bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer's disease is associated with disordered localization of ganglioside GM1 molecular species in the human dentate gyrus
Authors: Hirano-Sakamaki Wakako , Sugiyama Eiji , Hayasaka Takahiro , Ravid Rivka , Setou Mitsutoshi , Taki Takao
Published: October 2015

Alzheimer's disease (AD) is a progressive dementia associated with loss of memory and cognitive dysfunction. In a previous study, we demonstrated a decrease in b‐series gangliosides along with a change in ganglioside molecular species in the hippocampal grey matter of patients with AD. The present study demonstrates the use of imaging mass spectrometry for analyzing the spatial arrangement of ganglioside GM1 (GM1) molecular species in the hippocampus. In AD patients, we found a decrease in the ratio of GM1(d20:1/C18:0) to GM1 d18:1/C18:0) in the outer molecular layer (ML) of the dentate gyrus. Because the outer ML is the region of main input into the hippocampus, our findings may have a direct relationship to the mechanism of dysfunction in AD.
Cysteine is not a substrate but a specific modulator of human ASCT2 (SLC1A5) transporter
Authors: Scalise Mariafrancesca , Pochini Lorena , Pingitore Piero , Hedfalk Kristina , Indiveri Cesare
Published: October 2015

The Alanine Serine Cysteine Transporter 2 (ASCT2) is involved in balancing the intracellular amino acid pool. This function is allowed by the antiport mechanism and the asymmetric specificity towards different neutral amino acids, distinctive of this transporter. In the present work, the interaction of the putative substrate Cys with the human ASCT2 has been studied using the recombinant hASCT2 over‐produced inPichia pastorisand the native ASCT2 extracted from HeLa in both proteoliposomes and intact cells. It was found that Cys is a potent competitive inhibitor of hASCT2 but is not a substrate. Moreover, Cys binding to a second site, different from that of substrate, triggers a protein‐mediated unidirectional Gln efflux.
Immediate‐early response 5 (IER5) interacts with protein phosphatase 2A and regulates the phosphorylation of ribosomal protein S6 kinase and heat shock factor 1
Authors: Kawabata Shotaro , Ishita Yuichiro , Ishikawa Yukio , Sakurai Hiroshi
Published: October 2015

Immediate‐early response 5 (IER5) is a growth factor‐inducible protein with homology to the N‐terminus of IER2. Deletion analysis shows that a large region of IER5, including the N‐terminal region, is involved in cell growth and stress resistance. The N‐terminal region mediates IER5 oligomerization and binding to the B55 regulatory subunit of protein phosphatase 2A (PP2A). IER5 physically interacts with the PP2A target proteins ribosomal protein S6 kinase (S6K) and heat shock factor 1 (HSF1), and the interactions are essential for the reduced phosphorylation of S6K and HSF1. Our data indicate that oligomeric IER5 regulates PP2A activity and cell growth.
Prediction of microRNA target genes using an efficient genetic algorithm‐based decision tree
Authors: Rabiee-Ghahfarrokhi Behzad , Rafiei Fariba , Niknafs Ali Akbar , Zamani Behzad
Published: October 2015

MicroRNAs (miRNAs) are small, non‐coding RNA molecules that regulate gene expression in almost all plants and animals. They play an important role in key processes, such as proliferation, apoptosis, and pathogen–host interactions. Nevertheless, the mechanisms by which miRNAs act are not fully understood. The first step toward unraveling the function of a particular miRNA is the identification of its direct targets. This step has shown to be quite challenging in animals primarily because of incomplete complementarities between miRNA and target mRNAs. In recent years, the use of machine‐learning techniques has greatly increased the prediction of miRNA targets, avoiding the need for costly and time‐consuming experiments to achieve miRNA targets experimentally. Among the most important machine‐learning algorithms are decision trees, which classify data based on extracted rules. In the present work, we used a genetic algorithm in combination with C4.5 decision tree for prediction of miRNA targets. We applied our proposed method to a validated human datasets. We nearly achieved 93.9% accuracy of classification, which could be related to the selection of best rules.
The Wnt and Notch signalling pathways in the developing cochlea: Formation of hair cells and induction of regenerative potential
Authors: Żak Magdalena , Klis Sjaak F.L. , Grolman Wilko
Published: October 2015

The Wnt and Notch signalling pathways control proliferation, specification, and cell fate choices during embryonic development and in adult life. Hence, there is much interest in both signalling pathways in the context of stem cell biology and tissue regeneration. In the developing ear, the Wnt and Notch signalling pathways specify otic cells and refine the ventral boundary of the otic placode. Since both signalling pathways control events essential for the formation of sensory cells, such as proliferation and hair cell differentiation, these pathways could hold promise for the regeneration of hair cells in adult mammalian cochlea. Indeed, modulating either the Wnt or Notch pathways can trigger the regenerative potential of supporting cells. In the neonatal mouse cochlea, Notch‐mediated regeneration of hair cells partially depends on Wnt signalling, which implies an interaction between the pathways. This review presents how the Wnt and Notch signalling pathways regulate the formation of sensory hair cells and how modulating their activity induces regenerative potential in the mammalian cochlea.
Neonatal propofol anesthesia modifies activity‐dependent processes and induces transient hyperlocomotor response to d‐amphetamine during adolescence in rats
Authors: Pešić Vesna , Milanović Desanka , Popić Jelena , Smiljanić Kosara , Tešić Vesna , Kanazir Selma , Jevtović‐Todorović Vesna , Ruždijić Sabera
Published: October 2015

