bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanics of the optic nerve head and peripapillary sclera in a mouse model of glaucoma
Authors: Korneva Arina , Kimball Elizabeth C. , Jefferys Joan L. , Quigley Harry A. , Nguyen Thao D.
Published: December 2020

The deformation of the mouse astrocytic lamina (AL) and adjacent peripapillary sclera (PPS) was measured in response to elevated intraocular pressure. We subjected explanted mouse eyes to inflation testing, comparing control eyes to those 3 days and 6 weeks after induction of ocular hypertension (OHT) via ocular microbead injection. Laser scanning microscopy was used with second harmonic generation to image the collagenous PPS and two-photon fluorescence to image transgenic fluorescent astrocytes in the AL. Digital volume correlation was applied to calculate strains in the PPS and AL. The specimen-averaged strains were biaxial in the AL and PPS, with greater strain overall in the
x-
than
y-
direction in the AL and greater strain in the
θ-
than the
r
-direction in the PPS. Strains increased after 3-day OHT, with greater strain overall in the 3-day AL than control AL, and greater circumferential strain in the 3-day PPS than control PPS. In the 6-week OHT eyes, AL and PPS strains were similar overall to controls. This experimental glaucoma model demonstrated a dynamic change in the mechanical behaviour of the AL and PPS over time at the site of neuronal injury and remodelling in glaucoma.
‘Not only faces’: specialized visual representation of human hands revealed by adaptation
Authors: Conson Massimiliano , Polito Francesco , Di Rosa Alessandro , Trojano Luigi , Cordasco Gennaro , Esposito Anna , Turi Marco
Published: December 2020

Classical neurophysiological studies demonstrated that the monkey brain is equipped with neurons selectively representing the visual shape of the primate hand. Neuroimaging in humans provided data suggesting that a similar representation can be found in humans. Here, we investigated the selectivity of hand representation in humans by means of the visual adaptation technique. Results showed that participants' judgement of human-likeness of a visual probe representing a human hand was specifically reduced by a visual adaptation procedure when using a human hand adaptor but not when using an anthropoid robotic hand or a non-primate animal paw adaptor. Instead, human-likeness of the anthropoid robotic hand was affected by both human and robotic adaptors. No effect was found when using a non-primate animal paw as adaptor or probe. These results support the existence of specific neural mechanisms encoding human hand in the human's visual system.
Occupancy patterns in superorganisms: a spin-glass approach to ant exploration
Authors: Cristín Javier , Bartumeus Frederic , Méndez Vicenç , Campos Daniel
Published: December 2020

Emergence of collective, as well as superorganism-like, behaviour in biological populations requires the existence of rules of communication, either direct or indirect, between organisms. Because reaching an understanding of such rules at the individual level can be often difficult, approaches carried out at higher, or effective, levels of description can represent a useful alternative. In the present work, we show how a spin-glass approach characteristic of statistical physics can be used as a tool to characterize the properties of the spatial occupancy patterns of a biological population. We exploit the presence of pairwise interactions in spin-glass models for detecting correlations between occupancies at different sites in the media. Such correlations, we claim, represent a proxy to the existence of planned and/or social strategies in the spatial organization of the population. Our spin-glass approach does not only identify those correlations but produces a statistical
replica
of the system (at the level of occupancy patterns) that can be subsequently used for testing alternative conditions/hypothesis. Here, this methodology is presented and illustrated for a particular case of study: we analyse occupancy patterns of
Aphaenogaster senilis
ants during foraging through a simplified environment consisting of a discrete (tree-like) artificial lattice. Our spin-glass approach consistently reproduces the experimental occupancy patterns across time, and besides, an intuitive biological interpretation of the parameters is attainable. Likewise, we prove that pairwise correlations are important for reproducing these dynamics by showing how a null model, where such correlations are neglected, would perform much worse; this provides a solid evidence to the existence of superorganism-like strategies in the colony.
Synchronization-based control for a collaborative robot
Authors: Eberle Henry , Nasuto Slawomir J. , Hayashi Yoshikatsu
Published: December 2020

This article introduces a new control scheme for controlling a robotic manipulator in a collaborative task, allowing it to respond proactively to its partner’s movements. Unlike conventional robotic systems, humans can operate in an unstructured, dynamic environment due to their ability to anticipate changes before they occur and react accordingly. Recreating this artificially by using a forward model would lead to the huge computational task of simulating a world full of complex nonlinear dynamics and autonomous human agents. In this study, a controller based on anticipating synchronization, where a ‘leader’ dynamical system is predicted by a coupled ‘follower’ with delayed self-feedback, is used to modify a robot’s dynamical behaviour to follow that of a series of leaky integrators and harmonic oscillators. This allows the robot (follower) to be coupled with a collaborative partner (leader) to anticipate its movements, without a complete model of its behaviour. This is tested by tasking a simulated Baxter robot with performing a collaborative manual coordination task with an autonomous partner under a range of feedback delay conditions, confirming its ability to anticipate using oscillators instead of a detailed forward model.
Learned valuation during forage decision-making in cuttlefish
Authors: Kuo Tzu-Hsin , Chiao Chuan-Chin
Published: December 2020

