Rethinking the bile acid/gut microbiome axis in cancer

Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohort

Radiocarbon dating casts doubt on the late chronology of the Middle to Upper Palaeolithic transition in southern Iberia

It is commonly accepted that some of the latest dates for Neanderthal fossils and Mousterian industries are found south of the Ebro valley in Iberia at ca. 36 ka calBP (calibrated radiocarbon date ranges). In contrast, to the north of the valley the Mousterian disappears shortly before the Proto-Aurignacian appears at ca. 42 ka calBP. The latter is most likely produced by anatomically modern humans. However, two-thirds of dates from the south are radiocarbon dates, a technique that is particularly sensitive to carbon contaminants of a younger age that can be difficult to remove using routine pretreatment protocols. We have attempted to test the reliability of chronologies of 11 southern Iberian Middle and early Upper Paleolithic sites. Only two, Jarama VI and Zafarraya, were found to contain material that could be reliably dated. In both sites, Middle Paleolithic contexts were previously dated by radiocarbon to less than 42 ka calBP. Using ultrafiltration to purify faunal bone collagen before radiocarbon dating, we obtain ages at least 10 ka 14C years older, close to or beyond the limit of the radiocarbonmethod for the Mousterian at Jarama VI and Neanderthal fossils at Zafarraya. Unless rigorous pretreatment protocols have been used, radiocarbon dates should be assumed to be inaccurate until proven otherwise in this region. Evidence for the late survival of Neanderthals in southern Iberia is limited to one possible site, Cueva Antón, and alternative models of human occupation of the region should be considered

Biochemical characteristics and bacterial community structure of the sea surface microlayer in the South Pacific Ocean

The chemical and biological characteristics of the surface microlayer were determined during a transect across the South Pacific Ocean in October-December 2004. Concentrations of particulate organic carbon (1.3 to 7.6-fold) and nitrogen (1.4 to 7-fold), and POC:PON ratios were consistently higher in the surface microlayer as compared to surface waters (5 m). The large variability in particulate organic matter enrichment was negatively correlated to wind speed. No enhanced concentrations of dissolved organic carbon were detectable in the surface microlayer as compared to 5 m, but chromophoric dissolved organic matter was markedly enriched (by 2 to 4-fold) at all sites. Based on pigment analysis and cell counts, no consistent enrichment of any of the major components of the autotrophic and heterotrophic microbial community was detectable. CE-SSCP fingerprints and CARD FISH revealed that the bacterial communities present in the surface microlayer had close similarity (>76%) to those in surface waters. By contrast, bacterial heterotrophic production (<sup>3</sup>H-leucine incorporation) was consistently lower in the surface microlayer than in surface waters. By applying CARD-FISH and microautoradiography, we observed that <i>Bacteroidetes</i> and <i>Gammaproteobacteria</i> dominated leucine uptake in the surface microlayer, while in surface waters <i>Bacteroidetes</i> and <i>Alphaproteobacteria</i> were the major groups accounting for leucine incorporation. Our results demonstrate that the microbial community in the surface microlayer closely resembles that of the surface waters of the open ocean. Even a short residence in the surface microlayer influences leucine incorporation by different bacterial groups, probably as a response to the differences in the physical and chemical nature of the two layers

Effect of Ozonated Fertigation in Pepper Cultivation under Greenhouse Conditions

Ozone has a high oxidizing power avoiding the presence of residues, so it is a good candidate for use in organic farming. However, its application in fertigation has been little studied. Two experiments were conducted simultaneously to check the aims of this work. The aim of the first experiment was to study pepper response under the nutrient solution supply and the application of O3 and its interactions, and the aim of the second experiment was to determine the optimal dosage of O3 to be supplied, from the point of view of plant development and nutritional and physiological status in both experiments. We conclude that O3 supply via fertigation increased pepper biomass production. According to the results obtained, we recommend that the optimal dosage of O3 in pepper plants be from 0.18 to 0.36 mg L−1 due to its higher associated biomass production. Under these dosages, pepper plants showed a higher leaf area and higher photosynthetic pigment concentration. Similarly, under these dosages, N, P, and K plant uptake were higher, allowing a higher synthesis of bioassimilates

Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures: an architectural survey

Over the last couple of years, industry operators’ associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This arti- cle provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi- operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation

Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures: An architectural survey

Over the last couple of years, industry operators' associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This article provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi-operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisatio

Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures: An architectural survey

Over the last couple of years, industry operators' associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This article provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi-operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation

Description of two cultivated and two uncultivated new Salinibacter species, one named following the rules of the bacteriological code: Salinibacter grassmerensis sp. nov.; and three named following the rules of the SeqCode: Salinibacter pepae sp. nov., Salinibacter abyssi sp. nov., and Salinibacter pampae sp. nov.

