bluuebunny/crossref_metadata_2025 huggingface dataset:
Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging
Authors: Wanigasekera Vishvarani , Mezue Melvin , Andersson Jesper , Kong Yazhuo , Tracey Irene
Published: December 2015

AbstractAbstract

After development of experimental central sensitization, gabapentin reduces the activation of pain-related brain areas as well as functional connectivity between the thalamus and secondary somatosensory cortex, whereas ibuprofen does not when compared with placebo. Functional imaging may be a viable tool for evaluating analgesic efficacy during early stages of drug development.

Background

Attrition rates of new analgesics during drug development are high; poor assay sensitivity with reliance on subjective outcome measures being a crucial factor.

Methods

The authors assessed the utility of functional magnetic resonance imaging with capsaicin-induced central sensitization, a mechanism relevant in neuropathic pain, for obtaining mechanism-based objective outcome measures that can differentiate an effective analgesic (gabapentin) from an ineffective analgesic (ibuprofen) and both from placebo. The authors used a double-blind, randomized phase I study design (N = 24) with single oral doses.

Results

Only gabapentin suppressed the secondary mechanical hyperalgesia–evoked neural response in a region of the brainstem’s descending pain modulatory system (right nucleus cuneiformis) and left (contralateral) posterior insular cortex and secondary somatosensory cortex. Similarly, only gabapentin suppressed the resting-state functional connectivity during central sensitization between the thalamus and secondary somatosensory cortex, which was plasma gabapentin level dependent. A power analysis showed that with 12 data sets, when using neural activity from the left posterior insula and right nucleus cuneiformis, a statistically significant difference between placebo and gabapentin was detected with probability ≥ 0.8. When using subjective pain ratings, this reduced to less than or equal to 0.6.

Conclusions

Functional imaging with central sensitization can be used as a sensitive mechanism–based assay to guide go/no-go decisions on selecting analgesics effective in neuropathic pain in early human drug development. We also show analgesic modulation of neural activity by using resting-state functional connectivity, a less challenging paradigm that is ideally suited for patient studies because it requires no task or pain provocation.
G-protein–gated Inwardly Rectifying Potassium Channels Modulate Respiratory Depression by Opioids
Authors: Montandon Gaspard , Ren Jun , Victoria Nicole C. , Liu Hattie , Wickman Kevin , Greer John J. , Horner Richard L.
Published: December 2015

AbstractAbstract

By using genetic, pharmacological, and physiological approaches in rodents, this article identifies G-protein–gated inwardly rectifying potassium channels in the respiratory network of the ventrolateral medulla. G-protein–gated inwardly rectifying potassium channels contribute to respiratory depression by μ-opioid receptors and opioid analgesics.

Background

Drugs acting on μ-opioid receptors (MORs) are widely used as analgesics but present side effects including life-threatening respiratory depression. MORs are G-protein–coupled receptors inhibiting neuronal activity through calcium channels, adenylyl cyclase, and/or G-protein–gated inwardly rectifying potassium (GIRK) channels. The pathways underlying MOR-dependent inhibition of rhythmic breathing are unknown.

Methods

By using a combination of genetic, pharmacological, and physiological tools in rodents in vivo, the authors aimed to identify the role of GIRK channels in MOR-mediated inhibition of respiratory circuits.

Results

GIRK channels were expressed in the ventrolateral medulla, a neuronal population regulating rhythmic breathing, and GIRK channel activation with flupirtine reduced respiratory rate in rats (percentage of baseline rate in mean ± SD: 79.4 ± 7.4%, n = 7), wild-type mice (82.6 ± 3.8%, n = 3), but not in mice lacking the GIRK2 subunit, an integral subunit of neuronal GIRK channels (GIRK2−/−, 101.0 ± 1.9%, n = 3). Application of the MOR agonist [d-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) to the ventrolateral medulla depressed respiratory rate, an effect partially reversed by the GIRK channel blocker Tertiapin-Q (baseline: 42.1 ± 7.4 breath/min, DAMGO: 26.1 ± 13.4 breath/min, Tertiapin-Q + DAMGO: 33.9 ± 9.8 breath/min, n = 4). Importantly, DAMGO applied to the ventrolateral medulla failed to reduce rhythmic breathing in GIRK2−/− mice (percentage of baseline rate: 103.2 ± 12.1%, n = 4), whereas it considerably reduced rate in wild-type mice (62.5 ± 17.7% of baseline, n = 4). Respiratory rate depression by systemic injection of the opioid analgesic fentanyl was markedly reduced in GIRK2−/− (percentage of baseline: 12.8 ± 15.8%, n = 5) compared with wild-type mice (72.9 ± 27.3%).

Conclusions

Overall, these results identify that GIRK channels contribute to respiratory inhibition by MOR, an essential step toward understanding respiratory depression by opioids.
TEMPORAL INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR A MACULAR HOLE PATIENT UNABLE TO MAINTAIN POSTOPERATIVE PRONE POSITIONING
Authors: Takai Yasuyuki , Tanito Masaki , Sugihara Kazunobu , Kodama Tatsuo , Ohira Akihiro
Published: December 2015

Purpose:

To report the surgical technique and efficacy of the temporal inverted internal limiting membrane (ILM) flap technique for a patient with an idiopathic macular hole (MH) who is unable to maintain postoperative prone positioning.

