bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive capacity limits are remediated by practice-induced plasticity between the Putamen and Pre-Supplementary Motor Area
Authors: Garner K.G. , Garrido M.I. , Dux P.E. 
Published: March 2019

AbstractHumans show striking limitations in information processing when multitasking, yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 individuals and the plasticity caused by practice. We observed that multitasking costs, and their practice induced remediation, are best explained by modulations in information transfer between the striatum and the cortical areas that represent stimulus-response mappings. Specifically, our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). Moreover, we propose that modulations to information transfer between these two regions leads to practice-induced improvements in multitasking.Significance statementHumans show striking limitations in information processing when multitasking, yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 individuals and the plasticity caused by practice. Our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). We therefore show that models of cognitive capacity limits must consider how subcortical and cortical structures interface to produce cognitive behaviours, and we propose a novel neurophysiological substrate of multitasking limitations.
Streamlined low-input transcriptomics through EASY-RNAseq
Authors: Zhou Yiwen , Xu Hao , Wu Haiyang , Yu Haili , Zhou Peng , Qiu Xin , Zheng Zihan , Chen Qin , Xu Fa , Li Gang , Zhou Jianzhi , Cheng Gang , He Wei , Zou Liyun , Wan Ying 
Published: March 2019

ABSTRACTHigh-throughput sequencing for transcriptome profiling is an increasingly accessible and important tool for biological research. However, accurate profiling of small cell populations remains challenging due to issues with gene detection sensitivity and experimental complexity. Here we describe a streamlined RNAseq protocol (EASY RNAseq) for sensitive transcriptome assessment starting from low amount of input materials. EASY RNAseq is technically robust enough for sequencing small pools of homogenous and heterogeneous cells, recovering higher numbers of genes and with a more even expression distribution pattern than other commonly used methods. Application of EASY RNAseq to single human embryos at the 8-cell stage was able to achieve detection of 70% protein-coding genes. This workflow may thus serve as a useful tool for sensitive interrogation of rare cell populations.
Dynamic compression and expansion in a classifying recurrent network
Authors: Farrell Matthew , Recanatesi Stefano , Lajoie Guillaume , Shea-Brown Eric 
Published: March 2019

AbstractRecordings of neural circuits in the brain reveal extraordinary dynamical richness and high variability. At the same time, dimensionality reduction techniques generally uncover low-dimensional structures underlying these dynamics when tasks are performed. In general, it is still an open question what determines the dimensionality of activity in neural circuits, and what the functional role of this dimensionality in task learning is. In this work we probe these issues using a recurrent artificial neural network (RNN) model trained by stochastic gradient descent to discriminate inputs. The RNN family of models has recently shown promise in revealing principles behind brain function. Through simulations and mathematical analysis, we show how the dimensionality of RNN activity depends on the task parameters and evolves over time and over stages of learning. We find that common solutions produced by the network naturally compress dimensionality, while variability-inducing chaos can expand it. We show how chaotic networks balance these two factors to solve the discrimination task with high accuracy and good generalization properties. These findings shed light on mechanisms by which artificial neural networks solve tasks while forming compact representations that may generalize well.
LonP1 Orchestrates UPRmtand UPRERand Mitochondrial Dynamics to Regulate Heart Function
Authors: Lu Bin , Shangguan Fugen , Huang Dawei , Gong Shiwei , Shi Yingchao , Song Zhiying , Jia Lianqun , Xu Juan , Yan Chaojun , Chen Tongke , Xu Mingjie , Li Yujie , Han Shengnan , Song Nan , Chen Pingyi , Wang Lu , Liu Yongzhang , Huang Xingxu , Suzuki Carolyn K. , Yang Zhongzhou , Yang Guanlin 
Published: March 2019

AbstractProtein quality control is pivotal to cellular homeostasis and integrity of cardiomyocytes for maintenance of normal heart function. The unfolded protein response (UPR) is an adaptive process to modulate protein quality control in the endoplasmic reticulum (ER) and mitochondria, and is accordingly termed UPRERand UPRmt, respectively. Lon protease (LonP1) is a highly conserved mitochondrial protease to modulate UPRmt, which is involved in regulating metabolism, mitophagy, and stress response. However, whether LonP1 regulates UPRERremains elusive. To investigate the regulation of protein quality control in cardiomyocytes, we generated cardiac-specific LonP1 deletion mice. Our findings show that LonP1 deficiency caused impaired mitochondrial respiratory function and fragmentation. Surprisingly, both UPRERand UPRmtis substantially induced in LonP1-deletion heart suggesting of LonP1 as a novel regulator of UPRER; however, the activation of UPRERoccurs earlier than UPRmtin response to LonP1 deletion. Consequently, cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming of cardiomyocytes, pathological heart remodeling, as well as impeded heart function. Thus, we uncovered the novel function of LonP1 as an UPRmtmediator, and reciprocal orchestration of UPRmtand UPRERand mitochondrial dynamics regulated by LonP1 in the cardiomyocytes that is critical to maintain heart function, which offers exciting new insights into the potential therapeutic strategy for heart failure.
Glycosylation of Zika Virus Is Important in Host-Virus Interaction and Pathogenesis
Authors: Routhu Nanda Kishore , Lehoux Sylvain D. , Rouse Emily A. , Bidokhti Mehdi R. M. , Giron Leila B. , Anzurez Alit , Reid St Patrick , Abdel-Mohsen Mohamed , Cummings Richard D. , Byrareddy Siddappa N. 
Published: March 2019

