Potential of novel dextran oligosaccharides as prebiotics for obesity management through in vitro experimentation

The energy-salvaging capacity of the gut microbiota from dietary ingredients has been proposed as a contributing factor for the development of obesity. This knowledge generated interest in the use of non-digestible dietary ingredients such as prebiotics to manipulate host energy homeostasis. In the present study, the in vitro response of obese human faecal microbiota to novel oligosaccharides was investigated. Dextrans of various molecular weights and degrees of branching were fermented with the faecal microbiota of healthy obese adults in pH-controlled batch cultures. Changes in bacterial populations were monitored using fluorescent in situ hybridisation and SCFA concentrations were analysed by HPLC. The rate of gas production and total volume of gas produced were also determined. In general, the novel dextrans and inulin increased the counts of bifidobacteria. Some of the dextrans were able to alter the composition of the obese human microbiota by increasing the counts of Bacteroides–Prevotella and decreasing those of Faecalibacterium prausnitzii and Ruminococcus bromii/R. flavefaciens. Considerable increases in SCFA concentrations were observed in response to all substrates. Gas production rates were similar during the fermentation of all dextrans, but significantly lower than those during the fermentation of inulin. Lower total gas production and shorter time to attain maximal gas production were observed during the fermentation of the linear 1 kDa dextran than during the fermentation of the other dextrans. The efficacy of bifidobacteria to ferment dextrans relied on the molecular weight and not on the degree of branching. In conclusion, there are no differences in the profiles between the obese and lean human faecal fermentations of dextrans

Reproductive Failure in UK Harbour Porpoises Phocoena phocoena : Legacy of Pollutant Exposure?

This research was supported by a Marie Curie International Outgoing Fellowship within the Seventh European Community Framework Programme (Project Cetacean-stressors, PIOF-GA-2010-276145 to PDJ and SM). Additional funding was provided through the Agreement on the Conservation of Small Cetaceans of the Baltic, North East Atlantic, Irish and North Seas (ASCOBANS) (Grants SSFA/2008 and SSFA / ASCOBANS / 2010 / 5 to SM). Analysis of Scottish reproductive and teeth samples was funded by the EC-funded BIOCET project (BIOaccumulation of persistent organic pollutants in small CETaceans in European waters: transport pathways and impact on reproduction, grant EVK3-2000-00027 to GJP), and Marine Scotland (GJP). Samples examined in this research were collected under the collaborative Cetacean Strandings Investigation Programme (http://ukstrandings.org/), which is funded by the Department for Environment, Food and Rural Affairs (Defra) and the UK’s Devolved Administrations in Scotland and Wales (http://sciencesearch.defra.gov.uk/Defaul​t.aspx?Menu=Menu&Module=More&Location=No​ne&Completed=0&ProjectID=15331) (grants to PDJ, RD). UK Defra also funded the chemical analysis under a service-level agreement with the Centre for Environment, Fisheries and Aquaculture Science (grants to RJL, JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Major Histocompatibility Complex (MHC) Class II sequence polymorphism in long-finned pilot whale (Globicephala melas) from the North Atlantic

Funding Silvia S. Monteiro and Marisa Ferreira were supported by a Ph.D. grant from Fundação para a Ciência e Tecnologia (ref SFRH/BD/38735/2007 and SFRH/BD/30240/2006, respectively). Alfredo López was supported by a postdoctoral grant from Fundação para a Ciência e Tecnologia (ref SFRH/BPD/82407/2011). Catarina Eira is supported by CESAM (UID/AMB/50017), from FCT/MEC through national funds and FEDER (PT2020, Compete 2020). The work related with strandings and tissue collection in Portugal was partially supported by the SafeSea Project EEAGrants PT 0039 (supported by Iceland, Liechtenstein and Norway through the EEA Financial Mechanism), by the Project MarPro–Life09 NAT/PT/000038 (funded by the European Union–Program Life+) and by the project CetSenti FCT RECI/AAG-GLO/0470/2012; FCOMP-01-0124-FEDER-027472 (Funded by the Program COMPETE and Fundação para a Ciência e Tecnologia).Peer reviewedPostprin

Using network theory to identify the causes of disease outbreaks of unknown origin.

The identification of undiagnosed disease outbreaks is critical for mobilizing efforts to prevent widespread transmission of novel virulent pathogens. Recent developments in online surveillance systems allow for the rapid communication of the earliest reports of emerging infectious diseases and tracking of their spread. The efficacy of these programs, however, is inhibited by the anecdotal nature of informal reporting and uncertainty of pathogen identity in the early stages of emergence. We developed theory to connect disease outbreaks of known aetiology in a network using an array of properties including symptoms, seasonality and case-fatality ratio. We tested the method with 125 reports of outbreaks of 10 known infectious diseases causing encephalitis in South Asia, and showed that different diseases frequently form distinct clusters within the networks. The approach correctly identified unknown disease outbreaks with an average sensitivity of 76 per cent and specificity of 88 per cent. Outbreaks of some diseases, such as Nipah virus encephalitis, were well identified (sensitivity = 100%, positive predictive values = 80%), whereas others (e.g. Chandipura encephalitis) were more difficult to distinguish. These results suggest that unknown outbreaks in resource-poor settings could be evaluated in real time, potentially leading to more rapid responses and reducing the risk of an outbreak becoming a pandemic

Enhancer evolution across 20 mammalian species.

