bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurovascular uncoupling in schizophrenia: A bimodal meta-analysis of brain perfusion and glucose metabolism
Authors: Sukumar Niron , Sabesan Priyadharshini , Anazodo Udunna , Palaniyappan Lena 
Published: November 2019

ABSTRACTSUKUMAR, N., S. Priyadharshini, U. Anazodo, L. Palaniyappan. Neurovascular uncoupling in schizophrenia: A bimodal meta-analysis of brain perfusion and glucose metabolism. NEUROSCI BIOBEHAV REV X(X) XXX-XXX, XXXX. - The use of modern neuroimaging approaches has demonstrated resting-state regional cerebral blood flow (rCBF) to be tightly coupled to resting cerebral glucose metabolism (rCMRglu) in healthy brains. In schizophrenia, several lines of evidence point towards aberrant neurovascular coupling, especially in the prefrontal regions. To investigate this, we used Signed Differential Mapping to undertake a voxel-based bimodal meta-analysis examining the relationship between rCBF and rCMRglu in schizophrenia, as measured by Arterial Spin Labeling (ASL) and18Flurodeoxyglucose Positron Emission Tomography (FDG-PET) respectively. We used 19 studies comprised of data from 557 patients and 584 controls. Our results suggest that several key regions implicated in the pathophysiology of schizophrenia such as the frontoinsular cortex, dorsal ACC, putamen, and temporal pole show conjoint metabolic and perfusion abnormalities in patients. In contrast, discordance between metabolism and perfusion were seen in superior frontal gyrus and cerebellum, indicating that factors contributing to neurovascular uncoupling (e.g. inflammation, mitochondrial dysfunction, oxidative stress) are likely operates at these loci. Hybrid ASL-PET studies focusing on these regions could confirm our proposition.
Neural correlates of episodic memory modulated by temporally delayed rewards
Authors: Yoo Jungsun , Min Seokyoung , Lee Seung-Koo , Han Sanghoon 
Published: November 2019

AbstractWhen a stimulus is associated with an external reward, its chance of being consolidated into long-term memory is boosted via dopaminergic facilitation of long-term potentiation in the hippocampus. Given that higher temporal distance (TD) has been found to discount the subjective value of a reward, we hypothesized that memory performance associated with a more immediate reward will result in better memory performance. We tested this hypothesis by measuring both behavioral memory performance and brain activation using functional magnetic resonance imaging (fMRI) during memory encoding and retrieval tasks. Contrary to our hypothesis, both behavioral and fMRI results suggest that the TD of rewards might enhance the chance of the associated stimulus being remembered. The fMRI data demonstrate that the lateral prefrontal cortex, which shows encoding-related activation proportional to the TD, is reactivated when searching for regions that show activation proportional to the TD during retrieval. This is not surprising given that this region is not only activated to discriminate between future vs. immediate rewards, it is also a part of the retrieval-success network. These results provide support for the conclusion that the encoding-retrieval overlap provoked as the rewards are more delayed lead to better memory performance of the items associated with the rewards.
DeepSide: A Deep Learning Framework for Drug Side Effect Prediction
Authors: Uner Onur Can , Gokberk Cinbis Ramazan , Tastan Oznur , Cicek A. Ercument 
Published: November 2019

AbstractDrug failures due to unforeseen adverse effects at clinical trials pose health risks for the participants and lead to substantial financial losses. Side effect prediction algorithms have the potential to guide the drug design process. LINCS L1000 dataset provides a vast resource of cell line gene expression data perturbed by different drugs and creates a knowledge base for context specific features. The state-of-the-art approach that aims at using context specific information relies on only the high-quality experiments in LINCS L1000 and discards a large portion of the experiments. In this study, our goal is to boost the prediction performance by utilizing this data to its full extent. We experiment with 5 deep learning architectures. We find that a multi-modal architecture produces the best predictive performance among multi-layer perceptron-based architectures when drug chemical structure (CS), and the full set of drug perturbed gene expression profiles (GEX) are used as modalities. Overall, we observe that the CS is more informative than the GEX. A convolutional neural network-based model that uses only SMILES string representation of the drugs achieves the best results and provides 13.0% macro-AUC and 3.1% micro-AUC improvements over the state-of-the-art. We also show that the model is able to predict side effect-drug pairs that are reported in the literature but was missing in the ground truth side effect dataset. DeepSide is available at http://github.com/OnurUner/DeepSide.
Mosaic metabolic ageing: Basal and standard metabolic rate age in opposite directions and independent of environmental quality, sex or lifespan in a passerine
Authors: Briga Michael , Verhulst Simon 
Published: November 2019

