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Peaks in northern bottlenose whale, Hyperoodon ampullatus, strandings are found between August and September in the UK and August and November in The Netherlands, consistent with a hypothesized southward migration. However, results on diet suggest that several whales stranded during these months were not travelling from northern latitudes prior to stranding. We analysed the stomach contents of ten whales stranded in the north-east Atlantic (Scotland, N = 6, England, N = 1, Ireland, N = 2 and The Netherlands, N = 1). All but one of the analysed whales (live-stranded in the River Thames in January 2006) stranded between August and October. Food remains consisted almost entirely of cephalopod mandibles. Twenty-one cephalopod species (16 families) were recorded, the most abundant taxa being Gonatus spp., Teuthowenia spp. and Taonius pavo. No fish and few crustacean remains were found. Small amounts of cephalopod flesh were found in three of the stomachs and none in the others. Given that cephalopod beaks can remain within the stomach for several days, and that there was no evidence of inshore feeding (no coastal species were present among the prey), the whales may not have fed for several days prior to stranding. Three whales had remains of warm-temperate water cephalopods (e.g. Vampyroteuthis infernalis, Heteroteuthis sp.) in their stomachs, while three individuals showed a high diversity of prey in their stomachs, suggesting that several of the whales could have been either travelling north or consistently feeding in temperate latitudes prior to stranding. As previously recorded in other deep diving teuthophagous cetaceans, two animals had ingested small amounts of plastic debris.

Microbiology records for 1127 cetaceans stranded on English and Welsh beaches and examined at the Institute of Zoology between 1990 and 2019 were reviewed to identify cases of Erysipelothrix rhusiopathiae, an uncommon but potentially fatal zoonotic pathogen. Once cases were identified, prevalence was calculated, corresponding postmortem reports were reviewed, common gross and histopathological findings were identified, and antibiotic susceptibilities were determined. Overall prevalence for E. rhusiopathiae was 0.62% (7/1127; 95% CI: 0.30-1.28%). It was isolated from 3 bottlenose dolphins Tursiops truncatus, 3 harbor porpoises Phocoena phocoena, and 1 short-beaked common dolphin Delphinus delphis, with a prevalence of 21.4% (3/14; 95% CI: 7.6-47.9%), 0.39% (3/779; 95% CI: 0.13-1.13%), and 0.47% (1/212; 95% CI: 0.08-2.62%) for each species, respectively. E. rhusiopathiae resulted in septicemia in all cases from which it was isolated. Gross necropsy findings included pulmonary edema (5/7), hemorrhage (5/7) and/or congestion of various organs (4/7), and serosanguineous effusion (3/7; pericardial: 3/7, pleural: 2/6, abdominal: 2/6). Congestion (5/5), bacterial emboli (4/5), and hemorrhage (4/5) were commonly observed on histopathology, and acute renal tubular injury (2/5) and pulmonary edema (2/5) were occasionally observed. Routine bacterial cultures were vital in identifying E. rhusiopathiae, since gross lesions were often subtle and nonspecific. The liver, kidney, and brain were key organs from which E. rhusiopathiae was consistently isolated. Antibiotic resistance was uncommon and was only observed for amikacin and trimethoprim sulfonamide. Penicillins were consistently effective, along with fluoroquinolones, macrolides, clindamycin, cephalexin, and oxytetracycline.

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans1–7. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans8, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.

Polychlorinated biphenyls (PCBs) are toxic, persistent, and lipophilic chemical compounds that accumulate to high levels in harbor porpoises (Phocoena phocoena) and other cetaceans. It is important to monitor PCBs in wildlife, particularly in highly exposed populations to understand if concentrations are declining and how levels relate to toxicological thresholds and indices of health like infectious disease mortality. Here we show, using generalized additive models and tissue samples of 814 U.K.-stranded harbor porpoises collected between 1990 and 2017, that mean blubber PCB concentrations have fallen below the proposed thresholds for toxic effects. However, we found they are still associated with increased rates of infectious disease mortality such that an increase in PCB blubber concentrations of 1 mg kg-1 lipid corresponds with a 5% increase in risk of infectious disease mortality. Moreover, rates of decline and levels varied geographically, and the overall rate of decline is slow in comparison to other pollutants. We believe this is evidence of long-term preservation in the population and continued environmental contamination from diffuse sources. Our findings have serious implications for the management of PCB contamination in the U.K. and reinforce the need to prevent PCBs entering the marine environment to ensure that levels continue to decline.

