bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optic nerve tortuosity and displacements during horizontal eye movements in healthy and highly myopic subjects
Authors: Wang Xiaofei , Chang Stanley , Grinband Jack , Yannuzzi Lawrence A. , Freund K. Bailey , Hoang Quan V. , Girard Michaël J. A. 
Published: October 2020

ABSTRACTPurpose(1) To assess the morphology and 3D displacements of the eye globe and optic nerve (ON) in adduction/abduction using magnetic resonance imaging (MRI). (2) To assess differences between healthy emmetropic and highly myopic (HM) subjects.MethodsMRI volumes of both eyes from 18 controls and 20 HM subjects in primary gaze, abduction and adduction (15°) were postprocessed. All ONs were manually-segmented and fitted to a 3D curve to assess ON tortuosity. ON displacements were evaluated in 4 quasicoronal planes which were perpendicular to the ON in primary gaze and 3 mm apart.ResultsAxial length was higher in the HM group (28.62±2.60 vs 22.84±0.89 mm; p<0.0001). Adjusted ON tortuosities (i.e., ON tortuosities estimated before myopia onset) were lower in HM eyes (0.9063±0.0591) versus controls (1.0152±0.02981) in primary gaze, adduction (0.9023±0.05538 versus 1.0137±0.0299) and abduction (0.9100±0.0594 versus 1.0182±0.0316); p<0.0001 for all cases. In all eyes, ON displacements in adduction were significantly different from those in abduction in the naso-temporal direction (p<0.0001 in all planes) but not in the supero-inferior direction. ON displacements in the posterior segments of the ON were smaller in the HM group in both gaze directions and were larger in the anterior-most ON segment in adduction only.ConclusionsThe adjusted tortuosity of the ON was significantly lower in HM eyes, suggesting that eyes destined toward HM exhibited higher ON traction forces during eye movements before the onset of myopia. Our ON metrics may be valuable to explore a potential link between eye movements and axial elongation.
Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity
Authors: Yates Jennifer L. , Ehrbar Dylan J. , Hunt Danielle T. , Girardin Roxanne C. , Dupuis Alan , Payne Anne F. , Sowizral Mycroft , Varney Scott , Kulas Karen E. , Demarest Valerie L. , Howard Kelly M. , Carson Kyle , Hales Margaux , Ejemel Monir , Li Qi , Wang Yang , Mantis Nicholas J. , McDonough Kathleen A. , Lee William T. 
Published: October 2020

SummaryCOVID-19 is associated with a wide spectrum of disease severity, ranging from asymptomatic to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity, and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. Through a serological analysis of serum samples from 536 convalescent healthcare workers, we found that SARS-CoV-2-specific and virus-neutralizing antibody levels were indeed elevated in individuals that experienced severe disease. The severity-associated increase in SARS-CoV-2-specific antibody was dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. However, RBD- and S1-specific IgG1, rather than IgG3 were best correlated with virus-neutralizing titers.We propose that Spike-specific IgG3 subclass utilization contributes to COVID-19 disease severity through potent Fc-mediated effector functions. These results have significant implications for SARS-CoV-2 vaccine design, and convalescent plasma therapy.
Ancestral dietary change alters development ofDrosophilalarvae through MAPK signalling
Authors: Towarnicki Samuel G. , Youngson Neil A. , Corley Susan M. , St John Jus C. , Turner Nigel , Morris Margaret J. , Ballard J. William O. 
Published: October 2020

