bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of immune memory and learning in bacterial communities
Authors: Bonsma-Fisher Madeleine , Goyal Sidhartha 
Published: July 2022

1AbstractFrom bacteria to humans, adaptive immune systems provide learned memories of past infections. Despite their vast biological differences, adaptive immunity shares features from microbes to vertebrates such as emergent immune diversity, long-term coexistence of hosts and pathogens, and fitness pressures from evolving pathogens and adapting hosts, yet there is no conceptual model that addresses all of these together. To address these questions, we propose and solve a simple phenomenological model of CRISPR-based adaptive immunity in microbes. We show that in coexisting phage and bacteria populations, immune diversity in both populations emerges spontaneously and in tandem, that bacteria track phage evolution with a context-dependent lag, and that high levels of diversity are paradoxically linked to low overall CRISPR immunity. We define average immunity, an important summary parameter predicted by our model, and use it to perform synthetic time-shift analyses on available experimental data to reveal different modalities of coevolution. Finally, immune cross-reactivity in our model leads to qualitatively different states of evolutionary dynamics, including an influenza-like traveling wave regime that resembles a similar state in models of vertebrate adaptive immunity. Our results show that CRISPR immunity provides a tractable model, both theoretically and experimentally, to understand general features of adaptive immunity.
Immature human engineered heart tissues engraft in a guinea pig chronic injury model
Authors: von Bibra Constantin , Shibamiya Aya , Bähr Andrea , Geertz Birgit , Köhne Maria , Stuedemann Tim , Starbatty Jutta , Hornaschewitz Nadja , Li Xinghai , Wolf Eckhard , Klymiuk Nikolai , Krane Markus , Kupatt Christian , Hiebl Bernhard , Eschenhagen Thomas , Weinberger Florian 
Published: July 2022

AbstractEngineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and the first clinical trial has started in 2021. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in the subacute stage while transplantation in a chronic injury setting was less efficient. We hypothesized that the use of immature EHT patches (EHTIm) could improve cardiomyocytes (CM) engraftment. Chronic myocardial injury was induced in a guinea pig model (n=14). EHTIm (15×106 cells) were transplanted directly after casting. Functional consequences were assessed by serial echocardiography. Animals were sacrificed four weeks after transplantation and hearts were excised for histological analysis. Cryo-injury lead to large transmural scars amounting to 26% of the left ventricle. Grafts were identified by a positive staining for human Ku80 and dystrophin, remuscularizing 9% of the scar area on average. The CM density in the graft was higher compared to previous studies with in vitro-matured EHTs and showed a greater population of immature CM. Echocardiographic analysis showed a small improvement of left ventricular function after EHTIm transplantation. In a small translational proof-of-concept study human scale EHTIm patches (4.5×108 cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of immature EHT patches without pre-cultivation results in better cell engraftment.
Predicting and prioritizing community assembly: learning outcomes via experiments
Authors: Blonder Benjamin , Lim Michael H. , Godoy Oscar 
Published: July 2022

AbstractCommunity assembly provides the foundation for applications in biodiversity conservation, climate change, invasion ecology, restoration ecology, and synthetic ecology. Predicting and prioritizing community assembly outcomes remains challenging. We address this challenge via a mechanism-freeLOVE(Learning Outcomes Via Experiments) approach suitable for cases where little data or knowledge exist: we carry out actions (randomly-sampled combinations of species additions), measure abundance outcomes, and then train a model to predict arbitrary outcomes of actions, or prioritize actions that would yield the most desirable outcomes. When trained on <100 randomly-selected actions, LOVE predicts outcomes with 2-5% error across datasets, and prioritizes actions for maximizing richness, maximizing abundance, or minimizing abundances of unwanted species, with 94-99% true positive rate and 12-83% true negative rate across tasks. LOVE complements existing approaches for community ecology by providing a foundation for additional mechanism-first study, and may help address numerous ecological applications.
Dopamine Builds and Reveals Reward-Associated Latent Behavioral Attractors
Authors: Naudé J. , Sarazin MXB. , Mondoloni S. , Hanesse B. , Vicq E. , Amegandjin F. , Mourot A. , Faure P. , Delord B. 
Published: July 2022

ABSTRACTPhasic variations in dopamine levels are interpreted as a teaching signal reinforcing rewarded behaviors. However, behavior also depends on the online, neuromodulatory effect of phasic dopamine signaling. Here, we unravel a new neurodynamical principle that reconciles these roles. In a biophysical recurrent network-based decision architecture, we showed that dopamine-mediated synaptic plasticity stabilized neural assemblies representing rewarded locations as latent, local attractors. Dopamine-modulated synaptic excitability activated these attractors online, and they became accessible as internal goals, even from remote animal positions. We experimentally validated these predictions in mice, using optogenetics, by demonstrating that online dopamine signaling specifically attracts animals toward rewarded locations, without off-target motor effects. We therefore propose that online dopamine signaling reveals potential goals by widening and deepening the basin of dopamine-built attractors representing rewards.
The silent impact: codon usage bias and protein evolution in bacteria
Authors: Moutinho Ana Filipa , Eyre-Walker Adam 
Published: July 2022

