CFTR, an Ion Channel Evolved from an ABC Transporter

CFTR (cystic fibrosis transmembrane conductance regulator) is an integral membrane protein that functions as an epithelial Cl- channel, which is rendered defective 2 by inherited gene mutations in patients with cystic fibrosis (Riordan et al. 1989). Its function underlies fluid secretion in the airways, sweat ducts, pancreatic duct, and vas deferens, and it mediates the excessive intestinal water loss in secretory diarrhoeas (Verkman and Galietta 2009). CFTR belongs to the large ABC (ATP-binding cassette) transporter superfamily, of which most members are ATP-hydrolyzing pumps. CFTR is the sole ABC protein known to function as an ion channel. Despite this difference in function, the gates of CFTR channels are opened and closed by interactions with ATP similar to those that in other ABC proteins result in energetically uphill substrate transport

Discordance between physical symptoms versus perception of severity by women with nausea and vomiting in pregnancy (NVP)

BACKGROUND: Nausea and vomiting in pregnancy (NVP) is a multifaceted condition that affects more than half of pregnant women and can range in severity from mild nausea to severe dehydration. Presently physicians evaluate mostly physical symptoms of NVP in trying to assess the severity of the condition. The objective of this study was to investigate how factors, other than the physical morbidity of nausea and vomiting, influence self-perception of NVP by affected women. METHODS: Five hundred women with NVP calling a 1–800 NVP Healthline were asked to rate their NVP severity and report their nausea duration and number of vomiting/retching episodes. RESULTS: Nausea and vomiting/retching correlated significantly but very poorly with self-assessment of NVP severity. There was also a correlation between nausea duration and vomiting/retching frequency however the correlations were weak and overall physical symptoms could only explain 14% of the variability of women's feelings and perceptions through multivariate analysis. CONCLUSIONS: Physical symptoms weakly correlate with self-assessment of NVP severity. Other aspects of this condition, most probably psychosocial, influence women's perception of NVP severity

Comparison of engagement and emotional responses of older and younger adults interacting with 3D cultural heritage artefacts on personal devices

The availability of advanced software and less expensive hardware allows museums to preserve and share artefacts digitally. As a result, museums are frequently making their collections accessible online as interactive, 3D models. This could lead to the unique situation of viewing the digital artefact before the physical artefact. Experiencing artefacts digitally outside of the museum on personal devices may affect the user's ability to emotionally connect to the artefacts. This study examines how two target populations of young adults (18–21 years) and the elderly (65 years and older) responded to seeing cultural heritage artefacts in three different modalities: augmented reality on a tablet, 3D models on a laptop, and then physical artefacts. Specifically, the time spent, enjoyment, and emotional responses were analysed. Results revealed that regardless of age, the digital modalities were enjoyable and encouraged emotional responses. Seeing the physical artefacts after the digital ones did not lessen their enjoyment or emotions felt. These findings aim to provide an insight into the effectiveness of 3D artefacts viewed on personal devices and artefacts shown outside of the museum for encouraging emotional responses from older and younger people

Religious Vehicle Stickers in Nigeria: a discourse of identity, faith and social vision

This study focuses on analysing the ways in which vehicle stickers construct individual and group identities, people’s religious faith and social vision in the context of religious assumptions and practices in Nigeria. Data comprise 73 vehicle stickers collected in Lagos and Ota, between 2006 and 2007 and are analysed within the framework of the post-structuralist model of discourse analysis which views discourse as a product of a complex system of social and institutional practices that sustain its continuous existence (Derrida, 1982; Fairclough, 1989, 1992, 1995; Foucault, 1972, 1981). Results show that through stickers people define their individual and group identities within religious institutional practices. And as a means of group identification, they guarantee social security and privileges. In constructing social vision the stickers help mould the individual aspiration about a future which transcends the present. Significantly, stickers in the data also reveal the tension between Islam and Christianity and the struggle to propagate one above the other. KEY WORDS: assumption, discourse, discursive, practices, religion, stickers

Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia.

BACKGROUND: The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP. METHODS: Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns. RESULTS: Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients. CONCLUSIONS: Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy

Probing a Complex of Cytochromecand Cardiolipin by Magnetic Circular Dichroism Spectroscopy: Implications for the Initial Events in Apoptosis

Oxidation of cardiolipin (CL) by its complex with cytochrome c (cyt c) plays a crucial role in triggering apoptosis. Through a combination of magnetic circular dichroism spectroscopy and potentiometric titrations, we show that both the ferric and ferrous forms of the heme group of a CL:cyt c complex exist as multiple conformers at a physiologically relevant pH of 7.4. For the ferric state, these conformers are His/Lys- and His/OH–-ligated. The ferrous state is predominantly high-spin and, most likely, His/–. Interconversion of the ferric and ferrous conformers is described by a single midpoint potential of -80 ± 9 mV vs SHE. These results suggest that CL oxidation in mitochondria could occur by the reaction of molecular oxygen with the ferrous CL:cyt c complex in addition to the well-described reaction of peroxides with the ferric form

Regulation of Na+/K+ ATPase Transport Velocity by RNA Editing

Editing of Na+/K+ ATPase mRNAs modulates the Na+/K+ pump's turnover rate by selectively targeting the release of the final sodium to the outside