bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intent matters: how flow & forms of information impact collective navigation
Authors: Hodgson T. M. , Johnston S. T. , Ottobre M. , Painter K. J. 
Published: June 2023

AbstractThe phenomenon of collective navigation has received considerable interest in recent years. A common line of thinking, backed by theoretical studies, is that collective navigation can improve navigation efficiency through the ‘many-wrongs’ principle, whereby individual error is reduced by comparing the headings of neighbours. When navigation takes place in a flowing environment, each individual’s trajectory is influenced by drift. Consequently, a potential discrepancy emerges between an individual’s intended heading and its actual heading. In this study we develop a theoretical model to explore whether collective navigation benefits are altered according to the form of heading information transmitted between neighbours. Navigation based on each individual’s intended heading is found to confer robust advantages across a wide spectrum of flows, via both a marked improvement in migration times and a capacity for a group to overcome flows unnavigable by solitary individuals. Navigation based on individual’s actual headings is far less effective, only offering an improvement under highly favourable currents. For many currents, sharing actual heading information can even lead to journey times that exceed those of individual navigators.
Defects in Mitochondrial Biogenesis Drive Mitochondrial Alterations in PINK1-deficient Human Dopamine Neurons
Authors: Wang Hu , Chen Rong , Xiao Liming , Kumar Manoj , Acevedo-Cintrón Jesús , Siuda Joanna , Koziorowski Dariusz , Wszolek Zbigniew K. , Dawson Valina L. , Dawson Ted M. 
Published: June 2023

SummaryMutations and loss of activity in the protein kinase PINK1 play a role in the pathogenesis of Parkinson’s disease (PD). PINK1 regulates many aspects of mitochondrial quality control including mitochondrial autophagy (mitophagy), fission, fusion, transport, and biogenesis. Defects in mitophagy are though to play a predominant role in the loss of dopamine (DA) neurons in PD. Here we show that, although there are defects in mitophagy in human DA neurons lacking PINK1, mitochondrial deficits induced by the absence of PINK1 are primarily due to defects in mitochondrial biogenesis. Upregulation of PARIS and the subsequent down regulation of PGC-1α accounts for the mitochondrial biogenesis defects. CRISPR/Cas9 knockdown of PARIS completely restores the mitochondrial biogenesis defects and mitochondrial function without impacting the deficits in mitophagy due to the absence of PINK1. These results highlight the importance mitochondrial biogenesis in the pathogenesis of PD due to inactivation or loss of PINK1 in human DA neurons.
A co-ordinated transcriptional programme in the maternal liver supplies LC-PUFAs to the conceptus using phospholipids
Authors: Amarsi Risha , Furse Samuel , Cleaton Mary AM , Maurel Sarah , Mitchell Alice L , Ferguson-Smith Anne C. , Cenac Nicolas , Williamson Catherine , Koulman Albert , Charalambous Marika 
Published: June 2023

ABSTRACTEssential fatty acids (EFAs) and their derivatives, the long and very long chain polyunsaturated fatty acids (LC-PUFAs), are preferentially transported by the mother to the fetus. Failure to supply EFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary EFA intake and the molecular mechanisms of maternal supply. Here we combine untargeted lipidomics with transcriptional profiling of healthy and genetically-manipulated murine models to understand the maternal adaptations required to provide LC-PUFAs to the developing fetus. We discovered a late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway which dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduced LC-PUFA accumulation by the fetus. Overall our work suggests new molecular strategies for improving maternal-fetal transfer of these important lipids.
Adhesion energy controls lipid binding-mediated endocytosis
Authors: Groza Raluca , Schmidt Kita Valerie , Müller Paul Markus , Ronchi Paolo , Schlack-Leigers Claire , Neu Ursula , Puchkov Dmytro , Dimova Rumiana , Matthäus Claudia , Taraska Justin , Weikl Thomas R. , Ewers Helge 
Published: June 2023

