bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility
Authors: Lehmann Michael L. , Weigel Thaddeus K. , Cooper Hannah A. , Elkahloun Abdel G. , Kigar Stacey L. , Herkenham Miles 
Published: July 2018

AbstractAn animal’s ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brain’s immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglia were isolated and analyzed by microarray. Microglia transcriptomes from CSD-S mice were enriched for pathways associated with inflammation, phagocytosis, oxidative stress, and extracellular matrix remodeling. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or non-stressed control mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by extracellular matrix degradation, oxidative stress, microbleeds, and entry and phagocytosis of blood-borne substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.
The habu genome reveals accelerated evolution of venom protein genes
Authors: Shibata Hiroki , Chijiwa Takahito , Oda-Ueda Naoko , Nakamura Hitomi , Yamaguchi Kazuaki , Hattori Shousaku , Matsubara Kazumi , Matsuda Yoichi , Yamashita Akifumi , Isomoto Akiko , Mori Kazuki , Tashiro Kosuke , Kuhara Satoru , Yamasaki Shinichi , Fujie Manabu , Goto Hiroki , Koyanagi Ryo , Takeuchi Takeshi , Fukumaki Yasuyuki , Ohno Motonori , Shoguchi Eiichi , Hisata Kanako , Satoh Noriyuki , Ogawa Tomohisa 
Published: July 2018

AbstractEvolution of novel traits is a challenging subject in biological research. Several snake lineages developed elaborate venom systems to deliver complex protein mixtures for prey capture. To understand mechanisms involved in snake venom evolution, we decoded here the ~1.4-Gb genome of a habu, Protobothrops flavoviridis. We identified 60 snake venom protein genes (SV) and 224 non-venom paralogs (NV), belonging to 18 gene families. Molecular phylogeny reveals early divergence of SV and NV genes, suggesting that one of the four copies generated through two rounds of whole-genome duplication was modified for use as a toxin. Among them, both SV and NV genes in four major components were extensively duplicated after their diversification, but accelerated evolution is evident exclusively in the SV genes. Both venom-related SV and NV genes are significantly enriched in microchromosomes. The present study thus provides a genetic background for evolution of snake venom composition.
The Polynomial Volume Law of Complex Networks in the Context of Local and Global Optimization
Authors: Mocnik Franz-Benjamin 
Published: July 2018

AbstractMany complex networks expose global hub structures: for some nodes, the number of incident edges far exceeds the average, leading to a small average shortest path length. Such ‘small-world properties’ are often guided by a scale-free power-law distribution of the node degrees, and self-organization inside the network has been identified as a reason driving the emergence of this structure. Small-world networks have recently raised lots of interest, because they capture the global topology of the World-Wide Web, metabolic, and social networks. While small-world networks reflect global structures, little attention is paid to the local structure of complex networks. In this article neighbourhoods are demonstrated to share a common local structure in many real complex networks, manifested by a polynomial volume law. This law can, in case of networks that are embedded in space, be explained in terms of the embedding and the properties of Euclidean space. A model of hierarchical spatial networks is introduced to examine the effect of global structures, in particular of hierarchies, on the polynomial volume law. It turns out that the law is robust against the coexistence of such global structures. The local structure of space and global optimization can both be found in transport, brain, and communication networks, which suggests the polynomial volume law, often in combination with hierarchies or other global optimization principles, to be a generic property inherent to many networks.
Vrk1 partial Knockdown in Mice Results in Reduced Brain Weight and Mild Motor Dysfunction, and Indicates Neuronal VRK1 Target Pathways
Authors: Vinograd-Byk Hadar , Renbaum Paul , Levy-Lahad Ephrat 
Published: July 2018

