bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Acetate‐Free Citrate Hemodialysis and Bicarbonate Hemodialysis Regarding the Effect of Intra‐Dialysis Hypotension and Post‐Dialysis Malaise
Authors: Daimon Shoichiro , Dan Kazushi , Kawano Mitsuhiro
Published: September 2011

Compared with acetate dialysate, bicarbonate dialysate has shown beneficial effects in reducing the morbidity associated with dialysis, but a small amount of acetate in bicarbonate dialysate may evoke hypotension or malaise. Acetate‐free citrate hemodialysis (AFHD) may avoid these problems. In 44 hemodialysis patients bicarbonate hemodialysis (BHD) was conducted for three months, followed by a switch to AFHD for three months, and a further switch to bicarbonate hemodialysis (ReBHD). In BHD, AFHD and ReBHD, intra‐dialysis hypotension and post‐dialysis malaise were determined (hypotension: intra‐dialysis systolic blood pressure (SBP) was expressed as a percentage of SBP at the start of hemodialysis, malaise was assessed by a self‐reported 0 to 3 scale, 0: absence of malaise, 3: unbearable malaise). Compared with BHD, AFHD patients complained of less malaise but the intra‐dialysis blood pressure change did not differ significantly (malaise: BHD 0.73 ± 0.76 vs. AFHD 0.32 ± 0.47, P < 0.0001, end hemodialysis SBP: BHD 93.6 ± 8.9 vs. AFHD 93.8 ± 10.1, P = NS). After switching to ReBHD from AFHD, the malaise score increased (AFHD 0.32 ± 0.47 vs. ReBHD 0.77 ± 0.89, P < 0.0001) and the intra‐dialysis blood pressure dropped markedly (end hemodialysis SBP: AFHD 93.8 ± 10.1 vs. ReBHD 87.3 ± 10.5, P < 0.0001). Malaise was very severe in five patients who could not continue ReBHD. After ten days under ReBHD, ReBHD was changed to AFHD again in all patients. Although the exact mechanisms are not known, AFHD may be preferable to BHD to prevent hemodialysis‐induced hypotension and malaise.
Is the Spontaneously Hypertensive Stroke Prone Rat a Pertinent Model of Sub Cortical Ischemic Stroke? A Systematic Review
Authors: Bailey Emma L. , Smith Colin , Sudlow Cathie L. M. , Wardlaw Joanna M.
Published: September 2011

The spontaneously hypertensive stroke prone rat is best known as an inducible model of large artery stroke. Spontaneous strokes and stroke propensity in the spontaneously hypertensive stroke prone rat are less well characterized; however, could be relevant to human lacunar stroke. We systematically reviewed the literature to assess the brain tissue and small vessel pathology underlying the spontaneous strokes of the spontaneously hypertensive stroke prone rat. We searched systematically three online databases from 1970 to May 2010; excluded duplicates, reviews, and articles describing the consequences of induced middle cerebral artery occlusion or noncerebral pathology; and recorded data describing brain region and the vessels examined, number of animals, age, dietary salt intake, vascular and tissue abnormalities. Among 102 relevant studies, animals sacrificed after developing stroke-like symptoms displayed arteriolar wall thickening, subcortical lesions, enlarged perivascular spaces and cortical infarcts and hemorrhages. Histopathology, proteomics and imaging studies suggested that the changes not due simply to hypertension. There may be susceptibility to endothelial permeability increase that precedes arteriolar wall thickening, degeneration and perivascular tissue changes; systemic inflammation may also precede cerebrovascular changes. There were very few data on venules or tissue changes before hypertension. The spontaneously hypertensive stroke prone rat shows similar features to human lacunar stroke and may be a good spontaneous model of this complex human disorder. Further studies should focus on structural changes at early ages and genetics to identify factors that predispose to vascular and brain damage.
Barrett's esophagus registries
Authors: Gatenby Piers A.C. , Caygill Christine P.J. , Watson Anthony , Murray Liam , Romero Yvonne
Published: September 2011

The following on Barrett's esophagus registries contains commentaries on the data sets to be included, organizational issues, and the demographic, lifestyle, and diagnostic differences between the United States and Europe. The importance of collaborative studies is also discussed.
Barrett's esophagus and animal models
Authors: Macke Ryan A. , Nason Katie S. , Mukaisho Ken‐ichi , Hattori Takanori , Fujimura Takashi , Sasaki Shozo , Oyama Katsunobu , Miyashita Tomoharu , Ohta Tetsuo , Miwa Koichi , Gibson Michael K. , Zaidi Ali , Malhotra Usha , Atasoy Ajlan , Foxwell Tyler , Jobe Blair
Published: September 2011

The following on Barrett's esophagus (BE) and animal models contains commentaries on the factors of BE carcinogenesis; a duodenoesophageal reflux model; translation of targeted therapies for esophageal adenocarcinoma; and novel target regimens selected through a proteomics screen.
What Sherrington missed: the ubiquity of the neural integrator
Authors: Carpenter R. H. S.
Published: September 2011

