bluuebunny/crossref_metadata_2025_split huggingface dataset:
LIQ HD (Lick Instance Quantifier Home cage Device): An open-source tool for recording undisturbed two-bottle drinking behavior in a home cage environment
Authors: Petersen Nicholas , Adank Danielle N. , Raghavan Ritika , Winder Danny G. , Doyle Marie A. 
Published: December 2022

AbstractInvestigation of rodent drinking behavior has provided insight into drivers of thirst, circadian rhythms, anhedonia, and drug and ethanol consumption. Traditional methods of recording fluid intake involve weighing bottles, which is cumbersome and lacks temporal resolution. Several open-source devices have been designed to improve drink monitoring, particularly for two-bottle choice tasks. However, recent designs are limited by the use of infrared photobeam sensors and incompatibility with prolonged undisturbed use in ventilated home cages. Beam-break sensors lack accuracy for bout microstructure analysis and are prone to damage from rodents. Thus, we designed LIQ HD (Lick Instance Quantifier Home cage Device) with the goal of utilizing capacitive sensors to increase accuracy and analyze lick microstructure, building a device compatible with ventilated home cages, increasing scale with prolonged undisturbed recordings, and creating a design that is easy to build and use with an intuitive touchscreen graphical user interface. The system tracks two-bottle choice licking behavior in up to 18 rodent cages, or 36 single bottles, on a minute-to-minute timescale controlled by a single Arduino microcontroller. The data are logged to a single SD card, allowing for efficient downstream analysis. With sucrose, quinine, and ethanol two-bottle choice tasks, we validated that LIQ HD has superior accuracy compared to photobeam sensors. The system measures preference over time and changes in bout microstructure, with undisturbed recordings lasting up to 7 days. All designs and software are open-source to allow other researchers to build upon the system and adapt LIQ HD to their animal home cages.Significance StatementTwo-bottle choice drinking tasks are traditionally performed by periodically weighing bottles, which is cumbersome and lacks temporal resolution. Several open-source tools have been developed to improve drink monitoring in various settings. However, no open-source devices have been designed specifically to investigate temporally precise two-bottle choice drinking behavior and bout microstructure during prolonged undisturbed tasks in mouse ventilated home cages at a large scale. Our design, LIQ HD (Lick Instance Quantifier Home cage Device), is a home cage compatible system that utilizes capacitive sensors for highly accurate lick detection during two-bottle choice tasks in up to 18 cages driven by a single Arduino microcontroller. The system is low-cost, easy to build, and controlled via touchscreen with an intuitive graphical user interface.
Identification of a Non-Canonical Ciliate Nuclear Genetic Code Where UAA and UAG Code for Different Amino Acids
Authors: McGowan Jamie , Kilias Estelle S. , Alacid Elisabet , Lipscombe James , Jenkins Benjamin H. , Gharbi Karim , Kaithakottil Gemy G. , Macaulay Iain C. , McTaggart Seanna , Warring Sally D. , Richards Thomas A. , Hall Neil , Swarbreck David 
Published: December 2022

AbstractThe genetic code is one of the most highly conserved features across life. Only a few lineages have deviated from the “universal” genetic code. Amongst the few variants of the genetic code reported to date, the codons UAA and UAG virtually always have the same translation, suggesting that their evolution is coupled. Here, we report the genome and transcriptome sequencing of a novel ciliate, belonging to the Oligohymenophorea class, where the translation of the UAA and UAG stop codons have changed to specify different amino acids. Genomic and transcriptomic analyses revealed that UAA has been reassigned to encode lysine, while UAG has been reassigned to encode glutamic acid. We identified multiple suppressor tRNA genes with anticodons complementary to the reassigned codons. We show that the retained UGA stop codon is enriched in the 3’UTR immediately downstream of the coding region of genes, suggesting that there is functional drive to maintain tandem stop codons. Using a phylogenomics approach, we reconstructed the ciliate phylogeny and mapped genetic code changes, highlighting the remarkable number of independent genetic code changes within the Ciliophora group of protists. According to our knowledge, this is the first report of a genetic code variant where UAA and UAG encode different amino acids.
Population variation in lipid depletion during parental care in male threespine sticklebacks (Gasterosteus aculeatus)
Authors: Scott Robert 
Published: December 2022