Decision-making, when humans and other animals choose between two options, is not always based on the absolute values of the options but can also depend on their relative values. The present study examines whether decision-making by cuttlefish is dependent on relative values learned from previous experience. Cuttlefish preferred a larger quantity when making a choice between one or two shrimps (1 versus 2) during a two-alternative forced choice. However, after cuttlefish were primed under conditions where they were given a small reward for choosing one shrimp in a no shrimp versus one shrimp test (0 versus 1) six times in a row, they chose one shrimp significantly more frequently in the 1 versus 2 test. This reversed preference for a smaller quantity was not due to satiation at the time of decision-making, as cuttlefish fed a small shrimp six times without any choice test prior to the experiment still preferred two shrimps significantly more often in a subsequent 1 versus 2 test. This suggests that the preference of one shrimp in the quantity comparison test occurs via a process of learned valuation. Foraging preference in cuttlefish thus depends on the relative value of previous prey choices.
High-frequency homogenization in periodic media with imperfect interfaces
Authors: Assier Raphaël C. , Touboul Marie , Lombard Bruno , Bellis Cédric
Published: December 2020

In this work, the concept of high-frequency homogenization is extended to the case of one-dimensional periodic media with imperfect interfaces of the spring-mass type. In other words, when considering the propagation of elastic waves in such media, displacement and stress discontinuities are allowed across the borders of the periodic cell. As is customary in high-frequency homogenization, the homogenization is carried out about the periodic and antiperiodic solutions corresponding to the edges of the Brillouin zone. Asymptotic approximations are provided for both the higher branches of the dispersion diagram (second-order) and the resulting wave field (leading-order). The special case of two branches of the dispersion diagram intersecting with a non-zero slope at an edge of the Brillouin zone (occurrence of a so-called Dirac point) is also considered in detail, resulting in an approximation of the dispersion diagram (first-order) and the wave field (zeroth-order) near these points. Finally, auniform approximationvalid for both Dirac and non-Dirac points is provided. Numerical comparisons are made with the exact solutions obtained by the Bloch–Floquet approach for the particular examples of monolayered and bilayered materials. In these two cases, convergence measurements are carried out to validate the approach, and we show that the uniform approximation remains a very good approximation even far from the edges of the Brillouin zone.
Control of connectivity and rigidity in prismatic assemblies
Authors: Choi Gary P. T. , Chen Siheng , Mahadevan L.
Published: December 2020

How can we manipulate the topological connectivity of a three-dimensional prismatic assembly to control the number of internal degrees of freedom and the number of connected components in it? To answer this question in a deterministic setting, we use ideas from elementary number theory to provide a hierarchical deterministic protocol for the control of rigidity and connectivity. We then show that it is possible to also use a stochastic protocol to achieve the same results via a percolation transition. Together, these approaches provide scale-independent algorithms for the cutting or gluing of three-dimensional prismatic assemblies to control their overall connectivity and rigidity.
Timing precision in fly flight control: integrating mechanosensory input with muscle physiology
Authors: Dickerson Bradley H.
Published: December 2020

Animals rapidly collect and act on incoming information to navigate complex environments, making the precise timing of sensory feedback critical in the context of neural circuit function. Moreover, the timing of sensory input determines the biomechanical properties of muscles that undergo cyclic length changes, as during locomotion. Both of these issues come to a head in the case of flying insects, as these animals execute steering manoeuvres at timescales approaching the upper limits of performance for neuromechanical systems. Among insects, flies stand out as especially adept given their ability to execute manoeuvres that require sub-millisecond control of steering muscles. Although vision is critical, here I review the role of rapid, wingbeat-synchronous mechanosensory feedback from the wings and structures unique to flies, the halteres. The visual system and descending interneurons of the brain employ a spike rate coding scheme to relay commands to the wing steering system. By contrast, mechanosensory feedback operates at faster timescales and in the language of motor neurons, i.e. spike timing, allowing wing and haltere input to dynamically structure the output of the wing steering system. Although the halteres have been long known to provide essential input to the wing steering system as gyroscopic sensors, recent evidence suggests that the feedback from these vestigial hindwings is under active control. Thus, flies may accomplish manoeuvres through a conserved hindwing circuit, regulating the firing phase—and thus, the mechanical power output—of the wing steering muscles.
Lack of phenological shift leads to increased camouflage mismatch in mountain hares
Authors: Zimova Marketa , Giery Sean T. , Newey Scott , Nowak J. Joshua , Spencer Michael , Mills L. Scott
Published: December 2020

