bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Substrate to Surface: A Turbulence‐Based Model for Gas Transfer Across Sediment‐Water‐Air Interfaces in Vegetated Streams
Authors: Tseng Chien‐Yung , Tinoco Rafael O. 
Published: December 2021

AbstractDissolved Oxygen (DO) fluxes across the air‐water and sediment‐water interface (AWI and SWI) are two major processes that govern the amount of oxygen available to living organisms in aquatic ecosystems. Aquatic vegetation generates different scales of turbulence that change the flow structure and affect gas transfer mechanisms at AWI and SWI. A series of laboratory experiments with rigid cylinder arrays to mimic vegetation was conducted in a recirculating race‐track flume with a lightweight sediment bed. 2D Planar Particle Image Velocimetry was used to characterize the flow field under different submergence ratios and array densities to access the effect of vegetation‐generated turbulence on gas transfer. Gas transfer rate across AWI was determined by DO re‐aeration curves. The effective diffusion coefficient for gas transfer flux across SWI was estimated by the difference between near‐bed and near‐surface DO concentrations. When sediment begins to mobilize, near‐bed suspended sediment provides a negative buoyancy term that increases the critical Reynolds number for the surface gas transfer process according to a modified Surface Renewal model for vegetated flows. A new Reynolds number dependence model using near‐bed turbulent kinetic energy as an indicator is proposed to provide a universal prediction for the interfacial flux across SWI in flows with aquatic vegetation. This study provides critical information and useful models for future studies on water quality management and ecosystem restoration in natural water environments such as lakes, rivers, and wetlands.
Force measurement goes to femto-Newton sensitivity of single microscopic particle
Authors: Zhang Xiaohe , Gu Bing , Qiu Cheng-Wei 
Published: December 2021

AbstractHighly sensitive force measurements of a single microscopic particle with femto-Newton sensitivity have remained elusive owing to the existence of fundamental thermal noise. Now, researchers have proposed an optically controlled hydrodynamic manipulation method, which can measure the weak force of a single microscopic particle with femto-Newton sensitivity.
Exercise rather than fluoxetine promotes oligodendrocyte differentiation and myelination in the hippocampus in a male mouse model of depression
Authors: Tang Jing , Liang Xin , Dou Xiaoyun , Qi Yingqiang , Yang Chunmao , Luo Yanmin , Chao Fenglei , Zhang Lei , Xiao Qian , Jiang Lin , Zhou Chunni , Tang Yong 
Published: December 2021

AbstractAlthough selective serotonin reuptake inhibitor (SSRI) systems have been meaningfully linked to the clinical phenomena of mood disorders, 15–35% of patients do not respond to multiple SSRI interventions or even experience an exacerbation of their condition. As we previously showed, both running exercise and fluoxetine reversed depression-like behavior. However, whether exercise reverses depression-like behavior more quickly than fluoxetine treatment and whether this rapid effect is achieved via the promotion of oligodendrocyte differentiation and/or myelination in the hippocampus was previously unknown. Sixty male C57BL/6 J mice were used in the present study. We subjected mice with unpredictable chronic stress (UCS) to a 4-week running exercise trial (UCS + RN) or intraperitoneally injected them with fluoxetine (UCS + FLX) to address these uncertainties. At the behavioral level, mice in the UCS + RN group consumed significantly more sugar water in the sucrose preference test (SPT) at the end of the 7th week than those in the UCS group, while those in the UCS + FLX group consumed significantly more sugar water than mice in the UCS group at the end of the 8th week. The unbiased stereological results and immunofluorescence analyses revealed that running exercise, and not fluoxetine treatment, increased the numbers of CC1+ and CC1+/Olig2+/BrdU+ oligodendrocytes in the CA1 subfield in depressed mice exposed to UCS. Moreover, running exercise rather than fluoxetine increased the level of myelin basic protein (MBP) and the G-ratio of myelinated nerve fibers in the CA1 subfield in the UCS mouse model. Unlike fluoxetine, exercise promoted hippocampal myelination and oligodendrocyte differentiation and thus has potential as a therapeutic strategy to reduce depression-like behaviors induced by UCS.
MiRNA-132/212 regulates tight junction stabilization in blood–brain barrier after stroke
Authors: Yan Haomin , Kanki Hideaki , Matsumura Shigenobu , Kawano Tomohiro , Nishiyama Kumiko , Sugiyama Shintaro , Takemori Hiroshi , Mochizuki Hideki , Sasaki Tsutomu 
Published: December 2021

