bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary genomics of socially polymorphic populations ofPogonomyrmex californicus
Authors: Errbii Mohammed , Ernst Ulrich R. , Lajmi Aparna , Privman Eyal , Gadau Jürgen , Schrader Lukas 
Published: March 2021

AbstractSocial insects vary considerably in their social organization both between and within species. In the California harvester ant,Pogonomyrmex californicus(Buckley 1867), colonies are commonly founded and headed by a single queen (haplometrosis, primary monogyny). However, in some populations in California (USA), unrelated queens cooperate not only during founding (pleometrosis) but throughout the life of the colony (primary polygyny). The genetic architecture and evolutionary dynamics of this complex social niche polymorphism (haplometrosis vs pleometrosis) have remained unknown. Here, we provide a first analysis of its genomic basis and evolutionary history using population genomics comparing individuals from a haplometrotic population to those from a pleometrotic population. We discovered a recently evolved (< 200 k years), 8 Mb non-recombining region segregating with the observed social niche polymorphism. This region shares several characteristics with supergenes underlying social polymorphisms in other socially polymorphic ant species. However, we also find remarkable differences from previously described social supergenes. Particularly, four additional genomic regions not in linkage with the supergene show signatures of a selective sweep in the pleometrotic population. Within these regions, we find for example genes crucial for epigenetic regulation via histone modification (chameau) and DNA methylation (Dnmt1). These results suggest that social morph in this species is a polygenic trait involving a potential young supergene. Further studies targeting haplo- and pleometrotic individuals from a single population are however required to conclusively resolve whether these genetic differences underlie the alternative social phenotypes or have emerged through genetic drift.
Fast ATP-dependent Subunit Rotation in Reconstituted FoF1-ATP Synthase Trapped in Solution
Authors: Heitkamp Thomas , Börsch Michael 
Published: March 2021

ABSTRACTFoF1-ATP synthases are ubiquitous membrane-bound, rotary motor enzymes that can catalyze ATP synthesis and hydrolysis. Their enzyme kinetics are controlled by internal subunit rotation, by substrate and product concentrations, by mechanical inhibitory mechanisms, but also by the electrochemical potential of protons across the membrane. Single-molecule Förster resonance energy transfer (smFRET) has been used to detect subunit rotation within FoF1-ATP synthases embedded in freely diffusing liposomes. We now report that kinetic monitoring of functional rotation can be prolonged from milliseconds to seconds by utilizing an Anti-Brownian electrokinetic trap (ABEL trap). These extended observation times allowed us to observe fluctuating rates of functional rotation for individual FoF1-liposomes in solution. Broad distributions of ATP-dependent catalytic rates were revealed. The buildup of an electrochemical potential of protons was confirmed to limit the maximum rate of ATP hydrolysis. In the presence of ionophores or uncouplers, the fastest subunit rotation speeds measured in single reconstituted FoF1-ATP synthases were 180 full rounds per second. This was much faster than measured by biochemical ensemble averaging, but not as fast as the maximum rotational speed reported previously for isolated single F1complexes uncoupled from the membrane-embedded Focomplex. Further application of ABEL trap measurements should help resolve the mechanistic causes of such fluctuating rates of subunit rotation.TOC GRAPHICFigure 1.
The Central Importance of Hub Proteins in a Disease-Gene Network Model: A New Paradigm of Chronic Myeloid Leukemia Disease Study
Authors: Rahman K M Taufiqur , Islam Md. Fahmid , Saha Sanjib , Billah Md. Morsaline 
Published: March 2021

