bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing aptitude for interpreting
Authors: Pöchhacker Franz
Published: April 2011

Based on a review of some of the most promising approaches to aptitude testing in the literature this paper proposes a novel task piloted at the Center for Translation Studies of the University of Vienna. The SynCloze test combines an auditory cloze exercise with a task requiring high expressional fluency, that is, rapidly finding contextually appropriate synonymic sentence completions. The rationale and design of the SynCloze test as well as the scoring method, which takes into account both the degree of accuracy and the speed of response, are described. The results of four rounds of testing involving some 120 students in the final stage of their undergraduate studies show that the test effectively discriminates between undergraduate novices and a control group of interpreting students, and students for whom the test language (German) is the A vs. the B language. Most significantly, the test scores correlate, albeit moderately, with students’ performance on an intralingual consecutive interpreting exam at the end of the course.
Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system
Authors: Caillava Céline , Vandenbosch Renaud , Jablonska Beata , Deboux Cyrille , Spigoni Giulia , Gallo Vittorio , Malgrange Brigitte , Baron-Van Evercooren Anne
Published: April 2011

The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2−/− mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin.
Manifestations and mechanisms of stem cell aging
Authors: Liu Ling , Rando Thomas A.
Published: April 2011

Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases.
A 3D analysis of yeast ER structure reveals how ER domains are organized by membrane curvature
Authors: West Matt , Zurek Nesia , Hoenger Andreas , Voeltz Gia K.
Published: April 2011

We analyzed the structure of yeast endoplasmic reticulum (ER) during six sequential stages of budding by electron tomography to reveal a three-dimensional portrait of ER organization during inheritance at a nanometer resolution. We have determined the distribution, dimensions, and ribosome densities of structurally distinct but continuous ER domains during multiple stages of budding with and without the tubule-shaping proteins, reticulons (Rtns) and Yop1. In wild-type cells, the peripheral ER contains cytoplasmic cisternae, many tubules, and a large plasma membrane (PM)–associated ER domain that consists of both tubules and fenestrated cisternae. In the absence of Rtn/Yop1, all three domains lose membrane curvature, ER ribosome density changes, and the amount of PM-associated ER increases dramatically. Deletion of Rtns/Yop1 does not, however, prevent bloated ER tubules from being pulled from the mother cisterna into the bud and strongly suggests that Rtns/Yop1 stabilize/maintain rather than generate membrane curvature at all peripheral ER domains in yeast.
Cell Death Mediated by the N-Terminal Domains of a Unique and Highly Conserved Class of NB-LRR Protein
Authors: Collier Sarah M. , Hamel Louis-Philippe , Moffett Peter
Published: April 2011

Plant genomes encode large numbers of nucleotide-binding, leucine-rich repeat (NB-LRR) proteins, many of which are active in pathogen detection and defense response induction. NB-LRR proteins fall into two broad classes: those with a Toll and interleukin-1 receptor (TIR) domain at their N-terminus and those with a coiled-coil (CC) domain at the N-terminus. Within CC-NB-LRR-encoding genes, one basal clade is distinguished by having CC domains resembling the Arabidopsis thaliana RPW8 protein, which we refer to as CCR domains. Here, we show that CCR-NB-LRR-encoding genes are present in the genomes of all higher plants surveyed, and that they comprise two distinct subgroups: one typified by the Nicotiana benthamiana N-required gene 1 (NRG1) protein and the other typified by the Arabidopsis activated disease resistance gene 1 (ADR1) protein. We further report that, in contrast to CC-NB-LRR proteins, the CCR domains of both NRG1- and ADR1-like proteins are sufficient for the induction of defense responses, and that this activity appears to be SGT1-independent. Additionally, we report the apparent absence of both NRG1 homologs and TIR-NB-LRR-encoding genes from the dicot Aquilegia coerulea and the dicotyledonous order Lamiales as well as from monocotyledonous species. This strong correlation in occurrence is suggestive of a functional relationship between these two classes of NB-LRR proteins.
First Report of Pseudoperonospora cubensis on Cucurbita moschata in the Czech Republic
Authors: Pavelková J. , Lebeda A. , Sedláková B.
Published: April 2011

