bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast Agent–Induced High Signal Intensity in Dentate Nucleus on Unenhanced T1-Weighted Images
Authors: Ichikawa Shintaro , Motosugi Utaroh , Omiya Yoshie , Onishi Hiroshi
Published: February 2017

Objective

The aim of this study was to evaluate whether an association exists between T1-signal increase in the dentate nucleus (DN) on unenhanced magnetic resonance imaging and previous administration of gadoxetic acid and gadodiamide.

Materials and Methods

This retrospective study was approved by the institutional review board; the requirement for informed patient consent was waived. A total of 132 patients (male-female ratio, 86:46; mean age, 68.8 ± 11.6 years) who underwent imaging between December 2000 and April 2016 were divided into 4 groups: patients with 5 or more administrations of gadoxetic acid (“gadoxetic acid ≥5 administrations” group), only 1 administration of gadoxetic acid (“gadoxetic acid 1 administration” group), no gadolinium-based contrast agent (GBCA) administration or chronic liver disease (CLD; “no GBCA administration and no CLD” group), and 5 or more administrations of gadodiamide (“gadodiamide ≥5 administrations” group). Unenhanced T1-weighted images were quantitatively analyzed by 2 radiologists. Intergroup comparison of DN-to-pons signal intensity ratios was performed by the Dunn test, with the no GBCA administration and no CLD group as control. Interobserver agreement was assessed by intraclass correlation coefficients.

Results

The DN-to-pons ratio of the “gadodiamide ≥5 administrations” group was significantly higher (P < 0.0001) and those of the “gadoxetic acid ≥5 administrations” and “gadoxetic acid 1 administration” groups did not differ significantly (P = 0.3912 and 1.0000, respectively) compared with the DN-to-pons ratio of the “no GBCA administration and no CLD” group. The interobserver intraclass correlation coefficient for measurement of DN-to-pons ratio was excellent (0.835; 95% confidence interval, 0.767–0.883).

Conclusions

Hyperintensity in the DN on unenhanced T1-weighted images is associated with previous administration of gadodiamide but not gadoxetic acid. Although the number of administrations for the 2 GBCA groups was identical, the administered dose of gadoxetic acid was only a quarter the amount of gadolinium as those with gadodiamide. This difference might influence the results of this study.
The dual rod system of amphibians supports colour discrimination at the absolute visual threshold
Authors: Yovanovich Carola A. M. , Koskela Sanna M. , Nevala Noora , Kondrashev Sergei L. , Kelber Almut , Donner Kristian
Published: February 2017

The presence of two spectrally different kinds of rod photoreceptors in amphibians has been hypothesized to enable purely rod-based colour vision at very low light levels. The hypothesis has never been properly tested, so we performed three behavioural experiments at different light intensities with toads (Bufo) and frogs (Rana) to determine the thresholds for colour discrimination. The thresholds of toads were different in mate choice and prey-catching tasks, suggesting that the differential sensitivities of different spectral cone types as well as task-specific factors set limits for the use of colour in these behavioural contexts. In neither task was there any indication of rod-based colour discrimination. By contrast, frogs performing phototactic jumping were able to distinguish blue from green light down to the absolute visual threshold, where vision relies only on rod signals. The remarkable sensitivity of this mechanism comparing signals from the two spectrally different rod types approaches theoretical limits set by photon fluctuations and intrinsic noise. Together, the results indicate that different pathways are involved in processing colour cues depending on the ecological relevance of this information for each task.

This article is part of the themed issue ‘Vision in dim light’.
The Deubiquitylating Enzyme Ubp12 Regulates Rad23-Dependent Substrate Delivery at the Proteasome
Authors: Gödderz Daniela , Dantuma Nico P.
Published: February 2017

The consecutive actions of the ubiquitin-selective segregase Cdc48 and the ubiquitin shuttle factor Rad23 result in the delivery of ubiquitylated proteins at the proteasome. Here, we show that the deubiquitylating enzyme Ubp12 interacts with Cdc48 and regulates proteasomal degradation of Rad23-dependent substrates. Overexpression of Ubp12 results in stabilization of Rad23-dependent substrates. We show that Ubp12 removes short ubiquitin chains from the N-terminal ubiquitin-like domain (UbL) of Rad23. Preventing ubiquitylation of Rad23 by substitution of lysine residues within the UbL domain, Rad23UbLK0, does not affect the non-proteolytic role of Rad23 in DNA repair but causes an increase in ubiquitylated cargo bound to the UBA2 domains of Rad23 and recapitulates the stabilization of Rad23-dependent substrates observed upon overexpression of Ubp12. Expression of Rad23UbLK0or overexpression of Ubp12 impairs the ability of yeast to cope with proteotoxic stress consistent with inefficient clearance of misfolded proteins by the ubiquitin/proteasome system. Our data suggest that ubiquitylation of Rad23 plays a stimulatory role in facilitating the transfer of ubiquitylated substrates to the proteasome.

