bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Pattern of Gadodiamide-Related T1 Hyperintensity Increase Within the Deep Brain Nuclei
Authors: Marie Guillaume P.O. , Pozeg Polona , Meuli Reto A. , Maeder Philippe , Forget Joachim 
Published: July 2018

Objectives
The purpose of the study was to systematically evaluate the precise spatial and temporal pattern of gadolinium-related changes in T1-weighted signal intensity on unenhanced magnetic resonance (MR) images, occurring in the deep brain nuclei of adult patients exposed to at least 10 consecutive doses of gadodiamide.

Materials and Methods
In this monocentric retrospective longitudinal study, we analyzed the brain MR images of 30 patients (12 women, 18 men; mean age, 43 ± 11.6 years) acquired between December 1998 and March 2008. We drew the regions of interest in the dentate nucleus, globus pallidus, putamen, pulvinar, ventral posterior nucleus of the thalamus, superior colliculus, substantia nigra, and white matter on unenhanced T1-weighted images. Each region of interest’s mean signal intensity was normalized by the mean intensity of the pons. The normalized signal intensities were measured at the baseline before first gadodiamide administration and at each of 10 successive MR imaging examinations. We used linear mixed effects models to analyze the data.

Results
We observed a significant linear increase of signal intensity ratios across 10 successive gadodiamide administrations (all basal nuclei were significant at P < 0.001, except the ventral posterior thalamus, where P < 0.05), with the fastest signal intensity increase in the dentate nucleus (B = 0.010), followed by the globus pallidus (B = 0.0068), putamen (B = 0.0063), pulvinar (B = 0.0062), superior colliculus (B = 0.0057), substantia nigra (B = 0.0034), and ventral posterior nucleus of the thalamus (B = 0.0031). No significant signal increase was observed in the white matter (P > 0.05).

Conclusions
Multiple consecutive administration of gadodiamide is associated with an increase in T1-weighted hypersignal on the unenhanced scans, displaying a gradual and nonuniform pattern across different deep brain nuclei, including the ventral posterior thalamus, which was used as a reference tissue in previous studies.
Interictal Epileptiform Discharge Detection in EEG in Different Practice Settings
Authors: Halford Jonathan J. , Westover M. Brandon , LaRoche Suzette M. , Macken Micheal P. , Kutluay Ekrem , Edwards Jonathan C. , Bonilha Leonardo , Kalamangalam Giridhar P. , Ding Kan , Hopp Jennifer L. , Arain Amir , Dawson Rachael A. , Martz Gabriel U. , Wolf Bethany J. , Waters Chad G. , Dean Brian C. 
Published: July 2018

Objective:
The goal of the study was to measure the performance of academic and private practice (PP) neurologists in detecting interictal epileptiform discharges in routine scalp EEG recordings.

Methods:
Thirty-five EEG scorers (EEGers) participated (19 academic and 16 PP) and marked the location of ETs in 200 30-second EEG segments using a web-based EEG annotation system. All participants provided board certification status, years of Epilepsy Fellowship Training (EFT), and years in practice. The Persyst P13 automated IED detection algorithm was also run on the EEG segments for comparison.

Results:
Academic EEGers had an average of 1.66 years of EFT versus 0.50 years of EFT for PP EEGers (P < 0.0001) and had higher rates of board certification. Inter-rater agreement for the 35 EEGers was fair. There was higher performance for EEGers in academics, with at least 1.5 years of EFT, and with American Board of Clinical Neurophysiology and American Board of Psychiatry and Neurology-E specialty board certification. The Persyst P13 algorithm at its default setting (perception value = 0.4) did not perform as well at the EEGers, but at substantially higher perception value settings, the algorithm performed almost as well human experts.

Conclusions:
Inter-rater agreement among EEGers in both academic and PP settings varies considerably. Practice location, years of EFT, and board certification are associated with significantly higher performance for IED detection in routine scalp EEG. Continued medical education of PP neurologists and neurologists without EFT is needed to improve routine scalp EEG interpretation skills. The performance of automated detection algorithms is approaching that of human experts.
A Virus-Packageable CRISPR Screen Identifies Host Factors Mediating Interferon Inhibition of HIV
Authors: Ohainle Molly , Pendergast Louisa , Vermiere Jolien , Roesch Ferdinand , Humes Daryl , Basom Ryan , Delrow Jeffrey J. , Overbaugh Julie , Emerman Michael 
Published: July 2018

