bluuebunny/crossref_metadata_2025_split huggingface dataset:
N2O-respiring bacteria in biogas digestates for reduced agricultural emissions
Authors: Jonassen Kjell Rune , Hagen Live H. , Vick Silas H.W. , Arntzen Magnus Ø. , Eijsink Vincent G.H. , Frostegård Åsa , Lycus Pawel , Molstad Lars , Pope Phillip B. , Bakken Lars R. 
Published: November 2020

AbstractInoculating agricultural soils with N2O-respiring bacteria (NRB) can reduce N2O-emissions, but would be impractical as a standalone operation. Here we demonstrate that digestates obtained after biogas production are suitable substrates and vectors for NRB. We show that indigenous NRB in digestates grew to high abundance during anaerobic enrichment under N2O. Gas-kinetics and meta-omic analyses showed that these NRB's, recovered as metagenome-assembled genomes (MAGs), grew by harvesting fermentation intermediates of the methanogenic consortium. Three NRB's were isolated, one of which matched the recovered MAG of a Dechloromonas, deemed by proteomics to be the dominant producer of N2O-reductase in the enrichment. While the isolates harbored genes required for a full denitrification pathway and could thus both produce and sequester N2O, their regulatory traits predicted that they act as N2O sinks in soil, which was confirmed experimentally. The isolates were grown by aerobic respiration in digestates, and fertilization with these NRB-enriched digestates reduced N2O emissions from soil. Our use of digestates for low-cost and large-scale inoculation with NRB in soil can be taken as a blueprint for future applications of this powerful instrument to engineer the soil microbiome, be it for enhancing plant growth, bioremediation, or any other desirable function.
Protein turnover dynamics suggest a diffusion to capture mechanism for peri-basal body recruitment and retention of intraflagellar transport proteins
Authors: Hibbard Jaime V.K. , Vazquez Neftali , Satija Rohit , Wallingford John B. 
Published: November 2020

ABSTRACTIntraflagellar transport (IFT) is essential for construction and maintenance of cilia. IFT proteins concentrate at the basal body, where they are thought to assemble into trains and bind cargoes for transport. To study the mechanisms of IFT recruitment to this peri-basal body pool, we quantified protein dynamics of eight IFT proteins, as well as five other basal body localizing proteins, using fluorescence recovery after photobleaching in vertebrate multiciliated cells. We found that members of the IFT-A and IFT-B protein complexes show distinct turnover kinetics from other basal body components. Additionally, known IFT sub-complexes displayed shared dynamics, and these dynamics were not altered during cilia regeneration as compared to homeostasis. Finally, we evaluated the mechanisms of basal body recruitment by depolymerizing cytosolic MTs, which suggested that IFT proteins are recruited to basal bodies through a diffusion-to-capture mechanism. Our survey of IFT protein dynamics provides new insights into IFT recruitment to basal bodies, a crucial step in ciliogenesis.
Region-specific and state-dependent astrocyte Ca2+dynamics during the sleep-wake cycle in mice
Authors: Tsunematsu Tomomi , Sakata Shuzo , Sanagi Tomomi , Tanaka Kenji F. , Matsui Ko 
Published: November 2020