Summary statement

Ubiquitylation of a ubiquitin shuttle factor regulates the delivery of substrates at the proteasome, uncovering a novel regulatory link between ubiquitin and proteasomal degradation.
dRep: A tool for fast and accurate genome de-replication that enables tracking of microbial genotypes and improved genome recovery from metagenomes
Authors: Olm Matthew R. , Brown Christopher T. , Brooks Brandon , Banfield Jillian F.
Published: February 2017

The number of microbial genomes sequenced each year is expanding rapidly, in part due to genome-resolved metagenomic studies that routinely recover hundreds of draft-quality genomes. Rapid algorithms have been developed to comprehensively compare large genome sets, but they are not accurate with draft-quality genomes. Here we present dRep, a program that sequentially applies a fast, inaccurate estimation of genome distance and a slow but accurate measure of average nucleotide identity to reduce the computational time for pair-wise genome set comparisons by orders of magnitude. We demonstrate its use in a study where we separately assembled each metagenome from time series datasets. Groups of essentially identical genomes were identified with dRep, and the best genome from each set was selected. This resulted in recovery of significantly more and higher-quality genomes compared to the set recovered using the typical co-assembly method. Documentation is available athttp://drep.readthedocs.io/en/master/and source code is available athttps://github.com/MrOlm/drep.
In-cell NMR: a topical review
Authors: Luchinat Enrico , Banci Lucia
Published: February 2017

Classical structural biology approaches allow structural characterization of biological macromoleculesin vitro, far from their physiological context. Nowadays, thanks to the wealth of structural data available and to technological and methodological advances, the interest of the research community is gradually shifting from pure structural determination towards the study of functional aspects of biomolecules. Therefore, a cellular structural approach is ideally needed to characterize biological molecules, such as proteins, in their native cellular environment and the functional processes that they are involved in. In-cell NMR is a new application of high-resolution nuclear magnetic resonance spectroscopy that allows structural and dynamical features of proteins and other macromolecules to be analyzed directly in living cells. Owing to its challenging nature, this methodology has shown slow, but steady, development over the past 15 years. To date, several in-cell NMR approaches have been successfully applied to both bacterial and eukaryotic cells, including several human cell lines, and important structural and functional aspects have been elucidated. In this topical review, the major advances of in-cell NMR are summarized, with a special focus on recent developments in eukaryotic and mammalian cells.
(E)-2-{[(5-Chloro-2-methoxyphenyl)imino]methyl}-4-nitrophenol
Authors: Öv Bodur Gönül Sevde , Yavuz Metin , Dege Necmi , Bülbül Hakan , Ağar Erbil
Published: February 2017

The title compound, C14H11ClN2O4, is a Schiff base. Its molecule is approximatelly planar, with a maximum deviation of 0.096 (4) Å from planarity for the methyl C atom of the methoxy group. The dihedral angle between the 5-chloro-2-methoxyphenyl ring and the phenol ring is 2.40 (10)°. In the crystal structure, intermolecular C—H...O hydrogen bonds and π–π stacking interactions consolidate the crystal packing.
Ethyl (E)-2-(2,7-dimethyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-4-ylidene)acetate
Authors: Bassou Oulemda , Chicha Hakima , Bouissane Latifa , Rakib El Mostapha , Saadi Mohamed , El Ammari Lahcen
Published: February 2017

In the title compound, C14H14O5, the two heterocyclic rings are coplanar (r.m.s. deviation = 0.008 Å), with the largest deviation from the mean plane being 0.012 (1) Å. The mean plane through the acetate group is inclined slightly with respect to the oxopyrano[4,3-b]pyran-4-yl system, as indicated by the dihedral angle of 1.70 (7)° between them. Two intramolecular hydrogen bonds, completingS(6) ring motifs, are observed in the molecule. In the crystal, molecules are linked by weak C—H...O hydrogen bonds involving the same acceptor atom, forming chains propagating along thec-axis direction and enclosingR21(6) ring motifs. The chains are linkedviaoffset π–π interactions [intercentroid distance = 3.622 (1) Å], involving inversion-related oxopyrano[4,3-b]pyran-4-yl ring systems, forming slabs parallel to thebcplane.
Applications of the discrete element method and Fibonacci sequence on a banana screen
Authors: Li Zhanfu , Tong Xin
Published: February 2017

Purpose

The purpose of this paper is to design the geometrical structure of banana screen, and this study aims to improve the screen efficiency.

Design/methodology/approach

The discrete element method was used to simulate the sieving process of banana screen with the inclinations of decks improved by Fibonacci sequence. The effect of each deck along screen length on the screening efficiency of particles was studied in this paper.

Findings

The comparisons among three groups of industrial banana screens with five different consecutive Fibonacci numbers have been made, and the variations of fine particle ratio were also investigated. The results show that the banana screening improved by the 5 Fibonacci sequence, 3, 5, 8, 13 and 21, has the good screening performance in the simulation. It is found that the inclination degree of the first deck at the feed end is the key factor to determine screening efficiency of banana screens.

Practical implications

It is not possible to consider all real physical factors exactly in a virtual model. The experiment prototype of banana screen was used to simply verify the feasibility of the methodology.

Originality/value

This work is helpful for designing the geometric parameters of the curved screen and gives a broad perspective to improve the efficiency of banana screens.
PROD2UCT: an outcome-oriented dissertation study model for construction engineering students
Authors: Holt Gary D. , Goulding Jack S.
Published: February 2017

Purpose

This paper presents and describes an outcome-oriented dissertation study model called “PROD2UCT”, designed explicitly for students engaged in construction engineering and related subjects research.