AbstractBackgroundThe network biology of disease-gene association provides a holistic framework to decipher the intrinsic complexity of disease signaling pathways into cellular communication level. Different types of studies including large-scale genome-wide association, multifactor dimensional reduction analysis, whole genome, or exome-based sequencing strategies of diseases are striving to connect genes to diseases. Indeed, these approaches have had some accomplishments, but the cellular communication level needs a more streamlining outcome to understand the mechanistic impact of context. The higher-order combination of disease-gene interaction has a great potential to decipher the intricateness of diseases. The molecular interaction pattern of diseases at the genomic and proteomic level offers a revolutionized platform not only to understand the complexity of particular disease modules and pathways but also leading towards design novel therapeutics.ResultsThe enrichment and topology analysis was performed by JEPETTO a plugin of Cytoscape software. We identified the chronic myeloid leukemia (CML) disease signaling pathways that appeared first in the ranking order based on XD-score among the bone, breast, and colon genes set and second at kidney and liver. This result validates the highest proximity between CML and five cancerous tissue gene set clusters. The topology analysis also supports the results while (p<0.0001) is considered to be extremely significant between CML and fives cancerous tissues genes set. Enrichment analysis identified thatabl-gene acts as an overlapping node which is the major gene for inducing various mutations in CML. Amazingly, we identified 56 common path expansion/added genes among these five cancerous tissues which can be considered the direct cofactors of CML disease. By relative node degree, resolution, possible ligand, stoichiometry, Q-mean, and Z-score analysis we found 11 hubs proteins like SMAD3, GRB2, TP53, SMAD4, RB1, HDAC1, RAF1, ABL1, SHC1, TGFBR1, RELA which can be regarded for further drug target identification.ConclusionsOur proposed network analysis reflects on the gene set interaction pattern of disease signaling pathways of humans. The integrated multidrug computational and experimental approaches boost up to improve the novel drug target approach. Besides, such a trove can yield unprecedented insights to lead to an enhanced understanding of potential application both in drug target optimization and for drug dislodging.
Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC
Authors: Tang Kwan Ho , Li Shuai , Khodadadi-Jamayran Alireza , Jen Jayu , Han Han , Guidry Kayla , Chen Ting , Hao Yuan , Fedele Carmine , Zebala John , Maeda Dean , Christensen James , Olson Peter , Athanas Argus , Wong Kwok-Kin , Neel Benjamin G. 
Published: March 2021

AbstractClinical trials of SHP2 inhibitors (SHP2i) alone and in various combinations are ongoing for multiple tumors with over-activation of the RAS/ERK pathway. SHP2 plays critical roles in normal cell signaling; hence, SHP2is could influence the tumor microenvironment. We found that SHP2i treatment depleted alveolar and M2-like macrophages and promoted B and T lymphocyte infiltration inKras- andEgfr-mutant non-small cell lung cancer (NSCLC). However, treatment also increased intratumor gMDSCs via tumor-intrinsic, NF-kB-dependent production of CXCR2 ligands. Other RAS/ERK pathway inhibitors also induced CXCR2 ligands and gMDSC influx in mice, and CXCR2 ligands were induced in tumors from patients on KRASG12C-inhibitor trials. Combined SHP2(SHP099)/CXCR1/2(SX682) inhibition depleted a specific cluster ofS100a8/9highgMDSCs, generatedKlrg1+ CD8+ effector T cells with a strong cytotoxic phenotype but expressing the checkpoint receptor NKG2A, and enhanced survival inKras-andEgfr-mutant models. Our results argue for testing RAS/ERK pathway/CXCR1/2/NKG2A inhibitor combinations in NSCLC patients.Statement of SignificanceOur study shows that inhibiting the SHP2/RAS/ERK pathway triggers NF-kB-dependent up-regulation of CXCR2 ligands and recruitment of S100A8highgMDSCs, which suppress T cells in NSCLC. Combining SHP2 and CXCR2 inhibitors blocks this gMDSC immigration, resulting in enhanced Th1 polarization, induction of CD8+ KLRG1+ effector T cells with high cytotoxic activity and improved survival in multiple NSCLC models.
Genetic characteristics ofApodemus speciosusat Akiyoshidai Quasi-National Park in Yamaguchi Prefecture
Authors: Imai Hiroyuki , Tanaka Hiroshi , Matsuo Taiki , Seto Miho , Matsuya Sumito , Hyoto Muneyoshi , Kano Kiyoshi , Kusakabe Ken Takeshi 
Published: March 2021