AbstractZika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. Because ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry, these interactions could also be important for designing therapeutics and vaccines. Due to a lack of information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. ZIKV E proteins are extensively modified with oligomannose-, hybrid- and complex-N-glycans of a highly heterogeneous nature. Host cell-surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we discovered that ZIKV N-glycans are important in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
RB1 deletion in RB-pathway disrupted cells results in DNA damage and cancer progression
Authors: Marshall Aren E. , Roes Michael V. , Passos Daniel T. , DeWeerd Megan C. , Chaikovsky Andrea C. , Sage Julien , Howlett Christopher J. , Dick Frederick A. 
Published: March 2019

SummaryProliferative control in cancer cells is frequently disrupted by mutations in the RB-pathway. Intriguingly, RB1 mutations can arise late in tumorigenesis in cancer cells whose RB-pathway is already compromised by another mutation. In this study, we present evidence for increased DNA damage and instability in CDKN2A silenced cancer cells when RB1 mutations are induced. We generated isogenic RB1 mutant genotypes with CRISPR in a number of cell lines. Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. Elevated levels of reactive oxygen species as well as impaired homologous recombination repair underlie this DNA damage. When xenografted into immune compromised mice RB1 mutant cells exhibit an elevated propensity to seed new tumors in recipient lungs. This study offers evidence that late arising RB1 mutations can facilitate genome instability and cancer progression that are beyond the pre-existing proliferative control deficit.
High-throughput genotyping of a full voltage-gated sodium channel gene via genomic DNA using target capture sequencing and analytical pipeline MoNaS to discover novel insecticide resistance mutations
Authors: Itokawa Kentaro , Yatsu Koji , Sekizuka Tsuyoshi , Maekawa Yoshihide , Komagata Osamu , Sugiura Masaaki , Sasaki Tomonori , Tomita Takashi , Kuroda Makoto , Sawabe Kyoko , Kasai Shinji 
Published: March 2019

AbstractInsects’ voltage-gated sodium channel (VGSC) is the primary target site of pyrethroid insecticides. Various amino acid substitutions in the VGSC protein are known to confer insecticide resistance and are selected under insecticide pressure. In the genome, theVGSCgene consists of more than 30 exons sparsely distributed across a large genomic region, which often exceeds 100 kbp. Due to this complex genomic structure of geneVGSC, it is usually challenging to genotype full coding nucleotide sequences (CDSs) ofVGSCfrom individual genomic DNA (gDNA). In this study, we designed biotinylated oligonucleotide probes via annotated CDSs ofVGSCof Asian tiger mosquito,Aedes albopictus. The probe set effectively concentrated (>80,000-fold) all targeted regions of geneVGSCfrom pooled barcoded Illumina libraries each constructed from individualA. albopictusgDNAs. The probe set also captured all homologousVGSCCDSs except tiny exons from the gDNA of other Culicinae mosquitos,A. aegyptiandCulex pipienscomplex, with comparable efficiency by virtue of the high conservation ofVGSCat the nucleotide level. Furthermore, we developed an automated bioinformatic analysis pipeline to genotypeVGSCafter capture sequencing—MoNaS (MosquitoNa+channel mutationSearch)—which conducts mapping of reads, variant calling, and variant annotation for nonsynonymous mutations. The proposed method and our bioinformatic tool should facilitate the discovery of novel amino acid variants conferring insecticide resistance on VGSC and population genetics studies on resistance alleles with respect to the origin, selection, and migration of both clinically and agriculturally important insect pests.
Pluripotency factors regulate the onset of Hox cluster activation in the early embryo
Authors: Lopez-Jimenez Elena , de Aja Julio Sainz , Badia-Careaga Claudio , Barral Antonio , Rollan Isabel , Rouco Raquel , Santos Elisa , Tiana María , Victorino Jesus , Sanchez-Iranzo Hector , Acemel Rafael D , Torroja Carlos , Adan Javier , Andres-Leon Eduardo , Gomez-Skarmeta Jose Luis , Giovinazzo Giovanna , Sanchez-Cabo Fatima , Manzanares Miguel 
Published: March 2019

