Long distance root–shoot signalling in plant–insect community interactions

Plants mediate interactions between insects, including leaf- and root-feeders; yet the underlying mechanisms and connection with ecological theory remain unresolved. In this review, based on novel insights into long-distance (i.e., leaf–leaf, root–shoot) defence signalling, we explore the role of phytohormones in driving broad-scale patterns of aboveground–belowground interactions that can be extrapolated to general plant–insect relationships. We propose that the outcome of intra-feeding guild interactions is generally negative due to induction of similar phytohormonal pathways, whereas between-guild interactions are often positive due to negative signal crosstalk. However, not all outcomes could be explained by feeding guild; we argue that future studies should target ecologically representative plant–insect systems, distinguish subguilds, and include plant growth hormones to improve our understanding of plant-mediated interactions.

Systemic root signalling in a belowground, volatile-mediated tritrophic interaction

Plants attacked by leaf herbivores release volatile organic compounds (VOCs) both locally from the wounded site and systemically from non-attacked tissues. These volatiles serve as attractants for predators and parasitoids. This phenomenon is well described for plant leaves, but systemic induction of VOCs in the roots has remained unstudied. We assessed the spatial and temporal activation of the synthesis and release of (E)-β-caryophyllene (EβC) in maize roots upon feeding by larvae of Diabrotica virgifera virgifera, as well as the importance of systemically produced EβC for the attraction of the entomopathogenic nematode Heterorhabditis megidis. The production of EβC was found to be significantly stronger at the site of attack than in non-attacked tissues. A weak, but significant, increase in transcriptional activity of the EβC synthase gene tps23 and a corresponding increase in EβC content were observed in the roots above the feeding site and in adjacent roots, demonstrating for the first time that herbivory triggers systemic production of a volatile within root systems. In belowground olfactometers, the nematodes were significantly more attracted towards local feeding sites than systemically induced roots. The possible advantages and disadvantages of systemic volatile signalling in roots are discussed.

Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics.

BACKGROUND Endometriosis, the growth of endometrial tissue outside the uterine cavity, is associated with chronic pelvic pain, subfertility and an increased risk of ovarian cancer. Current treatments include the surgical removal of the lesions or the induction of a hypoestrogenic state. However, a reappearance of the lesion after surgery is common and a hypoestrogenic state is less than optimal for women of reproductive age. Additional approaches are required. Endometriosis lesions exist in a unique microenvironment characterized by increased concentrations of hormones, inflammation, oxidative stress and iron. This environment influences cell survival through the binding of membrane receptors and a subsequent cascading activation of intracellular kinases that stimulate a cellular response. Many of these kinase signalling pathways are constitutively activated in endometriosis. These pathways are being investigated as therapeutic targets in other diseases and thus may also represent a target for endometriosis treatment. METHODS To identify relevant English language studies published up to 2015 on kinase signalling pathways in endometriosis, we searched the Pubmed database using the following search terms in various combinations; 'endometriosis', 'inflammation', 'oxidative stress', 'iron', 'kinase', 'NF kappa', 'mTOR', 'MAPK' 'p38', 'JNK', 'ERK' 'estrogen' and progesterone'. Further citing references were identified using the Scopus database and finally current clinical trials were searched on the clinicaltrials.gov trial registry. RESULTS The current literature on intracellular kinases activated by the endometriotic environment can be summarized into three main pathways that could be targeted for treatments: the canonical IKKβ/NFκB pathway, the MAPK pathways (ERK1/2, p38 and JNK) and the PI3K/AKT/mTOR pathway. A number of pharmaceutical compounds that target these pathways have been successfully trialled in in vitro and animal models of endometriosis, although they have not yet proceeded to clinical trials. The current generation of kinase inhibitors carry a potential for adverse side effects. CONCLUSIONS Kinase signalling pathways represent viable targets for endometriosis treatment. At present, however, further improvements in clinical efficacy and the profile of adverse effects are required before these compounds can be useful for long-term endometriosis treatment. A better understanding of the molecular activity of these kinases, including the specific extracellular compounds that lead to their activation in endometriotic cells specifically should facilitate their improvement and could potentially lead to new, non-hormonal treatments of endometriosis.

