bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative modeling of the emergence of macroscopic grid-like representations
Authors: Bin Khalid Ikhwan , Reifenstein Eric T. , Auer Naomi , Kunz Lukas , Kempter Richard 
Published: December 2022

AbstractGrid cells are neurons in the entorhinal cortex that are thought to perform neural computations in support of spatial navigation. When subjects navigate through spatial environments, grid cells exhibit firing fields that are arranged in a triangular grid pattern. As direct recordings of grid cells from the human brain are only rarely possible, functional magnetic resonance imaging (fMRI) studies proposed and described an indirect measure of entorhinal grid-cell activity, which is quantified as a hexadirectional modulation of fMRI activity as a function of the subject’s movement direction. However, it still remains unclear how the activity of a population of grid cells may exhibit hexadirectional modulation and thus provides the basis for the hexadirectional modulation of entorhinal cortex activity measured with fMRI. Here, we thus performed numerical simulations and analytical calculations to better understand how the aggregated activity of many grid cells may be hexadirectionally modulated. Our simulations implemented three different hypotheses proposing that the hexadirectional modulation occurs because grid cells show head-direction tuning aligned with the grid axes; are subjected to repetition suppression; or exhibit a bias towards a particular grid phase offset. Our simulations suggest that hexadirectional modulation is best explained by the conjunctive grid by head-direction cell hypothesis, which can produce the strongest and most robust hexasymmetry. In contrast, our simulations including previously observed biological properties of grid cells do not provide clear support for the structure-function mapping hypothesis. Our observations on hexadirectional modulation generated by grid-cell adaptation effects and the available data on adaptation properties of grid cells are insufficient to substantiate or refute the repetition suppression hypothesis. Furthermore, we found that the magnitude of the hexadirectional modulation depends considerably on the subject’s navigation pattern. Our results thus indicate that future fMRI studies could be designed to test which of the three hypotheses most likely accounts for the fMRI measure of grid cells. These findings also underline the importance of quantifying the biological properties of single grid cells in humans to further elucidate how hexadirectional modulations of fMRI activity may emerge.
Signal detectability and boldness are not the same: the function of defensive colouration in nudibranchs is distance-dependent
Authors: van den Berg Cedric P. , Endler John A. , Cheney Karen L. 
Published: December 2022

AbstractAposematic signals advertise underlying defences in many species. They should be detectable (highly contrasting against the background) and bold (high internal pattern contrast) to enhance predator recognition, learning and memorisation. However, the signalling function of aposematic colour patterns may be distance-dependent: signals may be undetectable from a distance to reduce costs of increased attacks from naïve predators but bold when viewed up close. To test this hypothesis, we quantified the chromatic and achromatic detectability and boldness of colour patterns in 13 nudibranch species that varied in the strength of their chemical defences, in terms of unpalatability and toxicity, using Quantitative Colour Pattern Analysis (QCPA) and data on the visual perception of a triggerfish (Rhinecanthus aculeatus). When viewed from larger distances, there were no differences in detectability and boldness between well-defended and undefended species. However, when viewed at close distances, well-defended species were more detectable and bolder than undefended species. The detectability of defended species decreased more significantly with increased viewing distances compared to boldness but remained relatively consistent over viewing distances for undefended species. We provide evidence for distance-dependent signalling in aposematic nudibranchs and highlight the importance of distinguishing between signal detectability and boldness in studies of aposematism.
Acidovorax temperanspolarizes T17 cells and skews neutrophil maturation to promote lung adenocarcinoma development
Authors: Stone Joshua K. , von Muhlinen Natalia , Zhang Chenran , Robles Ana I. , Vega-Valle Eleazar , Miyanaga Akihiko , Matsumoto Masaru , Greathouse K. Leigh , Cooks Tomer , Trinchieri Giorgio , Harris Curtis C. 
Published: December 2022

SUMMARYDysbiosis, or changes within the microbiome, is a common feature of solid tumors, however whether this dysbiosis directly contributes to tumor development is largely unknown. We previously characterized the lung cancer microbiome and identifiedAcidovorax temperansas enriched in tumors. In this study, we instilledA. temperansin an animal model driven by mutantKrasandTp53alleles. This revealedA. temperansaccelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed toA. temperansdisplayed a mature, pro-tumorigenic genotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+T cells which polarized to an IL-17A+phenotype detectable in CD4+and γδ populations. T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate dysbiosis promotes tumor growth by modulating inflammation.
The trembling hand unraveled: motor and valuation elements in the neural sources of choice inconsistency
Authors: Kurtz-David Vered , Madar Asaf , Hakim Adam , Palmon Noa , Levy Dino J 
Published: December 2022

