bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fatigue of voluntary contraction and the peripheral electrical propagation of single motor units in man
Authors: Borg Jörgen , Grimby Lennart , Hannerz Jan 
Published: December 2014

1. Single human motor units from the short extensors of the toes were classified by their voluntary threshold and axonal conduction velocity. The voluntary discharge intervals, and the shortest discharge intervals at which action potentials were conducted to the muscle fibres, were studied during maximal voluntary effort maintained for 1 min, and were compared with the intervals calculated to be necessary for full fusion.2. Electromyographic techniques were used. High selectivity of the recordings was obtained after blocking of the main motor nerve with lidocaine in subjects with an accessory innervation of just a few motor units or 6 months after lesions to intramuscular nerve twigs, when the muscle‐fibre density within the motor units was increased.3. For a whole minute of maximal voluntary effort, motor units with low threshold and low conduction velocity fired tonically at a rate that should have been sufficient for maximal tension. These intervals were longer than the intervals at which blocking occurred.4. In ordinarily motivated and untrained subjects, motor units with high threshold and high conduction velocity fired tonically at intervals sufficient for full tension for some seconds. Under these circumstances the voluntary intervals were longer than the critical ones.5. Through extraordinary motivation and training, motor units with high threshold and high conduction velocity could also be driven tonically for 20‐60 s at the high rates required for full tension. The critical intervals then approached the voluntary ones. Blockings occurred and increased in frequency as the contraction continued.6. When motor units with high threshold and high conduction velocity were tetanized electrically at 20 Hz, which was the lowest discharge rate of these units in tonic voluntary contraction, blockings occurred within 60 s.7. The role of the peripheral block is discussed in relation to loss of tension in prolonged voluntary contraction.
Interaction of hypoxia and hypercapnia on ventilation, tidal volume and respiratory frequency in the anaesthetized rat
Authors: Cragg Patricia A. , Drysdale D. B. 
Published: December 2014

1. Ventilation (V̇E), tidal volume (VT), respiratory frequency (f) and arterial and end‐tidal gas tensions were measured in seventy‐one tracheostomized New Zealand white rats (∼ 405 g) anaesthetized with an initial dose of pentobarbitone followed by repeated small doses to ensure that a weak limb‐withdrawal reflex remained.2. O2 consumption (1.2 ml (s.t.p.d.) min−1 100 g−1), CO2 production (1.0 ml (s.t.p.d.) min−1 100 g−1), heart rate (357 min−1), V̇E (43 ml min−1 100 g−1), Pa,CO2 (34 mmHg) and Pa,O2 (84 mmHg) in the control periods did not change significantly during the course of the experiment.3. Inspirates of 21% O2 with 2‐10% CO2, 15, 10 or 7.5% O2 with either no or sufficient CO2 to maintain normocapnia and 15 or 10% O2 with 4, 6 or 8% CO2 were tested. Steady‐state responses were measured after 2 min of exposure.4. Hypoxic—hypercapnic interaction on V̇E, VT and f determined by a three‐inspirate test ((i) hypoxia alone, (ii) hypercapnia and (iii) these hypoxic and hypercapnic levels combined) yielded various conclusions depending on the level of asphyxia examined. Essentially, the milder the asphyxia the more the interaction appeared additive or even multiplicative and the stronger the asphyxia the more the interaction appeared occlusive. However, this test is unsuitable for accurately showing interactions because the Pa,O2 achieved in asphyxia was higher than in hypoxia and the asphyxial Pa,CO2 was lower than in hypercapnia.5. For isoxic conditions (Pa,O2 = 97, 77 and 51 mmHg), V̇E and VT were related linearly to Pa,CO2 whilst f was related hyperbolically with convexity upwards (Pa,O2 97 mmHg) or downwards (Pa,O2 77 and 51 mmHg).6. For isocapnic conditions (Pa,CO2 = 33, 40 and 48 mmHg), V̇E and VT were inversely related to Pa,O2 with a hyperbolic curve (convexity downwards) whilst f was inversely and linearly related (Pa,CO2 33 mmHg) or constant (Pa,CO2 40 and 48 mmHg).7. Multivariate analyses showed that the hypoxic—hypercapnic interaction was additive for VT but occlusive for V̇E and f and the occlusion was more severe in the latter. This was illustrated graphically for the variable plotted against Pa,CO2 or Pa,O2 as parallel shifts in regression lines for VT, flatter regression lines for V̇E during asphyxia and a virtually constant f during asphyxia.8. V̇E responses and sensitivities to hypoxia and hypercapnia, the shape of V̇E, VT and f regression lines against Pa,O2 and Pa,CO2 and the type of hypoxic—hypercapnic interaction on each variable in the rat were compared with other species.9. Possible causes of the occlusive hypoxic—hypercapnic interaction in the rat were considered.
Postsynaptic P2X3‐containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice
Authors: Vandenbeuch Aurelie , Larson Eric D. , Anderson Catherine B. , Smith Steven A. , Ford Anthony P. , Finger Thomas E. , Kinnamon Sue C. 
Published: December 2014

