bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gold-standard diagnostics are tarnished by lytic bacteriophage
Authors: Nelson E.J. , Grembi J.A. , Chao D.L. , Andrews J.R. , Alexandrova L. , Rodriguez P. H. , Ramachandran V.V. , Sayeed Md.A. , Wamala W. J. , Debes A.K. , Sack D.A. , Hryckowian A. J. , Haque F. , Khatun S. , Rahman M. , Chien A. , Spormann A.M. , Schoolnik G.K. 
Published: February 2020

ABSTRACTBackgroundA fundamental clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity.MethodsCholera was chosen as a model disease to investigate this important question. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection, as well as exposure to the first-line antibiotic azithromycin detected by mass spectrometry.ResultsAmong diarrheal samples positive by nanoliter quantitative PCR forVibrio cholerae(n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively.ConclusionsEstimations of cholera burden may improve by accommodating for the negative effect of antimicrobial exposure on diagnostic positivity. Furthermore, the findings herein challenge our current approach to interpreting and developing bacterial diagnostics given variable rates of lytic bacteriophage and antibiotic exposure.
Connectome-based predictive modeling of individual anxiety
Authors: Wang Zhihao , Goerlich Katharina S. , Ai Hui , Aleman André , Luo Yuejia , Xu Pengfei 
Published: February 2020

AbstractAnxiety-related illnesses are highly prevalent in human society. Being able to identify neurobiological markers signaling high trait anxiety could aid the assessment of individuals with high risk for mental illness. Here, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity (rsFC) data to predict the degree of anxiety in 76 healthy participants. Using a computational “lesion” method in CPM, we then examined the weights of the identified main brain areas as well as their connectivity. Results showed that the CPM could predict individual anxiety from whole-brain rsFC, especially from limbic areas-whole brain and prefrontal cortex-whole brain. The prediction power of the model significantly decreased from (simulated) lesions of limbic areas, lesions of the connectivity within the limbic system, and lesions of the connectivity between limbic regions and the prefrontal cortex.Although the same model also predicted depression, anxiety-specific networks could be identified independently, centered at the prefrontal cortex. These findings highlight the important role of the limbic system and the prefrontal cortex in the prediction of anxiety. Our work provides evidence for the usefulness of connectome-based modeling of rsFC in predicting individual personality differences and indicates its potential for identifying personality structures at risk of developing psychopathology.
Interpreting pathogen genetic diversity during measles epidemics
Authors: Worby CJ , Bozick BA , Gastañaduy PA , Yang Luojun , Rota PA , Grenfell BT 
Published: February 2020

AbstractWhile measles remains endemic in parts of the world, efforts to eliminate measles transmission continue, and viral sequence data may shed light on progress towards these goals. Genetic diversity has been used as a proxy for disease prevalence; however, seasonally-driven disease dynamics are typically characterized by deep population bottlenecks between epidemics, which severely disrupt the genetic signal. Here, we simulate measles metapopulation dynamics, and show that it is the population bottleneck, rather than epidemic size, which plays the largest role in observed pathogen diversity. While high levels of vaccination greatly reduces measles diversity, paradoxically, diversity increases with intermediate levels of vaccination, despite reducing incidence. We examined diversity and incidence using published data to compare our simulated outcomes with real observations, finding a significant relationship between harmonic mean incidence and genetic diversity. Our study demonstrates that caution should be taken when interpreting pathogen diversity, particularly for short-term, local dynamics.
Efficient Exact Inference for Dynamical Systems with Noisy Measurements using Sequential Approximate Bayesian Computation
Authors: Schälte Yannik , Hasenauer Jan 
Published: February 2020

AbstractMotivationApproximate Bayesian Computation (ABC) is an increasingly popular method for likelihood-free parameter inference in systems biology and other fields of research, since it allows analysing complex stochastic models. However, the introduced approximation error is often not clear. It has been shown that ABC actually gives exact inference under the implicit assumption of a measurement noise model. Noise being common in biological systems, it is intriguing to exploit this insight. But this is difficult in practice, since ABC is in general highly computationally demanding. Thus, the question we want to answer here is how to efficiently account for measurement noise in ABC.ResultsWe illustrate exemplarily how ABC yields erroneous parameter estimates when neglecting measurement noise. Then, we discuss practical ways of correctly including the measurement noise in the analysis. We present an efficient adaptive sequential importance sampling based algorithm applicable to various model types and noise models. We test and compare it on several models, including ordinary and stochastic differential equations, Markov jump processes, and stochastically interacting agents, and noise models including normal, Laplace, and Poisson noise. We conclude that the proposed algorithm could improve the accuracy of parameter estimates for a broad spectrum of applications.AvailabilityThe developed algorithms are made publicly available as part of the open-source python toolbox pyABC (https://github.com/icb-dcm/pyabc).Contactjan.hasenauer@uni-bonn.deSupplementary informationSupplementary information is available atbioRxivonline. Supplementary code and data are available online athttp://doi.org/10.5281/zenodo.3631120.
The challenge of distinguishing cell-cell complexes from singlet cells in non-imaging flow cytometry and single-cell sorting
Authors: Burel Julie G , Pomaznoy Mikhail , Arlehamn Cecilia S Lindestam , Seumois Gregory , Vijayanand Pandurangan , Sette Alessandro , Peters Bjoern 
Published: February 2020

