Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel

The voltage-gated sodium channel is the site of action of more than six classes of neurotoxins and drugs that alter its function by interaction with distinct, allosterically coupled receptor sites. Batrachotoxin (BTX) is a steroidal alkaloid that binds to neurotoxin receptor site 2 and causes persistent activation. BTX binding is inhibited allosterically by local anesthetics. We have investigated the interaction of BTX with amino acid residues I1760, F1764, and Y1771, which form part of local anesthetic receptor site in transmembrane segment IVS6 of type IIA sodium channels. Alanine substitution for F1764 (mutant F1764A) reduces tritiated BTX-A-20-α-benzoate binding affinity, causing a 60-fold increase in Kd. Alanine substitution for I1760, which is adjacent to F1764 in the predicted IVS6 transmembrane alpha helix, causes only a 4-fold increase in Kd. In contrast, mutant Y1771A shows no change in BTX binding affinity. For wild-type and mutant Y1771A, BTX shifted the voltage for half-maximal activation ≈40 mV in the hyperpolarizing direction and increased the percentage of noninactivating sodium current to ≈60%. In contrast, these BTX effects were eliminated completely for the F1764A mutant and were reduced substantially for mutant I1760A. Our data suggest that the BTX receptor site shares overlapping but nonidentical molecular determinants with the local anesthetic receptor site in transmembrane segment IVS6 as well as having unique molecular determinants in transmembrane segment IS6, as demonstrated in previous work. Evidently, BTX conforms to a domain–interface allosteric model of ligand binding and action, as previously proposed for calcium agonist and antagonist drugs acting on l-type calcium channels.

Interaction of the Doa4 Deubiquitinating Enzyme with the Yeast 26S Proteasome

The Saccharomyces cerevisiae Doa4 deubiquitinating enzyme is required for the rapid degradation of protein substrates of the ubiquitin–proteasome pathway. Previous work suggested that Doa4 functions late in the pathway, possibly by deubiquitinating (poly)-ubiquitin-substrate intermediates associated with the 26S proteasome. We now provide evidence for physical and functional interaction between Doa4 and the proteasome. Genetic interaction is indicated by the mutual enhancement of defects associated with a deletion of DOA4 or a proteasome mutation when the two mutations are combined. Physical association of Doa4 and the proteasome was investigated with a new yeast 26S proteasome purification procedure, by which we find that a sizeable fraction of Doa4 copurifies with the protease. Another yeast deubiquitinating enzyme, Ubp5, which is related in sequence to Doa4 but cannot substitute for it even when overproduced, does not associate with the proteasome. DOA4-UBP5 chimeras were made by a novel PCR/yeast recombination method and used to identify an N-terminal 310-residue domain of Doa4 that, when appended to the catalytic domain of Ubp5, conferred Doa4 function, consistent with Ubp enzymes having a modular architecture. Unlike Ubp5, a functional Doa4-Ubp5 chimera associates with the proteasome, suggesting that proteasome binding is important for Doa4 function. Together, these data support a model in which Doa4 promotes proteolysis through removal of ubiquitin from proteolytic intermediates on the proteasome before or after initiation of substrate breakdown.

Leading With the Relationship: The Role of the Therapeutic Relationship in Motivational Interviewing

Motivational Interviewing (MI) is a brief evidence-based treatment that is most commonly used to treat addictive behaviors and to encourage diet and lifestyle changes and treatment adherence in health care settings. In recent years MI's use has been expanded to multiple other client populations in clinical psychology, as well as to other sectors, such as in education, and international non-profit work (Hettema at al., 2005). MI was inspired by research that demonstrated a high correlation between therapist application of the client-centered skill of accurate empathy and a reduction in drinking behaviors (Miller et al., 1980). MI contains both relational and technical components that are intended to operate synergistically. Despite a large body of research on MI treatment outcomes, variation in effectiveness has been found among studies, and the active ingredients of MI, particularly the relational aspects, are not well understood. As a result, the use of MI in many treatment settings is limited to the technical components of MI without a theory-based integration of the therapeutic relationship. This paper focuses on the contribution of the relational component to the effectiveness of MI, and explores the synergistic relationship between the technical and relational components of MI. A literature review of MI and the trans-theoretical literature on the therapeutic relationship is followed by two case illustrations. The paper concludes with recommendations for the field.

