bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex difference in the facilitation of fear learning by prior fear conditioning
Authors: Cole Kehinde E. , Parsons Ryan G. 
Published: July 2023

AbstractThere is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour, but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference.
Machine learning reveals the control mechanics of an insect wing hinge
Authors: Melis Johan M. , Siwanowicz Igor , Dickinson Michael H. 
Published: July 2023

ABSTRACTInsects constitute the most species-rich radiation of metazoa, a success due to the evolution of active flight. Unlike pterosaurs, birds, and bats, the wings of insects did not evolve from legs1, but are novel structures attached to the body via a biomechanically complex hinge that transforms tiny, high-frequency oscillations of specialized power muscles into the sweeping back-and-forth motion of the wings2. The hinge consists of a system of tiny, hardened structures called sclerites that are interconnected to one another via flexible joints and regulated by the activity of specialized control muscles. Here, we imaged the activity of these muscles in a fly using a genetically encoded calcium indicator, while simultaneously tracking the 3D motion of the wings with high-speed cameras. Using machine learning approaches, we created a convolutional neural network3that accurately predicts wing motion from the activity of the steering muscles, and an encoder-decoder4that predicts the role of the individual sclerites on wing motion. By replaying patterns of wing motion on a dynamically scaled robotic fly, we quantified the effects of steering muscle activity on aerodynamic forces. A physics-based simulation that incorporates our model of the hinge generates flight maneuvers that are remarkably similar to those of free flying flies. This integrative, multi-disciplinary approach reveals the mechanical control logic of the insect wing hinge, arguably among the most sophisticated and evolutionarily important skeletal structures in the natural world.
Electron-counting in MicroED
Authors: Hattne Johan , Clabbers Max T. B. , Martynowycz Michael W. , Gonen Tamir 
Published: July 2023

AbstractThe combination of high sensitivity and rapid readout makes it possible for electron-counting detectors to record cryogenic electron microscopy data faster and more accurately without increasing the exposure. This is especially useful for MicroED of macromolecular crystals where the strength of the diffracted signal at high resolution is comparable to the surrounding background. The ability to decrease the exposure also alleviates concerns about radiation damage which limits the information that can be recovered from a diffraction measurement. However, the dynamic range of electron-counting detectors requires careful data collection to avoid errors from coincidence loss. Nevertheless, these detectors are increasingly deployed in cryo-EM facilities, and several have been successfully used for MicroED. Provided coincidence loss can be minimized, electron-counting detectors bring high potential rewards.
Engineering transposon-associated TnpB-ωRNA system for efficient gene editing and disease treatment in mouse
Authors: Li Zhifang , Guo Ruochen , Sun Xiaozhi , Li Guoling , Liu Yuanhua , Huo Xiaona , Yang Rongrong , Shao Zhuang , Zhang Hainan , Zhang Weihong , Zhang Xiaoyin , Ma Shuangyu , Yao Yinan , Liu Xinyu , Yang Hui , Hu Chunyi , Zhou Yingsi , Xu Chunlong 
Published: July 2023

AbstractTransposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (409 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently deliveredin vivowith single adeno-associated virus (AAV) and prevented the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.
Automated Microbial Classification System based on Deep Convolutional Neural Networks using Images from Colony Picker
Authors: Park Sehyun , Yeoh Jing Wui , Choo Ching Thong , Lim Cheng Kai , Dao Viet Linh , Poh Chueh Loo 
Published: July 2023

ABSTRACTColony screening in single and multi-species environments is an essential step for microbiome studies. However, it possesses a high possibility of inaccurately classifying the species of interest and demands a high degree of manpower and time. Thus, automating the classification of microbes is beneficial to minimize the time and inaccuracy in the colony screening/picking step. Here, we developed an automated microbial classification system for five target species, based on deep Convolutional Neural Networks (CNN) using images captured by an automated robotic colony picker. Multiple possible scenarios of colony culture and diverse morphologies of colonies were examined in building the training and test datasets to train and validate the model and performance on real-life implementations. The final model trained using 60,000 training images, with 12,000 images per species and 3-fold cross-validation, achieved a test accuracy of 94.2% and a test loss of 0.154. Upon testing using a deployment dataset of 4,500 images (900 images per species) with different methods of applying cells onto the agar plate, high accuracy of up to 96.6% was obtained. Five evaluation metrics were implemented to evaluate diverse scenarios of the test data to justify the validity of the model in real-life applications. This model forms a foundation for the classification of more species through transfer learning in the future.
Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS
Authors: Angrick Miguel , Luo Shiyu , Rabbani Qinwan , Candrea Daniel N. , Shah Samyak , Milsap Griffin W. , Anderson William S. , Gordon Chad R. , Rosenblatt Kathryn R. , Clawson Lora , Maragakis Nicholas , Tenore Francesco V. , Fifer Matthew S. , Hermansky Hynek , Ramsey Nick F. , Crone Nathan E. 
Published: July 2023