AbstractBias in synonymous codon usage has been reported across all kingdoms of life. Evidence across species suggests that codon usage bias is often driven by selective pressures, typically for translational efficiency. These selective pressures have been shown to depress the rate at which synonymous sites evolve. We hypothesise that selection on synonymous codon use could also slow the rate of protein evolution if two amino acids have different preferred codons. We test this hypothesis by looking at patterns of protein evolution using polymorphism and substitution data in bacteria. We found that non-synonymous mutations that change from unpreferred to preferred codons are more common than the opposite, but only amongst codons that vary substantially in their preference level. Overall, selection on codon bias seems to have little influence over non-synonymous polymorphism or substitution patterns.
Spatio-temporal development of the urban heat island in a socioeconomically diverse tropical city
Authors: Ramsay Emma E. , Duffy Grant A. , Burge Kerrie , Taruc Ruzka R. , Fleming Genie M. , Faber Peter A. , Chown Steven L. 
Published: July 2022

AbstractUrban heat islands, where temperatures are elevated relative to non-urban surrounds, are near-ubiquitous in cities globally. Yet, the magnitude and form of urban heat islands in the tropics, where heat has a large morbidity and mortality burden, is less well understood, especially for socioeconomically diverse communities such as those living in urban informal settlements. We utilised 29 years of Landsat satellite-derived surface temperature, corroborated by in situ measurements, to provide a detailed spatial and temporal assessment of urban heat islands in Makassar, Indonesia, a city that is representative of rapidly growing urban settlements across the tropics. We did so with explicit consideration of vulnerable communities living informally. Our analysis identified surface urban heat islands of up to 9.2 °C in long-urbanised parts of the city and 6.3 °C in informal settlements, the seasonal patterns of which were driven by change in non-urban areas rather than in urban areas themselves. In recently urbanised areas, the majority of urban heat island increase occurred before areas became 50% urbanised. As tropical cities continue to expand we expect that urban heat islands will develop quickly as land is urbanised, whereas the established heat island in long-urbanised areas will remain stable in response to city expansion. Green and blue space protect some informal settlements from the worst urban heat islands and maintenance of such space will be essential to mitigate the growing heat burden from urban expansion and anthropogenic climate change. We advocate for green space to be prioritised in urban planning, redevelopment and informal settlement upgrading programs, with consideration of the unique environmental and socioeconomic context of tropical cities.HighlightsLong-term, fine-scale data are essential to understand the dynamics of urban heatSurface heat islands reached 9.2 °C in the urban core, 6.3 °C in informal settlementsIn situ data support the use of remote sensing for heat island characterisationThe majority of heat island growth occurred before land was 50% urbanisedGreen and blue space can mitigate heat in informal settlements
A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing
Authors: Wilson Aaron , Hockney Sean , Parker Jess , Blair Helen , Pal Deepali 
Published: July 2022

AbstractPatient derived xenograft (PDX) models are regarded as gold standard preclinical models in leukaemia research, especially in testing new drug combinations where typically 45-50 animals are used per assay. 9000 animal experiments are performed annually in leukaemia research with these expensive procedures being described as moderate severity, meaning they cause significant pain, suffering and visible distress to animal’s state. Furthermore, not all clinical leukaemia samples engraft and when they do data turnaround time can be between 6-12 months. Heavy dependence on animal models is because clinical leukaemia samples do not proliferate in vitro. Alternative cell line models though popular for drug testing are not biomimetic – they are not dependent on the microenvironment for survival, growth and treatment response and being derived from relapse samples they do not capture the molecular complexity observed at disease presentation. Here we have developed an in vitro platform to rapidly establish co-cultures of patient-derived leukaemia cells with 3D bone marrow mesenchyme spheroids, BM-MSC-spheroids. We optimise protocols for developing MSC-spheroid leukaemia co-culture using clinical samples and deliver drug response data within a week. Using three patient samples representing distinct cytogenetics we show that patient-derived-leukaemia cells show enhanced proliferation when co-cultured with MSC-spheroids. In addition, MSC-spheroids provided improved protection against treatment. This makes our spheroids suitable to model treatment resistance – a major hurdle in current day cancer managementGiven this 3Rs approach is 12 months faster (in delivering clinical data), is a human cell-based biomimetic model and 45-50 animals/drug-response assay cheaper the anticipated target end-users would include academia and pharmaceutical industry. This animal replacement prototype would facilitate clinically translatable research to be performed with greater ethical, social and financial sustainability.Research HighlightsScientific BenefitA 3D spheroid-based approach for ex vivo co-culture of clinical leukaemia samples for further investigation into cancer biology such as blast-niche interactions, blast proliferation and treatment resistance3Rs BenefitTo replace moderate severity animal procedures in leukaemia research and drug testingPractical Benefit3Rs approach that yields drug response data quickly and is more ethically, socially and financially sustainable than its in vivo counterpartsCurrent applicationsExploration of leukaemia biology such as blasts proliferation, blast-niche interactions, niche-impacted treatment resistance and obtain drug response dataPotential applicationsExtend the approach to include other haematological cancers as well as bone cancers.
Highly sensitive quantitative phase microscopy and deep learning complement whole genome sequencing for rapid detection of infection and antimicrobial resistance
Authors: Ahmad Azeem , Hettiarachchi Ramith , Khezri Abdolrahman , Ahluwalia Balpreet Singh , Wadduwage Dushan N. , Ahmad Rafi 
Published: July 2022