AbstractMutations in Vaccinia-related kinase 1 (VRK1) have emerged as a cause of severe neuronal phenotypes in human, including brain developmental defects and degeneration of spinal motor neurons, leading to Spinal Muscular Atrophy (SMA) or early onset Amyotrophic Lateral Sclerosis (ALS). Vrk1 gene-trap partial Knockout (KO) mice (Vrk1GT3/GT3), which express decreased levels of Vrk1, are sterile due to impaired gamete production. Here, we examined whether this mouse model also presents neuronal phenotypes. We found a 20–50% reduction in Vrk1 expression in neuronal tissues of the Vrk1GT3/GT3 mice, leading to mild neuronal phenotypes including significant but small reduction in brain mass and motor (rotarod) impairment. Analysis of gene expression in the Vrk1GT3/GT3 cortex predicts novel roles for VRK1 in neuronal pathways including neurotrophin signaling, axon guidance and pathways implicated in the pathogenesis of ALS. Together, our studies of the partial KO Vrk1 mice reveal that even moderately reduced levels of Vrk1 expression result in minor neurological impairment and indicate new neuronal pathways likely involving VRK1.
Structural brain imaging in Alzheimer’s disease and mild cognitive impairment: biomarker analysis and shared morphometry database
Authors: Ledig Christian , Schuh Andreas , Guerrero Ricardo , Heckemann Rolf A. , Rueckert Daniel 
Published: July 2018

AbstractMagnetic resonance (MR) imaging is a powerful technique for non-invasive in-vivo imaging of the human brain. We employed a recently validated method for robust cross-sectional and longitudinal segmentation of MR brain images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Specifically, we segmented 5074 MR brain images into 138 anatomical regions and extracted time-point specific structural volumes and volume change during follow-up intervals of 12 or 24 months. We assessed the extracted biomarkers by determining their power to predict diagnostic classification and by comparing atrophy rates to published meta-studies. The approach enables comprehensive analysis of structural changes within the whole brain. The discriminative power of individual biomarkers (volumes/atrophy rates) is on par with results published by other groups. We publish all quality-checked brain masks, structural segmentations, and extracted biomarkers along with this article. We further share the methodology for brain extraction (pincram) and segmentation (MALPEM, MALPEM4D) as open source projects with the community. The identified biomarkers hold great potential for deeper analysis, and the validated methodology can readily be applied to other imaging cohorts.
Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats
Authors: Naves Lara Marques , Marques Stefanne Madalena , Mourão Aline Andrade , Fajemiroye James Oluwagbamigbe , Xavier Carlos Henrique , de Castro Carlos Henrique , Rebelo Ana Cristina Silva , Rosa Daniel Alves , Gomes Rodrigo Mello , Colombari Eduardo , Pedrino Gustavo Rodrigues 
Published: July 2018

AbstractThe infusion of hypertonic saline solution (HSS) is known to be beneficial to the treatment of hypovolemic hemorrhage (HH). The central mechanism of HSS-induced cardiovascular and autonomic recovery of animals subjected to HH remains unclear. Hence, the present study evaluated the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats. The wistar rats were subjected to specific lesion of noradrenergic neurons through the nanoinjections of anti-DβH-saporin into caudal ventrolateral medulla (A1 neurons) and nucleus of the solitary tract (A2 neurons). After recovery, mean arterial pressure (MAP) and renal sympathetic nervous activity were recorded. The HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. In sham rats, HSS infusion (3M NaCl) reestablished MAP without change in HH-induced sympathoinhibition. The muscimol (agonist of GABAA receptor) was nanoinjected in MnPO during HH and MnPO inhibition abolished the recovery of MAP and HSS-induced sympathoinhibition. Simultaneous lesions of A1 and A2 abolished MAP restoration and sympathoinhibition after HSS infusion. These results suggest that the recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.
Computational Design of Epitope-Enriched HIV-1 Gag Antigens with Preserved Structure and Function for Induction of Broad CD8+ T Cell Responses
Authors: Asbach Benedikt , Meier Johannes P. , Pfeifer Matthias , Köstler Josef , Wagner Ralf 
Published: July 2018

