bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Goliath beetles Fornasinius fornasini Bertoloni and Fornasinius hauseri Kraatz (Scarabaeidae: Cetoniinae)
Authors: De Palma Michele , Takano Hitoshi 
Published: January 2018

SummaryThe Goliath beetles (subtribe Goliathina) are large Cetoniinae comprising a few highly related genera broadly distributed in sub-Saharan Africa. The genus Fornasinius Bertoloni was established in 1853 by Giuseppe Bertoloni to receive a taxon that was sufficiently distinct from the known representatives of the genus Goliathus Lamarck to merit a different placement. In spite of their large size and showy appearance, the members of the genus Fornasinius are poorly known. Here, the type species of the genus, F. fornasini Bertoloni, 1853 (type locality: Mozambique), is identified and re-described. It has emerged that F. fornasini Bertoloni has been misidentified after its original description and that only a few specimens are known of this species. F. fornasini sensu auct. (nec Bertoloni) is instead referable to another taxon, F. hauseri Kraatz, 1896 sp. bon., of which three subspecies can be distinguished: F. hauseri s. str., from south-central Kenya and possibly Cameroon; F. hauseri ssp. hirthi Preiss, 1904 stat. rev., from the Lake Victoria region and northern Tanzania; and a new subspecies to be described from south-east Democratic Republic of the Congo.
Multiple Linear Regression: Bayesian Inference for Distributed and Big Data in the Medical Informatics Platform of the Human Brain Project
Authors: Melie-Garcia Lester , Draganski Bogdan , Ashburner John , Kherif Ferath 
Published: January 2018

ABSTRACTWe propose a Multiple Linear Regression (MLR) methodology for the analysis of distributed and Big Data in the framework of the Medical Informatics Platform (MIP) of the Human Brain Project (HBP). MLR is a very versatile model, and is considered one of the workhorses for estimating dependences between clinical, neuropsychological and neurophysiological variables in the field of neuroimaging. One of the main concepts behind MIP is to federate data, which is stored locally in geographically distributed sites (hospitals, customized databases, etc.) around the world. We restrain from using a unique federation node for two main reasons: first the maintenance of data privacy, and second the efficiency in management of big volumes of data in terms of latency and storage resources needed in the federation node. Considering these conditions and the distributed nature of data, MLR cannot be estimated in the classical way, which raises the necessity of modifications of the standard algorithms. We use the Bayesian formalism that provides the armamentarium necessary to implement the MLR methodology for distributed Big Data. It allows us to account for the heterogeneity of the possible mechanisms that explain data sets across sites expressed through different models of explanatory variables. This approach enables the integration of highly heterogeneous data coming from different subjects and hospitals across the globe. Additionally, it offers general and sophisticated ways, which are extendable to other statistical models, to suit high-dimensional and distributed multimodal data. This work forms part of a series of papers related to the methodological developments embedded in the MIP.
Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans
Authors: Charlesworth Carsten T. , Deshpande Priyanka S. , Dever Daniel P. , Dejene Beruh , Gomez-Ospina Natalia , Mantri Sruthi , Pavel-Dinu Mara , Camarena Joab , Weinberg Kenneth I. , Porteus Matthew H. 
Published: January 2018

