N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans

To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO2, equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans

A New Method to Address Unmet Needs for Extracting Individual Cell Migration Features from a Large Number of Cells Embedded in 3D Volumes

Background: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D), which is related to the spread of cancer and metastases. Methodology/Principal Findings: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift) trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6%). We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA) were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. Conclusions/Significance: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment. © 2011 Adanja et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Estimating required information size by quantifying diversity in random-effects model meta-analyses

<p>Abstract</p> <p>Background</p> <p>There is increasing awareness that meta-analyses require a sufficiently large information size to detect or reject an anticipated intervention effect. The required information size in a meta-analysis may be calculated from an anticipated <it>a priori </it>intervention effect or from an intervention effect suggested by trials with low-risk of bias.</p> <p>Methods</p> <p>Information size calculations need to consider the total model variance in a meta-analysis to control type I and type II errors. Here, we derive an adjusting factor for the required information size under any random-effects model meta-analysis.</p> <p>Results</p> <p>We devise a measure of diversity (<it>D</it>²) in a meta-analysis, which is the relative variance reduction when the meta-analysis model is changed from a random-effects into a fixed-effect model. <it>D</it>²is the percentage that the between-trial variability constitutes of the sum of the between-trial variability and a sampling error estimate considering the required information size. <it>D</it>²is different from the intuitively obvious adjusting factor based on the common quantification of heterogeneity, the inconsistency (<it>I</it>²), which may underestimate the required information size. Thus, <it>D</it>²and <it>I</it>²are compared and interpreted using several simulations and clinical examples. In addition we show mathematically that diversity is equal to or greater than inconsistency, that is <it>D</it>²≥ <it>I</it>², for all meta-analyses.</p> <p>Conclusion</p> <p>We conclude that <it>D</it>²seems a better alternative than <it>I</it>²to consider model variation in any random-effects meta-analysis despite the choice of the between trial variance estimator that constitutes the model. Furthermore, <it>D</it>²can readily adjust the required information size in any random-effects model meta-analysis.</p

Genes Selectively Up-Regulated by Pheromone in White Cells Are Involved in Biofilm Formation in Candida albicans

To mate, MTL-homozygous strains of the yeast pathogen Candida albicans must switch from the white to opaque phase. Mating-competent opaque cells then release pheromone that induces polarization, a G1 block and conjugation tube formation in opaque cells of opposite mating type. Pheromone also induces mating-incompetent white cells to become adhesive and cohesive, and form thicker biofilms that facilitate mating. The pheromone response pathway of white cells shares the upstream components of that of opaque cells, but targets a different transcription factor. Here we demonstrate that the genes up-regulated by the pheromone in white cells are activated through a common cis-acting sequence, WPRE, which is distinct from the cis-acting sequence, OPRE, responsible for up-regulation in opaque cells. Furthermore, we find that these white-specific genes play roles in white cell biofilm formation, and are essential for biofilm formation in the absence of an added source of pheromone, suggesting either an autocrine or pheromone-independent mechanism. These results suggest an intimate, complex and unique relationship between switching, mating and MTL-homozygous white cell biofilm formation, the latter a presumed virulence factor in C. albicans

Biochemistry and physiology of gastrointestinal somatostatin

Somatostatin, a tetradecapeptide initially isolated from the ovine hypothalamus, is widely distributed throughout the gastrointestinal tract where it may act as a hormone, local chemical messenger, or neurotransmitter to elicit many physiological actions. Release of somatostatin from D cells in the gut is regulated by mechanisms that are both dependent on and independent of cAMP. In most cases somatostatin acts to inhibit the function of its target cells. It performs this action in part via pertussis-toxin-sensitive inhibitory guanine nucleotide-binding proteins that regulate adenylate cyclase activity. Other mechanisms may involve sites of action distal to intracellular second messenger systems .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44411/1/10620_2005_Article_BF01536041.pd

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Mediated Plastid RNA Editing in Plant Immunity

[EN] Plant regulatory circuits coordinating nuclear and plastid gene expression have evolved in response to external stimuli. RNA editing is one of such control mechanisms. We determined the Arabidopsis nuclear-encoded homeodomain-containing protein OCP3 is incorporated into the chloroplast, and contributes to control over the extent of ndhB transcript editing. ndhB encodes the B subunit of the chloroplast NADH dehydrogenase-like complex (NDH) involved in cyclic electron flow (CEF) around photosystem I. In ocp3 mutant strains, ndhB editing efficiency decays, CEF is impaired and disease resistance to fungal pathogens substantially enhanced, a process recapitulated in plants defective in editing plastid RNAs encoding NDH complex subunits due to mutations in previously described nuclear-encoded pentatricopeptide-related proteins (i.e. CRR21, CRR2). Furthermore, we observed that following a pathogenic challenge, wild type plants respond with editing inhibition of ndhB transcript. In parallel, rapid destabilization of the plastidial NDH complex is also observed in the plant following perception of a pathogenic cue. Therefore, NDH complex activity and plant immunity appear as interlinked processes.This work was supported by the Spanish MICINN (CONSOLIDER and BFU2012 to PV), and Generalitat Valenciana (Prometeo2010/020 to PV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.García-Andrade Serrano, J.; Ramirez Garcia, V.; López Sánchez, A.; Vera Vera, P. (2013). Mediated Plastid RNA Editing in Plant Immunity. PLoS Pathogens. 9(10):1003713-1003713. https://doi.org/10.1371/ journal.ppat.1003713S1003713100371391

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research

Management strategies for Helicobacter pylori-seropositive patients with dyspepsia: clinical and economic consequences.

BACKGROUND: Noninvasive testing for Helicobacter pylori is widely available and has been considered as an initial management strategy for uninvestigated dyspepsia. However, data to guide clinicians in the management of patients with dyspepsia who are seropositive for H. pylori are lacking. OBJECTIVE: To examine the economic, clinical, and policy implications of alternative initial management strategies for patients with uninvestigated dyspepsia who are seropositive for H. pylori. DESIGN: Decision analysis comparing the costs and outcomes of initial anti-H. pylori therapy and initial endoscopy. PATIENTS: Helicobacter pylori-seropositive patients with dyspepsia. MEASUREMENTS: Cost estimates were obtained from the Medicare reimbursement schedule and a health maintenance organization pharmacy. Probability estimates were derived from the medical literature. RESULTS: Initial endoscopy costs an average of $1276 per patient, whereas initial anti-H, pylori therapy costs$820 per patient; the average saving is $456 per patient treated. The financial effect of a 252% increase in the use of antibiotics for initial H. pylori therapy is more than offset by reducing the endoscopy workload by 53%. Endoscopy-related costs must be reduced by 96% before the two strategies become equally cost-effective. In patients with nonulcer dyspepsia, the financial benefits of initial anti-H. pylori therapy are not substantially affected by varying the rates of H. pylori eradication, the complications of antibiotics, or the response of symptoms to cure of H. pylori infection. CONCLUSIONS: In H. pylori-seropositive patients with dyspepsia, initial anti-H. pylori therapy is the most cost, effective management strategy. Randomized studies of these strategies that evaluate outcomes and patient preferences are needed to optimize management decisions. In the meantime, unless physicians are concerned about resistance to antimicrobial agents or the lack of proven benefit of anti-H. pylori therapy in nonucler dyspepsia, the strategy outlined in this analysis can be used as a basis for management and policy decisions about H. pylori-seropositive patients with dyspepsia