bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms
Authors: Balasco Nicole , Esposito Luciana , Simone Alfonso De , Vitagliano Luigi 
Published: May 2013

AbstractIt has been recently discovered that the connection of secondary structure elements (ββ‐unit, βα‐ and αβ‐units) in proteins follows quite stringent principles regarding the chirality and the orientation of the structural units (Koga et al., Nature 2012;491:222–227). By exploiting these rules, a number of protein scaffolds endowed with a remarkable thermal stability have been designed (Koga et al., Nature 2012;491:222–227). By using structural databases of proteins isolated from either mesophilic or thermophilic organisms, we here investigate the influence of supersecondary associations on the thermal stability of natural proteins. Our results suggest that β‐hairpins of proteins from thermophilic organisms are very frequently characterized by shortenings of the loops. Interestingly, this shortening leads to states that display a very strong preference for the most common connectivity of the strands observed in native protein hairpins. The abundance of selective states in these proteins suggests that they may achieve a high stability by adopting a strategy aimed to reduce the possible conformations of the unfolded ensemble. In this scenario, our data indicate that the shortening is effective if it increases the adherence to these rules. We also show that this mechanism may operate in the stabilization of well‐known protein folds (thioredoxin and RNase A). These findings suggest that future investigations aimed at defining mechanism of protein stabilization should also consider these effects.
Functional studies of N‐terminally modified CYP2J2 epoxygenase in model lipid bilayers
Authors: McDougle Daniel R. , Palaria Amrita , Magnetta Eric , Meling Daryl D. , Das Aditi 
Published: May 2013

AbstractCYP2J2 epoxygenase is a membrane bound cytochrome P450 that converts omega‐3 and omega‐6 fatty acids into physiologically active epoxides. In this work, we present a comprehensive comparison of the effects of N‐terminal modifications on the properties of CYP2J2 with respect to the activity of the protein in model lipid bilayers using Nanodiscs. We demonstrate that the complete truncation of the N‐terminus changes the association of this protein with the E.coli membrane but does not disrupt incorporation in the lipid bilayers of Nanodiscs. Notably, the introduction of silent mutations at the N‐terminus was used to express full length CYP2J2 in E. coli while maintaining wild‐type functionality. We further show that lipid bilayers are essential for the productive use of NADPH for ebastine hydroxylation by CYP2J2. Taken together, it was determined that the presence of the N‐terminus is not as critical as the presence of a membrane environment for efficient electron transfer from cytochrome P450 reductase to CYP2J2 for ebastine hydroxylation in Nanodiscs. This suggests that adopting the native‐like conformation of CYP2J2 and cytochrome P450 reductase in lipid bilayers is essential for effective use of reducing equivalents from NADPH for ebastine hydroxylation.
Effects of the Fc‐III tag on activity and stability of green fluorescent protein and human muscle creatine kinase
Authors: Feng Shan , Gong Yiyi , Adilijiang Gulishana , Deng Haiteng 
Published: May 2013

AbstractThe Fc‐III tag is a newly developed fusion tag that can be applied to protein purification and detection. In the present work, we use the Fc‐III‐tagged green fluorescent protein (GFP) and human muscle creatine kinase (CK) as model systems to investigate effects of the Fc‐III tag on activities and stabilities of the expressed multicysteine‐containing proteins. Our results show the Fc‐III tag has no adverse effects on the fluorescence of GFP and reduces the occurrence of GFP misfolding due to incorrect Cys oxidation compared with the His‐tagged protein. The activity and stability of the Fc‐III‐tagged CK is slightly lower than that of the tag‐free CK, but is higher than that of the His‐tagged CK as determined by the ratio of the oxidized versus reduced CK. A major portion of His‐tagged CK is in its oxidized form, while that of the Fc‐III‐tagged CK is in its reduced form. A folding model of CK with different tags was proposed, which may provide insights into the effect of the Fc‐III tag on the conformations of disulfide‐bridged proteins.
Understanding large text corpora via sparse machine learning
Authors: El Ghaoui Laurent , Pham Vu , Li Guan‐Cheng , Duong Viet‐An , Srivastava Ashok , Bhaduri Kanishka 
Published: May 2013