AbstractCrucial to our understanding of the ageing process is identifying how traits change with age, which variables alter their ageing process and whether these traits associate with lifespan.We here investigated metabolic ageing in zebra finches. We longitudinally monitored 407 individuals during six years and collected 3213 measurements of two independent mass-adjusted metabolic traits: basal metabolic rate (BMRm) at thermoneutral temperatures and standard metabolic rate (SMRm), which is the same as BMRmbut at ambient temperatures below thermoneutrality.BMRmdecreasedlinearly with age, consistent with earlier reports. In contrast, SMRmincreasedlinearly with age. To the best of our knowledge, this is the first quantification of SMRmageing, and thereby of the contrast between SMRmand BMRmageing.Neither metabolic rate nor metabolic ageing rate were associated with individual lifespan. Moreover, experimental manipulations of environmental quality that decreased BMRmand SMRmand shortened lifespan with 6 months (12%) did not affect the ageing of either metabolic trait. Females lived 2 months (4%) shorter than males, but none of the metabolic traits showed sex-specific differences at any age.Our finding that ageing patterns of metabolic rate vary depending on the ambient temperature illustrates the importance of studying ageing in an ecologically realistic setting.Our results add to the mounting evidence that within an organism ageing is an asynchronous process.
A comprehensive online database for exploring ~20,000 public Arabidopsis RNA-Seq libraries
Authors: Zhang Hong , Zhang Fei , Feng Li , Jia Jinbu , Zhai Jixian 
Published: November 2019

AbstractApplication of Next Generating Sequencing (NGS) technology in transcriptome profiling has greatly improved our understanding of transcriptional regulation at genome-wide scale in the last decade, and tens of thousands of RNA-sequencing (RNA-seq) libraries have been produced by the research community. However, accessing such huge amount of RNA-seq data poses a big challenge for groups that lack dedicated bioinformatic personnel or expensive computational resources. Here, we introduce the Arabidopsis RNA-seq database (ARS), a free, web-accessible, and user-friendly to quickly explore expression level of any gene in 20,000+ publicly available Arabidopsis RNA-seq libraries.
S1P-S1PR1 activity controls VEGF-A signaling during lymphatic vessel development
Authors: Golding-Ochsenbein AM , Vidal S , Wilmering Wetter B , Guibourdenche C , Beerli C , Chang L , Leonhard S , Holway N , Seuwen K , Jurisic G 
Published: November 2019

AbstractSphingosine-1-phosphate (S1P), a lipid signaling molecule produced by endothelial cells, is required for development and homeostasis of blood vessels. However, its role during lymphatic vessel development is unclear. We show in murine newborns that pharmacologically enhanced S1P signaling increases VEGF-A-dependent LEC proliferation. In contrast, S1PR1 inhibition, mediated by the antagonist NIBR0213 or LEC-specific genetic deletion of S1pr1, promotes filopodia formation and vessel branching, independent of VEGF-A. To investigate the S1P and VEGF-A signaling crosstalk observed in vivo, we used LECs cultured in vitro. We demonstrate that S1P activates endogenous S1PR1 in a constitutive, autocrine manner. Importantly, S1P-S1PR1 activity was required for VEGF-A-induced LEC proliferation and strongly supported ERK1/2 activation and VEGFR-2 trafficking to the perinuclear area. In conclusion, S1P-S1PR1 signaling promotes VEGF-A-dependent LEC proliferation and limits migratory and filopodia-forming responses. Hence, S1P-S1PR1 signaling is required for balanced growth factor-induced lymphangiogenesis and correctly patterned lymphatic vessels during postnatal development.
Oxytocin Neurons Enable Social Transmission of Maternal Behavior
Authors: Carcea Ioana , Caraballo Naomi López , Marlin Bianca J. , Ooyama Rumi , Riceberg Justin S. , Mendoza Navarro Joyce M. , Opendak Maya , Diaz Veronica E. , Schuster Luisa , Alvarado Torres Maria I. , Lethin Harper , Ramos Daniel , Minder Jessica , Mendoza Sebastian L. , Hidema Shizu , Falkner Annegret , Lin Dayu , Mar Adam , Wadghiri Youssef Z. , Nishimori Katsuhiko , Kikusui Takefumi , Mogi Kazutaka , Sullivan Regina M. , Froemke Robert C. 
Published: November 2019

