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Bharadwaj et al. [1] present a comments paper evaluating the classification accuracy of several state-of-the-art methods using EEG data averaged over random class samples. According to the results, some of the methods achieve above-chance accuracy, while the method proposed in [2], that is the target of their analysis, does not. In this rebuttal, we address these claims and explain why they are not grounded in the cognitive neuroscience literature, and why the evaluation procedure is ineffective and unfair.
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Chronic viral infections cause thymic involution yet the potential for broader, longer-term impact on thymic composition remains unexplored. Here we show that chronic, but not acute, lymphocytic choriomeningitis virus infection promotes a unique population of immature B cells in the thymus. We show that chronic viral infection promotes signals within the thymus, including the expression of B-cell activating factor (BAFF), that favor the maturation of this population as these cells acquire expression of CD19 and immunoglobulin M. Mechanistically, type I interferon (IFN-I), predominantly IFNß, signals to thymic hematopoietic cells, strongly delaying T-cell development at the earliest precursor stage. Furthermore, IFN-I signaling to the nonhematopoietic compartment provides a second signal essential to favor B-cell differentiation and maturation within the thymus. Importantly, chronic infection yields changes in the B-cell population for at least 50 days following infection, long after thymic atrophy has subsided. Thus, the inflammatory milieu induced by chronic viral infection has a profound, and long-lasting, effect on thymic composition leading to the generation of a novel population of thymic B cells.
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Due to the low temperature, the Antarctic marine environment is challenging for protein functioning. Cold-adapted organisms have evolved proteins endowed with higher flexibility and lower stability in comparison to their thermophilic homologs, resulting in enhanced reaction rates at low temperatures. The Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) genome is one of the few examples of coexistence of multiple hemoglobin genes encoding, among others, two constitutively transcribed 2/2 hemoglobins (2/2Hbs), also named truncated Hbs (TrHbs), belonging to the Group II (or O), annotated as PSHAa0030 and PSHAa2217. In this work, we describe the ligand binding kinetics and their interrelationship with the dynamical properties of globin Ph-2/2HbO-2217 by combining experimental and computational approaches and implementing a new computational method to retrieve information from molecular dynamic trajectories. We show that our approach allows us to identify docking sites within the protein matrix that are potentially able to transiently accommodate ligands and migration pathways connecting them. Consistently with ligand rebinding studies, our modeling suggests that the distal heme pocket is connected to the solvent through a low energy barrier, while inner cavities play only a minor role in modulating rebinding kinetics.
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Proteínas de Bactérias , Pseudoalteromonas , Hemoglobinas Truncadas , Pseudoalteromonas/metabolismo , Pseudoalteromonas/genética , Pseudoalteromonas/química , Cinética , Hemoglobinas Truncadas/química , Hemoglobinas Truncadas/metabolismo , Hemoglobinas Truncadas/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Simulação de Dinâmica Molecular , Regiões Antárticas , LigantesRESUMO
Studies based on fish early life stages can provide information on spawning grounds and nursery areas, helping to determine the implications for stock biomass fluctuations of recruitment variability. This study describes the composition, abundance, spatial distribution and differences in day/night vertical distribution of ichthyoplankton in the southern Adriatic Sea. Samples were collected within the framework of the COCONET project (Towards COast to COast NETworks of marine protected areas) from 9 to 18 May 2013 by the R/V Urania, using the electronic multinet EZ-NET BIONESS (Bedford Institute of Oceanography Net Environmental Sampling System). A total of 20 species, belonging to 20 genera and 13 families, were identified. Of the collected larvae, 74.3% were meso- or bathypelagic species, 24.7% were epipelagic and 0.9% were demersal. The community was dominated by Gonostomatidae, followed by Engraulidae, Myctophidae and Photychthaidae. The most abundant species was Cyclothone braueri (45.6%), followed by Engraulis encrasicolus, Ceratoscopelus maderensis, Cyclothone pygmaea, Vinciguerria attenuata and Myctophum punctatum. An inshore/offshore increasing gradient in biodiversity and abundance was observed. Different weighted mean depths (WMDs) were observed for larvae and juveniles. No diel vertical migrations were observed. The high abundance of meso- or bathypelagic species in the upper 100 m confirms the epipelagic zone as an important environment for the development of the larval stages of these fish.