AbstractRecent studies have shown that speech can be reconstructed and synthesized using only brain activity recorded with intracranial electrodes, but until now this has only been done using retrospective analyses of recordings from able-bodied patients temporarily implanted with electrodes for epilepsy surgery. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a clinical trial participant (ClinicalTrials.gov,NCT03567213) with dysarthria due to amyotrophic lateral sclerosis (ALS). We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the user from a vocabulary of 6 keywords originally designed to allow intuitive selection of items on a communication board. Our results show for the first time that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words that are intelligible to human listeners while preserving the participants voice profile.
In vivocharacterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies
Authors: Cortese Lorenzo , Fernández Esteberena Pablo , Zanoletti Marta , Lo Presti Giuseppe , Aranda Velazquez Gloria , Ruiz Janer Sabina , Buttafava Mauro , Renna Marco , Di Sieno Laura , Tosi Alberto , Dalla Mora Alberto , Wojtkiewicz Stanislaw , Dehghani Hamid , de Fraguier Sixte , Nguyen-Dinh An , Rosinski Bogdan , Weigel Udo M. , Mesquida Jaume , Squarcia Mattia , Hanzu Felicia A. , Contini Davide , Mora Porta Mireia , Durduran Turgut 
Published: July 2023

AbstractThe non-invasive monitoring of the hemodynamics and metabolism of the sternocleidomastoid muscle (SCM) during respiration became a topic of increased interest partially due to the increased use of mechanical ventilation during the COVID-19 pandemic. Near-infrared diffuse optical spectroscopies were proposed as potential practical monitors of increased recruitment of SCM during respiratory distress. They can provide clinically relevant information on the degree of the patient’s respiratory effort that is needed to maintain an optimal minute ventilation, with potential clinical application ranging from evaluating chronic pulmonary diseases to more acute settings, such as acute respiratory failure, or to determine the readiness to wean from invasive mechanical ventilation.In this paper, we present a detailed characterization of the optical properties (wave-length dependent absorption and reduced scattering coefficients) and hemodynamic properties (oxy-, deoxy- and total hemoglobin concentrations, blood flow, blood oxygen saturation and metabolic rate of oxygen extraction) of the human SCM, obtained by measuring sixty-five subjects through ultrasound-guided near-infrared time-resolved and diffuse correlation spectroscopies.We provide detailed tables of the results related to SCM baseline (i.e. muscle at rest) properties, and reveal significant differences on the measured parameters due to variables such as side of the neck, sex, age, body mass index and thickness of the overlaying tissues, allowing future clinical studies to take into account such dependencies.
The successor representation subserves hierarchical abstraction for goal-directed behavior
Authors: Wientjes Sven , Holroyd Clay B. 
Published: July 2023

ABSTRACTHumans have the ability to craft abstract, temporally extended and hierarchically organized plans. For instance, when considering how to make spaghetti for dinner, we typically concern ourselves with useful “subgoals” in the task, such as cutting onions, boiling pasta, and cooking a sauce, rather than particulars such as how many cuts to make to the onion, or exactly which muscles to contract. A core question is how such decomposition of a more abstract task into logical subtasks happens in the first place. Previous research has shown that humans are sensitive to a form of higher-order statistical learning named “community structure”. Community structure is a common feature of abstract tasks characterized by a logical ordering of subtasks. This structure can be captured by a model where humans learn predictions of upcoming events multiple steps into the future, discounting predictions of events further away in time. One such model is the “successor representation”, which has been argued to be useful for hierarchical abstraction. As of yet, no study has convincingly shown that this hierarchical abstraction can be put to use for goal-directed behavior. Here, we investigate whether participants utilize learned community structure to craft hierarchically informed action plans for goal-directed behavior. Participants were asked to search for paintings in a virtual museum, where the paintings were grouped together in “wings” representing community structure in the museum. We find that participants’ choices accord with the hierarchical structure of the museum and that their response times are best predicted by a successor representation. The degree to which the response times reflect the community structure of the museum correlates with several measures of performance, including the ability to craft temporally abstract action plans. These results suggest that successor representation learning subserves hierarchical abstractions relevant for goal-directed behavior.AUTHOR SUMMARYHumans have the ability to achieve a diverse range of goals in a highly complex world. Classic theories of decision making focus on simple tasks involving single goals. In the current study, we test a recent theoretical proposal that aims to address the flexibility of human decision making. By learning to predict the upcoming events, humans can acquire a ‘model’ of the world which they can then leverage to plan their behavior. However, given the complexity of the world, planning directly over all possible events can be overwhelming. We show that, by leveraging this predictive model, humans group similar events together into simpler “hierarchical” representations, which makes planning over these hierarchical representations markedly more efficient. Interestingly, humans seem to learn and remember both the complex predictive model and the simplified hierarchical model, using them for distinct purposes.
Post-exposure intranasal IFNα suppresses replication and neuroinvasion of Venezuelan Equine Encephalitis virus within olfactory sensory neurons
Authors: Cain Matthew D. , Rubin Klein N. , Jiang Xiaoping , Klein Robyn S. 
Published: July 2023