AbstractNeural activity is diverse, and varies depending on brain regions and sleep/wakefulness states. However, whether astrocyte activity differs between sleep/wakefulness states, and whether there are differences in astrocyte activity among brain regions remain poorly understood. In this study, we recorded astrocyte intracellular calcium (Ca2+) concentrations of mice during sleep/wakefulness states in the cortex, hippocampus, hypothalamus, cerebellum, and pons using fiber photometry. For this purpose, male transgenic mice in which their astrocytes specifically express the genetically encoded ratiometric Ca2+sensor YCnano50 were used. We demonstrated that Ca2+levels in astrocytes significantly decrease during Rapid Eye Movement (REM) sleep and increase after the onset of wakefulness. In contrast, differences in Ca2+levels during non-Rapid Eye Movement (NREM) sleep were observed among different brain regions, and no significant decrease was observed in the hypothalamus and pons. Further analyses focusing on the transition between sleep/wakefulness states and correlation analysis with episode duration of REM showed that Ca2+dynamics differed among brain regions, suggesting the existence of several clusters. To quantify region-specific Ca2+dynamics, principal component analysis was performed to uncover three clusters; i.e., the first comprised the cortex and hippocampus, the second comprised the cerebellum, and the third comprised the hypothalamus and pons. Our study demonstrated that astrocyte Ca2+levels change substantially according to sleep/wakefulness states. These changes were generally consistent, unlike neural activity. However, we also clarified that Ca2+dynamics varies depending on the brain region, implying that astrocytes may play various physiological roles in sleep.Significance statementSleep is an instinctive behavior of many organisms. In the previous five decades, the mechanism of the neural circuits controlling sleep/wakefulness states and the neural activities associated with sleep/wakefulness states in various brain regions have been elucidated. However, whether astrocytes, which are a type of glial cell, change their activity during different sleep/wakefulness states is poorly understood. Here, we demonstrated that dynamic changes in intracellular Ca2+concentrations occur in the cortex, hippocampus, hypothalamus, cerebellum, and pons of genetically modified mice during natural sleep. Further analyses demonstrated that Ca2+dynamics slightly differ among different brain regions, implying that the physiological roles of astrocytes in sleep/wakefulness might vary depending on the brain region.
Community prevalence of antibodies to SARS-CoV-2 and correlates of protective immunity in an Indian metropolitan city
Authors: Ghose Aurnab , Bhattacharya Sankar , Karthikeyan Arun S. , Kudale Abhay , Monteiro Joy M. , Joshi Aparna , Medigeshi Guruprasad , Kang Gagandeep , Bal Vineeta , Rath Satyajit , Shashidhara L. S. , John Jacob , Chaudhuri Susmita , Nagarkar Aarti 
Published: November 2020

ABSTRACTObjectivesTo assess seroprevalence of anti-SARS-CoV-2 antibodies in a densely populated urban Indian settings and its implications for disease trends and protective immunity.DesignCross-sectional sero-epidemiological survey linked with administrative reporting of COVID-19 testing data.SettingsPune city in western IndiaMain outcome measurePrevalence of anti-SARS-CoV-2 spike protein antibodies were estimated and along with correlates of virus neutralisation and other immune and inflammatory markers.ResultsSeropositivity was extensive (51·3%; 95%CI 39·9 to 62·4) but varied widely in the five localities tested, ranging from 35·8% to 66·4%. Seropositivity was higher in crowded living conditions in the slums (OR 1·91), and was lower in those 65 years or older (OR 0·59). The infection-fatality ratio was estimated at 0.21%. Post survey, COVID-19 incidence was lower in areas noted to have higher seroprevalence. Substantial virus-neutralising activity was observed in seropositive individuals, but with considerable heterogeneity in the immune response and possible age-dependent diversity in the antibody repertoire.ConclusionDespite crowded living conditions having facilitated widespread transmission, the variability in seroprevalence in localities that are in geographical proximity indicates a heterogenous spread of infection. Declining infection rates in areas with high seropositivity suggest population-level protection. It is also supported by substantial neutralising activity in asymptomatically infected individuals. This is the first report of a significantly high proportion of protective immune response among asymptomatic individuals in the population. The heterogeneity in antibody levels and neutralisation capacity indicates the existence of immunological sub-groups of functional interest.Trial registrationRegistered with the Clinical Trials Registry of India (CTRI/2020/07/026509)
Hilbert-Envelope Features for Cardiac Disease Classification from Noisy Phonocardiograms
Authors: Nizam Nusrat Binta , Khan Nuhash Shoyad Ibn Sabur , Hasan Taufiq 
Published: November 2020