AbstractExtensive evidence shows that humans are inconsistent with their choices. Yet, the neural mechanism underlying this type of choices remains unknown. Here, we aim to show that inconsistent choice is tied to the valuation process, but can also arise from motor errors during task execution. We report the results from three behavioral and neuroimaging studies. Subjects completed a risky-choice task to test their inconsistency levels, followed by two novel tasks, explicitly designed to examine motor output. We recorded mouse trajectories during task execution and designed 34 features to analyze motor dynamics in an exploratory manner. We show that motor dynamics predict inconsistency levels, even when motor output was absent any valuation elements. In the neuroimaging study, we show that inconsistency is associated with value brain circuits, but at the same time, is also related to activity in motor circuits. These findings suggest that (at least) two neural sources of noise contribute to inconsistent choice behavior.
Structure adaptation in Omicron SARS-CoV-2/hACE2: Biophysical origins of evolutionary driving forces
Authors: Hsiao Ya-Wen , Taddese Tseden , Jiménez-Serratos Guadalupe , Bray David J. , Crain Jason 
Published: December 2022

AbstractSince its emergence, the Covid19 pandemic has been sustained by a series of transmission waves initiated by new variants of the SARS-CoV-2 virus. Some of these arise with higher transmissivity and/or increased disease severity. Here we use molecular dynamics simulations to examine the modulation of the fundamental interactions between the receptor binding domain (RBD) of the spike glycoprotein and the host cell receptor (human angiotensin-converting enzyme 2: hACE2) arising from Omicron variant mutations (BA.1 and BA.2) relative to the original wild type strain. We find significant structural differences in the complexes which overall bring the spike protein and its receptor into closer proximity. These are consistent with and attributed to the higher positive charge on the RBD conferred by BA.1 and BA.2 mutations relative to the wild type. However, further differences between sub-variants BA.1 and BA.2 (which have equivalent RBD charges) are also evident: Mutations affect interdomain interactions between the up-chain and its clockwise neighbor chain, resulting in enhanced flexibility for BA.2. Consequently, additional close contacts arise in BA.2 which include binding to hACE2 by a second spike protein monomer, in addition to the up-chain - a motif not found in BA.1. Finally, the mechanism by which the glycans stabilize the up state of the Spike protein differs for the wild type and the Omicrons. We also found the glycan on N90 of hACE2 turns from inhibiting, to facilitating the binding to Omicron spike protein. These structural and electrostatic differences offer further insight into the mechanisms by which viral mutations modulate host cell binding and provide a biophysical basis for evolutionary driving forces.
Endodermal suberin deposition restricts potassium leakage from roots
Authors: Vestenaa Morten Winther , Husted Søren , Minutello Francesco , Persson Daniel Pergament 
Published: December 2022

SUMMARYThe endodermis is a checkpoint for ions and water escaping or entering the root. It has been hypothesized that suberin acts as a physical barrier preventing potassium (K) leakage from the stele during translocation, but attempts to support this idea has yielded contradictory results.We developed a Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) based element bioimaging method to study K leakage from roots with different suberin deposition, where we show that cesium (Cs) is an excellent tracer for K.Element bioimaging of roots and total shoot concentrations from variousArabidopsis thalianamutants all showed a positive relationship between suberin deposition and K translocation efficiency. In addition, images from the fully suberized barley (Hordeum vulgare) seminal roots revealed a strongly reduced K leakage compared to less suberized root zones.Nodal roots form a scattered deposition of suberin towards the phloem in the mature root zone. This incomplete suberin deposition also restrict K leakage efficiently.Collectively, our findings provide experimental evidence that suberin act as a barrier for K leakage upon root-to-shoot translocation by restricting K movement over the endodermis from the stele to cortex.
Cost and benefits of being social: examining the influence of sociality on faecal parasites in free-ranging rhesus macaques
Authors: Pavez-Fox Melissa A. , Escabi-Ruiz Carla M. , Hart Jordan D. A. , Negron-Del Valle Josue E. , Phillips Daniel , Montague Michael J. , Platt Michael L. , Ruiz-Lambides Angelina , Martinez Melween I. ,   Cayo Biobank Research Unit, Higham James P. , Snyder-Mackler Noah , Brent Lauren J.N. 
Published: December 2022

