bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ciona Brachyuryproximal and distal enhancers have different FGF dose-response relationships
Authors: Harder Matthew J. , Hix Julie , Reeves Wendy M. , Veeman Michael T. 
Published: August 2020

AbstractMany genes are regulated by two or more enhancers that drive similar expression patterns. Evolutionary theory suggests that these seemingly redundant enhancers must have functionally important differences. In the simple ascidian chordateCiona, the transcription factor Brachyury is induced exclusively in the presumptive notochord downstream of lineage specific regulators and FGF-responsive Ets family transcription factors. Here we exploit the ability to finely titrate FGF signaling activity via the MAPK pathway using the MEK inhibitor U0126 to quantify the dependence of transcription driven by differentBrachyuryreporter constructs on this direct upstream regulator. We find that the more powerful promoter-adjacent proximal enhancer and a weaker distal enhancer have fundamentally different dose-response relationships to MAPK inhibition. The Distal enhancer is more sensitive to MAPK inhibition but shows a less cooperative response, whereas the Proximal enhancer is less sensitive and more cooperative. A longer construct containing both enhancers has a complex dose-response curve that supports the idea that the proximal and distal enhancers are moderately super-additive. We show that the overall expression loss from intermediate doses of U0126 is not only a function of the fraction of cells expressing these reporters, but also involves graded decreases in expression at the single-cell level. Expression of the endogenous gene shows a comparable dose-response relationship to the full length reporter, and we find that different notochord founder cells are differentially sensitive to MAPK inhibition. Together, these results indicate that although the twoBrachyuryenhancers have qualitatively similar expression patterns, they respond to FGF in quantitatively different ways and act together to drive high levels ofBrachyuryexpression with a characteristic input/output relationship. This indicates that they are fundamentally not redundant genetic elements.
Colour vision and information theory: the receptor noise-limited model implies optimal colour discrimination by opponent channels
Authors: Risau-Gusman Sebastián 
Published: August 2020

AbstractIn order to interpret animal behaviour we need to understand how they see the world. As colour discrimination is almost impossible to test directly in animals, it is important to develop theoretical models based in the properties of visual systems. One of the most successful is the receptor noise-limited (RNL) model, which depends only on the level of noise in photoreceptors and opponent mechanisms. Here optimal colour discrimination properties are obtained using information theoretical tools, for the early stages of visual systems with and without colour opponent mechanisms. For most biologically relevant conditions the optimal discrimination function of an ideal observer coincides with the one obtained with the RNL model. Many variants of the model can be cast into the same framework, which permits meaningful comparisons across species. For example, it is shown that the presence of opponency seems to be the preferred hypothesis for bees, but not for budgerigars. Since this is a consequence of the presence of oil droplets, this could also be true for most other species of birds.
Reduction of Short-Chain Fatty Acid-Producing Gut Microbiota Leads to Transition from Rapid-Eye-Movement Sleep Behavior Disorder to Parkinson’s Disease
Authors: Nishiwaki Hiroshi , Hamaguchi Tomonari , Ito Mikako , Ishida Tomohiro , Maeda Tetsuya , Kashihara Kenichi , Tsuboi Yoshio , Ueyama Jun , Shimamura Teppei , Mori Hiroshi , Kurokawa Ken , Katsuno Masahisa , Hirayama Masaaki , Ohno Kinji 
Published: August 2020

