bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural representations of covert attention across saccades: comparing pattern similarity to shifting and holding attention during fixation
Authors: Zhang Xiaoli , Golomb Julie D 
Published: May 2020

AbstractWe can focus visuospatial attention by covertly attending to relevant locations, moving our eyes, or both simultaneously. How does shifting versus holding covert attention during fixation compare with maintaining covert attention across saccades? We acquired fMRI data during a combined saccade and covert attention task. On Eyes-fixed trials, participants either held attention at the same initial location (“hold attention”) or shifted attention to another location midway through the trial (“shift attention”). On Eyes-move trials, participants made a saccade midway through the trial, while maintaining attention in one of two reference frames: The “retinotopic attention” condition involved holding attention at a fixation-relative location but shifting to a different screen-centered location, whereas the “spatiotopic attention” condition involved holding attention on the same screen-centered location but shifting relative to fixation. We localized the brain network sensitive to attention shifts (shift > hold attention), and used multivoxel pattern time course analyses to investigate the patterns of brain activity for spatiotopic and retinotopic attention. In the attention shift network, we found transient information about both whether covert shifts were made and whether saccades were executed. Moreover, in the attention shift network, both retinotopic and spatiotopic conditions were represented more similarly to shifting than to holding covert attention. An exploratory searchlight analysis revealed additional regions where spatiotopic was relatively more similar to shifting and retinotopic more to holding. Thus, maintaining retinotopic and spatiotopic attention across saccades may involve different types of updating that vary in similarity to covert attention “hold” and “shift” signals across different regions.Significance StatementTo our knowledge, this study is the first attempt to directly compare human brain activity patterns of covert attention (to a peripheral spatial location) across saccades and during fixation. We applied fMRI multivoxel pattern time course analyses to capture the dynamic changes of activity patterns, with specific focus on the critical timepoints related to attention shifts and saccades. Our findings indicate that both retinotopic and spatiotopic attention across saccades produce patterns of activation similar to “shifting” attention in the brain, even though both tasks could be interpreted as “holding” attention by the participant. The results offer a novel perspective to understand how the brain processes and updates spatial information under different circumstances to fit the needs of various cognitive tasks.
NOT ALL ANTIBODIES HAVE BEEN CREATED EQUAL: Antibodies validated for routinely processed tissue seldom apply to frozen tissue sections
Authors: Bolognesi Maddalena M , Mascadri Francesco , Perego Roberto , Bombelli Silvia , Bosisio Francesca M , Cattoretti Giorgio 
Published: May 2020

ABSTRACTA customized context-dependent validation of antibodies for the prospective use, rather than a general stamp of validity, is required for reproducibility and data validity, besides the need of standardized reagents. In-situ antibody staining is a technique broadly used in experimental settings and human diagnostic practice. The first typically, but not exclusively uses lightly fixed material (cell smears, frozen sections), the second, routinely processed formalin-fixed, paraffin-embedded (FFPE) tissue. Differently from techniques based on tissue extraction, there is little awareness of the context-dependent constraints inherent with either type of in situ staining except that antigen masking associated with routine tissue processing limits the range of useful antibodies. We applied a panel of 126 antibodies validated for FFPE to lightly fixed (acetone, formalin) frozen sections and found that less than 30% performed conservatively with all fixations, 35% preferred one fixation over another, 13% gave non-specific staining, 23% did not stain at all. Individual antibody variegation of the paratope fitness for the differentially fixed antigen may be the cause. Re-validation of established antibody panels is required when applied to sections whose fixation and processing is different from the tissue where they have been initially validated.
The complex optic lobe of dragonflies
Authors: Fabian Joseph M. , el Jundi Basil , Wiederman Steven D. , O’Carroll David C. 
Published: May 2020

