bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural hybridization generates mammalian lineage with species characteristics
Authors: Larsen Peter A. , Marchán-Rivadeneira María R. , Baker Robert J.
Published: June 2010

Most diploid species arise from single-species ancestors. Hybrid origins of new species are uncommon (except among polyploids) and are documented infrequently in animals. Examples of natural hybridization leading to speciation in mammals are exceedingly rare. Here, we show a Caribbean species of bat (Artibeus schwartzi) has a nuclear genome derived from two nonsister but congeneric species (A. jamaicensisandA. planirostris) and a mitochondrial genome that is from a third extinct or uncharacterized congener.Artibeus schwartziis self-sustaining, morphologically distinct, and exists in near geographic isolation of its known parent species. Island effects (i.e., area, reduced habitat variability, and geographic isolation) likely have restricted gene flow from parental species into the Caribbean populations of this hybrid lineage, thus contributing to local adaptation and isolation of this newly produced taxon. We hypothesize differential rates of the development of reproductive isolation within the genus and estimate that 2.5 million years was an insufficient amount of time for the development of postzygotic isolation among the three species that hybridized to produceA. schwartzi. Reticulated evolution thus has resulted in a genomic combination from three evolutionary lineages and a transgressive phenotype that is distinct from all other known species ofArtibeus. The data herein further demonstrate the phenomenon of speciation by hybridization in mammals is possible in nature.
Step-by-step growth of epitaxially aligned polythiophene by surface-confined reaction
Authors: Lipton-Duffin J. A. , Miwa J. A. , Kondratenko M. , Cicoira F. , Sumpter B. G. , Meunier V. , Perepichka D. F. , Rosei F.
Published: June 2010

One of the great challenges in surface chemistry is to assemble aromatic building blocks into ordered structures that are mechanically robust and electronically interlinked—i.e., are held together by covalent bonds. We demonstrate the surface-confined growth of ordered arrays of poly(3,4-ethylenedioxythiophene) (PEDOT) chains, by using the substrate (the 110 facet of copper) simultaneously as template and catalyst for polymerization. Copper acts as promoter for the Ullmann coupling reaction, whereas the inherent anisotropy of the fcc 110 facet confines growth to a single dimension. High resolution scanning tunneling microscopy performed under ultrahigh vacuum conditions allows us to simultaneously image PEDOT oligomers and the copper lattice with atomic resolution. Density functional theory calculations confirm an unexpected adsorption geometry of the PEDOT oligomers, which stand on the sulfur atom of the thiophene ring rather than lying flat. This polymerization approach can be extended to many other halogen-terminated molecules to produce epitaxially aligned conjugated polymers. Such systems might be of central importance to develop future electronic and optoelectronic devices with high quality active materials, besides representing model systems for basic science investigations.
The complete influenza hemagglutinin fusion domain adopts a tight helical hairpin arrangement at the lipid:water interface
Authors: Lorieau Justin L. , Louis John M. , Bax Ad
Published: June 2010

All but five of the N-terminal 23 residues of the HA2 domain of the influenza virus glycoprotein hemagglutinin (HA) are strictly conserved across all 16 serotypes of HA genes. The structure and function of this HA2 fusion peptide (HAfp) continues to be the focus of extensive biophysical, computational, and functional analysis, but most of these analyses are of peptides that do not include the strictly conserved residues Trp
21
-Tyr
22
-Gly
23
. The heteronuclear triple resonance NMR study reported here of full length HAfp of sero subtype H1, solubilized in dodecylphosphatidyl choline, reveals a remarkably tight helical hairpin structure, with its N-terminal α-helix (Gly
1
-Gly
12
) packed tightly against its second α-helix (Trp
14
-Gly
23
), with six of the seven conserved Gly residues at the interhelical interface. The seventh conserved Gly residue in position 13 adopts a positive
ϕ
angle, enabling the hairpin turn that links the two helices. The structure is stabilized by multiple interhelical C

α

H to C = O hydrogen bonds, characterized by strong interhelical H
N
-H

α

and H

α

-H

α

NOE contacts. Many of the previously identified mutations that make HA2 nonfusogenic are also incompatible with the tight antiparallel hairpin arrangement of the HAfp helices.
15
N relaxation analysis indicates the structure to be highly ordered on the nanosecond time scale, and NOE analysis indicates HAfp is located at the water-lipid interface, with its hydrophobic surface facing the lipid environment, and the Gly-rich side of the helix-helix interface exposed to solvent.
Bramante'sRuined Templeand the Dialectics of the Image*
Authors: Kleinbub Christian K.
Published: June 2010

