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  • 1
    Publication Date: 2019-02-01
    Description: Habitat-forming species sustain biodiversity and ecosystem functioning in harsh environments through the amelioration of physical stress. Nonetheless, their role in shaping patterns of species distribution under future climate scenarios is generally overlooked. Focusing on coastal systems, we assess how habitat-forming species can influence the ability of stress-sensitive species to exhibit plastic responses, adapt to novel environmental conditions, or track suitable climates. Here, we argue that habitat-former populations could be managed as a nature-based solution against climate-driven loss of biodiversity. Drawing from different ecological and biological disciplines, we identify a series of actions to sustain the resilience of marine habitat-forming species to climate change, as well as their effectiveness and reliability in rescuing stress-sensitive species from increasingly adverse environmental conditions.
    Type: Article , PeerReviewed
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  • 2
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-05
    Description: by Paul Wolff Mitchell The discovery of nearly 180-year-old cranial measurements in the archives of 19th century American physician and naturalist Samuel George Morton can address a lingering debate, begun in the late 20th century by paleontologist and historian of science Stephen Jay Gould, about the unconscious bias alleged in Morton’s comparative data of brain size in human racial groups. Analysis of Morton’s lost data and the records of his studies does not support Gould’s arguments about Morton’s biased data collection. However, historical contextualization of Morton with his scientific peers, especially German anatomist Friedrich Tiedemann, suggests that, while Morton’s data may have been unbiased, his cranial race science was not. Tiedemann and Morton independently produced similar data about human brain size in different racial groups but analyzed and interpreted their nearly equivalent results in dramatically different ways: Tiedemann using them to argue for equality and the abolition of slavery, and Morton using them to entrench racial divisions and hierarchy. These differences draw attention to the epistemic limitations of data and the pervasive role of bias within the broader historical, social, and cultural context of science.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 3
    Publication Date: 2018-10-05
    Description: by Ling Chen, Alexandra E. Fish, John A. Capra Genomic regions with gene regulatory enhancer activity turnover rapidly across mammals. In contrast, gene expression patterns and transcription factor binding preferences are largely conserved between mammalian species. Based on this conservation, we hypothesized that enhancers active in different mammals would exhibit conserved sequence patterns in spite of their different genomic locations. To investigate this hypothesis, we evaluated the extent to which sequence patterns that are predictive of enhancers in one species are predictive of enhancers in other mammalian species by training and testing two types of machine learning models. We trained support vector machine (SVM) and convolutional neural network (CNN) classifiers to distinguish enhancers defined by histone marks from the genomic background based on DNA sequence patterns in human, macaque, mouse, dog, cow, and opossum. The classifiers accurately identified many adult liver, developing limb, and developing brain enhancers, and the CNNs outperformed the SVMs. Furthermore, classifiers trained in one species and tested in another performed nearly as well as classifiers trained and tested on the same species. We observed similar cross-species conservation when applying the models to human and mouse enhancers validated in transgenic assays. This indicates that many short sequence patterns predictive of enhancers are largely conserved. The sequence patterns most predictive of enhancers in each species matched the binding motifs for a common set of TFs enriched for expression in relevant tissues, supporting the biological relevance of the learned features. Thus, despite the rapid change of active enhancer locations between mammals, cross-species enhancer prediction is often possible. Our results suggest that short sequence patterns encoding enhancer activity have been maintained across more than 180 million years of mammalian evolution.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 4
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-05
    Description: by Philip E. Bourne
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 5
    Publication Date: 2018-10-05
    Description: by Petra E. Deane-Coe, Erin T. Chu, Andrea Slavney, Adam R. Boyko, Aaron J. Sams Consumer genomics enables genetic discovery on an unprecedented scale by linking very large databases of personal genomic data with phenotype information voluntarily submitted via web-based surveys. These databases are having a transformative effect on human genomics research, yielding insights on increasingly complex traits, behaviors, and disease by including many thousands of individuals in genome-wide association studies (GWAS). The promise of consumer genomic data is not limited to human research, however. Genomic tools for dogs are readily available, with hundreds of causal Mendelian variants already characterized, because selection and breeding have led to dramatic phenotypic diversity underlain by a simple genetic structure. Here, we report the results of the first consumer genomics study ever conducted in a non-human model: a GWAS of blue eyes based on more than 3,000 customer dogs with validation panels including nearly 3,000 more, the largest canine GWAS to date. We discovered a novel association with blue eyes on chromosome 18 ( P = 1.3x10 -68 ) and used both sequence coverage and microarray probe intensity data to identify the putative causal variant: a 98.6-kb duplication directly upstream of the Homeobox gene ALX4 , which plays an important role in mammalian eye development. This duplication is largely restricted to Siberian Huskies, is strongly associated with the blue-eyed phenotype (chi-square P = 5.2x10 -290 ), and is highly, but not completely, penetrant. These results underscore the power of consumer-data-driven discovery in non-human species, especially dogs, where there is intense owner interest in the personal genomic information of their pets, a high level of engagement with web-based surveys, and an underlying genetic architecture ideal for mapping studies.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 6
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-05
    Description: by Nancy E. Breen, Julie Loewenstein, Rebecca Metivier, Lawrence Andrade, Andrew L. Rhyne
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2018-10-05
    Description: by The PLOS ONE Staff
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2018-10-05
    Description: by Naim Alkhouri, Casey Johnson, Leon Adams, Sachiko Kitajima, Chikayuki Tsuruno, Tracey L. Colpitts, Kazuki Hatcho, Eric Lawitz, Rocio Lopez, Ariel E. Feldstein
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2018-10-05
    Description: by Wenrong Lin, Zheng Jye Ling, Siqi Liu, Joel Tye Beng Lee, Marcus Lim, Aloysius Goh, Sean Lim, Peter George Manning, Mengling Feng, Tze Ping Loh
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2018-10-05
    Description: by Jayme Parker, Nisha Fowler, Mary Louise Walmsley, Terri Schmidt, Jason Scharrer, James Kowaleski, Teresa Grimes, Shanann Hoyos, Jack Chen
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 11
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    Public Library of Science (PLoS)
    Publication Date: 2018-09-18
    Description: by Petteri Nieminen, Reijo Käkelä, Tero Mäkinen, Olli Laine, Teemu Takalo, Anne-Mari Mustonen Fatty acid (FA) signatures (FAS) are important tools to assess the foraging ecology of wild animals. The present study was conducted to assess how well the general FAS and the proportions of individual FA are preserved in fat samples stored at different temperatures (–196, –80, –20, +4 and +20°C). Using three species (laboratory rat, American mink and rainbow trout), FAS were determined immediately upon sampling. Thereafter, eight subsamples per storage temperature from the inner part of the sample unaffected by oxygen and light were re-analyzed after 1, 2, 3, 7, 28, 84 and 168 days. Each time the remaining sample was sealed in its vial after replacing air with nitrogen gas. The results were tested with the mixed model and discriminant analyses. Generally, the FAS were well preserved regardless of storage temperature, and only a few major FA showed significant changes even after the 6-month period at room temperature. After an initial first-day change in proportions, presumably due to post-mortem enzymatic activities, the remaining minor changes could not be clearly attributed to either further autolysis, decomposition or autoxidation. In the discriminant analysis, the species-specific differences dominated and remained distinct even after 6 months. Furthermore, the analysis mostly classified the samples preserved at sub- and above-freezing temperatures separate from each other, and the general deviation from the initial analysis results was present as early as after 1 day. If FAS are to be analyzed in a very precise manner, the analysis should be performed immediately upon sampling. However, FAS remain adequately reliable for long periods of time even without preservation in deep freeze, widening the availability of potential samples for studies on foraging ecology and related disciplines.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 12
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    Public Library of Science (PLoS)
    Publication Date: 2018-09-18
    Description: by Yan Zhang, Xiaona Huang, Yuning Yang, Xiaoli Liu, Chenlu Yang, Anqi Wang, Yan Wang, Hong Zhou Objective The aim of this study was to investigate the nutritional status and its risk factors among children under 5 years, with special focus on the coexistence of under and over nutrition in population level. Methods We enrolled 6,570 children under 5 years among 26 counties in poor areas of China. Prevalences of malnutrition (stunting, underweight, wasting, overweight) were calculated. Overweight was evaluated using two indicators–weight for height Z score (WHZ) and body mass index for age Z score (BAZ), and results were compared. Results The total prevalence of malnutrition was 19.2%. The prevalence of stunting and overweight were as high as 8.4% and 8.8%, respectively. The BAZ-estimated prevalence of overweight was 9.9%, which was higher than the WHZ-estimated prevalence (p
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 13
    Publication Date: 2018-09-18
    Description: by Yanjun Lu, Cheng Liu, Yongfang Zhang, Jiahui Wang, Kangrui Yao, Yafeng Du, Norbert Müller In gasoline engines, CDA (cylinder deactivation) affects greatly the tribological performance of ring/liner system while reducing the emissions and improving the fuel economy. The analyses on the tribological performance of ring/liner system under the CDA mainly focus on the ideal circular cylinder liner and fixed fully flooded lubrication condition. In this study, a numerical investigation on the tribological performance of a compression ring-cylinder liner system is presented under the CDA with consideration of the cylinder liner deformation and the transition between the fully flooded and starved lubrication conditions. A mixed lubrication model coupled with oil transport model and JFO (Jacobson-Floberg-Olsson) conservative cavitation algorithm is proposed to evaluate the frictional properties. Based on the model, the tribological performance is investigated under the standard operation condition and the CDA. Meanwhile, the influence of cylinder liner deformation and oil supply on the tribological performance is also evaluated. Results show that the tribological performance of the compression ring-cylinder liner system is greatly changed when the CDA is adopted. In particular, under the CDA, the overall power loss and FMEP (friction mean effective pressure) value are increased about 27.29% and 53.51%. The study also demonstrates the necessity to consider the cylinder liner deformation and oil supply in the simulation of compression ring-cylinder liner system under the CDA.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 14
    Publication Date: 2018-09-18
    Description: by Georgia Kyriakidou, Mireen Friedrich-Rust, Dimitra Bon, Ishani Sircar, Christopher Schrecker, Dimitra Bogdanou, Eva Herrmann, Joerg Bojunga Purpose The aim of the study was to compare three different elastography methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave Elastography (2D-SWE), in the same study population for the differentiation of thyroid nodules. Materials and methods All patients received a conventional ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI-Imaging. Cytology/histology of thyroid nodules was used as a reference method. SE measures the relative stiffness within the region of interest (ROI) using the surrounding tissue as reference tissue. ARFI mechanically excites the tissue at the ROI using acoustic pulses to generate localized tissue displacements. 2D-SWE measures tissue elasticity using the velocity of many shear waves as they propagate through the tissue. Results 84 nodules (73 benign and 11 malignant) in 62 patients were analyzed. Sensitivity, specificity and NPV of SE were 73%, 70% and 94%, respectively. Sensitivity, specificity and NPV of ARFI and 2D-SWE were 90%, 79%, 98% and 73%, 67%, 94% respectively, using a cut-off value of 1.98m/s for ARFI and 2.65m/s (21.07kPa) for 2D-SWE. The AUROC (Area under the Receiver Operating Characteristic) of SE, ARFI and 2D-SWE for the diagnosis of malignant thyroid nodules were 52%, 86% and 71%, respectively. A significant difference in AUROC was found between SE and ARFI (p = 0.008), while no significant difference was found between ARFI and SWE (86% vs. 71%, p = 0.31), or SWE and SE (71% vs. 52%, p = 0.26). Conclusion pSWE using ARFI and 2D-SWE showed comparable results for the differentiation of thyroid nodules. ARFI was superior to elastography using SE.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 15
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    Public Library of Science (PLoS)
    Publication Date: 2018-09-18
    Description: by Enrico De Pieri, Morten E. Lund, Anantharaman Gopalakrishnan, Kasper P. Rasmussen, David E. Lunn, Stephen J. Ferguson Musculoskeletal models represent a powerful tool to gain knowledge on the internal forces acting at the joint level in a non-invasive way. However, these models can present some errors associated with the level of detail in their geometrical representation. For this reason, a thorough validation is necessary to prove the reliability of their predictions. This study documents the development of a generic musculoskeletal model and proposes a working logic and simulation techniques for identifying specific model features in need of refinement; as well as providing a quantitative validation for the prediction of hip contact forces (HCF). The model, implemented in the AnyBody Modeling System and based on the cadaveric dataset TLEM 2.0, was scaled to match the anthropometry of a patient fitted with an instrumented hip implant and to reproduce gait kinematics based on motion capture data. The relative contribution of individual muscle elements to the HCF and joint moments was analyzed to identify critical geometries, which were then compared to muscle magnetic resonance imaging (MRI) scans and, in case of inconsistencies, were modified to better match the volumetric scans. The predicted HCF showed good agreement with the overall trend and timing of the measured HCF from the instrumented prosthesis. The average root mean square error (RMSE), calculated for the total HCF was found to be 0.298*BW. Refining the geometries of the muscles thus identified reduced RMSE on HCF magnitudes by 17% (from 0.359*BW to 0.298*BW) over the whole gait cycle. The detailed study of individual muscle contributions to the HCF succeeded in identifying muscles with incorrect anatomy, which would have been difficult to intuitively identify otherwise. Despite a certain residual over-prediction of the final hip contact forces in the stance phase, a satisfactory level of geometrical accuracy of muscle paths has been achieved with the refinement of this model.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 16