Key points
Acute inhibition of purinergic receptors with a selective P2X3 antagonist prevents transmission of information from taste buds to sensory nerves.
The P2X3 antagonist has no effect on taste‐evoked release of ATP, confirming the effect is postsynaptic.
The results confirm previous results with P2X2/3 double knockout mice that ATP is required for transmission of all taste qualities, including sour and salty. Previously, ATP was confirmed to be required for bitter, sweet and umami tastes, but was questioned for salty and sour tastes due to pleomorphic deficits in the double knockout mice.
The geniculate ganglion in mouse contains two populations of ganglion cells with different subunit composition of P2X2 and P2X3 receptors making them differently susceptible to pharmacological block and, presumably, desensitization.
AbstractTaste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP‐gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF‐353, a selective antagonist of P2X3‐containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF‐353 for P2X3‐containing receptors was tested by recording Ca2+ transients to exogenously applied ATP in fura‐2 loaded isolated geniculate ganglion neurons from wild‐type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF‐353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2‐containing receptors. Furthermore, AF‐353 had no effect on taste‐evoked ATP release from taste buds. In wild‐type mice, i.p. injection of AF‐353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose‐dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC‐45647, was abolished following i.p. injection of AF‐353. These data indicate that activation of P2X3‐containing receptors is required for transmission of all taste qualities.
Draft Whole-Genome Sequences of 10 Serogroup O6 Enterotoxigenic Escherichia coli Strains
Authors: Pattabiraman Vaishnavi , Bopp Cheryl A. 
Published: December 2014

ABSTRACT

Entertotoxigenic
Escherichia coli
(ETEC) is a major cause of global diarrhea, resulting in approximately 200 million occurrences and 300,000 to 400,000 deaths annually, primarily in children under the age of five. Here, we announce the release of the draft genomes of 10 ETEC isolates belonging to serogroup O6.
Draft Genome Sequence of Acetobacter tropicalis Type Strain NBRC16470, a Producer of Optically Pure
d
-Glyceric Acid
Authors: Koike Hideaki , Sato Shun , Morita Tomotake , Fukuoka Tokuma , Habe Hiroshi 
Published: December 2014

ABSTRACT

Here we report the 3.7-Mb draft genome sequence of
Acetobacter tropicalis
NBRC16470
T
, which can produce optically pure
d
-glyceric acid (
d
-GA; 99% enantiomeric excess) from raw glycerol feedstock derived from biodiesel fuel production processes.
Complete Genome Sequences of Three Ebola Virus Isolates from the 2014 Outbreak in West Africa
Authors: Hoenen T. , Groseth A. , Feldmann F. , Marzi A. , Ebihara H. , Kobinger G. , Günther S. , Feldmann H. 
Published: December 2014

ABSTRACT

Here, we report the complete genome sequences, including the genome termini, of three Ebola virus isolates (species
Zaire ebolavirus
) originating from Guinea that are now being widely used in laboratories in North America for research regarding West African Ebola viruses.
Establishing a standard for assessing the appropriateness of trauma team activation: a retrospective evaluation of two outcome measures
Authors: Bressan Silvia , Franklin Katherine L , Jowett Helen E , King Sebastian K , Oakley Ed , Palmer Cameron S 
Published: December 2014