AbstractMicroRNA-132/212 has been supposed as a critical gene related to the blood–brain barrier (BBB) protection after stroke, but its regulation pathway including the upstream regulator and downstream targets is still unclear. Herein, we demonstrated the cAMP response element-binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) to be the upstream regulator of miRNA-132/212 using CRTC1 knockout and wild-type mice. CRTC1 deletion led to the reduction of miRNA-132/212 expression in mice brain after ischemic stroke, significantly increased infarct volume, and aggravated BBB permeability with worsening neurological deficits. Furthermore, we identified that miRNA-132 repressed Claudin-1, tight junction-associated protein-1 (TJAP-1), and RNA-binding Fox-1 (RBFox-1) by directly binding to their respective 3′-untranslated regions, which alleviated the ischemic damage by enhancing neuronal survival and BBB integrity. Moreover, the co-culture of endothelial cells with CRTC1-deficient neurons aggravated the cell vulnerability to hypoxia, also supporting the idea that miRNA-132/212 cluster is regulated by CRTC1 and acts as a crucial role in the mitigation of ischemic damage. This work is a step forward for understanding the role of miRNA-132/212 in neurovascular interaction and may be helpful for potential gene therapy of ischemic stroke.
Low immunogenicity of LNP allows repeated administrations of CRISPR-Cas9 mRNA into skeletal muscle in mice
Authors: Kenjo Eriya , Hozumi Hiroyuki , Makita Yukimasa , Iwabuchi Kumiko A. , Fujimoto Naoko , Matsumoto Satoru , Kimura Maya , Amano Yuichiro , Ifuku Masataka , Naoe Youichi , Inukai Naoto , Hotta Akitsu 
Published: December 2021

AbstractGenome editing therapy for Duchenne muscular dystrophy (DMD) holds great promise, however, one major obstacle is delivery of the CRISPR-Cas9/sgRNA system to skeletal muscle tissues. In general, AAV vectors are used for in vivo delivery, but AAV injections cannot be repeated because of neutralization antibodies. Here we report a chemically defined lipid nanoparticle (LNP) system which is able to deliver Cas9 mRNA and sgRNA into skeletal muscle by repeated intramuscular injections. Although the expressions of Cas9 protein and sgRNA were transient, our LNP system could induce stable genomic exon skipping and restore dystrophin protein in a DMD mouse model that harbors a humanized exon sequence. Furthermore, administration of our LNP via limb perfusion method enables to target multiple muscle groups. The repeated administration and low immunogenicity of our LNP system are promising features for a delivery vehicle of CRISPR-Cas9 to treat skeletal muscle disorders.
A nanoscale reciprocating rotary mechanism with coordinated mobility control
Authors: Bertosin Eva , Maffeo Christopher M. , Drexler Thomas , Honemann Maximilian N. , Aksimentiev Aleksei , Dietz Hendrik 
Published: December 2021

AbstractBiological molecular motors transform chemical energy into mechanical work by coupling cyclic catalytic reactions to large-scale structural transitions. Mechanical deformation can be surprisingly efficient in realizing such coupling, as demonstrated by the F1FO ATP synthase. Here, we describe a synthetic molecular mechanism that transforms a rotary motion of an asymmetric camshaft into reciprocating large-scale transitions in a surrounding stator orchestrated by mechanical deformation. We design the mechanism using DNA origami, characterize its structure via cryo-electron microscopy, and examine its dynamic behavior using single-particle fluorescence microscopy and molecular dynamics simulations. While the camshaft can rotate inside the stator by diffusion, the stator’s mechanics makes the camshaft pause at preferred orientations. By changing the stator’s mechanical stiffness, we accelerate or suppress the Brownian rotation, demonstrating an allosteric coupling between the camshaft and the stator. Our mechanism provides a framework for manufacturing artificial nanomachines that function because of coordinated movements of their components.
Pricing indirect emissions accelerates low—carbon transition of US light vehicle sector
Authors: Wolfram Paul , Weber Stephanie , Gillingham Kenneth , Hertwich Edgar G. 
Published: December 2021