In studying Donato Bramante'sRuined Temple(1481), this essay looks beyond the traditional question of its subject matter, considering this engraving as an image about images of all kinds. Taking the inconspicuous cross on the column as its focal point, it shows how the print offers a dialectical disquisition on the value of the Christian sign as measured against the alluring remains of pagan civilization. The vexed nature of this choice registers a profound artistic problem. Caught between the ideals of classical antiquarianism and contemporary devotion, Bramante here claims the ground between artistic fame and obscurity, righteousness and idolatrous ruin.
Florio's Montaigne and the Tyranny of “Custome”: Appropriation, Ideology, and Early English Readership of theEssayes*
Authors: Hamlin William M.
Published: June 2010

Early English readers of Michel de Montaigne (1533–92) annotated their copies of John Florio's (1553[?]–1625) translation with remarkable frequency and vehemence, creating a context within which printed appropriations of the essayist may be fruitfully examined. No topic intrigued these readers more than custom. Drawing from transcriptions of over 4,000 marginal annotations and situating the Montaignean borrowings of William Shakespeare (1564–1616), Sir Francis Bacon (1561–1626), and other English writers within a culture of active reader response, this essay treats the Montaignean account of custom as a case study wherein differences between manuscript and print appropriation may be investigated. Montaigne's reception in seventeenth-century England cannot be understood without scrupulous attention to both traditions.
Development of a measurement reference standard for neutron energies between 1 MeV and 20 MeV using time of flight method at the AMANDE facility
Authors: Cognet M-A , Gressier V
Published: June 2010

The variation of the response of instruments as a function of neutron energy has to be determined in well-characterized mono-energetic neutron fields. These fields are measured in terms of neutron fluence and mean energy of the mono-energetic neutron peak, providing values that are required to determine the related dosimetric quantities. At the IRSN AMANDE facility, the reference measurement standard for neutron energy is based on the time of flight (ToF) method, i.e. on a determination of the neutron velocity, requiring a pulsed beam and fast detectors. In this study, we describe the experimental and theoretical aspects of the development of this method for neutron energies above 1 MeV using liquid scintillators. We present the adopted experimental protocol and give full details of the estimation of uncertainties associated with the neutron energy measurement. To extract as accurately as possible the mean energy from the experimental neutron ToF distribution, a simulated energy distribution is fitted to the measurements. This simulation includes a detailed analysis of the energy resolution, taking into account all the contributions influencing the ToF measurements. Comparison with neutron energy calculated from kinematics leads to the conclusion that the ToF method at the AMANDE facility can be considered as a reference measurement standard for neutron energies between 1 MeV and 20 MeV, with a relative uncertainty lower than 1.5%.
Autosomal Recessive Polycystic Kidney Disease Epithelial Cell Model Reveals Multiple Basolateral Epidermal Growth Factor Receptor Sorting Pathways
Authors: Ryan Sean , Verghese Susamma , Cianciola Nicholas L. , Cotton Calvin U. , Carlin Cathleen R.
Published: June 2010

Sorting and maintenance of the EGF receptor on the basolateral surface of renal epithelial cells is perturbed in polycystic kidney disease and apical expression of receptors contributes to severity of disease. The goal of these studies was to understand the molecular basis for EGF receptor missorting using a well-established mouse model for the autosomal recessive form of the disease. We have discovered that multiple basolateral pathways mediate EGF receptor sorting in renal epithelial cells. The polycystic kidney disease allele in this model, Bicc1, interferes with one specific EGF receptor pathway without affecting overall cell polarity. Furthermore one of the pathways is regulated by a latent basolateral sorting signal that restores EGF receptor polarity in cystic renal epithelial cells via passage through a Rab11-positive subapical compartment. These studies give new insights to possible therapies to reconstitute EGF receptor polarity and function in order to curb disease progression. They also indicate for the first time that the Bicc1 gene that is defective in the mouse model used in these studies regulates cargo-specific protein sorting mediated by the epithelial cell specific clathrin adaptor AP-1B.
A Three-Dimensional Computer Simulation Model Reveals the Mechanisms for Self-Organization of Plant Cortical Microtubules into Oblique Arrays
Authors: Eren Ezgi Can , Dixit Ram , Gautam Natarajan
Published: June 2010

The noncentrosomal cortical microtubules (CMTs) of plant cells self-organize into a parallel three-dimensional (3D) array that is oriented transverse to the cell elongation axis in wild-type plants and is oblique in some of the mutants that show twisted growth. To study the mechanisms of CMT array organization, we developed a 3D computer simulation model based on experimentally observed properties of CMTs. Our computer model accurately mimics transverse array organization and other fundamental properties of CMTs observed in rapidly elongating wild-type cells as well as the defective CMT phenotypes observed in the Arabidopsis mor1-1 and fra2 mutants. We found that CMT interactions, boundary conditions, and the bundling cutoff angle impact the rate and extent of CMT organization, whereas branch-form CMT nucleation did not significantly impact the rate of CMT organization but was necessary to generate polarity during CMT organization. We also found that the dynamic instability parameters from twisted growth mutants were not sufficient to generate oblique CMT arrays. Instead, we found that parameters regulating branch-form CMT nucleation and boundary conditions at the end walls are important for forming oblique CMT arrays. Together, our computer model provides new mechanistic insights into how plant CMTs self-organize into specific 3D arrangements.
The Hemibiotroph Colletotrichum graminicola Locally Induces Photosynthetically Active Green Islands but Globally Accelerates Senescence on Aging Maize Leaves
Authors: Behr Michael , Humbeck Klaus , Hause Gerd , Deising Holger B. , Wirsel Stefan G. R.
Published: June 2010

