bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of nematocytes differs in two types of gonophores in hydrozoanSarsia lovenii
Authors: Vetrova Alexandra A. , Prudkovsky Andrey A. , Kremnyov Stanislav V. 
Published: March 2023

AbstractHydrozoan cnidarians are widely known for a diversity of life cycles. While some hydrozoan polyps produce medusae, in most species the gonophore remains attached to the polyp. Little is known about the mechanisms behind the loss of the medusal stage in hydrozoans. HydrozoanSarsia loveniiis a promising model for studying this issue. It is a polymorphic species with several haplogroups. One haplogroup produces attached eumedusoids and the other one buds free-swimming medusae. Here, we compared patterns of cell proliferation and distribution of nematocytes in medusoids, medusa buds and medusae ofS. lovenii.Cell proliferation is absent from exumbrella of late medusa buds and medusae, but presumably i-cells proliferate in exumbrella of medusoids. In exumbrella of medusoids, we also observed evenly distributed nematocytes with capsules and expression of late nematogenesis-associated gene,Nowa. Nematocyte capsules andNowaexpression were also observed in exumbrella of medusa bud, but we did not detect prominentNowasignal in the bell of developed medusa. It is also known that abundance of exumbrellar nematocysts signs immaturity in medusae ofSarsiagenus. Our data demonstrate that nematocyte distribution and associated gene expression in medusoids resemble medusa buds rather than developed medusae. Thus, sexually mature medusoids exhibit juvenile somatic characters, demonstrating signs of neoteny.Research highlightsHydrozoanSarsia loveniihas attached eumedusoids and free-swimming medusae. The distribution of nematocytes in eumedusoids resembles that in medusa buds. This may indicate neoteny of eumedusoids.
Mechanism of tension propagation in cell membranes
Authors: Barnoy Avishai , Tsaturyan Andrey K. , Kozlov Michael M. 
Published: March 2023

AbstractThe propagation of the membrane tension perturbations is a, potentially, essential mechanism of the mechanical signal transduction along surfaces of live cells. The efficiency of this process is determined by the propagation speed, which turned to be a hot and a controversial topic of the Cell Biophysics. In a stark contrast to the earlier results and expectations, the recent studies in several cell types revealed a wide range of the tension propagation speeds beginning from the strikingly low ones challenging the significance of the process and up to relatively high biologically relevant rates. The previously suggested models of the tension propagation have been based on assuming an unrealistic softness of the membranes for the stretching-compression deformations, which challenges the model ability to account for the observations. Here, we consider a different physics of the generation and the propagation of tension perturbations in cell membranes. We propose the tension to be controlled by an intra-cellular pressure and the propagation of the tension perturbations to be mediated by a membrane area redistribution between compartments, to which cell membranes are divided by the proteinic barriers, according to the picket-fence model. Using the established elastic features of cell membranes including their effective non-stretchability, this mechanism quantitatively accounts for the slowness of the propagation process and gives a natural explanation of the wide range of the observed propagation speeds. The model predictions are amenable to a direct experimental verification by controlled osmotic pressure variations.
Evolving antibody evasion and receptor affinity of the Omicron BA.2.75 sublineage of SARS-CoV-2
Authors: Wang Qian , Li Zhiteng , Guo Yicheng , Mellis Ian A. , Iketani Sho , Liu Michael , Yu Jian , Valdez Riccardo , Lauring Adam S. , Sheng Zizhang , Gordon Aubree , Liu Lihong , Ho David D. 
Published: March 2023

SummarySARS-CoV-2 Omicron BA.2.75 has diversified into multiple subvariants with additional spike mutations, and several are expanding in prevalence, particularly CH.1.1 and BN.1. Here, we investigated the viral receptor affinities and neutralization evasion properties of major BA.2.75 subvariants actively circulating in different regions worldwide. We found two distinct evolutionary pathways and three newly identified mutations that shaped the virological features of these subvariants. One phenotypic group exhibited a discernible decrease in viral receptor affinities, but a noteworthy increase in resistance to antibody neutralization, as exemplified by CH.1.1, which is apparently as resistant as XBB.1.5. In contrast, a second group demonstrated a substantial increase in viral receptor affinity but only a moderate increase in antibody evasion, as exemplified by BN.1. We also observed that all prevalent SARS-CoV-2 variants in the circulation presently, except for BN.1, exhibit profound levels of antibody evasion, suggesting this is the dominant determinant of virus transmissibility today.
Environmental selection overrides host selection in a horizontally acquired microbiota
Authors: Obeng Nancy , Schulenburg Hinrich 
Published: March 2023