AbstractParasites and infectious diseases constitute an important challenge to the health of group-living animals. Social contact and shared space can both increase disease transmission risk, while individual differences in social resources can help prevent infections. For example, high social status individuals and those with more or stronger social relationships may have better immunity and, thus, lower parasitic burden. To test for health trade-offs in the costs and benefits of sociality, we quantified how parasitic load varied with an individual’s social status, as well as with their weak and strong affiliative relationships in a free-ranging population of rhesus macaques (Macaca mulatta). Social resources may also protect against infection under environmentally challenging situations, such as natural disasters. We additionally examined the impact of a major hurricane on the sociality-parasite relationship in this system. We found that both weak and strong proximity partners, but not grooming partners, were associated with lower protozoa infection risk. Social status was not linked to infection risk, even after the hurricane. Overall, our study highlights the buffering against infection that affiliative partners may provide, suggesting individuals can compensate for the health costs of sociality by having partners who tolerate their presence.
Activity Map and Transition Pathways of G Protein Coupled Receptor Revealed by Machine Learning
Authors: Mollaei Parisa , Farimani Amir Barati 
Published: December 2022

AbstractApproximately, one-third of all FDA-approved drugs target G protein-coupled receptors (GPCRs). However, more knowledge of protein structure-activity correlation is required to improve the efficacy of the drugs targeting GPCRs. In this study, we developed a machine learning (ML) model to predict activation state and activity level of the receptors with high prediction accuracy. Furthermore, we applied this model to thousands of molecular dynamics trajectories to correlate residue-level conformational changes of a GPCR to its activity level. Finally, the most probable transition pathway between activation states of a receptor can be identified by using the state-activity information. In addition, with this model, we can associate the contribution of each amino acid to the activation process. Using this method we will be able to design drugs that mainly target principal amino acids driving the transition between activation states of GPCRs. Our advanced method is generalizable to all GPCR classes and provides mechanistic insight into the activation mechanism in the receptors.
XAP5 CIRCADIAN TIMEKEEPERregulates RNA splicing and the circadian clock via genetically separable pathways
Authors: Zhang (张弘韬) Hongtao , Kumimoto Roderick W. , Anver Shajahan , Harmer Stacey L. 
Published: December 2022

AbstractThe circadian oscillator allows organisms to synchronize their cellular and physiological activities with diurnal environmental changes. In plants, the circadian clock is primarily composed of multiple transcriptional-translational feedback loops. Regulators of post-transcriptional events, such as pre-mRNA splicing factors, are also involved in controlling the pace of the clock. However, in most cases the underlying mechanisms remain unclear. We have previously identifiedXAP5 CIRCADIAN TIMEKEEPER(XCT) as anArabidopsis thalianacircadian clock regulator with uncharacterized molecular functions. Here, we report that XCT physically interacts with components of the spliceosome, including members of the Nineteen Complex (NTC). PacBio Iso-Seq data show thatxctmutants have transcriptome-wide pre-mRNA splicing defects, predominantly aberrant 3’ splice site selection. Expression of a genomic copy ofXCTfully rescues those splicing defects, demonstrating that functionalXCTis important for splicing. Dawn-expressed genes are significantly enriched among those aberrantly spliced inxctmutants, suggesting that the splicing activity ofXCTmay be circadian regulated. Furthermore, we show that loss of function mutations inPRP19AorPRP19B, two homologous core NTC components, suppress the short circadian period phenotype ofxct-2. However, we do not see rescue of the splicing defects of core clock genes inprp19 xctmutants. Therefore, our results suggest thatXCTmay regulate splicing and the clock function through genetically separable pathways.
Beat processing in newborn infants cannot be explained by statistical learning based on transition probabilities
Authors: P. Háden Gábor , Bouwer Fleur L. , Honing Henkjan , Winkler István 
Published: December 2022

AbstractNewborn infants have been shown to extract temporal regularities from sound sequences, both in the form of learning regular sequential properties, and extracting periodicity in the input, commonly referred to as a beat. However, these two types of regularities are often indistinguishable in isochronous sequences, as both statistical learning and beat perception can be elicited by the regular alternation of accented and unaccented sounds. Here, we manipulated the isochrony of sound sequences in order to disentangle statistical learning from beat perception in sleeping newborn infants in an EEG experiment, as previously done in adults and macaque monkeys. We used a binary accented sequence that induces a beat when presented with isochronous timing, but not when presented with randomly jittered timing. We compared mismatch responses to infrequent deviants falling on either accented or unaccented (i.e., odd and even) positions. Results showed a clear difference between metrical positions in the isochronous sequence, but not in the equivalent jittered sequence. This suggests that beat processing is present in newborns. However, the current paradigm did not show effects of statistical learning, despite previous evidence for this ability in newborns. These results show that statistical learning does not explain beat processing in newborn infants.Research highlightsSleeping newborns process musical beat.Transition probabilities are not enough to explain beat perception in newborn infants.No evidence of statistical learning (based on transition probabilities) without isochronous stimulation in newborns.Results converge with previous evidence on beat perception of newborn infants.
A Pilot Survey of Authors’ Experiences with Poor Peer Review Practices
Authors: McCloskey Kyle , Merz Jon F. 
Published: December 2022

