bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in health-related quality of life among older adults aging with long-term spinal cord injury
Authors: Jörgensen Sophie , Costa Andersson Maria Valentina , Lexell Jan 
Published: November 2020

Abstract
Study design
Cross-sectional and longitudinal.

Objectives
To (i) describe health-related quality of life (HRQoL) and changes over 6 years in older adults aging with long-term spinal cord injury (SCI) and (ii) investigate how changes in HRQoL are associated with age, gender, and injury characteristics.

Setting
Community in southern Sweden.

Methods
From the initial 123 participants (years 2011–2012) in the Swedish Aging with Spinal Cord Injury Study (SASCIS), 77 individuals (32% women, C1-L3, AIS A–D, median age 66 years, median time since injury 31 years, 30% complete injuries) were assessed 6 years later. HRQoL was rated with the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23). Associations were investigated using multivariable linear regression analyses.

Results
The median rating of global QoL (scale range 0–100) was relatively high at both assessments (67 and 83, respectively). There was a large variability in all HRQoL-domains and no significant changes over 6 years. As compared to an AIS D injury, a tetraplegia AIS A–C injury and tetraplegia and paraplegia AIS A–C injuries were associated with positive change in depressive symptoms and global QoL, respectively.

Conclusions
Older adults aging with long-term SCI show large variations in all HRQoL-domains and have the potential to maintain a high and stable level of HRQoL over time. Persons with AIS D injuries may need increased attention to mitigate negative changes in depressive symptoms and global QoL. Further studies are needed to identify modifiable factors associated with changes in HRQoL in older adults aging with long-term SCI.
Disruption of estradiol regulation of orexin neurons: a novel mechanism in excessive ventilatory response to CO2 inhalation in a female rat model of panic disorder
Authors: Tenorio-Lopes Luana , Fournier Stéphanie , Henry Mathilde S. , Bretzner Frédéric , Kinkead Richard 
Published: November 2020

AbstractPanic disorder (PD) is ~2 times more frequent in women. An excessive ventilatory response to CO2 inhalation is more likely during the premenstrual phase. While ovarian hormones appear important in the pathophysiology of PD, their role remains poorly understood as female animals are rarely used in pre-clinical studies. Using neonatal maternal separation (NMS) to induce a “PD-like” respiratory phenotype, we tested the hypothesis that NMS disrupts hormonal regulation of the ventilatory response to CO2 in female rats. We then determined whether NMS attenuates the inhibitory actions of 17-β estradiol (E2) on orexin neurons (ORX). Pups were exposed to NMS (3 h/day; postnatal day 3–12). The ventilatory response to CO2-inhalation was tested before puberty, across the estrus cycle, and following ovariectomy. Plasma E2 and hypothalamic ORXA were measured. The effect of an ORX1 antagonist (SB334867; 15 mg/kg) on the CO2 response was tested. Excitatory postsynaptic currents (EPSCs) were recorded from ORX neurons using whole-cell patch-clamp. NMS-related increase in the CO2 response was observed only when ovaries were functional; the largest ventilation was observed during proestrus. SB334867 blocked this effect. NMS augmented levels of ORXA in hypothalamus extracts. EPSC frequency varied according to basal plasma E2 levels across the estrus cycle in controls but not NMS. NMS reproduces developmental and cyclic changes of respiratory manifestations of PD. NMS disrupts the inhibitory actions of E2 on the respiratory network. Impaired E2-related inhibition of ORX neurons during proestrus is a novel mechanism in respiratory manifestations of PD in females.
Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes
Authors: Sottini Andrea , Borgia Alessandro , Borgia Madeleine B. , Bugge Katrine , Nettels Daniel , Chowdhury Aritra , Heidarsson Pétur O. , Zosel Franziska , Best Robert B. , Kragelund Birthe B. , Schuler Benjamin 
Published: November 2020

AbstractHighly charged intrinsically disordered proteins can form complexes with very high affinity in which both binding partners fully retain their disorder and dynamics, exemplified by the positively charged linker histone H1.0 and its chaperone, the negatively charged prothymosin α. Their interaction exhibits another surprising feature: The association/dissociation kinetics switch from slow two-state-like exchange at low protein concentrations to fast exchange at higher, physiologically relevant concentrations. Here we show that this change in mechanism can be explained by the formation of transient ternary complexes favored at high protein concentrations that accelerate the exchange between bound and unbound populations by orders of magnitude. Molecular simulations show how the extreme disorder in such polyelectrolyte complexes facilitates (i) diffusion-limited binding, (ii) transient ternary complex formation, and (iii) fast exchange of monomers by competitive substitution, which together enable rapid kinetics. Biological polyelectrolytes thus have the potential to keep regulatory networks highly responsive even for interactions with extremely high affinities.
Low SARS-CoV-2 seroprevalence in blood donors in the early COVID-19 epidemic in the Netherlands
Authors: Slot Ed , Hogema Boris M. , Reusken Chantal B. E. M. , Reimerink Johan H. , Molier Michel , Karregat Jan H. M. , IJlst Johan , Novotný Věra M. J. , van Lier René A. W. , Zaaijer Hans L. 
Published: November 2020