Methods:

Case report.

Results:

A 73-year-old man with a Stage III MH in his left eye was scheduled to undergo surgery. Owing to his inability to maintain postoperative prone positioning for continuous placement of a transdermal bladder catheter after radical cystoprostatectomy to treat urinary bladder cancer, he underwent pars plana vitrectomy combined with the temporal inverted ILM flap technique and intraocular sulfur hexafluoride gas tamponade. The technique included ILM peeling at a temporal area of the macula to create one 2-disk-diameter semicircular ILM flap and inversion of the ILM flap nasally to cover the MH. Optical coherence tomography showed that MH closure started from the top of the MH just beneath the covered ILM flap; the closure process gradually extended toward the bottom of the MH. The well-aligned fovea recovered in 5 weeks postoperatively. The visual acuity was 20/200 preoperatively and improved to 20/50 postoperatively.

Conclusion:

The temporal inverted ILM flap technique, a simple surgery to treat MHs, provides scaffolding for retinal gliosis and may facilitate bridge formation between the walls of the MH beneath the flap. The procedure may be a good option to achieve MH closure without postoperative prone positioning.
CENTRAL VISUAL PHENOMENA AS CLUES TO VITREOMACULAR TRACTION IN PATIENTS WITH NORMAL FUNDUS OCULI
Authors: Scarinci Fabio , Sheyman Alan T. , Jampol Lee M.
Published: December 2015

Purpose:

To report two cases where the primary visual complaints were central visual phenomena, with normal fundus biomicroscopy.

Methods:

History and clinical examination, fundus autofluorescence, and spectral domain–optical coherence tomography.

Results:

The authors report 2 patients, a 66-year-old woman and a 77-year-old woman, who complained of a central visual disturbance in one eye. Best-corrected visual acuity was normal. Ophthalmoscopy in the first case was unremarkable and showed minimal retinal pigment epithelial mottling in Case 2. Spectral domain–optical coherence tomography revealed vitreomacular traction with foveal distortion in both eyes, associated with small cysts in the inner retinal layers and in one patient disruption of photoreceptors.

Conclusion:

Central visual phenomena are important clues for central vitreomacular traction, even in the presence of a normal fundus examination. The authors highlight the importance of performing spectral domain–optical coherence tomography evaluation in this setting before considering neurologic or systemic causes.
Early Childhood Education to Promote Health Equity: A Community Guide Systematic Review
Authors: Hahn Robert A. , Barnett W. Steven , Knopf John A. , Truman Benedict I. , Johnson Robert L. , Fielding Jonathan E. , Muntaner Carles , Jones Camara Phyllis , Fullilove Mindy T. , Hunt Pete C.
Published: December 2015

Context:

Children in low-income and racial and ethnic minority families often experience delays in development by 3 years of age and may benefit from center-based early childhood education.

Design:

A meta-analysis on the effects of early childhood education by Kay and Pennucci best met Community Guide criteria and forms the basis of this review.

Results:

There were increases in intervention compared with control children in standardized test scores (median = 0.29 SD) and high school graduation (median = 0.20 SD) and decreases in grade retention (median = 0.23 SD) and special education assignment (median = 0.28 SD). There were decreases in crime (median = 0.23 SD) and teen births (median = 0.46 SD) and increases in emotional self-regulation (median = 0.21 SD) and emotional development (median = 0.04 SD). All effects were favorable, but not all were statistically significant. Effects were also long-lasting.

Conclusions:

Because many programs are designed to increase enrollment for high-risk students and communities, they are likely to advance health equity.
Symbiont transmission entails the risk of parasite infection
Authors: Salem Hassan , Onchuru Thomas O. , Bauer Eugen , Kaltenpoth Martin
Published: December 2015

Like many animals, firebugs (Hemiptera, Pyrrhocoridae) rely on behavioural adaptations to successfully endow their offspring with microbial mutualists. To transmit the nutritionally beneficial Coriobacteriaceae symbionts, female firebugs smear egg surfaces with symbiont-containing faecal droplets that are subsequently ingested by newly hatched nymphs through active probing to initiate infection. Alternatively, the symbionts can be acquired horizontally through contact with faeces of infected conspecifics. Here, we report that these adaptations ensuring successful transmission of bacterial symbionts among firebugs are exploited by the specialized trypanosomatid parasite
Leptomonas pyrrhocoris
. Using comparative transcriptomics, fluorescence
in situ
hybridization (FISH) and controlled bioassays, we demonstrate that the transmission cycle of
L. pyrrhocoris
mirrors that of the bacterial mutualists, with high efficiency for both vertical and horizontal transmission. This indicates that the parasite capitalizes on pre-existing behavioural adaptations (egg smearing and probing) to facilitate its own transfer within host populations, adaptations that likely evolved to initiate and maintain an association with beneficial gut symbionts. Thus, the transmission of mutualistic microbes across host generations can entail a significant risk of co-transmitting pathogens or parasites, thereby exerting selective pressures on the host to evolve more specific mechanisms of transfer.
Engineering and technology of industrial water power at Castleford Mills from the seventeenth century to the twentieth century
Authors: Rollinson Andrew N.
Published: December 2015

