Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor vessel normalization (TVN) is emerging as an anti-cancer treatment. Here, we show that tumor endothelial cells (ECs) ...have a hyper-glycolytic metabolism, shunting intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell invasion, intravasation, and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors.
Display omitted
•Tumor endothelial cells (ECs) have a hyperglycolytic metabolism•Endothelial PFKFB3 haplodeficiency/blockade induces tumor vessel normalization•PFKFB3 inhibition tightens the EC barrier and promotes pericyte quiescence•PFKFB3 blockade reduces metastasis and promotes chemotherapy
Cantelmo et al. show that tumor endothelial cells have hyperglycolytic metabolism. Inactivation of the glycolytic activator PFKFB3 normalizes tumor vessels and improves vessel perfusion via tightening the vascular barrier, which reduces cancer cell intravasation and metastasis and improves chemotherapy response.
Display omitted
“Are new neurons added in the adult mammalian brain?” “Do neural stem cells activate following CNS diseases?” “How can we modulate their activation to promote recovery?” Recent ...findings in the field provide novel insights for addressing these questions from a new perspective. In this review, we will summarize the current knowledge about adult neurogenesis and neural stem cell niches in healthy and pathological conditions. We will first overview the milestones that have led to the discovery of the classical ventricular and hippocampal neural stem cell niches. In adult brain, new neurons originate from proliferating neural precursors located in the subventricular zone of the lateral ventricles and in the subgranular zone of the hippocampus. However, recent findings suggest that new neuronal cells can be added to the adult brain by direct differentiation (e.g., without cell proliferation) from either quiescent neural precursors or non-neuronal cells undergoing conversion or reprogramming to neuronal fate. Accordingly, in this review we will also address critical aspects of the newly described mechanisms of quiescence and direct conversion as well as the more canonical activation of the neurogenic niches and neuroblast reservoirs in pathological conditions. Finally, we will outline the critical elements involved in neural progenitor proliferation, neuroblast migration and differentiation and discuss their potential as targets for the development of novel therapeutic drugs for neurodegenerative diseases.
Italian society is undergoing significant demographic changes: on one hand, the widespread decrease in birth rates and extended life expectancies lead to a substantial aging of the population; on the ...other hand, rising immigration rates constitute an important factor behind the renewal and growth of young population segments. According to conventional disciplinary divisions, such changes are the established domain of demography; however, it mainly draws on ethno‐national categories to investigate them. In reference to the Italian context, this article specifically highlights the way national demography employs forecasts and value judgments derived from a qualitative and selective definition of population to address the marked increase in children born to foreign parents. By examining the reproductive behaviours of migrants in Italy, the article thus offers a wide‐ranging reflection on the social boundaries that shape the formation of an ‘other’ generation.
This article uses a qualitative approach to investigate how migration, marriages and births are intertwined in the life courses of Moroccan women living in Italy. The analysis offers an ...interpretation which differs from that traditionally characterizing demographic studies of migration and fertility. Specifically, rather than exploring whether and under what conditions the fertility of foreigners corresponds to that of native women, the article instead seeks to reconstruct the process through which foreigners come to have children in the contexts in which they settle. This research question is broken down as follows: a) theoretically, reconsidering and questioning the assimilationist perspective; and b) empirically, tracing how reproductive events and mobility trajectories are interrelated in Italy, a context characterized by both significantly diminished birth rates and prohibitively restrictive laws for granting citizenship to the Italianborn children of foreign nationals. In conclusion, the link between migration and fertility is analyzed in light of how the reproductive cycle these families deploy across the Mediterranean evolves over time.
Presence of neural stem cells in adult mammalian brains, including human, has been clearly demonstrated by several studies. The functional significance of adult neurogenesis is slowly emerging as new ...data indicate the sensitivity of this event to several "every day" external stimuli such as physical activity, learning, enriched environment, aging, stress and drugs. In addition, neurogenesis appears to be instrumental for task performance involving complex cognitive functions. Despite the growing body of evidence on the functional significance of NSC and despite the bulk of data concerning the molecular and cellular properties of NSCs and their niches, several critical questions are still open. In this work we review the literature describing i) old and new sites where NSC niche have been found in the CNS; ii) the intrinsic factors regulating the NSC potential; iii) the extrinsic factors that form the niche microenvironment. Moreover, we analyse NSC niche activation in iv) physiological and v) pathological conditions. Given the not static nature of NSCs that continuously change phenotype in response to environmental clues, a unique "identity card" for NSC identification is still lacking. Moreover, the multiple location of NSC niches that increase in diseases, leaves open the question of whether and how these structures communicate throughout long distance. We propose a model where all the NSC niches in the CNS may be connected in a functional network using the threads of the meningeal net as tracks.