Development of Drugs Targeting the PI3K Signalling Pathway in Leukaemias and Lymphomas

The phosphoinositide 3-kinase (PI3K) family of signalling enzymes play a key role in the transduction of signals from activated cell surface receptors controlling cell growth and proliferation, survival, metabolism, and migration. The intracellular signalling pathway from activated receptors to PI3K and its downstream targets v-akt murine thymoma viral oncogene homolog (Akt) and mechanistic target of rapamycin (mTOR) is very frequently deregulated by genetic and epigenetic mechanisms in human cancer, including leukaemia and lymphoma. In the past decade, an arsenal of small molecule inhibitors of key enzymes in this pathway has been developed and evaluated in pre-clinical studies and clinical trials in cancer patients. These include pharmacological inhibitors of Akt, mTOR, and PI3K, some of which are approved for the treatment of leukaemia and lymphoma. The PI3K family comprises eight different catalytic isoforms in humans, which have been subdivided into three classes. Class I PI3K isoforms have been extensively studied in the context of human cancer, and the isoforms p110α and p110δ are validated drug targets. The recent approval of a p110δ-specific PI3K inhibitor (idelalisib/Zydelig®) for the treatment of selected B cell malignancies represents the first success in developing these molecules into anti-cancer drugs. In addition to PI3K inhibitors, mTOR inhibitors are intensively studied in leukaemia and lymphoma, and temsirolimus (Torisel®) is approved for the treatment of a type of lymphoma. Based on these promising results it is hoped that additional novel PI3K pathway inhibitors will in the near future be further developed into new drugs for leukaemia and lymphoma.

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.

Analysis of BMP signalling through the receptor type IA in embryogenesis using conditional gene inactivation in mice

Although bone morphogenetic proteins (BMPs) were initially identified for their potent bone-inducing activity, their precise roles in processes of endochondral and intramembranous bone formation are far from being clear. Tissue-specific loss-of-function experiments using the BMP receptor type IA (BMPR-IA) are particularly attractive since this receptor is thought to be essential for signaling by the closely related BMPs -2, 4, and 7. To ablate signaling through this receptor during chondrogenesis, we have generated transgenic mice expressing Cre recombinase under the control of the collagen type II (Col2a1) gene regulatory sequences. Mice lacking BMPR-IA function in chondrocytes display a number of skeletal abnormalities, including defects in bones of the chondrocranium, abnormal dorsal vertebral processes, scapulae with severe hypoplasia of dorsal elements, and shortening of the long bones. Alterations in the growth plate of long bones in mutants suggest that BMPR-IA is not required for early steps of the chondrocyte specification, but is rather important in regulation of terminal differentiation. Molecular analysis revealed noticeable downregulation of the Ihh/Ptch signalling pathway, decreased chondrocyte proliferation rate and deregulation of hypertrophy. ^ In order to elucidate the role of BMP signalling in development of the limb and intramembranous ossification, we have used mice expressing Cre recombinase under control of the Prx1 (MHox) regulatory elements (M. Logan, pers comm.). Cre activity was found in those mice in the developing limb bud mesenchyme, as well as in a subset of cranial neural crest cells. Prx1-Cre-induced conditional mutants display prominent defects in distal limb outgrowth, as well as ossification defects in a number of neural crest-derived calvarial bones. Intriguingly, mutant limbs displayed alterations in patterning along all three axes. Molecular analysis revealed ectopic anterior Shh/Ptch signalling pathway activation and expression of some Hox genes. Observed loss of Msx1 and Msx2 expression in the progress zone correlates with downregulation of Cyclin D1 and decreased distal outgrowth. Abnormal ventral localization of Lmx1b-expressing cells along with observed later morphological abnormalities suggest a novel role for BMP signalling in establishment or maintaining of the dorso-ventral polarity in the limb mesoderm. ^

Development and validation of the Neuro Symptom Inventory in the primary brain tumor patient population

Symptoms has been shown to predict quality of life, treatment course and survival in solid tumor patients. Currently, no instrument exists that measures both cancer-related symptoms and the neurologic symptoms that are unique to persons with primary brain tumors (PBT). The aim of this study was to develop and validate an instrument to measure symptoms in patients who have PBT. A conceptual analysis of symptoms and symptom theories led to defining the symptoms experience as the perception of the frequency, intensity, distress, and meaning that occurs as symptoms are produced, perceived, and expressed. The M.D. Anderson Symptom Inventory (MDASI) measures both symptoms and how they interfere with daily functioning in patients with cancer, which is similar to the situational meaning defined in the analysis. A list of symptoms pertinent to the PBT population was added to the core MDASI and reviewed by a group of experts for validity. As a result, 18 items were added to the core MDASI (the MDASI-BT) for the next phase of instrument development, establishing validity and reliability through a descriptive, cross-sectional approach with PBT patients. Data were collected with a patient completed demographic data sheet, an investigator completed clinician checklist, and the MDASI-BT. Analysis evaluated the reliability and validity of the MDASI-BT in PBT patients. Data were obtained from 201 patients. The number of items was reduced to 22 by evaluation of symptom severity as well as cluster analysis. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the brain tumor module items. Factor analysis confirmed that the 22 item MDASI-BT measured six underlying constructs: (a) affective; (b) cognitive; (c) focal neurologic deficits; (d) constitutional symptoms; (e) treatment-related symptoms; and (f) gastrointestinal symptoms. The MDASI-BT was sensitive to disease severity and if the patient was hospitalized. The MDASI-BT is the first instrument to measure symptoms in PBT patients that has demonstrated reliability and validity. It is the first step in a program of research to evaluate the occurrence of symptoms and plan and evaluate interventions for PBT patients. ^

