bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Programmable Model for Exploring the Functional Logic of the Drosophila Antennal Lobe
Authors: Lazar Aurel A. , Turkcan Mehmet Kerem , Zhou Yiyin 
Published: September 2022

AbstractRecent progress on connectomics has resulted in huge datasets of brain structures in single-synapse scale. This calls for the modeling of executable circuits to discover the functional logic of these neural circuits in different scales. To provide an approach to standardize analyses of neuropils with multiple-input-multi-output channels, we put forward a programmable model focusing on the antennal lobe (AL), a circuit at the periphery of the olfactory system with nonlinear computation. We present an approach for constructing and analyzing antennal lobe circuits using models of glomeruli and local feedback loops. We establish the composability of the connectivity of glomeruli with local neuron feedback loops by combining pairs of glomeruli, and then by combining all glomeruli together to characterize the I/O of the entire AL. We thus provide a methodology for the quantitative characterization of the I/O of the AL as a function of feedback loop motifs.
Sequence-based Optimized Chaos Game Representation and Deep Learning for Peptide/Protein Classification
Authors: Huang Beibei , Zhang Eric , Chaudhari Rajan , Gimperlein Heiko 
Published: September 2022

AbstractAs an effective graphical representation method for 1D sequence (e.g., text), Chaos Game Representation (CGR) has been frequently combined with deep learning (DL) for biological analysis. In this study, we developed a unique approach to encode peptide/protein sequences into CGR images for classification. To this end, we designed a novel energy function and enhanced the encoder quality by constructing a Supervised Autoencoders (SAE) neural network. CGR was used to represent the amino acid sequences and such representation was optimized based on the latent variables with SAE. To assess the effectiveness of our new representation scheme, we further employed convolutional neural network (CNN) to build models to study hemolytic/non-hemolytic peptides and the susceptibility/resistance of HIV protease mutants to approved drugs. Comparisons were also conducted with other published methods, and our approach demonstrated superior performance.Supplementary informationavailable online
In-situ quality monitoring during embedded bioprinting using integrated microscopy and classical computer vision
Authors: Sergis Vasileios , Kelly Daniel , Britchfield Graham , Pramanick Ankita , Mason Karl , Daly Andrew 
Published: September 2022

AbstractDespite significant advances in bioprinting technology, current hardware platforms lack the capability for process monitoring and quality control. This limitation hampers the translation of the technology into industrial GMP-compliant manufacturing settings. To address this, we developed a novel bioprinting platform integrating a high-resolution camera for in-situ monitoring of extrusion outcomes during embedded bioprinting. Leveraging classical computer vision and image analysis techniques, we then created a custom software module for assessing print quality. This module enables quantitative comparison of printer outputs to input CAD models, measuring area and positional accuracy. To showcase the platform’s capabilities, we then investigated how the rheological properties of granular support hydrogels impact print quality during embedded bioprinting. Our results demonstrated that lower viscosity, faster thixotropy recovery, and smaller particle sizes significantly enhance print fidelity. This novel bioprinting platform, equipped with integrated process monitoring, holds great potential for establishing robust, reliable, and auditable biofabrication processes for industrial applications.
Regulation of oligodendrocyte lineage development by VAMP2/3 in the developing mouse spinal cord
Authors: Fekete Christopher D. , Horning Robert Z. , Doron Matan S. , Nishiyama Akiko 
Published: September 2022

AbstractIn the developing and adult CNS, new oligodendrocytes (OLs) are generated from a population of cells known as oligodendrocyte precursor cells (OPCs). As they begin to differentiate, OPCs undergo a series of highly regulated changes to morphology, gene expression, and membrane organization. This stage represents a critical bottleneck in oligodendrogenesis, and the regulatory program that guides it is still not fully understood. Here we show thatin vivotoxin-mediated cleavage of the vesicle associated SNARE proteins VAMP2/3 in the OL lineage of both male and female mice impairs the ability of early OLs to mature into functional, myelinating OLs. In the developing mouse spinal cord, many VAMP2/3-deficient OLs appeared to stall in the premyelinating, early OL stage, resulting in an overall loss of both myelin density and OL number. The Src kinase Fyn, a key regulator of oligodendrogenesis and myelination, is highly expressed among premyelinating OLs, but its expression decreases as OLs mature. We found that OLs lacking VAMP2/3 in the spinal cord white matter showed significantly higher expression of Fyn compared to neighboring control cells, potentially due to an extended premyelinating stage. Overall, our results show that functional VAMP2/3 in OL lineage cells is essential for proper myelin formation and plays a major role in controlling the maturation and terminal differentiation of premyelinating OLs.Significance StatementThe production of mature oligodendrocytes (OLs) is essential for CNS myelination during development, myelin remodeling in adulthood, and remyelination following injury or in demyelinating disease. Prior to myelin sheath formation, newly formed OLs undergo a series of highly regulated changes during a stage of their development known as the premyelinating, or early OL stage. This stage acts as a critical checkpoint in OL development, and much is still unknown about the dynamic regulatory processes involved. In this study, we show that VAMP2/3, SNARE proteins involved in vesicular trafficking and secretion, play an essential role in regulating premyelinating OL development and are required for healthy myelination in the developing mouse spinal cord.
Bull Trout passage at beaver dams in two Montana streams
Authors: Wolf J. Marshall , Clancy Niall G. , Rosenthal Leo R. 
Published: September 2022