This study examined the influence of propofol anesthesia on the expression of activity‐regulated molecules (BDNF and c‐Fos) and synaptic plasticity markers (synaptophysin, GAP‐43, drebrin) in the frontal cortex and thalamus of 7‐day‐old (P7) rats. Although these brain regions are the main targets of anesthetic action, they are contained in the cortico–striato–thalamo–cortical feedback loops, involved in naturally occurring and drug‐induced psychoses. Therefore, functional integrity of these loops was examined in adolescent and adult rats through d‐amphetamine‐induced hyperactivity. Propofol treatment (25 mg/kg) decreased exon‐specific and total BDNF mRNA expression in the frontal cortex and thalamus, in a time‐dependent manner. BDNF protein level was increased in the frontal cortex and decreased in the thalamus, which was accompanied by the change of phospho‐TrkB expression. Similarly to BDNF, the expression of c‐Fos was decreased in the frontal cortex while it was changed only at the protein level in the thalamus. Synaptic plasticity markers changed in a time‐ and region‐specific manner, indicating increased synaptogenesis in the frontal cortex and synapse elimination in the thalamus in P7 rats after the propofol anesthesia exposure. These early molecular changes were followed by time‐related, increased motor reaction to d‐amphetamine in adolescent, but not in adult rats. Our study revealed that exposure of immature brain to propofol anesthesia during the critical phase of development provoked immediate changes in activity‐dependent processes and synaptic adjustment, influencing brain capacity to integrate later developmental events and resulting in temporary altered response to acute psychotropic stimulation during adolescence.
Translation of a Motor Learning Walking Rehabilitation Program Into a Group‐Based Exercise Program for Community‐Dwelling Older Adults
Authors: Brach Jennifer S. , Francois Sara J. , VanSwearingen Jessie M. , Gilmore Sandra , Perera Subashan , Studenski Stephanie A.
Published: October 2015

Background

Traditional exercise programs for older adults, which focus on aerobic and strength training, have had only modest effects on walking. Recently, a motor learning exercise program was shown to have greater effects on walking compared with a traditional exercise program. Translating this novel motor learning exercise program into a group exercise program would allow it to be offered as an evidence‐based, community‐based program for older adults.

Objective

To translate a walking rehabilitation program based on motor learning theory from one‐on‐one to group delivery (On the Move) and evaluate multiple aspects of implementation in older adults with impaired mobility.

Design

The translation process involved multiple iterations, including meetings of experts in the field (Phase I), focus groups (Phase II), and implementation of the newly developed program (Phase III). Phase III was based on a one‐group model of intervention development for feasibility, safety, potential effects, and acceptability.

Setting

Community sites, including 2 independent living facilities, an apartment building, and a community center.

Participants

Adults 65 years of age or older who could ambulate independently and who were medically stable. Thirty‐one adults, mean age 82.3 ± 5.6 years, were eligible to participate.

Methods

The group exercise program was held twice a week for 12 weeks.

Main Outcome Measurements

Acceptability of the program was determined by retention and adherence rates and a satisfaction survey. Risk was measured by adverse events and questions on perceived challenge and safety. Mobility was assessed pre‐ and postintervention by gait speed, Figure of 8 Walk Test, and 6‐minute walk test.

Results

Modifications to the program included adjustments to format/length, music, education, and group interaction. The 12‐week program was completed by 24 of 31 entrants (77%). Adherence was high, with participants attending on average 83% of the classes. Safety was excellent, with only 1 subject experiencing a controlled, noninjurious fall. There was preliminary evidence for improved mobility after the intervention: gait speed improved from 0.76 ± 0.21 to 0.81 ± 0.22 m/s, P = .06; Figure of 8 Walk Test from 13.0 ± 3.9 to 12.0 ± 3.9 seconds, P = .07; and 6‐minute walk test from 246 ± 75 to 281 ± 67 m, P = .02.

Conclusions

The group‐based program was safe and acceptable to older adults with impaired mobility and resulted in potentially clinically meaningful improvements in mobility.
Acute Responses of Functional Electrical Stimulation Cycling on the Ventilation‐to‐CO2 Production Ratio and Substrate Utilization After Spinal Cord Injury
Authors: Gorgey Ashraf S. , Lawrence Justin
Published: October 2015

Background

Ventilation‐to‐carbon dioxide ratio is comparable with peak oxygen uptake in the prognosis of cardiovascular disorders. Currently, there are no established indices to determine the submaximal effects of functional electrical stimulation on cardiovascular performance in persons with spinal cord injury.