Typically, pathogenesis of the hemibiotroph Colletotrichum graminicola and defense responses of its host, Zea mays, are studied on young leaves. Equivalent studies have not been performed with leaves undergoing senescence, a situation that is relevant in the field. We discovered that, in contrast to anthracnose symptoms formed on young and mature leaves, green islands reminiscent of those known from obligate biotrophs were formed on senescing leaves. Microscopy revealed that the fungus grew in both symptoms from the epidermis towards the bundle sheath. In green islands, tissues remained intact for an extended time period. Imaging PAM (pulse-amplitude-modulation) fluorescence analyses revealed that photosynthesis is transiently maintained at green islands but declined in tissue surrounding the infection. In younger leaves however, photosynthesis was reduced only at infection sites. Support for the local modification of host physiology came from quantitative reverse transcription-polymerase chain reaction analyzing gene expression at high spatial resolution. Decreased transcript levels of the senescence markers see1 and ccp1 corroborated a pathogen-induced delay of senescence. Expression of several genes encoding proteins involved in photosynthesis was strongly reduced by infection. In contrast, transcript levels of incw1, encoding a cell-wall invertase, were increased 70-fold at green islands, suggesting that C. graminicola induced carbon sinks in senescing tissue.
Combination of Fluorescent Reporters for Simultaneous Monitoring of Root Colonization and Antifungal Gene Expression by a Biocontrol Pseudomonad on Cereals with Flow Cytometry
Authors: Rochat Laurène , Péchy-Tarr Maria , Baehler Eric , Maurhofer Monika , Keel Christoph
Published: June 2010

Some root-associated pseudomonads sustain plant growth by suppressing root diseases caused by pathogenic fungi. We investigated to which extent select cereal cultivars influence expression of relevant biocontrol traits (i.e., root colonization efficacy and antifungal activity) in Pseudomonas fluorescens CHA0. In this representative plant-beneficial bacterium, the antifungal metabolites 2,4-diacetylphloroglucinol (DAPG), pyrrolnitrin (PRN), pyoluteorin (PLT), and hydrogen cyanide (HCN) are required for biocontrol. To monitor host plant effects on the expression of biosynthetic genes for these compounds on roots, we developed fluorescent dual-color reporters suited for flow cytometric analysis using fluorescence-activated cell sorting (FACS). In the dual-label strains, the constitutively expressed red fluorescent protein mCherry served as a cell tag and marker for root colonization, whereas reporter fusions based on the green fluorescent protein allowed simultaneous recording of antifungal gene expression within the same cell. FACS analysis revealed that expression of DAPG and PRN biosynthetic genes was promoted in a cereal rhizosphere, whereas expression of PLT and HCN biosynthetic genes was markedly less sustained. When analyzing the response of the bacterial reporters on roots of a selection of wheat, spelt, and triticale cultivars, we were able to detect subtle species- and cultivar-dependent differences in colonization and DAPG and HCN gene expression levels. The expression of these biocontrol traits was particularly favored on roots of one spelt cultivar, suggesting that a careful choice of pseudomonad–cereal combinations might be beneficial to biocontrol. Our approach may be useful for selective single-cell level analysis of plant effects in other bacteria–root interactions.
Role of Hairy Nightshade in the Transmission of Different Potato virus Y Strains on Solanum tuberosum (L.)
Authors: Cervantes Felix A. , Alvarez Juan M.
Published: June 2010

The complexity of the Potato virus Y (PVY) (Potyviridae: Potyvirus) pathosystem is affected by the presence of several virus strains that differ in their ability to produce tuber necrosis and by the presence of an alternate host that could increase the amount of inoculum in potato fields. Solanum sarrachoides (Sendtner) is an invasive weed from South America present in Pacific Northwest potato agro-ecosystems. It serves as reservoir of PVY and its most efficient vectors: the green peach aphid, Myzus persicae (Sulzer), and the potato aphid, Macrosiphum euphorbiae (Thomas). The role of S. sarracoides as vector and virus reservoir in PVY epidemiology was investigated through a series of laboratory and greenhouse experiments. We studied the symptoms produced in S. sarracoides upon infection with necrotic and non-necrotic strains of PVY and looked at the percentage of infection and titer accumulation of these strains. PVY infection in S. sarrachoides produced symptoms similar to those produced in PVY-infected potato plants. Mottling and yellowing were the main symptoms of infection observed in S. sarrachoides plants, especially by PVYO and PVYNTN infection. Greenhouse transmission studies revealed that PVY-infected S. sarrachoides increased the transmission rate of PVY necrotic strains by M. persicae. The necrotic strain PVYNTN reached higher titer in S. sarrachoides than in potato plants when compared to PVYO and PVYN:O These findings have broadened our understanding of the role and importance of S. sarrachoides in the PVY epidemiology in the potato ecosystems and could potentially be included in the development or optimization of virus management programs.