AbstractMaternal care is profoundly important for mammalian survival, and non-biological parents can express it after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care by ensuring their nest presence, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin.One Sentence SummaryMother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.
RNA sequencing and lipidomic analysis of alveolar macrophages from normal and CD44 deficient mice
Authors: Dong Yifei , Arif Arif A. , Guo Jian , Ha Zongyi , Lee-Sayer Sally S. M. , Poon Grace F. T. , Dosanjh Manisha , Roskelley Calvin D. , Huan Tao , Johnson Pauline 
Published: November 2019

ABSTRACTAlveolar macrophages (AMs) are CD44 expressing cells that reside in the alveolar space where they maintain lung homeostasis by serving critical roles in immunosurveillance and lipid surfactant catabolism. AMs lacking CD44 are unable to bind the glycosaminoglycan, hyaluronan, which compromises their survival and leads to reduced numbers of AMs in the lung. Using RNA sequencing, lipidomics and multiparameter flow cytometry, we demonstrate that CD44-/- mice have impaired AM lipid homeostasis and increased surfactant lipids in the lung. CD44-/- AMs had increased expression of CD36, a lipid scavenger receptor, as well as increased intracellular lipid droplets, giving them a foamy appearance. RNA sequencing revealed the differential expression of genes associated with lipid efflux and metabolism in CD44-/- AMs. Lipidomic analysis showed increased lipids in both the supernatant and cell pellet extracted from the bronchoalveolar lavage of CD44-/- mice. Phosphatidylcholine species, cholesterol, oxidized phospholipids and levels of reactive oxygen species (ROS) were increased in CD44-/- AMs. Oxidized phospholipids were more cytotoxic to CD44-/- AMs and induced greater lung inflammation in CD44-/- mice. Reconstitution of CD44+/+ mice with CD44-/- bone marrow as well as adoptive transfer of CD44-/- AMs into CD44+/+ mice showed that lipid accumulation in CD44-/- AMs occurred irrespective of the lung environment, suggesting a cell intrinsic defect. Administration of colony stimulating factor 2 (CSF-2), a critical factor in AM development and maintenance, increased AM numbers in CD44-/- mice and decreased phosphatidylcholine levels in the bronchoalveolar lavage, but was unable to decrease intracellular lipid accumulation in CD44-/- AMs. Peroxisome proliferator-activated receptor gamma (PPARγ), downstream of CSF-2 signaling and a regulator of lipid metabolism, was reduced in the nucleus of CD44-/- AMs, and PPARγ inhibition in normal AMs increased their lipid droplets. Thus, CD44 deficiency causes defects in AMs that lead to abnormal lipid accumulation and oxidation, which exacerbates oxidized lipid-induced lung inflammation. Collectively, these findings implicate CD44 as a regulator of lung homeostasis and inflammation.
Automating parameter selection to avoid implausible biological pathway models
Authors: Magnano Chris S. , Gitter Anthony 
Published: November 2019

AbstractA common way to integrate and analyze large amounts of biological “omic” data is through pathway reconstruction: using condition-specific omic data to create a subnetwork of a generic background network that represents some process or cellular state. A challenge in pathway reconstruction is that adjusting pathway reconstruction algorithms’ parameters produces pathways with drastically different topological properties and biological interpretations. Due to the exploratory nature of pathway reconstruction, there is no ground truth for direct evaluation, so parameter tuning methods typically used in statistics and machine learning are inapplicable. We developed the pathway parameter advising algorithm to tune pathway reconstruction algorithms to minimize biologically implausible predictions. We leverage background knowledge in pathway databases to select pathways whose high-level structure resembles that of manually curated biological pathways. At the core of this method is a graphlet decomposition metric, which measures topological similarity to curated biological pathways. In order to evaluate pathway parameter advising, we compare its performance in avoiding implausible networks and reconstructing pathways from the NetPath database with other parameter selection methods across four pathway reconstruction algorithms. We also demonstrate how pathway parameter advising can guide construction of an influenza host factor network. Pathway parameter advising is method-agnostic; it is applicable to any pathway reconstruction algorithm with tunable parameters. Our pathway parameter advising software is available on GitHub athttps://github.com/gitter-lab/pathway-parameter-advisingand PyPI athttps://pypi.org/project/pathwayParameterAdvising/.
The influence of 2-aminoethoxydiphenyl borate on the electrical activity of the rat heart under hypoxia/reoxygenation conditions
Authors: Kharkovskaya Elena , Osipov Grigory V. , Mukhina Irina V. 
Published: November 2019

