Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities

In human tuberculosis (TB) neutrophils represent the most commonly infected phagocyte but their role in protection and pathology is highly contradictory. Moreover, a subset of low-density neutrophils (LDNs) has been identified in TB, but their functions remain unclear. Here, we have analyzed total neutrophils and their low-density and normal-density (NDNs) subsets in patients with active TB disease, in terms of frequency, phenotype, functional features, and gene expression signature. Full-blood counts from Healthy Donors (H.D.), Latent TB infected, active TB, and cured TB patients were performed. Frequency, phenotype, burst activity, and suppressor T cell activity of the two different subsets were assessed by flow cytometry while NETosis and phagocytosis were evaluated by confocal microscopy. Expression analysis was performed by using the semi-quantitative RT-PCR array technology. Elevated numbers of total neutrophils and a high neutrophil/lymphocyte ratio distinguished patients with active TB from all the other groups. PBMCs of patients with active TB disease contained elevated percentages of LDNs compared with those of H.D., with an increased expression of CD66b, CD33, CD15, and CD16 compared to NDNs. Transcriptomic analysis of LDNs and NDNs purified from the peripheral blood of TB patients identified 12 genes differentially expressed: CCL5, CCR5, CD4, IL10, LYZ, and STAT4 were upregulated, while CXCL8, IFNAR1, NFKB1A, STAT1, TICAM1, and TNF were downregulated in LDNs, as compared to NDNs. Differently than NDNs, LDNs failed to phagocyte live Mycobacterium tuberculosis (M. tuberculosis) bacilli, to make oxidative burst and NETosis, but caused significant suppression of antigen-specific and polyclonal T cell proliferation which was partially mediated by IL-10. These insights add a little dowel of knowledge in understanding the pathogenesis of human TB

Efficiency Enhancement for an S-Band Axial Vircator Using 5-Stage Two-Step Tapered Radiators

An S-band multistage axial virtual cathode oscillator with efficiency enhancement for high pulsed power electromagnetic applications is presented. The Particle-in-Cell (PIC) results of the designed 5-stage Vircator, with two-step negative tapering in the reflectors, carried out by CST Studio suite 2021 simulation code show a peak power value of 5.54 GW and an efficiency value of 13.65% at 2.45 GHz, under a beam voltage and current equal to 520 kV and 20 kA, respectively

Immune response to tick-borne hemoparasites: Host adaptive immune response mechanisms as potential targets for therapies and vaccines

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T-and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens

Ground effects induced by the 2012 seismic sequence in Emilia: implications for seismic hazard assessment in the Po Plain

Since May 16, 2012, a seismic sequence has affected a wide portion of the Emilia Region (northern Italy), chiefly for the Modena and Ferrara Provinces. The first mainshock (Ml 5.9; focal depth, ca. 6 km) occurred on May 20, 2012, with the epicenter located a few kilometers north of Finale Emilia. A second main shock (Ml 5.8; focal depth, ca. 10 km) occurred on May 29, 2012, about 12 km west of the first earthquake, with the epicenter near Medolla. The seismic sequence has been characterized by five other Ml 655 events, and more than 2,300 aftershocks of lower magnitude, until the end July 2012. The distribution of the aftershocks identifies a WNW-ESE-trending zone ca. 40 km long that is characterized by NNE-SSW nearly pure compression, as indicated by the focal mechanisms. This report focuses on the many ground effects that were induced by this seismic sequence, as mainly cracks, liquefaction-type phenomena, and hydrological anomalies. The aim is to provide a complete representation of such effects, to: illustrate their type, size and areal distribution; identify the zones in the affected area that were most prone to the occurrence of ground effects (i.e., more susceptible to local geological instability in the case of earthquake occurrence); carry out an independent assessment of the intensities of the earthquakes through the ESI 2007 intensity scale, which is based only on coseismic effects on the natural environment

Delivery of Mycobacterium tuberculosis epitopes by Bordetella pertussis adenylate cyclase toxoid expands HLA-E-restricted cytotoxic CD8+ T cells