Accepted for publication 15 March 2010. Published 26 May 2010.
Phase II Study to Evaluate the Safety and Efficacy of the Oral Neurokinin-1 Receptor Antagonist Casopitant (GW679769) Administered with Ondansetron for the Prevention of Postoperative and Postdischarge Nausea and Vomiting in High-risk Patients
Authors: Singla Neil K. , Singla Sonia K. , Chung Frances , Kutsogiannis Demetrios J. , Blackburn Linda , Lane Stephen R. , Levin Jeremey , Johnson Brendan , Pergolizzi Joseph V.
Published: June 2010

Background

In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride.

Methods

The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Subjects were randomized to one of five treatment arms: standard ondansetron 4 mg with casopitant at 0, 50, 100, or 150 mg, or 0 mg ondansetron with casopitant at 150 mg (the latter arm was considered an exploratory study group and was included in the safety analysis but not in the efficacy analysis).

Results

A significantly greater proportion of patients in all of the active casopitant plus ondansetron groups achieved a complete response (i.e., no vomiting, retching, rescue medication, or premature withdrawal) during the first 24 h postoperatively versus those in the ondansetron-alone group (59-62% vs. 40%, respectively; P = 0.0006). All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events.

Conclusions

Compared with ondansetron alone, the casopitant and ondansetron combination results in superior emesis prevention during the first 24 h postoperatively in female patients with known risk factors for postoperative nausea and vomiting.
Preconditioning and Postinsult Therapies for Perinatal Hypoxic–Ischemic Injury at Term
Authors: Sanders Robert D. , Manning Helen J. , Robertson Nicola J. , Ma Daqing , Edwards A. David , Hagberg Henrik , Maze Mervyn
Published: June 2010

Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.
Lidocaine, Carbamazepine, and Imipramine Have Partially Overlapping Binding Sites and Additive Inhibitory Effect on Neuronal Na+Channels
Authors: Yang Ya-Chin , Huang Chen-Syuan , Kuo Chung-Chin
Published: June 2010

Background

Despite the structural differences, local anesthetics, anticonvulsants, and tricyclic antidepressants exert similar use-dependent actions against voltage-gated Na channels, which may be contributory to pain control. The authors explore whether these drugs could doubly occupy the channel and exert synergic clinical effect.

Methods

The authors performed electrophysiologic recordings and quantitative analyses in mutant and native neuronal Na channels to investigate molecular interactions between different drugs.

Results

The authors demonstrate significant interactions between F1764 and W1716, two residues reported for local anesthetic binding, indicating uncertainties to conclude a common drug-binding site by mutation data. Therefore, the authors performed detailed functional studies in native neurons. Quantitative analyses of the inactivation curve shift argue against effective double occupancy of different drugs. For example, the shift of 20.9 +/- 1.3 mV in the simultaneous presence of 10 microm imipramine, 100 microm lidocaine, and 100 microm phenytoin is consistent with the one-site (21.5 mV) rather than the two-site (30.5-33.8 mV) or three-site (42.7 mV) predictions. However, there is a deviation from the recovery courses predicted by one site if lidocaine or imipramine coexists with anticonvulsants. Moreover, gating state dependence of macroscopic-binding rates markedly differs between imipramine and carbamazepine.

Conclusions

Carbamazepine, lidocaine, and imipramine bind to a common site with the common aromatic motif. External to the aromatic site, there is another weaker and less gating-dependent site for the tertiary amine chain in the latter two drugs. Concomitant clinical use of these drugs, thus, should have at most a simple additive but not a synergistic inhibitory action on Na currents.
Incidence of Epidural Catheter-associated Infections after Continuous Epidural Analgesia in Children
Authors: Sethna Navil F. , Clendenin David , Athiraman Umeshkumar , Solodiuk Jean , Rodriguez Diana P. , Zurakowski David , Warner David S.
Published: June 2010