Contribution To Signalling Of 3d Video Streams In Communication Systems Using The Session Initiation Protocol

Las tecnologías de vídeo en 3D han estado al alza en los últimos años, con abundantes avances en investigación unidos a una adopción generalizada por parte de la industria del cine, y una importancia creciente en la electrónica de consumo. Relacionado con esto, está el concepto de vídeo multivista, que abarca el vídeo 3D, y puede definirse como un flujo de vídeo compuesto de dos o más vistas. El vídeo multivista permite prestaciones avanzadas de vídeo, como el vídeo estereoscópico, el “free viewpoint video”, contacto visual mejorado mediante vistas virtuales, o entornos virtuales compartidos. El propósito de esta tesis es salvar un obstáculo considerable de cara al uso de vídeo multivista en sistemas de comunicación: la falta de soporte para esta tecnología por parte de los protocolos de señalización existentes, que hace imposible configurar una sesión con vídeo multivista mediante mecanismos estándar. Así pues, nuestro principal objetivo es la extensión del Protocolo de Inicio de Sesión (SIP) para soportar la negociación de sesiones multimedia con flujos de vídeo multivista. Nuestro trabajo se puede resumir en tres contribuciones principales. En primer lugar, hemos definido una extensión de señalización para configurar sesiones SIP con vídeo 3D. Esta extensión modifica el Protocolo de Descripción de Sesión (SDP) para introducir un nuevo atributo de nivel de medios, y un nuevo tipo de dependencia de descodificación, que contribuyen a describir los formatos de vídeo 3D que pueden emplearse en una sesión, así como la relación entre los flujos de vídeo que componen un flujo de vídeo 3D. La segunda contribución consiste en una extensión a SIP para manejar la señalización de videoconferencias con flujos de vídeo multivista. Se definen dos nuevos paquetes de eventos SIP para describir las capacidades y topología de los terminales de conferencia, por un lado, y la configuración espacial y mapeo de flujos de una conferencia, por el otro. También se describe un mecanismo para integrar el intercambio de esta información en el proceso de inicio de una conferencia SIP. Como tercera y última contribución, introducimos el concepto de espacio virtual de una conferencia, o un sistema de coordenadas que incluye todos los objetos relevantes de la conferencia (como dispositivos de captura, pantallas, y usuarios). Explicamos cómo el espacio virtual se relaciona con prestaciones de conferencia como el contacto visual, la escala de vídeo y la fidelidad espacial, y proporcionamos reglas para determinar las prestaciones de una conferencia a partir del análisis de su espacio virtual, y para generar espacios virtuales durante la configuración de conferencias.

Adaptive neuro-fuzzy inference systems (ANFIS) for supervised classification of competence in MIS based on psychomotor skills

INTRODUCTION: Objective assessment of motor skills has become an important challenge in minimally invasive surgery (MIS) training.Currently, there is no gold standard defining and determining the residents' surgical competence.To aid in the decision process, we analyze the validity of a supervised classifier to determine the degree of MIS competence based on assessment of psychomotor skills METHODOLOGY: The ANFIS is trained to classify performance in a box trainer peg transfer task performed by two groups (expert/non expert). There were 42 participants included in the study: the non-expert group consisted of 16 medical students and 8 residents (< 10 MIS procedures performed), whereas the expert group consisted of 14 residents (> 10 MIS procedures performed) and 4 experienced surgeons. Instrument movements were captured by means of the Endoscopic Video Analysis (EVA) tracking system. Nine motion analysis parameters (MAPs) were analyzed, including time, path length, depth, average speed, average acceleration, economy of area, economy of volume, idle time and motion smoothness. Data reduction was performed by means of principal component analysis, and then used to train the ANFIS net. Performance was measured by leave one out cross validation. RESULTS: The ANFIS presented an accuracy of 80.95%, where 13 experts and 21 non-experts were correctly classified. Total root mean square error was 0.88, while the area under the classifiers' ROC curve (AUC) was measured at 0.81. DISCUSSION: We have shown the usefulness of ANFIS for classification of MIS competence in a simple box trainer exercise. The main advantage of using ANFIS resides in its continuous output, which allows fine discrimination of surgical competence. There are, however, challenges that must be taken into account when considering use of ANFIS (e.g. training time, architecture modeling). Despite this, we have shown discriminative power of ANFIS for a low-difficulty box trainer task, regardless of the individual significances between MAPs. Future studies are required to confirm the findings, inclusion of new tasks, conditions and sample population.

