Symbiotic modeling: Linguistic Anthropology and the promise of chiasmus

Reflexive observations and observations of reflexivity: such agendas are by now standard practice in anthropology. Dynamic feedback loops between self and other, cause and effect, represented and representamen may no longer seem surprising; but, in spite of our enhanced awareness, little deliberate attention is devoted to modeling or grounding such phenomena. Attending to both linguistic and extra-linguistic modalities of chiasmus (the X figure), a group of anthropologists has recently embraced this challenge. Applied to contemporary problems in linguistic anthropology, chiasmus functions to highlight and enhance relationships of interdependence or symbiosis between contraries, including anthropology’s four fields, the nature of human being and facets of being human

Loss of Niemann-Pick C1 or C2 Protein Results in Similar Biochemical Changes Suggesting That These Proteins Function in a Common Lysosomal Pathway

Niemann-Pick Type C (NPC) disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal cholesterol with both proteins binding cholesterol in vitro but they may have unrelated lysosomal roles. To investigate this possibility, we compared biochemical consequences of the loss of either protein. Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. The subcellular distribution of both proteins was similar and paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted in similar alterations in the carbohydrate processing of the lysosomal protease, tripeptidyl peptidase I. These results highlight biochemical alterations in the lysosomal system of the NPC-mutant mice that appear secondary to lipid storage. In addition, the similarity in biochemical phenotypes resulting from either NPC1 or NPC2 deficiency supports models in which the function of these two proteins within lysosomes are linked closely

Improvements in Coded Aperture Thermal Neutron Imaging

ABSTRACT A new thermal neutron imaging system has been constructed, based on a 20-cm x 17-cm He-3 position-sensitive detector with spatial resolution better than 1 mm. New compact custom-designed position-decoding electronics are employed, as well as high-precision cadmium masks with Modified Uniformly Redundant Array patterns. Fast Fourier Transform algorithms are incorporated into the deconvolution software to provide rapid conversion of shadowgrams into real images. The system demonstrates the principles for locating sources of thermal neutrons by a stand-off technique, as well as visualizing the shapes of nearby sources. The data acquisition time could potentially be reduced two orders of magnitude by building larger detectors

Niemann-Pick Disease Type C: Spectrum of HE1 Mutations and Genotype/Phenotype Correlations in the NPC2 Group

In Niemann-Pick disease type C (NPC), a genetic heterogeneity with two complementation groups—NPC1, comprising ⩾95% of the families, and NPC2—has been demonstrated. Mutations in the NPC1 gene have now been well characterized. HE1 was recently identified as the gene underlying the very rare NPC2. Here we report the first comprehensive study of eight unrelated families with NPC2, originating from France, Algeria, Italy, Germany, the Czech Republic, and Turkey. These cases represent essentially all patients with NPC2 who have been reported in the literature, as well as those known to us. All 16 mutant alleles were identified, but only five different mutations, all with a severe impact on the protein, were found; these five mutations were as follows: two nonsense mutations (E20X and E118X), a 1-bp deletion (27delG), a splice mutation (IVS2+5G→A), and a missense mutation (S67P) resulting in reduced amounts of abnormal HE1 protein. E20X, with an overall allele frequency of 56%, was established as the common mutant allele. Prenatal diagnosis was achieved by mutation analysis of an uncultured chorionic-villus sample. All mutations except 27delG were observed in a homozygous state, allowing genotype/phenotype correlations. In seven families (with E20X, E118X, S67P, and E20X/27delG mutations), patients suffered a severe and rapid disease course, with age at death being 6 mo–4 years. A remarkable feature was the pronounced lung involvement, leading, in six patients, to early death caused by respiratory failure. Two patients also developed a severe neurological disease with onset during infancy. Conversely, the splice mutation corresponded to a very different clinical presentation, with juvenile onset of neurological symptoms and prolonged survival. This mutation generated multiple transcripts, including a minute proportion of normally spliced RNA, which may explain the milder phenotype