bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-Induced Conformational Changes in Herpes Simplex Virus Glycoprotein gD Reveal New Targets for Virus Neutralization
Authors: Lazear Eric , Whitbeck J. Charles , Ponce-de-Leon Manuel , Cairns Tina M. , Willis Sharon H. , Zuo Yi , Krummenacher Claude , Cohen Gary H. , Eisenberg Roselyn J. 
Published: December 2011

ABSTRACT
As the receptor-binding protein of herpes simplex virus (HSV), gD plays an essential role in virus entry. In its native state, the last 56 amino acids of the ectodomain C terminus (C-term) occlude binding to its receptors, herpesvirus entry mediator (HVEM) and nectin-1. Although it is clear that movement of the C-term must occur to permit receptor binding, we believe that this conformational change is also a key event for triggering later steps leading to fusion. Specifically, gD mutants containing disulfide bonds that constrain the C-term are deficient in their ability to trigger fusion following receptor binding. In this report, we show that two newly made monoclonal antibodies (MAbs), MC2 and MC5, have virus-neutralizing activity but do not block binding of gD to either receptor. In contrast, all previously characterized neutralizing anti-gD MAbs block binding of gD to a receptor(s). Interestingly, instead of blocking receptor binding, MC2 significantly enhances the affinity of gD for both receptors. Several nonneutralizing MAbs (MC4, MC10, and MC14) also enhanced gD-receptor binding. While MC2 and MC5 recognized different epitopes on the core of gD, these nonneutralizing MAbs recognized the gD C-term. Both the neutralizing capacity and rate of neutralization of virus by MC2 are uniquely enhanced when MC2 is combined with MAb MC4, MC10, or MC14. We suggest that MC2 and MC5 prevent gD from performing a function that triggers later steps leading to fusion and that the epitope for MC2 is normally occluded by the C-term of the gD ectodomain.
Two MicroRNAs Encoded within the Bovine Herpesvirus 1 Latency-Related Gene Promote Cell Survival by Interacting with RIG-I and Stimulating NF-κB-Dependent Transcription and Beta Interferon Signaling Pathways
Authors: da Silva Leticia Frizzo , Jones Clinton 
Published: December 2011

ABSTRACTSensory neurons latently infected with bovine herpesvirus 1 (BHV-1) abundantly express latency-related (LR) RNA (LR-RNA). Genetic evidence indicates that LR protein expression plays a role in the latency-reactivation cycle, because an LR mutant virus that contains three stop codons downstream of the first open reading frame (ORF2) does not reactivate from latency. The LR mutant virus induces higher levels of apoptotic neurons in trigeminal ganglia, and ORF2 interferes with apoptosis. Although ORF2 is important for the latency-reactivation cycle, other factors encoded by the LR gene are believed to play a supportive role. For example, two microRNAs (miRNAs) encoded within the LR gene are expressed in trigeminal ganglia of latently infected calves. These miRNAs interfere with bICP0 protein expression and productive infection in transient-transfection assays. In this report, we provide evidence that the two LR miRNAs cooperate with poly(I·C), interferon (IFN) regulatory factor 3 (IRF3), or IRF7 to stimulate beta interferon (IFN-β) promoter activity. Both miRNAs also stimulated IFN-β promoter activity and nuclear factor-kappa B (NF-κB)-dependent transcription when cotransfected with a plasmid expressing retinoic acid-inducible gene I (RIG-I). In the presence of RIG-I, the LR miRNAs enhanced survival of mouse neuroblastoma cells, which correlated with activation of the antiapoptosis cellular transcription factor, NF-κB. Immunoprecipitation assays demonstrated that both miRNAs stably interact with RIG-I, suggesting that this interaction directly stimulates the RIG-I signaling pathway. In summary, the results of these studies suggest that interactions between LR miRNAs and RIG-I promote the establishment and maintenance of latency by enhancing survival of infected neurons.
Accelerated Shedding of Prions following Damage to the Olfactory Epithelium
Authors: Bessen Richard A. , Wilham Jason M. , Lowe Diana , Watschke Christopher P. , Shearin Harold , Martinka Scott , Caughey Byron , Wiley James A. 
Published: December 2011

