bluuebunny/crossref_metadata_2025_split huggingface dataset:
SiGMoiD: A super-statistical generative model for binary data
Authors: Zhao Xiaochuan , Plata Germán , Dixit Purushottam D. 
Published: October 2020

AbstractIn modern computational biology, there is great interest in building probabilistic models to describe collections of a large number of co-varying binary variables. However, current approaches to build generative models rely on modelers’ identification of constraints and are computationally expensive to infer when the number of variables is large (N∼100). Here, we address both these issues withSuper-statisticalGenerativeModel for binaryData (SiGMoiD). SiGMoiD is a maximum entropy-based framework where we imagine the data as arising from super-statistical system; individual binary variables in a given sample are coupled to the same ‘bath’ whose intensive variables vary from sample to sample. Importantly, unlike standard maximum entropy approaches where modeler specifies the constraints, the SiGMoiD algorithm infers them directly from the data. Notably, unlike current approaches, SiGMoiD allows to model collections of a very large number (N> 1000) of binary variables. Finally, SiGMoiD offers a reduced dimensional description of the data, allowing us to identify clusters of similar data points as well as binary variables. We illustrate the versatility of SiGMoiD using several datasets spanning several time- and length-scales.
Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels
Authors: Duque Marc , Lee-Kubli Corinne A. , Tufail Yusuf , Magaram Uri , Patel Janki , Chakraborty Ahana , Lopez Jose Mendoza , Edsinger Eric , Vasan Aditya , Shiao Rani , Weiss Connor , Friend James , Chalasani Sreekanth H. 
Published: October 2020

AbstractUltrasound has been used to non-invasively manipulate neuronal functions in humans and other animals1–4. However, this approach is limited as it has been challenging to target specific cells within the brain or body5–8. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells. Ultrasound-evoked gating ofhsTRPA1 specifically requires its N-terminal tip region and cholesterol interactions; and target cells with an intact actin cytoskeleton, revealing elements of the sonogenetic mechanism. Next, we use calcium imaging and electrophysiology to show thathsTRPA1 potentiates ultrasound-evoked responses in primary neurons. Furthermore, unilateral expression ofhsTRPA1 in mouse layer V motor cortical neurons leads toc-fosexpression and contralateral limb responses in response to ultrasound delivered through an intact skull. Collectively, we demonstrate thathsTRPA1-based sonogenetics can effectively manipulate neurons within the intact mammalian brain, a method that could be used across species.
High dimensional immunotyping of the obese tumor microenvironment reveals model specific adaptation
Authors: Wogsland Cara E , Lien Hilde E , Pedersen Line , Hanjra Pahul , Grondal Sturla M , Brekken Rolf A , Lorens James B , Halberg Nils 
Published: October 2020

AbstractObesity is a disease characterized by chronic low-grade systemic inflammation and has been causally linked to the development of 13 cancer types. Several studies have been undertaken to determine if tumors evolving in obese environments adapt differential interactions with immune cells and if this can be connected to disease outcome. Most of these studies have been limited to single cell lines and tumor models and analysis of limited immune cell populations. Given the multicellular complexity of the immune system and its dysregulation in obesity, we applied high-dimensional suspension mass cytometry to investigate how obesity affects tumor immunity. We used a 36-marker immune-focused mass cytometry panel to interrogate the immune landscape of orthotopic syngeneic mouse models of pancreatic and breast cancer. Unanchored batch correction was implemented to enable simultaneous analysis of tumor cohorts to uncover the immunotypes of each cancer model and reveal remarkably model-specific immune regulation. In the E0771 breast cancer model, we demonstrate an important link to obesity with an increase in two T cell suppressive cell types and a decrease in CD8 T-cells.
TRex, a fast multi-animal tracking system with markerless identification, and 2D estimation of posture and visual fields
Authors: Walter Tristan , Couzin Iain D 
Published: October 2020

AbstractAutomated visual tracking of animals is rapidly becoming an indispensable tool for the study of behavior. It offers a quantitative methodology by which organisms’ sensing and decision-making can be studied in a wide range of ecological contexts. Despite this, existing solutions tend to be challenging to deploy in practice, especially when considering long and/or high-resolution video-streams. Here, we present TRex, a fast and easy-to-use solution for tracking a large number of individuals simultaneously using background-subtraction with real-time (60Hz) tracking performance for up to approximately 256 individuals and estimates 2D visual-fields, outlines, and head/rear of bilateral animals, both in open and closed-loop contexts. Additionally, TRex offers highly-accurate, deep-learning-based visual identification of up to approximately 100 unmarked individuals, where it is between 2.5-46.7 times faster, and requires 2-10 times less memory, than comparable software (with relative performance increasing for more organisms/longer videos) and provides interactive data-exploration within an intuitive, platform-independent graphical user-interface.
Ultrafast phasor-based hyperspectral snapshot microscopy for biomedical imaging
Authors: Hedde Per Niklas , Cinco Rachel , Malacrida Leonel , Kamaid Andrés , Gratton Enrico 
Published: October 2020