Pseudoperonospora cubensis (Berk. & M.A. Curtis) Rostovzev, the causal agent of cucurbit downy mildew, was observed for the first time on Cucurbita moschata Duchesne in the Czech Republic (CR) in August 2009 and repeatedly in September 2010. Recently, C. moschata has not been an economically important crop in the CR; however, related crops C. pepo and C. maxima have increased in importance. Infected plants with P. cubensis were found in two locations: in a hobby garden in north Moravia (Nový Jičín – Kojetín [49°33′48.088″N, 17°59′16.632″E], 2009 and 2010) and in a commercial field in central Moravia (Olomouc-Holice [49°34′31.95″N, 17°17′35.462″E], 2010). The pathogen caused small, angular, yellowish or pale green lesions on the upper leaf surfaces and produced sporangiophores and sporangia on the lower leaf surfaces. The lesions were delimited by leaf veins and later turned necrotic. Sporangiophores were hyaline, branched, and emerged in groups from stomata. Olive brown-to-dark brown sporangia were ellipsoidal to oblong. Our morphological observations confirmed that the pathogen was P. cubensis (2). No previous reports are available of P. cubensis on C. moschata in CR or anywhere in Central Europe. However, P. cubensis is common on C. moschata in some parts of Asia and the United States (1,2). P. cubensis exhibiting clear host specialization has been reported in different countries and geographic areas (2). A C. moschata isolate (PC 88/2009) originating from the naturally infected plants was inoculated (1 × 105 spores per ml and incubation temperature of 18/15°C during light/dark cycles) according to the methodology described by Lebeda and Urban (3) onto the abaxial surface of leaf discs of all genotypes of a differential set of cucurbits for P. cubensis pathotype determination (4). C. moschata (line Novo5, Nohel-Garden, CR) was added to this set. The isolate PC 88/2009 was highly pathogenic to all screened Cucurbita spp. genotypes (C. pepo, C. maxima, and C. moschata). However, no infection was detected on most of the Cucumis accessions; only Cucumis melo subsp. agrestis var. conomon was susceptible. Also, no infection was observed on other differentials (Citrullus, Benincasa, Luffa, and Lagenaria). The pathotype was classified as Pc 4/15/0. This pathotype had not been previously detected in CR.

References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.arsgrin. gov/fungaldatabases/ . December 16, 2010. (2) A. Lebeda and Y. Cohen. Eur. J. Plant Pathol. 129:157, 2011. (3) A. Lebeda and J. Urban. Page 285 in: Mass Screening Techniques for Selecting Crops Resistant to Disease. M. M. Spencer and A. Lebeda, eds. International Atomic Energy Agency (IAEA), Vienna, Austria, 2010 (4) A. Lebeda and M. P. Widrlechner. J. Plant Dis. Protect. 110:337, 2003.
Genetic Transformation of Passionflower and Evaluation of R1 and R2 Generations for Resistance to Cowpea aphid borne mosaic virus
Authors: Monteiro-Hara Alessandra C. B. A. , Jadão Adriana S. , Mendes Beatriz M. J. , Rezende Jorge A. M. , Trevisan Flavio , Mello Ana Paula O. A. , Vieira Maria Lucia C. , Meletti L. M. M. , De S. Piedade Sônia M.
Published: April 2011

We report on the production and evaluation of passionflower transgenic lines for resistance to Cowpea aphid borne mosaic virus (CABMV). Genetic transformation was done using Agrobacterium tumefaciens and transgene integration was confirmed by Southern blot analyses, resulting in nine transgenic lines for ‘IAC 275’ and three for ‘IAC 277’. Transgenic lines were clonally propagated and evaluated for resistance to CABMV. After the third inoculation, under higher inoculum pressure, only propagated plants of the transgenic line T16 remained asymptomatic, indicating a high resistance to infection with CABMV. This transgenic line was self-pollinated and the R1 generation was evaluated together with the R1 generation of another resistant transgenic line (T2) identified previously. Plants were inoculated with CABMV by means of viruliferous Myzus nicotianae. All 524 T2R1 plants became infected, whereas 13 of 279 T16R1 remained asymptomatic after four successive inoculations. A T16R2 generation was obtained and plants were inoculated with CABMV mechanically or by aphids. After successive inoculations, 118 of 258 plants were symptomless, suggesting that the resistance to CABMV was maintained in the plant genome as the homozygous condition was achieved. Five selected resistant T16R2 plants which contained the capsid protein gene are being crossed for further analyses.
Verification of greenhouse gas emission reductions: the prospect of atmospheric monitoring in polluted areas
Authors: Levin Ingeborg , Hammer Samuel , Eichelmann Elke , Vogel Felix R.
Published: April 2011

Independent verification of greenhouse gas emissions reporting is a legal requirement of the Kyoto Protocol, which has not yet been fully accomplished. Here, we show that dedicated long-term atmospheric measurements of greenhouse gases, such as carbon dioxide (CO
2
) and methane (CH
4
), continuously conducted at polluted sites can provide the necessary tool for this undertaking. From our measurements at the semi-polluted Heidelberg site in the upper Rhine Valley, we find that in the catchment area CH
4
emissions decreased on average by 32±6% from the second half of the 1990s until the first half of the 2000s, but the observed long-term trend of emissions is considerably smaller than that previously reported for southwest Germany. In contrast, regional fossil fuel CO
2
levels, estimated from high-precision
14
CO
2
observations, do not show any significant decreasing trend since 1986, in agreement with the reported emissions for this region. In order to provide accurate verification, these regional measurements would best be accompanied by adequate atmospheric transport modelling as required to precisely determine the relevant catchment area of the measurements. Furthermore, reliable reconciliation of reported emissions will only be possible if these are known at high spatial resolution in the catchment area of the observations. This information should principally be available in all countries that regularly report their greenhouse gas emissions to the United Nations Framework Convention on Climate Change.
The carbon balance of Africa: synthesis of recent research studies
Authors: Ciais P. , Bombelli A. , Williams M. , Piao S. L. , Chave J. , Ryan C. M. , Henry M. , Brender P. , Valentini R.
Published: April 2011

