bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing variability in along-tract analysis with diffusion profile realignment
Authors: St-Jean Samuel , Chamberland Maxime , Viergever Max A. , Leemans Alexander 
Published: February 2019

AbstractDiffusion weighted magnetic resonance imaging (dMRI) provides a non invasive virtual reconstruction of the brain’s white matter structures through tractography. Analyzing dMRI measures along the trajectory of white matter bundles can provide a more specific investigation than considering a region of interest or tract-averaged measurements. However, performing group analyses with this along-tract strategy requires correspondence between points of tract pathways across subjects. This is usually achieved by creating a new common space where the representative streamlines from every subject are resampled to the same number of points. If the underlying anatomy of some subjects was altered due to, e.g., disease or developmental changes, such information might be lost by resampling to a fixed number of points. In this work, we propose to address the issue of possible misalignment, which might be present even after resampling, by realigning the representative streamline of each subject in this 1D space with a new method, coined diffusion profile realignment (DPR). Experiments on synthetic datasets show that DPR reduces the coefficient of variation for the mean diffusivity, fractional anisotropy and apparent fiber density when compared to the unaligned case. Using 100 in vivo datasets from the human connectome project, we simulated changes in mean diffusivity, fractional anisotropy and apparent fiber density. Pairwise Student’s t-tests between these altered subjects and the original subjects indicate that regional changes are identified after realignment with the DPR algorithm, while preserving differences previously detected in the unaligned case. This new correction strategy contributes to revealing effects of interest which might be hidden by misalignment and has the potential to improve the specificity in longitudinal population studies beyond the traditional region of interest based analysis and along-tract analysis workflows.
Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
Authors: Chang Chi-Lun , Weigel Aubrey V. , Ioannou Maria S. , Pasolli H. Amalia , Xu C. Shan , Peale David R. , Shtengel Gleb , Freeman Melanie , Hess Harald F. , Blackstone Craig , Lippincott-Schwartz Jennifer 
Published: February 2019

AbstractLipid droplets (LDs) are neutral lipid storage organelles that transfer lipids to various organelles including peroxisomes. Here, we show that the hereditary spastic paraplegia protein M1 Spastin, a membrane-bound AAA ATPase found on LDs, coordinates fatty acid (FA) trafficking from LDs to peroxisomes through two inter-related mechanisms. First, M1 Spastin forms a tethering complex with peroxisomal ABCD1 to promote LD-peroxisome contact formation. Second, M1 Spastin recruits the membrane-shaping ESCRT-III proteins IST1 and CHMP1B to LDs via its MIT domain to facilitate LD-to-peroxisome FA trafficking, possibly through IST1 and CHMP1B modifying LD membrane morphology. Furthermore, M1 Spastin, IST1 and CHMP1B are all required to relieve LDs of lipid peroxidation. M1 Spastin’s dual roles in tethering LDs to peroxisomes and in recruiting ESCRT-components to LD-peroxisome contact sites for FA trafficking may help explain the pathogenesis of diseases associated with defective FA metabolism in LDs and peroxisomes.
Ancient RNA from Late Pleistocene permafrost and historical canids shows tissue-specific transcriptome survival
Authors: Smith Oliver , Dunshea Glenn , Sinding Mikkel-Holger S. , Fedorov Sergey , Germonpre Mietje , Bocherens Hervé , Gilbert M.T.P. 
Published: February 2019