Despite its numerous illustrations unequivocally demonstrating the phenomenon, in Sherrington's Integrative Action of the Nervous System, he considered “integration” only in its spatial and coordinative aspects, and failed to notice time integration as an equally pervasive feature of all motor systems. First demonstrated in the oculomotor system by Robinson and others, in the vestibulo‐ocular reflex, and then as a necessary component of the oculomotor “final common path” (another Sherringtonian concept), integration is manifested at two further levels: in generating optokinetic responses and in the mechanism of saccadic decision. But integration is not a purely oculomotor phenomenon: behind it lie two fundamental motor principles. First, that the brain operates in terms of change, implying differentiation in sensory systems and integration in motor ones. Second, that the molecular physiology of muscle contraction means that remaining still requires not only continual expenditure of energy but also continual computational effort—a firm and precise integrator.
Expanding repertoire in the oculomotor periphery: selective compartmental function in rectus extraocular muscles
Authors: Demer Joseph L. , Clark Robert A. , da Silva Costa Roberta M. , Kung Jennifer , Yoo Lawrence
Published: September 2011

Since connective tissue pulleys implement Listing's law by systematically changing rectus extraocular muscle (EOM) pulling directions, non‐Listing's law gaze dependence of the vestibulo‐ocular reflex is currently inexplicable. Differential activation of compartments within rectus EOMs may endow the ocular motor system with more behavioral diversity than previously supposed. Innervation to horizontal, but not vertical, rectus EOMs of mammals is segregated into superior and inferior compartments. Magnetic resonance imaging in normal subjects demonstrates contractile changes in the lateral rectus (LR) inferior, but not superior, compartment during ocular counter‐rolling (OCR) induced by head tilt. In human orbits ipsilesional to unilateral superior oblique palsy, neither LR compartment exhibits contractile change during head tilt, although the inferior compartment contracts normally in contralesional orbits. This suggests that differential compartmental LR contraction assists normal OCR. Computational simulation suggests that differential compartmental action in horizontal rectus EOMs could achieve more force than required by vertical fusional vergence.
Paraneoplastic disorders of eye movements
Authors: Wray Shirley H. , Dalmau Josep , Chen Athena , King Susan , Leigh R. John
Published: September 2011

Paraneoplastic syndromes affecting the brainstem and cerebellum are reported to cause a variety of abnormalities of eye movements. Recent studies have begun to account for the mechanisms underlying several syndromes, characterized by opsoclonus, slow, or dysmetric saccades, as well as downbeat nystagmus. We provide evidence that upbeat nystagmus in a female patient with pancreatic cancer reflected a cerebellar‐induced imbalance of otolithic pathways: she showed marked retropulsion, and her nystagmus was dependent on head position, being absent when supine, and suppressed with convergence. In addition to anti‐Hu antibodies, we demonstrated antibodies to a novel neuronal cell surface antigen. Taken with other recent studies, our findings suggest that paraneoplastic syndromes arise due to antibodies against surface neuronal antigens, including receptors and channels. Abnormal eye movements in paraneoplastic syndromes offer insights into the pathogenesis of these disorders and the opportunity to test potential therapies, such as new drugs with effects on neuronal channels.
Pharmacological tests of hypotheses for acquired pendular nystagmus
Authors: Shaikh Aasef G. , Thurtell Matthew J. , Optican Lance M. , Leigh R. John
Published: September 2011

Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for their pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus.
Three‐dimensional kinematics of saccadic eye movements in humans: is the “half‐angle rule” obeyed?
Authors: Thurtell Matthew J. , Joshi Anand C. , Leigh R. John , Walker Mark F.
Published: September 2011

The “half‐angle rule” must be satisfied for Listing's law to be obeyed during saccades: the eye velocity axis must tilt away from Listing's plane by half the angle of eye position eccentricity from primary position. We aimed to determine if this rule is satisfied during saccades. Horizontal and vertical saccades were recorded using the search coil technique, at different elevations and azimuths, in five normal humans. In all, eye positions were located on a twisted rather than planar surface. The mean tilt‐angle coefficients (TACs; ratio of angle of eye velocity axis tilt to angle of eye position eccentricity) were 0.57 and 0.34 for horizontal and vertical saccades, respectively. TACs were significantly lower for vertical saccades. Thus, Listing's law is not perfectly obeyed during saccades. We suggest that the discrepancy in horizontal and vertical TACs causes eye positions to lie on a twisted rather than planar surface in three‐dimensional space.
Patterns of dissociate torsional–vertical nystagmus in internuclear ophthalmoplegia
Authors: Jeong Seong‐Hae , Kim Eung Kyu , Lee Jun , Choi Kwang‐Dong , Kim Ji Soo
Published: September 2011

To explore the patterns and mechanisms of jerky seesaw nystagmus in internuclear ophthalmoplegia (INO), we analyzed the nystagmus patterns in 33 patients with dissociated torsional–vertical nystagmus and INO. In 11 (33%) patients, the nystagmus was ipsiversive torsional in both eyes with vertical components in the opposite directions. In contrast, 18 (55%) patients showed ipsiversive torsional nystagmus with a larger upbeat component in the contralesional eye. Four (12%) patients exhibited ipsiversive torsional nystagmus with a greater downbeat component in the ipsilesional eye. At least one component of contraversive ocular tilt reaction was associated in most patients (30/33, 91%). The patterns of jerky seesaw nystagmus in INO suggest a disruption of neural pathways from the contralateral vertical semicircular canals with or without concomitant damage to the fibers from the contralateral utricle in or near the medial longitudinal fasciculus.
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video‐oculographic diagnosis
Authors: Szmulewicz David J. , Waterston John A. , MacDougall Hamish G. , Mossman Stuart , Chancellor Andrew M. , McLean Catriona A. , Merchant Saumil , Patrikios Peter , Halmagyi G. Michael , Storey Elsdon
Published: September 2011

