Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells

Metastatic cancer cells typically fail to halt migration on contact with non-cancer cells. This invasiveness is in contrast to normal mesenchymal cells that retract on contact with another cell. Why cancer cells are defective in contact inhibition of locomotion is not understood. Here, we analyse the dynamics of prostate cancer cell lines co-cultured with fibroblasts, and demonstrate that a combinatorial code of Eph receptor activation dictates whether cell migration will be contact inhibited. The unimpeded migration of metastatic PC-3 cells towards fibroblasts is dependent on activation of EphB3 and EphB4 by ephrin-B2, which we show activates Cdc42 and cell migration. Knockdown of EphB3 and EphB4 restores contact inhibition of locomotion to PC-3 cells. Conversely, homotypic collisions between two cancer cells results in contact inhibition of locomotion, mediated by EphA-Rho-Rho kinase (ROCK) signalling. Thus, the migration of cancer cells can switch from restrained to invasive, depending on the Eph-receptor profile of the cancer cell and the reciprocal ephrin ligands expressed by neighbouring cells.     

Feeding through artificial membranes reduces fecundity for females of the blood‐feeding insect,Rhodnius prolixus

The blood‐feeding insect, Rhodnius prolixus, has been raised in the laboratory for close to 100 years. Various feeding techniques have been employed ranging from the use of warm‐blooded hosts, to the use of previously collected blood offered through artificial membranes. This study compared the fecundity in mated and unmated females fed rabbit blood directly from the shaved belly of a rabbit to that of females fed defibrinated rabbit blood through an artificial membrane. These results confirm previous reports that this insect's feeding efficacy is reduced using an artificial membrane. It also demonstrates for the first time that the fecundity index, which measures the efficiency of turning the blood meal into eggs, is significantly reduced. We suggest that the natural feeding on a warm‐blooded host may provide cues that have the short‐term effect of enhancing the act of feeding and the long‐term effect of increasing egg production efficiency. Until an artificial feeding method that does not interfere with feeding and fecundity is devised, experiments on reproduction in R. prolixus warrant the use of a warm‐blooded host to emulate feeding in its natural setting. © 2010 Wiley Periodicals, Inc.     

Enhanced prostacyclin formation and Wnt signaling in sclerostin deficient osteocytes and bone

We show that prostacyclin production is increased in bone and osteocytes from sclerostin (Sost) knockout mice which have greatly increased bone mass. The addition of prostacyclin or a prostacyclin analog to bone forming osteoblasts enhances differentiation and matrix mineralization of osteoblasts. The increase in prostacyclin synthesis is linked to increases in β-catenin concentrations and activity as shown by enhanced binding of lymphoid enhancer factor, Lef1, to promoter elements within the prostacyclin synthase promoter. Blockade of Wnt signaling reduces prostacyclin production in osteocytes. Increased prostacyclin production by osteocytes from sclerostin deficient mice could potentially contribute to the increased bone formation seen in this condition.     

A different path: Revealing the function of staphylococcal proteins in biofilm formation

Staphylococcus aureus and Staphylococcus epidermidis cause dangerous and difficult to treat medical device-related infections through their ability to form biofilms. Extracellular poly-N-acetylglucosamine (PNAG) facilitates biofilm formation and is a vaccination target, yet details of its biosynthesis by the icaADBC gene products is limited. IcaC is the proposed transporter for PNAG export, however a comparison of the Ica proteins to homologous exo-polysaccharide synthases suggests that the common IcaAD protein components both synthesise and transport the PNAG. The limited distribution of icaC to the Staphylococcaceae and its membership of a family of membrane-bound acyltransferases, leads us to suggest that IcaC is responsible for the known O-succinylation of PNAG that occurs in staphylococci, identifying a potentially new therapeutic target specific for these bacteria.     