AbstractThe CRISPR-Cas9 system has proven to be a powerful tool for genome editing, allowing for the precise modification of specific DNA sequences within a cell. Many efforts are currently underway to use the CRISPR-Cas9 system for the therapeutic correction of human genetic diseases. The most widely used homologs of the Cas9 protein are derived from the bacteriaStaphylococcus aureus(S. aureus) andStreptococcus pyogenes(S. pyogenes). Based on the fact that these two bacterial species cause infections in the human population at high frequencies, we looked for the presence of pre-existing adaptive immune responses to their respective Cas9 homologs, SaCas9 (S. aureushomolog of Cas9) and SpCas9 (S. pyogeneshomolog of Cas9). To determine the presence of anti-Cas9 antibodies, we probed for the two homologs using human serum and were able to detect antibodies against both, with 79% of donors staining against SaCas9 and 65% of donors staining against SpCas9. Upon investigating the presence of antigen-specific T-cells against the two homologs in human peripheral blood, we found anti-SaCas9 T-cells in 46% of donors. Upon isolating, expanding, and conducting antigen re-stimulation experiments on several of these donors’ anti-SaCas9 T-cells, we observed an SaCas9-specific response confirming that these T-cells were antigen-specific. We were unable to detect antigen-specific T-cells against SpCas9, although the sensitivity of the assay precludes us from concluding that such T-cells do not exist. Together, this data demonstrates that there are pre-existing humoral and cell-mediated adaptive immune responses to Cas9 in humans, a factor which must be taken into account as the CRISPR-Cas9 system moves forward into clinical trials.
Influence of switching rule on motor learning
Authors: Takiyama Ken , Ishii Koutaro , Hayshi Takuji 
Published: January 2018

AbstractHumans and animals can flexibly switch rules to generate appropriate motor commands; for example, actions can be flexibly produced toward a sensory stimulus (e.g., pro-saccade or pro-reaching) or away from a sensory stimulus (e.g., anti-saccade or anti-reaching). Distinct neural activities are related to pro- and anti-movement actions; however, the effects of switching rules on motor learning are unclear. Here, we study the effect of switching rules on motor learning using pro- and anti-arm-reaching movements and a visuomotor rotation task. Although previous results support the perfect availability of learning effects under the same required movements, we show that the learning effects trained in pro-reaching movements are partially rather than perfectly available in anti-reaching movements even under the same required movement direction between those two conditions. The partial transfer is independent of the difference in the visual cue, the cognitive demand, and the actual movement direction between the pro- and anti-reaching movements. We further demonstrate that the availability of learning effects trained with pro-reaching movements is partial not only in anti-reaching movements but in reaching movements with other rules and the availability of learning effects trained with anti-reaching movements is also partial in pro-reaching movements. We thus conclude that the switching rule causes the availability of learning effects to be partial rather than perfect even under same planned movements.New & NoteworthyMost motor learning experiments supported the involvement of planned movement directions in motor learning; the learning effects trained in a movement direction can be available at movement directions close to the trained one. Here, we show that the availability of motor learning effects is partial rather than perfect even under the same planned movements when rule is switched, which indicates that sports training and rehabilitation should include various situations under the same required motions.
The brown algaSaccharina japonicafeatures distinct vanadium-dependent bromoperoxidases and iodoperoxidases
Authors: Chi Shan , Liu Tao , Yin Hongxin , Xu Xin , Zhu Weiming , Wang Yi , Wang Cong , Lv Hui 
Published: January 2018

AbstractMarine algae have an extraordinary ability to absorb halogens which provide algae with an inorganic antioxidant impacting atmospheric chemistry. Although brown algal Laminariales species are the most efficient iodine accumulators among all living systems, andSaccharina japonicais the primary material used for iodine extraction, the functions and regulatory mechanisms of these species have not been fully documented. In this study, a functional genomics analysis of the algal vanadium-dependent haloperoxidase (vHPO) gene family was conducted; there genes can introduce halogen atoms into organic compounds. The comprehensive analyses regarding the bioinformatics and phylogenetics of novel genomic and transcriptomic sequencing data of 21 Rhodophyta and 19 Ochrophyta marine algal species revealed that brown algalvHPOshave two gene types, vanadium-dependent bromoperoxidase (vBPO) and vanadium-dependent iodoperoxidase (vIPO), with secondary endosymbiotic host origin. The enzyme activity ofS. japonicavBPO and vIPO were verified for the first time and were quite stable in a wide range of temperature and pH values. However, the specific activity and optimal conditions were considerably different between vBPO and vIPO. The transcript expression analysis in differentS. japonicatissues (including rhizoids), generations (sporophytes and gametophytes), sexes (male and female), and stress conditions (hyposaline and hyperthermia) also showed great differences betweenvBPOsandvIPOs. Most of thevBPOswere constitutively expressed with higher expression dose, which may be responsible for basal halogen metabolism. On the contrary,vIPOsmainly showed specific expression, which may be involved in tissue differentiation, generation differentiation, sex differentiation, and stress regulation. Comprehensive analysis of gene family evolution, enzyme biochemical characteristics, and complex transcriptional mechanisms were conducive to the environmental adaptation and sophisticated system evolution of Laminariales. The successful bromination of small-molecule compound substrate by SjavBPO provided high activity and efficient enzymatic tools for artificial synthesis of halogenated compounds.
Spatial gradient in activity within the insula reflects dissociable neural mechanisms underlying context-dependent advantageous and disadvantageous inequity aversion
Authors: Gao Xiaoxue , Yu Hongbo , Saez Ignacio , Blue Philip R. , Zhu Lusha , Hsu Ming , Zhou Xiaolin 
Published: January 2018

