bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome
Authors: Strydom Andre , Heslegrave Amanda , Startin Carla M , Mok Kin Y , Hardy John , Groet Jurgen , Nizetic Dean , Zetterberg Henrik ,   And The LonDownS Consortium
Published: March 2018

AbstractINTRODUCTIONDown syndrome (DS) may be considered a genetic form of Alzheimer’s disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions.METHODSWe measured blood NF-L concentration in 100 adults with DS using Simoa NF-light® assays, and examined relationships with age, and cross-sectional and longitudinal dementia diagnosis.RESULTSNF-L levels increased with age (Spearman’s rho = 0.789, p<0.001), with a steep increase after age 40, and were predictive of dementia status (p=0.022 adjusting for age, sex, and APOE4) but showed no relationship with longstanding epilepsy or premorbid ability. Baseline NF-L levels were associated with longitudinal dementia status.DISCUSSIONNF-L is a biomarker for neurodegeneration in DS, with potential for use in future clinical trials to prevent or delay dementia.Research in contextSystematic reviewThe authors reviewed the literature using PubMed searches supplemented with our knowledge of pending papers in this research area. While blood NF-L has been associated with clinical features of progression in a number of neurodegenerative conditions, we have not identified any reports of NF-L associated with cognitive decline in DS, a genetic form of AD.InterpretationOur findings demonstrate the potential utility of NF-L as a blood biomarker of neurodegeneration in DS, a population that may not be able to tolerate more invasive procedures such as neuroimaging and lumbar punctures to track progression.Future directionsThe association between NF-L and other markers of longitudinal AD progression should be explored further in future work.
Model-based analysis of the stiffness of the wrist joint in active and passive conditions
Authors: Zonnino Andrea , Sergi Fabrizio 
Published: March 2018

ABSTRACTThe control of joint stiffness is a fundamental mechanism used to control human movements. While many studies have observed how stiffness is controlled for tasks involving shoulder and elbow motion, a limited amount of knowledge is available for wrist movements, though the wrist plays a crucial role in fine manipulation.We have developed a computational framework based on a realistic musculoskeletal model, which allows to calculate the passive and active components of the wrist joint stiffness. We first used the framework to validate the musculoskeletal model against experimental measurements of the passive wrist joint stiffness, and then to study the contribution of different muscle groups on the passive joint stiffness. We finally used the framework to study the effect of muscle co - contraction on the active joint stiffness.The results show that thumb and finger muscles play a crucial role in determining the passive wrist joint stiff - ness: in the neutral posture, the direction of maximum stiffness aligns with the experimental measurements, and the magnitude increases by 113% when they are included. Moreover, the analysis of the controllability of joint stiffness showed that muscle co - contraction positively correlates with the stiffness magnitude and negatively correlates with the variability of the stiffness orientation (p < 0.01 in both cases). Finally, an exhaustive search showed that with appropriate selection of a muscle activation strategy, the joint stiffness orientation can be arbitrarily modulated. This observation suggests the absence of biomechanical constraints on the controllability of the orientation of the wrist joint stiffness.
Limited uptake of essential amino acid is effective for cancer therapy in metabolic networks of integrated constraint-based models
Authors: Tamura Takeyuki 
Published: March 2018

AbstractNam models are context-specific genome-scale metabolic models for nine types of cancer and corresponding normal cells reconstructed from RECON 2, genetic mutation information, and expression profile data. In this study, computational experiments were conducted using Nam models to find effective ratios of uptake reactions such that cancer cells do not grow while normal cells grow. The original Nam models were extended to consider interactions between cancer and normal cells using an approach developed for representing host-microbe interactions. When uptake ratio of only single reaction was allowed to change at a time, the results of computational experiments showed that every essential amino acid had effective ranges for almost all nine types of cancer, while the other uptake reactions rarely had such effective ranges.
Landscape-level DNA metabarcoding study in the Pannonian forests reveals differential effects of slope aspect on taxonomic and functional groups of fungi
Authors: Geml József 
Published: March 2018

