bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mechanistic Model for the Release of Ceramide from the CERT START Domain
Authors: Moqadam Mahmoud , Gartan Parveen , Talandashti Reza , Chiapparino Antonella , Titeca Kevin , Gavin Anne-Claude , Reuter Nathalie 
Published: December 2023

AbstractCeramide transfer protein CERT is the mediator of non-vesicular transfer of ceramide from ER to Golgi. In CERT, START is the domain responsible for the binding and transport of ceramide. A wealth of structural data has revealed a helix-grip fold surrounding a large hydrophobic holding the ceramide. Yet little is known about the mechanisms by which START releases the ceramide through the polar region and into the packed environment of cellular membranes. As such events do not lend themselves easily to experimental investigations we used multiple unbiased microsecond-long molecular simulations. We propose a membrane-assisted mechanism in which the passage of the ceramide acyl chains is facilitated by the intercalation of a single phosphatidylcholine lipid in the cavity, practically greasing the ceramide way out. We verify using experimental lipidomics data that CERT forms stable complexes with phosphatidylcholine lipids, in addition to ceramide, thus providing a validation for the proposed computational model.
Delta-Rhythmic Activity in the Medulla Develops Coincident with Cortical Delta in Sleeping Infant Rats
Authors: Ahmad Midha , Kim Jangjin , Dwyer Brett , Sokoloff Greta , Blumberg Mark S. 
Published: December 2023

SummaryIn early development, active sleep is the predominant sleep state before it is supplanted by quiet sleep. In rats, the developmental increase in quiet sleep is accompanied by the sudden emergence of the cortical delta rhythm (0.5-4 Hz) around postnatal day 12 (P12). We sought to explain the emergence of cortical delta by assessing developmental changes in the activity of the parafacial zone (PZ), a medullary structure thought to regulate quiet sleep in adults. We recorded from PZ in P10 and P12 rats and predicted an age-related increase in neural activity during increasing periods of delta-rich cortical activity. Instead, during quiet sleep we discovered sleep-dependent rhythmic spiking activity—with intervening periods of total silence—phase-locked to a local delta rhythm. Moreover, PZ and cortical delta were coherent at P12, but not at P10. PZ delta was also phase-locked to respiration, suggesting sleep-dependent modulation of PZ activity by respiratory pacemakers in the ventral medulla. Disconnecting the main olfactory bulbs from the cortex did not diminish cortical delta, indicating that the influence of respiration on delta at this age is not mediated indirectly through nasal breathing. Finally, we observed an increase in parvalbumin-expressing terminals in PZ across these ages, supporting a role for GABAergic inhibition in PZ’s rhythmicity. The discovery of delta-rhythmic neural activity in the medulla—when cortical delta is also emerging—opens a new path to understanding the brainstem’s role in regulating sleep and synchronizing rhythmic activity throughout the brain.
Chemotactile perception and associative learning of amino acids in yellowjacket workers
Authors: Mattiacci Analía , Pietrantuono Ana Laura , Masciocchi Maité , Corley Juan C. 
Published: December 2023

AbstractLearning and memory are essential for animal survival, influencing preferences, decision-making, and foraging behaviour. In this study, we explore the perceptual and learning abilities ofVespula germanica(yellowjacket wasps) to various amino acids. We hypothesize thatV. germanicacan qualitatively evaluate various amino acid solutions, given their scavenging habits and the possibility of metabolizing amino acids to fuel energy. Through chemo-tactile differential conditioning, we studied worker wasp’ maxilla labium extension response (MaLER) to essential (Lysine, Tryptophan, Arginine) and non-essential amino acids (Ornithine, Aspartic acid, Glycine). Conditioning sessions included individual amino acids against water and comparisons between different amino acids. Additionally, we tested retention, discrimination, and generalization abilities, 30 minutes later with conditioned and novel stimuli. Our results show that wasps exhibit the ability to learn and discriminate various amino acids. The discrimination capacity extended to differentiating between pairs of amino acids. Memory retention was generally robust, but certain associations observed during conditioning did not persist after a 30-minute interval. Moreover, when wasps were trained with essential amino acids, the acquired learning did not generally extend to other non-essential amino acids, except for Arginine, which exhibited generalization when tested with its precursor, Ornithine. Conversely, when trained with non-essential amino acids, the acquired learning generalized to other essential amino acids. These results suggest that, unlike other hymenopterans, wasps can detect, discriminate, and generalize free amino acids, crucial for their foraging decisions. This knowledge contributes to understanding the cognitive dimensions ofV. germanicaand their implications for targeted pest management.Summary statementThis study onVespula germanica’s amino acid perception enhances our understanding of foraging behaviours. The findings contribute to insect cognition studies, with potential implications for pest management.
Unveiling genome plasticity and a novel phage inMycoplasma felis: genomic investigations of four feline isolates
Authors: Klose Sara M. , Legione Alistair R. , Bushell Rhys N. , Browning Glenn F. , Vaz Paola K. 
Published: December 2023