Design/methodology/approach

The model is grounded in theory, underpinned by extant literature and reinforced with professional domain expertise.

Findings

PROD2UCT identifies seven key stages in outcome-oriented dissertation study: pick, recognise, organise, document and draft, undertake, consolidate and tell. These are described along with practical considerations for their effective implementation.

Research limitations/implications

The model’s primary influences stem from “best practice”, experiential knowledge, pedagogical ideals and academic views/values. Given this, it is acknowledged that “representation” and “inference” are typically governed by “subjectivity” (which naturally differs from person-to-person).

Originality/value

Originality is threefold: PROD2UCT encourages students to consider the “end” before the “beginning”; it serves as a road-map offering guidance at seven key chronological stages; finally, it is specifically designed to be outcome-oriented. The latter requires intended dissertation outcomes to align with evidence, research design decisions and implementation methods.
Computer aided weld seam tracking approach
Authors: Deepak B.B.V.L. , Bahubalendruni Raju M.V.A. , Rao Ch A. , Nalini Jalumuru
Published: February 2017

Purpose

This paper aims to automate the welding operation that motion control, sensor integration and coordination with the welding power source. Therefore, there is a need for sophisticated technologies to control precisely the process in terms of positioning the welding torch, and controlling the welding parameters through the use of correct devices which are aided by appropriate control tools and techniques.

Design/methodology/approach

A new seam tracking methodology, named sewing technique, has been introduced for the welded joints available in computer-aided design (CAD) environment. This methodology gives the seam path by drawing a line through the adjacent centroids of curve fitted in the weld joint volume. Obtained geometric path and kinematic constraints are given as input to the modeled robot for performing welding operation followed by desired trajectory.

Findings

In this investigation, a novel and efficient weld seam technique has been developed to produce uniform welded joints. The key feature of this approach is that the initial and end positions of the weld seams can be obtained easily. Because of this, the robot can be controlled flexibly during welding operation.

Originality/value

This investigation deals with the development of an automated seam tracking methodology for the welded joints available in CAD environment. Validation of the developed methodology has been done through simulation results while performing welding operations for different weld profiles.
Depth from extreme points method for gravity gradient tensor data
Authors: Zhou Wenna , Liu Chengying
Published: February 2017

The ‘depth from extreme points’ method is an important tool to estimate the depth of sources of gravity and magnetic data. In order to interpret gravity gradient tensor data conveniently, formulas for the tensor data form regarding depth from the extreme points method were calculated in this paper. Then, all of the gradient tensor components were directly used to interpret the causative source. Beyond the gzz component, also the gxx and gyy components can be used to obtain depth information. In addition, the total horizontal derivative of the depth from extreme points of the gradient tensor can be used to describe the edge information of geologic sources. In this paper, we investigated the consistency of the homogeneity degree calculated by using the different components, which leads to the calculated depth being confirmed. Therefore, a more integrated interpretation can be obtained by using the gradient tensor components. Different synthetic models were used with and without noise to test the new approach, showing stability, accuracy and speed. The proposed method proved to be a useful tool for gradient tensor data interpretation. Finally, the proposed method was applied to full tensor gradient data acquired over the Vinton Salt Dome, Louisiana, USA, and the results are in agreement with those obtained in previous research studies.
A population‐based study on epidemiology of intensive care unit treated traumatic brain injury in Iceland
Authors: Jonsdottir G. M. , Lund S. H. , Snorradottir B. , Karason S. , Olafsson I. H. , Reynisson K. , Mogensen B. , Sigvaldason K.
Published: February 2017

Background

Traumatic brain injury is a worldwide health issue and a significant cause of preventable deaths and disabilities. We aimed to describe population‐based data on intensive care treated traumatic brain injury in Iceland over 15 years period.

Methods

Retrospective review of all intensive care unit admissions due to traumatic brain injury at The National University Hospital of Iceland 1999–2013. Data were collected on demographics, mechanism of injury, alcohol consumption, glasgow come scale upon admission, Injury Severity Scoring, acute physiology and chronic health evaluation II score, length of stay, interventions and mortality (defined as glasgow outcome score one). All computerized tomography scans were reviewed for Marshall score classification.

Results

Intensive care unit admissions due to traumatic brain injury were 583. The incidence decreased significantly from 14/100.000/year to 12/100.000/year. Males were 72% and the mean age was 41 year. Majority of patients (42%) had severe traumatic brain injury. The most common mechanism of injury was a fall from low heights (36.3%). The mortality was 18.2%. Increasing age, injury severity score, Marshall score and acute physiology and chronic health evaluation II score are all independent risk factors for death. Glasgow coma scale was not an independent prognostic factor for outcome.

