Desensitization of the Neurokinin-1 Receptor (NK1-R) in Neurons: Effects of Substance P on the Distribution of NK1-R, Gαq/11, G-Protein Receptor Kinase-2/3, and β-Arrestin-1/2

Observations in reconstituted systems and transfected cells indicate that G-protein receptor kinases (GRKs) and β-arrestins mediate desensitization and endocytosis of G-protein–coupled receptors. Little is known about receptor regulation in neurons. Therefore, we examined the effects of the neurotransmitter substance P (SP) on desensitization of the neurokinin-1 receptor (NK1-R) and on the subcellular distribution of NK1-R, Gαq/11, GRK-2 and -3, and β-arrestin-1 and -2 in cultured myenteric neurons. NK1-R was coexpressed with immunoreactive Gαq/11, GRK-2 and -3, and β-arrestin-1 and -2 in a subpopulation of neurons. SP caused 1) rapid NK1-R–mediated increase in [Ca2+]i, which was transient and desensitized to repeated stimulation; 2) internalization of the NK1-R into early endosomes containing SP; and 3) rapid and transient redistribution of β-arrestin-1 and -2 from the cytosol to the plasma membrane, followed by a striking redistribution of β-arrestin-1 and -2 to endosomes containing the NK1-R and SP. In SP-treated neurons Gαq/11 remained at the plasma membrane, and GRK-2 and -3 remained in centrally located and superficial vesicles. Thus, SP induces desensitization and endocytosis of the NK1-R in neurons that may be mediated by GRK-2 and -3 and β-arrestin-1 and -2. This regulation will determine whether NK1-R–expressing neurons participate in functionally important reflexes.

Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice. Main methods Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1 +) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings Obesity and allergen-sensitization together increased the number of LYVE-1 + lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims: Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obeseallergen sensitized mice. Main methods: Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1+) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings: Obesity and allergen-sensitization together increased the number of LYVE-1+ lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance: The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Confirmatory factor analysis of the Way of Coping Checklist-Revised (WCCL-R) in the Asian context

Industrial employment growth has been one of the most dynamic areas of expansion in Asia; however, current trends in industrialised working environments have resulted in greater employee stress. Despite research showing that cultural values affect the way people cope with stress, there is a dearth of psychometrically established tools for use in non-Western countries to measure these constructs. Studies of the "Way of Coping Checklist-Revised" (WCCL-R) in the West suggest that the WCCL-R has good psychometric properties, but its applicability in the East is still understudied. A confirmatory factor analysis (CFA) is used to validate the WCCL-R constructs in an Asian population. This study used 1,314 participants from Indonesia, Sri Lanka, Singapore, and Thailand. An initial exploratory factor analysis revealed that original structures were not confirmed; however, a subsequent EFA and CFA showed that a 38-item, five-factor structure model was confirmed. The revised WCCL-R in the Asian sample was also found to have good reliability and sound construct and concurrent validity. The 38-item structure of the WCCL-R has considerable potential in future occupational stress-related research in Asian countries.

Curvilinear relationships between the job demands-resources (JD-R) model, and work engagement : a police service case study

The current study aims to investigate the non-linear relationship between the JD-R model and work engagement. Previous research has identified linear relationships between these constructs; however there are strong theoretical arguments for testing curvilinear relationships (e.g., Warr, 1987). Data were collected via a self-report online survey from officers of one Australian police service (N = 2,626). Results demonstrated a curvilinear relationship between job demands and job resources and engagement. Gender (as a control variable) was also found to be a significant predictor of work engagement. The results indicated that male police officers experienced significantly higher job demands and colleague support than female officers. However, female police officers reported significantly higher levels of work engagement than male officers. This study emphasises the need to test curvilinear relationships, as well as simple linear associations, when measuring psychological health.

Innovation adoption and fit, linking R&D and industry

Significant sums of money are invested in developing technological innovations that have low levels and rates of adoption. Several approaches have been put forward in an effort to improve rates of adoption. This paper presents the results of study that examined the innovation fit of key technological innovations in the beef industry. Findings indicate that be assessing the innovation fit throughout the R&D process researchers and end users can collaborate to improve the innovation fit and the rate of adoption. The paper also put forward a model that demonstrates the linkages between R&D, adoption and innovation fit.