BackgroundTrauma team activation (TTA) is a well-recognised standard of care to provide rapid stabilisation of patients with time-critical, life-threatening injuries. TTA is associated with a substantial use of valuable hospital resources that may adversely impact upon the care of other patients if not carefully balanced. This study aimed to determine which of the two outcome measures would be a better standard for assessing the appropriateness of TTA at a paediatric centre: retrospective major trauma classification as defined within our state, and the use of emergency department high-level resources as recently published by Falconeet al(Falcone Interventions; FI).MethodsTrauma registry data and patients’ charts between February 2011 and June 2013 were reviewed. Over-triage and under-triage rates for TTA, using both major trauma and FIs as outcome measures, were compared.ResultsTotallly, 280 patients received TTA, 243 met major trauma definition and 102 received one or more FIs. The rates of over-triage and under-triage were 39.7% (95% CI 35.0 to 44.6%) and 30.5% (95% CI 26.2 to 35.2%), when the major trauma definition was used as the outcome measure, and 67.5% (95% CI 62.2 to 72.5%) and 10.8% (95% CI 7.9 to 14.8%) when FI was used. Only 17.1% (95% CI 11.4% to 24.7%) of the under-triaged patients using the major trauma definition received one or more FIs.ConclusionsAssessment of TTA appropriateness varied significantly based on the outcome measure used. FIs better reflected the use of acute-care TTA-related resources compared with the major trauma definition, and it should be used as the gold standard to prospectively assess and refine TTA criteria.
Geotourism: an early photographic insight through the lens of the Geologists’ Association
Authors: Larwood Jonathan G. 
Published: December 2014

Abstract

From its earliest days in London in 1858, the Geologists’ Association (GA) brought together people from all backgrounds – amateur and professional geologists, men, women and children – to share their enthusiasm for geology and their desire to seek out and explore the geological world around them. The travels of the Geologists’ Association, in search of geological enlightenment, are documented in the
Proceedings of the Geologists’ Association
. These include accounts of organized excursions, detailing the geology seen and describing the discussion had, the refreshments taken and the transport used. Bringing these accounts to life is the Geologists’ Association’s Carreck Archive, which provides a rare insight into the world of the early geotourist documenting both familiar and lost places. Much is owed to the skill of the photographers such as T. W. Reader, whose albums document the field meetings between 1907 and 1919, while the spirit of the early travelling Geologists’ Association is captured in the albums of Miss M. S. Johnston. This paper explores the early travels of the Geologists’ Association through the literal views of the Carreck Archive and accounts in its literature, and the establishment of the GA as an inadvertent geotourism agent.
Cancer Immunotherapy and Breaking Immune Tolerance: New Approaches to an Old Challenge
Authors: Makkouk Amani , Weiner George J. 
Published: December 2014

Abstract
Cancer immunotherapy has proven to be challenging as it depends on overcoming multiple mechanisms that mediate immune tolerance to self-antigens. A growing understanding of immune tolerance has been the foundation for new approaches to cancer immunotherapy. Adoptive transfer of immune effectors such as antitumor mAb and chimeric antigen receptor T cells bypasses many of the mechanisms involved in immune tolerance by allowing for expansion of tumor-specific effectors ex vivo. Vaccination with whole tumor cells, protein, peptide, or dendritic cells has proven challenging, yet may be more useful when combined with other cancer immunotherapeutic strategies. Immunomodulatory approaches to cancer immunotherapy include treatment with agents that enhance and maintain T-cell activation. Recent advances in the use of checkpoint blockade to block negative signals and to maintain the antitumor response are particularly exciting. With our growing knowledge of immune tolerance and ways to overcome it, combination treatments are being developed, tested, and have particular promise. One example is in situ immunization that is designed to break tolerance within the tumor microenvironment. Progress in all these areas is continuing based on clear evidence that cancer immunotherapy designed to overcome immune tolerance can be useful for a growing number of patients with cancer. Cancer Res; 75(1); 5–10. ©2014 AACR.
Regulation of Epithelial–Mesenchymal Transition through SUMOylation of Transcription Factors
Authors: Bogachek Maria V. , De Andrade James P. , Weigel Ronald J. 
Published: December 2014