This article tells the story of engineering and technology at Castleford Water Mills from the seventeenth century to the twentieth century through the presentation of recently discovered design plans and deeds, supplemented by other historical research. One of Castleford's mills was operated by Dr Thomas Allinson's Natural Food Company and therefore retained stoneground milling when fashions for white flour prompted other mills to switch to roller systems. The millstones were powered by a high-efficiency breastshot wheel, believed to be the last of its type taken out of industrial service in Britain. Many of its features, and its subsequent longevity, can be attributed to the influential works of William Fairbairn and John Smeaton. Detailed colour designs show the construction specifications of this water-wheel and its civil housing, along with other engineering plans such as a previously unrecorded Henry Simon horizontal turbine. Links with John Smeaton and the entry in his catalogue of designs for Castleford Oil Mill are also explored, and a former flood mill is identified at the site.
RETRACTED: RNA editing of microRNA prevents RNA-induced silencing complex recognition of target mRNA
Authors: Cui Yalei , Huang Tianzhi , Zhang Xiaobo
Published: December 2015

MicroRNAs (miRNAs) integrate with Argonaut (Ago) to create the RNA-induced silencing complex, and regulate gene expression by silencing target mRNAs. RNA editing of miRNA may affect miRNA processing, assembly of the Ago complex and target mRNA binding. However, the function of edited miRNA, assembled within the Ago complex, has not been extensively investigated. In this study, sequence analysis of the Ago complex of
Marsupenaeus japonicus
shrimp infected with white spot syndrome virus (WSSV) revealed that host ADAR (adenosine deaminase acting on RNA) catalysed A-to-I RNA editing of a viral miRNA (WSSV-miR-N12) at the +16 site. This editing of the non-seed sequence did not affect association of the edited miRNA with the Ago protein, but inhibited interaction between the miRNA and its target gene (
wsv399
). The WSSV early gene
wsv399
inhibited WSSV infection. As a result, the RNA editing of miRNA caused virus latency. Our results highlight a novel example of miRNA editing in the miRNA-induced silencing complex.
Greater magnocellular saccadic suppression in high versus low autistic tendency suggests a causal path to local perceptual style
Authors: Crewther David P. , Crewther Daniel , Bevan Stephanie , Goodale Melvyn A. , Crewther Sheila G.
Published: December 2015

Saccadic suppression—the reduction of visual sensitivity during rapid eye movements—has previously been proposed to reflect a specific suppression of the magnocellular visual system, with the initial neural site of that suppression at or prior to afferent visual information reaching striate cortex. Dysfunction in the magnocellular visual pathway has also been associated with perceptual and physiological anomalies in individuals with autism spectrum disorder or high autistic tendency, leading us to question whether saccadic suppression is altered in the broader autism phenotype. Here we show that individuals with high autistic tendency show greater saccadic suppression of low versus high spatial frequency gratings while those with low autistic tendency do not. In addition, those with high but not low autism spectrum quotient (AQ) demonstrated pre-cortical (35–45 ms) evoked potential differences (saccade versus fixation) to a large, low contrast, pseudo-randomly flashing bar. Both AQ groups showed similar differential visual evoked potential effects in later epochs (80–160 ms) at high contrast. Thus, the magnocellular theory of saccadic suppression appears untenable as a general description for the typically developing population. Our results also suggest that the bias towards local perceptual style reported in autism may be due to selective suppression of low spatial frequency information accompanying every saccadic eye movement.
Izumo1 and Juno: the evolutionary origins and coevolution of essential sperm–egg binding partners
Authors: Grayson Phil
Published: December 2015

Reproductive proteins are among the most rapidly evolving classes of proteins. For a subset of these, rapid evolution is driven by positive Darwinian selection despite vital, well-conserved, reproductive functions. Izumo1 is the only essential sperm–egg fusion protein currently known on mammalian sperm, and its egg receptor (Juno; formerly Folr4) was recently discovered. Male knockout mice for Izumo1 and female knockout mice for Juno are both healthy but sterile. Here, both sperm–egg binding proteins are shown to be evolving under positive selection. Within mammals, coevolution of Izumo1 and Juno is also uncovered, suggesting that similar forces have shaped the evolutionary histories of these binding partners within Mammalia. Additionally, genomic analyses reveal an ancient origin for the Izumo gene family, initially reported as conserved exclusively in mammals. Newly identified Izumo1 orthologues could serve reproductive functions in birds, fish and reptiles. Surprisingly, these same analyses support Juno's presence in mammals alone, suggesting a recent mammalian-specific duplication and neofunctionalization of the ancestral folate receptor. Despite the indispensability of their reproductive interaction, and their apparent coevolution within Mammalia, this binding pair arose through strikingly different evolutionary forces.
Are microbes fundamentally different than macroorganisms? Convergence and a possible case for neutral phenotypic evolution in testate amoeba (Amoebozoa: Arcellinida)
Authors: Oliverio Angela M. , Lahr Daniel J. G. , Grant Jessica , Katz Laura A.
Published: December 2015

