Antibacterial activity of marine macroalgae against fish pathogenic Vibrio species

Abstract In mariculture, diseases of microbial origin can cause significant economic losses worldwide; the evolution of microorganism resistance to antibiotics has resulted in a growing need for new antibacterial compounds that are effective in veterinary medicine and characterized by limited undesirable side effects. Increased attention has recently been turned to seaweeds as a promising source for metabolites with antimicrobial activity. Vibriosis is a common disease, caused by bacteria of the genus Vibrio, that can result in high mortality in aquaculture. The aim of this study was to identify seaweeds with antibacterial activity against some pathogenic Vibrio species, in order to identify a possible alternative to the commonly used antibiotics in aquaculture. Chloroform/methanol lipidic extracts of six seaweed species (Chaetomorpha linum, Cladophora rupestris, Gracilaria dura, Gracilaria gracilis, Gracilariopsis longissima, Ulva prolifera) were tested for their antibacterial activities against six fish pathogenic Vibrio species using the disc diffusion method. Different susceptibilities to lipidic algal extracts were observed. All six of the seaweed extracts tested demonstrated inhibition of Vibrio ordalii. The best was that from Gracilariopsis longissima, showing activity against Vibrio ordalii, Vibrio salmonicida, Vibrio alginolyticus and Vibrio vulnificus. The results confirmed the potential use of seaweed extracts as a source of antibacterial compounds or as a health-promoting feed for aquaculture

The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma

Immunomodulatory drugs (IMiDs) have potent anti-tumor activities in multiple myeloma (MM) and are able to enhance the cytotoxic function of natural killer (NK) cells, important effectors of the immune response against MM. Here, we show that these drugs can enhance the expression of the NKG2D and DNAM-1 activating receptor ligands MICA and PVR/CD155 in human MM cell lines and primary malignant plasma cells. Depletion of cereblon (CRBN) by shRNA interference strongly impaired upregulation of these ligands and, more interestingly, IMiDs/CRBN-mediated downregulation of the transcription factors Ikaros (IKZF1), Aiolos (IKZF3) and IRF4 was critical for these regulatory mechanisms. Indeed, shRNA knockdown of IKZF1 or IKZF3 expression was both necessary and sufficient for the upregulation of MICA and PVR/CD155 expression, suggesting that these transcription factors can repress these genes; accordingly, the direct interaction and the negative role of IKZF1 and IKZF3 proteins on MICA and PVR/CD155 promoters were demonstrated. Finally, MICA expression was enhanced in IRF4-silenced cells, indicating a specific suppressive role of this transcription factor on MICA gene expression in MM cells. Taken together, these findings describe novel molecular pathways involved in the regulation of MICA and PVR/CD155 gene expression and identify the transcription factors IKZF-1/IKZF-3 and IRF4 as repressors of these genes in MM cells

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: role of HSP70/TLR2/NF-kB axis

Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM. Our findings show that melphalan, a genotoxic agent used in MM therapy, significantly induces an increased exosome release from MM cells. MM cell-derived exosomes are capable of stimulating IFNg production, but not the cytotoxic activity of NK cells through a mechanism based on the activation of NF-kB pathway in a TLR2/ HSP70-dependent manner. Interestingly, HSP70 positive exosomes are primarily found in the bone marrow (BM) of MM patients suggesting that they might have a crucial immunomodulatory action in the tumor microenvironment. We also provide evidence that the CD56high NK cell subset is more responsive to exosome-induced IFNg production mediated by TLR2 engagement. All together, these findings suggest a novel mechanism of synergism between chemotherapy and antitumor innate immune responses based on the drug-promotion of nanovesicles exposing DAMPs for innate receptors

Zero Fluoroscopy Arrhythmias Catheter Ablation: A Trend Toward More Frequent Practice in a High-Volume Center

