bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss ofslc39a14causes simultaneous manganese deficiency and hypersensitivity in zebrafish
Authors: Tuschl Karin , White Richard J , Valdivia Leonardo E , Niklaus Stephanie , Bianco Isaac H , Sealy Ian M , Neuhauss Stephan CF , Houart Corinne , Wilson Stephen W , Busch-Nentwich Elisabeth M 
Published: February 2020

AbstractMutations in SLC39A14, a manganese uptake transporter, lead to a neurodegenerative disorder characterised by accumulation of manganese in the brain and rapidly progressive dystonia-parkinsonism (Hypermanganesemia with Dystonia 2, HMNDYT2). Similar to the human phenotype, zebrafishslc39a14U801-/-mutants show prominent brain manganese accumulation and abnormal locomotor behaviour. In order to identify novel potential targets of manganese neurotoxicity, we performed transcriptome analysis of individual homozygous mutant and siblingslc39a14U801zebrafish at five days post fertilisation unexposed and exposed to MnCl2. Anatomical gene enrichment analysis confirmed that differentially expressed genes map to the central nervous system and eye. Biological interpretation of differentially expressed genes suggests that calcium dyshomeostasis, activation of the unfolded protein response, oxidative stress, mitochondrial dysfunction, lysosomal disruption, apoptosis and autophagy, and interference with proteostasis are key events in manganese neurotoxicity. Differential expression of visual phototransduction genes also predicted visual dysfunction in mutant larvae which was confirmed by the absence of visual background adaptation and a diminished optokinetic reflex. Surprisingly, we found a group of differentially expressed genes in mutant larvae that normalised upon MnCl2treatment suggesting that, in addition to neurotoxicity, manganese deficiency is present either subcellularly or in specific cells or tissues. This may have important implications for treatment as manganese chelation may aggravate neurological symptoms. Our analyses show thatslc39a14U801-/-mutant zebrafish present a powerful model to study the cellular and molecular mechanisms underlying disrupted manganese homeostasis.Significance statementManganese neurotoxicity leading to progressive dystonia-parkinsonism is a characteristic feature of Hypermanganesemia with dystonia 2 (HMNDYT2) caused by mutations in SLC39A14, a manganese uptake transporter. Transcriptional profiling inslc39a14U801loss-of-function zebrafish suggests that, in addition to manganese neurotoxicity, subcellular or cell type specific manganese deficiency contributes to the disease phenotype. Both manganese overload and deficiency appear to be associated with Ca2+dyshomeostasis. We further demonstrate that activation of the unfolded protein response, oxidative stress, mitochondrial dysfunction, apoptosis and autophagy, and disrupted proteostasis are likely downstream events in manganese neurotoxicity. Our study shows that the zebrafishslc39a14U801loss-of-function mutant is a powerful model to elucidate the mechanistic basis of diseases affected by manganese dyshomeostasis.
Quantifying protein-protein interactions by molecular counting with mass photometry
Authors: Soltermann Fabian , Foley Eric D.B. , Pagnoni Veronica , Galpin Martin R. , Benesch Justin L.P. , Kukura Philipp , Struwe Weston B. 
Published: February 2020

AbstractInteractions between biomolecules control the processes of life in health, and their malfunction in disease, making their characterization and quantification essential. Immobilization- and label-free analytical techniques are particular desirable because of their simplicity and minimal invasiveness, but struggle to quantify tight interactions. Here, we show that we can accurately count, distinguish by molecular mass, and thereby reveal the relative abundances of different un-labelled biomolecules and their complexes in mixtures at the single-molecule level by mass photometry. These measurements enable us to quantify binding affinities over four orders of magnitude at equilibrium for both simple and complex stoichiometries within minutes, as well as to determine the associated kinetics. Our results introduce mass photometry as a rapid, simple and label-free method for studying sub-μM binding affinities, with potential to be extended towards a universal approach for characterising complex biomolecular interactions.
Single cell transcriptome profiling of the Atlantic cod immune system
Authors: Guslund Naomi , Solbakken Monica Hongrø , Jakobsen Kjetill S. , Qiao Shuo-Wang 
Published: February 2020

