neutral superfluid and correctly includes informations on the Goldstone mode. Further it enables one to examine nonlocal conductivities perpendicular to the magnetic field in terms of Kubo formula. The nonlocal conductivities deviate from the usual vortex flow expressions typically when the nonlocality parallel to the field becomes weaker than the perpendicular one measuring a degree of positional correlations, and, for instance, the superconducting contribution of dc Hall conductivity nonlocal only in directions perpendicular to the field becomes vanishingly small in the situations with large shear viscosity, leading to an experimentally measurable relation $\rho_{xy} \sim {\rho_{xx}^2}$ among the total resistivity components. Other situations are also discussed on the basis of the resulting expressions.Comment: 12 pages, no figures, to appear in J. Phys. Soc. Jpn. in October, 199

Legacy of COVID‐19 – the opportunity to enhance surgical services for patients with colorectal disease

Description to be added.Cannot be left empt

Annotated checklist of the birds of Brazil by the Brazilian Ornithological Records Committee-second edition

An updated version of the checklist of birds of Brazil is presented, along with a summary of the changes approved by the Brazilian Ornithological Records Committee's Taxonomy Subcommittee since the first edition, published in 2015. In total, 1971 bird species occurring in Brazil are supported by documentary evidence and are admitted to the Primary List, 4.3% more than in the previous edition. Eleven additional species are known only from undocumented records (Secondary List). For each species on the Primary List, status of occurrence in the country is provided and, in the case of polytypic species, the respective subspecies present in Brazilian territory are listed. Explanatory notes cover taxonomic changes, nomenclatural corrections, new occurrences, and other changes implemented since the last edition. Ninety species are added to the Primary List as a result of species descriptions, new occurrences, taxonomic splits, and transfers from the Secondary List due to the availability of documentation. In contrast, eight species are synonymized or assigned subspecific status and thus removed from the Primary List. In all, 293 species are endemic to Brazil, ranked third among the countries with the highest rate of bird endemism. The Brazilian avifauna currently consists of 1742 residents or breeding migrants, 126 seasonal non-breeding visitors, and 103 vagrants. The category of vagrants showed the greatest increase (56%) compared to the previous list, mainly due to new occurrences documented in recent years by citizen scientists. The list updates the diversity, systematics, taxonomy, scientific and vernacular nomenclature, and occurrence status of birds in Brazil.Peer reviewe

Degradation of Cdc25A by \u3b2-TrCP during S phase and in response to DNA damage

The Cdc25A phosphatase is essential for cell-cycle progression because of its function in dephosphorylating cyclin-dependent kinases. In response to DNA damage or stalled replication, the ATM and ATR protein kinases activate the checkpoint kinases Chk1 and Chk2, which leads to hyperphosphorylation of Cdc25A1\u20133. These events stimulate the ubiquitin-mediated pro- teolysis of Cdc25A1,4,5 and contribute to delaying cell-cycle progression, thereby preventing genomic instability1\u20137. Here we report that b-TrCP is the F-box protein that targets phosphory- lated Cdc25A for degradation by the Skp1/Cul1/F-box protein complex. Downregulation of b-TrCP1 and b-TrCP2 expression by short interfering RNAs causes an accumulation of Cdc25A in cells progressing through S phase and prevents the degradation of Cdc25A induced by ionizing radiation, indicating that b-TrCP may function in the intra-S-phase checkpoint. Consistent with this hypothesis, suppression of b-TrCP expression results in radioresistant DNA synthesis in response to DNA damage\u2014a phenotype indicative of a defect in the intra-S-phase checkpoint that is associated with an inability to regulate Cdc25A properly. Our results show that b-TrCP has a crucial role in mediating the response to DNA damage through Cdc25A degradation

Ubiquitin sets the timer: impacts on aging and longevity

Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals

Clinical practice guidelines of the European Association for Endoscopic Surgery (EAES) on bariatric surgery: update 2020 endorsed by IFSO-EC, EASO and ESPCOP

Background: Surgery for obesity and metabolic diseases has been evolved in the light of new scientific evidence, long-term outcomes and accumulated experience. EAES has sponsored an update of previous guidelines on bariatric surgery. Methods: A multidisciplinary group of bariatric surgeons, obesity physicians, nutritional experts, psychologists, anesthetists and a patient representative comprised the guideline development panel. Development and reporting conformed to GRADE guidelines and AGREE II standards. Results: Systematic review of databases, record selection, data extraction and synthesis, evidence appraisal and evidence-to-decision frameworks were developed for 42 key questions in the domains Indication; Preoperative work-up; Perioperative management; Non-bypass, bypass and one-anastomosis procedures; Revisional surgery; Postoperative care; and Investigational procedures. A total of 36 recommendations and position statements were formed through a modified Delphi procedure. Conclusion: This document summarizes the latest evidence on bariatric surgery through state-of-the art guideline development, aiming to facilitate evidence-based clinical decisions

The Fossil Calibration Database—A New Resource for Divergence Dating

Fossils provide the principal basis for temporal calibrations, which are critical to the accuracy of divergence dating analyses. Translating fossil data into minimum and maximum bounds for calibrations is the most important—often least appreciated—step of divergence dating. Properly justified calibrations require the synthesis of phylogenetic, paleontological, and geological evidence and can be difficult for nonspecialists to formulate. The dynamic nature of the fossil record (e.g., new discoveries, taxonomic revisions, updates of global or local stratigraphy) requires that calibration data be updated continually lest they become obsolete. Here, we announce the Fossil Calibration Database (http://fossilcalibrations.org), a new open-access resource providing vetted fossil calibrations to the scientific community. Calibrations accessioned into this database are based on individual fossil specimens and follow best practices for phylogenetic justification and geochronological constraint. The associated Fossil Calibration Series, a calibration-themed publication series at Palaeontologia Electronica, will serve as a key pipeline for peer-reviewed calibrations to enter the databas