AbstractI examined changes in stored lipid over the parental care interval in several populations of threespine stickleback (Gasterosteus aculeatus). Males from the limnetic populations and the marine population decreased in stored lipids over the progression of the nesting interval. Of the two benthic populations, one (Hotel Lake) did not decrease stored lipids over the parental care interval, as predicted, whereas the other (Crystal Lake) showed declining stored lipids over the parental care interval. Though food resources are likely high in the nesting area of Crystal Lake, the high density of conspecific cannibal groups in the littoral zone likely contributes to reduced foraging and elevated guarding/diversionary display behaviour and dependency on stored lipids to fuel those behaviours in the Crystal Lake (benthic) population. This study demonstrates the value of considering different ecological conditions on behavioural and energetic constraints among populations of threespine stickleback.
Enhanced assembly of bacteriophage T7 produced in cell-free reactions under simulated microgravity
Authors: Lehr François-Xavier , Pavletić Bruno , Glatter Timo , Heimerl Thomas , Moeller Ralf , Niederholtmeyer Henrike 
Published: December 2022

AbstractOn-demand biomanufacturing has the potential to improve healthcare and self-sufficiency during space missions. Cell-free transcription and translation reactions combined with DNA blueprints can produce promising therapeutics like bacteriophages and virus-like particles. However, how space conditions affect the synthesis and self-assembly of such complex multi-protein structures is unknown. Here, we characterize the cell-free production of infectious bacteriophage T7 virions under simulated microgravity. Rotation in a 2D-clinostat increased the number of infectious particles compared to static controls. Quantitative analyses by mass spectrometry, immuno-dot-blot and real-time PCR showed no significant differences in protein and DNA contents, suggesting enhanced self-assembly of T7 phages in simulated microgravity. While the effects of genuine space conditions on the cell-free synthesis and assembly of bacteriophages remain to be investigated, our findings support the vision of a cell-free synthesis-enabled “astropharmacy”.
A scalable and robust system for Audience EEG recordings
Authors: Michalareas Georgios , Rudwan Ismat M.A. , Lehr Claudia , Gessini Paolo , Tavano Alessandro , Grabenhorst Matthias 
Published: December 2022

ABSTRACTThe neural mechanisms that unfold when humans form a large group defined by an overarching context, such as audiences in theater or sports, are largely unknown and unexplored. This is mainly due to the lack of availability of a scalable system that can record the brain activity from a significantly large portion of such an audience simultaneously. Although the technology for such a system has been readily available for a long time, the high cost as well as the large overhead in human resources and logistic planning have prohibited the development of such a system. However, during the recent years reduction in technology costs and size have led to the emergence of low-cost, consumer-oriented EEG systems, developed primarily for recreational use. Here by combining such a low-cost EEG system with other off-the-shelve hardware and tailor-made software, we develop in the lab and test in a cinema such a scalable EEG hyper-scanning system. The system has a robust and stable performance and achieves accurate unambiguous alignment of the recorded data of the different EEG headsets. These characteristics combined with small preparation time and low-cost make it an ideal candidate for recording large portions of audiences.HighlightsA scalable EEG hyper-scanning system for recording audiences and large groups is presented with the following characteristics.Off-the-shelve, low cost components, namely a MUSE EEG headset, a Raspberry Pi computer and Photodiode.A Python library, available to the public, has been specifically developed from first principles, optimized for facilitating robust recording over Bluetooth even when multiple EEG headsets are in close proximity.The use of photodiodes provides unambiguous data alignment between the different systems.A proof-of-concept system with 10 EEG headsets has been tested in the lab but also in naturalistic conditions, recording members of the audience in four different long movie screenings in the cinema of the German Film Museum.
Ythdf2 regulates cardiac remodeling through its m6A-mRNA target transcripts
Authors: Kmietczyk V. , Oelschläger J. , Varma E. , Hartl S. , Konstandin M. , Marx A. , Gupta P. , Loewenthal Z. , Kamuf-Schenk V. , Jürgensen L. , Stroh C. , Gorska A. , Jakobi T. , Frey N. , Völkers M. 
Published: December 2022