abstractThe large Japanese field mouse (Apodemus speciosus) is a small rodent endemic to Japan. The mice have a genetic characteristic in which the number of chromosomes differs between those from western Japan and those from eastern Japan.A. spesiosus, found throughout Japan, is used as a model animal for geogenetics and monitoring of radiation effects of wildlife. In this present study, to elucidate the genetic characteristics of the mice Akiyoshidai Quasi-National Park in Yamaguchi Prefecture, we investigated mitochondrial DNA and chromosome numbers. As a result,A. speciosusfrom Yamaguchi Prefecture were classified into the Honshu-Shikoku-Kyushu group and had a western Japan-type chromosome set of 2n=46; however, some Yamaguchi Prefecture mice formed a genetic cluster in Yamaguchi Prefecture, suggesting that continuous monitoring is needed to reveal the dynamics of genetic diversity.
Application of high dimensional flow cytometry and unsupervised analysis to define the immune cell landscape of early childhood respiratory and blood compartments
Authors: Shanthikumar Shivanthan , Ranganathan Sarath C. , Saffery Richard , Neeland Melanie R. 
Published: March 2021

SUMMARYThe cellular landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of highly prevalent childhood respiratory diseases remain poorly understood. A major limitation in defining mechanisms of disease has been the availability of tissue samples collected in early life, as well as technologies that permit deep immune analysis from limited sample volumes. In this work, we developed new experimental methods and applied unsupervised analytical tools to profile the local (bronchoalveolar lavage) and systemic (whole blood) immune response in childhood respiratory disease. We quantified and comprehensively phenotyped immune cell populations across blood and lung compartments in young children (under 6 years of age), showed that inflammatory cells in the BAL express higher levels of activation and migration markers relative to their systemic counterparts, and applied new analytical tools to reveal novel tissue-resident macrophage and infiltrating monocyte populations in the paediatric lung. To our knowledge, this is the first description of the use of these methods for paediatric respiratory samples. Combined with matched analysis of the systemic immune cell profile, the application of these pipelines will increase our understanding of childhood lung disease with potential to identify clinically relevant disease biomarkers.
A protease-activatable luminescent biosensor and reporter cell line for authentic SARS-CoV-2 infection
Authors: Gerber Pehuén Pereyra , Duncan Lidia M , Greenwood Edward JD , Marelli Sara , Naamati Adi , Teixeira-Silva Ana , Crozier Thomas WM , Gabaev Ildar , Zhan Jun R , Mulroney Thomas E , Horner Emily C , Doffinger Rainer , Willis Anne E , Thaventhiran James ED , Protasio Anna V , Matheson Nicholas J 
Published: March 2021

AbstractEfforts to define serological correlates of protection against COVID-19 have been hampered by the lack of a simple, scalable, standardised assay for SARS-CoV-2 infection and antibody neutralisation. Plaque assays remain the gold standard, but are impractical for high-throughput screening. In this study, we show that expression of viral proteases may be used to quantitate infected cells. Our assays exploit the cleavage of specific oligopeptide linkers, leading to the activation of cell-based optical biosensors. First, we characterise these biosensors using recombinant SARS-CoV-2 proteases. Next, we confirm their ability to detect viral protease expression during replication of authentic virus. Finally, we generate reporter cells stably expressing an optimised luciferase-based biosensor, enabling viral infection to be measured within 24 h in a 96- or 384-well plate format, including variants of concern. We have therefore developed a luminescent SARS-CoV-2 reporter cell line, and demonstrated its utility for the relative quantitation of infectious virus and titration of neutralising antibodies.Author summaryTechniques for measuring infection with SARS-CoV-2 in the laboratory are laborious and time-consuming, and different laboratories use different approaches. There is therefore no generally agreed way to quantitate neutralising antibodies against SARS-CoV-2, which block infection with the virus and protect people from COVID-19. In this study, we describe a new way to measure SARS-CoV-2 infection, which is much simpler and faster than existing methods. It relies on the production of a specific protease enzyme by the virus, which is able to cleave and activate an engineered protein biosensor in infected cells. This biosensor emits light in the presence of viral infection, and the amount of light released is used as a readout for the amount of infectious SARS-CoV-2 present. The signal is very sensitive, so the number of infected cells required is very small, and the method can be scaled-up to test many samples at once. In particular, we demonstrate how it can be used to detect different variants of SARS-CoV-2, and quantitate neutralising antibodies against these viruses.
Live Imaging of SARS-CoV-2 Infection in Mice Reveals Neutralizing Antibodies Require Fc Function for Optimal Efficacy
Authors: Ullah Irfan , Prévost Jérémie , Ladinsky Mark S , Stone Helen , Lu Maolin , Anand Sai Priya , Beaudoin-Bussières Guillaume , Symmes Kelly , Benlarbi Mehdi , Ding Shilei , Gasser Romain , Fink Corby , Chen Yaozong , Tauzin Alexandra , Goyette Guillaume , Bourassa Catherine , Medjahed Halima , Mack Matthias , Chung Kunho , Wilen Craig B , Dekaban Gregory A. , Dikeakos Jimmy D. , Bruce Emily A. , Kaufmann Daniel E , Stamatatos Leonidas , McGuire Andrew T. , Richard Jonathan , Pazgier Marzena , Bjorkman Pamela J. , Mothes Walther , Finzi Andrés , Kumar Priti , Uchil Pradeep D. 
Published: March 2021

SUMMARYNeutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We could visualize virus spread sequentially from the nasal cavity to the lungs and thereafter systemically to various organs including the brain, which culminated in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct Fab-mediated neutralization, Fc effector interactions of NAbs with monocytes, neutrophils and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimalin vivoefficacy against SARS-CoV-2.
Motion extrapolation in the flash-lag effect depends on perceived, rather than physical speed
Authors: Yook Jane , Lee Lysha , Vossel Simone , Weidner Ralph , Hogendoorn Hinze 
Published: March 2021

AbstractIn the flash-lag effect (FLE), a flash in spatiotemporal alignment with a moving object is misperceived as lagging behind the moving object. One proposed explanation for this illusion is based on predictive motion extrapolation of trajectories. In this interpretation, the diverging effects of velocity on the perceived position of the moving object suggest that FLE might be based on the neural representation of perceived, rather than physical, velocity. By contrast, alternative explanations based on differential latency or temporal averaging would predict that the FLE does not rely on such a representation of perceived velocity. Here we examined whether the FLE is sensitive to illusory changes in perceived speed that result in changes to perceived velocity, while physical speed is constant. The perceived speed of the moving object was manipulated using revolving wedge stimuli with variable pattern textures (Experiment 1) and luminance contrast (Experiment 2). The motion extrapolation interpretation would predict that the changes in FLE magnitude should correspond to the changes in the perceived speed of the moving object. In the current study, two experiments demonstrated that perceived speed and FLE magnitude increased in the dynamic pattern relative to the static pattern conditions, and that the same effect was found in the low contrast compared to the high contrast conditions. These results showed that manipulations of texture and contrast that are known to alter judgments of perceived speed also modulate perceived position. We interpret this as a consequence of motion extrapolation mechanisms and discuss possible explanations for why we observed no cross-effect correlation.
An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies
Authors: Hong H. Christian , Kim Kwang Sung , Park Shin Ae , Chun Min Jeong , Hong Eun Young , Chung Seung Won , Kim Hyun Jong , Shin Byeong Gyu , Braka Abdennour , Thanappan Jayaraman , Jang Sunghoon , Wu Sangwwok , Cho Yang Je , Kim Seok-Hyun 
Published: March 2021

AbstractIn addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based onin vitrodata, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.
A beta-glucosidase of an insect herbivore determines both toxicity and deterrence of a dandelion defense metabolite
Authors: Huber Meret , Roder Thomas , Irmisch Sandra , Riedel Alexander , Gablenz Saskia , Fricke Julia , Rahfeld Peter , Reichelt Michael , Paetz Christian , Liechti Nicole , Hu Lingfei , Meng Ye , Huang Wei , Robert Christelle A. M. , Gershenzon Jonathan , Erb Matthias 
Published: March 2021