This study reveals extensive phenotypic convergence based on the non-monophyly of genera and morphospecies of testate (shelled) amoebae. Using two independent markers, small subunit ribosomal DNA (ssu-rDNA) and mitochondrial cytochrome oxidase I (COI), we demonstrate discordance between morphology and molecules for ‘coreNebela’ species (Arcellinida; Amoebozoa). Prior work using just a single locus, ssu-rDNA, also supported the non-monophyly of the generaHyalospheniaandNebelaas well as for several morphospecies within these genera. Here, we obtained COI gene sequences of 59 specimens from seven morphospecies and ssu-rDNA gene sequences of 50 specimens from six morphospecies of hyalosphenids. Our analyses corroborate the prior ssu-rDNA findings of morphological convergence in test (shell) morphologies, as COI and ssu-rDNA phylogenies are concordant. Further, the monophyly of morphospecies is rejected using approximately unbiased tests. Given that testate amoebae are used as bioindicators in both palaeoecological and contemporary studies of threatened ecosystems such as bogs and fens, understanding the discordance between morphology and genetics in the hyalosphenids is essential for interpretation of indicator species. Further, while convergence is normally considered the result of natural selection, it is possible that neutrality underlies phenotypic evolution in these microorganisms.
A study of snake-like locomotion through the analysis of a flexible robot model
Authors: Cicconofri Giancarlo , DeSimone Antonio
Published: December 2015

We examine the problem of snake-like locomotion by studying a system consisting of a planar inextensible elastic rod with adjustable spontaneous curvature, which provides an internal actuation mechanism that mimics muscular action in a snake. Using a Cosserat model, we derive the equations of motion in two special cases: one in which the rod can only move along a prescribed curve, and one in which the rod is constrained to slide longitudinally without slipping laterally, but the path is not fixeda priori(free-path case). The second setting is inspired by undulatory locomotion of snakes on flat surfaces. The presence of constraints leads in both cases to non-standard boundary conditions that allow us to close and solve the equations of motion. The kinematics and dynamics of the system can be recovered from a one-dimensional equation, without any restrictive assumption on the followed trajectory or the actuation. We derive explicit formulae highlighting the role of spontaneous curvature in providing the driving force (and the steering, in the free-path case) needed for locomotion. We also provide analytical solutions for a special class of serpentine motions, which enable us to discuss the connection between observed trajectories, internal actuation and forces exchanged with the environment.
Supermassive black holes in the early Universe
Authors: Melia F. , McClintock T. M.
Published: December 2015

The recent discovery of the ultraluminous quasar SDSS J010013.02+280225.8 at redshift 6.3 has exacerbated the time compression problem implied by the appearance of supermassive black holes only approximately 900 Myr after the big bang, and only approximately 500 Myr beyond the formation of Pop II and III stars. Aside from heralding the onset of cosmic re-ionization, these first and second generation stars could have reasonably produced the approximately 5–20 M⊙seeds that eventually grew intozapproximately 6–7 quasars. But this process would have taken approximately 900 Myr, a timeline that appears to be at odds with the predictions ofΛCDM without an anomalously high accretion rate, or some exotic creation of approximately 105 M⊙seeds. There is no evidence of either of these happening in the local Universe. In this paper, we show that a much simpler, more elegant solution to the supermassive black hole anomaly is instead to view this process using the age–redshift relation predicted by theRh=ctUniverse, an Friedmann–Robertson–Walker (FRW) cosmology with zero active mass. In this context, cosmic re-ionization lasted fromtapproximately 883 Myr to approximately 2 Gyr (6≲z≲15), so approximately 5–20 M⊙black hole seeds formed shortly after re-ionization had begun, would have evolved into approximately 1010 M⊙quasars byzapproximately 6–7 simply via the standard Eddington-limited accretion rate. The consistency of these observations with the age–redshift relationship predicted byRh=ctsupports the existence of dark energy; but not in the form of a cosmological constant.
Behaviour of crystalline–amorphous interfaces in energetic aggregates subjected to coupled thermomechanical and laser loading
Authors: Brown Judith A. , Zikry M. A.
Published: December 2015

The behaviour of energetic aggregates was investigated for quasi-static compression and high strain rate thermomechanical compression behaviour that is coupled to laser irradiation. A dislocation-density-based crystal plasticity formulation was used to represent energetic crystalline behaviour, a finite viscoelastic formulation was used for the polymer binder and a coupled electromagnetic (EM)–thermomechanical computational scheme was used to predict aggregate response. Aggregates with different crystal sizes were considered to account for physically representative energetic microstructures and to understand the effects of crystal–crystal and crystal–binder interactions. The presence of smaller embedded crystals in the binder ligaments inhibited viscous sliding, and resulted in global hardening of the aggregate, which led to large stress gradients, localized plasticity and dislocation-density accumulation. The embedded crystals also increased scattering of the EM wave within the binder ligaments and increased the localization of EM energy and laser heat generation. Geometrically, necessary dislocation densities and stress gradients were calculated to characterize how hardening at the binder interfaces can lead to strengthening or defect nucleation.
Fisher transfer entropy: quantifying the gain in transient sensitivity
Authors: Prokopenko Mikhail , Barnett Lionel , Harré Michael , Lizier Joseph T. , Obst Oliver , Wang X. Rosalind
Published: December 2015