The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a distinct syndrome with a characteristic and measurable clinical sign—an absent visually enhanced vestibulo‐ocular reflex—in 2004. We reviewed 27 patients with this syndrome and show that a non‐length‐dependent sensory deficit with absent sensory nerve action potentials is an integral component of this syndrome, which we now call “cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome” (CANVAS). All patients had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I. Brain and temporal bone pathology in one patient showed marked loss of Purkinje cells and of vestibular, trigeminal, and facial ganglion cells, but not of spiral ganglion cells. There are two sets of sibling pairs, suggesting CANVAS is a late‐onset recessive disorder. The characteristic clinical sign—the visual vestibulo‐ocular reflex deficit—can be demonstrated and measured clinically using video‐oculography.
Vertical alignment in monkeys with unilateral IV section: effects of prolonged monocular patching and trigeminal deafferentation
Authors: Shan Xiaoyan , Hamasaki Ichiro , Tian Jing , Ying Howard S. , Tamargo Rafael J. , Zee David S.
Published: September 2011

We investigated monocular viewing and trigeminal (V) deafferentation on the vertical deviation (VD) in monkeys following intracranial IV section. Two monkeys wore a patch for four to six weeks, one over the paretic eye and the other over the normal eye following IV section. Two other monkeys had combined IV and V section with the paretic eye patched postlesion. In monkeys with IV section alone, the VD lessened within the first week postlesion but then increased gradually with the same eye still patched. Thus binocular viewing was unnecessary for the later VD increase. With combined IV and V section, the VD also transiently lessened postlesion. We have proposed that the decrease in VD after IV section is adaptive, driven by an error signal using ocular proprioception and efference copy. Since V section did not eliminate the early decrease in VD, we suggest some orbital afference is transmitted centrally via other cranial nerves. However, the later increase in VD suggests either that the proprioceptive effect cannot be sustained or that mechanical changes supervene to increase the VD.
Effects of unilateral midbrain lesions on gaze (eye and head) movements
Authors: Kremmyda Olympia , Glasauer Stefan , Guerrasio Lorenzo , Büttner Ulrich
Published: September 2011

The rostral midbrain, especially the rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF) and the interstitial nucleus of Cajal (INC), plays an important role in the control of eye movements. Although the effect of midbrain lesions on eye movements is well investigated, little is known about its effect on head movements. In this study, we measured eye and head (gaze) movements in five patients with unilateral, acute midbrain lesions and nine healthy controls. In all patients, vertical eye velocity was reduced as a result of the lesion compared to healthy subjects, whereas peak head velocity was not affected. Further, most patients displayed an increased contralesional torsion in peripheral head positions, independently of whether they presented a head tilt in the straight‐ahead position or not. Our results indicate that midbrain lesions affect the control of eye and head differently and independently.
Clinical, electrophysiological, and MRI findings in patients with cerebellar ataxia and a bilaterally pathological head‐impulse test
Authors: Kirchner Hanni , Kremmyda Olympia , Hüfner Katharina , Stephan Thomas , Zingler Vera , Brandt Thomas , Jahn Klaus , Strupp Michael
Published: September 2011

A significant number of patients with bilateral vestibulopathy suffer from cerebellar ataxia and central vestibular symptoms and vice versa. We examined 31 patients presenting with the combination of gait and stance ataxia, cerebellar ocular motor signs, and a bilaterally pathological head‐impulse test (HIT). Tests included neuro‐orthoptical examination, electromyography and neurography, caloric irrigation, pure‐tone audiogram, vestibular‐evoked myogenic potentials, and volumetric magnetic resonance imaging (MRI). Only 17 of 31 patients had a pathological caloric irrigation. Twenty‐three patients had evidence of polyneuropathy (predominantly mixed sensorimotor involving axonal loss and demyelination) and twenty of hypoacusis (1 unilateral and 19 bilateral). Voxel‐based morphometry comparing local gray matter brain volume between patients and controls revealed cerebellar atrophy involving both the vermis and the hemispheres. We conclude that there is a clinically relevant combination of cerebellar ataxia with cerebellar atrophy, bilaterally pathological HIT, polyneuropathy, and hypoacusis. This multisensory syndrome is most likely caused by a neurodegenerative disorder affecting different systems, leading to severe impairment of affected patients.
Triggering mechanisms in microsaccade and saccade generation: a novel proposal
Authors: Otero‐Millan Jorge , Macknik Stephen L. , Serra Alessandro , Leigh R. John , Martinez‐Conde Susana
Published: September 2011