IntroductionTuberculosis (TB) remains the first cause of death from infection caused by a bacterial pathogen. Chemotherapy does not eradicate Mycobacterium tuberculosis (Mtb) from human lungs, and the pathogen causes a latent tuberculosis infection that cannot be prevented by the currently available Bacille Calmette Guerin (BCG) vaccine, which is ineffective in the prevention of pulmonary TB in adults. HLA-E-restricted CD8+ T lymphocytes are essential players in protective immune responses against Mtb. Hence, expanding this population in vivo or ex vivo may be crucial for vaccination or immunotherapy against TB.MethodsThe enzymatically inactive Bordetella pertussis adenylate cyclase (CyaA) toxoid is an effective tool for delivering peptide epitopes into the cytosol of antigen-presenting cells (APC) for presentation and stimulation of specific CD8+ T-cell responses. In this study, we have investigated the capacity of the CyaA toxoid to deliver Mtb epitopes known to bind HLA-E for the expansion of human CD8+ T cells in vitro.ResultsOur results show that the CyaA-toxoid containing five HLA-E-restricted Mtb epitopes causes significant expansion of HLA-E-restricted antigen-specific CD8+ T cells, which produce IFN-γ and exert significant cytotoxic activity towards peptide-pulsed macrophages.DiscussionHLA-E represents a promising platform for the development of new vaccines; our study indicates that the CyaA construct represents a suitable delivery system of the HLA-E-binding Mtb epitopes for ex vivo and in vitro expansion of HLA-E-restricted CD8+ T cells inducing a predominant Tc1 cytokine profile with a significant increase of IFN-γ production, for prophylactic and immunotherapeutic applications against Mtb

Core/Shell CdSe/CdS bone‐shaped nanocrystals with a thick and anisotropic shell as optical emitters

Colloidal core/shell nanocrystals are key materials for optoelectronics, enabling control over essential properties via precise engineering of the shape, thickness, and crystal structure of their shell. Here, the growth protocol for CdS branched nanocrystals is applied on CdSe nanoplatelet seeds and bone-shaped heterostructures are obtained with a highly anisotropic shell. Surprisingly, the nanoplatelets withstand the high growth temperature of 350 degrees C and structures with a CdSe nanoplatelet core that is overcoated by a shell of cubic CdS are obtained, on top of which tetrahedral CdS structures with hexagonal lattice are formed. These complex core/shell nanocrystals show a band-edge emission around 657 nm with a photoluminescence quantum yield of approximate to 42% in solution, which is also retained in thin films. Interestingly, the nanocrystals manifest simultaneous red and green emission and the relatively long wavelength of the green emission indicates charge recombination at the cubic/hexagonal interface of the CdS shell. The nanocrystal films show amplified spontaneous emission, random lasing, and distributed feedback lasing when the material is deposited on suitable gratings. This work stimulates the design and fabrication of more exotic core/shell heterostructures where charge carrier delocalization, dipole moment, and other optical and electrical properties can be engineered

The effect of Auger heating on intraband carrier relaxation in semiconductor quantumrods

The rate at which excited charge carriers relax to their equilibrium state affects many aspects of the performance of nanoscale devices, including switching speed, carrier mobility and luminescent efficiency. Better understanding of the processes that govern carrier relaxation therefore has important technological implications. A significant increase in carrier-carrier interactions caused by strong spatial confinement of electronic excitations in semiconductor nanostructures leads to a considerable enhancement of Auger effects, which can further result in unusual, Auger-process-controlled recombination and energy-relaxation regimes. Here, we report the first experimental observation of efficient Auger heating in CdSe quantum rods at high pump intensities, leading to a strong reduction of carrier cooling rates. In this regime, the carrier temperature is determined by the balance between energy outflow through phonon emission and energy inflow because of Auger heating. This equilibrium results in peculiar carrier cooling dynamics that closely correlate with recombination dynamics, an effect never before seen in bulk or nanoscale semiconductors.Comment: 7 pages, 4 figure

Tsunami risk management for crustal earthquakes and non-seismic sources in Italy

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Tuning inflammation in tuberculosis: the role of decoy receptors

Decoy receptors are "silent scavengers" of CC chemokines and cytokines, which play a key role in damping inflammation and tissue damage. In this review we discuss on recent findings demonstrating that these receptors set the balance between antimicrobial resistance, immune activation and inflammatory response in Mycobacterium tuberculosis infection