Time Evolution of Plasmonic Features in Pentagonal Ag Clusters

In the present work, we apply recently developed real-time descriptors to study the time evolution of plasmonic features of pentagonal Ag clusters. The method is based on the propagation of the time-dependent Schrödinger equation within a singly excited TDDFT ansatz. We use transition contribution maps (TCMs) and induced density to characterize the optical longitudinal and transverse response of such clusters, when interacting with pulses resonant with the low-energy (around 2–3 eV, A (Formula presented.)) size-dependent or the high-energy (around 4 eV, E (Formula presented.)) size-independent peak. TCMs plots on the analyzed clusters, Ag (Formula presented.) and Ag (Formula presented.) show off-diagonal peaks consistent with a plasmonic response when a longitudinal pulse resonant at A (Formula presented.) frequency is applied, and dominant diagonal spots, typical of a molecular transition, when a transverse E (Formula presented.) pulse is employed. Induced densities confirm this behavior, with a dipole-like charge distribution in the first case. The optical features show a time delay with respect to the evolution of the external pulse, consistent with those found in the literature for real-time TDDFT calculations on metal clusters

Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma

The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from three groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD-related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the only pathway altered in CTRL-related treatment. Indeed, 36 different biological processes turned out to be deregulated after PT treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients' plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease

The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome

Objective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interaction with the inflammatory microenvironment seems to have a critical role. Design. To reproduce the inflammatory microenvironment, AMSCs were exposed to osteoarthritic synovial fluid (SF) for 48 h and the effect of their secretome on differentiation of monocytes (M0) into macrophages M1-like and mature dendritic cells (mDCs) was evaluated. Furthermore, the effect of the secretome of AMSCs exposed to SF was evaluated on the T cell population in terms of T cell proliferation and expansion of T regulatory cells (T reg). Results. Our data show that the exposure of AMSCs to SF activates cells and promotes the release of immunosuppressive factors, which induce macrophage polarization of M0 into the M2-like phenotype and inhibit differentiation of monocytes into mature dendritic cells (mDCs). Only the secretome of exposed AMSCs was able to inhibit T cell proliferation and promote T reg expansion. Conclusions. Our results suggest that the microenvironment plays a fundamental role for the development of anti-inflammatory and immunomodulatory properties of AMSCs

Tuberculosis in roe deer from Spain and Italy

TUBERCULOSIS (TB) is a chronic infectious disease caused by bacteria of the genus Mycobacterium (Grange and others 1990). The detection of wildlife reservoirs of disease is important, particularly in areas where there is a relatively low incidence of the disease in domestic animals. Tuberculosis cases in roe deer (Capreolus capreolus) are reported only sporadically, despite the wide distribution and the abundance of this cervid. Roe deer with TB have been reported in Germany (Schmidt 1938), Switzerland (Bouvier 1963), France (Zanella and others 2008) and the UK (Gunning 1985, Delahay and others 2007). This short communication is the first report of TB in roe deer in Spain and Italy, and discusses the implications of these findings for wildlife and livestock disease control. The prevalence of mycobacterial infections, such as TB and paratuberculosis, seems to be increasing in Spain. Wildlife species may act as disease reservoirs, so this short communication also elucidates the epidemiology of mycobacterial infections in species such as roe deer

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression

Ceramide releases exosomes with a specific miRNA signature for cell differentiation

Exosomes are well established effectors of cell–cell communication. Their role on maturation of embryonic cells located in hippocampus, seat of memory, is unknown. Here we show that ceramide facilitates release of exosomes from HN9.10e cells extending information for cell differentiation to neighboring cells. We found only 38 miRNAs differentially expressed in exosomes derived from ceramide-treated cells in comparison with control cells (including 10 up-regulated and 28 down-regulated). Some overexpressed miRNAs (mmu-let-7f-1-3p, mmu-let-7a-1-3p, mmu-let-7b-3p, mmu-let-7b-5p, mmu-miR-330-3p) regulate genes encoding for protein involved in biological, homeostatic, biosynthetic and small molecule metabolic processes, embryo development and cell differentiation, all phenomena relevant for HN9.10e cell differentiation. Notably, the overexpressed mmu-let-7b-5p miRNA appears to be important for our study based on its ability to regulate thirty-five gene targets involved in many processes including sphingolipid metabolism, sphingolipid-related stimulation of cellular functions and neuronal development. Furthermore, we showed that by incubating embryonic cells with exosomes released under ceramide treatment, some cells acquired an astrocytic phenotype and others a neuronal phenotype. We anticipate our study to be a start point for innovative therapeutic strategies to regulate the release of exosomes useful to stimulate delayed brain development in the newborn and to improve the cognitive decline in neurodegenerative disorders

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development