bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of multi-flip angle measurements to account for transmit inhomogeneity and non-Gaussian diffusion in DW-SSFP
Authors: Tendler Benjamin C. , Foxley Sean , Hernandez-Fernandez Moises , Cottaar Michiel , Scott Connor , Ansorge Olaf , Miller Karla , Jbabdi Saad 
Published: December 2019

AbstractDiffusion-weighted steady-state free precession (DW-SSFP) is an SNR-efficient diffusion imaging method. The improved SNR and resolution available at ultra-high field has motivated its use at 7T. However, these data tend to have severe B1 inhomogeneity, leading not only to spatially varying SNR, but also to spatially varying diffusivity estimates, confounding comparisons both between and within datasets. This study proposes the acquisition of DW-SSFP data at two-flip angles in combination with explicit modelling of non-Gaussian diffusion to address B1 inhomogeneity at 7T. DW-SSFP datasets were acquired from five fixed whole human post-mortem brains with a pair of flip angles that jointly optimize the diffusion contrast-to-noise across the brain. We compared one and two flip-angle DW-SSFP data using a diffusion tensor model that incorporates the full DW-SSFP Buxton signal model. The two-flip angle data were subsequently fitted using a modified DW-SSFP signal model that incorporates a Gamma distribution of diffusivities. This allowed us to generate tensor maps at a single, SNR-optimal effective b-value yielding more consistent SNR across tissue, in addition to eliminating the B1 dependence on diffusion coefficients and orientation maps. Our proposed approach will allow the use of DW-SSFP at 7T to derive diffusivity estimates that have greater interpretability, both within a single dataset and between experiments.HighlightsB1 inhomogeneity at 7T leads to spatially varying SNR & ADC estimates in DW-SSFP2-flip angle DW-SSFP data can address B1 effects in a cohort of post-mortem brainsOur approach reduces degradations in PDD estimates & improves whole brain coverageOur approach provides a means to define ADCs at an SNR-optimal effective b-value
Signaling compartment at the ciliary tip is formed and maintained by intraflagellar transport and functions as sensitive salt detector
Authors: van der Burght Servaas N. , Rademakers Suzanne , Johnson Jacque-Lynne , Li Chunmei , Kremers Gert-Jan , Houtsmuller Adriaan B. , Leroux Michel R. , Jansen Gert 
Published: December 2019

AbstractPrimary cilia are ubiquitous antenna-like organelles that mediate cellular signaling and represent hotspots for human diseases termed ciliopathies. How signaling subcompartments are established within the microtubule-based organelle, and for example support Hedgehog or cGMP signal transduction pathways, remains a central question. Here we show that a C. elegans salt-sensing receptor type guanylate cyclase, GCY-22, accumulates at a high concentration within the distal region of the cilium. This receptor uses DAF-25 (Ankmy2 in mammals) to cross the transition zone (TZ) membrane diffusion barrier in the proximal-most region of the ciliary axoneme. Targeting of GCY-22 to the ciliary tip is dynamic, requiring the cargo-mobilizing intraflagellar transport (IFT) system. Disruption of transit across the TZ barrier or IFT trafficking causes GCY-22 protein mislocalization and defects in the formation, maintenance, and function of the ciliary tip compartment required for chemotaxis to low NaCl concentrations. Together, our findings reveal how a previously undescribed cilium tip cGMP signaling compartment is established and contributes to the physiological function of a primary cilium.
Neural Encoding for Human Visual Cortex with Deep Neural Networks Learning “What” and “Where”
Authors: Wang Haibao , Huang Lijie , Du Changde , Li Dan , Wang Bo , He Huiguang 
Published: December 2019

