Marche Polytechnic University

About: Marche Polytechnic University is a education organization based out in Ancona, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 5905 authors who have published 15769 publications receiving 382286 citations. The organization is also known as: Universitá Politecnica delle Marche & Universita Politecnica delle Marche.

Impairment of TrkB-PSD-95 Signaling in Angelman Syndrome

Abstract: Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction.

Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis

Abstract: Background Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression.

The adipose organ: white-brown adipocyte plasticity and metabolic inflammation.

Abstract: White adipocytes can store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions are contained in multiple fat depots forming the adipose organ. In this review, we outline the plasticity of this organ in physiological (cold exposure, physical exercise and lactation) and pathological conditions (obesity). We also highlight molecules and signalling pathways involved in the browning phenomena of white adipose tissue. This phenotypic change has proved to be effective in the protection against the metabolic disorders associated to obesity and diabetes, not only because brown adipocytes are more 'healthy' than white adipocytes, but also because the simple size reduction of white adipocytes that characterizes the first steps of transdifferentiation can be useful in determining how to avoid triggering death based on critical size and the consequent chronic low-grade inflammation due to macrophage infiltration. Thus, a better understanding of the molecular mechanisms at the basis of white-brown transdifferentiation can be extremely useful to exploit new therapeutic strategies to combat the increasing incidence of metabolic diseases.

Algae lacking carbon-concentrating mechanisms

Abstract: Most of the algae and cyanobacteria that have been critically examined express a carbon-concentrating mechanism (CCM) when grown at, or below, the current atmospheric CO2 concentration. This paper considers algae that appear to lack a CCM. Critical examination of the evidence on which the presence or absence of a CCM is de- cided shows that more information is frequently needed before the criteria can be fully applied. Examples are the path- ways of glycolate metabolism in nongreen algae, and the 13 C/ 12 C discrimination shown by form ID Rubisco in vitro. The available evidence suggests that the algae lacking CCMs are some terrestrial green microalgae, some florideophyte freshwater red macroalgae, and a number of florideophyte red macroalgae from the supralittoral, littoral, and sublittoral, and almost all of the freshwater chrysophytes and synurophytes examined. Certain environmental, biochemi- cal, and biophysical factors may permit the occurrence of algae lacking CCMs. The absence of CCMs is presumably the plesiomorphic (i.e., ancestral) condition in cyanobacteria (and algae?). Resume : La plupart des algues et des cyanobacteries, qui ont ete examinees attentivement, possedent un mecanisme de concentration du carbone (CCM), lorsqu'elles sont cultivees a des concentrations de CO2 egales ou inferieures a celle de l'atmosphere. Les auteurs examinent ici les algues qui n'ont pas de CCM. Un examen critique des preuves sur lesquelles la presence ou l'absence d'un CCM est reconnue, montre qu'il faut souvent plus d'informations avant que le critere puisse etre applique. Par exemple, on note les sentiers metaboliques du glycolate chez les algues nonvertes, et la discrimination des 13 C/ 12 C manifestee par la forme ID de la Rubisco. Les preuves actuelles suggerent que les algues qui n'ont pas de CCM sont certaines microalgues vertes terrestres, certaines macro-algues rouges florideophytes d'eau douce, et un nombre de macroalgues rouges florideophytes du supralittoral, du littoral et du sublittoral, ainsi que la plupart des chrysophytes et des synurophytes d'eau douce examinees. Certains facteurs environnementaux, biochimiques et biophysiques peuvent permettre la presence d'algues depourvues de CCM. L'absence de CCM constitue vraisembla- blement la condition plesiomorphe (c.-a-d. ancestrale), chez les cyanobacteries. Mots cles : diffusion du CO2, algues chrysophytes, ecologie, evolution, algues vertes, photosynthese, algues rouges. (Traduit par la Redaction) Raven et al. 890

Therapeutic Failures of Antibiotics Used To Treat Macrolide-Susceptible Streptococcus pyogenes Infections May Be Due to Biofilm Formation

Abstract: Streptococcus pyogenes infections often fail to respond to antibiotic therapy, leading to persistent throat carriage and recurrent infections. Such failures cannot always be explained by the occurrence of antibiotic resistance determinants, and it has been suggested that S. pyogenes may enter epithelial cells to escape antibiotic treatment. We investigated 289 S. pyogenes strains isolated from different clinical sources to evaluate their ability to form biofilm as an alternative method to escape antibiotic treatment and host defenses. Up to 90% of S. pyogenes isolates, from both invasive and noninvasive infections, were able to form biofilm. Specific emm types, such as emm6, appeared to be more likely to produce biofilm, although variations within strains belonging to the same type might suggest biofilm formation to be a trait of individual strains rather than a general attribute of a serotype. Interestingly, erythromycin-susceptible isolates formed a significantly thicker biofilm than resistant isolates (P < 0.05). Among resistant strains, those carrying the erm class determinants formed a less organized biofilm than the mef(A)-positive strains. Also, prtF1 appeared to be negatively associated with the ability to form biofilm (P < 0.01). Preliminary data on a selection of strains indicated that biofilm-forming isolates entered epithelial cells with significantly lower efficiency than biofilm-negative strains. We suggest that prtF1-negative macrolide-susceptible or mef(A)-carrying isolates, which are poorly equipped to enter cells, may use biofilm to escape antimicrobial treatments and survive within the host. In this view, biofilm formation by S. pyogenes could be responsible for unexplained treatment failures and recurrences due to susceptible microorganisms.