AbstractSeveral bacterial toxins and viruses can deform membranes through multivalent binding to lipids for clathrin-independent endocytosis. However, it remains unclear, how membrane deformation and endocytic internalization are mechanistically linked. Here we show that many lipid-binding virions induce membrane deformation and clathrin-independent endocytosis, suggesting a common mechanism based on multivalent lipid binding by globular particles. We create a synthetic cellular system consisting of a lipid-anchored receptor in the form of GPI-anchored anti-GFP nanobodies and a multivalent globular binder exposing 180 regularly-spaced GFP molecules on its surface. We show that these globular, 40 nm diameter, particles bind to cells expressing the receptor, deform the plasma membrane upon adhesion and become endocytosed in a clathrin-independent manner. We explore the role of the membrane adhesion energy in endocytosis by using receptors with affinities varying over 7 orders of magnitude. Using this system, we find that once a threshold in adhesion energy is overcome to allow for membrane deformation, endocytosis occurs reliably. Multivalent, binding-induced membrane deformation by globular binders is thus sufficient for internalization to occur and we suggest it is the common, purely biophysical mechanism for lipid-binding mediated endocytosis of toxins and pathogens.
The highly and perpetually upregulated thyroglobulin gene is a hallmark of functional thyrocytes
Authors: Ullrich Simon , Leidescher Susanne , Feodorova Yana , Thanisch Katharina , Fini Jean-Baptiste , Kaspers Bernd , Weber Frank , Markova Boyka , Führer Dagmar , Romitti Mirian , Krebs Stefan , Blum Helmut , Leonhardt Heinrich , Costagliola Sabine , Heuer Heike , Solovei Irina 
Published: June 2023

ABSTRACTAbnormalities are indispensable for studying normal biological processes and mechanisms. In the present work, we draw attention to the remarkable phenomenon of a perpetually and robustly upregulated gene, the thyroglobulin gene (Tg). The gene is expressed in the thyroid gland and, as it has been recently demonstrated, forms so-called transcription loops, easily observable by light microscopy. Using this feature, we show thatTgis expressed at a high level from the moment a thyroid cell acquires its identity and both alleles remain highly active over the entire life of the cell, i.e. for months or years depending on the species. We demonstrate that this high upregulation is characteristic of thyroglobulin genes in all major vertebrate groups. We provide evidence thatTgis not influenced by the thyroid hormone status, does not oscillate round the clock and is expressed during both the exocrine and endocrine phases of thyrocyte activity. We conclude that the thyroglobulin gene represents a valuable model to study the maintenance of a high transcriptional upregulation.SUMMARY STATEMENTThe thyroglobulin gene is highly and permanently expressed in thyrocytes of all vertebrates, at any condition and round the clock, offering a unique model to study mechanisms of high upregulation maintenance and chromatin dynamics
A Chicken Tapasin ortholog can chaperone empty HLA molecules independently of other peptide-loading components
Authors: Papadaki Georgia F. , Woodward Claire H. , Young Michael C. , Winters Trenton J. , Burslem George M. , Sgourakis Nikolaos G. 
Published: June 2023

AbstractHuman Tapasin (hTapasin) is the main chaperone of MHC-I molecules, enabling peptide loading and antigen repertoire optimization across HLA allotypes. However, it is restricted to the endoplasmic reticulum (ER) lumen as part of the protein loading complex (PLC) and therefore is highly unstable when expressed in recombinant form. Additional stabilizing co-factors such as ERp57 are required to catalyze peptide exchangein vitro, limiting uses for the generation of pMHC-I molecules of desired antigen specificities. Here, we show that the chicken Tapasin (chTapasin) ortholog can be expressed recombinantly at high yields in stable form, independently of co-chaperones. chTapasin can bind the human HLA-B*37:01 with low micromolar-range affinity to form a stable tertiary complex. Biophysical characterization by methyl-based NMR methods reveals that chTapasin recognizes a conserved β2m epitope on HLA-B*37:01, consistent with previously solved X-ray structures of hTapasin. Finally, we provide evidence that the B*37:01/chTapasin complex is peptide-receptive and can be dissociated upon binding of high-affinity peptides. Our results highlight the use of chTapasin as a stable scaffold for future protein engineering applications aiming to expand the ligand exchange function on human MHC-I and MHC-like molecules.
Effect of Acute Stress on Working Memory in Pilots: Investigating the Modulatory Role of Memory Load
Authors: Liang Yaowei , Peng Xing , Liu Yueying , Zhu Qi , Xu Zhi , Yang Jiazhong 
Published: June 2023