AbstractMycoplasma felishas been isolated from diseased cats and horses, but to date only a single fully assembled genome of this species, of an isolate from a horse, has been characterised. This study aimed to characterise and compare the completely assembled genomes of four clinical isolates ofM. felisfrom three domestic cats, assembled with the aid of short and long read sequencing methods. The completed genomes encoded a median of 759 open reading frames (min, 743, max 777) and had a median average nucleotide identity (ANI) of 98.2% with the genome of the available equid origin reference strain. Comparative genomic analysis revealed the occurrence of multiple horizontal gene transfer (HGT) events and significant genome reassortment. This had resulted in the acquisition or loss of numerous genes within the Australian felid isolate genomes, encoding putative proteins involved in DNA transfer, metabolism, DNA replication, host cell interaction, and restriction modification systems. Additionally, a novel mycoplasma phage was detected in one Australian felidM. felisisolate by genomic analysis and visualised using cryo-transmission electron microscopy. This study has highlighted the complex genomic dynamics in different host environments. Furthermore, the sequences obtained in this work will enable the development of new diagnostic tools, and identification of future infection control and treatment options for the respiratory disease complex in cats.Data summaryAll genome data for this study have been deposited in GenBank under BioProject PRJNA906261. Genome assemblies, as well as Illumina and Oxford Nanopore sequence reads for each isolate, can be found under their respective BioSamples:SAMN32182834(isolate 047),SAMN32182835(isolate 219),SAMN32182836(isolate 329 and associated phage), andSAMN32182837(isolate 632). The authors confirm all supporting data and protocols have been provided within the article.Impact statementMycoplasma felisis commonly associated with clinical cases of conjunctivitis and feline respiratory disease complex in cats, the leading cause of euthanasia in animal shelters. In the absence of vaccines, infection control is currently limited to the prolonged treatment with antimicrobials. Prior to this study there was only one complete genome assembly of an isolate ofM. felis, which had been obtained from a horse. This study has provided the first high quality hybrid assembled genomes ofM. felisisolates from cats. This work adds four new genomes from clinical cases, as well as the identification and validation of the presence of a novel phage that utilises the mycoplasma translation code. The genomic data presented here can assist future projects investigating improved diagnostics and development of new treatment options for this significant feline pathogen.
Hyperosmolality tolerance of freshwater largemouth bass (Micropterus salmoides) to brackish at early ontogenetic stages: Eggs, embryos and yolk-sac larvae
Authors: Luo Du , Yang Dingtian 
Published: December 2023

AbstractSalinity is recognized as a pivotal factor limiting the migration of freshwater fish to brackish environments. The largemouth bass (LMB,Micropterus salmoides), a globally translocated freshwater fish, exhibits estuarine distribution, yet its hyperosmoregulatory capacity during early ontogenetic stages remains inadequately understood. To investigate the impact of freshwater salinization, a series of experiments were conducted in the Pearl River Delta, China. The study aimed to elucidate the osmoregulatory abilities of LMB eggs and embryos, assess the salinity toxicity on hatching, and explore the acute effects of hyperosmolality on yolk-sac larvae. Our results revealed that freshwater-activated mature eggs and naturally fertilized oocytes maintained nearly identical osmotic homeostasis, with diameters of 1.38 ± 0.068 mm and 1.37 ± 0.054 mm, respectively. Furthermore, both exhibited peak water excretion at a salinity of 15.0 ppt. Remarkably, a reduction in water permeability was observed in hyperosmotic environments. Spontaneous hatching rates increased from 27.5 ± 14.4% in the 1.0 ppt group to 75.1 ± 12.0% in the 6.0 ppt group under fluctuating temperature conditions. Yolk-sac LMB larvae consistently reduced survival time from 12.5 d at 1.0 ppt to 50.7 ± 2.1 min at 35.0 ppt. Similarly, more developed larvae also experienced a decrease in survival time. Logistic regression models fitting lethal time with salinity indicated a sharp decrease between 10.0 ppt and 20.0 ppt. These findings offer practical insights for predicting distribution patterns and enhancing aquaculture technology for LMB. Moreover, they may contribute theoretically to the broader understanding of the osmoregulatory mechanisms of freshwater fish.
Benchmarking Reverse Docking through AlphaFold2 Human Proteome
Authors: Luo Qing , Wang Sheng , Li Hoi Yeung , Zheng Liangzhen , Mu Yuguang , Guo Jingjing 
Published: December 2023