We introduce a novel measure, Fisher transfer entropy (FTE), which quantifies a gain in sensitivity to a control parameter of a state transition, in the context of another observable source. The new measure captures both transient and contextual qualities of transfer entropy and the sensitivity characteristics of Fisher information. FTE is exemplified for a ferromagnetic two-dimensional lattice Ising model with Glauber dynamics and is shown to diverge at the critical point.
Sensitivity of forces to wall transpiration in flow past an aerofoil
Authors: Mao X.
Published: December 2015

The adjoint-based sensitivity analyses well explored in hydrodynamic stability studies are extended to calculate the sensitivity of forces acting on an aerofoil with respect to wall transpiration. The magnitude of the sensitivity quantifies the controllability of the force, and the distribution of the sensitivity represents a most effective control when the control magnitude is small enough. Since the sensitivity to streamwise control is one order smaller than that to the surface-normal one, the work is concentrated on the normal control. In direct numerical simulations of flow around a NACA0024 aerofoil, the unsteady controls are far less effective than the steady control owing to the lock-in effect. At a momentum coefficient of 0.0008 and a maximum control velocity of 3.6% of the free-stream velocity, the steady surface-normal control reduces drag by 20% or enhances lift by up to 140% at
Re
=1000. A suction around the low-pressure region on the upper surface upstream of the separation point is found to reduce drag and enhance lift. At higher Reynolds numbers, the uncontrolled flow becomes three dimensional and the sensitivity diverges owing to the chaotic dynamics of the flow. Then the mechanism identified at lower Reynolds numbers is exploited to obtain the control, which is localized and can be generated by a limited number of actuators. The control to reduce drag or enhance lift is found to suppress unsteadiness, e.g. vortex shedding and three-dimensional developments. For example, at
Re
=2000 and
α
=10°, the control with a momentum coefficient of 0.0001 reduces drag by 20%, enhances lift by up to 200% and leads to a steady controlled flow.
Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour
Authors: Land Sander , Gurev Viatcheslav , Arens Sander , Augustin Christoph M. , Baron Lukas , Blake Robert , Bradley Chris , Castro Sebastian , Crozier Andrew , Favino Marco , Fastl Thomas E. , Fritz Thomas , Gao Hao , Gizzi Alessio , Griffith Boyce E. , Hurtado Daniel E. , Krause Rolf , Luo Xiaoyu , Nash Martyn P. , Pezzuto Simone , Plank Gernot , Rossi Simone , Ruprecht Daniel , Seemann Gunnar , Smith Nicolas P. , Sundnes Joakim , Rice J. Jeremy , Trayanova Natalia , Wang Dafang , Jenny Wang Zhinuo , Niederer Steven A.
Published: December 2015

Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.
Investigating the genetic architecture of conditional strategies using the environmental threshold model
Authors: Buzatto Bruno A. , Buoro Mathieu , Hazel Wade N. , Tomkins Joseph L.
Published: December 2015

The threshold expression of dichotomous phenotypes that are environmentally cued or induced comprise the vast majority of phenotypic dimorphisms in colour, morphology, behaviour and life history. Modelled as conditional strategies under the framework of evolutionary game theory, the quantitative genetic basis of these traits is a challenge to estimate. The challenge exists firstly because the phenotypic expression of the trait is dichotomous and secondly because the apparent environmental cue is separate from the biological signal pathway that induces the switch between phenotypes. It is the cryptic variation underlying the translation of cue to phenotype that we address here. With a ‘half-sib common environment’ and a ‘family-level split environment’ experiment, we examine the environmental and genetic influences that underlie male dimorphism in the earwigForficula auricularia. From the conceptual framework of the latent environmental threshold (LET) model, we use pedigree information to dissect the genetic architecture of the threshold expression of forceps length. We investigate for the first time the strength of the correlation between observable and cryptic ‘proximate’ cues. Furthermore, in support of the environmental threshold model, we found no evidence for a genetic correlation between cue and the threshold between phenotypes. Our results show strong correlations between observable and proximate cues and less genetic variation for thresholds than previous studies have suggested. We discuss the importance of generating better estimates of the genetic variation for thresholds when investigating the genetic architecture and heritability of threshold traits. By investigating genetic architecture by means of the LET model, our study supports several key evolutionary ideas related to conditional strategies and improves our understanding of environmentally cued decisions.
An ambusher's arsenal: chemical crypsis in the puff adder (Bitis arietans)
Authors: Miller Ashadee Kay , Maritz Bryan , McKay Shannon , Glaudas Xavier , Alexander Graham J.
Published: December 2015