The African continent contributes one of the largest uncertainties to the global CO
2
budget, because very few long-term measurements are carried out in this region. The contribution of Africa to the global carbon cycle is characterized by its low fossil fuel emissions, a rapidly increasing population causing cropland expansion, and degradation and deforestation risk to extensive dryland and savannah ecosystems and to tropical forests in Central Africa. A synthesis of the carbon balance of African ecosystems is provided at different scales, including observations of land–atmosphere CO
2
flux and soil carbon and biomass carbon stocks. A review of the most recent estimates of the net long-term carbon balance of African ecosystems is provided, including losses from fire disturbance, based upon observations, giving a sink of the order of 0.2 Pg C yr
−1
with a large uncertainty around this number. By comparison, fossil fuel emissions are only of the order of 0.2 Pg C yr
−1
and land-use emissions are of the order of 0.24 Pg C yr
−1
. The sources of year-to-year variations in the ecosystem carbon-balance are also discussed. Recommendations for the deployment of a coordinated carbon-monitoring system for African ecosystems are given.
Global atmospheric methane: budget, changes and dangers
Authors: Dlugokencky Edward J. , Nisbet Euan G. , Fisher Rebecca , Lowry David
Published: April 2011

A factor of 2.5 increase in the global abundance of atmospheric methane (CH
4
) since 1750 contributes 0.5 Wm
−2
to total direct radiative forcing by long-lived greenhouse gases (2.77 Wm
−2
in 2009), while its role in atmospheric chemistry adds another approximately 0.2 Wm
−2
of indirect forcing. Since CH
4
has a relatively short lifetime and it is very close to a steady state, reductions in its emissions would quickly benefit climate. Sensible emission mitigation strategies require quantitative understanding of CH
4
’s budget of emissions and sinks. Atmospheric observations of CH
4
abundance and its rate of increase, combined with an estimate of the CH
4
lifetime, constrain total global CH
4
emissions to between 500 and 600 Tg CH
4
 yr
−1
. While total global emissions are constrained reasonably well, estimates of emissions by source sector vary by up to a factor of 2. Current observation networks are suitable to constrain emissions at large scales (e.g. global) but not at the regional to national scales necessary to verify emission reductions under emissions trading schemes. Improved constraints on the global CH
4
budget and its break down of emissions by source sector and country will come from an enhanced observation network for CH
4
abundance and its isotopic composition (
δ
13
C,
δ
D (D=
2
H) and
δ
14
C). Isotopic measurements are a valuable tool in distinguishing among various sources that contribute emissions to an air parcel, once fractionation by loss processes is accounted for. Isotopic measurements are especially useful at regional scales where signals are larger. Reducing emissions from many anthropogenic source sectors is cost-effective, but these gains may be cancelled, in part, by increasing emissions related to economic development in many parts of the world. An observation network that can quantitatively assess these changing emissions, both positive and negative, is required, especially in the context of emissions trading schemes.
The atmospheric signature of carbon capture and storage
Authors: Keeling Ralph F. , Manning Andrew C. , Dubey Manvendra K.
Published: April 2011

Compared with other industrial processes, carbon capture and storage (CCS) will have an unusual impact on atmospheric composition by reducing the CO
2
released from fossil-fuel combustion plants, but not reducing the associated O
2
loss. CO
2
that leaks into the air from below-ground CCS sites will also be unusual in lacking the O
2
deficit normally associated with typical land CO
2
sources, such as from combustion or ecosystem exchanges. CCS may also produce distinct isotopic changes in atmospheric CO
2
. Using simple models and calculations, we estimate the impact of CCS or leakage on regional atmospheric composition. We also estimate the possible impact on global atmospheric composition, assuming that the technology is widely adopted. Because of its unique signature, CCS may be especially amenable to monitoring, both regionally and globally, using atmospheric observing systems. Measurements of the O
2
/N
2
ratio and the CO
2
concentration in the proximity of a CCS site may allow detection of point leaks of the order of 1000 ton CO
2
yr
−1
from a CCS reservoir up to 1 km from the source. Measurements of O
2
/N
2
and CO
2
in background air from a global network may allow quantification of global and hemispheric capture rates from CCS to the order of ±0.4 Pg C yr
−1
.
Monitoring and interpreting the ocean uptake of atmospheric CO
2
Authors: Watson Andrew J. , Metzl Nicolas , Schuster Ute
Published: April 2011