Clinical observation suggests that the number of serious epidural catheter-associated infections have increased recently in children. This increase is likely attributed to an increase in reporting and in frequency of epidural analgesia usage. Estimates of infection rates are difficult to determine primarily because of insufficient study of large pediatric populations. In this retrospective study, the authors investigated the incidence of epidural catheter-associated soft tissue and epidural infections after use of continuous epidural analgesia spanning 17 yr. A total of 10,653 epidural catheters were used in 7,792 children. The majority of catheters, 10,437 (98%), were placed for the management of postoperative pain, and 216 (2%) were placed for the management of chronic pain. The authors identified 13 cases of infections (nine cellulitis, two paravertebral musculature infections, one epidural inflammation, and one epidural abscess) between 3 and 11 days after catheter insertion. The incidence of infection was significantly higher in patients treated for chronic pain (7 of 216 = 3.2%) compared with postoperative pain (6 of 10,437 = 0.06%; P < 0.0001). Surgical drainage of subcutaneous pus was performed in three patients, and medical therapy was administered in the remainder of patients; all patients recovered without sequelae. Although rare, epidural catheter-associated infections remain a serious concern in high-risk children who may benefit the most from epidural analgesia. The findings of the authors support the low rate of epidural infection previously reported despite growing concerns of serious infections in children. These findings highlight the importance of vigilance to early diagnostic indicators of infection and provide practitioners and families with incidence data to guide informed medical decision-making.
Hypercapnic Acidosis Reduces Oxidative Reactions in Endotoxin-induced Lung Injury
Authors: Nichol Alistair D. , O'Cronin Donall F. , Naughton Finola , Hopkins Natalie , Boylan John , McLoughlin Paul
Published: June 2010

Background

Hypercapnic acidosis frequently occurs when patients with acute lung injury are initially ventilated with low tidal volume "protective" strategies. Hypercapnic acidosis per se, in the absence of any change in tidal volume or airway pressure, is protective when instituted before the onset of injury. However, the mechanisms by which hypercapnic acidosis confers this protection are incompletely understood, in particular, the effects on pulmonary oxidative reactions, which are potent mediators of tissue damage, have not been previously examined in vivo.

Methods

After anesthesia, tracheostomy, and the intratracheal instillation of endotoxin to establish lung injury, rats were mechanically ventilated for 6 h in normocapnia (21% O2, 0% CO2). Rats were then randomized to either normocapnic (21% O2, 0% CO2) or hypercapnic (21% O2, 5% CO2) ventilation and a nonspecific nitric oxide synthase inhibitor (N-monomethyl-L-arginine) or vehicle. Dihydrorhodamine was administered intravenously, and the lungs were removed for determination of the oxidative formation of rhodamine by spectrofluorimetry after 20 min. Thus, rats were randomly assigned to either: normocapnia-endotoxin (n = 12), normocapnia-endotoxin-N-monomethyl-L-arginine (n = 9), hypercapnia-endotoxin (n = 11), or hypercapnia-endotoxin-N-monomethyl-L-arginine (n = 10).

Results

Hypercapnic acidosis significantly reduced the pulmonary oxidative reactions in the inflamed lung compared with normocapnia. Nitric oxide synthase blockade did not alter endotoxin-induced oxidative reactions.

Conclusions

Hypercapnic acidosis reduced oxidative reactions in the acutely injured lung in vivo, within minutes of onset and was not reliant on nitric oxide-dependent peroxynitrite production. This rapid onset antioxidant action is a previously undescribed mechanism by which hypercapnic acidosis could act, even when acute lung injury is well established.
Calcium Signaling in Intact Dorsal Root Ganglia
Authors: Gemes Geza , Rigaud Marcel , Koopmeiners Andrew S. , Poroli Mark J. , Zoga Vasiliki , Hogan Quinn H.
Published: June 2010

Background

Ca is the dominant second messenger in primary sensory neurons. In addition, disrupted Ca signaling is a prominent feature in pain models involving peripheral nerve injury. Standard cytoplasmic Ca recording techniques use high K or field stimulation and dissociated neurons. To compare findings in intact dorsal root ganglia, we used a method of simultaneous electrophysiologic and microfluorimetric recording.

Methods

Dissociated neurons were loaded by bath-applied Fura-2-AM and subjected to field stimulation. Alternatively, we adapted a technique in which neuronal somata of intact ganglia were loaded with Fura-2 through an intracellular microelectrode that provided simultaneous membrane potential recording during activation by action potentials (APs) conducted from attached dorsal roots.

Results

Field stimulation at levels necessary to activate neurons generated bath pH changes through electrolysis and failed to predictably drive neurons with AP trains. In the intact ganglion technique, single APs produced measurable Ca transients that were fourfold larger in presumed nociceptive C-type neurons than in nonnociceptive Abeta-type neurons. Unitary Ca transients summated during AP trains, forming transients with amplitudes that were highly dependent on stimulation frequency. Each neuron was tuned to a preferred frequency at which transient amplitude was maximal. Transients predominantly exhibited monoexponential recovery and had sustained plateaus during recovery only with trains of more than 100 APs. Nerve injury decreased Ca transients in C-type neurons, but increased transients in Abeta-type neurons.

