Prediction of central nervous system embryonal tumour outcome based on gene expression.

Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.     

Western painted turtle in Grant County, Oregon

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Selection of ants by the American black bear ( Ursus americanus )

We examined selection of ants as food by black bears ( Ursus americanus ) in Utah by comparing the genera of ants we sampled from study plots in 5 vegetation types with those found in bear scats. In the plots we found 641 ant colonies representing 18 genera. Five genera comprised 85% of all colonies sampled: Formica, Lasius, Camponotus, Tapinoma, and Myrmica . Thirteen genera were found in scats, but 99% were composed of the same 5 listed above. Limited utilization of some ant genera by black bears may reflect body size, colony size, nest type, and presence or absence of a functional sting. Fifty-three percent of all ant colonies in sample plots were found under rocks. Energy values of ants ranged from 4.9 to 6.2 cal · g -1 dry weight. Pupae of Formica and Camponotus contained slightly more fat than respective workers, but the relationship was reversed for Lasius . Pupal cases were found in 33% of the scats, and bears may prefer ant brood because they are more digestible than adults and lack mechanisms of defense. Ants are a predictable and ubiquitous food source for black bears.     

A tidally distorted dwarf galaxy near NGC 4449

NGC 4449 is a nearby Magellanic irregular starburst galaxy with a B-band absolute magnitude of -18 and a prominent, massive, intermediate-age nucleus at a distance from Earth of 3.8?megaparsecs (ref. 3). It is wreathed in an extraordinary neutral hydrogen (H?I) complex, which includes rings, shells and a counter-rotating core, spanning ～90?kiloparsecs (kpc; refs 1, 4). NGC 4449 is relatively isolated, although an interaction with its nearest known companion--the galaxy DDO 125, some 40?kpc to the south--has been proposed as being responsible for the complexity of its H?I structure. Here we report the presence of a dwarf galaxy companion to NGC 4449, namely NGC 4449B. This companion has a V-band absolute magnitude of -13.4 and a half-light radius of 2.7?kpc, with a full extent of around 8?kpc. It is in a transient stage of tidal disruption, similar to that of the Sagittarius dwarf near the Milky Way. NGC 4449B exhibits a striking S-shaped morphology that has been predicted for disrupting galaxies but has hitherto been seen only in a dissolving globular cluster. We also detect an additional arc or disk ripple embedded in a two-component stellar halo, including a component extending twice as far as previously known, to about 20?kpc from the galaxy's centre.     

In vivo enhancer analysis of human conserved non-coding sequences

Identifying the sequences that direct the spatial and temporal expression of genes and defining their function in vivo remains a significant challenge in the annotation of vertebrate genomes. One major obstacle is the lack of experimentally validated training sets. In this study, we made use of extreme evolutionary sequence conservation as a filter to identify putative gene regulatory elements, and characterized the in vivo enhancer activity of a large group of non-coding elements in the human genome that are conserved in human-pufferfish, Takifugu (Fugu) rubripes, or ultraconserved in human-mouse-rat. We tested 167 of these extremely conserved sequences in a transgenic mouse enhancer assay. Here we report that 45% of these sequences functioned reproducibly as tissue-specific enhancers of gene expression at embryonic day 11.5. While directing expression in a broad range of anatomical structures in the embryo, the majority of the 75 enhancers directed expression to various regions of the developing nervous system. We identified sequence signatures enriched in a subset of these elements that targeted forebrain expression, and used these features to rank all approximately 3,100 non-coding elements in the human genome that are conserved between human and Fugu. The testing of the top predictions in transgenic mice resulted in a threefold enrichment for sequences with forebrain enhancer activity. These data dramatically expand the catalogue of human gene enhancers that have been characterized in vivo, and illustrate the utility of such training sets for a variety of biological applications, including decoding the regulatory vocabulary of the human genome.     

Effects of cholesterol-derived photoproducts on the incorporation of14C-acetate into human skin lipids

Zusammenfassung Hautbestrahlung beim Menschen mit Xenon- oder UV-Licht und die dabei beobachteten chemischen Vorgänge (Hemmung von 1-¹⁴C-Azetat und Einbau in die Gesamtlipide) legen eine mögliche Relation zwischen Photoproduktbildung und lichtinduzierter Hemmung der Lipogenese nahe.

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Supported in part by The Robert A. Welch Foundation Grant No. Q-253 and USPHS Grant No. EC00110-83.     

The mitigating effect of dietary antioxidants on chemically-induced carcinogenesis

Summary The effect of a dietary antioxidant mixture on 3-methylcholanthrene mediated carcinogenesis in hairless mice was investigated. The antioxidant mixture significantly reduced the frequency of premalignant lesions and their subsequent development into tumors. The similarities in response of chemical and UV light-carcinogenesis to these antioxidants suggest some congruity in the mechanisms of the carcinogenic process.This investigation was supported by National Research Service Award 1 F32 CA05062, awarded by the National Cancer Institute, DHEW and USPH grant CA13464 from the NCI, DHEW. We thank Dr John I. Thornby for statistical analysis of the data.