bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of using an impedance threshold device on hemodynamic parameters during cardiopulmonary resuscitation in dogs
Authors: Buckley Gareth J. , Shih Andre , Garcia‐Pereira Fernando L. , Bandt Carsten 
Published: July 2012

AbstractObjectiveTo investigate the hemodynamic effects following the use of an impedance threshold device (ITD) in a canine model of cardiopulmonary arrest.DesignExperimental, randomized crossover study.SettingCardiovascular research laboratory at a university veterinary center.AnimalsEight purpose bred beagle dogs.InterventionsDogs were anesthetized and instrumented for the measurement of right atrial pressure , systolic blood pressure, mean blood pressure, and diastolic arterial blood pressure, end‐tidalCO2, and carotid blood flow (CBF).CBFwas determined via ultrasonic flow probe placed around the carotid artery. Animals were taking part in an unassociated terminal study and following subsequent euthanasia with pentobarbital, standardized cardiopulmonary resuscitation (CPR) was performed with an impedance threshold device attached (ITD‐CPRgroup) and without (S‐CPRgroup). Order of treatment was randomized.Measurements and Main ResultsITDgroup had increasedCBF, coronary perfusion pressure, and a decrease in right atrial diastolic pressure. No differences in end‐tidalCO2, diastolic arterial blood pressure, mean blood pressure, or systolic blood pressure were seen. Return of spontaneous circulation was not observed in any of the animalsConclusionsUse of theITDresulted in favorable changes in hemodynamic parameters in dogs undergoingCPR. TheITDmay be a useful adjunct duringCPRin dogs and warrants clinical evaluation.
Wound Healing Society (WHS) venous ulcer treatment guidelines: What's new in five years?
Authors: Tang Jennifer C. , Marston William A. , Kirsner Robert S. 
Published: July 2012

AbstractSince the establishment of the guidelines for the treatment of venous ulcers by the Wound Healing Society in 2006, there has been an abundance of new literature, both in accord and discord with the guidelines. The goal of this update is to highlight new findings since the publication of these guidelines to assist practitioner and patient in appropriate health care decisions, as well as to drive future research endeavors.
Personal Identification of Cold Case Remains Through Combined Contribution from Anthropological, mtDNA, and Bomb‐Pulse Dating Analyses
Authors: Speller Camilla F. , Spalding Kirsty L. , Buchholz Bruce A. , Hildebrand Dean , Moore Jason , Mathewes Rolf , Skinner Mark F. , Yang Dongya Y. 
Published: July 2012

AbstractIn 1968, a child's cranium was recovered from the banks of a northern Canadian river and held in a trust until the “cold case” was reopened in 2005. The cranium underwent reanalysis at the Centre for Forensic Research, Simon Fraser University, using recently developed anthropological analysis, “bomb‐pulse” radiocarbon analysis, and forensic DNA techniques. Craniometrics, skeletal ossification, and dental formation indicated an age‐at‐death of 4.4 ± 1 year. Radiocarbon analysis of enamel from two teeth indicated a year of birth between 1958 and 1962. Forensic DNA analysis indicated the child was a male, and the obtained mitochondrial profile matched a living maternal relative to the presumed missing child. These multidisciplinary analyses resulted in a legal identification 41 years after the discovery of the remains, highlighting the enormous potential of combining radiocarbon analysis with anthropological and mtDNA analyses in producing confident personal identifications for forensic cold cases dating to within the last 60 years.
What digital games and literacy have in common: a heuristic for understanding pupils' gaming literacy
Authors: Apperley Thomas , Walsh Christopher 
Published: July 2012

AbstractThis article argues that digital games and school‐based literacy practices have much more in common than is reported in the research literature. We describe the role digital game paratexts – ancillary print and multimodal texts about digital games – can play in connecting pupils’ gaming literacy practices to ‘traditional’ school‐based literacies still needed for academic success. By including the reading, writing and design of digital game paratexts in the literacy curriculum, teachers can actively and legitimately include digital games in their literacy instruction. To help teachers understand pupils’ gaming literacy practices in relation to other forms of literacy practices, we present a heuristic for understanding gaming (HUG) literacy. We argue our heuristic can be used for effective teacher professional development because it assists teachers in identifying the elements of gameplay that would be appropriate for the demands of the literacy curriculum. The heuristic traces gaming literacy across the quadrants of actions, designs, situations and systems to provide teachers and practitioners with a knowledge of gameplay and a metalanguage for talking about digital games. We argue this knowledge will assist them in capitalising on pupils’ existing gaming literacy by connecting their out‐of‐school gaming literacy practices to the literacy and English curriculum.
A distinct de novo expression of Nav1.5 sodium channels in human atrial fibroblasts differentiated into myofibroblasts
Authors: Chatelier Aurélien , Mercier Aurélie , Tremblier Boris , Thériault Olivier , Moubarak Majed , Benamer Najate , Corbi Pierre , Bois Patrick , Chahine Mohamed , Faivre Jean François 
Published: July 2012