Abstractm6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytesin vivoleads to cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. Similarly,in vitrothe knockdown of Ythdf2 results in cardiomyocyte growth and remodeling. Mechanistically, we identified the eucaryotic elongation factor 2 as a major target of Ythdf2 using cell type specific Ribo-seq data. Our study expands our understanding on the regulatory functions of m6A methylation in cardiomyocytes and how cardiac function is controlled by the m6A reader protein Ythdf2.
High Throughput Detection of Capillary Stalling Events with Bessel Beam Two-Photon Microscopy
Authors: Giblin John , Kura Sreekanth , Nunuez Juan Luis Ugarte , Zhang Juncheng , Kureli Gulce , Jiang John , Boas David A. , Chen Ichun A. 
Published: December 2022

AbstractDisruptions in capillary flow have the potential to drive pathology across numerous diseases. But our understanding of the temporal and spatial dynamics of these events are hindered by slow volumetric imaging rates and the reliance on laborious manual analysis to process data. To address the challenges of increasing volumetric imaging speed, we use a custom-built Bessel beam two-photon microscope for efficient volumetric imaging of the capillary network. We demonstrate its ability to continuously monitor roughly 200 capillaries for capillary flow stoppages (i.e. stalling events) at a frame rate of approximately 0.5 Hz and develop a semi-automated correlation-based approach for identifying these stalling events. We applied our system and algorithm in a photothrombotic model of stroke and show elevated levels of stalling 1-week post-stroke in regions both within and outside of the stroke region, demonstrating that stalling may have impacts on stroke recovery that extend past the acute stage.
Controlled delivery of ultrasound through the head for effective and safe therapies of the brain
Authors: Riis Tom , Wilson Matthew , Kubanek Jan 
Published: December 2022

ABSTRACTTranscranial focused ultrasound provides noninvasive and reversible approaches for precise and personalized manipulations of brain circuits, with the potential to transform our understanding of brain function and treatments of brain dysfunction. However, the effectiveness and safety of these approaches have been limited by the human head, which attenuates and distorts ultrasound strongly and unpredictably. To address this lingering barrier, we have developed a “Relative Through-Transmit” (RTT) approach that directly measures and compensates for the attenuation and distortion of a given skull and scalp. We have implemented RTT in hardware and demonstrated that it accurately restores the operator’s intended intensities inside ex-vivo human skulls. Moreover, this functionality enabled effective and intensity-dependent transcranial modulation of nerves and effective release of defined doses of propofol inside the skull. RTT was essential for these new applications of transcranial ultrasound; when not applied, there were no significant differences from sham conditions. Moreover, RTT was safely applied in humans and accounted for all intervening obstacles including hair and ultrasound coupling. This method and hardware unlock the potential of ultrasound-based approaches to provide effective, safe, and reproducible precision therapies of the brain.
Having “multiple selves” helps learning agents explore and adapt in complex changing worlds
Authors: Dulberg Zack , Dubey Rachit , Berwian Isabel M. , Cohen Jonathan 
Published: December 2022