Abstract
Carcinoma cells can transition from an epithelial-to-mesenchymal differentiation state through a process known as epithelial–mesenchymal transition (EMT). The process of EMT is characterized by alterations in the pattern of gene expression and is associated with a loss of cell polarity, an increase in invasiveness, and an increase in cells expressing cancer stem cell (CSC) markers. The reverse process of mesenchymal-to-epithelial transition (MET) can also occur, though the transitions characterizing EMT and MET can be incomplete. A growing number of transcription factors have been identified that influence the EMT/MET processes. Interestingly, SUMOylation regulates the functional activity of many of the transcription factors governing transitions between epithelial and mesenchymal states. In some cases, the transcription factor is a small ubiquitin-like modifier conjugated directly, thus altering its transcriptional activity or cell trafficking. In other cases, SUMOylation alters transcriptional mechanisms through secondary effects. This review explores the role of SUMOylation in controlling transcriptional mechanisms that regulate EMT/MET in cancer. Developing new drugs that specifically target SUMOylation offers a novel therapeutic approach to block tumor growth and metastasis. Cancer Res; 75(1); 11–15. ©2014 AACR.
Bivalirudin for acute coronary syndromes: premises, promises and doubts
Authors: Capodanno Davide , Caterina Raffaele De 
Published: December 2014

SummaryBivalirudin is a valuable anticoagulant option in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Advantages over heparin as a parenteral anticoagulant include more predictable pharmacokinetics and pharmacodynamics, shorter half-life, no need for cofactors, some degree of antiplatelet effect, and the ability to inhibit clot-bound thrombin. Clinical evidence supporting the use of bivalirudin over heparin in current ACS guidelines, however, derives mostly from early randomised trials that may no longer reflect current management patterns, now including the use of oral antiplatelet agents more potent than clopidogrel (i.e. prasugrel or ticagrelor) and a broader implementation of strategies to reduce bleeding (i.e. radial access for percutaneous coronary intervention, and use of glycoprotein IIb/IIIa inhibitors only in bailout situations). Defining the fine balance between bivalirudin efficacy and safety over heparins in the context of other antithrombotic treatments remains a challenge in clinical practice, particularly in a fast-evolving scenario, such as ACS, where numerous new trials have been presented in very recent times. Here we provide an up-to-date overview of the evidence on the use of bivalirudin in ACS, with focus on new data, open issues, and future directions.
BubR1 Insufficiency Inhibits Neointimal Hyperplasia Through Impaired Vascular Smooth Muscle Cell Proliferation in Mice
Authors: Kyuragi Ryoichi , Matsumoto Takuya , Harada Yui , Saito Satoru , Onimaru Mitsuho , Nakatsu Yoshimichi , Tsuzuki Teruhisa , Nomura Masatoshi , Yonemitsu Yoshikazu , Maehara Yoshihiko 
Published: December 2014

Objective—

BubR1, a cell cycle–related protein, is an essential component of the spindle checkpoint that regulates cell division. Mice with BubR1 expression reduced to 10% of the normal level display a phenotype characterized by progeria; however, the involvement of BubR1 in vascular diseases is still unknown. We generated mice in which BubR1 expression was reduced to 20% (
BubR1
L/L
mice) of that in wild-type mice (
BubR1
+/+
) to investigate the effects of BubR1 on arterial intimal hyperplasia.

Approach and Results—

Ten-week-old male
BubR1
L/L
and age-matched wild-type littermates (
BubR1
+/+
) were used in this study. The left common carotid artery was ligated, and histopathologic examinations were conducted 4 weeks later. Bone marrow transplantation was also performed. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta to examine cell proliferation, migration, and cell cycle progression. Severe neointimal hyperplasia was observed after artery ligation in
BubR1
+/+
mice, whereas
BubR1
L/L
mice displayed nearly complete inhibition of neointimal hyperplasia. Bone marrow transplantation from all donors did not affect the reconstitution of 3 hematopoietic lineages, and neointimal hyperplasia was still suppressed after bone marrow transplantation from
BubR1
+/+
mice to
BubR1
L/L
mice. VSMC proliferation was impaired in
BubR1
L/L
mice because of delayed entry into the S phase. VSMC migration was unaffected in these
BubR1
L/L
mice. p38 mitogen–activated protein kinase–inhibited VSMCs showed low expression of BubR1, and BubR1-inhibited VSMCs showed low expression of p38.