ObjectivesTo develop a typology of poor peer review practices (PPRP) and assess researchers’ experiences with PPRP.DesignExploratory analysis of cross-sectional internet-based survey.ParticipantsWe solicited 500 researchers funded by the NIH extramural grants in 2018 by direct email and 600 bioethicists on a bioethics discussion forum (mcw.bioethics). 112 respondents (~10%) completed the survey.Primary and Secondary Outcomes MeasuresThe total number of reported PPRP and a five-point scale to assess participants’ views about the effect of PPRP on their ability to disseminate their research.ResultsThe mean number of PPRP experienced per author was 12.5 of 28 (44.6%; range 0–27; 95% CI = 11.2–13.8), with fourteen PPRP experienced by 50% or more of the sample. The number of reported PPRP increased with age (P = 0.01) and total number of published peer-reviewed manuscripts (P = 0.02). Authors belonging to underrepresented groups reported more PPRP compared to represented groups (P = 0.05). Most authors viewed the peer review process favorably, with 67% (74/111) of authors responding “sometimes” or “often” to having received insightful peer reviews that improved the quality of their final papers. However, a total of 57% (63/111) of respondents admitted to previously abandoning a manuscript after receiving what they perceived to be unfair peer reviews.ConclusionsThis study introduces a practical list of PPRP and a framework for a typology of PPRP, which could serve as an educational tool for editors and reviewers and further our understanding of poor peer review practices. Future researchers will expand authors’ experiences with constructive or helpful peer review practices.STRENGTHS AND LIMITATIONS OF THIS STUDYThe sample consisted primarily of experienced researchers from diverse fields, which aided in capturing a wide variety of poor peer review examples.This survey included a core set of 28 poor peer review practices and allowed respondents to add other practices they had experienced, which helped to generate an extensive list of poor peer review practices.The generalizability of the prevalence of poor review types and the degree of negative impact on authors should be interpreted with caution due to the low response rate and the potential for response bias.
A Transfer entropy-based methodology to analyze information flow under eyes-open and eyes-closed conditions with a clinical perspective
Authors: Restrepo Juan F. , Mateos Diego M. , Díaz López Juan M. 
Published: December 2022

AbstractStudying brain dynamics under normal or pathological conditions has proven to be a challenging task, as there is no unified consensus on the best approach. In this article, we present a methodology based on Transfer Entropy to study the information flow between different brain hemispheres in healthy subjects during eyes-open (EO) and eyes-closed (EC) resting states. We used an experimental setup that mimics the technical conditions found in clinical settings and collected data sets from short records of 24 channels electroencephalogram (EEG) at a sampling rate of 65 Hz. Our methodology accounts for interhemispheric and intrahemispheric information flow analysis in both conditions and relies on 4 indexes calculated from the transfer entropy estimations between EEG channels. These indexes provide information on the number, strength, and directionality of active connections. Our results suggest an increase in information transfer in the EC condition for the alpha, beta1, and beta2 frequency bands, but no preferred direction of interhemispheric information movement under either condition. These results are consistent with previously reported studies conducted with denser EEG recordings sampled at a higher rate. In conclusion, our methodology shows a significant difference in the brain’s dynamics of information transfer between EO and EC resting states, which can also be applied to regular clinical sessions.
GβγActivatesPIP2 Hydrolysis by Recruiting and OrientingPLCβon the Membrane Surface
Authors: Falzone Maria E. , MacKinnon Roderick 
Published: December 2022

SummaryPLCβscatalyze the hydrolysis ofPIP2 into IP3 and DAG.PIP2 regulates the activity of many membrane proteins, while IP3 and DAG lead to increased intracellular Ca2+levels and activate PKC, respectively.PLCβsare regulated by GPCRs through direct interaction withGαqandGβγ. This study addresses the mechanism by whichGβγactivatesPLCβ3. We show thatPLCβ3 functions as a slow Michaelis-Menten enzyme (kcat~2sec−1,KM~0.43mol%) on membrane surfaces. Its partition coefficient (Kx~2.9 * 104) is such that only a small quantity ofPLCβ3 exists in the membrane in the absence ofGβγ. WhenGβγis present, equilibrium binding (Keq~0.009mol%) increasesPLCβ3 in the membrane, increasingVmaxin proportion. Atomic structures on membrane vesicle surfaces show that twoGβγanchorPLCβ3 with its catalytic site oriented toward the membrane surface. This principle of activation explains rapid stimulated catalysis with low background catalysis.