Marine mammals are vulnerable to the bioaccumulation, biomagnification and lactational transfer of specific types of pollutants, such as industrial polychlorinated biphenyls (PCBs), due to their long-life spans, feeding at a high trophic level and unique fat stores that can serve as depots for these lipophilic contaminants. Currently, European countries are developing indicators for monitoring pollutants in the marine environment and assessing the state of biodiversity, requirements under both Regional Seas Conventions and European legislation. As sentinel species for marine ecosystem and human health, marine mammals can be employed to assess bioaccumulated contaminants otherwise below current analytical detection limits in water and lower trophic level marine biota. To aid the development of Regional Seas marine mammal contaminants indicators, as well as Member States obligations under descriptor 8 of the EU Marine Strategy Framework Directive, the current study aims to further develop appropriate methodological standards using data collected by the established UK marine mammal pollutant monitoring programme (1990 to 2017) to assess the trends and status of PCBs in harbour porpoises. Within this case study, temporal trends of PCB blubber concentration in juvenile harbour porpoises were analysed using multiple linear regression models and toxicity thresholds for the onset of physiological (reproductive and immunological) endpoints were applied to all sex-maturity groups. Mean PCB blubber concentrations were observed to decline in all harbour porpoise Assessment Units and OSPAR Assessment Areas in UK waters. However, a high proportion of animals were exposed to concentrations deemed to be a toxicological threat, though the relative proportion declined in most Assessment Units/Areas over the last 10 years of the assessment. Recommendations were made for improving the quality of the assessment going forward, including detailing monitoring requirements for the successful implementation of such an indicator.

Polychlorinated biphenyls (PCBs) are highly toxic and persistent aquatic pollutants that are known to bioaccumulate in a variety of marine mammals. They have been associated with reduced recruitment rates and population declines in multiple species. Evidence to date documents effects of PCB exposures on female reproduction, but few studies have investigated whether PCB exposure impacts male fertility. Using blubber tissue samples of 99 adult and 168 juvenile UK-stranded harbour porpoises (Phocoena phocoena) collected between 1991 and 2017, here we show that PCBs exposures are associated with reduced testes weights in adults with good body condition. In animals with poor body condition, however, the impact of PCBs on testes weights was reduced, conceivably due to testes weights being limited by nutritional stress. This is the first study to investigate the relationship between PCB contaminant burden and testes weights in cetaceans and represents a substantial advance in our understanding of the relationship between PCB exposures and male reproductive biology in cetaceans. As testes weight is a strong indicator of male fertility in seasonally breeding mammals, we suggest the inclusion of such effects in population level impact assessments involving PCB exposures. Given the re-emergent PCB threat our findings are globally significant, with potentially serious implications for long-lived mammals. We show that more effective PCB controls could have a substantial impact on the reproductive health of coastal cetacean species and that management actions may need to be escalated to ensure adequate protection of the most vulnerable cetacean populations. Defra; Natural Environment Research Council (NERC) grant NE/L002485/1; Bertarelli Foundation through the Bertarelli Programme in Marine Science; partially funded by NERC grant NE/S000100/1 supporting the ChemPop project.

Summary Cetacean morbillivirus (CeMV) is an important global cause of morbidity and mortality in cetacean populations, with four pathological presentations including non-suppurative encephalitis. We describe an unusual case of dolphin morbillivirus (DMV)-associated non-suppurative encephalitis in a long-finned pilot whale (Globicephala melas), in which the lesions were orientated on the periventricular white matter and comprised prominent multifocal syncytia formation in the absence of systemic lesions. DMV RNA was detected in brain tissue by qRT-PCR and immunohistochemistry for morbillivirus antigen yielded intense labelling of syncytia in periventricular sites, with sparse involvement of the deeper neuroparenchyma. The pattern of lesions raises the possibility of viral dissemination through the cerebrospinal fluid, as described for canine distemper virus, suggesting that similar pathogenic mechanisms may be implicated in lesion development. Further investigation is required to establish the pathogenesis of CeMV encephalitis and the behaviour of the virus within the central nervous system of cetaceans.