AbstractOur recent work has highlighted that care needs to be taken when interpreting single cell data originating from flow cytometry acquisition or cell sorting: We found that doublets of T cells bound to other immune cells are often present in the live singlet gate of human peripheral blood samples acquired by flow cytometry. This hidden ‘contamination’ generates atypical gene signatures of mixed cell lineage in what is assumed to be single cells, which can lead to data misinterpretation, such as the description of novel immune cell types. Here, based on the example of T cell-monocyte complexes, we identify experimental and data analysis strategies to help distinguishing between singlets and cell-cell complexes in non-imaging flow cytometry and single-cell sorting. We found robust molecular signatures in both T cell-monocyte and T cell-B cell complexes that can distinguish them from singlets at both protein and mRNA levels. Imaging flow cytometry with appropriate gating strategy (matching the one used in cell sorting) and direct microscopy imaging after cell sorting were the two methods of choice to detect the presence of cell-cell complexes in suspicious dual-expressing cells. We finally applied this knowledge to highlight the likely presence of T cell-B cell complexes in a recently published dataset describing a novel cell population with mixed T cell and B cell lineage properties.
Reducing shock imminence eliminates poor avoidance in rats
Authors: Laughlin Lindsay C. , Moloney Danielle M. , Samels Shanna B. , Sears Robert M. , Cain Christopher K. 
Published: February 2020

AbstractIn signaled active avoidance (SigAA), rats learn to suppress Pavlovian freezing and emit actions to escape threats and prevent footshocks. SigAA is critical for understanding aversively-motivated instrumental behavior and anxiety-related active coping. However, with standard protocols ∼25% of rats exhibit high freezing and poor avoidance. This has dampened enthusiasm for the paradigm and stalled progress. We demonstrate that reducing shock imminence with long-duration warning signals leads to greater freezing suppression and perfect avoidance in all subjects. This suggests that instrumental SigAA mechanisms evolved to cope with distant harm and protocols that promote inflexible Pavlovian reactions are poorly-designed to study avoidance.
Understanding population structure in an evolutionary context: population-specificFSTand pairwiseFST
Authors: Kitada Shuichi , Nakamichi Reiichiro , Kishino Hirohisa 
Published: February 2020

AbstractPopulations are shaped by their history. It is crucial to interpret population structure in an evolutionary context. PairwiseFSTmeasures population structure, whereas population-specificFSTmeasures deviation from the ancestral population. To understand the current population structure and a population’s history of range expansion, we propose a representation method that overlays population-specificFSTestimates on a sampling location map, and on an unrooted neighbor-joining tree and a multi-dimensional scaling plot inferred from a pairwiseFSTdistance matrix. We examined the usefulness of our procedure using simulations that mimicked population colonization from an ancestral population and by analyzing published human, Atlantic cod, and wild poplar data. Our results demonstrated that population-specificFSTvalues identify the source population and trace the evolutionary history of its derived populations. Conversely, pairwiseFSTvalues represent the current population structure. By integrating the results of both estimators, we obtained a new picture of the population structure that incorporates evolutionary history. The generalized least squares of genome-wide population-specificFSTindicated that the wild poplar population expanded its distribution to the north, where daylight hours are long in summer, to seashores with abundant rainfall, and to the south with dry summers. Genomic data highlight the power of the bias-corrected moment estimators ofFST, whether global, pairwise, or population-specific, that provide unbiased estimates ofFST. AllFSTmoment estimators described in this paper have reasonable process times and are useful in population genomics studies. The R codes for our method and simulations are available in the Supplemental Material.
Neurothreads: Cryogel carrier-based differentiation and delivery of mature neurons in the treatment of Parkinson’s disease
Authors: Filippova Aleksandra , Bonini Fabien , Efremova Liudmila , Preynat-Seauve Olivier , Béduer Amélie , Krause Karl-Heinz , Braschler Thomas 
Published: February 2020

