Subscribe: CiteULike: Everyone's library
Added By: Feedage Forager Feedage Grade B rated
Language: English
assembly order  assembly  cam  children  complex  data  dna  doi  epilepsy  exercise  medicine  physical  protein  proteins  vol 
Rate this Feed
Rate this feedRate this feedRate this feedRate this feedRate this feed
Rate this feed 1 starRate this feed 2 starRate this feed 3 starRate this feed 4 starRate this feed 5 star

Comments (0)

Feed Details and Statistics Feed Statistics
Preview: CiteULike: Everyone's library

CiteULike: Everyone's library

CiteULike: Everyone's library


Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies.


The British journal of psychiatry : the journal of mental science, Vol. 202, No. 5. (01 May 2013), pp. 329-335, doi:10.1192/bjp.bp.112.118307

Late-life depression may increase the risk of incident dementia, in particular of Alzheimer's disease and vascular dementia. To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer's disease and vascular dementia in individuals with late-life depression in population-based prospective studies. A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer's disease and vascular dementia in older adults with late-life depression. Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer's disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer's disease (P = 0.03). Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer's disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer's disease.
Breno Diniz, Meryl Butters, Steven Albert, Mary Amanda Dew, Charles Reynolds

Proximal Algorithms in Statistics and Machine Learning


(30 May 2015)

In this paper we develop proximal methods for statistical learning. Proximal point algorithms are useful in statistics and machine learning for obtaining optimization solutions for composite functions. Our approach exploits closed-form solutions of proximal operators and envelope representations based on the Moreau, Forward-Backward, Douglas-Rachford and Half-Quadratic envelopes. Envelope representations lead to novel proximal algorithms for statistical optimisation of composite objective functions which include both non-smooth and non-convex objectives. We illustrate our methodology with regularized Logistic and Poisson regression and non-convex bridge penalties with a fused lasso norm. We provide a discussion of convergence of non-descent algorithms with acceleration and for non-convex functions. Finally, we provide directions for future research.
Nicholas Polson, James Scott, Brandon Willard

Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion


mBio, Vol. 7, No. 1. (2 March 2016), doi:10.1128/mbio.02145-15

Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs). The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β) or gamma interferon (IFN-γ) significantly diminished the number of herpes simplex virus 1 (HSV-1) and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion.IMPORTANCE Neurons are highly polarized cells with long axonal processes that connect to distant targets. PNS axons that innervate peripheral tissues are exposed to various situations that follow infection, inflammation, and damage of the tissue. After viral infection in the periphery, axons represent potential front-line barriers to PNS infection and damage. Indeed, most viral infections do not spread to the PNS, yet the mechanisms responsible are not well studied. We devised an experimental system to study how axons respond to inflammatory cytokines that would be produced by infected tissues. We found that axons respond differentially to type I and type II interferons. The response to type I interferon (IFN-β) is a rapid axon-only response. The response to type II interferon (IFN-γ) involves long-distance signaling to the PNS cell body. These responses to two interferons erect an efficient and rapid barrier to PNS infection.
Ren Song, Orkide Koyuncu, Todd Greco, Benjamin Diner, Ileana Cristea, Lynn Enquist

What happens if measure the electron spin twice?


(21 Feb 2018)

The mainstream textbooks of quantum mechanics explains the quantum state collapses into an eigenstate in the measurement, while other explanations such as hidden variables and multi-universe deny the collapsing. Here we propose an ideal thinking experiment on measuring the spin of an electron with 3 steps. It is simple and straightforward, in short, to measure a spin-up electron in x-axis, and then in z-axis. Whether there is a collapsing predicts different results of the experiment. The future realistic experiment will show the quantum state collapses or not in the measurement.
YC Zou

A generalization of the FIFA World Cup effect


Tourism Management, Vol. 66 (June 2018), pp. 315-317, doi:10.1016/j.tourman.2017.12.014
Juan Nicolau, Abhinav Sharma

Budden's Paradox Resolved


(21 Feb 2018)

Budden's energy nonconservation paradox is dispelled herein by recognizing that pole approach to the spatial origin from below in the complex plane can be resolved into a real principal value plus $-iπ$ times a Dirac delta, the imaginary coefficient whereof supplies just the right amount of localized dissipation to equilibrate the energy budget precisely, regardless of whether wave incidence be up or down. Only the reflectionless downward wave incidence remains as a counterintuitive challenge to physical anticipation, but at least a challenge liberated from its former onus of energy nonconservation.
JA Grzesik

The economic, social, and environmental impacts of cruise tourism


Tourism Management, Vol. 66 (June 2018), pp. 387-404, doi:10.1016/j.tourman.2017.11.002
Timothy MacNeill, David Wozniak

Tourists' digital footprint in cities: Comparing Big Data sources


Tourism Management, Vol. 66 (June 2018), pp. 13-25, doi:10.1016/j.tourman.2017.11.001
María Salas-Olmedo, Borja Moya-Gómez, Juan García-Palomares, Javier Gutiérrez

Evolutionary origins of the blood vascular system and endothelium


J Thromb Haemost, Vol. 11 (1 June 2013), pp. 46-66, doi:10.1111/jth.12253

Every biological trait requires both a proximate and evolutionary explanation. The field of vascular biology is focused primarily on proximate mechanisms in health and disease. Comparatively little attention has been given to the evolutionary basis of the cardiovascular system. Here, we employ a comparative approach to review the phylogenetic history of the blood vascular system and endothelium. In addition to drawing on the published literature, we provide primary ultrastructural data related to the lobster, earthworm, amphioxus, and hagfish. Existing evidence suggests that the blood vascular system first appeared in an ancestor of the triploblasts over 600 million years ago, as a means to overcome the time-distance constraints of diffusion. The endothelium evolved in an ancestral vertebrate some 540–510 million years ago to optimize flow dynamics and barrier function, and/or to localize immune and coagulation functions. Finally, we emphasize that endothelial heterogeneity evolved as a core feature of the endothelium from the outset, reflecting its role in meeting the diverse needs of body tissues.
R Monahan-Earley, AM Dvorak, WC Aird

Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians.