AbstractNeural encoding, a crucial aspect to understand human brain information processing system, aims to establish a quantitative relationship between the stimuli and the evoked brain activities. In the field of visual neuroscience, with the ability to explain how neurons in primary visual cortex work, population receptive field (pRF) models have enjoyed high popularity and made reliable progress in recent years. However, existing models rely on either the inflexible prior assumptions about pRF or the clumsy parameter estimation methods, severely limiting the expressiveness and interpretability. In this paper, we propose a novel neural encoding framework by learning “what” and “where” with deep neural networks. The modeling approach involves two separate aspects: the spatial characteristic (“where”) and feature selection (“what”) of neuron populations in visual cortex. Specifically, we use the receptive field estimation and multiple features regression to learn these two aspects respectively, which are implemented simultaneously in a deep neural network. The two forms of regularizations: sparsity and smoothness, are also adopted in our modeling approach, so that the receptive field can be estimated automatically without prior assumptions about shapes. Furthermore, an attempt is made to extend the voxel-wise modeling approach to multi-voxel joint encoding models, and we show that it is conducive to rescuing voxels with poor signal-to-noise characteristics. Extensive empirical results demonstrate that the method developed herein provides an effective strategy to establish neural encoding for human visual cortex, with the weaker prior constraints but the higher encoding performance.Author summaryCharacterizing the quantitative relationship between the stimuli and the evoked brain activities usually involves learning the spatial characteristic (“where”) and feature selection (“what”) of neuron populations. As an effective strategy, we propose a novel end-to-end “what” and “where” architecture to perform neural encoding. The proposed modeling approach consists of receptive field estimation and multiple features regression, which learns “where” and “what” simultaneously in a deep neural network. Different from previous methods, we use the sparsity and smoothness regularizations in the deep neural network to guide the receptive field estimation, so that the receptive field for each voxel can be estimated automatically. Moreover, in consideration of computational similarities between adjacent voxels, we made an attempt to extend the proposed modeling approach to multi-voxel joint encoding models, improving the encoding performance of voxels with poor signal-to-noise characteristics. Empirical evaluations show that the proposed method outperforms other baselines to achieve the state-of-the-art performance.
Two-variable nullcline analysis of ionic general equilibrium predicts calcium homeostasis in ventricular myocytes
Authors: Conesa David , Echebarria Blas , Peñaranda Angelina , Cantalapiedra Inmaculada R. , Shiferaw Yohannes , Alvarez-Lacalle Enrique 
Published: December 2019

AbstractVentricular contraction is roughly proportional to the amount of calcium released from the Sarcoplasmic Reticulum (SR) during systole. While it is rather straightforward to measure calcium levels and contractibility under different physiological condition, the complexity of calcium handling during systole and diastole has made the prediction of its release at steady state impossible. Here we approach the problem analyzing the evolution of intracellular and extracellular calcium fluxes during a single beat which is away from homeostatic balance. Using an in-silico subcellular model of rabbit ventricular myocyte, we show that the high dimensional nonlinear problem of finding the steady state can be reduced to a two-variable general equilibrium condition where pre-systolic calcium level in the cytosol and in the SR must fulfill simultaneously two different equalities. This renders calcium homeostasis as a problem that can be studied in terms of its equilibrium structure, leading to precise predictions of steady state from single-beat measurements. We show how changes in ionic channels modify the general equilibrium as shocks would do in general equilibrium macroeconomic models. This allows us to predict when an enhanced entrance of calcium in the cell reduces its contractibility and explain why SERCA gene therapy, a change in calcium handling to treat heart failure, might fail to improve contraction even when it successfully increases SERCA expression.Author summaryCardiomyocytes, upon voltage excitation, release calcium, which leads to cell contraction. However, under some pathological conditions, calcium handling is impaired. Recently, SERCA gene therapy, whose aim is to improve Ca2+ sequestration by the Sarcoplasmic Reticulum (SR), has failed to improve the prognosis of patients with Heart Failure. This, together with recent counterintuitive results in calcium handling, has highlighted the need for a framework to understand calcium homeostasis across species and pathologies. We show here that the proper framework is a general equilibrium approach of two independent variables. The development of this framework allows us to find a possible mechanism for the failure of SERCA gene therapy even when it manages to increase Ca SERCA expression.
The association of self-reported sleep quality and obesity in Kuwait using the Pittsburgh Sleep Quality Index (PSQI)
Authors: Alghaith Abdulwahab , Azim Rafaat , Ahmad Rasheed , Al-Rashed Fatema 
Published: December 2019

