bluuebunny/crossref_metadata_2025 huggingface dataset:
Short‐term modern life‐like stress exacerbates Aβ‐pathology and synapse loss in 3xTg‐AD mice
Authors: Baglietto‐Vargas David , Chen Yuncai , Suh Dongjin , Ager Rahasson R. , Rodriguez‐Ortiz Carlos J. , Medeiros Rodrigo , Myczek Kristoffer , Green Kim N. , Baram Tallie Z. , LaFerla Frank M.
Published: June 2015

Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD‐related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short‐term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short‐term, multi‐modal ‘modern life‐like’ stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg‐AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild‐type mice and tended to impact it in already low‐performing 3xTg‐AD mice. This stress reduced the number of synapse‐bearing dendritic spines in 3xTg‐AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short‐term stress simulating modern‐life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers.

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Epidemiological evidence indicates that life experiences, including chronic stress, are a risk for Alzheimer disease (AD). However, it is unknown if short stress in the range of hours influences the onset or progression of AD. Here, we determined the effect of short, multi‐modal ‘modern‐lifelike'stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg‐AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild‐type mice and tended to impact it in already low‐performing 3xTg‐AD mice. This stress reduced the number of synapse‐bearing dendritic spines in 3xTg‐AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short stress simulating modern‐life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers.
Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats
Authors: Popovic Marjan , Stanojevic Zeljka , Tosic Jelena , Isakovic Aleksandra , Paunovic Verica , Petricevic Sasa , Martinovic Tamara , Ciric Darko , Kravic‐Stevovic Tamara , Soskic Vukic , Kostic‐Rajacic Sladjana , Shakib Kaveh , Bumbasirevic Vladimir , Trajkovic Vladimir
Published: June 2015

Arylpiperazine‐based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D2/5‐HT1A ligands, N‐{4‐[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl}‐phenyl]‐picolinamide (6a) and N‐{3‐[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate‐immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D2 and 5‐HT1A receptors. The protection was retained if treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0–7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL‐6, IL‐1, and GM‐CSF, TH1 cytokine IFN‐γ, TH17 cytokine IL‐17, as well as the signature transcription factors of TH1 (T‐bet) and TH17 (RORγt) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti‐apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN‐93 and neuronal cell line PC12 from mitogen‐activated normal T cells or myelin basic protein‐activated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease in CNS inflammation.

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Arylpiperazine dopaminergic/serotonergic ligands reduce neurological symptoms of acute autoimmune encephalomyelitis in rats without affecting the activation of autoreactive immune response, through mechanisms involving a decrease in CNS immune infiltration, as well as direct protection of CNS from immune‐mediated damage. These data indicate potential usefulness of arylpiperazine‐based compounds in the treatment of neuroinflammatory disorders such as multiple sclerosis.
Percutaneous Closure of Atrial Septal Defects Under Transthoracic Echocardiography Guidance Without Fluoroscopy or Intubation in Children
Authors: Pan Xiang‐Bin , Ou‐yang Wen‐Bin , Pang Kun‐Jing , Zhang Feng‐Wen , Wang Shou‐Zheng , Liu Yao , Zhang Da‐Wei , Guo Gai‐Li , Tian Peng‐Sheng , Hu Sheng‐Shou
Published: June 2015

Objective

Demonstrate the benefits of percutaneous atrial septal defect (ASD) closure under guidance of transthoracic echocardiography (TTE) without fluoroscopy.

Methods

From February 2013 to April 2014, 127 consecutive patients with an isolated type II ASD were recruited to undergo percutaneous closure under either TTE (n = 60, TTE group) or TEE (n = 67, TEE group) guidance. The TTE group received local anesthesia or sedation with propofol, and the TEE group received general anesthesia with endotracheal intubation. Follow‐up examinations were performed for both groups at 1 month, 3 months, 6 months, and 1 year after discharge and annually thereafter.

Results

The TTE group had a significantly shorter procedure time and respirator ventilation duration than the TEE group. The dose of propofol required, the cost, and the pharyngeal complication rate were significantly lower in the TTE group than in the TEE group. The median follow‐up of 11.6 months was uneventful in all patients.

Conclusions

Percutaneous ASD closure with TTE guidance as the only imaging tool avoids fluoroscopy, endotracheal intubation, and probe insertion and is associated with a satisfactory procedural success rate and lower costs. This procedure is a safe and reliable treatment for ASD.
Biological and Molecular Characterization of Alfalfa Mosaic Virus Infecting Trumpet Creeper (Campsis radicans) in Iran
Authors: Pourrahim Reza , Farzadfar Shirin
Published: June 2015