Conclusions

Refined observation of Ca signaling is possible through natural activation by conducted APs in undissociated sensory neurons and reveals features distinct to neuronal types and injury state.
Effect of Just-in-time Simulation Training on Tracheal Intubation Procedure Safety in the Pediatric Intensive Care Unit
Authors: Nishisaki Akira , Donoghue Aaron J. , Colborn Shawn , Watson Christine , Meyer Andrew , Brown Calvin A. , Helfaer Mark A. , Walls Ron M. , Nadkarni Vinay M.
Published: June 2010

Background

Tracheal intubation-associated events (TIAEs) are common (20%) and life threatening (4%) in pediatric intensive care units. Physician trainees are required to learn tracheal intubation during intensive care unit rotations. The authors hypothesized that "just-in-time" simulation-based intubation refresher training would improve resident participation, success, and decrease TIAEs.

Methods

For 14 months, one of two on-call residents, nurses, and respiratory therapists received 20-min multidisciplinary simulation-based tracheal intubation training and 10-min resident skill refresher training at the beginning of their on-call period in addition to routine residency education. The rate of first attempt and overall success between refresher-trained and concurrent non-refresher-trained residents (controls) during the intervention phase was compared. The incidence of TIAEs between preintervention and intervention phase was also compared.

Results

Four hundred one consecutive primary orotracheal intubations were evaluated: 220 preintervention and 181 intervention. During intervention phase, neither first-attempt success nor overall success rate differed between refresher-trained residents versus concurrent non-refresher-trained residents: 20 of 40 (50%) versus 15 of 24 (62.5%), P = 0.44 and 23 of 40 (57.5%) versus 18 of 24 (75.0%), P = 0.19, respectively. The resident's first attempt and overall success rate did not differ between preintervention and intervention phases. The incidence of TIAE during preintervention and intervention phases was similar: 22.0% preintervention versus 19.9% intervention, P = 0.62, whereas resident participation increased from 20.9% preintervention to 35.4% intervention, P = 0.002. Resident participation continued to be associated with TIAE even after adjusting for the phase and difficult airway condition: odds ratio 2.22 (95% CI 1.28-3.87, P = 0.005).

Conclusions

Brief just-in-time multidisciplinary simulation-based intubation refresher training did not improve the resident's first attempt or overall tracheal intubation success.
Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery
Authors: Schiffter Heiko , Condliffe Jamie , Vonhoff Sebastian
Published: June 2010

The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 µm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (<10 mg ml
−1
) and subsequent ultra-turrax homogenization. To prepare particles for needle-free ballistic injection, the insulin nanoparticles were suspended in matrix formulations with a high excipient content (>300 mg ml
−1
) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (
T
prod
) exceeded the glass transition temperature of the freeze concentrate (
T
g
′) of −29.4°C for TMDD (3∶3∶3∶1) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin loading, the
d
(
v
, 0.5) of the SFD powders increased and particle size distributions got wider. Insulin showed a good stability during the particle formation process with a maximum decrease in insulin monomer of only 0.123 per cent after SFD. In accordance with the SEC data, FTIR analysis showed only a small increase in the intermolecular β-sheet of 0.4 per cent after SFD. The good physical stability of the polydisperse particles made them suitable for ballistic injection into tissue-mimicking agar hydrogels, showing a mean penetration depth of 251.3 ± 114.7 µm.
Function of blue iridescence in tropical understorey plants
Authors: Thomas Katherine R. , Kolle Mathias , Whitney Heather M. , Glover Beverley J. , Steiner Ullrich
Published: June 2010

The blue colouration seen in the leaves ofSelaginella willdenowiiis shown to be iridescent. Transmission electron microscopy studies confirm the presence of a layered lamellar structure of the upper cuticle of iridescent leaves. Modelling of these multi-layer structures suggests that they are responsible for the blue iridescence, confirming the link between the observed lamellae and the recorded optical properties. Comparison of blue and green leaves from the same plant indicates that the loss of the blue iridescence corresponds to a loss of the multi-layer structure. The results reported here do not support the idea that iridescence in plants acts to enhance light capture of photosynthetically important wavelengths. The reflectance of light in the range 600–700 nm is very similar for both iridescent and non-iridescent leaves. However, owing to the occurrence of blue colouration in a wide variety of shade dwelling plants it is probable that this iridescence has some adaptive benefit. Possible adaptive advantages of the blue iridescence in these plants are discussed.
Inversion of higher order isotropic tensors with minor symmetries and solution of higher order heterogeneity problems
Authors: Monchiet Vincent , Bonnet Guy
Published: June 2010