    Publication Date: 2018-09-18
    Description: by Masato Koike, Hidetoshi Nojiri, Hiroaki Kanazawa, Hiroto Yamaguchi, Kei Miyagawa, Nana Nagura, Sammy Banno, Yoshiyuki Iwase, Hisashi Kurosawa, Kazuo Kaneko Recent studies have shown that superoxide dismutase 1 (SOD1), SOD2, and SOD3 are significantly decreased in human osteoarthritic cartilage. SOD activity is a marker that can be used to comprehensively evaluate the enzymatic capacities of SOD1, SOD2, and SOD3; however, the trend of SOD activity in end-stage osteoarthritic tissues remains unknown. In the present study, we found that SOD activity in end-stage osteoarthritic synovium of the knee was significantly lower than that in control synovium without the influence of age. The SOD activity was significantly lower in the end-stage knee osteoarthritic cartilage than in the control, but a weak negative correlation was observed between aging and SOD activity. However, SOD activity in end-stage hip osteoarthritic cartilage was significantly lower than that in control cartilage without the influence of aging. The relationship between osteoarthritis and SOD activity was stronger than the relationship between aging and SOD activity. These results indicate that direct regulation of SOD activity in joint tissues may lead to suppression of osteoarthritis progression.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 17
    Publication Date: 2018-09-18
    Description: by Lise Skåren, Xiaofang Wang, Åshild Bjørnerem Efforts to understand the pathophysiology of bone fragility must focus on bone traits during growth. We hypothesized that variance in individual trait ranking in the population distribution is established by genetic factors and is reflected in foetal trait ranking in early pregnancy, but intrauterine factors modify trait ranking in late pregnancy, followed by the reinstating of this ranking during the first postnatal year. Thus, relations with paternal factors are present in early pregnancy but are then lost and subsequently reinstated postnatal. We recruited 399 healthy pregnant women aged 20–42 years from The Mercy Hospital for Woman in Melbourne, Australia. Foetal femur length (FL) and knee-heel length (KHL) were measured by ultrasound during gestation, and FL, KHL, body length and weight were measured in neonates, infants, and parents. The z-scores were calculated using Royston models. Pearson correlation was used to assess tracking and linear mixed models to test the associations. Correlations between FL and KHL z-scores of the same trait at 20 and 30 weeks gestation, at birth, and at 12 and 24 months of age (r = 0.1–0.3) and of body length and weight at birth, and 6, 12 and 24 months (r = 0.3–0.5) became more robust after 6–12 months (r = 0.4–0.8). FL and KHL z-scores at 20 weeks gestation accounted for 4–5% of total variance, while FL, KHL, body length and weight z-scores at birth accounted for 13–26% of total variance in the same traits at 24 months. Maternal FL and KHL were associated with foetal FL and KHL at 20 and 30 weeks, but there were no such associations for paternal FL and KHL with foetal traits during gestation. Both maternal and paternal traits were associated with infant traits. Tracking in traits is not established antenatal but is robustly established at 6–12 months of age.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 18
    Publication Date: 2018-09-18
    Description: by Folusho Balogun, Olayemi Omotade Background Human Papilloma virus (HPV) vaccines for adolescents are pivotal in the control of cervical cancer, the commonest women specific malignancy in sub-Saharan Africa. Knowledge about cervical cancer have been reported to be low in Africa but expressed acceptability for HPV vaccines have been high. The reason for this mismatch is not clear. An understanding of the interpretation of cervical cancer and views about HPV vaccine are important as they can affect actual decision making regarding adolescents’ uptake of HPV vaccine. This study explored contextual interpretations of stakeholders regarding cervical cancer and HPV vaccines for adolescents in five selected communities in Ibadan, Nigeria. Methods Qualitative data were collected through twenty focus group discussions among parents of adolescents, religious and traditional leaders, school teachers and adolescents; and four key informant interviews with the identified traditional healers in the selected communities. Constant comparison analysis was done after transcription. Results Almost every group had at least one person who had seen a cervical cancer patient. Cervical cancer was widely viewed as being caused by promiscuity of women while older participants believed that the alteration of lifestyle by civilization was a major contributory factor. There was also a general notion that it was due to a curse. The role of HPV was generally not known. Most participants were favourable towards HPV immunization for adolescents but traditional healers and some religious leaders were not. The high cost of the vaccines and possibility of side effects where the main concerns about the introduction of HPV vaccine. Decision to take the vaccine rest with the fathers whose views were heavily influenced by traditional and religious leaders. Conclusions Awareness about cervical cancer may not be as low as earlier reported and there were many misconceptions about cervical cancer in the study communities. It is important to address these misconceptions to ensure successful introduction of HPV vaccine for adolescents in future.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 19
    Publication Date: 2018-09-18
    Description: by David Hendrickx, Asha C. Bowen, Julie A. Marsh, Jonathan R. Carapetis, Roz Walker Infectious diseases contribute a substantial burden of ill-health in Australia’s Aboriginal children. Skin infections have been shown to be common in remote Aboriginal communities, particularly in the Northern Territory, Australia. However, primary care data on skin and other infectious diseases among Aboriginal children living in remote areas of Western Australia are limited. We conducted a retrospective review of clinic presentations of all children aged 0 to 5 years presenting to four clinics located in the Western Desert region of Western Australia between 2007 and 2012 to determine this burden at a local level. Infectious diseases accounted for almost 50% of all clinic presentations. Skin infections (sores, scabies and fungal infections) were the largest proportion (16%), with ear infections (15%) and upper respiratory infections (13%) also high. Skin infections remained high in all age groups; 72% of children presented at least once with skin infections. Scabies accounted for only 2% of all presentations, although one-quarter of children presented during the study for management of scabies. Skin sores accounted for 75% of the overall burden of skin infections. Improved public health measures targeting bacterial skin infections are needed to reduce this high burden of skin infections in Western Australia.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 20
    Publication Date: 2018-09-18
    Description: by Gianluca Interlandi The protein von Willebrand factor (VWF) is key for the adhesion of blood platelets to sites of vascular injury. Recent studies have shown that the release of oxidative agents during inflammation increases the platelet-tethering activity of VWF contributing to a pro-thrombotic state. This has been linked to the oxidation of methionine residues in the A1, A2 and A3 domains of VWF. The A1 domain binds to platelet surface receptors glycoprotein Ib α (GpIb α ). This interaction has been shown to be inhibited under static conditions by the neighboring A2 domain. Tensile force exerted by blood flow unfolds the A2 domain normally leading to its cleavage by the metalloprotease ADAMTS13 preventing pathological thrombus formation. However, oxidizing conditions inhibit proteolysis through ADAMTS13. Here, molecular dynamics simulations tested the hypothesis whether methionine oxidation induced by inflammatory conditions favors unfolding of the A2 domain contributing to the experimentally observed activation of VWF. The results indicate that oxidation of methionine residues located near the C-terminal helix of the A2 domain reduce the force necessary to initiate unfolding. Furthermore, oxidation of methionine residues shifts the thermodynamic equilibrium of the A2 domain fold towards the denatured state. This work suggests a mechanism whereby oxidation reduces the kinetic and thermodynamic stability of the A2 domain removing its inhibitory function on the binding of the A1 domain to GpIb α .
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 21
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    Public Library of Science (PLoS)
    Publication Date: 2018-09-18
    Description: by Jianxia Liu, Jinxiang Wang, Shaochin Lee, Riyu Wen Copper (Cu) is a necessary trace element participated in many physiological processes in plants. But excessive Cu 2+ is toxic, which can activate intracellular signals that lead to cellular damage. The mitogen-activated protein kinase (MAPK) cascade is at the center of cell signal transduction and has been reported to be involved in stress-related signaling pathways. ZmMPK3, a kind of MAPKs in maize cells, can be activated by diverse abiotic stresses. In the present study, we investigated the effects of Cu 2+ on hydrogen peroxide (H 2 O 2 ) level, ZmMPK3 activity as well as the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and ascorbic acid peroxidase (APX) using maize leaf as an experimental model. The results demonstrated that acute Cu 2+ exposure for 24 hours led to rapid increases of H 2 O 2 level and the increase in ZmMPK3 activity as well as the total activities of antioxidant enzymes SOD, CAT and APX. H 2 O 2 scavenger, dimethylthiourea (DMTU), effectively inhibited the Cu 2+ -increased H 2 O 2 level and the activity of ZmMPK3 as well as the activities of the antioxidant enzymes SOD, CAT and APX. Pre-treatment with the MAPK inhibitor, PD98059, significantly blocked the Cu 2+ -increased activities of ZmMPK3, CAT, APX and SOD, but didn’t affect the accumulation of H 2 O 2 . Our results suggest that Cu 2+ causes oxidative stress to the maize leaves which then activates defense antioxidant enzymes via MAPK pathway. Thus, the signaling pathway is Cu 2+ —H 2 O2—ZmMPK3—antioxidant enzymes.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 22
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    Public Library of Science (PLoS)
    Publication Date: 2018-09-18
    Description: by Mirko Krüger Background A physical education (PE) intervention for young refugees was designed combining physical activity within the context of primary PE games with second language learning activities in German. The intervention was based on theoretical implications from the field of second language acquisition and evidence for positive effects of physical activity on cognitive outcomes (e.g. language acquisition). The aim of this study was to analyze short term effects on second language acquisition. Methods Sixty-one young refugees were included in the study ( age : 8.5 ± 1.4 years). The intervention group participated in language-enriched PE lessons based on an elaborated approach to second language learning acquisition. The control group did not receive any treatment. Both groups were pre-and post-tested in domain specific vocabulary, listening comprehension and use of local prepositions within the context of primary PE games. Results Results from linear mixed-effect modelling suggest that the intervention group significantly improved domain specific vocabulary and listening comprehension in comparison to the control group. Conclusions The intervention was successful since the PE lessons contributed to the second language acquisition of young refugees. Therefore, this learning approach might also be useful for physical activity based second language learning activities in other PE contexts for early second language learners in primary school.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 23
    Publication Date: 2018-09-18
    Description: by Siqiang Liu, Mei Yuan, Dingxing Jin, Zhisheng Wang, Huawei Zou, Lizhi Wang, Bai Xue, De Wu, Gang Tian, Jingyi Cai, Tianhai Yan, Quanhui Peng The world's annual output of rabbits is over 1.2 billion, therefore this sector is also one of the sources of greenhouse gases in livestock production. One hundred-twenty New Zealand rabbits were allocated into four treatments, five replicates in each treatment and six rabbits in each replicate to examine the effect of grinding alfalfa hay to different sizes on growth performance, methane production and cecal archaeal populations. The particle sizes of the alfalfa meal in the four treatment diets were 2500, 1000, 100 and 10 μm, while the other ingredients were ground through a 2.5 mm sieve. The average daily gain (ADG) and average daily feed intake (ADFI) increased ( P
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 24
    Publication Date: 2018-09-18
    Description: by M. Vaga, P. Huhtanen An in vitro method based on 15 N-labelled forage nitrogen (N) was developed to study ruminal N metabolism of soluble N (SN), insoluble N (ISN) and neutral detergent insoluble N (NDIN) fractions of timothy forage. Timothy grass was grown on replicated experimental plots with one plot receiving 15 N-labelled and the other unlabelled N fertilizer. Harvested grass was preserved as dried grass or as formic acid treated or untreated silage. The intact forages and their corresponding N fractions were incubated in buffered rumen fluid in vitro to determine degradation parameters based on the 15 N fluxes between labelled feed N and ammonia N pools. A high percentage (25–38%) of 15 N-labelled ammonia disappeared from ammonia N pool during the first 15 min of incubation. Microbial uptake of dried grass SN fraction was higher than of silage SN fractions. Fractional degradation rates of SN from formic acid treated silage, untreated silage and dried grass during the first 6 hours of incubation were 0.145, 0.125 and 0.115 /h, respectively. By the end of the incubation period (28 h), 69, 66 and 43%, of the SN fraction of formic acid treated silage, untreated silage and dried grass, respectively were recovered as ammonia. The percentage of ISN fractions degraded to ammonia N were 9, 34 and 27%, respectively. Based on the changes in 15 N-labelled ammonia N pool in blank incubation and appearance of 15 N to ammonia N pool from 15 N-labelled NDIN fractions, it was estimated that a significant portion of microbial lysis occurred when incubations were carried out for longer than 20 hours. With dried grass the contribution of ammonia N for microbial N synthesis was greater than with silages. Use of 15 N-labelled forages together with this in vitro method is a promising technique for determining soluble N degradation parameters, but it requires further development to be used for determining degradation parameters of insoluble N fractions and work with whole feeds.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 25