Samples of trumpet creeper (Campsis radicans) leaves showing mottling and mosaic were collected from plants growing in a private garden in Tehran province, Iran, in 2012. Symptomatic leaf samples were tested for Alfalfa mosaic virus (AMV), Cucumber mosaic virus (CMV) and Peanut stunt virus (PSV) infection in enzyme‐linked immunosorbent assay (ELISA), using specific antibodies. None of the samples were positive for CMV and PSV; however, all reacted positively with that of AMV antiserum. In biological assay, systemic infection was found on Datura stramonium, Nicotiana tabacum cvs., White Burley, and Xanthi, 21 days postinoculation (DPI), while necrotic local lesions were obtained following inoculation of Phaseolus vulgaris and Vigna unguiculata within three to four DPI. Using a pair of primers specific for AMV, a DNA fragment of 880 bp was RT‐PCR‐amplified. Analysis of the sequences revealed the presence of 657 nucleotides of AMV complete coat protein (CP) gene (translating 218 amino acid residues). Phylogenetic analysis using neighbour‐joining (NJ) method clustered AMV isolates into two main types and the IRN‐Tru (GenBank Accession No. JX865593) isolate fell into type I. Pairwise nucleotide distances also confirmed two main types with the highest and lowest similarities for type I and II, respectively. The association of AMV with mosaic disease of C. radicans represents the first record from the world.
Effects of dendrimer/cyclodextrin conjugates as gene transfer carriers on nitric oxide production from macrophages
Authors: Motoyama Keiichi , Sako Asumi , Ibrahim Abu Hashim Irhan , Higashi Taishi , Arima Hidetoshi
Published: June 2015

Objectives

The development of safe gene transfer carriers with high transfection efficiency, which does not affect the cell function, is a challenging issue. In this study, we examined the effects of α-cyclodextrin (α-CyD)/dendrimer conjugate (α-CDE (G3)) on nitric oxide (NO) production in murine macrophages J774.1 cells stimulated with toll-like receptors (TLR) ligands.

Methods

NO production from macrophages stimulated with TLR ligands was determined by the Griess method. Transfection efficiency of α-CDE (G3)/plasmid DNA (pDNA) complex was quantified by a luminometer.

Key findings

α-CDE (G3) significantly inhibited NO production from J774.1 cells stimulated with TLR ligands. α-CyD molecules in α-CDE (G3) had no effect on NO production. The inhibitory effect of α-CDE (G3) on NO production might be attributed to the dendrimer (G3). Increasing the degree of substitution (DS) of α-CyD in the α-CDE (G3) molecule was accompanied by a significant decrease in the inhibition of NO production. Furthermore, higher gene transfection efficiency of α-CDE (G3)/pDNA complex was observed upon increasing the DS of α-CyD.

Conclusions

α-CDE (G3) with high DS value of α-CyD may be considered as a safe gene transfer carrier that does not adversely affect NO production from macrophages stimulated with TLR ligands.
Analysis of rbcL sequences reveals the global biodiversity, community structure, and biogeographical pattern of thermoacidophilic red algae (Cyanidiales)
Authors: Hsieh Chia‐Jung , Zhan Shing Hei , Lin Yiching , Tang Sen‐Lin , Liu Shao‐Lun
Published: June 2015

Thermoacidophilic cyanidia (Cyanidiales) are the primary photosynthetic eukaryotes in volcanic areas. These red algae also serve as important model organisms for studying life in extreme habitats. The global biodiversity and community structure of Cyanidiales remain unclear despite previous sampling efforts. Here, we surveyed the Cyanidiales biodiversity in the Tatun Volcano Group (TVG) area in Taiwan using environmental DNA sequencing. We generated 174 rbcL sequences from eight samples from four regions in the TVG area, and combined them with 239 publicly available rbcL sequences collected worldwide. Species delimita‐tion using this large rbcL data set suggested at least 20 Cyanidiales OTUs (operational taxono‐mic units) worldwide, almost three times the presently recognized seven species. Results from environmental DNA showed that OTUs in the TVG area were divided into three groups: (i) dominant in hot springs with 92%–99% sequence identity to Galdieria maxima; (ii) largely distributed in drier and more acidic microhabitats with 99% identity to G. partita; and (iii) primarily distributed in cooler microhabitats and lacking identity to known cyanidia species (a novel Cyanidiales lineage). In both global and individual area analyses, we observed greater species diversity in non‐aquatic than aquatic habitats. Community structure analysis showed high similarity between the TVG community and West Pacific‐Iceland communities, reflecting their geographic proximity to each other. Our study is the first examination of the global species diversity and biogeographic affinity of cyanidia. Additionally, our data illuminate the influence of microhabitat type on Cyanidiales diversity and highlight intriguing questions for future ecological research.
Generic identity of Camptorrhiza indica (Colchicaceae) based on cytogenetics and molecular phylogenetics
Authors: Lekhak Manoj M. , Surveswaran Siddharthan , Yadav Shrirang R.
Published: June 2015