AbstractWhile sequencing ancient DNA from archaeological material is now commonplace, very few attempts to sequence ancient transcriptomes have been made, even from typically stable deposition environments such as permafrost. This is presumably due to assumptions that RNA completely degrades relatively quickly, particularly when dealing with autolytic, nuclease-rich mammalian tissues. However, given the recent successes in sequencing ancient RNA (aRNA) from various sources including plants and animals, we suspect that these assumptions may be incorrect or exaggerated. To challenge the underlying dogma, we generated shotgun RNA data from sources that might normally be dismissed for such study. Here we present aRNA data generated from two historical wolf skins, and permafrost-preserved liver tissue of a 14,300-year-old Pleistocene canid. Not only is the latter the oldest RNA ever to be sequenced, but also shows evidence of biologically relevant tissue-specificity and close similarity to equivalent data derived from modern-day control tissue. Other hallmarks of RNA-seq data such as exon-exon junction presence and high endogenous ribosomal RNA content confirms our data’s authenticity. By performing independent technical replicates using two high-throughput sequencing platforms, we show not only that aRNA can survive for extended periods in mammalian tissues, but also that it has potential for tissue identification, and possibly further uses such as in vivo genome activity and adaptation, when sequenced using this technology.
Indirect pathway of caudate tail for choosing good objects in periphery
Authors: Amita Hidetoshi , Hikosaka Okihide 
Published: February 2019

AbstractChoosing good objects is essential for real life, which is controlled mainly by the basal ganglia. For that, a subject need to not only find good objects, but ‘reject’ bad objects. To reveal this ‘rejection’ mechanism, we created a sequential saccade choice task for monkeys and studied the indirect pathway of caudate tail mediated by cvGPe (caudal-ventral globus pallidus externus). The inhibitory responses of cvGPe neurons to bad objects were smaller when the monkey made saccades to them by mistake. Moreover, experimental reduction of the inhibitory response by local injection of bicuculline (GABAA antagonist) disabled the monkey to reject bad objects. In conclusion, rejecting bad objects is crucial for goal-directed behavior, which is controlled by the indirect pathway in the basal ganglia.
Memory quality modulates the effect of aging on memory consolidation during sleep: Reduced maintenance but intact gain
Authors: Muehlroth Beate E. , Sander Myriam C. , Fandakova Yana , Grandy Thomas H. , Rasch Björn , Shing Yee Lee , Werkle-Bergner Markus 
Published: February 2019

AbstractSuccessful consolidation of associative memories relies on the coordinated interplay of slow oscillations and sleep spindles during non-rapid eye movement (NREM) sleep, enabling the transfer of labile information from the hippocampus to permanent memory stores in the neocortex. During senescence, the decline of the structural and functional integrity of the hippocampus and neocortical regions is paralleled by changes of the physiological events that stabilize and enhance associative memories during NREM sleep. However, the currently available evidence is inconclusive if and under which circumstances aging impacts memory consolidation. By tracing the encoding quality of single memories in individual participants, we demonstrate that previous learning determines the extent of age-related impairments in memory consolidation. Specifically, the detrimental effects of aging on memory maintenance were greatest for mnemonic contents of medium encoding quality, whereas memory gain of weakly encoded memories did not differ by age. Using multivariate techniques, we identified profiles of alterations in sleep physiology and brain structure characteristic for increasing age. Importantly, while both ‘aged’ sleep and ‘aged’ brain structure profiles were associated with reduced memory maintenance, inter-individual differences in neither sleep nor structural brain integrity qualified as the driving force behind age differences in sleep-dependent consolidation in the present study.
Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
Authors: Nordström Karl JV , Schmidt Florian , Gasparoni Nina , Salhab Abdulrahman , Gasparoni Gilles , Kattler Kathrin , Müller Fabian , Ebert Peter , Costa Ivan G. ,   DEEP consortium, Pfeifer Nico , Lengauer Thomas , Schulz Marcel H , Walter Jörn 
Published: February 2019