Objective

To determine the effects of an acute bout of functional electrical stimulation‐lower extremity cycling on ventilation, carbon dioxide production, ventilation‐to‐carbon dioxide ratio, and substrate utilization in people with motor complete spinal cord injury.

Design

Observational cross‐sectional design.

Setting

Clinical laboratory setting.

Participants

Ten individuals with motor complete spinal cord injury.

Methods

Participants were allowed to cycle until fatigue. The effects of functional electrical stimulation on ventilation, carbon dioxide production, ventilation‐to‐carbon dioxide ratio, and substrate utilization were measured with a portable metabolic cart (COSMED K4b2). Body composition was determined with bioelectrical impedance.

Results

Resting and warm‐up ventilation were 8.15 ± 3.5 L/min and 8.15 ± 2.8 L/min, respectively. Functional electrical stimulation increased ventilation significantly (14.5 ± 6.4 L/min), which remained significantly elevated (13.3 ± 4.3 L/min) during the recovery period. During resting and warm‐up phases, the ventilation‐to‐carbon dioxide ratios were 41 ± 4.8 and 38 ± 5.4, respectively. Functional electrical stimulation decreased the ventilation‐to‐carbon dioxide ratio significantly to 31.5 ± 4, which remained significantly reduced during the recovery period (34.4 ± 3). Functional electrical stimulation relied primarily on carbohydrate utilization (188 ± 160 g/day to 574 ± 324 g/day; P = .001) with no changes in fat utilization (77.5 ± 28 g/day to 93.5 ± 133.6 g/day; P = .7) from resting to exercise periods. Significant relationships were noted between carbohydrate utilization during functional electrical stimulation and carbon dioxide (r = 0.98; P = .00010) production. The percentage whole body fat‐free mass was negatively related to the exercise ventilation‐to‐carbon ratio (r = −0.66; P = .045).

Conclusions

An acute bout of functional electrical stimulation resulted in a significant drop in the ventilation‐to‐carbon ratio, accompanied with a reliance on carbohydrate utilization and a diminished capacity to utilize fat as a substrate. Fat‐free mass may be associated with a decrease in ventilation to carbon dioxide ratio and an increase in carbohydrate utilization in persons with spinal cord injury.
Burnout y engagement académico en fonoaudiología
Authors: Glaría López Rocío , Carmona-San Martín Lorena , Pérez Villalobos Cristhian
Published: October 2015

Introduction: Burnout has been described as a three-dimensional syndrome of emotional exhaustion, depersonalization or cynicism and reduced personal accomplishment, while engagement corresponds to a positive state of mind characterized by vigor, dedication and absorption.  Students are susceptible to these phenomena, which has not been extensively investigated in speech and language therapy Chilean students.
Objective: Compare levels of academic burnout and engagement in speech and language therapy students from different courses of a traditional Chilean university.
Method: Quantitative, non-experimental, cross sectional study. With prior informed consent, 220 students from 1st to 5th grade chosen by probabilistic quota sampling were surveyed. The Maslach Burnout Inventory for Students and Uthecht Work Engagement Scale-Student were used.Data were analyzed by the statistical package STATA 11.0 SE. 
Results: Fourth grade presented a significantly higher emotional exhaustion compared to the other courses level. In depersonalization, fourth year again reported a significantly higher level than the second grade. In the case of engagement, no significant differences were found per grade.
Conclusions: Fourth grade presented higher levels of burnout. No significant differences in the levels of engagement were found. The data obtained show the need for further research on this subject in this population and will collaborate to generate actions plans designed to ensure high levels of engagement and decrease burnout levels along the entire curriculum.
Vegetation and climate changes during the late Pliocene and early Pleistocene in SW Anatolia, Turkey
Authors: Jiménez-Moreno Gonzalo , Alçiçek Hülya , Alçiçek M. Cihat , van den Hoek Ostende Lars , Wesselingh Frank P.
Published: October 2015

Pollen analysis was done on lacustrine sedimentary sequences dated by micromammals as late Pliocene–early Pleistocene that outcrop in two Neogene graben basins from SW Turkey. This study shows vegetation changes from steppe-like to more forested environments, very similar to the cyclic oscillations related to late Pleistocene glacial–interglacial climate changes. Artemisia was abundant during cold–arid periods, indicating that this species was already widespread in this area during the latest Pliocene and the beginning of the Pleistocene. A review of pollen records from Anatolia agrees with this study, suggesting that the spreading of this arid species occurred during a major climatic change: the beginning of the first glaciations and probably a change in seasonality towards summer aridity. Artemisia temporarily disappeared from the region during warm–wet periods and thus we suggest that glacial–interglacial-type oscillations already occurred in the area during the late Pliocene–early Pleistocene.
The acute and medium-term effects of treatment with electroconvulsive therapy on memory in patients with major depressive disorder
Authors: Maric N. P. , Stojanovic Z. , Andric S. , Soldatovic I. , Dolic M. , Spiric Z.
Published: October 2015

Background

Current literature provides insufficient information on the degree of cognitive impairment during and after electroconvulsive therapy (ECT), mostly due to the fact that applied tests lacked sensitivity and flexibility. Our goal was to evaluate cognitive functioning in adult depressed patients treated with bi-temporal ECT, using tests sensitive for detection of possible acute and medium-term memory changes.

