SIGNOR 3.0, the SIGnaling network open resource 3.0: 2022 update

The SIGnaling Network Open Resource (SIGNOR 3.0, ) is a public repository that captures causal information and represents it according to an 'activity-flow' model. SIGNOR provides freely-accessible static maps of causal interactions that can be tailored, pruned and refined to build dynamic and predictive models. Each signaling relationship is annotated with an effect (up/down-regulation) and with the mechanism (e.g. binding, phosphorylation, transcriptional activation, etc.) causing the regulation of the target entity. Since its latest release, SIGNOR has undergone a significant upgrade including: (i) a new website that offers an improved user experience and novel advanced search and graph tools; (ii) a significant content growth adding up to a total of approx. 33,000 manually-annotated causal relationships between more than 8900 biological entities; (iii) an increase in the number of manually annotated pathways, currently including pathways deregulated by SARS-CoV-2 infection or involved in neurodevelopment synaptic transmission and metabolism, among others; (iv) additional features such as new model to represent metabolic reactions and a new confidence score assigned to each interaction

Myc Promoter-Binding Protein-1 (MBP-1) Is a Novel Potential Prognostic Marker in Invasive Ductal Breast Carcinoma

Background Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. \u3b1-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP) to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of \u3b1-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken. Methodology and Findings We analyzed \u3b1-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC) from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-\u3b1-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic \u3b1-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC. Conclusions MBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer

Theranostic biomarkers and PARP-inhibitors effectiveness in patients with non-BRCA associated homologous recombination deficient tumors: Still looking through a dirty glass window?

: Breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2) deleterious variants were the first and, still today, the main biomarkers of poly(ADP)ribose polymerase (PARP)-inhibitors (PARPis) benefit. The recent, increased, numbers of individuals referred for counseling and multigene panel testing, and the remarkable expansion of approved PARPis, not restricted to BRCA1/BRCA2-Pathogenic Variants (PVs), produced a strong clinical need for non-BRCA biomarkers. Significant limitations of the current testing and assays exist. The different approaches that identify the causes of Homologous Recombination Deficiency (HRD), such as the germline and somatic Homologous Recombination Repair (HRR) gene PVs, the testing showing its consequences, such as the genomic scars, or the novel functional assays such as the RAD51 foci testing, are not interchangeable, and should not be considered as substitutes for each other in clinical practice for guiding use of PARPi in non-BRCA, HRD-associated tumors. Today, the deeper knowledge on the significant relationship among all proteins involved in the HRR, not limited to BRCA, expands the possibility of a successful non-BRCA, HRD-PARPi synthetic lethality and, at the same time, reinforces the need for enhanced definition of HRD biomarkers predicting the magnitude of PARPi benefit

Práticas artísticas no ensino básico e secundário

A educação artística passa por circunstâncias paradoxais, que se originam na sua essencialidade plástica: o desenho cada vez é menos praticado no papel e cada vez é mais praticado no ecrã. A experiência plástica do corpo a corpo, da “afinidade” através da convenientia, da aemulatio, da analogia, e das simpatias (Foucault), pode já ser cada vez mais reduzida, ou mesmo residual. Hoje a experiência digital antecede a experiência analógica desde a mais tenra idade, e este é um novo contexto que nos mostra águas desconhecidas. Haverá uma “fraqueza analógica” contemporânea? Como fundar uma experiência quando o digital já quase antecede o analógico, na educação e no desenvolvimento da criança?Como compreender o desconhecido com base no desconhecido? Diga-se, no mínimo, que em Educação Artística, a Matéria-Prima complicou-se. Os 18 artigos aqui presentes dão um contributo vivo para uma reflexão, tanto sobre a sua operacionalização como sobre a sua concetualização, atenta às contradições e paradoxos, disponível para os novos contributos, as novas intervenções.info:eu-repo/semantics/publishedVersio

Arylamino Esters As P-Glycoprotein Modulators: SAR Studies to Establish Requirements for Potency and Selectivity