The Use of Therapeutic Assessment with Forensic Populations: Practitioners' Perspectives

Therapeutic Assessment is a semi-structured approach to collaborative assessment developed by Stephen E. Finn and colleagues. In Therapeutic Assessment, psychological assessment is used as a therapeutic intervention (Finn, 2007; Finn & Kamphuis, 2006). The Therapeutic Assessment model differs from traditional assessment with regard to procedure and the roles of both assessor and client. Therapeutic Assessment has yet to be explored in forensic settings, wherein assessors are required to take on a number of varying and conflicting roles. In the current study, five forensic psychologists completed a semi-structured interview to identify their perspectives of Therapeutic Assessment and its utility in forensic contexts. A phenomenological qualitative analysis of the interviews was conducted to derive themes about Therapeutic Assessment, forensic psychology, and the overlap between these two domains. General themes that emerged include (a) the role and the context of the practitioner's work with the forensic population; (b) the potential of using Therapeutic Assessment's paradigm in family law settings; and (c) the increased risk of harm when using Therapeutic Assessment with forensic populations. In addition to these themes, multiple respondents discussed components of collaborative/Therapeutic Assessment that they have found useful with this population. Finally, the implications of these results are discussed.

Shift Work and the United States Female Workforce: The Relationship Between Shift-Work and Ill-Health Effects

The present study was designed to determine the magnitude of the relationship between amount, frequency, and length of shift work completed by female transportation employees and the number, degree, and extent of problems related to physical, menstrual and psychological health including depression. It was hypothesized that workers that are employed in areas such as transportation who are working shift work on a regular basis place themselves at higher risk for developing health or psychosocial related effects. These health related outcomes can have a profound impact on an employee’s job performance, daily functioning, and personal life. The present study sought to understand the potential relationship between working shift work and higher disturbances to the bodies’ natural functioning. The present study has the potential for explaining new ways to decrease the risk factors for those working shift work by contributing to the overall understanding of this multifaceted relationship. This study has many important findings and implications. This study has implications for explaining that the effects of disturbances to the circadian rhythm as a result of certain shift work schedules can result in ill-related health effects. Additionally, this study sought to challenge limitations to current research that has been conducted on the topic as the majority of studies have been performed on men. The overall purpose of the study was to gain a better understanding of the negative effects of shift work on females working within the transportation industry. This study sought to explain the health implications specifically for female workers as fewer studies have been conducted with gender as a main effect in the analysis. The present study suggests that due to the circadian rhythm controlling hormone secretion within the body, disturbances to its natural rhythm can have additional effects on female cycles such as menstruation. Overall, this study offers implications for further research on females working shift work and highlights the continued importance for further exploration into recent developments. These implications have the potential to further our current understanding of the relationship between shift work and ill-health effects, particularly the factors that women face.

The Work of the Task Force to Implement Amendment 64: A Case Study

This short essay – taken from a keynote address given at the University of Denver’s Marijuana at the Crossroads Conference – describes the dynamics of marijuana law and policy in the United States with a particular eye toward the federalism implications of marijuana legalization in the states. The essay discusses the history of marijuana regulation in the United States, sets forth a number of possible scenarios going forward, and makes a few, tentative predictions about the future.

Satisfaction of clinical nurses with the formation of a university tutorial program

Degree in nursing from the Universitat Jaume I (UJI) maintains the continuity of learning with an integrated learning methodology (theory, simulated practice and clinical practice). The objective of this methodology is to achieve consistency between the knowledge, abilities and skills acquired in the classroom, laboratory and clinic to ensure skills related. Reference Nurse is a key figure in this process, you receive accredited training on Educational Methods, assessment of competence, and Evidence-Based Practice that plays the role of evaluating in conjunction with the subjects. It does not perceive economic remuneration. The main objective of this study is to determine the level of satisfaction of clinical nurses on the Nurses Training Program Reference in UJI (Castellon- Spain). A cross sectional study was performed and conducted on 150 nurses. 112 questionnaires were completed, collected and analysed at the end of training. The survey consists of 12 items measured with the Likert scale with 5 levels of response and two open questions regarding the positive and negative aspects of the course and to add in this formation. The training is always performed by the same faculty and it's used four sessions of 2012. We perform a quantitative analysis of the variables under study using measures of central tendency. The completion rate of the survey is 95.53% (n=107). Anonymity rate of 54,14% The overall satisfaction level of training was 3.65 (SD = 0.89) on 5 points. 54.2% (n = 58) of the reference nurses made a contribution in the open questions described in the overall results. The overall satisfaction level can be considered acceptable. It is considered necessary to elaborate a specific survey to detect areas of improvement of nurse training program reference and future recruitment strategies. The main objective of the present work is the selection and integration of different methodologies among those applicable within the framework of the European Higher Education Area to combine teaching methods with high implication from both lecturers and students.

