Regulation of gap junctions by protein phosphorylation

Gap junctions are constituted by intercellular channels and provide a pathway for transfer of ions and small molecules between adjacent cells of most tissues. The degree of intercellular coupling mediated by gap junctions depends on the number of gap junction channels and their activity may be a function of the state of phosphorylation of connexins, the structural subunit of gap junction channels. Protein phosphorylation has been proposed to control intercellular gap junctional communication at several steps from gene expression to protein degradation, including translational and post-translational modification of connexins (i.e., phosphorylation of the assembled channel acting as a gating mechanism) and assembly into and removal from the plasma membrane. Several connexins contain sites for phosphorylation for more than one protein kinase. These consensus sites vary between connexins and have been preferentially identified in the C-terminus. Changes in intercellular communication mediated by protein phosphorylation are believed to control various physiological tissue and cell functions as well as to be altered under pathological conditions.

Johtajan vuorovaikutusosaaminen suomalais-venäläisessä esimies-alaissuhteessa

The participants in the dynamic Finnish working environment are expected to display communication skills, which is emphasized when different cultures meet. The objective of this thesis was to study the required interpersonal communication competence of leaders in a Finnish-Russian superior-subordinate relationship. The leadership was approached from a communicational perspective where leadership emerges in a dyadic relationship between leader and subordinate. The research was conducted as a qualitative case study. The data was gathered from interviews in the target organization. Four superiors and five of their subordinates were interviewed. The qualitative data gathered from the interviews was analyzed by theory-driven content analysis. The representative data was organized and coded in order to establish the main categories, which form a basis of the conclusions of the thesis. Interpersonal communication competence has a significant role alongside substance in leadership. The superiors in the workplace perceive communication as contextual. The findings indicate that there are certain tensions in the relationship between the superiors and their subordinates. The tensions are described as distance, collectiveness and emotions, and verbal expression and understanding. Leadership communication competence is about finding a balance between the tensions based on cultural differences. From the interpersonal communication research tradition point of view, the efficient and appropriate communication competence in this context consists of the knowledge of tensions and challenges, as well as the ability to manage cultural tensions and the motivation to react positively to cultural differences.

Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells

Connexin43 (Cx43), the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension on the expression of Cx43 in aorta and heart in three different models of experimental hypertension. Rats were made hypertensive either by clipping one renal artery (two kidney, one-clip renal (2K,1C) model) by administration of deoxycorticosterone and salt (DOCA-salt model) or by inhibiting nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME model). After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respective controls. The same 2K,1C and DOCA-salt hypertensive animals expressed twice more Cx43 in aorta, and the 2K,1C rats showed an increase in arterial distensibility. In contrast, the aortae of L-NAME hypertensive rats were characterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was more phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or control rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell communication mediated by Cx43 channels may contribute to regulating the elasticity of the vascular wall.

Sera from chronic chagasic patients depress cardiac electrogenesis and conduction

We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23% of sera or AV block in 40%. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated.

Anxiolytic-like effects of 4-phenyl-2-trichloromethyl-3H-1,5-benzodiazepine hydrogen sulfate in mice

The pharmacological effects of 4-phenyl-2-trichloromethyl-3H-1,5-benzodiazepine hydrogen sulfate (PTMB), a novel synthetic benzodiazepine, were examined in mice. In the elevated plus-maze test of anxiety, 0.3-1 mg/kg diazepam ip (F(3,53) = 3.78; P<0.05) and 1-10 mg/kg PTMB ip increased (F(5,98) = 3.26; P<0.01), whereas 2 mg/kg picrotoxin ip decreased (F(3,59) = 8.32; P<0.001) the proportion of time spent in the open arms, consistent with an anxiolytic action of both benzodiazepines, and an anxiogenic role for picrotoxin. In the holeboard, 1.0 mg/kg diazepam ip increased (F(3,54) = 2.78; P<0.05) and 2 mg/kg picrotoxin ip decreased (F(3,59) = 4.69; P<0.01) locomotor activity. Rotarod assessment revealed that 1 mg/kg diazepam ip and 3, 10 and 30 mg/kg PTMB ip produced significant motor incoordination compared to vehicle control (F(4,70) = 7.6; P<0.001). These data suggest that the recently synthesized PTMB compound possesses anxiolytic activity and produces motor incoordination similar to those observed with diazepam.