Method

Thirty adult patients with major depressive disorder, treated with a course of bi-temporal ECT, underwent clinical and cognitive measurements three times: at baseline, immediately after a course of ECT, and 1 month later. For cognition assessment, we used learning and visual, spatial and figural memory tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Results

Bi-temporal ECT has proven to be an effective treatment. The linear mixed model, used to analyze changes in depression severity and patients’ cognitive performances over time and to assess dynamic correlations between aforementioned features, did not show any significant memory impairment as a potential acute or medium-term ECT effect. However, it yielded significant improvement on visual memory and learning at the follow-up, which positively correlated with the improvement of depression.

Conclusion

Good progress is being made in the search for ECT-related acute and medium-term cognitive side-effects by using the tests sensitive to detect memory dysfunction with parallel forms of the tasks (to counter practice effects on repeat testing). Our results on learning and memory in relation to ECT during treatment of depression did not bring forth any prolonged and significant bi-temporal ECT-related memory deficit.
High protein and cholesterol intakes associated with emergence of glucose intolerance in a low-risk Canadian Inuit population
Authors: Sefidbakht Saghar , Johnson-Down Louise , Young T Kue , Egeland Grace M
Published: October 2015

Objective

The rate of type 2 diabetes mellitus among Inuit is 12·2 % in individuals over 50 years of age, similar to the Canadian prevalence. Given marked dietary transitions in the Arctic, we evaluated the dietary and other correlates of not previously diagnosed glucose intolerance, defined as type 2 diabetes mellitus, impaired fasting glucose or impaired glucose tolerance.

Design

Cross-sectional analyses were limited to adults with a completed 2 h oral glucose tolerance test and without pre-existing diabetes. Anthropometric assessments, health and medication usage questionnaires and a 24 h dietary recall were administered.

Setting

Canadian International Polar Year Inuit Health Survey (2007–2008).

Subjects

Inuit adults (n777).

Results

Glucose intolerance was associated with older age and adiposity. Percentage of energy from protein above the Acceptable Macronutrient Distribution Range of 35 %, compared with intake within the range, was associated with increased odds of glucose intolerance (OR=1·98; 95 % CI 1·09, 3·61) in multivariable analyses. Further, cholesterol intake in the highest three quartiles combined (median exposures of 207, 416 and 778 mg/d, respectively) compared with the lowest quartile (median intake of 81 mg/d) was associated with glucose intolerance (OR=2·15; 95 % CI 1·23, 3·78) in multivariable analyses. Past-day traditional food consumption was borderline protective of glucose intolerance (P=0·054) and high fibre intake was not significantly protective (P=0·08).

Conclusions

The results contribute to the existing literature on high protein and cholesterol intakes as they may relate to diabetes risk.
A New Image Analysis Method Based on Morphometric and Fractal Parameters for Rapid Evaluation ofIn SituMammalian Mast Cell Status
Authors: Wedman Piper , Aladhami Ahmed , Beste Mary , Edwards Morgan K. , Chumanevich Alena , Fuseler John W. , Oskeritzian Carole A.
Published: October 2015

Apart from their effector functions in allergic disorders, tissue-resident mast cells (MC) are gaining recognition as initiators of inflammatory events through their distinctive ability to secrete many bioactive molecules harbored in cytoplasmic granules. Activation triggers mediator release through a regulated exocytosis named degranulation. MC activation is still substantiated by measuring systemic levels of MC-restricted mediators. However, identifying the anatomical location of MC activation is valuable for disease diagnosis. We designed a computer-assisted morphometric method based on image analysis of methylene blue (MB)-stained normal mouse skin tissue sections that quantitates actualin situMC activation status. We reasoned MC cytoplasm could be viewed as an object featuring unique relative mass values based on activation status. Integrated optical density and area (A) ratios were significantly different between intact and degranulated MC (p<0.001). The examination of fractal characteristics is of translational diagnostic/prognostic value in cancer and readily applied to quantify cytoskeleton morphology and vasculature. Fractal dimension (D), a measure of their comparative space filling capacity and structural density, also differed significantly between intact and degranulated MC (p<0.001). Morphometric analysis provides a reliable and reproducible method forin situquantification of MC activation status.
Subsurface Craters Expose the Moon's Dramatic Past
Authors: Strelich Lily
Published: October 2015

