bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal principal component analysis to identify major features of white matter structure and links to reading
Authors: Geeraert Bryce L. , Chamberland Maxime , Lebel R. Marc , Lebel Catherine 
Published: May 2020

ABSTRACTThe role of white matter fibers in reading has been established by diffusion tensor imaging (DTI), but DTI cannot identify specific microstructural features driving these relationships. Neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT) can be used to link more specific aspects of white matter microstructure and reading due to their sensitivity to axonal packing and fiber coherence (NODDI) and myelin (ihMT and mcDESPOT). We applied principal component analysis (PCA) to combine DTI, NODDI, ihMT and mcDESPOT measures (10 in total), identify major features of white matter structure, and link these features to both reading and age. Analysis was performed for nine reading-related tracts in 46 neurotypical 6-16 year olds. We identified three principal components (PCs) which explained 79.5% of variance in our dataset. PC1 probed tissue complexity, PC2 described myelin and axonal packing, while PC3 was related to axonal diameter. Mixed effects models regressions did not identify any relationships between principal components and reading skill. Further Bayes factor analysis revealed that absence of relationships was not due to low power. PC1 suggested increases in tissue complexity with age in the left arcuate fasciculus, while PC2 suggested increases in myelin and axonal packing with age in the bilateral arcuate, inferior longitudinal, inferior fronto-occipital fasciculi, and splenium. Multimodal white matter imaging and PCA produce microstructurally informative, powerful principal components which can be used by future studies of development and cognition.
Inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation
Authors: Radwan Mona , Lilley Jordan D. , Ang Ching-Seng , Reid Gavin E. , Hatters Danny M. 
Published: May 2020

ABSTRACTPoly(glycine-alanine) (polyGA) is one of the dipolypeptides expressed in Motor Neuron Disease caused by C9ORF72 mutations and accumulates as inclusion bodies in the brain of patients. Superficially these inclusions are similar to those formed by polyglutamine (polyQ) in Huntington’s disease and both have been reported to form an amyloid-like structure suggesting they might aggregate via similar mechanisms to confer cellular dysfunction similarly. Here we investigated which endogenous proteins were enriched in these inclusions and whether aggregation-prone lengths of polyQ (Q97), in context of Huntingtin exon 1, shared similar patterns to aggregation-prone lengths of polyGA (101GA). When co-expressed in the same cell, polyGA101and HttQ97inclusions adopted distinct phases with no overlap suggesting different endogenous proteins would be enriched. Proteomic analyses indeed yielded distinct sets of endogenous proteins recruited into the inclusion types. The proteosome, microtubules, TriC chaperones, and translational machinery were enriched in polyGA aggregates, whereas Dnaj chaperones, nuclear envelope and RNA splicing proteins were enriched in polyQ aggregates. Both structures revealed a synergy of degradation machinery including proteins in the polyQ aggregates that are risk factors for other neurodegenerative diseases involving protein aggregation when mutated, which suggests a convergence point in the pathomechanisms of these diseases.
The effect of odor enrichment on olfactory acuity: Olfactometric testing in mice using two mirror-molecular pairs
Authors: Blount Alyson , Coppola David M. 
Published: May 2020

AbstractIntelligent systems in nature like the mammalian nervous system benefit from adaptable inputs that can tailor response profiles to their environment that varies in time and space. Study of such plasticity, in all its manifestations, forms a pillar of classical and modern neuroscience. This study is concerned with a novel form of plasticity in the olfactory system referred to as induction. In this process, subjects unable to smell a particular odor, or unable to differentiate similar odors, gain these abilities through mere exposure to the odor(s) over time without the need for attention or feedback (reward or punishment). However, few studies of induction have rigorously documented changes in olfactory threshold for the odor(s) used for “enrichment.” We trained 36 CD-1 mice in an operant-olfactometer (go/no go task) to discriminate a mixture of stereoisomers from a lone stereoisomer using two enantiomeric pairs: limonene and carvone. We also measured each subject’s ability to detect one of the stereoisomers of each odor. In order to assess the effect of odor enrichment on enantiomer discrimination and detection, mice were exposed to both stereoisomers of limonene or carvone for 2 to 12 weeks. Enrichment was effected by adulterating the subject’s food (passive enrichment) with one pair of enantiomers or by exposing them to the enantiomers in daily operant discrimination testing (active enrichment). We found that neither form of enrichment altered discrimination nor detection. And this result pertained using either within-subject or between-subject experimental designs. Unexpectedly, our threshold measurements were among the lowest ever recorded for any species, which we attributed to the relatively greater amount of practice (task replication) we allowed our mice compared to other reports. Interestingly, discrimination thresholds were no greater (limonene) or only modestly greater (carvone) from detection thresholds suggesting chiral-specific olfactory receptors determine thresholds for these compounds. The super-sensitivity of mice, shown in this study, to the limonene and carvone enantiomers, compared to the much lesser acuity of humans for these compounds, reported elsewhere, may resolve the mystery of why the former group with four-fold more olfactory receptors have tended, in previous studies, to have similar thresholds to the latter group. Finally, our results are consistent with the conclusion that supervised-perceptual learning i.e. that involving repeated feedback for correct and incorrect decisions, rather than induction, is the form of plasticity that allows animals to fully realize the capabilities of their olfactory system.
Ripasudil in a model of pigmentary glaucoma
Authors: Wang C , Dang Y , Waxman S , Hong Y , Shah P , Loewen RT , Xia X , Loewen NA 
Published: May 2020