The oceans are an important sink for anthropogenically produced CO
2
, and on time scales longer than a century they will be the main repository for the CO
2
that humans are emitting. Our knowledge of how ocean uptake varies (regionally and temporally) and the processes that control it is currently observation-limited. Traditionally, and based on sparse observations and models at coarse resolution, ocean uptake has been thought to be relatively invariant. However, in the few places where we have enough observations to define the uptake over periods of many years or decades, it has been found to change substantially at basin scales, responding to indices of climate variability. We illustrate this for three well-studied regions: the equatorial Pacific, the Indian Ocean sector of the Southern Ocean, and the North Atlantic. A lesson to take from this is that ocean uptake is sensitive to climate (regionally, but presumably also globally). This reinforces the expectation that, as global climate changes in the future owing to human influences, ocean uptake of CO
2
will respond. To evaluate and give early warning of such carbon–climate feedbacks, it is important to track trends in both ocean and land sinks for CO
2
. Recent coordinated observational programmes have shown that, by organization of an observing network, the atmosphere–ocean flux of CO
2
can, in principle, be accurately tracked at seasonal or better resolution, over at least the Northern Hemisphere oceans. This would provide a valuable constraint on both the ocean and (by difference) land vegetation sinks for atmospheric CO
2
.
Movement mechanics as a determinate of muscle structure, recruitment and coordination
Authors: Wakeling James M. , Blake Ollie M. , Wong Iris , Rana Manku , Lee Sabrina S. M.
Published: April 2011

During muscle contractions, the muscle fascicles may shorten at a rate different from the muscle-tendon unit, and the ratio of these velocities is its gearing. Appropriate gearing allows fascicles to reduce their shortening velocities and allows them to operate at effective shortening velocities across a range of movements. Gearing of the muscle fascicles within the muscle belly is the result of rotations of the fascicles and bulging of the belly. Variable gearing can also occur as a result of tendon length changes that can be caused by changes in the relative timing of muscle activity for different mechanical tasks. Recruitment patterns of slow and fast fibres are crucial for achieving optimal muscle performance, and coordination between muscles is related to whole limb performance. Poor coordination leads to inefficiencies and loss of power, and optimal coordination is required for high power outputs and high mechanical efficiencies from the limb. This paper summarizes key studies in these areas of neuromuscular mechanics and results from studies where we have tested these phenomena on a cycle ergometer are presented to highlight novel insights. The studies show how muscle structure and neural activation interact to generate smooth and effective motion of the body.
Red muscle function in stiff-bodied swimmers: there and almost back again
Authors: Syme Douglas A. , Shadwick Robert E.
Published: April 2011

Fishes with internalized and endothermic red muscles (i.e. tunas and lamnid sharks) are known for a stiff-bodied form of undulatory swimming, based on unique muscle–tendon architecture that limits lateral undulation to the tail region even though the red muscle is shifted anteriorly. A strong convergence between lamnid sharks and tunas in these features suggests that thunniform swimming might be evolutionarily tied to this specialization of red muscle, but recent observations on the common thresher shark (Alopias vulpinus) do not support this view. Here, we review the fundamental features of the locomotor systems in lamnids and tunas, and present data onin vivomuscle function and swimming mechanics in thresher sharks. These results suggest that the presence of endothermic and internalized red muscles alone in a fish does not predict or constrain the swimming mode to be thunniform and, indeed, that the benefits of this type of muscle may vary greatly as a consequence of body size.
Fibre operating lengths of human lower limb muscles during walking
Authors: Arnold Edith M. , Delp Scott L.
Published: April 2011

Muscles actuate movement by generating forces. The forces generated by muscles are highly dependent on their fibre lengths, yet it is difficult to measure the lengths over which muscle fibres operate during movement. We combined experimental measurements of joint angles and muscle activation patterns during walking with a musculoskeletal model that captures the relationships between muscle fibre lengths, joint angles and muscle activations for muscles of the lower limb. We used this musculoskeletal model to produce a simulation of muscle–tendon dynamics during walking and calculated fibre operating lengths (i.e. the length of muscle fibres relative to their optimal fibre length) for 17 lower limb muscles. Our results indicate that when musculotendon compliance is low, the muscle fibre operating length is determined predominantly by the joint angles and muscle moment arms. If musculotendon compliance is high, muscle fibre operating length is more dependent on activation level and force–length–velocity effects. We found that muscles operate on multiple limbs of the force–length curve (i.e. ascending, plateau and descending limbs) during the gait cycle, but are active within a smaller portion of their total operating range.
Muscle function in avian flight: achieving power and control
Authors: Biewener Andrew A.
Published: April 2011

Flapping flight places strenuous requirements on the physiological performance of an animal. Bird flight muscles, particularly at smaller body sizes, generally contract at high frequencies and do substantial work in order to produce the aerodynamic power needed to support the animal's weight in the air and to overcome drag. This is in contrast to terrestrial locomotion, which offers mechanisms for minimizing energy losses associated with body movement combined with elastic energy savings to reduce the skeletal muscles' work requirements. Muscles also produce substantial power during swimming, but this is mainly to overcome body drag rather than to support the animal's weight. Here, I review the function and architecture of key flight muscles related to how these muscles contribute to producing the power required for flapping flight, how the muscles are recruited to control wing motion and how they are used in manoeuvring. An emergent property of the primary flight muscles, consistent with their need to produce considerable work by moving the wings through large excursions during each wing stroke, is that the pectoralis and supracoracoideus muscles shorten over a large fraction of their resting fibre length (33–42%). Both muscles are activated while being lengthened or undergoing nearly isometric force development, enhancing the work they perform during subsequent shortening. Two smaller muscles, the triceps and biceps, operate over a smaller range of contractile strains (12–23%), reflecting their role in controlling wing shape through elbow flexion and extension. Remarkably, pigeons adjust their wing stroke plane mainly via changes in whole-body pitch during take-off and landing, relative to level flight, allowing their wing muscles to operate with little change in activation timing, strain magnitude and pattern.
Mechanics, modulation and modelling: how muscles actuate and control movement
Authors: Higham Timothy E. , Biewener Andrew A. , Delp Scott L.
Published: April 2011