AbstractThe world is combating an ongoing COVID-19 pandemic with health-care systems, society and economies impacted in an unprecedented way. It is unclear how many people have contracted the causative coronavirus (SARS-CoV-2) unknowingly and are asymptomatic. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of the Netherlands, which is a highly affected country, using a high-performance immunoassay. Our results indicate that one month into the outbreak (i) the seroprevalence in the Netherlands was 2.7% with substantial regional variation, (ii) the hardest-hit areas showed a seroprevalence of up to 9.5%, (iii) the seroprevalence was sex-independent throughout age groups (18–72 years), and (iv) antibodies were significantly more often present in younger people (18–30 years). Our study provides vital information on the extent of exposure to SARS-CoV-2 in a country where social distancing is in place.
Exceptional non-Hermitian topological edge mode and its application to active matter
Authors: Sone Kazuki , Ashida Yuto , Sagawa Takahiro 
Published: November 2020

AbstractTopological materials exhibit edge-localized scattering-free modes protected by their nontrivial bulk topology through the bulk-edge correspondence in Hermitian systems. While topological phenomena have recently been much investigated in non-Hermitian systems with dissipations and injections, the fundamental principle of their edge modes has not fully been established. Here, we reveal that, in non-Hermitian systems, robust gapless edge modes can ubiquitously appear owing to a mechanism that is distinct from bulk topology, thus indicating the breakdown of the bulk-edge correspondence. The robustness of these edge modes originates from yet another topological structure accompanying the branchpoint singularity around an exceptional point, at which eigenvectors coalesce and the Hamiltonian becomes nondiagonalizable. Their characteristic complex eigenenergy spectra are applicable to realize lasing wave packets that propagate along the edge of the sample. We numerically confirm the emergence and the robustness of the proposed edge modes in the prototypical lattice models. Furthermore, we show that these edge modes appear in a model of chiral active matter based on the hydrodynamic description, demonstrating that active matter can exhibit an inherently non-Hermitian topological feature. The proposed general mechanism would serve as an alternative designing principle to realize scattering-free edge current in non-Hermitian devices, going beyond the existing frameworks of non-Hermitian topological phases.
Mus81-Mms4 endonuclease is an Esc2-STUbL-Cullin8 mitotic substrate impacting on genome integrity
Authors: Waizenegger Anja , Urulangodi Madhusoodanan , Lehmann Carl P. , Reyes Teresa Anne Clarisse , Saugar Irene , Tercero José Antonio , Szakal Barnabas , Branzei Dana 
Published: November 2020

AbstractThe Mus81-Mms4 nuclease is activated in G2/M via Mms4 phosphorylation to allow resolution of persistent recombination structures. However, the fate of the activated phosphorylated Mms4 remains unknown. Here we find that Mms4 is engaged by (poly)SUMOylation and ubiquitylation and targeted for proteasome degradation, a process linked to the previously described Mms4 phosphorylation cycle. Mms4 is a mitotic substrate for the SUMO-Targeted Ubiquitin ligase Slx5/8, the SUMO-like domain-containing protein Esc2, and the Mms1-Cul8 ubiquitin ligase. In the absence of these activities, phosphorylated Mms4 accumulates on chromatin in an active state in the next G1, subsequently causing abnormal processing of replication-associated recombination intermediates and delaying the activation of the DNA damage checkpoint. Mus81-Mms4 mutants that stabilize phosphorylated Mms4 have similar detrimental effects on genome integrity. Overall, our findings highlight a replication protection function for Esc2-STUbL-Cul8 and emphasize the importance for genome stability of resetting phosphorylated Mms4 from one cycle to another.
Molecular structure and interactions within amyloid-like fibrils formed by a low-complexity protein sequence from FUS
Authors: Lee Myungwoon , Ghosh Ujjayini , Thurber Kent R. , Kato Masato , Tycko Robert 
Published: November 2020