AbstractHorizontally acquired symbionts need to succeed both within hosts and the free-living environment. Microbes might invest differentially in these habitats, thus shaping fitness within host-associated microbiota communities. In this study, we investigated how host and environmental selection affect microbiota composition in a two-member model community ofPseudomonas luridaMYb11 andOchrobactrum vermisMYb71 from the natural microbiota ofCaenorhabditis elegans. Fitness characterizations in the host and non-host environment revealed distinct ecological strategies: while MYb11 dominated free-living by rapidly growing, it was quickly outcompeted within worms by MYb71. Using mathematical modeling and experimental evolution, we assessed how these distinct strategies affect microbiota composition over time. We found that MYb11 enriches in the host via its advantage in the environment and additionally adapts to the host. This community shift was mirrored in host fitness. Overall, this highlights the importance of the symbiont pool and shows that environmental selection can overwhelm host adaptation.
Validation of a Commercial Radioimmunoassay for Measurement of Human Peripheral Oxytocin
Authors: Gerred Keenan , Kapoor Amita 
Published: March 2023

ABSTRACTOxytocin (OT) is a peptide hormone synthesized in the hypothalamus and released into systemic circulation or other areas of the brain. It has a variety of physiological roles such as stimulation of uterine contractions, involvement in social behaviors, and regulation of mood. Its small size and low levels within biological matrices make it challenging to accurately measure. The goal of this study was to demonstrate the specificity of the antibody, sensitivity, and reproducibility of the Phoenix Pharmaceuticals (PP) OT radioimmunoassay (RIA) for use in human urine, serum, and saliva. Specificity of the antibody was assessed by high pressure liquid chromatography with ultraviolet (HPLC-UV) separation and assay of the fractions. Immunoreactivity was evaluated using the percent OT bound, and the fraction retention times were compared to the retention time of an intact OT standard to determine which fractions contained OT in the extracted samples. Reproducibility was assessed by running replicates of pools of each biomatrix over several assays. Sensitivity was assessed by repeated measurement of physiologically relevant low-concentration specimens. In all tested specimens the greatest reactivity in assay corresponded to the same fraction(s) as the OT standard. Only minimal reactivity was found in the other fractions, suggesting that in an unfractionated sample the antibody reacts mostly with intact OT. Reproducibility was acceptable for all specimens and the coefficient of variation (CV) ranged from 3.72-8.04% and 5.89-12.8%, for intra and inter-assay, respectively. The limits of quantitation (LOQ) were sufficient for measurement of normal values in urine (0.643 & 1.43 pg/mL), serum (1.90 pg/mL), and saliva pools (0.485 & 4.42 pg/mL). In conclusion, the PP OT RIA is specific and sensitive enough for reproducible measurement of intact OT in human peripheral biological matrices.HIGHLIGHTSThe oxytocin radioimmunoassay kit from Phoenix Pharmaceuticals is specific for intact oxytocin measured in human urine, serum, and saliva.Basal levels of oxytocin are low in peripheral biomatrices, and the sensitivity of the assay is sufficient for reproducible measurement.
Visual working memory models of delayed estimation do not generalize to whole-report tasks
Authors: Cuthbert Benjamin , Standage Dominic , Paré Martin , Blohm Gunnar 
Published: March 2023

AbstractWhole-report working memory tasks provide a measure of recall for all stimuli in a trial, and afford single-trial analyses that are not possible with single-report delayed estimation tasks. However, most whole-report studies assume that trial stimuli are encoded and reported independently, and do not consider the relationships between stimuli presented and reported within the same trial. Here, we present the results of two independently conducted whole-report experiments. The first dataset was recorded by Adam, Vogel, and Awh, 2017, and required participants to report color and orientation stimuli using a continuous response wheel. We recorded the second dataset, which required participants to report color stimuli using a set of discrete buttons. We find that participants often group their reports by color similarity, contradicting the assumption of independence implicit in most encoding models of working memory. Next, we show that this behavior is consistent across participants and experiments when reporting color but not orientation, two circular variables often assumed to be equivalent. Finally, we implement an alternative to independent encoding where stimuli are encoded as a hierarchical Bayesian ensemble, and show that this model predicts biases that are not present in either dataset. Our results suggest that assumptions made by both independent and hierarchical ensemble encoding models—which were developed in the context of single-report delayed estimation tasks—do not hold for the whole-report task. This failure to generalize highlights the need to consider variations in task structure when inferring fundamental principles of visual working memory.
Self-formation of concentric zones of telencephalic and ocular tissues and directional retinal ganglion cell axons
Authors: Liu Wei , Shrestha Rupendra , Lowe Albert , Zhang Xusheng , Spaeth Ludovic 
Published: March 2023

