bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using TrackMate to Analyze Drosophila Larval and Adult Locomotion
Authors: Omelchenko Alisa A. , Huda Ainul , Castaneda Allison N. , Vaden Thomas J. , Ni Lina 
Published: October 2021

AbstractDrosophila adult and larvae exhibit sophisticated behaviors that are widely used in development, synaptic transmission, sensory physiology, and learning and memory research. Many of these behaviors depend on locomotion, the ability of an animal to move. However, the statistical analysis of locomotion is not trivial. Here we use an open-source Fiji plugin TrackMate to track the locomotion of Drosophila adults and larvae. We build optimal experimental setups to rapidly process recordings by Fiji and analyze by TrackMate. We also provide tips for analyzing non-optimal recordings. TrackMate extracts the X and Y positions of an animal on each frame of an image sequence or a video. This information allows for generating moving trajectories, calculating moving distances, and determining preference indices in two-choice assays. Notably, this free-cost analysis method does not require programming skills.Summary statementThis study uses an open-source Fiji plugin TrackMate to computationally analyze Drosophila adult and larval behavioral assays, which does not require programming skills.
Sustained Released of Bioactive Mesenchymal Stromal Cell-Derived Extracellular Vesicles from 3D-Printed Gelatin Methacrylate Hydrogels
Authors: Born Louis J. , McLoughlin Shannon T. , Dutta Dipankar , Mahadik Bhushan , Jia Xiaofeng , Fisher John P. , Jay Steven M. 
Published: October 2021

AbstractExtracellular vesicles (EVs) represent an emerging class of therapeutics with significant potential and broad applicability. However, a general limitation is their rapid clearance after administration. Thus, methods to enable sustained EV release are of great potential value. Here, we demonstrate that EVs from mesenchymal stem/stromal cells (MSCs) can be incorporated into 3D-printed gelatin methacrylate (GelMA) hydrogel bioink, and that the initial burst release of EVs can be reduced by increasing the concentration of crosslinker during gelation. Further, the data show that MSC EV bioactivity in an endothelial gap closure assay is retained after the 3D printing and photocrosslinking processes. Our group previously showed that MSC EV bioactivity in this assay correlates with pro-angiogenic bioactivity in vivo, thus these results indicate therapeutic potential of MSC EV-laden GelMA bioinks.
Ex VivoandIn VivoCD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)
Authors: Hemsath Jack R. , Liaci A. Manuel , Rubin Jeffrey D. , Parrett Brian J. , Lu Shao-Chia , Nguyen Tien V. , Turner Mallory A. , Chen Christopher Y. , Cupelli Karolina , Reddy Vijay S. , Stehle Thilo , Liszewski M. Kathryn , Atkinson John P. , Barry Michael A. 
Published: October 2021

ABSTRACTHuman adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against SARS-CoV-2 and HIV-1. Yet, its primary receptor portfolio remains controversial, potentially including sialic acid, CAR, integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned by the inability to co-crystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infectionin vitroandin vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domains CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (IM) injection, but not after intranasal (IN) administration. Ad26 transduction was 10-fold lower than Ad5 after intratumoral (IT) injection of CD46-expressing tumors. Ad26 transduction of liver was 1000-fold lower than Ad5 after intravenous (IV) injection. These data demonstrate the use of CD46 by Ad26 under certain situations, but also show that the receptor has little consequence by other routes of administration. Finally, IV injection of high doses of Ad26 into CD46 mice induced release of liver enzymes in the bloodstream and reduced white blood cell counts, but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during COVID-19 vaccination with this serotype of adenovirus.IMPORTANCEHuman species D Ad26 is being pursued as a low seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection, and its role in virus biology, vaccine efficacy, and importantly, in vaccine safety.
A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex
Authors: Yao Shenqin , Wang Quanxin , Hirokawa Karla E. , Ouellette Benjamin , Ahmed Ruweida , Bomben Jasmin , Brouner Krissy , Casal Linzy , Caldejon Shiella , Cho Andy , Dotson Nadezhda I. , Daigle Tanya L. , Egdorf Tom , Enstrom Rachel , Gary Amanda , Gelfand Emily , Gorham Melissa , Griffin Fiona , Gu Hong , Hancock Nicole , Howard Robert , Kuan Leonard , Lambert Sophie , Lee Eric Kenji , Luviano Jennifer , Mace Kyla , Maxwell Michelle , Mortrud Marty T. , Naeemi Maitham , Nayan Chelsea , Ngo Nhan-Kiet , Nguyen Thuyanh , North Kat , Ransford Shea , Ruiz Augustin , Seid Sam , Swapp Jackie , Taormina Michael J , Wakeman Wayne , Zhou Thomas , Nicovich Philip R. , Williford Ali , Potekhina Lydia , McGraw Medea , Ng Lydia , Groblewski Peter A. , Tasic Bosiljka , Mihalas Stefan , Harris Julie A , Cetin Ali , Zeng Hongkui 
Published: October 2021