AbstractThe current state-of-the-art infection and antimicrobial resistance diagnostics (AMR) is based mainly on culture-based methods with a detection time of 48-96 hours. Slow diagnoses lead to adverse patient outcomes that directly correlate with the time taken to administer optimal antimicrobials. Mortality risk doubles with a 24-hour delay in providing appropriate antibiotics in cases of bacteremia. Therefore, it is essential to develop novel methods that can promptly and accurately diagnose microbial infections at both species and strain levels in clinical settings. Here, we demonstrate that the complimentary use of label-free optical assay with whole-genome sequencing (WGS) can enable high-speed culture-free diagnosis of infection and AMR. Our assay is based on microscopy methods exploiting label-free, highly sensitive quantitative phase microscopy (QPM) followed by deep convolutional neural networks (DCNNs) based classification. We benchmarked our proposed workflow on 21 clinical isolates from four WHO priority pathogens (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, andAcinetobacter baumannii) that were antibiotic susceptibility testing (AST) phenotyped, and their antimicrobial resistance (AMR) profile was determined by WGS. The proposed optical assay was in good agreement with the WGS characterization. Highly accurate classification based on the gram staining (100% for gram-negative and 83.4% for gram-positive), species (98.6%), and resistant/susceptible type (96.4%), as well as at the individual strain level (100% accurate in predicting 19 out of the 21 strains). These results demonstrate the potential of the QPM assay as a rapid and first-stage tool for species, presence, and absence of AMR, and strain-level classification, which WGS can follow up for confirmation of the pathogen ID and the characterization of the AMR profile and susceptibility antibiotic. Taken together, all this information is of high clinical importance. Such a workflow could potentially facilitate efficient antimicrobial stewardship and prevent the spread of AMR.
Asymmetric voltage attenuation in dendrites can enable hierarchical heterosynaptic plasticity
Authors: Moldwin Toviah , Kalmenson Menachem , Segev Idan 
Published: July 2022

AbstractLong-term synaptic plasticity has been shown to be mediated via cytosolic calcium concentrations ([Ca2+]). Using a synaptic model which implements calcium-based long-term plasticity via two sources of Ca2+, NMDA receptors and voltage-gated calcium channels (VGCCs), we show in dendritic cable simulations, that the interplay between these two calcium sources can result in a diverse array of heterosynaptic effects. When spatially clustered synaptic input produces a local NMDA spike, the resulting dendritic depolarization can activate VGCCs at non-activated spines, resulting in heterosynaptic plasticity. NMDA spike activation at a given dendritic location will tend to depolarize dendritic regions that are located distally to the input site more than dendritic sites that are proximal to it. This asymmetry produces a hierarchical effect in branching dendrites, where an NMDA spike at a proximal branch can induce heterosynaptic plasticity primarily at branches that are distal to it. We also explored how simultaneously activated synaptic clusters located at different dendritic locations synergistically affect the plasticity at these locations, as well as the heterosynaptic plasticity of an inactive synapse “sandwiched” between them. We conclude that the inherent electrical asymmetry of dendritic trees enables sophisticated schemes for spatially targeted supervision of heterosynaptic plasticity.
Architecture and dynamics of a novel desmosome-endoplasmic reticulum organelle
Authors: Bharathan Navaneetha Krishnan , Giang William , Aaron Jesse S. , Khuon Satya , Chew Teng-Leong , Preibisch Stephan , Trautman Eric T. , Heinrich Larissa , Bogovic John , Bennett Davis , Ackerman David , Park Woohyun , Petruncio Alyson , Weigel Aubrey V. , Saalfeld Stephan ,   COSEM Project Team, Vogl A. Wayne , Stahley Sara N. , Kowalczyk Andrew P. 
Published: July 2022