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Clinical evidence points to a function for B cell-activating factor (BAFF) in pregnancy. However, direct roles for BAFF-axis members in pregnancy have not been examined. Here, via utility of genetically modified mice, we report that BAFF promotes inflammatory responsiveness and increases susceptibility to inflammation-induced preterm birth (PTB). In contrast, we show that the closely related A proliferation-inducing ligand (APRIL) decreases inflammatory responsiveness and susceptibility to PTB. Known BAFF-axis receptors serve a redundant function in signaling BAFF/APRIL presence in pregnancy. Treatment with anti-BAFF/APRIL monoclonal antibodies or BAFF/APRIL recombinant proteins is sufficient to manipulate susceptibility to PTB. Notably, macrophages at the maternal-fetal interface produce BAFF, while BAFF and APRIL presence divergently shape macrophage gene expression and inflammatory function. Overall, our findings demonstrate that BAFF and APRIL play divergent inflammatory roles in pregnancy and provide therapeutic targets for mitigating risk of inflammation-induced PTB.
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Nascimento Prematuro , Animais , Feminino , Camundongos , Gravidez , Fator Ativador de Células B , Inflamação , Transdução de Sinais , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genéticaRESUMO
Purpose and methods: B cell-activating factor (BAFF) contributes to the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE). Although several anti-BAFF Abs and derivatives have been developed for the treatment of SLE, the specific sources of BAFF that sustain autoantibody (auto-Ab) producing cells have not been definitively identified. Using BAFF-RFP reporter mice, we identified major changes in BAFF-producing cells in two mouse spontaneous lupus models (Tlr7 Tg mice and Sle1), and in a pristane-induced lupus (PIL) model. Results: First, we confirmed that similar to their wildtype Tlr7 Tg and Sle1 mice counterparts, BAFF-RFP Tlr7 Tg mice and BAFF-RFP Sle1 mice had increased BAFF serum levels, which correlated with increases in plasma cells and auto-Ab production. Next, using the RFP reporter, we defined which cells had dysregulated BAFF production. BAFF-producing neutrophils (Nphs), monocytes (MOs), cDCs, T cells and B cells were all expanded in the spleens of BAFF-RFP Tlr7 Tg mice and BAFF-RFP Sle1 mice compared to controls. Furthermore, Ly6Chi inflammatory MOs and T cells had significantly increased BAFF expression per cell in both spontaneous lupus models, while CD8- DCs up-regulated BAFF expression only in the Tlr7 Tg mice. Similarly, pristane injection of BAFF-RFP mice induced increases in serum BAFF levels, auto-Abs, and the expansion of BAFF-producing Nphs, MOs, and DCs in both the spleen and peritoneal cavity. BAFF expression in MOs and DCs, in contrast to BAFF from Nphs, was required to maintain homeostatic and pristane-induced systemic BAFF levels and to sustain mature B cell pools in spleens and BMs. Although acting through different mechanisms, Nph, MO and DC sources of BAFF were each required for the development of auto-Abs in PIL mice. Conclusions: Our findings underscore the importance of considering the relative roles of specific myeloid BAFF sources and B cell niches when developing treatments for SLE and other BAFF-associated autoimmune diseases.
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Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Animais , Camundongos , Autoanticorpos , Doenças Autoimunes/metabolismo , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Interleucina-4/metabolismo , Monócitos/metabolismo , Neutrófilos , Receptor 7 Toll-Like/metabolismoRESUMO
Heme proteins are a diverse group that includes several unrelated families. Their biological function is mainly associated with the reactivity of the heme group, which-among several other reactions-can bind to and react with nitric oxide (NO) and other nitrogen compounds for their production, scavenging, and transport. The S-nitrosylation of cysteine residues, which also results from the reaction with NO and other nitrogen compounds, is a post-translational modification regulating protein activity, with direct effects on a variety of signaling pathways. Heme proteins are unique in exhibiting this dual reactivity toward NO, with reported examples of cross-reactivity between the heme and cysteine residues within the same protein. In this work, we review the literature on this interplay, with particular emphasis on heme proteins in which heme-dependent nitrosylation has been reported and those for which both heme nitrosylation and S-nitrosylation have been associated with biological functions.
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The paper aims to highlight the new indications introduced in the 4th edition of the "Laboratory Biosafety Manual" of World Health Organization. The authors propose a new vision to improve biosafety and biosecurity in the laboratory aligned with the technical standards ISO 35001:2019 "Biorisk management for laboratories and other related organizations" and ISO 45001:2018 "Occupational health and safety management systems-Requirements with guidelines for use" framework. The current edition has a more innovative approach compared to the previous ones, more attention is given to training awareness and providing skills, to promote the culture of safety by adopting an approach based on risk analysis, rather than the prescriptive approach that has been used previously.