Railways, Urban Development and Town Planning in Britain: 1948–2008, Haywood R. Ashgate (2009). £65.00, ISBN: 9780754673927

This book is a thorough investigation of the relationship between land use planning and the railways in Britain, through review of the factors affecting the two sectors and their integration during the period of public ownership. The rationale behind the book is explained as a timely analysis of the dynamic correlation involving town planning and management of the railway in a period when growing congestion on the road network is forcing people to look for alternative modes and capacity is badly needed to accommodate this increased demand for travel. The book calls for a modal shift from road to rail for passenger and freight traffic.

Crystallographic characterization of the first reported crystalline form of the potent hallucinogen (R)-2-amino-1-(8-bromobenzo[1,2-b;5,4-b']difuran-4-yl)propane or `bromodragonfly': the 1:1 anhydrous proton-transfer compound with 3,5-dinitrosalicylic acid

The 1:1 proton-transfer compound of the potent substituted amphetamine hallucinogen (R)-1-(8-bromobenzo[1,2-b; 4,5-b']difuran-4-yl)-2-aminopropane (common trivial name 'bromodragonfly') with 3,5-dinitrosalicylic acid, 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-mmoniopropane 2-carboxy-4,6-dinitrophenolate, C13H13BrNO2+ C7H3N2O7- forms hydrogen-bonded cation-anion chain substructures comprising undulating head-to-tail anion chains formed through C(8) carboxyl O-H...O(nitro) associations and incorporating the aminium groups of the cations. The intra-chain cation-anion hydrogen-bonding associations feature proximal cyclic R33(8) interactions involving both a N+-H...O(phenolate) and the carboxyl O--H...O(nitro)associations. Also present are aromatic pi-pi ring interactions [minimum ring centroid separation, 3.566(2)A; inter-plane dihedral angle, 5.13(1)deg]. A lateral hydrogen-bonding interaction between the third aminium proton and a carboxyl O acceptor link the chain substructures giving a two-dimensional sheet structure. This determination represents the first of any form of this compound and confirms that it has the (R) absolute configuration. The atypical crystal stability is attributed both to the hydrogen-bonded chain substructures provided by the anions, which accommodate the aminium proton-donor groups of the cations and give cross-linking, and to the presence of cation--anion aromatic ring pi-pi interactions.

Encyclopedia contributions: entries N-R in Oxford Companion to Australian

New Farm Park; p.436 Oakman, H.O. (with Jan Seto); p.449 Paranella, Jose; p.463 Perrott family; p.469 Pink, James; p.475 Queensland; pp.495-497 The Queenslander; pp.497-498 The Queensland Horticulturist; p.498 Rawson, Mina; p.502 Rockhampton Botanic Gardens; p.572

A regional construction R&D evaluation system for China

Expenditure on R&D in the China construction industry has been relatively low in comparison with many developed countries for a number of years – a situation considered to be a major barrier to the industry’s competitiveness in general and unsatisfactory industry development of the 31 regions involved. A major problem with this is the lack of a sufficiently sophisticated method of objectively evaluating R&D activity in what are quite complex circumstances considering the size and regional differences that exist in this part of the world. A regional construction R&D evaluation system (RCRES) is presented aimed at rectifying the situation. This is based on 12 indicators drawn from the Chinese Government’s R&D Inventory of Resources in consultation with a small group of experts in the field, and further factor analysed into three groups. From this, the required evaluation is obtained by a simple formula. Examination of the results provides a ranking list of the R&D performance of each of the 31 regions, indicating a general disproportion between coastal and inland regions and highlighting regions receiving special emphasis or currently lacking in development. The understanding on this is vital for the future of China’s construction industry.

The social media (r)evolution : Obama's political campaign

This paper addresses how social media was used to leverage votes in new media environments. Barack Obama’s social media campaign is analysed and illustrates how the Obama brand benefited from integrating social media into the campaign. Voting behaviour has changed; politicians are continually seeking new ways to communicate with their constituents. Voting on political ‘brands’ is based on an identity or image, rather than central issues. While political parties rely upon an integrated marketing communication (IMC) approach, with a focus on building the (political) brand of the party and brand relationships, communication is no longer fully controlled by the marketers.