A Y chromosome census of the British Isles

The degree of population replacement in the British Isles associated with cultural changes has been extensively debated. Recent work has demonstrated that comparisons of genetic variation in the British Isles and on the European Continent can illuminate specific demographic processes in the history of the British Isles. For example, Wilson et al. used the similarity of Basque and Celtic Y chromosomes to argue for genetic continuity from the Upper Palaeolithic to the present in the paternal history of these populations (see also ). Differences in the Y chromosome composition of these groups also suggested genetic signatures of Norwegian influence in the Orkney Islands north of the Scottish mainland, an important center of Viking activities between 800 and 1300 A.D. More recently, Weale et al. argued for substantial Anglo-Saxon male migration into central England based on the analysis of eight British sample sets collected on an east-west transect across England and Wales. To provide a more complete assessment of the paternal genetic history of the British Isles, we have compared the Y chromosome composition of multiple geographically distant British sample sets with collections from Norway (two sites), Denmark, and Germany and with collections from central Ireland, representing, respectively, the putative invading and the indigenous populations. By analyzing 1772 Y chromosomes from 25 predominantly small urban locations, we found that different parts of the British Isles have sharply different paternal histories; the degree of population replacement and genetic continuity shows systematic variation across the sampled areas.     

Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study

Background  

Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity.     

A collaborative assay of the proposed third British Reference Preparation for Pertussis Vaccine and of the relative potencies of the second International Standard and the second British Reference Preparation for Pertussis Vaccine

A collaborative assay has been carried out to estimate the mouse protective potency of a freeze-dried preparation of Bordetella pertussis (88/522) intended to serve as the third British Reference Preparation for Pertussis Vaccine (third BRP). The opportunity was also taken of reassessing the relationship between the second International Standard for Pertussis Vaccine and the second British Reference Preparation for Pertussis Vaccine (second BRP). Workers in nine laboratories took part in the study and together completed 19 assays which were considered to be statistically valid. Based on the results of the study it is proposed that ampouled preparation code number 88/522 be established as the third BRP with an assigned potency of 50 IU per ampoule. The evidence of this study also suggests that the relationship between the second International Standard for Pertussis Vaccine and the second BRP has not changed significantly since they were originally established.     

Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine.

OBJECTIVE--To determine the persistence of antibody to diphtheria, tetanus, and pertussis in children receiving an accelerated schedule of primary immunisation. DESIGN--Controlled study of antibody testing of blood samples from children immunised according to various schedules: three doses of triple vaccine completed at 8-13 calendar months, 6-7 calendar months, before 6 calendar months, or three doses followed by diphtheria/tetanus before age 2. SETTING--Plymouth Health Authority. SUBJECTS--129 children aged 4 years who had received three doses of diphtheria/tetanus/pertussis vaccine with or without a diphtheria/tetanus booster. MAIN OUTCOME MEASURES--Diphtheria and tetanus antitoxin concentrations and antibody titres to pertussis toxin, filamentous haemagglutinin, and agglutinogens 2 and 3. RESULTS--All children had protective concentrations of antitoxin to diphtheria and tetanus (greater than or equal to 0.01 IU/ml). There was no evidence of a significant difference in diphtheria or tetanus antitoxin concentrations and pertussis antibody titres in children immunised with an accelerated course (third dose of triple vaccine before 6 months) compared with those who received a longer course (third dose at 8-13 months) with no booster (geometric mean antitoxin concentration 0.411 (95% confidence interval 0.273 to 0.618) v 0.426 (0.294 to 0.616) for diphtheria and 0.358 (0.231 to 0.556) v 0.299 (0.197 to 0.453) for tetanus; geometric mean antibody titres 903 (500 to 1631) v 1386 (848 to 2266) for pertussis filamentous haemagglutinin, 179 (130 to 248) v 232 (167 to 322) for pertussis toxin, and 2002 (1276 to 3142) v 3591 (2220 to 5809) for agglutinogens 2 and 3). CONCLUSION--Immunisation with three doses of triple vaccine at monthly intervals completed before 6 months of age probably provides adequate protection against diphtheria, tetanus, and whooping cough which will persist until the age of the preschool booster.     