BACKGROUND: Awareness of radiation exposure risks associated to interventional cardiology procedures is growing. The availability of new technologies in electrophysiology laboratories has reduced fluoroscopy usage during arrhythmias ablations. The aim of this study was to describe procedures with and without X-Rays and to assess feasibility, safety, and short-term efficacy of zero fluoroscopy intervention in a high-volume center oriented to keep exposure to ionizing radiation as low as reasonably achievable. METHODS: Cardiac catheter ablations performed in our hospital since January 2017 to June 2021. RESULTS: A total of 1,853 procedures were performed with 1,957 arrhythmias treated. Rate of fluoroless procedures was 15.4% (285 interventions) with an increasing trend from 8.5% in 2017 to 22.9% of first semester 2021. The most frequent arrhythmia treated was atrial fibrillation (646; 3.6% fluoroless) followed by atrioventricular nodal reentrant tachycardia (644; 16.9% fluoroless), atrial flutter (215; 8.8% fluoroless), ventricular tachycardia (178; 17.4% fluoroless), premature ventricular contraction (162; 48.1% fluoroless), and accessory pathways (112; 31.3% fluoroless). Although characteristics of patients and operative details were heterogeneous among treated arrhythmias, use of fluoroscopy did not influence procedure duration. Moreover, feasibility and efficacy were 100% in fluoroless ablations while the rate of major complications was very low and no different with or without fluoroscopy (0.45 vs. 0.35%). CONCLUSION: Limiting the use of X-Rays is necessary, especially when the available technologies allow a zero-use approach. A lower radiation exposure may be reached, reducing fluoroscopy usage whenever possible during cardiac ablation procedures with high safety, full feasibility, and efficacy

Causal evidence that intrinsic beta frequency is relevant for enhanced signal propagation in the motor system as shown through rhythmic TMS

Correlative evidence provides support for the idea that brain oscillations underpin neural computations. Recent work using rhythmic stimulation techniques in humans provide causal evidence but the interactions of these external signals with intrinsic rhythmicity remain unclear. Here, we show that sensorimotor cortex precisely follows externally applied rhythmic TMS (rTMS) stimulation in the beta-band but that the elicited responses are strongest at the intrinsic individual beta-peak-frequency. While these entrainment effects are of short duration, even subthreshold rTMS pulses propagate through the network and elicit significant cortico-spinal coupling, particularly when stimulated at the individual beta-frequency. Our results show that externally enforced rhythmicity interacts with intrinsic brain rhythms such that the individual peak frequency determines the effect of rTMS. The observed downstream spinal effect at the resonance frequency provides evidence for the causal role of brain rhythms for signal propagation

The two-process theory of face processing: modifications based on two decades of data from infants and adults

Johnson and Morton (1991) used Gabriel Horn’s work on the filial imprinting model to inspire a two-process theory of the development of face processing in humans. In this paper we review evidence accrued over the past two decades from infants and adults, and from other primates, that informs this two-process model. While work with newborns and infants has been broadly consistent with predictions from the model, further refinements and questions have been raised. With regard to adults, we discuss more recent evidence on the extension of the model to eye contact detection, and to subcortical face processing, reviewing functional imaging and patient studies. We conclude with discussion of outstanding caveats and future directions of research in this field

Electric effects induced by artificial seismic sources at Somma-Vesuvius volcano

In this paper, we present a series of self-potential measurements at Somma-Vesuvius volcanic area acquired in conjunction with an active seismic tomography survey. The aim of our study is both to provide further confirmation to the occurrence of seismo-electric coupling and to identify sites suitable for self-potential signal monitoring at Somma-Vesuvius district. The data, which were collected along two perpendicular dipoles, show significant changes on the natural electric field pattern. These variations, attributable to electrokinetic processes triggered by the artificial seismic waves, were observed after explosions occurred at a distance less than 5 km from the SP dipole arrays. In particular, we found that the NW-SE component of the natural electric field was more sensible to the shots than the NE-SW one, and the major effects did not correspond to the nearest shots. Such evidences were interpreted considering the underground electrical properties as deduced by previous detailed resistivity and self-potential surveys performed in the study area