Ambush foragers use a hunting strategy that places them at risk of predation by both visual and olfaction-oriented predators. Resulting selective pressures have driven the evolution of impressive visual crypsis in many ambushing species, and may have led to the development of chemical crypsis. However, unlike for visual crypsis, few studies have attempted to demonstrate chemical crypsis. Field observations of puff adders (Bitis arietans) going undetected by several scent-orientated predator and prey species led us to investigate chemical crypsis in this ambushing species. We trained dogs (Canis familiaris) and meerkats (Suricata suricatta) to test whether a canid and a herpestid predator could detectB. arietansusing olfaction. We also tested for chemical crypsis in five species of active foraging snakes, predicted to be easily detectable. Dogs and meerkats unambiguously indicated active foraging species, but failed to correctly indicate puff adder, confirming thatB. arietansemploys chemical crypsis. This is the first demonstration of chemical crypsis anti-predatory behaviour, though the phenomenon may be widespread among ambushers, especially those that experience high mortality rates owing to predation. Our study provides additional evidence for the existence of an ongoing chemically mediated arms race between predator and prey species.
The hyoid arch and braincase anatomy of
Acanthodes
support chondrichthyan affinity of ‘acanthodians’
Authors: Brazeau Martin D. , de Winter Valerie
Published: December 2015

Solving the evolutionary relationships of the acanthodians is one of the key problems in reconstructing ancestral anatomical conditions for the jawed vertebrates (gnathostomes). Current debate concerns whether acanthodians are an assemblage of stem chondrichthyans, or a more generalized grade encompassing some early stem osteichthyans. The skull anatomy of
Acanthodes bronni
has been pivotal in these debates, owing to tension between chondrichthyan- and osteichthyan-like models of reconstruction. We use computed tomography scanning and traditional palaeontological techniques to resolve the long-standing debate about the anatomy of the jaw suspension. We establish the correct length of the hyomandibula and show that it attaches to a process on the ventrolateral angle of the braincase below the jugular vein groove. This condition corresponds precisely to that in chondrichthyans. This character represents an unambiguously optimized synapomorphy with chondrichthyans given current gnathostome phylogenies, corroborating the growing consensus of the chondrichthyan affinity of acanthodians.
Evidence for carry-over effects of predator exposure on pathogen transmission potential
Authors: Roux Olivier , Vantaux Amélie , Roche Benjamin , Yameogo Koudraogo B. , Dabiré Kounbobr R. , Diabaté Abdoulaye , Simard Frederic , Lefèvre Thierry
Published: December 2015

Accumulating evidence indicates that species interactions such as competition and predation can indirectly alter interactions with other community members, including parasites. For example, presence of predators can induce behavioural defences in the prey, resulting in a change in susceptibility to parasites. Such predator-induced phenotypic changes may be especially pervasive in prey with discrete larval and adult stages, for which exposure to predators during larval development can have strong carry-over effects on adult phenotypes. To the best of our knowledge, no study to date has examined possible carry-over effects of predator exposure on pathogen transmission. We addressed this question using a natural food web consisting of the human malaria parasite
Plasmodium falciparum
, the mosquito vector
Anopheles coluzzii
and a backswimmer, an aquatic predator of mosquito larvae. Although predator exposure did not significantly alter mosquito susceptibility to
P. falciparum
, it incurred strong fitness costs on other key mosquito life-history traits, including larval development, adult size, fecundity and longevity. Using an epidemiological model, we show that larval predator exposure should overall significantly decrease malaria transmission. These results highlight the importance of taking into account the effect of environmental stressors on disease ecology and epidemiology.
Crystal structure of 1-(5-amino-2H-tetrazol-2-yl)-2-methylpropan-2-ol
Authors: Park Hyun Sik , Ryu Ji Yeon , Lee Junseong
Published: December 2015

The title compound, C5H11N5O, crystallized with two independent molecules in the asymmetric unit. The two molecules differ in the orientation of the 2-methylpropan-2-ol unit, with the hydroxy H atoms pointing in opposite directions. In the crystal, molecules are linkedviaO—H...O and N—H...O hydrogen bonds, forming ribbons propagating along [10-1]. The ribbons are linkedviaN—H...N hydrogen bonds, forming a three-dimensional structure.
Crystal structure of 4,8-di-tert-butyl-6,6-dichloro-13-ethyl-2,10-dimethyl-13,14-dihydro-12H-dibenzo[d,i][1,3,7,2]dioxazasilecine toluene 0.25-solvate
Authors: Kuchuk Ekaterina A. , Zaitsev Kirill V. , Karlov Sergey S. , Egorov Mikhail P. , Churakov Andrei V.
Published: December 2015