AbstractLarge–scale electric vehicle adoption can greatly reduce emissions from vehicle tailpipes. However, analysts have cautioned that it can come with increased indirect emissions from electricity and battery production that are not commonly regulated by transport policies. We combine integrated energy modeling and life cycle assessment to compare optimal policy scenarios that price emissions at the tailpipe only, versus both tailpipe and indirect emissions. Surprisingly, scenarios that also price indirect emissions exhibit higher, rather than reduced, sales of electric vehicles, while yielding lower cumulative tailpipe and indirect emissions. Expected technological change ensures that emissions from electricity and battery production are more than offset by reduced emissions of gasoline production. Given continued decarbonization of electricity supply, results show that a large–scale adoption of electric vehicles is able to reduce CO2 emissions through more channels than previously expected. Further, carbon pricing of stationary sources will also favor electric vehicles.
Molecular basis for redox control by the human cystine/glutamate antiporter system xc−
Authors: Parker Joanne L. , Deme Justin C. , Kolokouris Dimitrios , Kuteyi Gabriel , Biggin Philip C. , Lea Susan M. , Newstead Simon 
Published: December 2021

AbstractCysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step in cellular GSH synthesis is the availability of cysteine. However, circulating cysteine exists in the blood as the oxidised di-peptide cystine, requiring specialised transport systems for its import into the cell. System xc− is a dedicated cystine transporter, importing cystine in exchange for intracellular glutamate. To counteract elevated levels of reactive oxygen species in cancerous cells system xc− is frequently upregulated, making it an attractive target for anticancer therapies. However, the molecular basis for ligand recognition remains elusive, hampering efforts to specifically target this transport system. Here we present the cryo-EM structure of system xc− in both the apo and glutamate bound states. Structural comparisons reveal an allosteric mechanism for ligand discrimination, supported by molecular dynamics and cell-based assays, establishing a mechanism for cystine transport in human cells.
Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors
Authors: Chen Wenhan , Wu Yang , Zheng Zhili , Qi Ting , Visscher Peter M. , Zhu Zhihong , Yang Jian 
Published: December 2021

AbstractSummary statistics from genome-wide association studies (GWAS) have facilitated the development of various summary data-based methods, which typically require a reference sample for linkage disequilibrium (LD) estimation. Analyses using these methods may be biased by errors in GWAS summary data or LD reference or heterogeneity between GWAS and LD reference. Here we propose a quality control method, DENTIST, that leverages LD among genetic variants to detect and eliminate errors in GWAS or LD reference and heterogeneity between the two. Through simulations, we demonstrate that DENTIST substantially reduces false-positive rate in detecting secondary signals in the summary-data-based conditional and joint association analysis, especially for imputed rare variants (false-positive rate reduced from >28% to <2% in the presence of heterogeneity between GWAS and LD reference). We further show that DENTIST can improve other summary-data-based analyses such as fine-mapping analysis.
Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection
Authors: Mistry Jayna J. , Hellmich Charlotte , Moore Jamie A. , Jibril Aisha , Macaulay Iain , Moreno-Gonzalez Mar , Di Palma Federica , Beraza Naiara , Bowles Kristian M. , Rushworth Stuart A. 
Published: December 2021