Animal movement is often complex, unsteady and variable. The critical role of muscles in animal movement has captivated scientists for over 300 years. Despite this, emerging techniques and ideas are still shaping and advancing the field. For example, sonomicrometry and ultrasound techniques have enhanced our ability to quantify muscle length changes underin vivoconditions. Robotics and musculoskeletal models have benefited from improved computational tools and have enhanced our ability to understand muscle function in relation to movement by allowing one to simulate muscle–tendon dynamics under realistic conditions. The past decade, in particular, has seen a rapid advancement in technology and shifts in paradigms related to muscle function. In addition, there has been an increased focus on muscle function in relation to the complex locomotor behaviours, rather than relatively simple (and steady) behaviours. Thus, this Theme Issue will explore integrative aspects of muscle function in relation to diverse locomotor behaviours such as swimming, jumping, hopping, running, flying, moving over obstacles and transitioning between environments. Studies of walking and running have particular relevance to clinical aspects of human movement and sport. This Theme Issue includes contributions from scientists working on diverse taxa, ranging from humans to insects. In addition to contributions addressing locomotion in various taxa, several manuscripts will focus on recent advances in neuromuscular control and modulation during complex behaviours. Finally, some of the contributions address recent advances in biomechanical modelling and powered prostheses. We hope that our comprehensive and integrative Theme Issue will form the foundation for future work in the fields of neuromuscular mechanics and locomotion.
The anatomical arrangement of muscle and tendon enhances limb versatility and locomotor performance
Authors: Wilson Alan , Lichtwark Glen
Published: April 2011

The arrangement of muscles and tendons has been studied in detail by anatomists, surgeons and biomechanists for over a century, and the energetics and mechanics of muscle contraction for almost as long. Investigation of how muscles function during locomotion and the relative length change in muscle fibres and the associated elastic tendon has, however, been more challenging. In recent years, novelin vivomeasurement methods such as ultrasound and sonomicrometry have contributed to our understanding of the dynamics of the muscle tendon unit during locomotion. Here, we examine both published and new data to explore how muscles are arranged to deliver the wide repertoire of locomotor function and the trade-offs between performance and economy that result.
Awareness in children: a secondary analysis of five cohort studies
Authors: Davidson A. J. , Smith K. R. , Blussé van Oud‐Alblas H. J. , Lopez U. , Malviya S. , Bannister C. F. , Galinkin J. L. , Habre W. , Ironfield C. , Voepel‐Lewis T. , Weber F.
Published: April 2011

Five recent cohort studies have shown a frequency of awareness in paediatric anaesthesia of between 0.2% and 1.2%, but they were not individually large enough to identify risk factors. This study pooled raw data from these five studies to identify factors associated with awareness in children. The outcome of awareness was taken as the cases judged to be most likely awareness cases in each study. Logistic regression was used to identify awareness‐associated factors. A combined sample of 4486 anaesthetics revealed 33 cases of awareness. Unadjusted analysis demonstrated weak evidence that nitrous oxide used as an anaesthetic maintenance adjunct was associated with awareness (OR 2.04 (95% CI 0.97–4.33), p = 0.06), and some evidence that use of a tracheal tube was associated with awareness (OR 2.78 (95% CI 1.11–6.94), p = 0.03). Multivariable regression analysis revealed that nitrous oxide maintenance and use of a tracheal tube were independently associated with awareness (nitrous oxide, OR 2.4 (95% CI 1.08–5.32), p = 0.03; tracheal tube, OR 3.0 (95% CI 1.20–7.56), p = 0.02).
A comparison of pressure‐controlled and volume‐controlled ventilation for laparoscopic cholecystectomy*
Authors: Tyagi A. , Kumar R. , Sethi A. K. , Mohta M.
Published: April 2011

The potential advantages of pressure‐controlled over volume‐controlled ventilation during laparoscopic surgery have yet to be proven. We randomly assigned 42 patients with BMI < 30 kg.m−2 scheduled for laparoscopic cholecystectomy to receive either pressure‐ or volume‐controlled ventilation. Compared with volume‐controlled ventilation, pressure‐controlled ventilation resulted in a significant decrease in mean (SD) peak airway pressure at 10 min (20.4 (2.7) vs 24.0 (4.7) cmH2O, p = 0.004) and 30 min (20.7 (3.0) vs 23.9 (4.9) cmH2O, p = 0.015) and an increase in mean airway pressure at 10 min (10.5 (0.9) vs 9.6 (1.1) cmH2O, p = 0.007) and 30 min (10.5 (1.1) vs 9.6 (1.2) cmH2O, p = 0.016) after the start of surgery. Gas exchange and haemodynamic stability were similar. We conclude that pressure‐controlled ventilation is a safe alternative and offers some advantages to volume‐controlled ventilation during laparoscopic cholecystectomy in non‐obese patients.
Neurotoxic effects associated with antibiotic use: management considerations
Authors: Grill Marie F. , Maganti Rama K.
Published: April 2011

