bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental platform for the functional investigation of membrane proteins in giant unilamellar vesicles
Authors: Dolder Nicolas , Müller Philipp , von Ballmoos Christoph 
Published: December 2021

AbstractGiant unilamellar vesicles (GUVs) are micrometer-sized model membrane systems that can be viewed directly under the microscope. They serve as scaffolds for the bottom-up creation of synthetic cells, targeted drug delivery and have been used in many in vitro studies of membrane related phenomena. GUVs are also of interest for the functional investigation of membrane proteins that carry out many key cellular functions. A major hurdle to a wider application of GUVs in this field is the diversity of existing protocols that are optimized for individual proteins. Here, we compare PVA assisted and electroformation techniques for GUV formation under physiologically relevant conditions, and analyze the effect of immobilization on vesicle structure and membrane tightness towards small substrates and protons. There, differences in terms of yield, size, and leakage of GUVs produced by PVA assisted swelling and electroformation were found, dependent on salt and buffer composition. Using fusion of oppositely charged membranes to reconstitute a model membrane protein, we find that empty vesicles and proteoliposomes show similar fusion behavior, which allows for a rapid estimation of protein incorporation using fluorescent lipids.
Exploratory growth in Streptomyces venezuelae involves a unique transcriptional program, enhanced oxidative stress response, and profound acceleration in response to glycerol
Authors: Shepherdson Evan M. F. , Netzker Tina , Stoyanov Yordan , Elliot Marie A. 
Published: December 2021

ABSTRACTExploration is a recently discovered mode of growth and behaviour exhibited by some Streptomyces species that is distinct from their classical sporulating life cycle. While much has been uncovered regarding initiating environmental conditions and the phenotypic outcomes of exploratory growth, how this process is coordinated at a genetic level remains unclear. We used RNA-sequencing to survey global changes in the transcriptional profile of exploring cultures over time in the model organism Streptomyces venezuelae. Transcriptomic analyses revealed widespread changes in gene expression impacting diverse cellular functions. Investigations into differentially expressed regulatory elements revealed specific groups of regulatory factors to be impacted, including the expression of several extracytoplasmic function (ECF) sigma factors, second messenger signalling pathways, and members of the whiB-like (wbl) family of transcription factors. Dramatic changes were observed among primary metabolic pathways, especially among respiration-associated genes and the oxidative stress response; enzyme assays confirmed that exploring cultures exhibit an enhanced oxidative stress response compared with classically growing cultures. Changes in expression of the glycerol catabolic genes in S. venezuelae led to the discovery that glycerol supplementation of the growth medium promotes a dramatic acceleration of exploration. This effect appears to be unique to glycerol as an alternative carbon source and this response is broadly conserved across other exploration-competent species.
Taking stock of the past: A psychometric evaluation of the Autobiographical Interview
Authors: Lockrow Amber W. , Setton Roni , Spreng Karen A.P. , Sheldon Signy , Turner Gary R. , Spreng R. Nathan 
Published: December 2021

AbstractAutobiographical memory (AM) involves a rich phenomenological re-experiencing of a spatio-temporal event from the past, which is challenging to objectively quantify. The Autobiographical Interview (AI; Levine etal., 2002,Psychology & Aging) is a manualized performance-based assessment designed to quantify episodic (internal) and semantic (external) features of recalled and verbally conveyed prior experiences. The AI has been widely adopted yet has not undergone a comprehensive psychometric validation. We investigated the reliability, validity, association to individual differences measures, and factor structure in healthy younger and older adults (N=352). Evidence for the AI’s reliability was strong: the subjective scoring protocol showed high inter-rater reliability and previously identified age effects were replicated. Internal consistency across timepoints was robust, suggesting stability in recollection. Central to our validation, internal AI scores were positively correlated with standard, performance-based measures of episodic memory, demonstrating convergent validity. The two-factor structure for the AI was not well-supported by confirmatory factor analysis. Adjusting internal and external detail scores for the number of words spoken (detail density) improved trait estimation of AM performance. Overall, the AI demonstrated sound psychometric properties for inquiry into the qualities of autobiographical remembering.
Post-error slowing reflects the joint impact of adaptive and maladaptive processes during decision making
Authors: Fievez Fanny , Derosiere Gerard , Verbruggen Frederick , Duque Julie 
Published: December 2021

