bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG surface mobility promotes antibody dependent cellular phagocytosis by Syk and Arp2/3 mediated reorganization of Fcγ receptors in macrophages
Authors: Jo Seongwan , Cronin Nicholas M. , Dewi Nurmalasari Ni Putu , Kerkvliet Jason G. , Bailey Elizabeth M. , Anderson Robert B. , Scott Brandon L. , Hoppe Adam D. 
Published: July 2021

AbstractBy visualizing the movements of Rituximab during Antibody dependent cellular phagocytosis (ADCP) of B lymphoma cells by macrophages, we found that Fcγ receptors (FcγR) on the macrophage surface microcluster, recruit Syk and undergro large-scale reorganization at the phagocytic synapse prior to and during engulfment of the target cell. Given these dramatic rearrangements, we analyzed how the surface mobility of Rituximab contributes to FcγR signal amplification and ADCP efficiency. Depolymerization of the target cell actin cytoskeleton resulted in free diffusion of Rituximab docked to CD20, enhanced microcluster reorganization, Syk recruitment and ADCP. Conversely, immobilization of Rituximab by chemical fixation impaired microcluster formation and diminished Syk recruitment and ADCP. In macrophages lacking Syk, Rituximab accumulated at the base of the phagosome and were trogocytosed, consistent with Syk kinase activity being necessary to trigger redistribution of Rituximab-FcγR during engulfment and to prevent antigenic modulation of the target. Total internal reflection fluorescence analysis of FcγR-IgG on fluid supported lipid bilayers revealed a membrane topography displaying inward reaching leading edges and protruding contact sites reminiscent of podosomes. This topography was distinct from the closely apposed macrophage/target membranes observed during engagement of IgG displayed on immobile supported lipid bilayers. The organization of this contact, pseudopod extension and the rearrangement of microclusters depended critically on Arp 2/3. Thus, Syk and Arp2/3 coordinate actin rearrangements and FcγR-IgG complexes that were of previously unrecognized complexity for the clearance of cells displaying surface-mobile antigens.Significance StatementADCP is an important effector mechanism for the removal of malignant, immunologically aberrant, and infected cells during treatment with therapeutic antibodies or adaptive immune responses. Most transmembrane protein antigens are mobile with transient confinement from the actin of the target cell. This work demonstrates that macrophage forces overcome these confinements to rearrange FcγR-IgG-antigen complexes before and during ADCP. Thus, new paradigms are needed as ADCP has largely been studied using model target particles that display immobile antigens. Moreover, we found that the mobility of the therapeutic antibody, Rituximab, on the surface of B lymphoma cells foretells ADCP efficacy, with lower densities of IgG mediating ADCP on increasingly mobile antigens.
Disentangling microbial networks across pelagic zones in the global ocean
Authors: Deutschmann Ina M. , Delage Erwan , Giner Caterina R. , Sebastián Marta , Poulain Julie , Arístegui Javier , Duarte Carlos M. , Acinas Silvia G. , Massana Ramon , Gasol Josep M. , Eveillard Damien , Chaffron Samuel , Logares Ramiro 
Published: July 2021

AbstractMicrobial interactions underpin ocean ecosystem function, but they remain barely known. Multiple studies have analyzed microbial interactions using static association networks based on omics data, yet microbial interactions are dynamic and can change across spatiotemporal scales. Understanding the dynamics of microbial interactions is needed for a better comprehension of ocean ecosystems. Here, we explored associations between archaea, bacteria, and picoeukaryotes along the water column, from the surface to the deep ocean, across the northern subtropical to the southern temperate ocean and the Mediterranean Sea by defining sample-specific subnetworks, which allowed us to examine changes in microbial associations across space. We found that associations tend to change with depth as well as with geographical scale, with a few associations being global (i.e., present across regions within the same depth layer) and 11-36% being regional within specific water layers. The lowest fraction of global associations was found in the bathypelagic zone, while associations restricted to certain regions increased with depth. The majority of associations observed in surface waters disappeared with depth, suggesting that surface ocean associations are not transferred to the deep sea, despite microbial sinking. Altogether, our results suggest that microbial associations have highly heterogeneous distributions in the horizontal and vertical dimensions of the ocean and that such distributions do not mirror taxonomic distributions. Our work contributes to better understand the dynamics of microbial interactions in the global ocean, which is urgently needed in a context of global change.
Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer
Authors: Bell Emily S. , Shah Pragya , Zuela-Sopilniak Noam , Kim Dongsung , Varlet Alice-Anais , Morival Julien L.P. , McGregor Alexandra L. , Isermann Philipp , Davidson Patricia M. , Elacqua Joshua J. , Lakins Jonathan N. , Vahdat Linda , Weaver Valerie M. , Smolka Marcus B. , Span Paul N. , Lammerding Jan 
Published: July 2021

AbstractAberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression.
Genome-resolved metagenomic analyses reveal the presence of a bacterial endosymbiont in an avian nasal mite (Rhinonyssidae; Mesostigmata)
Authors: Osuna-Mascaró Carolina , Doña Jorge , Johnson Kevin P. , Rojas Manuel de 
Published: July 2021

AbstractRhinonyssidae (Mesostigmata) is a family of nasal mites only found in birds. All species are hematophagous endoparasites, which may damage the nasal cavities of birds, and also could be potential reservoirs or vectors of other infections. However, the role of members of Rhinonyssidae as disease vectors in wild bird populations remains uninvestigated, with studies of the microbiomes of Rhinonyssidae being almost non-existent. In the nasal mite (Tinaminyssus melloi) from rock doves (Columba livia), a previous study found evidence of a highly abundant putatively endosymbiotic bacteria from Class Alphaproteobacteria. Here, we expanded the sample size of this species, incorporated contamination controls, and increased sequencing depth in shotgun sequencing and genome-resolved metagenomic analyses. Our goal was to increase the information regarding this mite species with its putative endosymbiont. Our results support the endosymbiotic nature of this bacterial taxon, which is the first described for bird’s nasal mites to date, and improve the overall understanding of the microbiota inhabiting these mites.
An integrated analysis tool reveals intrinsic biases in gene set enrichment
Authors: Thakur Nishant , Pujol Nathalie , van Helden Jacques , Waterston Robert H. , Hillier LaDeana W. , Tichit Laurent , Ewbank Jonathan J. 
Published: July 2021

ABSTRACTGenerating meaningful interpretations of gene lists remains a challenge for all large-scale studies. Many approaches exist, often based on evaluating gene enrichment among pre-determined gene classes. Here, we conceived and implemented yet another analysis tool (YAAT), specifically for data from the widely-used model organism C. elegans. YAAT extends standard enrichment analyses, using a combination of co-expression data and profiles of phylogenetic conservation, to identify groups of functionally-related genes. It additionally allows class clustering, providing inference of functional links between groups of genes. We give examples of the utility of YAAT for uncovering unsuspected links between genes and show how the approach can be used to prioritise genes for in-depth study. Our analyses revealed several limitations to the meaningful interpretation of gene lists, specifically related to data sources and the “universe” of gene lists used. We hope that YAAT will represent a model for integrated analysis that could be useful for large-scale exploration of biological function in other species.
Joint analysis of microsatellites and flanking sequences enlightens complex demographic history of interspecific gene flow and vicariance in rear-edge oak populations
Authors: Lepais Olivier , Aissi Abdeldjalil , Véla Errol , Beghami Yassine 
Published: July 2021

AbstractInference of recent population divergence requires fast evolving markers and necessitates to differentiate shared genetic variation caused by ancestral polymorphism and gene flow. Theoretical research shows that the use of compound marker systems integrating linked polymorphisms with different mutational dynamics, such as a microsatellite and its flanking sequences, can improve estimation of population structure and inference of demographic history, especially in the case of complex population dynamics. However, empirical application in natural populations has so far been limited by lack of suitable methods for data collection. A solution comes from the development of sequence-based microsatellite genotyping which we used to study molecular variation at 36 sequenced nuclear microsatellites in sevenQuecus canariensisand fourQuercus faginearear-edge populations across Algeria, to decipher their taxonomic relationship, past evolutionary history and recent demographic trajectory. First, we compare the estimation of population genetics parameters and simulation-based inference of demographic history from microsatellite sequence alone, flanking sequence alone or the combination of linked microsatellite and flanking sequence variation. Second, we measure variable importance from random forest approximate Bayesian computation to identify which of these sequence types is most informative. Whereas the analysis of microsatellite variation alone indicates recent interspecific gene flow, additional information gained from combining with nucleotide variation in flanking sequences, by reducing homoplasy, suggests ancient interspecific gene flow followed by drift in isolation instead. The weight of each polymorphism in the inference also demonstrates the value of linked variations with contrasted mutation dynamic to improve estimation of both demographic and mutational parameters.
High throughput and affordable genome-wide methylation profiling of circulating cell-free DNA by Methylated DNA sequencing (MeD-seq) of LpnPI digested fragments
Authors: Deger Teoman , Boers Ruben G , de Weerd Vanja , Angus Lindsay , van der Put Marjolijn MJ , Boers Joachim B , Azmani Zakia , Ijcken Wilfred FJ van , Grünhagen Dirk J , van Dessel Lisanne F , Lolkema Martijn PJK , Verhoef Cornelis , Sleijfer Stefan , Martens John WM , Gribnau Joost , Wilting Saskia M 
Published: July 2021