AbstractIncreasing evidence in animal species ranging from mammals to insects has revealed phenotypes that are caused by ancestral life experiences including stress and diet. The descendent phenotypes themselves are wide ranging, and include changes to behaviour, disease risk, metabolism, and growth. Ancestral dietary macronutrient composition, and quantity (over- and under-nutrition) have been shown to alter descendent growth, metabolism and behaviour. Several studies have identified inherited molecules in gametes which are altered by ancestral diet and are required for the transgenerational effect. However, there is less understanding of the developmental pathways in the period between fertilisation and adulthood that are altered by the inherited molecules. Here we identify a key role of the MAPK signalling pathway in mediating changes toDrosophilalarval developmental timing due to variation in ancestral diet. We exposed grand-parental and great grand-parental generations to defined protein to carbohydrate (P:C) dietary ratios and measured developmental timing. Descendent developmental timing was consistently faster in the period between the embryonic and pupal stages when the ancestor had a higher P:C ratio diet. Transcriptional analysis of embryos, larvae and adults revealed extensive and long-lasting changes to the MAPK signalling pathway which controlled growth rate through regulation of ribosomal RNA transcription. The importance of these processes was supported by pharmacological inhibition of MAPK and rRNA proteins which reproduced the ancestral diet-induced developmental changes. This work provides insight into the role of developmental growth signalling networks in mediating non-genetic inheritance in the period between fertilisation and adult.Summary statementAncestral, diet-induced descendent developmental timing changes are caused by alteration of MAPK signalling pathways in the period between the embryo and pupal stages inDrosophila.
Screening of Cultivars for Tissue Culture Response and Establishment of Genetic Transformation in a High-yielding and Disease-resistant Cultivar ofTheobroma cacao
Authors: Jones Jesse , Zhang Elaine , Tucker Dominick , Rietz Daniel , Dahlbeck Doug , Gomez Michael , Garcia Claudia , Marelli Jean-Philippe , Livingstone Donald , Schnell Ray , Staskawicz Brian , Cho Myeong-Je 
Published: October 2020

AbstractA highly efficient transformation protocol is a prerequisite to developing genetically modified and genome-edited crops. A tissue culture system spanning the initiation of floral material to the regeneration of plantlets into soil has been tested and improved in cacao. Fourteen cultivars were screened for their tissue culture response and transfer DNA (T-DNA) delivery efficiency viaAgrobacterium. These key factors were used to determine the genetic transformability of various cultivars. The high-yielding, disease-resistant cultivar INIAPG-038 was selected for stable transformation and the method was further optimized. Multiple transgenic events were produced using two vectors containing both yellow fluorescent protein and neomycin phosphotransferase II genes. A two-fold strategy to improve both T-DNA delivery and secondary somatic embryogenesis rates was conducted to improve overall transformation frequency. The use ofAgrobacteriumstrain AGL1 and cotyledon tissue derived from immature somatic embryos ranging in size between 4-10 mm resulted in the highest T-DNA delivery efficiency. Furthermore, the use of higher concentrations of basal salts and cupric sulfate in secondary callus growth medium increased the percentage of explants producing greater than ten embryos by 504% and 443%, respectively. Consequently, an optimal combination of all these components resulted in a successful transformation of INIAPG-038 with 3.7% frequency at the T0plant level. Grafting transgenic scions with undeveloped roots to wild-type seedlings with strong, healthy roots helped make plantlets survive and facilitated quick transplantation to the soil. The present methods can be applied to improve tissue culture response and transformation frequency in other cacao cultivars.Key messageTissue culture and genetic transformation methods for a high-yielding, disease-resistant cultivar ofTheobroma cacaowere established while factors affecting T-DNA delivery and somatic embryogenesis were identified.
Permeabilization-freeen blocimmunohistochemistry for correlative microscopy
Authors: Fulton Kara A , Briggman Kevin L 
Published: October 2020

AbstractA dense reconstruction of neuronal synaptic connectivity typically requires high-resolution 3D electron microscopy (EM) data, but EM data alone lacks functional information about neurons and synapses. One approach to augment structural EM datasets is with the fluorescent immunohistochemical (IHC) localization of functionally relevant proteins. We describe a protocol that obviates the requirement of tissue permeabilization in thick tissue sections, a major impediment for correlative pre-embedding IHC and EM. We demonstrate the permeabilization-free labeling of neuronal cell types, intracellular enzymes, and synaptic proteins in tissue sections hundreds of microns thick in multiple brain regions while simultaneously retaining the ultrastructural integrity of the tissue. Finally, we explore the utility of this protocol by performing proof-of-principle correlative experiments combining two-photon imaging of protein distributions and 3D electron microscopy.
Granger Causality Inference in EEG Source Connectivity Analysis: A State-Space Approach
Authors: Manomaisaowapak Parinthorn , Nartkulpat Anawat , Songsiri Jitkomut 
Published: October 2020