Subcellular distribution and targeting of the intracellular chloride channel p64.

p64 is an intracellular chloride channel originally identified in bovine kidney microsomes. Using a combination of immunofluorescent and electron microscopic technique, we demonstrate that p64 resides in the limiting membranes of perinuclear dense core vesicles which appear to be regulated secretory vesicles. Heterologous expression of p64 in PancI cells, a cell type which does not normally express p64, results in targeting to a similar compartment. Mutagenesis experiments demonstrate that both the N- and C-terminal domains of the protein independently contribute to subcellular distribution of the protein. The C-terminal domain functions to prevent expression of p64 on the plasma membrane and the N-terminal domain is necessary to deliver p64 to the appropriate membrane compartment.     

First report of metazoan parasites from the cichlid Pseudocrenilabrus philander and the cyprinid Enteromius paludinosus in a South African Ramsar wetland

Parasites of two small fish species from a Ramsar wetland in South Africa were studied in 2014–2015. The cichlid Pseudocrenilabrus philander (Weber, 1897) was parasitised by the copepod Lernaea cyprinacea Linnaeus, 1758, the monogenean Gyrodactylus thlapi Christison, Shinn & van As, 2005 and four gryporhynchid metacestode (Cyclophyllidea) species: Paradilepis scolecina (Rudolph, 1819), Paradilepis maleki Khalil, 1961, Neogryporhynchus lasiopeius Baer & Bona, 1960 and Valipora campylancristrota (Wedl, 1855). The cyprinid Enteromius paludinosus (syn. Barbus paludinosus) (Peters, 1852) was infected with the monogenean parasites Dogielius intorquens Crafford, Luus-Powell & Avenant-Oldewage, 2012, Dactylogyrus teresae Mashego, 1983, and three Dactylogyrus spp. These results represent several new locality as well as host records and further contribute information on the parasitic diversity in the Barberspan Ramsar wetland.     

Correction of liver dysfunction in DNA repair-deficient mice with an ERCC1 transgene

The ERCC1 gene is essential for the repair of UV-induced DNA damage. Unlike most genes in the nucleotide excision repair (NER) pathway, ERCC1 is also involved in recombinational repair. Perhaps for this reason, ERCC1 knockout mice are not a model for the human NER deficiency disorder, xeroderma pigmentosum. Instead, ERCC1 null mice are severely runted and die before weaning from liver failure with accelerated hepatocyte polyploidy that is more reminiscent of a premature ageing disorder. To permit study of the role of ERCC1 in other tissues we have corrected the liver ERCC1 deficiency with a transgene under the control of a liver-specific promoter. The transgene alleviated runting and extended the lifespan. The elevated level of oxidative DNA damage and premature liver polyploidy were reversed and liver function was corrected. A widespread mitochondrial dysfunction was identified and an essential role for ERCC1 in the kidney was also revealed with transgene-containing ERCC1-deficient animals going on to die of renal failure. The nuclei of kidney proximal tubule cells became polyploid in a similar way to the premature liver polyploidy observed in younger ERCC1-deficient animals. We believe that this is a response to the accumulation of endogenous DNA damage in these particularly susceptible tissues which cannot be repaired in ERCC1-deficient animals.     

Fine‐scale spatial genetic structure of common and declining bumble bees across an agricultural landscape

Land‐use changes have threatened populations of many insect pollinators, including bumble bees. Patterns of dispersal and gene flow are key determinants of species' ability to respond to land‐use change, but have been little investigated at a fine scale (<10 km) in bumble bees. Using microsatellite markers, we determined the fine‐scale spatial genetic structure of populations of four common Bombus species (B. terrestris, B. lapidarius, B. pascuorum and B. hortorum) and one declining species (B. ruderatus) in an agricultural landscape in Southern England, UK. The study landscape contained sown flower patches representing agri‐environment options for pollinators. We found that, as expected, the B. ruderatus population was characterized by relatively low heterozygosity, number of alleles and colony density. Across all species, inbreeding was absent or present but weak (F_IS = 0.01–0.02). Using queen genotypes reconstructed from worker sibships and colony locations estimated from the positions of workers within these sibships, we found that significant isolation by distance was absent in B. lapidarius, B. hortorum and B. ruderatus. In B. terrestris and B. pascuorum, it was present but weak; for example, in these two species, expected relatedness of queens founding colonies 1 m apart was 0.02. These results show that bumble bee populations exhibit low levels of spatial genetic structure at fine spatial scales, most likely because of ongoing gene flow via widespread queen dispersal. In addition, the results demonstrate the potential for agri‐environment scheme conservation measures to facilitate fine‐scale gene flow by creating a more even distribution of suitable habitats across landscapes.