The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.We thank Stephen Watt, Frances Connor, the CRUK-CI Genomics and Bioinformatics cores, Biological Resources Unit (Matthew Clayton), Margaret Brown (West Yorkshire bat hospital), Julie E. Horvath (North Carolina Central University), and Chris Dillingham (University of Cardiff) for technical assistance; Matthieu Muffato for assistance with whole-genome alignments; Claudia Kutter, Gordon Brown, Christine Feig, and Christina Ernst for useful comments and discussions, and the EBI systems team for management of computational resources. This research was supported by Cancer Research UK (D.V., D.T.O.), the European Molecular Biology Laboratory (C.B., P.F.), the Wellcome Trust (WT095908) (P.F.) and (WT098051) (P.F., D.T.O.), the European Research Council, EMBO Young Investigator Programme (D.T.O.), the National Science Foundation (0744979) (T.J.P.), NIH (P40 OD010965, R01 OD010980, R37 MH060233) (A.J.J.) and MRC (U117588498) (J.M.A.T.). Cetacean samples were collected by the UK Cetacean Strandings Investigation Programme, funded by Defra and the Governments of Scotland and Wales.This is the final version. It originally appeared at http://www.sciencedirect.com/science/article/pii/S0092867415000070

Smooth muscle actin and vimentin as markers of testis development in the harbour porpoise (Phocoena phocoena)

Testicular development in the harbour porpoise Phocoena phocoena was examined using animals (n = 192) stranded or by-caught off the coast of England, Wales and Scotland. Classification of animals according to their stage of sexual development was undertaken using gonadal morphology and the distribution of cytoskeletal proteins. Smooth muscle actin (SMA) and vimentin proved particularly useful in this respect; SMA was prominent in the myoid peritubular cells of the adult testis, and two stages of peritubular cell SMA expression could be recognized ('absent' or 'incomplete'). The initial appearance of SMA in peritubular cells was associated with significant increases in body length and body weight (P < 0.001), and occurred during the second year of life. Vimentin, which was prominent in prespermatogonia and spermatogonia, sometimes showed a polarized cytoplasmic distribution. This correlated with a developmental stage at which the seminiferous tubule epithelium becomes populated by germ cells (mean age 1.8 years). Several antibodies were tested for their utility as Sertoli cell markers, but none was found to be specific or useful. Nevertheless, immunohistochemical localization of desmin, GATA-4, Ki67 and androgen receptor was possible despite the poor quality of tissue preservation. This study showed that immunohistochemical classification of these individuals provides a robust basis for the recognition of key physiological stages of sexual development in the male harbour porpoise. This may provide an alternative to the estimation of age, body weight and body length in future analyses aimed at detecting possible adverse effects of environmental pollutants on the reproductive potential of wild marine mammals

A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C

Background/Aims: In chronic hepatitis C, interferon alfa (IFN-α) therapy fails to achieve a sustained response in approximately 75% of patients. Similarly, ribavirin induces only a transient response. The aim of this study was to evaluate whether ribavirin and IFN-α in combination could be effective in IFN-α-resistant chronic hepatitis C. Methods: Twenty patients with chronic hepatitis C resistant to a previous course of IFN-α were randomly assigned to receive either ribavirin combined with IFN-α or IFN-α alone for 6 months. Results: Serum alanine aminotransferase levels decreased significantly during therapy in both treatment groups, but after therapy, the levels remained significantly decreased only in the combination therapy group. Nine months after treatment, sustained normalization of aminotransferase levels, associated with sustained loss of serum hepatitis C virus RNA, was observed in 40% of the patients in the combination therapy group but in none of the patients treated with IFN-α alone (P < 0.05). The sustained response was accompanied by reduced hepatic necroinflammatory activity on biopsy. Conclusions: These findings suggest that ribavirin plus IFN-α combination therapy is able to induce a sustained biochemical and virological response in a significant proportion of patients with IFN-α-resistant chronic hepatitis C. © 1994

Relationships between polychlorinated biphenyls and health status in harbor porpoises (Phocoena phocoena) stranded in the United Kingdom

To investigate possible relationships between polychlorinated biphenyl (PCB) exposure and infectious disease mortality in harbor porpoises (Phocoena phocoena) in United Kingdom waters, summed blubber concentrations of 25 chlorobiphenyl congeners (Sigma25CB) in healthy harbor porpoises that died of acute physical trauma (mainly by-catch; n = 175) were compared with Sigma25CB values in animals that died of infectious disease (n = 82). The infectious disease group had significantly greater Sigma25CB values (mean, 27.6 mg/kg lipid) than the physical trauma group (mean, 13.6 mg/kg lipid; p 0.55). These findings are consistent with a causal (immunotoxic) relationship between PCB exposure and infectious disease mortality, and they provide a framework for future quantitative risk-assessment analyses of porpoise populations of known size and PCB exposure

A note on the unprecedented strandings of 56 deep-diving whales along the UK and Irish coast

In the first seven months of 2008, eighteen Cuvier’s beaked whales (Ziphius cavirostris), four Sowerby’s beaked whales (Mesoplodon bidens), five unidentified beaked whales and twenty-nine long-finned pilot whales (Globicephala melas) were reported stranded in the UK and Ireland. Decomposition of those animals investigated puts the predicted time of death at mid-January. Concerns that an unusual mortality event had taken place prompted further investigations. Most carcasses were too decomposed for necropsy. A summary of findings is presented here. Although the initial stranding of five Cuvier’s beaked whales in Scotland shared some similarities with atypical mass stranding events linked in time and space to mid-frequency naval sonars, there were two important differences with the remaining strandings during this period. First, the geographical range of the event was very wide and second, the strandings occurred over a prolonged period of several months. Both of these factors could be related to the fact that the mortalities occurred offshore and the carcasses drifted ashore. The cause(s) of this high number of strandings of mixed offshore cetacean species during this period remain undetermined