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    Public Library of Science (PLoS)
    Publication Date: 2018-09-18
    Description: by Samir Huseynov, Marco A. Palma The Low Carbon Fuel Standards (LCFS) represents a new policy approach designed to reduce carbon dioxide emissions by applying standards to all stages of motor fuel production. We use the synthetic control and difference-in-differences econometric methods, and Lasso machine learning to analyze the effect of the LCFS on emissions in California’s transportation sector. The three different techniques provide robust evidence that the LCFS reduced carbon dioxide emissions in California’s transportation sector by around 10%. Furthermore, our calculations show that improved air quality, due to the application of the LCFS, may have benefited California in the magnitude of hundreds of millions of dollars through an increase in worker’s productivity.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 26
    Publication Date: 2018-09-18
    Description: by Arthur Mpimbaza, Andrew Walakira, Grace Ndeezi, Anne Katahoire, Charles Karamagi, Samuel L. Nsobya, Stephen Tukwasibwe, Victor Asua, Philip J. Rosenthal Background Evidence for association between sickle cell and alpha thalassemia trait and severe malaria is compelling. However, for these polymorphisms associations with uncomplicated malaria, and for G6PD deficiency associations with uncomplicated and severe malaria, findings have been inconsistent. We studied samples from a three-arm case-control study with the objective of determining associations between common host erythrocyte polymorphisms and both uncomplicated and severe malaria, including different severe malaria phenotypes. Method We assessed hemoglobin abnormalities, α-thalassemia, and G6PD deficiency by molecular methods in 325 children with severe malaria age-matched to 325 children with uncomplicated malaria and 325 healthy community controls. Conditional logistic regression was used to measure associations between specified genotypes and malaria outcomes. Results No tested polymorphisms offered significant protection against uncomplicated malaria. α-thalassemia homozygotes (_α/_α) had increased risk of uncomplicated malaria (OR 2.40; 95%CI 1.15, 5.03, p = 0.020). HbAS and α-thalassemia heterozygous (_α/αα) genotypes protected against severe malaria compared to uncomplicated malaria (HbAS OR 0.46; 0.23, 0.95, p = 0.036; _α/αα OR 0.51; 0.24, 0.77; p = 0.001) or community (HbAS OR 0.23; 0.11, 0.50; p
    Electronic ISSN: 1932-6203
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  • 27
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-06
    Description: by Istvan T. Kleijn, Laurens H. J. Krah, Rutger Hermsen In bacterial cells, gene expression, metabolism, and growth are highly interdependent and tightly coordinated. As a result, stochastic fluctuations in expression levels and instantaneous growth rate show intricate cross-correlations. These correlations are shaped by feedback loops, trade-offs and constraints acting at the cellular level; therefore a quantitative understanding requires an integrated approach. To that end, we here present a mathematical model describing a cell that contains multiple proteins that are each expressed stochastically and jointly limit the growth rate. Conversely, metabolism and growth affect protein synthesis and dilution. Thus, expression noise originating in one gene propagates to metabolism, growth, and the expression of all other genes. Nevertheless, under a small-noise approximation many statistical quantities can be calculated analytically. We identify several routes of noise propagation, illustrate their origins and scaling, and establish important connections between noise propagation and the field of metabolic control analysis. We then present a many-protein model containing 〉1000 proteins parameterized by previously measured abundance data and demonstrate that the predicted cross-correlations between gene expression and growth rate are in broad agreement with published measurements.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 28
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    Publication Date: 2018-10-06
    Description: by William K. Scott, Felix Mba Medie, Felicia Ruffin, Batu K. Sharma-Kuinkel, Derek D. Cyr, Shengru Guo, Derek M. Dykxhoorn, Robert L. Skov, Niels E. Bruun, Anders Dahl, Christian J. Lerche, Andreas Petersen, Anders Rhod Larsen, Trine Kiilerich Lauridsen, Helle Krogh Johansen, Henrik Ullum, Erik Sørensen, Christian Hassager, Henning Bundgaard, Henrik C. Schønheyder, Christian Torp-Pedersen, Louise Bruun Østergaard, Magnus Arpi, Flemming Rosenvinge, Lise T. Erikstrup, Mahtab Chehri, Peter Søgaard, Paal S. Andersen, Vance G. Fowler Jr. The role of host genetic variation in the development of complicated Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome sequencing (WES) to examine the cumulative effect of coding variants in each gene on risk of complicated SAB in a discovery sample of 168 SAB cases (84 complicated and 84 uncomplicated, frequency matched by age, sex, and bacterial clonal complex [CC]), and then evaluated the most significantly associated genes in a replication sample of 240 SAB cases (122 complicated and 118 uncomplicated, frequency matched for age, sex, and CC) using targeted sequence capture. In the discovery sample, gene-based analysis using the SKAT-O program identified 334 genes associated with complicated SAB at p
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
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  • 29
    Publication Date: 2018-10-06
    Description: by Fei Yao, Endong Zhang, Zhaolin Gao, Hongpei Ji, Mahmoud Marmouri, Xiaobo Xia Cholera toxin subunit B (CTB) and Fluorogold(FG) are two widely utilized retrograde tracers to assess the number and function of retinal ganglion cells (RGCs). However, the relative advantages and disadvantages of these tracers remain unclear, which may lead to their inappropriate application. In this study, we compared these tracers by separately injecting the tracer into the superior Colliculi (SC) in rats, one or 2 weeks later, the rats were sacrificed, and their retinas, brains, and optic nerves were collected. From the first to second week, FG displayed a greater number of labeled RGCs and a larger diffusion area in the SC than CTB; The number of CTB labeled RGCs and the diffusion area of CTB in the SC increased significantly, but there was no distinction between FG; Furthermore, CTB exhibited more labeled RGC neurites and longer neurites than FG, but no difference was evident between the same trace; The optic nerves labeled using CTB were much clearer than those labeled using FG. In conclusion, both CTB and FG can be used for the retrograde labeling of RGCs in rats at 1 or 2 weeks. FG achieves retrograde labeling of a greater number of RGCs than CTB, whereas CTB better delineates the morphology of RGCs. Furthermore, CTB seems more suitable for retrograde labeling of some small, non-image forming nuclei in the brain to which certain RGC subtypes project their axons.
    Electronic ISSN: 1932-6203
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  • 30
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    Publication Date: 2018-10-06
    Description: by Annelore Sacreas, Joshua Y. C. Yang, Bart M. Vanaudenaerde, Tara K. Sigdel, Juliane M. Liberto, Izabella Damm, Geert M. Verleden, Robin Vos, Stijn E. Verleden, Minnie M. Sarwal Rationale Recent studies suggest that similar injury mechanisms are in place across different solid organ transplants, resulting in the identification of a common rejection module (CRM), consisting of 11 genes that are overexpressed during acute and, to a lesser extent, chronic allograft rejection. Objectives We wanted to evaluate the usefulness of the CRM module in identifying acute rejection (AR) and different phenotypes of chronic lung transplant rejection (CLAD), i.e., bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), using transbronchial brushings, broncho-alveolar lavage (BAL) samples, and explant tissue. Methods Gene expression measurements for the 11 CRM genes (CD6, TAP1, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, and BASP1) were performed via qRT-PCR in 14 transbronchial brushings (AR, n = 4; no AR, n = 10), 32 BAL samples (stable, n = 13; AR, n = 8; BOS, n = 9; RAS, n = 10), and 44 tissue specimens (unused donor lungs, n = 15; BOS, n = 13; RAS, n = 16). A geometric mean score was calculated to quantitate overall burden of immune injury and a new computational model was built for the most significant genes in lung transplant injury. Results Acute rejection showed a significant difference in almost every gene analysed, validating previous observations from microarray analysis. RAS tissue demonstrated a higher geometric mean score (6.35) compared to donor tissue (4.09, p = 0.018). Analysis of individual CRM genes showed an increased expression of ISG20, CXCL10 and CXCL9 in RAS. In BAL samples, no differences were detected in gene expression or geometric mean scores between the various groups (stable, 5.15; AR, 5.81; BOS, 5.62; RAS, 7.31). A newly modelled 2-gene tissue CRM score did not demonstrate any difference between BOS and RAS (p〉0.05). However, the model was able to discriminate RAS from BOS tissue (AUC = 0.75, 95% CI = 0.55–0.94, p = 0.025). Conclusion Transcriptional tissue analysis for CRM genes in CLAD can identify acute rejection and distinguish RAS from BOS. The immune activation in RAS seems similar to acute rejection after kidney/liver/heart transplantation.
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  • 31
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    Publication Date: 2018-10-06
    Description: by Michelle A. Kominiarek, Linda C. O’Dwyer, Melissa A. Simon, Beth A. Plunkett Background Providers need to be comfortable addressing obesity and gestational weight gain so they may give appropriate care; however, health care providers lack guidelines for the most effective educational strategies to assist in providing optimal care. Objective To identify studies that involved the obstetric provider in interventions for either the perinatal management of obesity and/or gestational weight gain in a systematic review. Search strategy A keyword search of databases was performed up to April 2017. Selection criteria Obstetric providers who participated in an intervention with the aim to change a provider’s clinical practice, knowledge, and/or satisfaction with the intervention in relation to the perinatal management of obesity or gestational weight gain were included. Provider intervention could include training or education, changes in systems or organization of care, or resources to support practice. PROSPERO database #42016038921. Data collection and analysis Bias was assessed according to the validated Mixed Methods Appraisal Tool. The following variables were synthesized: study location and setting, provider and patient characteristics, intervention features, outcomes and efficacy, and strengths and weakness. Main results Of the 6,821 abstracts screened, seven studies (4 quantitative, 3 mixed-methods) with a total of 335 providers met the inclusion criteria; two of which focused on the management of obesity, three focused on gestational weight gain, and two focused on both topics. Interventions that incorporated motivational interviewing skills (n = 2), required additional training for the research study and addressed specific knowledge deficits such as nutrition and exercise (n = 3), and interfaced with the electronic medical record (n = 1) demonstrated the greatest impact on provider outcomes. Provider reported satisfaction scores were generally favorable, but none addressed provider-level efficacy in practice change. Conclusions Given the limited number of studies, varying range of provider participation, and lack of provider-level efficacy, further evaluation of provider training and involvement in interventions for perinatal obesity or gestational weight gain is indicated to determine best practices for provider and patient outcomes.
    Electronic ISSN: 1932-6203
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  • 32
    Publication Date: 2018-10-06
    Description: by Constantia Aristidou, Athina Theodosiou, Mads Bak, Mana M. Mehrjouy, Efthymia Constantinou, Angelos Alexandrou, Ioannis Papaevripidou, Violetta Christophidou-Anastasiadou, Nicos Skordis, Sophia Kitsiou-Tzeli, Niels Tommerup, Carolina Sismani The majority of apparently balanced translocation (ABT) carriers are phenotypically normal. However, several mechanisms were proposed to underlie phenotypes in affected ABT cases. In the current study, whole-genome mate-pair sequencing (WG-MPS) followed by Sanger sequencing was applied to further characterize de novo ABTs in three affected individuals. WG-MPS precisely mapped all ABT breakpoints and revealed three possible underlying molecular mechanisms. Firstly, in a t(X;1) carrier with hearing loss, a highly skewed X-inactivation pattern was observed and the der(X) breakpoint mapped ~87kb upstream an X-linked deafness gene namely POU3F4 , thus suggesting an underlying long-range position effect mechanism. Secondly, cryptic complexity and a chromothripsis rearrangement was identified in a t(6;7;8;12) carrier with intellectual disability. Two translocations and a heterozygous deletion disrupted SOX5 ; a dominant nervous system development gene previously reported in similar patients. Finally, a direct gene disruption mechanism was proposed in a t(4;9) carrier with dysmorphic facial features and speech delay. In this case, the der(9) breakpoint directly disrupted NFIB , a gene involved in lung maturation and development of the pons with important functions in main speech processes. To conclude, in contrast to familial ABT cases with identical rearrangements and discordant phenotypes, where translocations are considered coincidental, translocations seem to be associated with phenotype presentation in affected de novo ABT cases. In addition, this study highlights the importance of investigating both coding and non-coding regions to decipher the underlying pathogenic mechanisms in these patients, and supports the potential introduction of low coverage WG-MPS in the clinical investigation of de novo ABTs.
    Electronic ISSN: 1932-6203
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  • 33
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-06
    Description: by Eyleen Nabyla Alvarenga Niitsuma, Gabriel da Rocha Fernandes, Francisco Carlos Félix Lana Leprosy is an infectious disease with a complex genetic and immunological background. Polymorphisms in genes that encode cytokines and receptors involved in the immune response, such as the Toll-like receptor 1 ( TLR1 ), may be associated with disease risk. We hypothesized that polymorphisms in innate immunity genes confer susceptibility to leprosy that differs between women and men. In this study, we investigate sex differences in the association between a single nucleotide polymorphism (SNP) in TLR1 and Nucleotide-binding oligomerization domain containing 2 ( NOD2 ) genes and leprosy susceptibility in 256 clinically classified leprosy patients and 233 control subjects in a Brazilian population. Our results showed no association between the SNP rs8057341 in NOD2 and leprosy in this population. However, the heterozygous genotype of the TLR1 SNP ( rs4833095 ) showed a statistically significant association in women (OR = 0.54, P = 0.02). Our findings suggest that the TLR1 polymorphism was associated with an increased protection from leprosy in women.
