bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tuning of tuning: how adaptation influences single cell information transfer
Authors: Zeldenrust Fleur , Calcini Niccolò , Yan Xuan , Bijlsma Ate , Celikel Tansu 
Published: November 2020

AbstractSensory neurons reconstruct the world from action potentials (spikes) impinging on them. To effectively transfer information about the stimulus to the next processing level, a neuron needs to be able to adapt its working range to the properties of the stimulus. Here, we focus on the intrinsic neural properties that influence information transfer in cortical neurons and how tightly their properties need to be tuned to the stimulus statistics for them to be effective. We start by measuring the intrinsic information encoding properties of putative excitatory and inhibitory neurons in L2/3 of the mouse barrel cortex. Excitatory neurons show high thresholds and strong adaptation, making them fire sparsely and resulting in a strong compression of information, whereas inhibitory neurons that favour fast spiking transfer more information. Next, we turn to computational modelling and ask how two properties influence information transfer: 1) spike-frequency adaptation and 2) the shape of the IV-curve. We find that a subthreshold (but not threshold) adaptation, the ‘h-current’, and a properly tuned leak conductance can increase the information transfer of a neuron, whereas threshold adaptation can increase its working range. Finally, we verify the effect of the IV-curve slope in our experimental recordings and show that excitatory neurons form a more heterogeneous population than inhibitory neurons. These relationships between intrinsic neural features and neural coding that had not been quantified before will aid computational, theoretical and systems neuroscientists in understanding how neuronal populations can alter their coding properties, such as through the impact of neuromodulators. Why the variability of intrinsic properties of excitatory neurons is larger than that of inhibitory ones is an exciting question, for which future research is needed.Author summaryIntracellular information transfer from synaptic input to output spike train is necessarily lossy. Here, we explicitly measure the mutual information between a neuron’s input and spike output and show that information transfer is more lossy and heterogeneous for excitatory than for inhibitory neurons. By using computational modelling we show that the shape of the input-output curve as well as how fast a neuron adapts to its input collectively determine the rate of information loss. These insights will help both experimentalists and modellers in designing and simulating experiments that investigate how network coding properties can adapt to the environment, for instance through the effects of neuromodulators.
SPHERIOUSLY?The challenges of estimating spherical pore size non-invasively in the human brain from diffusion MRI
Authors: Afzali Maryam , Nilsson Markus , Palombo Marco , Jones Derek K 
Published: November 2020

AbstractThe Soma and Neurite Density Imaging (SANDI) three-compartment model was recently proposed to disentangle cylindrical and spherical geometries, attributed to neurite and soma compartments, respectively, in brain tissue. The approach could also enable estimation of microstructure parameters such as the apparent size (radius) of the soma. There are some recent advances in diffusion-weighted MRI signal encoding and analysis (including the use of multiple so-called ‘b-tensor’ encodings and analysing the signal in the frequency-domain) that have not yet been applied in the context of SANDI. In this work, using: (i) ultra-strong gradients; (ii) a combination of linear, planar, and spherical b-tensor encodings; and (iii) analysing the signal in the frequency domain, three main challenges to robust estimation of soma size were identified:First, the Rician noise floor in magnitude-reconstructed data biases estimates of soma properties in a non-uniform fashion. It may cause overestimation or underestimation of the soma size and density. This can be partly ameliorated by accounting for the noise floor in the estimation routine.Second, even when using the strongest diffusion-encoding gradient strengths available for human MRI, there is anempiricallower bound on the spherical signal fraction and pore-size that can be detected and estimated robustly. For the experimental setup used here, the lower bound on the signal fraction was approximately 10%. We employed two different ways of establishing the lower bound for spherical radius estimates in white matter. The first, examining power-law relationships between the DW-signal and diffusion weighting in empirical data, yielded a lower bound of 7μm, while the second, pure Monte Carlo simulations, yielded a lower limit of 3μmand in this low radii domain, there is little differentiation in signal attenuation.Third, if there is sensitivity to the transverse intra-cellular diffusivity in cylindrical structures, e.g., axons and cellular projections, then trying to disentangle two diffusion-time-dependencies using one experimental parameter (i.e., change in frequency-content of the encoding waveform) makes spherical pore-size estimates particularly challenging.We conclude that due to the aforementioned challenges spherical pore size estimates may be biased when the corresponding signal fraction is low, which must be considered when using them as biomarkers in clinical/research studies.
Obligate mutualistic cooperation limits evolvability
Authors: Pauli Benedikt , Oña Leonardo , Hermann Marita , Kost Christian 
Published: November 2020