Breast cancer research and treatment, Vol. 161, No. 3. (February 2017), pp. 491-499

Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC. Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data. 1104 patients were identified, of which 178 had TNBC. TNBC was more frequent in African Americans than Caucasians (33.3 vs 14.9%). Although more African Americans than Caucasians overall were classified as basal-like from PAM50 gene expression (34.8 vs 16.1%), no differences in the TNBC cohort were observed. Median tumor somatic mutation counts were higher in African Americans versus Caucasians (39.5 vs 34), but no racial differences in the mutation counts in TNBC were observed. Somatic mutation analysis revealed racial differences in specific high prevalence genes in all patients (TP53 46% in African Americans vs 27% in Caucasians; PIK3CA 23% in African Americans vs 34% in Caucasians; and MLL3 12% in African Americans vs 6% in Caucasians). TNBC patients did not have any specific high prevalence genes associated with racial differences. There were no racial differences in gene expression patterns in selected genes involved in breast cancer biology. Overall, African Americans had shorter TTP and worse DFS. Racial differences in clinical outcomes were not observed in TNBC. The mutational landscape of TNBC is similar between African Americans and Caucasians. The higher frequency of TNBC in African Americans is therefore not associated with a different genomic profile of commonly established tumor regulatory pathway genes. Other modifiable factors may exist that contribute to the racial disparity in TNBC.
Foluso Ademuyiwa, Yu Tao, Jingqin Luo, Katherine Weilbaecher, Cynthia Ma

Modeling the assembly order of multimeric heteroprotein complexes


PLOS Computational Biology, Vol. 14, No. 1. (12 January 2018), e1005937, doi:10.1371/journal.pcbi.1005937

Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number of protein complex structures have been determined using experimental methods, relatively fewer studies have been performed to determine the assembly order of complexes. In addition to the insights into the molecular mechanisms of biological function provided by the structure of a complex, knowing the assembly order is important for understanding the process of complex formation. Assembly order is also practically useful for constructing subcomplexes as a step toward solving the entire complex experimentally, designing artificial protein complexes, and developing drugs that interrupt a critical step in the complex assembly. There are several experimental methods for determining the assembly order of complexes; however, these techniques are resource-intensive. Here, we present a computational method that predicts the assembly order of protein complexes by building the complex structure. The method, named Path-LzerD, uses a multimeric protein docking algorithm that assembles a protein complex structure from individual subunit structures and predicts assembly order by observing the simulated assembly process of the complex. Benchmarked on a dataset of complexes with experimental evidence of assembly order, Path-LZerD was successful in predicting the assembly pathway for the majority of the cases. Moreover, when compared with a simple approach that infers the assembly path from the buried surface area of subunits in the native complex, Path-LZerD has the strong advantage that it can be used for cases where the complex structure is not known. The path prediction accuracy decreased when starting from unbound monomers, particularly for larger complexes of five or more subunits, for which only a part of the assembly path was correctly identified. As the first method of its kind, Path-LZerD opens a new area of computational protein structure modeling and will be an indispensable approach for studying protein complexes. Protein-protein interactions, particularly those involving multiple proteins, are the cornerstone of numerous biological processes. Although an increasing number of multi-chain protein complex structures have been determined, fewer studies have been performed to determine the assembly order of complexes. Knowing the assembly order of a complex provides insights into the process of complex formation. Assembly order is also practically useful for reconstructing and determining the structure of a subcomplex of a large protein complex. It also has important applications including designing artificial protein complexes and drugs that prevent the assembly of protein complexes. We present a computational method, Path-LZerD, which predicts the assembly order of a protein complex by simulating its assembly process. This is the first method of this kind. A strong advantage of Path-LZerD is that the assembly order can be predicted even when the overall complex structure is not known. Path-LZerD opens a new area of computational protein structure modeling and will be an indispensable approach for studying protein complexes.
Lenna Peterson, Yoichiro Togawa, Juan Esquivel-Rodriguez, Genki Terashi, Charles Christoffer, Amitava Roy, Woong-Hee Shin, Daisuke Kihara

Reactome graph database: Efficient access to complex pathway data


PLOS Computational Biology, Vol. 14, No. 1. (29 January 2018), e1005968, doi:10.1371/journal.pcbi.1005968

Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage. By adopting graph database technology we are providing a high performance pathway data resource to the community. The Reactome graph database use case shows the power of NoSQL database engines for complex biological data types. To better support genome analysis, modeling, systems biology and education, we now offer our knowledgebase of biomolecular pathways as a graph database. We have developed a tool to migrate the Reactome content from the relational database used in curation to a graph database during each quarterly release process. The new graph database has two main advantages; higher performance and simpler ways to perform complex queries. Reactome has already adapted its software infrastructure to benefit from this growing in popularity storage technology, significantly improving query efficiency, by reducing the average query time by 93%. We strongly believe that the successful adoption of a graph database by Reactome demonstrates the positive impact this new technology could potentially have in the field and could provide a practical example for other community projects with similar complex data models to move their storage to a graph database while retaining their data models.
Antonio Fabregat, Florian Korninger, Guilherme Viteri, Konstantinos Sidiropoulos, Pablo Marin-Garcia, Peipei Ping, Guanming Wu, Lincoln Stein, Peter D'Eustachio, Henning Hermjakob

What is the state of hospitality and tourism research – 2018?


International Journal of Contemporary Hospitality Management (06 February 2018), pp. 00-00, doi:10.1108/ijchm-12-2017-0809
Bob McKercher

Two Levels of Metacognition


Philosophia, Vol. 39, No. 1. (1 March 2011), pp. 71-82, doi:10.1007/s11406-010-9279-0

Two main theories about metacognition are reviewed, each of which claims to provide a better explanation of this phenomenon, while discrediting the other theory as inappropriate. The paper claims that in order to do justice to the complex phenomenon of metacognition, we must distinguish two levels of this capacity—each having a different structure, a different content and a different function within the cognitive architecture. It will be shown that each of the reviewed theories has been trying to explain only one of the two levels and that, consequently, the conflict between them can be dissolved. The paper characterizes the high-level as a rationalizing level where the subject uses concepts and theories to interpret her own behavior and the low-level as a controlling level where the subject exploits epistemic feelings to adjust her cognitive activities. Finally, the paper explores three kinds of interaction between the levels.
Santiago Arango-Muñoz

How we know our own minds: The relationship between mindreading and metacognition


Behavioral and Brain Sciences, Vol. 32, No. 02. (April 2009), pp. 121-138, doi:10.1017/s0140525x09000545