SummaryDragonflies represent an ancient lineage of visual predators, which last shared a common ancestor with insect groups such as dipteran flies in the early Devonian, 406 million years ago [1,2]. Despite their important evolutionary status, and recent interest in them as a model for complex visual physiology and behavior, the most recent detailed description of the dragonfly optic lobe is itself more than a century old [3]. Many insects process visual information in optic lobes comprising 4 sequential, retinotopically organized neuropils: the lamina, medulla, lobula and a posterior lobula plate devoted to processing information about wide-field motion stimuli [4, 5]. Recent reports suggest that the dragonflies also follow this basic plan, with a divided lobula similar to those of flies, moths and butterflies [6, 7]. Here we refute this claim, showing that dragonflies have an unprecedentedly complex lobula comprising at least 4 sequential synaptic neuropils, in addition to two lobula plate like structures located on opposite sides of the brain. The second and third optic ganglia contain approximately twice as many synaptic layers as any other insect group yet studied. Using intracellular recording and labeling of neurons we further show that the most anterior lobe contains wide-field motion processing tangential neurons similar to those of the posterior lobula plate of dipteran flies. In addition to describing what is probably the most complex and unique optic lobe of any insect to date, our findings provide interesting insights to understanding the evolution of the insect optic lobe and serve as a reminder that the highly studied visual circuits of dipteran flies represent just a single derived form of these brain structures.
Chrna5is essential for a rapid and protected response to optogenetic release of endogenous acetylcholine in prefrontal cortex
Authors: Venkatesan Sridevi , Lambe Evelyn K. 
Published: May 2020

AbstractOptimal attention performance requires cholinergic modulation of corticothalamic neurons in the prefrontal cortex. These pyramidal cells express specialized nicotinic acetylcholine receptors containing the α5 subunit encoded byChrna5. Disruption of this gene impairs attention, but the advantage α5 confers for the detection ofendogenouscholinergic signaling is unknown. To ascertain this underlying mechanism, we used optogenetics to stimulate cholinergic afferents in prefrontal cortex brain slices from compound-transgenic wild-type andChrna5knockout mice of both sexes. These electrophysiological experiments identify thatChrna5is critical for therapid onsetof the postsynaptic cholinergic response. Loss of α5 slows cholinergic excitation and delays its peak, and these effects are observed in two different optogenetic mouse lines. Disruption ofChrna5does not otherwise perturb the magnitude of the response, which remains strongly mediated by nicotinic receptors and tightly controlled by autoinhibition via muscarinic M2 receptors. However, when conditions are altered to promotesustainedcholinergic receptor stimulation, it becomes evident that α5 also works to protect nicotinic responses againstdesensitization. RescuingChrna5disruption thus presents the double challenge of improving the onset of cholinergic signaling without triggering desensitization. Here, we identify that an agonist for the unorthodox α-α nicotinic binding site can allosterically enhance this cholinergic pathway considered vital for attention. Minimal NS9283 treatment restores the rapid onset of the postsynaptic cholinergic response without triggering desensitization. Taken together, this work demonstrates the advantages of speed and resilience thatChrna5confers on endogenous cholinergic signaling, defining a critical window of interest for cue detection and attentional processing.Significance statementThe α5 nicotinic receptor subunit (Chrna5) is important for attention, but its advantage in detecting endogenous cholinergic signals is unknown. Here, we show that α5 subunits permit rapid cholinergic responses in prefrontal cortex and protect these responses from desensitization. Our findings clarify whyChrna5is required for optimal attentional performance under demanding conditions. To treat the deficit arising fromChrna5disruption without triggering desensitization, we enhanced nicotinic receptor affinity using NS9283 stimulation at the unorthodox α-α nicotinic binding site. This approach successfully restored the rapid-onset kinetics of endogenous cholinergic neurotransmission. In summary, we reveal a previously unknown role ofChrna5as well as an effective approach to compensate for genetic disruption and permit fast cholinergic excitation of prefrontal attention circuits.
Neural network modelling reveals changes in directional connectivity between cortical and hypothalamic regions in obesity
Authors: Voigt Katharina , Razi Adeel , Harding Ian H. , Andrews Zane B. , Verdejo-Garcia Antonio 
Published: May 2020