AbstractThe effect of acute stress on working memory (WM) has not been extensively investigated in demanding tasks, although many practitioners, such as pilots, frequently face varying working memory demands. The current study investigated how acute stress modulates pilots’ WM performance. Forty-two pilots were randomly assigned to the stress group or the control group. The stress group experienced acute stress induced by the modified Trier Social Stress Test (TSST), whereas the control group did not receive any stress induction. Both groups performed N-back tasks under varying degrees of memory load (0-back, 1-back, and 2-back). State-Trait Anxiety Inventory scores, heart rates, and salivary cortisol concentrations were measured in the experiment to determine the extent of induced stress. The results revealed that (1) The modified TSST effectively induced acute stress in the stress group. (2) As rising of memory load, the reaction time expectedly increased while accuracy decreased. (3) An interaction between the stress and control group was found for accuracy, indicating that acute stress might contribute to higher accuracy in moderate WM load (1-back). These suggestions support the emotion regulation hypothesis, in which acute stress induces heightened emotional states that impact WM performance. Furthermore, the current study explored the interplay between acute stress and memory load in a specific population, offering insights into potential pilots’ stress management strategies and training programs to improve pilots’ WM abilities. These applications would be beneficial for strengthening pilots’ coping mechanisms in emergencies and guaranteeing flight safety.
Cellular endosomal potassium ion flux regulates arenavirus uncoating during virus entry
Authors: Shaw Amelia B. , Tse Hiu Nam , Byford Owen , Plahe Grace , Moon-Walker Alex , Ollmann-Saphire Erica , Whelan Sean P. J. , Mankouri Jamel , Fontana Juan , Barr John N. 
Published: June 2023

ABSTRACTLymphocytic choriomeningitis virus (LCMV) is a model arenavirus that causes fatalities within immunocompromised populations. To enter cells, the LCMV envelope fuses with endosomal membranes, for which two requirements are low pH and interaction between LCMV GP spike and receptor CD164. LCMV subsequently uncoats, where genome-associated NP separates from Z matrix. To further examine LCMV entry, an siRNA screen identified K+channels as important for LCMV infection, and pharmacological inhibition confirmed K+involvement during entry. We tracked incoming virions along their entry pathway under physiological conditions, where uncoating was signified by separation of NP and Z. In contrast, K+channel blockade, prevented uncoating, trapping virions within Rab7 and CD164-positive endosomes, identifying K+as a third LCMV entry requirement. K+did not increase GP/CD164 binding, thus we suggest K+mediates uncoating by modulating NP/Z interactions within the virion interior. These results suggest repurposing licensed K+channel inhibitors represents a potential anti-arenaviral strategy.
Extensible benchmarking of methods that identify and quantify polyadenylation sites from RNA-seq data
Authors: Bryce-Smith Sam , Burri Dominik , Gazzara Matthew R. , Herrmann Christina J. , Danecka Weronika , Fitzsimmons Christina M. , Wan Yuk Kei , Zhuang Farica , Fansler Mervin M. , Fernández José M. , Ferret Meritxell , Gonzalez-Uriarte Asier , Haynes Samuel , Herdman Chelsea , Kanitz Alexander , Katsantoni Maria , Marini Federico , McDonnel Euan , Nicolet Ben , Poon Chi-Lam , Rot Gregor , Schärfen Leonard , Wu Pin-Jou , Yoon Yoseop , Barash Yoseph , Zavolan Mihaela 
Published: June 2023

ABSTRACTThe tremendous rate with which data is generated and analysis methods emerge makes it increasingly difficult to keep track of their domain of applicability, assumptions, and limitations and consequently, of the efficacy and precision with which they solve specific tasks. Therefore, there is an increasing need for benchmarks, and for the provision of infrastructure for continuous method evaluation. APAeval is an international community effort, organized by the RNA Society in 2021, to benchmark tools for the identification and quantification of the usage of alternative polyadenylation (APA) sites from short-read, bulk RNA-sequencing (RNA-seq) data. Here, we reviewed 17 tools and benchmarked eight on their ability to perform APA identification and quantification, using a comprehensive set of RNA-seq experiments comprising real, synthetic, and matched 3′-end sequencing data. To support continuous benchmarking, we have incorporated the results into the OpenEBench online platform, which allows for seamless extension of the set of methods, metrics, and challenges. We envisage that our analyses will assist researchers in selecting the appropriate tools for their studies. Furthermore, the containers and reproducible workflows generated in the course of this project can be seamlessly deployed and extended in the future to evaluate new methods or datasets.
Researcher effects on the biological structure and edaphic conditions of field sites and implications for management
Authors: Rinehart Shelby A , Dybiec Jacob M , Richardson Parker , Walker Janet B , Peabody James D , Cherry Julia A 
Published: June 2023