Saccades are rapid eye movements that change the line of sight between successive points of fixation. Even as we attempt to fixate our gaze precisely, small rapid eye movements called microsaccades interrupt fixation one or two times each second. Although the neural pathway controlling saccade generation is well understood, the specific mechanism for triggering microsaccades is unknown. Here, we review the evidence suggesting that microsaccades and saccades are generated by the same neural pathway. We also discuss current models of how the saccadic system produces microsaccades. Finally, we propose a new mechanism for triggering both microsaccades and saccades, based on a circuit formed by omnipause and long‐lead burst neurons and driven by activity in the superior colliculus. Our model differs from previous proposals in that it does not require superior colliculus activity to surpass a particular threshold to trigger microsaccades and saccades. Rather, we propose that the reciprocal inhibition between omnipause and long‐lead burst neurons gates each microsaccadic or saccadic event, triggering the eye movement whenever the activity in the long‐lead burst neurons overcomes the inhibition from the omnipause neurons.
Geological Setting and Origin of Mo–W–Cu Deposits in the Honggor–Shamai District, Inner Mongolia, North China
Authors: NIE Feng‐Jun , JIANG Si‐Hong
Published: September 2011

Twenty‐one Mo–W–Cu deposits and prospects have been discovered in the Honggor–Shamai district, Inner Mongolia, north China during past 5 years. This district is located in the central and western parts of the Chagan Obo–Aoyoute–Chaobulen tectono‐magmatic belt, which is part of the Central Asian Orogenic Belt. The Mo–W–Cu deposits in the district are associated with Mesozoic granitoid intrusions and occur as veins, stockwork, and dissemination. The geological features of these newly discovered deposits are similar to porphyry‐type deposits worldwide. Two mineralization events have been identified: Indosinian (235–224 Ma) and Yanshanian (137–131 Ma). It is proposed that these deposits and prospects in the Honggor–Shamai district were related to the post‐collisional extension linked to the Indosinian orogeny during the Middle–Late Triassic period, but some of those deposits were overprinted by mineralization associated with the Cretaceous magmatic‐hydrothermal (Yanshanian) event.
He–Ar Isotope Composition of Pyrite and Wolframite in the Tieshanlong Tungsten Deposit, Jiangxi, China: Implications for Fluid Evolution
Authors: LI Guanglai , HUA Renmin , ZHANG Wenlan , HU Dongquan , WEI Xinglin , HUANG Xiao'e , XIE Lei , YAO Junming , WANG Xudong
Published: September 2011

The Tieshanlong tungsten‐polymetallic deposit is a large wolframite deposit of quartz vein type located in southern Jiangxi, South China. It is genetically related to a high‐K S‐type granite. Seven pyrite and two wolframite samples, selected for He and Ar isotope analyses, yielded 3He/4He values of 0.04–0.98 Ra, 40Ar/36Ar ratios of 293.5–368.0, and 38Ar/36Ar ratios of 0.176–0.193. These data indicate that the ore‐forming fluids associated with the deposit did not result from a simple mixing of the crustal‐ and mantle‐derived end‐member fluids, but that primeval meteoric fluids were also involved in the generation of the associated granitic magma by partial melting of crustal metasedimentary rocks. Further investigations show that only minimal He from the mantle was added during generation of the associated granitic magma. It is postulated that boiling and second mixing with “new” meteoric fluids took place during migration of magmatic‐hydrothermal fluids into wall‐rock fractures, resulting in a drastic decrease of their metal transport capacity, which triggered the tungsten‐polymetallic mineralization.
Formation of the Dongmozhazhua Pb–Zn Deposit in the Thrust‐Fold Setting of the Tibetan Plateau, China: Evidence from Fluid Inclusion and Stable Isotope Data
Authors: LIU YingChao , HOU ZengQian , YANG ZhuSen , TIAN ShiHong , YANG TianNan , SONG YuCai , ZHANG HongRui , CARRANZA Emmanuel John M.
Published: September 2011

The Dongmozhazhua deposit, the largest Pb–Zn deposit in south Qinghai, China, is stratabound, carbonate‐hosted and associated with epigenetic dolomitization and silicification of Lower–Middle Permian—Upper Triassic limestones in the hanging walls of a Cenozoic thrust fault system. The mineralization is localized in a Cenozoic thrust‐folded belt along the northeastern edge of the Tibetan plateau, which was formed due to the India–Asia plate collision during the early Tertiary. The deposit comprises 16 orebodies with variable thicknesses (1.5–26.3 m) and lengths (160–1820 m). The ores occur as dissemination, vein, and breccia cement. The main sulfide assemblage is sphalerite + galena + pyrite + marcasite ± chalcopyrite ± tetrahedrite, and gangue minerals consist mainly of calcite, dolomite, barite, and quartz. Samples of pre‐ to post‐ore stages calcite yielded δ13C and δ18O values that are, respectively, similar to and lower than those yielded by the host limestones, suggesting that the calcite formed from fluids derived from carbonate dissolution. Fluid inclusions in calcite and sphalerite in the polymetallic sulfidization stage mostly comprise liquid and gas phases at room temperature, with moderate homogenization temperatures (100–140°C) and high salinities (21–28 wt% NaCl eq.). Micro‐thermometric fluid inclusion data point to polysaline brines as ore‐forming fluids. The δD and δ18O values of ore fluids, cation compositions of fluid inclusions, and geological information suggest two main possible fluid sources, namely basinal brines and evaporated seawater. The fluid inclusion data and regional geology suggest that basinal brines derived from Tertiary basins located southeast of the Dongmozhazhua deposit migrated along deep detachment zones of the regional thrust system, leached substantial base metals from country rocks, and finally ascended along thrust faults at Dongmozhazhua. There, the base‐metal‐rich basinal brines mixed with bacterially‐reduced H2S‐bearing fluids derived from evaporated seawater preserved in the Permo–Triassic carbonate strata. The mixing of the two fluids resulted in Pb–Zn mineralization. The Dongmozhazhua Pb–Zn deposit has many characteristics that are similar to MVT Pb–Zn deposits worldwide.
DNA barcoding of endangered Indian Paphiopedilum species
Authors: PARVEEN IFFAT , SINGH HEMANT K. , RAGHUVANSHI SAURABH , PRADHAN UDAI C. , BABBAR SHASHI B.
Published: September 2011

