Overexpression of manganese or copper-zinc superoxide dismutase inhibits breast cancer growth

We have studied the effects of overexpression of superoxide dismutase (SOD), a tumor suppressor protein that dismutes superoxide radical to H2O2, on breast cancer cell growth in vitro and xenograft growth in vivo. No previous work has directly compared the growth-suppressive effects of manganese SOD (MnSOD) and copper-zinc SOD (CuZnSOD). We hypothesized that either adenoviral MnSOD (AdMnSOD) or adenoviral CuZnSOD (AdCuZnSOD) gene therapy would suppress the growth of human breast cancer cells. After determining the antioxidant profiles of three human breast cell lines, MCF 10A, MDA-MB231, and MCF-7, we measured the effects of MnSOD or CuZnSOD overexpression on cell growth and survival in vitro and in vivo. Results demonstrated that infection with AdMnSOD or AdCuZnSOD increased the activity of the respective enzyme in all three cell lines. In vitro, overexpression of MnSOD or CuZnSOD decreased not only cell growth but also clonogenic survival in a dose- and transgene-dependent manner. In vivo, treatment of tumors with AdMnSOD or AdCuZnSOD decreased xenograft growth compared to controls. The first direct comparison of MnSOD to CuZnSOD overexpression indicated that CuZnSOD and MnSOD were similarly effective at suppressing cancer cell growth.     

Efficient gene delivery and silencing of mouse and human pancreatic islets

Background  

In view of the importance of beta cells in glucose homeostasis and the profound repercussions of beta cell pathology on human health, the acquisition of tools to study pancreatic islet function is essential for the design of alternative novel therapies for diabetes. One promising approach toward this goal involves the modification of gene expression profile of beta cells.     

The genome of deep-sea vent chemolithoautotroph Thiomicrospira crunogena XCL-2

Presented here is the complete genome sequence of Thiomicrospira crunogena XCL-2, representative of ubiquitous chemolithoautotrophic sulfur-oxidizing bacteria isolated from deep-sea hydrothermal vents. This gammaproteobacterium has a single chromosome (2,427,734 base pairs), and its genome illustrates many of the adaptations that have enabled it to thrive at vents globally. It has 14 methyl-accepting chemotaxis protein genes, including four that may assist in positioning it in the redoxcline. A relative abundance of coding sequences (CDSs) encoding regulatory proteins likely control the expression of genes encoding carboxysomes, multiple dissolved inorganic nitrogen and phosphate transporters, as well as a phosphonate operon, which provide this species with a variety of options for acquiring these substrates from the environment. Thiom. crunogena XCL-2 is unusual among obligate sulfur-oxidizing bacteria in relying on the Sox system for the oxidation of reduced sulfur compounds. The genome has characteristics consistent with an obligately chemolithoautotrophic lifestyle, including few transporters predicted to have organic allocrits, and Calvin-Benson-Bassham cycle CDSs scattered throughout the genome.     

Cuttlefish use visual cues to control three-dimensional skin papillae for camouflage

Cephalopods (octopus, squid and cuttlefish) are known for their camouflage. Cuttlefish Sepia officinalis use chromatophores and light reflectors for color change, and papillae to change three-dimensional physical skin texture. Papillae vary in size, shape and coloration; nine distinct sets of papillae are described here. The objective was to determine whether cuttlefish use visual or tactile cues to control papillae expression. Cuttlefish were placed on natural substrates to evoke the three major camouflage body patterns: Uniform/Stipple, Mottle and Disruptive. Three versions of each substrate were presented: the actual substrate, the actual substrate covered with glass (removes tactile information) and a laminated photograph of the substrate (removes tactile and three-dimensional information because depth-of-field information is unavailable). No differences in Small dorsal papillae or Major lateral mantle papillae expression were observed among the three versions of each substrate. Thus, visual (not tactile) cues drive the expression of papillae in S. officinalis. Two sets of papillae (Major lateral mantle papillae and Major lateral eye papillae) showed irregular responses; their control requires future investigation. Finally, more Small dorsal papillae were shown in Uniform/Stipple and Mottle patterns than in Disruptive patterns, which may provide clues regarding the visual mechanisms of background matching versus disruptive coloration.     

Hematopoietic progenitors and hemocyte lineages in the Drosophila lymph gland

The Drosophila lymph gland (LG) is a model system for studying hematopoiesis and blood cell homeostasis. Here, we investigated the patterns of division and differentiation of pro-hemocytes in normal developmental conditions and response to wasp parasitism, by combining lineage analyses and molecular markers for each of the three hemocyte types. Our results show that the embryonic LG contains primordial hematopoietic cells which actively divide to give rise to a pool of pro-hemocytes. We found no evidence for the existence of bona fide stem cells and rather suggest that Drosophila pro-hemocytes are regulated as a group of cells, rather than individual stem cells. The fate-restriction of plasmatocyte and crystal cell progenitors occurs between the end of embryogenesis and the end of the first larval instar, while Notch activity is required for the differentiation of crystal cells in third instar larvae only. Upon parasitism, lamellocyte differentiation prevents crystal cell differentiation and lowers plasmatocyte production. We also found that a new population of intermediate progenitors appears at the onset of hemocyte differentiation and accounts for the increasing number of differentiated hemocytes in the third larval instar. These findings provide a new framework to identify parameters of developmental plasticity of the Drosophila lymph gland and hemocyte homeostasis in physiological conditions and in response to immunological cues.     

