Rewiring of the phosphoproteome executes two meiotic divisions in budding yeast

The cell cycle is ordered by a controlled network of kinases and phosphatases. To generate gametes via meiosis, two distinct and sequential chromosome segregation events occur without an intervening S phase. How canonical cell cycle controls are modified for meiosis is not well understood. Here, using highly synchronous budding yeast populations, we reveal how the global proteome and phosphoproteome change during the meiotic divisions. While protein abundance changes are limited to key cell cycle regulators, dynamic phosphorylation changes are pervasive. Our data indicate that two waves of cyclin-dependent kinase (Cdc28Cdk1) and Polo (Cdc5Polo) kinase activity drive successive meiotic divisions. These two distinct phases of phosphorylation are ensured by the meiosis-specific Spo13 protein, which rewires the phosphoproteome. Spo13 binds to Cdc5Polo to promote phosphorylation in meiosis I, particularly of substrates containing a variant of the canonical Cdc5Polo motif. Overall, our findings reveal that a master regulator of meiosis directs the activity of a kinase to change the phosphorylation landscape and elicit a developmental cascade.</p

Using Visual Methods to Capture Patient Perspectives in Interprofessional Team-Based Care for Chronic Disease Management

Background: Understanding how patients perceive their role in the healthcare team can improve overall satisfaction of care and health outcomes. However, it has been challenging to capture the diversity of patient experiences using traditional research approaches. The goal of this study was to explore the perspectives of patients involved in an interprofessional team-based chronic disease management program for chronic obstructive pulmonary disease using visual research techniques. Methods: Our visual approach began with patients autonomously drawing (or mapping) experiences with their healthcare team. The maps were explored with the patients through focus group discussions. Maps were inductively coded to identify similarities and differences between participants’ perceptions. Focus group transcripts were first analyzed independently, then compared to and integrated into the map analysis. Findings: Overall, participants (n = 13) were satisfied as patients of team-based care. Participants drew multiple healthcare providers, sources of information, and themselves to represent their teams. Relationships and significance were represented using arrows, the size of each team member, facial expressions, and symbols. Four key elements of effective team-based models of care emerged: 1) effective information sharing, 2) diversity of providers’ roles, 3) empowerment through self-management, and 4) enhanced access to care. Conclusion: This study used visualization methodology to obtain patient feedback on the program’s performance, elicit patients’ experiences, and attempt to mitigate some of the limitations of isolated survey and focus group methodology, subsequently obtaining rich data on team-based care. Our research also informs ongoing quality improvement of the team nbased model for chronic disease management

A Magnetohydrodynamic Model of the M87 Jet I: Superluminal Knot Ejections from HST-1 as Trails of Quad Relativistic MHD Shocks

This is the first in a series of papers that introduces a new paradigm for understanding the jet in M87: a collimated relativistic flow in which strong magnetic fields play a dominant dynamical role. Here wefocus on the flow downstream of HST-1 - an essentially stationary flaring feature that ejects trails of superluminal components. We propose that these components are quad relativistic magnetohydrodynamic shock fronts (forward/reverse fast and slow modes) in a narrow jet with a helically twisted magnetic structure. And we demonstrate the properties of such shocks with simple one-dimensional numerical simulations. Quasi-periodic ejections of similar component trails may be responsible for the M87 jet substructures observed further downstream on 100 - 1,000 pc scales. This new paradigm requires the assimilation of some new concepts into the astrophysical jet community, particularly the behavior of slow/fast-mode waves/shocks and of current-driven helical kink instabilities. However, the prospects of these ideas applying to a large number of other jet systems may make this worth the effort.Comment: 7 pages, 4 figures, Accepted for Publication in Ap

The SynergEyes hybrid contact lens fitting guide and information

Historically, creating a lens with the optics of a rigid contact lens and the comfort of a soft contact lens has been fraught with difficulty. New technology, however has enabled us to create a hybrid lens that would greatly benefit people who suffer from corneal problems that prevent them from using conventional contact lenses. This paper describes a fitting guide for the new SynergEyes A hybrid contact lens based on a two part series of on-eye fitting trials

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated, but not rhinovirus infected, primary human airway smooth muscle

Background: Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE4) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations.Methods: In the present study we investigated whether the PDE4 inhibitor piclamilast (10-6 M) could alter RV or viral mimetic (5 μg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E2 and cAMP production were assayed by ELISA and RV replication was assayed by viral titration.Results: We found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL-6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines.Conclusion: By extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE4 inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV. © 2013 Van Ly et al.; licensee BioMed Central Ltd

Activity and Process Stability of Purified Green Pepper (Capsicum annuum) Pectin Methylesterase