ABSTRACTVenezuelan Equine Encephalitis virus(VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied. Here, we utilized an established murine model of intranasal infection with VEEV to assess the cellular targets and IFN signaling responses after VEEV exposure. We found that immature OSN, which express higher levels of the VEEV receptor LDLRAD3 than mature OSN, are the first cells infected by VEEV. Despite rapid VEEV neuroinvasion after intranasal exposure, olfactory neuroepithelium (ONE) and olfactory bulb (OB) IFN responses, as assessed by evaluation of expression of interferon signaling genes (ISG), are delayed for up to 48 hours during VEEV neuroinvasion, representing a potential therapeutic window. Indeed, a single intranasal dose of recombinant IFNα triggers early ISG expression in both the nasal cavity and OB. When administered at the time of or early after infection, IFNα treatment delayed onset of sequelae associated with encephalitis and extended survival by several days. VEEV replication after IFN treatment was also transiently suppressed in the ONE, which inhibited subsequent invasion into the CNS. Our results demonstrate a critical and promising first evaluation of intranasal IFNα for the treatment of human encephalitic alphavirus exposures.AUTHOR SUMMARYVenezuelan Equine Encephalitis virus (VEEV) may enter the brain through the nasal cavity upon intranasal exposure. The nasal cavity normally displays brisk antiviral immune responses, thus it is unclear why this type of exposure leads to fatal VEEV infection. Using an established murine model of intranasal infection with VEEV we identified the initial targets of infection within the nasal cavity and found that antiviral immune responses to virus at this site and during brain infection are delayed for up to 48 hours. Thus, administration of a single intranasal dose of recombinant IFNα at the time of or early after infection improved early antiviral immune responses and suppressed viral replication, which delayed onset of brain infection and extended survival by several days. VEEV replication after IFN treatment was also transiently suppressed in the nasal cavity, which inhibited subsequent invasion into the CNS. Our results demonstrate a critical and promising first evaluation of intranasal IFNα for the treatment of human VEEV exposures.
Bridges instead of boats? The Mla system of diderm FirmicuteVeillonella parvulareveals an ancestral transenvelope core of phospholipid trafficking
Authors: Grasekamp Kyrie P. , Beaud Basile , Taib Najwa , Audrain Bianca , Bardiaux Benjamin , Rossez Yannick , Izadi-Pruneyre Nadia , Lejeune Maylis , Trivelli Xavier , Chouit Zina , Guerardel Yann , Ghigo Jean-Marc , Gribaldo Simonetta , Beloin Christophe 
Published: July 2023

AbstractDespite extensive characterisation of envelope biogenesis systems in diderm bacteria, glycerophospholipid (GPL) trafficking remains poorly understood, and has only been studied in a handful of model species. Within the Proteobacteria, the maintenance of lipid asymmetry (Mla) system facilitates retrograde GPL trafficking via six proteins, MlaA-F. GPLs are extracted from the outer leaflet of the outer membrane by the lipoprotein MlaA which associates with porin trimers, then shipped through the periplasmic space by the chaperone MlaC, which finally delivers GPLs to the inner membrane complex formed by MlaBDEF. Here, we investigate GPL trafficking inVeillonella parvula, a diderm member of the Firmicutes which encodes an Mla system devoid of MlaA and MlaC.V. parvulaΔmlamutants display phenotypes characteristic of disrupted lipid asymmetry such as hypervesiculation and detergent hypersensitivity, and lipid content analysis from outer membrane vesicles reveals an enrichment for the major lipid component phosphatidylethanolamine. Interestingly, suppressor analysis identifies mutations intamBthat rescue detergent hypersensitivity and hypervesiculation of Δmlastrains, supporting the involvement of these two systems in antagonistic GPL trafficking functions across diverse bacterial lineages. A combination of structural modeling and subcellular localisation assays shows that MlaDVpis longer than in classical diderm models and forms a transenvelope bridge, encoding both an inner membrane-localised MCE domain and an outer membrane ß-barrel. These results strongly suggest thatV. parvulapossesses a minimal Mla system for GPL trafficking, replacing the need for chaperones and outer membrane lipoproteins by directly connecting the two membranes. Finally, phylogenomic analysis indicates that this MlaEFD self-contained architecture is widely distributed in diderm bacteria and most likely represents the ancestral functional core of the Mla system, which subsequently increased in complexity in Proteobacteria and closely related phyla following the emergence of MlaABC. Our work broadens the diversity of current models of GPL trafficking in diderm bacteria, challenging the paradigm set by classical models and shedding light on the evolution of a crucial system in the biogenesis and maintenance of the bacterial outer membrane.
How Myosin VI Traps its Off-State, is Activated and Dimerizes
Authors: Canon Louise , Kikuti Carlos , Planelles-Herrero Vicente J. , Lin Tianming , Mayeux Franck , Sirkia Helena , Lee Young il , Heidsieck Leila , Velikovsky Léonid , David Amandine , Liu Xiaoyan , Moussaoui Dihia , Forest Emma , Höök Peter , Petersen Karl J. , Di Cicco Aurélie , Sires-Campos Julia , Lévy Daniel , Delevoye Cédric , Sweeney H. Lee , Houdusse Anne 
Published: July 2023