Conclusions—
BubR1 may represent a new target molecule for treating pathological states of vascular remodeling, such as restenosis after angioplasty.
MicroRNA 302a Is a Novel Modulator of Cholesterol Homeostasis and Atherosclerosis
Authors: Meiler Svenja , Baumer Yvonne , Toulmin Emma , Seng Kosal , Boisvert William A. 
Published: December 2014

Objective—
Macrophage foam cell formation is a key feature of atherosclerosis. Recent studies have shown that specific microRNAs (miRs) are regulated in modified low-density lipoprotein–treated macrophages, which can affect the cellular cholesterol homeostasis. Undertaking a genome-wide screen of miRs regulated in primary macrophages by modified low-density lipoprotein, miR-302a emerged as a potential candidate that may play a key role in macrophage cholesterol homeostasis.

Approach and Results—

The objective of this study was to assess the involvement of miR-302a in macrophage lipid homeostasis and if it can influence circulating lipid levels and atherosclerotic development when it is inhibited in a murine atherosclerosis model. We found that transfection of primary macrophages with either miR-302a or anti–miR-302a regulated the expression of ATP-binding cassette (ABC) transporter ABCA1 mRNA and protein. Luciferase reporter assays showed that miR-302a repressed the 3′ untranslated regions (UTR) activity of mouse Abca1 by 48% and human ABCA1 by 45%. In addition, transfection of murine macrophages with miR-302a attenuated cholesterol efflux to apolipoprotein A-1 (apoA-1) by 38%. Long-term in vivo administration of anti–miR-302a to mice with low-density lipoprotein receptor deficiency (
Ldlr
−/−
) fed an atherogenic diet led to an increase in ABCA1 in the liver and aorta as well as an increase in circulating plasma high-density lipoprotein levels by 35% compared with that of control mice. The anti–miR-302a–treated mice also displayed reduced atherosclerotic plaque size by ≈25% and a more stable plaque morphology with reduced signs of inflammation.

Conclusions—
These studies identify miR-302a as a novel modulator of cholesterol efflux and a potential therapeutic target for suppressing atherosclerosis.
Left Atrial Transcriptional Changes Associated With Atrial Fibrillation Susceptibility and Persistence
Authors: Deshmukh Amrish , Barnard John , Sun Han , Newton David , Castel Laurie , Pettersson Gosta , Johnston Douglas , Roselli Eric , Gillinov A. Marc , McCurry Kenneth , Moravec Christine , Smith Jonathan D. , Van Wagoner David R. , Chung Mina K. 
Published: December 2014

Background—
Prior transcriptional studies of atrial fibrillation (AF) have been limited to specific transcripts, animal models, chronic AF, right atria, or small samples. We sought to characterize the left atrial transcriptome in human AF to distinguish changes related to AF susceptibility and persistence.

Methods and Results—

Left atrial appendages from 239 patients stratified by coronary artery disease, valve disease, and AF history (no history of AF, AF history in sinus rhythm at surgery, and AF history in AF at surgery) were selected for genome-wide mRNA microarray profiling. Transcripts were examined for differential expression with AF phenotype group. Enrichment in differentially expressed genes was examined in 3 gene set collections: a transcription factor collection, defined by shared conserved
cis
-regulatory motifs, a miRNA collection, defined by shared 3′ untranslated region motifs, and a molecular function collection, defined by shared Gene Ontology molecular function. AF susceptibility was associated with decreased expression of the targets of CREB/ATF family, heat-shock factor 1, ATF6, SRF, and E2F1 transcription factors. Persistent AF activity was associated with decreased expression in genes and gene sets related to ion channel function consistent with reported functional changes.

Conclusions—
AF susceptibility was associated with decreased expression of targets of several transcription factors related to inflammation, oxidation, and cellular stress responses. In contrast, changes in ion channel expression were associated with AF activity but were limited in AF susceptibility. Our results suggest that significant transcriptional remodeling marks susceptibility to AF, whereas remodeling of ion channel expression occurs later in the progression or as a consequence of AF.