The tribe Iphigenieae (Colchicaceace, Liliales) includes two genera, viz. Camptorrhiza and Iphigenia, which are distributed in Africa, India, and Australasia. Iphigenia is represented by 12 species, of which six occur in India while Camptorrhiza comprises one species each in Africa (C. strumosa) and India (C. indica). The genus Camptorrhiza possesses a knee‐shaped tuber attached to the corms, filaments with a thick bulge in the middle and styles with single stigma. Iphigenia on the other hand lacks knee‐shaped tuber, bears linear filaments and has styles with three stigmas. Camptorrhiza indica possesses ovoid corms, linear filaments and styles with a single stigma. These characters are intermediate between Iphigenia and Camptorrhiza and hence we studied the cytogenetics and phylogenetic placement of this species to ascertain its generic identity. Somatic chromosome count (2n = 22) and karyotypic features of C. indica are very similar to that of Iphigenia species. Molecular phylogenetic studies based on atpB‐rbcL, rps16, trnL, and trnL‐F regions showed that C. indica is nested within a lineage of Indian Iphigenia species. Thus, C. indica was reduced to a species of Iphigenia, i.e., I. ratnagirica. Camptorrhiza is now a monotypic genus restricted only to southern Africa. A key to the Indian Iphigenia species is provided. In addition, a new combination Wurmbea novae‐zelandiae is proposed for Iphigenia novae‐zelandiae.
Effect of Defatted Wheat Germ Content and Its Particle Size on the Rheological and Textural Properties of the Cookie Dough
Authors: Petrović Jovana , Fišteš Aleksandar , Rakić Dušan , Pajin Biljana , Lončarević Ivana , Šubarić Drago
Published: June 2015

The Box–Behnken experimental design and modern instrumental methods were applied to examine the rheological and textural characteristics of the cookie dough, depending on the amount of flour replaced with wheat germ (5, 10 and 15%), different particle sizes of wheat germ (<150, 150–1,000, 800–2,000 μm) and varying moisture content of the dough (20, 22 and 24%). The results showed that increasing particle size of the wheat germ reduces deformation compliance of the dough. Moisture content had the greatest impact on dough elastic and viscous modulus. Particle size of wheat germ had an impact on resistance to extension and on extensibility of the dough. Wheat germ content up to 15% had no influence on the rheological and textural characteristics of the cookie dough.

Practical Applications

Wheat germ is nutritionally the most valuable part of the grain of wheat. It is a rich source of vitamin E, B vitamins, protein, dietary fiber and minerals (calcium, iron, potassium, magnesium, zinc). Unfortunately, wheat germ is one of the main by‐products of milling because of its high oil content. Using defatted wheat germ (by‐product of the wheat germ oil removing process), we can nutritionally enrich cookies that are ready‐to‐eat, have long shelf life and widely consumed food. The present results indicate that the combination of wheat germ content, its particle size and moisture of the dough can be used to improve the nutritional quality of the cookies, without a negative effect on the physical characteristics of the dough.
Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs
Authors: Nabity M.B. , Lees G.E. , Boggess M.M. , Yerramilli M. , Obare E. , Yerramilli M. , Rakitin A. , Aguiar J. , Relford R.
Published: June 2015

Background

Symmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation.SDMAis primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR).

Objectives

To validate an assay forSDMAmeasurement, determine stability ofSDMAin blood, and compareSDMAwith serum creatinine concentration (sCr) andGFRfor early detection of decreasing kidney function in dogs with chronic kidney disease (CKD).

Animals

Eight male dogs affected with X‐linked hereditary nephropathy and 4 unaffected male littermates.

Methods

Prospective study validatingSDMAmeasurement using liquid chromatography‐mass spectrometry, assessing stability ofSDMAin serum and plasma, and serially determiningsCr,SDMA, andGFR(using iohexol clearance) in dogs during progression from preclinical disease to end‐stage renal failure. Correlations were determined using linear regression. Timepoints at whichsCr,SDMA, andGFRidentified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates.

Results

Symmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs,SDMAremained unchanged whereas in affected dogs,SDMAincreased during disease progression, correlating strongly with an increase insCr (r = 0.95) and decrease inGFR(r = −0.95). Although trending improvedsCr's sensitivity,SDMAidentified, on average, <20% decrease inGFR, which was earlier thansCr using any comparison method.

Conclusions and Clinical Importance

Symmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs withCKD.
Risk factors for primary sclerosing cholangitis
Authors: Boonstra Kirsten , de Vries Elisabeth M. G. , van Geloven Nan , van Erpecum Karel J. , Spanier Marcel , Poen Alexander C. , van Nieuwkerk Carin M. , Witteman Ben J. , Tuynman Hans A. , Naber Anton H. , Kingma Paul J. , Beuers Ulrich , Ponsioen Cyriel Y. ,   the Epi PSC PBC Study Group
Published: June 2015

Background & Aims

Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease of unknown cause, but strongly associated with inflammatory bowel disease (IBD). Potential risk factors triggering PSC have never been studied on a population level. The aim of this study was to evaluate smoking, appendectomy, family history and geographical distribution in a population‐based cohort of PSC patients, as compared to IBD control patients and healthy controls (HC).

Methods

For this case–control study 343 PSC patients, 370 IBD controls and 232 HC's living in a geographically defined area in the Netherlands filled‐out a questionnaire concerning smoking, appendectomy and family history of IBD and autoimmune liver diseases.

Results

Smoking was associated with a lower risk of developing PSC in PSC‐ulcerative colitis (UC) patients (adjusted OR 0.21; 95% CI 0.12–0.34; P < 0.001). Comparable results were found for PSC‐Crohn's disease (CD) patients (16% former smokers) compared to CD patients (55% former smokers) (adjusted OR 0.17; 95% CI 0.08–0.39; P < 0.001). Frequency of appendectomy did not differ between PSC and HC, but PSC‐UC patients had undergone appendectomy more often than UC patients (13% vs. 6%) (adjusted OR 2.51; 95%CI 1.04–6.07; P = 0.041). We found no association between family history of IBD or autoimmune liver disease and risk of PSC. Degree of urbanization was not associated with PSC incidence.