The indiscriminate collections of Paphiopedilum species from the wild for their exotic ornamental flowers have rendered these plants endangered. Although the trade of these endangered species from the wild is strictly forbidden, it continues unabated in one or other forms that elude the current identification methods. DNA barcoding that offers identification of a species even if only a small fragment of the organism at any stage of development is available could be of great utility in scrutinizing the illegal trade of both endangered plant and animal species. Therefore, this study was undertaken to develop DNA barcodes of Indian species of Paphiopedilum along with their three natural hybrids using loci from both the chloroplast and nuclear genomes. The five loci tested for their potential as effective barcodes were RNA polymerase‐β subunit (rpoB), RNA polymerase‐β’ subunit (rpoC1), Rubisco large subunit (rbcL) and maturase K (matK) from the chloroplast genome and nuclear ribosomal internal transcribed spacer (nrITS) from the nuclear genome. The intra‐ and inter‐specific divergence values and species discrimination rates were calculated by Kimura 2 parameter (K2P) method using mega 4.0. The matK with 0.9% average inter‐specific divergence value yielded 100% species resolution, thus could distinguish all the eight species of Paphiopedilum unequivocally. The species identification capability of these sequences was further confirmed as each of the matK sequences was found to be unique for the species when a blast analysis of these sequences was carried out on NCBI. nrITS, although had 4.4% average inter‐specific divergence value, afforded only 50% species resolution. DNA barcodes of the three hybrids also reflected their parentage.
Chelex without boiling, a rapid and easy technique to obtain stable amplifiable DNA from small amounts of ethanol‐stored spiders
Authors: CASQUET JULIANE , THEBAUD CHRISTOPHE , GILLESPIE ROSEMARY G.
Published: September 2011

DNA barcoding projects require high‐throughput generation of sequence data to assemble the comprehensive reference databases that are required to perform large‐scale biodiversity inventories and molecular ecology studies. With the advent of new sequencing technologies, the extraction step, which often requires a considerable amount of time and money, represents a significant bottleneck in many studies. Here, we present a one‐step Chelex double‐stranded DNA extraction protocol that is quick, cheap, easy and works with a small quantity of ethanol‐stored tissue. We developed this protocol by removing the denaturation step appearing in classic methods. This modification reduces the number of handling steps to one, thus simplifying the extraction procedure and reducing the risk of sample contamination, and yields double‐stranded DNA instead of the single‐stranded form that classical Chelex extraction protocols usually release. DNA obtained through our method is then suitable for long‐term conservation (over 1.5 years). We tested our protocol on a highly diverse genus of spiders comprised of mainly very small species. We also apply the method to two other genera of spiders, one with average size species, the other one with giant species, to test the efficacy of the method with varying amounts of input tissue. We also discuss the advantages and limitations of this DNA extraction technique when working with arthropods.
Deficiency of NG2+ Cells Contributes to the Susceptibility of Stroke‐Prone Spontaneously Hypertensive Rats
Authors: Wang Pei , Tian Wei‐Wei , Song Jie , Guan Yun‐Feng , Miao Chao‐Yu
Published: September 2011

Aims: The purpose of this study is to investigate whether the NG2+ cells, a class of oligodendrocyte progenitor cells, is involved in the pathophysiology of stroke in stroke‐prone spontaneously hypertensive rat (SHR‐SP). Methods: SHR‐SP, SHR, Wistar‐Kyoto rats (WKY), and C57BJ/6 mice were used. Immunohistochemistry was conducted to evaluate the number of NG2+ cells in frozen brain sections. Demyelination was evaluated by Sudan black staining and serum level of myelin basic protein. Middle cerebral artery occlusion (MCAO) was performed to prepare experimental stroke model. Results: The number of NG2+ cells was significantly decreased in infarct core and increased in penumbra in WKY rats after MCAO. In brain sections of 6‐month‐old SHR‐SP, the number of NG2+ cells was significantly (P < 0.01) less than that in age‐matched SHR and WKY rats. However, this phenomenon was not observed in 3‐month‐old rats. Demyelination was found in 6‐month‐old SHR‐SP but not in 3‐month‐old SHR‐SP. Pharmacological treatment of cuprizone in mice induced demyelination and enlargement of cerebral infarction after MCAO. Conclusion: The decline of NG2+ cells may cause demyelination and contribute to the susceptibility of SHR‐SP to ischemic brain injury.
Efficacy of pitavastatin for the treatment of non‐alcoholic steatohepatitis with dyslipidemia: An open‐label, pilot study
Authors: Hyogo Hideyuki , Ikegami Tadashi , Tokushige Katsutoshi , Hashimoto Etsuko , Inui Kazuo , Matsuzaki Yasushi , Tokumo Hironori , Hino Fumiaki , Tazuma Susumu
Published: September 2011

Aim:  Non‐alcoholic fatty liver disease (NAFLD) that encompasses a spectrum of liver disorders characterized by simple steatosis, non‐alcoholic steatohepatitis (NASH) through cirrhosis, is becoming an important chronic liver disease in Japan. Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of statin therapy in NASH patients with dyslipidemia.