Four different accounts of the relationship between third-person mindreading and first-person metacognition are compared and evaluated. While three of them endorse the existence of introspection for propositional attitudes, the fourth (defended here) claims that our knowledge of our own attitudes results from turning our mindreading capacities upon ourselves. Section 1 of this target article introduces the four accounts. Section 2 develops the “mindreading is prior” model in more detail, showing how it predicts introspection for perceptual and quasi-perceptual (e.g., imagistic) mental events while claiming that metacognitive access to our own attitudes always results from swift unconscious self-interpretation. This section also considers the model's relationship to the expression of attitudes in speech. Section 3 argues that the commonsense belief in the existence of introspection should be given no weight. Section 4 argues briefly that data from childhood development are of no help in resolving this debate. Section 5 considers the evolutionary claims to which the different accounts are committed, and argues that the three introspective views make predictions that are not borne out by the data. Section 6 examines the extensive evidence that people often confabulate when self-attributing attitudes. Section 7 considers “two systems” accounts of human thinking and reasoning, arguing that although there are introspectable events within System 2, there are no introspectable attitudes. Section 8 examines alleged evidence of “unsymbolized thinking”. Section 9 considers the claim that schizophrenia exhibits a dissociation between mindreading and metacognition. Finally, section 10 evaluates the claim that autism presents a dissociation in the opposite direction, of metacognition without mindreading.
Peter Carruthers

Executive Attention and Metacognitive Regulation


Consciousness and Cognition, Vol. 9, No. 2. (June 2000), pp. 288-307, doi:10.1006/ccog.2000.0447

Metacognition refers to any knowledge or cognitive process that monitors or controls cognition. We highlight similarities between metacognitive and executive control functions, and ask how these processes might be implemented in the human brain. A review of brain imaging studies reveals a circuitry of attentional networks involved in these control processes, with its source located in midfrontal areas. These areas are active during conflict resolution, error correction, and emotional regulation. A developmental approach to the organization of the anatomy involved in executive control provides an added perspective on how these mechanisms are influenced by maturation and learning, and how they relate to metacognitive activity.
Diego Fernandez-Duque, Jodie Baird, Michael Posner

Analysis of deep learning methods for blind protein contact prediction in CASP12


Proteins, Vol. 86 (1 March 2018), pp. 67-77, doi:10.1002/prot.25377

Here we present the results of protein contact prediction achieved in CASP12 by our RaptorX-Contact server, which is an early implementation of our deep learning method for contact prediction. On a set of 38 free-modeling target domains with a median family size of around 58 effective sequences, our server obtained an average top L/5 long- and medium-range contact accuracy of 47% and 44%, respectively (L = length). A complete implementation has an average accuracy of 59% and 57%, respectively. Our deep learning method formulates contact prediction as a pixel-level image labeling problem and simultaneously predicts all residue pairs of a protein using a combination of two deep residual neural networks, taking as input the residue conservation information, predicted secondary structure and solvent accessibility, contact potential, and coevolution information. Our approach differs from existing methods mainly in (1) formulating contact prediction as a pixel-level image labeling problem instead of an image-level classification problem; (2) simultaneously predicting all contacts of an individual protein to make effective use of contact occurrence patterns; and (3) integrating both one-dimensional and two-dimensional deep convolutional neural networks to effectively learn complex sequence-structure relationship including high-order residue correlation. This paper discusses the RaptorX-Contact pipeline, both contact prediction and contact-based folding results, and finally the strength and weakness of our method.
Sheng Wang, Siqi Sun, Jinbo Xu

Assessment of contact predictions in CASP12: Co-evolution and deep learning coming of age


Proteins, Vol. 86 (1 March 2018), pp. 51-66, doi:10.1002/prot.25407

Following up on the encouraging results of residue-residue contact prediction in the CASP11 experiment, we present the analysis of predictions submitted for CASP12. The submissions include predictions of 34 groups for 38 domains classified as free modeling targets which are not accessible to homology-based modeling due to a lack of structural templates. CASP11 saw a rise of coevolution-based methods outperforming other approaches. The improvement of these methods coupled to machine learning and sequence database growth are most likely the main driver for a significant improvement in average precision from 27% in CASP11 to 47% in CASP12. In more than half of the targets, especially those with many homologous sequences accessible, precisions above 90% were achieved with the best predictors reaching a precision of 100% in some cases. We furthermore tested the impact of using these contacts as restraints in ab initio modeling of 14 single-domain free modeling targets using Rosetta. Adding contacts to the Rosetta calculations resulted in improvements of up to 26% in GDT_TS within the top five structures.
Joerg Schaarschmidt, Bohdan Monastyrskyy, Andriy Kryshtafovych, Alexandre Bonvin

Reduction of Nonspecificity Motifs in Synthetic Antibody Libraries.


Journal of molecular biology, Vol. 430, No. 1. (05 January 2018), pp. 119-130

Successful antibody development requires both functional binding and desirable biophysical characteristics. In the current study, we analyze the causes of one hurdle to clinical development, off-target reactivity, or nonspecificity. We used a high-throughput nonspecificity assay to isolate panels of nonspecific antibodies from two synthetic single-chain variable fragment libraries expressed on the surface of yeast, identifying both individual amino acids and motifs within the complementarity-determining regions which contribute to the phenotype. We find enrichment of glycine, valine, and arginine as both individual amino acids and as a part of motifs, and additionally enrichment of motifs containing tryptophan. Insertion of any of these motifs into the complementarity-determining region H3 of a "clean" antibody increased its nonspecificity, with greatest increases in antibodies containing Trp or Val motifs. We next applied these rules to the creation of a synthetic diversity library based on natural frameworks with significantly decreased incorporation of such motifs and demonstrated its ability to isolate binders to a wide panel of antigens. This work both provides a greater understanding of the drivers of nonspecificity and provides design rules to increase efficiency in the isolation of antibodies with drug-like properties. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ryan Kelly, Doris Le, Jessie Zhao, Dane Wittrup



Journal of molecular biology (16 January 2018)