Polychlorinated biphenyls (PCBs) are toxic, persistent, and lipophilic chemical compounds that accumulate to high levels in harbor porpoises (

Determining how intra-specific genetic diversity is apportioned among natural populations is essential for detecting local adaptation and identifying populations with inherently low levels of extant diversity which may become a conservation concern. Sequence polymorphism at two adaptive loci (MHC DRA and DQB) was investigated in long-finned pilot whales (Globicephala melas) from four regions in the North Atlantic and compared with previous data from New Zealand (South Pacific). Three alleles were resolved at each locus, with trans-species allele sharing and higher levels of non-synonymous to synonymous substitution, especially in the DQB locus. Overall nucleotide diversities of 0.49 ± 0.38% and 4.60 ± 2.39% were identified for the DRA and DQB loci, respectively, which are relatively low for MHC loci in the North Atlantic, but comparable to levels previously described in New Zealand (South Pacific). There were significant differences in allele frequencies within the North Atlantic and between the N...

The evolution of cetaceans, from their early transition to an aquatic lifestyle to their subsequent diversification, has been the subject of numerous studies. However, although the higher-level relationships among cetacean families have been largely settled, several aspects of the systematics within these groups remain unresolved. Problematic clades include the oceanic dolphins (37 spp.), which have experienced a recent rapid radiation, and the beaked whales (22 spp.), which have not been investigated in detail using nuclear loci. The combined application of high-throughput sequencing with techniques that target specific genomic sequences provide a powerful means of rapidly generating large volumes of orthologous sequence data for use in phylogenomic studies. To elucidate the phylogenetic relationships within the Cetacea, we combined sequence capture with Illumina sequencing to generate data for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\sim $\end{document}3200 protein-coding genes for 68 cetacean species and their close relatives including the pygmy hippopotamus. By combining data from \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$>$\end{document}38,000 exons with existing sequences from 11 cetaceans and seven outgroup taxa, we produced the first comprehensive comparative genomic data set for cetaceans, spanning 6,527,596 aligned base pairs (bp) and 89 taxa. Phylogenetic trees reconstructed with maximum likelihood and Bayesian inference of concatenated loci, as well as with coalescence analyses of individual gene trees, produced mostly concordant and well-supported trees. Our results completely resolve the relationships among beaked whales as well as the contentious relationships among oceanic dolphins, especially the problematic subfamily Delphinidae. We carried out Bayesian estimation of species divergence times using MCMCTree and compared our complete data set to a subset of clocklike genes. Analyses using the complete data set consistently showed less variance in divergence times than the reduced data set. In addition, integration of new fossils (e.g., Mystacodon selenensis) indicates that the diversification of Crown Cetacea began before the Late Eocene and the divergence of Crown Delphinidae as early as the Middle Miocene. [Cetaceans; phylogenomics; Delphinidae; Ziphiidae; dolphins; whales.]

Organochlorines, such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), are persistent organic pollutants that both bioaccumulate and biomagnify within marine food webs. These legacy pollutants are known endocrine disruptors and have been reported to have adverse effects on endocrine, reproductive, and immune functions in humans, laboratory animals, and wildlife. This chapter will review evidence of pollutant-mediated effects on the reproductive system in cetaceans from exposure to PCBs and DDT. In addition, an assessment of reproductive failure and reproductive dysfunction was undertaken on stranded and bycaught female common dolphins from the Northeast Atlantic, and their association with exposure to PCBs was investigated. Within the sample, 16.8% (18 out of 107) of females presented with reproductive system pathologies that were associated with higher blubber ΣPCB lw concentrations, above the threshold for the onset of adverse health effects in marine mammals. Cases of reproductive failure were also reported that may be linked to exposure to these endocrine-disrupting chemicals. The continued exposure to legacy pollutants, and new emerging pollutants, raises concerns about the current and future population-level pollutant effects on Northeast Atlantic common dolphins.

An immature unilateral hermaphrodite common dolphin (Delphinus delphis) was found stranded on the southwest coast of the UK. The external phenotype was that of a female, but internally there was one ovotestis, containing both ovarian follicles and testicular tubular elements, and a contralateral ovary. Ovarian portions of the ovotestis appeared normal and demonstrated follicular development, whereas the testicular tissue exhibited hypoplasia and degeneration. This is the first reported case of an ovotestis in a cetacean species.