AbstractHumans are capable of integrating social contextual information into decision-making processes to adjust their attitudes towards inequity. This context-dependency emerges both when individual is better off (i.e. advantageous inequity) and worse off (i.e. disadvantageous inequity) than others. It is not clear however, whether the context-dependent processing of advantageous and disadvantageous inequity rely on dissociable or shared neural mechanisms. Here, by combining an interpersonal interactive game that gave rise to interpersonal guilt and different versions of the dictator games that enabled us to characterize individual weights on aversion to advantageous and disadvantageous inequity, we investigated the neural mechanisms underlying the two forms of inequity aversion in the interpersonal guilt context. In each round, participants played a dot-estimation task with an anonymous co-player. The co-players received pain stimulation with 50% probability when anyone responded incorrectly. At the end of each round, participants completed a dictator game, which determined payoffs of him/herself and the co-player. Both computational model-based and model-free analyses demonstrated that when inflicting pain upon co-players (i.e., the guilt context), participants cared more about advantageous inequity and became less sensitive to disadvantageous inequity, compared with other social contexts. The contextual effects on two forms of inequity aversion are uncorrelated with each other at the behavioral level. Neuroimaging results revealed that the context-dependent representation of inequity aversion exhibited a spatial gradient in activity within the insula, with anterior parts predominantly involved in the aversion to advantageous inequity and posterior parts predominantly involved in the aversion to disadvantageous inequity. The dissociable mechanisms underlying the two forms of inequity aversion are further supported by the involvement of right dorsolateral prefrontal cortex and dorsomedial prefrontal cortex in advantageous inequity processing, and the involvement of right amygdala and dorsal anterior cingulate cortex in disadvantageous inequity processing. These results extended our understanding of decision-making processes involving inequity and the social functions of inequity aversion.
Identifying biomarkers of anti-cancer drug synergy using multi-task learning
Authors: Aben Nanne , de Ruiter Julian R. , Bosdriesz Evert , Kim Yongsoo , Bounova Gergana , Vis Daniel J. , Wessels Lodewyk F.A. , Michaut Magali 
Published: January 2018

