bluuebunny/crossref_metadata_2025_split huggingface dataset:
Background food influences rate of encounter and efficacy of rodenticides in wild house mice
Authors: Brown Peter R. , Henry Steve , Hinds Lyn A. , Robinson Freya , Duncan Richard P. , Ruscoe Wendy A. 
Published: January 2024

AbstractBaiting is widely used in wildlife management for various purposes, including lethal control, fertility control, disease and parasite control, and conditioned aversion programs for many invasive vertebrate species. The efficacy of baiting programs relies on the likelihood that target animals will encounter the bait, consume it, and receive an appropriate dose of the active ingredient. However, there has been little focus on encounter rate of toxic baits combined with behavioural aversion, which are likely to be significant factors affecting efficacy.The likelihood of an animal encountering and consuming a toxic grain bait should theoretically increase in proportion to its availability relative to background food quantity if it is neither more or less detectable or palatable. Furthermore, the probability of consuming toxic baits might also be influenced by bait aversion following ingestion of a non-lethal dose of toxin.Using a model system of wild house mice (Mus musculusL.) in mouse-proof enclosures in Australia, we manipulated background food, applied zinc phosphide (ZnP) baits and measured the mortality of mice. When background food was scarce, mouse mortality was high, whereas an increasing abundance of background food led to reduced mortality. A scenario modelling random encounters and including bait aversion explained 78% of the variation in observed mortality outcomes and achieved a closer fit to the data. Mortality rates were predicted to be higher with a higher strength bait which overcomes behavioural aversion.Ensuring that animals locate and consume a lethal dose of toxic bait is a critical factor for successful bait delivery and efficacy. This is particularly significant in toxic baiting programs, where sublethal doses can make animals feel sick, leading to a negative association with the bait, and the development of aversion.Synthesis and applications:Our findings explain why some toxic baiting programs might fail. To achieve successful control, efforts should be directed at reducing the availability of background food to increase the probability of encounter and uptake of toxic baits. It is important to measure and understand the role of background food on toxic baiting programs to explain variable outcomes and inform strategies for successful bait delivery.Graphical abstractOur findings explain why some toxic baiting programs might fail. To achieve successful control, efforts should be directed at reducing the availability of background food to increase the probability of encounter and uptake of toxic baits. It is important to measure and understand the role of background food on toxic baiting programs to explain variable outcomes and inform strategies for successful bait delivery.
Metabolomics unveiled the impact of alterations in nucleotide glucose metabolism on palmitic acid-induced TLR4 activation in THP-1 macrophages
Authors: Wu Niting , Ran Xiaodong , Wang Jiawei , Wang Pengbo , Li Lin , She Yuanting , Luo Yadan , Li Xiaohui , Jia Yi , Huang Yan 
Published: January 2024

ABSTRACTOBJECTIVEThe association of palmitic acid with macrophage inflammation and its promotion of the expression of inflammatory factors through TLR4 have been demonstrated. It has been observed that immature TLR4 localizes to the endoplasmic reticulum and Golgi apparatus, necessitating glycosylation for migration to the cell membrane. The objective of this study was to identify potential biomarkers associated with N-glycosylation subsequent to the activation of TLR4 inflammatory signaling in human macrophages by palmitic acid.APPROACH AND RESULTSThe co-cultivation of palmitic acid with THP-1 macrophages was conducted for a duration of 24 hours, followed by the collection of cell extracts for subsequent metabolomic and lipidomic analyses using high performance liquid chromatography-tandem mass spectrometry. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers, in accordance with established scientific protocols. The impact of palmitic acid on the TLR4 signaling pathway and macrophage N-glycosylation was assessed at various time points using Western blot analysis, immunofluorescence staining, Elisa assays, and chemical labeling techniques. The TLR4 inflammatory signaling pathway was examined in macrophages at different time points, revealing that PA induced the upregulation of MyD88 and TRAF6 expression as well as NF-κB phosphorylation, indicating the activation of classical NF-κB signaling. After 24 hours, TLR4 translocated from the cell membrane to the cytoplasm and initiated internalization, accompanied by significant colocalization with GalAz in the cytosol. In addition, the metabolites in the cell extract were found to be altered in both the control and model groups. Significantly alterations in two N-glycosylation related metabolites were observed in the model group, including guanosine diphosphate-L-fucose and uridine diphosphate-N-acetylglucosamine/uridine diphosphate-N-acetylgalactosamine.CONCLUSIONSTHP-1 macrophages incubated with palmitic acid exhibited a distinct metabolomic profile compared to the control group. Our findings suggest that metabolomics analysis holds promise in identifying disease-specific biomarkers for diagnosing fatty acid-induced inflammatory responses in macrophages.
Spatiotemporal Mapping and Molecular Basis of Whole-brain Circuit Maturation
Authors: Xue Jian , Brawner Andrew T. , Thompson Jacqueline R. , Yelhekar Tushar D. , Newmaster Kyra T. , Qiu Qiang , Cooper Yonatan A. , Yu C. Ron , Ahmed-Braima Yasir H. , Kim Yongsoo , Lin Yingxi 
Published: January 2024