Methods:  Twenty patients with biopsy‐proven NASH with dyslipidemia who agreed to participate in this multicentric prospective study were enrolled. The patients were treated for 12 months with pitavastatin 2 mg/day. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight loss counseling was continued during the treatment period. Follow‐up liver biopsy was performed in 13 patients.

Results:  Twenty‐five percent of patients had hyperlipoproteinemia type IIa and 75% had hyperlipoproteinemia type IIb at baseline. The levels of alanine aminotransferase, γ‐glutamyl transpeptidase and lipid profiles were significantly improved by the treatment with pitavastatin for 12 months. Especially, these improvements were prominent in NASH patients with hyperlipoproteinemia type IIb. While non‐alcoholic fatty liver disease activity score and fibrosis stage did not change significantly in all patients, they did improve in 54% and 42% in individual patients, respectively.

Conclusion:  NASH‐related metabolic parameters improved with therapy including histology in some patients. However, three of 13 patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of pitavastatin for the treatment of NASH with dyslipidemia, especially with hyperlipoproteinemia type IIb and controlled trials are needed in the future.
Anti‐hypoalbuminemic effect of branched‐chain amino acid granules in patients with liver cirrhosis is independent of dietary energy and protein intake
Authors: Yatsuhashi Hiroshi , Ohnishi Yoshifumi , Nakayama Seiichi , Iwase Hiroaki , Nakamura Teiji , Imawari Michio
Published: September 2011

Aim:  A multicenter prospective intervention study was conducted in 204 patients with uncompensated liver cirrhosis to explore the influence of dietary intake and patient clinical characteristics on improvement of hypoalbuminemia at weeks 12 and 24 of treatment with branched‐chain amino acid (BCAA) granules.

Methods:  The primary endpoint set in this study was improvement of hypoalbuminemia in patients with liver cirrhosis. The dietary energy and protein intake per day were estimated based on the results of a survey on diet during a 3‐day period preceding the start of the study.

Results:  As for the primary endpoint, the mean serum albumin level increased significantly at weeks 12 and 24 of BCAA treatment, compared with the baseline level. The mean Child–Pugh score decreased significantly at weeks 12 and 24 of treatment as compared to the mean baseline score. There was a significant increase in the serum albumin level following treatment with BCAA granules regardless of energy intake and of protein intake. The incidence of ascites and edema significantly decreased in the overall patient population both at weeks 12 and 24 of treatment, compared with the baseline incidence. A subgroup analysis conducted in patients stratified according to changes in the serum albumin level at week 12 of treatment as against baseline showed that the incidence of ascites/edema was significantly reduced not only in the increased albumin group but in the unchanged albumin group.

Conclusion:  The present data suggest that the anti‐hypoalbuminemic effect of BCAA treatment in patients with liver cirrhosis is independent of dietary intake.
Clinicopathological features of non‐alcoholic fatty liver disease
Authors: Sugimoto Kazushi , Takei Yoshiyuki
Published: September 2011

Non‐alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide and its incidence is increasing concomitantly with the increase in the prevalence of metabolic syndrome. Fatty liver encompasses a broad pathological spectrum of disease, from relatively benign accumulation of fat (simple steatosis) to progressive non‐alcoholic steatohepatitis (NASH), which is associated with necroinflammation and fibrosis. Approximately 20–30% of the Japanese population is estimated to have NAFLD, 10% of which is suggested to have NASH. The most worrisome feature of NASH is the potential progression to cirrhosis, hepatocellular carcinoma (HCC), and finally, mortality. Several factors, such as insulin resistance, adipokines, endotoxins and oxidative stress, are involved in the pathogenesis of NASH. However, the precise etiological mechanism of NAFLD/NASH has yet to be elucidated. This article reviews the clinical background, pathogenesis, new diagnostic approaches and future directions regarding NAFLD/NASH.
Incorporating spirituality in psychosocial group intervention for women undergoingin vitrofertilization: A prospective randomized controlled study
Authors: Chan Celia H. Y. , Chan Cecilia L. W. , Ng Ernest H. Y. , Ho P. C. , Chan Timothy H. Y. , Lee G. L. , Hui W. H. C.
Published: September 2011

Objectives. This study examined the efficacy of a group intervention, the Integrative Body‐Mind‐Spirit (I‐BMS) intervention, which aims at improving the psychosocial and spiritual well‐being of Chinese women undergoing their first IVF treatment cycle.Design.  The I‐BMS intervention facilitates the search of meaning of life in the context of family and childbearing, as well as the letting go of high IVF expectations. A randomized controlled study of 339 women undergoing first IVF treatment cycle in a local Hong Kong hospital was conducted (intervention:n= 172; no‐intervention control:n= 167).

Methods. Assessments of anxiety, perceived importance of childbearing, and spiritual well‐being were made at randomization (T0), on the day starting ovarian stimulations (T1), and on the day undertaking embryo transfer (T2).

Results. Comparing T0and T2, interaction analyses showed women who had received the intervention reported lower levels of physical distress, anxiety, and disorientation. They reported being more tranquil and satisfied with their marriage, and saw childbearing as less important compared to women in the control group.