Structure of the p53 C-terminus bound to 14-3-3: Implications for stabilization of the p53 tetramer

The adaptor protein 14-3-3 binds to and stabilizes the tumor suppressor p53 and enhances its anti-tumour activity. In the regulatory C-terminal domain of p53 several 14-3-3 binding motifs have been identified. Here, we report the crystal structure of the extreme C-terminus (residues 385-393, p53pT387) of p53 in complex with 14-3-3σ at a resolution of 1.28 Å. p53pT387 is accommodated by 14-3-3 in a yet unrecognized fashion implying a rationale for 14-3-3 binding to the active p53 tetramer. The structure exhibits a potential binding site for small molecules that could stabilize the p53/14-3-3 protein complex suggesting the possibility for therapeutic intervention.

Structured summary

MINT-7711943: 14-3-3 sigma (uniprotkb:P31947) and p53 (uniprotkb:P04637) bind (MI:0407) by X-ray crystallography (MI:0114)MINT-7711931: 14-3-3 sigma (uniprotkb:P31947) and p53 (uniprotkb:P04637) bind (MI:0407) by isothermal titration calorimetry (MI:0065)     

Cryptic species of <Emphasis Type="Italic">Euryakaina</Emphasis> n. g. (Digenea: Cryptogonimidae) from sympatric lutjanids in the Indo-West Pacific

A survey of the endohelminth fauna of Indo-West Pacific Lutjanidae (Perciformes) revealed the presence of the species Siphoderina manilensis (Velasquez, 1961) Miller & Cribb, 2008 and S. marina (Hafeezullah & Siddiqi, 1970) Miller & Cribb, 2008 in seven Lutjanus spp. from sites off the Great Barrier Reef, the Maldives, New Caledonia and Ningaloo Reef, Western Australia. A combination of morphological and ribosomal DNA analyses of these cryptogonimids prompted the transfer of these taxa to a new genus, Euryakaina n. g., as E. manilensis n. comb. and E. marina n. comb., based on comparative analysis with other cryptogonimid taxa. Euryakaina n. g. is distinguished from all other cryptogonimid genera by the combination of a fusiform body, the few relatively small, widely spaced oral spines (sometimes absent), a highly lobed ovary, opposite to slightly oblique testes, vitelline follicles that extend from the anterior margin of the testes to slightly posterior to the intestinal bifurcation, and an excretory vesicle that bifurcates dorsal to the ovary and reunites briefly slightly posterior to the intestinal bifurcation. Morphometric analysis of these taxa alone suggests they should be reduced to synonymy, but DNA sequence analyses and ecological niche partitioning provide evidence that they form a cryptic species complex in sympatric lutjanids in the Indo-West Pacific. The secondary structure of the ITS2 rDNA for species of Euryakaina was also modelled and analysed for the presences of compensatory base changes (CBCs) or hemi-CBCs in order to explore the usefulness of these changes as a tool to help elucidate the taxonomy of this complex system. We also report what we interpret here as intraspecific variation in the ITS2 rDNA between individuals of E. manilensis from Lutjanus vitta recovered off the Great Barrier Reef and New Caledonia.     

Identical consensus sequence and conserved genomic polymorphism of hepatitis E virus during controlled interspecies transmission

High-throughput sequencing of bile and feces from two pigs experimentally infected with human hepatitis E virus (HEV) of genotype 3f revealed the same full-length consensus sequence as in the human sample. Twenty-nine percent of polymorphic sites found in HEV from the human sample were conserved throughout the infection of the heterologous host. The interspecies transmission of HEV quasispecies is the result of a genomic negative-selection pressure on random mutations which can be deleterious to the viral population. HEV intrahost nucleotide diversity was found to be in the lower range of other human RNA viruses but correlated with values found for zoonotic viruses. HEV transmission between humans and pigs does not seem to be modulated by host-specific mutations, suggesting that adaptation is mainly regulated by ecological drivers.     

Vertical Distribution of Plant-Parasitic Nematodes in Sweet Potato

Plant-parasitic nematodes (PPN) are harmful pests that have become a severe threat to crop production worldwide. Diversity of PPN at horizontal and spatial scales influence the effectiveness of control strategies. This study evaluated the vertical distribution of PPN genera at 0 cm to 30 cm and 30 cm to 60 cm in sweet potato fields in Central, Manyatta, and Nembure regions of Embu County, Kenya. A significant region × depth interaction was observed for Tylenchus. For all the other nematode genera, there were no significant variations in the abundance at 0 cm to 30 cm and 30 cm to 60 cm depths. However, Helicotylenchus, Meloidogyne, and Scutellonema occurred in greater numbers at both depths in all regions. Shannon and Simpson diversity indices were higher at 0 cm to 30 cm depth while Pielou’s evenness was similar at both depths in the three regions. Diversity partitioning of genus richness, Shannon, and Simpson diversities across all regions at 0 cm to 30 cm, indicated that β component contributed 61.9%, 35.6%, and 22.6% of γ diversity, respectively. Coinertia analysis indicated a significant covariation between nematode genera and soil properties. The results show that management of PPN in sweet potato fields should be targeted at soil depths that are not less than 60 cm.