Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.     

Autophagy is required for lipid homeostasis during dark-induced senescence

Autophagy is an evolutionarily conserved mechanism that mediates the degradation of cytoplasmic components in eukaryotic cells. In plants, autophagy has been extensively associated with the recycling of proteins during carbon-starvation conditions. Even though lipids constitute a significant energy reserve, our understanding of the function of autophagy in the management of cell lipid reserves and components remains fragmented. To further investigate the significance of autophagy in lipid metabolism, we performed an extensive lipidomic characterization of Arabidopsis (Arabidopsis thaliana) autophagy mutants (atg) subjected to dark-induced senescence conditions. Our results revealed an altered lipid profile in atg mutants, suggesting that autophagy affects the homeostasis of multiple lipid components under dark-induced senescence. The acute degradation of chloroplast lipids coupled with the differential accumulation of triacylglycerols (TAGs) and plastoglobuli indicates an alternative metabolic reprogramming toward lipid storage in atg mutants. The imbalance of lipid metabolism compromises the production of cytosolic lipid droplets and the regulation of peroxisomal lipid oxidation pathways in atg mutants.

Autophagy is required for the mobilization of membrane lipid components and lipid droplet dynamics during extended darkness in Arabidopsis.     

Microbial digestion in the herbivorous lizard Uromastyx aegyptius (Agamidae)

The utilization of a diet rich in plant cell walls was studied in a large, desert-dwelling, herbivorous lizard, Uromastyx aegyptius (Agamidae). The diet eaten by U. aegyptius in spring in the 'Arava Valley, Israel, consisted almost entirely of leaves and fruits of short-lived annual plant species. The leaves contained only moderate levels of fibre compared with grasses and tree leaves, but those fruits eaten were markedly higher in fibre and lignin. All items had notably high contents of ash.
Following oral doses of [¹⁴C] cellulose, ¹⁴CO₂ was detected in respired air from U. aegyptius , demonstrating that the cellulose was digested and that the lizards gained oxidative energy from cellulose degradation. The hind gut was the principal site of microbial activity and the apparent digestibility of the cell-wall fraction was 69%. Similarly, the caecum/proximal colon had the highest concentrations of SCFA (76–120 mM).
The mean rate of SCFA production at 40 C in vitro was 31 mmol/1 h^-1. Assuming that this is representative of daily production rate, 69 kJ/kg d^-1 would be made available to the animal. This is 47% of the mean digestible energy intake estimated in free-living animals. Microbial fermentation contributes an important part of the energy budget of U. aegyptius but the effects of variation in body temperature on digestion and fermentation need further consideration.     

Post-fertilization changes in the zona pellucida glycoproteins of rat eggs

The zona pellucida (ZP) is the extracellular coat surrounding the mammalian egg. Numerious evidence supports the role of ZP carbohydrate residues as the specific sperm receptors. In this study we used lectins to study different distribution patterns of carbohydrate residues in the rat ZP, and to follow changes at fertilization. ZP were collected from follicular, ovulated, and fertilized eggs, incubated with one of 11 different biotin-labeled lectins, followed by avidin-fluorescein isothiocyanate (FITC) complex, and visualized by epifluorescent microscopy. For electron microscope (EM) histochemistry, eggs were embedded in LR white and ultrathin sections were stained with the complexRicinus communis lectin (RCA-1)-colloidal gold. Some lectins (RCA-I,Glycine max) bound to the entire ZP while others were restricted to the inner or outer zones [Griffonia simplicifolia, Concanovalia ensiformis, Triticum vulgaris (WGA), succinyl-WGA]. Other lectins (Lens culinaris, Ulex europhaeus) were totally excluded. The RCA-1 binding pattern changed following sperm penetration, from homogeneous in ZP of ovulated eggs (57%) to uneven in ZP of fertilized (71%) or activated (68%) eggs. Our results demonstrate an uneven distribution of different sugar residues in the rat ZP, and a post-fertilization change in the distribution of β-galactose, which is specifically recognized by RCA-I, presumably correlated with other changes in the ZP that lead to the block to polyspermy. This work is in partial fulfillment of the requirements for the PhD degree of Tamar Raz at the Sackler School of Medicine, Tel Aviv University     

There are two mechanisms of achiasmate segregation in Drosophila females,one of which requires heterochromatic homology

There are numerous examples of the regular segregation of achiasmate chromosomes at meiosis I in Drosophila melanogaster females. Classically, the choice of achiasmate segregational partners has been thought to be independent of homology, but rather made on the basis of availability or similarities in size and shape. To the contrary, we show here that heterochromatic homology plays a primary role in ensuring the proper segregation of achiasmate homologs. We observe that the heterochromatin of chromosome 4 functions as, or contains, a meiotic pairing site. We show that free duplications carrying the 4th chromosome pericentric heterochromatin induce high frequencies of 4th chromosome nondisjunction regardless of their size. Moreover, a duplication from which some of the 4th chromosome heterochromatin has been removed is unable to induce 4th chromosome nondisjunction. Similarly, in the absence of either euchromatic homology or a size similarity, duplications bearing the X chromosome heterochromatin also disrupt the segregation of two achiasmate X chromosome centromeres. Although heterochromatic regions are sufficient to conjoin nonexchange homologues, we confirm that the segregation of heterologous chromosomes is determined by size, shape, and availability. The meiotic mutation Axs differentiates between these two processes of achiasmate centromere coorientation by disrupting only the homology-dependent mechanism. Thus there are two different mechanisms by which achiasmate segregational partners are chosen. We propose that the absence of diplotene-diakinesis during female meiosis allows heterochromatic pairings to persist until prometaphase and thus to co-orient homologous centromeres. We also propose that heterologous disjunctions result from a separate and homology-independent process that likely occurs during prometaphase. The latter process, which may not require the physical association of segregational partners, is similar to those observed in many insects, in Saccharomyces cerevisiae and in C. elegans males. We also suggest that the physical basis of this process may reflect known properties of the Drosophila meiotic spindle. © 1993 Wiley-Liss, Inc.     

Lipid-mediated motor-adaptor sequestration impairs axonal lysosome delivery leading to autophagic stress and dystrophy in Niemann-Pick type C

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Comparative metabolic diversity in two solar salterns

The purpose of this study was to compare the metabolic diversity of the whole microbial community in an oligotrophic saltern (Eilat, Israel) and in a saltern with a more enriched source water (Newark, California). Between 1993 and 1998 water samples were taken from selected locations within the solar salterns of the Cargill Solar Salt Plant, Newark, California, and the Israel Salt Co. in Eilat, Israel. To examine the whole community metabolic diversity, we used the 96-well BIOLOG GN^{{ TM}} plates which contain 95 different carbon sources and a control well. Plates from samples containing greater than 15% salt were excluded from the final analyses because of a lack of reproducibility when multiple plates were inoculated with the same sample. The data were analyzed by simple matching coefficient and principal component analysis. Both methods gave similar results. Two major clusters were formed. These could be subdivided into 10 sub-clusters with only three samples from the Newark saltern in December 1997 joining at the 95% similarity level. Most of the inlet and lower salinity samples from the Cargill samples comprised one large subcluster. Several carbon sources were used by 85% of the microbial community from the California samples, while 85% of the Eilat samples had no commonly used carbon sources. These results suggest that ponds in different geographic locations may have communities with different microbial populations despite the similarities in salt content and processing for salt production.