Key point
Fibroblasts play a major role in heart physiology. In pathological conditions, they can lead to cardiac fibrosis when they differentiate into myofibroblasts.
This differentiated status is associated with changes in expression profile leading to neo‐expression of proteins such as ionic channels.
The present study investigates electrophysiological changes associated with fibroblast differentiation focusing on voltage‐gated sodium channels in human atrial fibroblasts and myofibroblasts.
We show that human atrial fibroblast differentiation in myofibroblasts is associated with de novo expression of voltage gated sodium current. Multiple arguments support that this current is predominantly supported by the Nav1.5 α‐subunit which may generate a persistent sodium entry into myofibroblasts.
Our data revealed that Nav1.5 α‐subunit expression is not restricted to cardiac myocytes within the atrium. Since fibrosis is one of the fundamental mechanisms implicated in atrial fibrillation, it is of great interest to investigate how this channel could influence myofibroblasts function.
Abstract  Fibroblasts play a major role in heart physiology. They are at the origin of the extracellular matrix renewal and production of various paracrine and autocrine factors. In pathological conditions, fibroblasts proliferate, migrate and differentiate into myofibroblasts leading to cardiac fibrosis. This differentiated status is associated with changes in expression profile leading to neo‐expression of proteins such as ionic channels. The present study investigates further electrophysiological changes associated with fibroblast differentiation focusing on the activity of voltage‐gated sodium channels in human atrial fibroblasts and myofibroblasts. Using the patch clamp technique we show that human atrial myofibroblasts display a fast inward voltage gated sodium current with a density of 13.28 ± 2.88 pA pF−1 whereas no current was detectable in non‐differentiated fibroblasts. Quantitative RT‐PCR reveals a large amount of transcripts encoding the Nav1.5 α‐subunit with a fourfold increased expression level in myofibroblasts when compared to fibroblasts. Accordingly, half of the current was blocked by 1 μm of tetrodotoxin and immunocytochemistry experiments reveal the presence of Nav1.5 proteins. Overall, this current exhibits similar biophysical characteristics to sodium currents found in cardiac myocytes except for the window current that is enlarged for potentials between −100 and −20 mV. Since fibrosis is one of the fundamental mechanisms implicated in atrial fibrillation, it is of great interest to investigate how this current could influence myofibroblast properties. Moreover, since several Nav1.5 mutations are related to cardiac pathologies, this study offers a new avenue on the fibroblasts involvement of these mutations.
Heterotypic connexin50/connexin50 mutant gap junction channels reveal interactions between two hemichannels during transjunctional voltage‐dependent gating
Authors: Xin Li , Sun Yiguo , Bai Donglin 
Published: July 2012