AbstractThe Atlantic cod’s unusual immune system, entirely lacking the Major Histocompatibility class II pathway, has prompted intriguing questions about what mechanisms are used to combat bacterial infections and how immunological memory is generated. Here, we examine the diversity of 8,180 spleen cells and peripheral blood leukocytes by single cell RNA sequencing. Unbiased transcriptional clustering revealed eleven distinct immune cell signatures. Resolution at the single cell level enabled characterisation of the major cell subsets including the cytotoxic T cells, B cells, erythrocytes, thrombocytes, neutrophils and macrophages. Further, we describe for the first time rare cell subsets which may represent dendritic cells, natural killer-like cells and a population of cytotoxic cells expressing GATA-3. We propose putative gene markers for each cluster and describe the relative proportions of each cell type in the spleen and peripheral blood leukocytes. By single cell analysis, this study provides the most detailed molecular and cellular characterization of the immune system of the Atlantic cod so far.
What the Zebrafish’s Eye Tells the Zebrafish’s Brain: Retinal Ganglion Cells for Prey Capture and Colour Vision
Authors: Zhou M , Bear J , Roberts PA , Janiak FK , Semmelhack J , Yoshimatsu T , Baden T 
Published: February 2020

ABSTRACTIn vertebrate vision, the tetrachromatic larval zebrafish permits non-invasive monitoring and manipulating of neural activity across the nervous systemin vivoduring ongoing behaviour. However, despite a perhaps unparalleled understanding of links between zebrafish brain circuits and visual behaviours, comparatively little is known about what their eyes send to the brain in the first place via retinal ganglion cells (RGCs). Major gaps in knowledge include any information on spectral coding, and information on potentially critical variations in RGC properties across the retinal surface to acknowledge asymmetries in the statistics of natural visual space and behavioural demands. Here, we usein vivotwo photon (2P) imaging during hyperspectral visual stimulation as well as photolabeling of RGCs to provide the first eye-wide functional and anatomical census of RGCs in larval zebrafish.We find that RGCs’ functional and structural properties differ across the eye and include a notable population of UV-responsive On-sustained RGCs that are only found in the acute zone, likely to support visual prey capture of UV-bright zooplankton. Next, approximately half of RGCs display diverse forms of colour opponency - long in excess of what would be required to satisfy traditional models of colour vision. However, most information on spectral contrast was intermixed with temporal information. To consolidate this series of unexpected findings, we propose that zebrafish may use a novel “dual-achromatic” strategy segregated by a spectrally intermediate background subtraction system. Specifically, our data is consistent with a model where traditional achromatic image-forming vision is mainly driven by long-wavelength sensitive circuits, while in parallel UV-sensitive circuits serve a second achromatic system of foreground-vision that serves prey capture and, potentially, predator evasion.
Oviposition in flight: theSabethes albiprivusincredible egg-throwing behavior
Authors: Vieira Genilton , Bersot Maria Ignez Lima , Pereira Glauber Rocha , de Abreu Filipe Vieira Santos , Nascimento-Pereira Agostinho Cardoso , Santos Neves Maycon Sebastião Alberto , Rosa-Freitas Maria Goreti , de Albuquerque Motta Monique , Lourenço-de-Oliveira Ricardo 
Published: February 2020

ABSTRACTMosquitoes display highly variable oviposition strategies and behavior. By using a high-speed camera, we detailly documented for the first time the egg-throwing strategy of the sylvatic yellow fever vectorSabethes albiprivusTheobald in laboratory. An oviposition trap made with sapucaia nut for field collection of tree-hole mosquitoes and obtainingSa. albiprivuseggs either in the field or in the laboratory colony is described.
A Self-Attention Model for Inferring Cooperativity between Regulatory Features
Authors: Ullah Fahad , Ben-Hur Asa 
Published: February 2020