Borrelia burgdorferi outer surface protein C (OspC) binds complement component C4b and confers bloodstream survival

Borrelia burgdorferi (Bb) is the causative agent of Lyme disease in the United States, a disease that can result in carditis, and chronic and debilitating arthritis and/or neurologic symptoms if left untreated. Bb survives in the midgut of the Ixodes scapularis tick, or within tissues of immunocompetent hosts. In the early stages of infection, the bacteria are present in the bloodstream where they must resist clearance by the innate immune system of the host. We have found a novel role for outer surface protein C (OspC) from B. burgdorferi and B. garinii in interactions with the complement component C4b and bloodstream survival in vivo. Our data show that OspC inhibits the classical and lectin complement pathways and competes with complement protein C2 for C4b binding. Resistance to complement is important for maintenance of the lifecycle of Bb, enabling survival of the pathogen within the host as well as in the midgut of a feeding tick when ospC expression is induced.     

Evaluation of two communication tools,slideshow and theater,to improve participants’ understanding of a clinical trial in the informed consent procedure on Pemba Island,Tanzania

BackgroundClinical trial participants are required to sign an informed consent form (ICF). However, information is lacking on the most effective methods to convey trial relevant information prior to inviting participants to sign the ICF, being particularly pertinent in low-income countries. A previous study on Pemba Island, Tanzania, found that a verbal information session (IS) was significantly better than providing an ICF alone. However, knowledge gaps remained. Building on these findings, we investigated the effect of adding a slideshow or a theater to the IS in the informed consent procedure of an anthelminthic clinical trial.Methodology/principal findingsA total of 604 caregivers were randomized into the control group that only received an ICF (n = 150) or an ICF plus one of three intervention strategies: (i) verbal IS (n = 135), (ii) verbal IS with a slideshow (n = 174) or (iii) verbal IS followed by a theater (n = 145). All modes of information covered the same key messages. Participants’ understanding was assessed using a semi-structured questionnaire. The mean score of caregivers in the control group (ICF only) was 4.41 (standard deviation = 1.47). Caregivers attending the IS alone were more knowledgeable than those in the control group (estimated difference in mean scores: 2.40, 95% confidence interval (CI) 1.95 to 2.86, p < 0.01). However, there was no evidence of an improvement compared to the IS only when participants attended a slideshow (0.09, 95% CI -0.53 to 0.35, p = 0.68) or a theater (0.28, 95% CI -0.27 to 0.82, p = 0.32). Three out of 10 key messages remained largely misunderstood, regardless of the mode of information group.Conclusions/significanceOur study confirmed that, in this setting, an ICF alone was not sufficient to convey clinical trial-related information. An IS was beneficial, however, additional theater and slideshows did not further improve understanding. Future research should explore methods to improve communication between study teams and participants for different key messages, study types and settings.     

Algivirga pacifica gen. nov., sp. nov., a Novel Agar-Degrading Marine Bacterium of the Family Flammeovirgaceae Isolated from Micronesia

An aerobic, Gram-negative, coccoid to short rod-shaped and non-flagellated marine bacterial strain S354^T was isolated from seawater of Micronesia. The strain was capable to degrade agar-forming slight depression into agar plate. Growth occurred at a temperature range of 12–44 °C, a pH range of 5–9, and a salinity range of 1–7 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences suggested that S354^T belongs to the family Flammeovirgaceae. The novel strain was most closely related to Limibacter armeniacum YM 11-185^T with similarity of 92.5 %. The DNA G+C content was 43.8 mol%. The major fatty acids (>10 %) were iso-C_15:0 and C_16:1 ω5c. The predominant isoprenoid quinone was determined to be MK-7. Polar lipid profile of S354^T consisted of phosphatidylethanolamine, unknown polar lipid, and unknown glycolipids. Based on the phenotypic, phylogenetic, biochemical, and physiological tests conducted in this study, S354^T is proposed to represent a type strain of a novel genus and species. The 16S rRNA gene sequence of S354^T is registered in GenBank under the accession number JQ639084. The type of strain Algivirga pacifica gen. nov., sp. nov. is S354^T (=KCCM 90107^T=JCM 18326^T).