bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of low-grade glioma: a systematic review and meta-analysis
Authors: Brown Timothy J , Bota Daniela A , van Den Bent Martin J , Brown Paul D , Maher Elizabeth , Aregawi Dawit , Liau Linda M , Buckner Jan C , Weller Michael , Berger Mitchel S , Glantz Michael 
Published: August 2018

Abstract

Background
Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma.

Methods
A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy.

Results
Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas.

Conclusions
Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.
MicroRNA regulation of CTP synthase and cytoophidium inDrosophila melanogaster
Authors: Dzaki Najat , Kan Woo Wai , Azzam Ghows 
Published: August 2018

AbstractCTPsyn is a crucial metabolic enzyme which synthesizes CTP molecules through thede novoor salvage pathway. It has the extraordinary ability to compartmentalize into filaments termed cytoophidia. Although this property is retained amongst orthologues, and cytoophidia are therefore found across kingdoms, the mechanisms behind their formation remain unknown. Micro-RNAs (miRNAs) are single-stranded RNA with length of 20 – 22 nucleotides, capable of exerting mRNA silencing and degradation as a form of regulation.D. melanogasteritself has a high total gene count to miRNA gene number ratio, alluding to the possibility thatCTPsynmay too come under the regulatory effects of these small RNAs. A thorough miRNA overexpression involving 123 UAS-miRNA lines, followed by staining of ovarian cytoophidiadme-egg chambers, revealed a small group of candidates which confer either a lengthening or truncating effect on the structure. Prime candidates are identified on the basis of consistency. MiR-975 and miR-1014 are both cytoophidia-elongating, whereas miR-190 and miR-932 are cytoophidia-shortening. Though target prediction shows that miR-975 and miR-932 do indeed have binding sites onCTPsynmRNA,in vitroassays instead revealed that none of the four candidates may actually do so. This suggests that the effects asserted by overexpressed miRNAs indirectly reach CTPsyn and its cytoophidia through the actions of middling elements.In silicotarget prediction and qPCR quantification indicated that, at least for miR-932 and miR-1014, these undetermined elements may be players in fat metabolism. This is the first study to thoroughly investigate miRNAs in connection to CTPsyn expression and activity in any species. The findings presented could serve as a basis for further queries into not only the fundamental aspects of the enzyme’s regulation, but may uncover new facets of closely related pathways as well.
Emergence of Directional Actomyosin Flows from Active Matter Vibrations
Authors: Vogel Sven K. , Wölfer Christian , Ramirez-Diaz Diego A. , Flassig Robert J. , Sundmacher Kai , Schwille Petra 
Published: August 2018

AbstractCortical actomyosin flows play pivotal roles in cell motility, cell division and animal morphogenesis. According to many model systems, myosin motor induced local contractions are key for generating cortical flows. However, the original mechanism how large-scale directed flows emerge from local motor activity in an apparently isotropic cortex is unknown. We reconstituted and confined minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced cortical contractions that self-organize into directed flow-like actomyosin motions. By combining our experiments with theory, we found that the large-scale directional motion of actomyosin clusters emerges from individual asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption, in conjunction with spherical confinement. By tracking individual actomyosin clusters, we identified fingerprints of vibrational states as the basis of directed motions. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinementin vitroand in living systems.
Neuronal constituents and putative interactions within the Drosophila ellipsoid body neuropil
Authors: Omoto Jaison Jiro , Minh Nguyen Bao-Chau , Kandimalla Pratyush , Lovick Jennifer Kelly , Donlea Jeffrey Michael , Hartenstein Volker 
Published: August 2018

