bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feedback in the β-catenin destruction complex imparts bistability and cellular memory
Authors: Cantoria Mary Jo , Alizadeh Elaheh , Ravi Janani , Bunnag Nawat , Kettenbach Arminja N. , Ahmed Yashi , Paek Andrew L , Tyson John J. , Doubrovinski Konstantin , Lee Ethan , Thorne Curtis A. 
Published: January 2022

ABSTRACTWnt ligands are considered classical morphogens, for which the strength of the cellular response is proportional to the concentration of the ligand. Herein, we show an emergent property of bistability arising from feedback among the Wnt destruction complex proteins that target the key transcriptional co-activator β-catenin for degradation. Using biochemical reconstitution, we identified positive feedback between the scaffold protein Axin and the kinase GSK3. Theoretical modeling of this feedback between Axin and GSK3 predicted that the activity of the destruction complex exhibits bistable behavior. We experimentally confirmed these predictions by demonstrating that cellular cytoplasmic β-catenin concentrations exhibit an “all-or-none” response with sustained memory (hysteresis) of the signaling input. This bistable behavior was transformed into a graded response and memory was lost through inhibition of GSK3. These findings provide a mechanism for establishing decisive, switch-like cellular response and memory upon Wnt pathway stimulation.One Sentence SummaryPositive feedback within the β-catenin destruction complex gives rise to bistability and memory in response to Wnt stimulation, imparting signal transduction accuracy and insulation.
Modular and programmable RNA sensing using ADAR editing in living cells
Authors: Kaseniit K. Eerik , Katz Noa , Kolber Natalie S. , Call Connor C. , Wengier Diego L. , Cody Will B. , Sattely Elizabeth S. , Gao Xiaojing J. 
Published: January 2022

AbstractWith the increasing availability of single-cell transcriptomes, RNA signatures offer a promising basis for targeting living cells. Molecular RNA sensors would enable the study of and therapeutic interventions for specific cell types/stats in diverse contexts, particularly in human patients and non-model organisms. Here we describe a modular and programmable design for live RNA sensing using adenosine deaminases acting on RNA (RADAR). We validated and then expanded our basic design, characterized its performance, and thoroughly analyzed its compatibility with the human/mouse transcriptomes. We also identified strategies to further boost output levels and improve the dynamic range. We show that RADAR is programmable and modular, and uniquely enables compact AND logic. In addition to being quantitative, RADAR can distinguish disease-relevant point mutations. Finally, we demonstrate that RADAR is a self-contained system with the potential to function in diverse organisms.
Transcriptome Analysis of the Nematode Caenorhabditis elegans and Litoditis marina in a Chemically Defined Food Environment
Authors: Sun Peiqi , Cao Xuwen , Zhang Liusuo 
Published: January 2022

AbstractDiets regulate animal development, reproduction, and lifespan. However, the underlying molecular mechanisms remain elusive. A chemically defined CeMM diet attenuates development and promotes longevity of C. elegans, but whether it impact on other nematodes is unknown. Here, we studied the effect of the CeMM diet on the development and longevity of the marine nematode Litoditis marina, which belongs to the same family as C. elegans. We further investigated genome-wide transcriptional responses to CeMM and OP50 diet for both nematodes, respectively. We observed that the CeMM diet attenuated L. marina development but did not extend its lifespan. We found that many of the FOXO DAF-16 target genes, lysosome and xenobiotic metabolism related genes were significantly increased on the CeMM, which might contribute to the lifespan extension of C. elegans. Notably, we found that the expression of lysosome and xenobiotic metabolism pathway genes was significantly down regulated in L. marina on CeMM, which might explain why the CeMM diet could not promote the lifespan of L. marina compared to bacterial feeding. Additionally, down-regulation of several RNA transcription and protein generation and related processes genes might not only be involved in extending longevity but also contribute to attenuating development of C. elegans on CeMM, while down-regulation of unsaturated fatty acids synthesis genes might contribute to slow down the growth of L. marina on CeMM. Further genetic analysis of candidate gene(s) of longevity and development in C. elegans and L. marina will provide the molecular mechanisms underlying how diets regulate animal physiology and health in the context of global climate change with variable nutritional environments.
Inner membrane complex proteomics reveals a palmitoylation cascade regulating intraerythrocytic development of malaria parasite
Authors: Qian Pengge , Wang Xu , Zhong Chuan-Qi , Wang JiaXu , Cai Mengya , Nguitragool Wang , Li Jian , Cui Huiting , Yuan Jing 
Published: February 2022