Scientists use the gravity signature of the lunar surface to trace the history of impact cratering and its role in the Moon's evolution.
Non-pathogenic Rhizobium radiobacter F4 deploys plant beneficial activity independent of its host Piriformospora indica
Authors: Glaeser Stefanie P , Imani Jafargholi , Alabid Ibrahim , Guo Huijuan , Kumar Neelendra , Kämpfer Peter , Hardt Martin , Blom Jochen , Goesmann Alexander , Rothballer Michael , Hartmann Anton , Kogel Karl-Heinz
Published: October 2015

The Alphaproteobacterium Rhizobium radiobacter F4 (RrF4) was originally characterized as an endofungal bacterium in the beneficial endophytic Sebacinalean fungus Piriformospora indica. Although attempts to cure P. indica from RrF4 repeatedly failed, the bacterium can easily be grown in pure culture. Here, we report on RrF4’s genome and the beneficial impact the free-living bacterium has on plants. In contrast to other endofungal bacteria, the genome size of RrF4 is not reduced. Instead, it shows a high degree of similarity to the plant pathogenic R. radiobacter (formerly: Agrobacterium tumefaciens) C58, except vibrant differences in both the tumor-inducing (pTi) and the accessor (pAt) plasmids, which can explain the loss of RrF4’s pathogenicity. Similar to its fungal host, RrF4 colonizes plant roots without host preference and forms aggregates of attached cells and dense biofilms at the root surface of maturation zones. RrF4-colonized plants show increased biomass and enhanced resistance against bacterial leaf pathogens. Mutational analysis showed that, similar to P. indica, resistance mediated by RrF4 was dependent on the plant’s jasmonate-based induced systemic resistance (ISR) pathway. Consistent with this, RrF4- and P. indica-induced pattern of defense gene expression were similar. In clear contrast to P. indica, but similar to plant growth-promoting rhizobacteria, RrF4 colonized not only the root outer cortex but also spread beyond the endodermis into the stele. On the basis of our findings, RrF4 is an efficient plant growth-promoting bacterium.
Structurally driven one-dimensional electron confinement in sub-5-nm graphene nanowrinkles
Authors: Lim Hyunseob , Jung Jaehoon , Ruoff Rodney S. , Kim Yousoo
Published: October 2015

Graphene-based carbon materials such as fullerenes, carbon nanotubes, and graphenes have distinct and unique electronic properties that depend on their dimensionality and geometric structures. Graphene wrinkles with pseudo one-dimensional structures have been observed in a graphene sheet. However, their one-dimensional electronic properties have never been observed because of their large widths. Here we report the unique electronic structure of graphene nanowrinkles in a graphene sheet grown on Ni(111), the width of which was small enough to cause one-dimensional electron confinement. Use of spatially resolved, scanning tunnelling spectroscopy revealed bandgap opening and a one-dimensional van Hove singularity in the graphene nanowrinkles, as well as the chemical potential distribution across the graphene nanowrinkles. This observation allows us to realize a metallic-semiconducting-metallic junction in a single graphene sheet. Our demonstration of one-dimensional electron confinement in graphene provides the novel possibility of controlling its electronic properties not by chemical modification but by ‘mechanical structuring’.
Direct observation of ultrafast coherent exciton dynamics in helical π-stacks of self-assembled perylene bisimides
Authors: Sung Jooyoung , Kim Pyosang , Fimmel Benjamin , Würthner Frank , Kim Dongho
Published: October 2015

Ever since the discovery of dye self-assemblies in nature, there have been tremendous efforts to exploit biomimetic supramolecular assemblies for tailored artificial photon processing materials. This feature necessarily has resulted in an increasing demand for understanding exciton dynamics in the dye self-assemblies. In a sharp contrast with J-type aggregates, however, the detailed observation of exciton dynamics in H-type aggregates has remained challenging. In this study, as we succeed in measuring transient fluorescence from Frenkel state of π-stacked perylene tetracarboxylic acid bisimide dimer and oligomer aggregates, we present an experimental demonstration on Frenkel exciton dynamics of archetypal columnar π–π stacks of dyes. The analysis of the vibronic peak ratio of the transient fluorescence spectra reveals that unlike the simple π-stacked dimer, the photoexcitation energy in the columnar π-stacked oligomer aggregates is initially delocalized over at least three molecular units and moves coherently along the chain in tens of femtoseconds, preceding excimer formation process.
Large magnetocaloric effect and adiabatic demagnetization refrigeration with YbPt2Sn
Authors: Jang Dongjin , Gruner Thomas , Steppke Alexander , Mitsumoto Keisuke , Geibel Christoph , Brando Manuel
Published: October 2015