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  • 34
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    Publication Date: 2018-10-06
    Description: by Anita Bosak, Alma Ramić, Tamara Šmidlehner, Tomica Hrenar, Ines Primožič, Zrinka Kovarik This paper describes the synthesis and anticholinesterase potency of Cinchona -based alkaloids; ten quaternary derivatives of cinchonines and their corresponding pseudo -enantiomeric cinchonidines. The quaternization of quinuclidine moiety of each compound was carried out with groups diverse in their size: methyl, benzyl and differently meta- and para- substituted benzyl groups. All of the prepared compounds reversibly inhibited human butyrylcholinesterase and acetylcholinesterase with K i constants within nanomolar to micromolar range. Five cinchonidine derivatives displayed 95–510 times higher inhibition selectivity to butyrylcholinesterase over acetylcholinesterase and four were potent butyrylcholinesterase inhibitors with K i constants up to 100 nM, of which N - para -bromobenzyl cinchonidinium bromide can be considered a lead for further modifications and optimizations for possible use in the treatment of neurodegenerative diseases.
    Electronic ISSN: 1932-6203
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  • 35
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    Publication Date: 2018-10-06
    Description: by Cassandra N. Glaspie, Rochelle D. Seitz In Chesapeake Bay, the soft-shell clam Mya arenaria (thin-shelled, deep-burrowing) exhibits population declines when predators are active, and it persists at low densities. In contrast, the hard clam Mercenaria mercenaria (thick-shelled, shallow-burrowing) has a stable population and age distribution. We examined the potential for habitat and predators to control densities and distributions of bivalves in a field caging experiment ( Mya only) and laboratory mesocosm experiments (both species). In the field, clams exposed to predators experienced 76.3% greater mortality as compared to caged individuals, and blue crabs were likely responsible for most of the mortality of juvenile Mya . In mesocosm experiments, Mya had lower survival in sand and seagrass than in shell hash or oyster shell habitats. However, crabs often missed one or more prey items in seagrass, shell, and oyster shell habitats. Predator search times and encounter rates declined when prey were at low densities, likely due to the added cost of inefficient foraging; however, this effect was more pronounced for Mya than for Mercenaria . Mercenaria had higher survival than Mya in mesocosm experiments, likely because predators feeding on Mercenaria spent less time foraging than those feeding on Mya . Mya may retain a low-density refuge from predation even with the loss of structurally complex habitats, though a loss of habitat refuge may result in clam densities that are not sustainable. A better understanding of density-dependent predator-prey interactions is necessary to prevent loss of food-web integrity and to conserve marine resources.
    Electronic ISSN: 1932-6203
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  • 36
    Publication Date: 2018-10-06
    Description: by Noriko Fujiwara, Michiru Wagatsuma, Naoto Oba, Daisaku Yoshihara, Eiichi Tokuda, Haruhiko Sakiyama, Hironobu Eguchi, Motoko Ichihashi, Yoshiaki Furukawa, Tadashi Inoue, Keiichiro Suzuki Under certain conditions, amyloid-like fibrils can develop into three-dimensional networks and form hydrogels by a self-assembly process. When Cu/Zn superoxide dismutase (SOD1), an anti-oxidative enzyme, undergoes misfolding, fibrillar aggregates are formed, which are a hallmark of a certain form of familial amyotrophic lateral sclerosis (ALS). However, the issue of whether SOD1 fibrils can be assembled into hydrogels remains to be tested. Here, we show that the SOD1 polypeptides undergo hydrogelation accompanied by the formation of thioflavin T-positive fibrils at pH 3.0 and 4.0, but not at pH 5.0 where precipitates are formed. The results of viscoelastic analyses indicate that the properties of SOD1 hydrogels (2%) were similar to and slightly more fragile than a 0.25% agarose gel. In addition, monitoring by a quartz crystal microbalance with admittance analysis showed that the denaturing of immobilized SOD1 on a sensor under the hydrogelation conditions at pH 3.0 and 4.0 resulted in an increase in the effective acoustic thickness from ~3.3 nm (a folded rigid form) to ~50 and ~100 nm (an extended water-rich state), respectively. In contrast, when SOD1 was denatured under the same conditions at pH 5.0, a compact water-poor state with an effective acoustic thickness of ~10 nm was formed. The addition of physiological concentrations of NaCl to the pH 4.0 sample induced a further extension of the SOD1 with larger amounts of water molecules (with an effective acoustic thickness of ~200 nm) but suppressed hydrogel formation. These results suggest that different denatured intermediate states of the protein before self-assembly play a major role in determining the characteristics of the resulting aggregates and that a conformational change to a suitable level of extended water-rich intermediate state before and/or during intermolecular assembling is required for fibrillation and hydrogelation in the case of globular proteins.
    Electronic ISSN: 1932-6203
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  • 37
    Publication Date: 2018-10-06
    Description: by Xuefei Bai, David Ewins, Andrew David Crocombe, Wei Xu Slope ambulation is a challenge for trans-femoral amputees due to a relative lack of knee function. The assessment of prosthetic ankles on slopes is required for supporting the design, optimisation, and selection of prostheses. This study assessed two hydraulic ankle-foot devices (one of the hydraulic ankles is controlled by a micro-processor that allows real-time adjustment in ankle resistance and range of motion) used by trans-femoral amputees in ascending and descending a 5-degree slope walking, against a rigid ankle-foot device. Five experienced and active unilateral trans-femoral amputees performed ascending and descending slope tests with their usual prosthetic knee and socket fitted with a rigid ankle-foot, a hydraulic ankle-foot without a micro-processor, and a hydraulic ankle-foot with a micro-processor optimised for ascending and descending slopes. Peak values in hip, knee and ankle joint angles and moments were collected and the normalcy Trend Symmetry Index of the prosthetic ankle moments (as an indication of bio-mimicry) were calculated and assessment. Particular benefits of the hydraulic ankle-foot devices were better bio-mimicry of ankle resistance moment, greater range of motion, and improved passive prosthetic knee stability according to the greater mid-stance external knee extensor moment (especially in descending slope) compared to the rigid design. The micro-processor controlled device demonstrated optimised ankle angle and moment patterns for ascending and descending slope respectively, and was found to potentially further improve the ankle moment bio-minicry and prosthetic knee stability compared to the hydraulic device without a micro-processor. However the difference between the micro-processor controlled device and the one without a micro-processor does not reach a statistically significant level.
    Electronic ISSN: 1932-6203
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  • 38
    Publication Date: 2018-10-10
    Description: by Tatiana V. Tkatchenko, David Troilo, Alexandra Benavente-Perez, Andrei V. Tkatchenko Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
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  • 39
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    Publication Date: 2018-10-10
    Description: by J. Jackowska, H. Klimza, P. Winiarski, K. Piersiala, M. Wierzbicka Objectives/Hypothesis Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus 6 and 11. The characteristic feature of this disease are wart-like lesions covering the respiratory epithelium with a predilection for the larynx. There is no curative treatment for the disease. The goal of the treatment is a total surgical removal of the papillomatous lesions in order to reduce the number of relapses. Therefore, a good visualization method of papillomas is crucial during surgery. The aim of the study was to compare the accuracy of narrow band imaging (NBI) to the use of white light alone in detecting RRP. Methods The study was carried out between April 2013 and November 2015 at Poznan University of Medical Sciences, Department of Otolaryngology, Poland. Rigid endoscopy with conventional white light (WL) and NBI (CV-260SL processor and CLV- 260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan) was performed in all patients during direct laryngoscopy. All anatomical sites of the larynx and trachea were assessed using the Dikkers scale and Derkay total site scoring system with WL and NBI. The consensus was reached as to the number of lesions seen in WL compared to NBI. Results During 36 microlaryngoscopies, the number of papillomas detected in the larynx (by Derkay total site score) differed significantly between white light endoscopy and NBI (Wilcoxon test p = 0.000655). In endoscopy with NBI, a mean of 1.3 more papillomas in Derkay total site score was detected in comparison to white light endoscopy NBI showed additional areas of diseased tissue in 15/36 (41.67%) patients. Conclusions NBI as an additional tool during microlaryngoscopy can improve the detection of papillomatous lesions.
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  • 40
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    Publication Date: 2018-10-10
    Description: by Kamban Hirasen, Rebecca Berhanu, Denise Evans, Sydney Rosen, Ian Sanne, Lawrence Long Introduction Treatment success rates of rifampicin resistant (RR)/multi-drug resistant (MDR) tuberculosis (TB) in South Africa range from 43–48%, falling short of the World Health Organization’s target of ≥75%. We present rates and assess predictors of attrition by 12 months on treatment. Methods Prospective observational cohort analysis of adults (≥18 years) initiating RR/MDR-TB treatment from 01 March 2013 to 30 September 2016. Attrition was defined as a combination of death and loss to follow-up (LTFU; treatment interruption ≥2 months) by 12 months on treatment. Predictors of attrition were identified using Cox Proportional Hazards models to estimate crude (HR) and adjusted hazard ratios (aHR) with corresponding 95% confidence intervals. Results By 12 months on treatment, 75/240 (31.3%) patients had either died (37/240; 15.4%) or been LTFU (38/240; 15.8%). Patients with moderate/severe anaemia (aHR: 2.10; 95% CI 1.00–4.39), and those who were smear positive at baseline (aHR: 2.04; 95% CI 1.01–4.12) were significantly more likely to die or be lost from care. Conclusion At this outpatient DR-TB treatment site, there was a high rate of attrition halfway through the standard treatment course at 12 months of 31%. High rates of attrition by 12 months on treatment may continue during the second-half of therapy.
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  • 41
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    Publication Date: 2018-10-10
    Description: by Feifei Li, Zhe Xu A two-stage decomposition approach based on a novel multi-agent system (MAS) is proposed for the distributed resource constrained multi-project scheduling problem (DRCMPSP). In stage one, from the point of view of each local project manager, a forward-backward hybrid genetic algorithm (FBHGA) is developed to generate an initial local schedule with the objective of minimizing individual project makespan. In stage two, from the global perspective of project management office, a sequential game-based negotiation mechanism is employed to eliminate global resource conflicts with the objective of minimizing total tardiness cost ( TTC ). The proposed approach is tested on 140 benchmark problem instances. According to the computational results, high-quality local project schedules can be obtained by FBHGA in stage one. Furthermore, it is observed that our method is capable of dealing with various complex multi-project instances under different degrees of resource conflicts in reasonable CPU running time. Compared to the existing decentralized methods for DRCMPSP, the proposed approach with sequential game-based negotiation mechanism shows the superiority in producing multi-project schedules with lower TTC , especially for large-size and strong conflicting instances.
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  • 42
    Publication Date: 2018-10-10
    Description: by Kristin A. Lambert, Alanna N. Roff, Ronaldo P. Panganiban, Scott Douglas, Faoud T. Ishmael Background MicroRNAs (miRNAs) are emerging as central regulators of inflammation, but their role in asthma and airway epithelial cells is not well studied. Glucocorticoids are the cornerstone of therapy in asthma and other inflammatory disease, yet their mechanisms of action are not completely elucidated, and it is not clear whether miRNAs modulate their effects. Objective We aimed to identify miRNAs that regulate cytokine and chemokine expression in airway epithelial cells and whether these miRNAs are subject to the effects of glucocorticoids. Methods and results MicroRNAomic analyses of immortalized, normal human bronchial epithelial cells identified 7 miRNAs that were altered by inflammatory cytokine treatment and 22 that were regulated by glucocorticoids (n = 3 for each treatment condition). MiR-146a emerged as a central candidate, whose expression was induced by TNF-α and repressed by glucocorticoids. Its role as a candidate in asthmatic inflammation was supported by expression profiling in human asthmatics, which showed that plasma miR-146a expression was elevated in asthma and associated with measures related to worse asthma outcomes, including elevated blood eosinophil counts, higher asthma control questionnaire scores, and need for higher doses of inhaled glucocorticoids. However, transfection of miR-146a in A549 cells treated with TNF-α +/- glucocorticoids produced an anti-inflammatory effect and increased efficacy of glucocorticoids. Conclusions We propose a model whereby miR-146a is induced by inflammatory conditions as a feedback mechanism to limit inflammation. Exogenous administration of miR-146a augmented the effects of glucocorticoids and could be a novel therapeutic strategy to enhance efficacy of these medications.