AbstractAcute infection is known to induce rapid expansion of hematopoietic stem cells (HSCs), but the mechanisms supporting this expansion remain incomplete. Using mouse models, we show that inducible CD36 is required for free fatty acid uptake by HSCs during acute infection, allowing the metabolic transition from glycolysis towards β-oxidation. Mechanistically, high CD36 levels promote FFA uptake, which enables CPT1A to transport fatty acyl chains from the cytosol into the mitochondria. Without CD36-mediated FFA uptake, the HSCs are unable to enter the cell cycle, subsequently enhancing mortality in response to bacterial infection. These findings enhance our understanding of HSC metabolism in the bone marrow microenvironment, which supports the expansion of HSCs during pathogenic challenge.
Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R
Authors: Dankovich Tal M. , Kaushik Rahul , Olsthoorn Linda H. M. , Petersen Gabriel Cassinelli , Giro Philipp Emanuel , Kluever Verena , Agüi-Gonzalez Paola , Grewe Katharina , Bao Guobin , Beuermann Sabine , Hadi Hannah Abdul , Doeren Jose , Klöppner Simon , Cooper Benjamin H. , Dityatev Alexander , Rizzoli Silvio O. 
Published: December 2021

AbstractThe brain extracellular matrix (ECM) consists of extremely long-lived proteins that assemble around neurons and synapses, to stabilize them. The ECM is thought to change only rarely, in relation to neuronal plasticity, through ECM proteolysis and renewed protein synthesis. We report here an alternative ECM remodeling mechanism, based on the recycling of ECM molecules. Using multiple ECM labeling and imaging assays, from super-resolution optical imaging to nanoscale secondary ion mass spectrometry, both in culture and in brain slices, we find that a key ECM protein, Tenascin-R, is frequently endocytosed, and later resurfaces, preferentially near synapses. The TNR molecules complete this cycle within ~3 days, in an activity-dependent fashion. Interfering with the recycling process perturbs severely neuronal function, strongly reducing synaptic vesicle exo- and endocytosis. We conclude that the neuronal ECM can be remodeled frequently through mechanisms that involve endocytosis and recycling of ECM proteins.
Unlucky punches: the vulnerability-stress model for the development of impulse control disorders in Parkinson’s disease
Authors: Theis Hendrik , Probst Catharina , Fernagut Pierre-Olivier , van Eimeren Thilo 
Published: December 2021

AbstractImpulse-control disorders are commonly observed during dopamine-replacement therapy in Parkinson’s disease, but the majority of patients seems “immune” to this side effect. Epidemiological evidence suggests that a major risk factor may be a specific difference in the layout of the dopaminergic-reinforcement system, of which the ventral striatum is a central player. A series of imaging studies of the dopaminergic system point toward a presynaptic reduction of dopamine-reuptake transporter density and dopamine synthesis capacity. Here, we review current evidence for a vulnerability-stress model in which a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons represent a predisposing (hypodopaminergic) vulnerability. Stress (hyperdopaminergic) is delivered when dopamine replacement therapy leads to a relative overdosing of the already-sensitized ventral striatum. These alterations are consistent with consecutive changes in reinforcement mechanisms, which stimulate learning from reward and impede learning from punishment, thereby fostering the development of impulse-control disorders. This vulnerability-stress model might also provide important insights into the development of addictions in the non-Parkinsonian population.
A class-contrastive human-interpretable machine learning approach to predict mortality in severe mental illness
Authors: Banerjee Soumya , Lio Pietro , Jones Peter B. , Cardinal Rudolf N. 
Published: December 2021

