bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct bioenergetic features of human invariant natural killer T (iNKT) cells enable retained functions in nutrient-deprived states
Authors: Khurana Priya , Burudpakdee Chakkapong , Grupp Stephan A. , Beier Ulf H. , Barrett David M. , Bassiri Hamid 
Published: April 2021

ABSTRACTInvariant natural killer T (iNKT) cells comprise a unique subset of lymphocytes that are primed for activation and possess innate NK-like functional features. Currently, iNKT cell-based immunotherapies remain in early clinical stages, and little is known about the ability of these cells to survive and retain effector functions within the solid tumor microenvironment (TME) long-term. In conventional T cells (TCONV), cellular metabolism is linked to effector functions and their ability to adapt to the nutrient-poor TME. In contrast, the bioenergetic requirements of iNKT cells – particularly those of human iNKT cells – at baseline and upon stimulation are not well understood; neither is how these requirements affect cytokine production or anti-tumor effector functions. We find that unlike TCONV, human iNKT cells are not dependent upon glucose or glutamine for cytokine production and cytotoxicity upon stimulation with anti-CD3 and anti-CD28. Additionally, transcriptional profiling revealed that stimulated human iNKT cells are less glycolytic than TCONVand display higher expression of fatty acid oxidation (FAO) and adenosine monophosphate-activated protein kinase (AMPK) pathway genes. Furthermore, stimulated iNKT cells displayed higher mitochondrial mass and membrane potential relative to TCONV. Real-time Seahorse metabolic flux analysis revealed that stimulated human iNKT cells utilize fatty acids as substrates for oxidation more than stimulated TCONV. Together, our data suggest that human iNKT cells possess different bioenergetic requirements from TCONVand display a more memory-like metabolic program relative to effector TCONV. Importantly, iNKT cell-based immunotherapeutic strategies could co-opt such unique features of iNKT cells to improve their efficacy and longevity of anti-tumor responses.
Hunter-gatherer foraging networks promote information transmission
Authors: Garg Ketika , Padilla-Iglesias Cecilia , Ochoa Nicolás Restrepo , Knight V. Bleu 
Published: April 2021

AbstractCentral-place foraging, where foragers return to a central location (or home), is a key feature of hunter-gatherer social organization. Central-place foraging could have significantly changed hunter-gatherers’ use of space and mobility, and altered social networks and increased opportunities for information exchange. We evaluated whether central-place foraging patterns facilitate information transmission and considered the potential roles of environmental conditions and mobility strategies. We built an agent-based central-place foraging model where agents move according to a simple optimal foraging rule, and can encounter other agents as they move across the environment. They either forage close to their home within a given radius or move the location of their home to new areas. We analyzed the interaction networks arising across different environments and mobility strategies. We found that, at intermediate levels of environmental heterogeneity and mobility, central-place foraging increased global and local network efficiencies as well as the rate of contagion-based information transmission (simple and complex). We also assessed the effect of population density on the resultant networks and found that central-place mobility strategies can further improve information transmission in larger populations. Our findings suggest that the combination of foraging and movement strategies, as well as the underlying environmental conditions that characterized early human societies, may have been a crucial precursor in our species’ unique capacity to innovate, accumulate and rely on complex culture.
Caveolae Impacts Cellular RNA Levels through Transcription and Translational Processes
Authors: Qifti Androniqi , Balaji Shravani , Scarlata Suzanne 
Published: April 2021