AbstractSparse machine learning has recently emerged as powerful tool to obtain models of high‐dimensional data with high degree of interpretability, at low computational cost. The approach has been successfully used in many areas, such as signal and image processing. This article posits that these methods can be extremely useful in the analysis of large collections of text documents, without requiring user expertise in machine learning. Our approach relies on three main ingredients: (i) multidocument text summarization; (ii) comparative summarization of two corpora, both using sparse regression or classification; (iii) sparse principal components and sparse graphical models for unsupervised analysis and visualization of large text corpora. We validate our methods using a corpus of Aviation Safety Reporting System (ASRS) reports and demonstrate that the methods can reveal causal and contributing factors in runway incursions. Furthermore, we show that the methods automatically discover four main tasks that pilots perform during flight, which can aid in further understanding the causal and contributing factors to runway incursions and other drivers for aviation safety incidents. We also provide a comparative study involving other commonly used datasets, and report on the competitiveness of sparse machine learning compared to state‐of‐the‐art methods such as latent Dirichlet allocation (LDA). © 2013 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 6: 221–242, 2013
Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC-, hiPSC-, and Non-Human Primate iPSC-Derived Dopaminergic Neurons
Authors: Sundberg Maria , Bogetofte Helle , Lawson Tristan , Jansson Johan , Smith Gaynor , Astradsson Arnar , Moore Michele , Osborn Teresia , Cooper Oliver , Spealman Roger , Hallett Penelope , Isacson Ole 
Published: May 2013

Abstract
The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM+/CD29low sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations. NCAM+/CD29low DA neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM+/CD29low DA neurons were able to restore motor function of 6-hydroxydopamine (6-OHDA) lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future.
Polycomb Determines Responses to Smad2/3 Signaling in Embryonic Stem Cell Differentiation and in Reprogramming
Authors: Dahle Øyvind , Kuehn Michael R. 
Published: May 2013

Abstract
Integration of extrinsic signals, epigenetic regulators, and intrinsic transcription factors establishes pluripotent stem cell identity. Interplay between these components also underlies the capacity of stem cells to undergo differentiation, and of differentiated cells to re-establish the pluripotent state in direct reprogramming. Polycomb repressive complexes are epigenetic regulators that play key roles in stem cell identity and in differentiated cell fates. Smad2 and Smad3 (Smad2/3), the intracellular mediators of the Nodal/Activin/transforming growth factor (TGF) β cell-cell signaling pathway also are implicated in stem cell pluripotency and in differentiation. Here, we show that Polycomb imposes responses to Smad2/3-mediated signaling to selectively regulate expression of the master pluripotency factor Oct4 during initiation of differentiation, but not in the self-renewing pluripotent ground state. During reprogramming back to the ground state, we find that the enhancement of reprogramming efficiency stemming from blocking Nodal/Activin/TGFβ signaling also depends on Polycomb. These context-dependent responses to Smad2/3 imposed by Polycomb action provide a mechanism for selective gene regulation that can reconcile the apparently conflicting roles of this signaling pathway in pluripotency, differentiation, and reprogramming.
Evolving graph‐based chromosome by means of variable size genetic network programming with binomial distribution
Authors: Li Bing , Li Xianneng , Mabu Shingo , Hirasawa Kotaro 
Published: May 2013

AbstractGenetic network programming (GNP) is a graph‐based evolutionary algorithm with fixed size, which has been proven to solve complicated problems efficiently and effectively. In this paper, variable size genetic network programming (GNPvs) with binomial distribution has been proposed, which will change the size of the individuals and obtain their optimal size during evolution. The proposed method will select the number of nodes to move from one parent GNP to another parent GNP during crossover to implement the new feature of GNP. The probability of selecting the number of nodes to move satisfies a binomial distribution. The proposed method can keep the effectiveness of crossover, improve the performance of GNP, and find the optimal size of the individuals. The well‐known testbed Tileworld is used to show the numerical results in the simulations. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
In silico applications of bioisosterism in contemporary medicinal chemistry practice
Authors: Papadatos George , Brown Nathan 
Published: May 2013

AbstractBioisosterism is a key concept in medicinal chemistry, as it allows medicinal chemists to interchange structural fragments without significant perturbation in biological activity. Not surprisingly, given the vast amount of bioactivity data and chemoinformatics resources now available, there has been a significant surge in the number of computational approaches available to mine and identify bioisosteric replacements for fragments of bioactive compounds. Such methods have certainly provided medicinal chemists with a diverse arsenal of in‐house, commercial, and academic tools and interfaces to aid in the optimization across a number of end points such as bioactivity; selectivity; and absorption, distribution, metabolism, excretion, and toxicity properties for effective and efficient drug design. These in silico bioisosteric replacement mining approaches can generally be divided into two categories, namely ligand based and structure based. The approaches of the former category use information that is derived from ligands, whereas the latter category requires knowledge of the biological target, as well as specific knowledge of the interactions between ligand and target in the binding pocket. Ligand‐based methodologies are also typically divided into similarity‐based and database mining (or knowledge‐based) approaches. In general, the former provide an assessment of putative bioisosteric fragments and substructures, in terms of molecular topology and descriptors, whereas the latter extract structural transformations from large chemical repositories and associate them with the induced change in biological or any other property of interest. Following systematic retrospective studies, a large number of nonclassical bioisosteric equivalents have been reported in the literature.This article is categorized under:

Computer and Information Science > Chemoinformatics
Synthesis and Molecular Structure of the New Green Emitting Complex [Ir2(μ2‐oxamidato‐N,N′,O,O′)(2‐(p‐tolyl)pyridinato)4]
Authors: Graf Marion , Czerwieniec Rafał , Sünkel Karlheinz 
Published: May 2013

AbstractThe reaction of the complex [{Ir(μ‐Cl)(ptpy)2}2] (1) with oxamide in methanol in the presence of sodium methylate as the base was investigated. During the reaction the new complex [Ir2(μ2‐oxamidato‐N,N′,O,O′)(ptpy)4] (2), ptpy = 2‐(p‐tolyl)pyridinato was obtained. The molecular structure of compound 2 was determined by an X‐ray diffraction study. 2 crystallized from dichloromethane/methanol as a dihydrate in the orthorhombic space group Pbcm. This new compound displays intense green phosphorescence, with φPL = 60 %, stemming from the lowest triplet state of the 3MLCT/LC character.
Perinatal undernutrition stimulates seeking food reward
Authors: da Silva Amanda Alves Marcelino , Borba Tássia Karin Ferreira , de Almeida Lira Lívia , Cavalcante Taisy Cinthia Ferro , de Freitas Manuela Figueiroa Lyra , Leandro Carol Gois , do Nascimento Elizabeth , de Souza Sandra Lopes 
Published: May 2013

AbstractExperiments in animals have revealed that perinatal nutritional restriction, which manifests in adulthood, increases food intake and preference for palatable foods. Considering this, we aimed to evaluate the effects of perinatal malnutrition on hedonic control of feeding behavior. In this study, we divided Wistar rats into two groups according to the diet provided to their mothers during pregnancy and lactation: the control group (diet with 17% casein) and low‐protein group (diet with 8% casein). We assessed the animals’ motivational behavior in adulthood by giving them a stimulus of food reward. We also assessed their neuronal activation triggered by the stimulus of palatable food using FOS protein labeling of neurons activated in the caudate putamen, paraventricular, dorsomedial, ventromedial, and lateral hypothalamic nuclei and amygdala. Evaluation of body weight in malnourished animals showed reduction from the 6th day of life until adulthood. Analysis of feeding behavior revealed that these animals were more motivated by food reward, but they had delays during learning of the task. This finding correlated with the number of c‐FOS‐immunoreactive neurons, which indicated that malnourished animals had an increase in the number of neurons activated in response to the palatable diet, especially in the amygdala and caudate putamen. The study therefore confirmed our hypothesis that early nutritional insults promote changes in encephalic control mechanisms, especially those related to food intake and search for reward.
God, the devil, and the details: Fleshing out the predictive processing framework
Authors: Rasmussen Daniel , Eliasmith Chris 
Published: May 2013

AbstractThe predictive processing framework lacks many of the architectural and implementational details needed to fully investigate or evaluate the ideas it presents. One way to begin to fill in these details is by turning to standard control-theoretic descriptions of these types of systems (e.g., Kalman filters), and by building complex, unified computational models in biologically realistic neural simulations.
God is in the details— Mies van der RoheThe devil is in the details— Anonymous
Distinguishing theory from implementation in predictive coding accounts of brain function
Authors: Spratling Michael W. 
Published: May 2013

AbstractIt is often helpful to distinguish between a theory (Marr's computational level) and a specific implementation of that theory (Marr's physical level). However, in the target article, a single implementation of predictive coding is presented as if this were the theory of predictive coding itself. Other implementations of predictive coding have been formulated which can explain additional neurobiological phenomena.
Schizophrenia-related phenomena that challenge prediction error as the basis of cognitive functioning
Authors: Silverstein Steven M. 
Published: May 2013

AbstractThere are aspects of schizophrenia that pose challenges for Clark's model. These include: (1) evidence for excitatory activity underlying self-organizing neural ensembles that support coordinating functions, and their impairment in schizophrenia; (2) evidence regarding hallucinations that suggest they are not due to excessive prediction error; and (3) the critical role of emotional factors as setting conditions for delusion formation.
Applications of predictive control in neuroscience
Authors: Bridgeman Bruce 
Published: May 2013