SummaryThe telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along a spatial axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report the self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ optic-disc cells. Single-cell RNA sequencing of CONCEPT organoids not only confirmed telencephalic and ocular identities but also identified expression signatures of early optic-disc, optic-stalk, and RGCs. These signatures were similar to those in human fetal retinas. Optic-disc cells in CONCEPT organoids differentially expressedFGF8andFGF9; FGFR inhibitions drastically decreased RGC differentiation and directional axon growth. Through the identified RGC-specific cell-surface marker CNTN2, electrophysiologically-excitable RGCs were isolated under a native condition. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma.Impact statementA human telencephalon-eye organoid model that exhibited axon growth and pathfinding from retinal ganglion cell (RGC) axons is reported; via cell surface marker CNTN2 identified using scRNA-seq, early RGCs were isolated under a native condition.
Discovery of a cryptic pocket in the AI-predicted structure of PPM1D phosphatase explains the binding site and potency of its allosteric inhibitors
Authors: Meller Artur , de Oliveira Saulo , Davtyan Aram , Abramyan Tigran , Bowman Gregory R. , van den Bedem Henry 
Published: March 2023

AbstractVirtual screening is a widely used tool for drug discovery, but its predictive power can vary dramatically depending on how much structural data is available. In the best case, crystal structures of a ligand-bound protein can help find more potent ligands. However, virtual screens tend to be less predictive when only ligand-free crystal structures are available, and even less predictive if a homology model or other predicted structure must be used. Here, we explore the possibility that this situation can be improved by better accounting for protein dynamics, as simulations started from a single structure have a reasonable chance of sampling nearby structures that are more compatible with ligand binding. As a specific example, we consider the cancer drug target PPM1D/Wip1 phosphatase, a protein that lacks crystal structures. High-throughput screens have led to the discovery of several allosteric inhibitors of PPM1D, but their binding mode remains unknown. To enable further drug discovery efforts, we assessed the predictive power of an AlphaFold-predicted structure of PPM1D and a Markov state model (MSM) built from molecular dynamics simulations initiated from that structure. Our simulations reveal a cryptic pocket at the interface between two important structural elements, the flap and hinge regions. Using deep learning to predict the pose quality of each docked compound for the active site and cryptic pocket suggests that the inhibitors strongly prefer binding to the cryptic pocket, consistent with their allosteric effect. The predicted affinities for the dynamically uncovered cryptic pocket also recapitulate the relative potencies of the compounds (τb=0.70) better than the predicted affinities for the static AlphaFold-predicted structure (τb=0.42). Taken together, these results suggest that targeting the cryptic pocket is a good strategy for drugging PPM1D and, more generally, that conformations selected from simulation can improve virtual screening when limited structural data is available.
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
Authors: Nixon-Abell Jonathon , Ruggeri Francesco S. , Qamar Seema , Herling Therese W. , Czekalska Magdalena A. , Shen Yi , Wang Guozhen , King Christopher , Fernandopulle Michael S. , Sneideris Tomas , Watson Joseph L. , Pillai Visakh V.S. , Meadows William , Henderson James W. , Chambers Joseph E. , Wagstaff Jane L. , Williams Sioned H. , Coyle Helena , Lu Yuqian , Zhang Shuyuan , Marciniak Stefan J. , Freund Stefan M.V. , Derivery Emmanuel , Ward Michael E. , Vendruscolo Michele , Knowles Tuomas P.J. , St George-Hyslop Peter 
Published: March 2023

SUMMARYPhase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. The frequent juxtaposition of proteinaceous biomolecular condensates to cellular membranes raises the intriguing prospect that phase transitions in proteins and lipids could be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granule condensates to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induce a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system offers an important template to understand the numerous other examples across the cell whereby biomolecular condensates closely juxtapose cell membranes.GRAPHICAL ABSTRACT
Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking
Authors: Meckel Katherine R. , Simpson Sierra S. , Godino Arthur , Peck Emily G. , George Olivier , Calipari Erin S. , Hofford Rebecca S. , Kiraly Drew D. 
Published: March 2023