AbstractPredicting binding of a small molecule to the human proteome by reverse docking methods, we can predict the target interactions of drug compounds in the human body, as well as further evaluate their potential off-target effects or toxic side effects. In this study, we constructed 11 pipelines to evaluate and benchmark thoroughly the predictive capabilities of these reverse docking pipelines. The pipelines were built using site prediction tools (PointSite and SiteMap) based on the AF2 human proteome, docking programs (Glide and AutoDock Vina), and scoring functions (Glide, Autodock Vina, RTMScore, DeepRMSD, OnionNet-SFCT). The results show that pipeline glide_sfct (PS) exhibited the best target prediction ability and successfully predicted the similar proteins of native targets. This finding provides important clues for understanding the promiscuity between the drug ligand and the whole human proteome. In general, our study has the potential to increase the success rate and reduce the development timeline of drug discovery, thereby saving costs.
Action history and target uncertainty co-determine human reaching direction under time pressure
Authors: Keane B , Smith L , Carroll TJ 
Published: December 2023

AbstractGiven the inaccuracies that are inherent in biological sensory and motor functions, animal sensorimotor control should be probabilistic. Effective neural control systems for movement must estimate the most likely true state of the world on the basis of uncertain sensory information, and to select and execute movements that are most likely to be successful given motor variability. Bayesian inference dictates that if sensory information is ambiguous (e.g. low light conditions), animals should rely more on their past experience of target locations to guide motor planning, and less on their current sensory information about target location. Here we investigated how time pressure affects degree to which the precision of sensory information about a target influences movement direction bias towards previous target locations. We used a paradigm developed by Dekleva et al. (2016) that involved uncertain cues to the location of a hidden target for reaching with movement preparation time strictly controlled. One group of participants (n=10) were required to initiate their reaches within 150-300ms of target presentation, and a second group (n=10) were required to initiate their reaches with 1150-1300ms of target presentation. We found that participants relied more on prior target location information when target precision was reduced under time pressure, which suggests that integration of target uncertainty information according to Bayesian principles is an inherent component of sensorimotor transformation and does not require time-consuming cognitive processes.
In situstructural determination of cyanobacterial phycobilisome-PSII supercomplex by STAgSPA strategy
Authors: Zhang Xing , Xiao Yanan , You Xin , Sun Shan , Sui Sen-Fang 
Published: December 2023

SummaryPhotosynthesis converting solar energy to chemical energy is one of the most important chemical reactions on earth1. In cyanobacteria, light energy is captured by antenna system phycobilisomes (PBSs) and transferred to photosynthetic reaction centers of photosystem II (PSII) and photosystem I (PSI)2. While most of the protein complexes involved in photosynthesis have been characterized byin vitrostructural analyses, how these protein complexes function togetherin vivois not well understood. Here we developed anin situstructural analysis strategy “STAgSPA” to successfully solve thein situstructure of PBS-PSII supercomplex from the cyanobacteriaSpirulina platensisFACHB-439 at resolution of ∼3.5Å. The structure reveals the unprecedented coupling details among adjacent PBSs and PSII dimers, and the collaborative energy transfer mechanism mediated by multiple “super-PBS” in cyanobacteria. Our results not only provide the insights for understanding the diversity of photosynthesis-related systems between prokaryotic cyanobacteria and eukaryotic red algae, but also a valuable methodological demonstration forin situhigh-resolution structural analysis in cellular or tissue samples.
Incorporation of the HIV-1 envelope glycoprotein into viral particles is regulated by the tubular recycling endosome in a cell type-specific manner
Authors: Lerner Grigoriy , Ding Lingmei , Candor Kathleen , Spearman Paul 
Published: December 2023