Conclusions

Incidence decreased with a shift in injury mechanism from road traffic accidents to falls and an increased rate of traumatic brain injury in older patients following a fall from standing or low heights. Mortality was higher in older patients falling from low heights than in younger patients suffering multiple injuries in road traffic accidents. Age, injury severity score, acute physiology and chronic health evaluation II score and Marshall score are good prognostic factors for outcome. Traumatic brain injury continues to be a considerable problem and the increase in severe traumatic brain injury in the middle age and older age groups after a seemingly innocent accident needs a special attention.
Cannabidiol reduces ethanol consumption, motivation and relapse in mice
Authors: Viudez‐Martínez Adrián , García‐Gutiérrez María S. , Navarrón Carmen María , Morales‐Calero María Isabel , Navarrete Francisco , Torres‐Suárez Ana Isabel , Manzanares Jorge
Published: February 2017

This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling‐induced convulsions associated to acute ethanol administration were evaluated. The two‐bottle choice paradigm was performed to assess the effects of CBD (30, 60 and 120 mg/kg/day, i.p.) on ethanol intake and preference. In addition, an oral ethanol self‐administration experiment was carried out to evaluate the effects of CBD [a single s.c. administration of a microparticle formulation providing CBD continuous controlled release (30 mg/kg/day)] on the reinforcement and motivation for ethanol. The effects of CBD (60 and 120 mg/kg/day, i.p.) on ethanol‐induced relapse were also evaluated. Gene expression analyses of tyrosine hydroxylase in ventral tegmental area and μ‐opioid (Oprm1), cannabinoid (CB1r and CB2r) and GPR55 receptors in nucleus accumbens (NAcc) were carried out by real‐time polymerase chain reaction.

Cannabidiol reduced the ethanol‐induced hypothermia and handling‐induced convulsion but failed to modify blood ethanol concentration. CBD reduced ethanol consumption and preference in the two‐bottle choice, significantly decreased ethanol intake and the number of effective responses in the oral ethanol self‐administration, and reduced ethanol‐induced relapse. Furthermore, the administration of CBD significantly reduced relative gene expression of tyrosine hydroxylase in the ventral tegmental area, Oprm1, CB1r and GPR55 in the NAcc and significantly increased CB2r in the NAcc.

Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol. These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.
GABA Inhibits Inhalation Anaesthetic‐induced Membrane Fluidization: A Spin Label Study in Synaptic and Phospholipid Membranes
Authors: Rosenberg P. H. , Alila A.
Published: February 2017

The hydrophobic interaction of GABA (10−3–10−9M) with the inhalation anaesthetic enflurane was studied in synaptic plasma membranes of whole rat brain or of the striatum, synaptic mitochondrial membranes and dipalmitoyl lecithin (DPL) vesicles. Stearic acid spin labels, probing either the C‐5 level (hydrophilic end) or the C‐12 level (hydrophobic end) of the lipid bilayer, were used as indicators of fluidity. Inhalation anaesthetic at 2 mM fluidized the C‐5 and the C‐12 level of the membranes. A concentration of 0.4 mM produced consistently an increased order (stabilization) at the C‐5 level in synaptic plasma membranes. GA BA, added prior to the anaesthetic, caused a dose‐related inhibition of the anaesthetic‐induced fluidization. This restorative effect, which also occurred in DPL vesicles, was not prevented by the GABAa antagonists bicuculline or picrotoxin and was therefore probably not related to receptor mechanisms. When GABA was added after the anaesthetic (2 mM) the inhibition was seen only with 10−3M GABA. GABA did not influence (potentiate) the fluidity changes caused by 0.4 mM inhalation anaesthetic in synaptic membranes. Glutamate had a fluidizing effect, but no interaction with enflurane, at the C‐5 level of DPL only at a high concentration (10−3M). The observed fluidization by enflurane and the restorative effect of GABA, probably through non‐receptor‐hydrophobic interaction, may be involved in the mechanisms of toxic CNS effects.
Differences in Pulmonary Metabolism of Benzo(a)pyrene in Inbred Mouse Strains, Using the Isolated Perfused Lung
Authors: Skelly Michael F. , Shertzer Howard G.
Published: February 2017

The metabolism of benzo(a)pyrene (BaP) was studied in isolated perfused and ventilated lungs from two inbred strains of mice. C57BL/6 and DBA/2 mice were treated with β‐naphthoflavone (BNF) or corn oil alone in order to reveal strain differences in inducibility of the microsomal enzymes responsible for BaP oxidation. BaP metabolism was quantified by the rate of appearance of free and conjugated 14C‐metabolites released into the perfusion medium, and the production of nonextractible metabolites covalently bound to lung macromolecules. In both strains, lungs from mice pretreated with BNF released BaP metabolites at a rate somewhat greater than vehicle‐treated controls, without a distinct change in the profile of metabolites. However, the amount of BaP covalently bound to lung macromolecules was increased by BNF pretreatment in C57BL/6 mice only. Thus, release of BaP metabolites into the perfusion medium was not a predictor of the rate of production of reactive metabolites.
Hepatic and Renal Effects of Prolonged Exposure of Rats to 50 p.p.m. Methoxyflurane
Authors: Plummer John L. , de la M. Hall Pauline , Jenner Mark A. , Ilsley Anthony H. , Cousins Michael J.
Published: February 2017

