This study indicates that disconnection precedes GM atrophy in the PCC, which is a critical area of the DMN, and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflects a long term effect of brain disconnection. In this context, our study indicates that GM atrophy in PCC accompanies the conversion from MCI to AD.

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA A receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.

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We have studied the complexation process taking place in cationic liposomes in the presence of anionic polyelectrolytes, in the polyion concentration range from the dilute to the concentrated regime, by combining dynamic light scattering and transmission electron microscopy techniques. We employed as the cationic lipid a two-chained amphiphile (Dioleoyltrimethylammoniumpropane) and sodium polyacrylate salt as the flexible anionic polyelectrolyte. The results evidence a variety of different structures, mainly depending on the liposome-polyion charge ratio, whose peculiar dynamical and structural features are briefly described. In particular, three different polyion concentration regions are found, within which a monomodal or bimodal distribution of aggregates, with a well-defined time evolution, is present. At low polyion content, close to the isoelectric point, large aggregates are formed, deriving from the collapse of the liposomal bilayers into extended charged surfaces, where adsorbed polyions form a two-dimensional strongly correlated array and organize into a two-dimensional Wigner liquid. At high polyion content, above a critical concentration, the size distributions of the complexes are clearly bimodal and a large-component aggregate, continuously increasing with time, coexists with a population of smaller-size aggregates. At an intermediate polyion concentration, spherical, small-size vesicular structures are reformed, connected in a network by polymer chains. A brief discussion tries to summarize our results into a consistent picture.

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

No abstract

The d.c. electrical conductivity of polyacrylate sodium salt and poly(acrylic acid) aqueous solutions of different molecular weights from 2 to 200 kD has been investigated in a wide range of polymer concentration, covering both the semidilute (unentangled and entangled) and concentrated regimes. The data have been analyzed on the basis of a modified version of the Manning theory of counterion condensation, to cover the semidilute regime, taking into account scaling arguments recently proposed by Dobrynin et al. (Macromolecules 1995, 28, 1859). This analysis, on the basis of the conductivity model we have adopted, provides evidence for a fraction of free counterions that increases with the polymer concentration until the semidilute-concentrated crossover concentration is reached, suggesting that, in the concentration range investigated, the effective charge on the polyion is dependent on the polymer concentration. Moreover, at the higher concentrations investigated, our data suggest that a regime is attained where electrostatic blobs overlap, strongly affecting the electrical transport properties of the solution and causing a progressive reduction of the free counterion concentration.

Several studies have already shown that transcranial direct current stimulation (tDCS) is a useful tool for enhancing recovery in aphasia. However, no reports to date have investigated functional connectivity changes on cortical activity because of tDCS language treatment. Here, nine aphasic persons with articulatory disorders underwent an intensive language therapy in two different conditions: bilateral anodic stimulation over the left Broca's area and cathodic contralesional stimulation over the right homologue of Broca's area and a sham condition. The language treatment lasted 3 weeks (Monday to Friday, 15 sessions). In all patients, language measures were collected before (T0) and at the end of treatment (T15). Before and after each treatment condition (real vs. sham), each participant underwent a resting-state fMRI study. Results showed that, after real stimulation, patients exhibited the greatest recovery not only in terms of better accuracy in articulating the treated stimuli but also for untreated items on different tasks of the language test. Moreover, although after the sham condition connectivity changes were confined to the right brain hemisphere, real stimulation yielded to stronger functional connectivity increase in the left hemisphere. In conclusion, our data provide converging evidence from behavioral and functional imaging data that bilateral tDCS determines functional connectivity changes within the lesioned hemisphere, enhancing the language recovery process in stroke patients.