bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of Neural Activity in the Posterior Insula Encodes the Passage of Time
Authors: Wittmann Marc , Simmons Alan , Aron Jennifer , Paulus Martin 
Published: July 2019

AbstractThe experience of time, i.e. the estimation of duration, is fundamental for perception and behavior and, therefore, essential for the survival of the individual organism. Over the last decades, neuroimaging, neurophysiological and clinical neuropsychological studies have pointed to many different brain areas involved in the processing of time. However, the core neural substrates and the processes accounting for the encoding of duration, which could form a timekeeping mechanism (essentially, a neural clock), are still unknown. Here we present evidence of neurophysiological activity in circumscribed areas of the human brain that is involved in the encoding of duration. Time-activity curves of neural activation derived from event-related functional magnetic resonance imaging (fMRI) during a time estimation task show that bilateral posterior insula as well as superior temporal and inferior parietal cortices build up activation when individuals are presented with 9 or 18 seconds tone intervals. Since the build up of neuronal activation peaks at the end of the interval, it appears that this accumulator-type activity encodes duration. Because of the close connection between posterior insula and ascending internal body signals, the accumulation of physiological changes in body states might constitute our experience of time. These results could be the starting point for a neural model of human time perception in the multiple-seconds range in which specific brain regions accumulate brain activity for the representation of duration.
Introduction of Transmembrane Inner Ear (tmie) Gene Can Recover the Hearing Impairment and Abnormal Behavior in the Circling Mouse
Authors: Shin Mi Jung , Lee Jeong-Han , Yu Dong Hoon , Kim Bong Soo , Kim Hei Jung , Kim Sung Hyun , Kim Myoung Ok , Park Channy , Hyun Byung-Hwa , Lee Sanggyu , Suh Jun-Gyo , So Hong-Seob , Park Raekil , Ryoo Zae Young 
Published: July 2019

AbstractThe spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing the causative gene, transmembrane inner ear (tmie), for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir -tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir -tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse.
A coordinated phosphorylation cascade initiated by MSK1 directs RAR alpha recruitment to target gene promoters
Authors: Bruck Nathalie , Vitoux Dominique , Ferry Christine , Duong Vanessa , Bauer Annie , de The Hughes , Rochette-Egly Cecile 
Published: July 2019

AbstractThe nuclear retinoic acid (RA) receptor alpha (RAR&x03B1;) is a transcriptional transregulator that controls the expression of specific gene subsets through binding at response elements and dynamic interactions with coregulators, which are coordinated by the ligand. Here, we highlighted a novel paradigm in which the transcription of RAR&x03B1;-target genes is controlled by phosphorylation cascades initiated by the rapid RA activation of the p38MAPK/MSK1 pathway. We demonstrate that MSK1 phosphorylates RAR&x03B1; at S369 located in the Ligand Binding Domain, allowing the binding of TFIIH and thereby phosphorylation of the N-terminal domain at S77 by cdk7/cyclin H. MSK1 also phosphorylates Histone H3 at S10. Finally, the phosphorylation cascade initiated by MSK1 is required for the recruitment of RAR&x03B1;/TFIIH complexes to response elements and subsequently for RAR&x03B1; target genes activation. Cancer cells characterized by a deregulated p38MAPK/MSK1 pathway, do not respond to RA, outlining the essential contribution of the RA-triggered phosphorylation cascade in RA signaling.
A Physiological Role for Amyloid Beta Protein: Enhancement of Learning and Memory
Authors: Morley John , Farr Susan , Banks William , Johnson Steven , Yamada Kelvin , Xu Lin 
Published: July 2019