AbstractIdentification of the structural connections between neurons is a prerequisite to understanding brain function. We developed a pipeline to systematically map brain-wide monosynaptic inputs to specific neuronal populations using Cre-driver mouse lines and the recombinant rabies tracing system. We first improved the rabies virus tracing strategy to accurately identify starter cells and to efficiently quantify presynaptic inputs. We then mapped brain-wide presynaptic inputs to different excitatory and inhibitory neuron subclasses in the primary visual cortex and seven higher visual areas. Our results reveal quantitative target-, layer- and cell-class-specific differences in the retrograde connectomes, despite similar global input patterns to different neuronal populations in the same anatomical area. The retrograde connectivity we define is consistent with the presence of the ventral and dorsal visual information processing streams and reveals further subnetworks within the dorsal stream. The hierarchical organization of the entire visual cortex can be derived from intracortical feedforward and feedback pathways mediated by upper- and lower-layer input neurons, respectively. This study expands our knowledge of the brain-wide inputs regulating visual areas and demonstrates that our improved rabies virus tracing strategy can be used to scale up the effort in dissecting connectivity of genetically defined cell populations in the whole mouse brain.
Ensemble–function relationships to evaluate catalysis in the ketosteroid isomerase oxyanion hole
Authors: Yabukarski Filip , Doukov Tzanko , Pinney Margaux , Biel Justin , Fraser James , Herschlag Daniel 
Published: October 2021

ABSTRACTFollowing decades of insights from structure–function studies, there is now a need to progress from a static to dynamic view of enzymes. Comparison of prior cryo X-ray structures suggested that deleterious effects from ketosteroid isomerase (KSI) mutants arise from misalignment of the oxyanion hole catalytic residue, Y16. However, multi-conformer models from room temperature X-ray diffraction revealed an ensemble of Y16 conformers indistinguishable from WT for Y32F/Y57F KSI and a distinct, non-native ensemble for Y16 in Y57F KSI. Functional analyses suggested rate effects arise from weakened hydrogen bonding, due to disruption of the Y16/Y57/Y32 hydrogen bond network, and repositioning of the general base. In general, catalytic changes can be deconvoluted into effects on the probability of occupying a state (P-effects) and the reactivity of each state (k-effects). Our results underscore the need for ensemble–function analysis to decipher enzyme function and ultimately manipulate their extraordinary capabilities.
Real-time Noise-suppressed Wide-Dynamic-Range Compression in Ultrahigh-Resolution Neuronal Imaging
Authors: Borah Bhaskar Jyoti , Sun Chi-Kuang 
Published: October 2021