The clinical manifestations of antibiotic‐induced neurotoxic effects, the underlying mechanisms and management strategies have been reviewed. PubMed and OVID searches (January 1960–June 2010) were conducted using search terms such as antibiotics, side effects, neurotoxicity and encephalopathy which yielded approximately 300 articles. All relevant case reports, case series, letters and retrospective reviews describing neurotoxic effects and those discussing mechanisms of neurotoxicity were included. Antibiotic‐induced neurotoxic side effects can have a myriad of neurologic presentations. Patients with prior central nervous system (CNS) disease, renal insufficiency and advanced age may be particularly vulnerable. Treatment consists of discontinuation of the offending agent, use of antiepileptic drugs in the case of seizures or status epilepticus and haemodialysis in certain cases. The risk of CNS toxicity may be reduced via dosage adjustments in high risk populations. Awareness of the potential neurotoxic clinical manifestations of various antibiotics and high degree of vigilance in critically ill patients is essential in identifying a potentially serious, though reversible complications of antibiotic therapy particularly with the advent of newer antimicrobial agents.
Road traffic accidents and psychotropic medication use in the Netherlands: a case–control study
Authors: Ravera Silvia , van Rein Nienke , de Gier Johan J. , de Jong‐van den Berg Lolkje T. W.
Published: April 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Some psychotropic medications (e.g. benzodiazepines, sedative antidepressants, etc.) can impair cognitive and psychomotor functions and, therefore, endanger traffic safety.

• There is a lack of knowledge concerning the role in traffic safety of first and new generations of psychotropic medications, new and chronic users, young and old drivers, and polypharmacy.

WHAT THIS STUDY ADDS

• There is an increased risk of having a traffic accident after being exposed to some psychotropic medicine classes and, in particular, to SSRIs.

• Health care professionals and patients should be properly informed about the potential effects of some psychoactive medications on driving abilities.

• The role of SSRIs in traffic safety has to be investigated further.

AIM To examine the association between the use of commonly prescribed psychotropic medications and road traffic accident risk.

METHODS A record‐linkage database was used to perform a case–control study in the Netherlands. The data came from three sources: pharmacy prescription data, police traffic accident data and driving licence data. Cases were defined as drivers, who had a traffic accident that required medical assistance between 2000 and 2007. Controls were defined as adults, who had a driving licence and had no traffic accident during the study period. Four controls were matched for each case. The following psychotropic medicine groups were examined: antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants stratified in the two groups, SSRIs and other antidepressants. Various variables, such as age, gender, medicine half‐life and alcohol use, were considered for the analysis.

RESULTS Three thousand nine hundred and sixty‐three cases and 18 828 controls were included in the case–control analysis. A significant association was found between traffic accident risk and exposure to anxiolytics (OR = 1.54, 95% CI 1.11, 2.15), and SSRIs (OR = 2.03, 95% CI 1.31, 3.14). A statistically significant increased risk was also seen in chronic anxiolytic users, females and young users (18 to 29 years old), chronic SSRI users, females and middle‐aged users (30 to 59 years old), and intermediate half‐life hypnotic users.

CONCLUSIONS The results of this study support previous findings and confirm that psychoactive medications can constitute a problem in traffic safety. Both health care providers and patients should be properly informed of the potential risks associated with the use of these medicines.
Additional safety risk to exceptionally approved drugs in Europe?
Authors: Arnardottir Arna H. , Haaijer‐Ruskamp Flora M. , Straus Sabine M. J. , Eichler Hans‐Georg , de Graeff Pieter A. , Mol Peter G. M.
Published: April 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The safety profile of new drugs is not well known at the time of market approval and serious safety issues are regularly identified for marketed drugs.

• Drugs intended to meet an unmet medical need can be approved for the market with less safety data than is usually required, using the Exceptional Circumstances and Conditional Approval applications in European Central procedure.

• It is unknown whether for drugs approved using Exceptional Circumstances and Conditional Approval procedures have an increased probability of serious safety issues identified post approval than for drugs approved through the standard procedures.

WHAT THIS STUDY ADDS

• Using the Exceptional Circumstances and Conditional Approval procedures does not lead to more post‐marketing safety alerts or safety‐related withdrawals when used for drugs with unmet medical needs.

AIMS Regulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear ‘unmet medical need’. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues.

METHODS A retrospective cohort study was performed of new drugs approved in Europe between 1999 and 2009. The determinant was EC/CA vs. standard procedure approval. Outcome variables were frequency and timing of a first Direct Healthcare Professional Communication (DHPC). An association between approval procedure and the time from market approval to DHPC was assessed using Kaplan‐Meyer survival analysis and Cox‐regression to correct for covariates.

