bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational dissociation of dopaminergic and cholinergic effects on action selection and inhibitory control
Authors: Aponte Eduardo A. , Schöbi Dario , Stephan Klaas E. , Heinzle Jakob 
Published: May 2019

AbstractBackgroundPatients with schizophrenia make more errors than healthy subjects on the antisaccade task. In this paradigm, participants are required to inhibit a reflexive saccade to a target and to select the correct action (a saccade in the opposite direction). While the precise origin of this deficit is not clear, it has been connected to aberrant dopaminergic and cholinergic neuromodulation.MethodsTo study the impact of dopamine and acetylcholine on inhibitory control and action selection, we administered two selective drugs (levodopa 200mg/galantamine 8mg) to healthy volunteers (N=100) performing the antisaccade task. A computational model (SERIA) was employed to separate the contribution of inhibitory control and action selection to empirical reaction times and error rates.ResultsModeling suggested that levodopa improved action selection (at the cost of increased reaction times) but did not have a significant effect on inhibitory control. By contrast, according to our model, galantamine affected inhibitory control in a dose dependent fashion, reducing inhibition failures at low doses and increasing them at higher levels. These effects were sufficiently specific that the computational analysis allowed for identifying the drug administered to an individual with 70% accuracy.ConclusionsOur results do not support the hypothesis that elevated tonic dopamine strongly impairs inhibitory control. Rather levodopa improved the ability to select correct actions. Instead, inhibitory control was modulated by cholinergic drugs. This approach may provide a starting point for future computational assays that differentiate neuromodulatory abnormalities in heterogeneous diseases like schizophrenia.
Whole genome sequencing of dog specific assemblages C and D of Giardia duodenalis from single and pooled cysts indicates host associated genes
Authors: Kooyman F.N.J. , Wagenaar J.A. , Zomer A. 
Published: May 2019

AbstractGiardia duodenalis (Syn. G. intestinalis or G. lamblia) infects over 280 million people each year and numerous animals. G. duodenalis can be subdivided into 8 assemblages with different host specificity. Unculturable assemblages have so far resisted genome sequencing efforts. In this study we isolated single and pooled cysts of assemblage C and D from dog faeces by FACS and sequenced them using multiple displacement amplification and Illumina paired end sequencing. The genomes of assemblages C and D were compared with genomes of assemblages A and B from humans and assemblage E from ruminants and pigs. The genomes obtained from the pooled cysts and from the single cysts were considered complete (>99% marker genes observed) and the allelic sequence heterozygosity (ASH) of assemblage C and D was 0.89% and 0.74%, respectively. Higher than for assemblage B (> 0.43%) and much higher than for assemblages A and E (<0.01%). The flavohemoglobin and 4Fe-4S binding domain family gene involved in O2 and NO detoxification were only present in assemblages A, B and E. Cathepsin-B orthologs were found in all genomes. Six clades of cathepsin-B orthologs contained one gene of each genome, while in three clades not all assemblages were represented. We conclude that whole genome sequencing from a single Giardia cyst results in complete draft genomes making the genomes of unculturable Giardia assemblages accessible. Observed differences between the genomes of assemblage C and D on one hand and the assemblages A, B and E on the other hand are possibly associated with host specificity.
Taxonomic Bias and Traits of the Global Amphibian Pet-Trade
Authors: Mohanty Nitya Prakash , Measey John 
Published: May 2019

AbstractThe pet-trade is recognized as the major pathway for amphibian introductions worldwide, yet our understanding of the trade is limited. In this study, we systematically assess amphibian species in the pet-trade, i) characterising taxonomic bias and ii) evaluating species-traits as predictors of traded species and trade volume. We collated a global list of 443 traded amphibians and a regional dataset on trade volume. Species-traits (body size, native range size, clutch size, and breeding type) and conservation status, were considered as predictors of traded species and volume. We found a strong bias for certain Families, along with a preference for large-bodied and widely distributed species with a larval phase, in the pet-trade. However, species-traits performed poorly in predicting trade volume of pet amphibians in the USA. The identified species-traits and taxonomic bias of the trade is used to predict species likely to be traded as pets in the future.
DHTKD1 and OGDH display in vivo substrate overlap and form a hybrid ketoacid dehydrogenase complex
Authors: Leandro João , Dodatko Tetyana , Aten Jan , Hendrickson Ronald C. , Sanchez Roberto , Yu Chunli , DeVita Robert J. , Houten Sander M. 
Published: May 2019