AbstractHyperspectral imaging is highly sought after in many fields including mineralogy and geology, environment and agriculture, astronomy and, importantly, biomedical imaging and biological fluorescence. We developed ultrafast phasor-based hyperspectral snapshot microscopy based on sine/cosine interference filters for biomedical imaging not feasible with conventional hyperspectral detection methods. Current approaches rely on slow spatial or spectral scanning limiting their application in living biological tissues, while faster snapshot methods such as image mapping spectrometry and multispectral interferometry are limited in spatial and/or spectral resolution, are computationally demanding, and imaging devices are very expensive to manufacture. Leveraging light sheet microscopy, phasor-based hyperspectral snapshot microscopy improved imaging speed 10-100 fold which, combined with minimal light exposure and high detection efficiency, enabled hyperspectral metabolic imaging of live, three-dimensional mouse tissues not feasible with other methods. As a fit-free method that does not require anya prioriinformation often unavailable in complex and evolving biological systems, the rule of linear combinations of the phasor could spectrally resolve subtle differences between cell types in the developing zebrafish retina and spectrally separate and track multiple organelles in 3D cultured cells over time. The sine/cosine snapshot method is adaptable to any microscope or imaging device thus making hyperspectral imaging and fit-free analysis based on linear combinations broadly available to researchers and the public.
Higher-order epistasis and phenotypic prediction
Authors: Zhou Juannan , Wong Mandy S. , Chen Wei-Chia , Krainer Adrian R. , Kinney Justin B. , McCandlish David M. 
Published: October 2020

AbstractContemporary high-throughput mutagenesis experiments are providing an increasingly detailed view of the complex patterns of genetic interaction that occur between multiple mutations within a single protein or regulatory element. By simultaneously measuring the effects of thousands of combinations of mutations, these experiments have revealed that the genotype-phenotype relationship typically reflects genetic interactions not only between pairs of sites, but also higher-order interactions among larger numbers of sites. However, modeling and understanding these higher-order interactions remains challenging. Here, we present a method for reconstructing sequence-to-function mappings from partially observed data that can accommodate all orders of genetic interaction. The main idea is to make predictions for unobserved genotypes that match the type and extent of epistasis found in the observed data. This information on the type and extent of epistasis can be extracted by considering how phenotypic correlations change as a function of mutational distance, which is equivalent to estimating the fraction of phenotypic variance due to each order of genetic interaction (additive, pairwise, three-way, etc.). Using these estimated variance components, we then define an empirical Bayes prior that in expectation matches the observed pattern of epistasis, and reconstruct the genotype-phenotype mapping by conducting Gaussian process regression under this prior. To demonstrate the power of this approach, we present an application to the antibody-binding domain GB1 and also provide a detailed exploration of a dataset consisting of high-throughput measurements for the splicing efficiency of human pre-mRNA5′ splice sites, for which we also validate our model predictions via additional low-throughput experiments.
Protein Structure Determination via Distance Geometry Structural Similarity based Initialization
Authors: Tasissa Abiy , Benavides Tiburon , Lai Rongjie , Wang Chunyu 
Published: October 2020

AbstractThe problem of finding the configuration of points given partial information on pairwise inter-point distances, the Euclidean distance geometry problem, appears in multiple applications. In this paper, we propose an approach that integrates structural similarity and a nonconvex distance geometry algorithm for the protein structure determination problem. When initialized with a homologous structure, reconstruction of ubiquitin structure with our non convex algorithm resulted in an RMSE of less than 2 Å with 1.5% available inter proton distance and up to 20% relative error in the input distances. To test the robustness of this algorithm with regard to initialization, we also initialized with a nonhomologous structure on a larger protein with pdb coordinate 1W2E. Even though the initialization structure 1JYB is far different from 1W2E with an RMSE of 25 Å, reconstruction generated structures with RMSE of close to 2 Å, using 1.7% available proton distances and up to 10% relative error in input distances. These results suggest EDG-based approach may be applied to fast NMR structure determination in the future.
CRIMSON: An Open-Source Software Framework for Cardiovascular Integrated Modelling and Simulation
Authors: Arthurs C.J. , Khlebnikov R. , Melville A. , Marčan M. , Gomez A. , Dillon-Murphy D. , Cuomo F. , Vieira M.S. , Schollenberger J. , Lynch S.R. , Tossas-Betancourt C. , Iyer K. , Hopper S. , Livingston E. , Youssefi P. , Noorani A. , Ahmed S. Ben , Nauta F.J.H. , van Bakel T.M.J. , Ahmed Y. , van Bakel P.A.J. , Mynard J. , Di Achille P. , Gharahi H. , Lau K. D. , Filonova V. , Aguirre M. , Nama N. , Xiao N. , Baek S. , Garikipati K. , Sahni O. , Nordsletten D. , Figueroa C.A. 
Published: October 2020