AbstractCardiovascular disease (CVD) is considered a significant public health concern around the world. Automated early diagnostic tools for CVDs can provide substantial benefits, especially in low-resource countries. In this study, we propose a time-domain Hilbert envelope feature (HEF) extraction scheme that can effectively distinguish among different cardiac anomalies from heart sounds even in highly noisy recordings. The method is motivated by how a cardiologist listens to the heart murmur configuration, e.g., the intensity of the heart sound envelope over a cardiac cycle. The proposed feature is invariant to the heart rate, the position of the first and second heart sounds, and robust in extracting the murmur configuration pattern in the presence of respiratory noise. Experimental evaluations are performed compared to two different state-of-the-art methods in the presence of respiratory noise with signal-to-noise ratio (SNR) values ranging from 0-15dB. The proposed HEF, fused with standard acoustic and Resnet features, yields an average accuracy, sensitivity, specificity, and F1-score of, 94.78%(±2.63), 87.48%(±6.07), 96.87%(±1.51) and 87.47%(±5.94), respectively, while using a random forest (RF) classifier. Compared to the best-performing baseline model, this feature-fusion scheme provides a significant performance improvement (p <0.05), notably achieving an absolute improvement of 6.16% in averaged sensitivity. In the case of 0dB SNR, the proposed feature alone provides a 9.2% absolute improvement in sensitivity compared to the top baseline system demonstrating the robustness of the HEF. The developed methods can significantly impact computer-aided auscultation (CAA) systems when deployed in noisy conditions, especially in low-resource settings.
Viral-structured models of dividing cells shows cell-virus coexistence via viral load partitioning between cell progeny
Authors: Ford Hugh Z. 
Published: November 2020

AbstractThe present study develops and analyses a system of partial differential equations that model a single population of dividing cells infected by lytic viruses in a closed system. This mean-field model stratifies cells by cell size (continuous) and number of virus particles per cell (discrete) to couple the cell cycle and the lytic cycle under mass conservation. We present numerical solutions to the mean-field model and an equivalent stochastic model for parameter values representative ofEscherichia Coliand lytic bacteriophages such as Escherichia virus T4. This analysis suggests that dividing cells and lytic virus populations in isolation can coexist in the absence of evolutionary, ecological and biochemical processes. Coexistence emerges because viral load dilution via cell growth and viral load partitioning via cell division both counteract viral load growth via viral synthesis and hence cell death by lysis. Furthermore, we analytically determine the quasi-steady state solution of the mean-field model in the continuum limit with respect to viral loads. From this solution we derive a condition for cell-virus coexistence through viral load partitioning: that the product of the viral synthesis rate, cell lysis rate and the time between cell divisions must be less than the product of log(2) and the cell growth rate. Overall, the present study provides a theoretical argument for a stable relationship between cells and lytic viruses simply by virtue of cell growth and division.
GSAP regulates mitochondrial function through the Mitochondria-associated ER membrane in the pathogenesis of Alzheimer’s disease
Authors: Xu Peng , Chang Jerry C. , Zhou Xiaopu , Wang Wei , Bamkole Michael , Wong Eitan , Bettayeb Karima , Jiang Lu-Lin , Huang Timothy , Luo Wenjie , Xu Huaxi , Nairn Angus C. , Flajolet Marc , Ip Nancy , Li Yue-Ming , Greengard Paul 
Published: November 2020

ABSTRACTBiochemical, pathogenic and human genetic data confirm that GSAP (γ-secretase activating protein), a selective γ-secretase modulatory protein, plays important roles in Alzheimer’s disease (AD) and Down syndrome. However, the molecular mechanism(s) underlying GSAP-dependent pathogenesis remains largely elusive. Here, through unbiased proteomics and single-nuclei RNA-seq, we identified that GSAP regulates multiple biological pathways, including protein phosphorylation, trafficking, lipid metabolism, and mitochondrial function. We demonstrated that GSAP physically interacts with Fe65:APP complex to regulate APP trafficking/partitioning. GSAP is enriched in the mitochondria-associated membrane (MAM) and regulates lipid homeostasis through the amyloidogenic processing of APP. GSAP deletion generates a lipid environment unfavorable for AD pathogenesis, leading to improved mitochondrial function and the rescue of cognitive deficits in an AD mouse model. Finally, we identified a novel GSAP single-nucleotide polymorphism that regulates its brain transcript level and is associated with an increased AD risk. Together, our findings indicate that GSAP impairs mitochondrial function through its MAM localization, and lowering GSAP expression reduces pathological effects associated with AD.
Thiol-ene cross-linked alginate hydrogel encapsulation modulates the extracellular matrix of kidney organoids by reducing abnormal type 1a1 collagen deposition
Authors: Geuens Thomas , Ruiter Floor A.A. , Schumacher Anika , Morgan Francis L. C. , Rademakers Timo , Wiersma Loes E. , van den Berg Cathelijne W. , Rabelink Ton J. , Baker Matthew B. , LaPointe Vanessa L.S. 
Published: November 2020