Key points
Gap junctions (GJs) composed of two hemichannels are intercellular channels that provide a direct pathway for the exchange of ions and signalling molecules between adjoining cells.
GJ conductance is regulated by transjunctional voltage (Vj, the voltage difference between the interiors of adjoining cells), known as Vj‐dependent gating.
The GJs made up of two identical hemichannels show mirror symmetrical Vj‐dependent gating to positive and negative Vj polarities; GJs formed by two non‐identical hemichannels show novel Vj‐gating properties that cannot be simply ascribed to the predicted functional properties of the component hemichannels.
We provide experimental evidence at both macroscopic and single channel levels that two hemichannels interact with each other in a complex manner for the Vj‐dependent gating phenotype of a GJ.
The results help reveal the molecular mechanisms of the gating properties of GJs formed by two non‐identical hemichannels.
Abstract  To investigate transjunctional voltage (Vj)‐dependent gating mechanisms of connexin50 (Cx50) gap junction (GJ) channels and to elucidate the relative contribution of each hemichannel of a heterotypic GJ channel to Vj‐dependent gating, we performed dual voltage‐clamp recordings on heterotypic GJ channels formed by Cx50 and a mutant, Cx50N9R or a chimera, Cx50‐Cx36N. Our results provide evidence that the two component hemichannels interact with each other during Vj‐dependent gating. Cx50/Cx50N9R heterotypic GJ channels exhibited asymmetrical Vj‐dependent gating which cannot be ascribed to the function of an individual hemichannel for a certain polarity of voltage; instead it can only be ascribed to the combined effects of both hemichannels. Single GJ channel open dwell‐time analyses showed that homotypic Cx50 channels adopted short‐lived and long‐lived open states. Heterotypic combinations of Cx50/Cx50N9R gave rise to shorter mean dwell‐times when Cx50‐expressing cells received relatively positive Vj, and longer mean dwell‐times when positive Vj was applied at the Cx50N9R side. In contrast, Cx50/Cx50‐Cx36N heterotypic channels showed asymmetrical Vj‐dependent gating, which appears to be caused by enhanced and reduced Vj‐gating sensitivity of Cx50‐Cx36N and Cx50 hemichannels, respectively. Unitary conductance of the main open state of both types of heterotypic GJ channel cannot be simply predicted by assuming a Vj redistribution across the two hemichannels arranged in series in heterotypic GJ channels. Our data also reveal reasons for the invisibility of fast Vj‐gating transitions from open to substate in homotypic Cx50N9R and Cx50‐Cx36N channels.
A universally conserved residue in the SUR1 subunit of the KATP channel is essential for translating nucleotide binding at SUR1 into channel opening
Authors: de Wet Heidi , Shimomura Kenju , Aittoniemi Jussi , Ahmad Nawaz , Lafond Mathilde , Sansom Mark S.P. , Ashcroft Frances M. 
Published: July 2012

Key points
The sulphonylurea receptor (SUR1) subunit of the ATP‐sensitive potassium (KATP) channel is a member of the ATP‐binding cassette (ABC) protein family. Binding of MgADP to nucleotide‐binding domain 2 (NBD2) is critical for channel activation.
We identified a residue in the SUR1 subunit of the KATP channel that is essential for translating nucleotide binding to SUR1 into activation of the channel pore.
The ability of ATP to block KATP channel activity by binding to the Kir6.2 subunit of the channel was also altered by the mutation. This effect was dependent on the integrity of the NBDs of SUR1. This suggests SUR1 also modulates nucleotide inhibition of the channel at Kir6.2.
G1401 in SUR1 is one of 23 residues which are conserved throughout all ABC transporter proteins suggesting that it may have a universal role in coupling substrate binding to protein function.
Abstract  The sulphonylurea receptor (SUR1) subunit of the ATP‐sensitive potassium (KATP) channel is a member of the ATP‐binding cassette (ABC) protein family. Binding of MgADP to nucleotide‐binding domain 2 (NBD2) is critical for channel activation. We identified a residue in NBD2 (G1401) that is fully conserved among ABC proteins and whose functional importance is unknown. Homology modelling places G1401 on the outer surface of the protein, distant from the nucleotide‐binding site. The ATPase activity of purified SUR1‐NBD2‐G1410R (bound to maltose‐binding protein) was slightly inhibited when compared to the wild‐type protein, but its inhibition by MgADP was unchanged, indicating that MgADP binding is not altered. However, MgADP activation of channel activity was abolished. This implies that the G1401R mutation impairs the mechanism by which MgADP binding to NBD2 is translated into opening of the KATP channel pore. The location of G1401 would be consistent with interaction of this residue with the pore‐forming Kir6.2 subunit. Channel activity in the presence of MgATP reflects the balance between the stimulatory (at SUR1) and inhibitory (at Kir6.2) effects of nucleotides. Mutant channels were 2.5‐fold less sensitive to MgATP inhibition and not activated by MgATP. This suggests that ATP block of the channel is reduced by the SUR1 mutation. Interestingly, this effect was dependent on the functional integrity of the NBDs. These results therefore suggest that SUR1 modulates both nucleotide inhibition and activation of the KATP channel.
ATP‐sensitive potassium channels mediate the thermosensory response of orexin neurons
Authors: Parsons Matthew P. , Belanger‐Willoughby Natasha , Linehan Victoria , Hirasawa Michiru 
Published: July 2012