AbstractThe partially protective phenotype observed in HIV-infected long-term-non-progressors is often associated with certain HLA alleles, thus indicating that cytotoxic T lymphocyte (CTL) responses play a crucial role in combating virus replication. However, both the vast variability of HIV and the HLA diversity impose a challenge on elicitation of broad and effective CTL responses. Therefore, we conceived an algorithm for the enrichment of CD8+T cell epitopes in HIV’s Gag protein, respecting functional preservation to enable cross-presentation. Experimentally identified epitopes were compared to a Gag reference sequence. Amino-acid-substitutions (AAS) were assessed for their impact on Gag’s budding-function using a trained classifier that considers structural models and sequence conservation. Experimental assessment of Gag-variants harboring selected AAS demonstrated an apparent classifier-precision of 100%. Compatible epitopes were assigned an immunological score that incorporates features such as conservation or HLA-association in a user-defined weighted manner. Using a genetic algorithm, the epitopes were incorporated in an iterative manner into novel T-cell-epitope-enriched Gag sequences (TeeGag). Computational evaluation showed that these antigen candidates harbor a higher fraction of epitopes with higher score as compared to natural Gag isolates and other artificial antigen designs. Thus, these designer sequences qualify as next-generation antigen candidates for induction of broader CTL responses.
Prognostication and Risk Factors for Cystic Fibrosis via Automated Machine Learning
Authors: Alaa Ahmed M. , van der Schaar Mihaela 
Published: July 2018

AbstractAccurate prediction of survival for cystic fibrosis (CF) patients is instrumental in establishing the optimal timing for referring patients with terminal respiratory failure for lung transplantation (LT). Current practice considers referring patients for LT evaluation once the forced expiratory volume (FEV1) drops below 30% of its predicted nominal value. While FEV1 is indeed a strong predictor of CF-related mortality, we hypothesized that the survival behavior of CF patients exhibits a lot more heterogeneity. To this end, we developed an algorithmic framework, which we call AutoPrognosis, that leverages the power of machine learning to automate the process of constructing clinical prognostic models, and used it to build a prognostic model for CF using data from a contemporary cohort that involved 99% of the CF population in the UK. AutoPrognosis uses Bayesian optimization techniques to automate the process of configuring ensembles of machine learning pipelines, which involve imputation, feature processing, classification and calibration algorithms. Because it is automated, it can be used by clinical researchers to build prognostic models without the need for in-depth knowledge of machine learning. Our experiments revealed that the accuracy of the model learned by AutoPrognosis is superior to that of existing guidelines and other competing models.
Statistical modelling of navigational decisions based on intensity versus directionality in Drosophila larval phototaxis
Authors: de Andres-Bragado Lucia , Mazza Christian , Senn Walter , Sprecher Simon G. 
Published: July 2018

AbstractOrganisms use environmental cues for directed navigation. Understanding the basic logic behind navigational decisions critically depends on the complexity of the nervous system. Due to the comparably simple organization of the nervous system of the fruit fly larva, it stands as a powerful model to study decision-making processes that underlie directed navigation. We have quantitatively measured phototaxis in response to well-defined sensory inputs. Subsequently, we have formulated a statistical stochastic model based on biased Markov chains to characterize the behavioural basis of negative phototaxis. Our experiments show that larvae make navigational decisions depending on two independent physical variables: light intensity and its spatial gradient. Furthermore, our statistical model quantifies how larvae balance two potentially-contradictory factors: minimizing exposure to light intensity and at the same time maximizing their distance to the light source. We find that the response to the light field is manifestly non-linear, and saturates above an intensity threshold. The model has been validated against our experimental biological data yielding insight into the strategy that larvae use to achieve their goal with respect to the navigational cue of light, an important piece of information for future work to study the role of the different neuronal components in larval phototaxis.
Investigation on Anti-Autofluorescence, Osteogenesis and Long-Term Tracking of HA-Based Upconversion Material
Authors: Li Xiyu , Zou Qin , Li Wei , Chen Haifeng 
Published: July 2018