ABSTRACTCaveolae are membrane domains that provide mechanical strength to cells and localize signaling molecules. Caveolae are composed of caveolin-1 or −3 (Cav1/3) molecules that assemble into domains with the help of cavin-1. Besides organizing caveolae, cavin-1, also known as Polymerase I and Transcript Release Factor (PTRF), promotes ribosomal RNA transcription in the nucleus. Cell expression of Cav1 and cavin-1 are linked. Here, we find that deforming caveolae by subjecting cells to mild osmotic stress (300 to 150 mOsm), changes the levels of cellular proteins (GAPDH, Hsp90 and Ras) change only when Cav1/cavin-1 levels are reduced suggesting link between caveolae deformation and protein expression. We find that this link may be due to relocalization of cavin-1 from the plasma membrane to the nucleus upon caveolae deformation caused by osmotic stress. Cavin-1 relocalization is also seen when Cav1-Gαq contacts change upon stimulation with carbachol. Cav1 and cavin-1 levels have profound effects on the amount of cytosolic RNA and the size distribution of these RNAs that in turn impact the ability of cells to form stress granules and RNA-processing bodies (p-bodies) that protect mRNA when cells are subjected to environmental stress. Studies using a cavin-1 knock-out cell line show adaptive changes in cytosolic RNA levels but a reduced ability to form stress granules. Our studies show that caveolae, through release of cavin-1, communicates mechanical and chemical cues to the cell interior to impact transcriptional and translational processes.
Ornament, armament, or toolkit? Modelling how population size drives the evolution of birdsong, a functional cultural trait
Authors: Hudson Emily J. , Creanza Nicole 
Published: April 2021

AbstractOscine songbirds have been an important study system for social learning, particularly because their learned songs provide an analog for human languages and music. Here we propose a different analogy; from an evolutionary perspective, could a bird’s song be more like an arrowhead than an aria? We modify a model of human tool evolution to accommodate cultural evolution of birdsong: each song learner chooses the most skilled available tutor to emulate, and each is more likely to produce an inferior copy than a superior one. Similarly to human tool evolution, we show that larger populations foster improvements in song over time, even when learners restrict their pool of tutors to a subset of individuals. We also demonstrate that songs could be simplified instead of lost after population bottlenecks if lower-quality traits are easier to imitate than higher-quality ones. We show that these processes could plausibly generate empirically observed patterns of song evolution, and we make predictions about the types of song elements most likely to be lost when populations shrink. More broadly, we aim to connect the modeling approaches used in human and non-human systems, moving toward a cohesive theoretical framework that accounts for both cognitive and demographic processes.
Tissue fixation effects on human retinal lipid analysis by MALDI imaging and LC-MS/MS technologies
Authors: Kotnala Ankita , Anderson David M.G. , Patterson Nathan Heath , Cantrell Lee S. , Messinger Jeffrey D. , Curcio Christine A. , Schey Kevin L. 
Published: April 2021

ABSTRACTImaging mass spectrometry (IMS) allows the location and abundance of lipids to be mapped across tissue sections of human retina. For reproducible and accurate information, sample preparation methods need to be optimized. Paraformaldehyde fixation of a delicate multilayer structure like human retina facilitates the preservation of tissue morphology by forming methylene bridge cross-links between formaldehyde and amine/ thiols in biomolecules; however, retina sections analyzed by IMS are typically fresh-frozen. To determine if clinically significant inferences could be reliably based on fixed tissue, we evaluated the effect of fixation on analyte detection, spatial localization, and introduction of artefactual signals. Hence, we assessed the molecular identity of lipids generated by matrix-assisted laser desorption ionization (MALDI-IMS) and liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) for fixed and fresh-frozen retina tissues in positive and negative ion modes. Based on MALDI-IMS analysis, more lipid signals were observed in fixed compared to fresh-frozen retina. More potassium adducts were observed in fresh-frozen tissues than fixed as the fixation process caused displacement of potassium adducts to protonated and sodiated species in ion positive ion mode. LC-MS/MS analysis revealed an overall decrease in lipid signals due to fixation that reduced glycerophospholipids and glycerolipids and conserved most sphingolipids and cholesteryl esters. The high quality and reproducible information from untargeted lipidomics analysis of fixed retina informs on all major lipid classes, similar to fresh-frozen retina, and serves as a steppingstone towards understanding of lipid alterations in retinal diseases.
Marker-assisted mapping enables effective forward genetic analysis in the arboviral vector Aedes aegypti, a species with vast recombination deserts
Authors: Chen Chujia , Compton Austin , Nikolouli Katerina , Wang Aihua , Aryan Azadeh , Sharma Atashi , Qi Yumin , Delinger Camden , Hempel Melanie , Augustinos Antonios , Severson David W. , Bourtzis Kostas , Tu Zhijian 
Published: April 2021