AbstractAmyloid beta protein (A[beta]) is well recognized as having a significant role in the pathogenesis of Alzheimer's disease (AD). The reason for the presence of A[beta] and its physiological role in non-disease states is not clear. In these studies, low doses of A[beta] enhanced memory retention in two memory tasks and enhanced acetylcholine production in the hippocampus in vivo. We then tested whether endogenous A[beta] has a role in learning and memory in young, cognitively intact mice by blocking endogenous A[beta] in healthy 2-month-old CD-1 mice. Blocking A[beta] with antibody to A[beta] or DFFVG (which blocks A[beta] binding) or decreasing A[beta] expression with an antisense directed at the A[beta] precursor APP all resulted in impaired learning in T-maze foot-shock avoidance. Finally, A[beta]1-42 facilitated induction and maintenance of long term potentiation in hippocampal slices, whereas antibodies to A[beta] inhibited hippocampal LTP. These results indicate that in normal healthy young animals the presence of A[beta] is important for learning and memory.
A Targeted Therapeutic Rescues Botulinum Toxin-A Poisoned Neurons
Authors: Ray Prabhati , Singh Bal Ram , Ray Radharaman , Zhang Peng , Li Dan , Keller James , Adler Michael 
Published: July 2019

AbstractBotulinum neurotoxin (BoNT), a Category A biothreat agent, is the most potent poison known to mankind. Currently no antidote is available to rescue poisoned synapses. BoNT acts specifically by blocking neurotransmission primarily at peripheral nerve-muscle junctions causing severe flaccid muscle paralysis, which is fatal if proper medical care is not provided. The neurotoxin acts by specifically entering the presynaptic nerve endings where it interferes with the biochemical machinery involved in the process of neurotransmitter release, i.e., neuroexocytosis. Most serotypes of BoNT are known to remain active for weeks to months after entering the nerves, but BoNT/A is the most potent and long lasting in causing muscle paralysis. An effective medical countermeasure strategy requires developing a drug that could rescue poisoned neuromuscular synapses, and would include its efficient delivery specifically to presynaptic nerve terminals. Here we report rescuing of botulinum poisoned nerve cells by Mastoparan-7 (Mas-7), a peptide constituent of bee venom, that was delivered through a drug delivery vehicle (DDV) constructed from the non-toxic fragment of botulinum neurotoxin itself. We found that Mas-7 that was delivered into BoNT/A intoxicated cultured mouse spinal cord cells restored over 40% of stimulated neurotransmitter release. The rescue of the cell poisoning did not occur from inhibition of the endopeptidase activity of BoNT/A against its well known substrate, SNAP-25 that is mechanistically involved in the exocytosis process. Rather, Mas-7 induced a physiological host response apparently unrelated to SNAP-25, but linked to the phospholipase signal transduction pathway. In addition to providing the first effective antidote against botulism, our results open new avenues to study the mechanism of exocytosis, and also to examine an alternative cellular mechanism of botulinum neurotoxin action. An effective BoNT-based DDV can also be utilized for drug delivery against many neuronal and neuromuscular disorders.
Dimension-based attention in the recognition of facial identity and facial expression
Authors: Lin Zhicheng 
Published: July 2019

AbstractAlthough the human visual system is constantly flooded with sensory information, the brain is remarkable in inferring structures from the massive inputs and selectively attending to behaviorally relevant information. However, how the two processes interact remains largely unknown. Can top-down attention efficiently select the task-relevant dimension (e.g. gender) during face recognition to override interference in the task-irrelevant dimension (e.g. expression)? To address this issue, participants were asked to classify real face images according to gender or expression, which were preceded by other faces (masked priming task) or words (face-word Stroop task). Results show that face classification was 1) affected by the task-relevant but not the task-irrelevant dimension of the preceding faces, and 2) modulated by words depicting the task-relevant but not the task-irrelevant dimension of the face. These results suggest that high level dimensions such as facial expression and facial identity can serve as units of attentional selection, possibly due to the late binding of the two dimensions.
Optimization of the Ugi reaction using parallel synthesis and automated liquid handling
Authors: Bradley Jean-Claude , Mirza Khalid , Owens Kevin , Osborne Tom , Williams Antony 
Published: July 2019