AbstractChromatin accessibility maps are important for the functional interpretation of the genome. Here, we systematically analysed assay specific differences between DNase I-Seq, ATAC-Seq and NOMe-Seq in a side by side experimental and bioinformatic setup. We observe that most prominent nucleosome depleted regions (NDRs, e.g. in promoters) are roboustly called by all three or at least two assays. However we also find a high proportion of assay specific NDRs that are often “called” by only one of the assays. We show evidence that these assay specific NDRs are indeed genuine open chromatin sites and contribute important information for accurate gene expression prediction. While technically ATAC-Seq and DNAse I-Seq provide a high NDR calling rate for relatively low sequencing costs in comparison to NOMe-Seq, NOMe-Seq singles out as it provides a multitude of information: it allows to not only detect NDRs but also endogenous DNA methylation, genome wide segmentation into heterochromatic A/B domains and local phasing of nucleosomes outside of NDRs. In summary our comparison strongly suggest to consider assay specific differences for the experimental desgin and for generalized and comparative functional interpretations.
Maize brace root mechanics vary by whorl, genotype, and reproductive stage
Authors: Hostetler Ashley N. , Erndwein Lindsay , Ganji Elahe , Reneau Jonathan W. , Killian Megan L. , Sparks Erin E. 
Published: February 2019

ABSTRACTRoot lodging is responsible for significant crop losses world-wide. During root lodging, roots fail by breaking, buckling, or pulling out of the ground. In maize, above-ground roots, called brace roots, have been shown to reduce root lodging susceptibility. However, the underlying structural-functional properties of brace roots that prevent root lodging are poorly defined. In this study, we quantified structural mechanical properties, geometry, and bending moduli for brace roots from different whorls, genotypes, and reproductive stages. Using 3-point bend tests, we show that brace root mechanics are variable by whorl, genotype, and reproductive stage. Generally, we find that within each genotype and reproductive stage, the brace roots from the whorl closest to the ground had higher structural mechanical properties and a lower bending modulus than brace roots from the second whorl. There was additional variation between genotypes and reproductive stages. Specifically, genotypes with higher structural mechanical properties also had a higher bending modulus, and senesced brace roots had lower structural mechanical properties than hydrated brace roots. Collectively these results highlight the importance of considering whorl-of-origin, genotype, and reproductive stage for quantification of brace root mechanics, which is important for mitigating crop loss due to root mechanical failure.
The number of lateral hypothalamus orexin/hypocretin neurons contributes to individual differences in cocaine demand
Authors: Pantazis Caroline B. , James Morgan H. , Bentzley Brandon S. , Aston-Jones Gary 
Published: February 2019

AbstractLateral hypothalamus (LH) orexin neuron signaling has been implicated in the motivation to seek and take drugs of abuse. The number of LH orexin neurons has been shown to vary with behavioral state and can be upregulated with exposure to drugs of abuse. We sought to determine if the number of LH orexin neurons related to individual differences in motivation (demand) for cocaine in our behavioral economics (BE) paradigm, and whether knockdown of these cells predicted changes in economic demand. We quantified LH orexin cell numbers in animals immediately following our BE paradigm, as well as BE-experienced animals after a two-week period of abstinence to relate the number of LH orexin cells to economic demand for cocaine. We also unilaterally knocked down LH orexin expression prior to BE with an orexin morpholino antisense to determine how reduced orexin numbers impacted cocaine demand. Animals with greater motivation for cocaine (lower demand elasticity) had more LH orexin neurons. Following a two-week abstinence from BE, the number of LH orexin neurons predicted economic demand for cocaine prior to abstinence. Reducing LH orexin cell numbers with antisense decreased motivation for cocaine (increased demand elasticity) without affecting baseline consumption. In addition, the number of spared LH orexin neurons after antisense treatment correlated with individual demand for cocaine. These studies point to a role for the endogenous number of LH orexin neurons in individual differences in motivation for cocaine.
Convergent seed color adaptation during repeated domestication of an ancient new world grain
Authors: Stetter Markus G , Vidal-Villarejo Mireia , Schmid Karl J 
Published: February 2019