AbstractAedes aegypti is a major vector of arboviruses that cause dengue, chikungunya, yellow fever and Zika. Although recent success in reverse genetics has facilitated rapid progress in basic and applied research, integration of forward genetics with modern technologies remains challenging in this important species, as up-to-47% of its chromosome is refractory to genetic mapping due to extremely low rate of recombination. Here we report the development of a marker-assisted-mapping (MAM) strategy to readily screen for and genotype only the rare but informative recombinants, drastically increasing both the resolution and signal-to-noise ratio. Using MAM, we mapped a transgene that was inserted in a >100 Mb recombination desert and a sex-linked spontaneous red-eye (re) mutation just outside the region. We subsequently determined, by CRISPR/Cas9-mediated knockout, that cardinal is the causal gene of re, which is the first forward genetic identification of a causal gene in Ae. aegypti. This study provides the molecular foundation for using gene-editing to develop versatile and stable genetic sexing methods by improving upon the current re-based genetic sexing strains. MAM does not require densely populated markers and can be readily applied throughout the genome to facilitate the mapping of genes responsible for insecticide- and viral-resistance. By enabling effective forward genetic analysis, MAM bridges a significant gap in establishing Ae. aegypti as a model system for research in vector biology. As large regions of suppressed recombination are also common in other plant and animal species including those of economic significance, MAM will have broad applications beyond vector biology.
Stability of microbiota in vineyard soils across consecutive years
Authors: Cestaro Alessandro , Coller Emanuela , Albanese Davide , Stefani Erika , Pindo Massimo , Ioriatti Cluadio , Zanzotti Roberto , Donati Caludio 
Published: April 2021

AbstractAgricultural soils harbor rich and diverse microbial communities that have a deep influence on soil properties and productivity. Large scale studies have shown the impact of environmental parameters like climate or chemical composition on the distribution of bacterial and fungal species. Comparatively, little data exists documenting how soil microbial communities change between different years. Quantifying the temporal stability of soil microbial communities will allow us to better understand the relevance of the differences between environments and their impact on ecological processes on the global and local scale.We characterized the bacterial and fungal components of the soil microbiota in ten vineyards in two consecutive years. Despite differences of species richness and diversity between the two years, we found a general stability of the taxonomic structure of the soil microbiota. Temporal differences were smaller than differences due to geographical location, vineyard land management or differences between sampling sites within the same vineyard. Using machine learning, we demonstrated that each site was characterized by a distinctive microbiota, and we identified a reduced set of indicator species that could classify samples according to their geographic origin across different years with high accuracy.ImportanceThe temporal stability of the soil microbiota is important to understand the relevance of the differences that are found in response to a variety of environmental factors. By comparing fungal and bacterial microbiota from samples collected in the same sites in two consecutive years, we found a remarkable stability of both components, with characteristic differences between bacteria and fungi. Our work fills an important gap toward the definition of a microbial cartography of agricultural soils.
Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength
Authors: Ramsey A.M. , Tang A.H. , LeGates T.A. , Gou X.Z. , Carbone B.E. , Thompson S.M. , Biederer T. , Blanpied T.A. 
Published: April 2021

AbstractRecent evidence suggests that nanoorganization of proteins within synapses may control the strength of communication between neurons in the brain. The unique subsynaptic distribution of glutamate receptors, which cluster in nanoalignment with presynaptic sites of glutamate release, supports this idea. However, testing it has been difficult because mechanisms controlling subsynaptic organization remain unknown. Reasoning that transcellular interactions could position AMPA receptors, we targeted a key transsynaptic adhesion molecule implicated in controlling AMPAR number, LRRTM2, using engineered, rapid proteolysis. Severing the LRRTM2 extracellular domain led quickly to nanoscale de-clustering of AMPARs away from release sites, not prompting their escape from synapses until much later. This rapid remodeling of AMPAR position produced significant deficits in evoked, but not spontaneous, postsynaptic receptor activation. These results dissociate receptor numbers from their nanopositioning in determination of synaptic function, and support the novel concept that adhesion molecules acutely position AMPA receptors to dynamically control synaptic strength.
Glucose Uptake as an Alternative to Stop-Flow Respirometry for Measuring Metabolic Rate inDanio rerioLarvae
Authors: Evans Bridget L , Hurlstone Adam F L , Clayton Peter E , Stevens Adam , Shiels Holly A 
Published: April 2021