Male Fischer 344 rats were exposed to air or to 50 p.p.m. methoxyflurane vapour for a period of 14 weeks. At the end of this period, half of the rats in each group were killed; the remainder breathed air only for a further four weeks (recovery period) before being killed. During the exposure period, growth of the methoxyflurane‐exposed rats was markedly depressed, though food consumption was similar in the two groups. Both water consumption and urine volume were increased by methoxyflurane, possibly due to the nephrotoxic effect of fluoride, the concentration of which exceeded 50 micromolar in the sera of all exposed rats. At the end of the exposure period, livers of all exposed rats, but no controls, showed focal hepatocellular degeneration and necrosis, and evidence of liver cell regeneration. Fatty change was prominent. During the recovery period, water consumption and urine volumes returned to near‐normal levels. At the end of the recovery period, focal necrosis was still observed in the livers, although fatty change was no longer present. No histological abnormalities were observed in the kidneys of any rats.
Effect of Dinitrophenol and Anoxia on Isometric Tension in Rabbit Colon Smooth Muscle
Authors: Pettersson Göran
Published: February 2017

In a previous study, it was suggested that inhibition of oxidative phosphorylation in smooth muscle is accompanied by a release of Ca2+ from mitochondria (Pettersson 1983); in this investigation, the effects of 2,4‐dinitrophenol (DNP) and anoxia on isometric tension in pieces of smooth muscle from rabbit colon were studied. Addition of DNP to the bathing medium elicited a transient and dose‐dependent contraction with an ED50 value of 2 × 10−4 M. The contraction was not inhibited by pretreatment with atropine (1 × 10−6M). The removal of external Ca2+ did not reduce the contracting action of DNP. Addition of the local anaesthetic D‐mepivacaine (1 × 10−3 M), which reduces the Ca2+ efflux through the plasma membrane of the smooth muscle cells, augmented the response to DNP. Gassing the bathing medium with 95% N2+ 5% CO2 (anoxia) for 60 min. did not affect the basal tension, but markedly reduced the contractile response to DNP. The results indicate that DNP increased cytoplasmic Ca2+ significantly enough to induce a contraction of rabbit colon smooth muscle by a large release from an intracellular store, probably from the mitochondria. Since anoxia did not mimic the contracting action of DNP, it is suggested that a high concentration of DNP would be a more effective stimulus for mitochondrial Ca2+ release than anoxia.
Vitamin E Protects against Metasystox‐induced Adverse Effect on Lipid Metabolism in the Rat Brain and Spinal Cord
Authors: Tayyaba K. , Hasan Mahdi
Published: February 2017

The effects of vitamin E (α‐tocopherol) on the rate of lipid peroxidation and lipase activity in the discrete areas of the brain and spinal cord were studied. Administration of metasystox in two different doses 1.0 and 2.0 mg/kg body weight intraperitoneally daily for 10 days have shown a dose‐related depletion of total lipids, cholesterol and esterified fatty acids in the rat cerebral hemisphere, cerebellum, brain stem and spinal cord. The rate of lipid peroxidation and lipase activity showed dose‐dependent increase in different regions of the CNS. Administration of α‐tocopherol alone caused significant reduction of lipid peroxidation and lipase activity. When it was administered simultaneously with metasystox, α‐tocopherol prevented the metasystox‐induced increase of lipid peroxidation and lipase activity.
Dual Inhibitory Action of ATP on Adrenergic Neuroeffector Transmission in Rabbit Pulmonary Artery
Authors: Husted Steen E. , Nedergaard Ove A.
Published: February 2017

The aim of this study was to determine whether the inhibitory action of ATP on sympathetic neuroeffector transmission in the isolated pulmonary artery is due to ATP itself or one of its dephosphorylated breakdown products, ADP, AMP or adenosine. Furthermore, the mechanism of the inhibitory action was investigated. ATP (10−6−3 × 10−4 M), the degradation‐resistant ATP‐analogue, β, γ‐methylene‐5′‐triphosphate (10−5−3 × 10−4 M), ADP (10−6−3 × 10−4 M), AMP (10−5−3 × 10−4 M), adenosine (10−5−3 × 10−4 M) and 2‐chloroadenosine (10−7−3 × 10−4 M) reduced the contractions evoked by field‐stimulation. This was also the case for prostaglandin E2 (3 × 10−9−3 × 10−7 M), while prostaglandin F2α(1.4 × 10−8 M) slightly augmented the neurogenic response. The time course of the inhibitory effect of purinergic compounds on the stimulation evoked contractions was studied. In the case of ATP and ADP the inhibition was biphasic: an initial marked block (1 min. after drug addition) which in the continued presence of either compound recovered partially 10 min. later and then remained almost constant for another 90 min. The other purinergic agents caused a monophasic reduction. In the presence of indomethacin (5 × 10−5 M), ATP and ADP also reduced the neurogenic contractions in a monophasic manner. Indomethacin did not alter the β,γ‐methylene‐5′‐triphosphate‐induced inhibition. Dilazep (3 × 10−6 M) plus deoxycoformycin (3.6 × 10−6 M), augmented the inhibitory effect of ATP. In contrast, theophylline (5 × 10−5 M) did not alter the effect of ATP. The inhibitory effect of ATP (10−4 M) on stimulation‐evoked contractions was inversely proportional to the extracellular Ca2+ concentration (0.3–5.2 mM) and to frequency of stimulation (3–15 Hz). These results suggest that ATP initially causes a presynaptic inhibition of noradrenaline release evoked by field‐stimulation. This phase I block is probably mainly due to an ADP‐mediated short‐lasting release of prostaglandins of the E type. The continuous inhibition (phase II) is probably due to ATP and its metabolites, possibly mainly adenosine. The phase II inhibition may possibly involve a decreased entry of Ca2+ into adrenergic nerve terminals during depolarization.
Genetic Differences in Susceptibility to Anticonvulsant Drug‐Induced Developmental Defects
Authors: Finnell Richard H.
Published: February 2017