Conclusion

In this large population‐based case–control study we confirm that smoking is associated with a lower risk of developing PSC, independent of its protective effect for developing UC. Appendectomy is not associated with the risk of developing PSC.
AN ANALYTICAL SOLUTION FOR THE TWO‐SIDED PARISIAN STOPPING TIME, ITS ASYMPTOTICS, AND THE PRICING OF PARISIAN OPTIONS
Authors: Dassios Angelos , Lim Jia Wei
Published: June 2015

In this paper, we obtain a recursive formula for the density of the two‐sided Parisian stopping time. This formula does not require any numerical inversion of Laplace transforms, and is similar to the formula obtained for the one‐sided Parisian stopping time derived in Dassios and Lim. However, when we study the tails of the two distributions, we find that the two‐sided stopping time has an exponential tail, while the one‐sided stopping time has a heavier tail. We derive an asymptotic result for the tail of the two‐sided stopping time distribution and propose an alternative method of approximating the price of the two‐sided Parisian option.
Testing the role of ecology and life history in structuring genetic variation across a landscape: a trait‐based phylogeographic approach
Authors: Paz Andrea , Ibáñez Roberto , Lips Karen R. , Crawford Andrew J.
Published: June 2015

Hypotheses to explain phylogeographic structure traditionally invoke geographic features, but often fail to provide a general explanation for spatial patterns of genetic variation. Organisms' intrinsic characteristics might play more important roles than landscape features in determining phylogeographic structure. We developed a novel comparative approach to explore the role of ecological and life‐history variables in determining spatial genetic variation and tested it on frog communities in Panama. We quantified spatial genetic variation within 31 anuran species based on mitochondrial DNA sequences, for which hierarchical approximate Bayesian computation analyses rejected simultaneous divergence over a common landscape. Regressing ecological variables, on genetic divergence allowed us to test the importance of individual variables revealing that body size, current landscape resistance, geographic range, biogeographic origin and reproductive mode were significant predictors of spatial genetic variation. Our results support the idea that phylogeographic structure represents the outcome of an interaction between organisms and their environment, and suggest a conceptual integration we refer to as trait‐based phylogeography.
Characterization of postdive recovery using sound recordings and its relationship to dive duration, exertion, and foraging effort of southern elephant seals (Mirounga leonina)
Authors: Génin Alexandre , Richard Gaëtan , Jouma'a Joffrey , Picard Baptiste , El Ksabi Nory , Vacquié Garcia Jade , Guinet Christophe
Published: June 2015

It is notoriously difficult to measure physiological parameters in cryptic free‐ranging marine mammals. However, it is critical to understand how marine mammals manage their energy expenditure and their diving behavior in environments where the predation risks are low and where survival is mainly linked to capacities to maintain physiological homeostasis and energy budget balance. Elephant seals are top marine predators that dive deeply and continuously when at sea. Using acoustic recorders deployed on two postbreeding southern elephant seals (SES) females, we developed methods to automatically estimate breathing frequency at the surface. Using this method, we found that seals took successive identical breaths at high frequency (0.29 Hz) when recovering at the surface and that breath count was strongly related to postdive surfacing time. In addition, dive depth was the main factor explaining surfacing time through the effects of dive duration and total underwater swimming effort exerted. Finally, we found that recovery does not only occur over one dive timescale, but over a multidive time scale for one individual. The way these predators manage their recovery will determine how they respond to the change in oceanic water column structure in the future.
CULTURE AS A MEDIATOR OF HEALTH DISPARITIES: CULTURAL CONSONANCE, SOCIAL CLASS, AND HEALTH
Authors: Dressler William W. , Balieiro Mauro C. , Ribeiro Rosane P. , dos Santos José Ernesto
Published: June 2015

Health disparities or health inequalities refer to enduring differences between population groups in health status, well‐being, and mortality. Health inequalities have been described by race, ethnic group, gender, and social class. A variety of theories have been proposed to account for health inequalities, including access to medical care and absolute material deprivation. Several theorists (including Michael Marmot and Richard Wilkinson) have argued that relative deprivation is the primary factor. By this they mean the inability of individuals to achieve the kind of lifestyle that is valued and considered normative in their social context. In this article, we show that the concept and measurement of cultural consonance can operationalize what Marmot and Wilkinson mean by relative deprivation. Cultural consonance is the degree to which individuals approximate, in their own beliefs and behaviors, the prototypes for belief and behavior encoded in shared cultural models. Widely shared cultural models in society describe what is regarded both as appropriate and desirable in many different domains. These cultural models are both directive and motivating: people try to achieve the goals defined in these models; however, as a result of both social and economic constraints, some individuals are unable to effectively incorporate these cultural goals into their own lives. The result is an enduring loss of coherence in life, because life is not unfolding in the way that it, culturally speaking, “should.” The resulting chronic stress is associated with psychobiological distress. We illustrate this process with data collected in urban Brazil. A theory of cultural consonance provides a uniquely biocultural contribution to the understanding of health inequalities.
Medial temporal regional argyrophilic grain as a possible important factor affecting dementia in Parkinson's disease
Authors: Homma Taku , Mochizuki Yoko , Takahashi Kazushi , Komori Takashi
Published: June 2015