AbstractWe presentin-vivotransplantation of mature dopaminergic neurons by means of macroporous, injectable carriers, to enhance cell therapy in Parkinson’s disease. The carriers are synthesized by crosslinking carboxymethylcellulose at subzero temperatures, resulting in cylindrical, highly resilient porous cryogels, which we term Neurothreads. We develop efficient covalent immobilization of the neural adhesion proteins laminin 111, collagen IV and fibronectin, as well as of the extracellular matrix extract Matrigel to the Neurothreads. We observe the highest neural spreading on laminin 111 and Matrigel. We show compatibility with established dopaminergic differentiation of both HS420 human embryonic stem cells and the LUHMES midbrain model cell line. The porous Neurothread carriers withstand compression during minimally invasive stereotactic injection, and ensure viability of mature neurons including extended neurites. Implanted into the striatum in mice, the Neurothreads enable survival of transplanted mature neurons obtained by directed differentiation of the HS420 human embryonic stem cells, as a dense tissuein situ, including dopaminergic cells. With the successfulin-vivotransfer of intact, mature and fully open 3D neural networks, we provide a powerful tool to extend established differentiation protocols to higher maturity and to enhance preconfigured neural network transplantation.
Biotic and abiotic drivers of soil microbial functions across tree diversity experiments
Authors: Cesarz Simone , Craven Dylan , Auge Harald , Bruelheide Helge , Castagneyrol Bastien , Hector Andy , Jactel Hervé , Koricheva Julia , Messier Christian , Muys Bart , O’Brien Michael J. , Paquette Alain , Ponette Quentin , Potvin Catherine , Reich Peter B. , Scherer-Lorenzen Michael , Smith Andrew R , Verheyen Kris , Eisenhauer Nico 
Published: February 2020

AbstractAimSoil microorganisms are essential for the functioning of terrestrial ecosystems. Although soil microbial communities and functions may be linked to the tree species composition and diversity of forests, there has been no comprehensive study of how general potential relationships are and if these are context-dependent. A global network of tree diversity experiments (TreeDivNet) allows for a first examination of tree diversity-soil microbial function relationships across environmental gradients.LocationGlobalMajor Taxa StudiedSoil microorganismsMethodsSoil samples collected from eleven tree diversity experiments in four biomes across four continents were used to measure soil basal respiration, microbial biomass, and carbon use efficiency using the substrate-induced respiration method. All samples were measured using the same analytical device in the same laboratory to prevent measurement bias. We used linear mixed-effects models to examine the effects of tree species diversity, environmental conditions, and their interactions on soil microbial functions.ResultsAcross biodiversity experiments, abiotic drivers, mainly soil water content, significantly increased soil microbial functions. Potential evapotranspiration (PET) increased, whereas soil C-to-N ratio (CN) decreased soil microbial functions under dry soil conditions, but high soil water content reduced the importance of other abiotic drivers. Tree species richness and phylogenetic diversity had overall similar, but weak and context-dependent (climate, soil abiotic variables) effects on soil microbial respiration. Positive tree diversity effects on soil microbial respiration were most pronounced at low PET, low soil CN, and high tree density. Soil microbial functions increased with the age of the experiment.Main conclusionsOur results point at the importance of soil water content for maintaining high levels of soil microbial functions and modulating effects of other environmental drivers. Moreover, overall tree diversity effects on soil microbial functions seem to be negligible in the short term (experiments were 1-18 years old). However, context-dependent tree diversity effects (climate, soil abiotic variables) have greater importance at high tree density, and significant effects of experimental age call for longer-term studies. Such systematic insights are key to better integrate soil carbon dynamics into the management of afforestation projects across environmental contexts, as today’s reforestation efforts remain focused largely on aboveground carbon storage and are still dominated by less diverse forests stands of commercial species.
Highly efficient cardiac differentiation and maintenance by thrombin-coagulated fibrin hydrogels enriched with decellularized porcine heart extracellular matrix
Authors: Navaee Fatemeh , Renaud Philippe , Braschler Thomas 
Published: February 2020

AbstractWe provide a blend of cardiac decellularized extracellular matrix (dECM) from porcine ventricular tissue and fibrinogen for the formation of anin-vitro3D cardiac cell culture model. Rapid and specific coagulation with thrombin allows gentle inclusion of cells while avoiding sedimentation during formation of the dECM-fibrin composite. We use the system in co-culture with Nor-10 fibroblasts to enhance cardiogenic differentiation of the H9c2 myoblast cell line. The combination of co-culture and appropriate substrate allows to abrogate the use of retinoids, classically considered necessary for cardiogenic H9c2 differentiation. Further enhancement of differentiation efficiency is obtained by 3D embedding. We then proceed with culture of rat neonatal cardiomyocytes in the 3D system. While for H9c2 cells, the collagen content of the dECM was the key factor required for efficient differentiation, the use of dECM-fibrin has specific advantages regarding the culture of neonatal cardiomyocytes. Calcium imaging and analysis of beating motion both indicate that the dECM-fibrin composite significantly enhances recovery, frequency, synchrony and maintenance of spontaneous beating, as compared to various controls including matrigel, pure fibrin and collagen I, but also a fibrin-collagen I blend.
Discovery of an evolutionarily conserved smooth muscle cell-specific lncRNACARMN
Authors: Dong Kunzhe , Shen Jian , He Xiangqin , Wang Liang , Hu Guoqing , Bunting Kirstopher M. , Dixon-Melvin Rachael , Zheng Zeqi , Xin Hongbo , Xiang Meixiang , Vazdarjanova Almira , Zhou Jiliang 
Published: February 2020