In this paper, the derivation of irreducible bases for a class of isotropic 2
n
th-order tensors having particular ‘minor symmetries’ is presented. The methodology used for obtaining these bases consists of extending the concept of deviatoric and spherical parts, commonly used for second-order tensors, to the case of an
n
th-order tensor. It is shown that these bases are useful for effecting the classical tensorial operations and especially the inversion of a 2
n
th-order tensor. Finally, the formalism introduced in this study is applied for obtaining the closed-form expression of the strain field within a spherical inclusion embedded in an infinite elastic matrix and subjected to linear or quadratic polynomial remote strain fields.
Nucleotide diversity inSilene latifoliaautosomal and sex-linked genes
Authors: Qiu Suo , Bergero Roberta , Forrest Alan , Kaiser Vera B. , Charlesworth Deborah
Published: June 2010

The plantSilene latifoliahas separate sexes and sex chromosomes, and is of interest for studying the early stages of sex chromosome evolution, especially the evolution of non-recombining regions on the Y chromosome. Hitch-hiking processes associated with ongoing genetic degeneration of the non-recombining Y chromosome are predicted to reduce Y-linked genes' effective population sizes, andS. latifoliaY-linked genes indeed have lower diversity than X-linked ones. We tested whether this represents a true diversity reduction on the Y, versus the alternative possibility, elevated diversity at X-linked genes, by collecting new data on nucleotide diversity for autosomal genes, which had previously been little studied. We find clear evidence that Y-linked genes have reduced diversity. However, another alternative explanation for a low Y effective size is a high variance in male reproductive success. Autosomal genes should then also have lower diversity than expected, relative to the X, but this is not found in our loci. Taking into account the higher mutation rate of Y-linked genes, their low sequence diversity indicates a strong effect of within-population hitch-hiking on the Y chromosome.
Bargaining babblers: vocal negotiation of cooperative behaviour in a social bird
Authors: Bell M. B. V. , Radford A. N. , Smith R. A. , Thompson A. M. , Ridley A. R.
Published: June 2010

Wherever individuals perform cooperative behaviours, each should be selected to adjust their own current contributions in relation to the likely future contributions of their collaborators. Here, we use the sentinel system of pied babblers (Turdoides bicolor) to show that individuals anticipate contributions by group mates, adjusting their own contribution in response to information about internal state broadcast by others. Specifically, we show that (i) short-term changes in state influence contributions to a cooperative behaviour, (ii) individuals communicate short-term changes in state, and (iii) individuals use information about the state of group mates to adjust their own investment in sentinel behaviour. Our results demonstrate that individual decisions about contributions to a cooperative effort can be influenced by information about the likely future contribution of others. We suggest that similar pre-emptive adjustments based on information obtained from collaborators will be a common feature of cooperative behaviour, and may play an important role in the development of complex communication in social species.
Bayesian species delimitation in West African forest geckos (Hemidactylus fasciatus)
Authors: Leaché Adam D. , Fujita Matthew K.
Published: June 2010

Genealogical data are an important source of evidence for delimiting species, yet few statistical methods are available for calculating the probabilities associated with different species delimitations. Bayesian species delimitation uses reversible-jump Markov chain Monte Carlo (rjMCMC) in conjunction with a user-specified guide tree to estimate the posterior distribution for species delimitation models containing different numbers of species. We apply Bayesian species delimitation to investigate the speciation history of forest geckos (Hemidactylus fasciatus) from tropical West Africa using five nuclear loci (and mtDNA) for 51 specimens representing 10 populations. We find that species diversity inH. fasciatusis currently underestimated, and describe three new species to reflect the most conservative estimate for the number of species in this complex. We examine the impact of the guide tree, and the prior distributions on ancestral population sizes (θ) and root age (τ0), on the posterior probabilities for species delimitation. Mis-specification of the guide tree or the prior distribution forθcan result in strong support for models containing more species. We describe a new statistic for summarizing the posterior distribution of species delimitation models, called speciation probabilities, which summarize the posterior support for each speciation event on the starting guide tree.
Bovine tuberculosis: the genetic basis of host susceptibility
Authors: Allen A. R. , Minozzi G. , Glass E. J. , Skuce R. A. , McDowell S. W. J. , Woolliams J. A. , Bishop S. C.
Published: June 2010

The prevalence of bovine tuberculosis (BTB) in the UK remains a significant economic burden and problem for the agri-food industry. Much effort has been directed towards improving diagnostics, finding vaccine candidates and assessing the usefulness of badger culling. The contribution that host genotype makes to disease outcome has, until recently, been overlooked; yet, it is biologically untenable that genetic variation does not play a role. In this review, we highlight the evidence, past and present, for a role of host genetics in determining susceptibility to BTB in livestock. We then address some of the major issues surrounding the design of future studies tasked with finding the exact causative genetic variation underpinning the TB susceptibility phenotype. Finally, we discuss some of the potential future benefits, and problems, that a knowledge of the genetic component to BTB resistance/susceptibility may bring to the agricultural industries and the wider scientific community.
Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients
Authors: Rehman Ateequr , Lepage Patricia , Nolte Andreas , Hellmig Stephan , Schreiber Stefan , Ott Stephan J.
Published: June 2010