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Laboratórios , Exposição Ocupacional , Humanos , Contenção de Riscos Biológicos , Gestão da Segurança , Organização Mundial da SaúdeRESUMO
Nitric oxide was once considered to be of marginal interest to the biological sciences and medicine; however, there is now wide recognition, but not yet a comprehensive understanding, of its functions and effects. NO is a reactive, toxic free radical with numerous biological targets, especially metal ions. However, NO and its reaction products also play key roles as reductant and oxidant in biological redox processes, in signal transduction, immunity and infection, as well as other roles. Consequently, it can be sensed, metabolized and modified in biological systems. Here, we present a brief overview of the chemistry and biology of NO-in particular, its origins in geological time and in contemporary biology, its toxic consequences and its critical biological functions. Given that NO, with its intrinsic reactivity, appeared in the early Earth's atmosphere before the evolution of complex lifeforms, we speculate that the potential for toxicity preceded biological function. To examine this hypothesis, we consider the nature of non-biological and biological targets of NO, the evolution of biological mechanisms for NO detoxification, and how living organisms generate this multifunctional gas.
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The production of recombinant proteins in bacteria made possible to obtain large quantities of proteins essential for basic and applied research. Escherichia coli remains one of the organisms of choice for recombinant proteins because of its ability to grow at high density and availability of a vast catalog of cloning vectors and mutant host strains. Here, we describe the protocols for the expression of cold-adapted (hemo)globins in Escherichia coli.
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Escherichia coli , Globinas , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Vetores Genéticos/genética , Globinas/metabolismo , Proteínas Recombinantes/metabolismoRESUMO
Marine organisms have developed physiological and biochemical strategies to survive under the exposure of UV-B radiation. In particular, Antarctic marine bacteria, exposed to extremes of temperature, UV and ice, have adapted to cope with UV radiation by producing photoprotective molecules. Here, we describe (1) the sampling strategy to collect marine samples (surface water/ice and sediment samples) and (2) the selection strategy to isolate in these samples only UV-resistant marine bacteria.
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Gelo , Raios Ultravioleta , Organismos Aquáticos , Bactérias/genéticaRESUMO
Nitric Oxide (NO) is a free radical with numerous critical signaling roles in vertebrate physiology. Similar to mammals, in the teleost system the generation of sufficient amounts of NO is critical for the physiological function of the cardiovascular system. At the same time, NO amounts are strictly controlled and kept within basal levels to protect cells from NO toxicity. Changes in oxygen tension highly influence NO bioavailability and can modulate the mechanisms involved in maintaining the NO balance. While NO production and signaling appears to have general similarities with mammalian systems, the wide range of environmental adaptations made by fish, particularly with regards to differing oxygen availabilities in aquatic habitats, creates a foundation for a variety of in vivo models characterized by different implications of NO production and signaling. In this review, we present the biology of NO in the teleost cardiovascular system and summarize the mechanisms of NO production and signaling with a special emphasis on the role of globin proteins in NO metabolism.
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The present paper aims to investigate the ecological role of Merluccius merluccius, Linnaeus, 1758, in southern and central Tyrrhenian Sea (GSA 10, Resolution GFCM/33/2009/2 General Fisheries Commission for the Mediterranean), analyzing ontogenetic diet shifts, geographical variations on prey composition, and feeding habits. A total of 734 hake specimens ranging in size between 6 cm and 73 cm (Total Length, TL) were collected in 2018. In order to evaluate ontogenetic shifts in prey composition, samples were divided into five size classes and for each class the quantitative feeding indices have been calculated. The statistical analysis, based on index of relative importance percentage (%IRI), resulted in three trophic groups. The most abundant prey found in the immature hake specimens (size class I) were the Euphausiids, Stylocheiron longicorne and Mysidacea, while for samples with a total length over 10.5 cm were crustaceans and fish. Engraulis encrasicolus was the most abundant fish prey identified, followed by Boops boops and Myctophids. The high presence of Euphausiids, Mysids, Myctophidae, and Sternoptychidae in classes I, II, II, and IV (6-23 cm) showed the relevant role of mesopelagic fauna in hake diets, with an essential organic matter and energy flow from the mesopelagic to the epipelagic environment. Additionally, decapod crustaceans were found in the stomach contents of hakes belonging to class V (with size over 36 cm TL), which is notable considering that our study area includes an important decapod crustacean fishing area.
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Marine organisms are known to produce a wide variety of natural products that are unique in terms of diversity, structural, and functional properties [...].