SUMMARYGlutaric aciduria type 1 (GA1) is an inborn error of lysine degradation characterized by a specific encephalopathy that is caused by toxic accumulation of lysine degradation intermediates. Substrate reduction through inhibition of DHTKD1, an enzyme upstream of the defective glutaryl-CoA dehydrogenase, has been investigated as a potential therapy, but revealed the existence of an alternative enzymatic source of glutaryl-CoA. Here we show that loss ofDHTKD1in GCDH-deficient HEK-293 cells leads to a 2-fold decrease in the established GA1 clinical biomarker glutarylcarnitine, and demonstrate that OGDH is responsible for this remaining glutarylcarnitine production. We furthermore show that DHTKD1 interacts with OGDH, DLST and DLD to form a hybrid α-ketoglutaric and α-ketoadipic acid dehydrogenase complex. In summary, α-ketoadipic acid is an in vivo substrate for DHTKD1, but also OGDH. The classic α-ketoglutaric dehydrogenase complex can exist as a previously undiscovered hybrid containing DHTKD1 displaying improved kinetics towards α-ketoadipic acid.
Novel Strategies for Glutamate Clearance in the Glia-Deprived Synaptic Hub ofC. elegans
Authors: Chan Joyce , Lee Kirsten KyungHwa , Wong Jenny Chan Ying , Morocho Paola , Mano Itzhak 
Published: May 2019

AbstractBrain function requires the ability to form neuronal circuits that mediate focused and accurate communication. Since the vast majority of brain synapses use Glutamate (Glu) as their neurotransmitter, unintended spillover of Glu between adjacent synapses is a critical challenge. To ensure accurate neurotransmission and avert synaptic mix-up, specialized Glu Transporters (GluTs) clear the synapse of released Glu. While classical views of neuronal morphology and physiology depict isolated spiny synapses enwrapped by GluT-expressing glia, in reality, a considerable portion of synapses are flat, glial coverage in some parts of the brain is rather sparse, and extracellular space is larger than previously estimated. This suggests that diffusion in interstitial fluids might have an important role in Glu clearance in these synapses. To understand basic principles of Glu clearance in flat-, glia-deprived synapses, we study the physiology of neuronal circuits in theC. elegansnerve ring, the nematode’s aspiny synaptic hub. We use behavioral assays, Ca2+imaging, and iGluSnFR to follow synaptic activity in intact animals. We find that synapses in a nociceptive avoidance circuit are dramatically affected by distal GluTs, while an adjacent chemoattraction circuit is controlled by proximal GluTs. We also find that pharyngeal pulsatility and mobility, which could agitate interstitial fluids, are critical for synaptic physiology. We therefore conclude that robust Glu clearance in the nematode is provided differentially by distal and proximal GluTs, aided by agitation of interstitial fluids. Such principles might be informative in determining additional factors that contribute to robust Glu clearance in other neuronal systems.Significance StatementThe nervous system depends on faithful relay of information without inadvertent mixing of signals between neuronal circuits. Classical views of the nervous system depict isolated synapses, enwrapped by glia that express neurotransmitter-transporters. However, this view is incomplete, since many synapses are flat, deprived of glia, and exposed to a larger-than-expected extracellular space. We use optogenetic tools to investigate glutamate clearance strategies in the aspiny and glia-deprived synaptic hub of intact nematodes. We find a division of labor among Glutamate transporters: while some transporters display classical localization near the synapses, others are distal, and cooperate with agitation of interstitial fluids to prevent glutamate accumulation. These novel principles might contribute to synaptic clearance in higher animals, affecting normal neuronal physiology and disease.
Inhibition ofde novoceramide biosynthesis affects aging phenotype in anin vitromodel of neuronal senescence
Authors: Granzotto Alberto , Bomba Manuela , Castelli Vanessa , Navarra Riccardo , Massetti Noemi , Onofrj Marco , Cicalini Ilaria , del Boccio Piero , Cimini Annamaria , Piomelli Daniele , Sensi Stefano L. 
Published: May 2019