The molecular basis of polyspecificity of Mdr1p, a major drug/H+antiporter of Candida albicans, is not elucidated. We have probed the nature of the drug-binding pocket by performing systematic mutagenesis of the 12 transmembrane segments. Replacement of the 252 amino acid residues with alanine or glycine yielded 2/3 neutral mutations while 1/3 led to the complete or selective loss of resistance to drugs or substrates transported by the pump. Using the GlpT-based 3D-model of Mdr1p, we roughly categorized these critical residues depending on their type and localization, 1°/ main structural impact ("S" group), 2°/ exposure to the lipid interface ("L" group), 3°/ buried but not facing the main central pocket, inferred as critical for the overall H+/drug antiport mechanism ("M" group) and finally 4°/ buried and facing the main central pocket ("B" group). Among "B" category, 13 residues were essential for the large majority of drugs/substrates, while 5 residues were much substrate-specific, suggesting a role in governing polyspecificity (P group). 3D superposition of the substrate-specific MFS Glut1 and XylE with the MDR substrate-polyspecific MdfA and Mdr1p revealed that the B group forms a common substrate interaction core while the P group is only found in the 2 MDR MFS transporters, distributed into 3 areas around the B core. This specific pattern has let us to propose that the structural basis for polyspecificity of MDR MFS transporters is the extended capacity brought by residues located at the periphery of a binding core to accomodate compounds differing in size and type. Copyright © 2018 Elsevier Ltd. All rights reserved.
Archana Kumari Redhu, Atanu Banerjee, Abdul Haseeb Shah, Alexis Moreno, Manpreet Kaur Rawal, Remya Nair, Pierre Falson, Rajendra Prasad

High Free-Energy Barrier of 1D Diffusion Along DNA by Architectural DNA-Binding Proteins.


Journal of molecular biology (04 January 2018)

Architectural DNA-binding proteins function to regulate diverse DNA reactions and have the defining property of significantly changing DNA conformation. Although the 1D movement along DNA by other types of DNA-binding proteins has been visualized, the mobility of architectural DNA-binding proteins on DNA remains unknown. Here, we applied single-molecule fluorescence imaging on arrays of extended DNA molecules to probe the binding dynamics of three structurally distinct architectural DNA-binding proteins: Nhp6A, HU, and Fis. Each of these proteins was observed to move along DNA, and the salt concentration independence of the 1D diffusion implies sliding with continuous contact to DNA. Nhp6A and HU exhibit a single sliding mode, whereas Fis exhibits two sliding modes. Based on comparison of the diffusion coefficients and sizes of many DNA binding proteins, the architectural proteins are categorized into a new group distinguished by an unusually high free-energy barrier for 1D diffusion. The higher free-energy barrier for 1D diffusion by architectural proteins can be attributed to the large DNA conformational changes that accompany binding and impede rotation-coupled movement along the DNA grooves. Copyright © 2018 Elsevier Ltd. All rights reserved.
Kiyoto Kamagata, Eriko Mano, Kana Ouchi, Saori Kanbayashi, Reid Johnson

Nautilus multi-grain model: Importance of cosmic-ray-induced desorption in determining the chemical abundances in the ISM


(22 Feb 2018)

Species abundances in the interstellar medium (ISM) strongly depend on the chemistry occurring at the surfaces of the dust grains. To describe the complexity of the chemistry, various numerical models have been constructed. In most of these models, the grains are described by a single size of 0.1$μ$m. We study the impact on the abundances of many species observed in the cold cores by considering several grain sizes in the Nautilus multi-grain model. We used grain sizes with radii in the range of $0.005μ$m to $0.25μ$m. We sampled this range in many bins. We used the previously published, MRN and WD grain size distributions to calculate the number density of grains in each bin. Other parameters such as the grain surface temperature or the cosmic-ray-induced desorption rates also vary with grain sizes. We present the abundances of various molecules in the gas phase and also on the dust surface at different time intervals during the simulation. We present a comparative study of results obtained using the single grain and the multi-grain models. We also compare our results with the observed abundances in TMC-1 and L134N clouds. We show that the grain size, the grain size dependent surface temperature and the peak surface temperature induced by cosmic ray collisions, play key roles in determining the ice and the gas phase abundances of various molecules. We also show that the differences between the MRN and the WD models are crucial for better fitting the observed abundances in different regions in the ISM. We show that the small grains play a very important role in the enrichment of the gas phase with the species which are mainly formed on the grain surface, as non-thermal desorption induced by collisions of cosmic ray particles is very efficient on the small grains.
Wasim Iqbal, Valentine Wakelam

Attributes and Dynamic Development Phases of Informal ICT Standards Consortia


Social Science Research Network Working Paper Series (1 March 2013)

Standards consortia are private industry alliances that serve a certain purpose and gather likeminded companies that share the same interest to sponsor and develop technologies for standardization. Compared to formal standard setting, participation in consortia is less bureaucratic, more efficient in reacting to market needs and allows, in respect to the tiered membership structures, a strategic influence of standard setting outcomes. Formal standardization is in contrast an often protracted process of development and negotiation. This paper tries to provide a broad and comprehensive picture of standards consortia and their dynamic development in the past ten years. Analyses show that consortia have distinct characteristics which help to explain and justify their presence in the standard setting context. The observation of consortia existence over time identifies relationships between the formation, termination and merger of consortia with respect to market and technology development. Furthermore the paper seeks to measure consortia performance with respect to organizational structures and market position. Therefore we test the likelihood of consortia termination. Results of a survival analysis reveal that the probability of consortia success is especially connected to structures that determine coordination among members. Additionally the scope and focus on technology and markets also influences if consortia remain in business over time.
Tim Pohlmann

Complementary and alternative medicine in paediatrics in daily practice--a European perspective.


Complementary therapies in medicine, Vol. 21 Suppl 1 (April 2013)

Complementary and alternative medicine (CAM) is used by both adults and children in Europe. Diverse cultural, ethnic and historical preconditions in European countries result in broad differences between the types of CAM practiced, prevalence of CAM use and integration in the health system. To date, no survey of CAM availability to paediatric patients in Europe exists. We present an overview of CAM integration within the different levels of the European paediatric health systems as a narrative review. Paediatric CAM specialists in 20 European countries provided information about CAM integration in their countries in semi-structured interviews. Data from 20 European countries were available, representing 68% of the European population. CAM is offered in private practices in all 20 (100%) countries, and 80% described some form of CAM training for health professionals. While CAM is offered in outpatient clinics treating adults in 80% of these countries, only 35% offer CAM in paediatric outpatient clinics. Dedicated CAM inpatient wards exist in 65% of the countries for adults, but only in Germany and the Netherlands for children. Groups conducting some CAM research or CAM research focussed on paediatrics exist in 65% and 50% of the 20 countries, respectively. Homeopathy, acupuncture and anthroposophic medicine were most often named. Every child in Europe has access to CAM treatment, mainly in private practices, whereas CAM outpatient clinics and inpatient services for children are rare. This is in contrast to adult treatment facilities, many of which offer CAM services, and the high percentage of European children using CAM. Copyright © 2012 Elsevier Ltd. All rights reserved.
Alfred Längler, Tycho Zuzak

Use of complementary and alternative medicine in healthy children and children with chronic medical conditions in Germany.