ABSTRACTDifferentiated kidney organoids from induced pluripotent stem cells hold promise as a treatment for patients with kidney diseases. Before these organoids can be translated to the clinic, shortcomings regarding their cellular, extracellular compositions and developmental plateau needs to be overcome. We performed a proteomic analysis on kidney organoids cultured for a prolonged culture time and we found a specific change in the extracellular matrix composition with increased expression of types 1a1, 2 and 6a1 collagen. Such an excessive accumulation of specific collagen types is a hallmark of renal fibrosis that causes a life-threatening pathological condition by compromising key functions of the human kidney. Here we hypothesized the need for a three-dimensional environment to grow the kidney organoids, which could better mimic the in vivo surroundings of the developing kidney than standard culture on a transwell filter. Encapsulating organoids for four days in a soft, thiol-ene cross-linked alginate hydrogel resulted in decreased type 1a1 collagen expression. Furthermore, the encapsulation did not result in any changes of organoid structural morphology. Using a biomaterial to modulate collagen expression allows for a prolonged kidney organoid culture in vitro and a reduction of abnormal type 1a1 collagen expression bringing kidney organoids closer to clinical application.HIGHLIGHTSProlonging kidney organoid culture results in a developmental plateau instead of improvedin vitromaturation.Proteomic analyses point to an increased expression of specific collagen subtypes associated with renal fibrosis.Encapsulating kidney organoids using a soft thiol-ene cross-linked alginate hydrogel reduces collagen type 1a1 and αSMA deposition.
In exogenous attention, time is the clue: brain and heart interactions to survive threatening stimuli
Authors: Ruiz-Padial Elisabeth , Mercado Francisco 
Published: November 2020

AbstractThe capture of exogenous attention by negative stimuli has been interpreted as adaptive for survival in a diverse and changing environment. In the present paper, we investigate the neural responses towards two discrete negative emotions with different biological meanings, disgust and fear, and its potential relationships with heart rate variability (HRV) as an index of emotional regulation. With that aim, 30 participants performed a digit categorization task while fear, disgust and neutral distractor pictures were presented. Resting HRV at baseline, behavioral responses, and event-related potentials were recorded. Whereas P1 amplitudes were highest to fear distractors, the disgust stimulation led to augmented P2 amplitudes compared to the rest of distractors. Interestingly, increased N2 amplitudes were also found to disgust distractors, but only in high HRV participants. Neural source estimation data point to the involvement of the insula in this exogenous attentional response to disgust. Additionally, disgust distractors provoked longer reaction times than fear and neutral distractors in the high HRV group. Present findings are interpreted in evolutionary terms suggesting that exogenous attention is captured by negative stimuli following a different time course for fear and disgust. Possible HRV influences on neural mechanisms underlying exogenous attention are discussed considering the potential important role of this variable in emotional regulation processes.
A generalised mechano-kinetic model for use in multiscale simulation protocols
Authors: Hanson Benjamin S. , Dougan Lorna , Harlen Oliver G. , Harris Sarah A. , Read Daniel J. 
Published: November 2020