The coordination polyhedron at the silicon atom in the title compound, C26H37Cl2NO2Si·0.25C7H8, is typical for pentacoordinated silicon derivatives and represents a slightly distorted trigonal bipyramid with an N atom and a Cl atom in the apical positions and the two O atoms and the other Cl atom occupying the equatorial sites. There are two independent molecules in the asymmetric unit. The N–Si–Cl fragment in each is close to linear [178.24 (5) and 178.71 (5)°], in good agreement with 4e–3ctheory, as is the elongation of the apical bond lengths [Si—Cl = 2.1663 (7) and 2.1797 (7) Å] in comparison with the equatorial bonds [Si—Cl = 2.0784 (7) and 2.0748 (7) Å]. Orthogonal least-squares fitting of the two independent molecules resulted in r.m.s. deviation of 0.017 Å. The conformations of the two molecules are almost the same, with corresponding torsion angles differing by less than 5.5°. The toluene solvent molecule is disordered about an inversion centre.
Innovation-receiving subsidiaries and dual embeddedness: impact on business performance
Authors: Bresciani Stefano , Ferraris Alberto
Published: December 2015

Purpose

– The purpose of this paper is to investigate the relationship between the degree of subsidiary’s external and internal embeddedness and the contribution on subsidiary’s business performance of a received innovation. In particular it focusses on dual embeddedness of the subsidiary that receives an innovation from the rest of the MNC’s network.

Design/methodology/approach

– Using Amadeus databases were selected 93 CEE subsidiaries located in six countries. Data were collected through a standardized questionnaire and three hypothesis were tested through an OLS regression model.

Findings

– The results indicate that the two types of embeddedness positively affect the received innovation’s contribution on business performance. Moreover, the inclusion of the interaction term shows how a simultaneously high level of embeddedness in both external and internal business networks lead to a multiplicative and positive effect on subsidiary’s business performance. This means that external and internal embeddedness are not mutually exclusive suggesting, at the same time, the presence of interdependencies between the two networks that leads the “dual embedded” subsidiary to better received innovation performance.

Research limitations/implications

– The results are limited due to the sample characteristics and the conceptual focus of network theory. Regarding the first point, the results are derived from MNC coming from developed European countries that are geographically proximate. Regarding the second point, this approach neglects the limitations of networks.

Practical implications

– These results, therefore, propose to management the need to force the subsidiary toward a dual embeddedness in order to achieve better performance when an innovation has been received.

Social implications

– This study puts in evidence how Eastern European policy makers should increase the knowledge sharing and accumulation in the local clusters between all the stakeholders with the aim at increasing the “appeal” of this area.

Originality/value

– The specific contest in which the embedddedness component is analyzed is the main contribution of the paper because most of the previous research have been focussed on subsidiaries that develop and transfer the innovation. Moreover, the specific area where subsidiaries are located (Central and East Europe) may be another important contribution.
An ontology-based computer-aided diagnosis system in African traditional medicine
Authors: Tekemetieu Armel Ayimdji , KOUSSOUBE Souleymane , FOTSO Laure Pauline
Published: December 2015

Purpose

– The purpose of this paper is to describe an AI (Artificial Intelligence) that can “think like an African traditional doctor”. The system proposes to model and to use attitudes taken and concepts used by African traditional doctors when facing cases. It is designed to go deep into the concepts of African traditional medicine (ATM) by dealing with all the possible interpretations of those concepts, and to produce more much satisfying and accurate support for medical diagnosis and prescription than existing systems.

Design/methodology/approach

– To take into account the sometimes strange concepts used and attitudes taken by African traditional healers, including mystical considerations, the system relies on a deep ontology describing all those concepts and attitudes in a more computer readable manner allowing a multi-agent system to have full access to ATM knowledge. Ethnological inquiries, literary analysis and interviews of traditional doctors (the holders of African medicine knowledge) were performed to gather sufficient data to achieve the work.

Findings

– The paper addresses this question of how to build a practical large-scope computer-aided diagnosis and prescription system which can exploit deep descriptions of ATM concepts, including mystical considerations. The system also provides scientific interpretations to some concepts sometimes considered as mystical facts. It is a java web-based platform combined to a Java Agent Development framework multi-agent system accessing an ontology to provide its results.

Research limitations/implications

– Because of the origins of healers involved in this research (from Gabon and Cameroon, countries of Central Africa), the ontology and the collected data may lack generalizability in the African scope and then it is a prototype. Therefore, ATM experts all over the continent are encouraged to participate to improve and standardize the ATM ontology and to populate the knowledge base. On the other side, the system cannot give scientific explanations to all the mystical considerations in ATM, there still some facts which cannot be rationally explained for now.

Practical implications

– The paper demonstrates the practical usability of the implemented system on the diagnosis and the treatment of a patient case.

Social implications

– The research describes a system which once validated by traditional experts, will serve as a tool to assist them in their day-to-day diagnosis and prescription tasks and will also serve as a reference on ATM practices for all interested users.