AbstractErrors and their consequences are typically studied by investigating changes in decision speed and accuracy in trials that follow an error, commonly referred to as “post-error adjustments”. Many studies have reported that subjects slow down following an error, a phenomenon called “post-error slowing” (PES). However, the functional significance of PES is still a matter of debate as it is not always adaptive. That is, it is not always associated with a gain in performance and can even occur with a decline in accuracy. Here, we hypothesized that the nature of PES is influenced by one’s speed-accuracy tradeoff policy, which determines the overall level of choice accuracy in the task at hand. To test this hypothesis, we investigated post-error adjustments in subjects performing the same task while they were required to either emphasize speed (low accuracy) or cautiousness (high accuracy) in two distinct contexts (hasty and cautious contexts, respectively) experienced on separate days. Accordingly, our data indicate that post-error adjustments varied according to the context in which subjects performed the task, with PES being solely significant in the hasty context. In addition, we only observed a gain in performance after errors in a specific trial type, suggesting that post-error adjustments depend on a complex combination of processes that affect the speed of ensuing actions as well as the degree to which such PES comes with a gain in performance.
Theta oscillations in the prefrontal-hippocampal circuit do not couple to respiration-related oscillations
Authors: Srikanth Sunandha , Le Dylan , Hu Yudi , Leutgeb Jill K. , Leutgeb Stefan 
Published: December 2021

ABSTRACTOscillatory activity is thought to coordinate neural computations across brain regions, and theta oscillations are critical for learning and memory. Because the frequency of respiratory-related oscillations (RROs) in rodents can overlap with the frequency of theta in the prefrontal cortex (PFC) and the hippocampus, we asked whether odor-cued working memory may be supported by coupling between these two oscillations. We first confirmed that RROs are propagated to the hippocampus and PFC and that RRO frequency overlaps with canonical theta frequency. However, we found low coherence between RROs and local theta oscillations in the hippocampus-PFC network when the two types of oscillations overlapped in frequency. This effect was observed during all behavioral phases including during movement and while odors were actively sampled when stationary. Despite the similarity in frequency, RROs and theta oscillations therefore appear to be limited to supporting computation in distinct networks, which suggests that sustained long-range coordination between oscillation patterns that depend on separate pacemakers is not necessary to support at least one type of working memory.
Network design principle for robust oscillatory behaviors with respect to biological noise
Authors: Qiao Lingxia , Zhang Zhi-Bo , Zhao Wei , Wei Ping , Zhang Lei 
Published: December 2021

ABSTRACTOscillatory behaviors, which are ubiquitous in transcriptional regulatory networks, are often subject to inevitable biological noise. Thus a natural question is how transcriptional regulatory networks can robustly achieve accurate oscillation in the presence of biological noise. Here, we search all two- and three-node transcriptional regulatory network topologies for those robustly capable of accurate oscillation against the parameter variability (extrinsic noise) or stochasticity of chemical reactions (intrinsic noise). We find that, no matter what source of the noise is applied, the topologies containing the repressilator with positive auto-regulation show higher robustness of accurate oscillation than those containing the activator-inhibitor oscillator, and additional positive auto-regulation enhances the robustness against noise. Nevertheless, the attenuation of different sources of noise is governed by distinct mechanisms: the parameter variability is buffered by the long period, while the stochasticity of chemical reactions is filtered by the high amplitude. Furthermore, we analyze the noise of a synthetic human nuclear factor κB (NF-κB) signaling network by varying three different topologies, and verify that the addition of a repressilator to the activator-inhibitor oscillator, which leads to the emergence of high-robustness motif—the repressilator with positive auto-regulation, improves the oscillation accuracy in comparison to the topology with only an activator-inhibitor oscillator. These design principles may be applicable to other oscillatory circuits.
Antibody-Independent Antitumor Effects of Cd32A-Chimeric Receptor T Cells: Implications for Breast Cancer Prognosis and Treatment
Authors: Sconocchia Giuseppe , Lanzilli Giulia , Cesarini Valeriana , Silvestris Domenico Alessandro , Arriga Roberto , Rezvani Katayoun , Caratelli Sara , Chen Ken , Dou Jinzhuang , Cenciarelli Carlo , Toietta Gabriele , Baldari Silvia , Sconocchia Tommaso , Paolis Francesca De , Aureli Anna , Iezzi Giandomenica , del Principe Maria Ilaria , Venditti Adriano , Ottaviani Alessio , Spagnoli Giulio Cesare 
Published: December 2021