AbstractInterferon (IFN) inhibits HIV replication by inducing an array of antiviral effectors. Here we describe a novel CRISPR knockout screening approach to identify the ensemble of these HIV restriction factors. We assembled a CRISPR sgRNA library specific for Interferon Stimulated Genes (ISGs) into a modified lentiviral vector that allows for packaging of sgRNA-encoding genomesin transinto budding HIV-1 particles. We observed that knockout of Zinc Antiviral Protein (ZAP) improved the performance of the screen due to ZAP-mediated inhibition of the vector. We identify a small panel of IFN-induced HIV restriction factors, including MxB, IFITM1, Tetherin/BST2 and TRIM5 which together explain the inhibitory effects of IFN on the HIV-1 LAI strain in THP-1 cells. Further, we identify novel HIV dependency factors, including SEC62 and TLR2. The ability of IFN-induced restriction factors to inhibit an HIV strain to replicate in human cells suggests that these human restriction factors are incompletely antagonized.
In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells
Authors: Ashraf Sumaira , Taylor Arthur , Sharkey Jack , Barrow Michael , Murray Patricia , Wilm Bettina , Poptani Harish , Rosseinsky Matthew J. , Adams Dave , Lévy Raphaël 
Published: July 2018

AbstractNanoparticle contrast agents are useful tools to label stem cells and monitor the in vivo bio-distribution of labeled cells in pre-clinical models of disease. In this context, understanding the in vivo fate of the particles after injection of labelled cells is important for their eventual clinical use as well as for the interpretation of imaging results. We examined how the formulation of superparamagnetic iron oxide nanoparticles (SPIONs) impacts the labelling efficiency, magnetic characteristics and fate of the particles by comparing individual SPIONs with polyelectrolyte multilayer capsules containing SPIONs. At low labelling concentration, encapsulated SPIONs served as an efficient labelling agent for stem cells. The bio-distribution after intra-cardiac injection of labelled cells was monitored longitudinally by MRI and as an endpoint by inductively coupled plasma-optical emission spectrometry. The results suggest that, after being released from labelled cells after cell death, both formulations of particles are initially stored in liver and spleen and are not completely cleared from these organs 2 weeks post-injection.
γ-proteobacteria eject their polar flagella under nutrient depletion, retaining flagellar motor relic structures
Authors: Ferreira Josie L. , Gao Forson Z. , Rossmann Florian M. , Nans Andrea , Brenzinger Susanne , Hosseini Rohola , Briegel Ariane , Thormann Kai M. , Rosenthal Peter B. , Beeby Morgan 
Published: July 2018

AbstractBacteria switch only intermittently to motile planktonic lifestyles under favourable conditions. Under chronic nutrient deprivation, however, bacteria orchestrate a switch to stationary phase, conserving energy by altering metabolism and stopping motility. About two-thirds of bacteria use flagella to swim, but how bacteria deactivate this large-molecular machine remains poorly studied. Here we describe the previously unreported ejection of polar sodium-driven motors by γ-proteobacteria. We show that these bacteria eject their flagella at the base of the flagellar hook when nutrients are depleted, leaving a relic of a former flagellar motor in the outer membrane. Subtomogram averages of the full motor and relic reveal that this is an active process, as a plug protein appears in the relic, likely to prevent leakage across their outer membrane. We show that this is a widespread phenomenon demonstrated by the appearance of relic structures in varied γ-proteobacteria including Plesiomonas shigelloides, Vibrio cholerae, Vibrio fischeri, Shewanella putrefaciens and Pseudomonas aeruginosa.
Preservation of cellular nano-architecture by the process of chemical fixation for nanopathology
Authors: Zhou Xiang , Almassalha Luay , Li Yue , Eshein Adam , Cherkezyan Lusik , Viswanathan Parvathi , Subramanian Hariharan , Szleifer Igal , Backman Vadim 
Published: July 2018

AbstractTransformation in chromatin organization is one of the most universal markers of carcinogenesis. Microscale chromatin alterations have been a staple of histopathological diagnosis of neoplasia, and nanoscale alterations have emerged as a promising marker for cancer prognostication and the detection of predysplastic changes. While numerous methods have been developed to detect these alterations, most methods for sample preparation remain largely validated via conventional microscopy, and have not been examined with nanoscale sensitive imaging techniques. For these nanoscale sensitive techniques to become standard of care screening tools, new histological protocols must be developed that preserve nanoscale information. Partial Wave Spectroscopic (PWS) microscopy has recently emerged as a novel imaging technique sensitive to length scales ranging between 20 and 200 nanometers. As a label-free, high-throughput, and non-invasive imaging technique, PWS microscopy offers many advantages for risk stratification of early cancer, and is an ideal tool to quantify structural information during sample preparation. Therefore, in this work we applied PWS microscopy to systematically evaluate the effects of cytological preparation on the nanoscales changes of chromatin using two cell line models: Hela cells differentially treated with daunorubicin and TP53 differentially mutated ovarian carcinoma cells. Notably, we show that existing cytological preparation can be modified in order to maintain clinically relevant nanoscopic differences, paving the way for the emerging field of nanopathology.
MHCSeqNet: A deep neural network model for universal MHC binding prediction
Authors: Phloyphisut Poomarin , Pornputtanapong Natapol , Sriswasdi Sira , Chuangsuwanich Ekapol 
Published: July 2018