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Organismos Aquáticos , Produtos Biológicos , Organismos Aquáticos/química , Produtos Biológicos/química , Ambientes ExtremosRESUMO
Mice lacking B cells are more susceptible to S. typhimurium infection. How B cells contribute to protective immunity against Salmonella and what signals drive their activation are still unclear. Neutrophils (Nphs), monocytes (MOs), and dendritic cells (DCs) are involved in early immune responses to control the initial replication of S. typhimurium. These cells can produce B cell activating factor (BAFF) required for mature B cell survival and may help regulate B cell responses during Salmonella infection. Using BAFF reporter mice (BAFF-RFP+/-), we discovered that an i.p. infection with a virulent strain of S. typhimurium increased BAFF expression in splenic conventional DCs (cDC) and inflammatory Ly6Chi MOs/DCs four days post-infection. S. typhimurium infection induced the release of BAFF from Nphs, a decrease of BAFF-RFP expression and expansion of BAFF-RFP+ Nphs in the spleen and peritoneal cavity. After S. typhimurium infection, serum BAFF levels and immature and mature B cell subsets and plasma cells increased substantially. Conditional knockout (cKO) mice lacking BAFF in either Nphs or cDCs compared to control Bafffl/fl mice had reduced up-regulation of systemic BAFF levels and reduced expansion of mature and germinal center B cell subsets after infection. Importantly, the cKO mice lacking BAFF from either Nphs or cDCs had impaired induction of Salmonella-specific IgM Abs, and were more susceptible to S. typhimurium infection. Thus, Nphs and cDCs are major cellular sources of BAFF driving B cell responses, required for mounting optimal protective immunity against lethal Salmonella infection.
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Fator Ativador de Células B/metabolismo , Células Dendríticas/imunologia , Neutrófilos/imunologia , Infecções por Salmonella/imunologia , Animais , Fator Ativador de Células B/genética , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Salmonella/microbiologia , Salmonella typhimurium/patogenicidade , Baço/citologia , Baço/imunologiaRESUMO
Sponges are known to produce a series of compounds with bioactivities useful for human health. This study was conducted on four sponges collected in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November-December 2018, i.e., Mycale (Oxymycale) acerata, Haliclona (Rhizoniera) dancoi, Hemimycale topsenti, and Hemigellius pilosus. Sponge extracts were fractioned and tested against hepatocellular carcinoma (HepG2), lung carcinoma (A549), and melanoma cells (A2058), in order to screen for antiproliferative or cytotoxic activity. Two different chemical classes of compounds, belonging to mycalols and suberitenones, were identified in the active fractions. Mycalols were the most active compounds, and their mechanism of action was also investigated at the gene and protein levels in HepG2 cells. Of the differentially expressed genes, ULK1 and GALNT5 were the most down-regulated genes, while MAPK8 was one of the most up-regulated genes. These genes were previously associated with ferroptosis, a programmed cell death triggered by iron-dependent lipid peroxidation, confirmed at the protein level by the down-regulation of GPX4, a key regulator of ferroptosis, and the up-regulation of NCOA4, involved in iron homeostasis. These data suggest, for the first time, that mycalols act by triggering ferroptosis in HepG2 cells.
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Antineoplásicos/farmacologia , Álcoois Graxos/farmacologia , Poríferos , Animais , Regiões Antárticas , Organismos Aquáticos , Linhagem Celular Tumoral/efeitos dos fármacos , Células Hep G2/efeitos dos fármacos , Humanos , FitoterapiaRESUMO
Marine sponges commonly host a repertoire of bacterial-associated organisms, which significantly contribute to their health and survival by producing several anti-predatory molecules. Many of these compounds are produced by sponge-associated bacteria and represent an incredible source of novel bioactive metabolites with biotechnological relevance. Although most investigations are focused on tropical and temperate species, to date, few studies have described the composition of microbiota hosted by Antarctic sponges and the secondary metabolites that they produce. The investigation was conducted on four sponges collected from two different sites in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November-December 2018. Collected species were characterized as Mycale (Oxymycale) acerata, Haliclona (Rhizoniera) dancoi, Hemigellius pilosus and Microxina sarai by morphological analysis of spicules and amplification of four molecular markers. Metataxonomic analysis of these four Antarctic sponges revealed a considerable abundance of Amplicon Sequence Variants (ASVs) belonging to the phyla Proteobacteria, Bacteroidetes, Actinobacteria and Verrucomicrobia. In particular, M. (Oxymycale) acerata, displayed several genera of great interest, such as Endozoicomonas, Rubritalea, Ulvibacter, Fulvivirga and Colwellia. On the other hand, the sponges H. pilosus and H. (Rhizoniera) dancoi hosted bacteria belonging to the genera Pseudhongella, Roseobacter and Bdellovibrio, whereas M. sarai was the sole species showing some strains affiliated to the genus Polaribacter. Considering that most of the bacteria identified in the present study are known to produce valuable secondary metabolites, the four Antarctic sponges could be proposed as potential tools for the discovery of novel pharmacologically active compounds.