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  • 43
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    Publication Date: 2018-10-10
    Description: by Courtney Schiffman, Cliona M. McHale, Alan E. Hubbard, Luoping Zhang, Reuben Thomas, Roel Vermeulen, Guilan Li, Min Shen, Stephen M. Rappaport, Songnian Yin, Qing Lan, Martyn T. Smith, Nathaniel Rothman Background Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational exposure to a range of benzene levels perturbed gene expression in peripheral blood mononuclear cells. Objectives In the current study, we sought to identify gene expression biomarkers predictive of benzene exposure below 1 part per million (ppm), the occupational standard in the U.S. Methods First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to benzene (
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-10
    Description: by Shushuai Yi, Jiangting Niu, Hualei Wang, Guoying Dong, Yanbing Guo, Hao Dong, Kai Wang, Guixue Hu Feline astrovirus (FeAstV) which belonged to the genus Mamastrovirus was first identified in the feces of kittens with diarrhea in the USA in 1981 by electron microscopy, and had been reported in many countries. Presently, there are no any reports of the circulation of FeAstV in mainland China. We performed this study to investigate the apparent prevalence and genetic variability of FeAstV infected in cats in mainland China for the first time. We tested fecal samples of 105 cats with diarrhea and 92 asymptomatic cats in five cities in northeast China by RT-PCR targeting RNA-dependent RNA polymerase ( RdRp ) gene of FeAstV, and analyzed sequences variability and phylogenetic evolution based on the complete capsid gene of FeAstV strains obtained from positive samples. The overall prevalence of FeAstV was 23.4% (46/197) of which 38 were tested in cats with diarrhea (36.2%, 38/105) and 8 were in asymptomatic cats (8.7%, 8/92). Mixed infection with other enteroviruses including feline parvovirus (FPV), feline bocavirus (FBoV) and feline kobuvirus (FeKoV) was found in 38 FeAstV-positive samples. Phylogenetic analysis based on the complete capsid gene revealed all FeAstV strains were divided into two different groups with a 0.454±0.016 of mean amino acid genetic distance between two groups, suggesting that FeAstVs should be classified into two different genotype species. This study provided the first molecular evidence that FeAstV with considerable genetic diversity was circulating in northeast China, and analyzed genetic variability and classification of FeAstVs for the first time.
    Electronic ISSN: 1932-6203
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-10
    Description: by Jin Kyung Hwang, Dong Seop Jeong, Hye Bin Gwag, Kyoung-min Park, Joonghyun Ahn, Keumhee Carriere, Seung-Jung Park, June Soo Kim, Young Keun On The treatment effect of the hybrid procedure, consisting of a thoracoscopic ablation followed by an endocardial radiofrequency catheter ablation (RFCA), is unclear. A total of 117 ablation-naïve patients who underwent either the staged hybrid procedure (n = 72) or RFCA alone (n = 105) for drug-refractory, non-valvular persistent or long-standing persistent atrial fibrillation (AF) were enrolled. The primary outcome is occurrence of total atrial arrhythmia, defined as a composite of AF, sustained atrial tachycardia (AT), and atypical atrial flutter (AFL) after index procedure. The mean age was 52.7 years. Eighty-four percentage of the patients were male. Patients with prior history of stroke and long-standing persistent AF were more prevalent in the hybrid group than RFCA group. The left atrial volume index was larger in the hybrid group (P
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  • 46
    Publication Date: 2018-10-10
    Description: by Cho Naing, Norah Htet Htet, Wong Siew Tung, Arun Kumar Basavaraj, Joon Wah Mak Individual studies have assessed the association between TNF-α -308G〉A and TNF-α -238 G〉A polymorphisms and severity of dengue infection. However, the results are inconclusive and most studies had small sample sizes. The objective of this study was to summarize the evidence of association between TNF-α -308 G〉A and TNF-α -238 G〉A and severity of dengue infection. This study follows the preferred reporting items for systematic reviews and meta- analyses of genetic association studies, recommended by PLOS One. We calculated pooled odds ratio and its 95% confidence interval (CI) to estimate the association between TNF-α -308 G〉A or TNF-α -238 G〉A and the risk of severe dengue infections. To determine the information size required for this meta-analysis study, a trial sequential analysis (TSA) was done. Eight studies (640 cases and 1275 controls), which assessed the association of TNF-α -308 G〉A or TNF-α -238 G〉A and the risk of DHF were included. Overall, we found no significant association between TNF-α -308 G〉A and the DHF risk in the allelic model (OR, 0.91; 95% CI, 0.51–1.63), the recessive model (OR,1.32;95%CI,0.73–2.37), the dominant model (OR,0.93;95%CI:0.59–1.47) or the additive model (OR,1.43,95;95%CI:0.79–2.59). There was also no significant association between TNF-α -238 G〉A and DHF risk under the allele contrast model (OR:1.51;95%CI:0.88–2.58), the recessive model (OR,1.48,95% CI:0.33–6.58), the dominant model (OR,1.48;95%CI:0.56–3.92), or the additive model (OR:1.5;95%CI:0.34–6.69). On subgroup analysis, neither the Asian population nor the non-Asian population showed significant association between TNF-α -308 G〉A/ TNF-α -238 G〉A and the DHF risk under any genetic models. Leave-one-out meta-analysis showed stability of the results. TSA plots suggested that the sample size in this meta-analysis study was below the required information size. The findings suggest an inclusive evidence of the association between TNF-α -308/ TNF-α -238 G〉A and the risk of developing severe dengue infection. Large studies with evidence of Hardy-Weinberg equilibrium, assessing gene-gene interactions are recommended.
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  • 47
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-10
    Description: by Agatha Liévin-Bazin, Maxime Pineaux, Olivier Clerc, Manfred Gahr, Auguste M. P. von Bayern, Dalila Bovet Vocal communication is used across the animal kingdom to transfer information from emitters to receivers, such as size, sex, age, dominance status or even emotional states. The transmission of an emotional state from one individual to another is called “emotional contagion” and is classified as the first level of empathy. Emotional contagion is thought to be stronger between familiar individuals. While affiliation represents a stronger relation between individuals than mere familiarity, it remains understudied whether affiliation modulates emotional reactions as well. Using cockatiels ( Nymphicus hollandicus) , we played back three types of audio stimuli to individual birds: a partner’s distress call (emitted when birds are caught or forcibly restrained), a non-partner’s distress call, and a control sound (white noise). The calls were recorded from familiar birds with either low (non–partners) or high levels of affiliation (partners). The subjects’ response was scored using four behavioural parameters: the time spent near the loudspeaker, the amount of movements, the number of calls emitted, and the position of the crest. Across all variables, birds were more attentive and active when confronted to distress calls compared to control sounds, particularly when the distress call was emitted from a partner rather than a non-partner. These results raise the possibility that distress calls do not only function as a stimulus-triggering automatic reaction in cockatiels but also transmit emotions. Moreover, affiliation enhanced emotional reactions to conspecific distress calls. Our data provides first insights into the mechanisms of emotional contagion in parrots.
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  • 48
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-10
    Description: by Aitor Blanco-Míguez, Florentino Fdez-Riverola, Borja Sánchez, Anália Lourenço Background The wide range of potential applications has made the Basic Local Alignment Search Tool (BLAST) a ubiquitous tool in the field of Molecular Biology. Within this context, it is increasingly appealing to embed BLAST services within larger Web applications. Results This work introduces BlasterJS viewer, a new JavaScript library for the lightweight development of Web-based applications supporting the visualisation of BLAST outputs. BlasterJS detaches from similar data viewers by focusing on the visual and interactive display of sequence similarity results and being completely independent of BLAST services. BlasterJS is compatible with the text outputs generated by the BLAST family of programs, namely BLASTp, BLASTn, BLASTx, tBLASTn, and tBLASTx, and works in all major Web browsers. Furthermore, BlasterJS is available through the EBI’s BioJS registry 5, which extends its potential use to a wider scope of bioinformatics applications. Conclusions BlasterJS is new Javascript library that enables easy and seamless integration of visual and interactive representations of BLAST outputs in Web-based applications supporting sequence similarity search. BlasterJS is free accessible at http://sing-group.org/blasterjs/.
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  • 49
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-11
    Description: by Nicole Hellbach, Suzanne Peterson, Daniel Haehnke, Aditi Shankar, Samuel LaBarge, Cullen Pivaroff, Stefanie Saenger, Carolin Thomas, Kathleen McCarthy, Martin Ebeling, Monica Hayhurst Bennett, Uli Schmidt, Friedrich Metzger Spinal muscular atrophy (SMA) is a severe genetic disorder that manifests in progressive neuromuscular degeneration. SMA originates from loss-of-function mutations of the SMN1 (Survival of Motor Neuron 1) gene. Recent evidence has implicated peripheral deficits, especially in skeletal muscle, as key contributors to disease progression in SMA. In this study we generated myogenic cells from two SMA-affected human embryonic stem cell (hESC) lines with deletion of SMN1 bearing two copies of the SMN2 gene and recapitulating the molecular phenotype of Type 1 SMA. We characterized myoblasts and myotubes by comparing them to two unaffected, control hESC lines and demonstrate that SMA myoblasts and myotubes showed altered expression of various myogenic markers, which translated into an impaired in vitro myogenic maturation and development process. Additionally, we provide evidence that these SMN1 deficient cells display functional deficits in cholinergic calcium signaling response, glycolysis and oxidative phosphorylation. Our data describe a novel human myogenic SMA model that might be used for interrogating the effect of SMN depletion during skeletal muscle development, and as model to investigate biological mechanisms targeting myogenic differentiation, mitochondrial respiration and calcium signaling processes in SMA muscle cells.
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    Publication Date: 2018-10-11
    Description: by Yongsheng Lan, Zhaoyuan Huang, Yanjie Jiang, Xuehua Zhou, Jingyu Zhang, Dianyu Zhang, Bo Wang, Guangqing Hou Aerobic exercise improves cognitive function and adult hippocampal neurogenesis. However, the effects of aerobic exercise combined with strength exercise on cognitive function and adult hippocampal neurogenesis are still unknown. In this study, we established exercise paradigms in rats to mimic aerobic exercise combined with low- and high-intensity strength exercise. We found that aerobic exercise improved spatial learning and memory as well as adult hippocampal neurogenesis, whereas strength exercise suppressed aerobic exercise-induced cognitive improvements and adult hippocampal neurogenesis in an intensity-dependent manner. Furthermore, the levels of β-hydroxybutyrate (β-HB) and its downstream effector brain-derived neurotrophic factor (BDNF) were increased in the aerobic exercise group, and strength exercise impaired the aerobic exercise-induced increases in β-HB and BDNF mRNA levels. Taken together, these results demonstrated that strength exercise weakened aerobic exercise-induced cognitive improvements and adult hippocampal neurogenesis in rats.
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  • 51
    Publication Date: 2018-10-11
    Description: by Ronaldo Valdir Briani, Danilo De Oliveira Silva, Carolina Silva Flóride, Fernando Amâncio Aragão, Carlos Eduardo de Albuquerque, Fernando Henrique Magalhães, Fábio Mícolis de Azevedo The present study aimed at investigating whether the neuromuscular system behaves differently (in terms of force and muscle activity generation) as a function of the task being performed (i.e. maximal voluntary efforts vs stair negotiation) and the presence of patellofemoral pain (PFP) and possible influences of pain intensity. Thirty-eight women with (n = 19) and without PFP (n = 19) had their knee strength (extension joint torque) measured during maximal voluntary isometric contractions (MVIC) and electromyography (EMG) data recorded during both MVIC and stair ascent tasks, which were performed before and after a loading protocol designed to exacerbate pain symptoms. Women with PFP displayed lower levels of vastus medialis (p = 0.002) and vastus lateralis (p = 0.032) EMG activation during MVIC assessments. Conversely, the PFP group showed higher levels of vastus medialis muscle activity during stair climbing (p = 0.007), which happened exclusively after the loading protocol. Similarly, women with PFP displayed lower knee extensor torque only during the MVIC tests performed after the loading protocol, which was moderately correlated with the increase in self-reported pain (p = 0.041, r = 0.37), whereas the changes in EMG activity during stair ascent were not correlated with changes in pain intensity (p = 0.215, r = 0.12). These results suggest that, in comparison to pain-free controls, women with PFP display lower levels of quadriceps EMG activation during maximal contractions, but higher activation during dynamic tasks (stair ascent). In addition, the moderate association between the decrease in knee extensor torque and increase in self-reported pain indicates that care should be taken by clinicians during quadriceps strength evaluation in women with PFP, as misleading outcomes may emerge if the intensity of knee pain is not considered during screening. Additionally, rehabilitation strategies should focus on both restoring neuromuscular control and increasing muscle strength.
    Electronic ISSN: 1932-6203
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  • 52
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-11
    Description: by Jan Huebinger Rapid cooling and re-warming has been shown promising to cryopreserve living cells, which cannot be preserved by conventional slow freezing methods. However, success is limited by the cytotoxicity of highly concentrated cryoprotective agents. Recent results have shown that cryoprotective agents do not need to suppress intracellular ice crystals completely to allow for survival after cryopreservation. Cryoprotective agents like DMSO or ethylene glycol can also lead to a tolerance of cells towards intracellular ice. It is however unclear by which mechanism this tolerance is achieved. These substances are also known to modulate properties of cellular membranes. It is shown here that cryoprotective DMSO and ethylene glycol have a clear influence on the mobility of lipids in the plasma membrane of HeLa cells. To isolate changes of the properties of plasma membranes from effects on ice formation, the membrane properties were modulated in absence of cryoprotective agents. This was achieved by changing their sterol content. In cells with elevated sterol content, an immobile lipid fraction was present, similar to cells treated with DMSO and ethylene glycol. These cells showed also significantly increased plasma membrane integrity after rapid freezing and thawing in the absence of classical cryoprotective agents. However, their intracellular lysosomes, which cannot be enriched with sterols, still got ruptured. These results clearly indicate that a modulation of membrane properties can convey cryoprotection. Upon slow cooling, elevated sterol content had actually an adverse effect on the plasma membranes, which shows that this effect is specific for rapid, non-equilibrium cooling processes. Unraveling this alternative mode of action of cryoprotection should help in the directed design of novel cryoprotective agents, which might be less cytotoxic than classical, empirically-found cryoprotective agents.