AbstractAlthough aging is considered to be an unavoidable event, recent experimental evidence suggests that the process can be delayed, counteracted, if not completely interrupted. Aging is the primary risk factor for the onset and development of neurodegenerative conditions like Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Intracellular calcium (Ca2+i) dyshomeostasis, mitochondrial dysfunction, oxidative stress, and lipid dysregulation are critical factors that contribute to senescence-related processes. Ceramides, a class of sphingolipids involved in a wide array of biological functions, are important mediators of cellular senescence, but their role in neuronal aging is still largely unexplored.In this study, we investigated the effects of L-cycloserine (L-CS), an inhibitor ofde novoceramide biosynthesis, on the aging phenotype of cortical neurons that have been maintained in culture for 22 days, a setting employed as anin vitromodel of cellular senescence. Our findings indicate that ‘aged’ neurons display, when compared to control cultures, overt dysregulation of cytosolic and subcellular [Ca2+]ilevels, mitochondrial dysfunction, increased reactive oxygen species generation, altered synaptic activity as well as the activation of neuronal death-related molecules. Treatment with L-CS (30 µM) positively affected the senescent phenotype, a result accompanied by recovery of neuronal [Ca2+]isignaling, and reduction of mitochondrial dysfunction and reactive oxygen species generation.The results suggest that thede novoceramide biosynthesis may represent a critical intermediate in the molecular and functional cascade leading to neuronal senescence. Our findings also identify ceramide biosynthesis inhibitors as promising pharmacological tools to decrease age-related neuronal dysfunctions.
Genomic analysis of the tryptome reveals molecular mechanisms of gland cell evolution
Authors: Babonis Leslie S. , Ryan Joseph F. , Enjolras Camille , Martindale Mark Q. 
Published: May 2019

AbstractUnderstanding the drivers of morphological diversity is a persistent challenge in evolutionary biology. Here, we investigate functional diversification of secretory cells in the sea anemone Nematostella vectensis to understand the mechanisms promoting cellular specialization across animals. We demonstrate regionalized expression of gland cell subtypes in the internal ectoderm of N. vectensis and show that adult gland cell identity is acquired very early in development. A phylogenetic survey of trypsins across animals suggests this gene family has undergone numerous expansions. We reveal unexpected diversity in trypsin protein structure and show that trypsin diversity arose through independent acquisitions of non-trypsin domains. Finally, we show that trypsin diversification in N. vectensis was effected through a combination of tandem duplication, exon shuffling, and retrotransposition. Together we reveal that numerous evolutionary mechanisms drove trypsin duplication and divergence during the morphological specialization of cell types and suggest the secretory cell phenotype is highly adaptable as a vehicle for novel secretory products.
Combinatorial design of chemical-dependent protein switches for controlling intracellular electron transfer
Authors: Wu Bingyan , Atkinson Joshua T. , Kahanda Dimithree , Bennett George. N. , Silberg Jonathan J. 
Published: May 2019

ABSTRACTOne challenge with controlling electron flow in cells is the lack of biomolecules that directly couple the sensing of environmental conditions to electron transfer efficiency. To overcome this protein component limitation, we randomly inserted the ligand binding domain (LBD) from the human estrogen receptor (ER) into a thermostable 2Fe-2S ferredoxin (Fd) fromMastigocladus laminosusand used a bacterial selection to identify Fd-LBD fusion proteins that support electron transfer from a Fd-NADP reductase (FNR) to a Fd-dependent sulfite reductase (SIR). Mapping LBD insertion sites onto structure revealed that Fd tolerates domain insertion adjacent to or within the tetracysteine motif that coordinates the 2Fe-2S metallocluster. With both classes of the fusion proteins, cellular ET was enhanced by the ER antagonist 4-hydroxytamoxifen. In addition, one of Fds arising from ER-LBD insertion within the tetracysteine motif acquires an oxygen-tolerant 2Fe-2S cluster, suggesting that ET is regulated through post-translational ligand binding.
The neuropeptide Drosulfakinin regulates social isolation-induced aggression inDrosophila
Authors: Agrawal Pavan , Kao Damian , Chung Phuong , Looger Loren L. 
Published: May 2019