AbstractThe aim of the study was to apply the multi-electrode mapping method to investigate the effect of 2-aminoethoxydiphenyl borate (2-apb) on the electrical activity and vessels of the isolated rat heart under hypoxia/reoxygenation injury (H/R). To date, the ability to influence on the calcium currents and condition of gap junctions has been shown for 2-apb. Changes in the intracellular calcium concentration in the heart play the pivotal role in the development of H/R.As a result, it was shown that 2-apb influences on the myocardial conduction velocity, sinus rhythm and coronary blood flow in the isolated rat heart. 2-apb caused heart fibrillation during normoxia but not under hypoxia, and attenuated the effect of the H/R on heart rate and vascular function.
Motor learning and transfer: from feedback to feedforward control
Authors: Maeda Rodrigo S. , Gribble Paul L. , Pruszynski J. Andrew 
Published: November 2019

AbstractPrevious work has demonstrated that when learning a new motor task, the nervous system modifies feedforward (ie. voluntary) motor commands and that such learning transfers to fast feedback (ie. reflex) responses evoked by mechanical perturbations. Here we show the inverse, that learning new feedback responses transfers to feedforward motor commands. Sixty human participants (34 females) used a robotic exoskeleton and either 1) received short duration mechanical perturbations (20 ms) that created pure elbow rotation or 2) generated self-initiated pure elbow rotations. They did so with the shoulder joint free to rotate (normal arm dynamics) or locked (altered arm dynamics) by the robotic manipulandum. With the shoulder unlocked, the perturbation evoked clear shoulder muscle activity in the long-latency stretch reflex epoch (50-100ms post-perturbation), as required for countering the imposed joint torques, but little muscle activity thereafter in the so-called voluntary response. After locking the shoulder joint, which alters the required joint torques to counter pure elbow rotation, we found a reliable reduction in the long-latency stretch reflex over many trials. This reduction transferred to feedforward control as we observed 1) a reduction in shoulder muscle activity during self-initiated pure elbow rotation trials and 2) kinematic errors (ie. aftereffects) in the direction predicted when failing to compensate for normal arm dynamics, even though participants never practiced self-initiated movements with the shoulder locked. Taken together, our work shows that transfer between feedforward and feedback control is bidirectional, furthering the notion that these processes share common neural circuits that underlie motor learning and transfer.
Developmental transcriptomic analysis of the cave-dwelling crustacean,Asellus aquaticus
Authors: Gross Joshua B. , Sun Dennis A. , Carlson Brian M. , Brodo-Abo Sivan , Protas Meredith E. 
Published: November 2019

AbstractCave animals are a fascinating group of species often demonstrating characteristics including reduced eyes and pigmentation, metabolic efficiency, and enhanced sensory systems.Asellus aquaticus, an isopod crustacean, is an emerging model for cave biology. Cave and surface forms of this species differ in many characteristics, including eye size, pigmentation and antennal length. Existing resources for this species include a linkage map, mapped regions responsible for eye and pigmentation traits, sequenced adult transcriptomes, and comparative embryological descriptions of the surface and cave forms. Our ultimate goal is to identify genes and mutations responsible for the differences between the cave and surface forms. To advance this goal, we decided to use a transcriptomic approach. Because many of these changes first appear during embryonic development, we sequenced embryonic transcriptomes of cave, surface, and hybrid individuals at the stage when eyes and pigment become evident in the surface form. We generated a cave, a surface, a hybrid, and an integrated transcriptome to identify differentially expressed genes in the cave and surface forms. Additionally, we identified genes with allele-specific expression in hybrid individuals. These embryonic transcriptomes are an important resource to assist in our ultimate goal of determining the genetic underpinnings of the divergence between the cave and surface forms.
A nanobody-based fluorescent reporter reveals human α-synuclein in the cell cytosol
Authors: Gerdes Christoph , Waal Natalia , Offner Thomas , Fornasiero Eugenio F. , Wender Nora , Verbarg Hannes , Manzini Ivan , Trenkwalder Claudia , Mollenhauer Brit , Strohäker Timo , Zweckstetter Markus , Becker Stefan , Rizzoli Silvio O. , Basmanav Buket , Opazo Felipe 
Published: November 2019