Argyrophilic grain (ArG) is the main pathological feature of argyrophilic grain disease (AGD) and is clinically characterized by cognitive impairment, behavioral abnormalities, personality changes, and emotional imbalances. However, ArG can not only be found in AGD but also in various other neurological disorders, including Parkinson's disease (PD). The association of ArG with psychosis and/or dementia in various neurological disorders remains unknown; in this study, we have investigated this in PD. The distribution and degree of ArG deposition, spongiform change in the transentorhinal cortex (TER SpC), and phosphorylated alpha‐synuclein‐positive neurites in CA2/3 were assessed, and we used formalin‐fixed, paraffin‐embedded specimens obtained from the anterior/posterior medial temporal region of 20 autopsy cases diagnosed as PD. These cases were clinically divided into two groups: PD without dementia (PDND) and PD with dementia (PDD). Most PDD cases revealed scattered to numerous ArG or moderate to severe TER SpC, both of which were rarely observed in the PDND group. Furthermore, by the degree of ArG density and TER SpC, the PDD group was further divided into three subtypes: PDD with ArG, with TER SpC and without ArG/TER SpC. Scattered‐to‐numerous ArG and/or moderate‐to‐severe TER SpC were observed only in PDD, which suggested that both ArG and TER SpC could be important factors affecting dementia in PD and that their distribution and degree are equally important.
Significance of gray matter brain lesions in multiple sclerosis and neuromyelitis optica
Authors: Kawachi Izumi , Nishizawa Masatoyo
Published: June 2015

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the two main autoimmune diseases of the CNS. In patients with NMO, the target antigen is aquaporin‐4 (AQP4), the most abundant water channel protein in the CNS. AQP4 is mainly expressed on astrocytic endfoot processes at the blood‐brain barrier and in subpial and subendymal regions. MS and NMO are distinct diseases, but they have some common clinical features: both have long been considered autoimmune diseases that primarily affect the white matter (WM). However, because WM demyelination by itself cannot explain the full extent of the clinical disabilities, including cognitive decline in patients with MS and NMO, renewed interest in gray matter (GM) pathology in MS and NMO is emerging. Important hallmarks of WM and GM lesions in MS and NMO may differentially influence neuronal degeneration and demyelination in the brain and spinal cord, given different detrimental effects, including cytokine diffusion, disruption of water homeostasis associated with or without AQP4 (the target antigen in NMO) dynamics, or other unidentified mechanisms. An increase in knowledge of the structure of GM and WM lesions in MS and NMO will result in more targeted therapeutic approaches to these two diseases.
Modeling development and quantitative trait mapping reveal independent genetic modules for leaf size and shape
Authors: Baker Robert L. , Leong Wen Fung , Brock Marcus T. , Markelz R. J. Cody , Covington Michael F. , Devisetty Upendra K. , Edwards Christine E. , Maloof Julin , Welch Stephen , Weinig Cynthia
Published: June 2015

Improved predictions of fitness and yield may be obtained by characterizing the genetic controls and environmental dependencies of organismal ontogeny. Elucidating the shape of growth curves may reveal novel genetic controls that single‐time‐point (STP) analyses do not because, in theory, infinite numbers of growth curves can result in the same final measurement.

We measured leaf lengths and widths in Brassica rapa recombinant inbred lines (RILs) throughout ontogeny. We modeled leaf growth and allometry as function valued traits (FVT), and examined genetic correlations between these traits and aspects of phenology, physiology, circadian rhythms and fitness. We used RNA‐seq to construct a SNP linkage map and mapped trait quantitative trait loci (QTL).

We found genetic trade‐offs between leaf size and growth rate FVT and uncovered differences in genotypic and QTL correlations involving FVT vs STPs. We identified leaf shape (allometry) as a genetic module independent of length and width and identified selection on FVT parameters of development.

Leaf shape is associated with venation features that affect desiccation resistance. The genetic independence of leaf shape from other leaf traits may therefore enable crop optimization in leaf shape without negative effects on traits such as size, growth rate, duration or gas exchange.
Changes of masseter muscle activity following injection of botulinum toxin type A in adult rats
Authors: Tsai C. Y. , Lei Y. Y. , Yang L. Y. , Chiu W. C.
Published: June 2015

Structured Abstract

Objectives

To investigate changes in masseter muscle function following intramuscular injection of different dose‐dependent botulinum toxin type A (BTXA).

Setting and Sample Population

Department of Orthodontics at Taipei Medical University. Fifty‐two, 70‐day‐old male Wistar rats were randomly divided into four groups. Group I received 7.5 U of BTXA (0.3 ml), Group II received 5.0 U, and Group III received 2.5 U in the right masseter muscle, respectively. Group IV is the control and received no BTXA injection.

Materials and Methods

A wire electrode device was implanted to record muscle activity. One week after implantation, the rats were fed every 2 h and EMG signals were recorded during the first hour. All signals were recorded for 12 weeks. Thereafter, EMG data were analyzed for statistical calculation and weights of masseter muscles were measured.