ABSTRACTDeep learning has demonstrated its predictive power in modeling complex biological phenomena such as gene expression. The value of these models hinges not only on their accuracy, but also on the ability to extract biologically relevant information from the trained models. While there has been much recent work on developing feature attribution methods that discover the most important features for a given sequence, inferring cooperativity between regulatory elements, which is the hallmark of phenomena such as gene expression, remains an open problem. We present SATORI, a Self-ATtentiOn based model to detect Regulatory element Interactions. Our approach combines convolutional layers with a self-attention mechanism that helps us capture a global view of the landscape of interactions between regulatory elements in a sequence. A comprehensive evaluation demonstrates the ability of SATORI to identify numerous statistically significant TF-TF interactions, many of which have been previously reported. Our method is able to detect higher numbers of experimentally verified TF-TF interactions than existing methods, and has the advantage of not requiring a computationally expensive post-processing step. Finally, SATORI can be used for detection of any type of feature interaction in models that use a similar attention mechanism, and is not limited to the detection of TF-TF interactions.
Functional signatures of evolutionarily young CTCF binding sites
Authors: Azazi Dhoyazan , Mudge Jonathan M. , Odom Duncan T. , Flicek Paul 
Published: February 2020

ABSTRACTThe introduction of novel CTCF binding sites in gene regulatory regions in the rodent lineage is partly the effect of transposable element expansion. The exact mechanism and functional impact of evolutionarily novel CTCF binding sites are not yet fully understood. We investigated the impact of novel species-specific CTCF binding sites in twoMusgenus subspecies,Mus musculus domesticusandMus musculus castaneus,that diverged 0.5 million years ago. The activity of the B2-B4 family of transposable elements independently in both lineages leads to the proliferation of novel CTCF binding sites. A subset of evolutionarily young sites may harbour transcriptional functionality, as evidenced by the stability of their binding across multiple tissues inM. musculus domesticus(BL6), while overall the distance of species-specific CTCF binding to the nearest transcription start sites and/or topologically-associated domains (TADs) is largely similar tomusculus-common CTCF sites. Remarkably, we discovered a recurrent regulatory architecture consisting of a CTCF binding site and an interferon gene that appears to have been tandemly duplicated to create a 15-gene cluster on chromosome 4, thus forming a novel BL6 specific immune locus, in which CTCF may play a regulatory role. Our results demonstrate that thousands of CTCF binding sites show multiple functional signatures rapidly after incorporation into the genome.
Species boundaries and molecular markers for the classification of 16SrI phytoplasmas inferred by genome analysis
Authors: Cho Shu-Ting , Kung Hung-Jui , Huang Weijie , Hogenhout Saskia A. , Kuo Chih-Horng 
Published: February 2020

AbstractPhytoplasmas are plant-pathogenic bacteria that impact agriculture worldwide. The commonly adopted classification system for phytoplasmas is based on the restriction fragment length polymorphism (RFLP) analysis of their 16S rRNA genes. With the increased availability of phytoplasma genome sequences, the classification system can now be refined. This work examined 11 strains in the 16SrI group within the genus ‘CandidatusPhytoplasma’ and investigated the possible species boundaries. We confirmed that the RFLP classification method is problematic due to intragenomic variation of the 16S rRNA genes and uneven weighing of different nucleotide positions. Importantly, our results based on the molecular phylogeny, differentiations in chromosomal segments and gene content, and divergence in homologous sequences, all supported that these strains may be classified into multiple operational taxonomic units (OTUs) equivalent to species. Strains assigned to the same OTU share >97% genome-wide average nucleotide identity (ANI) and >78% of their protein-coding genes. In comparison, strains assigned to different OTUs share <94% ANI and <75% of their genes. Reduction in homologous recombination between OTUs is one possible explanation for the discontinuity in genome similarities, and these findings supported the proposal that 95% ANI could serve as a cutoff for distinguishing species in bacteria. Additionally, critical examination of these results and the raw sequencing reads led to the identification of one genome that was presumably mis-assembled by combining two sequencing libraries built from phytoplasmas belonging to different OTUs. This finding provided a cautionary tale for working on uncultivated bacteria. Based on the new understanding of phytoplasma divergence and the current genome availability, we developed five molecular markers that could be used for multilocus sequence analysis (MLSA). By selecting markers that are short yet highly informative, and are distributed evenly across the chromosome, these markers provided a cost-effective system that is robust against recombination. Finally, examination of the effector gene distribution further confirmed the rapid gains and losses of these genes, as well as the involvement of potential mobile units (PMUs) in their molecular evolution. Future improvements on the taxon sampling of phytoplasma genomes will allow further expansions of similar analysis, and thus contribute to phytoplasma taxonomy and diagnostics.
Gjd2b-mediated gap junctions promote glutamatergic synapse formation and dendritic elaboration in Purkinje neurons
Authors: Sitaraman Sahana , Yadav Gnaneshwar , Jabeen Shaista , Agarwal Vandana , Thirumalai Vatsala 
Published: February 2020