ABSTRACTSocial isolation strongly modulates behavior across the animal kingdom. We utilized the fruit flyDrosophila melanogasterto study social isolation-driven changes in animal behavior and gene expression in the brain. RNA-seq identified several head-expressed genes strongly responding to social isolation or enrichment. Of particular interest, social isolation downregulated expression of the gene encoding the neuropeptideDrosulfakinin(Dsk), the homologue of vertebrate cholecystokinin (CCK), which is critical for many mammalian social behaviors.Dskknockdown significantly increased social isolation-induced aggression. Genetic activation or silencing ofDskneurons each similarly increased isolation-driven aggression. Our results suggest a U-shaped dependence of social isolation-induced aggressive behavior onDsksignaling, similar to the actions of many neuromodulators in other contexts.Data availabilityThe raw sequence data from RNA-seq experiments has been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra) with accession number: PRJNA481582. Supplementary files and figures accompany this article.
Angiogenic activity of cytochalasin B-induced membrane vesicles of human mesenchymal stem cells
Authors: Gomzikova M.O. , Zhuravleva M.N. , Vorobev V.V. , Salafutdinov I.I. , Laikov A.V. , Kletukhina S.K. , Martynova E.V. , Tazetdinova L.G. , Ntekim A.I. , Khaiboullina S.F. , Rizvanov A.A. 
Published: May 2019

AbstractBackgroundThe cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown.ObjectivesThe objectives of this study were to analyzed the morphology, size distribution, molecular composition and angiogenic properties of CIMVs-MSCs.MethodsThe morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix.ResultsHuman CIMVs-MSCs retain parental MSCs content such as growth factors, cytokines, chemokines: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNα2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-α, TNF-β, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cellsin vitro. Finally, CIMVs-MSCs can induce angiogenesisin vivoafter subcutaneous injection into adult rats.ConclusionsHuman CIMVs-MSCs have similar content, immunophenotype and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.
Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion
Authors: Del Rosario Mario , Periz Javier , Pavlou Georgios , Lyth Oliver , Latorre-Barragan Fernanda , Das Sujaan , Pall Gurman S. , Stortz Johannes Felix , Lemgruber Leandro , Baum Jake , Tardieux Isabelle , Meissner Markus 
Published: May 2019

AbstractThe obligate intracellular parasites Toxoplasma gondii and Plasmodium spp. invade host cells by injecting a protein complex into the membrane of the targeted cell that bridges the two cells through the assembly of a ring-like junction. This circular junction stretches while the parasites applies a traction force to pass through; a step that typically concurs with transient constriction of the parasite body. Here we show that the junction can oppose resistance to the passage of the parasite’s nucleus. Super-resolution microscopy and real time imaging highlighted an F-actin pool at the apex of pre-invading parasite, an F-actin ring at the junction area during invasion but also networks of perinuclear and posteriorly localized F-actin. Mutant parasites with dysfunctional acto-myosin showed significant decrease of junctional and perinuclear F-actin and are coincidently affected in nuclear passage through the junction. We propose that the F-actin machinery eases nuclear passage by stabilising the junction and pushing the nucleus through the constriction, providing first evidence for a dual contribution of actin-forces during host cell invasion by apicomplexan parasites.
β-Actin and Nuclear Myosin I are responsible for nucleolar reorganization during DNA Repair
Authors: Cerutti Elena , Daniel Laurianne , Donnio Lise-Marie , Neuillet Damien , Magnani Charlene , Mari Pierre-Olivier , Giglia-Mari Giuseppina 
Published: May 2019