ABSTRACTThe HIV-1 envelope glycoprotein (Env) is incorporated into particles during assembly on the plasma membrane (PM). Env initially reaches the PM through the secretory pathway, after which it is rapidly endocytosed via an AP-2- and clathrin-dependent mechanism. Here we show that endocytosed cell surface Env enters the tubular recycling endosome compartment (TRE). Trafficking to the TRE was dependent upon motifs within the CT previously implicated in Env recycling and particle incorporation. Depletion of TRE components MICAL-L1 or EHD1 led to defects in Env incorporation, particle infectivity, and viral replication. Remarkably, defects were limited to cell types defined as nonpermissive for incorporation of CT-deleted Env, including monocyte-derived macrophages, and not observed in 293T, HeLa, or MT-4 cells. This work identifies the TRE as an essential component of Env trafficking and particle incorporation, and provides evidence that the cell type-dependent incorporation of Env is defined by interactions with components of the TRE.
Activation of plant immunity through conversion of a helper NLR homodimer into a resistosome
Authors: Selvaraj Muniyandi , Toghani AmirAli , Pai Hsuan , Sugihara Yu , Kourelis Jiorgos , Yuen Enoch Lok Him , Ibrahim Tarhan , Zhao He , Xie Rongrong , Maqbool Abbas , Concepcion Juan Carlos De la , Banfield Mark J. , Derevnina Lida , Petre Benjamin , Lawson David M. , Bozkurt Tolga O. , Wu Chih-Hang , Kamoun Sophien , Contreras Mauricio P. 
Published: December 2023

AbstractNucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 accumulatesin vivoas a homodimer that converts into a higher order oligomer upon activation by its upstream virus disease resistance protein Rx. The Cryo-EM structure of NRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network nodes and enable redundant immune pathways. Our results expand the molecular mechanisms of NLR activation pointing to transition from homodimers to higher-order oligomeric resistosomes.
Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin
Authors: Salib Anne-Mary N , Crane Meredith J , Lee Sang Hun , Wainger Brian J , Jamieson Amanda M , Lipscombe Diane 
Published: December 2023

AbstractNeurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness ofTrpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.
Dynamically adjusted cell fate decisions and resilience to mutant invasion during steady state hematopoiesis revealed by an experimentally parameterized mathematical model
Authors: Komarova Natalia L. , Rignot Chiara , Fleischman Angela G. , Wodarz Dominik 
Published: December 2023

AbstractA major next step in hematopoietic stem cell (HSC) biology is to obtain a thorough quantitative understanding of cellular and evolutionary dynamics involved in undisturbed hematopoiesis. Mathematical models are key in this respect, and are most powerful when parameterized experimentally and containing sufficient biological complexity. Mathematical models of hematopoiesis have either been parameterized experimentally without non-linear dynamics, or they include these complexities but have not been parameterized to the same extent. We bridge this gap using mouse data to parameterize a mathematical model of hematopoiesis that includes homeostatic control mechanisms as well as clonal evolution. We find that non-linear feedback control drastically changes the interpretation of kinetic estimates at homeostasis. This suggests that short-term HSC and multipotent progenitors (MPPs) can dynamically adjust to sustain themselves in the absence of long-term HSCs, even if they differentiate more often than they self-renew in undisturbed homeostasis. Additionally, the presence of feedback control in the model renders the system resilient against mutant invasion. Invasion barriers, however, can be overcome by a combination of age-related changes in stem cell differentiation and a mutant-associated inflammatory environment. This helps us understand the evolution of e.g.TET2, DNMT3A, orJAK2mutants, and how to potentially reduce mutant burden.
Effects of novelty and temporal distance on post-experience reactivation of hippocampal place cells encoding multiple environments
Authors: Yokoi Taiki , Shikano Yu , Yagishita Haruya , Ikegaya Yuji , Sasaki Takuya 
Published: December 2023

SUMMARYThe hippocampus plays a crucial role in consolidating episodic memories from diverse experiences that encompass spatial, temporal, and novel information. This study analyzed the spike patterns of hippocampal place cells in the CA3 and CA1 areas of rats that sequentially foraged in five rooms, including familiar and novel rooms, followed by a rest period. Across multiple rooms, the generation of place fields by CA1 place cells was coordinated with other place cells. In the subsequent rest period, CA3 place cells that encoded novel environments exhibited stronger and more coordinated reactivation during sharp wave ripples (SWRs) than CA1 place cells. In contrast, CA1 place cells that encoded more recent environments exhibited stronger SWR-associated reactivation, independent of spikes of other cells, with weaker influences from novelty compared to CA3 place cells. These results suggest that post-experience SWR-associated reactivation of CA3 and CA1 neurons primarily processes novelty-related and temporal distance-related aspects of memory, respectively.