AbstractThe Ugi reaction has proved to be a convenient way to quickly create diverse libraries of compounds. It involves the reaction of an amine, an aldehyde, a carboxylic acid and an isonitrile typically in methanol at room temperature. The Ugi reaction has often been used as a tool in the synthesis of pharmacologically active molecules. It has been observed that Ugi products sometimes precipitate in pure form from the reaction mixture. This is a very fortunate outcome since the reaction can then be easily scaled up without requiring costly purification procedures such as chromatography. It would be most beneficial to optimize the Ugi product yield as obtained directly from filtering the reaction mixture without further treatment. To this end we utilized a 48-slot Mettler-Toledo MiniBlock equipped with filtration tubes. A Mettler-Toledo MiniMapper automated liquid handler was used to deliver the reagents and solvent. The parameters of interest were the concentration, the solvent composition and the excess of some of the reagents. This work was performed under Open Notebook Science conditions and links to relevant laboratory notebook pages are provided.
Proposing a life cycle land use impact calculation methodology
Authors: Achten Wouter , Vandenbempt Pieter , Lemaître Patrick , Mathijs Erik , Muys Bart 
Published: July 2019

AbstractThe Life Cycle Assessment (LCA) community is yet to come to a consensus on a methodology to incorporate land use in LCA. Earlier our research group presented a methodology based on the ecosystem exergy concept. The ecosystem exergy concept suggests that ecosystems develop towards more effective degradation of energy fluxes passing through the system. The concept is argued to be derivable from two axioms: the principles of (i) maximum exergy storage and the (ii) maximum exergy dissipation. In this paper we present a methodology to assess impacts of human induced land use occupation, in which we make a difference between functional and structural land use impacts. The methodology follows a dynamic multi-indicator approach looking at mid-point impacts on soil fertility, soil structure, biomass production, vegetation structure, on-site water balance and biodiversity. The impact scores are calculated as a relative difference with a reference system. We propose to calculate the impact by calculating the land quality change between the former and the actual land use relative to the quality of the potential natural vegetation. Impact scores are then aggregated, as endpoint impacts, in (i) structural land use impact (exergy storage capacity) and (ii) functional land use impact (exergy dissipation capacity). For aggregation of the relative mid-point impact scores no characterization factor is used. In order to fit this impact calculation in the LCA framework the end-point impact scores are multiplied by a LCA component, a component that enables us to report the impact per functional unit.
Working memory: Is it the new IQ?
Authors: Alloway Tracy Packiam , Alloway Ross 
Published: July 2019

AbstractWorking memory, our ability to process and remember information, is linked to a range of cognitive activities from reasoning tasks to verbal comprehension. There is also extensive evidence of the relationship between working memory and learning outcomes. However, some researchers suggest that working memory is simply a proxy for IQ and does not make a unique contribution to learning outcomes. Here we show that children's working memory skills at 5 years of age was the best predictor of reading, spelling, and math outcomes six years later. IQ, in contrast, accounted for a smaller portion of unique variance to reading and math skills, and was not a significant predictor of spelling performance. Our results demonstrate that working memory is not a proxy for IQ, but rather represents a dissociable cognitive skill with unique links to learning outcomes. Critically, we find that working memory at the start of formal education is a more powerful predictor of subsequent academic success than IQ. This result has important implications for education, particularly with respect to developing intervention and training. It appears that we should target our efforts in developing working memory skills in order to see gains in learning.
Identification of 22 novel mutations in patients with Glanzmann's thrombasthenia
Authors: Kannan Meganathan , Ahmad Firdos , Yadav Birendra , Ethayathulla Abdul , Kumar Rajive , Choudhry Ved , Saxena Renu 
Published: July 2019

AbstractGlanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect that characterized by reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists. GT is characterized by normal platelet count, prolonged bleeding time, and abnormal clot retraction. The defect is caused by mutations in the genes encoding GPIIb or GPIIIa that result in qualitative or quantitative abnormalities of the platelet membrane GPIIb/IIIa. GT occurs in high frequency in certain ethnic populations with an increased incidence of consanguinity, such as Indians, Iranians, Iraqi Jews, Palastinian and Jordanian Arabs and French gypsies. Forty-five unrelated patients of GT were enrolled in the study to identify the causative molecular defects and also to correlate the genotype with the phenotype. Molecular modeling was performed for the novel missense mutations. The current study identifies 22 novel mutations in these patients. Missense mutations were identified as the defects responsible for most of the GT patients (59%). Even though missense was common, the study concludes that the genetic defect is heterogeneous in nature and difficult to design a DNA marker for carrier detection in GT.
Estimating body Mass and Nutritional Status from Subadult Hominin Skeletons
Authors: Robbins Gwendolyn 
Published: July 2019