AbstractGut dysbiosis has been reported repeatedly in Parkinson’s disease (PD), but once in rapid-eye-movement sleep behavior disorder (RBD) from Germany. Abnormal aggregation of α-synuclein fibrils causing PD possibly starts from the intestine. RBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in RBD. We analyzed gut microbiota in 26 RBD patients and 137 controls by 16S rRNA-seq. Our RBD dataset was meta-analyzed with the German RBD dataset, and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA-seq analysis, revealed four enterotypes in controls, RBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and RBD, whereas they were less in enterotypes observed in PD. GenusAkkermansiaand familyAkkermansiaceaewere consistently increased in both RBD in two countries and PD in five countries. No short-chain fatty acid (SCFA)-producing bacteria were significantly changed in RBD in two counties. In contrast, we previously reported that recognized and putative SCFA-producing generaFaecalibacterium,Roseburia, andLachnospiraceae ND3007 groupwere consistently decreased in PD in five countries. Increased mucin-layer-degrading genusAkkermansiapossibly accounts for the development of RBD, and an additional decrease of SCFA-producing genera is likely to be associated with the transition from RBD to PD.ImportanceNineteen studies have been reported on gut microbiota in PD, whereas only one study has been reported in RBD from Germany. RBD has the highest likelihood ratio to develop PD. Our meta-analysis of RBD in Japan and Germany revealed increased mucin-layer-degrading genusAkkermansiain RBD. GenusAkkermansiamay increase the intestinal permeability, as we previously observed in PD patients, and make the intestinal neural plexus exposed to oxidative stress, which can lead to abnormal aggregation of prion-like α-synuclein fibrils in the intestine. In contrast to PD, SCFA-producing bacteria were not decreased in RBD. As SCFA induces Treg cells, a decrease of SCFA-producing bacteria may be a prerequisite for the development of PD. We propose that prebiotic and/or probiotic therapeutic strategies to increase the intestinal mucin layer and to increase intestinal SCFA potentially retard the development of RBD and PD.
Constitutive Androstane Receptor and Hepatitis B Virus X Protein Cooperatively Induce β-catenin-Activated Liver Tumors
Authors: Scott Jessica D. , Liu Silvia , Klatt Kevin C. , Sun Zhen , Guo Qi , Grimm Sandra L. , Coarfa Cristian , Dong Bingning , Moore David D. 
Published: August 2020

AbstractBackground and AimsThe xenobiotic nuclear receptor Constitutive Androstane Receptor (CAR) is essential for xenobiotic tumor promotion in mouse models. In these models, β-catenin is genetically activated in approximately 80% of tumors. Chronic Hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and β-catenin activation is also frequently activated in HBV-associated HCCs. The goal of this research was to determine whether activation of CAR in a mouse model of chronic HBV infection would result in tumor formation and whether these tumors would display increased β-catenin activation.Approach and ResultsWe treated transgenic mice expressing the HBV X protein (HBx) in hepatocytes with a single dose of the potent CAR agonist TCPOBOP. After 10 months, these mice developed large liver tumors that are characterized by β-catenin nuclear localization and upregulation of β-catenin targets. The β-catenin regulator FoxM1 and the oxidative stress master regulator Nrf2, both of which are CAR gene targets, were also overactivated in tumors. The CAR/HBx tumors share a conserved gene signature with HBV-related human hepatocellular carcinoma.ConclusionsActivation of CAR in the presence of HBx results in tumors with strong β-catenin activation. The mouse model we have described reflects the gene expression patterns seen in human HBV-associated HCC and presents an attractive basis for future studies.
Deep Learning assisted Peak Curation for large scale LC-MS Metabolomics
Authors: Gloaguen Yoann , Kirwan Jennifer , Beule Dieter 
Published: August 2020

ABSTRACTAvailable automated methods for peak detection in untargeted metabolomics suffer from poor precision. We present NeatMS which uses machine learning to replace peak curation by human experts. We show how to integrate our open source module into different LC-MS analysis workflows and quantify its performance. NeatMS is designed to be suitable for large scale studies and improves the robustness of the final peak list.
Engineered Reproductively Isolated Species Drive Reversible Population Replacement
Authors: Buchman Anna , Shriner Isaiah , Yang Ting , Liu Junru , Antoshechkin Igor , Marshall John M. , Perry Michael W. , Akbari Omar S. 
Published: August 2020

AbstractEngineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. To overcome this challenge, we engineered SPECIES (SyntheticPostzygotic barriersExploitingCRISPR-basedIncompatibilities forEngineeringSpecies) to generate postzygotic reproductive barriers. Using this approach, we engineer multiple reproductively isolated SPECIES and demonstrate their threshold-dependent gene drive capabilities inD. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.One Sentence SummarySynthetically engineered SPECIES drive confinable population replacement.
Action Potentials and Na+ voltage-gated ion channels in Placozoa
Authors: Romanova Daria Y. , Smirnov Ivan V. , Nikitin Mikhail A. , Kohn Andrea B. , Borman Alisa I. , Malyshev Alexey Y. , Balaban Pavel M. , Moroz Leonid L. 
Published: August 2020