AbstractMalaria is caused by infection of the erythrocytes by the parasitesPlasmodium. Inside the erythrocytes, the parasites multiply via schizogony, an unconventional cell division mode. The Inner Membrane Complex (IMC), an organelle located beneath the parasite plasma membrane, serving as the platform for protein anchorage, is essential for schizogony. So far, complete repertoire of IMC proteins and their localization determinants remain unclear. Here we used biotin ligase (TurboID)-based proximity labelling to compile the proteome of the schizont IMC of rodent malaria parasitePlasmodium yoelii.In total, 300 TurboID-interacting proteins were identified. 19 of the 22 selected candidates were confirmed to localize in the IMC, indicating good reliability. In light of the existing palmitome ofPlasmodium falciparum, 83 proteins of theP. yoeliiIMC proteome are potentially palmitoylated. We further identified DHHC2 as the major resident palmitoyl-acyl-transferase of the IMC. Depletion of DHHC2 led to defective schizont segmentation and growth arrest bothin vitroandin vivo. DHHC2 was found to palmitoylate two critical IMC proteins CDPK1 and GAP45 for their IMC localization. In summary, this study reports an inventory of new IMC proteins and demonstrates a central role of DHHC2 in governing IMC localization of proteins during the schizont development.
Learning the Vector Coding of Egocentric Boundary Cells from Visual Data
Authors: Lian Yanbo , Williams Simon , Alexander Andrew S. , Hasselmo Michael E. , Burkitt Anthony N. 
Published: January 2022

AbstractThe use of spatial maps to navigate through the world requires a complex ongoing transformation of egocentric views of the environment into position within the allocentric map. Recent research has discovered neurons in retrosplenial cortex and other structures that could mediate the transformation from egocentric views to allocentric views. These egocentric boundary cells respond to the egocentric direction and distance of barriers relative to an animals point of view. This egocentric coding based on the visual features of barriers would seem to require complex dynamics of cortical interactions. However, computational models presented here show that egocentric boundary cells can be generated with a remarkably simple synaptic learning rule that forms a sparse representation of visual input as an animal explores the environment. Simulation of this simple sparse synaptic modification generates a population of egocentric boundary cells with distributions of direction and distance coding that strikingly resemble those observed within the retrosplenial cortex. This provides a framework for understanding the properties of neuronal populations in the retrosplenial cortex that may be essential for interfacing egocentric sensory information with allocentric spatial maps of the world formed by neurons in downstream areas including the grid cells in entorhinal cortex and place cells in the hippocampus.
A novel genomic DNA library preparation method with low GC bias
Authors: Kelly S. Thomas , Hakoyama Tsuneo , Kumaishi Kie , Okuda-Yabukami Haruka , Kato Sachi , Hayashi Makoto , Minoda Aki , Ichihashi Yasunori 
Published: February 2022

AbstractThe amount of input DNA available to prepare next-generation sequencing (NGS) libraries is often limited, which can lead to GC content bias and enrichment of specific genomic regions with currently available protocols. In this study, we used breath capture technology to incorporate sequencing adapters into DNA to develop a novel cost-effective protocol for the preparation of genomic DNA libraries. We performed a benchmarking experiment comparing our protocol with common commercially available kits for genomic DNA library preparation with input DNA amount in the range of 1 to 50 ng. Our protocol can generate high-quality genomic sequence data with a marked improvement in coverage breadth and low GC bias, in contrast to standard protocols. Further, our protocol reduces sample handling time and reagent costs, and requires comparatively fewer enzymatic steps relative to other protocols, making it suitable for a range of genomics applications.
Synthetic glycans that control gut microbiome structure mitigate colitis in mice
Authors: Tolonen Andrew C , Beauchemin Nicholas , Bayne Charlie , Li Lingyao , Tan Jie , Lee Jackson , Meehan Brian , Meisner Jeffrey , Millet Yves , LeBlanc Gabrielle , Kottler Robert , Rapp Erdmann , Murphy Chris , Turnbaugh Peter J , von Maltzahn Geoffrey , Liu Christopher M , van Hylckama Vlieg Johan ET 
Published: January 2022

AbstractRelative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. We describe the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures resulted in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increased survival, reduced weight loss, and improved clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome.
Complex and critical roles for the AtrR transcription factor in control of cyp51A expression in Aspergillus fumigatus
Authors: Paul Sanjoy , Verweij Paul E. , Melchers Willem J.G. , Moye-Rowley W. Scott 
Published: January 2022