Abstract: The teratogenicity associated with gestational exposure to anticonvulsant medications remains a significant clinical therapeutic concern. Although most effective antiepileptic agents have been implicated as potential teratogens, the adverse developmental effects associated with phenytoin, trimethadione and valproic acid remain unequivocal. Although approximately 12,000 infants are exposed in utero annually in the United States to these compounds, only 10% will present with the clinical features associated with anticonvulsant drug embryopathies, clearly suggesting the presence of a genetic basis of susceptibility that certain infants inherit. In this article, the genetic basis for such variability in expression, with emphasis on the biochemical and morphological differences that might predominate, are examined in light of recent experimental evidence.
Axonal Transport of Cadmium in the Olfactory Nerve of the Pike
Authors: Gottofrey James , Tjälve Hans
Published: February 2017

109Cd2+ was applied in the olfactory chambers of pikes (Esox lucius) and the dynamics of the axoplasmic flow of the metal was determined in the olfactory nerves by gamma spectrometry and autoradiography. The results showed that the
109Cd2+ is transported at a constant rate along the olfactory nerves. The profile of the 109Cd2+ in the nerves showed a wave front of transported metal followed by a saddle region. When the nasal chambers were washed 2 hr after application of the 109Cd2+ well‐defined transport peaks for the metal were seen in the olfactory axons. The maximal velocity for the transport of 109Cd2+, which corresponds to the movement of the wave front, was 2.38±0.10 mm hr (mean±S.E.) at the experimental temperature (10 C). The average velocity for the transport of the 109Cd2+, which corresponds to the peak apex movement of the wave, was 2.18±0.05 mm/hr (mean±S.E.) at 10 C. The transported 109Cd2+ was strongly accumulated in the anterior parts of the olfactory bulbs, whereas in other brain areas the levels of the metal remained low. Autoradiography of a pike exposed to 109Cd2+ via the water showed a strong labelling in the receptor‐cell‐containing olfactory rosettes, whereas other structures in the olfactory chambers were only weakly labelled. The accumulation and axonal transport in the olfactory neurons may be noxious and constitute an important component in the toxicology of cadmium in fish, and this may apply also to some other heavy metals.
Biological Responses of Isolated Macrophages to Cobalt Metal and Tungsten Carbide‐Cobalt Powders
Authors: Lison D. , Lauwerys R.
Published: February 2017

A previous study from this laboratory, using morphological and biochemical (LDH release) parameters, has shown that tungsten carbide‐cobalt dust exhibits a greater cytotoxicity toward isolated macrophages than cobalt metal powder alone. The present study extends this comparison by examining additional biological parameters. Glucose uptake and superoxide anion production by isolated macrophages were significantly more depressed by the tungsten carbidecobalt mixture (WC—Co) than by cobalt alone (Co) while pure tungsten carbide (WC) had no effect or even stimulated the cells. For glucose‐6‐phosphate dehydrogenase and cell‐associated plasminogen activator (PA) activities, no difference between Co and WC—Co dusts was observed. These observations add further evidence to our previous findings regarding the different biological reactivity of cobalt metal alone or mixed with tungsten carbide.
Protective Effect of Vitamin A against the MethotrexateInduced Damage to Small Intestine: A Study on the Crypt Cells
Authors: Kosakai Yoshinori , Horie Toshiharu , Awazu Shoji
Published: February 2017

Vitamin A (VA) protects the small intestine from the methotrexate (MTX)‐induced damage. The in vivo effects of MTX and/or VA on crypt cells of small intestine were investigated using rats orally administered MTX (15 mg/kg body weight) and/or VA (5,000 IU/kg body weight). The thymidine kinase activity of crypt cells separated from villus cells of small intestine of MTX plus VA‐treated rats was lower than that from control rats but higher than that from MTX‐treated rats. VA‐treated rats showed almost the same activity of thymidine kinase as control rats. The amounts of the end products, adenosine monophosphate (AMP) and guanosine monophosphate (GMP), contained in crypt cells of treated rats were determined to investigate the in vivo effects of MTX and/or VA on de novo purine synthesis. MTX treatment significantly decreased the amounts of both AMP and GMP but both amounts were not affected by MTX plus VA treatment. Treatment with VA alone appeared to increase their amounts slightly. Thus, although the oral administration of MTX to rats inhibited DNA synthesis in crypt cells, VA coadministration protected the salvage pathway of pyrimidine synthesis and the de novo purine synthesis in crypt cells.
Dimensions of personalisation in technology‐enhanced learning: A framework and implications for design
Authors: FitzGerald Elizabeth , Kucirkova Natalia , Jones Ann , Cross Simon , Ferguson Rebecca , Herodotou Christothea , Hillaire Garron , Scanlon Eileen
Published: February 2017

Personalisation of learning is a recurring trend in our society, referred to in government speeches, popular media, conference and research papers and technological innovations. This latter aspect—of using personalisation in technology‐enhanced learning (TEL)—has promised much but has not always lived up to the claims made. Personalisation is often perceived to be a positive phenomenon, but it is often difficult to know how to implement it effectively within educational technology.