AbstractHominin body size and shape are key components to reconstructing phylogeny, life history, adaptation, and behavior in ancestral populations^1^. For adults, geometric properties of the femoral midshaft cross-section are used to infer locomotor behavior^2-5^, subsistence practices^6-7^, and functional adaptations^8-10^. Recently research has focused on patterns of compact bone ontogeny, particularly in regard to changes in bone strength with the acquisition of bipedal locomotion^11-13^ and examining population differences in ontogenetic trajectories for subadult humans^14-16^ and Neandertals^16^. Because femoral midshaft geometry is primarily shaped by biomechanical strains-weight bearing, locomotion, and muscle action-ontogenetic research requires estimates of body mass from the skeleton. Currently we use the width of the distal end of the femur to estimate subadult body mass but articular ends are constrained by pressures for joint congruence. Here I demonstrate the strong and consistent scaling relationship between body mass and femoral torsional strength (J) derived from measurement of midshaft cross-section geometry. Bone ends are most significantly affected by locomotor strain during the second year of life, during the initial acquisition of obligate bipedalism, after that time they are increasingly constrained by joint congruence. Results of a comparison of body mass for body size in prehistoric populations support the hypothesis that the midshaft is also a more sensitive indicator of population differences in body mass and activity levels during ontogeny. The femoral midshaft can be used to detect starvation and growth disruption in past populations because there is a mechano-biological interaction effect whereby disruptions in nutritional, metabolic and hormonal status lead to low body mass and activity levels^1, 11-13, 17-22^.
Tumor induction by disruption of the Dnmt1, PCNA and UHRF1 interactions.
Authors: Hervouet Eric , Lalier Lisenn , Debien Emilie , Cheray Mathilde , Geairon Audrey , Rogniaux Helene , Vallette Francois , Cartron Pierre-Francois 
Published: July 2019

AbstractThe low level of DNA methylation in tumors compared to the level of DNA methylation in their normal-tissue counterparts or global DNA hypomethylation was one of the first epigenetic alterations to be found in human cancer^1,2^. While the contribution of genome hypomethylation in cancer development and progression is explained by several mechanisms: chromosomal instability, loss of imprinting, and reactivation of transposable elements^3, 4^, the molecular causes of genome hypomethylation remain unclear. Indeed, despite the central roles of the DNA methyltransferases (Dnmts) in the establishment and maintenance of the DNA methylation, no clear consensus appears between the reduction of the Dnmts expression and the genome hypomethylation in human cancers^5^. Nevertheless, the cancer-associated genome hypomethylation could be explained by the disruption of interactions existing between Dnmts and the DNA replication and DNA repair proteins because these interactions play a crucial role in the DNA methylation in mammalian cells^6-8^. We here demonstrate that the disruption of the Dnmt1/PCNA and Dnmt1/UHRF1 interactions induce the genome hypomethylation and act as oncogenic factors promoting the tumorigenesis. We also identify the Akt- and/or PKC-mediated phosphorylations of Dnmt1 as both initiators of these disruptions and as a hallmark conferring poor prognosis in glioma patients.
Global warming affected some morphological characters of Pistachio trees (Pistacia vera L.)
Authors: Javanshah Amanollah 
Published: July 2019