Tool wear monitoring using neuro-fuzzy techniques: a comparative study in a turning process

Tool wear detection is a key issue for tool condition monitoring. The maximization of useful tool life is frequently related with the optimization of machining processes. This paper presents two model-based approaches for tool wear monitoring on the basis of neuro-fuzzy techniques. The use of a neuro-fuzzy hybridization to design a tool wear monitoring system is aiming at exploiting the synergy of neural networks and fuzzy logic, by combining human reasoning with learning and connectionist structure. The turning process that is a well-known machining process is selected for this case study. A four-input (i.e., time, cutting forces, vibrations and acoustic emissions signals) single-output (tool wear rate) model is designed and implemented on the basis of three neuro-fuzzy approaches (inductive, transductive and evolving neuro-fuzzy systems). The tool wear model is then used for monitoring the turning process. The comparative study demonstrates that the transductive neuro-fuzzy model provides better error-based performance indices for detecting tool wear than the inductive neuro-fuzzy model and than the evolving neuro-fuzzy model.

Vibration reduction for vision systems on board unmanned aerial vehicles using a neuro-fuzzy controller

In this paper, an intelligent control approach based on neuro-fuzzy systems performance is presented, with the objective of counteracting the vibrations that affect the low-cost vision platform onboard an unmanned aerial system of rotating nature. A scaled dynamical model of a helicopter is used to simulate vibrations on its fuselage. The impact of these vibrations on the low-cost vision system will be assessed and an intelligent control approach will be derived in order to reduce its detrimental influence. Different trials that consider a neuro-fuzzy approach as a fundamental part of an intelligent semi-active control strategy have been carried out. Satisfactory results have been achieved compared to those obtained by means of vibration reduction passive techniques.

Arabidopsis DELLA and two HD-ZIP transcription factors regulate GA signalling in the epidermis through the L1 cis-element

Gibberellins (GAs) are plant hormones that affect plant growth and regulate gene expression differentially across tissues. To study the molecular mechanisms underlying GA signaling in Arabidopsis thaliana, we focused on a GDSL lipase gene (LIP1) induced by GA and repressed by DELLA proteins. LIP1 contains an L1 box promoter sequence, conserved in the promoters of epidermis-specific genes, that is bound by ATML1, an HD-ZIP transcription factor required for epidermis specification. In this study, we demonstrate that LIP1 is specifically expressed in the epidermis and that its L1 box sequence mediates GA-induced transcription. We show that this sequence is overrepresented in the upstream regulatory regions of GA-induced and DELLA-repressed transcriptomes and that blocking GA signaling in the epidermis represses the expression of L1 box–containing genes and negatively affects seed germination. We show that DELLA proteins interact directly with ATML1 and its paralogue PDF2 and that silencing of both HD-ZIP transcription factors inhibits epidermal gene expression and delays germination. Our results indicate that, upon seed imbibition, increased GA levels reduce DELLA protein abundance and release ATML1/PDF2 to activate L1 box gene expression, thus enhancing germination potential.

Dehydroepiandrosterone: A potential signalling molecule for neocortical organization during development

Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEAS) are the most abundant steroids produced by the human adrenal, but no receptors have been identified for these steroids, and no function for them has been established, other than as precursors for sex steroid synthesis. DHEA and DHEAS are found in brains from many species, and we have shown that enzymes crucial for their synthesis, especially P450c17 (17α-hydroxylase/c17,20 lyase), are expressed in a developmentally regulated, region-specific fashion in the developing rodent brain. One region of embryonic expression of P450c17, the neocortical subplate, has been postulated to play a role in guiding cortical projections to their appropriate targets. We therefore determined if products of P450c17 activity, DHEA and DHEAS, regulated the motility and/or growth of neocortical neurons. In primary cultures of mouse embryonic neocortical neurons, DHEA increased the length of neurites containing the axonal marker Tau-1, and the incidence of varicosities and basket-like process formations in a dose-dependent fashion. These effects could be seen at concentrations normally found in the brain. By contrast, DHEAS had no effect on Tau-1 axonal neurites but increased the length of neurites containing the dendritic marker microtubule-associated protein-2. DHEA rapidly increased free intracellular calcium via activation of N-methyl-d-aspartate (NMDA) receptors. These studies provide evidence of mechanisms by which DHEA and DHEAS exert biological actions, show that they have specific functions other than as sex steroid precursors, mediate their effects via non-classic steroid hormone receptors, and suggest that their developmentally regulated synthesis in vivo may play crucial and different roles in organizing the neocortex.

A homeostatic function of CXCR2 signalling in articular cartilage

Funding This work was funded by Arthritis Research UK (grants 17859, 17971, 19654), INNOCHEM EU FP6 (grant LSHB-CT-2005-51867), MRC (MR/K013076/1) and the William Harvey Research Foundation