ABSTRACTPluripotent cells are a transient population present in the early mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while simultaneously suppressing lineage specification. Interestingly, these factors are not exclusive to uncommitted cells, but are also expressed during early phases of differentiation. However, their role in the transition from pluripotency to lineage specification is largely unknown. Using genetic models for controlledOct4orNanogexpression during postimplantation stages, we found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that the HoxB cluster is coordinately regulated in this way by OCT4 binding sites located at the 3’ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the pre-committed epiblast, but are also necessary for the proper deployment of subsequent developmental programs.
Dopaminergic signalling is necessary, but not sufficient for cued fear memory destabilisation
Authors: Flavell Charlotte R. , Lee Jonathan L. C. 
Published: March 2019

AbstractPharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. Here, we show that the nootropic nefiracetam stimulates tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Moreover, the enhancing effect of nefiracetam was dependent upon dopamine D1 receptor activation, although direct D1 receptor agonism was not sufficient to facilitate destabilisation. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. Therefore, the use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear.
Neph/Nephrin-like adhesion and tissue level pulling forces regulate cell intercalation during Drosophila retina development
Authors: Blackie Laura , Tozluoglu Melda , Trylinski Mateusz , Walther Rhian F. , Mao Yanlan , Schweisguth François , Pichaud Franck 
Published: March 2019

SUMMARYIntercalation between neighboring cells contributes to shaping epithelial tissues and is regulated by the contractile actomyosin cytoskeleton. While intercalation typically occurs over minutes, instances of much slower cell intercalation have been reported during organogenesis. This is observed, for example, for the four glial-like cone cells (CC) that intercalate during Drosophila retinal patterning. Here we show that Myosin-II activity in the CCs is largely dispensable for their intercalation. Instead, we find that differential activity of the Notch-signaling pathway within the CC quartet regulates intercalation, which also depends on the cell adhesion proteins Roughest and Hibris. In addition, mathematical modeling predicts that forces external to the intercalating CC quartet are necessary for intercalation. Consistent with this prediction we show that the surrounding primary pigment cells are under significant contractile tension. Altogether, our work elucidates a novel mode of cell intercalation that relies on Neph/Nephrin-like adhesion and forces external to the intercalating cells.
Lifespan trajectories and relationships to memory of the macro- and microstructure of the anterior and posterior hippocampus – a longitudinal multi-modal imaging study
Authors: Langnes Espen , Sneve Markus H. , Sederevicius Donatas , Amlien Inge K. , Walhovd Kristine B , Fjell Anders M 
Published: March 2019

AbstractThere is evidence for a hippocampal long axis anterior-posterior (AP) differentiation in memory processing, which may have implications for the changes in episodic memory performance typically seen across development and aging. The hippocampal formation shows substantial structural changes with age, but the lifespan trajectories of hippocampal sub-regions along the AP axis are not established. The aim of the present study was to test whether the micro- and macro-structural age-trajectories of the anterior (aHC) and posterior (pHC) hippocampus are different. In a single-center longitudinal study, 1790 cognitively healthy participants, 4.1-93.4 years of age, underwent a total of 3367 MRI examinations and 3033 memory tests sessions over 1-6 time points, spanning an interval up to 11.1 years. T1-weighted scans were used to estimate the volume of aHC and pHC, and diffusion tensor imaging to measure mean diffusion (MD) within each region. We found that the macro- and microstructural lifespan-trajectories of aHC and pHC were clearly distinguishable, with partly common and partly unique variance shared with age. aHC showed a protracted period of microstructural development, while pHC microstructural development as indexed by MD was more or less completed in early childhood. In contrast, pHC showed larger unique aging-related changes. A similar aHC – pHC difference was observed for volume, although not as evident as for microstructure. All sub-regions showed age-dependent relationships to episodic memory function. For aHC micro- and macrostructure, the relationships to verbal memory performance varied significantly with age, being stronger among the older participants. Future research should disentangle the relationship between these structural properties and different memory processes – encoding vs. retrieval in particular – across the lifespan.
Spatial co-fragmentation pattern of cell-free DNA recapitulatesin vivochromatin organization and identifies tissues-of-origin
Authors: Liu Yaping , Liu Tzu-Yu , Weinberg David E. , White Brandon W. , De La Torre Chris J. , Tan Catherine L. , Schmitt Anthony D. , Selvaraj Siddarth , Tran Vy , Laurent Louise C. , Cabel Luc , Bidard François-Clément , Putcha Girish , Haque Imran S. 
Published: March 2019