SUMMARYBrain development is highly dynamic and asynchronous, marked by the sequential maturation of functional circuits across the brain. The timing and mechanisms driving circuit maturation remain elusive due to an inability to identify and map maturing neuronal populations. Here we create DevATLAS (Developmental Activation Timing-based Longitudinal Acquisition System) to overcome this obstacle. We develop whole-brain mapping methods to construct the first longitudinal, spatiotemporal map of circuit maturation in early postnatal mouse brains. Moreover, we uncover dramatic impairments within the deep cortical layers in a neurodevelopmental disorders (NDDs) model, demonstrating the utility of this resource to pinpoint when and where circuit maturation is disrupted. Using DevATLAS, we reveal that early experiences accelerate the development of hippocampus-dependent learning by increasing the synaptically mature granule cell population in the dentate gyrus. Finally, DevATLAS enables the discovery of molecular mechanisms driving activity-dependent circuit maturation.
Dynamical constraints on neural population activity
Authors: Oby Emily R. , Degenhart Alan D. , Grigsby Erinn M. , Motiwala Asma , McClain Nicole T. , Marino Patrick J. , Yu Byron M. , Batista Aaron P. 
Published: January 2024

AbstractThe manner in which neural activity unfolds over time is thought to be central to sensory, motor, and cognitive functions in the brain. Network models have long posited that the brain’s computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate. We leveraged a brain-computer interface (BCI) to challenge monkeys to violate the naturally-occurring time courses of neural population activity that we observed in motor cortex. This included challenging animals to traverse the natural time course of neural activity in a time-reversed manner. Animals were unable to violate the natural time courses of neural activity when directly challenged to do so. These results provide empirical support for the view that activity time courses observed in the brain indeed reflect the underlying network-level computational mechanisms that they are believed to implement.
YY1 is a transcriptional activator of mouse LINE-1 Tf subfamily
Authors: Saha Karabi , Nielsen Grace I. , Nandani Raj , Kong Lingqi , Ye Ping , An Wenfeng 
Published: January 2024

AbstractLong interspersed element type 1 (LINE-1, L1) is an active autonomous transposable element (TE) in the human genome. The first step of L1 replication is transcription, which is controlled by an internal RNA polymerase II promoter in the 5’ untranslated region (UTR) of a full-length L1. It has been shown that transcription factor YY1 binds to a conserved sequence motif at the 5’ end of the human L1 5’UTR and dictates where transcription initiates but not the level of transcription. Putative YY1-binding motifs have been predicted in the 5’UTRs of two distinct mouse L1 subfamilies, Tf and Gf. Using site-directed mutagenesis, in vitro binding, and gene knockdown assays, we experimentally tested the role of YY1 in mouse L1 transcription. Our results indicate that Tf, but not Gf subfamily, harbors functional YY1-binding sites in its 5’UTR monomers. In contrast to its role in human L1, YY1 functions as a transcriptional activator for the mouse Tf subfamily. Furthermore, YY1-binding motifs are solely responsible for the synergistic interaction between monomers, consistent with a model wherein distant monomers act as enhancers for mouse L1 transcription. The abundance of YY1-binding sites in Tf elements also raise important implications for gene regulation at the genomic level.
Suppression of epileptic seizures by transcranial activation of K+-selective channelrhodopsin
Authors: Duan Xiaodong , Zhang Chong , Wu Yujie , Ju Jun , Xu Zhe , Li Xuanyi , Liu Yao , Ohdah Schugofa , Constantin Oana M. , Lu Zhonghua , Wang Cheng , Chen Xiaojing , Gee Christine E. , Nagel Georg , Hou Sheng-Tao , Gao Shiqiang , Song Kun 
Published: January 2024

AbstractOptogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive K+-conductive channelrhodopsin (hsKCR) by molecular engineering of the recently discoveredHyphochytrium catenoideskalium (potassium) channelrhodopsin 1. Transcranial activation of hsKCR significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several mouse epileptic models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings.
Medial prefrontal cortex suppresses reward-seeking behavior with risk of positive punishment by reducing sensitivity to reward
Authors: Nishio Monami , Kondo Masashi , Yoshida Eriko , Matsuzaki Masanori 
Published: January 2024

AbstractReward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive, resulting in an unpleasant outcome, and negative, resulting in omission of a reinforcing outcome. Although the medial prefrontal cortex (mPFC) is important in avoiding punishment, whether it is important for avoiding both positive and negative punishment and how it contributes to such avoidance are not clear. In this study, we trained male mice to perform decision-making tasks under the risks of positive (air-puff stimulus) and negative (reward omission) punishment. We found that pharmacological inactivation of mPFC enhanced the reward-seeking choice under the risk of positive, but not negative, punishment. In reinforcement learning models, this behavioral change was well-explained by hypersensitivity to the reward, rather than a decrease in the strength of aversion to punishment. Our results suggest that mPFC suppresses reward-seeking behavior by reducing sensitivity to reward under the risk of positive punishment.
A combinatory genetic strategy for targeting neurogliaform neurons in the mouse basolateral amygdala
Authors: Ozsvár Attila , Sieburg Meike Claudia , Sietam Monica Dahlstrup , Hou Wen-Hsien , Capogna Marco 
Published: January 2024

AbstractThe mouse basolateral amygdala (BLA) contains various GABAergic interneuron subpopulations, which have distinctive roles in the neuronal microcircuit controlling numerous behavioral functions.In mice, roughly 15% of the BLA GABAergic interneurons express neuropeptide Y (NPY), a reasonably characteristic marker for neurogliaform cells (NGFCs) in cortical-like brain structures. However, genetically labeled putative NPY-expressing interneurons in the BLA yield a mixture of interneuron subtypes besides NGFCs. Thus, selective molecular markers are lacking for genetically accessing NGFCs in the BLA.Here, we validated the NGFC-specific labeling with a molecular marker, neuron-derived neurotrophic factor (NDNF), in the mouse BLA, as such specificity has been demonstrated in the neocortex and hippocampus. We characterized genetically defined NDNF-expressing (NDNF+) GABAergic interneurons in the mouse BLA by combining the Ndnf-IRES2-dgCre-D transgenic mouse line with viral labeling, immunohistochemical staining, and in vitro electrophysiology.We found that BLA NDNF+ GABAergic cells mainly expressed NGFC neurochemical markers NPY and reelin (Reln) and exhibited small round soma and dense axonal arborization. Whole-cell patch clamp recordings indicated that most NDNF+ interneurons showed late spiking and moderate firing adaptation. Moreover, ∼81% of BLA NDNF+ cells generated retroaxonal action potential after current injections or optogenetic stimulations, frequently developing into persistent barrage firing. Optogenetic activation of the BLA NDNF+ cell population yielded both GABAA- and GABABreceptor-mediated currents onto BLA pyramidal neurons (PNs). We demonstrate a combinatory strategy combining the NDNF-cre mouse line with viral transfection to specifically target adult mouse BLA NGFCs and further explore their functional and behavioral roles.
Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age
Authors: Wells Steven B. , Rainbow Daniel B. , Mark Michal , Szabo Peter A. , Ergen Can , Maceiras Ana Raquel , Caron Daniel P. , Rahmani Elior , Benuck Eli , Amiri Valeh Valiollah Pour , Chen David , Wagner Allon , Howlett Sarah K. , Jarvis Lorna B. , Ellis Karen L. , Kubota Masaru , Matsumoto Rei , Mahbubani Krishnaa , Saeb-Parsy Kouresh , Dominguez-Conde Cecilia , Richardson Laura , Xu Chuan , Li Shuang , Mamanova Lira , Bolt Liam , Wilk Alicja , Teichmann Sarah A. , Farber Donna L. , Sims Peter A. , Jones Joanne L. , Yosef Nir 
Published: January 2024