AbstractDuring DNA Repair, ribosomal DNA and RNA polymerase I (rDNA/RNAP1) are reorganized within the nucleolus. Until now, the proteins and the molecular mechanism governing this reorganisation remained unknown.Here we show that Nuclear Myosin I (NMI) and Nuclear Beta Actin (ACTβ) are essential for the proper reorganisation of the nucleolus, after completion of the DNA Repair reaction.In NMI and ACTβ depleted cells, the rDNA/RNAP1 complex can be displaced at the periphery of the nucleolus after DNA damage but cannot re-enter within the nucleolus after completion of the DNA Repair. Both proteins act concertedly in this process. NMI binds the damaged rDNA at the periphery of the nucleolus, while ACTβ brings the rDNA back within the nucleolus after DNA repair completion. Our results reveal a previously unidentified function for NMI and ACTβ and disclose how these two proteins work in coordination to re-establish the proper rDNA position after DNA repair.
Pelvic bone structures in free-ranging Eurasian lynx (Lynx lynx) from Switzerland: a radiological pelvimetry study
Authors: Morend Fanny , Lang Johann , Vidondo Beatriz , Ryser-Degiorgis Marie-Pierre 
Published: May 2019

AbstractThe observation of severe pelvic malformations in Eurasian lynx (Lynx lynx) from a population reintroduced to Switzerland raised the question as to whether inbreeding may contribute to the development of congenital pelvic malformations. We aimed at providing baseline data on the pelvic morphology of Eurasian lynx from the reintroduced populations in Switzerland, at assessing potential differences in pelvic conformation between the two main Swiss populations, among age classes and between sexes, and at detecting pelvic anomalies. We performed measurements of 10 pelvic parameters on the radiographs of 57 lynx of both sexes and different ages taken from 1997-2015. We calculated two ratios (vertical diameter/acetabula; sagittal diameter/transversal diameter) and two areas (pelvic outlet and inlet) to describe the shape of the pelvis. Our results showed that the Eurasian lynx is a mesatipelvic species, with a pelvis length corresponding to approximatively 20% of the body length. We found no statistically significant differences between the two examined populations but observed growth-related pelvis size differences among age groups. Sexual dimorphism was obvious in the adult age group only: two parameters reflecting pelvic width were larger in females, likely to meet the physiological requirements of parturition. By contrast, pelvis length, conjugata vera, diagonal conjugata, vertical diameter and sagittal diameter were larger in males, in agreement with their larger body size. Accordingly, the ratio between the sagittal and transversal diameters was significantly larger in males, i.e. adult males have a different pelvic shape than adult females. Furthermore, pelvimetry highlighted one adult individual with values outside the calculated reference range, suggesting a possible congenital or developmental pathological morphology of the internal pelvis. Our work generated baseline data of the pelvic morphology including growth and sexual dimorphism of the Eurasian lynx. These data could also be useful for estimating age and sex in skeletal remains.
Length-dependent disassembly maintains four different flagellar lengths in Giardia
Authors: McInally SG , Kondev J , Dawson Scott C. 
Published: May 2019

AbstractHow flagellar length regulation is achieved in multiciliated eukaryotic cells with flagella of different equilibrium lengths is unknown. The protist Giardia lamblia is an ideal model to evaluate length regulation as it has flagella of four different lengths. Giardia axonemes have both non-membrane-bound and membrane-bound regions, but lack transition zones. Here we quantified the contributions of intraflagellar transport (IFT)-mediated assembly and kinesin-13-mediated disassembly to length control. IFT particles assemble and inject at Giardia’s flagellar pore complexes, which act as diffusion barriers functionally analogous to the transition zone to compartmentalize the membrane-bound regions of flagella. IFT-mediated assembly is length-independent as train size, speed, and injection frequencies are similar between flagella of different lengths. In Giardia, kinesin-13 mediates a length-dependent disassembly mechanism of length regulation to balance length-independent IFT-mediated assembly, resulting in different lengths. We anticipate that similar control mechanisms are widespread in multiciliated cells where cytoplasmic precursor pools are not limiting.