Understanding whether organisms will be able to adapt to human-induced stressors currently endangering their existence is an urgent priority. Globally, multiple species moult from a dark summer to white winter coat to maintain camouflage against snowy landscapes. Decreasing snow cover duration owing to climate change is increasing mismatch in seasonal camouflage. To directly test for adaptive responses to recent changes in snow cover, we repeated historical (1950s) field studies of moult phenology in mountain hares (
Lepus timidus
) in Scotland. We found little evidence that population moult phenology has shifted to align seasonal coat colour with shorter snow seasons, or that phenotypic plasticity prevented increases in camouflage mismatch. The lack of responses resulted in 35 additional days of mismatch between 1950 and 2016. We emphasize the potential role of weak directional selection pressure and low genetic variability in shaping the scope for adaptive responses to anthropogenic stressors.
Phenomenon of music-induced opening of the blood-brain barrier in healthy mice
Authors: Semyachkina-Glushkovskaya O. , Esmat A. , Bragin D. , Bragina O. , Shirokov A. A. , Navolokin N. , Yang Y. , Abdurashitov A. , Khorovodov A. , Terskov A. , Klimova M. , Mamedova A. , Fedosov I. , Tuchin V. , Kurths J.
Published: December 2020

Music plays a more important role in our life than just being an entertainment. For example, it can be used as an anti-anxiety therapy of human and animals. However, the unsafe listening of loud music triggers hearing loss in millions of young people and professional musicians (rock, jazz and symphony orchestra) owing to exposure to damaging sound levels using personal audio devices or at noisy entertainment venues including nightclubs, discotheques, bars and concerts. Therefore, it is important to understand how loud music affects us. In this pioneering study on healthy mice, we discover that loud rock music below the safety threshold causes opening of the blood-brain barrier (OBBB), which plays a vital role in protecting the brain from viruses, bacteria and toxins. We clearly demonstrate that listening to loud music during 2 h in an intermittent adaptive regime is accompanied by delayed (1 h after music exposure) and short-lasting to (during 1–4 h) OBBB to low and high molecular weight compounds without cochlear and brain impairments. We present the systemic and molecular mechanisms responsible for music-induced OBBB. Finally, a revision of our traditional knowledge about the BBB nature and the novel strategies in optimizing of sound-mediated methods for brain drug delivery are discussed.
Sedimentation and overfishing drive changes in early succession and coral recruitment
Authors: Wakwella Ama , Mumby Peter J. , Roff George
Published: December 2020

Sedimentation and overfishing are important local stressors on coral reefs that can independently result in declines in coral recruitment and shifts to algal-dominated states. However, the role of herbivory in driving recovery across environmental gradients is often unclear. Here we investigate early successional benthic communities and coral recruitment across a sediment gradient in Palau, Micronesia over a 12-month period. Total sedimentation rates measured by ‘TurfPods’ varied from 0.03 ± 0.1 SE mg cm−2d−1at offshore sites to 1.32 ± 0.2 mg cm−2d−1at inshore sites. To assess benthic succession, three-dimensional settlement tiles were deployed at sites with experimental cages used to exclude tile access to larger herbivorous fish. Benthic assemblages exhibited rapid transitions across the sediment gradient within three months of deployment. At low levels of sedimentation (less than 0.6 mg cm−2d−1), herbivory resulted in communities dominated by coral recruitment inducers (short turf algae and crustose coralline algae), whereas exclusion of herbivores resulted in the overgrowth of coral inhibitors (encrusting and upright foliose macroalgae). An ‘inducer threshold’ was found under increasing levels of sedimentation (greater than 0.6 mg cm−2d−1), with coral inducers having limited to no presence in communities, and herbivore access to tiles resulted in sediment-laden turf algal assemblages, while exclusion of herbivores resulted in invertebrates (sponges, ascidians) and terrestrial sediment accumulation. A ‘coral recruitment threshold’ was found at 0.8 mg cm−2d−1, below which net coral recruitment was reduced by 50% in the absence of herbivores, while recruitment was minimal above the threshold. Our results highlight nonlinear trajectories of benthic succession across sediment gradients and identify strong interactions between sediment and herbivory that have cascading effects on coral recruitment. Local management strategies that aim to reduce sedimentation and turbidity and manage herbivore fisheries can have measurable effects on benthic community succession and coral recruitment, enhancing reef resilience and driving coral recovery.
A dynamic over games drives selfish agents to win–win outcomes
Authors: Frey Seth , Atkisson Curtis
Published: December 2020

