Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis

We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies.     

ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis

We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.     

Dog owners and hydatid disease in Sanpete County, Utah

A questionnaire survey was conducted in Sanpete County, Utah, to determine the knowledge of dog owners concerning hydatid disease and an identification of some basic sheep management practices there. The households surveyed included 21 (Group I) that had one or more dogs infected with Echinococcus granulosus tapeworms at more than one annual field clinic, and 19 others (Group II) that had one or more dogs infected when the study first began in 1971–72, but had not had any infected dogs identified at field clinics during subsequent years. The results showed that 92.5 percent of households knew the cause of the disease and how it is transmitted, and that 90 percent knew of someone who had been operated on for surgical removal of hydatid cysts. There was no significant difference in the level of knowledge of the disease between the two groups of respondents, nor in their sheep management practices. Even though the level of infection of the parasite in dogs has decreased since the project started, certain sheep management practices persist among respondents in both groups that allow for continued transmission of the parasite in this region.     

Field clinic procedures for diagnosing Echinococcus granulosus in dogs

Echinococcus granulosus is the causative parasite of hydatid disease in humans and represents a significant public health problem within endemic foci in all major continents of the world. This report gives a detailed set of instructions whereby four trained individuals can examine 15–20 dogs per hour for the presence of this organism. The procedure permits the baseline determination of the prevalence of this parasite within any specific population of dogs and also allows the periodic examination of the same animals to determine if recommended preventive and control measures for hydatid disease are being followed by sheep and dog owners in any region where the parasite is known to occur.     

Three-year surveillance for cestode infections in sheep dogs in central Utah

During the summers of 1982, 1983, and 1984, 269 sheep dogs from an area endemic for hydatid disease were examined for cestodes ( Echinococcus granulosus and Taenia spp.). Each dog was given an oral purge of arecoline hydrobromide and then following purgation received a subcutaneous injection of praziquantel (Droncit ® ). During the three-year study period, 205 dogs were examined one time only, 48 dogs were examined two of the three years, and 16 dogs were examined each of the three years (= 349 separate examinations). In 1982, 45 of 91 dogs examined (49.5%) harbored at least one species of cestode. Those data for 1983 and 1984 were 55 positive of 141 examined (39.0%) and 34 positive of 117 examined (29.1%), respectively. The marked drop in dogs infected during the second and third year of the study suggests that many sheep ranchers were implementing some of the control measures recommended for prevention of E. granulosus infections. The numbers of separate purgations showing specific cestodes detected in all positive dogs (some dogs naturally with more than one species of cestode) were: E. granulosus, 16 (4.6%); T. hydatigena, 34 (9.7%); T. ovis krabbei, 46 (13.2%); T. pisiformis, 47 (13.5%); and T. serialis, 24 (6.9%).     

The search for signs of recovery of the ozone layer

Evidence of mid-latitude ozone depletion and proof that the Antarctic ozone hole was caused by humans spurred policy makers from the late 1980s onwards to ratify the Montreal Protocol and subsequent treaties, legislating for reduced production of ozone-depleting substances. The case of anthropogenic ozone loss has often been cited since as a success story of international agreements in the regulation of environmental pollution. Although recent data suggest that total column ozone abundances have at least not decreased over the past eight years for most of the world, it is still uncertain whether this improvement is actually attributable to the observed decline in the amount of ozone-depleting substances in the Earth's atmosphere. The high natural variability in ozone abundances, due in part to the solar cycle as well as changes in transport and temperature, could override the relatively small changes expected from the recent decrease in ozone-depleting substances. Whatever the benefits of the Montreal agreement, recovery of ozone is likely to occur in a different atmospheric environment, with changes expected in atmospheric transport, temperature and important trace gases. It is therefore unlikely that ozone will stabilize at levels observed before 1980, when a decline in ozone concentrations was first observed.     

Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints

Recent studies have indicated the existence of tumorigenesis barriers that slow or inhibit the progression of preneoplastic lesions to neoplasia. One such barrier involves DNA replication stress, which leads to activation of the DNA damage checkpoint and thereby to apoptosis or cell cycle arrest, whereas a second barrier is mediated by oncogene-induced senescence. The relationship between these two barriers, if any, has not been elucidated. Here we show that oncogene-induced senescence is associated with signs of DNA replication stress, including prematurely terminated DNA replication forks and DNA double-strand breaks. Inhibiting the DNA double-strand break response kinase ataxia telangiectasia mutated (ATM) suppressed the induction of senescence and in a mouse model led to increased tumour size and invasiveness. Analysis of human precancerous lesions further indicated that DNA damage and senescence markers cosegregate closely. Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression.     

Proteomic characterization of the human centrosome by protein correlation profiling

The centrosome is the major microtubule-organizing centre of animal cells and through its influence on the cytoskeleton is involved in cell shape, polarity and motility. It also has a crucial function in cell division because it determines the poles of the mitotic spindle that segregates duplicated chromosomes between dividing cells. Despite the importance of this organelle to cell biology and more than 100 years of study, many aspects of its function remain enigmatic and its structure and composition are still largely unknown. We performed a mass-spectrometry-based proteomic analysis of human centrosomes in the interphase of the cell cycle by quantitatively profiling hundreds of proteins across several centrifugation fractions. True centrosomal proteins were revealed by both correlation with already known centrosomal proteins and in vivo localization. We identified and validated 23 novel components and identified 41 likely candidates as well as the vast majority of the known centrosomal proteins in a large background of nonspecific proteins. Protein correlation profiling permits the analysis of any multiprotein complex that can be enriched by fractionation but not purified to homogeneity.     

Chromosome-scale selective sweeps shape Caenorhabditis elegans genomic diversity

The nematode Caenorhabditis elegans is central to research in molecular, cell and developmental biology, but nearly all of this research has been conducted on a single strain of C. elegans. Little is known about the population genomic and evolutionary history of this species. We characterized C. elegans genetic variation using high-throughput selective sequencing of a worldwide collection of 200 wild strains and identified 41,188 SNPs. Notably, C. elegans genome variation is dominated by a set of commonly shared haplotypes on four of its six chromosomes, each spanning many megabases. Population genetic modeling showed that this pattern was generated by chromosome-scale selective sweeps that have reduced variation worldwide; at least one of these sweeps probably occurred in the last few hundred years. These sweeps, which we hypothesize to be a result of human activity, have drastically reshaped the global C. elegans population in the recent past.