Tacrolimus (FK506) reduces ischemia-induced hippocampal damage in rats: a 7- and 30-day study

The neuroprotective effect of the immunosuppressant agent FK506 was evaluated in rats after brain ischemia induced for 15 min in the 4-vessel occlusion model. In the first experimental series, single doses of 1.0, 3.0 or 6.0 mg FK506/kg were given intravenously (iv) immediately after ischemia. In the second series, FK506 (1.0 mg/kg) was given iv at the beginning of reperfusion, followed by doses applied intraperitoneally (ip) 6, 24, 48, and 72 h post-ischemia. The same protocol was used in the third series except that all 5 doses were given iv. Damage to the hippocampal field CA1 was assessed 7 or 30 days post-ischemia on three different stereotaxic planes along the septotemporal axis of the hippocampus. Ischemia caused marked neurodegeneration on all planes (P<0.001). FK506 failed to provide neuroprotection to CA1 both when applied iv as a single dose of 1.0, 3.0 or 6.0 mg/kg (experiment 1), and after five iv injections of 1.0 mg/kg (experiment 3). In contrast, the repeated administration of FK506 combining iv plus ip administration reduced CA1 cell death on all stereotaxic planes both 7 and 30 days post-ischemia (experiment 2; P<=0.01). Compared to vehicle alone, FK506 reduced rectal temperature in a dose-dependent manner (P<=0.05); however, this effect did not alter normothermia (37ºC). FK506 reduced ischemic brain damage, an effect sustained over time and apparently dependent on repeated doses and on delivery route. The present data extend previous findings on the rat 4-vessel occlusion model, further supporting the possible use of FK506 in the treatment of ischemic brain damage.

Effect of antipyrine on the gastric emptying of liquid in rats

Antipyrine (At) and dipyrone (Dp) delay gastric emptying (GE) in rats. The objective of the present study was to assess the effects of intravenous (iv) and intracerebroventricular (icv) administration of At and Dp on the GE of liquid by rats. GE was assessed in male Wistar rats (5-10 in each group) 10 min after the icv or iv drug injection by measuring percent gastric retention (%GR) of a saline test meal labeled with phenol red 10 min after administration by gavage. The At iv group was significantly higher (64.4 ± 2.6%) compared to control (33.4 ± 1.5%) but did not differ from the Dp group (54.3 ± 3.8%). After icv administration of At, %GR (34.2 ± 2%) did not differ from control (32.6 ± 1.9%), but was significantly higher after Dp (54.5 ± 2.3%). Subdiaphragmatic vagotomy significantly reduced %GR in the At group (30.2 ± 0.7%) compared to the sham group, but was significantly higher than in the controls (23.0 ± 0.5%). In the animals treated with At iv, baclofen significantly reduced %GR (28.3 ± 2.4%) compared to vehicle-treated animals (55.2 ± 3.2%). The same occurred in the animals treated iv with vehicle and icv with baclofen. Although vagotomy and baclofen reduced %GR per se, the reduction was twice more marked in the animals treated with At. The results suggest that At administered iv, but not icv, delays GE of liquid in rats with the participation, at least in part, of the vagus nerve and that this phenomenon is blocked by the activation of GABA B receptors in the central nervous system.

Evaluating the Strategic Objectives of Cameroonian Higher Education: An application of the Balanced Scorecard