Originality/value

– The paper provides an in-depth description of a computer-aided diagnosis system (CADS) that promotes indigenous technology from an African perspective. Comparing to the former systems identified in the literature, the proposed system is the first which deals with believes and mystical considerations in ATM, and also the first which provides a function to rank its results.
Toxicity of chlorpyrifos‐methyl to Sitophilus zeamais collected in Korea and biochemical differences
Authors: Choi Won‐Sik , Lee Sung‐Eun
Published: December 2015

In this study, lethal concentration (LC50) values of chlorpyrifos‐methyl (CPM) were determined for two Korean strains (CBNU and KNU) of Sitophilus zeamais. The two strains had similar susceptibilities (1.70 and 1.86 μg a.i./cm2, respectively) to CPM. Carboxylesterase (CE) activity was twice as high in the CBNU strain as in the KNU strain. Lower acetylcholinesterase (AChE) activity was also noted in the latter; however, the activity of glutathione S‐transferase (GST) was twice as high as in the CBNU strain. Gel electrophoresis of CE of crude extracts from adults of the two strains of S. zeamais showed clearly different band patterns, with molecular weights of 60 kDa and 71 kDa in the CBNU and KNU strains, respectively. MALDI‐TOF MS/MS was used to profile small proteins (less than 10 kDa), with results indicating that 206 proteins are expressed differently in the two strains. The peak of interest of 2247.7 m/z was applied to TOF‐TOF MS and its de novo peptide sequence was identified as a tyrosine phosphatase fragment. Phospholipids from the two strains were analyzed and 34 phospholipids were found to be significantly different between strains. Results suggest that the two strains collected from Korea showed different biochemical results, presumably differences in insecticide selection by different living locations.
Frequency, natural course and clinical significance of symptomatic terminal ileitis
Authors: Kedia Saurabh , Kurrey Lalit , Pratap Mouli Venigalla , Dhingra Rajan , Srivastava Saurabh , Pradhan Rajesh , Sharma Raju , Das Prasenjit , Tiwari Veena , Makharia Govind , Ahuja Vineet
Published: December 2015

Objective

Treatment guidelines for managing symptomatic terminal ileitis (TI) are lacking. We followed up a cohort of symptomatic TI patients to conduct an algorithm for their management.

Methods

Consecutive patients with symptomatic TI from July 2007 to October 2013 were included. Symptomatic TI was defined as isolated terminal ileum ulceration (superficial or deep) and/or nodularity with abdominal symptoms. Patients were diagnosed either with intestinal tuberculosis (ITB) or Crohn's disease (CD) using standard criteria or received only symptomatic treatment according to their clinical manifestations, endoscopic, imaging and histological (specific to ITB/CD vs non‐specific) features. Based upon above findings, an algorithm was conducted to differentiate non‐specific TI from those with specific etiology (ITB/CD).

Results

In all, 63/898 (7.0%) patients with ulcero‐constrictive intestinal disease had TI, of which 45 (26 males and 19 females) were included. Fever, diarrhea, weight loss, deep ulcers, and ileal thickening were more frequently observed in patients with ITB or CD having specific treatments compared with those receiving symptomatic treatments. All patients with deep ulcers and those with superficial ulcer and specific histology had ITB/CD. In patients with superficial ulcers and/or nodularity and non‐specific inflammation (n = 31), the absence of fever, diarrhea, GI bleeding or weight loss had a negative predictive value of 92% in excluding ITB/CD.

Conclusions

In symptomatic TI patients with superficial ulcers and a non‐specific histology, the absence of fever, diarrhea, GI bleeding or weight loss rules out the possibility of significant diagnoses like ITB/CD.
Accuracy of the Broselow Tape in South Sudan, “The Hungriest Place on Earth”
Authors: Clark Melissa C. , Lewis Roger J. , Fleischman Ross J. , Ogunniyi Adedamola A. , Patel Dipesh S. , Donaldson Ross I.
Published: December 2015

Objectives

The Broselow tape is a length‐based tool used for the rapid estimation of pediatric weight and was developed to reduce dosage‐related errors during emergencies. This study seeks to assess the accuracy of the Broselow tape and age‐based formulas in predicting weights of South Sudanese children of varying nutritional status.

Methods

This was a retrospective, cross‐sectional study using data from existing acute malnutrition screening programs for children less than 5 years of age in South Sudan. Using anthropometric measurements, actual weights were compared with estimated weights from the Broselow tape and three age‐based formulas. Mid‐upper arm circumference was used to determine if each child was malnourished. Broselow accuracy was assessed by the percentage of measured weights falling into the same color zone as the predicted weight. For each method, accuracy was assessed by mean percentage error and percentage of predicted weights falling within 10% of actual weight. All data were analyzed by nutritional status subgroup.

Results

Only 10.7% of malnourished and 26.6% of nonmalnourished children had their actual weight fall within the Broselow color zone corresponding to their length. The Broselow method overestimated weight by a mean of 26.6% in malnourished children and 16.6% in nonmalnourished children (p < 0.001). Age‐based formulas also overestimated weight, with mean errors ranging from 16.2% over actual weight (Advanced Pediatric Life Support in nonmalnourished children) to 70.9% over actual (Best Guess in severely malnourished children).

Conclusions

The Broselow tape and age‐based formulas selected for comparison were all markedly inaccurate in both the nonmalnourished and the malnourished populations studied, worsening with increasing malnourishment. Additional studies should explore appropriate methods of weight and dosage estimation for populations of low‐ and low‐to‐middle‐income countries and regions with a high prevalence of malnutrition.