AbstractIn temperate regions, slope aspect is one of the most influential drivers of environmental conditions at landscape level. The effect of aspect on vegetation has been well studied, but virtually nothing is known about how fungal communities are shaped by aspect-driven environmental conditions. I carried out DNA metabarcoding of fungi from soil samples taken in a selected study area of Pannonian forests to compare richness and community composition of taxonomic and functional groups of fungi between slopes of predominantly southerly vs. northerly aspect and to assess the influence of selected environmental variables on fungal community composition. The deep sequence data presented here (i.e. 980 766 quality-filtered sequences) indicate that both niche (environmental filtering) and neutral (stochastic) processes shape fungal community composition at landscape level. Fungal community composition correlated strongly with aspect, with many fungi showing preference for either south-facing or north-facing slopes. Several taxonomic and functional groups showed significant differences in richness between north-and south-facing slopes and strong compositional differences were observed in all functional groups. The effect of aspect on fungal communities likely is mediated through contrasting mesoclimatic conditions, that in turn influence edaphic processes as well as vegetation. Finally, the data presented here provide an unprecedented insight into the diversity and landscape-level community dynamics of fungi in the Pannonian forests.
Radioprotective role of cyanobacterial phycobilisomes
Authors: Klementiev Konstantin E. , Maksimov Eugene G. , Gvozdev Danil A. , Tsoraev Georgy V. , Protopopov Fedor F. , Elanskaya Irina V. , Abramov Sergey M. , Dyakov Maksim Yu. , Ilyin Vyacheslav K. , Nikolaeva Nadezhda A. , Slonimskiy Yury B. , Sluchanko Nikolai N. , Lebedev Victor M. , Spassky Andrew V. , Friedrich Thomas , Maksimov Georgy V. , Paschenko Vladimir Z. , Rubin Andrew B. 
Published: March 2018

AbstractIt is now generally accepted that cyanobacteria are responsible for production of oxygen, which led to the so-called “Great Oxygenation Event”. Appearance of dioxygen in Earth’s atmosphere resulted in formation of the ozone layer and the ionosphere, which caused significant reduction of ionizing radiation levels at the surface of our planet. This event not only increased biological diversity but also canceled the urgency of previously developed mechanisms of DNA protection, which allowed to survive and develop in harsh environmental conditions including exposure to cosmic rays. In order to test the hypothesis if one of the oldest organisms on Earth retained ancient protection mechanisms, we studied the effect of ionizing radiation (IoR, here: α-particles with a kinetic energy of about 30 MeV) and space flight during the mission of the Foton-M4 satellite on cells of Synechocystis sp. PCC6803. By analyzing spectral and functional characteristics of photosynthetic membranes we revealed numerous similarities between cells exposed to IoR and after the space mission. In both cases, we found that excitation energy transfer from phycobilisomes to photosystems was interrupted and the concentration of phycobiliproteins was significantly reduced. Although photosynthetic activity was severely suppressed, the effect was reversible and the cells were able to rapidly recover from stress under normal conditions. Moreover, in vitro experiments demonstrated that the effect of IoR on isolated phycobilisomes was completely different from such in vivo. These observations suggest that the actual existence and the uncoupling of phycobilisomes under irradiation stress could play specific role not only in photo-, but also in radioprotection, which was crucial for early stages of evolution and the development of Life on Earth.
Effect of buspirone on the H-reflex in acute spinal decerebrated mice
Authors: Develle Yann , Leblond Hugues 
Published: March 2018

ABSTRACTPharmacological treatment facilitating locomotor expression also modulates reflex expression through the re-arrangement of spinal networks. Buspirone, a partial serotonin receptor agonist (5-HT1A), was recently shown to facilitate and even trigger locomotor movements in mice after complete spinal lesion (Tx). Here, we studied its effect on the H-reflex after acute Tx in adult mice. To avoid possible impacts of anesthetics on H-reflex depression, experiments were performed after decerebration in un-anesthetized mice (N=13). The H-reflex in plantar muscles of the hind-paw was recorded after tibial nerve stimulation 2 h after Tx at the 8ththoracic vertebrae. Average H/M ratio was compared before and every 10 min after buspirone (8 mg/kg, i.p.) for 60 min. Frequency-dependent depression (FDD) of the H-reflex was assessed before and 50 min after buspirone. Before buspirone, a stable H-reflex could be elicited in acute spinal mice and FDD of the H-reflex was observed at 5Hz (68%) and 10Hz (70%) relative to 0.2Hz. After buspirone, the H/M ratio was initially significantly decreased to 69% of pre-treatment. It then increased significantly 30 to 60 min after exposure to buspirone, reaching 170% 60 min after injection. FDD 50 min after buspirone was not significantly different that FDD without treatment. Altogether results suggest that the reported pro-locomotor effect of buspirone occurs at a time where there is a reflex depression followed by a second phase marked by enhancement of reflex excitability, denoting functional inhibitory control.KEY POINTS SUMMARYBuspirone, a partial serotoninergic agonist (5HT1A), exerts a considerable acute facilitation of spinally-mediated locomotion after a complete spinal lesion in mice.Since locomotion is associated with reflex modulation, we focused in this study on the effect of buspirone on H-reflex in acute spinal mice after decerebration and removal of anesthesia.Buspirone injection resulted in a depression of the H-reflex during the first 20 minutes followed, 40 minutes later, by an increase of the reflex.The H-reflex increase is not due to a disinhibition since buspirone had no effect on the frequency dependent depression (FDD) of the H-reflex.The use of a model of adult decerebrate mouse with complete spinal cord injury allows to establish that buspirone has a biphasic effect on the H-reflex and that the inhibitory action on sensory information concurs with an excitatory action on locomotion.Abbreviations5-HT5-Hydroxytryptamine5-HT1A1A subunit in 5-Hydroxytryptamine receptor8-OHDPAT8-Hydroxy-2-DI-n-Propylamino-Tetraline CPG Central Pattern GeneratorEMGelectromyographicFDDFrequency Dependent DepressionGABAGamma-Aminobutyric-Acid TASK-1 acid-sensitiv-K-1Txcomplete transection
Epithelial micro-invasion byStreptococcus pneumoniaeinduces epithelial-derived innate immunity during colonisation at the human mucosal surface
Authors: Weight Caroline M , Venturini Cristina , Pojar Sherin , Jochems Simon P. , Reiné Jesús , Nikolaou Elissavet , Solórzano Carla , Noursadeghi Mahdad , Brown Jeremy S , Ferreira Daniela M. , Heyderman Robert S 
Published: March 2018