AbstractRespirometry is the current gold-standard for measuring metabolic rate. However, there is a growing need for metabolic rate measurements suitable for developmental studies, particularly inDanio rerio, where many important developmental stages occur at < 4 mm. While many metabolic studies rely on respirometry, the cost and complexity of the equipment limits its appeal in non-specialist labs, and background respiration becomes increasingly problematic as the size of the organism reduces. Here, glucose uptake was compared to stop-flow respirometry as an alternative measure of metabolic rate more suitable to the small scale required for developmental studies. A Passing-Bablok regression revealed the rate of glucose uptake can be considered equivalent to oxygen consumption as a measure of metabolic rate inDanio reriolarvae within a 95% limit of agreement. Therefore, glucose uptake is a valid alternative to the gold-standard in small organisms where conventional respirometry is problematic.Summary statementThe rate of glucose uptake is a valid alternative to respirometry for metabolic rate measurements in small larval fish.
Sampling touch DNA from human skin following skin‐to‐skin contact in mock assault scenarios—A comparison of nine collection methods
Authors: Kallupurackal Venus , Kummer Sonja , Voegeli Pamela , Kratzer Adelgunde , Dørum Guro , Haas Cordula , Hess Sabine 
Published: April 2021

AbstractCollection of touch DNA from an offender on the victim's skin can provide relevant evidence for investigations of criminal cases. Therefore, the choice of the optimal sample collection method is crucial. In this study, we investigated the recovery of STR profiles from touch DNA on human skin by comparing nine different collection methods: the dry and wet cotton swabs in three different movements, the double‐swab (wet–dry) method, the wet and dry Copan FLOQSwabs™, and the Scene Safe FAST™ minitapes. Mock assault scenarios were conducted with a male offender grasping the forearms of a female victim. Samples were collected from the assaulted area of the victim's skin, and the recovery of the offender's STR profile was evaluated. Our results indicate that the different swabs and swabbing techniques did not have a distinct impact on the STR recovery; however, the lowest STR recovery was achieved with Scene Safe FAST™ minitapes. In addition, we compared the double‐swab method to the single‐swab method by analyzing the DNA quantity of the wet and dry swabs separately. We found on average 13.7% more offender DNA using the double‐swab method, but this did not translate into higher STR recovery. Our findings indicate that several methods perform equally well when collecting touch DNA from human skin, although SceneSafe FAST™ minitapes seem to be the least adequate for this purpose.
Biochemical properties of extracellular protease from Staphylococcus carnosus RT6 isolated from Harbin dry sausages, and its hydrolysis of meat proteins
Authors: Wang Hui , Wang Qiang , Xia Xiufang , Sun Fangda , Kong Baohua 
Published: April 2021

AbstractThe characteristics of the extracellular protease, produced by Staphylococcus carnosus RT6 isolated from Harbin dry sausages, and its hydrolysis of meat proteins were investigated. The protease was purified by ammonium sulfate, ion exchange, and gel filtration chromatography to obtain a 20.0 kDa extracellular protease. The protease reached maximal activity at pH 9.0 and 50 °C and was stable at pH 7.0 to 11.0 and 20 to 40 °C. Its protease activity was easily inhibited in the presence of Zn2+, Fe2+, and Fe3+. The enzymatic characterization of the protease revealed a Vmax 49.50 U/ml·min, Km 8.19 mg/ml, and the half‐life = 28.06 min, ΔH*d = 114.11 kJ/mol, ΔG*d = 89.24 kJ/mol, and ΔS*d = 77.00 J/mol·K at 50 °C. In addition, the protease hydrolyzed meat protein into small particles and produced soluble peptides. This study provides a basis for understanding the biochemical characteristics of the S. carnosus RT6 protease and its future application for fermented meat products.
CD8+ T cells actively penetrate hepatocytes via the CD44/p‐ERM/F‐actin pathway in autoimmune hepatitis
Authors: Liang Ju Bo , Chen Yong , Chen Rui Ling , Li Yi Kang , Li Bo , You Zheng Rui , Li You , Zhang Jun , Huang Bing Yuan , Wei Yi Ran , Lyu Zhu Wan , Lian Min , Xiao Xiao , Wang Qi Xia , Tang Ru Qi , Fang Jing Yuan , Chen Xiao Yu , Ma Xiong , Miao Qi 
Published: April 2021