    Electronic ISSN: 1932-6203
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  • 53
    Publication Date: 2018-10-11
    Description: by Kenji Rimpo, Aki Tanaka, Masayasu Ukai, Yuichi Ishikawa, Miyuki Hirabayashi, Toshihiro Shoyama Reference interval for thrombin-antithrombin complex (TAT) level was determined using an in-house TAT measurement device, and its validity for diagnosis of disseminated intravascular coagulation (DIC) was evaluated in dogs. One hundred and two clinically healthy dogs and 247 diseased dogs with conditions that potentially caused DIC were recruited in the study. Six diagnostic testing for DIC were evaluated in diseased dogs and the diseased dogs were categorized into five groups depending on abnormal findings. TAT was measured in all study animals and between-group differences were evaluated. TAT level was positively associated with severity of DIC. There were no significant differences in TAT levels among clinically healthy dogs, diseased dogs without any abnormal finding and diseased dogs with one abnormal finding in the DIC diagnostic testing. TAT levels in groups with two or more abnormal findings were significantly higher than clinically healthy dogs. Reference interval of TAT level for clinically healthy dogs was ≤ 0.25 ng/ml. Validity of using TAT for early detection of DIC was evaluated. In-house TAT measurement was suggested to be a clinically relevant and useful tool for early detection of canine DIC.
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    Publication Date: 2018-10-11
    Description: by Takamasa Tsuzuki, Toshinori Yoshihara, Noriko Ichinoseki-Sekine, Ryo Kakigi, Yuri Takamine, Hiroyuki Kobayashi, Hisashi Naito This study examined the effect of changes in body temperature during exercise on signal transduction-related glucose uptake in the skeletal muscle of type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty rats (25 weeks of age), which have type 2 diabetes, were divided into the following four weight-matched groups; control (CON, n = 6), exercised under warm temperature (WEx, n = 8), exercised under cold temperature (CEx, n = 8), and heat treatment (HT, n = 6). WEx and CEx animals were subjected to running on a treadmill at 20 m/min for 30 min under warm (25°C) or cold (4°C) temperature. HT animals were exposed to single heat treatment (40–41°C for 30 min) in a heat chamber. Rectal and muscle temperatures were measured immediately after exercise and heat treatment, and the gastrocnemius muscle was sampled under anesthesia. Rectal and muscle temperatures increased significantly in rats in the WEx and HT, but not the CEx, groups. The phosphorylation levels of Akt, AS160, and TBC1D1 (Thr590) were significantly higher in the WEx and HT groups than the CON group ( p 〈 0.05). In contrast, the phosphorylation levels of AMP-activated protein kinase, ACC, and TBC1D1 (Ser660) were significantly higher in rats in the WEx and CEx groups than the CON group ( p 〈 0.05) but did not differ significantly between rats in the WEx and CEx groups. Body temperature elevation by heat treatment did not activate the AMPK signaling. Our data suggest that body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of rats with type 2 diabetic rats.
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-11
    Description: by Sarah van de Berg, Niesje Jansen-Aaldring, Gerard de Vries, Susan van den Hof Background Patient support during tuberculosis treatment is expected to be more often available and more customized in low tuberculosis incidence, high-resource settings than in lower-resource settings. The aim of this systematic review is to provide an overview of tuberculosis patient support interventions implemented in low-incidence countries and an evaluation of their effects on treatment-related outcomes as well as their acceptability by patients and providers. Methods PubMed, Social Science Citation Index and Cumulative Index to Nursing and Allied Health and Literature were searched for the period 01.2006–05.2016 on publications describing tuberculosis patient support interventions in low-incidence countries (
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  • 56
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    Publication Date: 2018-10-11
    Description: by Alexandra Ingendoh-Tsakmakidis, Lena Nolte, Andreas Winkel, Heiko Meyer, Anastasia Koroleva, Anastasia Shpichka, Tammo Ripken, Alexander Heisterkamp, Meike Stiesch It is estimated that two million new dental implants are inserted worldwide each year. Innovative implant materials are developed in order to minimize the risk of peri-implant inflammations. The broad range of material testing is conducted using standard 2D, terminal, and invasive methods. The methods that have been applied are not sufficient to monitor the whole implant surface and temporal progress. Therefore, we built a 3D peri-implant model using a cylindrical implant colonized by human gingival fibroblasts. In order to monitor the cell response over time, a non-toxic LIVE/DEAD staining was established and applied to the new 3D model. Our LIVE/DEAD staining method in combination with the time resolved 3D visualization using Scanning Laser Optical Tomography (SLOT), allowed us to monitor the cell death path along the implant in the 3D peri-implant model. The differentiation of living and dead gingival fibroblasts in response to toxicity was effectively supported by the LIVE/DEAD staining. Furthermore, it was possible to visualize the whole cell-colonized implant in 3D and up to 63 hours. This new methodology offers the opportunity to record the long-term cell response on external stress factors, along the dental implant and thus to evaluate the performance of novel materials/surfaces.
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  • 57
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    Publication Date: 2018-10-11
    Description: by Cristina Ruiz-Iruela, Ariadna Padró-Miquel, Xavier Pintó-Sala, Neus Baena-Díez, Assumpta Caixàs-Pedragós, Roser Güell-Miró, Rosa Navarro-Badal, Xavier Jusmet-Miguel, Pilar Calmarza, José Luis Puzo-Foncilla, Pedro Alía-Ramos, Beatriz Candás-Estébanez Introduction The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T〉 C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins. Aim The aim of this study was to investigate whether or not the c.2155T〉 C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin. Materials and methods This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment. Results The c.2155T〉 C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T〉 C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008). Conclusion Being a carrier of the c.2155T〉 C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T〉 C variant.
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    Publication Date: 2018-10-12
    Description: by Neir Eshel, Elizabeth E. Steinberg Most decisions share a common goal: maximize reward and minimize punishment. Achieving this goal requires learning which choices are likely to lead to favorable outcomes. Dopamine is essential for this process, enabling learning by signaling the difference between what we expect to get and what we actually get. Although all animals appear to use this dopamine prediction error circuit, some do so more than others, and this neural heterogeneity correlates with individual variability in behavior. In this issue of PLOS Biology , Lee and colleagues show that manipulating a simple task parameter can bias the animals’ behavioral strategy and modulate dopamine release, implying that how we learn is just as flexible as what we learn.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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    Publication Date: 2018-10-12
    Description: by Lars Ole Schwen, Sabrina Rueschenbaum Most studies in the life sciences and other disciplines involve generating and analyzing numerical data of some type as the foundation for scientific findings. Working with numerical data involves multiple challenges. These include reproducible data acquisition, appropriate data storage, computationally correct data analysis, appropriate reporting and presentation of the results, and suitable data interpretation. Finding and correcting mistakes when analyzing and interpreting data can be frustrating and time-consuming. Presenting or publishing incorrect results is embarrassing but not uncommon. Particular sources of errors are inappropriate use of statistical methods and incorrect interpretation of data by software. To detect mistakes as early as possible, one should frequently check intermediate and final results for plausibility. Clearly documenting how quantities and results were obtained facilitates correcting mistakes. Properly understanding data is indispensable for reaching well-founded conclusions from experimental results. Units are needed to make sense of numbers, and uncertainty should be estimated to know how meaningful results are. Descriptive statistics and significance testing are useful tools for interpreting numerical results if applied correctly. However, blindly trusting in computed numbers can also be misleading, so it is worth thinking about how data should be summarized quantitatively to properly answer the question at hand. Finally, a suitable form of presentation is needed so that the data can properly support the interpretation and findings. By additionally sharing the relevant data, others can access, understand, and ultimately make use of the results. These quick tips are intended to provide guidelines for correctly interpreting, efficiently analyzing, and presenting numerical data in a useful way.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
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    Publication Date: 2018-10-12
    Description: by Philippa J. Karoly, Levin Kuhlmann, Daniel Soudry, David B. Grayden, Mark J. Cook, Dean R. Freestone We present the results of a model inversion algorithm for electrocorticography (ECoG) data recorded during epileptic seizures. The states and parameters of neural mass models were tracked during a total of over 3000 seizures from twelve patients with focal epilepsy. These models provide an estimate of the effective connectivity within intracortical circuits over the time course of seizures. Observing the dynamics of effective connectivity provides insight into mechanisms of seizures. Estimation of patients seizure dynamics revealed: 1) a highly stereotyped pattern of evolution for each patient, 2) distinct sub-groups of onset mechanisms amongst patients, and 3) different offset mechanisms for long and short seizures. Stereotypical dynamics suggest that, once initiated, seizures follow a deterministic path through the parameter space of a neural model. Furthermore, distinct sub-populations of patients were identified based on characteristic motifs in the dynamics at seizure onset. There were also distinct patterns between long and short duration seizures that were related to seizure offset. Understanding how these different patterns of seizure evolution arise may provide new insights into brain function and guide treatment for epilepsy, since specific therapies may have preferential effects on the various parameters that could potentially be individualized. Methods that unite computational models with data provide a powerful means to generate testable hypotheses for further experimental research. This work provides a demonstration that the hidden connectivity parameters of a neural mass model can be dynamically inferred from data. Our results underscore the power of theoretical models to inform epilepsy management. It is our hope that this work guides further efforts to apply computational models to clinical data.
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  • 61
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    Publication Date: 2018-10-12
    Description: by Marcos Méndez
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    Publication Date: 2018-10-12
    Description: by The PLOS ONE Editors
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  • 63
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    Publication Date: 2018-10-12
    Description: by Stefan Wallner, Evelyn Orsó, Margot Grandl, Tatiana Konovalova, Gerhard Liebisch, Gerd Schmitz Background Plasmalogens are either phosphatidylcholine (PC P) or phosphatidylethanolamine (PE P) glycerophospholipids containing a vinyl ether moiety in sn-1-position and an esterified fatty acid in sn-2 position. Multiple functions have been proposed, including reservoir of precursors for inflammatory mediators, modulation of membrane fluidity, and anti-oxidative properties. They could therefore play a role under conditions of metabolic stress. Especially enzymatically modified LDL (eLDL) and oxidatively modified LDL (oxLDL) represent modifications of LDL that are taken up by macrophages in atherosclerotic plaques. The aim of this study was to analyze plasmalogen related effects of eLDL and oxLDL in human monocyte derived macrophages, as well as the effects of HDL 3 mediated deloading. Methods Elutriated monocytes from nine healthy donors were differentiated in vitro for four days. Macrophages were then loaded with native LDL, eLDL and oxLDL for 24h and subsequently deloaded with HDL 3 for another 24h. Lipidomic and transcriptomic profiles were obtained. Results Loading of macrophages with eLDL and oxLDL led to a transient but strong elevation of lysophosphatidylcholine (LPC) most likely through direct uptake. Only eLDL induced increased levels of total PC, presumably through an induction of PC synthesis. On the other hand treatment with oxLDL led to a significant increase in PC P. Analysis of individual lipid species showed lipoprotein and saturation specific effects for LPC, PC P and PE P species. Membrane fluidity was decreased by the large amount of FC contained in the lipoproteins, as indicated by a lower PC to FC ratio after lipoprotein loading. In contrast the observed changes in the saturated to mono-unsaturated fatty acid (SFA to MUFA) and saturated to poly-unsaturated fatty acid (SFA to PUFA) ratios in PE P could represent a cellular reaction to counteract this effect by producing more fluid membranes. Transcriptomic analysis showed considerable differences between eLDL and oxLDL treated macrophages. As a common feature of both lipoproteins we detected a strong downregulation of pathways for endogenous lipid synthesis as well as for exogenous lipid uptake. Deloading with HDL 3 had only minor effects on total lipid class as well as on individual lipid species levels, most of the time not reaching significance. Interestingly treatment with HDL 3 had no effect on membrane fluidity under these conditions, although incubation with HDL 3 was partially able to counteract the oxLDL induced transcriptomic effects. To investigate the functional effect of lipoprotein treatment on macrophage polarization we performed surface marker flow cytometry. Under our experimental conditions oxLDL was able to partially shift the surface marker pattern towards a pro-inflammatory M1-like phenotype. This is consistent with the consumption of arachidonic acid containing PE P species in oxLDL treated cells, presumably for the synthesis of inflammatory mediators. Summary Our findings provide novel data on the lipoprotein induced, lipidomic and transcriptomic changes in macrophages. This can help us better understand the development of metabolic, inflammatory diseases as well as improve our background knowledge on lipid biomarkers in serum.