Satisfying a variety of conflicting needs in a changing environment is a fundamental challenge for any adaptive agent. Here, we show that designing an agent in a modular fashion as a collection of subagents, each dedicated to a separate need, powerfully enhanced the agent’s capacity to satisfy its overall needs. We used the formalism of deep reinforcement learning to investigate a biologically relevant multi-objective task: continually maintaining homeostasis of a set of physiologic variables. We then conducted simulations in a variety of environments and compared how modular agents performed relative to standard monolithic agents (i.e., agents that aimed to satisfy all needs in an integrated manner using a single aggregate measure of success). Simulations revealed that modular agents: a) exhibited a form of exploration that was intrinsic and emergent rather than extrinsically imposed; b) were robust to changes in non-stationary environments, and c) scaled gracefully in their ability to maintain home-ostasis as the number of conflicting objectives increased. Supporting analysis suggested that the robustness to changing environments and increasing numbers of needs were due to intrinsic exploration and efficiency of representation afforded by the modular architecture. These results suggest that the normative principles by which agents have adapted to complex changing environments may also explain why humans have long been described as consisting of ‘multiple selves’.Significance StatementAdaptive agents must continually satisfy a range of distinct and possibly conflicting needs. In most models of learning, a monolithic agent tries to maximize one value that measures how well it balances its needs. However, this task is difficult when the world is changing and needs are many. Here, we considered an agent as a collection of modules each dedicated to a particular need and competing for control of action. Compared to the standard monolithic approach, modular agents were much better at maintaining homeostasis of a set of internal variables in simulated environments, both static and changing. These results suggest that having ‘multiple selves’ may represent an evolved solution to the universal problem of balancing multiple needs in changing environments.
Motion Impact Score for Detecting Spurious Brain-Behavior Associations
Authors: Kay Benjamin P. , Montez David F. , Marek Scott , Tervo-Clemmens Brenden , Siegel Joshua S. , Adeyemo Babatunde , Laumann Timothy O. , Metoki Athanasia , Chauvin Roselyne J. , Van Andrew N. , Suljic Vahdeta , Krimmel Samuel R. , Miller Ryland L. , Newbold Dillan J. , Zheng Annie , Seider Nicole A. , Scheidter Kristen M. , Monk Julia , Feczko Eric , Randolph Anita , Miranda-Dominguez Oscar , Moore Lucille A. , Perrone Anders J. , Earl Eric A. , Malone Stephen M. , Cordova Michaela , Doyle Olivia , Lynch Benjamin J. , Wilgenbusch James C. , Pengo Thomas , Graham Alice M. , Roland Jarod L. , Gordon Evan M. , Snyder Abraham Z. , Barch Deanna M. , Fair Damien A. , Dosenbach Nico U.F. 
Published: December 2022

AbstractBetween-participant differences in head motion introduce systematic bias to resting state fMRI brain-wide association studies (BWAS) that is not completely removed by denoising algorithms. Researchers who study traits, or phenotypes associated with in-scanner head motion (e.g. psychiatric disorders) need to know if trait-functional connectivity (FC) effects are biased by residual motion artifact in order to avoid reporting false positive results. We devised an adaptable method, Split Half Analysis of Motion Associated Networks (SHAMAN), to assign a motion impact score to specific trait-FC effects. The SHAMAN approach distinguishes between motion artifact causing overestimation or underestimation of trait-FC effects. SHAMAN was > 95% specific at sample sizes of n = 100 and above. SHAMAN was powered to detect motion overestimation scores 80% of the time at sample sizes of n = 5,000 but could detect motion underestimation scores only 50% of the time at n = 5000, making it most useful for researchers seeking to avoid overestimating trait-FC effects in large BWAS. We computed motion impact scores for trait-FC effect with 45 demographic, biophysical, cognitive, and personality traits from n = 7,270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without motion censoring, 42% (19/45) of traits had significant (p < 0.05) motion overestimation scores and 38% (17/45) of traits had significant motion underestimation scores. Censoring at framewise displacement (FD) < 0.2 mm reduced the proportion of traits with significant motion overestimation scores from 42% to 2% (1/45) but did not decrease the number of traits with significant motion underestimation scores.
Histidine 73 methylation coordinatesβ-actin plasticity in response to key environmental factors
Authors: Schahl Adrien , Lagardère Louis , Walker Brandon , Ren Pengyu , Wioland Hugo , Ballet Maya , Jégou Antoine , Chavent Matthieu , Piquemal Jean-Philip 
Published: December 2022