In order to address this problem, we propose a framework for the analysis and creation of personalised TEL. This article outlines and explains this framework with examples from a series of case studies. The framework serves as a valuable resource in order to change or consolidate existing practice and suggests design guidelines for effective implementations of future personalised TEL.
Long noncoding RNA SchLAH suppresses metastasis of hepatocellular carcinoma through interacting with fused in sarcoma
Authors: Ge Zhouhong , Cheng Zhuoan , Yang Xinrong , Huo Xisong , Wang Ning , Wang Hui , Wang Cun , Gu Dishui , Zhao Fangyu , Yao Ming , Fan Jia , Qin Wenxin
Published: February 2017

Emerging evidence has indicated that deregulation of long non‐coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells. Knockdown of SchLAH by siRNA pool promoted the migration of HCC cells. RNA pull‐down and RNA immunoprecipitation assays demonstrated SchLAH physically interacted with fused in sarcoma (FUS). PCR array analysis showed that RhoA and Rac1 were the downstream effector molecules of SchLAH during HCC metastasis. Knockdown of FUS rescued the mRNA levels of RhoA and Rac1 that were repressed by SchLAH. These results suggest that SchLAH may suppress the metastasis of HCC cells by interacting with FUS, which indicates potential of SchLAH for the prognosis and treatment of HCC.
Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism
Authors: Xu C. , Lang‐Muritano M. , Phan‐Hug F. , Dwyer A.A. , Sykiotis G.P. , Cassatella D. , Acierno J. , Mohammadi M. , Pitteloud N.
Published: February 2017

Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin‐releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle‐stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell‐based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss‐of‐function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood.
The current spectrum of contact sensitization in patients with chronic leg ulcers or stasis dermatitis – new data from the Information Network of Departments of Dermatology (IVDK)
Authors: Erfurt‐Berge Cornelia , Geier Johannes , Mahler Vera
Published: February 2017

Background

Patients with lower leg dermatitis, chronic venous insufficiency or chronic leg ulcers have a high prevalence of contact sensitization.

Objectives

To identify the current spectrum of contact allergens in these patients.

Patients and methods

Data of the Information Network of Departments of Dermatology on 5264 patients with the above diagnoses from the years 2003 to 2014 (study group) were compared with data on 4881 corresponding patients from 1994 to 2003 (historical control group) and with a current control group without these diagnoses (n = 55 510).

Results

Allergic contact dermatitis was diagnosed less frequently in the study group than in the historical control group (25.9% versus 16.9%; p < 0.001), and contact sensitization to most allergens had declined. The allergen spectrum, however, was largely unchanged. Important allergens are Myroxylon pereirae (balsam of Peru) (14.8% positive reactions), fragrance mix I (11.4%), lanolin alcohol (7.8%), colophonium (6.6%), neomycin sulfate (5.0%), cetearyl alcohol (4.4%), oil of turpentine (3.1%), and paraben mix (2.6%). Patch testing with additional series showed sensitization to Amerchol L‐101 (9.7%), tert‐butyl hydroquinone (8.7%), framycetin sulfate (5.0%), and gentamicin sulfate (3.1%).

Conclusions

Topical preparations for treating the above‐mentioned conditions should not contain fragrances, Myroxylon pereirae, and colophonium. The special allergen spectrum has to be considered in patch testing.
Aid Effectiveness: On the Radar and Off the Radar
Authors: Husain Matt M.
Published: February 2017

Poverty is a human construct, yet the Euro‐American development assistance programmes that aim to reduce poverty remain a function of systemic problems, profit and politics. Critics argue that widened global income inequality and neoliberalism's ineffectiveness in the Global South can be reflected in recent geopolitical and epistemic tensions. China's rise as an economic and military power and its authority in setting up the Asian Infrastructure and Investment Bank directly threaten Euro‐American dominance in development discourse. These changes can bring multiple perspectives in the aid effectiveness debate. While these views introduce alternatives to the business approach of poverty reduction, they also make the Sustainable Development Goals appear more significant than ever.
Multilateral Trade Liberalisation and Foreign Direct Investment Inflows
Authors: Gnangnon Sèna Kimm
Published: February 2017