ABSTRACTFcγ RIIA (CD32A) and their ligands, including the immunoglobulin Fc fragment and pentraxins, are key players in a variety of innate immune responses. Still unclear is whether additional ligands of CD32A do exist. The objective of this study is to demonstrate that CD32A-chimeric receptor (CR) can be utilized for the identification of CD32A cell surface ligand(s). Among fifteen cancer cell lines tested, CD32A-CR T cells recognized three of breast cancer (BC) including the MDA-MB-468 and one colorectal carcinoma (HT29) in the absence of targeting antibodies. Conjugation of sensitive BC cells with CD32A-CR T cells induced CD32A polarization and down-regulation, CD107 release, and mutual cell eliminationin vitro. Conversely, normal fibroblasts and myoblasts were not affected while normal HUVEC cells promoted CD32A down-regulation. CD32A-CR T cell activity was not inhibited by human IgGs or human serum, but; it was rather enhanced by cetuximab antibody. RNAseq analysis of sensitive vs resistant BC cells identified a fingerprint of 42 genes predicting the sensitivity of BC cells to CD32A-CR T cells and their association with favorable prognostic significance in advanced BC patients. Our data also identify ICAM 1 as a major regulator of CD32A-CR T cell-mediated cytotoxicity. Finally, CD32A-CR T cell administration protected immunodeficient mice from subcutaneous growth of MDA-MB-468 cells in the absence of tumor-specific antibodies. These data indicate that CD32A-CR can be utilized for the identification of (1) cell surface CD32A ligand(s); (2) rational therapeutic strategies to target BC; and (3) novel transcriptomic signatures prognostically relevant for advanced BC patients.
Multi-omics Topic Modeling for Breast Cancer Classification
Authors: Valle Filippo , Osella Matteo , Caselle Michele 
Published: December 2021

AbstractThe integration of transcriptional data with other layers of information, such as the post-transcriptional regulation mediated by microRNAs, can be crucial to identify the driver genes and the subtypes of complex and heterogeneous diseases such as cancer. This paper presents an approach based on topic modeling to accomplish this integration task. More specifically, we show how an algorithm based on a hierarchical version of stochastic block modeling can be naturally extended to integrate any combination of ‘omics data. We test this approach on breast cancer samples from the TCGA database, integrating data on messenger RNA, microRNAs and copy number variations. We show that the inclusion of the microRNA layer significantly improves the accuracy of subtype classification. Moreover, some of the hidden structures or “topics” that the algorithm extracts actually correspond to genes and microRNAs involved in breast cancer development, and are associated to the survival probability.Simple SummaryTopic models are algorithms introduced for discovering hidden topics or latent variables in large unstructured text corpora. Leveraging on analogies between texts and gene expression profiles, these algorithms can be used to find structures in expression data. This work presents an application of topic modeling techniques to the identification of breast cancer subtypes. In particular, we extended a specific class of topic models to allow a multi-omics approach. As an illustrative example, considering both messenger RNA and microRNA expression levels, we were able to clearly distinguish healthy from tumor samples, as well as the different breast cancer subtypes. The integration of different layers of information is crucial for the observed classification accuracy. Our approach naturally provides the genes and the microRNAs associated to the specific topics that are used for the sample organization. We show that indeed these topics often contain genes involved in breast cancer development, and are associated to different survival probabilities.
Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism
Authors: Thorn Trista L. , Mitchell Samuel B. , Kim Yongeun , Lee Min-Ting , Comrie Janine M. C. , Johnson Elizabeth L. , Aydemir Tolunay B. 
Published: December 2021