SummaryWith a limited dynamic range of an imaging system, there are always regions with signal intensities comparable to the noise level, if the signal intensity distribution is close to or even wider than the available dynamic range. Optical brain/neuronal imaging is such a case where weak-intensity ultrafine structures, such as, nerve fibers, dendrites and dendritic spines, often coexist with ultrabright structures, such as, somas. A high fluorescence-protein concentration makes the soma order-of-magnitude brighter than the adjacent ultrafine structures resulting in an ultra-wide dynamic range. A straightforward enhancement of the weak-intensity structures often leads to saturation of the brighter ones, and might further result in amplification of high-frequency background noises. An adaptive illumination strategy to real-time-compress the dynamic range demands a dedicated hardware to operate and owing to electronic limitations, might encounter a poor effective bandwidth especially when each digitized pixel is required to be illumination optimized. Furthermore, such a method is often not immune to noise-amplification while locally enhancing a weak-intensity structure. We report a dedicated-hardware-free method for rapid noise-suppressed wide-dynamic-range compression so as to enhance visibility of such weak-intensity structures in terms of both contrast-ratio and signal-to-noise ratio while minimizing saturation of the brightest ones. With large-FOV aliasing-free two-photon fluorescence neuronal imaging, we validate its effectiveness by retrieving weak-intensity ultrafine structures amidst a strong noisy background. With compute-unified-device-architecture (CUDA)-acceleration, a time-complexity of <3 ms for a 1000×1000-sized 16-bit data-set is secured, enabling a real-time applicability of the same.
The use of barcodedAsaiabacteria in mosquitoin vivoscreens for identification of systemic insecticides and inhibitors of malaria transmission
Authors: Sturm Angelika , Vos Martijn W. , Henderson Rob , Eldering Maarten , Koolen Karin M.J. , Sheshachalam Avinash , Favia Guido , Samby Kirandeep , Herreros Esperanza , Dechering Koen J. 
Published: October 2021

AbstractThis work addresses the need for new chemical matter in product development for control of pest insects and vector-borne diseases. We present a barcoding strategy that enables phenotypic screens of blood-feeding insects against small molecules in microtiter plate-based arrays and apply this to discovery of novel systemic insecticides and compounds that block malaria parasite development in the mosquito vector. Encoding of the bloodmeals was achieved through recombinant DNA-taggedAsaiabacteria that successfully colonizedAedesandAnophelesmosquitoes. An arrayed screen of a collection of pesticides showed that chemical classes of avermectins, phenylpyrazoles and neonicotinoids were enriched for compounds with systemic adulticide activity againstAnopheles. Using a luminescentPlasmodium falciparumreporter strain, barcoded screens identified 48 drug-like transmission blocking compounds from a 400-compound antimicrobial library. The approach significantly increases the throughput in phenotypic screening campaigns using adult insects, and identifies novel candidate small molecules for disease control.
The evolutionary maintenance of Lévy flight foraging
Authors: Campeau Winston , Simons Andrew M. , Stevens Brett 
Published: October 2021