Conclusions. These findings suggest that I‐BMS intervention was successful at improving the psychosocial and spiritual well‐being of women undergoing their first IVF treatment cycle. This study highlights the importance of providing integrative fertility treatment that incorporates psychosocial and spiritual dimensions.
Breaking the rules: Do infants have a true understanding of false belief?
Authors: Yott Jessica , Poulin‐Dubois Diane
Published: September 2011

It has been suggested that infants’ performance on the false belief task can be explained by the use of behavioural rules. To test this hypothesis, 18‐month‐old infants were trained to learn the new rule that an object that disappeared in location A could be found in location B. Infants were then administered a false belief task based on the violation of expectation (VOE) paradigm, an intention understanding task, and a modified detour‐reaching task. Results revealed that infants looked significantly longer at the display when the experimenter looked for the toy in the full box (box with the toy) compared to infants who observed the experimenter search in the empty box (box without the toy). Results also revealed significant correlations between infants’ looking time at the display and their scores on the intention task and on the detour‐reaching task. Taken together, these findings suggest that infants possess an implicit understanding of false belief. In addition, they challenge the view that success on the implicit false belief task does not require executive functioning abilities.
Paying the piper: the cost of Ca2+ pumping during the mating call of toadfish
Authors: Harwood Claire L. , Young Iain S. , Tikunov Boris A. , Hollingworth Stephen , Baylor Stephen M. , Rome Lawrence C.
Published: September 2011

Non‐Technical Summary  The fastest contracting vertebrate muscle known is found in toadfish. This muscle surrounds the gas‐filled swimbladder of males and contracts and relaxes at 100–200 times per second, producing a mating call. Because calcium ions, the trigger for muscle contraction, must be released and taken up (‘pumped’) on each contraction, this muscle would seem to require a prodigious rate of Ca2+ pumping. Previous work, however, indicates that (1) the pumping proteins in toadfish are not particularly fast, and (2) the mating calls are short (400 ms), interleaved with long (5–15 s) intercall intervals. The present study shows that the Ca2+ pumping paradox is solved in two ways: (1) the amount of Ca2+ released per stimulus is reduced (which also avoids running out of Ca2+), and (2) the muscle's high concentration of the protein parvalbumin binds released Ca2+ during a call, thereby allowing most pumping to occur during the intercall interval.
The role of skeletal muscle mTOR in the regulation of mechanical load‐induced growth
Authors: Goodman Craig A. , Frey John W. , Mabrey Danielle M. , Jacobs Brittany L. , Lincoln Hannah C. , You Jae‐Sung , Hornberger Troy A.
Published: September 2011

Non‐Technical Summary  Chronic mechanical loading (CML) of skeletal muscle induces growth and this effect can be blocked by the drug rapamycin. Rapamycin is considered to be a highly specific inhibitor of the mammalian target of rapamycin (mTOR), and thus, many have concluded that mTOR plays a key role in CML‐induced growth. However, direct evidence that mTOR confers the CML‐induced activation of growth promoting events such as hypertrophy, hyperplasia and ribosome biogenesis is lacking. This study addressed that gap in knowledge by using a specialized line of transgenic mice. Surprisingly, the results indicate that only a few of the growth promoting events induced by CML are fully dependent on mTOR signalling (e.g. hypertrophy). These results advance our understanding of the molecular mechanisms that regulate skeletal muscle mass and should help future studies aimed at identifying targets for therapies that can prevent the loss of muscle mass during conditions such as bedrest, immobilization, and ageing.
Multidisciplinary Design Optimization for Complex Engineered Systems: Report From a National Science Foundation Workshop
Authors: Simpson Timothy W. , Martins Joaquim R. R. A.
Published: September 2011

Complex engineered systems are typically designed using a systems engineering framework that is showing its limitations. Multidisciplinary design optimization (MDO), which has evolved remarkably since its inception 25 years ago, offers alternatives to complement and enhance the systems engineering approach to help address the challenges inherent in the design of complex engineered systems. To gain insight into these challenges, a one-day workshop was organized that gathered 48 people from industry, academia, and government agencies. The goal was to examine MDO’s current and future role in designing complex engineered systems. This paper summarizes the views of five distinguished speakers on the “state of the research” and discussions from an industry panel comprised of representatives from Boeing, Caterpillar, Ford, NASA Glenn Research Center, and United Technologies Research Center on the “state of the practice.” Future research topics to advance MDO are also identified in five key areas: (1) modeling and the design space, (2) metrics, objectives, and requirements, (3) coupling in complex engineered systems, (4) dealing with uncertainty, and (5) people and workflow. Finally, five overarching themes are offered to advance MDO practice. First, MDO researchers need to engage disciplines outside of engineering and target opportunities outside of their traditional application areas. Second, MDO problem formulations must evolve to encompass a wider range of design criteria. Third, effective strategies are needed to put designers “back in the loop” during MDO. Fourth, the MDO community needs to do a better job of publicizing its successes to improve the “buy in” that is needed to advance MDO in academia, industry, and government agencies. Fifth, students and practitioners need to be better educated on systems design, optimization, and MDO methods and tools along with their benefits and drawbacks.
Development of Bi-Metal Anode Microtubular Supports for Solid Oxide Fuel Cells
Authors: Suzuki Toshio , Liang Bo , Hamamoto Koichi , Yamaguchi Toshiaki , Fujishiro Yoshinobu , Awano Masanobu
Published: September 2011