AbstractPlacozoa are small disc-shaped animals, representing the simplest known, possibly ancestral, organization of free-living animals. With only six morphological distinct cell types, without any recognized neurons or muscle, placozoans exhibit fast effector reactions and complex behaviors. However, little is known about electrogenic mechanisms in these animals. Here, we showed the presence of rapid action potentials in four species of placozoans (Trichoplax adhaerens [H1 haplotype], Trichoplax sp.[H2], Hoilungia hongkongensis [H13], and Hoilungia sp. [H4]). These action potentials are sodium-dependent and can be inducible. The molecular analysis suggests the presence of 5-7 different types of voltage-gated sodium channels, which showed substantial evolutionary radiation compared to many other metazoans. Such unexpected diversity of sodium channels in early-branched animal lineages reflect both duplication events and parallel evolution of unique behavioral integration in these nerveless animals.HighlightsPlacozoans are the simplest known animals without recognized neurons and musclesWith only six morphological cell types, placozoans showed complex & rapid behaviorsSodium-dependent action potentials have been discovered in intact animalsVoltage-gated sodium channels (Nav) in Placozoa support a rapid behavioral integrationPlacozoans have more Nav channels that any studied invertebrate animal so farDiversification of Nav-channels highlight the unique evolution of these nerveless animals
A hardware/software system for electrophysiology “supersessions” in marmosets
Authors: Muthmann Jens-Oliver , Levi Aaron J. , Carney Hayden C. , Huk Alexander C. 
Published: August 2020

AbstractWe introduce a straightforward, robust method for recording and analyzing spiking activity over timeframes longer than a single session, with primary application to the marmoset (Callithrix jacchus). Although in theory the marmoset’s smooth brain allows for broad deployment of powerful tools in primate cortex, in practice marmosets do not typically engage in long experimental sessions akin to rhesus monkeys. This potentially limits their value for detailed, quantitative neurophysiological study. Here we describe chronically-implanted arrays with a 3D arrangement of electrodes yielding stable single and multi-unit responses, and an analytic method for creating “supersessions” combining that array data across multiple experiments. We could match units across different recording sessions over several weeks, demonstrating the feasibility of pooling data over sessions. This could be a key tool for extending the viability of marmosets for dissecting neural computations in primate cortex.
Long-read transcriptome and other genomic resources for the angiospermSilene noctiflora
Authors: Williams Alissa M. , Itgen Michael W. , Broz Amanda K. , Carter Olivia G. , Sloan Daniel B. 
Published: August 2020

AbstractThe angiosperm genusSileneis a model system for several traits of ecological and evolutionary significance in plants, including breeding system and sex chromosome evolution, host-pathogen interactions, invasive species biology, heavy metal tolerance, and cytonuclear interactions. Despite its importance, genomic resources for this large genus of approximately 850 species are scarce, with only one published whole-genome sequence (from the dioecious speciesS. latifolia). Here, we provide genomic and transcriptomic resources for a hermaphroditic representative of this genus (S. noctiflora), including a PacBio Iso-Seq transcriptome, which uses long-read, single-molecule sequencing technology to analyze full-length mRNA transcripts and identify paralogous genes and alternatively spliced genes. Using these data, we have assembled and annotated high-quality full-length cDNA sequences for approximately 17,000S. noctifloragenes and 27,000 isoforms. We demonstrated the utility of these data to distinguish between recent and highly similar gene duplicates by identifying novel paralogous genes in an essential protease complex. Further, we provide a draft assembly for the approximately 2.7-Gb genome of this species, which is near the upper range of genome-size values reported for diploids in this genus and three-fold larger than the 0.9-Gb genome ofS. conica, another species in the same subgenus. Karyotyping confirmed thatS. noctiflorais a diploid, indicating that its large genome size is not due to polyploidization. These resources should facilitate further study and development of this genus as a model in plant ecology and evolution.
Susceptibility to gingipains and transcriptomic response toP. gingivalishighlights the ribosome, hypothalamus, and cholinergic neurons
Authors: Patel Sejal , Howard Derek , French Leon 
Published: August 2020

