Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor

Cholesterol influences ion-channel function, distribution and clustering in the membrane, endocytosis, and exocytic sorting of the nicotinic acetylcholine receptor (AChR). We report the occurrence of a cholesterol recognition motif, here coined “CARC”, in the transmembrane regions of AChR subunits that bear extensive contact with the surrounding lipid, and are thus optimally suited to convey cholesterol-mediated signaling from the latter. Three cholesterol molecules could be docked on the transmembrane segments of each AChR subunit, rendering a total of 15 cholesterol molecules per AChR molecule. The CARC motifs contribute each with an energy of interaction between 35 and 52 kJ.mol−1, adding up to a total of about 200 kJ.mol−1 per receptor molecule, i.e. ∼40% of the lipid solvation free energy/ AChR molecule. The CARC motif is remarkably conserved along the phylogenetic scale, from prokaryotes to human, suggesting that it could be responsible for some of the above structural/functional properties of the AChR

Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report

BACKGROUND: Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. CASE PRESENTATION: We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. CONCLUSION: This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach

Code Status Discussions Between Attending Hospitalist Physicians and Medical Patients at Hospital Admission

BackgroundBioethicists and professional associations give specific recommendations for discussing cardiopulmonary resuscitation (CPR).ObjectiveTo determine whether attending hospitalist physicians' discussions meet these recommendations.DesignCross-sectional observational study on the medical services at two hospitals within a university system between August 2008 and March 2009.ParticipantsAttending hospitalist physicians and patients who were able to communicate verbally about their medical care.Main measuresWe identified code status discussions in audio-recorded admission encounters via physician survey and review of encounter transcripts. A quantitative content analysis was performed to determine whether discussions included elements recommended by bioethicists and professional associations. Two coders independently coded all discussions; Cohen's kappa was 0.64-1 for all reported elements.Key resultsAudio-recordings of 80 patients' admission encounters with 27 physicians were obtained. Eleven physicians discussed code status in 19 encounters. Discussions were more frequent in seriously ill patients (OR 4, 95% CI 1.2-14.6), yet 66% of seriously ill patients had no discussion. The median length of the code status discussions was 1 min (range 0.2-8.2). Prognosis was discussed with code status in only one of the encounters. Discussions of patients' preferences focused on the use of life-sustaining interventions as opposed to larger life goals. Descriptions of CPR as an intervention used medical jargon, and the indication for CPR was framed in general, as opposed to patient-specific scenarios. No physician quantitatively estimated the outcome of or provided a recommendation about the use of CPR.ConclusionsCode status was not discussed with many seriously ill patients. Discussions were brief, and did not include elements that bioethicists and professional associations recommend to promote patient autonomy. Local and national guidelines, research, and clinical practice changes are needed to clarify and systematize with whom and how CPR is discussed at hospital admission

A Qualitative Exploration of Factors Affecting Group Cohesion and Team Play in Multiplayer Online Battle Arenas (MOBAs)

Previous research examining the social psychology of video-gaming has tended to focus on Massively Multiplayer Online Role Playing Game (MMORPG) environments, such as World of Warcraft. Although many online group processes have been examined using this game, this genre does not enforce cooperative play and studies tend to be based on very large groups. Newer genres are being developed and played which have so far not been studied. The genre known as Multiplayer Online Battle Arenas (MOBAs) are attracting large numbers of players and success depends on effective team playing within smaller groups. The study reported here explores team play within MOBAs. Due to the lack of literature examining this genre, Corbin and Strauss’ (2008) Grounded Theory was used to analyse participants’ subjective experiences of playing MOBAs to create a conceptual model. A focus group pilot study informed the development of questions and then semi-structured interviews took place with twelve participants; 1 female and 11 male students aged between 18-21 years. Participants were required to have recent and frequent MOBA exposure, but with different preferences regarding roles and experience. Data was analysed using open, axial and selective coding and the resulting model depicts a scale, as optimal team performance was linked to a balance between factors. The core category “Communication” was heavily influenced by the relationship between teammates (friends or strangers). The balance of “Communication” affected the balance of the final three categories: “Team Composition”, “Psychological State” and “Level of Play”. The conceptual model is critically linked with traditional group processes, such as Belbin’s (1993) team roles, Tuckman’s (1965) model of group development and the perceptions and behaviour during the state of deindividuation (Taylor & MacDonald, 2002). The model has real-world application in both social and professional virtual environments, whilst contributing more broadly to research in Cyberpsychology and Social Psychology. Further research is suggested which will test predictions based on a predictive model

From adaptive to generative learning in small and medium enterprises-a network perspective

Organizational learning has been playing an important role for competitive advantages for the organization. Managing learning and change in the unique context of small and medium enterprises (SMEs) can obtain benefits from network alliance. The paper seeks to draw attention to learning approaches from adaptive learning to generative learning in a SME in the context of asymmetric learning relationship. A qualitative research is conducted on a towing company of Taiwan with 14 in-depth interviews on persons of strategic alliances. This study discusses an asymmetric learning relationship where a large enterprise dominates the central place of the network, decides the learning policies and practices and guides learning involving adaptive and generative learning. This case of the SME assumes adaptive learning to ensure the development of network capability and adopts generative learning through communication channels and resources provided by the central firm. The outcomes of generative learning are the enhancement of absorptive capacity, the transfer of knowledge, shared identities, and shared contextual understanding in the towing industry. Though acquiring generative learning development, the case of the SME gets a competitive advantage but chooses to stay small and to be a business owner. This situation meets the psychological needs of the Chinese people

Alcohol-related blackouts among college students: impact of low level of response to alcohol, ethnicity, sex, and environmental characteristics

Objective: To explore how a genetically-influenced characteristic (the level of response to alcohol [LR]), ethnicity, and sex relate to environmental and attitudinal characteristics (peer drinking [PEER], drinking to cope [COPE], and alcohol expectancies [EXPECT]) regarding future alcohol-related blackouts (ARBs). Methods: Structural equation models (SEMs) were used to evaluate how baseline variables related to ARB patterns in 462 college students over 55 weeks. Data were extracted from a longitudinal study of heavy drinking and its consequences at a U.S. university. Results: In the SEM analysis, female sex and Asian ethnicity directly predicted future ARBs (beta weights 0.10 and -0.11, respectively), while all other variables had indirect impacts on ARBs through alcohol quantities (beta weights ~ 0.23 for European American ethnicity and low LR, 0.21 for cannabis use and COPE, and 0.44 for PEER). Alcohol quantities then related to ARBs with beta = 0.44. The SEM explained 23% of the variance. Conclusion: These data may be useful in identifying college students who are more likely to experience future ARBs over a 1-year period. They enhance our understanding of whether the relationships of predictors to ARBs are direct or mediated through baseline drinking patterns, information that may be useful in prevention strategies for ARBs

MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the in situ analysis of tissue sections. MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement and enables the acquisition of cellular expression profiles while maintaining the cellular and molecular integrity. In recent years, a great many advances in the practice of imaging mass spectrometry have taken place, making the technique more sensitive, robust, and ultimately useful. In this review, we focus on the current state of the art of MALDI-IMS, describe basic technological developments for MALDI-IMS of animal and human tissues, and discuss some recent applications in basic research and in clinical settings