ABSTRACTObesity is an epidemic problem facing Kuwait and other neighboring countries within the region. Lifestyle and social structure in this region differ in comparison to the western world. The hot chalinging climate favor night time activities while working hours still force a stringent early attendence. This study is specifically conducted for Kuwait’s population to investigate the link between Sleep Quality (SQ) and obesity. A cross-sectional study was conducted for a sample of 1002 participants. Structured questionnaires were used in the study as a tool of research. The participants were asked about their sleep habits, sleep problems, medications, job nature and demographics. All participants consented prior to conducting the survey. In order to measure sleep quality (SQ), the Pittsburgh Sleep Quality Index (PQSI) was used. Statistical analysis was conducted between variables and the data were compared using either two-tailed t-test or one-way ANOVA followed by Tukeys multiple comparison test. Pearson’s correlation coefficient ‘r’ was used to assess linear dependence. 59.4% of Kuwait population reported a PSQI score higher than 5, with 57.3% of the participants reporting less than 6 hours of sleep per day. The presented data shows that both sleep quality and sleep duration are considered inadequate in comparison to international sleep quality standards. None the less, we also found strong a significant association between sleep quality and its component and obesity, while other factors such as age and gender were found insignificant. These finding suggest that sleep deprivation and disturbance could be an indirect inducing factor of obesity in Kuwait. The researchers are of the view that there is a need for more study in the area of obesity and SQ in order to handle the obesity epidemic in the country.
Muscle Mitochondrial Capacity and Endurance in Adults with Type 1 Diabetes
Authors: Hewgley Riley A. , Moore Bethany T. , Willingham T. Bradley , Jenkins Nathan T. , McCully Kevin K. 
Published: December 2019

ABSTRACTThe impact of type 1 diabetes (T1D) on muscle endurance and oxidative capacity is currently unknown.PurposeMeasure muscle endurance and oxidative capacity of adults with T1D compared to controls.MethodsA cross-sectional study design with a control group was used. Subjects (19-37 years old) with T1D (n=17) and controls (n=17) were assessed with hemoglobin A1c (HbA1c) and casual glucose. Muscle endurance was measured with an accelerometer at stimulation frequencies of 2, 4, and 6 Hz for a total of nine minutes. Mitochondrial capacity was measured using near-infrared spectroscopy after exercise as the rate constant of the rate of recovery of oxygen consumption.ResultsT1D and control groups were similar in age, sex, height, and race. The T1D group had slightly higher BMI values and adipose tissue thickness over the forearm muscles. Casual glucose was 150±70 mg/dL for T1D and 98±16 mg/dL for controls (P=0.006). HbA1c of T1D subjects was 7.1±0.9% and 5.0±0.4% for controls (P<0.01). Endurance indexes at 2, 4, and 6 Hz were 94.5±5.2%, 81.8±8.4%, and 68.6±13.5% for T1D and 94.6±4.1%, 85.9±6.3%, and 68.7±15.4% for controls (p = 0.97, 0.12, 0.99, respectively). There were no differences between groups in mitochondrial capacity (T1D= 1.9±0.5 min−1 and control=1.8±0.4 min−1, P=0.29) or reperfusion rate (T1D= 8.8±2.8s and control=10.3±3.0s, P=0.88). There were no significant correlations between HbA1c and either muscle endurance, mitochondrial capacity or reperfusion rate.ConclusionsAdults with T1D did not have reduced oxidative capacity, muscle endurance or muscle reperfusion rates compared to controls. HbA1c also did not correlate with muscle endurance, mitochondrial capacity or reperfusion rates. Future studies should extend these measurements to older people or people with poorly-controlled T1D.
Effects of host plants nutrient on the nutrient in Bradysia cellarum and Bradysia impatiens
Authors: Gou Yuping , Quandahor Peter , Zhang Yanxia , Liu Changzhong 
Published: December 2019