ABSTRACTThe immune system comprises multiple cell lineages and heterogeneous subsets found in blood and tissues throughout the body. While human immune responses differ between sites and over age, the underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach to comprehensively profile RNA and surface protein expression of over 1.25 million immune cells isolated from blood, lymphoid organs, and mucosal tissues of 24 organ donors aged 20-75 years. We applied a multimodal classifier to annotate the major immune cell lineages (T cells, B cells, innate lymphoid cells, and myeloid cells) and their corresponding subsets across the body, leveraging probabilistic modeling to define bases for immune variations across donors, tissue, and age. We identified dominant tissue-specific effects on immune cell composition and function across lineages for lymphoid sites, intestines, and blood-rich tissues. Age-associated effects were intrinsic to both lineage and site as manifested by macrophages in mucosal sites, B cells in lymphoid organs, and T and NK cells in blood-rich sites. Our results reveal tissue-specific signatures of immune homeostasis throughout the body and across different ages. This information provides a basis for defining the transcriptional underpinnings of immune variation and potential associations with disease-associated immune pathologies across the human lifespan.
TIR domains produce histidine-ADPR conjugates as immune signaling molecules in bacteria
Authors: Sabonis Dziugas , Avraham Carmel , Lu Allen , Herbst Ehud , Silanskas Arunas , Leavitt Azita , Yirmiya Erez , Zaremba Mindaugas , Amitai Gil , Kranzusch Philip J. , Sorek Rotem , Tamulaitiene Giedre 
Published: January 2024

AbstractTIR domains are central components of pattern recognition immune proteins across all domains of life. In both bacteria and plants, TIR-domain proteins were shown to recognize pathogen invasion and then produce immune signaling molecules exclusively comprising nucleotide moieties. Here we show that the TIR domain protein of the type II Thoeris defense system in bacteria produces a unique signaling molecule comprising the amino acid histidine conjugated to ADP-ribose (His-ADPR). His-ADPR is generated in response to phage infection and activates the cognate Thoeris effector by binding a Macro domain located at the C-terminus of the effector protein. By determining the crystal structure of a ligand-bound Macro domain, we describe the structural basis for His-ADPR recognition. Our analyses furthermore reveal a family of phage proteins that bind and sequester His-ADPR signaling molecules, allowing phages to evade TIR- mediated immunity. These data demonstrate diversity in bacterial TIR signaling and reveal a new class of TIR-derived immune signaling molecules combining nucleotide and amino acid moieties.
Spatially resolved quantification of oxygen consumption rate in ex vivo lymph node slices
Authors: Anbaei Parastoo , Stevens Marissa G. , Ball Alexander G. , Bullock Timothy N.J. , Pompano Rebecca R. 
Published: January 2024