Population genetic structure of North Atlantic killer whale samples was resolved from differences in allele frequencies of 17 microsatellite loci, mtDNA control region haplotype frequencies and for a subset of samples, using complete mitogenome sequences. Three significantly differentiated populations were identified. Differentiation based on microsatellite allele frequencies was greater between the two allopatric populations than between the two pairs of partially sympatric populations. Spatial clustering of individuals within each of these populations overlaps with the distribution of particular prey resources: herring, mackerel and tuna, which each population has been seen predating. Phylogenetic analyses using complete mitogenomes suggested two populations could have resulted from single founding events and subsequent matrilineal expansion. The third population, which was sampled at lower latitudes and lower density, consisted of maternal lineages from three highly divergent clades. Pairwise population differentiation was greater for estimates based on mtDNA control region haplotype frequencies than for estimates based on microsatellite allele frequencies, and there were no mitogenome haplotypes shared among populations. This suggests low or no female migration and that gene flow was primarily male mediated when populations spatially and temporally overlap. These results demonstrate that genetic differentiation can arise through resource specialization in the absence of physical barriers to gene flow.

In small birds, mass-dependent predation risk (MDPR) is known to make the trade-off between avoiding starvation and avoiding predation dependent on individual mass. This occurs because carrying increased fat reserves not only reduces starvation risk but also results in a higher predation risk due to reduced escape flight performance and/or the increased foraging exposure needed to maintain a higher body mass. In principle, the theory of MDPR could also apply to any animal capable of storing energy reserves to reduce starvation and whose escape performance decreases with increasing mass. We used a unique situation along certain parts of coastal Britain, where harbour porpoises ( Phocoena phocoena ) are pursued and killed but crucially not eaten by bottlenose dolphins ( Tursiops truncatus ), to investigate whether a MDPR effect can occur in non-avian species. We show that where high levels of dolphin ‘predation’ occur, porpoises carry significantly less energy reserves than would otherwise be expected and this equates to reducing by approximately 37% the length of time that a porpoise could survive without feeding. These results provide the first evidence that a mass-dependent starvation–predation risk trade-off may be a general ecological principle that can apply to widely different animal types rather than, as is currently thought, only to birds.

Previous studies have indicated that the common European pipistrelle bat ( Pipistrellus pipistrellus ) comprises two cryptic species, P. pipistrellus and Pipistrellus pygmaeus , which differ in echolocation call frequency and mitochon- drial DNA sequence. However, levels of divergence based on nuclear markers have not been examined, and hence the potential for male-mediated gene flow between the species cannot be discounted. Moreover, little is known about pop- ulation structure and migration patterns in either species. Here, we describe the use of microsatellites to investigate nuclear DNA differentiation between, and the pattern of population genetic structure within, the two cryptic pip- istrelle species. In total, 1300 individuals from 82 maternity colonies were sampled across the British Isles and Con- tinental Europe. We show, using multivariate analyses, that colonies of the same species are generally genetically more similar to each other than to those from the other species regardless of geographical location. Our findings sup- port the hypothesis that the species are reproductively isolated. Significant patterns of genetic isolation by distance were identified in both species, indicating that mating may occur before any long-distance autumnal migration. The presence of a sea channel does not confer higher levels of genetic differentiation among colonies over and above dis- tance alone in either species. Differences in genetic population structure were identified between the species, with P. pipistrellus showing a wider range of levels of genetic differentiation among colonies and a stronger relationship between genetic and geographical distance than P. pygmaeus . Differences in dispersal, mating behaviour, colony size and/or postglacial colonization patterns could contribute to the differences observed. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society , 2007, 90 , 539-550. ADDITIONAL KEYWORDS: Chiroptera - isolation by distance - microsatellite - migration.

Reproductive failure in mammals due to exposure to polychlorinated biphenyls (PCBs) can occur either through endocrine disrupting effects or via immunosuppression and increased disease risk. To investigate further, full necropsies and determination of summed 25 polychlorinated biphenyls congeners (∑PCBs lipid weight) in blubber were undertaken on 329 UK-stranded female harbour porpoises (1990-2012). In sexually mature females, 25/127 (19.7%) showed direct evidence of reproductive failure (foetal death, aborting, dystocia or stillbirth). A further 21/127 (16.5%) had infections of the reproductive tract or tumours of reproductive tract tissues that could contribute to reproductive failure. Resting mature females (non-lactating or non-pregnant) had significantly higher mean ∑PCBs (18.5 mg/kg) than both lactating (7.5 mg/kg) and pregnant females (6 mg/kg), though not significantly different to sexually immature females (14.0 mg/kg). Using multinomial logistic regression models ΣPCBs was found to be a significant predictor of mature female reproductive status, adjusting for the effects of confounding variables. Resting females were more likely to have a higher PCB burden. Health status (proxied by “trauma” or “infectious disease” causes of death) was also a significant predictor, with lactating females (i.e. who successfully reproduced) more likely to be in good health status compared to other individuals. Based on contaminant profiles (>11 mg/kg lipid), at least 29/60 (48%) of resting females had not offloaded their pollutant burden via gestation and primarily lactation. Where data were available, these non-offloading females were previously gravid, which suggests foetal or newborn mortality. Furthermore, a lower pregnancy rate of 50% was estimated for “healthy” females that died of traumatic causes of death, compared to other populations. Whether or not PCBs are part of an underlying mechanism, we used individual PCB burdens to show further evidence of reproductive failure in the North-east Atlantic harbour porpoise population, results that should inform conservation management.