Pectin methylesterase (PME) from green bell peppers (Capsicum annuum) was extracted and purified by affinity chromatography on a CNBr-Sepharose-PMEI column. A single protein peak with pectin methylesterase activity was observed. For the pepper PME, a biochemical characterization in terms of molar mass (MM), isoelectric points (pI), and kinetic parameters for activity and thermostability was performed. The optimum pH for PME activity at 22 °C was 7.5, and its optimum temperature at neutral pH was between 52.5 and 55.0 °C. The purified pepper PME required the presence of 0.13 M NaCl for optimum activity. Isothermal inactivation of purified pepper PME in 20 mM Tris buffer (pH 7.5) could be described by a fractional conversion model for lower temperatures (55?57 °C) and a biphasic model for higher temperatures (58?70 °C). The enzyme showed a stable behavior toward high-pressure/temperature treatments. Keywords: Capsicum annuum; pepper; pectin methylesterase; purification; characterization; thermal and high-pressure stabilit

Effects of β2 Agonists, Corticosteroids, and Novel Therapies on Rhinovirus-Induced Cytokine Release and Rhinovirus Replication in Primary Airway Fibroblasts

Rhinovirus-(RV-) induced asthma exacerbations account for high asthma-related health costs and morbidity in Australia. The cellular mechanism underlying this pathology is likely the result of RV-induced nuclear-factor-kappa-B-(NF-κB-) dependent inflammation. NF-κB may also be important in RV replication as inhibition of NF-κB inhibits replication of other viruses such as human immunodeficiency virus and cytomegalovirus. To establish the role of NF-κB inhibitors in RV-induced IL- 6 and IL-8 and RV replication, we used pharmacological inhibitors of NF-κB, and steroids and/or β2 agonists were used for comparison. Primary human lung fibroblasts were infected with RV-16 in the presence of NF-κB inhibitors: BAY-117085 and dimethyl fumarate; β2 agonist: salmeterol; and/or corticosteroids: dexamethasone; fluticasone. RV-induced IL-6 and IL-8 and RV replication were assessed using ELISAs and virus titration assays. RV replicated and increased IL-6 and IL-8 release. Salmeterol increased, while dexamethasone and fluticasone decreased RV-induced IL-6 and IL-8 (P<0.05). The NF-κB inhibitor BAY-117085 inhibited only RV-induced IL-6 (P<0.05) and dimethyl fumarate did not alter RV-induced IL-6 and IL-8. Dimethylfumarate increased RV replication whilst other drugs did not alter RV replication. These data suggest that inhibition of NF-κB alone is unlikely to be an effective treatment compared to current asthma therapeutics

Retrieval of material properties of monolayer transition-metal dichalcogenides from magnetoexciton energy spectra

Reduced exciton mass, polarizability, and dielectric constant of the surrounding medium are essential properties for semiconduction materials, and they can be extracted recently from the magnetoexciton energies. However, the acceptable accuracy of the previously suggested method requires very high magnetic intensity. Therefore, in the present paper, we propose an alternative method of extracting these material properties from recently available experimental magnetoexciton s-state energies in monolayer transition-metal dichalcogenides (TMDCs). The method is based on the high sensitivity of exciton energies to the material parameters in the Rytova-Keldysh model. It allows us to vary the considered material parameters to get the best fit of the theoretical calculation to the experimental exciton energies for the $1s$, $2s$, and $3s$ states. This procedure gives values of the exciton reduced mass and 2D polarizability. Then, the experimental magnetoexciton spectra compared to the theoretical calculation gives also the average dielectric constant. Concrete applications are presented only for monolayers WSe$_2$ and WS$_2$ from the recently available experimental data. However, the presented approach is universal and can be applied to other monolayer TMDCs. The mentioned fitting procedure requires a fast and effective method of solving the Schr\"{o}dinger of an exciton in monolayer TMDCs with a magnetic field. Therefore, we also develop such a method in this study for highly accurate magnetoexciton energies.Comment: 8 pages, 4 figures, 4 table

A Case-Based Approach to Business Process Monitoring

International audienceThe agile workflow technology deals with flexible workflow adaptation and overriding, in case of foreseen as well as unforeseen changes and problems in the operating business environment. One key issue that an agile workflow system should address is Business Process (BP) monitoring. This consists in properly highlighting and organizing non-compliances and adaptations with respect to the default process schema. Such an activity can be the starting point for other very critical tasks, such as quality assessment and process reengineering. In this paper, we introduce an automated support to BP monitoring, which exploits the Case-based Reasoning (CBR) methodology. CBR is particularly well suited for managing exceptional situations, and has been proposed in the literature for process change reuse and workflow adaptation support. Our work extends these functionalities by retrieving traces of process execution similar to the current one, which can then be automatically clustered. Retrieval and clustering results can provide support both to end users, in the process instance execution phase, and to process engineers, in (formal) process quality evaluation and long term process schema redefinition. Our approach in practice is illustrated by means of a case study in the field of stroke management