Phototransduction in Drosophila Is compromised by Gal4 expression but not by InsP3 receptor knockdown or mutation

Drosophila phototransduction is mediated by phospholipase C, leading to activation of transient receptor potential (TRP) and TRP-like (TRPL) channels by mechanisms that are unresolved. A role for InsP(3) receptors (IP(3)Rs) had been excluded because IP3R mutants (itpr) appeared to have normal light responses; however, this was recently challenged by Kohn et al. ("Functional cooperation between the IP3 receptor and phospholipase C secures the high sensitivity to light of Drosophila photoreceptors in vivo," Journal of Neuroscience 35: 2530), who reported defects in phototransduction after IP3R-RNAi knockdown. They concluded that InsP3-induced Ca2+ release plays a critical role in facilitating channel activation, and that previous failure to detect IP3R phenotypes resulted from trace Ca2+ in electrodes substituting for InsP(3)-induced Ca2+ release. In an attempt to confirm this, we performed electroretinograms, whole-cell recordings, and GCaMP6f Ca2+ imaging from both IP3R-RNAi flies and itpr-null mutants. Like Kohn et al., we used GMRGal4 to drive expression of UAS-IP3R-RNAi, but we also used controls expressing GMRGal4 alone. We describe several GMRGal4 phenotypes suggestive of compromised development, including reductions in sensitivity, dark noise, potassium currents, and cell size and capacitance, as well as extreme variations in sensitivity between cells. However, we found no effect of IP3R RNAi or mutation on photoreceptor responses or Ca2+ signals, indicating that the IP3R plays little or no role in Drosophila phototransduction

Phototransduction in Drosophila Is Compromised by Gal4 Expression but not by InsP3 Receptor Knockdown or Mutation

$\textit{Drosophila}$ phototransduction is mediated by phospholipase C, leading to activation of transient receptor potential (TRP) and TRP-like (TRPL) channels by mechanisms that are unresolved. A role for InsP$_3$ receptors (IP$_3$Rs) had been excluded because IP$_3$R mutants ($\textit{itpr}$) appeared to have normal light responses; however, this was recently challenged by Kohn et al. ("Functional cooperation between the IP3 receptor and phospholipase C secures the high sensitivity to light of $\textit{Drosophila}$ photoreceptors in vivo," Journal of Neuroscience 35:2530), who reported defects in phototransduction after IP$_3$R-RNAi knockdown. They concluded that InsP$_3$-induced Ca$^{2+}$ release plays a critical role in facilitating channel activation, and that previous failure to detect IP$_3$R phenotypes resulted from trace Ca$^{2+}$ in electrodes substituting for InsP$_3$-induced Ca$^{2+}$ release. In an attempt to confirm this, we performed electroretinograms, whole-cell recordings, and GCaMP6f Ca$^{2+}$ imaging from both IP$_3$R-RNAi flies and $\textit{itpr}$-null mutants. Like Kohn et al., we used GMRGal4 to drive expression of UAS-IP$_3$R-RNAi, but we also used controls expressing GMRGal4 alone. We describe several GMRGal4 phenotypes suggestive of compromised development, including reductions in sensitivity, dark noise, potassium currents, and cell size and capacitance, as well as extreme variations in sensitivity between cells. However, we found no effect of IP$_3$R RNAi or mutation on photoreceptor responses or Ca$^{2+}$ signals, indicating that the IP$_3$R plays little or no role in $\textit{Drosophila}$ phototransduction.Biotechnology and Biological Sciences Research Council: 501100000268, BB/G0092531/1, BB/M007006/1 (RCH, MKB, C-HL) European Union’s Horizon 2020 (EU Framework Programme for Research and Innovation), 501100007601 (RCH, SA: EU Grant 658818), and the Erasmus program (MEK)

A two-component signal-transduction cascade in Carnobacterium piscicola LV17B:two signaling peptides and one sensor-transmitter

In the lactic acid bacterium Carnobacterium piscicola LV17B a peptide-pheromone dependent quorum-sensing mode is involved in the regulation of bacteriocin production. Bacteriocin CB2 was identified as an environmental signal that induces bacteriocin production. Here, we demonstrate that a second 24 amino acid peptide (CS) also induces bacteriocin production. Transcription activation of several carnobacteriocin operons is triggered by CB2 or CS via a two-component signal transduction system composed of CbnK and CbnR. (C) 2001 Elsevier Science Inc. All rights reserved