Contemporary higher education operates in an environment of dwindling and parsimonious resources; the increasing need for accountability and relevance to varying stakeholders with differing expectations. These relatively new trends in higher education have been faced by business organizations which have developed different ways of operating in response. This study outlines one way by which business organizations have addressed similar circumstances to show how the Cameroon higher education (HE) could learn from business organizations to manage strategic objectives. The balanced scorecard (BSC) has been used by business organizations to address similar trends. This study evaluates the strategic objectives of Cameroonian higher education using the balanced scorecard. The system level is used to identify the general strategic objectives and one state university is used to represent the translation and implementation of the objectives at the institution level. The BSC principles used include: operational strategic objectives; organizational alignment to the strategy; making strategy everyone’s everyday job; making strategy continual and; mobilizing the leadership for change. The underlying concepts in these principles are communication, consensus, relevance, and a participatory approach. The study employs data from policy documents, relevant literature, websites and semi-structured interviews. The research approach is qualitative and the analyses are done by making meaning of phenomena in their natural contexts. The results show that there is a general knowledge of the strategic objectives but there is disagreement on the relevance of these objectives to HE and on the type of approaches used in implementing the objectives. It was also found that the relevant stakeholders are known, but not all the respondents agree on the importance of these stakeholders. All stakeholders do not have the same level of influence-the state is the most influential. Reporting is sufficiently done but there are insufficient provisions for feedback from stakeholders. The study concludes that the BSC principles can be applied to the management of strategic objectives in Cameroon HE. For Cameroonian higher education, it is recommended that the focus should be first, on developing tools for strategy before the strategy itself. Even though the need for the BSC is confirmed the context does not seem sufficiently ready to implement the BSC as a strategic management tool. The proposed BSC framework can only be used as a communication tool. The barriers to managing strategic objectives in Cameroon HE are related to the communication, consensus, clarity and relevance. However, the system has prospects for improved management and eventual adoption of the BSC as both a strategic management and communication tool. In line with other BSC applications to higher education, this study concluded that it is more feasible to apply the balanced scorecard to a single higher education institution than to a higher education system. The study makes a contribution to the BSC by showing how its principles can be used in a non-business context. The study also opens up possibilities for future research on the same topic in a different context or the same context with a wider scope (more institutions and respondents); the same study with a deeper focus on the interrelationships between the different strategic objectives (strategy maps). The study could also be extended by including the perspectives of the identified stakeholders who are not directly part of the higher education system but constitute the environment in which higher education operates.

Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS) in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage) to male Wistar rats (3 months old, 200-250 g) 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water) during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001). The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist) or atropine (cholinergic antagonist). These drugs were administered 1 h prior to ethanol (3.5 g/kg) or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats

The efficacy of endothelin receptor antagonists in protecting against myocardial ischemia/reperfusion (I/R) injury is controversial, and the mechanisms remain unclear. The aim of this study was to investigate the effects of CPU0123, a novel endothelin type A and type B receptor antagonist, on myocardial I/R injury and to explore the mechanisms involved. Male Sprague-Dawley rats weighing 200-250 g were randomized to three groups (6-7 per group): group 1, Sham; group 2, I/R + vehicle. Rats were subjected to in vivo myocardial I/R injury by ligation of the left anterior descending coronary artery and 0.5% sodium carboxymethyl cellulose (1 mL/kg) was injected intraperitoneally immediately prior to coronary occlusion. Group 3, I/R + CPU0213. Rats were subjected to identical surgical procedures and CPU0213 (30 mg/kg) was injected intraperitoneally immediately prior to coronary occlusion. Infarct size, cardiac function and biochemical changes were measured. CPU0213 pretreatment reduced infarct size as a percentage of the ischemic area by 44.5% (I/R + vehicle: 61.3 ± 3.2 vs I/R + CPU0213: 34.0 ± 5.5%, P < 0.05) and improved ejection fraction by 17.2% (I/R + vehicle: 58.4 ± 2.8 vs I/R + CPU0213: 68.5 ± 2.2%, P < 0.05) compared to vehicle-treated animals. This protection was associated with inhibition of myocardial inflammation and oxidative stress. Moreover, reduction in Akt (protein kinase B) and endothelial nitric oxide synthase (eNOS) phosphorylation induced by myocardial I/R injury was limited by CPU0213 (P < 0.05). These data suggest that CPU0123, a non-selective antagonist, has protective effects against myocardial I/R injury in rats, which may be related to the Akt/eNOS pathway.