ABSTRACTCellular metabolism has been closely linked to activation state in cells of the immune system, and the oxygen consumption rate (OCR) in particular serves as a valuable metric for assessing metabolic activity. Several oxygen sensing assays have been reported for cells in standard culture conditions. However, none have provided a spatially resolved, optical measurement of local oxygen consumption in intact tissue samples, making it challenging to understand regional dynamics of consumption. Therefore, here we established a system to monitor the rates of oxygen consumption in ex vivo tissue slices, using murine lymphoid tissue as a case study. By integrating an optical oxygen sensor into a sealed perfusion chamber and incorporating appropriate correction for photobleaching of the sensor and of tissue autofluorescence, we were able to visualize and quantify rates of oxygen consumption in tissue. This method revealed for the first time that the rate of oxygen consumption in naïve lymphoid tissue was higher in the T cell region compared to the B cell and cortical regions. To validate the method, we measured OCR in the T cell regions of naïve lymph node slices using the optical assay and estimated the consumption rate per cell. The predictions from the optical assay were similar to reported values and were not significantly different from those of the Seahorse metabolic assay, a gold standard method for measuring OCR in cell suspensions. Finally, we used this method to quantify the rate of onset of tissue hypoxia for lymph node slices cultured in a sealed chamber and showed that continuous perfusion was sufficient to maintain oxygenation. In summary, this work establishes a method to monitor oxygen consumption with regional resolution in intact tissue explants, suitable for future use to compare tissue culture conditions and responses to stimulation.TOC image
Interspecies surfactants serve as public goods enabling surface motility inPseudomonas aeruginosa
Authors: Warrell Delayna L. , Zarrella Tiffany M. , Machalek Christopher , Khare Anupama 
Published: January 2024

ABSTRACTIn most natural environments, bacteria live in polymicrobial communities where secreted molecules from neighboring species alter bacterial behaviors including motility, but such interactions are understudied.Pseudomonas aeruginosais a motile opportunistic pathogen that exists in diverse multispecies environments such as the soil and is frequently found in human wound and respiratory tract co-infections with other bacteria includingStaphylococcus aureus. Here we show thatP. aeruginosacan co-opt secreted surfactants from other species for flagellar-based surface motility. We found that exogenous surfactants fromS. aureus, other bacteria, and interkingdom species enabledP. aeruginosato switch from swarming to an alternative surface spreading motility on semi-solid surfaces and allowed for the emergence of surface motility on hard agar whereP. aeruginosawas otherwise unable to move. This motility was distinct from the response of other motile bacteria in the presence of exogenous surfactants. Mutant analysis indicated that thisP. aeruginosamotility was similar to a previously described mucin-based motility, ‘surfing’, albeit with divergent regulation. Thus, our study demonstrates that secreted surfactants from the host as well as neighboring bacterial and interkingdom species act as public goods facilitatingP. aeruginosaflagella-mediated surfing-like surface motility, thereby allowing it to access different environmental niches.
SAXS/MC studies of the mixed-folded protein Cdt1 reveal monomeric, folded over conformations
Authors: Smith Kyle P. , Chakravarthy Srinivas , Rahi Amit , Chakraborty Manas , Vosberg Kristen M. , Tonelli Marco , Plach Maximilian G. , Grigorescu Arabela A. , Curtis Joseph E. , Varma Dileep 
Published: January 2024

AbstractCdt1 is a protein critical for DNA replication licensing and is well-established to be a binding partner of the minichromosome maintenance (MCM) complex. Cdt1 has also been demonstrated to have an emerging, “moonlighting” role at the kinetochore via direct binding to microtubules and to the Ndc80 complex. However, it is not known how the structure and conformations of Cdt1 could allow for these multiple, completely unique sets of protein complexes. And while there exist multiple robust methods to study entirely folded or entirely unfolded proteins, structure-function studies of combined, mixed folded/disordered proteins remain challenging. It this work, we employ multiple orthogonal biophysical and computational techniques to provide a detailed structural characterization of human Cdt1 92-546. DSF and DSCD show both folded winged helix (WH) domains of Cdt1 are relatively unstable. CD and NMR show the N-terminal and the linker regions are intrinsically disordered. Using DLS and SEC-MALS, we show that Cdt1 is polydisperse, monomeric at high concentrations, and without any apparent inter-molecular self-association. SEC-SAXS of the monomer in solution enabled computational modeling of the proteinin silico. Using the program SASSIE, we performed rigid body Monte Carlo simulations to generate a conformational ensemble. Using experimental SAXS data, we filtered for conformations which did and did not fit our data. We observe that neither fully extended nor extremely compact Cdt1 conformations are consistent with our SAXS data. The best fit models have the N-terminal and linker regions extended into solution and the two folded domains close to each other in apparent “folded over” conformations. The best fit Cdt1 conformations are consistent with a function as a scaffold protein which may be sterically blocked without the presence of binding partners. Our studies also provide a template for combining experimental and computational biophysical techniques to study mixed-folded proteins.