Topological robot localization in a large-scale water pipe network

Topological localization is well suited to robots operating in water pipe networks because the environment is well defined as a set of discrete connected places like junctions, customer connections, and access points. Topological methods are more computationally efficient than metric methods, which is important for robots operating in pipes as they will be small with limited computational power. A Hidden Markov Model (HMM) based localization method is presented here, with novel incorporation of measured distance travelled. Improvements to the method are presented which use a reduced definition of the robot state to improve computational efficiency and an alternative motion model where the probability of transitioning to each other state is uniform. Simulation in a large realistic map shows that the use of measured distance travelled improves the localization accuracy by around 70%, that the reduction of the state definition gives an reduction in computational requirement by 75% with only a small loss to accuracy dependant on the robot parameters, and that the alternative motion model gives a further improvement to accuracy

Update on the Endoscopic Management of Peptic Ulcer Bleeding

Upper gastrointestinal bleeding is the most common gastrointestinal emergency, with peptic ulcer as the most common cause. Appropriate resuscitation followed by early endoscopy for diagnosis and treatment are of major importance in these patients. Endoscopy is recommended within 24 h of presentation. Endoscopic therapy is indicated for patients with high-risk stigmata, in particular those with active bleeding and visible vessels. The role of endoscopic therapy for ulcers with adherent clots remains to be elucidated. Ablative or mechanical therapies are superior to epinephrine injection alone in terms of prevention of rebleeding. The application of an ulcer-covering hemospray is a new promising tool. High dose proton pump inhibitors should be administered intravenously for 72 h after endoscopy in high-risk patients. Helicobacter pylori should be tested for in all patients with peptic ulcer bleeding and eradicated if positive. These recommendations have been captured in a recent international guideline

Using a logical model to predict the growth of yeast

<p>Abstract</p> <p>Background</p> <p>A logical model of the known metabolic processes in <it>S. cerevisiae </it>was constructed from iFF708, an existing Flux Balance Analysis (FBA) model, and augmented with information from the KEGG online pathway database. The use of predicate logic as the knowledge representation for modelling enables an explicit representation of the structure of the metabolic network, and enables logical inference techniques to be used for model identification/improvement.</p> <p>Results</p> <p>Compared to the FBA model, the logical model has information on an additional 263 putative genes and 247 additional reactions. The correctness of this model was evaluated by comparison with iND750 (an updated FBA model closely related to iFF708) by evaluating the performance of both models on predicting empirical minimal medium growth data/essential gene listings.</p> <p>Conclusion</p> <p>ROC analysis and other statistical studies revealed that use of the simpler logical form and larger coverage results in no significant degradation of performance compared to iND750.</p

Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics

Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 μg l−1; PGC, 13.2 μg l−1; PGA/PGC, 6.7; and gastrin, 62.4 ng l−1. For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test

SdrF, a Staphylococcus epidermidis Surface Protein, Contributes to the Initiation of Ventricular Assist Device Driveline–Related Infections

Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneous driveline entry site acts as a potential portal of entry for bacteria, allowing development of either localized or systemic infections. A novel in vitro binding assay using explanted drivelines obtained from patients undergoing transplantation and a heterologous lactococcal system of surface protein expression were used to identify S. epidermidis surface components involved in the pathogenesis of driveline infections. Of the four components tested, SdrF, SdrG, PIA, and GehD, SdrF was identified as the primary ligand. SdrF adherence was mediated via its B domain attaching to host collagen deposited on the surface of the driveline. Antibodies directed against SdrF reduced adherence of S. epidermidis to the drivelines. SdrF was also found to adhere with high affinity to Dacron, the hydrophobic polymeric outer surface of drivelines. Solid phase binding assays showed that SdrF was also able to adhere to other hydrophobic artificial materials such as polystyrene. A murine model of infection was developed and used to test the role of SdrF during in vivo driveline infection. SdrF alone was able to mediate bacterial adherence to implanted drivelines. Anti-SdrF antibodies reduced S. epidermidis colonization of implanted drivelines. SdrF appears to play a key role in the initiation of ventricular assist device driveline infections caused by S. epidermidis. This pluripotential adherence capacity provides a potential pathway to infection with SdrF-positive commensal staphylococci first adhering to the external Dacron-coated driveline at the transcutaneous entry site, then spreading along the collagen-coated internal portion of the driveline to establish a localized infection. This capacity may also have relevance for other prosthetic device–related infections