ABSTRACT

In this study, we investigated the role of damage to the nasal mucosa in the shedding of prions into nasal samples as a pathway for prion transmission. Here, we demonstrate that prions can replicate to high levels in the olfactory sensory epithelium (OSE) in hamsters and that induction of apoptosis in olfactory receptor neurons (ORNs) in the OSE resulted in sloughing off of the OSE from nasal turbinates into the lumen of the nasal airway. In the absence of nasotoxic treatment, olfactory marker protein (OMP), which is specific for ORNs, was not detected in nasal lavage samples. However, after nasotoxic treatment that leads to apoptosis of ORNs, both OMP and prion proteins were present in nasal lavage samples. The cellular debris that was released from the OSE into the lumen of the nasal airway was positive for both OMP and the disease-specific isoform of the prion protein, PrP
Sc
. By using the real-time quaking-induced conversion assay to quantify prions, a 100- to 1,000-fold increase in prion seeding activity was observed in nasal lavage samples following nasotoxic treatment. Since neurons replicate prions to higher levels than other cell types and ORNs are the most environmentally exposed neurons, we propose that an increase in ORN apoptosis or damage to the nasal mucosa in a host with a preexisting prion infection of the OSE could lead to a substantial increase in the release of prion infectivity into nasal samples. This mechanism of prion shedding from the olfactory mucosa could contribute to prion transmission.
The importance of preparation for doctors' handovers in an acute medical assessment unit: a hierarchical task analysis
Authors: Raduma-Tomàs Michelle A , Flin Rhona , Yule Steven , Close Steven 
Published: December 2011

AimTo examine the ideal and actual processes of doctors' handovers in an acute medical assessment unit by means of a hierarchical task analysis (HTA) to identify any discrepancies between the ideal shift handover process as described by doctors, and the actual shift handover process as observed by the researcher.MethodThe HTA was constructed using information gathered from interviews (n=13) describing the activities doctors said they should ideally perform in preparation for the shift handover meeting, during the meeting and after the meeting has finished. Observations (n=32) were made pre handover, during handover and post handover to capture the actual handover process in the acute medical assessment unit. Furthermore, a focus group discussion was included to validate the researcher's observations of the actual handover process and to provide content validity to the constructed HTA of the ideal handover process.ResultsFindings as represented by the HTA diagram showed the complexity of the process. The diagram revealed critical tasks that should be completed at each phase of the handover process, but observations revealed that these were sometimes omitted, mainly due to work demands and time pressure. These omissions were most apparent in the pre-handover stage, resulting in interrupted, extended and/or delayed handover meetings.ConclusionThe pre-handover phase is critical in providing a foundation for a thorough handover meeting and potentially helping doctors who have started a shift to prioritise patient care. These findings suggest that quality improvements for clinical handovers should include a designated time for preparation of care transfer information.
The effects of exercise training on γ-butyrobetaine hydroxylase and novel organic cation transporter-2 gene expression in the rat
Authors: Broderick Tom L. , El Midaoui Adil , Chiasson Jean-Louis , Wang Donghao , Jankowski Marek , Gutkowska Jolanta 
Published: December 2011

The concentration of carnitine in plasma is generally increased with exercise training, suggesting that either carnitine biosynthesis is stimulated or renal reabsorption of carnitine is enhanced, or both. Carnitine, an essential cofactor in the oxidation of fatty acids, is released into the plasma following hydroxylation by γ-butyrobetaine hydroxylase (BBH), the final enzyme in the biosynthetic pathway found primarily in the liver. The organic cation transporter (OCTN2), the carnitine transporter found in kidney, is important in the distribution of carnitine by facilitating its renal reabsorption from urine. In this study, we tested the hypothesis that exercise training increases gene and protein expression of BBH and OCTN2, resulting in enhanced plasma carnitine levels. Male Wistar rats were subjected to 2 daily exercise sessions of treadmill running, 5 days per week, for a 10-week period. The concentration of total carnitine in plasma was significantly increased in trained rats compared with sedentary rats. In trained rats, mRNA and protein expression of BBH were increased in liver, whereas only BBH mRNA expression was increased in kidney. Liver of trained rats demonstrated increased mRNA and protein expression of OCTN2 compared with sedentary rats. In kidney of trained rats, however, only an increase in mRNA expression of OCTN2 was observed. Our results suggest that the improved plasma carnitine status in the trained rat is associated with increased carnitine biosynthesis in liver and kidney. The observation that OCTN2 expression was increased in kidney suggests a potential role of the kidney in the reabsorption of carnitine from the urine.
Repetitive magnetic stimulation of the phrenic nerves for diaphragm conditioning: a normative study of feasibility and optimal settings
Authors: Adler Dan , Gottfried Stewart B. , Bautin Nathalie , Mirkovic Tomislav , Schmidt Matthieu , Raux Mathieu , Pavlovic Dragan , Similowski Thomas , Demoule Alexandre 
Published: December 2011