Understanding human institutions, animal cultures and other social systems requires flexible formalisms that describe how their members change them from within. We introduce a framework for modelling how agents change the games they participate in. We contrast this between-game ‘institutional evolution’ with the more familiar within-game ‘behavioural evolution’. We model institutional change by following small numbers of persistent agents as they select and play a changing series of games. Starting from an initial game, a group of agents trace trajectories through game space by navigating to increasingly preferable games until they converge on ‘attractor’ games. Agents use their ‘institutional preferences' for game features (such as stability, fairness and efficiency) to choose between neighbouring games. We use this framework to pose a pressing question: what kinds of games does institutional evolution select for; what is in the attractors? After computing institutional change trajectories over the two-player space, we find that attractors have disproportionately fair outcomes, even though the agents who produce them are strictly self-interested and indifferent to fairness. This seems to occur because game fairness co-occurs with the self-serving features these agents do actually prefer. We thus present institutional evolution as a mechanism for encouraging the spontaneous emergence of cooperation among small groups of inherently selfish agents, without space, reputation, repetition, or other more familiar mechanisms. Game space trajectories provide a flexible, testable formalism for modelling the interdependencies of behavioural and institutional evolutionary processes, as well as a mechanism for the evolution of cooperation.
Submarine groundwater discharge alters coral reef ecosystem metabolism
Authors: Silbiger Nyssa J. , Donahue Megan J. , Lubarsky Katie
Published: December 2020

Submarine groundwater discharge (SGD) influences near-shore coral reef ecosystems worldwide. SGD biogeochemistry is distinct, typically with higher nutrients, lower pH, cooler temperature and lower salinity than receiving waters. SGD can also be a conduit for anthropogenic nutrients and other pollutants. Using Bayesian structural equation modelling, we investigate pathways and feedbacks by which SGD influences coral reef ecosystem metabolism at two Hawai'i sites with distinct aquifer chemistry. The thermal and biogeochemical environment created by SGD changed net ecosystem production (NEP) and net ecosystem calcification (NEC). NEP showed a nonlinear relationship with SGD-enhanced nutrients: high fluxes of moderately enriched SGD (Wailupe low tide) and low fluxes of highly enriched SGD (Kūpikipiki'ō high tide) increased NEP, but high fluxes of highly enriched SGD (Kūpikipiki'ō low tide) decreased NEP, indicating a shift toward microbial respiration. pH fluctuated with NEP, driving changes in the net growth of calcifiers (NEC). SGD enhances biological feedbacks: changes in SGD from land use and climate change will have consequences for calcification of coral reef communities, and thereby shoreline protection.
Sex pheromone biosynthesis, storage and release in a female moth: making a little go a long way
Authors: Foster Stephen P. , Anderson Karin G.
Published: December 2020

Moth pheromone research has pioneered much of our understanding of long-distance chemical communication. Two important characteristics of this communication have, however, remained largely unaddressed: the release of small quantities of pheromone by most moth species, despite potential advantages of releasing greater amounts, and the intermittency of release in some species, limiting the time of mate attraction. We addressed the proximate mechanisms underlying these characteristics by manipulating biosynthesis, storage and release of pheromone in females of the noctuid mothChloridea virescens. We found that (i) mass release is determined by pheromone mass on the gland surface; (ii) amounts synthesized are limited by pheromone biosynthesis activating neuropeptide concentration, not precursor availability; (iii) some gland structural feature limits mass release rate; (iv) intermittent calling enables release at a mass rate greater than biosynthetic rate; and (v) at typical mass release rates, the periodicity of pheromone availability on the gland surface roughly matches the periodicity (intermittency) of calling. We conclude that mass release inC.virescensand possibly many other species is low because of constraints on biosynthesis, storage and gland structure. Further, it appears the behaviour of intermittent calling in C.virescensmay have evolved as a co-adaptation with pheromone availability, allowing females to release pheromone intermittently at higher mass rates than the biosynthesis rate.
SnapHiC: a computational pipeline to map chromatin contacts from single cell Hi-C data
Authors: Yu Miao , Abnousi Armen , Zhang Yanxiao , Li Guoqiang , Lee Lindsay , Chen Ziyin , Fang Rongxin , Wen Jia , Sun Quan , Li Yun , Ren Bing , Hu Ming
Published: December 2020

Single cell Hi-C (scHi-C) analysis has been increasingly used to map the chromatin architecture in diverse tissue contexts, but computational tools to define chromatin contacts at high resolution from scHi-C data are still lacking. Here, we describe SnapHiC, a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. We benchmark SnapHiC against HiCCUPS, a common tool for mapping chromatin contacts in bulk Hi-C data, using scHi-C data from 742 mouse embryonic stem cells. We further demonstrate its utility by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells. We uncover cell-type-specific chromatin loops and predict putative target genes for non-coding sequence variants associated with neuropsychiatric disorders. Our results suggest that SnapHiC could facilitate the analysis of cell-type-specific chromatin architecture and gene regulatory programs in complex tissues.
Rapid SARS-CoV-2 Detection and Classification Using Phase Imaging with Computational Specificity
Authors: Goswami Neha , He Yuchen R. , Deng Yu-Heng , Oh Chamteut , Sobh Nahil , Valera Enrique , Bashir Rashid , Ismail Nahed , Kong Hyun J. , Nguyen Thanh H. , Best-Popescu Catherine , Popescu Gabriel
Published: December 2020