AbstractGap junctions between neurons serve as electrical synapses, in addition to conducting metabolites and signaling molecules. These functions of gap junctions have led to the idea that during development, gap junctions could prefigure chemical synapses. We present evidence for this idea at a central, glutamatergic synapse and provide some mechanistic insights. Here, we show that reduction or loss of Gjd2b-containing gap junctions led to a decrease in glutamatergic synapse density in cerebellar Purkinje neurons (PNs) in larval zebrafish. Gjd2b-/-larvae exhibited faster mEPSCs and a consistent decrease in dendritic arbor size. These PNs also showed decreased branch elongations but normal rate of branch retractions. Further, the dendritic growth deficits in gjd2b-/-mutants were rescued by expressing full length Gjd2b in single PNs. This suggests that Gjd2b may form heterotypic channels with other connexins in gjd2b-/-larvae, though it is not clear if PNs in wild type animals make homotypic or heterotypic gap junction channels. Dendritic growth deficits were not rescued by expressing a deletion mutant of Gjd2b unable to form functional channels. Finally, the expression levels of five isoforms ofcamkiiwere increased in gjd2b-/-larvae and inhibition of CaMKII restored dendritic arbor lengths of mutant larvae to wild type levels. These results suggest a link between signaling via Gjd2b-containing gap junctions, CaMKII function and dendritic growth. In sum, our results demonstrate that Gjd2b-mediated gap junctions are key regulators of glutamatergic synapse formation and dendritic elaboration in PNs.
Crocus Sativusand Its Active Compound, Crocin Inhibits the Endothelial Activation and Monocyte-Endothelial Cells Interaction in Stimulated Human Coronary Artery Endothelial Cells
Authors: Mohd Kasim Noor Alicezah , Abu Bakar Nurul Ain , Ahmad Radzi , Abd Rahim Iman Nabilah , Abdul Rahman Thuhairah Hasrah , Anisah Froemming Gabriele Ruth , Nawawi Hapizah Mohd 
Published: February 2020

AbstractCrocus sativus L.or saffron has been shown to have anti-atherogenic effects. However, its effects on key events in atherogenesis such as endothelial activation and monocyte-endothelial cell binding in lipolysaccharides (LPS)-stimulatedin vitromodel have not been extensively studied.ObjectivesTo investigate the effects of saffron and its bioactive derivative crocin on the gene and protein expressions of biomarkers of endothelial activation in LPS stimulated human coronary artery endothelial cells (HCAECs).MethodologyHCAECs were incubated with different concentrations of aqueous ethanolic extracts of saffron and crocin together with LPS. Protein and gene expressions of endothelial activation biomarkers were measured using ELISA and qRT-PCR, respectively. Adhesion of monocytes to HCAECs was detected by Rose Bengal staining. Methyl-thiazol-tetrazolium assay was carried out to assess cytotoxicity effects of saffron and crocin.ResultsSaffron and crocin up to 25.0 and 1.6 μg/ml respectively exhibited >85% cell viability. Saffron treatment reduced sICAM-1, sVCAM-1 and E-selectin proteins (concentrations: 3.13, 6.25, 12.5 and 25.0 μg/ml; 3.13, 12.5 and 25.0 μg/ml; 12.5 and 25.0, respectively) and gene expressions (concentration: 12.5 and 25.0μg/ml; 3.13, 6.25 and 25.0 μg/ml; 6.25, 12.5 25.0; respectively). Similarly, treatment with crocin reduced protein expressions of sICAM-1, sVCAM-1 and E-selectin (concentration: 0.2, 0.4, 0.8 and 1.6 μg/ml; 0.4, 0.8 and 1.6 μg/ml; 0.8 and 1.6 μg/ml; respectively] and gene expression (concentration: 0.8 and 1.6 μg/ml; 0.4, 0.8 and 1.6 μg/ml; and 1.6 μg/ml, respectively). Monocyte-endothelial cell interactions were reduced following saffron treatment at concentrations 6.3, 12.5 and 25.00 μg/ml. Similarly, crocin also suppressed cellular interactions at concentrations 0.04, 0.08, 1.60 μg/ml.ConclusionSaffron and crocin exhibits potent inhibitory action for endothelial activation and monocyte-endothelial cells interaction suggesting its potential anti-atherogenic properties.
Sero-prevalence of brucellosis, Q-fever and Rift Valley Fever in humans and livestock in Somali region, Ethiopia
Authors: Ibrahim Mohammed , Schelling Esther , Zinsstag Jakob , Hattendorf Jan , Andargie Emawayish , Tschopp Rea 
Published: February 2020