Electrical stimulation can enhance muscle function. We applied repetitive cervical magnetic phrenic stimulation (rCMS) to induce diaphragm contractions in 7 healthy subjects (800 ms trains; transdiaphragmatic pressure (Pdi) measurements; tolerance ratings). Each rCMS train produced a sustained diaphragm contraction. Sixty-five percent of the maximal available output at 15 Hz proved the best compromise between Pdi and discomfort with nonfatiguing contractions. rCMS appears feasible and should be investigated for diaphragm conditioning in appropriate clinical populations.
Preserved muscle metaboreflex in chronic obstructive pulmonary disease
Authors: Sherman Megan F.B. , Road Jeremy D. , McKenzie Donald C. , Sheel A. William 
Published: December 2011

The objective of this study was to measure the magnitude of the muscle metaboreflex in people with chronic obstructive pulmonary disease (COPD) compared with healthy controls and to assess the relationships between disease severity, exercise capacity, and the magnitude of the muscle metaboreflex. Nine people with mild-to-severe COPD and 11 age- and gender-matched healthy controls performed isometric handgrip exercise (IHG), followed by postexercise circulatory occlusion (PECO) while hemodynamic changes were measured. Continuous measures of heart rate, arterial pressure, leg blood flow, leg vascular resistance, and total peripheral resistance were obtained. Participants then performed a cycle test to exhaustion. Heart rate, blood pressure, and blood flow responses during IHG and PECO were similar between the COPD group and healthy controls (p > 0.05). There was no association between disease severity or exercise capacity and the magnitude of the muscle metaboreflex. We observed a preserved muscle metaboreflex in mild-to-severe COPD, suggesting the metaboreflex is not a contributing factor to the development of exercise intolerance in this population.
The effect of branched chain amino acids on psychomotor performance during treadmill exercise of changing intensity simulating a soccer game
Authors: Wiśnik Piotr , Chmura Jan , Ziemba Andrzej Wojciech , Mikulski Tomasz , Nazar Krystyna 
Published: December 2011

The present study was designed to determine changes in the multiple-choice reaction time (MRT) during treadmill running simulating locomotor activity during a soccer game and to examine the effect of branched chain amino acids (BCAA) ingestion on psychomotor performance during the effort. Ten male soccer players were submitted to BCAA and placebo trials at 1-week intervals in a randomized order. BCAA (7 g) or placebo were given 1 h before exercise in a double blind manner. The running test consisted of two 45 min exercise bouts separated by a 15-min passive rest period and the whole test ended with 20-min active recovery. Running–walking speed changed from 0 to 6.4 m·s–1 according to the time-motion analysis of soccer match. During the test, blood samples were taken for lactate, glucose, free fatty acid, and catecholamine determination. Following placebo treatment, MRT shortened from 320 ± 18 to 271 ± 11 ms (p < 0.001) during the first exercise bout then it increased during the resting break to 303 ± 138 ms (p < 0.05). During the second bout, MRT decreased to 280 ± 13 ms (p < 0.001). During active recovery, further shortening of MRT was noted. During BCAA trial, MRT was shorter than during placebo trial by ~10% (p < 0.05) before and during exercise. No significant differences were found between BCAA and placebo trials in biochemical indices. It is concluded that BCAA supplementation might be recommended in sport activities that change in intensity and require quick responses to external signals (e.g., soccer and other team games).
Is peak oxygen uptake a determinant of moderate-duration self-paced exercise performance in the heat?
Authors: Schlader Zachary J. , Stannard Stephen R. , Mündel Toby 
Published: December 2011