AbstractCooperative mutualisms are widespread in nature and play fundamental roles in many ecosystems. Due to the often obligate nature of these interactions, the Darwinian fitness of the participating individuals is not only determined by the information encoded in their own genomes, but also the traits and capabilities of their corresponding interaction partners. Thus, a major outstanding question is how obligate cooperative mutualisms affect the ability of organisms to respond to environmental change with evolutionary adaptation. Here we address this issue using a mutualistic cooperation between two auxotrophic genotypes ofEscherichia colithat reciprocally exchange costly amino acids. Amino acid-supplemented monocultures and unsupplemented cocultures were exposed to stepwise increasing concentrations of different antibiotics. This selection experiment revealed that metabolically interdependent bacteria were generally less able to adapt to environmental stress than autonomously growing strains. Moreover, obligate cooperative mutualists frequently regained metabolic autonomy, thus resulting in a collapse of the mutualistic interaction. Together, our results identify a limited evolvability as a significant evolutionary cost that individuals have to pay when entering into an obligate mutualistic cooperation.
Clonal expansion of personalized anti-tumor T cells from circulation using tumor organoid-immune co-cultures
Authors: Meng Qingda , Xie Shanshan , Gray G. Kenneth , Li Weilin , Huang Ling , Akshinthala Dipikaa , Dezfulian Mohammad H. , Ferrer Elizabeth , Conahan Catherine , Del Pino Sofia Perea , Grossman Joseph , Elledge Stephen , Hidalgo Manuel , Muthuswamy Senthil K 
Published: November 2020

AbstractTumor-specific cytotoxic T cells are effective tools for cancer immunotherapy, but the ability to generate them continues to be a challenge. Furthermore, there are no compelling approaches to empirically identify tumor-targeting T cells and T cell receptors by exploiting the multitude of antigens on tumor cell surfaces. Here, we use patients’ peripheral blood and autologous tumor organoids to enrich tumor-specific cytotoxic T cells with patient-specific killing mechanisms and a tissue-resident memory phenotype. We further demonstrate that these organoid-primed T (opT) cells undergo several orders of magnitude of clonal expansion and express T cells receptors and check-point proteins unique to each patient. Importantly, transferring the TCRs to heterologous T cells was sufficient to confer tumor recognition in a patient-specific manner. Thus, we report a patient-specific and antigen-agnostic platform for expansion of tumor-targeting T cells and identification of cancer-targeting TCRs from the peripheral blood of pancreatic cancer patients that can be exploited for immunotherapy applications.
With Childhood Hemispherectomy, One Hemisphere Can Support--But is Suboptimal for--Word and Face Recognition
Authors: Granovetter Michael C. , Robert Sophia , Ettensohn Leah , Behrmann Marlene 
Published: November 2020