ABSTRACTGut enzymes can metabolize plant defense metabolites and thereby affect the growth and fitness of insect herbivores. Whether these enzymes also influence herbivore behavior and feeding preference is largely unknown. We studied the metabolization of taraxinic acid β-D-glucopyranosyl ester (TA-G), a sesquiterpene lactone of the common dandelion (Taraxacum officinale) that deters its major root herbivore, the common cockchafer larva (Melolontha melolontha). We demonstrate that TA-G is rapidly deglycosylated and conjugated to glutathione in the insect gut. A broad-spectrumM. melolonthaβ-glucosidase, Mm_bGlc17, is sufficient and necessary for TA-G deglycosylation. Using plants and insect RNA interference, we show that Mm_bGlc17 reduces TA-G toxicity. Furthermore, Mm_bGlc17 is required for the preference ofM. melolonthalarvae for TA-G deficient plants. Thus, herbivore metabolism modulates both the toxicity and deterrence of a plant defense metabolite. Our work illustrates the multifacteted roles of insect digestive enzymes as mediators of plant-herbivore interactions.
Dependence of an aquatic insect population on contemporaneous primary production
Authors: Phillips Joseph S. , McCormick Amanda R. , Botsch Jamieson C. , Ives Anthony R. 
Published: March 2021

AbstractCharacterizing the dynamics of energy flow through ecosystems requires quantifying the degree to which primary and secondary production are coupled. This coupling is expected to be tight in ecosystems with high internal production relative to external carbon and energy inputs.We experimentally quantified the dependence of aquatic insect emergence on fresh primary production, specifically for the midge population in Lake Mývatn, Iceland. Using field mesocosms, we manipulated algal primary production by reducing light availability via shading. We then used dissolved oxygen incubations to estimate fluxes of carbon through photosynthesis (i.e., gross primary production or “GPP”) over the course of the experiment.We found that elevated GPP was associated with higher emergence rates of adults, as judged both by comparison of emergence across the experimental shading treatments and estimates of in situ GPP within the mesocosms. Furthermore, larger adults emerged earlier than smaller ones, suggesting that asymmetries in resource availability among individuals affected the timing of emergence. Nonetheless, midge emergence was substantial under light-limiting conditions, indicating that while midges benefit from primary production contemporaneous with larval development, they are also capable of completing their life cycles on carbon already existing in the organic matter pool.Our results show that even in systems with limited allochthonous inputs, contemporaneous primary production may be not necessary for high secondary production and insect emergence. Instead, consumers can develop from consumption of biomass derived from past autochthonous primary production. This suggests that primary production and consumer dynamics can be partially decoupled in time in systems that depend on internal production.
Benchtop Carbon Fiber Microelectrode Array Fabrication Toolkit
Authors: Richie Julianna M. , Patel Paras R. , Welle Elissa J. , Dong Tianshu , Chen Lei , Shih Albert J. , Chestek Cynthia A. 
Published: March 2021

AbstractBackgroundConventional neural probes are primarily fabricated in a cleanroom, requiring the use of multiple expensive and highly specialized tools.New methodWe propose a cleanroom “light” fabrication process of carbon fiber neural electrode arrays that can be learned quickly by an inexperienced cleanroom user. This carbon fiber electrode array fabrication process requires just one cleanroom tool, a parylene-c deposition machine, that can be learned quickly or outsourced to a commercial processing facility at marginal cost. Our fabrication process also includes hand-populating printed circuit boards, insulation, and tip optimization.ResultsThe three different tip optimizations explored here (Nd:YAG laser, blowtorch, and UV laser) result in a range of tip geometries and 1kHz impedances, with blowtorched fibers resulting in the lowest impedance. While previous experiments have proven laser and blowtorch electrode efficacy, this paper also shows UV laser cut fibers can record neural signalsin vivo.Comparison with existing methodsExisting carbon fiber arrays either do not have individuated electrodes in favor of bundles or require cleanroom fabricated guides for population and insulation. The proposed arrays use only tools that can be used at a benchtop for fiber population.ConclusionsThis carbon fiber electrode array fabrication process allows for quick customization of bulk array fabrication at a reduced price compared to commercially available probes.