RESULTS In total 289 new drugs were approved. Forty‐six (16.4%) were approved under EC or CA, of which seven received a DHPC (15%). This was similar to the standard approval drugs (243), of which 33 received one or more DHPC (14%, P= 0.77). The probability of acquiring a DHPC for standard approval drugs vs. EC/CA drugs during 11‐year follow‐up is 22% (95% CI 14%, 29%) and 26% (95% CI 8%, 44%), respectively (log‐rank P= 0.726). This difference remained not significant in the Cox‐regression model: hazard ratio 0.94 (95% CI 0.40, 2.20). Only drug type was identified as a confounding covariate.

CONCLUSION The EC/CA procedure is not associated with a higher probability of DHPCs despite limited clinical development data. These data do not support the view that early drug approval increases the risk of serious safety issues emerging after market approval.
Aortic root ectasia in patients with acromegaly: experience at a single center
Authors: Casini Alessandra Ferri , Neto Leonardo Vieira , Fontes Rosita , França Rodrigo Fraguas , Xavier Sérgio Salles , Gadelha Mônica Roberto
Published: April 2011

Background  Acromegaly is associated with increased cardiovascular mortality, and increased aortic root diameter has been recently described in the literature as a possible feature of acromegalic cardiomyopathy.

Objective  To assess the aortic root diameter and the prevalence of aortic ectasia in acromegalic patients.

Patients and methods  This paper presents a transversal analysis of 42 acromegalic patients by Doppler echocardiogram and comparison with 42 age, sex, body surface area and hypertension matched controls.

Results  The mean aortic root diameter at the level of the aortic leaflets was increased in acromegalic patients when compared to controls (3·4 ± 0·5 vs 2·9 ± 0·4 cm, respectively, P < 0·0001). The aortic root diameter was significantly greater in men than in women (3·6 ± 0·6 cm vs 3·2 ± 0·4 cm, respectively, P = 0·004), and the left ventricular mass index was positively correlated with the diameter of the aorta (r = 0·37, P = 0·01). Using a cut‐off point ≥ 3·8 cm, an aortic ectasia prevalence of 26·1 vs 2·3% was found in acromegalic patients and controls, respectively (P = 0·002). Only acromegaly was associated with aortic ectasia (P = 0·01).

Conclusion  The aortic root diameter was higher, and the prevalence of aortic ectasia was more common in acromegalic patients than in controls. In addition, only acromegalic disease was associated with aortic ectasia, suggesting the direct effects of GH and insulin‐like growth factor‐I excess on the cardiovascular system.
Reproductive Experience Affects Parental Retrieval Behaviour Associated with Increased Plasma Oxytocin Levels in Wild‐Type and Cd38‐Knockout Mice
Authors: Lopatina O. , Inzhutova A. , Pichugina Y. A. , Okamoto H. , Salmina A. B. , Higashida H.
Published: April 2011

The transition to motherhood results in a number of hormonal, neurological and behavioural changes necessary to ensure offspring growth. Once motherhood is established, further neurological and behavioural changes may result in long‐term memory in mothering. Recent research has shown that postpartum motherhood enhances both nurturing behaviour and oxytocin activities. The transmembrane glycoprotein, CD38, is expressed on many neuronal cells and has been shown to play a role in social behaviours through stimulating the release of oxytocin in the hypothalamus. The present study was performed to investigate the effects of reproductive experience (primi‐ and multiparity, dams and sires) on the degree of parental behaviour, such as retrieval. Comparisons were performed between wild‐type (Cd38 +/+) and Cd38 knockout (Cd38 −/−) mice of the ICR strain. Multiparous Cd38 −/− dams retrieved pups much faster than primiparous mice, whereas there were no significant differences between primi‐ and multiparous Cd38 +/+ dams. Plasma oxytocin levels were significantly increased in multiparous dams of both genotypes. In addition, oxytocin levels in the hypothalamus and pituitary were lower in Cd38 −/− than in wild‐type mice. ADP‐ribosyl cyclase activity in the hypothalamus, but not in the pituitary, was slightly increased in Cd38 +/+ dams. In an identical test, 40% of first‐time Cd38 +/+ sires showed retrieval. The time required to retrieval was shorter in second‐time Cd38 +/+ sires. Both first‐ and second‐time Cd38 −/− sires showed only 10% retrieval behaviour. These results indicate that parental behaviour is improved by reproductive experience, especially in Cd38 −/− dams, and suggest that these effects may be a result of increased oxytocin levels.
The dksA promoter is negatively feedback regulated by DksA and ppGpp
Authors: Chandrangsu Pete , Lemke Justin J. , Gourse Richard L.
Published: April 2011

Escherichia coli DksA is an RNA polymerase (RNAP)‐binding protein required for the regulation of a number of promoters, including those for the biosynthesis of rRNA, many ribosomal proteins, components of the flagellum, and several amino acids. Previous work demonstrated that DksA protein levels do not vary greatly in different growth conditions. We show here that DksA is a stable protein whose levels are kept constant by a negative feedback loop in which transcription from the dksA promoter is inhibited by DksA protein in conjunction with its cofactor ppGpp. We map the primary dksA promoter by primer extension, show that its activity increases in a strain lacking DksA, that the DksA protein accumulates when expressed from an exogenous promoter, that inhibition of transcription by DksA is direct since it occurs with purified components in vitro, and that inhibition correlates with effects of DksA on the lifetime of the dksA promoter complex. This work provides a mechanistic basis for the maintenance of constant cellular levels of DksA in E. coli and supports the model that transcription regulation by ppGpp/DksA derives from fluctuations in the concentrations of the small molecule cofactor rather than of DksA itself.
Influence of cultivar resistance and inoculum density on root hair infection of canola (Brassica napus) by Plasmodiophora brassicae
Authors: Hwang S. F. , Ahmed H. U. , Zhou Q. , Strelkov S. E. , Gossen B. D. , Peng G. , Turnbull G. D.
Published: April 2011