AbstractPorphyromonas gingivalis, a keystone species in the development of periodontal disease, is a suspected cause of Alzheimer’s disease. This bacterium is reliant on gingipain proteases, which cleave host proteins after arginine and lysine residues. To characterize gingipain susceptibility, we performed enrichment analyses of arginine and lysine proportion proteome-wide. Proteins in the SRP-dependent cotranslational protein targeting to membrane pathway were enriched for these residues and previously associated with periodontal and Alzheimer’s disease. These ribosomal genes are up-regulated in prefrontal cortex samples with detectedP. gingivalissequences. Other differentially expressed genes have been previously associated with dementia (ITM2B, MAPI, ZNF267, andDHX37). For an anatomical perspective, we characterized the expression of theP. gingivalisassociated genes in the mouse and human brain. This analysis highlighted the hypothalamus, cholinergic neurons, and the basal forebrain. Our results suggest markers of neuralP. gingivalisinfection and link the gingipain and cholinergic hypotheses of Alzheimer’s disease.
Urinary proteome profiling for stratifying patients with familial Parkinson’s disease
Authors: Winter Sebastian Virreira , Karayel Ozge , Strauss Maximilian T , Padmanabhan Shalini , Surface Matthew , Merchant Kalpana , Alcalay Roy N. , Mann Matthias 
Published: August 2020

SUMMARYThe prevalence of Parkinson’s disease (PD) is increasing but the development of novel treatment strategies and therapeutics altering the course of the disease would benefit from specific, sensitive and non-invasive biomarkers to detect PD early. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomic workflow for urinary proteome profiling. Our workflow enabled the reproducible quantification of more than 2,000 proteins in more than 200 urine samples using minimal volumes from two independent patient cohorts. The urinary proteome was significantly different between PD patients and healthy controls, as well as betweenLRRK2G2019S carriers and non-carriers in both cohorts. Interestingly, our data revealed lysosomal dysregulation in individuals with theLRRK2G2019S mutation. When combined with machine learning, the urinary proteome data alone was sufficient to classify mutation status and disease manifestation in mutation carriers remarkably well, identifying VGF, ENPEP and other PD-associated proteins as the most discriminating features. Taken together, our results validate urinary proteomics as a valuable strategy for biomarker discovery and patient stratification in PD.
Varying intestinal absorption curves of glucose and fat with different plasma insulin curves in different positions
Authors: Yang Junhua , Wang Ling , Song Linyang , Li Guoying , Jin Xiaobao , Tian Sumin 
Published: August 2020

AbstractIt has been shown that posture could affect the rehabilitation of some diseases, and even affect the physiological metabolism and function of certain systems of the human body, including gastrointestinal absorption of glucose. Studies attributed the different gastrointestinal absorption rate in different positions to the varying rate of gastric emptying in different positions. However, it is still unknown whether the absorption rate of nutrients from the intestine varies in different positions. To verify this hypothesis, the present study was conducted using rats as subjects. After injection of glucose or chyme of safflower oil into the upper segment of jejunum of rats, curves of plasma glucose or triglyceride were drawed to evaluate and compare the potential influences on intestinal absorption by postures. We found varying intestinal absorption curves of glucose and fat with different plasma insulin curves in different positions. To be specific, the right lateral decubitus resulted in the most sharp curves, whereas the supine position the most obtuse curves with a delayed peak, both in case of glucose and fat absorption. These findings contribute to understand the position-related absorption kinetics of substances in the intestinal tract. According to this study, posture may be important for the prevention and nursing intervention of some diseases related to metabolic kinetics of glucose and lipids. It may also be important for the absorption and transport of lipophilic drugs through the mesentery lymphatic vessels.
Durable Control of HIV-1 Using aStaphylococcus aureusCas9-Expressing Lentivirus Co-Targeting Viral Latency and Host Susceptibility
Authors: Chavez Leonard R. , Reddy Nishith R. , Raymond Kyle A. , Bouzidi Mohamed S. , Desai Shivani , Dossani Zain Y. , Sperber Hannah S. , Theiler James , Korber Bette , Pillai Satish K. 
Published: August 2020