Complementary therapies in medicine, Vol. 21 Suppl 1 (April 2013)

Use of complementary and alternative medicine (CAM) in children is common and probably increasing. However little is known about differences between healthy and chronically ill children with a focus on prevalence, reasons for use/non-use, costs, adverse effects and socio-demographic factors. A questionnaire-based survey with 500 participants visiting the outpatient clinic of the University Children's Hospital Homburg, Germany was conducted over a 4-week period in 2004. Recruitment was stopped when 500 questionnaires were handed out in total. Of the 405 (81%) respondents (242 with chronic conditions, 163 healthy children incidentally visiting the hospital for minor ailments) 229 (57%) reported lifetime CAM use (59% with chronic conditions versus 53% healthy children). Among CAM users the most prevalent therapies were homeopathy (25%), herbal remedies (8%), anthroposophic medicine (7%), vitamin preparations (6%) and acupuncture (5%). The main reasons for use were to strengthen the immune system, physical stabilisation and to increase healing chances/maintain health. Socio-demographic factors associated with CAM use were tertiary education (mother: p=0.017; father: p>0.001), higher family income (p=0.001) and being Protestant (p=0.01). Expectations towards CAM were high and most parents would recommend certain CAM (94%). 79% of the users informed a physician about CAM use. Side effects were rarely reported (4%), minor and self-limiting. Clinical care and the physician-patient relation would benefit from an enhanced understanding of CAM and a greater candidness towards the parental needs. The safety and efficacy especially of CAM with high prevalence rates should be determined in rigorous basic and clinical researches. Copyright © 2011 Elsevier Ltd. All rights reserved.
Sven Gottschling, Benjamin Gronwald, Sarah Schmitt, Christine Schmitt, Alfred Längler, Eberhard Leidig, Sascha Meyer, Annette Baan, Ghiath Shamdeen, Jens Berrang, Norbert Graf

Pediatric lead poisoning from folk prescription for treating epilepsy.


Clinica chimica acta; international journal of clinical chemistry, Vol. 461 (01 October 2016), pp. 130-134

A case of lead poisoning resulting from the ingestion of a folk remedy for treating epilepsy is reported. The initial blood lead concentration of this 6-y-old boy was 63.6μg/dl upon admission. He presented with abdominal pain, constipation, and irritability. The patient's liver function tests were significantly increased. Through chelation therapy, the blood lead concentration dropped markedly and clinical symptoms greatly improved. His blood and urine samples were collected for the kinetic analysis of lead elimination. Folk prescriptions for epilepsy should be considered as potential sources of lead intoxication. Lead poisoning should be taken into consideration for unknown causes of abdominal pain. Copyright © 2016. Published by Elsevier B.V.
Xiao-Lan Ying, Jian Xu, Morri Markowitz, Chong-Huai Yan

Review of the use of botanicals for epilepsy in complementary medical systems--Traditional Chinese Medicine.


Epilepsy & behavior : E&B, Vol. 52, No. Pt B. (November 2015), pp. 281-289

In traditional Chinese medicine, botanical remedies have been used for centuries to treat seizures. This review aimed to summarize the botanicals that have been used in traditional Chinese medicine to treat epilepsy. We searched Chinese online databases to determine the botanicals used for epilepsy in traditional Chinese medicine and identified articles using a preset search syntax and inclusion criteria of each botanical in the PubMed database to explore their potential mechanisms. Twenty-three botanicals were identified to treat epilepsy in traditional Chinese medicine. The pharmacological mechanisms of each botanical related to antiepileptic activity, which were mainly examined in animal models, were reviewed. We discuss the use and current trends of botanical treatments in China and highlight the limitations of botanical epilepsy treatments. A substantial number of these types of botanicals would be good candidates for the development of novel AEDs. More rigorous clinical trials of botanicals in traditional Chinese medicine for epilepsy treatment are encouraged in the future. This article is part of a Special Issue entitled "Botanicals for Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.
Fenglai Xiao, Bo Yan, Lei Chen, Dong Zhou

Does exercise correct dysregulation of neurosteroid levels induced by epilepsy?


Annals of neurology, Vol. 68, No. 6. (December 2010), pp. 971-972
Ricardo Mario Arida, Fulvio Alexandre Scorza, Michelle Toscano-Silva, Esper Abrão Cavalheiro

Can people with epilepsy enjoy sports?


Epilepsy research, Vol. 98, No. 1. (January 2012), pp. 94-95
Ricardo Arida, Fulvio Scorza, Esper Cavalheiro, Emilio Perucca, Solomon Moshé

Experimental and clinical findings from physical exercise as complementary therapy for epilepsy.


Epilepsy & behavior : E&B, Vol. 26, No. 3. (March 2013), pp. 273-278

Complementary therapies for preventing or treating epilepsy have been extensively used. This review focuses on the positive effects of physical exercise programs observed in clinical studies and experimental models of epilepsy and their significance as a complementary therapy for epilepsy. Information about the antiepileptogenic and neuroprotective effects of exercise is highlighted. Considering that exercise can exert beneficial actions such as reduction of seizure susceptibility, reduction of anxiety and depression, and consequently, improvement of quality of life of individuals with epilepsy, exercise can be a potential candidate as non-pharmacological treatment of epilepsy. Copyright © 2012 Elsevier Inc. All rights reserved.
Ricardo Mario Arida, Antonio-Carlos Guimarães de Almeida, Esper Abrão Cavalheiro, Fulvio Alexandre Scorza

Physical activity and epilepsy: proven and predicted benefits.