AbstractThe chive maggots Bradysia cellarum the fungus gnats Bradysia impatiens are two main root pests of plants. They can coexist on same host plants and have become devastating pests on liliaceous crops and edible fungi. Their growth and development are affected by nutrients of their host plants. We studied the effects of different host plant nutrients on the nutrient contents of these two Bradysia species. We assayed the nutrients in the roots of chive, board bean (B-bean), lettuce, cabbage, wild cabbage (W-cabbage) and pepper, and analysed the nutrient content of the two Bradysia species after three continuous generations of feeding on these different host plants. There chive and B-bean had higher contents of protein, free amino acid and starch than in other host plants. Soluble sugar, fat and protein contents were significantly higher in both Bradysia species when they were reared on chive and B-bean than when reared on cabbage, lettuce, W-cabbage and pepper. Our study provides a reference for further studies on the host range of the two Bradysia species, as well as knowledge for consideration in field crop rotations.
The geometry and genetics of hybridization
Authors: Schneemann Hilde , De Sanctis Bianca , Roze Denis , Bierne Nicolas , Welch John J. 
Published: December 2019

AbstractWe develop an analytical framework for predicting the fitness of hybrid genotypes, based on Fisher’s geometric model. We first show that all of the model parameters have a simple geometrical and biological interpretation. Hybrid fitness decomposes into intrinsic effects of hybridity and heterozygosity, and extrinsic measures of the (local) adaptedness of the parental lines; and all of these correspond to distances in a phenotypic space. We also show how these quantities change over the course of divergence, with convergence to a characteristic pattern of intrinsic isolation. Using individual-based simulations, we then show that the predictions apply to a wide range of population genetic regimes, and divergence conditions, including allopatry and parapatry, local adaptation and drift. We next connect our results to the quantitative genetics of line crosses in variable or patchy environments. This relates the geometrical distances to quantities that can be estimated from cross data, and provides a simple interpretation of the “composite effects” in the quantitative genetics partition. Finally, we develop extensions to the model, involving selectively-induced disequilibria, and variable phenotypic dominance. The geometry of fitness landscapes provides a unifying framework for understanding speciation, and wider patterns of hybrid fitness.
AlphaBeta: Computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants
Authors: Shahryary Yadollah , Symeonidi Aikaterini , Hazarika Rashmi R. , Denkena Johanna , Mubeen Talha , Hofmeister Brigitte , van Gurp Thomas , Colomé-Tatché Maria , Verhoeven Koen , Tuskan Gerald , Schmitz Robert J , Johannes Frank 
Published: December 2019

AbstractIntroductionHeritable changes in cytosine methylation can arise stochastically in plant genomes independently of DNA sequence alterations. These so-called ‘spontaneous epimutations’ appear to be a byproduct of imperfect DNA methylation maintenance during mitotic or meitotic cell divisions. Accurate estimates of the rate and spectrum of these stochastic events are necessary to be able to quantify how epimutational processes shape methylome diversity in the context of plant evolution, development and aging.MethodHere we describe AlphaBeta, a computational method for estimating epimutation rates and spectra from pedigree-based high-throughput DNA methylation data. The approach requires that the topology of the pedigree is known, which is typically the case in the experimental construction of mutation accumulation lines (MA-lines) in sexually or clonally reproducing species. However, this method also works for inferring somatic epimutation rates in long-lived perennials, such as trees, using leaf methylomes and coring data as input. In this case, we treat the tree branching structure as an intra-organismal phylogeny of somatic lineages and leverage information about the epimutational history of each branch.ResultsTo illustrate the method, we applied AlphaBeta to multi-generational data from selfing- and asexually-derived MA-lines in Arabidopsis and dandelion, as well as to intra-generational leaf methylome data of a single poplar tree. Our results show that the epimutation landscape in plants is deeply conserved across angiosperm species, and that heritable epimutations originate mainly during somatic development, rather than from DNA methylation reinforcement errors during sexual reproduction. Finally, we also provide the first evidence that DNA methylation data, in conjunction with statistical epimutation models, can be used as a molecular clock for age-dating trees.ConclusionAlphaBeta faciliates unprecedented quantitative insights into epimutational processes in a wide range of plant systems. Software implementing our method is available as a Bioconductor R package at http://bioconductor.org/packages/3.10/bioc/html/AlphaBeta.html
Disrupting female flight in the vectorAedes aegypti
Authors: O’Leary Sarah , Adelman Zach N. 
Published: December 2019