ABSTRACTControl ofStreptococcus pneumoniaecolonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Using an Experimental Human Pneumococcal Carriage Model (EHPC), we show thatS. pneumoniaecolonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epitheliumin vitroshaped the host transcriptomic response. Using epithelial modules from a human epithelial cell model that recapitulates ourin vivofindings, comprising of innate signalling/ regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. These results show that rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances the inflammatory/ innate immune response associated with clearance.
An Open-source Tool for Analysis and Automatic Identification of Dendritic Spines Using Machine Learning
Authors: Smirnov Michael S , Garrett Tavita R , Yasuda Ryohei 
Published: March 2018

AbstractSynaptic plasticity, the cellular basis for learning and memory, is mediated by a complex biochemical network of signaling proteins. These proteins are compartmentalized in dendritic spines, the tiny, bulbous, post-synaptic structures found on neuronal dendrites. The ability to screen a high number of molecular targets for their effect on dendritic spine structural plasticity will require a high-throughput imaging system capable of stimulating and monitoring hundreds of dendritic spines in various conditions. For this purpose, we present a program capable of automatically identifying dendritic spines in live, fluorescent tissue. Our software relies on a machine learning approach to minimize any need for parameter tuning from the user. Custom thresholding and binarization functions serve to “clean” fluorescent images, and a neural network is trained using features based on the relative shape of the spine perimeter and its corresponding dendritic backbone. Our algorithm is rapid, flexible, has over 90% accuracy in spine detection, and bundled with our user-friendly, open-source, MATLAB-based software package for spine analysis.
Multimodal modeling of neural network activity: computing LFP, ECoG, EEG and MEG signals with LFPy2.0
Authors: Hagen Espen , Næss Solveig , Ness Torbjørn V. , Einevoll Gaute T. 
Published: March 2018

AbstractRecordings of extracellular electrical, and later also magnetic, brain signals have been the dominant technique for measuring brain activity for decades. The interpretation of such signals is however nontrivial, as the measured signals result from both local and distant neuronal activity. In volume-conductor theory the extracellular potentials can be calculated from a distance-weighted sum of contributions from transmembrane currents of neurons. Given the same transmembrane currents, the contributions to the magnetic field recorded both inside and outside the brain can also be computed. This allows for the development of computational tools implementing forward models grounded in the biophysics underlying electrical and magnetic measurement modalities.LFPy (LFPy.readthedocs.io) incorporated a well-established scheme for predicting extracellular potentials of individual neurons with arbitrary levels of biological detail. It relies on NEURON (neuron.yale.edu) to compute transmembrane currents of multicompartment neurons which is then used in combination with an electrostatic forward model. Its functionality is now extended to allow for modeling of networks of multicompartment neurons with concurrent calculations of extracellular potentials and current dipole moments. The current dipole moments are then, in combination with suitable volume-conductor head models, used to compute non-invasive measures of neuronal activity, like scalp potentials (electroencephalographic recordings; EEG) and magnetic fields outside the head (magnetoencephalographic recordings; MEG). One such built-in head model is the four-sphere head model incorporating the different electric conductivities of brain, cerebrospinal fluid, skull and scalp.We demonstrate the new functionality of the software by constructing a network of biophysically detailed multicompartment neuron models from the Neocortical Microcircuit Collaboration (NMC) Portal (bbp.epfl.ch/nmc-portal) with corresponding statistics of connections and synapses, and computein vivo-like extracellular potentials (local field potentials, LFP; electrocorticographical signals, ECoG) and corresponding current dipole moments. From the current dipole moments we estimate corresponding EEG and MEG signals using the four-sphere head model. We also show strong scaling performance of LFPy with different numbers of message-passing interface (MPI) processes, and for different network sizes with different density of connections.The open-source software LFPy is equally suitable for execution on laptops and in parallel on high-performance computing (HPC) facilities and is publicly available onGitHub.com.
Data-theoretical Synthesis of the Early Developmental Process
Authors: Alicea Bradly , Gordon Richard , Portegys Thomas E. 
Published: March 2018