Results

Masseter muscle activity decreased 99% during the first week after BTXA injection and gradually recovered from the 3rd week on in Groups I‐III. By the 12th week, muscle activity recovered to 41% in Groups I and II and 56.26% in Group III. No significant changes of muscle activity were observed in Group IV.

Conclusion

BTXA induced a reduction in masseter muscle activity and an increased toxin dose resulted in greater depression of muscle activity.
Silencing of vacuolar invertase and asparagine synthetase genes and its impact on acrylamide formation of fried potato products
Authors: Zhu Xiaobiao , Gong Huiling , He Qunyan , Zeng Zixian , Busse James S. , Jin Weiwei , Bethke Paul C. , Jiang Jiming
Published: June 2015

Acrylamide is produced in a wide variety of carbohydrate‐rich foods during high‐temperature cooking. Dietary acrylamide is a suspected human carcinogen, and health concerns related to dietary acrylamide have been raised worldwide. French fries and potato chips contribute a significant proportion to the average daily intake of acrylamide, especially in developed countries. One way to mitigate health concerns related to acrylamide is to develop potato cultivars that have reduced contents of the acrylamide precursors asparagine, glucose and fructose in tubers. We generated a large number of silencing lines of potato cultivar Russet Burbank by targeting the vacuolar invertase gene VInv and the asparagine synthetase genes StAS1 and StAS2 with a single RNA interference construct. The transcription levels of these three genes were correlated with reducing sugar (glucose and fructose) and asparagine content in tubers. Fried potato products from the best VInv/StAS1/StAS2‐triple silencing lines contained only one‐fifteenth of the acrylamide content of the controls. Interestingly, the extent of acrylamide reduction of the best triple silencing lines was similar to that of the best VInv‐single silencing lines developed previously from the same potato cultivar Russet Burbank. These results show that an acrylamide mitigation strategy focused on developing potato cultivars with low reducing sugars is likely to be an effective and sufficient approach for minimizing the acrylamide‐forming potential of French fry processing potatoes.
Systematic Review of Measles and Rubella Serology Studies
Authors: Thompson Kimberly M. , Odahowski Cassie L.
Published: June 2015

Serological tests provide information about individual immunity from historical infection or immunization. Cross‐sectional serological studies provide data about the age‐ and sex‐specific immunity levels for individuals in the studied population, and these data can provide a point of comparison for the results of transmission models. In the context of developing an integrated model for measles and rubella transmission, we reviewed the existing measles and rubella literature to identify the results of national serological studies that provided cross‐sectional estimates of population immunity at the time of data collection. We systematically searched PubMed, the Science Citation Index, and references we identified from relevant articles published in English. We extracted serological data for comparison to transmission model outputs. For rubella, serological studies of women of child‐bearing age provide information about the potential risks of infants born with congenital rubella syndrome. Serological studies also document the loss of maternal antibodies, which occurs at different rates for the different viruses and according to the nature of the induced immunity (i.e., infection or vaccine). The serological evidence remains limited for some areas, with studies from developed countries representing a disproportionate part of the evidence. The collection and review of serological evidence can help program managers identify immunity gaps in the population, which may help them better understand the characteristics of individuals within their populations who may participate in transmission and manage risks.
Initial‐Boundary Value Problems for the Coupled Nonlinear Schrödinger Equation on the Half‐Line
Authors: Geng Xianguo , Liu Huan , Zhu Junyi
Published: June 2015

Initial‐boundary value problems for the coupled nonlinear Schrödinger equation on the half‐line are investigated via the Fokas method. It is shown that the solution can be expressed in terms of the unique solution of a matrix Riemann–Hilbert problem formulated in the complex k‐plane, whose jump matrix is defined in terms of the matrix spectral functions and that depend on the initial data and all boundary values, respectively. If there exist spectral functions satisfying the global relation, it can be proved that the function defined by the above Riemann–Hilbert problem solves the coupled nonlinear Schrödinger equation and agrees with the prescribed initial and boundary values. The most challenging problem in the implementation of this method is to characterize the unknown boundary values that appear in the spectral function . For a particular class of boundary conditions so‐called linearizable boundary conditions, it is possible to compute the spectral function in terms of and given boundary conditions by using the algebraic manipulation of the global relation. For the general case of boundary conditions, an effective characterization of the unknown boundary values can be obtained by employing perturbation expansion.
Nonlinear Fourier Transforms and the mKdV Equation in the Quarter Plane
Authors: Lenells Jonatan
Published: June 2015

The unified transform method introduced by Fokas can be used to analyze initial‐boundary value problems for integrable evolution equations. The method involves several steps, including the definition of spectral functions via nonlinear Fourier transforms and the formulation of a Riemann‐Hilbert problem. We provide a rigorous implementation of these steps in the case of the mKdV equation in the quarter plane under limited regularity and decay assumptions. We give detailed estimates for the relevant nonlinear Fourier transforms. Using the theory of L2‐RH problems, we consider the construction of quarter plane solutions which are C1 in time and C3 in space.
The combined influence of hardiness and cohesion on mental health in a military peacekeeping mission: A prospective study
Authors: Thomassen Ådne G. , Hystad Sigurd W. , Johnsen Bjørn Helge , Johnsen Grethe E. , Laberg Jon C. , Eid Jarle
Published: June 2015