AbstractCombining anti-cancer drugs has the potential to increase treatment efficacy. Because patient responses to drug combinations are highly variable, predictive biomarkers of synergy are required to identify which patients are likely to benefit from a drug combination. To aid biomarker identification, the DREAM challenge consortium has recently released data from a screen containing 85 cell lines and 167 drug combinations. The main challenge of these data is the low sample size: per drug combination, a median of 14 cell lines have been screened. We found that widely used methods in single drug response prediction, such as Elastic Net regression per drug, are not predictive in this setting. Instead, we propose to use multi-task learning: training a single model simultaneously on all drug combinations, which we show results in increased predictive performance. In contrast to other multi-task learning approaches, our approach allows for the identification of biomarkers, by using a modified random forest variable importance score, which we illustrate using artificial data and the DREAM challenge data. Notably, we find that mutations in MYO15A are associated with synergy between ALK / IGFR dual inhibitors and PI3K pathway inhibitors in triple-negative breast cancer.Author summaryCombining drugs is a promising strategy for cancer treatment. However, it is often not known which patients will benefit from a particular drug combination. To identify patients that are likely to benefit, we need to identify biomarkers, such as mutations in the tumor’s DNA, that are associated with favorable response to the drug combination. In this work, we identified such biomarkers using the drug combination data released by the DREAM challenge consortium, which contain 85 tumor cell lines and 167 drug combinations. The main challenge of these data is the extremely low sample size: a median of 14 cell lines have been screened per drug combination. We found that traditional methods to identify biomarkers for monotherapy response, which analyze each drug separately, are not suitable in this low sample size setting. Instead, we used a technique called multi-task learning to jointly analyze all drug combinations in a single statistical model. In contrast to existing multi-task learning algorithms, which are black-box methods, our method allows for the identification of biomarkers. Notably, we find that, in a subset of breast cancer cell lines,MYO15Amutations associate with response to the combination of ALK / IGFR dual inhibitors and PI3K pathway inhibitors.
Naa10p promotes metastasis by stabilizing matrix metalloproteinase-2 protein in human osteosarcomas
Authors: Chien Ming-Hsien , Lee Wei-Jiunn , Yang Yi-Chieh , Tan Peng , Pan Ke-Fan , Tsai Hsiao-Chi , Hsu Chun-Hua , Hsiao Michael , Hua Kuo-Tai 
Published: January 2018

AbstractN-α-Acetyltransferase 10 protein (Naa10p) mediates N-terminal acetylation of nascent proteins. Oncogenic or tumor suppressive roles of Naa10p were reported in cancers. Here, we report an oncogenic role of Naa10p in promoting metastasis of osteosarcomas. HigherNAA10transcripts were observed in metastatic osteosarcoma tissues compared to non-metastatic tissues and were also correlated with a worse prognosis of patients. Knockdown and overexpression of Naa10p in osteosarcoma cells respectively led to decreased and increased cell migratory/invasive abilities. Re-expression of Naa10p, but not an enzymatically inactive mutant, relieved suppression of the invasive abilityin vitroand metastasisin vivoimposed by Naa10p-knockdown. According to protease array screening, we identified that matrix metalloproteinase (MMP)-2 was responsible for the Naa10p-induced invasive phenotype. Naa10p was directly associated with MMP-2 protein through its acetyltransferase domain and maintained MMP-2 protein stability via NatA complex activity. MMP-2 expression levels were also significantly correlated with Naa10p levels in osteosarcoma tissues. These results reveal a novel function of Naa10p in the regulation of cell invasiveness by preventing MMP-2 protein degradation that is crucial during osteosarcoma metastasis.
Universal temporal rate of DNA replication origin firing: A balance between origin activation and passivation
Authors: Arbona Jean-Michel , Goldar Arach , Hyrien Olivier , Arneodo Alain , Audit Benjamin 
Published: January 2018

AbstractThe time-dependent rate I(t) of origin firing per length of unreplicated DNA presents a universal bell shape in eukaryotes that has been interpreted as the result of a complex time-evolving interaction between origins and limiting firing factors. Here we show that a normal diffusion of replication fork components towards localized potential replication origins (p-oris) can more simply account for the I(t) universal bell shape, as a consequence of a competition between the origin firing time and the time needed to replicate DNA separating two neighboring p-oris. We predict the I(t) maximal value to be the product of the replication fork speed with the squared p-ori density. We show that this relation is robustly observed in simulations and in experimental data for several eukaryotes. Our work underlines that fork-component recycling and potential origins localization are sufficient spatial ingredients to explain the universality of DNA replication kinetics.
OTX2 signals from the choroid plexus to regulate adult neurogenesis
Authors: Planques Anabelle , Moreira Vanessa Oliveira , Dubreuil Chantal , Prochiantz Alain , Di Nardo Ariel A 
Published: January 2018