AbstractThe central complex (CX) is a midline-situated collection of neuropil compartments in the arthropod central brain, implicated in higher-order processes such as goal-directed navigation. Here, we provide a systematic genetic-neuroanatomical analysis of the ellipsoid body (EB), a compartment which represents a major afferent portal of the Drosophila CX. The neuropil volume of the EB, along with its prominent input compartment, called the bulb, is subdivided into precisely tessellated domains, distinguishable based on intensity of the global marker DN-cadherin. EB tangential elements (so-called ring neurons), most of which are derived from the DALv2 neuroblast lineage, interconnect the bulb and EB domains in a topographically-organized fashion. Using the DN-cadherin domains as a framework, we first characterized the bulb-EB connectivity by Gal4 driver lines expressed in different DALv2 ring neuron (R-neuron) subclasses. We identified 11 subclasses, 6 of which correspond to previously described projection patterns, and 5 novel patterns. These subclasses both spatially (based on EB innervation pattern) and numerically (cell counts) summate to the total EB volume and R-neuron cell number, suggesting that our compilation of R-neuron subclasses approaches completion. EB columnar elements, as well as non-DALv2 derived extrinsic ring neurons (ExR-neurons), were also incorporated into this anatomical framework. Finally, we addressed the connectivity between R-neurons and their targets, using the anterograde trans-synaptic labeling method, trans-Tango. This study demonstrates putative interactions of R-neuron subclasses and reveals general principles of information flow within the EB network. Our work will facilitate the generation and testing of hypotheses regarding circuit interactions within the EB and the rest of the CX.
Protein-Ligand Docking with Protein-based and Ligand-based Structure Activity Relationships
Authors: Fu Darwin Y. , Meiler Jens 
Published: August 2018

AbstractProtein-small molecule docking programs predict the interaction interface and energy between a given protein target and a small molecule ligand. The accuracy of docking predictions generally improve with the guidance of experimentally derived restraints. One available source of such restraints is structure-activity relationships (SARs). SARs provide information on changes in binding affinity or biological response corresponding to a chemical change in the protein and/or ligand. These chemical changes frequently refer to amino acid mutations on the protein side and functional group modifications on the ligand side. Theoretically, predicted interaction energies should correlate with SARs though in practice, this is challenging due to the difficulties in scoring protein-ligand interactions. We have previously developed RosettaLigandEnsemble (RLE), a protein-ligand docking method that simultaneously docks a congeneric ligand series to a single protein target. RLE is capable of identifying native-like binding modes for a ligand series that match the available ligand SARs. This work in progress reports on the extension of RLE to factor in SARs derived from protein mutagenesis data. The new method, ProteinLigEnsemble (PLE), is also part of the Rosetta Biomolecular Modeling Suite available at https://www.rosettacommons.org/. We have also developed protein ensemble docking features that allow for docking or screening against multiple receptor variants at the same time. We have included a proof of concept study and a tutorial for interested users.
Challenge data set for macromolecular multi-microcrystallography
Authors: Holton James M. 
Published: August 2018

AbstractA synthetic data set demonstrating a particularly challenging case of indexing ambiguity in the context of radiation damage was generated in order to serve as a standard benchmark and reference point for the ongoing development of new methods and new approaches to solving this problem. Of the 100 short wedges of data only the first 71 are currently necessary to solve the structure by “cheating”, or using the correct reference structure as a guide. The total wall-clock time and number of wedges required to solve the structure without cheating is proposed as a metric for the efficacy and efficiency of a given multi-crystal automation pipeline.SynopsisA synthetic dataset demonstrating the challenges of combining multiple data sets with indexing ambiguity in the context of heavy radiation damage in multi-crystal macromolecular crystallography was generated and described, and the problems encountered using contemporary data processing programs were summarized.
Xolotl: An Intuitive and Approachable Neuron and Network Simulator for Research and Teaching
Authors: Gorur-Shandilya Srinivas , Hoyland Alec , Marder Eve 
Published: August 2018

ABSTRACTConductance-based models of neurons are used extensively in computational neuroscience. Working with these models can be challenging due to their high dimensionality and large number of parameters. Here, we present a neuron and network simulator built on a novel automatic type system that binds object-oriented code written in C++ to objects in MATLAB. Our approach builds on the tradition of uniting the speed of languages like C++ with the ease-of-use and feature-set of scientific programming languages like MATLAB. Xolotl allows for the creation and manipulation of hierarchical models with components that are named and searchable, permitting intuitive high-level programmatic control over all parts of the model. The simulator’s architecture allows for the interactive manipulation of any parameter in any model, and for visualizing the effects of changing that parameter immediately. Xolotl is fully featured with hundreds of ion channel models from the electrophysiological literature, and can be extended to include arbitrary conductances, synapses, and mechanisms. Several core features like bookmarking of parameters and automatic hashing of source code facilitate reproducible and auditable research. Its ease of use and rich visualization capabilities make it an attractive option in teaching environments. Finally, xolotl is written in a modular fashion, includes detailed tutorials and worked examples, and is freely available at https://github.com/sg-s/xolotl, enabling seamless integration into the workflows of other researchers.
Centromeric CENP-A loading requires accurate mitotic timing, which is linked to checkpoint proteins
Authors: Pauleau Anne Laure , Bergner Andrea , Kajtez Janko , Erhardt Sylvia 
Published: August 2018