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  • 64
    Publication Date: 2018-10-12
    Description: by Rika Ito, Masaki Higa, Ayumi Goto, Megumi Aoshima, Akihiro Ikuta, Kazuya Ohashi, Shingo Yokoyama, Yoshitaka Ohno, Tatsuro Egawa, Hirofumi Miyata, Katsumasa Goto This study investigated the effects of AdipoRon, which is an agonist for adiponectin receptor 1 (AdipoR1) and AdipoR2, on the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells and skeletal muscle mass in C57BL/6J mice. AdipoRon suppressed the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells of C2C12 myotubes in a dose-dependent manner. Adiponectin-associated decline of protein content, diameter, and number of nuclei per myotube in C2C12 myotubes was partially rescued by knockdown of AdipoR1 and/or AdipoR2. Phosphorylation level of AMPK showed a trend to be increased by AdipoRon. A significant increase in phosphorylation level of AMPK was observed at 20 μM AdipoRon. Knockdown of AdipoR1 and/or AdipoR2 rescued AdipoRon-associated decrease in protein content of C2C12 myotubes. AdipoRon-associated increase in phosphorylation level of AMPK in C2C12 myotubes was suppressed by knockdown of AdipoR1 and/or AdipoR2. Successive intravenous injections of AdipoRon into mice caused a decrease in the wet weight of plantaris muscle (PLA), but not in soleus muscle (SOL). Mean fiber cross-sectional area of PLA, but not of SOL, was significantly decreased by AdipoRon administration. On the one hand, the expression level of phosphorylated AMPK and ubiquitinated protein in SOL and PLA muscles was upregulated by AdipoRon administration. On the other hand, AdipoRon administration induced no changes in the expression level of puromycin-labeled proteins in both SOL and PLA muscles. Expression level of adiponectin in extensor digitorum longus (EDL) muscle was increased by aging, but not in SOL muscle. Aging had no effect on the expression level of AdipoR1 and AdipoR2 in both muscles. Phosphorylation level of AMPK in EDL was increased by aging, but not SOL muscle. Results from this study suggest that high level of circulating adiponectin may induce skeletal muscle atrophy, especially fast-type muscle.
    Electronic ISSN: 1932-6203
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  • 65
    Publication Date: 2018-10-12
    Description: by Benjamin A. Kamala, Hege L. Ersdal, Ingvild Dalen, Muzdalifat S. Abeid, Matilda M. Ngarina, Jeffrey M. Perlman, Hussein L. Kidanto Background Intrapartum Fetal Heart Rate (FHR) monitoring is crucial for the early detection of abnormal FHR, facilitating timely obstetric interventions and thus the potential reduction of adverse perinatal outcomes. We explored midwifery practices of intrapartum FHR monitoring pre and post implementation of a novel continuous automatic Doppler device (the Moyo). Methodology A pre/post observational study among low-risk pregnancies at a tertiary hospital was conducted from March to December 2016. In the pre-implementation period, intermittent monitoring was conducted with a Pinard stethoscope (March to June 2016, n = 1640 women). In the post-implementation period, Moyo was used for continuous FHR monitoring (July-December 2016, n = 2442 women). The primary outcome was detection of abnormal FHR defined as absent, FHR 160bpm. The secondary outcomes were rates of assessment/documentation of FHR, obstetric time intervals and intrauterine resuscitations. Chi-square test, Fishers exact test, t-test and Mann-Whitney U test were used in bivariate analysis whereas binary and multinomial logistic regression were used for multivariate. Results Moyo use was associated with greater detection of abnormal FHR (8.0%) compared with Pinard (1.6%) ( p
    Electronic ISSN: 1932-6203
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  • 66
    Publication Date: 2018-10-12
    Description: by Alice Yu, Jose Joao Mansure, Shraddha Solanki, D. Robert Siemens, Madhuri Koti, Ana B. T. Dias, Miguel M. Burnier, Fadi Brimo, Wassim Kassouf Tumor-Infiltrating Lymphocytes (TILs) has been shown to be essential to predict disease outcome in several types of cancers. Moreover, the distribution of cytotoxic T lymphocytes (CD8+) and T cells in general (CD3+) have been used to establish an Immunoscore, as a new cancer prognosticator for survival in colon and lung cancer. In bladder cancer, immune activation has been shown to be associated with genomic subtypes of muscle invasive bladder cancer (MIBC). We sought to evaluate the prognostic impact of these immune cell types in MIBC patients treated with radical cystectomy. For this purpose, cystectomy sections (n = 67) with identifiable invasive margin were selected and stained for CD8 + and CD3 + tumour infiltrating lymphocytes (TILs); both tumor core (CT) and invasive margin (IM) were assessed. Immunoscore was calculated based on previously defined criteria and used to illustrate differences in survival. High density of CD8 IM TILs was associated with better disease-free (DFS) ( P = 0.01) and overall survival (OS) ( P = 0.02) whereas CD3 IM TILs were associated with better OS ( P = 0.05). Immunoscore was associated with improved DFS ( P = 0.02) and OS ( P = 0.05). The expression of cytotoxic T cells (CD8+ T cells) in TCGA bladder cancer was also investigated from RNA-Seq profiles of 344 cases. T cell cytotoxicity associated genes (n = 113) were derived from MSig GSEA database. Luminal (n = 121) and basal (n = 68) samples were used to evaluate expression differences. Differential expression (P
    Electronic ISSN: 1932-6203
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  • 67
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-12
    Description: by Yiping Li, Fangfang Liu, Xiao Du, Zhumei Li, Junxiang Wu Three fruit borers Conogethes punctiferalis (Guenée) (Crambidae), Grapholita molesta Busck (Tortricidae), and Spilonota albicana Motschulsky (Tortricidae) are serious pests of fruit trees. In this study, their antennal morphology, types of sensilla, and distributions were observed by using SEM (Scanning Electron Microscope). Nine types of sensilla were found on the antennae of C . punctiferalis , while eight types of sensilla were presented on each of G . molesta and S . albicana . The sensilla trichodea with two subtypes were the most abundant sensilla among three fruit borers. Two subtypes of sensillum coeloconica (type I with spines and type II without spines) were observed on the antennae of C . punctiferalis and G . molesta . However, sensilla coeloconica (type I) were only found in S . albicana . Although the sensilla campaniformia were only found on the antennae of C . punctiferalis , our observations confirm sensilla campaniformia presence in the moths. In addition, the functions of these sensilla were discussed based on previously reported lepidopteran insects. As a result, our study may provide useful information for advanced electrophysiological and behavioral experiments to better understand the mechanisms related to pests control.
    Electronic ISSN: 1932-6203
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  • 68
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-12
    Description: by Marlène Sauget, Xavier Bertrand, Didier Hocquet Antibiotic resistance is a major public health problem requiring the early optimization of antibiotic prescriptions. Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS) has been shown to accurately identify bacteria from positive blood culture. Here, we developed a rapid detection of Escherichia coli resistance to amoxicillin (AMX) and cefotaxime (CTX) from positive blood culture based on MALDI-TOF MS. Potential sparing of broad-spectrum antibiotics was also evaluated. We tested 103 E . coli -positive blood cultures. Blood cultures were subculture 1-hour in antibiotic-free rich liquid media before further incubation with and without AMX for 2.5 h or CTX for 2 h. Protein extracts associated with an internal control were spotted on a MALDI-TOF target and spectra were analyzed with the MBT-ASTRA prototype software (Bruker Daltonik GmbH, Bremen, Germany). Bacterial growth ratio was calculated from the AUC spectra obtained in the presence and absence of the antibiotic and compared to a threshold which classified E . coli as susceptible or resistant. Results were interpreted with MICs determined using agar dilution method as reference technique. MBT-ASTRA recognized 95% and 84% of the AMX- and CTX-susceptible isolates, respectively. Overall, quantitative analysis of mass spectra allows susceptibility testing within 4 hours after the positivity of blood culture with E . coli . At the first report of positive blood culture, MALDI-TOF MS would then provide the prescribers with the bacterial identification and the susceptibility to AMX and CTX, thus limiting the use of broad-spectrum compounds.
    Electronic ISSN: 1932-6203
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  • 69
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-12
    Description: by Iulia Blaj, Jens Tetens, Siegfried Preuß, Jörn Bennewitz, Georg Thaller Genome-wide association studies (GWAS) have been widely used in the genetic dissection of complex traits. As more genomic data is being generated within different commercial or resource pig populations, the challenge which arises is how to collectively investigate the data with the purpose to increase sample size and implicitly the statistical power. This study performs an individual population GWAS, a joint population GWAS and a meta-analysis in three pig F 2 populations. D1 is derived from European type breeds (Piétrain, Large White and Landrace), D2 is obtained from an Asian breed (Meishan) and Piétrain, and D3 stems from a European Wild Boar and Piétrain, which is the common founder breed. The traits investigated are average daily gain, backfat thickness, meat to fat ratio and carcass length. The joint and the meta-analysis did not identify additional genomic clusters besides the ones discovered via the individual population GWAS. However, the benefit was an increased mapping resolution which pinpointed to narrower clusters harboring causative variants. The joint analysis identified a higher number of clusters as compared to the meta-analysis; nevertheless, the significance levels and the number of significant variants in the meta-analysis were generally higher. Both types of analysis had similar outputs suggesting that the two strategies can complement each other and that the meta-analysis approach can be a valuable tool whenever access to raw datasets is limited. Overall, a total of 20 genomic clusters that predominantly overlapped at various extents, were identified on chromosomes 2, 7 and 17, many confirming previously identified quantitative trait loci. Several new candidate genes are being proposed and, among them, a strong candidate gene to be taken into account for subsequent analysis is BMP2 (bone morphogenetic protein 2).
    Electronic ISSN: 1932-6203
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  • 70
    Publication Date: 2018-10-12
    Description: by Bo-Hye Nam, Jisung Jang, Kelsey Caetano-Anolles, Young-Ok Kim, Jung Youn Park, Hawsun Sohn, Sook Hee Yoon, Heebal Kim, Woori Kwak Haliotis discus hannai , a species of Pacific abalone, is a highly valuable food source throughout Northeast Asia. As H . discus hannai primarily feed on brown algae and largely extract their energy from algal polysaccharides, understanding the mechanisms by which they digest algal polysaccharides is essential for elucidating their energy metabolism. Gut microbes, as well as the host animal, are involved in the process of polysaccharide degradation. To identify algal polysaccharide-digestion mechanisms and their origin, we analyzed the metagenome and metatranscriptome of abalone visceral extracts. Microbial communities were characterized using the 16S rRNA gene sequences in the metagenome and our results differed significantly from those of previous studies using traditional microbiological methods such as bacterial cultivation and cloning. A greater diversity of bacterial taxa was identified here than was previously identified using cultivation methods. Furthermore, the most abundant bacterial taxa also differed from previous studies, which is not common when comparing the results of bacterial culturing with those of molecular methodologies. Based on the metatranscriptome, overall functions were identified and additional analyses were performed on the coding sequences of algal polysaccharide-digestive enzymes, including alginate lyase. Results of the transcriptomic analyses suggest that alginate lyase in the visceral extracts of H . discus hannai was produced by the host itself, not by visceral bacteria. This is the first next-generation sequencing study performed on abalone to characterize the visceral microbiota and the source of the ability to digest algal polysaccharides by analyzing the metagenome and metatranscriptome together.
    Electronic ISSN: 1932-6203
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  • 71
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-13
    Description: by Gareth Frank Difford, Damian Rafal Plichta, Peter Løvendahl, Jan Lassen, Samantha Joan Noel, Ole Højberg, André-Denis G. Wright, Zhigang Zhu, Lise Kristensen, Henrik Bjørn Nielsen, Bernt Guldbrandtsen, Goutam Sahana Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH 4 ) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH 4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH 4 emission is not yet well known. This study confirms individual variation in CH 4 production was influenced by individual host (cow) genotype, as well as the host’s rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host’s genotype and certain taxa were associated with CH 4 emissions. However, the cumulative effect of all bacteria and archaea on CH 4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH 4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH 4 emissions in the cattle industry.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 72
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-13
    Description: by Raquel Barajas-Azpeleta, Jianping Wu, Jason Gill, Ryan Welte, Chris Seidel, Sean McKinney, Stephane Dissel, Kausik Si Antimicrobial peptides act as a host defense mechanism and regulate the commensal microbiome. To obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Surprisingly, we found that Diptericin B, an immune peptide with antimicrobial activity, is upregulated following behavioral training. Deletion and knock down experiments revealed that Diptericin B and another immune peptide, Gram-Negative Bacteria Binding Protein like 3, regulate long-term but not short-term memory or instinctive behavior in Drosophila . Interestingly, removal of DptB in the head fat body and GNBP-like3 in neurons results in memory deficit. That putative antimicrobial peptides influence memory provides an example of how some immune peptides may have been repurposed to influence the function of nervous system.