Adiabatic demagnetization is currently gaining strong interest in searching for alternatives to 3He-based refrigeration techniques for achieving temperatures below 2 K. The main reasons for that are the recent shortage and high price of the rare helium isotope 3He. Here we report the discovery of a large magnetocaloric effect in the intermetallic compound YbPt2Sn, which allows adiabatic demagnetization cooling from 2 K down to 0.2 K. We demonstrate this with a home-made refrigerator. Other materials, for example, paramagnetic salts, are commonly used for the same purpose but none of them is metallic, a severe limitation for low-temperature applications. YbPt2Sn is a good metal with an extremely rare weak magnetic coupling between the Yb atoms, which prevents them from ordering above 0.25 K, leaving enough entropy free for use in adiabatic demagnetization cooling. The large volumetric entropy capacity of YbPt2Sn guarantees also a good cooling power.
Defective titanium dioxide single crystals exposed by high-energy {001} facets for efficient oxygen reduction
Authors: Pei Dan-Ni , Gong Li , Zhang Ai-Yong , Zhang Xing , Chen Jie-Jie , Mu Yang , Yu Han-Qing
Published: October 2015

The cathodic material plays an essential role in oxygen reduction reaction for energy conversion and storage systems. Titanium dioxide, as a semiconductor material, is usually not recognized as an efficient oxygen reduction electrocatalyst owning to its low conductivity and poor reactivity. Here we demonstrate that nano-structured titanium dioxide, self-doped by oxygen vacancies and selectively exposed with the high-energy {001} facets, exhibits a surprisingly competitive oxygen reduction activity, excellent durability and superior tolerance to methanol. Combining the electrochemical tests with density-functional calculations, we elucidate the defect-centred oxygen reduction reaction mechanism for the superiority of the reductive {001}-TiO2−x nanocrystals. Our findings may provide an opportunity to develop a simple, efficient, cost-effective and promising catalyst for oxygen reduction reaction in energy conversion and storage technologies.
Non-destructive mapping of grain orientations in 3D by laboratory X-ray microscopy
Authors: McDonald S. A. , Reischig P. , Holzner C. , Lauridsen E. M. , Withers P. J. , Merkle A. P. , Feser M.
Published: October 2015

The ability to characterise crystallographic microstructure, non-destructively and in three-dimensions, is a powerful tool for understanding many aspects related to damage and deformation mechanisms in polycrystalline materials. To this end, the technique of X-ray diffraction contrast tomography (DCT) using monochromatic synchrotron and polychromatic laboratory X-ray sources has been shown to be capable of mapping crystal grains and their orientations non-destructively in 3D. Here we describe a novel laboratory-based X-ray DCT modality (LabDCT), enabling the wider accessibility of the DCT technique for routine use and in-depth studies of, for example, temporal changes in crystallographic grain structure non-destructively over time through ‘4D’ in situ time-lapse studies. The capability of the technique is demonstrated by studying a titanium alloy (Ti-β21S) sample. In the current implementation the smallest grains that can be reliably detected are around 40 μm. The individual grain locations and orientations are reconstructed using the LabDCT method and the results are validated against independent measurements from phase contrast tomography and electron backscatter diffraction respectively. Application of the technique promises to provide important insights related to the roles of recrystallization and grain growth on materials properties as well as supporting 3D polycrystalline modelling of materials performance.
Detecting Lateral Motion using Light’s Orbital Angular Momentum
Authors: Cvijetic Neda , Milione Giovanni , Ip Ezra , Wang Ting
Published: October 2015

Interrogating an object with a light beam and analyzing the scattered light can reveal kinematic information about the object, which is vital for applications ranging from autonomous vehicles to gesture recognition and virtual reality. We show that by analyzing the change in the orbital angular momentum (OAM) of a tilted light beam eclipsed by a moving object, lateral motion of the object can be detected in an arbitrary direction using a single light beam and without object image reconstruction. We observe OAM spectral asymmetry that corresponds to the lateral motion direction along an arbitrary axis perpendicular to the plane containing the light beam and OAM measurement axes. These findings extend OAM-based remote sensing to detection of non-rotational qualities of objects and may also have extensions to other electromagnetic wave regimes, including radio and sound.
Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise
Authors: Yamazaki Masahiko , Kusano Kanichi , Ishibashi Toru , Kiuchi Masataka , Koyama Katsuhiro
Published: October 2015

Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses.
Comparison of medetomidine, thiopental and ketamine/midazolam anesthesia in chick embryos for in ovo Magnetic Resonance Imaging free of motion artifacts
Authors: Waschkies Conny , Nicholls Flora , Buschmann Johanna
Published: October 2015