AbstractCocaine use disorder represents a public health crisis with no FDA-approved medications for its treatment. A growing body of research has detailed the important connections between the brain and the resident population of bacteria in the gut, the gut microbiome in psychiatric disease models. Acute depletion of gut bacteria results in enhanced reward in a mouse cocaine place preference model, and repletion of bacterially-derived short-chain fatty acid (SCFA) metabolites reverses this effect. However, the role of the gut microbiome and its metabolites in modulating cocaine-seeking behavior after prolonged abstinence is unknown. Given that relapse prevention is the most clinically challenging issue in treating substance use disorders, studies examining the effects of microbiome manipulations in relapse-relevant models are critical. Here, Sprague-Dawley rats received either untreated water or antibiotics to deplete the gut microbiome and its metabolites. Rats were trained to self-administer cocaine and subjected to either within-session threshold testing to evaluate motivation for cocaine or 21 days of abstinence followed by a cue-induced cocaine-seeking task to model relapse behavior. Microbiome depletion did not affect cocaine acquisition on an FR1 schedule. However, microbiome-depleted subjects exhibited significantly enhanced motivation for low dose cocaine on a within-session threshold task. Similarly, microbiome depletion increased cue-induced cocaine-seeking following prolonged abstinence. In the absence of a normal microbiome, repletion of bacterially-derived SCFA metabolites reversed the behavioral and transcriptional changes associated with microbiome depletion. These findings suggest that gut bacteria, via their metabolites, are key regulators of drug-seeking behaviors, positioning the microbiome as a potential translational research target.
Germination responses to changing rainfall timing reveal potential climate vulnerability in a clade of wildflowers
Authors: Worthy Samantha J. , Miller Arquel , Ashlock Sarah R. , Ceviker Eda , Maloof Julin N. , Strauss Sharon Y. , Schmitt Johanna , Gremer Jennifer R. 
Published: March 2023

AbstractThe timing of germination, driven by seasonal cues, is critical for the life cycle of plants. Variation among species in germination responses can reflect evolutionary processes and adaptation to local climate and can affect vulnerability to changing conditions. Indeed, climate change is altering the timing of precipitation and associated temperatures, which may interact with germination cueing to affect the timing, quantity, and speed of germination. Germination responses to change can then have consequences for individual fitness, population dynamics, and species distributions. Here, we assessed responses to the timing of germination-triggering rains and corresponding temperatures for 11 species spanning theStreptanthus(s.l.) clade (Brassicaceae). To do so, we experimentally manipulated the onset date of rainfall events, measured effects on germination fraction and rate, and evaluated whether responses were constrained by evolutionary relationships across the phylogeny. We then explored the possible consequences of these responses to contemporary shifts in precipitation timing. Later onset rains and cooler temperatures significantly reduced germination rates for all species. Germination fractions decreased with later rains and cooler temperatures for all but threeCaulanthusspecies. Species’ germination responses to the timing of rainfall and seasonal temperatures were phylogenetically constrained, withCaulanthusspecies appearing less sensitive. Further, six species are likely already experiencing significant decreases in germination fractions or rates (or both) with observed climate change, which has shifted the timing of rainfall towards the cooler, winter months in California. Overall, our findings highlight the importance of the germination responses to seasonal timing, how they have evolved across the clade, and their implications under climate change.
Rapid systemic responses of Arabidopsis to waterlogging stress
Authors: Peláez-Vico María Ángeles , Tukuli Adama , Singh Pallav , Mendoza-Cózatl David G , Joshi Trupti , Mittler Ron 
Published: March 2023

ABSTRACTWaterlogging stress (WLS) negatively impacts the growth and yield of crops resulting in heavy losses to agricultural production. Previous studies revealed that WLS induces a systemic response in shoots that is partially dependent on the plant hormones ethylene and abscisic acid. However, the role of rapid cell-to-cell signaling pathways, such as the reactive oxygen species (ROS) and calcium waves, in systemic responses of plants to WLS is unknown at present. Here we reveal that an abrupt WLS treatment ofArabidopsis thalianaplants growing in peat moss triggers systemic ROS and calcium wave responses, and that the WLS-triggered ROS wave response of Arabidopsis is dependent on the ROS generating RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD), calcium-permeable channels GLUTAMATE-LIKE RECEPTOR 3.3 and 3.6 (GLR3.3 and GLR3.6), and aquaporin PLASMA MEMBRANE INTRINSIC PROTEIN 2;1 (PIP2;1) proteins. We further show that WLS is accompanied by a rapid systemic transcriptomic response that is evident as early as 10 min following waterlogging initiation, includes many hypoxia-response transcripts, and is partially dependent on RBOHD. Interestingly, the abrupt WLS of Arabidopsis resulted in the triggering of a rapid hydraulic wave response and the transient opening of stomata on leaves. Taken together, our findings reveal that the initiation of WLS in plants is accompanied by rapid systemic physiological and transcriptomic responses that involve the ROS, calcium, and hydraulic waves. These findings reveal that systemic plant responses to WLS are rapid and at least partially dependent on cell-to-cell signaling mechanisms.