The objective of this study was to determine whether the risk of mortality from infectious disease in harbor porpoise in U.K. waters increased with high exposure to polychlorinated biphenyls (PCBs), using a case-control study design. This is the first time that data from a long-term marine mammal strandings scheme have been used to estimate any increase in risk. The exposure odds ratio (OR) from a logistic regression model with infectious disease deaths as cases and physical trauma deaths as controls, after controlling for the effect of confounding factors, was 1.048 [95% confidence interval (CI), 1.02-1.07]. To further adjust for the difference in energetic status between cases and controls and account for the negative relationship between PCBs (sum of 25 chlorobiphenyl congeners) and blubber mass, we also "standardized" the blubber PCBs to an optimal blubber mass. This lowered the OR to 1.02 (95% CI, 1.00-1.03). Thus, for each 1 mg/kg increase in blubber PCBs, the average increase in risk of infectious disease mortality was 2%. A doubling of risk occurred at approximately 45 mg/kg lipid. In this study, we have endeavored to avoid selection bias by using controls that died of physical trauma as representative of the exposure prevalence in the population that gave rise to the cases. In addition, we controlled for the effect of variation in energetic status among the cases and controls. However, as with case-control studies in human and veterinary epidemiology, unforeseen misclassification errors may result in biased risk estimates in either direction.

The Atlantic salmon (Salmo salar) has been widely used as a model species in studies of olfactory signal transduction and processing. Here we report the isolation and characterisation of salmon olfactory receptor (SOR) and salmon vomeronasal receptor (SVR) partial sequences from Atlantic salmon. Six groups of SOR sequences (SORA–F) and three groups of SVR sequences (SVRA–C) were identified. All SORB, SORF, SVRB and SVRC sequences contained uninterrupted open reading frames. However, all SORA sequences and members of the SVRA sequence family contained multiple stop codons while SORC and SORE sequences were truncated in the 3′ region of the sequence. Full length SORF and almost complete SORB sequences displayed amino acid residues and motifs conserved in fish olfactory receptor genes. In sequence phylogenies, SOR sequences fell into the main olfactory receptor (MOR) type I clade and were most closely related to either δ or ζ reference sequences, while all SVR sequences grouped within a clade of fish type 2 vomeronasal receptor (V2R) sequences. A family of sequences (Sasa CaSR1–6), isolated using the same degenerate primers that amplified SVR sequences, clustered within a group of calcium sensing receptor (CaSR) sequences. Analysis of tissue expression patterns of sequences by reverse transcriptase polymerase chain reaction showed that they were transcribed in olfactory epithelium (SORB, SORF, all SVR and Sasa CaSR sequences), testis (SORB, SORD and Sasa CaSR) and/or anterior kidney (SORB and Sasa CaSR). Similar analysis of expression supported the identification of SORA sequences as non-transcribed pseudogene(s). Although the level of occurrence of OR pseudogenes is within the range found for other, well-characterised vertebrate OR genomes, it does not seem to reflect the importance of olfaction in the biology of the Atlantic salmon.