Efforts to mitigate the COVID-19 crisis revealed that fast, accurate, and scalable testing is crucial for curbing the current impact and that of future pandemics. We propose an optical method for directly imaging unlabeled viral particles and using deep learning for detection and classification. An ultrasensitive interferometric method was used to image four virus types with nanoscale optical pathlength sensitivity. Pairing these data with fluorescence images for ground truth, we trained semantic segmentation models based on U-Net, a particular type of convolutional neural network. The trained network was applied to classify the viruses from the interferometric images only, containing simultaneously SARS-CoV-2, H1N1 (influenza-A), HAdV (adenovirus), and ZIKV (Zika). Remarkably, due to the nanoscale sensitivity in the input data, the neural network was able to identify SARS-CoV-2 vs. the other viruses with 96% accuracy. The inference time for each image is 60 ms, on a common graphic processing unit. This approach of directly imaging unlabeled viral particles may provide an extremely fast test, of less than a minute per patient. As the imaging instrument operates on regular glass slides, we envision this method as potentially testing on patient breath condensates.

The necessary high throughput can be achieved by translating concepts from digital pathology, where a microscope can scan hundreds of slides automatically.

One Sentence Summary

This work proposes a rapid (<1 min.), label-free testing method for SARS-CoV-2 detection, using quantitative phase imaging and deep learning.
Novel virus-like particle vaccine encoding the circumsporozoite protein ofPlasmodium falciparumis immunogenic and induces functional antibody responses
Authors: Kurtovic Liriye , Wetzel David , Reiling Linda , Drew Damien R. , Palmer Catherine , Kouskousis Betty , Hanssen Eric , Wines Bruce D. , Hogarth P. Mark , Suckow Manfred , Jenzelewski Volker , Piontek Michael , Chan Jo-Anne , Beeson James G.
Published: December 2020

RTS,S is the leading malaria vaccine in development, but has demonstrated only moderate protective efficacy in clinical trials. RTS,S is a virus-like particle (VLP) that uses the human hepatitis B virus as scaffold to display the malaria sporozoite antigen, circumsporozoite protein (CSP). Particle formation requires fourfold excess scaffold antigen, and as a result, CSP represents only a small portion of the final vaccine construct. Alternative VLP or nanoparticle platforms that reduce the amount of scaffold antigen and increase the amount of the target CSP antigen present in particles may enhance vaccine immunogenicity and efficacy. Here, we describe the production and characterization of a novel VLP that uses the small surface antigen (dS) of duck hepatitis B virus to display CSP. The CSP-dS fusion protein successfully formed VLPs without the need for excess scaffold antigen, and thus CSP represented a larger portion of the vaccine construct. Importantly, this is the first report of a dS-based vaccine that formed particles without excess scaffold protein. CSP-dS formed large particles approximately 31-74 nm in size and were confirmed to display CSP on the surface. The CSP-dS VLP was highly immunogenic in mice and induced antibodies to multiple regions of CSP, even when administered at a lower vaccine dosage. Vaccine-induced antibodies demonstrated functional activity, including the ability to interact with complement and Fcγ-receptors, both previously identified as important in malaria immunity. Our novel platform to produce VLPs without excess scaffold protein has wide implications for the future development of innovative vaccines for malaria and other infectious diseases.
Effects of temperature on development, reproduction and size ofTrichogramma achaeae: implications for biological control
Authors: Chen Long , Sørensen Jesper Givskov , Enkegaard Annie
Published: December 2020

The performance of biological control agents (BCAs) in outdoor crops is strongly regulated by ambient temperature. Understanding the thermal biology of BCAs and manipulating their thermal performance could improve biological control efficacy. In this study, the effects of temperature on several life history parameters (longevity, fecundity, development time, wing size) of the recently commercialised egg parasitoidTrichogramma achaeaeNagaraja & Nagarkatti (Hymenoptera: Trichogrammatidae) was examined. First, parasitoids were reared at 23 °C and tested in the laboratory at four constant temperatures (15, 20, 25 and 30 °C). Results demonstrated that temperature significantly altered all above parameters. Second, developmental acclimation was applied to manipulate the laboratory performance. Parasitoids were allowed to develop at either of the above four temperatures and their performance were compared at 23 °C. Results showed that developmental acclimation had a significant impact on fecundity, development time and wing size but not on female longevity. Our results have implications for improving the performance ofT. achaeaein mass production and for its application for biological control under different thermal conditions.

Highlights

The temperature dependent performance ofTrichogramma achaeaewas characterised

Acclimation significantly influenced fecundity, development and body size

The overall performance was not improved by acclimation

The female fecundity could be a proxy for the overall performance ofT. achaeae
Hapo-G, Haplotype-Aware Polishing Of Genome Assemblies
Authors: Aury Jean-Marc , Istace Benjamin
Published: December 2020