ABSTRACTBeaver (Castor canadensis) translocation and mimicry is an increasingly popular tool for process-based restoration of degraded streams. Processes influenced by beaver restoration include stream-floodplain connectivity, multi-threaded channel formation, enhanced riparian condition and fire resiliency, and streamflow attenuation. Beaver activity can also be a nuisance in agricultural settings, increase invasive species abundance, and create in-stream barriers to fish. Previous studies indicate that spring-spawning salmonid species can pass beaver dams in higher proportions than fall-spawning species. Thus, restoration or mimicry of beavers in streams containing fall-spawning, threatened Bull Trout (Salvelinus confluentus) is of concern to many biologists. We evaluated Bull Trout passage at beaver dams in two Montana streams: Meadow Creek (East Fork Bitterroot River drainage) in summer 2020 and Morrison Creek (Middle Fork Flathead River drainage) from 1997 to 2011. In Meadow Creek, 16% of PIT-tagged Bull Trout which entered a large beaver dam complex were detected upstream of some dams, but no fish moved through the entire 1 km complex. In Morrison Creek, redds were more likely than random to be located below dams, but two or more redds were found upstream of at least one dam in 6 of 9 years dams were present. These results suggest that beaver dams can affect the movement of Bull Trout, but that passage depends on the characteristics of individual dams and reach geomorphology. Our methods cannot distinguish between inhibition of fish movement and selection of beaver-created habitats by fish. Therefore, we suggest future research on beaver restoration in streams with Bull trout.
Drivers of interlineage variability in mitogenomic evolutionary rates in flatworms (Platyhelminthes) are multifactorial
Authors: Jakovlić Ivan , Zou Hong , Ye Tong , Wang Gui-Tang , Li Wen-Xiang , Zhang Dong 
Published: September 2022

AbstractThe forces driving interlineage variability in the evolutionary rates (both sequence and architecture) of mitochondrial genomes are often inconsistent and unpredictable. Herein we studied the impacts of multiple variables using 223 flatworm (Platyhelminthes) species and phylogenetic multilevel regression models. We found that: 1. Mitogenomic sequence evolution is faster in parasites associated with the thermally stable environment of endothermic hosts, but the overall impact of thermic habitat is small; 2. Mitogenome sizes are smaller in parasites of endothermic hosts, but the effects are small and inconsistent; 3. Mitogenomic gene order rearrangements (GORR) are positively correlated with mitogenomic size; 4. The expected positive correlation between GORR and sequence evolution is lineage-specific, and non-parasitic species exhibited a strong negative correlation; 5. Longevity has negligible impacts on mitogenomic evolution; 6. Parasitic (Neodermata) flatworm lineages exhibit higher evolutionary rates than non-parasitic lineages; 7. The effective population size has negligible impacts on mitogenomic evolution; 8. Comparatively, parasitism had by far the greatest impact on the mitogenomic evolution, but due to the monophyletic origin of this life-history strategy, alternative hypotheses cannot be rejected. A large number of factors impact the mitogenomic evolution in flatworms, with lineage-specific relative contributions, which sometimes produces incongruent lineage-specific mitogenomic evolution patterns.
Two-color live-cell STED nanoscopy by click labeling with cell-permeable fluorophores
Authors: Gregor Carola , Grimm Florian , Rehman Jasmin , Wurm Christian A. , Egner Alexander 
Published: September 2022

AbstractSTED nanoscopy allows for the direct observation of dynamic processes in living cells and tissues with diffraction-unlimited resolution. Although fluorescent proteins can be used for STED imaging, these labels are often outperformed in photostability by organic fluorescent dyes. This feature is especially crucial for time-lapse imaging. Unlike fluorescent proteins, organic fluorophores cannot be genetically fused to a target protein but require different labeling strategies. To achieve simultaneous imaging of more than one protein in the interior of the cell with organic fluorophores, bioorthogonal labeling techniques and cell-permeable dyes are required. In addition, the fluorophores should preferentially emit in the red spectral range to reduce potential phototoxic effects that can be induced by the STED light, which further restricts the choice of suitable markers. Here we demonstrate two-color STED imaging of living cells using various pairs of dyes that fulfill all of the above requirements. To this end, we combine click-chemistry-based protein labeling with other orthogonal and highly specific labeling methods, enabling long-term STED imaging of different target structures in living specimens.
Basolateral amygdala astrocytes are engaged by the acquisition and expression of a contextual fear memory
Authors: Suthard Rebecca L. , Senne Ryan A. , Buzharsky Michelle D. , Pyo Angela Y. , Dorst Kaitlyn E. , Diep Anh (Mia) H. , Cole Rebecca H. , Ramirez Steve 
Published: September 2022