AbstractPurposeTo investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma.MethodsHallmark features of trabecular meshwork (TM), the principle structure of the outflow system affected in this model, were analyzed. In vitro TM cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to sham-treated controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115.ResultsIn vitro, the percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8 +/- 2.9%; PK115: 11.6 +/- 3.3%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7+/-2.1%, PK115: 33.4+/-0.8%, P <0.01). Migration recuperated at 12h with K-115 treatment (P: 19.1+/-4.6 cells/high-power field, PK115: 42.5+/-1.6 cells/high-power field, P <0.001). Ex vivo, eyes became hypertensive from pigment dispersion but were normotensive after treatment with K-115 (P: 20.3 +/- 1.2 mmHg, PK115: 8.9 +/- 1.7 mmHg; P< 0.005).ConclusionIn vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure.
Punctuated Aneuploidization of the Budding Yeast Genome
Authors: Heasley Lydia R. , Watson Ruth A. , Argueso Juan Lucas 
Published: May 2020

AbstractRemarkably complex patterns of aneuploidy have been observed in the genomes of many eukaryotic cell types, ranging from brewing yeasts to tumor cells (1, 2). Such aberrant karyotypes are generally thought to take shape progressively over many generations, but evidence also suggests that genomes may undergo faster modes of evolution (2, 3). Here, we used diploidSaccharomyces cerevisiaecells to investigate the dynamics with which aneuploidies arise. We found that cells selected for the loss of a single chromosome often acquired additional unselected aneuploidies concomitantly. The degrees to which these genomes were altered fell along a spectrum, ranging from simple events affecting just a single chromosome, to systemic events involving many. The striking complexity of karyotypes arising from systemic events, combined with the high frequency at which we detected them, demonstrates that cells can rapidly achieve highly altered genomic configurations during temporally restricted episodes of genomic instability.
Data-driven learning how oncogenic gene expression locally alters heterocellular networks
Authors: Klinke David J. , Fernandez Audry , Deng Wentao , Latifizadeh Habibolla , Pirkey Anika C. 
Published: May 2020

ABSTRACTDiscovering and developing pharmaceutical drugs increasingly relies on mechanistic mathematical modeling and simulation. In immuno-oncology, models that capture causal relations among genetic drivers of oncogenesis, functional plasticity, and host immunity provide an important complement to wet experiments, given the cellular complexity and dynamics within tumors. Unfortunately, formulating such mechanistic cell-level models currently relies on hand curation by experts, which can bias how data is interpreted or the priority of drug targets. In modeling molecular-level networks, rules and algorithms have been developed to limit a priori biases in formulating mechanistic models. To realize an equivalent approach for cell-level networks, we combined digital cytometry with Bayesian network inference to generate causal models that link an increase in gene expression associated with onco-genesis with alterations in stromal and immune cell subsets directly from bulk transcriptomic datasets. To illustrate, we predicted how an increase in expression of Cell Communication Network factor 4 (CCN4/WISP1) altered the tumor microenvironment using data from patients diagnosed with breast cancer and melanoma. Digital cytometry and network inference predictions were then tested using two immunocompetent mouse models for melanoma, which provided consistent experimental results.
Yellow-Fruited Phenotype is Caused by an Insertion Event at 5’ UTR ofYFT1 Alleleinyft1Mutant Tomato1
Authors: Zhao Weihua , Gao Lei , Li Yuhang , Wang Minghui , Zhang Lida , Zhao Lingxia 
Published: May 2020