Single-molecule sequencing technologies have recently been commercialized by Pacific Biosciences and Oxford Nanopore with the promise of sequencing long DNA fragments (kilobases to megabases order) and then, using efficient algorithms, provide high quality assemblies in terms of contiguity and completeness of repetitive regions. However, the error rate of long-read technologies is higher than that of short-read technologies. This has a direct consequence on the base quality of genome assemblies, particularly in coding regions where sequencing errors can disrupt the coding frame of genes. In the case of diploid genomes, the consensus of a given gene can be a mixture between the two haplotypes and can lead to premature stop codons. Several methods have been developed to polish genome assemblies using short reads and generally, they inspect the nucleotide one by one, and provide a correction for each nucleotide of the input assembly. As a result, these algorithms are not able to properly process diploid genomes and they typically switch from one haplotype to another. Herein we proposed Hapo-G (Haplotype-Aware Polishing Of Genomes), a new algorithm capable of incorporating phasing information from short reads to polish genome assemblies and in particular assemblies of diploid and heterozygous genomes.
Toward asleep DBS: Cortico basal-ganglia neural activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity
Authors: Guang Jing , Baker Halen , Nizri Orilia Ben-Yishay , Firman Shimon , Werner-Reiss Uri , Kapuller Vadim , Israel Zvi , Bergman Hagai
Published: December 2020

Deep brain stimulation (DBS) is currently a standard long-term treatment for advanced motor symptoms in Parkinson’s disease (PD). In an effort to enable DBS under sedation, asleep DBS, we characterized the cortico-basal ganglia neuronal network of two non-human primates under propofol, ketamine and interleaved propofol-ketamine (IPK) sedation. Further, we compared these sedation states in the healthy and Parkinsonian condition to those of healthy sleep. Ketamine increases high frequency power and synchronization while propofol increases low frequency power and synchronization in polysomnography and neuronal activity recordings. Thus, ketamine does not mask the low frequency oscillations used for physiological navigation toward basal ganglia DBS targets. The brain state under ketamine and propofol mimicked rapid eye movement (REM) and Non-REM (NREM) sleep activity, respectively, and the IPK protocol imitates the NREM-REM sleep cycle. These promising results are the first step towards asleep DBS with non-distorted physiological navigation.
IOBR: Multi-omics Immuno-Oncology Biological Research to decode tumor microenvironment and signatures
Authors: Zeng Dongqiang , Ye Zilan , Yu Guangchuang , Wu Jiani , Xiong Yi , Zhou Rui , Qiu Wenjun , Huang Na , Sun Li , Bin Jianping , Liao Yulin , Shi Min , Liao Wangjun
Published: December 2020

Motivation: Recent advance in next generation sequencing has triggered the rapid accumulation of publicly available multi-omics datasets. The application of integrated omics to exploring robust signatures for clinical translation is increasingly highlighted, attributed to the clinical success of immune checkpoint blockade in diverse malignancies. However, effective tools to comprehensively interpret multi-omics data is still warranted to provide increased granularity into intrinsic mechanism of oncogenesis and immunotherapeutic sensitivity. Results: We developed a computational tool for effective Immuno-Oncology Biological Research (IOBR), providing comprehensive investigation of estimation of reported or user-built signatures, TME deconvolution and signature construction base on multi-omics data. Notably, IOBR offers batch analyses of these signatures and their correlations with clinical phenotypes, lncRNA profiling, genomic characteristics and signatures generated from single-cell RNA sequencing data in different cancer settings. Additionally, IOBR also integrates multiple existing microenvironmental deconvolution methodologies and signature construction tools for convenient comparison and selection. Collectively, IOBR is a user-friendly tool, to leverage multi-omics data to facilitate immuno-oncology exploration and unveiling of tumor-immune interactions and accelerating precision immunotherapy.
Circadian Rhythm Disruption Results in Visual Dysfunction
Authors: Mathew Deepa , Bhatwadekar Ashay D.
Published: December 2020

Circadian rhythm disruption (CRD) contributes to the development of multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; ‘entrained’, ‘freerunning’, and ‘zigzagging.’ These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of rod photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting ‘entrained’ behavior. The retinal proteome showed distinct changes with each entrainment behavior. These results demonstrate that CRD leads to photoreceptor degeneration and visual dysfunction. We uniquely show the effect of entrainment behavior on retinal protein composition and physiology. Our data has broader implications in understanding and mitigating the effect of CRD on vision health.

Significance Statement

Artificial light is increasingly in use for the past 70 years. The aberrant light exposure and round-the-clock nature of work lead to the disruption of a biological clock. The mammalian retina possesses an autonomous clock that could reset with light exposure. Yet, the effect of altered light exposure on vision is not studied. Here, we report visual dysfunction after exposure to a circadian disrupting altered light/dark cycle. We also report behavior dependent changes in retinal protein composition and function. Our data provide evidence for the negative impact of CRD on vision and its potential role in retinal diseases’ etiology.
Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43
Authors: Li Qiuye , Michael Babinchak W. , Surewicz Witold K.
Published: December 2020

Amyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of TDP-43 aggregates. Cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain reveals single protofilament fibrils containing a large (138-residue), tightly packed core with structural features that differ from those previously found for fibrils formed from short protein fragments. The atomic model provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.
AdRoit: an accurate and robust method to infer complex transcriptome composition
Authors: Yang Tao , Alessandri-Haber Nicole , Fury Wen , Schaner Michael , Breese Robert , LaCroix-Fralish Michael , Kim Jinrang , Adler Christina , Macdonald Lynn E. , Atwal Gurinder S. , Bai Yu
Published: December 2020

Bulk RNA sequencing technology provides the opportunity to understand biology at the whole transcriptome level without the prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable to dissect tissue organization and function by genome-wide gene expressions. However, the readout of both technologies is the overall gene expression across potentially many cell types without directly providing the information of cell type constitution. Although several in-silico approaches have been proposed to deconvolute RNA-Seq data composed of multiple cell types, many suffer a deterioration of performance in complex tissues. Here we present AdRoit, anaccurate and robust method infer the cell composition fromtranscriptome data comprised of multiple cell types. AdRoit uses gene expression profile obtained from single cell RNA sequencing as a reference. It employs an adaptive learning approach to correct the sequencing technique difference between the single cell data and the bulk or spatial transcriptome data, enabling cross-platform readout comparability. Our systematic benchmarking and applications, which include deconvoluting complex mixtures that encompass 30 cell types, demonstrate its superior sensitivity and specificity compared to other existing methods as well as its utilities. In addition, AdRoit is computationally efficient and runs orders of magnitude faster than many existing methods.
Decoding neurobiological spike trains using recurrent neural networks; a case study with electrophysiological auditory cortex recordings
Authors: Szabó Péter , Barthó Péter
Published: December 2020

Recent advancements in multielectrode methods and spike-sorting algorithms enable the in vivo recording of the activities of many neurons at a high temporal resolution. These datasets offer new opportunities in the investigation of the biological neural code, including the direct testing of specific coding hypotheses, but they also reveal the limitations of present decoder algorithms. Classical methods rely on a manual feature extraction step, resulting in a feature vector, like the firing rates of an ensemble of neurons. In this paper, we present a recurrent neural-network based decoder and evaluate its performance on experimental and artificial datasets. The experimental datasets were obtained by recording the auditory cortical responses of rats exposed to sound stimuli, while the artificial datasets represent preset encoding schemes. The task of the decoder was to classify the action potential timeseries according to the corresponding sound stimuli. It is illustrated that, depending on the coding scheme, the performance of the recurrent-network based decoder can exceed the performance of the classical methods. We also show how randomized copies of the training datasets can be used to reveal the role of candidate spike-train features. We conclude that artificial neural network decoders can be a useful alternative to classical population vector based techniques in studies of the biological neural code.
Development of an Antiepileptogenesis Drug Screening Platform: Effects of Everolimus and Phenobarbital
Authors: Barker-Haliski Melissa , Knox Kevin , Zierath Dannielle , Koneval Zachery , Metcalf Cameron , Wilcox Karen S. , White H. Steve
Published: December 2020

Objective

The kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. Just as in patients, who develop temporal lobe epilepsy (TLE) following SE, this rat model of KA-induced SE very closely recapitulates many of the clinical and pathological characteristics of human TLE that arise following SE or another neurological insult. Spontaneous recurrent seizures (SRS) in TLE can present after a latent period following a neurological insult (TBI, SE event, viral infection, etc.). Moreover, this rat model of TLE is ideally suited for preclinical studies to evaluate the long-term process of epileptogenesis and screen putative disease-modifying/antiepileptogenic agents. This report details the pharmacological characterization and methodological refinement of a moderate-throughput drug screening program using the post KA-induced SE model of epileptogenesis in male Sprague Dawley rats to identify potential agents that may prevent or modify the onset or severity of SRS. Specifically, we sought to demonstrate whether our protocol could prevent the development of SRS, or lead to a reduced frequency/severity of SRS.

Methods

Rats were administered everolimus (2-3 mg/kg, P.O. commencing at 1, 2, or 24-hrs after SE onset) or phenobarbital (60 mg/kg, beginning 1 hr after SE onset). The rats in all studies (n=12/treatment dose/study) were then followed intermittently by video-EEG monitoring; i.e., 2-weeks on/2-weeks off, 2-weeks on epochs to determine latency to onset of SRS, and disease burden following SRS onset.

Results

While there were no adverse side effects observed in any of our studies, no treatment conferred a significant disease modifying effect, nor did any agent prevent the presentation of SRS by 6 weeks post-SE onset.

Conclusions

While neither phenobarbital nor everolimus administered at several time points post-SE onset prevented the development of SRS, we herein demonstrate a moderate-throughput screen for potential antiepileptogenic agents in an etiologically-relevant rodent model of TLE.

Key Points

Disease-modifying therapies are needed to prevent or attenuate the burden of epilepsy in at-risk individuals.

We report a moderate-throughput screening protocol to identify disease-modifying agents in a rat post-kainic acid status epilepticus model.

Everolimus was administered at multiple time points post-status epilepticus with no effect on spontaneous seizures up to 6 weeks later.