AbstractThe endoplasmic reticulum (ER) forms a dynamic network that contacts other cellular membranes to regulate stress responses, calcium signaling, and lipid transfer. Using high-resolution volume electron microscopy, we find that the ER forms a previously unknown association with keratin intermediate filaments and desmosomal cell-cell junctions. Peripheral ER assembles into mirror image-like arrangements at desmosomes and exhibits nanometer proximity to keratin filaments and the desmosome cytoplasmic plaque. ER tubules exhibit stable associations with desmosomes, and perturbation of desmosomes or keratin filaments alters ER organization and mobility. These findings indicate that desmosomes and the keratin cytoskeleton pattern the distribution of the ER network. Overall, this study reveals a previously unknown subcellular architecture defined by the structural integration of ER tubules with an epithelial intercellular junction.One-Sentence SummaryThe desmosome adhesive junction regulates the organization and dynamics of the endoplasmic reticulum network.
Object-centered population coding in CA1 of the hippocampus
Authors: Nagelhus Anne , Andersson Sebastian O. , Cogno Soledad Gonzalo , Moser Edvard I. , Moser May-Britt 
Published: July 2022

SUMMARYObjects and landmarks are crucial for guiding navigation and must be integrated into the cognitive map of space. Studies of object coding in the hippocampus have primarily focused on activity of single cells. Here we record simultaneously from large numbers of hippocampal CA1 neurons to determine how the presence of a salient object in the environment alters single-neuron and neural-population dynamics of the area. Only a small number of cells fired consistently at the object location, or at a fixed distance and direction from it; yet the majority of the cells showed some change in their spatial firing patterns when the object was introduced. At the neural population level, these changes were systematically organized according to the animal’s distance from the object. This organization was widely distributed across the cell sample, suggesting that some features of cognitive maps – including object representation – are best understood as emergent properties of neural populations.
Predicting the principal components of cortical morphological variables
Authors: Mello V. B. B. , de Moraes F. H. , Mota B. 
Published: July 2022

AbstractThe generating mechanism for the gyrification of the mammalian cerebral cortex remains a central open question in neuroscience. Although many models have been proposed over the years, very few were able to provide empirically testable predictions. In this paper, we assume a model in which the cortex folds for all species of mammals according to a simple mechanism of effective free energy minimization of a growing self-avoiding surface subjected to inhomogeneous bulk stresses, to derive a new set of summary morphological variables that capture the most salient aspects of cortical shape and size. In terms of these new variables, we seek to understand the variance present in two morphometric datasets: a human MRI harmonized multi-site dataset comprised by 3324 healthy controls (CTL) from 4 to 96 years old and a collection of different mammalian cortices with morphological measurements extracted manually. This is done using a standard Principal Component Analysis (PCA) of the cortical morphometric space. We prove there is a remarkable coincidence (typically less than 8◦) between the resulting principal components vectors in each datasets and the directions corresponding to the new variables. This shows that the new, theoretically-derived variables are a set of natural and independent morphometrics with which to express cortical shape and size.
Can I touch the clothes on the screen? The mental simulation for touch in online fashion shopping
Authors: Lee Ha Kyung , Choi Dooyoung 
Published: July 2022

PurposeThis study aims to explore consumers' vicarious experience of touch, namely, mental simulation for touch, through product pictures as visual stimuli and the use of touch devices as motion stimuli in the context of online fashion shopping.Design/methodology/approachParticipants were randomly exposed to one of the two texture conditions (weak vs strong tactile sensitivity). The responses from the participants who used a laptop as a non-touch device and a touch device were considered in the analysis. A total of 179 responses were analyzed with analysis of variance and the PROCESS procedure for path analysis using SPSS 20.0.FindingsThe interaction effects of tactile sensitivity and device types on mental simulation for touch were significant; seeing a less tactile-sensitive product facilitated a greater mental simulation for touch when using a touch device; however, seeing a tactile-sensitive product produced a similar mental simulation for touch, regardless of device types. Furthermore, browsing a less tactile-sensitive product using a touch device increased favorable product attitudes, fully mediated by mental simulation for touch.Originality/valueThis study contributes to the literature on online shopping behaviors of fashion consumers by showing the role of mental simulation for touch that is shaped by the tactile qualities of products and device types. Exploration of this topic can contribute significantly to online fashion retailers because studies on consumers' mental simulation for touch are limited.