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Bactérias/genética , Genoma Bacteriano , Metagenoma , Microbiota , Poríferos/microbiologia , Animais , Regiões Antárticas , Bactérias/classificação , Bactérias/metabolismo , Filogenia , Metabolismo SecundárioRESUMO
This work presents a novel method of exploring human brain-visual representations, with a view towards replicating these processes in machines. The core idea is to learn plausible computational and biological representations by correlating human neural activity and natural images. Thus, we first propose a model, EEG-ChannelNet, to learn a brain manifold for EEG classification. After verifying that visual information can be extracted from EEG data, we introduce a multimodal approach that uses deep image and EEG encoders, trained in a siamese configuration, for learning a joint manifold that maximizes a compatibility measure between visual features and brain representations. We then carry out image classification and saliency detection on the learned manifold. Performance analyses show that our approach satisfactorily decodes visual information from neural signals. This, in turn, can be used to effectively supervise the training of deep learning models, as demonstrated by the high performance of image classification and saliency detection on out-of-training classes. The obtained results show that the learned brain-visual features lead to improved performance and simultaneously bring deep models more in line with cognitive neuroscience work related to visual perception and attention.
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Algoritmos , Redes Neurais de Computação , Atenção , Encéfalo/diagnóstico por imagem , Humanos , Percepção VisualRESUMO
In the freezing waters of the Southern Ocean, Antarctic teleost fish, the Notothenioidei, have developed unique adaptations to cope with cold, including, at the extreme, the loss of hemoglobin in icefish. As a consequence, icefish are thought to be the most vulnerable of the Antarctic fish species to ongoing ocean warming. Some icefish also fail to express myoglobin but all appear to retain neuroglobin, cytoglobin-1, cytoglobin-2, and globin-X. Despite the lack of the inducible heat shock response, Antarctic notothenioid fish are endowed with physiological plasticity to partially compensate for environmental changes, as shown by numerous physiological and genomic/transcriptomic studies over the last decade. However, the regulatory mechanisms that determine temperature/oxygen-induced changes in gene expression remain largely unexplored in these species. Proteins such as globins are susceptible to environmental changes in oxygen levels and temperature, thus playing important roles in mediating Antarctic fish adaptations. In this study, we sequenced the full-length transcripts of myoglobin, neuroglobin, cytoglobin-1, cytoglobin-2, and globin-X from the Antarctic red-blooded notothenioid Trematomus bernacchii and the white-blooded icefish Chionodraco hamatus and evaluated transcripts levels after exposure to high temperature and low oxygen levels. Basal levels of globins are similar in the two species and both stressors affect the expression of Antarctic fish globins in brain, retina and gills. Temperature up-regulates globin expression more effectively in white-blooded than in red-blooded fish while hypoxia strongly up-regulates globins in red-blooded fish, particularly in the gills. These results suggest globins function as regulators of temperature and hypoxia tolerance. This study provides the first insights into globin transcriptional changes in Antarctic fish.
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Proteínas de Peixes/genética , Regulação da Expressão Gênica/fisiologia , Globinas/genética , Perciformes/genética , Sequência de Aminoácidos , Animais , Feminino , Proteínas de Peixes/química , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Globinas/química , Globinas/metabolismo , Masculino , Perciformes/metabolismo , Filogenia , Alinhamento de Sequência/veterináriaRESUMO
Marine organisms inhabiting extreme habitats are a promising reservoir of bioactive compounds for drug discovery. Extreme environments, i.e., polar and hot regions, deep sea, hydrothermal vents, marine areas of high pressure or high salinity, experience conditions close to the limit of life. In these marine ecosystems, "hot spots" of biodiversity, organisms have adopted a huge variety of strategies to cope with such harsh conditions, such as the production of bioactive molecules potentially valuable for biotechnological applications and for pharmaceutical, nutraceutical and cosmeceutical sectors. Many enzymes isolated from extreme environments may be of great interest in the detergent, textile, paper and food industries. Marine natural products produced by organisms evolved under hostile conditions exhibit a wide structural diversity and biological activities. In fact, they exert antimicrobial, anticancer, antioxidant and anti-inflammatory activities. The aim of this Special Issue "Bioactive Molecules from Extreme Environments" was to provide the most recent findings on bioactive molecules as well as enzymes isolated from extreme environments, to be used in biotechnological discovery pipelines and pharmaceutical applications, in an effort to encourage further research in these extreme habitats.