ObjectiveEmperipolesis is a pathological feature for the diagnosis of autoimmune hepatitis (AIH). We have previously found that CD8+ T cells participated in the emperipolesis in AIH. In this study we aimed to clarify the characteristics and molecular mechanisms of emperipolesis in patients with AIH in vitro and in mice with α‐Galactosylceramide (α‐GalCer)‐induced acute hepatitis.MethodsThe peripheral blood mononuclear cells (PBMC) of patients with various chronic liver diseases and healthy controls were co‐cultured with hepatic cell lines to induce emperipolesis in vitro. Confocal staining was performed to illustrate the cellular types and potential mechanisms of emperipolesis in AIH. In addition, a murine model of α‐GalCer‐induced acute hepatitis that mimics human AIH was used to confirm the role of CD44/p‐ERM/F‐actin in the emperipolesis process in vivo.ResultsIn the co‐cultured system of PBMC and hepatic cell line, emperipolesis was observed most commonly in patients with AIH. The main cells participating in emperipolesis were CD8+ T cells, and they penetrated hepatic cells actively via the CD44/p‐ERM/F‐actin pathway. As a result, most CD8+ T cells engulfed by hepatic cells underwent apoptosis. In the α‐GalCer‐induced acute hepatitis model, emperipolesis was observed around the inflammatory foci and was inhibited by the ezrin phosphorylation inhibitor NSC668394. Similarly, activated murine CD8+ T cells penetrated primary hepatocytes via the CD44/p‐ERM/F‐actin pathway in vitro.ConclusionsCD8+ T cells penetrate hepatic cells actively via the CD44/p‐ERM/F‐actin signaling pathway and undergo apoptosis. This may be a compensatory mechanism to attenuate the overwhelming immune attack in AIH.
A multiplex antigen microarray for simultaneous IgG and IgM detection against SARS‐CoV‐2 reveals higher seroprevalence than reported
Authors: Ruano‐Gallego David , García‐Villadangos Miriam , Moreno‐Paz Mercedes , Gómez‐Elvira Javier , Postigo Marina , Simón‐Sacristán María , Reyburn Hugh T. , Carolis Carlo , Rodrigo Natalia , Codeseira Yaiza B. , Rueda Paloma , Zúñiga Sonia , Enjuanes Luis , Parro Victor 
Published: April 2021

SummaryThe surge of SARS‐CoV‐2 has challenged health systems worldwide and efficient tests to detect viral particles, as well as antibodies generated against them, are needed. Specificity, sensitivity, promptness or scalability are the main parameters to estimate the final performance, but rarely all of them match in a single test. We have developed SCOVAM, a protein microarray with several viral antigens (spike, nucleocapsid, main protease Nsp5) as capturing probes in a fluorescence immunoassay for COVID‐19 serological testing. SCOVAM depicts IgG and IgM antibody responses against each of these proteins of 22 individuals in a single microscope slide. It detects specific IgM (0.094 μg ml‐1) and IgG (~0.017 μg ml‐1) and is scalable and cost‐effective. We validated SCOVAM by comparing with a widely used chemiluminescent commercial serological test (n = 742). SCOVAM showed twice the sensitivity and allowed following seroconversion in a single assay. By analysing the prevalence 4 months later in a subset of 76 positive sera, we still detected 93.42% of positives, almost doubling the detection of the commercial assay. The higher sensitivity of SCOVAM is especially relevant to screen sera for convalescent plasma‐based treatments, high‐throughput antibody response monitoring after vaccination or evaluation of vaccine efficiency.