Repeated administration of phenobarbital also did not prevent the development of spontaneous recurrent seizures up to 6 weeks post SE.

While we did not identify any effect of either agent, our approach provides a moderate-throughput screen for antiepileptogenesis.
Safeguarding pollinators requires specific habitat prescriptions and substantially more land area than current policy suggests
Authors: Pindar Alana , Hogg Adam , Raine Nigel E.
Published: December 2020

Habitat loss and fragmentation are major drivers of global pollinator declines, yet even after recent unprecedented periods of anthropogenic land-use intensification the amount of habitat needed to support pollinators remains unknown. Here we use comprehensive datasets to determine the extent and amount of habitat needed. Safeguarding wild bee communities in a Canadian landscape requires 11.6-16.7% land-cover from a diverse range of habitats (~1.8-3.6x current policy guidelines), irrespective of whether conservation aims are enhancing species richness or abundance. Sensitive habitats, like tallgrass woodlands and wetlands, were important predictors of bee biodiversity. Conservation strategies that under-estimate the extent of habitat, spatial scale and specific habitat needs of functional guilds are unlikely to protect bee communities and the essential pollination services they provide to crops and wild plants.

One sentence summary

Safeguarding wild bee communities requires 11.6-16.7% of the area in common North American landscapes to provide targeted habitat prescriptions for different functional guilds over a variety of spatial scales.
Scalable Analysis of Multi-Modal Biomedical Data
Authors: Smith Jaclyn , Shi Yao , Benedikt Michael , Nikolic Milos
Published: December 2020

Targeted diagnosis and treatment options are dependent on insights drawn from multi-modal analysis of large-scale biomedical datasets. Advances in genomics sequencing, image processing, and medical data management have supported data collection and management within medical institutions. These efforts have produced large-scale datasets and have enabled integrative analyses that provide a more thorough look of the impact of a disease on the underlying system. The integration of large-scale biomedical data commonly involves several complex data transformation steps, such as combining datasets to build feature vectors for learning analysis. Thus, scalable data integration solutions play a key role in the future of targeted medicine. Though large-scale data processing frameworks have shown promising performance for many domains, they fail to support scalable processing of complex datatypes. To address these issues and achieve scalable processing of multi-modal biomedical data, we present TraNCE, a framework that automates the difficulties of designing distributed analyses with complex biomedical data types. We outline research and clinical applications for the platform, including data integration support for building feature sets for classification. We show that the system is capable of outperforming the common alternative, based on “flattening” complex data structures, and runs efficiently when alternative approaches are unable to perform at all.

Key Points

Modern biomedical analyses are integrated pipelines of data access mechanisms and analysis components that operate on and produce datasets in a variety of complex, domain specific formats.

Scalable data integration and aggregation solutions that support joint inference on such large-scale datasets play a key role advancing biomedical analysis.

Query compilation techniques that optimize nested data processing are essential for scaling multi-modal, biomedical analysis.
Longitudinal profiling of the macaque vaginal microbiome reveals similarities to diverse human vaginal communities: implications for use as a pre-clinical model for bacterial vaginosis
Authors: Rhoades Nicholas S. , Hendrickson Sara M. , Gerken Danielle R. , Martinez Kassandra , Slayden Ov D. , Slifka Mark K. , Messaoudi Ilhem
Published: December 2020

The vaginal microbiota plays an important role in women’s reproductive and urogenital health. Disturbances in this microbial community can lead to several adverse outcomes including pelvic inflammatory disease, bacterial vaginosis (BV) as well as increased susceptibility to sexually transmitted infections, miscarriage, and pre-term births. It is now well accepted that while the microbiome of healthy women in the developed world is dominated byLactobacillusspecies, vaginal communities in asymptomatic women, especially those in the developing world, can be comprised of a diverse set of micro-organisms. The presence of a diverse vaginal microbiome has been associated with increased susceptibility to HIV infection but their implications for women’s health remain poorly understood. Rhesus macaques are an excellent translational animal model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive age female rhesus macaques. Many animals showed hallmarks of BV, including Nugent scores above 7 and high vaginal pH. At both the taxonomic and functional level, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic gram-negative bacteria, including;Snethia,Prevotella, Porphyromonas, andMobilluncus. Interestingly, some animals were transiently colonized byLactobacillusand some withGardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to test interventions for manipulating the vaginal microbiome.

IMPORTANCE

It is widely accepted that the “healthy” vaginal microbiome of the majority of women in the developed world is dominated byLactobacillusspecies. However, in the developing world, a majority of women are colonized by diverse microbial communities, typically associated with bacterial vaginosis, but remain asymptomatic. Many questions remain about the drivers of this disparity and potential interventions to alter the vaginal microbiome. Rhesus macaques provide an excellent translational model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive age rhesus macaques. At the taxonomic, genomic, and functional level, the rhesus macaque vaginal microbiome was most similar to that of humans who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques to test interventions for manipulating the vaginal microbiome.