ABSTRACTAggregation and spreading of α-Synuclein (αSyn) are hallmarks of several neurodegenerative diseases, thus monitoring human αSyn (hαSyn) in animal models or cell cultures is vital for the field. However, the detection of native hαSyn in such systems is challenging. We found that the nanobody NbSyn87, previously-described to bind hαSyn, also shows cross-reactivity for the proteasomal subunit Rpn10. As such, when the NbSyn87 is expressed in the absence of hαSyn, it is continuously degraded by the proteasome, while it is stabilized when it binds to hαSyn. Here, we exploited this feature to design a new Fluorescent Reporter for hαSyn (FluoReSyn) by coupling NbSyn87 to fluorescent proteins, which results in fluorescence signal fluctuations depending on the presence and amounts of intracellular hαSyn. We characterized this biosensor in cells and tissues, and finally, revealed the presence of transmittable αSyn in human cerebrospinal fluid demonstrating the potential of FluoReSyn for clinical research and diagnostics.
HIV-1 RNA genomes initiate host protein packaging in the cytosol independently of Gag capsid proteins
Authors: Becker Jordan T. , Evans Edward L. , Benner Bayleigh E. , Pritzl Stephanie L. , Smith Laura E. , Bates Andra E. , Sherer Nathan M. 
Published: November 2019

ABSTRACTHIV-1 RNA genomes interact with diverse RNA binding proteins (RBPs) in the cytoplasm including antiviral factor APOBEC3G (A3G) that, in the absence of viral Vif proteins, is packaged into virions. Where and when HIV-1-A3G interactions are initiated for packaging inside the cell is unknown, and the relative contributions of genome vs. Gag capsid proteins to this process remains controversial. Here we visualized A3G responses to HIV-1 infection over an entire replication cycle using long-term (up to 72 h) live single cell imaging. We show that Vif-deficient HIV-1 dramatically shifts A3G and a second RNA surveillance factor, MOV10, from the cytoplasm to virus particle assembly sites with little to no net discernible effects on general markers of cytoplasmic processing bodies (DCP1A), stress granules (TIA-1), or a marker of the nonsense-mediated decay machinery (UPF1). Using a new live cell RNA-protein interaction assay based on RNA tethering (the in-cell RNA-protein interaction protocol, or IC-IP), we provide evidence that A3G- and MOV10- genome interactions are selective, strong, occur in presence or absence of Gag, and are initiated in the cytosol soon if not immediately after genome nuclear export. Finally, although Gag is sufficient to package A3G into virions even in the absence of genomes, single virion imaging indicates that selective A3G-genome interactions promote much more consistent per virion delivery of A3G to assembly sites. Collectively, these studies suggest a paradigm for early, strong, and persistent cytosolic detection of select HIV-1 RNA signatures by A3G, MOV10 and other host RBPs that are enriched in virions.IMPORTANCEHost-pathogen interactions determine the success of viral replication. While extensive work has identified many interactions between HIV-1 and cellular factors, our understanding of where these interactions in cells occur during the course of infection is incomplete. Here, we show that multiple RNA-binding proteins (including the antiviral restriction factor, APOBEC3G, and MOV10 helicase) bind HIV-1 RNA genomes in the cytoplasm and co-traffic with them into progeny virions. Furthermore, we show that these interactions with HIV-1 RNA occur in the absence of Gag and are sufficiently strong to recruit these to otherwise non-native subcellular locales. Together, these data begin to illuminate the intracellular trafficking pathways shared by host RNA binding proteins and the viral RNAs they preferentially bind.