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Non-angiogenic tumors grow in the absence of angiogenesis by two main mechanisms: cancer cells infiltrating and occupying the normal tissues to exploit pre-existing vessels (vascular co-option); the cancer cells themselves forms channels able to provide blood flow (the so called vasculogenic mimicry). In the original work on vascular co-option initiated by Francesco Pezzella, the non-angiogenic cancer cells were described as “exploiting” pre-existing vessels. Vascular co-option has been described in primary and secondary (metastatic) sites. Vascular co-option is defined as a process in which tumor cells interact with and exploit the pre-existing vasculature of the normal tissue in which they grow. As part of this process, cancer cells first migrate toward vessels of the primary tumor, or extravasate at a metastatic site and rest along the ab-luminal vascular surface. The second hallmark of vascular co-option is the interaction of cancer cells with the ab-luminal vascular surface. The first evidence for this was provided in a rat C6 glioblastoma model, showing that the initial tumor growth phase was not always avascular as these initial tumors can be vascularized by pre-existing vessels. The aim of this review article is to analyze together with vascular co-option, other alternative mode of vascularization occurring in glioblastoma multiforme (GBM), including vasculogenic mimicry, angiotropism and trans-differentiation of glioblastoma stem cells.

Abstract Poisson-Lie T-duality of the Wess-Zumino-Witten (WZW) model having the group manifold of SU(2) as target space is investigated. The whole construction relies on the deformation of the affine current algebra of the model, the semi-direct sum su 2 ℝ ⊕ ⋅ a $$ \mathfrak{su}(2)\left(\mathrm{\mathbb{R}}\right)\overset{\cdot }{\oplus}\mathfrak{a} $$ , to the fully semisimple Kac-Moody algebra sl 2 ℂ ℝ $$ \mathfrak{sl}\left(2,\mathrm{\mathbb{C}}\right)\left(\mathrm{\mathbb{R}}\right) $$ . A two-parameter family of models with SL(2, ℂ) as target phase space is obtained so that Poisson-Lie T-duality is realised as an O(3, 3) rotation in the phase space. The dual family shares the same phase space but its configuration space is SB(2, ℂ), the Poisson-Lie dual of the group SU(2). A parent action with doubled degrees of freedom on SL(2, ℂ) is defined, together with its Hamiltonian description.

Abstract In Double Field Theory, the mass-squared of doubled fields associated with bosonic closed string states is proportional to N L + N R − 2. Massless states are therefore not only the graviton, anti-symmetric, and dilaton fields with (N L = 1, N R = 1) such theory is focused on, but also the symmetric traceless tensor and the vector field relative to the states (N L = 2, N R = 0) and (N L = 0, N R = 2) which are massive in the lower-dimensional non-compactified space. While they are not even physical in the absence of compact dimensions, they provide a sample of states for which both momenta and winding numbers are non-vanishing, differently from the states (N L = 1, N R = 1). A quadratic action is therefore here built for the corresponding doubled fields. It results that its gauge invariance under the linearized double diffeomorphisms is based on a generalization of the usual weak constraint, giving rise to an extra mass term for the symmetric traceless tensor field, not otherwise detectable: this can be interpreted as a mere stringy effect in target space due to the simultaneous presence of momenta and windings. Furthermore, in the context of the generalized metric formulation, a non-linear extension of the gauge transformations is defined involving the constraint extended from the weak constraint that can be uniquely defined in triple products of fields. Finally, we show that the above mentioned stringy effect does not appear in the case of only one compact doubled space dimension.

Summary: We postulate that a significant part of circulating DNA (cirDNA) originates in the degradation of neutrophil extracellular traps (NETs). In this study, we examined the plasma level of two markers of NETs (myeloperoxidase (MPO) and neutrophil elastase (NE)), as well as cirDNA levels in 219 patients with a metastatic colorectal cancer (mCRC), and in 114 healthy individuals (HI). We found that in patients with mCRC the content of these analytes was (i) highly correlated, and (ii) all statistically different (p < 0.0001) than in HI (N = 114). These three NETs markers may readily distinguish between patients with mCRC from HI, (0.88, 0.86, 0.84, and 0.95 AUC values for NE, MPO, cirDNA, and NE + MPO + cirDNA, respectively). Concomitant analysis of anti-phospholipid (anti-cardiolipin), NE, MPO, and cirDNA plasma concentrations in patients with mCRC might have value for thrombosis prevention, and suggested that NETosis may be a critical factor in the immunological response/phenomena linked to tumor progression.