This study aimed to identify whether reductions in peak oxygen uptake (VO2peak) dictate performance outcomes during 30 min of self-paced exercise in the heat, which is expected to induce minimal hyperthermia. On 4 occasions, 11 male subjects completed peak and self-paced exercise in both hot (HOT, 40.2 ± 0.3 °C) and moderate (MOD; 20.4 ± 0.7 °C) conditions. During peak exercise, submaximal oxygen uptake (VO2) was ∼8% higher in HOT, but VO2peak (MOD, 4.64 ± 0.83 L·min–1; HOT, 4.54 ± 0.77 L·min–1) and peak cardiac output (Qpeak) were similar. Self-paced exercise performance was reduced by ∼21% in HOT. VO2 was similar through 15 min, but lower in HOT thereafter. Relative to MOD, this represented a higher and lower %VO2peak during the initial and latter stages. Cardiac output was similar in both trials (MOD, 31.6 ± 6.6 L·min–1; HOT, 30.1 ± 6.0 L·min–1), representing a similar percentage of Qpeak throughout. Rectal temperature was similar in both conditions until 30 min (MOD, 38.5 ± 0.3 °C; HOT, 38.7 ± 0.3 °C), while skin temperature was higher throughout in HOT (mean: MOD, 32.4 ± 1.1 °C; HOT, 37.3 ± 0.4 °C). Perceived exertion rose similarly in both conditions, while thermal discomfort was higher in HOT. These data indicate that when only skin temperature is elevated, reductions in exercise performance during moderate-duration self-paced exercise are not associated with changes in VO2peak. Rather, increases in VO2 at a given submaximal external workload and (or) thermal discomfort appear to play a larger role.
Exercise metabolism during moderate-intensity exercise in children with cystic fibrosis following heavy-intensity exercise
Authors: Stevens Daniel , Oades Patrick J. , Armstrong Neil , Williams Craig A. 
Published: December 2011

Muscle metabolism is increased following exercise in healthy individuals, affecting exercise metabolism during subsequent physical work. We hypothesized that following heavy-intensity exercise (HIE), disease factors in children with cystic fibrosis (CF) would further exacerbate exercise metabolism and perceived exertion during subsequent exercise. Nineteen children with CF (age, 13.4 ± 3.1 years; 10 female) and 19 healthy controls (age, 13.8 ± 3.5 years; 10 female) performed 10 bouts of HIE interspersed with 1 min of recovery between each bout. Three minutes later participants completed a 10-min moderate-intensity exercise (MIE) test (test 1). The MIE test was subsequently repeated 1 h (test 2) and 24 h (test 3) later. Each MIE test was identical and participants exercised at individualized work rates, calibrated by an initial graded maximal cardiopulmonary exercise test, while metabolic and perceived exertion measurements were taken. Following HIE, mixed-model ANOVAs showed a significant difference in oxygen uptake (VO2) and rating of perceived exertion (RPE) between the 2 groups across the MIE tests (p < 0.01). In controls, VO2 (L·min–1) and RPE decreased significantly from test 1 to test 2 (p < 0.01) and test 2 to test 3 (p < 0.05). However, in children with CF, VO2 (L·min–1) increased significantly from test 1 to test 2 (p < 0.01), while RPE did not differ, both VO2 and RPE decreased significantly from test 2 to test 3 (p < 0.01). In conclusion, following HIE the metabolic and perceptual responses to MIE in both groups decreased 24 h later during test 3. These data show that children with mild-to-moderate CF have the capability to perform HIE and 24 h allows sufficient time for recovery.
Effects of a daily mixed nutritional supplement on physical performance, body composition, and circulating anabolic hormones during 8 weeks of arduous military training
Authors: Fortes Matthew B. , Diment Bethany C. , Greeves Julie P. , Casey Anna , Izard Rachel , Walsh Neil P. 
Published: December 2011