This paper investigates two questions: how does multilateral trade liberalisation affect inward foreign direct investment, and does this impact (if any) depend on the domestic trade policy? The analysis uses a panel data set comprising 171 countries spanning the period 1995–2012. Results indicate that multilateral trade policy liberalisation is conducive to higher FDI inflows in host countries. Furthermore, our evidence suggests that domestic trade policy almost always positively drives inward FDI in a context of multilateral trade policy liberalisation. Countries which initially have the most restrictive trade policy regimes appear to be the greatest beneficiaries of FDI inflows when they liberalise their trade policy in the context of multilateral trade liberalisation.
Plant–pollinator networks in semi‐natural grasslands are resistant to the loss of pollinators during blooming of mass‐flowering crops
Authors: Magrach Ainhoa , Holzschuh Andrea , Bartomeus Ignasi , Riedinger Verena , Roberts Stuart P. M. , Rundlöf Maj , Vujić Ante , Wickens Jennifer B. , Wickens Victoria J. , Bommarco Riccardo , González‐Varo Juan P. , Potts Simon G. , Smith Henrik G. , Steffan‐Dewenter Ingolf , Vilà Montserrat
Published: February 2017

Mass‐flowering crops lead to spatial redistributions of pollinators and to transient shortages within nearby semi‐natural grasslands, but the impacts on plant–pollinator interactions remain largely unexplored. Here, we characterised which pollinator species are attracted by oilseed rape and how this affected the structure of plant–pollinator networks in nearby grasslands. We surveyed 177 networks from three countries (Germany, Sweden and United Kingdom) in 24 landscapes with high crop cover, and compared them to 24 landscapes with low or no oilseed rape during and after crop blooming. On average 55% of grassland pollinator species were found on the crop, which attracted 8–35% of individuals away from grasslands. However, networks in the grasslands were resistant to these reductions, since mainly abundant and highly mobile species were attracted. Nonetheless, simulations indicated that network structural changes could be triggered if > 50% of individuals were attracted to the crop (a value well‐above that found in our study system), which could affect community stability and resilience to further disturbance.
The twilight of the setter? Public school budgets in a time of institutional change
Authors: Corcoran Sean , Romer Thomas , Rosenthal Howard
Published: February 2017

We use a policy change that occurred in Oregon in the late 1980s to re‐visit the budget‐maximizing agenda setter theory of local public expenditure. Prior to 1987, Oregon school districts held operating levy elections with an exogenous, often zero or very low, spending reversion. From 1987 through 1990, districts experienced a “safety net” regime where the reversion was at least the previous year's nominal spending. We find that the “safety net” sharply limited the agenda setter's ability to use the reversion as a threat to obtain voter approval of relatively large expenditures.
Spring predictability explains different leaf‐out strategies in the woody floras of North America, Europe and East Asia
Authors: Zohner Constantin M. , Benito Blas M. , Fridley Jason D. , Svenning Jens‐Christian , Renner Susanne S.
Published: February 2017

Intuitively, interannual spring temperature variability (STV) should influence the leaf‐out strategies of temperate zone woody species, with high winter chilling requirements in species from regions where spring warming varies greatly among years. We tested this hypothesis using experiments in 215 species and leaf‐out monitoring in 1585 species from East Asia (EA), Europe (EU) and North America (NA). The results reveal that species from regions with high STV indeed have higher winter chilling requirements, and, when grown under the same conditions, leaf out later than related species from regions with lower STV. Since 1900, STV has been consistently higher in NA than in EU and EA, and under experimentally short winter conditions NA species required 84% more spring warming for bud break, EU ones 49% and EA ones only 1%. These previously unknown continental‐scale differences in phenological strategies underscore the need for considering regional climate histories in global change models.
Atgl deficiency induces podocyte apoptosis and leads to glomerular filtration barrier damage
Authors: Chen Wen , Jiang Youzhao , Han Jian , Hu Jiongyu , He Ting , Yan Tiantian , Huang Na , Zhang Qiong , Mei Hao , Liao Yong , Huang Yuesheng , Chen Bing
Published: February 2017

Abnormal lipid metabolism, renal lipid accumulation and lipotoxicity are associated with the pathological features of glomerulopathy. However, the mechanisms by which lipid accumulation leads to the development or progression of this disease have not been fully elucidated. In this work, we have identified a role for the rate‐limiting enzyme in lipolysis, adipose triglyceride lipase (ATGL; also called patatin‐like phospholipase domain‐containing protein 2), in renal lipid metabolism and kidney disease. ATGL‐deficient (Atgl(−/−)) mice displayed albuminuria, accompanied by ectopic deposition of fat in the kidney. Magnetic resonance imaging demonstrated that the contrast agent gadopentetic acid was retained in kidney tissue, suggesting defects in the glomerular filtration barrier. Furthermore, transmission electron microscopy revealed lipid deposits in the podocyte, along with foot process fusion and morphological changes suggestive of apoptosis. Indeed, shRNA‐mediated depletion of ATGL promoted podocyte apoptosis, accompanied by increased levels of intracellular reactive oxygen species (ROS) and F‐actin fibre redistribution. These effects could be partially reversed by treatment with the antioxidant N‐acetylcysteine. These data suggest that ATGL deficiency induces renal lipid accumulation, proteinuria and glomerular filtration barrier dysfunction and implicate increased intracellular ROS levels in inducing podocyte F‐actin rearrangement, foot process fusion and apoptosis that underlie these pathological features.

Enzymes

Adipose triglyceride lipase, EC3.1.1.3.