Current -omics methods allow the collection of a large amount of information that helps in describing the microbial diversity in nature. Here, and as a result of a culturomic approach that rendered the collection of thousands of isolates from 5 different hypersaline sites (in Spain, USA and New Zealand), we obtained 21 strains that represent two new Salinibacter species. For these species we propose the names Salinibacter pepae sp. nov. and Salinibacter grassmerensis sp. nov. (showing average nucleotide identity (ANI) values < 95.09% and 87.08% with Sal. ruber M31T, respectively). Metabolomics revealed species-specific discriminative profiles. Sal. ruber strains were distinguished by a higher percentage of polyunsaturated fatty acids and specific N-functionalized fatty acids; and Sal. altiplanensis was distinguished by an increased number of glycosylated molecules. Based on sequence characteristics and inferred phenotype of metagenome-assembled genomes (MAGs), we describe two new members of the genus Salinibacter. These species dominated in different sites and always coexisted with Sal. ruber and Sal. pepae. Based on the MAGs from three Argentinian lakes in the Pampa region of Argentina and the MAG of the Romanian lake Fără Fund, we describe the species Salinibacter pampae sp. nov. and Salinibacter abyssi sp. nov. respectively (showing ANI values 90.94% and 91.48% with Sal. ruber M31T, respectively). Sal. grassmerensis sp. nov. name was formed according to the rules of the International Code for Nomenclature of Prokaryotes (ICNP), and Sal. pepae, Sal. pampae sp. nov. and Sal. abyssi sp. nov. are proposed following the rules of the newly published Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode). This work constitutes an example on how classification under ICNP and SeqCode can coexist, and how the official naming a cultivated organism for which the deposit in public repositories is difficult finds an intermediate solution.This study was funded by the Spanish Ministry of Science, Innovation and Universities projects PGC2018-096956-B-C41, RTC-2017-6405-1 and PID2021-126114NB-C42, which were also supported by the European Regional Development Fund (FEDER). RRM acknowledges the financial support of the sabbatical stay at Georgia Tech and HelmholzZentrum München by the grants PRX18/00048 and PRX21/00043 respectively also from the Spanish Ministry of Science, Innovation and Universities. This research was carried out within the framework of the activities of the Spanish Government through the “Maria de Maeztu Centre of Excellence” accreditation to IMEDEA (CSIC-UIB) (CEX2021-001198). KTK’s research was supported, in part, by the U.S. National Science Foundation (Award No. 1831582 and No. 2129823). IMG. AC and HLB were financially supported by a grant of the Ministry of Research, Innovation and Digitization, CNCS/CCCDI – UEFISCDI, project number PN-III-P4-ID-PCE-2020-1559, within PNCDI III. HLB acknowledges Ocna Sibiului City Hall (Sibiu County, Romania) for granting the access to Fără Fund Lake and A. Baricz and D.F. Bogdan for technical support during sampling and sample preparation. MBS thanks Dominion Salt for their assistance in sample Lake Grassmere. MELL acknowledges the financial support of the Argentinian National Scientific and Technical Research Council (Grant CONICET-NSFC 2017 N° IF-2018-10102222-APN-GDCT-CONICET) and the National Geographic Society (Grant # NGS 357R-18). BPH was supported by NASA (award 80NSSC18M0027). TV acknowledges the “Margarita Salas” postdoctoral grant, funded by the Spanish Ministry of Universities, within the framework of Recovery, Transformation and Resilience Plan, and funded by the European Union (NextGenerationEU), with the participation of the University of Balearic Islands (UIB)

The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota

Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.Stephen J. Blake, Jane James, Feargal J. Ryan, Jose Caparros-Martin, Georgina L. Eden, Yee C. Tee, John R. Salamon, Saoirse C. Benson, Damon J. Tumes, Anastasia Sribnaia, Natalie E. Stevens, John W. Finnie, Hiroki Kobayashi, Deborah L. White, Steve L. Wesselingh, Fergal O’Gara, Miriam A. Lynn, and David J. Lyn

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, setting, and participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main outcomes and measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.info:eu-repo/semantics/publishedVersio