AbstractField studies are necessary for understanding natural processes, but they can disturb the environment. Despite researchers acknowledging these effects, no studies have empirically tested the direct (e.g., harvesting plants) and indirect effects (i.e., trampling) of researcher activities on biological structure and edaphic conditions. We leveraged field studies in Alabama and California to monitor the recovery of tidal marshes following research activities. Researcher effects on animals, plants, and sediment conditions remained prevalent almost one year after the disturbance ended. For instance, trampled plots had 14-97% lower plant cover than undisturbed plots after >10 months of recovery. Researcher effects also impacted plant composition, leading to increased subordinate species abundance. We encourage field researchers to adopt strategies that reduce their scientific footprints, including reducing field visits, limiting field team size, and considering ways to limit potential environmental impacts during study design.
The activation of INF2 by Piezo1/Ca2+is required for mesenchymal to amoeboid transition in confined environments
Authors: Kar Neelakshi , Caruso Alexa P. , Prokopiou Nicos , Logue Jeremy S. 
Published: June 2023

AbstractTo invade heterogenous tissues, transformed cells may undergo a mesenchymal to amoeboid transition (MAT). However, the molecular mechanisms regulating this transition are poorly defined. In invasive melanoma cells, we demonstrate that intracellular [Ca2+] increases with the degree of confinement in a Piezo1 dependent fashion. Moreover, Piezo1/Ca2+is found to drive amoeboid and not mesenchymal migration in confined environments. Consistent with a model in which Piezo1 senses tension at the plasma membrane, the percentage of cells using amoeboid migration is further increased in undulating microchannels. Surprisingly, amoeboid migration was not promoted by myosin light chain kinase (MLCK), which is sensitive to intracellular [Ca2+]. Instead, we report that Piezo1/Ca2+activates inverted formin-2 (INF2) to induce widespread actin cytoskeletal remodeling. Strikingly, the activation of INF2 is found to promote de-adhesion, which in turn facilitates MAT. Using micropatterned surfaces, we demonstrate that cells require INF2 to effectively migrate in environments with challenging mechanochemical properties.Summary StatementMigrating melanoma cells are found to rely on the activation of inverted formin-2 (INF2) by Piezo1/Ca2+for mesenchymal to amoeboid transition (MAT) in confined environments.
TECPR1 provides E3-ligase like activity to the ATG5-ATG12 complex to conjugate LC3/ATG8 to damaged lysosomes
Authors: Wang Yingxue , Jefferson Matthew , Whelband Matthew , Kreuzer Kristine , Mccoll James , Verkade Paul , Mayer Ulrike , Wileman Thomas 
Published: June 2023