Once the sheets of newspaper had disintegrated to the point of liquefaction, he would, armed with a drill, grind the resulting mass before carefully mixing in some amount of glue in order to make it ...denser. Marc Décimo, E-mail: marc.decimo@gmail.com This Section of Epidemiology and Psychiatric Sciences appears in each issue of the Journal and is dedicated to all forms of creative production born of an intimate and individual urge, often secretive, unbound from the conventional art system rules. Through short descriptions of the Outsider art work of prominent artists and new protagonists often hosted in community mental health services, this Section intends to investigate the latest developments of the contemporary art scene, where the distances between the edge and the centre are becoming more and more vague.
Clinical and epidemiological data show that biological sex is one of the major determinants for the development and progression of cardiovascular disease (CVD). Impaired endothelial function, ...characterized by an imbalance in endothelial Nitric Oxide Synthase (eNOS) activity, precedes and accelerates the development of CVD. However, whether there is any sexual dimorphism in eNOS activity and function in endothelial cells (ECs) is still unknown. Here, by independently studying human male and female ECs, we found that female ECs expressed higher eNOS mRNA and protein levels both in vitro and ex vivo. The increased eNOS expression was associated to higher enzymatic activity and nitric oxide production. Pharmacological and genetic inhibition of eNOS affected migratory properties only in female ECs. In vitro angiogenesis experiments confirmed that sprouting mostly relied on eNOS-dependent migration in female ECs. At variance, capillary outgrowth from male ECs was independent of eNOS activity but required cell proliferation. In this study, we found sex-specific differences in the EC expression, activity, and function of eNOS. This intrinsic sexual dimorphism of ECs should be further evaluated to achieve more effective and precise strategies for the prevention and therapy of diseases associated to an impaired endothelial function such as CVD and pathological angiogenesis.
Bacterial resistance to antibiotics is a major global health problem and resistance of Pseudomonadaceae and Enterobacteriaceae is a serious concern. We investigated the prevalence of drug‐resistance ...in a total of 80 psychrotrophic strains from bulk milk belonging to Pseudomonas genus (n. 63) and Enterobacteriaceae group (n. 17). All the strains were tested against 16 antibiotics. Pseudomonas were further investigated for their sensitivity against 12 additional antibiotics. Pseudomonas showed a high susceptibility toward fluoroquinolones, aminoglycosides, and piperacillin and, to a lesser extent, to imipenem, ceftazidime, cefepime. Thirty‐five out of 63 Pseudomonas strains were susceptible to meropenem, while among antibiotics for which recommended breakpoints are not yet available, 55% of Pseudomonas strains had no inhibition halo in presence of nitrofurantoin, highlighting a resistance toward this drug. The results obtained in this study indicate a high efficiency of fluoroquinolones, chloramphenicol (94%), and kanamycin (76%) for Enterobacteriaceae while a high prevalence of resistant strains was found to ampicillin (13/17). Serratia marcescens is highly susceptible to fluoroquinolones, chloramphenicol, and kanamycin. Moreover, mupirocin seems to be the new antibiotic with the less efficacy for Enterobacteriaceae, with 41% of strains without halo, pointing out an important resistance. Further knowledge on resistance to known and new antibiotics among Pseudomonas species and Enterobacteriaceae of milk origin was acquired.
Practical Application
Antibiotic resistance is a serious public health problem in food‐related bacteria. Resistance of Pseudomonadaceae and Enterobacteriaceae of dairy origin is a growing concern. A likely new resistance against nitrofurantoin for Pseudomonas strains. Evidence of resistant Enterobacteriaceae strains against mupirocin. Further knowledge on AR patterns of psychrotrophic strains was provided.
The notion of social remittances has gained a central position, discursively at least, in the literature on the effects of emigration on home societies. In this editorial we briefly review the ...strengths and limitations that this concept has displayed, since its early coinage in transnational migration studies. More often than not, social remittances have been treated in the literature in a peripheral vein, ancillary to different foci of research. This Migration Letters special issue aims to move the debate on the theme beyond this unsatisfactory state of things. More specifically, we argue for four lines of research on social remittances to be further developed: the tensions between individualization and home-society based obligations and pressures, which shape the development and circulation of social remittances; the need to explore the embeddedness of economic remittances within a broader range of socio-cultural remittances (rather than vice versa); the interfaces between the categories of social remittances and social capital; the complex ways in which physical and social distance between senders and recipients affects the circulation of social remittances, as well as their impact on migrants' communities of origin. PUBLICATION ABSTRACT
PDF