Sports medicine (Auckland, N.Z.), Vol. 38, No. 7. (2008), pp. 607-615

Epilepsy is a common disease found in 2% of the population, affecting people from all ages. Unfortunately, persons with epilepsy have previously been discouraged from participation in physical activity and sports for fear of inducing seizures or increasing seizure frequency. Despite a shift in medical recommendations toward encouraging rather than restricting participation, the stigma remains and persons with epilepsy continue to be less active than the general population. For this purpose, clinical and experimental studies have analysed the effect of physical exercise on epilepsy. Although there are rare cases of exercise-induced seizures, studies have shown that physical activity can decrease seizure frequency, as well as lead to improved cardiovascular and psychological health in people with epilepsy. The majority of physical activities or sports are safe for people with epilepsy to participate in with special attention to adequate seizure control, close monitoring of medications, and preparation of family or trainers. The evidence shows that patients with good seizure control can participate in both contact and non-contact sports without harmfully affecting seizure frequency. This article reviews the risks and benefits of physical activity in people with epilepsy, discusses sports in which persons with epilepsy may participate, and describes the positive effect of physical exercise in experimental models of epilepsy.
Ricardo Arida, Esper Cavalheiro, Antonio da Silva, Fulvio Scorza

Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.


Science (New York, N.Y.), Vol. 332, No. 6031. (13 May 2011), pp. 848-852, doi:10.1126/science.1203919

Genomic imprinting causes parental origin-specific monoallelic gene expression through differential DNA methylation established in the parental germ line. However, the mechanisms underlying how specific sequences are selectively methylated are not fully understood. We have found that the components of the PIWI-interacting RNA (piRNA) pathway are required for de novo methylation of the differentially methylated region (DMR) of the imprinted mouse Rasgrf1 locus, but not other paternally imprinted loci. A retrotransposon sequence within a noncoding RNA spanning the DMR was targeted by piRNAs generated from a different locus. A direct repeat in the DMR, which is required for the methylation and imprinting of Rasgrf1, served as a promoter for this RNA. We propose a model in which piRNAs and a target RNA direct the sequence-specific methylation of Rasgrf1.
Toshiaki Watanabe, Shin-ichi Tomizawa, Kohzoh Mitsuya, Yasushi Totoki, Yasuhiro Yamamoto, Satomi Kuramochi-Miyagawa, Naoko Iida, Yuko Hoki, Patrick Murphy, Atsushi Toyoda, Kengo Gotoh, Hitoshi Hiura, Takahiro Arima, Asao Fujiyama, Takashi Sado, Tatsuhiro Shibata, Toru Nakano, Haifan Lin, Kenji Ichiyanagi, Paul Soloway, Hiroyuki Sasaki

Physiological and electroencephalographic responses to acute exhaustive physical exercise in people with juvenile myoclonic epilepsy.


Epilepsy & behavior : E&B, Vol. 22, No. 4. (December 2011), pp. 718-722

Although the available evidence suggests that exercise may positively affect epilepsy, whether this effect is applicable to different types of epilepsy has not been established. Physiological responses during rest, acute physical effort, and a recovery period were studied by concomitant analysis of cerebral electric activity using EEGs in subjects with juvenile myoclonic epilepsy (JME) and healthy controls. In addition, level of habitual physical activity, body composition, and 1 week of actigraphy monitoring data were evaluated. Twenty-four subjects (12 with JME and 12 controls) participated in this study. Compared with the control group, the JME group had a significantly lower V˙O(2) at rest (13.3%) and resting metabolic rate (15.6%). The number of epileptiform discharges in the JME group was significantly reduced during the recovery period (72%) compared with the resting state. There were no significant differences between the JME and control groups in behavioral outcomes and sleep parameters evaluated by actigraphy monitoring. The positive findings of our study strengthen the evidence for the benefits of physical exercise for people with JME. Copyright © 2011. Published by Elsevier Inc.
Cristiano de Lima, Rodrigo Luiz Vancini, Ricardo Mario Arida, Laura Guilhoto, Marco Túlio de Mello, Amaury Tavares Barreto, Mirian Salvadori Bittar Guaranha, Elza Márcia Targas Yacubian, Sergio Tufik

Pinpointing the expression of piRNAs and function of the PIWI protein subfamily during spermatogenesis in the mouse.


Developmental biology, Vol. 355, No. 2. (15 July 2011), pp. 215-226

PIWI proteins and piRNAs have been linked to transposon silencing in the primordial mouse testis, but their function in the adult testis remains elusive. Here we report the cytological characterization of piRNAs in the adult mouse testis and the phenotypic analysis of Miwi(-/-); Mili(-/-) mice. We show that piRNAs are specifically present in germ cells, especially abundant in spermatocytes and early round spermatids, regardless of the type of the genomic sequences to which they correspond. piRNAs and PIWI proteins are present in both the cytoplasm and nucleus. In the cytoplasm, they are enriched in the chromatoid body; whereas in the nucleus they are enriched in the dense body, a male-specific organelle associated with synapsis and the formation of the XY body during meiosis. Moreover, by generating Miwi(-/-); Mili(-/-) mice, which lack all PIWI proteins in the adult, we show that PIWI proteins and presumably piRNAs in the adult are required only for spermatogenesis. Spermatocytes without PIWI proteins are arrested at the pachytene stage, when the sex chromosomes undergo transcriptional silencing to form the XY body. These results pinpoint a function of the PIWI protein subfamily to meiosis during spermatogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.
Ergin Beyret, Haifan Lin

MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells.


Cell reports, Vol. 16, No. 11. (13 September 2016), pp. 2819-2828

During the development of mammalian embryonic germ cells, global demethylation and de novo DNA methylation take place. In mouse embryonic germ cells, two PIWI family proteins, MILI and MIWI2, are essential for the de novo DNA methylation of retrotransposons, presumably through PIWI-interacting RNAs (piRNAs). Although piRNA-associated MIWI2 has been reported to play critical roles in the process, its molecular mechanisms have remained unclear. To identify the mechanism, transgenic mice were produced; they contained a fusion protein of MIWI2 and a zinc finger (ZF) that recognized the promoter region of a type A LINE-1 gene. The ZF-MIWI2 fusion protein brought about DNA methylation, suppression of the type A LINE-1 gene, and a partial rescue of the impaired spermatogenesis of MILI-null mice. In addition, ZF-MIWI2 was associated with the proteins involved in DNA methylation. These data indicate that MIWI2 functions as an effector of de novo DNA methylation of the retrotransposon. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Kanako Kojima-Kita, Satomi Kuramochi-Miyagawa, Ippei Nagamori, Narumi Ogonuki, Atsuo Ogura, Hidetoshi Hasuwa, Takashi Akazawa, Norimitsu Inoue, Toru Nakano

Continuous Glucose Monitoring: Impact on Hypoglycemia.