Key points
High body temperature accompanies sleepiness, and loss of appetite and motivation.
Suppression of orexin neurons has been suggested to be involved in such behavioural responses.
In this study we determined that orexin neurons are inhibited by an increase in temperature itself.
The effect of warming is mediated by a novel temperature sensing mechanism involving ATP‐sensitive potassium (KATP) channels.
As KATP channels are also sensitive to energy balance, our results suggest that orexin neurons play an important role in regulating energy balance by inducing sickness behaviour when body temperature is elevated.
Abstract  High body temperatures are generally associated with somnolence, lethargy, hypophagia and anhedonia. Orexin neurons have been suggested to play a role in such sickness behaviours due to their known functions in appetite, behavioural and autonomic activation. Furthermore, the activity of orexin neurons is inhibited by lipopolysaccharide that induces fever. However, the cellular mechanism(s) underlying this suppression of orexin neurons was unknown. We used patch‐clamp recordings in acute rat brain slices to demonstrate that orexin neurons, including those projecting to the wake‐promoting locus coeruleus, are inhibited by increasing the ambient temperature by a 2–4°C increment between 26 and 40°C. This effect was not mediated by conventional thermosensing mechanisms but instead involved the activation of ATP‐sensitive potassium (KATP) channels. Since KATP channels can also sense energy substrate levels and cellular metabolism, our results suggest that orexin neurons can integrate the state of energy balance and body temperature, and adjust their output accordingly. Thus, the thermosensitivity of orexin neurons may be an important part of maintaining energy homeostasis during hyperthermia and fever.
Basolateral chloride loading by the anion exchanger type 2: role in fluid secretion by the human airway epithelial cell line Calu‐3
Authors: Huang Junwei , Shan Jiajie , Kim Dusik , Liao Jie , Evagelidis Alexandra , Alper Seth L. , Hanrahan John W. 
Published: July 2012

Key points
The companion paper provided evidence for basolateral anion exchange during cAMP stimulation of chloride and fluid secretion by Calu‐3 monolayers; however, the molecular basis of this transport was not identified.
To test the role of AE2, an anion exchanger expressed at the basolateral membrane of Calu‐3 and many other epithelial cells, we used lentivirus‐mediated RNA interference to generate a stable Calu‐3 AE2 knock‐down cell line and characterized its fluid and anion transport properties.
AE2 knock‐down suppressed fluid secretion and increased the fraction of cAMP‐stimulated anion secretion that was sensitive to bumetanide inhibition.
Basolateral Cl−/HCO3− exchange was nearly abolished in AE2 knock‐down cells.
We conclude that AE2 is active during forskolin‐stimulated fluid secretion and mediates chloride uptake and bicarbonate recycling at the basolateral membrane.
Abstract  Anion exchanger type 2 (AE2 or SLC4A2) is an electroneutral Cl−/HCO3− exchanger expressed at the basolateral membrane of many epithelia. It is thought to participate in fluid secretion by airway epithelia. However, the role of AE2 in fluid secretion remains uncertain, due to the lack of specific pharmacological inhibitors, and because it is electrically silent and therefore does not contribute directly to short‐circuit current (Isc). We have studied the role of AE2 in Cl− and fluid secretion by the airway epithelial cell line Calu‐3. After confirming expression of its mRNA and protein, a knock‐down cell line called AE2‐KD was generated by lentivirus‐mediated RNA interference in which AE2 mRNA and protein levels were reduced ≥90%. Suppressing AE2 increased the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) by ∼70% without affecting the levels of NKCC1 (Na+–K+–2Cl− cotransporter) or NBCe1 (Na+–nHCO3− cotransporter). cAMP agonists stimulated fluid secretion by parental Calu‐3 and scrambled shRNA cells >6.5‐fold. In AE2‐KD cells this response was reduced by ∼70%, and the secreted fluid exhibited elevated pH and [HCO3−] as compared with the control lines. Unstimulated equivalent short‐circuit current (Ieq) was elevated in AE2‐KD cells, but the incremental response to forskolin was unaffected. The modest bumetanide‐induced reductions in both Ieq and fluid secretion were more pronounced in AE2‐KD cells. Basolateral Cl−/HCO3− exchange measured by basolateral pH‐stat in cells with permeabilized apical membranes was abolished in AE2‐KD monolayers, and the intracellular alkalinization resulting from basolateral Cl− removal was reduced by ∼80% in AE2‐KD cells. These results identify AE2 as a major pathway for basolateral Cl− loading during cAMP‐stimulated secretion of Cl− and fluid by Calu‐3 cells, and help explain the large bumetanide‐insensitive component of fluid secretion reported previously in airway submucosal glands and some other epithelia.
Consequences of Noncompliance for Therapy Efficacy and Emergence of Resistance in Murine Tuberculosis Caused by the Beijing Genotype of Mycobacterium tuberculosis
Authors: de Steenwinkel Jurriaan E. M. , ten Kate Marian T. , de Knegt Gerjo J. , Verbrugh Henri A. , Aarnoutse Rob E. , Boeree Martin J. , den Bakker Michael A. , van Soolingen Dick , Bakker-Woudenberg Irma A. J. M. 
Published: July 2012