The impact of cultivar resistance and inoculum density on the incidence of primary infection of canola root hairs by Plasmodiophora brassicae, the causal agent of clubroot, was assessed by microscopy. The incidence of root hair infection in both a resistant and a susceptible cultivar increased with increasing inoculum density, but was two‐ to threefold higher in the susceptible cultivar; the relationship between root hair infection and inoculum density was also substantially stronger and more consistent in the susceptible cultivar. In the susceptible cultivar, the root hair infection rate peaked between 6 and 8 days after sowing and then declined. In the resistant cultivar, it increased over the 14‐day duration of each study. It appears that examination of root hair infection by microscopy in a bait crop of susceptible canola could serve as a useful tool for estimating P. brassicae inoculum levels in soil. In a separate trial, the relationship between inoculum density and clubroot severity, plant growth parameters, and seed yield was assessed under greenhouse conditions. Inoculum density in the susceptible genotype was strongly and positively correlated with clubroot severity and negatively correlated with plant height and seed yield. In addition, a single cropping cycle of the susceptible cultivar contributed significantly higher levels of resting spores to the soil in a greenhouse test than did a cycle of the resistant cultivar, as assessed by quantitative PCR and microscope analysis.
Computational analysis of storage synthesis in developing Brassica napus L. (oilseed rape) embryos: flux variability analysis in relation to 13C metabolic flux analysis
Authors: Hay Jordan , Schwender Jörg
Published: April 2011

Plant oils are an important renewable resource, and seed oil content is a key agronomical trait that is in part controlled by the metabolic processes within developing seeds. A large‐scale model of cellular metabolism in developing embryos of Brassica napus (bna572) was used to predict biomass formation and to analyze metabolic steady states by flux variability analysis under different physiological conditions. Predicted flux patterns are highly correlated with results from prior 13C metabolic flux analysis of B. napus developing embryos. Minor differences from the experimental results arose because bna572 always selected only one sugar and one nitrogen source from the available alternatives, and failed to predict the use of the oxidative pentose phosphate pathway. Flux variability, indicative of alternative optimal solutions, revealed alternative pathways that can provide pyruvate and NADPH to plastidic fatty acid synthesis. The nutritional values of different medium substrates were compared based on the overall carbon conversion efficiency (CCE) for the biosynthesis of biomass. Although bna572 has a functional nitrogen assimilation pathway via glutamate synthase, the simulations predict an unexpected role of glycine decarboxylase operating in the direction of NH4+ assimilation. Analysis of the light‐dependent improvement of carbon economy predicted two metabolic phases. At very low light levels small reductions in CO2 efflux can be attributed to enzymes of the tricarboxylic acid cycle (oxoglutarate dehydrogenase, isocitrate dehydrogenase) and glycine decarboxylase. At higher light levels relevant to the 13C flux studies, ribulose‐1,5‐bisphosphate carboxylase activity is predicted to account fully for the light‐dependent changes in carbon balance.
Metabolic network reconstruction and flux variability analysis of storage synthesis in developing oilseed rape (Brassica napus L.) embryos
Authors: Hay Jordan , Schwender Jörg
Published: April 2011

Computational simulation of large‐scale biochemical networks can be used to analyze and predict the metabolic behavior of an organism, such as a developing seed. Based on the biochemical literature, pathways databases and decision rules defining reaction directionality we reconstructed bna572, a stoichiometric metabolic network model representing Brassica napus seed storage metabolism. In the highly compartmentalized network about 25% of the 572 reactions are transport reactions interconnecting nine subcellular compartments and the environment. According to known physiological capabilities of developing B. napus embryos, four nutritional conditions were defined to simulate heterotrophy or photoheterotrophy, each in combination with the availability of inorganic nitrogen (ammonia, nitrate) or amino acids as nitrogen sources. Based on mathematical linear optimization the optimal solution space was comprehensively explored by flux variability analysis, thereby identifying for each reaction the range of flux values allowable under optimality. The range and variability of flux values was then categorized into flux variability types. Across the four nutritional conditions, approximately 13% of the reactions have variable flux values and 10–11% are substitutable (can be inactive), both indicating metabolic redundancy given, for example, by isoenzymes, subcellular compartmentalization or the presence of alternative pathways. About one‐third of the reactions are never used and are associated with pathways that are suboptimal for storage synthesis. Fifty‐seven reactions change flux variability type among the different nutritional conditions, indicating their function in metabolic adjustments. This predictive modeling framework allows analysis and quantitative exploration of storage metabolism of a developing B. napus oilseed.