ABSTRACTBackgroundDNA methylation detection in liquid biopsies provides a highly promising and much needed means for real-time monitoring of disease load in advanced cancer patient care. Compared to the often-used somatic mutations, tissue- and cancer-type specific epigenetic marks affect a larger part of the cancer genome and generally have a high penetrance throughout the tumour. Here we describe the successful application of the recently described MeD-seq assay for genome-wide DNA methylation profiling on cell-free DNA (cfDNA). The compatibility of the MeD-seq assay with different types of blood collection tubes, cfDNA input amounts, cfDNA isolation methods, and vacuum-concentration of samples was evaluated using plasma from both metastatic cancer patients and healthy blood donors (HBDs). To investigate the potential value of cfDNA methylation profiling for tumour load monitoring, we profiled paired samples from 8 patients with resectable colorectal liver metastases (CRLM) before and after surgery.ResultsThe MeD-seq assay worked on plasma-derived cfDNA from both EDTA and CellSave blood collection tubes when at least 10 ng of cfDNA was used. From the 3 evaluated cfDNA isolation methods, both the manual QIAamp Circulating Nucleic Acid Kit (Qiagen) and the semi-automated Maxwell® RSC ccfDNA Plasma Kit (Promega) were compatible with MeD-seq analysis, whereas the QIAsymphony DSP Circulating DNA Kit (Qiagen) yielded significantly fewer reads when compared to the QIAamp kit (P<0.001). Vacuum-concentration of samples before MeD-seq analysis was possible with samples in AVE buffer (QIAamp) or water, but yielded inconsistent results for samples in EDTA-containing Maxwell buffer. Principal component analysis showed that pre-surgical samples from CRLM patients were very distinct from HBDs, whereas post-surgical samples were more similar. Several described methylation markers for colorectal cancer monitoring in liquid biopsies showed differential methylation between pre-surgical CRLM samples and HBDs in our data, supporting the validity of our approach. Results for MSC, ITGA4, GRIA4, and EYA4, were validated by quantitative methylation specific PCR.ConclusionsThe MeD-seq assay provides a promising new method for cfDNA methylation profiling. Potential future applications of the assay include marker discovery specifically for liquid biopsy analysis as well as direct use as a disease load monitoring tool in advanced cancer patients.
In situ solid-liquid extraction enhances recovery of taxadiene from engineered S. cerevisiae cell factories
Authors: Santoyo-Garcia Jorge H. , Walls Laura E. , Nowrouzi Behnaz , Ochoa-Villareal Marisol , Loake Gary J. , Dimartino Simone , Rios-Solis Leonardo 
Published: July 2021

AbstractA novel in situ solid phase adsorption strategy was investigated for enhanced recovery of taxadiene, a precursor to the blockbuster anticancer drug, paclitaxel, from engineered Saccharomyces cerevisiae. A synthetic adsorbent resin (HP-20) was employed to capture taxadiene across a range of cultivation scales. Cultivations from 12 % (w/v) resin concentration resulted in bead fragmentation which were found to be detrimental to cellular growth. After cultivation, the use of acetone for desorption captured intracellular and secreted taxadiene, achieving an integration of the bioprocess. Implementation of the proposed method at microscale (2 mL) and benchtop bioreactor scale (250 mL) resulted in 1.9-fold and 1.4-fold increments in taxadiene titer, respectively, compared to the extraction method using a dodecane overlay. Taxadiene was found to be distributed between resin beads and biomass in a ratio of 50 %. Finally, a maximum taxadiene titer of 76 ± 19 mg/L was achieved in the benchtop bioreactor cultivations.
The presence of corticomuscular coherence during unipedal stance
Authors: Alkaff Sylmina Dalily , Ushiyama Junichi 
Published: July 2021

AbstractStanding in unipedal stance requires higher effort to maintain posture balance within narrow base-of-support. Although changes in cortical activity are known to occur as standing task difficulty increased, it is unclear whether it indicates a change in cortical control of muscle activity. To elucidate this point, this study examined corticomuscular coherence (CMC) between the sensorimotor cortex and ankle joint muscles during three tasks such as bipedal stance, unipedal stance, and isometric contraction tasks. For twenty-one healthy participants, we measured the maximal peak of CMC (CMCmax) between electroencephalograms overlying the foot representation area and surface electromyograms from the tibialis anterior (TA), medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL), respectively, for each task. We also measured the center of pressure (COP) during both stance tasks. Although there was no significant CMC during bipedal stance in all participants, most participants (n = 14) showed significant CMC for all muscles during unipedal stance with larger COP fluctuation in most participants. Indeed, there was significant difference in CMCmax between unipedal and bipedal stance tasks. The greater CMC would indicate increased cortical control of muscle activity to compensate for postural instability during unipedal stance.
The spatial landscape of clonal somatic mutations in benign and malignant tissue
Authors: Erickson Andrew , Berglund Emelie , He Mengxiao , Marklund Maja , Mirzazadeh Reza , Schultz Niklas , Bergenstråhle Ludvig , Kvastad Linda , Andersson Alma , Bergenstråhle Joseph , Larsson Ludvig , Shamikh Alia , Basmaci Elisa , De Ståhl Teresita Diaz , Rajakumar Timothy , Thrane Kim , Ji Andrew L , Khavari Paul A , Tarish Firaz , Tanoglidi Anna , Maaskola Jonas , Colling Richard , Mirtti Tuomas , Hamdy Freddie C , Woodcock Dan J , Helleday Thomas , Mills Ian G. , Lamb Alastair D , Lundeberg Joakim 
Published: July 2021