AbstractThe right and left cerebral hemispheres are important for face and word recognition, respectively—a specialization that emerges over human development. The question is whether this bilateral distribution is necessary or whether a single hemisphere, be it left or right, can support both face and word recognition. Here, face and word recognition accuracy in patients with a single hemisphere following childhood hemispherectomy was compared against matched typical controls. In Experiment 1, participants viewed stimuli in central vision. Across both face and word tasks, accuracy of both left and right hemispherectomy patients, while significantly lower than controls’ accuracy, averaged above 80% and did not differ from each other. To compare patients’ single hemisphere more directly to one hemisphere of controls, in Experiment 2, participants viewed stimuli in one visual field to constrain initial processing chiefly to a single (contralateral) hemisphere. Whereas controls had higher word accuracy when words were presented to the right than to the left visual field, there was no field/hemispheric difference for faces. In contrast, left and right hemispherectomy patients, again, showed comparable performance to one another on both face and word recognition, albeit significantly lower than controls. Altogether, the findings indicate that a single developing hemisphere, either left or right, may be sufficiently plastic for comparable representation of faces and words. However, perhaps due to increased competition or “neural crowding,” constraining cortical representations to one hemisphere may collectively hamper face and word recognition, relative to that observed in typical development with two hemispheres.Significance StatementAdults show right and left cerebral hemispheric biases for face and word recognition, respectively, a division of labor that emerges over development. Here, face and word recognition were assessed in childhood hemispherectomy patients to study the consequences of development with a single hemisphere. While these patients showed above 80% accuracy on face and word recognition tasks, which is surprisingly high relative to the brain volume resected, they nonetheless performed more poorly than typically developing controls. Importantly, patient performance was independent of which hemisphere was removed, suggesting that their single, preserved hemisphere subserves face and word recognition comparably, albeit somewhat inferiorly relative to controls. This demonstrates the remarkable plasticity of the developing brain but, at the same time, highlights plasticity’s constraints.
SECANT: a biology-guided semi-supervised method for clustering, classification, and annotation of single-cell multi-omics
Authors: Wang Xinjun , Xu Zhongli , Zhou Xueping , Zhang Yanfu , Huang Heng , Ding Ying , Duerr Richard H. , Chen Wei 
Published: November 2020

AbstractThe recent advance of single cell sequencing (scRNA-seq) technology such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) allows researchers to quantify cell surface protein abundance and RNA expression simultaneously at single cell resolution. Although CITE-seq and other similar technologies have quickly gained enormous popularity, novel methods for analyzing this new type of single cell multi-omics data are still in urgent need. A limited number of available tools utilize data-driven approach, which may undermine the biological importance of surface protein data. In this study, we developed SECANT, a biology-guided SEmi-supervised method for Clustering, classification, and ANnoTation of single-cell multi-omics. SECANT can be used to analyze CITE-seq data, or jointly analyze CITE-seq and scRNA-seq data. The novelties of SECANT include 1) using confident cell type labels identified from surface protein data as guidance for cell clustering, 2) providing general annotation of confident cell types for each cell cluster, 3) fully utilizing cells with uncertain or missing cell type labels to increase performance, and 4) accurate prediction of confident cell types identified from surface protein data for scRNA-seq data. Besides, as a model-based approach, SECANT can quantify the uncertainty of the results, and our framework can be easily extended to handle other types of multi-omics data. We successfully demonstrated the validity and advantages of SECANT via simulation studies and analysis of public and in-house real datasets. We believe this new method will greatly help researchers characterize novel cell types and make new biological discoveries using single cell multi-omics data.
Costly induction of defense reduces plant growth and alters reproductive traits in mixed-matingDatura stramonium
Authors: Jacobsen Deidra J. 
Published: November 2020