The local hydration around tetrameric hemoglobin (Hb) in its T0 and R4 conformational substates is analyzed based on molecular dynamics simulations. Analysis of the local hydrophobicity (LH) for all residues at the α1β2 and α2β1 interfaces, responsible for the quaternary T → R transition, which is encoded in the Monod–Wyman–Changeux model, as well as comparison with earlier computations of the solvent accessible surface area, makes clear that the two quantities measure different aspects of hydration. Local hydrophobicity quantifies the presence and structure of water molecules at the interface, whereas "buried surface" reports on the available space for solvent. For simulations with Hb frozen in its T0 and R4 states, the correlation coefficient between LH and buried surface is 0.36 and 0.44, respectively, but it increases considerably if the 95% confidence interval is used. The LH with Hb frozen and flexible changes little for most residues at the interfaces but is significantly altered for a few select ones: Thr41α, Tyr42α, Tyr140α, Trp37β, Glu101β (for T0) and Thr38α, Tyr42α, Tyr140α (for R4). The number of water molecules at the interface is found to increase by ∼ 25 % for T0 → R4, which is consistent with earlier measurements. Since hydration is found to be essential to protein function, it is clear that hydration also plays an essential role in allostery. [ABSTRACT FROM AUTHOR]

The identification of factors associated with functional outcome of subjects with schizophrenia is a great challenge in current research oriented to the personalization of care. The Italian Network for Research on Psychoses (NIRP) is a network of 26 university psychiatric clinics and/or mental health departments aimed to carry out multicenter research projects to improve the standards of prevention, diagnosis, and treatments of schizophrenia. The network has promoted 2 main studies, a cross-sectional one and a longitudinal one and seven “add-on” studies. The cross-sectional study of the network included 921 subjects with schizophrenia, 379 unaffected first-degree relatives of these patients, and 780 healthy controls. Results from this study documented that social and non-social cognition, functional capacity, negative symptoms, resilience, and family or social incentives strongly influence a measure of global functioning. The follow-up study included 618 patients from the original sample and has produced evidence of the key role of cognition, functional capacity, the experiential domain of negative symptoms, and everyday life skills in predicting functional outcome. The longitudinal study demonstrated that social cognition and the experiential domain of negative symptoms had an impact on interpersonal functioning, while non-social cognition had an impact on everyday life skills. Both non-social cognition and social cognition predicted work skills. The research question concerning the relationships of cognitive impairment and negative symptoms has been investigated with an innovative approach, using a structural equation model (SEM) and a network analysis. Both analyses demonstrated that only the experiential domain of negative symptoms had a distinct direct effect on functioning. The network analysis showed that expressive deficit was connected to functional capacity, as were social and non-social cognitive variables, and to disorganization. These findings were confirmed by the follow-up study. The add-on studies showed distinct electrophysiological correlates of the two negative symptom domains and the partial overlap between disorganization and neurocognitive impairment. Moreover, they identified and characterized a specific subgroup of patients suffering from schizophrenia with autism spectrum symptoms. The NIRP studies have implications for personalized management of patients with schizophrenia and highlight the need for a careful assessment of several domains rarely evaluated in clinical settings.

Background: Negative symptoms represent a heterogeneous dimension with a strong impact on functioning of subjects with schizophrenia (SCZ). Five constructs are included in this dimension: anhedonia, asociality, avolition, blunted affect, and alogia. Factor analyses revealed that these symptoms cluster in two domains: experiential domain (avolition, asociality, and anhedonia) and the expressive deficit (alogia and blunted affect), that might be linked to different neurobiological alterations. Few studies investigated associations between N100, an electrophysiological index of early sensory processing, and negative symptoms, reporting controversial results. However, none of these studies investigated electrophysiological correlates of the two negative symptom domains.Objectives: The aim of our study was to evaluate, within the multicenter study of the Italian Network for Research on Psychoses, the relationships between N100 and negative symptom domains in SCZ.Methods: Auditory N100 was analyzed in 114 chronic stabilized SCZ and 63 healthy controls (HCs). Negative symptoms were assessed with the Brief Negative Symptom Scale (BNSS). Repeated measures ANOVA and correlation analyses were performed to evaluate differences between SCZ and HCs and association of N100 features with negative symptoms.Results: Our findings demonstrated a significant N100 amplitude reduction in SCZ compared with HCs. In SCZ, N100 amplitude for standard stimuli was associated with negative symptoms, in particular with the expressive deficit domain. Within the expressive deficit, blunted affect and alogia had the same pattern of correlation with N100.Conclusion: Our findings revealed an association between expressive deficit and N100, suggesting that these negative symptoms might be related to deficits in early auditory processing in SCZ.

An extensive literature regarding gender differences relevant to several aspects of schizophrenia is nowadays available. It includes some robust findings as well as some inconsistencies. In the present review, we summarize the literature on gender differences in schizophrenia relevant to clinical and social outcome as well as their determinants, focusing on clinical variables, while gender differences on biological factors which may have an impact on the outcome of the disorder were not included herewith. Consistent findings include, in male with respect to female patients, an earlier age of illness onset limited to early- and middle-onset schizophrenia, a worse premorbid functioning, a greater severity of negative symptoms, a lower severity of affective symptoms and a higher rate of comorbid alcohol/substance abuse. Discrepant findings have been reported on gender differences in positive symptoms and in social and non-social cognition, as well as in functional outcome and rates of recovery. In fact, despite the overall finding of a more severe clinical picture in males, this does not seem to translate into a worse outcome. From the recent literature emerges that, although some findings on gender differences in schizophrenia are consistent, there are still aspects of clinical and functional outcome which need clarification by means of further studies taking into account several methodological issues.