AbstractHydroxyapatite (HA) material will be long-standing once implanted in bone tissue of the body. It should be considered to endow the osteogenic HA material with traceable fluorescence to realize a lifelong in vivo tracking. We prepared and utilized lanthanides-doped HA upconversion material, and revealed for the first time that the lanthanides (ytterbium (Yb) and holmium (Ho)) co-doped HA upconversion material was suitable for long-term or lifelong in vivo tracking, the lanthanide ions doped in the HA matrix would not affect the biocompatibility and osteogenesis, and the tissue autofluorescence could be effectively avoided by the HA:Yb/Ho upconversion material. Also the distribution in bone and osteointegration with bone of the HA:Yb/Ho material could be clearly discriminated by its bright fluorescence under NIR irradiation. The upconversion characteristic of the HA:Yb/Ho material provides a feasibility and promising prospect for lifelong in vivo tracking, and has an advantage in revealing the material-tissue interrelation. The material has important clinical application value in addition to its usefulness for scientific investigation.
Bacterial inactivation by plasma treated water enhanced by reactive nitrogen species
Authors: Shaw Priyanka , Kumar Naresh , Kwak Hyong Sin , Park Ji Hoon , Uhm Han Sup , Bogaerts Annemie , Choi Eun Ha , Attri Pankaj 
Published: July 2018

AbstractThere is a growing body of literature that recognizes the importance of plasma treated water (PTW) for inactivation of microorganism. However, very little attention has been paid to the role of reactive nitrogen species (RNS) in deactivation of bacteria. The aim of this study is to explore the role of RNS in bacterial killing, and to develop a plasma system with increased sterilization efficiency. To increase the concentration of reactive oxygen and nitrogen species (RONS) in solution, we have used vapor systems (DI water/HNO3 at different wt%) combined with plasma using N2 as working gas. The results show that the addition of the vapor system yields higher RONS contents. Furthermore, PTW produced by N2 + 0.5 wt% HNO3 vapor comprises a large amount of both RNS and ROS, while PTW created by N2 + H2O vapor consists of a large amount of ROS, but much less RNS. Interestingly, we observed more deactivation of E. Coli with PTW created by N2 + 0.5 wt% HNO3 vapor plasma as compared to PTW generated by the other plasma systems. This work provides new insight into the role of RNS along with ROS for deactivation of bacteria.
Driven nonlinear nanomechanical resonators as digital signal detectors
Authors: Tadokoro Yukihiro , Tanaka Hiroya , Dykman M. I. 
Published: July 2018

AbstractBecause of their nonlinearity, vibrational modes of resonantly driven nanomechanical systems have coexisting stable states of forced vibrations in a certain range of the amplitude of the driving force. Depending on its phase, which encodes binary information, a signal at the same frequency increases or decreases the force amplitude. The resulting force amplitude can be outside the range of bistability. The values of the mode amplitude differ significantly on the opposite sides of the bistability region. Therefore the mode amplitude is very sensitive to the signal phase. This suggests using a driven mode as a bi-directional bifurcation amplifier, which switches in the opposite directions depending on the signal phase and provides an essentially digital output. We study the operation of the amplifier near the critical point where the width of the bistability region goes to zero and thus the threshold of the signal amplitude is low. We also develop an analytical technique and study the error rate near the threshold. The results apply to a broad range of currently studied systems and extend to micromechanical systems and nonlinear electromagnetic cavities.
Playing with universality classes of Barkhausen avalanches
Authors: Bohn Felipe , Durin Gianfranco , Correa Marcio Assolin , Machado Núbia Ribeiro , Della Pace Rafael Domingues , Chesman Carlos , Sommer Rubem Luis 
Published: July 2018