ABSTRACT

Despite great effort by health organizations worldwide in fighting tuberculosis (TB), morbidity and mortality are not declining as expected. One of the reasons is related to the evolutionary development of
Mycobacterium tuberculosis
, in particular the Beijing genotype strains. In a previous study, we showed the association between the Beijing genotype and an increased mutation frequency for rifampin resistance. In this study, we use a Beijing genotype strain and an East-African/Indian genotype strain to investigate with our mouse TB model whether the higher mutation frequency observed in a Beijing genotype strain is associated with treatment failure particularly during noncompliance therapy. Both genotype strains showed high virulence in comparison to that of
M. tuberculosis
strain H37Rv, resulting in a highly progressive infection with a rapid lethal outcome in untreated mice. Compliance treatment was effective without relapse of TB irrespective of the infecting strain, showing similar decreases in the mycobacterial load in infected organs and similar histopathological changes. Noncompliance treatment, simulated by a reduced duration and dosing frequency, resulted in a relapse of infection. Relapse rates were correlated with the level of noncompliance and were identical for Beijing infection and East African/Indian infection. However, only in Beijing-infected mice, isoniazid-resistant mutants were selected at the highest level of noncompliance. This is in line with the substantial selection of isoniazid-resistant mutants
in vitro
in a wide isoniazid concentration window observed for the Beijing strain and not for the EAI strain. These results suggest that genotype diversity of
M. tuberculosis
may be involved in emergence of resistance and indicates that genotype-tailor-made treatment should be investigated.
Altering the Proclivity towards Daptomycin Resistance in Methicillin-Resistant Staphylococcus aureus Using Combinations with Other Antibiotics
Authors: Berti Andrew D. , Wergin Justine E. , Girdaukas Gary G. , Hetzel Scott J. , Sakoulas George , Rose Warren E. 
Published: July 2012

ABSTRACT

Daptomycin (DAP) is increasingly used as a part of combination therapy, particularly in complex methicillin-resistant
Staphylococcus aureus
(MRSA) infections. While multiple studies have reported the potential for synergy between DAP and adjunctive anti-infectives, few have examined the influence of adjunctive therapy on the emergence of DAP resistance. This study examined eight adjunctive antimicrobial combinations with DAP
in vitro
and the emergence of DAP resistance over time (up to 4 weeks) using clinical isolates of DAP-susceptible MRSA (MIC, 0.5 μg/ml) in which DAP resistance subsequently developed during patient therapy (MIC, 3 μg/ml). In addition to DAP susceptibility testing, selected strains were examined for phenotypic changes associated with DAP resistance, including changes to cell wall thickness (CWT) and cell membrane alterations. The addition of either oxacillin or clarithromycin in medium containing DAP significantly inhibited the development of DAP resistance through the entirety of the 4-week exposure (10- to 32-fold MIC reduction from that of DAP alone). Combinations with rifampin or fosfomycin were effective in delaying the emergence of DAP resistance through the end of week one only (week one MIC, 0.5 μg/ml; week four MIC, 24 μg/ml). Cell wall thickening was observed for all antibiotic combinations regardless of their effect on the DAP MIC (14 to 70% increase in CWT), while changes in cell membrane fluidity were variable and treatment dependent. DAP showed reduced activity against strains with DAP MICs of 1 to 12 μg/ml, but cell membrane integrity was still disrupted at concentrations achieved with doses greater than 10 mg/kg of body weight. The emergence of DAP resistance in MRSA is strongly influenced by the presence of subinhibitory concentrations of adjunctive antimicrobials. These data suggest that combining DAP with oxacillin or clarithromycin may delay the development of DAP resistance in cases requiring prolonged antibiotic therapy.