More than 10,000 Caspian seals ( Phoca caspica) were reported dead in the Caspian Sea during spring and summer 2000. We performed necropsies and extensive laboratory analyses on 18 seals, as well as examination of the pattern of strandings and variation in weather in recent years, to identify the cause of mortality and potential contributory factors. The monthly stranding rate in 2000 was up to 2.8 times the historic mean. It was preceded by an unusually mild winter, as observed before in mass mortality events of pinnipeds. The primary diagnosis in 11 of 13 seals was canine distemper, characterized by broncho-interstitial pneumonia, lymphocytic necrosis and depletion in lymphoid organs, and the presence of typical intracytoplasmic inclusion bodies in multiple epithelia. Canine distemper virus infection was confirmed by phylogenetic analysis of reverse transcriptase-polymerase chain reaction products. Organochlorine and zinc concentrations in tissues of seals with canine distemper were comparable to those of Caspian seals in previous years. Concurrent bacterial infections that may have contributed to the mortality of the seals included Bordetella bronchiseptica (4/8 seals), Streptococcus phocae (3/8), Salmonella dublin (1/8), and S. choleraesuis (1/8). A newly identified bacterium, Corynebacterium caspium, was associated with balanoposthitis in one seal. Several infectious and parasitic organisms, including poxvirus, Atopobacter phocae, Eimeria- and Sarcocystis-like organisms, and Halarachne sp. were identified in Caspian seals for the first time.

Summary 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., Graphical Abstract, Highlights • Rapid enhancer and slow promoter evolution across genomes of 20 mammalian species • Enhancers are rarely conserved across these mammals • Recently evolved enhancers dominate mammalian regulatory landscapes • Unbiased mapping links candidate enhancers with lineage-specific positive selection, Comparative functional genomic analysis in 20 mammalian species reveals distinct features for the evolution of enhancers, in comparison to those of promoters, across 180 million years.

Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.

Interferon alpha (IFN-α) therapy is currently the treatment of choice for chronic hepatitis C (HCV) infection, but it fails to achieve a sustained response in approximately 75% of those treated. The factors which determine whether or not an individual will respond to IFN-α are uncertain, although a number of potentially predictive factors have been proposed. In this study a wide range of clinical, demographic, and virological parameters were evaluated in relation to therapeutic outcome in a group of 30 Italian patients with chronic hepatitis C. All patients received 3 MU leukocyte-derived IFN-α three times a week for 6 months and were then followed prospectively for at least 12 months. 53% of patients responded initially, but a sustained response was observed in only 17%. Responders were found to be significantly younger than nonresponders (45.6 ± 3.1 vs. 55.4 ± 2.7), and less frequently cirrhotic (2/16 vs. 7/14). Sustained responders had a mean pretreatment HCV-RNA titer approximately tenfold lower than that of those who did not have a sustained response, but the difference was not statistically significant. HCV genotype was found to be significantly associated with both initial and sustained response. Patients infected with HCV-2a were more likely to respond (89%) than those who were infected with HCV-1 b (37%), and they were also more likely to sustain that response (33% vs. 6%). Geometric mean titers did not vary significantly between the different genotypes. © 1995 Wiley-Liss, Inc.

A cohort of 66 patients on maintenance haemodialysis was examined for serological (anti-HCV) and virological (HCV-RNA) evidence of infection with hepatitis C virus (HCV). Nine (13.6%) were anti-HCV positive, all of whom had detectable HCV-RNA in their serum. Statistical analysis of various risk factors (including length of time on haemodialysis, history of blood transfusion, history of renal transplantation and of previous hepatitis B infection) showed that only the length of time on haemodialysis was significantly associated with the acquisition of HCV infection. Genotypic analysis showed that five patients were infected with genotype 1 and a further two were infected with genotype 4. The latter finding is of significance because strains of genotype 4 are extremely uncommon in Western Europe. These results demonstrate that intra-unit transmission of HCV-infection took place in a group of patients on maintenance haemodialysis.

This study employed a second-generation anti-HCV ELISA, and a second-generation recombinant immunoblot assay and hepatitis C virus RNA detection by polymerase chain reaction to investigate the anti-HCV prevalence in 554 British organ donors and the transmission of hepatitis C virus to heart, liver and kidney recipients between 1984 and 1991. Serum samples from six (1.08%) donors were reactive in the second-generation anti-HCV ELISA and four (67%) of these gave positive or indeterminate results in the recombinant immunoblot assay-2. Of the 15 recipients of these organs from hepatitis C virus-confirmed positive/indeterminate donors, 14 (93%) acquired hepatitis C virus infection and seven (47%) had evidence of hepatitis C virus-related liver disease after transplantation and no evidence of blood transfusion-related transmission. Only six of the 15 (40%) recipients had detectable anti-HCV after transplantation, while 12 of 14 (86%) patients tested had hepatitis C virus RNA in their serum detectable by "nested" polymerase chain reaction. These data indicate a very high rate of transmission with a major risk of the development of liver disease. We believe our study supports the testing of all British organ donors for anti-HCV and that organs from anti-HCV-positive patients should not be transplanted unless the recipient has life-threatening disease and there is a donor shortage, when their use may be justified. Since there are time constraints on organ donor testing, which may frequently be done on call during unsocial hours, we would recommend second-generation ELISA as the current screening test of choice.(ABSTRACT TRUNCATED AT 250 WORDS)