B2B-yritysten maineenhallinnan käytänteet sosiaalisessa mediassa

Tässä tutkimuksessa tutkittiin neljän suomalaisen pörssilistatun kansainvälisesti toimivan B2B-yrityksen maineenhallintaa sosiaalisessa mediassa. Tutkimuksen tavoitteena oli selvittää miksi, mistä lähtökohdista ja miten suomalaiset B2B-yritykset hallitsevat mainettaan sosiaalisessa mediassa. Yritysten maineenhallinta rajattiin koskemaan yrityksen ulkoisen viestinnän keinoja, joilla yritykset pyrkivät vaikuttamaan maineeseensa. Tutkimus toteutettiin kvalitatiivisena, vertailevana tapaustutkimuksena. Tutkimuksen empiirinen aineisto kerättiin puolistrukturoiduilla teemahaastatteluilla tapausyritysten viestinnän johto- ja asiantuntijatehtävissä työskenteleviltä henkilöiltä. Tutkimus osoitti, että hyvä maine on yrityksille tärkeää aineetonta pääomaa ja sitä voi ja tulee johtaa sekä hallita sosiaalisessa mediassa. B2B-yritykset hallitsevat mainettaan sosiaalisessa mediassa monitoroimalla sosiaalisen media keskusteluja tavoitteenaan suojella yritystä mainekriiseiltä ja tuottamalla tavoitemainekuvansa mukaista sisältöä rakentaakseen itsestään kuvaa vastuullisena ja innovatiivisena yrityksenä sekä hyvänä kumppanina. B2B-yritysten maineenhallinnan käytänteiksi tutkimuksessa tunnistettiin sosiaalisen median monitorointi, keskusteleminen ja sisällöntuotanto, mittaaminen, kriisinhallinta sekä yhteistyönhallinta.

China: crescimento econômico de longo prazo

China: long-run economic growth. The paper aims to understand on theoretical and empirical grounds the main determinants of China´s long run growth. The econometric analysis suggests the exchange rate as the most important variable in explaining China´s economic growth and in a different model specification using growth rates of exports instead of trade openness, the exchange rate remains as the main variable but export performance has almost the same relevance. Exchange rate policy seems to be a direct road to explain economic growth in China and there is no clear sign that China will increase exchange rate flexibility in the same pattern and pace suggested by most trade partners, which cannot be criticized based on China´s own interest in sustaining its export performance and economic growth.

Understanding the financial status of a group of high performance athletes

With the 2010 Vancouver Winter Olympic Games quickly approaching, there has been a heightened interest in the performance of Canadian athletes at international competitions (Duffy, 2007; Fidlin, 2005; Longley, 2006). Two significant documents outline Canada's goal to become the number one sporting nation at the 2010 Olympic Games, and improve Canada's performance at the 2008 Olympic Games: Own the Podium and Road to Excellence (Priestner Allinger & Allinger, 2004; Road to Excellence, 2006). These two documents represent heightened interest in the performance of our elite athletes, in conjunction with Canada's hosting status of the Vancouver 2010 Winter Olympic Games. The requirements to train and compete at the international level have become more demanding both in terms of financial resources and time commitment. The need to financially assist athletes with their training and competition costs has been an important topic of debate over the past decades (Beamish & Borowy, 1987; Gatehouse, 2004; Macintosh, 1996; Munro, 1970; Owens, 2004). Two sources of fiinding for high performance athletes in Canada are the Athlete Assistance Program (AAP) provided by the Federal Government and the Canadian Olympic Excellence Fund provided by the Canadian Olympic Committee. The importance of these fiinds for athletes has been discussed in various forums (Ekos, 1992, 1997, 2005; Priestner Allinger & Allinger, 2004; Thibault «& Babiak, 2005). However, alternative sources of funds for high performance athletes have never been the object of research. As such the purpose of this study was to describe a group of athlete applicants from the time period of November 2004 to April 2006, and to contextualize these applications within the development of the Charitable Fund for Athletes.

A possible role for intrinsic calcium buffers in the long- term adaptation of crayfish neurons