ABSTRACTOut of the almost 2,000 plants that have been selected as crops, only few are fully domesticated, and many intermediates between wild plants and domesticates exist. Genetic constraints might be the reason why incompletely domesticated plants have few characteristic crop traits, and retained numerous wild plant features. Here, we investigate the incomplete domestication of an ancient grain from the Americas, amaranth. We sequenced 121 genomes of the crop and its wild ancestors to show that grain amaranth has been selected three times independently from a single wild ancestor, but has not been fully domesticated. Our analysis identified a MYB-like transcription factor gene as key regulator for seed color variation and shows that the trait was independently converted in Central and South America. We suggest a low effective population size at the time of domestication as potential cause for the lack of adaptation of complex domestication traits. Our results show how genetic constraints influenced domestication and might have set the fate of hundreds of crops.
Reduced competition between tool action neighbors in left hemisphere stroke
Authors: Garcea Frank E. , Stoll Harrison , Buxbaum Laurel J. 
Published: February 2019

AbstractWhen pantomiming the use of tools, patients with limb apraxia after left hemisphere stroke (LCVA) produce more spatiotemporal hand action errors with tools associated with conflicting actions for use versus grasp-to-pick-up (e.g., corkscrew) than tools having a single action for both use and grasp (e.g., hammer). There are two possible accounts for this pattern of results. Reduced performance with ‘conflict’ tools may simply reflect weakened automaticity of use action activation, which is evident only when the use and grasp actions are not redundant. Alternatively, poor use performance may reflect reduced ability of appropriate tool use actions to compete with task-inappropriate action representations. To address this issue, we developed a Stroop-like experiment in which 21 LCVA and 8 neurotypical participants performed pantomime actions in blocks containing two tools that were similar (“neighbors”) in terms of hand action or function, or unrelated on either dimension. In a congruent condition, they pantomimed the use action associated with the visually presented tool, whereas in an incongruent condition, they pantomimed the use action for the other tool in the block. Relative to controls and other task conditions, LCVA participants showed reductions in hand action errors in incongruent relative to congruent action trials; furthermore, the degree of reduction in this incongruence effect was related to the participants’ susceptibility to grasp-on-use conflict in a separate test of pantomime to the sight of tools. Support vector regression lesion-symptom mapping analyses identified the left inferior frontal gyrus, supramarginal gyrus, and superior longitudinal fasciculus as core neuroanatomical sites associated with abnormal performance on both tasks. Collectively, the results indicate that weakened activation of tool use actions in limb apraxia gives rise to reduced ability of these actions to compete for task-appropriate selection when competition arises within single tools (grasp-on-use conflict) as well as between two tools (reduced neighborhood effects).
Investigation of the effect of estradiol and subculturing on the receptor expression within hormone-dependent breast cancer cells
Authors: Mallick Avijit , Ahmed Sabbir 
Published: February 2019

SUMMARYIt is now known that a very crucial role in breast cancer development, prognosis and occurrence is played by the estrogen receptor (ER). The steroid hormone estradiol (E2) acts via two nuclear receptors, estrogen receptor-α (ERα) and estrogen receptor-β (ERβ). E2 was shown previously to increase breast cancer cell proliferation in a dose-dependent manner and also induce apoptosis in long term estrogen deprived breast cancer cells. Studies have also shown that the degree of subculturing affects cell line property including gene expression. The aim of this study was to investigate the effect of E2 concentration on cell proliferation, morphology and ER expression and to investigate the effect of subculturing on the expression of ER. Our results have shown that an increase in E2 concentration was found to increase MCF-7 cell proliferation, but extreme concentrations caused significantly low cell proliferation and induced apoptosis. Moreover, ERα expression was significantly upregulated with an increase in E2 concentration, whereas ERβ2 expression was found to be unchanged at low E2 concentration and significantly upregulated at higher E2 concentration. ERα expression at passage 3 ([E2]=1nM) was significantly downregulated compared to the cells at passage 0, in addition to the significant downregulation of the same at E2 concentrations of 1nM and 10µM compared to the untreated control sample. Overall, our data suggests that high concentration of E2 can reduce proliferation and induce apoptosis in the breast cancer cells. Increased E2 exposure and subculturing also appear to change the ERα expression significantly in the breast cancer cell line.
Work Flows for Cellular Epidemiology, From Conception to Translation
Authors: Nathanson Anton D. , Ngo Lucy , Garbowski Tomasz , Srikantha Abhilash , Wojek Christian , Zeidler Dirk , Knothe Tate Melissa L. 
Published: February 2019