AbstractProtein domains without the usual distribution of amino acids, called low complexity (LC) domains, can be prone to self-assembly into amyloid-like fibrils. Self-assembly of LC domains that are nearly devoid of hydrophobic residues, such as the 214-residue LC domain of the RNA-binding protein FUS, is particularly intriguing from the biophysical perspective and is biomedically relevant due to its occurrence within neurons in amyotrophic lateral sclerosis, frontotemporal dementia, and other neurodegenerative diseases. We report a high-resolution molecular structural model for fibrils formed by the C-terminal half of the FUS LC domain (FUS-LC-C, residues 111-214), based on a density map with 2.62 Å resolution from cryo-electron microscopy (cryo-EM). In the FUS-LC-C fibril core, residues 112-150 adopt U-shaped conformations and form two subunits with in-register, parallel cross-β structures, arranged with quasi-21 symmetry. All-atom molecular dynamics simulations indicate that the FUS-LC-C fibril core is stabilized by a plethora of hydrogen bonds involving sidechains of Gln, Asn, Ser, and Tyr residues, both along and transverse to the fibril growth direction, including diverse sidechain-to-backbone, sidechain-to-sidechain, and sidechain-to-water interactions. Nuclear magnetic resonance measurements additionally show that portions of disordered residues 151-214 remain highly dynamic in FUS-LC-C fibrils and that fibrils formed by the N-terminal half of the FUS LC domain (FUS-LC-N, residues 2-108) have the same core structure as fibrils formed by the full-length LC domain. These results contribute to our understanding of the molecular structural basis for amyloid formation by FUS and by LC domains in general.
A convolutional neural network segments yeast microscopy images with high accuracy
Authors: Dietler Nicola , Minder Matthias , Gligorovski Vojislav , Economou Augoustina Maria , Joly Denis Alain Henri Lucien , Sadeghi Ahmad , Chan Chun Hei Michael , Koziński Mateusz , Weigert Martin , Bitbol Anne-Florence , Rahi Sahand Jamal 
Published: November 2020

AbstractThe identification of cell borders (‘segmentation’) in microscopy images constitutes a bottleneck for large-scale experiments. For the model organismSaccharomyces cerevisiae, current segmentation methods face challenges when cells bud, crowd, or exhibit irregular features. We present a convolutional neural network (CNN) named YeaZ, the underlying training set of high-quality segmented yeast images (>10 000 cells) including mutants, stressed cells, and time courses, as well as a graphical user interface and a web application (www.quantsysbio.com/data-and-software) to efficiently employ, test, and expand the system. A key feature is a cell-cell boundary test which avoids the need for fluorescent markers. Our CNN is highly accurate, including for buds, and outperforms existing methods on benchmark images, indicating it transfers well to other conditions. To demonstrate how efficient large-scale image processing uncovers new biology, we analyze the geometries of ≈2200 wild-type and cyclin mutant cells and find that morphogenesis control occurs unexpectedly early and gradually.
Phenotypic variation of transcriptomic cell types in mouse motor cortex
Authors: Scala Federico , Kobak Dmitry , Bernabucci Matteo , Bernaerts Yves , Cadwell Cathryn René , Castro Jesus Ramon , Hartmanis Leonard , Jiang Xiaolong , Laturnus Sophie , Miranda Elanine , Mulherkar Shalaka , Tan Zheng Huan , Yao Zizhen , Zeng Hongkui , Sandberg Rickard , Berens Philipp , Tolias Andreas S. 
Published: November 2020

AbstractCortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties1,2. Most existing neural taxonomies are based on either transcriptomic3,4 or morpho-electric5,6 criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells7. Here we used Patch-seq8 to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.
County-level CO2 emissions and sequestration in China during 1997–2017
Authors: Chen Jiandong , Gao Ming , Cheng Shulei , Hou Wenxuan , Song Malin , Liu Xin , Liu Yu , Shan Yuli 
Published: November 2020

AbstractWith the implementation of China’s top-down CO2 emissions reduction strategy, the regional differences should be considered. As the most basic governmental unit in China, counties could better capture the regional heterogeneity than provinces and prefecture-level city, and county-level CO2 emissions could be used for the development of strategic policies tailored to local conditions. However, most of the previous accounts of CO2 emissions in China have only focused on the national, provincial, or city levels, owing to limited methods and smaller-scale data. In this study, a particle swarm optimization-back propagation (PSO-BP) algorithm was employed to unify the scale of DMSP/OLS and NPP/VIIRS satellite imagery and estimate the CO2 emissions in 2,735 Chinese counties during 1997–2017. Moreover, as vegetation has a significant ability to sequester and reduce CO2 emissions, we calculated the county-level carbon sequestration value of terrestrial vegetation. The results presented here can contribute to existing data gaps and enable the development of strategies to reduce CO2 emissions in China.
Extracellular vesicles from amyloid-β exposed cell cultures induce severe dysfunction in cortical neurons
Authors: Beretta Chiara , Nikitidou Elisabeth , Streubel-Gallasch Linn , Ingelsson Martin , Sehlin Dag , Erlandsson Anna 
Published: November 2020

AbstractAlzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that spreading of amyloid-β (Aβ) pathology via extracellular vesicles (EVs) may contribute to disease progression. We have previously shown that an incomplete degradation of Aβ42 protofibrils by astrocytes results in the release of EVs containing neurotoxic Aβ. Here, we describe the cellular mechanisms behind EV-associated neurotoxicity in detail. EVs were isolated from untreated and Aβ42 protofibril exposed neuroglial co-cultures, consisting mainly of astrocytes. The EVs were added to cortical neurons for 2 or 4 days and the neurodegenerative processes were followed with immunocytochemistry, time-lapse imaging and transmission electron microscopy (TEM). Addition of EVs from Aβ42 protofibril exposed co-cultures resulted in synaptic loss, severe mitochondrial impairment and apoptosis. TEM analysis demonstrated that the EVs induced axonal swelling and vacuolization of the neuronal cell bodies. Interestingly, EV exposed neurons also displayed pathological lamellar bodies of cholesterol deposits in lysosomal compartments. Taken together, our data show that the secretion of EVs from Aβ exposed cells induces neuronal dysfunction in several ways, indicating a central role for EVs in the progression of Aβ-induced pathology.
Context aware deep learning for brain tumor segmentation, subtype classification, and survival prediction using radiology images
Authors: Pei Linmin , Vidyaratne Lasitha , Rahman Md Monibor , Iftekharuddin Khan M. 
Published: November 2020

AbstractA brain tumor is an uncontrolled growth of cancerous cells in the brain. Accurate segmentation and classification of tumors are critical for subsequent prognosis and treatment planning. This work proposes context aware deep learning for brain tumor segmentation, subtype classification, and overall survival prediction using structural multimodal magnetic resonance images (mMRI). We first propose a 3D context aware deep learning, that considers uncertainty of tumor location in the radiology mMRI image sub-regions, to obtain tumor segmentation. We then apply a regular 3D convolutional neural network (CNN) on the tumor segments to achieve tumor subtype classification. Finally, we perform survival prediction using a hybrid method of deep learning and machine learning. To evaluate the performance, we apply the proposed methods to the Multimodal Brain Tumor Segmentation Challenge 2019 (BraTS 2019) dataset for tumor segmentation and overall survival prediction, and to the dataset of the Computational Precision Medicine Radiology-Pathology (CPM-RadPath) Challenge on Brain Tumor Classification 2019 for tumor classification. We also perform an extensive performance evaluation based on popular evaluation metrics, such as Dice score coefficient, Hausdorff distance at percentile 95 (HD95), classification accuracy, and mean square error. The results suggest that the proposed method offers robust tumor segmentation and survival prediction, respectively. Furthermore, the tumor classification results in this work is ranked at second place in the testing phase of the 2019 CPM-RadPath global challenge.
Characterization of the ExoU activation mechanism using EPR and integrative modeling
Authors: Tessmer Maxx H. , DeCero Samuel A. , del Alamo Diego , Riegert Molly O. , Meiler Jens , Frank Dara W. , Feix Jimmy B. 
Published: November 2020

AbstractExoU, a type III secreted phospholipase effector of Pseudomonas aeruginosa, serves as a prototype to model large, dynamic, membrane-associated proteins. ExoU is synergistically activated by interactions with membrane lipids and ubiquitin. To dissect the activation mechanism, structural homology was used to identify an unstructured loop of approximately 20 residues in the ExoU amino acid sequence. Mutational analyses indicate the importance of specific loop amino acid residues in mediating catalytic activity. Engineered disulfide cross-links show that loop movement is required for activation. Site directed spin labeling EPR and DEER (double electron–electron resonance) studies of apo and holo states demonstrate local conformational changes at specific sites within the loop and a conformational shift of the loop during activation. These data are consistent with the formation of a substrate-binding pocket providing access to the catalytic site. DEER distance distributions were used as constraints in RosettaDEER to construct ensemble models of the loop in both apo and holo states, significantly extending the range for modeling a conformationally dynamic loop.