Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6

Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive. We hypothesized that GACI and PXE are in a closely related spectrum of disease. We used a standardized questionnaire to retrospectively evaluate the phenotype of 92 probands with a clinical history of GACI. We obtained the ENPP1 genotype by conventional sequencing. In those patients with less than two disease-causing ENPP1 mutations, we sequenced ABCC6. We observed that three GACI patients who carried biallelic ENPP1 mutations developed typical signs of PXE between 5 and 8 years of age; these signs included angioid streaks and pseudoxanthomatous skin lesions. In 28 patients, no disease-causing ENPP1 mutation was found. In 14 of these patients, we detected pathogenic ABCC6 mutations (biallelic mutations in eight patients, monoallelic mutations in six patients). Thus, ABCC6 mutations account for a significant subset of GACI patients, and ENPP1 mutations can also be associated with PXE lesions in school-aged children. Based on the considerable overlap of genotype and phenotype of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification and other organ pathologies, rather than two distinct disorders. ABCC6 and ENPP1 mutations might lead to alterations of the same physiological pathways in tissues beyond the artery.     

Effects of Probiotic Lactobacillus acidophilus Strain INMIA 9602 Er 317/402 and Putative Probiotic Lactobacilli on DNA Damages in the Small Intestine of Wistar Rats In Vivo

Probiotics and Antimicrobial Proteins - Double-strand breaks in the DNA of the small intestine in male Wistar rats were studied using a neutral comet assay after 7 days of feeding with a...     

Mycorrhizal dynamics under elevated CO2 and nitrogen fertilization in a warm temperate forest

We examined the response of mycorrhizal fungi to free-air CO₂ enrichment (FACE) and nitrogen (N) fertilization in a warm temperate forest to better understand potential influences over plant nutrient uptake and soil carbon (C) storage. In particular, we hypothesized that mycorrhizal fungi and glomalin would become more prevalent under elevated CO₂ but decrease under N fertilization. In addition, we predicted that N fertilization would mitigate any positive effects of elevated CO₂ on mycorrhizal abundance. Overall, we observed a 14% increase in ectomycorrhizal (ECM) root colonization under CO₂ enrichment, which implies that elevated CO₂ results in greater C investments in these fungi. Arbuscular mycorrhizal (AM) hyphal length and glomalin stocks did not respond substantially to CO₂ enrichment, and effects of CO₂ on AM root colonization varied by date. Nitrogen effects on AM fungi were not consistent with our hypothesis, as we found an increase in AM colonization under N fertilization. Lastly, neither glomalin concentrations nor ECM colonization responded significantly to N fertilization or to an N-by-CO₂ interaction. A longer duration of N fertilization may be required to detect effects on these parameters.