AbstractThe sensory cortex has been interpreted as coding information rather than stimulus properties since Sokolov in 1960 showed increased response to an unexpected stimulus decrement. The motor cortex is also organized around expectation, coding the goal of an act rather than a set of muscle movements. Expectation drives not only immediate responses but also the very structure of the cortex, as demonstrated by development of receptive fields that mirror the structure of the visual world.
Predictions in the light of your own action repertoire as a general computational principle
Authors: König Peter , Wilming Niklas , Kaspar Kai , Nagel Saskia K. , Onat Selim 
Published: May 2013

AbstractWe argue that brains generate predictions only within the constraints of the action repertoire. This makes the computational complexity tractable and fosters a step-by-step parallel development of sensory and motor systems. Hence, it is more of a benefit than a literal constraint and may serve as a universal normative principle to understand sensorimotor coupling and interactions with the world.
Whenever next: Hierarchical timing of perception and action
Authors: Holm Linus , Madison Guy 
Published: May 2013

AbstractThe target article focuses on the predictive coding of “what” and “where” something happened and the “where” and “what” response to make. We extend that scope by addressing the “when” aspect of perception and action. Successful interaction with the environment requires predictions of everything from millisecond-accurate motor timing to far future events. The hierarchical framework seems appropriate for timing.
The brain is not an isolated “black box,” nor is its goal to become one
Authors: Froese Tom , Ikegami Takashi 
Published: May 2013

AbstractIn important ways, Clark's “hierarchical prediction machine” (HPM) approach parallels the research agenda we have been pursuing. Nevertheless, we remain unconvinced that the HPM offers the best clue yet to the shape of a unified science of mind and action. The apparent convergence of research interests is offset by a profound divergence of theoretical starting points and ideal goals.
Backwards is the way forward: Feedback in the cortical hierarchy predicts the expected future
Authors: Muckli Lars , Petro Lucy S. , Smith Fraser W. 
Published: May 2013

AbstractClark offers a powerful description of the brain as a prediction machine, which offers progress on two distinct levels. First, on an abstract conceptual level, it provides a unifying framework for perception, action, and cognition (including subdivisions such as attention, expectation, and imagination). Second, hierarchical prediction offers progress on a concrete descriptive level for testing and constraining conceptual elements and mechanisms of predictive coding models (estimation of predictions, prediction errors, and internal models).
Affect and non-uniform characteristics of predictive processing in musical behaviour
Authors: Schaefer Rebecca S. , Overy Katie , Nelson Peter 
Published: May 2013

AbstractThe important roles of prediction and prior experience are well established in music research and fit well with Clark's concept of unified perception, cognition, and action arising from hierarchical, bidirectional predictive processing. However, in order to fully account for human musical intelligence, Clark needs to further consider the powerful and variable role of affect in relation to prediction error.
What else can brains do?
Authors: Sloman Aaron 
Published: May 2013

AbstractThe approach Clark labels “action-oriented predictive processing” treats all cognition as part of a system of on-line control. This ignores other important aspects of animal, human, and robot intelligence. He contrasts it with an alleged “mainstream” approach that also ignores the depth and variety of AI/Robotic research. I don't think the theory presented is worth taking seriously as a complete model, even if there is much that it explains.
Maternal and perinatal factors associated with subsequent meningococcal, Haemophilus or enteroviral meningitis in children: database study
Authors: GOLDACRE M. J. , WOTTON C. J. , MAISONNEUVE J. J. 
Published: May 2013

SUMMARYWe used a database of 248 659 births, with follow-up to subsequent disease, in the Oxford record linkage archive (1979–1999) to study the influence of family, maternal, and perinatal factors on subsequent hospital admission for meningococcal, Haemophilus, and enteroviral meningitis in the children. In this summary, we report key findings that were significant in multivariate analysis. Meningococcal meningitis was significantly associated with maternal smoking [odds ratio (OR) 2·1, 95% confidence interval (CI) 1·2–3·7]. Haemophilus meningitis was associated with having older siblings (e.g. second child compared to first-born, OR 3·3, 95% CI 2·0–5·6). Enteroviral meningitis was associated with low birth weight (OR 2·2, 95% CI 1·3–3·6) and male sex (OR 1·7, 95% CI 1·2–2·3). The mothers of six of the 312 children with enteroviral meningitis had previously had enteroviral meningitis themselves. We concluded that several maternal characteristics influence the risk of these types of meningitis.