Journal of diabetes science and technology, Vol. 10, No. 6. (November 2016), pp. 1251-1258

The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia. © 2016 Diabetes Technology Society.
Cornelis van Beers, Hans DeVries

DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes


Genes & Development, Vol. 22, No. 7. (01 April 2008), pp. 908-917, doi:10.1101/gad.1640708

A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields
Satomi Kuramochi-Miyagawa, Toshiaki Watanabe, Kengo Gotoh, Yasushi Totoki, Atsushi Toyoda, Masahito Ikawa, Noriko Asada, Kanako Kojima, Yuka Yamaguchi, Takashi Ijiri, Kenichiro Hata, En Li, Yoichi Matsuda, Tohru Kimura, Masaru Okabe, Yoshiyuki Sakaki, Hiroyuki Sasaki, Toru Nakano

CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation.


Genes & Development, Vol. 3, No. 5. (01 May 1989), pp. 612-619, doi:10.1101/gad.3.5.612

A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields
SM Iguchi-Ariga, W Schaffner

Mitf is a transcriptional activator of medaka germ genes in culture


Biochimie, Vol. 94, No. 3. (March 2012), pp. 759-767, doi:10.1016/j.biochi.2011.11.007

Germ cells express a unique subset of genes called germ genes mostly encoding RNA-binding proteins such as Dazl, Dnd and Vasa. How germ gene expression is controlled remains illusive, because in no organism has a transcription factor been identified that regulate expression of these genes. Microphthalmia-associated transcription factor (Mitf) has been reported to show expression in male mouse germ cells of the adult testis. Here we report in the fish medaka (Oryzias latipes) that Mitf is a transcription activator of germ gene expression. Mitf is a master regulator of melanocyte development, which activates melanogenic genes through binding to the E-box containing consensus CANNTG. The E-box was found to be present in 23∼26 copies in the promoters of medaka germ genes dazl, dnd and vasa. Importantly, forced Mitf expression enhanced the transcriptional activity of the three gene promoters by up to more than 10 fold and remarkably increased the level of endogenous dazl, dnd and vasa transcripts in cell culture. Transfection of Mitf expression vectors was sufficient to induce directed differentiation of medaka embryonic stem cells into melanocytes. Fluorescence in situ hybridization revealed the expression of both medaka mitf genes in adult germ cells of male and female gonads. Mitf is well-known as the melanocyte master regulator. Our results offer first evidence that Mitf may act as a transcriptional activator of germ gene expression in medaka.
Haobin Zhao, Mingyou Li, Yovita Purwanti, Rong Liu, Tiansheng Chen, Zhendong Li, Ni Hong, Guijun Guan, Ao Yin, Ling Xiao, Ruowen Ge, Jianxing Song, Yunhan Hong

Does physical exercise influence the occurrence of epileptiform EEG discharges in children?


Epilepsia, Vol. 38, No. 3. (March 1997), pp. 279-284

To determine if, and how, epileptiform EEG discharges in children were influenced by physical exercise. Twenty-six children with intractable partial and generalized epilepsy exercised during video-telemetry recording, aiming at exhaustion after approximately 10 min. During the exercise, epileptiform discharges decreased in 20 of 26 children (17 children had at least 25% reduction) and showed a rebound increase after the exercise (17 of 26 children) compared to baseline conditions. This exercise-induced reduction in epileptiform discharges reached statistical significance only in the 16 patients with localization-related epilepsy. Five patients showed an atypical EEG response to exercise with either unchanged or increased epileptiform activity while exercising. As compared to the other patients, these 5 children had experienced frequent clinical seizures during or immediately after exercise in their leisure time. In the majority of the tested children, epileptiform EEG discharges decreased during exercise. "Exercise-EEG" may be a helpful diagnostic tool to identify patients who are disposed to have exercise-induced seizures.
KO Nakken, A Løyning, T Løyning, G Gløersen, PG Larsson

Epilepsy, seizures, physical exercise, and sports: A report from the ILAE Task Force on Sports and Epilepsy.


Epilepsia, Vol. 57, No. 1. (January 2016), pp. 6-12

People with epilepsy (PWEs) are often advised against participating in sports and exercise, mostly because of fear, overprotection, and ignorance about the specific benefits and risks associated with such activities. Available evidence suggests that physical exercise and active participation in sports may favorably affect seizure control, in addition to producing broader health and psychosocial benefits. This consensus paper prepared by the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy offers general guidance concerning participation of PWEs in sport activities, and provides suggestions on the issuance of medical fitness certificates related to involvement in different sports. Sports are divided into three categories based on potential risk of injury or death should a seizure occur: group 1, sports with no significant additional risk; group 2, sports with moderate risk to PWEs, but no risk to bystanders; and group 3, sports with major risk. Factors to be considered when advising whether a PWE can participate in specific activities include the type of sport, the probability of a seizure occurring, the type and severity of the seizures, seizure precipitating factors, the usual timing of seizure occurrence, and the person's attitude in accepting some level of risk. The Task Force on Sports and Epilepsy considers this document as a work in progress to be updated as additional data become available. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Giuseppe Capovilla, Kenneth Kaufman, Emilio Perucca, Solomon Moshé, Ricardo Arida

The Savage Mind (Nature of Human Society)


(15 September 1968)
Claude Lévi-Strauss

A pharmacological basis of herbal medicines for epilepsy.