AbstractDifferentiated vascular smooth muscle cells (VSMCs) are critical in maintaining vascular homeostasis by expressing a unique repertoire of contractile genes. Despite the well-defined coding transcriptome in differentiated VSMCs, little is known about the non-coding gene expression signature. Herein, by de novo analyzing publicly available RNA-seq and single cell RNA-seq datasets generated from different tissues and cell types, we unambiguously identifiedCARMN(CARdiac Mesoderm Enhancer-associated Non-coding RNA) as an evolutionarily conserved, SMC-specific lncRNA.CARMNwas initially annotated as the host gene ofMIR143/145cluster and recently reported to play roles in cardiac differentiation. Here, we generated aCarmnGFP knock-in reporter mouse model and confirmed its specific expression in SMCsin vivo. In addition, we foundCarmnis transcribed independently fromMir143/145and only expressed transiently in embryonic cardiomyocytes and thereafter becomes restricted to adult SMCs in both human and mouse. Furthermore, we demonstrated thatCARMNexpression is not only dramatically decreased in human vascular diseases but functionally critical in maintaining VSMC contractile phenotypein vitro. In conclusion, we provided the first evidence showing thatCARMNis an evolutionarily conserved SMC-specific lncRNA, down-regulated in different human vascular diseases, and a key lncRNA for maintaining SMC contractile phenotype.
Alteration of perivascular spaces in early cognitive decline
Authors: Sepehrband Farshid , Barisano Giuseppe , Sheikh-Bahaei Nasim , Choupan Jeiran , Cabeen Ryan P , Crawford Malcolm S , Mack Wendy J , Chui Helena C , Ringman John M , Toga Arthur W ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2020

AbstractVascular contributions to early cognitive decline are increasingly recognized, prompting further investigation into the nature of related changes in perivascular space. Using magnetic resonance imaging, we show that, compared to a cognitively normal sample, individuals with early cognitive dysfunction have altered perivascular space presence and distribution, irrespective of Amyloid-β. Surprisingly, we noted decreased perivascular space presence in the anterosuperior medial temporal lobe, which was associated with neurofibrillary tau tangle deposition in the entorhinal cortex, one of the hallmarks of early Alzheimer’s disease pathology. Our results suggest that anatomically-specific alteration of the perivascular spaces may provide an early biomarker of cognitive impairment in aging adults.
Targeting Reactive Aldehyde Detoxification by Aldehyde Dehydrogenase 2 (ALDH2) as a Treatment Strategy for Endometriosis
Authors: McAllister Stacy L. , Sinharoy Pritam , Vasu Megana 
Published: February 2020

AbstractEndometriosis affects ∼176 million women worldwide, yet on average, women experience pain ∼10 years from symptom onset before being properly diagnosed. Standard treatments (drugs or surgery) often fail to provide long-term pain relief. Elevated levels of reactive aldehydes such as 4-hydroxynonenal (4-HNE) have been implicated in the peritoneal fluid of women with endometriosis and upon accumulation, reactive aldehydes can form protein-adducts and/or generate pain. A key enzyme in detoxifying reactive aldehydes to less reactive forms, is the mitochondrial enzyme aldehyde dehydrogenase-2 (ALDH2). Here, we tested the hypothesis that aberrant reactive aldehyde detoxification by ALDH2, underlies endometriosis and its associated pain. We determined, in the eutopic and ectopic endometrium of women with severe (stage IV) peritoneal endometriosis, that ALDH2 enzyme activity was decreased, which was associated with decreased ALDH2 expression and increased 4-HNE adduct formation compared to the eutopic endometrium of controls in the proliferative phase. Using a rodent model of endometriosis and an ALDH2*2 knock-in mouse with decreased ALDH2 activity, we determined that increasing ALDH2 activity with the enzyme activator Alda-1 could prevent endometriosis lesion development as well as alleviate pain-associated behaviors in proestrus. Overall, our findings suggest that targeting the ALDH2 enzyme in endometriosis may lead to better treatment strategies and in the proliferative phase, that increased 4-HNE adduct formation within the endometrium may serve as a less invasive diagnostic biomarker to reduce years of suffering in women.One Sentence SummaryALDH2 activity influences endometriosis and its associated pain.