AbstractThe functional importance of the methylation of histidine 73 (H73) in actin remains unclear. Focusing on cytoplasmicβ-actin, present in all mammalian cells, we use molecular dynamics simulations with a polarizable force field and adaptive sampling to examine the effects of H73 methylation. Our results show that methylation enhances nucleotide binding cleft opening, alters allosteric pathways connecting subdomains 2 and 4 (SD2 and SD4) in G-actin, and affects backdoor openings and inorganic phosphate release in F-actin, as validated by biochemical assays. These effects depend on the nucleotide and ions interacting with the actin. Together, our findings reveal how H73 methylation regulatesβ-actin plasticity and integrates environmental cues.
An important role for triglyceride in regulating spermatogenesis
Authors: Chao Charlotte F. , Pesch Yanina-Yasmin , Yu Huaxu , Wang Chenjingyi , Aristizabal Maria J. , Huan Tao , Tanentzapf Guy , Rideout Elizabeth J. 
Published: December 2022

ABSTRACTDrosophilais a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear. Here, we show LD are present in early-stage somatic and germline cells within theDrosophilatestis. We identified a role for triglyceride lipasebrummer(bmm) in regulating testis LD, and found that whole-body loss ofbmmleads to defects in sperm development. Importantly, these represent cell-autonomous roles forbmmin regulating testis LD and spermatogenesis. Because lipidomic analysis ofbmmmutants revealed excess triglyceride accumulation, and spermatogenic defects inbmmmutants were rescued by genetically blocking triglyceride synthesis, our data suggest thatbmm-mediated regulation of triglyceride influences sperm development. This identifies triglyceride as an important neutral lipid that contributes toDrosophilasperm development, and reveals a key role forbmmin regulating testis triglyceride levels during spermatogenesis.
A combined biochemical and cellular approach reveals Zn2+-dependent hetero- and homodimeric CD4 and Lck assemblies in T cells
Authors: Kocyła Anna , Czogalla Aleksander , Wessels Inga , Rink Lothar , Krężel Artur 
Published: December 2022

AbstractThe CD4 or CD8 co-receptors’ interaction with the protein-tyrosine kinase Lck is widely accepted as the initiator of the tyrosine phosphorylation cascade leading to T-cell activation. These co-receptors potentially enhance T-cell antigen sensitivity, but how they function is still debated. A critical question is: to what extent are co-receptors and signal-initiating Lck coupled? Our contribution concerns the small – but indispensable for CD4- and CD8-Lck formation – element Zn2+. The intracellular Zn2+pool is strictly buffered but undergoes dynamic changes, also reported during T-cell activation. Furthermore, the identical Zn2+-binding cysteinyl residues may alter co-receptor dimerization or heterodimerization with Lck. Following initial research demonstrating a significant difference in the affinity of Zn2+to CD4 and CD4-Lck in solution, we combined biochemical and cellular approaches to show that fluctuations of buffered Zn2+in physiological ranges indeed influence Zn(CD4)2and Zn(CD4)(Lck). This conclusion was supported by the simulation of complexes’ equilibria, demonstrating that Zn2+changes can alter the molar ratio between those complexes. In T cells, increased intracellular free Zn2+concentration causes higher CD4 partitioning in the plasma membrane by a still unknown mechanism. We additionally found that CD4 palmitoylation decreases the specificity of CD4-Lck formation in the reconstituted membrane model, suggesting that this reversible modification may also be involved. Our findings help elucidate co-receptor-Lck coupling stoichiometry and demonstrate that intracellular free Zn2+has a major role in the interplay between CD4 dimers and CD4-Lck assembly.