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
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  • 73
    Publication Date: 2018-10-13
    Description: by Jeanette E. Villanueva, Ling Gao, Hong C. Chew, Mark Hicks, Aoife Doyle, Min Ru Qui, Kumud K. Dhital, Peter S. Macdonald, Andrew Jabbour The ryanodine receptor antagonist dantrolene inhibits calcium release from the sarcoplasmic reticulum and reduces cardiac ischaemia-reperfusion injury (IRI) in global warm ischaemia models however the cardioprotective potential of dantrolene under hypothermic conditions is unknown. This study addresses whether the addition of dantrolene during cardioplegia and hypothermic storage of the donor heart can improve functional recovery and reduce IRI. Using an ex vivo isolated working heart model, Wistar rat (3 month and 12 month) hearts were perfused to acquire baseline haemodynamic measurements of aortic flow, coronary flow, cardiac output, pulse pressure and heart rate. Hearts were arrested and stored in Celsior preservation solution supplemented with 0.2–40 μM dantrolene for 6 hours at 4°C, then reperfused (15 min Langendorff, 30 min working mode). In 3-month hearts, supplementation with 1 μM dantrolene significantly improved aortic flow and cardiac output compared to unsupplemented controls however lactate dehydrogenase (LDH) release and contraction bands were comparable. In contrast, 40 μM dantrolene-supplementation yielded poor cardiac recovery, increased post-reperfusion LDH but reduced contraction bands. All 3-month hearts stored in dantrolene displayed significantly reduced cleaved-caspase 3 intensities compared to controls. Analysis of cardioprotective signalling pathways showed no changes in AMPKα however dantrolene increased STAT3 and ERK1/2 signaling in a manner unrelated to functional recovery and AKT activity was reduced in 1 μM dantrolene-stored hearts. In contrast to 3-month hearts, no significant improvements were observed in the functional recovery of 12-month hearts following prolonged storage in 1 μM dantrolene. Conclusions : Dantrolene supplementation at 1 μM during hypothermic heart preservation improved functional recovery of young, but not older (12 month) hearts. Although the molecular mechanisms responsible for dantrolene-mediated cardioprotection are unclear, our studies show no correlation between improved functional recovery and SAFE and RISK pathway activation.
    Electronic ISSN: 1932-6203
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  • 74
    Publication Date: 2018-10-13
    Description: by Lara A. Aqrawi, Xiangjun Chen, Janicke Liaaen Jensen, Mathias Kaurstad Morthen, Bernd Thiede, Øygunn Aass Utheim, Øyvind Palm, Behzod Tashbayev, Tor Paaske Utheim, Hilde Kanli Galtung Ocular dryness is a characteristic feature of primary Sjögren’s syndrome (pSS). This may result in dry eye disease (DED), leading to damage of the ocular surface. Additional, non-invasive diagnostic techniques are needed when evaluating pSS patients. Hence, screening for disease-specific biomarkers in biological fluid could be promising. We have previously examined the proteome of tear fluid from pSS patients through Liquid chromatography-mass spectrometry (LC-MS), and conducted a thorough ocular evaluation of patients with pSS. In this study we further explored the association between dry eye manifestations and protein expression in tear fluid of pSS patients. Medical history of 27 patients and 32 healthy controls was gathered. Subjective complaints were registered through questionnaires. Objective findings including tear osmolarity, tear film break up time (TFBUT), Schirmer’s test, and ocular and corneal surface staining were also recorded. LC-MS was conducted formerly on tear fluid from all subjects in order to generate proteomic biomarker profiles. Scaffold was employed to analyse the LC-MS data for quantitative differences between patient and control groups, and the mean spectral counts were calculated for the five most upregulated proteins in relation to DED manifestations. Dysregulated cellular processes were identified in pSS patients using FunRichv3 enrichment analysis. The five most upregulated proteins previously identified in pSS patients were DNA (apurinic or apyrimidinic site) lyase (APEX1), thioredoxin-dependent peroxidase reductase (PRDX3), copine (CPNE1), aconitate hydratase (ACO2), and LIM domain only protein 7 (LMO7), in descending order. A significant increase in mean spectral counts for these proteins were observed in pSS patients with pathological DED manifestations compared to healthy controls (p
    Electronic ISSN: 1932-6203
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  • 75
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-13
    Description: by Caroline Bradbury-Jones, Peter Ogik, Jane Betts, Julie Taylor, Patricia Lund Albinism includes a group of inherited conditions that result in reduced melanin production. It has been documented across the world, with a high frequency in sub-Saharan Africa. There is very little published research about the lives of people with albinism, but available evidence shows that myths abound regarding their condition. They are feared, viewed with suspicion and believed to have supernatural powers. In this study we explored the links between beliefs, myths, traditions and positive/negative attitudes that surround people with albinism in Uganda. The study was located philosophically within Ubuntu—an Afrocentric worldview—and theoretically within the Common-Sense Model of self-regulation of health and illness that originates from the work of Leventhal in 2003. This qualitative study took place in eight districts of Busoga sub-region, Uganda between 2015 and 2017. Data collection comprised eight group discussions and 17 individual interviews with a range of informants, capturing the viewpoints of 73 participants. Findings lend support to previous research, highlighting the life-time discrimination and disadvantage experienced by many people with albinism. It shows that there is still much to be done to address the pervasive and potentially harmful beliefs and misconceptions about people with albinism.
    Electronic ISSN: 1932-6203
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  • 76
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-13
    Description: by Yusuke Koizumi, Kohei Watabe, Kenji Nakagawa We propose a method to accelerate a response of structured overlay networks by reducing the number of hops required to answer multi-queries. In the proposed method, by copying data items to the redundant storage spaces in other storages, a good data placement reflecting co-occurrence structures in the structured overlay network is achieved. We formulate the optimization problem of the data placement in the limited redundant space of the storages as an integer programming. A greedy approach to solve the optimization problem is also proposed. Through several simulations, it is confirmed that the proposed method can reduce the average number of hops required to answer multi-queries by about 30% at the maximum in our simulation settings. The reduction rate of the average number of hops depends on the level of co-occurrence. Further, the reduction of the computation time to solve the optimization problem with the greedy approach is evaluated. We also confirm that the proposed method does not affect load balancing of structured overlay networks.
    Electronic ISSN: 1932-6203
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  • 77
    Publication Date: 2018-10-13
    Description: by Lin-Jie Shu, Jui-Yu Liao, Nai-Chun Lin, Chia-Lin Chung Hormonal modulation plays a central role in triggering various resistant responses to biotic and abiotic stresses in plants. In cultivated strawberry ( Fragaria x ananassa ), the salicylic acid (SA)-dependent defense pathway has been associated with resistance to Colletotrichum spp. and the other pathogens. To better understand the SA-mediated defense mechanisms in strawberry, we analyzed two strawberry cultivars treated with SA for their resistance to anthracnose and gene expression profiles at 6, 12, 24, and 48 hr post-treatment. Strawberry genes related to SA biosynthesis, perception, and signaling were identified from SA-responsive transcriptomes of the two cultivars, and the induction of 17 candidate genes upon SA treatment was confirmed by qRT-PCR. Given the pivotal role of the non-expressor of pathogenesis-related (NPR) family in controlling the SA-mediated defense signaling pathway, we then analyzed NPR orthologous genes in strawberry. From the expression profile, FaNPRL-1 [ortholog of FvNPRL-1 ( gene20070 in F . vesca )] was identified as an NPR -like gene significantly induced after SA treatment in both cultivars. With a conserved BTB/POZ domain, ankyrin repeat domain, and nuclear localization signal, FvNPRL-1 was found phylogenetically closer to NPR3/NPR4 than NPR1 in Arabidopsis. Ectopic expression of FvNPRL-1 in the Arabidopsis thaliana wild type suppressed the SA-mediated PR1 expression and the resistance to Pseudomonas syringae pv. tomato DC3000. Transient expression of FvNPRL-1 fused with green fluorescent protein in Arabidopsis protoplasts showed that SA affected nuclear translocation of FvNPRL-1. FvNPRL-1 likely functions similar to Arabidopsis NPR3/NPR4 as a negative regulator of the SA-mediated defense.
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  • 78
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-13
    Description: by Wing-Kai Lam, Ki-Kwang Lee, Sang-Kyoon Park, Jaejin Ryue, Suk-Hoon Yoon, Jiseon Ryu Background The rapid and repetitive badminton lunges would produce strenuous impact loading on the lower extremities of players and these loading are thought to be the contributing factors of chronic knee injuries. This study examined the impact loading characteristics in various groups of badminton athletes performing extreme lunges. Methods Fifty-two participants classified into male skilled, female skilled, male unskilled, and female unskilled groups performed badminton lunge with their maximum-effort. Shoe-ground kinematics, ground reaction forces, and knee moments were measured by using synchronised force platform and motion analysis system. A 2 (gender) x 2 (skill-level) factorial ANOVA was performed to determine the effects of different gender and different playing levels, as well as the interaction of two factors on all variables. Results Male athletes had faster approaching speed (male 3.87 and female 1.08 m/s), longer maximum lunge distance (male 1.47 and female 1.16 m), larger maximum (male 215.7 and female 121.65 BW/s) and mean loading rate (male 178.43 and female 81.77 BW/s) and larger peak knee flexion moment (male 0.75 and female 0.69) compared with female athletes ( P 〈 0.001). Unskilled athletes exhibited smaller footstrike angle (skilled 45.78 and unskilled 32.35°), longer contact time (skilled 0.69 and unskilled 0.75 s), larger peak horizontal GRF (skilled 1.61 and unskilled 2.40 BW), smaller mean loading rate (skilled 150.15 and unskilled 110.05 BW/s) and larger peak knee flexion moment ( P 〈 .05; skilled 0.69 and unskilled 0.75 Nm/BW) than the skilled athletes. In addition, the interaction indicated greater peak GRF impact in female unskilled athletes compared with female skilled athletes ( P 〈 0.001; female skilled 2.01 and female unskilled 2.95 BW), while there was no difference between male participants ( P 〉 0.05; male skilled 2.19 and male unskilled 2.49 BW). Conclusions These data suggested that male athletes and/or unskilled athletes experience greater impact loading rates and peak knee flexion moment during lunge compared with female and skilled athletes, respectively. This may expose them to higher risk of overuse injuries. Furthermore, female unskilled athletes seemed to be more vulnerable to lower extremity injuries.
    Electronic ISSN: 1932-6203
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  • 79
    Publication Date: 2018-10-13
    Description: by Xinjuan Wu, Zhen Li, Jing Cao, Jing Jiao, Yingli Wang, Ge Liu, Ying Liu, Fangfang Li, Baoyun Song, Jingfen Jin, Yilan Liu, Xianxiu Wen, Shouzhen Cheng, Xia Wan Purpose To describe the association between major complications of immobility (pressure ulcer, pneumonia, deep vein thrombosis and urinary tract infection) during hospitalization and the patients’ health-related quality of life after discharge. Methods The data were obtained from a multi-center study conducted in 2015. Complications of immobility during hospitalization was measured by case report form and quality of life after discharge was measured using the EQ-5D scale by telephone interview. Multilevel mixed-effects models were used to explore the association of complications and responses in the EQ-5D dimensions after controlling for important covariates. Results Among the 20,515 bedridden patients, 2,601(12.72%) patients experienced at least one of the major complications of immobility during hospitalization, including pressure ulcer (527, 2.57%), deep vein thrombosis (343, 1.67%), pneumonia (1647, 8.16%), and urinary tract infection (265, 1.29%). Patients with any of the four complications during hospitalization reported more problems in all EQ-5D dimensions except for pain/discomfort , and had lower mean EQ-VAS scores than those without any complications. The four complications all showed significant associations with the proportion of reported problems in certain dimensions after adjustment for confounding variables. Conclusions Major complications of immobility were significantly associated with reduced health related quality of life. Prevention of complications is critical to reduce the burden of decreased quality of life for bedridden patients.
    Electronic ISSN: 1932-6203
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  • 80
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    Public Library of Science (PLoS)
    Publication Date: 2018-10-13
    Description: by Vega Jovani, Mar Blasco-Blasco, Eliseo Pascual, M. Teresa Ruiz-Cantero Background Diagnostic delay is well-known in spondyloarthritis and studies have demonstrated a longer deferral in women. The aim of this study was to explore whether diagnostic delay of spondyloarthritis depends on clinical manifestations expressed by patients according to sex or whether it is related to a doctor’s misdiagnosis bias. Methods A cross-sectional study of 96 men and 54 women with spondyloarthritis was performed at Alicante University General Hospital in Spain using a semistructured interview and clinical records. Comparative sex analysis were done via Student’s T and Mann-Whitney U tests for parametric and nonparametric continuous variables, chi-square and Fisher’s exact tests for unpaired categorical variables, and McNemar’s test for paired ones. Findings The median diagnostic delay in women 7.5 (11.5) years is higher than men 4 (11) years, with a difference close to statistical significance (p = 0.053). A total of 30.2% of men received a first correct diagnosis of spondyloarthritis versus 11.1% of women ( p = 0.016), indicating that men have higher probability of not having a misdiagnosis of spondyloarthritis (odds ratio = 3.5; 1.3–9). Eleven different health services referred male patients to the rheumatology clinic but only six in the case of female. No sex differences were detected in patients’ manifestations of back pain at onset. However, medical records registered differences (women 44.4%, men 82.1%; p 〈 0.001). There were differences between patients (women 57.7%, men 35.2%; p = 0.008) and medical records in peripheral signs/symptoms at onset (women 55.6%, men 17.9%; p 〈 0.001).