AbstractTheyft1tomato mutant has a yellow-fruited phenotype controlled by a recessive gene (YFT1), which has been shown by map-based cloning to be a homolog ofETHYLENE INSENSITIVE 2(EIN2). The genetic lesion of theYFT1allele ofyft1is attributed to a 573 bp DNA fragment (IF573) insertion at 1,200 bp downstream of the transcription start site (TSS). Transcriptome analysis revealed that the mutation resulted in 5,053 differentially expressed genes (DEGs) in the fruit pericarp compared with the M82 wild type cultivar. These were annotated as being involved in ethylene synthesis, chromoplast development, and carotenoid synthesis. Genetic lesion inYFT1caused a reduction in its own transcript levels inyft1and impaired ethylene emission and signal transduction, delayed chromoplast development and decreased carotenoid accumulation. The molecular mechanism underlying the reduced expression ofYFT1inyft1was examined at both the RNA and DNA levels. The IF573event was shown to introduce two negative regulatory sequences located at -272 to -173 bp and -172 to -73 bp in theYFT1allele promoter, causing alterative splicing due to aberrant splicing sites, and also altering the structure of the open reading frame in the 5’-UTR. This study contributes to the understanding of color formation in tomato fruit.One-sentence summaryLesion happened in regulatory region impairs expression of a key gene of ethylene signal pathway, and alters fruit color in tomato due to effect of carotenoids accumulation and ethylene synthesis.
Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats
Authors: Mofleh Rola , Kocsis Bernat 
Published: May 2020

AbstractAn explosion of recent findings firmly demonstrated that brain activity and cognitive function in rodents and humans are modulated synchronously with nasal respiration. Rhythmic respiratory (RR) coupling of wide-spread forebrain activity was confirmed using advanced techniques, including current source density analysis, single unit firing, and phase modulation of local gamma activity, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) allowing dynamic PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate (∼2 Hz) at rest, outside of the short sniffing bouts. We found strong and stable OB-PFC coherence, contrasting OB-HC coherence which was low but highly variable. PFC-HC coupling, however, primarily correlated with the latter, indicating that HC access to the PFC output is dynamically regulated by the responsiveness of HC to the common rhythmic drive. This pattern was present in both theta and non-theta states of waking, whereas PFC-HC communication appeared protected from RR synchronization in sleep states. The findings help to understand the mechanism of rhythmic modulation of non-olfactory cognitive processes by the on-going regular respiration, reported in rodents as well as humans. These mechanisms may be impaired when nasal breathing is limited or in OB-pathology, including malfunctions of the OB epithelium due to infections, such as in COVID-19.
Temporal signal and the phylodynamic threshold of SARS-CoV-2
Authors: Duchene Sebastian , Featherstone Leo , Haritopoulou-Sinanidou Melina , Rambaut Andrew , Lemey Philippe , Baele Guy 
Published: May 2020

AbstractThe ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real-time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus’s evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at 8 different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by February 2nd2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 to 122 genomes, converged at an evolutionary rate of about 1.1×10−3subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.
Retrograde labeling illuminates distinct topographical organization of D1 and D2 receptor-positive neurons in the prefrontal cortex of mice
Authors: Green Sara M. , Nathani Sanya , Zimmerman Joseph , Fireman David , Urs Nikhil M. 
Published: May 2020

ABSTRACTThe cortex plays an important role in regulating motivation and cognition, and does so by regulating multiple subcortical brain circuits. Glutamatergic pyramidal neurons in the prefrontal cortex (PFC) are topographically organized in different subregions such as the prelimbic, infralimbic and orbitofrontal, and project to topographically-organized subcortical target regions. Dopamine D1 and D2 receptors are expressed on glutamatergic pyramidal neurons in the PFC. However, it is unclear whether D1 and D2 receptor-expressing pyramidal neurons in the PFC are also topographically organized. We used a retrograde adeno-associated virus (AAVRG)-based approach to illuminate the topographical organization of D1 and D2 receptor-expressing neurons, projecting to distinct striatal and midbrain subregions. Our experiments reveal that AAVRG injection in the nucleus accumbens (NAcc) or dorsal striatum (dSTR) of D1Cre mice labeled distinct neuronal subpopulations in medial orbitofrontal or prelimbic PFC, respectively. However, AAVRG injection in NAcc or dSTR of D2Cre mice labeled medial orbitofrontal, but not medial prelimbic PFC, respectively. Additionally, D2R+ but not D1R+ PFC neurons were labeled upon injection of AAVRG in substantia nigra pars compacta (SNpc). Thus, our data are the first to highlight a unique dopamine receptor-specific topographical pattern in the PFC, which could have profound implications for corticostriatal signaling in the basal ganglia.SIGNIFICANCE STATEMENTCorticostriatal connections play an important role in regulating goal-directed and habitual behavior, and neuromodulators such as cortical dopamine play an important role in behavioral flexibility. Dopamine receptor expressing D1R+ and D2R+ projection neurons in the cortex mediate the effects of cortical dopamine, but whether these neurons are anatomically organized in a manner that would explain how these neurons mediate these complex effects, is not clear. Our results show a distinct topographical organization of D1R+ and D2R+ PFC pyramidal neurons that project to distinct striatal and midbrain subregions. These results suggest that effects of cortical dopamine are mediated by anatomically localized distinct receptor- and target-defined subcircuits.
Sexually monomorphic wing pigmentation pattern does not contribute to mate choice inDrosophila guttifera
Authors: Niida Takuma , Koshikawa Shigeyuki 
Published: May 2020

