Protein aggregation as primary and characteristic cell reaction to various stresses

Ehrlich carcinoma and EL-4 thymoma ascites cells were subjected in vitro to heat shock, ATP depletion, oxidative stress, Ca²⁺ overlading and iodoacetamide treatment. After the transient stresses, Triton (X-100)-insoluble TIS) fractions were isolated from the cells and analysed by electrophoresis and immunoblotting. All stresses used caused rapid aggregation of cell proteins. This was manifested in a signficant rise in protein content in the TIS fractions. The protein increase was mostly due to and increase in the insolubility of actin, 57 kDa protein of intermediate filaments, 70 kDa heat shock protein (HSP 70), and some specific proteins whose insolubilization was a characteristic sign for each type of cell injury. Different survival rates in the cell lines after either stress corrlated well with differences in their TIS protein accretion. Possible mechanisms for stress-induced protein aggregation and its relationship with cell viability are suggested.     

Effects of corpora cardiaca extract,furosemide and ion substitution on sodium and chloride flux in perfused Malpighian tubules ofLocusta

Treatment with the co-transport inhibitor, furosemide decreased³⁶Cl^– flux across perfused Malpighian tubules ofLocusta. However, exclusion of³⁶Cl^– from the bathing medium had not effect on²²Na⁺ flux whereas substitution of bathing medium Na⁺ by K⁺ increased³⁶Cl^– flux. Diuretic extract of corpora cardiaca increased²²Na⁺ (by 106%) and³⁶Cl^– (by 335%) fluxes differentially.     

Extraordinary levels of cadmium and zinc in a marine sponge,Tedania charcoti Topsent: inorganic chemical defense agents

The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria.     

The temporal requirement for endothelin receptor-B signalling during neural crest development

Endothelin receptor B (EDNRB) is a G-protein-coupled receptor with seven transmembrane domains which is required for the development of melanocytes and enteric neurons. Mice that are homozygous for a null mutation in the Ednrb gene are almost completely white and die as juveniles from megacolon. To determine when EDNRB signalling is required during embryogenesis, we have exploited the tetracycline-inducible system to generate strains of mice in which the endogenous Ednrb locus is under the control of the tetracycline-dependant transactivators tTa or rtTA. By using this system to express Ednrb at different stages of embryogenesis, we have determined that EDNRB is required during a restricted period of neural crest development between embryonic days 10 and 12.5. Moreover, our results imply that EDNRB is required for the migration of both melanoblasts and enteric neuroblasts.     

Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts

Asymmetric cell division generates daughter cells with different developmental fates from progenitor cells that contain localized determinants. During this division, the asymmetric localization of cell-fate determinants and the orientation of the mitotic spindle must be precisely coordinated. In Drosophila neuroblasts, inscuteable controls both spindle orientation and the asymmetric localization of the cell-fate determinants Prospero and Numb. Inscuteable itself is localized in an apical cortical crescent and thus reflects the intrinsic asymmetry of the neuroblast. Here we show that localization of Inscuteable depends on Bazooka, a protein containing three PDZ domains with overall sequence similarity to Par-3 of Caenorhabditis elegans. Bazooka and Inscuteable form a complex that also contains Staufen, a protein responsible for the asymmetric localization of prospero messenger RNA. We propose that, after delamination of the neuroblast from the neuroepithelium, Bazooka provides an asymmetric cue in the apical cytocortex that is required to anchor Inscuteable. As Bazooka is also responsible for the maintenance of apical-basal polarity in epithelial tissues, it may be the missing link between epithelial polarity and neuroblast polarity.     

A telomerase component is defective in the human disease dyskeratosis congenita

The X-linked form of the human disease dyskeratosis congenita (DKC) is caused by mutations in the gene encoding dyskerin. Sufferers have defects in highly regenerative tissues such as skin and bone marrow, chromosome instability and a predisposition to develop certain types of malignancy. Dyskerin is a putative pseudouridine synthase, and it has been suggested that DKC may be caused by a defect in ribosomal RNA processing. Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif. Telomerase adds simple sequence repeats to chromosome ends using an internal region of its RNA as a template, and is required for the indefinite proliferation of primary human cells. We find that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomerase activity and have shorter telomeres than matched normal cells. The pathology of DKC is consistent with compromised telomerase function leading to a defect in telomere maintenance, which may limit the proliferative capacity of human somatic cells in epithelia and blood.     

Distribution of spatial and nonspatial information in dorsal hippocampus

The hippocampus in the mammalian brain is required for the encoding of current and the retention of past experience. Previous studies have shown that the hippocampus contains neurons that encode information required to perform spatial and nonspatial short-term memory tasks. A more detailed understanding of the functional anatomy of the hippocampus would provide important insight into how such encoding occurs. Here we show that hippocampal neurons in the rat are distributed anatomically in distinct segments along the length of the hippocampus. Each longitudinal segment contains clusters of neurons that become active when the animal performs a task with spatial attributes. Within these same segments are ordered arrangements of neurons that encode the nonspatial aspects of the task appropriate to those spatial features. Thus, anatomical segregation of spatial information, together with the interleaved representation of nonspatial information, represents a structural framework that may help to resolve conflicting views of hippocampal function.     

Central inputs mask multiple adult neural networks within a single embryonic network

It is usually assumed that, after construction of basic network architecture in embryos, immature networks undergo progressive maturation to acquire their adult properties. We examine this assumption in the context of the lobster stomatogastric nervous system. In the lobster, the neuronal population that will form this system is at first orgnanized into a single embryonic network that generates a single rhythmic pattern. The system then splits into different functional adult networks controlled by central descending systems; these adult networks produce multiple motor programmes, distinctively different from the single output of the embryonic network. We show here that the single embryonic network can produce multiple adult-like programmes. This occurs after the embryonic network is silenced by removal of central inputs, then pharmacologically stimulated to restore rhythmicity. Furthermore, restoration of the flow of descending information reversed the adult-like pattern to an embryonic pattern. This indicates that the embryonic network possesses the ability to express adult-like network characteristics, but descending information prevents it from doing so. Functional adult networks may therefore not necessarily be derived from progressive ontogenetic changes in networks themselves, but may result from maturation of descending systems that unmask preexisting adult networks in an embryonic system.     

Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.