AbstractLévy flight is a type of random walk that models the behaviour of many phenomena across a multiplicity of academic disciplines; within biology specifically, the behaviour of fish, birds, insects, mollusks, bacteria, plants, slime molds, t-cells, and human populations. The Lévy flight foraging hypothesis states that because Lévy flights can maximize an organism’s search efficiency, natural selection should result in Lévy-like behaviour. Empirical and theoretical research has provided ample evidence of Lévy walks in both extinct and extant species, and its efficiency across models with a diversity of resource distributions. However, no model has addressed the maintenance of Lévy flight foraging through evolutionary processes, and existing models lack ecological breadth. We use numerical simulations, including lineage-based models of evolution with a distribution of move lengths as a variable and heritable trait, to test the Lévy flight foraging hypothesis. We include biological and ecological contexts such as population size, searching costs, lifespan, resource distribution, speed, and consider both energy accumulated at the end of a lifespan and averaged over a lifespan. We demonstrate that selection often results in Lévy-like behaviour, although conditional; smaller populations, longer searches, and low searching costs increase the fitness of Lévy-like behaviour relative to Brownian behaviour. Interestingly, our results also evidence a bet-hedging strategy; Lévy-like behaviour reduces fitness variance, thus maximizing geometric mean fitness over multiple generations.Author summaryIn heterotrophs, incuding animals, survival depends on the net energy gained through foraging. The expectation, then, is that natural selection results in adaptations for efficient foraging that optimize the balance of searching costs and rewards. Lévy flight foraging has been proposed as an optimal foraging solution. The hypothesis states, if no information about resource locations are available, and the locations are re-visitable, then selection will result in adaptations for Lévy flight foraging, a type of random walk. It has been argued that Levy-like foraging behaviour may simply reflect how resources are distributed, but empirical and theoretical research suggests that this behaviour is intrinsic or innate. However, this research does not address evolutionary mechanisms, and lacks ecological breadth. We extend the current theoretical framework by including evolutionary ecological contexts. We treat an organism’s random walk as a heritable trait, and explore ecological contexts such as population size, lifespan, carrying capacity, searching costs, reproductive strategies, and different distributions of food. Our evolutionary simulations overwhelmingly resulted in selection for Lévy-like foraging, regardless of the distribution of food, and evidences Lévy flight foraging as a bet-hedging strategy. Thus, here we provide some of the first evidence for the evolutionary maintenance of Lévy flight foraging.
Towards integration of time-resolved confocal microscopy of a 3D in vitro microfluidic platform with a hybrid multiscale model of tumor angiogenesis
Authors: Phillips Caleb M. , Lima Ernesto A. B. F. , Gadde Manasa , Jarrett Angela M. , Rylander Marissa Nichole , Yankeelov Thomas E. 
Published: October 2021

AbstractThe goal of this study is to calibrate a multiscale model of tumor angiogenesis with time-resolved data to allow for systematic testing of mathematical predictions of vascular sprouting. The multi-scale model consists of an agent-based description of tumor and endothelial cell dynamics coupled to a continuum model of vascular endothelial growth factor concentration. First, we calibrate ordinary differential equation models to time-resolved protein expression data to estimate the rates of secretion and consumption of vascular endothelial growth factor by endothelial and tumor cells, respectively. These parameters are then input into the multiscale tumor angiogenesis model, and the remaining model parameters are then calibrated to time resolved confocal microscopy images obtained within a 3D vascularized microfluidic platform. The microfluidic platform mimics a functional blood vessel with a surrounding collagen matrix seeded with inflammatory breast cancer cells, which induce tumor angiogenesis. Once the multi-scale model is fully parameterized, we forecast the spatiotemporal distribution of vascular sprouts at future time points and directly compare the predictions to experimentally measured data. We assess the ability of our model to globally recapitulate angiogenic vasculature density, resulting in an average relative calibration error of 17.7% ± 6.3% and an average prediction error of 20.2% ± 4% and 21.7% ± 3.6% using one and four calibrated parameters, respectively. We then assess the model’s ability to predict local vessel morphology (individualized vessel structure as opposed to global vascular density), initialized with the first time point and calibrated with two intermediate time points. To the best of our knowledge, this represents the first study to integrate well-controlled, experimental data into a mechanism-based, multiscale, mathematical model of angiogenic sprouting to make specific, testable predictions.
tiRNA-Val promotes angiogenesis via Sirt1–Hif-1α axis in mice with diabetic retinopathy
Authors: Xu Yan , Zou Haidong , Ding Qi , Zou Yuelan , Tang Chun , Lu Yuyu , Xu Xun 
Published: October 2021