ABSTRACTThree-dimensional chromatin organization varies across cell types and is essential for gene regulation. However, current technologies are unable to assessin vivogenome-wide chromatin organization non-invasively. Here we show that distant correlations in the fragment length of cell-free DNA (cfDNA) recapitulate three-dimensional chromatin organization. The inferred organization is highly concordant with that measured by Hi-C in white blood cells from healthy donors, and is not explained by technical bias or sequence composition. Furthermore, the inferred organization reflects different genomic organization in the various cell types contributing to cfDNA, allowing identification and quantification of tissues of origin. This approach is concordant with previous methods, but with more complete representations of cfDNA. Our results, demonstrated in cfDNA from healthy individuals and cancer patients, may enable noninvasive monitoring ofin vivogenome organization and accurate quantification of cell death in different clinical conditions.
Cue-induced effects on decision-making distinguish subjects with gambling disorder from healthy controls
Authors: Genauck Alexander , Andrejevic Milan , Brehm Katharina , Matthis Caroline , Heinz Andreas , Weinreich André , Kathmann Norbert , Romanczuk-Seiferth Nina 
Published: March 2019

ABSTRACTWhile an increased impact of cues on decision-making has been associated with substance dependence, it is yet unclear whether this is also a phenotype of non-substance related addictive disorders, such as gambling disorder. To better understand the basic mechanisms of impaired decision-making in addiction, we investigated whether cue-induced changes in decision-making could distinguish gambling disorder (GD) from healthy control (HC) subjects. We expected that cue-induced changes in gamble acceptance and specifically in loss aversion would distinguish GD from HC subjects.30 GD subjects and 30 matched HC subjects completed a mixed gambles task where gambling and other emotional cues were shown in the background. We used machine learning and classification to carve out the importance of cue-dependency of decision-making and of loss aversion for distinguishing GD from HC subjects.Cross-validated classification yielded an area under the receiver operating curve (AUC-ROC) of 68.9% (p=0.002). Applying the classifier to an independent sample yielded an AUC-ROC of 65.0% (p=0.047). As expected, the classifier used cue-induced changes in gamble acceptance to distinguish GD from HC. Especially increased gambling during the presentation of gambling cues was characteristic of GD subjects. However, unexpectedly, cue-induced changes in loss aversion were irrelevant for distinguishing GD from HC subjects. To our knowledge, this is the first study to investigate the classificatory power of addiction-relevant behavioral task parameters when distinguishing GD from HC subjects. The results indicate that cue-induced changes in decision-making are a characteristic feature of addictive disorders, independent of a substance of abuse.
siRNA containing a unique 5-nucleotide motif acts as a quencher of IFI16-mediated innate immune response
Authors: Sui Hongyan , Yang Jun , Hu Xiaojun , Chen Qian , Imamichi Tomozumi 
Published: March 2019

AbstractWe previously reported that small interfering RNA (siRNA) enhances DNA or DNA virus mediated-interferon (IFN)-λ1 induction through retinoic acid-inducible gene I (RIG-I) and interferon gamma-inducible protein 16 (IFI16) crosstalk-signalling pathway. Here we provide further evidence of a new role for siRNA. siRNA containing a 5-nucleotide (nt) motif sequence suppresses DNA-mediated IFNs and inflammatory cytokines. We determined that motif siRNA inhibits the induction when the motif is located at the 3’ or 5’-terminus of siRNA. Using THP1-Lucia ISG cells with various DNA stimulants, it is demonstrated that motif siRNA inhibits DNA or DNA virus but not RNA virus-mediated signaling. Motif siRNA specifically interrupts IFI16 binding to DNA and has 2.5-fold higher affinity to IFI16 than that of siRNA without the motif. Collectively, these findings may shed lights on a novel function of siRNA with the 5-nt motif as a quencher of innate immunity and facilitate the development of potential therapeutics to treat diseases in which this pathway is dysregulated.
Mannitol ingestion causes concentration-dependent, sex-specific mortality in adults of the fruit fly (Drosophila melanogaster)
Authors: Fiocca Katherine , Barrett Meghan , Waddell Edward A. , McNair Cheyenne , O’Donnell Sean , Marenda Daniel R. 
Published: March 2019

AbstractMannitol, a sugar alcohol used in commercial food products, induced sex-specific mortality in the fruit flyDrosophila melanogasterwhen ingested at a single concentration (1M), and female mortality was greater than male mortality. We hypothesized that sex differences in energy needs, related to reproductive costs, contribute to increased mortality in females compared to males. To test for the effects of reproductive costs, we compared longevity to 21 days of actively mating and non-mating flies fed various concentrations of mannitol. We also asked whether mannitol-induced mortality was concentration-dependent for both males and females, and if mannitol’s sex-specific effects were consistent across concentrations. Females and males both showed concentration-dependent increases in mortality, but female mortality was consistently higher at all concentrations above 0.75M. Fly longevity to 21 days decreased further for both sexes when housed in mixed sex vials (as compared to single sex vials), suggesting the increased energetic demands of reproduction for both sexes may increase ingestion of mannitol. Mannitol fed to larvae did not alter emerging adult sex ratios, suggesting that sex-specific mortality due to mannitol occurs only in adults.