Use of microtubular design in solid oxide fuel cells is considered to be ideal for small power application up to kW scale since it has shown to have high thermal shock resistance and high electrode area per volume, resulting in high volumetric power density. In this study, using a form of microtubular, NiO-Fe2O3 based material has been used as an anode material and investigated the microstructure and the fuel cell performance.
Multi-Rigid Image Segmentation and Registration for the Analysis of Joint Motion From Three-Dimensional Magnetic Resonance Imaging
Authors: Hu Yangqiu , Ledoux William R. , Fassbind Michael , Rohr Eric S. , Sangeorzan Bruce J. , Haynor David
Published: September 2011

We report an image segmentation and registration method for studying joint morphology and kinematics from in vivo magnetic resonance imaging (MRI) scans and its application to the analysis of foot and ankle joint motion. Using an MRI-compatible positioning device, a foot was scanned in a single neutral and seven other positions ranging from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. A segmentation method combining graph cuts and level set was developed. In the subsequent registration step, a separate rigid body transformation for each bone was obtained by registering the neutral position dataset to each of the other ones, which produced an accurate description of the motion between them. The segmentation algorithm allowed a user to interactively delineate 14 foot bones in the neutral position volume in less than 30 min total (user and computer processing unit [CPU]) time. Registration to the seven other positions took approximately 10 additional minutes of user time and 5.25 h of CPU time. For validation, our results were compared with those obtained from 3DViewnix, a semiautomatic segmentation program. We achieved excellent agreement, with volume overlap ratios greater than 88% for all bones excluding the intermediate cuneiform and the lesser metatarsals. For the registration of the neutral scan to the seven other positions, the average overlap ratio is 94.25%, while the minimum overlap ratio is 89.49% for the tibia between the neutral position and position 1, which might be due to different fields of view (FOV). To process a single foot in eight positions, our tool requires only minimal user interaction time (less than 30 min total), a level of improvement that has the potential to make joint motion analysis from MRI practical in research and clinical applications.
New Role of the Disulfide Stress Effector YjbH in β-Lactam Susceptibility of Staphylococcus aureus
Authors: Göhring Nadine , Fedtke Iris , Xia Guoqing , Jorge Ana M. , Pinho Mariana G. , Bertsche Ute , Peschel Andreas
Published: September 2011

Staphylococcus aureus
is exposed to multiple antimicrobial compounds, including oxidative burst products and antibiotics. The various mechanisms and regulatory pathways governing susceptibility or resistance are complex and only superficially understood.
Bacillus subtilis
recently has been shown to control disulfide stress responses by the thioredoxin-related YjbH protein, which binds to the transcriptional regulator Spx and controls its degradation via the proteasome-like ClpXP protease. We show that the
S. aureus
YjbH homolog has a role in susceptibility to the disulfide stress-inducing agent diamide that is similar to that in
B. subtilis
, and we demonstrate that the four cysteine residues in YjbH are required for this activity. In addition, the inactivation of YjbH led to moderate resistance to oxacillin and other β-lactam antibiotics, and this phenotypic change was associated with higher penicillin-binding protein 4 levels and increased peptidoglycan cross-linking. Of note, the impact of YjbH on β-lactam susceptibility still was observed when the four cysteines of YjbH were mutated, indicating that the roles of YjbH in disulfide stress and β-lactam resistance rely on different types of interactions. These data suggest that the ClpXP adaptor YjbH has more target proteins than previously thought, and that oxidative burst and β-lactam resistance mechanisms of
S. aureus
are closely linked.
A Novel Benzodioxole-Containing Inhibitor of Toxoplasma gondii Growth Alters the Parasite Cell Cycle
Authors: Kamau Edwin , Meehan Tracy , Lavine Mark D. , Arrizabalaga Gustavo , Mustata Wilson Gabriela , Boyle Jon
Published: September 2011

Toxoplasma gondii
is an obligate intracellular parasite that can cause disease in the developing fetus and in immunocompromised humans. Infections can last for the life of the individual, and to date there are no drugs that eliminate the chronic cyst stages that are characteristic of this parasite. In an effort to identify new chemical scaffolds that could form the basis for new therapeutics, we carried out a chemoinformatic screen for compounds that had the potential to interact with members of a superfamily of parasite-secreted kinases and assayed them for growth inhibition
in vitro
. Of 17 candidate compounds, we identified one with potent antiparasitic activity. The compound has a 50% inhibitory concentration (IC
50
) of ∼2 nM, and structure-function analyses implicate the benzodioxole moiety in its action. The compound does not appear to be cytotoxic to host cells. Using microarray analyses of both parasites and host cells treated with the compound, we found that the levels of very few host cell transcripts are altered by the compound, while a large number of parasite transcripts have a different abundance after compound treatment. Gene ontology analyses of parasite transcripts with a different abundance revealed an enrichment of cell cycle-related genes, suggesting that the compound alters progression of the parasite through the cell cycle. Assaying the nuclear content of treated parasites demonstrated that compound treatment significantly increased the percentage of parasites in the S/M phase of the cell cycle compared to controls. This compound and its analogs represent a novel scaffold with antiparasitic activity.