AbstractAutophagosomes deliver cytosolic material to lysosomes to provide amino acids during starvation and to degrade damaged proteins and organelles to maintain tissue homeostasis. Delivery to lysosomes requires LC3/ATG8 (LC3), the major membrane protein of the autophagosome, that uses adaptor proteins to capture cargo and recruits tethering and SNARE proteins to promote fusion with lysosomes. LC3 is also recruited to endo-lysosome compartments in response to increases in vacuolar pH to facilitate degradation of material entering cells by endocytosis. A series of ubiquitin-like reactions conjugate LC3 to amino groups exposed by phosphatidylethanolamine (PE) or phosphatidylserine (PS) in target membranes. The E1 and E2-ubiquitin-like activities of ATG7 and ATG3 use thioester bonds to transfer LC3 to the ATG5-ATG12 conjugate. At the same time binding of ATG16L1 to ATG5-ATG12 provides the E3 ubiquitin-ligase like activity necessary to conjugate LC3 to PE or PS. The ATG5-ATG12 conjugate can also bind TECPR1 (tectonin beta propeller repeat-containing protein) which shares an ATG5 interaction (AIR) region with ATG16L1 and can binds LC3 directly through a LC3 interaction region (LIR). In this study we have used cells lacking ATG16L1 to determine if TECPR1 can substitute for ATG16L1 during LC3 conjugation. The results show that ATG16L1-/-MEFS can conjugate LC3 to lysosomes damaged by chloroquine or LLOMes and conjugation is dependent on the ubiquitin-like enzymes ATG3, ATG5 and ATG7 upstream of ATG16L1. TECPR1, ATG5 and galectin 3 are recruited to LAMP positive damaged lysosomes in the absence of ATG16L1 suggesting that TECPR-1 recruits ATG5-ATG12 to conjugate LC3 to damaged lysosomes. This was confirmed when truncation of TECPR1 at the central PH domain required for lysosome binding prevented LC3 conjugation, and LC3 conjugation could be restored by full length TECPR1. Recruitment of TECPR1 to damaged lysosomes required the N-terminal LIR motif and was partially dependent on the central PH domain that binds PI4P exposed during lysosome repair. TECPR1 can therefore conjugate LC3 to damaged lysosomes independently of ATG16L1 by providing E3 ligase-like activity to ATG5-ATG12. Direct conjugation of LC3 by TECPR1 may contribute to the autophagosome tethering functions reported for TECPR1 by increasing recruitment of cargo receptors, tethering proteins and SNARE proteins required for fusion with lysosomes and protein degradation. TECPR1-dependent conjugation of LC3 may also facilitate lysosome repair pathways involving autophagic lysosomal reformation and transcriptional activation of autophagy by TFEB.
Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation
Authors: Bragg Robert M. , Coffey Sydney R. , Cantle Jeffrey P. , Hu Shikai , Singh Sucha , Legg Samuel R.W. , McHugh Cassandra A. , Toor Amreen , Zeitlin Scott O. , Kwak Seung , Howland David , Vogt Thomas F. , Monga Satdarshan P. , Carroll Jeffrey B. 
Published: June 2023

AbstractHuntington’s disease arises from a toxic gain of function in thehuntingtin(HTT) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes. Lifelong hepatocyte HTT loss is associated with multiple physiological changes, including increased circulating bile acids, cholesterol and urea, hypoglycemia, and impaired adhesion. HTT loss causes a clear shift in the normal zonal patterns of liver gene expression, such that pericentral gene expression is reduced. These alterations in liver zonation in livers lacking HTT are observed at the transcriptional, histological and plasma metabolite level. We have extended these phenotypes physiologically with a metabolic challenge of acetaminophen, for which the HTT loss results in toxicity resistance. Our data reveal an unexpected role for HTT in regulating hepatic zonation, and we find that loss of HTT in hepatocytes mimics the phenotypes caused by impaired hepatic β-catenin function.Graphical Abstract
Generation of a robust reference gut microbiome dataset for an urban population in Argentina optimized by a machine learning approach
Authors: Rohr Cristian , Sciara Mariela , Brun Bianca , Fay Fabian , Vazquez Martín P. 
Published: June 2023

AbstractRobust human microbiome analysis requires robust reference datasets obtained from a population that presents similar habits to the one we are trying to assess.We reported here the construction of a robust reference dataset of healthy individuals from urban and surrounding rural areas of the Argentine population. We screened 200 volunteers with strict inclusion/exclusion criteria. Volunteers were also screened with routine blood clinical test analysis and a complete metabolome profile from blood and urine to remove outliers before inclusion in the Next Generation Sequencing dataset. Sequencing was done on an Illumina MiSeq using the V3-V4 16S rRNA. Using these data, we performed de novo community structure prediction by applying clustering methodology based on seven distance and dissimilarity metrics and two clustering methods to the reference set. Using this approach, we discovered four different enterotypes in this community structure. We then trained a model for the classification of any new sample into the structure of the reference set. Once the new sample was classified, it was compared to the reference ranges of both the enterotype-specific subset and the whole reference set.Finally, we challenged the robustness of this methodology using samples from two test case volunteers with clinically proven gut dysbiosis in a time-series sampling with dietary interventions. Our results pointed to the need to carefully analyze the results of gut microbiome in the context of enterotype-specific rather than to a whole population dataset.