Epilepsy & behavior : E&B, Vol. 52, No. Pt B. (11 November 2015), pp. 308-318

Epilepsy is the most common chronic neurological disease, affecting about 1% of the world's population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs). Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures. Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals. Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs. Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays. To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids. Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs. Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites. Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy. Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development. In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds. This article is part of a Special Issue entitled "Botanicals for Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.
Nikolaus Sucher, Maria Carles

B-Vitamine und Epilepsie


In Zeitschrift für Epileptologie, Vol. 27, No. 3. (2014), pp. 178-185, doi:10.1007/s10309-014-0371-5
B Fiedler

The novel mouse microphthalmia mutations Mitfmi-enu5 and Mitfmi-bcc2 produce dominant negative Mitf proteins


Genomics, Vol. 83, No. 5. (May 2004), pp. 932-935, doi:10.1016/j.ygeno.2003.10.013
Adalheidur Hansdottir, Karen Pálsdóttir, John Favor, Angelika Neuhäuser-Klaus, Helmut Fuchs, Martin de Angelis, Eirı́kur Steingrı́msson

Four Challenges in the Future of Restorative Justice


Victims & Offenders, Vol. 11, No. 1. (2 January 2016), pp. 149-172, doi:10.1080/15564886.2016.1145610

Restorative justice (RJ) emerged in the late 1970s as an alternative to conventional youth and criminal justice practices. Since this time, RJ has experienced rapid growth in theory and practice. At the same time, much of this growth has come from expansion in lower-end criminal justice responses to crime, and in the increasing use of the term "restorative" for a widening host of practices and interventions. RJ has also faced problems related to its increasing institutionalization, resulting in divergence from earlier aims and goals. In this article, we set forth what we see as the four biggest challenges facing the future of RJ, namely problems related to definition, institutionalization, displacement, and relevance of RJ practices. We follow with discussion of possible future directions of RJ.
William Wood, Masahiro Suzuki

Patterns of complementary and alternative medicine use in children with common neurological conditions.


Global advances in health and medicine, Vol. 3, No. 1. (January 2014), pp. 18-24

Recent literature suggests that one in nine children in the United States uses some type of complementary and alternative medicine (CAM). Children with challenging neurological conditions such as headache, migraine, and seizures may seek CAM in their attempts at self-care. Our objective was to describe CAM use in children with these conditions. We compared use of CAM among children aged 3 to 17 years with and without common neurological conditions (headaches, migraines, seizures) where CAM might plausibly play a role in their self-management using the 2007 National Health Interview Survey (NHIS) data. Children with common neurological conditions reported significantly more CAM use compared to the children without these conditions (24.0% vs 12.6%, P<.0001). Compared to other pediatric CAM users, children with neurological conditions report similarly high use of biological therapies and significantly higher use of mind-body techniques (38.6% vs 20.5%, P<.007). Of the mind-body techniques, deep breathing (32.5%), meditation (15.1%), and progressive relaxation (10.1%) were used most frequently. About one in four children with common neurological conditions use CAM. The nature of CAM use in this population, as well as its risks and benefits in neurological disease, deserve further investigation.
Lauren Treat, Juliette Liesinger, Jeanette Ziegenfuss, Katherine Humeniuk, Kavita Prasad, Jon Tilburt

The Dark Side of Long-Term Relationships in Marketing Services


Journal of Marketing Research, Vol. 36, No. 1. (1999), doi:10.2307/3151921

In their study of marketing services relationships, Moorman, Zaltman, and Deshpandé (1992) are unable to support a hypothesized link between relational factors (such as clients' trust in their service providers) and clients' use of marketing services. This finding runs counter to relationship marketing theory. To explain their result, Moorman, Zaltman, and Deshpandé (1992) suggest that, as a relationship becomes more long-term, it becomes prone to negative influences that dampen the positive impact of relational factors. This study replicates and extends Moorman, Zaltman, and Deshpandé's (1992) work by examining relationships between advertising agencies and their clients. The results replicate findings on seven of ten hypotheses proposed in the original article. The authors also extend the original study by supporting the general hypothesis that long-term relationships have a negative impact on service use, which dampens the impact of trust. The results shed light on the mediating role that certain "dark side" constructs play in marketing services relationships.
Kent Grayson, Tim Ambler

Yoga for epilepsy.


The Cochrane database of systematic reviews, No. 5. (02 May 2015)This is an updated version of the original Cochrane review published in The Cochrane Library, Issue 1, 2002.Yoga may induce relaxation and stress reduction, and influence the electroencephalogram and the autonomic nervous system, thereby controlling seizures. Yoga would be an attractive therapeutic option for epilepsy if proved effective. To assess whether people with epilepsy treated with yoga:(a) have a greater probability of becoming seizure free;(b) have a significant reduction in the frequency or duration of seizures, or both; and(c) have a better quality of life. We searched the Cochrane Epilepsy Group Specialized Register (26 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 26 March 2015), MEDLINE (Ovid, 1946 to 26 March 2015), SCOPUS (1823 to 9 January 2014), (26 March 2015), the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP (26 March 2015), and also registries of the Yoga Biomedical Trust and the Research Council for Complementary Medicine. In addition, we searched the references of all the identified studies. No language restrictions were imposed. The following study designs were eligible for inclusion: randomised controlled trials (RCT) of treatment of epilepsy with yoga. Eligible participants were adults with uncontrolled epilepsy comparing yoga with no treatment or different behavioural treatments. Three review authors independently selected trials for inclusion and extracted data. The following outcomes were assessed: (a) percentage of people rendered seizure free; (b) seizure frequency and duration; (c) quality of life. Analyses were on an intention-to-treat basis. Odds ratio (OR) with 95% confidence intervals (95% Cl) were estimated for the outcomes. Two unblinded trials recruited a total of 50 people (18 treated with yoga and 32 to control interventions). Antiepileptic drugs were continued in all the participants. Baseline phase lasted 3 months in both studies and treatment phase from 5 weeks to 6 months in the two trials. Randomisation was by roll of a die in one study and using a computerised randomisation table in the other one but neither study provided details of concealment of allocation and were rated as unclear risk of bias. Overall, the two studies were rated as low risk of bias (all participants were included in the analysis; all expected and pre-expected outcomes were reported; no other sources of bias). The overall OR with 95% confidence interval (CI) was: (i) seizure free for six months - for yoga versus sham yoga ORs of 14.54 (95% CI 0.67 to 316.69) and for yoga versus no treatment group 17.31 (95% CI 0.80 to 373.45); for Acceptance and [...]

Marijuana: a time-honored but untested treatment for epilepsy.


The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, Vol. 42, No. 2. (March 2015), pp. 88-91

The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures. However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done. Proper dosage and means of administration remain unknown. Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy. This is a review of this topic from a Canadian perspective.
Richard McLachlan