AbstractA defining feature of centromeres is the presence of the histone H3 variant CENP-A that replaces H3 in a subset of centromeric nucleosomes. InDrosophilacultured cells CENP-A deposition at centromeres takes place during the metaphase stage of the cell cycle and strictly depends on the presence of its specific chaperone CAL1. How CENP-A loading is restricted to mitosis is unknown. We found that overexpression of CAL1 is associated with increased CENP-A levels at centromeres and completely uncouples CENP-A loading from mitosis. Moreover, CENP-A levels inversely correlate with mitosis duration. We found that CAL1 interacts with the spindle assembly checkpoint protein and RZZ complex component Zw10 and thus constitutes the anchor for the recruitment of RZZ. Therefore, CAL1 controls CENP-A incorporation at centromeres both quantitatively and temporally, connecting it to the spindle assembly checkpoint to ensure mitotic fidelity.
Triggering visually-guided behavior by holographic activation of pattern completion neurons in cortical ensembles
Authors: Carrillo-Reid Luis , Han Shuting , Yang Weijian , Akrouh Alejandro , Yuste Rafael 
Published: August 2018

AbstractNeuronal ensembles are building blocks of cortical activity yet it is unclear if they have any causal role in behavior. Here we tested if the precise activation of neuronal ensembles with two-photon holographic optogenetics in mouse primary visual cortex alters behavioral performance in a visual task. Disruption of behaviorally relevant cortical ensembles by activation of non-selective neurons decreased behavioral performance whereas optogenetic targeting of as few as two neurons with pattern completion capability from behaviorally relevant ensembles improved task performance by reliably recalling the whole ensemble. Moreover, in some cases, activation of two pattern completion neurons, in the absence of visual stimulus, triggered correct behavioral responses. Our results demonstrate a causal role of neuronal ensembles in a visually guided behavior and suggest that ensembles could represent perceptual states.
Elevated P2×7r and P2×4r transcripts levels in the Flinders Sensitive Line Rats, a genetic animal model of depression
Authors: Ribeiro Deidiane Elisa , Müller Heidi Kaastrup , Elfving Betina , Joca Samia Regiane Lourenço , Wegener Gregers 
Published: August 2018

AbstractP2×7 and P2×4 receptors (P2×7R and P2×4R, respectively) are ligand-gated ion channels activated by adenosine triphosphate (ATP), which have been associated to dysfunctional processes in stress responses linked to depression, such as neurotransmitter release, cognition, sleep, energy, appetite, immune and endocrine dysfunction. Clinical studies indicate that polymorphisms in the P2×7r gene results in increased susceptibility for development of depression. Existing studies have investigated the role of P2×7R and P2×4R in animal models based on stress exposure. Therefore, the present work aimed to investigate the transcript and protein levels of these receptors in a genetic animal model of depression, the Flinders Sensitive Line (FSL) and its control group, the Flinders Resistant Line (FRL) rats. We found that FSL rats have increased transcript levels of P2×7R and P2×4R in frontal cortex (FC), ventral and dorsal hippocampus (vHip and dHip, respectively) compared to FRL rats. There were no alterations in the protein levels in the FC and dHip, but the P2×7R was lower in FSL than in FRL rats in the vHip. The results suggest that increased transcripts levels of P2×7r and P2×4r in the FSL rats may contribute to the stress-susceptibility observed in these animals.
Cartilaginous and osteochondral tissue formation by human mesenchymal stem cells on three-dimensionally woven scaffolds
Authors: Larson Benjamin L. , Yu Sarah N. , Park Hyoungshin , Estes Bradley T. , Moutos Franklin T. , Bloomquist Cameron J. , Wu Patrick B. , Welter Jean F. , Langer Robert , Guilak Farshid , Freed Lisa E. 
Published: August 2018