A large number of studies have shown that hardiness and cohesion are associated with mental health in a military context. However, most of them are presented without controlling for baseline mental health symptoms, which is their most significant source of error. The present study investigates the combined effect of hardiness and cohesion in a prospective design, controlling for baseline levels of symptoms among Norwegian personnel serving in a peacekeeping operation in Kosovo. Multivariate regression analyses were performed in which self‐reported mental health complaints were regressed on our explanatory variables. Our findings suggest that both cohesion and hardiness contributed to increased stress resiliency, as measured by a lower level of reported mental health complaints. Our baseline measure of mental health accounted for a larger proportion of the variance than our other predictors. A significant interaction between cohesion and hardiness suggested a combined effect, over and above the individual contributions of the predictors. For individuals who scored high on hardiness, cohesion levels did not influence levels of mental health complaints. Individuals who scored low on hardiness, on the other hand, reported lower levels of mental health complaints when cohesion levels were high.
Wii Fit™ exercise therapy for the rehabilitation of ankle sprains: Its effect compared with physical therapy or no functional exercises at all
Authors: Punt I. M. , Ziltener J.‐L. , Monnin D. , Allet L.
Published: June 2015

Lateral ankle sprains represent the most common sports‐related injuries. The Nintendo Wii Fit™ could be useful in the treatment of ankle sprains. The aim of this study was to compare the effectiveness of exercise training using the Wii Fit™ in ankle sprain patients: (a) with physical therapy; and (b) a control group not receiving any treatment. Ninety lateral ankle sprain patients were randomized to a Wii Fit™, physical therapy, or control group. We assessed the following outcome measures before, and 6 weeks after starting the allocated treatment: Foot and Ankle Ability Measure, pain during rest and walking, delay before return to sport, patient satisfaction, and effectiveness of the allocated treatment. Six weeks after the baseline measures, foot and ankle ability scores had improved in all groups, and pain had decreased during walking (P < 0.050). No between‐group differences were detected between Wii Fit™ treatment, and both other groups (P > 0.050). In conclusion, the Wii Fit™ could be used as an exercise therapy to treat ankle sprain patients. However, Wii Fit™ was not more effective than only physical therapy, or no exercise therapy at all. Patients who did not receive treatment showed similar results as people who got any kind of exercise therapy.
Fabrication of ion conductive tin oxide-phosphate amorphous thin films by atomic layer deposition
Authors: Park Suk Won , Jang Dong Young , Kim Jun Woo , Shim Joon Hyung
Published: June 2015

This work reports the atomic layer deposition (ALD) of tin oxide-phosphate films using tetrakis(dimethylamino)tin and trimethyl phosphate as precursors. The growth rates were 1.23–1.84 Å/cycle depending upon the deposition temperature and precursor combination. The ionic conductivity of the ALD tin oxide-phosphate films was evaluated by cross-plane impedance measurements in the temperature range of 50–300 °C under atmospheric air, with the highest conductivity measured as 1.92 × 10−5 S cm−1 at 300 °C. Furthermore, high-resolution x-ray photoelectron spectroscopy exhibited two O1s peaks that were classified as two subpeaks of hydroxyl ions and oxygen ions, revealing that the quantity of hydroxyl ions in the ALD tin oxide-phosphate films influences their ionic conductivity.
Developing and Implementing a Coaching Philosophy: Guidance from Award-Winning Strength and Conditioning Coaches
Authors: Gillham Andy , Schofield Gary , Doscher Michael , Dalrymple Dan , Kenn Joe
Published: June 2015

Traditional examinations of coaching philosophies consider the perspective of sport coaches (e.g., soccer, cricket, rugby). The focus on sport coaches’ coaching philosophy has advanced the study of coaching effectiveness while simultaneously omitting strength and conditioning coaches from the larger body of literature on coaching philosophy. The purpose of this paper is to reveal how award winning strength and conditioning coaches shape and use their coaching philosophy. The participants include four renowned strength and conditioning coaches, one at the high school, one at the college, and two at the professional level. A summary is provided at the end that examines commonalities (e.g., all the respondents expressed the need to have a specific coaching philosophy) and differences (e.g., how discipline factors into their coaching philosophy) across the respondents’ views and connects their viewpoints to the broader literature on sport coaching.
A shot in the arm for damaged tissue
Authors: Kiberstis Paula A.
Published: June 2015

A compound that inhibits prostaglandin degradation enhances tissue regeneration in multiple organs in mice.
Gβ proteins as components of E3 ubiquitin ligases
Authors: Prabakaran Sudhakaran
Published: June 2015

The G protein β subunit functions as an adaptor subunit for an E3 ligase that ubiquitylates the G protein–coupled receptor kinase GRK2.
Impact of Ceftiofur Injection on Gut Microbiota and Escherichia coli Resistance in Pigs
Authors: Fleury M. A. , Mourand G. , Jouy E. , Touzain F. , Le Devendec L. , de Boisseson C. , Eono F. , Cariolet R. , Guérin A. , Le Goff O. , Blanquet-Diot S. , Alric M. , Kempf I.
Published: June 2015