AbstractIn this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization. CRIMSON binaries for Microsoft Windows 10, documentation and example input files are freely available for download fromwww.crimson.software, and the source code with compilation instructions is available on GitHubhttps://github.com/carthurs/CRIMSONFlowsolver(CRIMSON Flowsolver) under the GPL v3.0 license, andhttps://github.com/carthurs/CRIMSONGUI(CRIMSON GUI), under the AGPL v3.0 license. Support is available on the CRIMSON Google Groups forum, located athttps://groups.google.com/forum/#!forum/crimson-users.
A high throughput RNA displacement assay for screening SARS-CoV-2 nsp10-nsp16 complex towards developing therapeutics for COVID-19
Authors: Perveen Sumera , Yazdi Aliakbar Khalili , Devkota Kanchan , Li Fengling , Ghiabi Pegah , Hajian Taraneh , Loppnau Peter , Bolotokova Albina , Vedadi Masoud 
Published: October 2020

AbstractSARS-CoV-2, the coronavirus that causes COVID-19, evades the human immune system by capping its RNA. This process protects the viral RNA and is essential for its replication. Multiple viral proteins are involved in this RNA capping process including the nonstructural protein 16 (nsp16) which is an S-adenosyl-L-methionine (SAM)-dependent 2’-O-methyltransferase. Nsp16 is significantly active when in complex with another nonstructural protein, nsp10, which plays a key role in its stability and activity. Here we report the development of a fluorescence polarization (FP)-based RNA displacement assay for nsp10-nsp16 complex in 384-well format with a Z′-Factor of 0.6, suitable for high throughput screening. In this process, we purified the nsp10-nsp16 complex to higher than 95% purity and confirmed its binding to the methyl donor SAM, product of the reaction, SAH, and a common methyltransferase inhibitor, sinefungin using Isothermal Titration Calorimetry (ITC). The assay was further validated by screening a library of 1124 drug-like compounds. This assay provides a cost-effective high throughput method for screening nsp10-nsp16 complex for RNA-competitive inhibitors towards developing COVID-19 therapeutics.
Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain
Authors: Okerman T. , Jurgenson T. , Moore M. , Klein A. H. 
Published: October 2020

AbstractBackgroundOpioid management of chronic pain can cause opioid-induced analgesic tolerance and hyperalgesia, complicating clinical pain-management treatments. Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems.MethodsMorphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated-JNK levels, cGMP, and gene expression analysis.ResultsGene expression for the PI3Kγ-AKT-cGMP-JNK signaling pathway including,Akt1, Akt2, Akt3, Pik3cg,Pten, Jnk3, andnNos1were decreased in the spinal cord with varied expression changes in the dorsal root ganglia and sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We observed significant increases in total and phosphorylated-JNK levels in the spinal cord, total JNK in dorsal root ganglia, and cGMP in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K, nNOS, or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal.ConclusionsOverall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance. Continued research into this pathway will contribute to the development of new analgesic drug therapies.
Impulsivity and Thought Suppression in Behavioral Addiction: Associated Neural Connectivity and Neural Networks
Authors: Wan Li , Zha Rujing , Ren Jiecheng , Li Ying , Zhao Qian , Zuo Huilin , Zhang Xiaochu 
Published: October 2020