AbstractObesity has been ascribed to corticostriatal regions taking control over homeostatic areas. To test this assumption, we applied an effective connectivity approach to reveal the direction of information flow between brain regions and the valence of connections (excitatory versus inhibitory) as a function of adiposity and homeostatic state. Forty-one participants (21 overweight/obese) underwent two resting-state fMRI scans: after overnight fasting (hunger) and following a standardised meal (satiety). We used spectral dynamic causal modelling to unravel hunger and adiposity related changes in directed connectivity between cortical, insular, striatal and hypothalamic regions. During hunger, as compared to satiety, we found increased excitation of the ventromedial prefrontal cortex over the ventral striatum and hypothalamus, suggesting enhanced top-down modulation compensating energy depletion. Adiposity was associated with increased excitation of the anterior insula over the hypothalamus across the hunger and satiety conditions. The interaction of hunger and adiposity yielded decreased intra-cortical excitation from the dorsolateral to the ventromedial prefrontal cortex. Our findings suggest that obesity is associated with persistent top-down excitation of the hypothalamus, regardless of homeostatic state, and hunger-related reductions of dorsolateral to ventromedial prefrontal inputs. These findings are compatible with eating without hunger and reduced self-regulation views of obesity.Significance StatementObesity is a leading contributor to morbidity and mortality. Neurobiological theories propose that, in obese people, corticostriatal regions take over homeostatic areas. Neuroimaging-based functional connectivity is well-poised to unravel such abnormalities by examining between-regions communication, but existing studies have only measured signal covariance, not direction and valence of connectivity. We applied computational modelling to reveal the direction of information flow between brain regions and excitatory/inhibitory valence of connections in obese versus healthy-weight participants. Obesity associated with heightened top-down excitation from the insula to hypothalamus, and reduced excitation within prefrontal regions. Findings have two advantages relative to current knowledge: demonstrate theory-based directional abnormalities, i.e. cortical regions taking over homeostatic areas; and inform brain stimulation therapies targeting cortical input to lower-level regions.
Huntington’s disease-specific mis-splicing captured by human-mouse intersect-RNA-seq unveils pathogenic effectors and reduced splicing factors
Authors: Elorza Ainara , Márquez Yamile , Cabrera Jorge R. , Sánchez-Trincado José Luis , Santos-Galindo María , Hernández Ivó H. , Díaz-Hernández Juan Ignacio , García-Escudero Ramón , Irimia Manuel , Lucas José J. 
Published: May 2020

AbstractDeregulated alternative splicing has been implicated in a wide range of pathologies. Deep RNA-sequencing has revealed global mis-splicing signatures in multiple human diseases; however, for neurodegenerative diseases, these analyses are intrinsically hampered by neuronal loss and neuroinflammation in post-mortem brains. To infer splicing alterations relevant to Huntington’s disease (HD) pathogenesis, here we performed intersect-RNA-seq analyses of human post-mortem striatal tissue and of an early symptomatic mouse model in which neuronal loss and gliosis are not yet present. Together with a human/mouse parallel motif scan analysis, this approach allowed us to identify the shared mis-splicing signature triggered by the HD-causing mutation in both species and to infer upstream deregulated splicing factors. Moreover, we identified a plethora of downstream neurodegeneration-linked effector genes, whose aberrant splicing is associated with decreased protein levels in HD patients and mice. In summary, our intersect-RNA-seq approach unveiled the pathogenic contribution of mis-splicing to HD and could be readily applied to other neurodegenerative diseases for which bona fide animal models are available.
Lumi-Map, a real-time luciferase bioluminescence screen of mutants combined with MutMap, revealsArabidopsisgenes involved in PAMP-triggered immunity
Authors: Kato Hiroaki , Onai Kiyoshi , Abe Akira , Shimizu Motoki , Takagi Hiroki , Tateda Chika , Utsushi Hiroe , Singkarabanit-Ogawa Suthitar , Kitakura Saeko , Ono Erika , Zipfel Cyril , Takano Yoshitaka , Ishiura Masahiro , Terauchi Ryohei 
Published: May 2020