AbstractMachine learning (ML), one aspect of artificial intelligence (AI), involves computer algorithms that train themselves. They have been widely applied in the healthcare domain. However, many trained ML algorithms operate as ‘black boxes’, producing a prediction from input data without a clear explanation of their workings. Non-transparent predictions are of limited utility in many clinical domains, where decisions must be justifiable. Here, we apply class-contrastive counterfactual reasoning to ML to demonstrate how specific changes in inputs lead to different predictions of mortality in people with severe mental illness (SMI), a major public health challenge. We produce predictions accompanied by visual and textual explanations as to how the prediction would have differed given specific changes to the input. We apply it to routinely collected data from a mental health secondary care provider in patients with schizophrenia. Using a data structuring framework informed by clinical knowledge, we captured information on physical health, mental health, and social predisposing factors. We then trained an ML algorithm and other statistical learning techniques to predict the risk of death. The ML algorithm predicted mortality with an area under receiver operating characteristic curve (AUROC) of 0.80 (95% confidence intervals [0.78, 0.82]). We used class-contrastive analysis to produce explanations for the model predictions. We outline the scenarios in which class-contrastive analysis is likely to be successful in producing explanations for model predictions. Our aim is not to advocate for a particular model but show an application of the class-contrastive analysis technique to electronic healthcare record data for a disease of public health significance. In patients with schizophrenia, our work suggests that use or prescription of medications like antidepressants was associated with lower risk of death. Abuse of alcohol/drugs and a diagnosis of delirium were associated with higher risk of death. Our ML models highlight the role of co-morbidities in determining mortality in patients with schizophrenia and the need to manage co-morbidities in these patients. We hope that some of these bio-social factors can be targeted therapeutically by either patient-level or service-level interventions. Our approach combines clinical knowledge, health data, and statistical learning, to make predictions interpretable to clinicians using class-contrastive reasoning. This is a step towards interpretable AI in the management of patients with schizophrenia and potentially other diseases.
Understanding the impact of dog ownership on autistic adults: implications for mental health and suicide prevention
Authors: Barcelos Ana Maria , Kargas Niko , Packham Chris , Mills Daniel S. 
Published: December 2021

AbstractMental health problems and suicide are more frequent in autistic adults than general population. Dog ownership can improve human well-being. This study aimed to generate a framework of well-being outcomes for dog-related activities in autistic adults and compare it to the framework generated for a general adult population. Thirty-six autistic dog owners (18–74 years old, 18 males) from diverse UK regions were interviewed and transcripts thematically analysed. 16.7% reported that their dogs prevented them from taking their own lives, mainly due to the dog's affection and the need to care for the animal. Close dog-owner interactions (e.g., cuddling, walking, dog's presence) were the most frequent activities improving emotions/moods and life functioning, whereas routine-like activities (e.g., feeding the animal) particularly enhanced life functioning. Well-being worsening was mainly linked to dog behaviour problems, dog poor health/death and obligations to the dog. Despite some negatives associated with ownership, having a dog could improve the well-being of many autistic adults and assist suicide prevention strategies in this high-risk group. The framework was consistent with that generated previously, indicating its robustness and the potential opportunity to focus on dog-related activities rather than the vague concept of “ownership” when considering the impact of ownership on well-being.
Cardiac myocyte intrinsic contractility and calcium handling deficits underlie heart organ dysfunction in murine cancer cachexia
Authors: Law Michelle L. , Metzger Joseph M. 
Published: December 2021

AbstractCachexia is a muscle wasting syndrome occurring in many advanced cancer patients. Cachexia significantly increases cancer morbidity and mortality. Cardiac atrophy and contractility deficits have been observed in patients and in animal models with cancer cachexia, which may contribute to cachexia pathophysiology. However, underlying contributors to decreased in vivo cardiac contractility are not well understood. In this study, we sought to distinguish heart-intrinsic changes from systemic factors contributing to cachexia-associated cardiac dysfunction. We hypothesized that isolated heart and cardiac myocyte functional deficits underlie in vivo contractile dysfunction. To test this hypothesis, isolated heart and cardiac myocyte function was measured in the colon-26 adenocarcinoma murine model of cachexia. Ex vivo perfused hearts from cachectic animals exhibited marked contraction and relaxation deficits during basal and pacing conditions. Isolated myocytes displayed significantly decreased peak contraction and relaxation rates, which was accompanied by decreased peak calcium and decay rates. This study uncovers significant organ and cellular-level functional deficits in cachectic hearts outside of the catabolic in vivo environment, which is explained in part by impaired calcium cycling. These data provide insight into physiological mechanisms of cardiomyopathy in cachexia, which is critical for the ultimate development of effective treatments for patients.