ABSTRACTImpulsivity and thought suppression are two psychological traits that have great variation in healthy population. In extreme cases, both are closely related to mental illness and play an important role in behavioral addiction. We have known the role of the top-down mechanism in impulsivity and thought suppression, but we do not know how the related neural nuclei are functionally connected and interact with each other. In the study, we selected excessive internet users (EIU) as our target population and investigated the relationship between thought suppression and impulsivity in the following aspects: their correlations to psychological symptoms; the associated neural networks; and the associated brain morphometric changes. We acquired data from 131 excessive internet users, with their psychological, resting-state fMRI and T1-MRI data collected. With the whole brain analysis, graph theory analysis, replication with additional brain atlas, replication with additional MRI data, and analysis of brain structure, we found that: (i) implusivity and thought suppression shared common neural connections in the top-down mechanism; (ii) thought suppression was associated with the neural network that connected to the occipital lobe in the resting-state brain but not the morphometric change of the occipital lobe. The study confirmed the overlap between impulsivity and thought suppression in terms of neural connectivity and suggested the role of thought suppression and the occipital network in behavioral addiction. Studying thought suppression provided a new insight into behavioral addiction research. The neural network study helped further understanding of behavioral addiction in terms of information interaction in the brain.
Identification of subfunctionalized aggregate-remodeling J-domain proteins in plants
Authors: Tak Yogesh , Lal Silviya S. , Gopan Shilpa , Balakrishnan Madhumitha , Verma Amit K. , Cole Sierra J. , Brown Rebecca E. , Hayward Rachel E. , Hines Justin K. , Sahi Chandan 
Published: October 2020

AbstractHsp70s and J-domain proteins (JDPs) are among the most critical components of the cellular protein quality control machinery, playing crucial roles in preventing and solubilizing cytotoxic protein aggregates. Bacteria, yeast and plants additionally have large, multimeric Hsp100-class disaggregases which, allow the resolubilization of otherwise “dead-end” aggregates, including amyloids. JDPs interact with aggregated proteins and specify the aggregate remodeling activities of Hsp70s and Hsp100s. Plants have a complex network of cytosolic Hsp70s and JDPs, however the aggregate remodeling properties of plant JDPs are not well understood. Here we identify evolutionary-conserved Class II JDPs in the model plantArabidopsis thalianawith distinct aggregate remodeling functionalities. We identify eight plant orthologs of the yeast protein, Sis1, the principal JDP responsible for directing the yeast chaperone machinery for remodeling protein aggregates. Expression patterns vary dramatically among the eight paralogous proteins under a variety of stress conditions, indicating their subfunctionalization to address distinct stressors. Consistent with a role in solubilizing cytotoxic protein aggregates, six of these plant JDPs associate with heat-induced protein aggregatesin vivoas well as colocalize with plant Hsp101 to distinct heat-induced protein aggregate centers. Finally, we show that these six JDPs can differentially remodel multiple model protein aggregates in yeast confirming their involvement in aggregate resolubilization. These results demonstrate that compared to complex metazoans, plants have a robust network of JDPs involved in aggregate remodeling activities with the capacity to process a variety of protein aggregate conformers.
COVID-19 and frontline health workers in West Africa: a scoping review
Authors: Pereko Kingsley K. A. , Ameyaw Edward Kwabena , Bukari Shaibu , Acquaye Victoria , Dai-Kosi Alfred Dickson 
Published: October 2020

AbstractIntroductionThe novel Coronavirus 2019 (COVID-19) has become a severe global health threat since its emergence. Overcoming the virus is partly dependent on the holistic wellbeing of frontline health workers. Implications of COVID-19 on frontline health workers in West Africa could be substantial given the limited resources and logistics. This scoping review maps available literature on the impact of COVID-19 on frontline health workers in West Africa.Materials and methodsLiterature on the impact of COVID-19 on frontline health workers in West Africa were searched in six databases namely Cochrane Library, PubMed, EMBASE, Google Scholar, Africa Journals Online (AJOL) and CINAHL. Further search was done across websites of the ministries of health of West African countries and notable organisations. We conducted a narrative synthesis of the findings taking cognisance of the overarching purpose of the study and the research question.ResultsOf the 67 studies identified, 19 were included in the final synthesis. Three main themes emerged and these are impact of COVID-19 on frontline health workers, drivers of susceptibility to COVID-19 and government/donor support. A greater number of the studies originated from Nigeria. Each study reported at least one impact of COVID-19 on frontline health workers in West Africa. The impacts included death, fear, unwillingness to attend to COVID-19 patients and stigmatisation. Some health workers were not adhering to the safety protocols coupled with periodic shortage of personal protective equipment (PPE) and thereby had an increased susceptibility.ConclusionBeing the first scoping review on the impact of COVID-19 on frontline health workers in West Africa, the study has illustrated the urgent need for West African governments to enact laws/rules that would compel all frontline health workers to adhere to all the COVID-19 protocols at the workplace. To end intermittent shortage or issue of inadequate PPEs, governments ought to liaise with local industries by empowering them, providing financial support and creating a conducive atmosphere for them to produce cost effective PPEs using available local resources.Scoping review registrationDOI 10.17605/OSF.IO/B9NXZ (Open Science Framework)