AbstractDefining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
Drug-free nasal spray as a barrier against SARS-CoV-2 infection: safety and efficacy in human nasal airway epithelia
Authors: Fais Fabio , Juskeviciene Reda , Francardo Veronica , Mateos Stéphanie , Constant Samuel , Borelli Massimo , Hohenfeld Ilja P. , Meyer Thomas 
Published: July 2021

AbstractBackgroundFor SARS-CoV-2 and other respiratory viruses, the nasal epithelium is a key portal for infection. Therefore, the nose is an important target of prophylactic and therapeutic interventions against these viruses. We developed a nasal spray (AM-301, a medical device marketed as Bentrio) to protect against infection by SARS-CoV-2 and potentially other viruses.Aims of the studyTo test the safety and efficacy of AM-301 against SARS-CoV-2 infection.MethodsAM-301 was tested on an in vitro 3D model of primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in prophylaxis and infection mitigation assays.ResultsAM-301 did not have any detrimental effect on the nasal epithelium. Prophylactic treatment with AM-301 reduced viral titer significantly vs. controls over 4 days, reaching a maximum reduction of 99%. When treatment with AM-301 was started 24 or 30 h after infection, epithelia that received the formulation had a 12- or 14-fold lower titer than controls.ConclusionAM-301 was found to be safe in vitro, and it significantly decelerated viral titer growth in experimental models of prophylaxis and mitigation. Its physical (non-pharmaceutical) mechanism of action, safety and efficacy pave the way for further investigation of its possible use against a broad spectrum of viruses, allergens and pollutants.
Serial dependence tracks objects and scenes in parallel and independently
Authors: Collins Thérèse 
Published: July 2021

AbstractThe visual world is made up of objects and scenes. Object perception requires both discriminating an individual object from others and binding together different perceptual samples of that object across time. Such binding manifests by serial dependence, the attraction of the current perception of a visual attribute towards values of that attribute seen in the recent past. Scene perception is subserved by global mechanisms like ensemble perception, the rapid extraction of the average feature value of a group of objects. The current study examined to what extent the perception of single objects in multi-object scenes depended on previous feature values of that object, or on the average previous attribute of all objects in the scene. Results show that serial dependence occurs independently on two simultaneously present objects, that ensemble perception depends only on previous ensembles, and that serial dependence of an individual object occurs only on the features of that particular object. These results suggest that the temporal integration of successive perceptual samples operates simultaneously at independent levels of visual processing.
Creating a bottleneck: Robust LC3B lipidation analysis by adjusting autophagic flux with low concentrations of Bafilomycin A1
Authors: Liebl Martina P. , Meister Sarah C. , Frey Lisa , Hendrich Kristina , Klemmer Anja , Pohl Christian , Lakics Viktor 
Published: July 2021

AbstractAutophagic flux can be quantified based on the accumulation of lipidated LC3B in the presence of late-stage autophagy inhibitors. This method has been widely applied to identify novel compounds that activate autophagy. Here we scrutinize this approach and show that bafilomycin A1 (BafA) but not chloroquine is suitable for flux quantification due to the stimulating effect of chloroquine on non-canonical LC3B-lipidation. Significant autophagic flux increase by rapamycin could only be observed when combining it with BafA concentrations not affecting basal flux, a condition which created a bottleneck, rather than fully blocking autophagosome-lysosome fusion, concomitant with autophagy stimulation. When rapamycin was combined with saturating concentrations of BafA, no significant further increase of LC3B lipidation could be detected over the levels induced by the late-stage inhibitor. The large assay window obtained by this approach enables an effective discrimination of autophagy activators based on their cellular potency. To demonstrate the validity of this approach, we show that a novel inhibitor of the acetyltransferase EP300 activates autophagy in a mTORC1-dependent manner. We propose that the creation of a sensitized background rather than a full block of autophagosome progression is required to quantitatively capture changes in autophagic flux.