A set of basic aryl-group-containing compounds was synthesized with the aim of developing potent and selective P-glycoprotein (P-gp) modulators that are able to reverse multidrug resistance (MDR). The natures of the spacer (dicyclohexylamine or dialkylamine) and the aryl moieties were modified to investigate selectivity and the mechanism of P-gp interaction. The inhibitory activities of the compounds toward P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), the most relevant ATP binding cassette (ABC) transporters for MDR, were evaluated. The mechanism of P-gp interaction for each compound was investigated with three biological assays: apparent permeability (Papp ) determination (B→A/A→B) in Caco-2 cell monolayers, ATP cell depletion, and inhibition of Calcein-AM transport in MDCK-MDR1 cells. These assays allowed us to estimate the selectivity of the compounds for the three efflux pumps and to identify the structural requirements that define the P-gp-interaction profile. All dicyclohexylamine derivatives were found to be P-gp substrates, whereas one dialkylamine derivative was shown to be a P-gp inhibitor. The good MRP1 activity of one cis/cis isomer highlighted this as a lead candidate for the development of MRP1 ligands

Servizi di base per le biblioteche delle università

È opinione ormai largamente condivisa che gli elementi essenziali per il buon funzionamento di un sistema bibliotecario moderno e automatizzato siano, da un lato, un catalogo on-line (OPAC) completo ed integrato nei moderni sistemi di ricerca in Rete, dall’altro infrastrutture informatiche dedicate ai servizi di biblioteca, che siano flessibili e ricche di funzionalità. L’adozione diffusa di strumenti informatici sempre più evoluti in questo settore esprime la crescente consapevolezza, che gli atenei ed i centri di ricerca, hanno rispetto alla centralità dei servizi di biblioteca. Grazie alle molteplici collaborazioni con il mondo delle biblioteche ed al conseguente sviluppo dei servizi ad esse associati, il CASPUR, nell’arco di un decennio, è divenuto un punto di riferimento per questo settore

SERVIZI DI AUTOMAZIONE PER LE BIBLIOTECHE

Le biblioteche, da oltre un ventennio, offrono alla propria utenza servizi che vengono “declinati” attraverso strumenti informatici sempre più avanzati e interconnessi con quelli di ricerca e di information retrieval. Dai primi sistemi dedicati alla catalogazione informatica, si è passati ai cataloghi on-line (OPAC) e agli strumenti di “ricerca federata”, fino ad arrivare a portali personalizzati sul singolo utente. Dall’elenco in rete delle riviste cartacee disponibili in biblioteca, si è giunti ai primi esempi di riviste on-line, per approdare alle moderne strutture di archivi istituzionali e di biblioteche digitali. Interessante notare, quindi, come buona partedell’evoluzione tecnologica in campo informatico e di ingegneria dei sistemi si sia di fatto realizzata nel contesto “culturalmente vivace” del mondo delle biblioteche. Il CASPUR, per sua naturale inclinazione e per statuto, ha sempre speso notevoli risorse in questo specifico settore, sia dal punto di vista delle risorse umane impiegate che da quello delle risorse economiche investite. L’esperienza e il credito acquisito nel settore delle biblioteche universitarie e della Pubblica Amministrazione, la numerosità dei servizi offerti e le diverse collaborazioni avviate, sia nel pubblico che nel privato, con altri “fornitori” di analoghi servizi sono prova del buon lavoro fin’ora svolto

Risk Factors for Anaplastic Thyroid Carcinoma: A Case Series From a Tertiary Referral Center for Thyroid Surgery and Literature Analysis

Anaplastic thyroid carcinoma (ATC) is a very rare and extremely aggressive disease with a very poor prognosis. Several risk factors have been hypothesized, but there is no clear-cut literature data on it. We reviewed the literature concerning risk factors for ATC and analyzed the institutional database from 2005 to 2022. In total, 15 papers were suitable for review, while the retrospective data collection search, conducted on our institutional database, provided 13 results. In our experience, in agreement with literature data, ATC seems to be a neoplasm peculiar to old age (in our database, mean age is 72 years), with a higher prevalence in subjects with a low level of education and a long history of multinodular goiter (MNG). The role of cigarette smoking and blood group, hypothesized on some literature data, was more uncertain, although the small sample size evaluated probably had a great influence on these results. The higher incidence of the disease in individuals with a history of MNG could suggest more aggressive choices in the treatment of a benign disease, in contrast to current practice. However, this may be a highly questionable point considering that ATC accounts for no more than 2% of all thyroid neoplasms in surgical departments, even those dedicated to endocrine neck surgery. Further studies are therefore necessary for a step forward in this direction