AbstractInformation on zoonotic diseases in humans and livestock are limited in pastoral/agro-pastoral communities in Ethiopia. A multi-stage cross sectional cluster design study was implemented with the aim to establish the seroprevalence of zoonotic diseases including brucellosis, Q-fever and Rift Valley Fever (RVF) in humans and livestock in Adadle woreda of the Somali region, Ethiopia. Blood samples were collected from humans and livestock and tested by relevant serological tests. For brucellosis, Rose Bengal test (RBT) and indirect ELISA was used for screening and confirmatory diagnosis respectively. Indirect and competitive ELISA were also used for Q-fever and RVF respectively. The individual seropositivity of Q-fever in livestock was 9.6% (95% CI 5.9-15.1) in cattle, 55.7% (95% CI 46.0-65.0) in camels, 48.8% (95% CI 42.5-55.0) in goats, and 28.9% (95% CI 25.0-33.2) in sheep. In humans, seropositivity of Q-fever was 27.0% (95% CI 20.4-34.0), with prevalence in males of 28.9% vs 24.2% in females (OR= 1.3; 95% CI 0.6-2.5). Camel seropositivity of Q-fever was significantly associated with age (OR= 8.1; 95% CI 2.8-23.7). The individual apparent seroprevalence of RVF was 13.2% (95% CI 8.7-18.8) in humans, 17.9 % (95% CI 11.0-27.8) in cattle, 42.6% (95% CI 34.8-50.7) in camels, 6.3% (95% CI 3.3-11.6) in goats and 7.4% (95% CI 4.7-11.5) in sheep. Camels had the highest seropositivity of both Q-fever (55.7%; 95% CI 46.0-65.0) and RVF (42.6%; 95% CI 34.8-50.7). Only a weak correlation was observed between human and livestock seropositivity for both Q-fever and RVF. Only cattle and camels were seropositive for brucellosis by iELISA. The individual seroprevalence of brucellosis was 2.8(0.9-6.4) in humans, 1.5% (95% CI 0.2-5.2) in cattle and 0.6% (95% CI 0.0-3.2) in camels. This study showed the importance of zoonoses in Somali regional state and is the first published study to describe RVF exposure in humans and livestock in the country. Collaboration between public and animal health sectors for further investigation on these zoonoses using the One Health concept is indispensable.
Two dominant brain states reflect optimal and suboptimal attention
Authors: Yamashita Ayumu , Rothlein David , Kucyi Aaron , Valera Eve M. , Esterman Michael 
Published: February 2020

AbstractAttention is not constant but fluctuates from moment to moment. Previous studies dichotomized these fluctuations into optimal and suboptimal states based on behavioral performance and investigated the difference in brain activity between these states. Although these studies implicitly assume there are two states, this assumption is not guaranteed. Here, we reversed the logic of these previous studies and identified unique states of brain activity during a sustained attention task. We demonstrate a systematic relationship between dynamic brain activity patterns (brain states) and behavioral underpinnings of sustained attention by explaining behavior from two dominantly observed brain states. In four independent datasets, a brain state characterized by default mode network activity was behaviorally optimal and a brain state characterized by dorsal attention network activity was suboptimal. Thus, our study provides compelling evidence for behaviorally optimal and suboptimal attentional states from the sole viewpoint of brain activity. We further demonstrated how these brain states were impacted by motivation, mind wandering, and attention-deficit hyperactivity disorder. Within-subject level modulators (motivation and mind wandering) impacted the optimality of behavior in the suboptimal brain state. In contrast, between-subject level differences (ADHD vs healthy controls) impacted the optimal brain state character, namely its frequency.