ABSTRACTImmunotherapy is an emerging approach in cancer treatment that activates the host immune system to destroy cancer cells that express unique peptide signatures (neoepitopes). Administrations of cancer-specific neoepitopes in the form of synthetic peptide vaccine have been proven effective in both mouse models and human patients. Because only a tiny fraction of cancer-specific neoepitopes actually elicit immune response, selection of potent, immunogenic neoepitopes remains a challenging step in cancer vaccine development. A basic approach for immunogenicity prediction is based on the premise that effective neoepitope should bind with the Major Histocompatibility Complex (MHC) with high affinity. In this study, we developed MHCSeqNet, an open-source deep learning model, which not only competes favorably with state-of-the-art predictors but also exhibits promising generalization to new MHC class I and class II alleles. MHCSeqNet employed neural network architectures developed for natural language processing to model amino acid sequence representations of MHC allele and epitope peptide as sentences with amino acids as individual words. This consideration allows MHCSeqNet to accept new MHC alleles as well as peptides of any length. The flexibility offered by MHCSeqNet should make it a valuable tool for screening effective neoepitopes in cancer vaccine development.Availability and implementationhttps://github.com/cmbcu/MHCSeqNet
Using SMOG 2 to simulate complex biomolecular assemblies
Authors: Levi Mariana , Bandarkar Prasad , Yang Huan , Wang Ailun , Mohanty Udayan , Noel Jeffrey K. , Whitford Paul C. 
Published: July 2018

SummaryOver the last 20 years, the application of structure-based (Gō-like) models has ranged from protein folding with coarse-grained models to all-atom representations of large-scale molecular assemblies. While there are many variants that may be employed, the common feature of these models is that some (or all) of the stabilizing energetic interactions are defined based on knowledge of a particular experimentally-obtained conformation. With the generality of this approach, there was a need for a versatile computational platform for designing and implementing this class of models. To this end, the SMOG 2 software package provides an easy-to-use interface, where the user has full control of the model parameters. This software allows the user to edit XML-formatted files in order to provide definitions of new structure-based models. SMOG 2 reads these “template” files and maps the interactions onto specific structures, which are provided in PDB format. The force field files produced by SMOG 2 may then be used to perform simulations with a variety of popular molecular dynamics suites. In this chapter, we describe some of the key features of the SMOG 2 package, while providing examples and strategies for applying these techniques to complex (often large-scale) molecular assemblies, such as the ribosome.
How fluorescent tags modify oligomer size distributions of the Alzheimer-peptide Aβ(1-40)
Authors: Wägele J. , De Sio S. , Voigt B. , Balbach J. , Ott M. 
Published: July 2018

ABSTRACTWithin the complex aggregation process of Aβ-peptides into fibrils, oligomeric species, play a central role and reveal fundamental properties of the underlying mechanism of aggregation. In particular, low molecular weight aggregates have attracted increasing interest because of their role in cytotoxicity and neuronal apoptosis, typical of aggregation related diseases. One of the main techniques used to characterize such early stages of aggregation is fluorescence spectroscopy. To this end, Aβ-peptide chains are functionalized with fluorescent tags, often covalently bound to the disordered N-terminus region of the peptide, with the assumption that functionalization and presence of the fluorophore will not modify the process of self-assembly nor the final fibrillar structure. Up to date, experimental findings reveal size distributions of thermodynamically stable oligomers ranging from very narrow distributions of dimers to octamers, to very broad distributions up to 50-mers. In the present investigation we systematically study the effects of five of the most commonly used fluorophores on the aggregation of Aβ(1-40)-peptides. Time-resolved and single-molecule fluorescence spectroscopy have been chosen to monitor the oligomer populations at different fibrillation times, TEM, AFM and X-ray diffraction to investigate the structure of mature fibrils. While the structures of the mature fibrils were only slightly affected by the fluorescent tags, the sizes of the detected oligomeric species varied significantly depending on the chosen fluorophore. In particular, we relate the presence of high molecular weight oligomers (as found for the fluorophores HiLyte 647, Atto 647N and Atto 655) to net-attractive, hydrophobic fluorophore-peptide interactions, which are weak in the case of HiLyte 488, and Atto 488. The latter form low molecular weight oligomers only. Our findings reveal the potentially high impact of the properties of fluorophores on transient aggregates which needs to be included in the interpretation of experimental data of oligomers of fluorescently labeled peptides.
Corrective muscle activity reveals subject-specific sensorimotor recalibration
Authors: Iturralde Pablo A. , Torres-Oviedo Gelsy 
Published: July 2018