AbstractBiological development is often described as a dynamic, emergent process. This is evident across a variety of phenomena, from the temporal organization of cell types in the embryo to compounding trends that affect large-scale differentiation. To better understand this, we propose combining quantitative investigations of biological development with theory-building techniques. This provides an alternative to the gene-centric view of development: namely, the view that developmental genes and their expression determine the complexity of the developmental phenotype. Using the model systemCaenorhabditis elegans, we examine time-dependent properties of the embryonic phenotype and utilize the unique life-history properties to demonstrate how these emergent properties can be linked together by data analysis and theory-building. We also focus on embryogenetic differentiation processes, and how terminally-differentiated cells contribute to structure and function of the adult phenotype. Examining embryogenetic dynamics from 200 to 400 minutes post-fertilization provides basic quantitative information on developmental tempo and process. To summarize, theory construction techniques are summarized and proposed as a way to rigorously interpret our data. Our proposed approach to a formal data representation that can provide critical links across life-history, anatomy and function.
Association of whole-genome and NETRIN1 signaling pathway-derived polygenic risk scores for Major Depressive Disorder and thalamic radiation white matter microstructure in UK Biobank
Authors: Barbu Miruna C. , Zeng Yanni , Shen Xueyi , Cox Simon R. , Clarke Toni-Kim , Gibson Jude , Adams Mark J. , Johnstone Mandy , Haley Chris S. , Lawrie Stephen M. , Deary Ian J. ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,   23andMe Research Team, McIntosh Andrew M. , Whalley Heather C. 
Published: March 2018

AbstractBackgroundMajor Depressive Disorder (MDD) is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome, and growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide an important route for identification of disease mechanisms by focusing on a specific process excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether MDD polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRS) and the whole genome excluding NETRIN1 pathway genes (genomic-PRS) were associated with white matter integrity.MethodsWe used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: N = 6,401; MD: N = 6,390).ResultsWe found significantly lower FA in the superior longitudinal fasciculus (β = -0.035, pcorrected = 0.029) and significantly higher MD in a global measure of thalamic radiations (β = 0.029, pcorrected = 0.021), as well as higher MD in the superior (β = 0.034, pcorrected = 0.039) and inferior (β = 0.029, pcorrected = 0.043) longitudinal fasciculus and in the anterior (β = 0.025, pcorrected = 0.046) and superior (β = 0.027, pcorrected = 0.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.ConclusionsOur findings indicate that variation in the NETRIN1 signaling pathway may confer risk for MDD through effects on thalamic radiation white matter microstructure.
The mitochondrial genomes of the mesozoansIntoshia linei, Dicyemasp., andDicyema japonicum
Authors: Robertson Helen. E. , Schiffer Philipp. H. , Telford Maximilian. J. 
Published: March 2018

AbstractThe Dicyemida and Orthonectida are two groups of tiny, simple, vermiform parasites that have historically been united in a group named the Mesozoa. Both Dicyemida and Orthonectida have just two cell layers and appear to lack any defined tissues. They were initially thought to be evolutionary intermediates between protozoans and metazoans but more recent analyses indicate that they are protostomian metazoans that have undergone secondary simplification from a complex ancestor. Here we describe the first almost complete mitochondrial genome sequence from an orthonectid,Intoshia linei, and describe nine and eight mitochondrial protein-coding genes fromDicyemasp. andDicyema japonicum, respectively. The 14,247 base pair longI. lineisequence has typical metazoan gene content, but is exceptionally AT-rich, and has a divergent gene order compared to other metazoans. The data we present from the Dicyemida provide very limited support for the suggestion that dicyemid mitochondrial genes are found on discrete mini-circles, as opposed to the large circular mitochondrial genomes that are typical across the Metazoa. Thecox1gene from dicyemid species has a series of conserved in-frame deletions that is unique to this lineage. Usingcox1genes from across the genusDicyema, we report the first internal phylogeny of this group.Key FindingsWe report the first almost-complete mitochondrial genome from an orthonectid parasite,Intoshia linei, including 12 protein-coding genes; 20 tRNAs and putative sequences for large and small subunit rRNAs. We find that theI. lineimitochondrial genome is exceptionally AT-rich and has a novel gene order compared to other published metazoan mitochondrial genomes. These findings are indicative of the rapid rate of evolution that has occurred in theI. lineimitochondrial genome.We also report nine and eight protein-coding genes, respectively, from the dicyemid speciesDicyemasp. andDicyema japonicum, and use thecox1genes from both species for phylogenetic inference of the internal phylogeny of the dicyemids.We find that thecox1gene from dicyemids has a series of four conserved in-frame deletions which appear to be unique to this group.