AbstractMany biophysical systems and proteins undergo mesoscopic conformational changes in order to perform their biological function. However, these conformational changes often result from a cascade of atomistic interactions within a much larger overall object. For simulations of such systems, the computational cost of retaining high-resolution structural and dynamical information whilst at the same time observing large scale motions over long times is high. Furthermore, this cost is only going to increase as ever larger biological objects are observed experimentally at high resolution.We derive a generalised mechano-kinetic simulation framework which aims to compensate for these disparate time scales, capable of dynamically exploring a defined mechanical energy landscape whilst at the same time performing kinetic transitions between discretely defined states. With insight from the theory of Markov state models and transition state theory, the framework models continuous dynamical motion at coarse-grained length scales whilst simultaneously including fine-detail, chemical reactions or conformational changes implicitly using a kinetic model. The kinetic model is coupled to the dynamic model in a highly generalised manner, such that kinetic transition rates are continuously modulated by the dynamic simulation. Further, it can be applied to any defined continuous energy landscape, and hence, any existing dynamic simulation framework. We present a series of analytical examples to validate the framework, and showcase its capabilities for studying more complex systems by simulating protein unfolding via single-molecule force spectroscopy on an atomic force microscope.Author summaryOur intention with this work is to provide a generalised, highly coarse-grained model to allow kinetic processes (conformational changes, protein unfolding, chemical reactions etc) to occur within the context of a dynamic simulation. Performing computationally intensive dynamic simulations to obtain kinetic information can be unjustifiably costly and scientifically inefficient, and so we instead want to emphasise that experimentally available kinetic information can be used to infer the underlying dynamics they result from. We hope our work can begin a discussion on the topic of computationally efficient science, and continue the drive towards collaborative science between theory and experimentation.
LRP1 and SORL1 regulate tau internalization and degradation and enhance tau seeding
Authors: Cooper Joanna M. , Lathuiliere Aurelien , Migliorini Mary , Arai Allison L. , Wani Mashhood M. , Dujardin Simon , Muratoglu Selen C. , Hyman Bradley T. , Strickland Dudley K. 
Published: November 2020

ABSTRACTThe identification of the apoE receptor, LRP1, as an endocytic receptor for tau raises several questions about LRP1s’ role in tauopathies. Is internalized tau, like other LRP1 ligands, delivered to lysosomes for degradation? Does LRP1 internalize pathological tau leading to cytosolic seeding? Do other, related receptors participate in these processes? We confirm that LRP1 rapidly internalizes tau, leading to efficient lysosomal degradation. Employing brain homogenates from human Alzheimer brain, we find that LRP1 also mediates cytosolic tau seeding. We additionally found that another apoE receptor,SORL1, a gene implicated in AD risk, also mediates tau endocytosis, degradation, and release into the cytoplasm of seed competent species. These data suggest a role for these apoE receptors in tau uptake, as well as the competing processes of degradation and release to the cytoplasm. The balance of these processes may be fundamental to spread of neuropathology across the brain in Alzheimer disease.
Localized automation solutions in response to the first wave of COVID-19: a story from Vietnam
Authors: Cao Hoang-Long , Nguyen Huynh Anh Duy , Luu Trong Hieu , Vu Huong Thi Thu , Pham Diep , Vu Van Thi Ngoc , Le Hoang Hai , Nguyen Duy Xuan Bach , Truong Trong Toai , Nguyen Hoang-Dung , Nguyen Chi-Ngon 
Published: November 2020

Purpose
COVID-19 hits every country’s health-care system and economy. There is a trend toward using automation technology in response to the COVID-19 crisis not only in developed countries but also in those with lower levels of technology development. However, current studies mainly focus on the world level, and only a few ones report deployments at the country level. The purpose of this paper is to investigate the use of automation solutions in Vietnam with locally available materials mainly in the first wave from January to July 2020.

Design/methodology/approach
The authors collected COVID-related automation solutions during the first wave of COVID-19 in Vietnam from January to July 2020 through a search process. The analysis and insights of a panel consisting of various disciplines (i.e. academia, health care, government, entrepreneur and media) aim at providing a clear picture of how and to what extent these solutions have been deployed.

Findings
The authors found seven groups of solutions from low to high research and development (R&D) levels deployed across the country with various funding sources. Low R&D solutions were widely spread owing to simplicity and affordability. High R&D solutions were mainly deployed in big cities. Most of the solutions were deployed during the first phases when international supply chains were limited with a significant contribution of the media. Higher R&D solutions have opportunities to be deployed in the reopening phase. However, challenges can be listed as limited interdisciplinary research teams, market demand, the local supporting industry, end-user validation and social-ethical issues.

Originality/value
To the authors’ best knowledge, this is the first study analyzing the use of automation technology in response to COVID-19 in Vietnam and also in a country in Southeast Asia. Lessons learned from these current deployments are useful for future emerging infectious diseases. The reality of Vietnam’s automation solutions in response to COVID-19 might be a reference for other developing countries with similar social-economic circumstances and contributes to the global picture of how different countries adopt technology to combat COVID-19.