AbstractDiabetic retinopathy (DR) is a specific microvascular complication arising from diabetes, and its pathogenesis is notcompletely understood. tRNA-derived stress-induced RNAs (tiRNAs), a new type of small noncoding RNA generated by specific cleavage of tRNAs, has become a promising target forseveral diseases. However, the regulatory function of tiRNAs in DR and its detailed mechanism remain unknown. Here, we analyzed the tiRNA profiles of normal and DR retinal tissues. The expression level of tiRNA-Val was significantly upregulated in DR retinal tissues. Consistently, tiRNA-Val was upregulated in human retinal microvascular endothelial cells (HRMECs) under high glucose conditions. The overexpression of tiRNA-Val enhanced cell proliferation and inhibited cell apoptosis in HRMECs, but the knockdown of tiRNA-Val decreased cell proliferation and promoted cell apoptosis. Mechanistically, tiRNA-Val, derived from mature tRNA-Val with Ang cleavage, decreased Sirt1 expression level by interacting with sirt1 3’UTR, leading to the accumulation of Hif-1α, a key target for DR. In addition, subretinal injection of adeno-associated virus to knock down tiRNA-Val in DR mice ameliorated the symptoms of DR. Therefore, these data suggest that tiRNA-Val is a potential target in treating diabetic retinopathy.
Disrupted dynamic network reconfiguration of the executive and reward networks in internet gaming disorder: Why IGD subjects cannot control their gaming cravings
Authors: Wang Min , Zheng Hui , Zhou Weiran , Yang Bo , Wang Lingxiao , Chen Shuaiyu , Dong Guang-Heng 
Published: October 2021

AbstractBackgroundStudies have shown that people with internet gaming disorder (IGD) show impaired executive control over their gaming cravings; however, the neural mechanisms underlying this process remain unknown. In addition, these conclusions were based on the hypothesis that brain networks were temporally stationary and neglected changes in cognitive processes.MethodsResting-state fMRI data were collected from 402 subjects (162 subjects with IGD and 240 recreational game users (RGUs)). The community structure (recruitment and integration) of the executive control network and the basal ganglia network (BGN, representing the reward network) of patients with IGD and healthy controls were analyzed and compared. Mediation effects were analyzed among the different networks.ResultsWhen compared to RGUs, subjects with IGD had a lower recruitment coefficient within the right executive control network (ECN). Further analysis showed that only male subjects had a lower recruitment coefficient. Mediation analysis showed that the integration coefficient of the right ECN mediated the relationship between the recruitment coefficients of both the right ECN and the BGN in RGUs.ConclusionsSubjects with IGD had a lower recruitment coefficient than RGUs, and this feature was only observed in male subjects, making them less efficient at impulse control. The meditation results suggest a top-down control mechanism of the ECN is missing in subjects with IGD. All of these findings could explain why subjects with IGD have impaired executive control over their gaming cravings.
Sound disrupts sleep-associated brain oscillations in rodents according to its meaning
Authors: van Kronenberg Philipp , Milinski Linus , Kruschke Zoë , de Hoz Livia 
Published: October 2021

SummarySleep is essential but poses a risk to the animal. Filtering acoustic information according to its relevance, a process generally known as sensory gating, is crucial during sleep to ensure a balance between rest and danger detection. The mechanisms of this sensory gating and its specificity are not understood. Here, we tested the effect that sounds of different meaning had on sleep-associated ongoing oscillations. We recorded EEG and EMG from mice during rapid-eye movement (REM) and non-REM (NREM) sleep while presenting sounds with or without behavioural relevance. We found that sound presentation per se, in the form of an unfamiliar neutral sound, elicited a weak or no change in the sleep-dependent EEG power during NREM and REM sleep. In contrast, the presentation of a sound previously conditioned in an aversive task, elicited a clear and fast decrease in the sleep-dependent EEG power during both sleep phases, suggesting a transition to lighter sleep without awakening. The observed changes generally weakened over training days and were not present in animals that failed to learn. Interestingly, the effect could be generalized to unfamiliar neutral sounds if presented following conditioned training, an effect that depended on sleep phase and sound type. The data demonstrate that sounds are differentially gated during sleep depending on their meaning and that this process is reflected in disruption of sleep-associated brain oscillations without an effect on behavioural arousal.