Performance Assessment of a Polymer Electrolyte Membrane Electrochemical Reactor under Alkaline Conditions – A Case Study with the Electrooxidation of Alcohols

A novel polymer electrolyte membrane electrochemical reactor (PEMER) configuration has been employed for the direct electrooxidation of propargyl alcohol (PGA), a model primary alcohol, towards its carboxylic acid derivatives in alkaline medium. The PEMER configuration comprised of an anode and cathode based on nanoparticulate Ni and Pt electrocatalysts, respectively, supported on carbonaceous substrates. The electrooxidation of PGA was performed in 1.0 M NaOH, where a cathode based on a gas diffusion electrode was manufactured for the reduction of oxygen in alkaline conditions. The performance of a novel alkaline anion-exchange membrane based on Chitosan (CS) and Poly(vinyl) alcohol (PVA) in a 50:50 composition ratio doped with a 5 wt.% of poly (4-vinylpyridine) organic ionomer cross-linked, methyl chloride quaternary salt resin (4VP) was assessed as solid polymer electrolyte. The influence of 4VP anionic ionomer loading of 7, 12 and 20 wt.% incorporated into the electrocatalytic layers was examined by SEM and cyclic voltammetry (CV) upon the optimisation of the electroactive area, the mechanical stability and cohesion of the catalytic ink onto the carbonaceous substrate for both electrodes. The performance of the 4VP/CS:PVA membrane was compared with the commercial alkaline anion-exchange membrane FAA −a membrane generally used in direct alcohol alkaline fuel cells- in terms of polarisation plots in alkaline conditions. Furthermore, preparative electrolyses of the electrooxidation of PGA was performed under alkaline conditions of 1 M NaOH at constant current density of 20 mA cm−2 using a PEMER configuration to provide proof of the principle of the feasibility of the electrooxidation of other alcohols in alkaline media. PGA conversion to Z isomers of 3-(2-propynoxy)-2-propenoic acid (Z-PPA) was circa 0.77, with average current efficiency of 0.32. Alkaline stability of the membranes within the PEMER configuration was finally evaluated after the electrooxidation of PGA.

Oceanic ichthyology : a treatise on the deep-sea and pelagic fishes of the world, based chiefly upon the collections made by the steamers "Blake," "Albatross," and "Fishhawk" in the northwestern Atlantic, with an atlas containing 417 figures / by George Brown Goode and Tarleton H. Bean. Pub. in connection with the National Museum and the Smithsonian institution.

v.22 (1896) text

Oceanic ichthyology : a treatise on the deep-sea and pelagic fishes of the world, based chiefly upon the collections made by the steamers "Blake," "Albatross," and "Fishhawk" in the northwestern Atlantic, with an atlas containing 417 figures / by George Brown Goode and Tarleton H. Bean. Pub. in connection with the National Museum and the Smithsonian institution.

v.22 (1896) atlas

The Turkish Empire in Europe, Asia, and Africa: dividid into all its governments, together with the other territories that are tributary to it, as also the dominions of ye Emperor of Marocco [sic] according to the newest and most exact observations

by H. Moll.

Flexicurity e valorizzazione delle capability: l'impulso alla ri-regolamentazione del lavoro a termine = Flexicurity and enhancement of work capability: the impulse to re-regulation of labor. WP C.S.D.L.E. “Massimo D’Antona”.INT – 97/2012

The paper analyzes the evolution of the concept of flexicurity in the european context. In this perspective, flexicurity is expressed through the language of the policies, showing an inherent weakness in influencing national reform processes. The essay compare also with the possibility of a re-reading of flexicurity policies, in the light of the theory of capabilities developed by Amartya Sen.

Fighting Deflation: Would QE work in the euro area? CEPS Commentary, 9 October 2014

With inflation in the eurozone stubbornly remaining on a downward trajectory, pressure is growing on the ECB to do “something” to prevent outright deflation. But, given the financial structure of eurozone countries, would the preferred "something" – quantitative easing – actually do the trick?

Turkey after the start of negotiations with the European Union - foreign relations and the domestic situation, Part I. OSW Report, June 2007

The start of accession negotiations between Ankara and the EU is vital for the future of both Turkey and the Union, including Poland as its member state, as well as for the geopolitical situation in Eurasia (the Black Sea region, Caucasus, Central Asia and the Middle East). Appreciating the significance of these issues, the Centre for Eastern Studies in early 2005 decided to launch a project entitled "Turkey after the start of negotiations with the European Union - foreign relations and the domestic situation". The goal of this project is to present, within the context of accession negotiations, Turkey's greatest internal challenges as well as Ankara's relations with its neighbour regions, the EU and the USA. This Report is the first of three which will be published as part of the project. The Report includes texts on Turkish-US relations since 2003, major political and social challenges on Turkey's path towards the EU and the current condition of the Turkish economy. The Report was developed between July 2005 and November 2006, over which time CES workers and associates searched for publicly available materials in Poland, Turkey and EU countries, and went on three research trips to Turkey, where they met local researchers, analysts, politicians and officials. The authors of the Report would like to express their gratitude to everyone who have shared their opinions with them, and to the Polish Embassy in Ankara, especially to Ambassador Grzegorz Michalski and Minister Andrzej Ananicz for their expert support and assistance in the authors' work on this Report. This Report does not present the official stance of the Polish government on the issues discussed therein; instead it reflects the personal views of its authors, who have made their best efforts to ensure that their work is reliable.