AbstractMyosin VI (Myo6) is the only minus-end directed nanomotor on actin, allowing it to uniquely contribute to numerous cellular functions. As for other nanomotors, proper functioning of Myo6 relies on precise spatio-temporal control of motor activity via a poorly defined off-state and interactions with partners. Our structural, functional, and cellular studies reveal key features of myosin regulation and indicate that not all partners can activate Myo6. TOM1 and Dab2 cannot bind the off-state while, GIPC1 binds Myo6, releases its auto-inhibition and triggers proximal dimerization. Myo6 partners thus differentially recruit Myo6. We solved a crystal structure of the proximal dimerization domain, and show that its disruption compromises endocytosis in HeLa cells, emphasizing the importance of Myo6 dimerization. Finally, we show that the L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly impairs proximal dimerization. Our study thus demonstrates the importance of partners in the control of Myo6 auto-inhibition, localization, and activation.
BiodecomposingSpirulina platensisby ade novodesignedBacillus subtilis-based method to develop a medium for the high cell-density cultivation ofEscherichia coliin batch mode
Authors: Li Xiaowen , Wei Zhengqi , Ge Jingyi , Pan Yingying , Chu Xiang , Huang Baolin , Zhao Jiawei , Li Yanzhao , Zhou Yizhuang 
Published: July 2023

AbstractHigh cell-density cultivation (HCDC) is fundamental to basic research and industrial applications, especially in batch mode. However, limited media are available for batch culture of HCDC, because the media for batch culture must contain extremely sufficient nutrients on the one hand and few or even no substrates to generate detrimental metabolite on the other hand to attain HCDC.Spirulina platensis(SP), a new media material, is considered ideal for the development of such media. Here, we develop a biolysis method for SP degradation based on the cultivation supernatant ofBacillus subtilisand extensively demonstrate its higher degradation (indicated by the production of more small peptides and free amino acids) and cultivation effectiveness with three other methods. Based on its SP hydrolysates, a modified SP-based broth (MSP) is then formulated. Tests onEscherichia coliK-12 show that MSP achieves HCDC with several benefits: (i) its maximum optical density at 600 nm is ∼16.67, significantly higher than that of Luria-Bertani (LB) broth (only ∼6.30); (ii) MSP requires only 36 h to reach peak growth, much faster than that of LB (48 h); (iii) its maximum growth (1.12 ± 0.01 h−1) is significantly higher than that of LB (0.20 ± 0.00 h−1); (v) MSP initiates growth immediately after inoculation (lag time <0), comparable to LB; (iv) the number of viable cells in MSP is high (∼2.16 × 1011ml-1), ∼10.19 times the amount in LB. Consequently, we envision MSP will become the first choice forE. coliHCDC batch culture in the future.ImportanceSo far, it is the first time to develop a high-efficiency method for transformingSpirulina platensis(SP) into medium ingredients. Based on its SP hydrolysates, a high cell-density cultivation (HCDC) medium for the batch culture ofEscherichia coliis formulated for the first time, which is greatly beneficial for both basic research and industrial applications. In addition to HCDC, the SP hydrolysates can be extended to a wide range of applications, due to their rich nutrient content. Besides, this study demonstrates for the first time that SP is an ideal material to develop HCDC media. Furthermore, this study demonstrates that medium development and modification for batch culture can attain HCDC, without the development of new culture technologies. Therefore, this study highlights the importance of the rebirth of medium development and modification and supports the shift from developing new culture technologies to medium development and modification for HCDC in batch mode.