AbstractAstrocytes are key cellular regulators within the brain. The basolateral amygdala (BLA) is implicated in fear memory processing, yet most research has entirely focused on neuronal mechanisms, despite a significant body of work implicating astrocytes in learning and memory. In the present study, we usedin vivofiber photometry to record from amygdalar astrocytes across fear learning, recall, and three separate periods of extinction. We found that BLA astrocytes robustly responded to foot shock during acquisition, that their activity remained remarkably elevated across days in comparison to unshocked control animals, and that their increased activity persisted throughout extinction. Further, we found that astrocytes responded to the initiation and termination of freezing bouts during contextual fear conditioning and recall, and this behavior-locked pattern of activity did not persist throughout the extinction sessions. Importantly, astrocytes do not display these changes while exploring a novel context, suggesting that these observations are context or memory-dependent. Chemogenetic inhibition of fear ensembles in the BLA did not affect freezing behavior or astrocytic calcium dynamics. Overall, our work presents a real-time role for amygdalar astrocytes in fear processing and provides new insight into the emerging role of these cells in cognition and behavior.Significance StatementWe show that basolateral amygdala astrocytes are robustly responsive to footshock, exhibit unique calcium event characteristics following contextual fear acquisition, and ramp up activity at the initiation and termination of freezing bouts during fear conditioning and recall. This astrocytic calcium response to freezing behavior is not observed during extinction sessions, despite unique calcium events continuing through three days of training compared to no-shock controls. We find that astrocytes display context specific changes in calcium signaling, but chemogenetic inhibition of BLA fear ensembles does not impact freezing behavior or calcium dynamics. These findings show that astrocytes play a key, real-time role in fear learning and memory.
Structures of RecBCD in complex with phage-encoded inhibitor proteins reveal distinctive strategies for evasion of a bacterial immunity hub
Authors: Wilkinson M. , Wilkinson O.J. , Feyerherm C. , Fletcher E.E. , Wigley D.B. , Dillingham M.S. 
Published: September 2022

AbstractFollowing infection of bacterial cells, bacteriophage modulate double-stranded DNA break repair pathways to protect themselves from host immunity systems and prioritise their own recombinases. Here we present biochemical and structural analysis of two phage proteins, gp5.9 and Abc2, which target the DNA break resection complex RecBCD. These exemplify two contrasting mechanisms for control of DNA break repair in which the RecBCD complex is either inhibited or co-opted for the benefit of the invading phage. Gp5.9 completely inhibits RecBCD by preventing it from binding to DNA. The RecBCD-gp5.9 structure shows that gp5.9 acts by substrate mimicry, binding predominantly to the RecB arm domain and competing sterically for the DNA binding site. Gp5.9 adopts a parallel coiled-coil architecture that is unprecedented for a natural DNA mimic protein. In contrast, binding of Abc2 does not substantially affect the biochemical activities of isolated RecBCD. The RecBCD-Abc2 structure shows that Abc2 binds to the Chi-recognition domains of the RecC subunit in a position that might enable it to mediate the loading of phage recombinases onto its single-stranded DNA products.
Subthreshold serotonin signals combined by the G proteins Gαq and Gαs activate the C. elegans egg-laying muscles
Authors: Olson Andrew C. , Butt Allison M. , Christie Nakeirah T.M. , Shelar Ashish , Koelle Michael R. 
Published: September 2022

AbstractIndividual neuron or muscle cells express many G protein coupled receptors (GPCRs) for neurotransmitters and neuropeptides. It remains unclear how these cells integrate multiple GPCR signals that all must act through the same few G proteins. We investigated how two serotonin GPCRs, Gαq-coupled SER-1 and Gαs-coupled SER-7, function together on the C. elegans egg-laying muscles to promote contraction and thus cause eggs to be laid. Using receptor null mutations and cell-specific knockdowns, we found that serotonin signaling through either SER-1/Gαq or SER-7/Gαs alone does not induce egg laying, but these subthreshold signals can combine to promote egg laying. However, using designer receptors or optogenetics to artificially induce high levels of either Gαq signaling or Gαs signaling in the muscles was sufficient to induce egg laying. Conversely, knocking down both Gαq and Gαs in the egg-laying muscle cells induced egg-laying defects stronger than those of a ser-7 ser-1 double knockout. These results suggest that, in the egg-laying muscles, multiple GPCRs for serotonin and other signals each produce weak effects that individually do not result in strong behavioral outcomes. However, they can combine to produce sufficient levels of Gαq and Gαs signaling to promote muscle activity and egg laying.
Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity
Authors: Briffa Amy , Hollwey Elizabeth , Shahzad Zaigham , Moore Jonathan D. , Lyons David B. , Howard Martin , Zilberman Daniel 
Published: September 2022