AbstractZinc (Zn) plays a critical role in maintaining intestinal homeostasis by regulating intestinal epithelial cells, host immune cells, and gut microbiome community composition. Deletion of metal transporter Slc39a14/Zip14 causes spontaneous intestinal permeability with low-grade chronic inflammation, mild hyperinsulinemia, and greater body fat with insulin resistance in adipose, suggesting a role for ZIP14-mediated intestinal metal transport in regulating both intestinal homeostasis and systemic metabolism. Here, we showed the function of ZIP14-mediated Zn transport in the gut microbiome composition and how ZIP14-linked changes to gut microbiome community composition are correlated with changes in host metabolism. Deletion of Zip14 generated Zn-deficient epithelial cells and luminal content in the entire intestinal tract; reduced bacterial diversity and Saccharomyces cerevisiae (S. cerevisiae) overgrowth; altered host metabolome; and shifted host energy metabolism toward glucose utilization. This work provides evidence for the regulation of gut microbiome composition, host metabolome, and energy metabolism by metal transporter ZIP14.SignificanceIntestinal permeability, gut dysbiosis, and Zn dyshomeostasis are emerging signatures of inflammatory bowel diseases and metabolic disorders such as type-2-diabetes and obesity. Zn deficiency is a common clinical finding among these diseases. Zn is essential for the regulation of the intestinal epithelial cells, host immune cells, and the gut microbiome. Transporter-mediated mobilization of Zn plays a critical role in maintaining intestinal homeostasis by facilitating the targeted tissue/cell-specific function. However, studies are lacking in linking transporter-mediated Zn mobilization, gut microbiome, host’s intestinal health, and metabolism. Using the systems-level approach, this study revealed novel findings that deletion of Slc39a14/Zip14 resulted in altered intestinal Zn homeostasis, gut microbiome composition, host metabolome and energy metabolism.
Heterogeneity of network and coding states in CA1
Authors: Guardamagna Matteo , Stella Federico , Battaglia Francesco P. 
Published: December 2021

AbstractTheta sequences and phase precession shape the activity time course of hippocampal place cells. Theta sequences are rapid sweeps of spikes from multiple cells, tracing trajectories from past to future. Phase precession is the correlation between a place cell’s theta firing phase and animal position. Here we present an analysis of the strongly variable character of these features in CA1. We identify a cell group that do not phase precess but reliably express theta sequences. The cells that do phase precess only do so when the medium gamma oscillations (60-90 Hz, linked to Entorhinal inputs) dominates but then they show less theta sequences. The same cells express more sequences but not precession when slow gamma (20-45 Hz, linked to CA3 inputs) dominates. Moreover, sequences occur independently in the two groups. Our results challenge a causal relationship between precession and sequences and highlights the highly heterogeneous character of the hippocampal output.
Single-cell RNA-seq analysis reveals lung epithelial cell-specific contributions of Tet1 to allergic inflammation
Authors: Zhu Tao , Brown Anthony P. , Cai Lucy , Quon Gerald , Ji Hong 
Published: December 2021

ABSTRACTTet1 protects against house dust mite (HDM)-induced lung inflammation in mice and alters the lung methylome and transcriptome. In order to explore the role of Tet1 in individual lung epithelial cell types in HDM-induced inflammation, we established a model of HDM-induced lung inflammation in Tet1 knockout and littermate wildtype mice and studied EpCAM+ lung epithelial cells using single-cell RNA-seq analysis. We identified eight EpCAM+ lung epithelial cell types, among which AT2 cells were the most abundant. HDM challenge increased the percentage of alveolar progenitor cells (AP), broncho alveolar stem cells (BAS), and goblet cells, and decreased the percentage of AT2 and ciliated cells. Bulk and cell-type-specific analysis identified genes subject to Tet1 regulation and linked to augmented lung inflammation, including alarms, detoxification enzymes, oxidative stress response genes, and genes in tissue repair. The transcriptomic regulation was accompanied by alterations in TF activities. Trajectory analysis supports that HDM may enhance the differentiation of AP and BAS cells into AT2 cells, independent of Tet1. Collectively, our data showed that lung epithelial cells had common and unique transcriptomic signatures of allergic lung inflammation. Tet1 deletion altered transcriptomic networks in various lung epithelial cells, with an overall effect of promoting allergen-induced lung inflammation.
Vicia faba TPC1, a genetically encoded variant of the vacuole Two Pore Channel 1, is hyperexcitable
Authors: Lu Jinping , Dreyer Ingo , Dickinson Miles Sasha , Panzer Sabine , Jaslan Dawid , Navarro-Retamal Carlos , Geiger Dietmar , Terpitz Ulrich , Becker Dirk , Stroud Robert M. , Marten Irene , Hedrich Rainer 
Published: December 2021