The authors have withdrawn their manuscript after issues with the cell viability validation (Fig. 8) were found. In the interest of furthering science and ensuring that clinical decisions are based on best practices and evidence, the issue is described in more detail in the peer-reviewed, published paper: https://www.frontiersin.org/articles/10.3389/fphys.2021.647603/fullKnothe Tate ML, Srikantha A, Wojek C, Zeidler D (2021) Connectomics of Bone to Brain— Probing Physical Renderings of Cellular Experience, Frontiers in Physiology 12: 1018, doi: 10.3389/fphys.2021.647603As noted in that published work: “Osteocyte coordinates can be extracted from the YOLO classified image set, enabling high throughput analyses of massive datasets, which in the future could include other cellular inhabitants of tissues including blood cells, immune cells, chondrocytes, etc. While the method shows great promise for automated detection of cells, the greatest limitation of the method is the definition of appropriate and unbiased classifiers. The definition of osteocytes as pyknotic and viable based on the number of cell processes was shown to be flawed in a parallel study testing the assumption using biochemical based viability measures (Anastopolous and Knothe Tate, 2021).”Therefore, the authors do not wish this work to be cited as reference for the project.If you have any questions, please contact the corresponding author.
Phylogeographic parallelism: concordance of patterns in closely related species illuminates underlying mechanisms in the historically glaciated Tasmanian landscape
Authors: Kreger K. , Shaban B. , Wapstra E. , Burridge C.P. 
Published: February 2019

AbstractPhylogeography provides a means to understand mechanisms that shaped the distribution and abundance of species, including the role of past climate change. While concordant phylogeographic relationships across diverse taxa suggest shared underlying mechanisms (“phylogeographic parallelism”), it is also possible that similar patterns are the product of different mechanisms (“phylogeographic convergence”), reflecting variation among taxa in factors such as environmental tolerances, life histories, and vagility. Hence, phylogeographic concordance among closely related and ecologically similar species can yield a more confident understanding of the past mechanisms which shaped their distribution and abundance. This study documented mitochondrial and nuclear phylogeographic patterns in the ectotherm skink,Niveoscincus metallicus, which occupies historically glaciated regions of Tasmania, and contrasted these with the closely related and broadly sympatricN. ocellatus. Major phylogeographic breaks were similar in location between the two species, and indicative of isolation caused by retreat from high elevation areas during glaciations, but with long-term persistence at multiple low elevation sites. Hence, Pleistocene glacial refugia were altitudinal rather than latitudinal, a pattern mirrored in other temperate Southern Hemisphere taxa. This study also examined phylogeographic patterns across the intermittently inundated Bassian Isthmus between mainland Australia and the island of Tasmania, and revealed that structuring is similarly maintained when populations were physically isolated during interglacial rather than glacial stages.
Dynamic membrane topology in an unassembled membrane protein
Authors: Seurig Maximilian , Ek Moira , von Heijne Gunnar , Fluman Nir 
Published: February 2019

AbstractHelical membrane proteins constitute roughly a quarter of all proteomes and perform diverse biological functions. To avoid aggregation, they undergo cotranslational membrane insertion and are typically assumed to attain stable transmembrane topologies immediately upon insertion. To what extent post-translational changes in topology are possible in-vivo and how they may affect biogenesis is incompletely understood. Here, we show that monomeric forms of Small Multidrug Resistance (SMR) proteins display topological dynamics, where the N-terminal transmembrane helix equilibrates between membrane-inserted and non-inserted states. We characterize the kinetics of the process and show how the composition of the helix regulates the topological dynamics. We further show that topological dynamics is a property of the unassembled monomeric protein, as the N-terminal helix becomes fixed in a transmembrane disposition upon dimerization. Membrane protein topology can thus remain dynamic long after cotranslational membrane insertion, and can be regulated by later assembly processes.