AbstractThe development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remain important challenges for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSC) in large, three dimensionally woven poly(ε-caprolactone) (PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations: PCL alone, PCL-bone, “point-of- care” seeded MSC-PCL-bone, and chondrogenically pre-cultured Ch-MSC-PCL-bone constructs were implanted in a dorsal, ectopic pouch in a nude rat. After eight weeks, only cells in the Ch- MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, while both tissue profiles were present, constructs that had been chondrogenically pre- cultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions, and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.
Higher-order thalamic circuits channel parallel streams of visual information in mice
Authors: Bennett Corbett , Gale Samuel D. , Garrett Marina E. , Newton Melissa L. , Callaway Edward M. , Murphy Gabe J. , Olsen Shawn R. 
Published: August 2018

SummaryHigher-order thalamic nuclei, such as the visual pulvinar, play essential roles in cortical function by connecting functionally-related cortical and subcortical brain regions. Yet a coherent framework describing pulvinar function remains elusive due to its anatomical complexity and involvement in diverse cognitive processes. Here we combined large-scale anatomical circuit mapping with high-density electrophysiological recordings to dissect a homolog of pulvinar in mice, the lateral posterior nucleus (LP). We define three broad LP subregions based on correspondence between input/output connectivity and functional properties. These subregions form corticothalamic loops biased towards ventral or dorsal stream cortical areas and contain separate representations of visual space. To reveal which input sources drive LP activity, we silenced visual cortex or superior colliculus and found they drive visual tuning properties in separate LP subregions. Thus, by specifying the driving input sources, functional properties, and downstream targets of LP circuits, our data provide a roadmap for understanding the mechanisms of higher-order thalamic function in vision.
Distinct structure of cortical population activity on fast and infraslow timescales
Authors: Okun Michael , Steinmetz Nicholas A. , Lak Armin , Dervinis Martynas , Harris Kenneth D. 
Published: August 2018

AbstractCortical activity is organised across multiple spatial and temporal scales. Most research on the dynamics of neuronal spiking is concerned with timescales of 1 ms − 1 s, and little is known about spiking dynamics on timescales of tens of seconds and minutes. Here, we used frequency domain analyses to study the structure of individual neurons’ spiking activity and its coupling to local population rate and to arousal level across frequencies ranging from 0.01 to 100 Hz. In mouse medial prefrontal cortex (mPFC), the spiking dynamics of individual neurons could be quantitatively captured by a combination of interspike interval and firing rate power spectrum distributions. The relative strength of coherence with local population often differed across timescales: a neuron strongly coupled to population rate on fast timescales could be weakly coupled on slow timescales, and vice versa. On slow but not fast timescales, a substantial proportion of neurons showed firing anti-correlated with the population. Infraslow firing rate changes were largely determined by arousal rather than by local factors, which could explain the timescale dependence of population coupling strength of individual neurons. These observations demonstrate how individual neurons simultaneously partake in fast local dynamics, and slow brain-wide dynamics, extending our understanding of infraslow cortical activity beyond the mesoscale resolution of fMRI studies.
A diencephalic pathway for movement initiation and rescue of Parkinsonian symptoms
Authors: Watson Glenn D.R. , Hughes Ryan N. , Petter Elijah A. , Yin Henry H. 
Published: August 2018

SummaryThe parafascicular nucleus (Pf) of the thalamus projects to the subthalamic nucleus (STN), a major target for deep brain stimulation (DBS) in Parkinson’s disease (PD), but the function of this projection remains unknown. Here, we used optogenetics, 3D motion capture, in vivo electrophysiology and 1-photon calcium imaging, unsupervised behavioral classification, and viral-based neuroanatomical tracing to examine the contribution of Pf efferents to movement generation in mice. We discovered that Pf neurons are highly correlated with movement velocity and excitation of Pf neurons generates turning and orienting movements. Movement initiation was not due to Pf projections to the striatum, but rather its projections to the STN. Optogenetic excitation of the Pf-STN pathway restores movement in a common mouse model of PD with complete akinesia. Collectively, our results reveal a thalamo-subthalamic pathway regulating movement initiation, and demonstrate a circuit mechanism that could potentially explain the clinical efficacy of DBS for relief of PD motor symptoms.