The aim of this work was to investigate the effect of a daily mixed nutritional supplement upon body composition, physical performance, and circulating anabolic hormones in soldiers undergoing arduous training. Thirty males received either a habitual diet alone (CON, n = 15) or with the addition of a daily mixed supplement (SUP, n = 15) of ∼5.1 MJ·d–1 during 8 weeks of training. Body composition (DEXA), maximal dynamic lift strength (MDLS), and vertical jump (VJ) were assessed, and resting blood samples were collected before and after training. Blood analysis included insulin-like growth factors (IGF-1, IGF BP-1, and IGF BP-3), testosterone, and cortisol. There were no group differences at baseline. Body mass loss (mean ± SD) (CON 5.0 ± 2.3, SUP 1.6 ± 1.5 kg), lean mass loss (CON 2.0 ± 1.5, SUP 0.7 ± 1.5 kg), and fat mass loss (CON 3.0 ± 1.6, SUP 0.9 ± 1.8 kg) were significantly blunted by SUP. CON experienced significant decrements in MDLS (14%), VJ (10%), and explosive leg power (11%) that were prevented by SUP. Military training significantly reduced circulating IGF-1 (28%), testosterone (19%), and the testosterone:cortisol ratio (24%) with no effect of SUP. Circulating IGF BP-1 concentration and cortisol remained unchanged throughout, although SUP abolished the significant decrease in circulating IGF BP-3 (20%) on CON. In conclusion, a daily mixed nutritional supplement attenuated decreases in body mass and lean mass and prevented the decrease in physical performance during an arduous military training program.
Chapter 2 A history of Neoproterozoic glacial geology, 1871–1997
Authors: Hoffman Paul F. 
Published: December 2011

Abstract
Neoproterozoic glacial records have been discovered on 23 palaeocontinents, their rate of discovery changing little since 1871. Yet, half of all the resulting publications appeared since 2000. The history of research before 1998 is described in five stages defined by publication spikes; subsequent work is not covered because historical perspective is lacking. In stage 1 (1871–1907), ‘Cambrian’ (now Neoproterozoic) glaciation was recognized successively in Scotland, Australia, India, Norway, Svalbard and China. Criteria for recognition included faceted and striated pebbles in matrix-supported conglomerates resting on ice-worn bedrock pavements. In stage 2 (1908–1940), Neoproterozoic glaciation was shown to have been widespread in Africa, Asia and the Americas. Major textbooks summarized these findings, but the rejection of continental drift (to account for late Palaeozoic glacial dynamics) put a chill on research. In stage 3 (1942–1964), the occurrence of glacial deposits within carbonate successions, as well as nascent palaeomagnetic observations, suggested that Neoproterozoic glaciers reached sea-level at low palaeolatitudes, but the belated recognition of sediment gravity flowage caused glacial interpretations to be prematurely abandoned in key areas. In stage 4 (1965–1981), the extent of Neoproterozoic glaciation was rethought in light of plate tectonics. Distinctive chemical sediments (iron±manganese formations and cap carbonates) were identified. In basic climate models, modest lowering of solar luminosity resulted in global glaciation due to ice-albedo feedback, and deglaciation due to greenhouse forcing resulted from silicate-weathering feedback in the carbon cycle. Neoproterozoic glacial geologists were blind to these ideas. In stage 5 (1982–1997), reliable palaeomagnetic data combined with glacial marine sedimentation models confirmed that Neoproterozoic ice sheets reached sea level close to the palaeoequator.
Chapter 20 The Abu Mahara Group (Ghubrah and Fiq formations), Jabal Akhdar, Oman
Authors: Allen Philip A. , Leather Jonathan , Brasier Martin D. , Rieu Ruben , McCarron Margaret , Guerroué Erwan le , Etienne James L. , Cozzi Andrea 
Published: December 2011

Abstract

The Abu Mahara Group (
c.
725–<645 Ma) of the Huqf Supergroup in the Jabal Akhdar of northern Oman hosts two glacial successions in the Ghubrah and Fiq formations, separated by the <50-m-thick volcanogenic Saqlah Member. The >400-m-thick Ghubrah Formation is dominated by distal glaciogenic rainout diamictites, laminites and turbiditic siltstones, whereas the <1.5-km-thick Fiq Formation exhibits a cyclical stratigraphy of proximal and distal marine glaciogenic facies, and non-glacial sediment gravity flow and shallow marine facies. The Fiq Formation is overlain by a transgressive, isotopically light carbonate known as the Hadash Formation. A tuffaceous ash interbedded with glacial diamictites of the Ghubrah Formation in Wadi Mistal has yielded a U–Pb zircon age of 713.7±0.5 Ma. The Fiq Formation contains detrital zircons as young as 645 Ma. The use of the CIA (Chemical Index of Alteration) shows the Fiq Formation to be climatically cyclic, with alternations of high and low chemical weathering of contemporary land surfaces driven by phases of glaciation and deglaciation. The transgression into the post-glacial Masirah Bay Formation is marked by a major increase in chemical weathering.