Non-invasive assessment of the perfusion capacity of tissue engineered constructs grown on the chorioallantoic membrane by MRI is often hampered by motion artifacts. Therefore, we examined the suitability of three anesthetic regimes for sufficient sedation of the chick embryo. Medetomidine at a dosage of 0.3 mg/kg, was compared to thiopental at 100 mg/kg and ketamine/midazolam at 50 mg/kg and 1 mg/kg, respectively. These soluble anesthetics were applied by dropping a total volume of 0.3 mL onto the surface of the CAM. Motion was videotaped through the window of the eggshell and scored semi-quantitatively. Medetomidine performed best in terms of reduced motion; onset of anesthesia occurred within 10 minutes and for the following 30 minutes, allowing proper in vivo MRI measurements. The other regimen were not sedating deep enough (ketamine/midazolam) and not long enough (thiopental). In sum, medetomidine allows proper sedation for MRI assessment of the perfusion capacity in a tissue engineered construct placed on the CAM.
Lactate dehydrogenase-A inhibition induces human glioblastoma multiforme stem cell differentiation and death
Authors: Daniele Simona , Giacomelli Chiara , Zappelli Elisa , Granchi Carlotta , Trincavelli Maria Letizia , Minutolo Filippo , Martini Claudia
Published: October 2015

Therapies that target the signal transduction and metabolic pathways of cancer stem cells (CSCs) are innovative strategies to effectively reduce the recurrence and significantly improve the outcome of glioblastoma multiforme (GBM). CSCs exhibit an increased rate of glycolysis, thus rendering them intrinsically more sensitive to prospective therapeutic strategies based on the inhibition of the glycolytic pathway. The enzyme lactate dehydrogenase-A (LDH-A), which catalyses the interconversion of pyruvate and lactate, is up-regulated in human cancers, including GBM. Although several papers have explored the benefits of targeting cancer metabolism in GBM, the effects of direct LDH-A inhibition in glial tumours have not yet been investigated, particularly in the stem cell subpopulation. Here, two representative LDH-A inhibitors (NHI-1 and NHI-2) were studied in GBM-derived CSCs and compared to differentiated tumour cells. LDH-A inhibition was particularly effective in CSCs isolated from different GBM cell lines, where the two compounds blocked CSC formation and elicited long-lasting effects by triggering both apoptosis and cellular differentiation. These data demonstrate that GBM, particularly the stem cell subpopulation, is sensitive to glycolytic inhibition and shed light on the therapeutic potential of LDH-A inhibitors in this tumour type.
Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein
Authors: Hao Ge-Fei , Xu Wei-Fang , Yang Sheng-Gang , Yang Guang-Fu
Published: October 2015

Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation.
Spontaneous symmetry breaking in vortex systems with two repulsive lengthscales
Authors: Curran P. J. , Desoky W. M. , Milos̆ević M. V. , Chaves A. , Laloë J.-B. , Moodera J. S. , Bending S. J.
Published: October 2015

Scanning Hall probe microscopy (SHPM) has been used to study vortex structures in thin epitaxial films of the superconductor MgB2. Unusual vortex patterns observed in MgB2 single crystals have previously been attributed to a competition between short-range repulsive and long-range attractive vortex-vortex interactions in this two band superconductor; the type 1.5 superconductivity scenario. Our films have much higher levels of disorder than bulk single crystals and therefore both superconducting condensates are expected to be pushed deep into the type 2 regime with purely repulsive vortex interactions. We observe broken symmetry vortex patterns at low fields in all samples after field-cooling from above Tc. These are consistent with those seen in systems with competing repulsions on disparate length scales and remarkably similar structures are reproduced in dirty two band Ginzburg-Landau calculations, where the simulation parameters have been defined by experimental observations. This suggests that in our dirty MgB2 films, the symmetry of the vortex structures is broken by the presence of vortex repulsions with two different lengthscales, originating from the two distinct superconducting condensates. This represents an entirely new mechanism for spontaneous symmetry breaking in systems of superconducting vortices, with important implications for pinning phenomena and high current density applications.
Detecting the existence of an invisibility cloak using temporal steering
Authors: Chen Shin-Liang , Chao Ching-Shiang , Chen Yueh-Nan
Published: October 2015

An invisibility cloak provides a way to hide an object under the detection of waves. A good cloak guides the incident waves through the cloaking shell with few distortion. Even if one day a nearly perfect cloak is built, some important quantum effects, such as dephasing of the electron spin or photon polarization, may still remain. In this work, we consider the possibility that using the temporal steering of these degrees of freedom to detect the existence of an invisibility cloak.
The SUMO Protease SENP3 Orchestrates G2-M Transition and Spindle Assembly in Mouse Oocytes
Authors: Huang Chun-Jie , Wu Di , Khan Faheem Ahmed , Huo Li-Jun
Published: October 2015