AbstractProliferation and migration during adult neurogenesis are regulated by a microenvironment of signaling molecules originating from local vasculature, from cerebrospinal fluid produced by the choroid plexus, and from local supporting cells including astrocytes. Here, we focus on the function of OTX2 homeoprotein transcription factor in the mouse adult ventricular-subventricular zone (V-SVZ) which generates olfactory bulb neurons. We find that OTX2 secreted by choroid plexus is transferred to supporting cells of the V-SVZ and rostral migratory stream. Deletion ofOtx2in choroid plexus affects neuroblast migration and reduces the number of olfactory bulb newborn neurons. Adult neurogenesis was also decreased by expressing secreted single-chain antibodies to sequester OTX2 in the cerebrospinal fluid, demonstrating the importance of non-cell autonomous OTX2. We show that OTX2 activity modifies extracellular matrix components and signaling molecules produced by supporting astrocytes. Thus, we reveal a multi-level and non-cell autonomous role of a homeoprotein and reinforce the choroid plexus and astrocytes as key niche compartments affecting adult neurogenesis.Significance StatementCerebrospinal fluid, local vasculature and non-neurogenic astrocytes are niche compartments that provide a microenvironment for regulating adult mouse neurogenesis. We show that OTX2 homeoprotein secreted by choroid plexus into the cerebrospinal fluid is transferred into non-neurogenic astrocytes of the ventricular-subventricular zone and rostral migratory stream where it regulates extracellular matrix and signaling factors. This non-cell-autonomous activity impacts the number of newborn neurons that integrate the olfactory bulb. Thus, we reveal a multi-level role for OTX2 and reinforce the choroid plexus as a key niche compartment affecting adult neurogenesis.
Neural evidence for representationally specific prediction in language processing
Authors: Wang Lin , Kuperberg Gina , Jensen Ole 
Published: January 2018

AbstractPrevious studies suggest that people generate predictions during language comprehension at multiple linguistic levels. It has been hypothesized that, under some circumstances, this can result in the pre-activation of specific lexico-semantic representations. We asked whether such representationally specific semantic pre-activation can be detected in the brain ahead of encountering bottom-up input. We measured MEG activity as participants read highly constraining sentences in which the final word could be predicted. We found that both spatial and temporal patterns of the brain activity prior to the onset of this word were more similar when the same words were predicted than when different words were predicted. This pre-activation was transient and engaged a left inferior and medial temporal region. These results suggest that unique spatial patterns of neural activity associated with the pre-activation of distributed semantic representations can be detected prior to the appearance of new sensory input, and that the left inferior and medial temporal regions may play a role in temporally binding such representations, giving rise to specific lexico-semantic predictions.
Homology-directed repair of a defective glabrous gene in Arabidopsis with Cas9-based gene targeting
Authors: Hahn Florian , Eisenhut Marion , Mantegazza Otho , Weber Andreas P.M. 
Published: January 2018

ABSTRACTThe CRISPR/Cas9 system has emerged as a powerful tool for targeted genome editing in plants and beyond. Double-strand breaks induced by the Cas9 enzyme are repaired by the cell’s own repair machinery either by the non-homologous end joining pathway or by homologous recombination. While the first repair mechanism results in random mutations at the double-strand break site, homologous recombination uses the genetic information from a highly homologous repair template as blueprint for repair of the break. By offering an artificial repair template, this pathway can be exploited to introduce specific changes at a site of choice in the genome. However, frequencies of double-strand break repair by homologous recombination are very low. In this study, we compared two methods that have been reported to enhance frequencies of homologous recombination in plants. The first method boosts the repair template availability through the formation of viral replicons, the second method makes use of an in planta gene targeting approach. Additionally, we comparatively applied a nickase instead of a nuclease for target strand priming. To allow easy, visual detection of homologous recombination events, we aimed at restoring trichome formation in a glabrous Arabidopsis mutant by repairing a defective glabrous1 gene. Using this efficient visual marker, we were able to regenerate plants repaired by homologous recombination at frequencies of 0.12% using the in planta gene targeting approach, while both approaches using viral replicons did not yield any trichome-bearing plants.