AbstractPlants recognize pathogen-associated molecular patterns (PAMPs) to activate PAMP-triggered immunity (PTI). However, our knowledge of PTI signaling remains limited. In this report, we introduce Lumi-Map, a high-throughput platform for identifying causative single nucleotide polymorphisms (SNPs) to studying PTI signaling components. In Lumi-Map, a transgenic reporter plant line is produced that contains a fireflyluciferase(LUC) gene driven by a defense gene promoter, which generates luminescence upon PAMP treatment. The line is mutagenized and the mutants with altered luminescence patterns are screened by a high-throughput real-time bioluminescence monitoring system. Selected mutants are subjected to MutMap analysis, a whole genome sequencing (WGS)-based method of rapid mutation identification, to identify the causative SNP responsible for the luminescence pattern change. We generated nine transgenicArabidopsisreporter lines expressingLUCgene fused to multiple promoter sequences of defense-related genes. These lines generate luminescence upon activation of FLAGELLIN-SENSING 2 (FLS2) by flg22, a PAMP derived from bacterial flagellin. We selected theWRKY29-promoter reporter line to identify mutants in the signaling pathway downstream ofFLS2. After screening 24,000 ethylmethanesulfonate (EMS)-induced mutants of the reporter line, we isolated 22 mutants with alteredWRKY29expression upon flg22 treatment (abbreviated asawfmutants). While five flg22-insensitiveawfmutants harbored mutations inFLS2itself, Lumi-Map revealed three genes not previously associated with PTI. Lumi-Map has the potential to identify novel PAMPs and their receptors as well as signaling components downstream of the receptors.
Meta-Align: A Novel HMM-based Algorithm for Pairwise Alignment of Error-Prone Sequencing Reads
Authors: Tomii Kentaro , Kumar Shravan , Zhi Degui , Brenner Steven E. 
Published: May 2020

AbstractBackgroundInsertion and deletion sequencing errors are relatively common in next-generation sequencing data and produce long stretches of mistranslated sequence. These frameshifting errors can cause very serious damages to downstream data analysis of reads. However, it is possible to obtain more precise alignment of DNA sequences by taking into account both coding frame and sequencing errors estimated by quality scores.ResultsHere we designed and proposed a novel hidden Markov model (HMM)-based pairwise alignment algorithm, Meta-Align, that aligns DNA sequences in the protein space, incorporating quality scores from the DNA sequences and allowing frameshifts caused by insertions and deletions. Our model is based on both an HMM transducer of a pair HMM and profile HMMs for all possible amino acid pairs. A Viterbi algorithm over our model produces the optimal alignment of a pair of metagenomic reads taking into account all possible translating frames and gap penalties in both the protein space and the DNA space. To reduce the sheer number of states of this model, we also derived and implemented a computationally feasible model, leveraging the degeneracy of the genetic code. In a benchmark test on a diverse set of simulated reads based on BAliBASE we show that Meta-Align outperforms TBLASTX which compares the six-frame translations of a nucleotide query sequence against the six-frame translations of a nucleotide sequence database using the BLAST algorithm. We also demonstrate the effects of incorporating quality scores on Meta-Align.ConclusionsMeta-Align will be particularly effective when applied to error-prone DNA sequences. The package of our software can be downloaded athttps://github.com/shravan-repos/Metaalign.
Ppd-1Remodels Spike Architecture by Regulating Floral Development in wheat
Authors: Liu Yangyang , Zhang Lili , Melzer Michael , Shen Liping , Sun Zhiwen , Wang Ziying , Schnurbusch Thorsten , Guo Zifeng 
Published: May 2020