Thousands of Caspian seals (Phoca caspica) died in the Caspian Sea from April to August 2000. Lesions characteristic of morbillivirus infection were found in tissue specimens from dead seals. Canine distemper virus infection was identified by serologic examination, reverse transcriptase- polymerase chain reaction, and sequencing of selected P gene fragments. These results implicate canine distemper virus infection as the primary cause of death.

The squirrel poxvirus (SQPV) is the probable mediator of apparent competition between the introduced invading gray squirrel (Sciurus carolinensis) and the red squirrel (Sciurus vulgaris) in the UK, and modeling studies have shown that this viral disease has had a significant impact on the decline of the red squirrel in the UK. However, given our limited understanding of the epidemiology of the disease, and more generally the effects of invasive species on parasite ecology, there is a need to investigate the transmission dynamics and the relative pathogenicity of the virus between species. We aimed to increase our knowledge of these processes through an empirical study in which we: (i) used pathological signs and transmission electron microscopy (TEM) to diagnose SQPV disease in red squirrels found dead during scanning surveillance between 1993 and 2005; (ii) detected antibody to SQPV using an enzyme-linked immunosorbent assay (ELISA) in the same animals; and (iii) mapped cases of the disease, and the gray squirrel distribution, using a geographical information system. We analyzed the distribution of cases of SQPV disease according to woodland type, a measure of squirrel density. SQPV disease occurred only in areas of England also inhabited by seropositive gray squirrels, and as the geographical range of gray squirrels expanded, SQPV disease occurred in these new gray squirrel habitats, supporting a role for the gray squirrel as a reservoir host of the virus. There was a delay between the establishment of invading gray squirrels and cases of the disease in red squirrels which implies gray squirrels must reach a threshold number or density before the virus is transmitted to red squirrels. The spatial and temporal trend in SQPV disease outbreaks suggested that SQPV disease will have a significant effect on Scottish populations of red squirrels within 25 years. The even spread of cases of disease across months suggested a direct rather than vector-borne transmission route is more likely. Eight juvenile and sub-adult free-living red squirrels apparently survived exposure to SQPV by mounting an immune response, the first evidence of immunity to SQPV in free-living red squirrels, which possibly suggests a changing host-parasite relationship and that the use of a vaccine may be an effective management tool to protect remnant red squirrel populations.

A pregnant woman developed an acute hepatitis C virus (HCV) type 3a infection during the second trimester of pregnancy. The clinical virological features are presented, including HCV RNA quantification of maternal serum samples collected during pregnancy. These findings are discussed in light of the child's remaining uninfected after 5 years of follow-up.

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.

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.

On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06:30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a "two-stage process" where a group of normally pelagic dolphins entered Falmouth Bay and, after 3-4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE.

In chronic hepatitis C, interferon alfa (IFN-alpha) 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-alpha in combination could be effective in IFN-alpha-resistant chronic hepatitis C.Twenty patients with chronic hepatitis C resistant to a previous course of IFN-alpha were randomly assigned to receive either ribavirin combined with IFN-alpha or IFN-alpha alone for 6 months.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-alpha alone (P0.05). The sustained response was accompanied by reduced hepatic necroinflammatory activity on biopsy.These findings suggest that ribavirin plus IFN-alpha combination therapy is able to induce a sustained biochemical and virological response in a significant proportion of patients with IFN-alpha-resistant chronic hepatitis C.

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; p0.001). This association occurred independently of other potentially confounding variables, including age, sex, two indices of nutritional status, season, region, and year found. Total blubber PCB levels (as Aroclor 1254) were also calculated, enabling direct comparison with a proposed threshold for adverse health effects (including immunosuppression) in marine mammals of 17 mg/kg lipid. In porpoises with total PCB levels greater than 17 mg/kg lipid (n = 154), total PCB levels were significantly higher in the infectious disease group compared to the physical trauma group (p0.001). This association was no longer significant in porpoises with total PCB levels of less than 17 mg/kg lipid (n = 103; p0.55). 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.