AbstractAedes aegyptiis a vector of dengue, chikungunya, and Zika viruses. Current vector control strategies such as community engagement, source reduction, and insecticides have not been sufficient to prevent viral outbreaks. Thus, interest in novel strategies involving genetic engineering is growing. Female mosquitoes rely on flight to mate with males and obtain a bloodmeal from a host. We hypothesized that knockout of genes specifically expressed in female mosquitoes associated with the indirect flight muscles would result in a flightless female mosquito. With the CRISPR-Cas9 system, we performed embryonic microinjections of Cas9 protein and guide RNAs specific to genes hypothesized to control flight in mosquitoes, and have obtained genetic knockouts in several genes specifically expressed in the flight-muscle, including those specific to female flight muscle. Analysis of the phenotype of these female-specific gene knockout mutants resulted in flightless females and flying males. While further assessment is required, this work lays the groundwork for a mechanism of population control that is female-specific for theAe. aegyptivector.
Role of protein dynamics in enthalpy-driven recognition of topologically distinct dsRNAs by dsRBDs
Authors: Paithankar H , Chugh J 
Published: December 2019

AbstractTaking leads from the fact that a handful of double-stranded RNA-binding domains (dsRBDs) interact with a massive number of topologically distinct double-stranded RNAs (dsRNAs) in crucial biological pathways, and to understand the adaptability required by dsRBDs to target the pool of dsRNA substrates, we employed two independent model dsRBDs in an ITC and NMR spectroscopy based study. Our previous study revealed the presence of microsecond timescale dynamics in RNA-binding regions in the two dsRBDs studied. In the current study, results from ITC-based titrations showed that the binding of dsRBD with topologically distinct dsRNAs is enthalpy-driven, with each dsRNA-dsRBD pair having distinct combination of enthalpy-entropy yielding a similar change in free energy upon RNA-binding. We also show that the each of the dsRNA, used in this study, binds to the dsRBD in a unique mode. Further, intrinsic conformational exchange present in the RNA-binding regions of the apo-dsRBD was shown to quench upon binding with a dsRNA, while conformational exchange got induced at the residues that are in close proximity to where exchange was present in the apo-protein. This apparent relay of conformational exchange from one site to the other site upon dsRNA-binding thus suggests the importance of intrinsic dynamics to adapt to target a variety of dsRNA-shapes.Statement of SignificanceThis study reports that the interaction between dsRBDs and dsRNAs is enthalpy-driven, is perturbed by subtle changes in dsRNA shapes, and exhibits a classic case of enthalpy-entropy compensation. Further, the intrinsic microsecond timescale conformational exchange present in the apo-dsRBD was observed to get quenched upon RNA-binding. An apparent relay of conformational exchange was also observed from quenched sites to spatially proximal sites upon RNA-binding, suggesting highly adaptive nature of the dsRBD, a critical feature required to target topologically distinct dsRNA.
Prolonged anesthesia alters brain synaptic architecture
Authors: Wenzel Michael , Leunig Alexander , Han Shuting , Peterka Darcy S. , Yuste Rafael 
Published: December 2019

SUMMARYProlonged medically-induced coma (pMIC), a procedure performed in millions of patients worldwide, leads to cognitive impairment, yet the underlying brain mechanism remains unknown. No experimental studies of medically-induced coma (MIC) exceeding ~6 hours exist. For MIC of less than 6 hours, studies in developing rodents have documented transient changes of cortical synapse formation. However, in adulthood, cortical synapses are thought to become stabilized. Here, we establish pMIC (up to 24 hrs) in adolescent and mature mice, and combine repeated behavioral object recognition assessments with longitudinal two-photon imaging of cortical synapses. We find that pMIC affects cognitive function, and is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the post-anesthetic period is dominated by synaptic loss. These results carry profound implications for intensive medical care, as they point out at significant structural side effects of pMIC on cortical brain synaptic architecture across age levels.