AbstractIn many animal groups, sexually dimorphic ornaments are thought to be evolved by intraspecific competition or mate choice. Some researchers pointed out that sexually monomorphic ornaments could also be evolved by mate choice by both sexes or either sex. Many species of fruit fly have sexually monomorphic wing pigmentation. However, involvement of their sexually monomorphic ornaments in mate choice has not been tested. We aimed to examine whether the sexually monomorphic polka-dotted pattern on wings ofDrosophila guttiferacontributes to mate choice. BecauseD. guttiferadoes not mate in the dark condition at all and courtship sound was not observed, some visual information is likely to be used in mating behaviour. We compared the number of mates between individuals with and without wings, and found that presence of wings influenced mate choice in both sexes. We then compared the number of mates between individuals bearing replaced wings, one group for conspecificD. guttiferawings and another group for heterospecificD. melanogasterwings with no pigmentation pattern. The effect of conspecific/heterospecific wings was only detected in mate choice by females. By comparison between wild-type and black-painted wings, we found no evidence of contribution of wing pigmentation pattern to mate choice in either sex.
HGF-induced activation of NEPHRIN and NEPH1 serves as a novel mechanism for recovery of podocytes from injury
Authors: Solanki Ashish K. , Srivastava Pankaj , Arif Ehtesham , Furcht Christopher M. , Rahman Bushra , Wen Pei , Singh Avinash , Holzman Lawrence B , Fitzgibbon Wayne R. , Lobo Glenn , Lipschutz Joshua H. , Kwon Sang-Ho , Han Zhe , Lazzara Matthew J , Nihalani Deepak 
Published: May 2020

ABSTRACTWhen activated, slit diaphragm proteins NEPHRIN and NEPH1 enable signaling pathways leading to podocyte actin cytoskeleton reorganization, which is critical for podocyte recovery from injury. However, the mechanisms through which these proteins are activated remain unknown. This study presents a novel concept showing ligand-induced activation of NEPHRIN and NEPH1. We first identified phosphatase SHP-2, which directly dephosphorylated these proteins. We next identified HGF, a known SHP-2 modulator, as a rapid inducer of NEPHRIN and NEPH1 phosphorylation. Using baculovirus expressed recombinant purified proteins, SPR (surface plasma resonance), molecular modeling and peptide binding approaches, we show that HGF directly binds NEPHRIN and NEPH1 extracellular domains. Further, using cultured podocytes and Drosophila nephrocytes, we demonstrate that while HGF treatment repaired injured podocytes, the addition of inhibitory NEPH1 or NEPHRIN peptides blocked HGF-induced recovery. Overall, this study shows novel activation and deactivation mechanisms for NEPHRIN and NEPH1 that are required for their function.
ai-corona: Radiologist-Assistant Deep Learning Framework for COVID-19 Diagnosis in Chest CT Scans
Authors: Yousefzadeh M. , Esfahanian P. , Movahed S. M. S. , Gorgin S. , Rahmati D. , Kiani A. , Nadji S. A. , Haseli S. , Hoseinyazdi M. , Roshandel J. , Karam M. Bakhshayesh , Abedini A. , Lashgari R. 
Published: May 2020

AbstractGeneration of medical assisting tools using recent artificial intelligence advances is beneficial for the medical workers in the global fight against COVID-19 outbreak. In this article we introduceai-corona, a radiologist-assistant deep learning framework for COVID-19 infection diagnosis using the chest CT scans. Our framework incorporates an Efficient NetB3-based feature extractor. We employed three independent dataset in this work named: CC-CCII, MDH, and MosMedData; all includes 7184 scans from 5693 subjects which contained pneumonia, common pneumonia (CP), non-pneumonia, normal and COVID-19 classes. We evaluatedai-coronaon test sets from the CC-CCII set and MDH cohort and the entirety of the MosMedData cohort, for which it gained AUC score of 0.997, 0.989, and 0.954, respectively. We further compared our framework’s performance with other deep learning models developed on our employed data sets, as well as RT-PCR. Our results show thatai-coronaoutperforms all. Lastly, our framework’s diagnosis capabilities was evaluated as assistant to several experts. We demonstrated an increase in both speed and accuracy of expert diagnosis when incorporatingai-corona’s assistance.