Resistance to extended-spectrum cephalosporins (ESCs) is an important health concern. Here, we studied the impact of the administration of a long-acting form of ceftiofur on the pig gut microbiota and ESC resistance in
Escherichia coli
. Pigs were orally inoculated with an ESC-resistant
E. coli
M63 strain harboring a conjugative plasmid carrying a gene conferring resistance,
bla
CTX-M-1
. On the same day, they were given or not a unique injection of ceftiofur. Fecal microbiota were studied using quantitative PCR analysis of the main bacterial groups and quantification of short-chain fatty acids.
E. coli
and ESC-resistant
E. coli
were determined by culture methods, and the ESC-resistant
E. coli
isolates were characterized. The copies of the
bla
CTX-M-1
gene were quantified. After ceftiofur injection, the main change in gut microbiota was the significant but transitory decrease in the
E. coli
population. Acetate and butyrate levels were significantly lower in the treated group. In all inoculated groups,
E. coli
M63 persisted in most pigs, and the
bla
CTX-M-1
gene was transferred to other
E. coli
. Culture and PCR results showed that the ceftiofur-treated group shed significantly more resistant strains 1 and 3 days after ESC injection. Thereafter, on most dates, there were no differences between the groups, but notably, one pig in the nontreated group regularly excreted very high numbers of ESC-resistant
E. coli
, probably leading to a higher contamination level in its pen. In conclusion, the use of ESCs, and also the presence of high-shedding animals, are important features in the spread of ESC resistance.
Mobile Genetic Elements Related to the Diffusion of Plasmid-Mediated AmpC β-Lactamases or Carbapenemases from Enterobacteriaceae: Findings from a Multicenter Study in Spain
Authors: Zamorano L. , Miró E. , Juan C. , Gómez L. , Bou G. , González-López J. J. , Martínez-Martínez L. , Aracil B. , Conejo M. C. , Oliver A. , Navarro F.
Published: June 2015

We examined the genetic context of 74 acquired
ampC
genes and 17 carbapenemase genes from 85 of 640
Enterobacteriaceae
isolates collected in 2009. Using S1 pulsed-field gel electrophoresis and Southern hybridization, 37 of 74
bla
AmpC
genes were located on large plasmids of different sizes belonging to six incompatibility groups. We used sequencing and PCR mapping to investigate the regions flanking the acquired
ampC
genes. The
bla
CMY-2
-like genes were associated with IS
Ecp1
; the surrounding
bla
DHA
genes were similar to
Klebsiella pneumoniae
plasmid pTN60013 associated with IS
26
and the
psp
and
sap
operons; and the
bla
ACC-1
genes were associated with IS
26
elements inserted into IS
Ecp1
. All of the carbapenemase genes (
bla
VIM-1
,
bla
IMP-22
, and
bla
IMP-28
) were located in class 1 integrons. Therefore, although plasmids are the main cause of the rapid dissemination of
ampC
genes among
Enterobacteriaceae
, we need to be aware that other mobile genetic elements, such as insertion sequences, transposons, or integrons, can be involved in the mobilization of these genes of chromosomal origin. Additionally, three new integrons (In846 to In848) are described in this study.
Insights into the Mechanism of Inhibition of Novel Bacterial Topoisomerase Inhibitors from Characterization of Resistant Mutants of Staphylococcus aureus
Authors: Lahiri Sushmita D. , Kutschke Amy , McCormack Kathy , Alm Richard A.
Published: June 2015

The type II topoisomerases DNA gyrase and topoisomerase IV are clinically validated bacterial targets that catalyze the modulation of DNA topology that is vital to DNA replication, repair, and decatenation. Increasing resistance to fluoroquinolones, which trap the topoisomerase-DNA complex, has led to significant efforts in the discovery of novel inhibitors of these targets. AZ6142 is a member of the class of novel bacterial topoisomerase inhibitors (NBTIs) that utilizes a distinct mechanism to trap the protein-DNA complex. AZ6142 has very potent activity against Gram-positive organisms, including
Staphylococcus aureus
,
Streptococcus pneumoniae
, and
Streptococcus pyogenes
. In this study, we determined the frequencies of resistance to AZ6142 and other representative NBTI compounds in
S. aureus
and
S. pneumoniae
. The frequencies of selection of resistant mutants at 4× the MIC were 1.7 × 10
−8
for
S. aureus
and <5.5 × 10
−10
for
S. pneumoniae
. To improve our understanding of the NBTI mechanism of inhibition, the resistant
S. aureus
mutants were characterized and 20 unique substitutions in the topoisomerase subunits were identified. Many of these substitutions were located outside the NBTI binding pocket and impact the susceptibility of AZ6142, resulting in a 4- to 32-fold elevation in the MIC over the wild-type parent strain. Data on cross-resistance with other NBTIs and fluoroquinolones enabled the differentiation of scaffold-specific changes from compound-specific variations. Our results suggest that AZ6142 inhibits both type II topoisomerases in
S. aureus
but that DNA gyrase is the primary target. Further, the genotype of the resistant mutants suggests that domain conformations and DNA interactions may uniquely impact NBTIs compared to fluoroquinolones.