The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009

Out of tune: the dangers of aligning proxy archives

Tuning is a widespread technique to combine, date and interpret multiple fossil proxy archives through aligning supposedly synchronous events between the archives. The approach will be reviewed by discussing a number of literature examples, ranging from peat and tephra layers to orbital tuning and d¹⁸O series from marine and ice deposits. Potential problems will be highlighted such as the dangers of circular reasoning and unrecognised chronological uncertainties, and some solutions suggested. Fossil proxy research could become enhanced if tuning were approached in a more quantitative, reliable and objective way, and especially if individual proxy archives were non-tuned and kept on independent time-scales.

Out-of-field cell survival following exposure to intensity-modulated radiation fields

PURPOSE:
To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication.
METHODS AND MATERIALS:
Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator.
RESULTS:
Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the a-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response.
CONCLUSIONS:
These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

Archiving Qualitative Data in the Context of a Society Coming out of Conflict: Some Lessons from Northern Ireland.

ARK (‘Access Research Knowledge’) was set up with a single goal: to make social science information on Northern Ireland available to the widest possible audience. The most well-known and widely used part of the ARK resource is CAIN (Conflict Archive on the INternet), which is one of the largest on-line collections of source material and information and about the Northern Ireland conflict. The compilation of CAIN's new Remembering: Victims, Survivors and Commemoration section raised issues related to the sensitivity of the material, as it feeds into the fundamental debate on the legacy of the Northern Ireland conflict. It also fundamentally raises the question to what extent archiving is a neutral or political activity and necessitates a discourse on responsibility and ethics among social researchers. Experiences from the establishment of the Northern Ireland Qualitative Archive (NIQA) shed light on future possibilities with regard to qualitative archives on the Northern Ireland conflict.