AbstractTo fire action-potential-like electrical signals, the vacuole membrane requires the depolarization-activated two-pore channel TPC1, also called Slowly activating Vacuolar SV channel. The TPC1/SV channel, encoded by the TPC1 gene, functions as a voltage-dependent and Ca2+-regulated potassium channel. TPC1 currents are activated by a rise in cytoplasmic Ca2+ but inhibited by luminal Ca2+. In search for species-dependent functional TPC1 channel variants, we studied polymorphic amino acids contributing to luminal Ca2+ sensitivity. We found that the acidic residues E457, E605 and D606 of the Ca2+-sensitive Arabidopsis AtTPC1 channel were neutralized by either asparagine or alanine in Vicia faba and many other Fabaceae as well. When expressed in the Arabidopsis loss-of-AtTPC1 function background, the wild type VfTPC1 was hypersensitive to vacuole depolarization and insensitive to blocking luminal Ca2+. When AtTPC1 was mutated for the three VfTPC1-homologous polymorphic site residues, the Arabidopsis At-VfTPC1 channel mutant gained VfTPC1-like voltage and luminal Ca2+ insensitivity that together made vacuoles hyperexcitable. These findings indicate that natural TPC1 channel variants in plant families exist which differ in vacuole excitability and very likely respond to changes in environmental settings of their ecological niche.Significance statementVacuolar electrical excitability and stress-related Ca2+ signaling depends on the activity of the vacuolar cation channel TPC1. Until now, the regulatory features of AtTPC1 from the model plant Arabidopsis thaliana was believed to apply to the TPC1 channels of other species. However, here we now show that, surprisingly, the VfTPC1 channel of the economic broad bean, in contrast to AtTPC1, proves to be hyperactive and confers hyperexcitability to the vacuole. The different gating behavior is most likely related to an impaired Ca2+ sensor site in the vacuolar pore vestibule, rising the probability to open at more negative membrane voltages. These natural variants of the TPC1 channel could help the plant adapt and respond to environmental challenges.
Multimodal fusion analysis of functional, cerebrovascular and structural neuroimaging in healthy ageing subjects
Authors: Liu Xulin , Tyler Lorraine K ,   Cam-CAN, Rowe James B , Tsvetanov Kamen A 
Published: December 2021

AbstractBrain ageing is a complex process which requires a multimodal approach. Neuroimaging can provide insights into brain morphology, functional organization and vascular dynamics. However, most neuroimaging studies of ageing have focused on each imaging modality separately, limiting the understanding of interrelations between processes identified by different modalities and their relevance to cognitive decline in ageing. Here, we used a data-driven multimodal approach, linked independent component analysis (ICA), to jointly analyze magnetic resonance imaging of grey matter volume, cerebrovascular, and functional network topographies in relation to measures of fluid intelligence. Neuroimaging and cognitive data from the Cambridge Centre for Ageing and Neuroscience study were used, with healthy participants aged 18 to 88 years (main dataset n = 215; secondary dataset n = 433). Using linked ICA, functional network activities were characterized in independent components but not captured in the same component as structural and cerebrovascular patterns. Split-sample (n = 108/107) and out-of-sample (n = 433) validation analyses using linked ICA were also performed. Global grey matter volume with regional cerebrovascular changes and the right frontoparietal network activity were correlated with age-related and individual differences in fluid intelligence. This study presents the insights from linked ICA to bring together measurements from multiple imaging modalities, with independent and additive information. We propose that integrating multiple neuroimaging modalities allows better characterization of brain pattern variability and changes associated with healthy ageing.