AbstractHerbivory shapes plant trait evolution by altering allocation to growth and defense in ways that affect plant reproduction and fitness. Initiation of these trade-offs may be particularly strong in juvenile plants with high phenotypic plasticity. Herbivory costs are often measured in terms of plant size or flower numbers, but other herbivore-induced floral changes can alter interactions with pollinators and have important implications for mating systems. In mixed-mating plants that can both self-fertilize and outcross, herbivory can maintain mating system variation if herbivore damage and defensive induction change a plant’s likelihood of selfing versus outcrossing. Here, I use mixed-matingDatura stramoniumto evaluate how early defensive induction and herbivory result in trade-offs among plant defense, growth and reproduction. I used a 2×2 factorial manipulation of early chemical defense induction and season-long insecticide in the field. Growth costs of chemical induction were seen even before plants received damage, indicating an inherent cost of defense. Induction and herbivory changed multiple aspects of floral biology associated with a plant’s selfing or outcrossing rate. This including reduced floral allocation, earlier flowering, and reduced anther-stigma separation (herkogamy). Although these floral changes are associated with decreased attractiveness to pollinators, plants exposed to natural herbivory did not have decreased seed set. This is likely because their floral morphologies became more conducive to selfing (via reduced herkogamy). These vegetative and floral changes following damage and defensive induction can impact interactions among plants (by altering mating environment) and interactions with pollinators (via changes in floral allocation and floral phenology).
A general technique for the detection of switch-like bistability in chemical reaction networks governed by mass action kinetics with conservation laws
Authors: Reyes Brandon C , Otero-Muras Irene , Petyuk Vladislav A 
Published: November 2020

AbstractBackgroundTheoretical analysis of signaling pathways can provide a substantial amount of insight into their function. One particular area of research considers signaling pathways capable of assuming two or more stable states given the same amount of signaling ligand. This phenomenon of bistability can give rise to switch-like behavior, a mechanism that governs cellular decision making. Investigation of whether or not a signaling pathway can confer bistability and switch-like behavior, without knowledge of specific kinetic rate constant values, is a mathematically challenging problem. Recently a technique based on optimization has been introduced, which is capable of finding example parameter values that confer switch-like behavior for a given pathway. Although this approach has made it possible to analyze moderately sized pathways, it is limited to reaction networks that presume a uniterminal structure. It is this limited structure we address by developing a general technique that applies to any mass action reaction network with conservation laws.ResultsIn this paper we developed a generalized method for detecting switch-like bistable behavior in any mass action reaction network with conservation laws. The method involves 1) construction of a constrained optimization problem using the determinant of the Jacobian of the underlying rate equations, 2) minimization of the objective function to search for conditions resulting in a zero eigenvalue 3) computation of a confidence level that describes if the global minimum has been found and 4) evaluation of optimization values, using either numerical continuation or directly simulating the ODE system, to verify that a bistability region exists. The generalized method has been tested on three motifs known to be capable of bistability.ConclusionsWe have developed a variation of an optimization-based method for discovery of bistability, which is not limited to the structure of the chemical reaction network. Successful completion of the method provides an S-shaped bifurcation diagram, which indicates that the network acts as a bistable switch for the given optimization parameters.
Newly identified proviruses in Thermotogota suggest that viruses are the vehicles on the highways of interphylum gene sharing
Authors: Haverkamp Thomas H. A. , Lossouarn Julien , Zhaxybayeva Olga , Lyu Jie , Bienvenu Nadège , Geslin Claire , Nesbø Camilla L. 
Published: November 2020

ABSTRACTPhylogenomic analyses of bacteria from the phylum Thermotogota have shown extensive lateral gene transfer (LGT) with distantly related organisms, particularly with Firmicutes. One likely mechanism of such DNA transfer is viruses. However, to date only three temperate viruses have been characterized in this phylum, all infecting bacteria from the Marinitoga genus. Here we report 17 proviruses integrated into genomes of eight Thermotogota genera and induce viral particle production from one of the proviruses. The proviruses fall into two groups based on sequence similarity, gene synteny and taxonomic classification. Proviruses of one group are found in six genera and are similar to the previously identified Marinitoga viruses, while proviruses from the second group are only distantly related to the proviruses of the first group, have different genome organization and are found in only two genera. Both groups are closely related to Firmicutes in genomic and phylogenetic analyses, and one of the groups show evidence of very recent LGT and are therefore likely capable of infecting cells from both phyla. We conjecture that viruses are responsible for a large portion of the observed gene flow between Firmicutes and Thermotogota.
Acute radiofrequency electromagnetic radiation exposures cause neuronal DNA damage and impair neurogenesis in the young adolescent rat brain
Authors: Singh Kumari Vandana , Prakash Chandra , Nirala Jay Prakash , Nanda Ranjan Kumar , Rajamani Paulraj 
Published: November 2020