AbstractMany systems crackle, from earthquakes and financial markets to Barkhausen effect in ferromagnetic materials. Despite the diversity in essence, the noise emitted in these dynamical systems consists of avalanche-like events with broad range of sizes and durations, characterized by power-law avalanche distributions and typical average avalanche shape that are fingerprints describing the universality class of the underlying avalanche dynamics. Here we focus on the crackling noise in ferromagnets and scrutinize the traditional statistics of Barkhausen avalanches in polycrystalline and amorphous ferromagnetic films having different thicknesses. We show how scaling exponents and average shape of the avalanches evolve with the structural character of the materials and film thickness. We find quantitative agreement between experiment and theoretical predictions of models for the magnetic domain wall dynamics, and then elucidate the universality classes of Barkhausen avalanches in ferromagnetic films. Thereby, we observe for the first time the dimensional crossover in the domain wall dynamics and the outcomes of the interplay between system dimensionality and range of interactions governing the domain wall dynamics on Barkhausen avalanches.
Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei
Authors: Kehrer Jessica , Kuss Claudia , Andres-Pons Amparo , Reustle Anna , Dahan Noa , Devos Damien , Kudryashev Mikhail , Beck Martin , Mair Gunnar R. , Frischknecht Friedrich 
Published: July 2018

AbstractThe nuclear pore complex (NPC) is a large macromolecular assembly of around 30 different proteins, so-called nucleoporins (Nups). Embedded in the nuclear envelope the NPC mediates bi-directional exchange between the cytoplasm and the nucleus and plays a role in transcriptional regulation that is poorly understood. NPCs display modular arrangements with an overall structure that is generally conserved among many eukaryotic phyla. However, Nups of yeast or human origin show little primary sequence conservation with those from early-branching protozoans leaving those of the malaria parasite unrecognized. Here we have combined bioinformatic and genetic methods to identify and spatially characterize Nup components in the rodent infecting parasite Plasmodium berghei and identified orthologs from the human malaria parasite P. falciparum, as well as the related apicomplexan parasite Toxoplasma gondii. For the first time we show the localization of selected Nups throughout the P. berghei life cycle. Largely restricted to apicomplexans we identify an extended C-terminal poly-proline extension in SEC13 that is essential for parasite survival and provide high-resolution images of Plasmodium NPCs obtained by cryo electron tomography. Our data provide the basis for full characterization of NPCs in malaria parasites, early branching unicellular eukaryotes with significant impact on human health.
Mediation analysis reveals common mechanisms of RUNX1 point mutations and RUNX1/RUNX1T1 fusions influencing survival of patients with acute myeloid leukemia
Authors: Hornung Roman , Jurinovic Vindi , Batcha Aarif M. N. , Bamopoulos Stefanos A. , Rothenberg-Thurley Maja , Amler Susanne , Sauerland Maria Cristina , Berdel Wolfgang E. , Wörmann Bernhard J. , Bohlander Stefan K. , Braess Jan , Hiddemann Wolfgang , Lehmann Sören , Mareschal Sylvain , Spiekermann Karsten , Metzeler Klaus H. , Herold Tobias , Boulesteix Anne-Laure 
Published: July 2018

AbstractAlterations of RUNX1 in acute myeloid leukemia (AML) are associated with either a more favorable outcome in the case of the RUNX1/RUNX1T1 fusion or unfavorable prognosis in the case of point mutations. In this project we aimed to identify genes responsible for the observed differences in outcome that are common to both RUNX1 alterations. Analyzing four AML gene expression data sets (n = 1514), a total of 80 patients with RUNX1/RUNX1T1 and 156 patients with point mutations in RUNX1 were compared. Using the statistical tool of mediation analysis we identified the genes CD109, HOPX, and KIAA0125 as candidates for mediator genes. In an analysis of an independent validation cohort, KIAA0125 again showed a significant influence with respect to the impact of the RUNX1/RUNX1T1 fusion. While there were no significant results for the other two genes in this smaller validation cohort, the observed relations linked with mediation effects (i.e., those between alterations, gene expression and survival) were almost without exception as strong as in the main analysis. Our analysis demonstrates that mediation analysis is a powerful tool in the identification of regulative networks in AML subgroups and could be further used to characterize the influence of genetic alterations.