AbstractMethylation of CG dinucleotides (mCG), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity remains mysterious. Here we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes. MET1 activity is restricted by active demethylation and suppressed by histone variant H2A.Z. Based on these observations, we develop a mathematical model that precisely recapitulates mCG inheritance dynamics and predicts intragenic mCG patterns and their population-scale variation given only CG site spacing as input. The model reveals that intragenic mCG undergoes large, millennia-long epigenetic fluctuations, and can therefore mediate evolution on this timescale. Our results demonstrate how genic methylation patterns are created, reconcile imperfect mCG maintenance with long-term stability, and establish a quantitative model that unifies the establishment and epigenetic inheritance of mCG.HighlightsMET1 mediates a unified process of mCG establishment and maintenance within genesROS1 and H2A.Z regulate the epigenetic dynamics of genic mCGA mathematical model predicts genic mCG patterns and their population varianceGenic mCG undergoes large epigenetic fluctuations that can last thousands of years
Differential role of dopamine D3 receptor through balanced modulation of Akt/mTOR and ERK1/2 activity in the reactivation of cocaine rewarding memories evoked by psychological versus physiological stress
Authors: Franco-García Aurelio , Guerrero-Bautista Rocío , Hidalgo Juana María , Milanés María Victoria , Gómez-Murcia Victoria , Núñez Cristina 
Published: September 2022

AbstractStress is an important trigger of relapses in cocaine use. These relapses engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the dentate gyrus (DG). Further, preclinical research signals D3 receptor (D3R) antagonists as promising therapeutic tools to attenuate cocaine reward and relapse. Therefore, we assessed the effect of SB-277011-A, a D3R antagonist, in the activity of Akt/mTOR and MEK/ERK1/2 pathways in these areas during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by psychological (restraint) and physiological (tail pinch) stress. Both stimuli reactivated the extinguished cocaine-CPP, but only restrained animals decreased their locomotor activity during reinstatement. Moreover, p-Akt, p-mTOR and p-ERK1/2 activity in the BLA and DG of restrained animals decreased during the reactivation of cocaine memories, contrasting to tail-pinched mice. While D3R blockade prevented stress-induced CPP reactivation and plasmatic corticosterone enhancement, SB-277011-A distinctly modulated Akt, mTOR and ERK1/2 activities in the BLA and DG based on the stressor and the dose of antagonist. Corticosterone may be partially responsible for these variations as we found high correlations among its levels and mTOR and/or Akt activity in the BLA and DG of restrained animals receiving SB-277011-A. Besides, locomotor activity of animals receiving 48 mg/kg of the antagonist highly correlated with p-mTOR/mTOR and p-ERK1/2 /ERK1/2 in the BLA during restraint- and tail pinch-induced relapse in cocaine-CPP, respectively. Hence, our study endorses D3R antagonists as therapeutic tools to prevent stress-induced relapses in drug use through a complex balance of Akt/mTOR and MEK/ERK1/2 pathways in memory-processing brain nuclei.
Stimulation-responsive enhancers regulate inflammatory gene activation through retention and modification of H2A.Z-variant accessible nucleosomes
Authors: Sporrij Audrey , Prasad Meera , Muhire Brejnev , Fast Eva M. , Manning Margot E. , Choudhuri Avik , Weiss Jodi D. , Koh Michelle , Yang Song , Kingston Robert E. , Tolstorukov Michael Y. , Clevers Hans , Zon Leonard I. 
Published: September 2022

AbstractProstaglandin E2 (PGE2) and 16,16-dimethyl-PGE2 (dmPGE2) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies1,2. The mechanism of gene regulation in response to dmPGE2 is poorly understood. Here, we show that dmPGE2 regulates inflammatory gene induction by modulating the chromatin architecture and activity of enhancer elements in human HSPCs. We identified the specific genomic reorganization at stimuli-responsive enhancers that permits rapid transcriptional activation. We found that dmPGE2-inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes that are permissive to binding of the transcription factor CREB. CREB binding to enhancer nucleosomes is concomitant with deposition of the histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone variant nucleosomes retained within inducible enhancers facilitate transcription factor (TF) binding. Acetylation of histone variant nucleosomes by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism by which inflammatory mediators such as dmPGE2 lead to acute transcriptional changes and alter HSPC behavior.