AbstractPistachio is one of the main horticulture crops in Iran where have the first cultivation and exportation position in the world. Climate change has already affected species distribution shifts in many parts of the world and more impacts are expected for the future, yet few studies have aimed for a general understanding of the regional basis for species vulnerability. In this research meteorology data of four months (December, January, February and March) from 1991 to 2008 and Phenology data of six pistachio cultivars that ranked in 3 groups: early flowering (Kalehghoochi and Ahmadaghaei), mid flowering (Momtaz and Amiri) and late flowering (Akbari and Shahpasand) during summer of 1997, 2001-5, and 2007 were studied in Kerman province. The evaluated factors included leaf area, normal and abnormal leaves. The results showed the mean of temperature on March has significant increasing during 1991 to 2008 and fluctuations between years increased after 1999 in December, January and February. Phenological characters including leaf area and number of normal and abnormal leaves were different each year that abnormality leaves in early and late flowering cultivars had negative correlation with mean temperature of December and mid flowering cultivars had positive correlation with mean temperature of February. The level of leaf area changing in Ahamadaghaei cultivar was less than other cultivars but kallehghoochi and Akbari had the highest range which can probably be a good marker for determining the effects of temperature changes in winter on production level.
Polar Mapper: a computational tool for integrated visualization of protein interaction networks and mRNA expression data
Authors: Gonçalves Joana P. , Grãos Mário , Valente Andre 
Published: July 2019

AbstractPolar Mapper is a computational application for exposing the architecture of protein interaction networks. It facilitates the system-level analysis of mRNA expression data in the context of the underlying protein interaction network. Preliminary analysis of a human protein interaction network and comparison of yeast oxidative stress and heat shock gene expression responses are addressed as case studies.
Down-regulation of Survivin enhances sensitivity to BPR0L075 in human cancer cells via caspase-independent mechanisms
Authors: Cheung Chun Hei Antonio , Kuo Ching-Chuan , Chang Chi-Yen , Coumar Mohane Selvaraj , Hsieh Hsing-Pang , Chang Jang-Yang 
Published: July 2019

Abstract
Background:
BPR0L075 [6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole] is a novel anti-cancer compound. It inhibits tubulin polymerization and induces mitochondrial-dependent apoptosis in various human cancer cells with different multi-drug resistance (MDR) status. Over-expression of an anti-apoptotic molecule, survivin, causes drug-resistance in various cancers. Survivin inhibits apoptosis by interfering caspase-3 and promotes cell growth by stabilizing microtubule networks. Here, we determined the effects of down-regulation of survivin in BPR0L075 (L075) treatment. Methods: Western blot analysis was used to determine the expression level of survivin in L075-untreated/-treated human oral carcinoma KB and nasopharyngeal carcinoma HONE-1 cancer cells. siRNA was used to down-regulate endogenous survivin. MTT cell viability assay, real-time caspase-3 activity assay and immuno-fluorescence microscopy were used to analyze downstream effects.

Results:
Survivin expression was up-regulated in both KB and HONE-1 cells in response to L075 treatment. Down-regulation of survivin induced hyper-sensitivity to L075 in KB and re-stored sensitivity to L075 in KB-derived L075-resistant KB-L30 cancer cells. At the molecular level, down-regulation of survivin induced changes in microtubule dynamics in both KB and KB-L30 cells. Surprisingly, down-regulation of survivin did not enhance the activity of caspase-3 in L075 therapy. Instead, down-regulation of survivin induced translocation of the apoptosis-inducing factor (AIF) from cytoplasm to nucleus. Conclusion: Down-regulation of survivin improved drug sensitivity to L075 in both KB and L075-resistant KB-L30 cancer cells, possibly through a tubulin-dependent and caspase-independent mechanism. We suggest that combining BPR0L075 and survivin inhibitor may give better clinical outcome than the use of BPR0L075 monotherapy in future clinical trials.
Rabbit Muscle Actin Polymerization changes by Ultraviolet –B radiation
Authors: Mukherjee Anita , Attri Arun Kumar 
Published: July 2019

AbstractIncrease in Ultraviolet-B flux from the Sun has the potential to alter the protein in mammals. Rabbit muscle was processed and filtered to extract G-actin, which was tested for its protein concentration before exposing to UV-B. It was found that polymerization of actin does get affected exposure of actin monomers to UV-B radiation. Inside the cell, there are many actin binding proteins which might be playing crucial role in G-actin to F-actin formation.