Oocyte meiosis is a transcription quiescence process and the cell-cycle progression is coordinated by multiple post-translational modifications, including SUMOylation. SENP3 an important deSUMOylation protease has been intensively studied in ribosome biogenesis and oxidative stress. However, the roles of SENP3 in cell-cycle regulation remain enigmatic, particularly for oocyte meiotic maturation. Here, we found that SENP3 co-localized with spindles during oocyte meiosis and silencing of SENP3 severely compromised the M phase entry (germinal vesicle breakdown, GVBD) and first polar body extrusion (PBI). The failure in polar body extrusion was due to the dysfunction of γ-tubulin that caused defective spindle morphogenesis. SENP3 depletion led to mislocalization and a substantial loss of Aurora A (an essential protein for MTOCs localization and spindle dynamics) while irregularly dispersed distribution of Bora (a binding partner and activator of Aurora A) in cytoplasm instead of concentrating at spindles. The SUMO-2/3 but not SUMO-1 conjugates were globally decreased by SENP3 RNAi. Additionally, the spindle assembly checkpoint remained functional upon SENP3 RNAi. Our findings renew the picture of SENP3 function by exploring its role in meiosis resumption, spindle assembly and following polar body emission during mouse oocyte meiotic maturation, which is potentially due to its proteolytic activity that facilitate SUMO-2/3 maturation.
Single Canonical Model of Reflexive Memory and Spatial Attention
Authors: Patel Saumil S. , Red Stuart , Lin Eric , Sereno Anne B.
Published: October 2015

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey’s task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes.
Toxicological and biochemical analyses demonstrate no toxic effect of Cry1C and Cry2A to Folsomia candida
Authors: Yang Yan , Chen Xiuping , Cheng Lisheng , Cao Fengqin , Romeis Jörg , Li Yunhe , Peng Yufa
Published: October 2015

Collembolans are common soil arthropods that may be exposed to insecticidal proteins produced in genetically engineered (GE) plants by ingestion of crop residues or root exudates. In the present study, a dietary exposure assay was validated and used to assess the lethal and sublethal effects of twoBacillus thuringiensis(Bt) insecticidal proteins, Cry1C and Cry2A, onFolsomia candida. Using the insecticidal compounds potassium arsenate (PA), protease inhibitor (E-64) andGalanthus nivalisagglutinin (GNA) mixed into Baker’s yeast, we show that the assay used can detect adverse effects onF. candida. Survival and development were significantly reduced whenF. candidawas fed a diet containing PA, E-64 and GNA at 9, 75 and 100 μg/g diet, respectively, but not when fed a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A. The activities of test antioxidant-, detoxification- and digestion-related enzymes inF. candidawere unaltered by a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A, but were significantly increased by a diet containing 75 μg/g E-64. The results confirm that Cry1C and Cry2A are not toxic toF. candidaat concentrations that are much higher than those encountered under field conditions.
Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass and Bone Strength of Intact Bones in Adult Male Rats
Authors: Suen Pui Kit , Zhu Tracy Y. , Chow Dick Ho Kiu , Huang Le , Zheng Li-Zhen , Qin Ling
Published: October 2015

We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25 mg/kg, 2 times per week) treatment for 9 weeks. Compared with vehicle control, Scl-Ab treatment significantly improved trabecular and cortical bone mass and microarchitecture at L5 vertebrae and left femora by micro-CT at week 6 and 9. Mechanical testing showed that Scl-Ab treatment resulted in significantly higher stiffness, energy to failure and ultimate load at the femora at week 9. Mineral apposition rate, mineralizing surface and bone formation rate on the trabecular bone in the distal femora was significantly increased in Scl-Ab group at week 6 and 9. The administered Scl-Ab was localized in the osteocytes and beta-catenin was strongly expressed in osteoblasts. Scl-Ab treatment significantly increased serum P1NP level and there was no between-group difference in serum level of CTX-1. In conclusion, Scl-Ab treatment could induce rapid and sustained increase in bone formation, bone mass and bone strength in non-operated bones. Sclerostin inhibition might be advantageous to prevent secondary fracture(s).
Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
Authors: Mosli Hala H. , Esmat Ahmed , Atawia Reem T. , Shoieb Sherif M. , Mosli Hisham A. , Abdel-Naim Ashraf B.
Published: October 2015

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.
From light-harvesting to photoprotection: structural basis of the dynamic switch of the major antenna complex of plants (LHCII)
Authors: Liguori Nicoletta , Periole Xavier , Marrink Siewert J. , Croce Roberta
Published: October 2015

Light-Harvesting Complex II (LHCII) is largely responsible for light absorption and excitation energy transfer in plants in light-limiting conditions, while in high-light it participates in photoprotection. It is generally believed that LHCII can change its function by switching between different conformations. However, the underlying molecular picture has not been elucidated yet. The available crystal structures represent the quenched form of the complex, while solubilized LHCII has the properties of the unquenched state. To determine the structural changes involved in the switch and to identify potential quenching sites, we have explored the structural dynamics of LHCII, by performing a series of microsecond Molecular Dynamics simulations. We show that LHCII in the membrane differs substantially from the crystal and has the signatures that were experimentally associated with the light-harvesting state. Local conformational changes at the N-terminus and at the xanthophyll neoxanthin are found to strongly correlate with changes in the interactions energies of two putative quenching sites. In particular conformational disorder is observed at the terminal emitter resulting in large variations of the excitonic coupling strength of this chlorophyll pair. Our results strongly support the hypothesis that light-harvesting regulation in LHCII is coupled with structural changes.