AbstractThe determination of spike architecture is critical to grain yield in wheat (Triticum aestivum), yet the underlying mechanisms remain largely unknown. Here, we measured 51 traits associated with spike architecture and floral development in 197 wheat accessions with photoperiod sensitive and insensitive alleles. We included five distinct allele combinations at thePhotoperiod-1(Ppd-1) loci. A systematic dissection of all recorded phenotypes revealed connections between floral development, spike architecture and grain yield. Modifying the durations of spikelet primordia initiation did not necessarily affect spikelet number. In addition,Ppd-1loci clearly influenced rachis dry weight, pointing to the rachis vascular system as a potential target for higher yield.Ppd-1displayed opposite effects on the durations of pre and post-anthesis phases.Ppd-1controlled carpel size, but not anther size. Finally, the photoperiod-insensitive alleles ofPpd-1triggered floral degeneration. In parallel, we profiled the spike transcriptome at six stages and four positions in threePpd-1genotypes which consists of 234 samples. Integrating phenotypic and expression data suggested that loss of function inPpd-1loci delayed floral degeneration by regulating autophagy and extended floret development by regulating genes in different families. Therefore, we concluded thatPpd-1remodels spike architecture by regulating floral development in wheat.
The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals a new Arpp19/PP2A-B55 feedback loop
Authors: Labbé Jean Claude , Vigneron Suzanne , Méchali Francisca , Robert Perle , Genoud Cindy , Goguet-Rubio Perrine , Barthe Phillipe , Labesse Gilles , Cohen-Gonsaud Martin , Castro Anna , Lorca Thierry 
Published: May 2020

ABSTRACTArpp19 is a potent inhibitor of PP2A-B55 that regulates this phosphatase to ensure the stable phosphorylation of mitotic/meiotic substrates. At G2-M, Arpp19 is phosphorylated by Greatwall on S67. This phosphorylated Arpp19 form displays a high affinity to PP2A-B55 and a slow dephosphorylation rate, acting as an “unfair” competitor of PP2A-B55 substrates. The molecular determinants conferring slow dephosphorylation kinetics to S67 are unknown. PKA also phosphorylates Arpp19. This phosphorylation performed on S109 is essential to maintain prophase I-arrest in Xenopus oocytes although the underlying signaling mechanism is elusive. Here, we characterized the molecular determinants conferring slow dephosphorylation to S67 and controlling PP2A-B55 inhibitory activity of Arpp19. Moreover, we showed that phospho-S109 restricts S67 phosphorylation by increasing its catalysis by PP2A-B55. Finally, we discovered a double feed-back loop between these two phospho-sites which is essential to coordinate the temporal pattern of Arpp19-dependent PP2A-B55 inhibition and Cyclin B/Cdk1 activation during cell division.
Δ9-Tetrahydrocannabinolic Acid markedly alleviates liver fibrosis and inflammation in murine models of chemically- and obesity-induced liver injury
Authors: Carmona-Hidalgo Beatriz , González-Mariscal Isabel , García-Martín Adela , Ruiz-Pino Francisco , Appendino Giovanni , Tena-Sempere Manuel , Muñoz Eduardo 
Published: May 2020

ABSTRACTBackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, and it is closely associated to obesity, type 2 diabetes mellitus, and dyslipidemia. Hepatocellular stellate cells (HSCs) activation by oxidative stress and inflammation is the hallmark of liver fibrosis and leads to cirrhosis and liver failure resistant to pharmacological management. Cannabinoids have been suggested as a potential therapy for liver fibrosis, prompting us to explore the antifibrotic and anti-inflammatory effects of Δ9-THCA-A, a major non-psychotropic cannabinoid fromCannabis sativaL., in animal models of NAFLD.MethodsNon-alcoholic liver fibrosis was induced in mice by CCl4treatment or, alternatively, by 23-week high fat diet (HFD) feeding. Δ9-THCA was administered daily intraperitoneally during the CCl4treatment or during the last 3 weeks in HFD-fed mice. Liver fibrosis and inflammation were assessed by immunochemistry and qPCR. Blood glucose and plasma insulin, leptin and triglyceride levels were measured in HFD mice.ResultsΔ9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. Δ9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration.ConclusionsΔ9-THCA prevents liver fibrogenesisin vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, in the treatment of liver fibrosis and the management of NAFLD.