Dysbiosis of the gut mucosa-associated microbiota (MAM) plays a pivotal role in the pathogenesis of chronic inflammatory bowel diseases (IBD). To date, dysbiosis only describes the altered composition of the different bacterial populations, but little is known about transcriptional activity, metabolism and the ‘live’ status of the MAM. In this study we investigated the transcriptional activity of the dominant intestinal bacterial populations in patients with IBD. Colonic mucosal biopsies from patients with active Crohn's disease (CD; n=10), active ulcerative colitis (UC; n=10) and healthy individuals (HI; n=10) were compared by 16S rRNA gene and rRNA profiles using clone libraries with more than 1700 sequenced clones. Bacterial richness was significantly lower in clone libraries based on rRNA compared to those based on the rRNA genes in the CD group (3.01 vs 3.91) and the UC group (3.61 vs 4.15), but showed no difference in HI (3.81 vs 3.85). The qualitative composition of rRNA and rRNA gene clone libraries was significantly different, with the phylum Bacteroidetes being the most active (P<0.01) compared to other populations in all clinical groups. In contrast, Actinobacteria and Firmicutes were inactive in the CD group, while Escherichia sp. were both abundant and active in the CD and UC groups. Most of the phylotypes showing the highest activity index ratios represented less than 1 % of the microbiota. Our findings indicate that specific bacterial populations are activated in IBD patients, while other groups are in an inactive or ‘dormant’ state. The transcriptional activity points to a more functional role of the intestinal mucosal microbiota and may lead to the identification of therapeutic targets in the active modulation of microbial factors.
The tra locus of streptomycete plasmid pIJ101 mediates efficient transfer of a circular but not a linear version of the same replicon
Authors: Wang Jing , Pettis Gregg S.
Published: June 2010

Conjugal transfer of circular plasmids in Streptomyces involves a unique mechanism employing few plasmid-encoded loci and the transfer of double-stranded DNA by an as yet uncharacterized intercellular route. Efficient transfer of the circular streptomycete plasmid pIJ101 requires only two plasmid loci: the pIJ101 tra gene, and as a cis-acting function known as clt. Here, we compared the ability of the pIJ101 transfer apparatus to promote conjugal transfer of circular versus linear versions of the same replicon. While the pIJ101 tra locus readily transferred the circular form of the replicon, the linear version was transferred orders of magnitude less efficiently and all plasmids isolated from the transconjugants were circular, regardless of their original configuration in the donor. Additionally, relatively rare circularization of linear plasmids was detectable in the donor cells, which is consistent with the notion that this event was a prerequisite for transfer by TraB(pIJ101). Linear versions of this same replicon did transfer efficiently, in that configuration, from strains containing the conjugative linear plasmid SLP2. Our data indicate that functions necessary and sufficient for transfer of circular DNA were insufficient for transfer of a related linear DNA molecule. The results here suggest that the conjugation mechanisms of linear versus circular DNA in Streptomyces spp. are inherently different and/or that efficient transfer of linear DNA requires additional components.
Strand-specific deep sequencing of the transcriptome
Authors: Vivancos Ana P. , Güell Marc , Dohm Juliane C. , Serrano Luis , Himmelbauer Heinz
Published: June 2010

Several studies support that antisense-mediated regulation may affect a large proportion of genes. Using the Illumina next-generation sequencing platform, we developed DSSS (direct strand specific sequencing), a strand-specific protocol for transcriptome sequencing. We tested DSSS with RNA from two samples, prokaryotic (Mycoplasma pneumoniae) as well as eukaryotic (Mus musculus), and obtained data containing strand-specific information, using single-read and paired-end sequencing. We validated our results by comparison with a strand-specific tiling array data set for strain M129 of the simple prokaryote M. pneumoniae, and by quantitative PCR (qPCR). The results of DSSS were very well supported by the results from tiling arrays and qPCR. Moreover, DSSS provided higher dynamic range and single-base resolution, thus enabling efficient antisense detection and the precise mapping of transcription start sites and untranslated regions. DSSS data for mouse confirmed strand specificity of the protocol and the general applicability of the approach to studying eukaryotic transcription. We propose DSSS as a simple and efficient strategy for strand-specific transcriptome sequencing and as a tool for genome annotation exploiting the increased read lengths that next-generation sequencing technology now is capable to deliver.
The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis
Authors: KURASHIMA Kazuyoshi , TAKAYANAGI Noboru , TSUCHIYA Noriko , KANAUCHI Tetsu , UEDA Miyuki , HOSHI Toshiko , MIYAHARA Yosuke , SUGITA Yutaka
Published: June 2010

Background and objective:  In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated.

Methods:  Consecutive patients with usual interstitial pneumonia (UIP) on high‐resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (≥2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (≥1/3 of the area of the base of the lungs).

Results:  Among 660 patients with UIP on HRCT, 221 showed upper‐lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DLCO, 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group.

Conclusions:  Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.