AbstractThis paper considers a problem of estimating brain effective connectivity from EEG signals using a Granger causality (GC) concept characterized on state-space models. We propose a state-space model for explaining coupled dynamics of the source and EEG signals where EEG is a linear combination of sources according to the characteristics of volume conduction. Our formulation has a sparsity prior on the source output matrix that can further classify active and inactive sources. The scheme is comprised of two main steps: model estimation and model inference to estimate brain connectivity. The model estimation consists of performing a subspace identification and the active source selection based on a group-norm regularized least-squares. The model inference relies on the concept of state-space GC that requires solving a discrete-time Riccati equation for the covariance of estimation error. We verify the performance on simulated data sets that represent realistic human brain activities under several conditions including percentages of active sources, a number of EEG electrodes and the location of active sources. The performance of estimating brain networks is compared with a two-stage approach using source reconstruction algorithms and VAR-based Granger analysis. Our method achieved better performances than the two-stage approach under the assumptions that the true source dynamics are sparse and generated from state-space models. The method is applied to a real EEG SSVEP data set and we found that the temporal lobe played a role of a mediator of connections between temporal and occipital areas, which agreed with findings in previous studies.
RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit
Authors: Cerezo Emilie L. , Houles Thibault , Lié Oriane , Sarthou Marie-Kerguelen , Audoynaud Charlotte , Lavoie Geneviève , Halladjian Maral , Cantaloube Sylvain , Froment Carine , Burlet-Schiltz Odile , Henry Yves , Roux Philippe P. , Henras Anthony K. , Romeo Yves 
Published: October 2020

AbstractRibosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK promotes cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.
Global prevalence and phylogeny of hepatitis B virus (HBV) drug and vaccine resistance mutations
Authors: Mokaya Jolynne , Vasylyeva Tetyana I , Barnes Eleanor , Ansari M. Azim , Pybus Oliver G , Matthews Philippa C 
Published: October 2020

ABSTRACTIntroductionVaccination and anti-viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations.MethodsWe analysed sequences downloaded from the Hepatitis B Virus Database, and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution of selected mutations across tree branches. We performed phylogenetic molecular clock analyses using BEAST to estimate the age of mutations.ResultsRAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our dataset, and a significantly higher rate in genotype C sequence at 5.4% (60/1102, p=0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p=0.002) and 1.6% (34/2109; p=0.009) respectively. Phylogenetic analysis suggested that most RAM/VEMs arose independently, however RAMs including A194T, M204V and L180M formed clusters in genotype B. We show evidence that polymorphisms associated with drug and vaccine resistance may have been present in the mid 20thcentury suggesting that they can arise independently of treatment/ vaccine exposure.DiscussionHBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C variants. Screening for the genotype and for resistant mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.
Leafminer attack induces plant-mediated facilitation of conspecific pupae in the soil
Authors: Escobar-Bravo Rocío , Schimmel Bernardus CJ , Glauser Gaétan , Klinkhamer Peter GL , Erb Matthias 
Published: October 2020

SummaryHerbivore population dynamics are strongly influenced by the interactions established through their shared host. Such plant-mediated interactions can occur between different herbivore species and between different life developmental stages of the same herbivore. Yet, whether these interactions occur between leaf-feeding herbivores and their soil-dwelling pupae is unknown.We studied whether tomato (Solanum lycopersicum) leaf-herbivory by the American serpentine leafminerLyriomiza trifoliiaffects the performance of conspecific pupae in the soil adjacent to the plant. To gain mechanistic insights, we performed insect bioassays with the jasmonate-deficient tomato mutantdef-1and its wild type, along with the analysis of phytohormones, gene expression and root volatiles.Leafminer metamorphosis in the soil was accelerated when wild type plants were attacked aboveground by conspecifics, but the opposite was observed indef-1. Changes in pupal developmental rate were mediated by belowground volatiles. Accordingly, leafminer herbivory differentially modulated jasmonate and abscisic acid signaling and the accumulation of specific volatiles in the roots of wild type versusdef-1plantsOur results demonstrate that aboveground herbivores can facilitate their soil-dwelling pupae by inducingdef-1-dependent systemic responses. This study expands the repertoire of plant-herbivore interactions to herbivory-induced modulation of metamorphosis, with potentially important consequences for plant and herbivore community dynamics.
Transcranial Random Noise Stimulation acutely lowers the response threshold of human motor circuits
Authors: Potok Weronika , Bächinger Marc , van der Groen Onno , Cretu Andreea Loredana , Wenderoth Nicole 
Published: October 2020

AbstractTranscranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioural effect is stochastic resonance, a mechanism that explains how signal processing in non-linear systems can benefit from added noise. While acute noise benefits of electrical random noise stimulation have been demonstrated at the behavioural level as well as inin vitropreparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Here we hypothesized that acute tRNS will increase the responsiveness of primary motor cortex (M1) when probed with transcranial magnetic stimulation. Neural responsiveness was operationalized via the well-known concept of the resting motor threshold (RMT). We showed that tRNS acutely decreases RMT. This effect was small, but it was consistently replicated across four experiments including different cohorts (total N=81, 46 females, 35 males), two tRNS electrode montages, and different control conditions. Our experiments provide critical neurophysiological evidence that tRNS can acutely generate noise benefits by enhancing the neural population response of human M1.Significance statementA hallmark feature of stochastic resonance is that signal processing can benefit from added noise. This has mainly been demonstrated at the single-cell levelin vitrowhere the neural response to weak input signals can be enhanced by simultaneously applying random noise. Our finding that tRNS acutely increases the excitability of corticomotor circuits extends the principle of noise benefits to the neural population level in human cortex. Our finding is in line with the notion that tRNS might affect cortical processing via the stochastic resonance phenomenon. It suggests that enhancing the response of cortical populations to an external stimulus might be one neurophysiological mechanism mediating performance improvements when tRNS is applied to sensory cortex during perception tasks.
Gene Therapy Reforms Photoreceptor Structure and Restores Vision in NPHP5-associated Leber Congenital Amaurosis
Authors: Aguirre Gustavo D. , Cideciyan Artur V. , Dufour Valérie L. , García Ana Ripolles , Sudharsan Raghavi , Swider Malgorzata , Nikonov Roman , Iwabe Simone , Boye Sanford L. , Hauswirth William W. , Jacobson Samuel G. , Beltran William A. 
Published: October 2020

AbstractThe inherited childhood blindness caused by mutations in NPHP5, a form of Leber congenital amaurosis, results in abnormal development, dysfunction and degeneration of photoreceptors. A naturally occurring NPHP5 mutation in dogs results in a phenotype that very nearly duplicates the human retinopathy in terms of the photoreceptors involved, spatial distribution of degeneration and the natural history of vision loss. We show that AAV-mediated NPHP5 gene augmentation of mutant canine retinas at the time of active degeneration and peak cell death stably restores photoreceptor structure, function, and vision with either the canine or human NPHP5 transgenes. Mutant cone photoreceptors, which failed to form outer segments during development, reform this structure after treatment. Degenerating rod photoreceptor outer segments are stabilized and develop normal structure. This process begins within 8 weeks following treatment, and remains stable throughout the 6 month post treatment period. In both photoreceptor cell classes, mislocalization of rod and cone opsins is minimized or reversed. Retinal function and functional vision are restored. Efficacy of gene therapy in this large animal ciliopathy model of Leber congenital amaurosis provides a path for translation to human treatment.
Constraint-based modelling revealed changes in metabolic flux modes associated with the Kok effect
Authors: Ong Wei Qiang , Cheung C. Y. Maurice 
Published: October 2020

AbstractConstraint-based modelling was applied to provide a mechanistic understanding of the possible metabolic origins of the ‘Kok effect’ – the change in quantum yield of net photosynthesis at low light intensity. The well-known change in quantum yield near the light-compensation point (LCP) was predicted as an emergent behaviour from a purely stoichiometric model. From our modelling results, we discovered another subtle change in quantum yield at a light intensity lower than the LCP. Our model predicted a series of changes in metabolic flux modes in central carbon metabolism associated with the changes in quantum yields. We demonstrated that the Kok effect can be explained by changes in metabolic flux modes between catabolism and photorespiration. Changes in RuBisCO carboxylation to oxygenation ratio resulted in a change in quantum yield at light intensities above the LCP, but not below the LCP, indicating the role of photorespiration in producing the Kok effect. Cellular energy demand was predicted to have no impact on the quantum yield. Our model showed that the Kok method vastly overestimates day respiration – the CO2released by non-photorespiratory processes in illuminated leaves. The theoretical maximum quantum yield at low light intensity was higher than typical measured values, suggesting that leaf metabolism at low light may not be regulated to optimise for energetic efficiency. Our model predictions gave insights into the set of energetically optimal changes in flux modes in low light as light intensity increases from darkness.One sentence summaryThe Kok effect can be explained by the changes in flux modes between catabolism and photorespiration.