ABSTRACTCRISPR/Cas9 gene editing has the potential to revolutionize the clinical management of HIV-1 infection, and may eliminate the need for antiretroviral therapy (ART). Current gene therapies attempt to either excise HIV-1 provirus or target HIV-1 entry receptors to prevent infection of new cells. Using a viral dynamic model, we determined that combining these two interventions, in the presence or absence of ART, significantly lowers the gene editing efficacy thresholds required to achieve an HIV-1 cure. To implement this dual-targeting approach, we engineered a single lentiviral vector that simultaneously targets multiple highly-conserved regions of the provirus and the host CXCR4 coreceptor, and developed a novel coculture system enabling real-time monitoring of latent infection, viral reactivation, and infection of new target cells. Simultaneous dual-targeting depleted HIV-1-infected cells with significantly greater potency than vectors targeting either virus or host independently, highlighting its potential as an HIV-1 cure strategy.
Waiting for love but not forever: modelling the evolution of waiting time to selfing in hermaphrodites
Authors: Blüml Chantal , Ramm Steven A. , van Benthem Koen J. , Wittmann Meike J. 
Published: August 2020

AbstractAlthough mixed mating systems involving both selfing and outcrossing are fairly common in hermaphrodites, it is unclear how they are maintained. In some species, individuals delay self-fertilization while they have not found a mating partner. The ‘waiting time’ is subject to two opposing selection pressures: waiting helps to avoid inbreeding depression in offspring by increasing the density-dependent probability to encounter a mate, but also increases the risk of dying before reproduction. In some species waiting time can vary between individuals and be heritable. We therefore used an individual-based model to explore how delayed selfing evolves in response to density and density fluctuations. We find that at high density, when individuals meet often, drift drives waiting time; at intermediate densities, strong inbreeding depression causes waiting time to increase; and at low densities, inbreeding depression is purged, and waiting time approaches zero. Positive feedback loops drive the system to either complete selfing or complete outcrossing. Fluctuating density can slow down convergence to these alternative stable states. However, mixed mating, in the sense of either a stable polymorphism in waiting times, or stable intermediate times, was never observed. Thus, additional factors need to be explored to explain the persistence of delayed selfing.
Quantity and quality of suitable matrices matter in reducing the negative effect of fragmentation on populations extinction risk
Authors: Travassos-Britto Bruno , Hohlenwerger Camila , Miranda José , Rocha Pedro Luís Bernardo da 
Published: August 2020

AbstractThe negative effect of fragmentation is one of the main concerns in the study of biodiversity loss in landscape ecology. The use of the matrix has been considered an important factor because it can change the relationship of a population with the configuration of the landscape. A systematic way to assess the effect of matrix quality in fragmented landscapes could lead to a better understanding of how matrices can be used to suppress the negative effect of fragmentation. We built a computational individual-based model capable of simulating bi-dimensional landscapes with three types of land cover (habitat, suitable matrix and hostile matrix) and individuals that inhabit those landscapes. We explored in which situations changes in the proportion of the suitable matrix in the landscape and the degree of usability of this suitable matrix can mitigate the negative effect of fragmentation per se. We observed that (i) an increase in the matrix quality (increases in the suitable matrix proportion and/or usability) can suppress the fragmentation effect in 47% of the simulated scenarios; (ii) the less usable the matrix is the more of it is needed to suppress the fragmentation effect; (iii) there is a level of usability below which increasing the suitable matrix proportion does cause the fragmentation effect to cease. These results point toward a landscape management that considers the similarity of the matrix to the native habitat under management. We suggest that an index to measure the usability of elements of the matrix could be an important tool to further the use of computational models in landscape management.