AbstractMobile phone is now a commonly used communication device in all age groups. Young adolescents use it for longer duration and effect of its radiofrequency electromagnetic radiation (RF-EMR) on their brain structure and function need detailed investigation. In the present study, we investigated the effect of RF-EMR emitted from mobile phones, on young adolescent rat brain. Wistar rats (5 weeks, male) were exposed to RF-EMR signal (2,115 MHz) from a mobile phone at a whole body averaged specific absorption rate (SAR) of 1.15 W/kg continuously for 8 h. Higher level of lipid peroxidation, carbon centered lipid radicals and DNA damage were observed in the brain of rat exposed to RF-EMR. Number of neural progenitor cells (NPCs) in dentate gyrus (DG) were found to be relatively low in RF-EMR exposed rats that may be due to reduced neurogenesis. Acute exposure to RF-EMR induced neuronal degeneration in DG region with insignificant variation in CA3, CA1 and cerebral cortex sub regions of hippocampus. Findings of this study, indicate that acute exposure of high frequency RF-EMR at relatively higher SAR may adversely impact the neurogenesis and function of adolescent rat brain. Generation of carbon centered lipid radicals, and nuclear DNA damage might be playing critical role in reduced neurogenesis and higher neuronal degeneration in the cortex and hippocampus of brain. Detailed understanding of RF-EMR induced alteration in brain function will be useful to develop appropriate interventions for reducing the impact caused by RF-EMR damage.
Prime Editing in Mice Reveals the Essentiality of a Single Base in Driving Tissue-Specific Gene Expression
Authors: Gao Pan , Lyu Qing , Ghanam Amr R. , Lazzarotto Cicera R. , Newby Gregory A. , Zhang Wei , Choi Mihyun , Slivano Orazio J. , Holden Kevin , Walker John A. , Kadina Anastasia P. , Munroe Rob J. , Abratte Christian M. , Schimenti John C. , Liu David R. , Tsai Shengdar Q. , Long Xiaochun , Miano Joseph M. 
Published: November 2020

AbstractMost single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Several genome editing platforms have emerged to evaluate the functionality of TFBS in animals. Here, a comparative analysis of CRISPR-mediated homology-directed repair (HDR) versus the recently reported prime editing 2 (PE2) system was carried out in mice to demonstrate the essentiality of a single TFBS, called a CArG box, in the promoter region of theTspan2gene. HDR-mediated substitution of three base pairs in theTspan2CArG box resulted in 20/37 (54%) founder mice testing positive for the correct edit. Mice homozygous for this edit showed near loss ofTspan2expression in aorta and bladder with no change in heart or brain. Using the same protospacer, PE2-mediated editing of a single base in theTspan2CArG box yielded 12/47 (26%) founder mice testing positive for the correct edit. This single base substitution resulted in ∼90% loss ofTspan2expression in aorta and bladder with no change in heart or brain. Targeted sequencing demonstrated all PE2 and HDR founders with some frequency of on-target editing. However, whereas no spurious on-target indels were detected in any of the PE2 founders, many HDR founders showed variable levels of on-target indels. Further, off-target analysis by targeted sequencing revealed mutations in 5/11 (45%) HDR founders but none in PE2 founders. These results demonstrate high fidelity editing of a TFBS with PE2 and suggest a new paradigm for Cre/loxP-free tissue-specific gene inactivation via single base substitution in a TFBS. The PE2 platform of genome editing represents a powerful approach for modeling and correcting relevant noncoding SNVs in the mouse.