Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.     

A record of Permian subaqueous vent activity in southeastern Brazil

The remarkable occurrence of more than 4,500 conical siliceous mounds in an area of less than 1.5 square kilometres has been reported in the Paraná basin, near Anhembi, S?o Paulo, in southeastern Brazil. These structures, which are up to two metres high, are thought to have been formed at the margin of a very shallow, broad but waning internal sea, and it was originally suggested that they are stromatolites. Yet their restricted occurrence, unusual abundance and nearly pure siliceous composition have never been satisfactorily explained by this hypothesis. Here we report field and laboratory observations on their shape, construction, composition and mineralogy. On the basis of our data we suggest that the conical mounds are the result of subaqueous Late Permian vent activity in southwestern Gondwana. The present siliceous cone field differs considerably from other Palaeozoic siliceous hot spring deposits, such as those at Rhynie, Scotland, and the Drummond basin, Australia, and therefore represents an unusual occurrence of vent activity.     

Tumour biology: senescence in premalignant tumours

Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.     

XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer

TRF2 is a telomere-binding protein that has a role in telomere protection. We generated mice that overexpress TRF2 in the skin. These mice had a severe phenotype in the skin in response to light, consisting of premature skin deterioration, hyperpigmentation and increased skin cancer, which resembles the human syndrome xeroderma pigmentosum. Keratinocytes from these mice were hypersensitive to ultraviolet irradiation and DNA crosslinking agents. The skin cells of these mice had marked telomere shortening, loss of the telomeric G-strand overhang and increased chromosomal instability. Telomere loss in these mice was mediated by XPF, a structure-specific nuclease involved in ultraviolet-induced damage repair and mutated in individuals with xeroderma pigmentosum. These findings suggest that TRF2 provides a crucial link between telomere function and ultraviolet-induced damage repair, whose alteration underlies genomic instability, cancer and aging. Finally, we show that a number of human skin tumors have increased expression of TRF2, further highlighting a role for TRF2 in skin cancer.     

Acid-base equilibrium in the heart-lung preparation

Résumé Etude de l'équilibre acide-basique de la préparation cur-poumon de l'étourneau, réalisée avec la technique habituelle et les moyens de corriger les altérations constatées. La recherche des causes de ces altérations a permis de conclure que l'alcalose respiratoire est due à la ventilation dont on se sert habituellement, tandis que l'acidose métabolique est due à une production de métabolites acides déclanchés surtout par la saignée des animaux donneurs et par la glucolyse qui se produit à partir de l'extraction du sang et jusqu'au moment de son emploi dans la préparation.

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This work has been supported by a grant from the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.     

Effect of ethidium bromide onDrosophila melanogaster andDrosophila simulans

Summary Ethidium bromide was fed toD. melanogaster andD. simulans males in order to test its toxic capacity and potency for the induction of dominant lethals. Our results show that ethidium bromide has a high toxicity and likewise produces dominant lethals to a significant extent in both species, but more effectively inD. melanogaster.