Increasing the impulse activity of neurons in vivo over 3 or more days causes a reduction in transmitter release that persists for days or weeks (eg. Mercier and Atwood, 1989). This effect is usually accompanied by decreased synaptic fatigue. These two changes involve presynaptic mechanisms and indicate "long-term adaptation" (LTA) of nerve terminals. Previous experiments have shown that LTA requires extracellular calcium and protein synthesis (eg. Hong and Lnenicka, Soc. Neurosci. Abstr. 17:1322) and appears to involve communication between the cell body and the nerve terminals. The present study examines the possibility that the reduction in transmitter release is caused by an -increase in the calcium buffering ability within the nerve terminals. It examines the responses of adapted and control nerve terminals to exogenously applied calcium buffer, BAPTA-AM, which decreases transmitter release (Robitialle and Charlton, 1992). If LTA increases intrinsic Ca2+-buffering, the membrane permeant form of BAPTA should have less effect on adapted nerve terminals than on controls. Experiments are performed on the phasic abdominal extensor motor neurons of the crayfish, Procambarns clarkii. BAPTA-AM decreases excitatory postsynaptic potentials (EPSP's) of the phasic extensor muscles in a dosedependent manner between 5 and 50 JLM. LTA is elicited by in vivo stimulation at 2.5 Hz for 2-4 h per day over 3 days, which reduces EPSP's by over 50%. Experiments indicate that BAPTA-AM produces no significant change in EPSP reduction in adapted neurons when compared to controls. These results do not support the hypothesis that increased daily activity alters rapid intrinsic calcium buffers, that are able to reduce transmitter output in the same manner as BAPTA.

John W. Fisher Fonds, 1937-1961, 1964-1989, 1993, n.d.

Norah and Fred Fisher welcomed John Fisher into the world on November 29, 1912, not knowing what an influential role he would play in shaping Canada's history. John Fisher grew up as the middle child of five brothers and sisters in Frosty Hollow, New Brunswick, close to today’s town of Sackville. Sackville’s main industry was the Enterprise Foundry which the Fisher family owned and operated; however, Fisher had no plans of going into the family business. He was more inspired by his maternal grandfather, Dr. Cecil Wiggins, who lived with the family after retiring from the Anglican ministry. Wiggins encouraged all his grandchildren to be well read and to take part in discussions on current events. There were often visitors in the Fisher household taking part in discussions about politics, religion, and daily life. Fisher forced himself to take part in these conversations to help overcome his shyness in social settings. These conversations did help with his shyness and also in forming many opinions and observations about Canada. It put Fisher on the road to becoming Mr. Canada and delivering the many eloquent speeches for which he was known. Fisher did not venture far from home to complete his first degree. In 1934 he graduated from Mount Allison University in Sackville, NB with an Arts degree. The same year Fisher enrolled in Dalhousie’s law school. During his time at Dalhousie, Fisher discovered radio through Hugh Mills. Mills or “Uncle Mel” was on CHNS, Halifax’s only radio station at the time. Fisher began by making appearences on the radio drama show. By 1941 he had begun writing and broadcasting his own works and joined the staff as an announcer and continuity writer. In 1936 the Canadian Broadcasting Corporation was formed, the first National radio station. Fisher joined the CBC shortly after it’s beginning and remained with them, as well as the Halifax Herald newspaper, even after his law school graduation in 1937. By 1943 Fisher’s talks became a part of the CBC’s programming for a group of maritime radio stations. Fisher once described his talks as follows “my talks weren’t meant to be objective. . . they were meant to be favourable. They were ‘pride builders’” He began his famed John Fisher Reports at CBC Toronto when he transfered there shortly after the war. This program brought emmence pride to the fellow Canadians he spoke about leading to approximately 3500 requests per year to speak at banquets and meeting throughout Canada and the United States. Fisher was a well travelled indivdual who would draw on personal experiences to connect with his audience. His stories were told in simple, straight forward language for anyone to enjoy. He became a smooth, dynamic and passionate speaker who sold Canada to Canadians. He became a renowned journalist, folk historian, writer and broadcaster. Fisher was able to reach a vast array of people through his radio work and build Canadian pride, but he did not stop there. Other ways Fisher has contributed to Canada and the Canadian people include: Honoured by five Canadian Universities. 1956, became the Director of the Canadian Tourist Association. 1961, was appointed Special Assistant to the Prime Minister of Canada. 1963, Commissioner of the Centennial Commission (the Federal Agency Responsible for Canada’s 100th birthday) 1968, received the Service Medal , a coveted Order of Canada. President of John Fisher Enterprises Ltd., private consultant work, specializing in Centennial planning, broadcasts, lectures and promotion. John Fisher continued recording radio broadcasts even after his diagnosis with cancer. He would record 3 or 4 at a time so he was free to travel across Canada, the U.S., Europe and Mexico in search of treatments. Fisher passed away from the disease on February 15, 1981 and he is buried at Mount Pleasant Cemetery in Toronto.