AbstractRecent studies suggest that planned and corrective actions are recalibrated during some forms of motor adaptation. However, corrective (a.k.a., reactive) movements in human locomotion are thought to simply reflect sudden environmental changes independently from sensorimotor recalibration. Thus, we asked if corrective responses can indicate the motor system’s adapted state following prolonged exposure to a novel walking situation inducing sensorimotor adaptation. We recorded electromyographic signals bilaterally on 15 leg muscles before, during, and after split-belts walking (i.e., novel walking situation), in which the legs move at different speeds. We exploited the rapid temporal dynamics of corrective responses upon introduction or removal of an unexpected speed transition to isolate them from the overall motor output. We found that corrective muscle activity was structurally different following short vs. long exposures to split-belts walking. Only after a long exposure, removal of the novel environment elicited corrective muscle patterns that matched those expected in response to a perturbation opposite to the one originally experienced. This indicated that individuals who recalibrated their motor system adopted split-belts environment as their new “normal” and transitioning back to the original walking environment causes subjects to react as if it was novel to them. Interestingly, this learning declined with age, but steady state modulation of muscle activity during split-belts walking did not, suggesting potentially different neural mechanisms underlying these motor patterns. Taken together, our results show that corrective motor commands reflect the adapted state of the motor system, which is less flexible as we age.Significance statementWe showed that corrective muscle activity elicited by sudden environmental transitions is revealing of the underlying recalibration process during sensorimotor adaptation. This allowed us to identify age-related decline in motor learning that was not discernible from kinematic measures conventionally used in motor adaptation studies. These findings suggest that older populations may have limited potential to correct their movements through error-based protocols simply given their age. Moreover, we describe the distinct motor patterns recruited during and after the split condition, informing our understanding of the therapeutic effect of this task. Therefore, our detailed EMG characterization provides valuable normative data of muscle activity that could be reinforced with repeated exposure of split-belts walking.
Cortical suppressive waves shape the representation of long-range apparent motion
Authors: Chemla S , Reynaud A , di Volo M , Zerlaut Y , Perrinet L , Destexhe A , Chavane F 
Published: July 2018

SummaryHow does the brain link visual stimuli across space and time? Visual illusions provide an experimental paradigm to study these processes. When two stationary dots are flashed in close spatial and temporal succession, human observers experience a percept of motion. Large spatio-temporal separation challenges the visual system to keep track of object identity along the apparent motion path. Here, we utilize voltage-sensitive dye imaging in primary visual cortex (V1) of the awake monkey to investigate whether intra-cortical connections within V1 can shape cortical dynamics to represent the illusory motion. We find that the arrival of the second stimulus in V1 creates a suppressive wave traveling toward the retinotopic representation of the first. Computational approaches show that this suppressive wave can be explained by recurrent gain control fed by the intra-cortical network and contributes to precisely encode the expected motion velocity. We suggest that non-linear intra-cortical dynamics preformat population responses in V1 for optimal read-out by downstream areas.
G protein-coupled estrogen receptor is not required for sex determination or ovary function in zebrafish
Authors: Crowder Camerron M. , Romano Shannon N. , Gorelick Daniel A. 
Published: July 2018

ABSTRACTEstrogens regulate vertebrate development and function through binding to nuclear estrogen receptors alpha and beta (ERα, ERβ) and the G protein-coupled estrogen receptor (GPER). Studies in mutant animal models demonstrated that ERα and ERβ are required for normal ovary development and function. However, the degree to which GPER signaling contributes to ovary development and function is less well understood. Previous studies using cultured fish oocytes found that estradiol inhibits oocyte maturation in a GPER-dependent manner, but whether GPER regulates oocyte maturation in vivo is not known. To test the hypothesis that GPER regulates oocyte maturation in vivo, we assayed ovary development and function in gper mutant zebrafish. We found that homozygous mutant gper embryos developed into male and female adults with normal sex ratios and fertility. Adult mutant fish exhibited normal secondary sex characteristics and fertility. Additionally, mutant ovaries were histologically normal. We observed no differences in the number of immature versus mature oocytes in mutant versus wild-type ovaries from both young and aged adults. Furthermore, expression of genes associated with sex determination and ovary function were normal in gper mutant ovaries compared to wild type. Our findings suggest that GPER is not required for sex determination, ovary development or fertility in zebrafish.