AbstractAspergillus fumigatus is the major filamentous fungal pathogen in humans. The gold standard treatment of A. fumigatus is based on azole drug use but the appearance of azole-resistant isolates is increasing at an alarming rate. The cyp51A gene encodes the enzymatic target of azole drugs and azole-resistant alleles of cyp51A often have an unusual genetic structure containing a duplication of a 34 or 46 bp region in the promoter causing enhanced gene transcription. These tandem repeats are called TR34/TR46 and produce duplicated binding sites for the SrbA and AtrR transcription factors. Using site-directed mutagenesis, we demonstrate that both the SrbA (sterol response element: SRE) and AtrR binding sites (AtrR response element: ATRE) are required for normal cyp51A gene expression. Loss of either the SRE or ATRE from the distal 34 bp repeat of the TR34 promoter (further 5’ from the transcription start site) caused loss of expression of cyp51A and decreased voriconazole resistance. Surprisingly, loss of these same binding sites from the proximal 34 or 46 bp repeat led to increased cyp51A expression and voriconazole resistance. These data indicate that these duplicated regions in the cyp51A promoter function differently. Our findings suggest that the proximal 34 or 46 bp repeat in cyp51A recruits a corepressor that requires multiple factors to act while the distal repeat is free of this repression and provides the elevated cyp51A expression caused by these promoter duplications.ImportanceAspergillus fumigatus is the most common human filamentous fungal pathogen. Azole drugs are the current therapy of choice for A. fumigatus but the prevalence of azole resistance is increasing. The main genetic alteration causing azole resistance is a change in the cyp51A gene that encodes the target of these drugs. Azole-resistant cyp51A alleles routinely contain duplications in their promoter regions that cause increased gene transcription. Here, we demonstrate that clinical isolates containing a 34 or 46 bp duplication in the cyp51A promoter required the presence of the transcription factor-encoding atrR gene to exhibit elevated azole resistance. Elimination of transcription factor binding sites in the cyp51A gene have differential actions on expression of the resulting mutant allele. These data dissect the molecular inputs to cyp51A transcription and reveal a complicated function of the promoter of this gene that is critical in azole resistance.
Sensory plasticity in a socially plastic bee
Authors: Boulton Rebecca A , Field Jeremy 
Published: January 2022

AbstractThe social Hymenoptera have contributed much to our understanding of the evolution of sensory systems. Attention has focussed chiefly on how sociality and sensory systems have evolved together. In the Hymenoptera, the antennal sensilla are important for optimising the perception of olfactory social information. Social species have denser antennal sensilla than solitary species, which is thought to enhance social cohesion through nest-mate recognition. In the current study, we test whether sensilla numbers vary between populations of the socially plastic sweat bee Halictus rubicundus from regions that vary in climate and the degree to which sociality is expressed. We found region level differences in both olfactory and hygro/thermoreceptive sensilla numbers. We also found evidence that olfactory sensilla density is developmentally plastic: when we transplanted bees from Scotland to the south-east of England, their offspring (which developed in the south) had more olfactory hairs than the transplanted individuals themselves (which developed in Scotland). The transplanted bees displayed a mix of social (a queen plus workers) and solitary nesting, but neither individual nor nest phenotype was related to sensilla density. We suggest that this general, rather than caste-specific sensory plasticity provides a flexible means to optimise sensory perception according to the most pressing demands of the environment. Sensory plasticity may support social plasticity in H. rubicundus but does not appear to be causally related to it.
Oncogene expression from extrachromosomal DNA is driven by copy number amplification and does not require spatial clustering
Authors: Purshouse Karin , Friman Elias T. , Boyle Shelagh , Dewari Pooran Singh , Grant Vivien , Hamdan Alhafidz , Morrison Gillian M. , Brennan Paul M , Beentjes Sjoerd V. , Pollard Steven M. , Bickmore Wendy A. 
Published: January 2022

SummaryExtrachromosomal DNA (ecDNA) are frequently observed in human cancers and are responsible for high levels of oncogene expression. In glioblastoma (GBM), ecDNA copy number correlates with poor prognosis. It is hypothesized that their copy number, size and chromatin accessibility facilitate clustering of ecDNA and colocalization with transcriptional condensates, and that this underpins their elevated transcriptional activity. Here, we use super-resolution imaging and quantitative image analysis to evaluate GBM stem cells harboring distinct ecDNA species (EGFR, MYC, PDGFR). We found no evidence that ecDNA cluster with one another or closely interact with transcriptional condensates. Cells with EGFR-containing ecDNA have increased EGFR transcriptional output, but transcription per gene copy was similar in ecDNA compared to the endogenous chromosomal locus. These data suggest that is the increased copy number of oncogene-harbouring ecDNA that primarily drives high levels of oncogene transcription, rather than specific interactions of ecDNA with the cellular transcriptional machinery.
A guide to sampling design for GPS-based studies of animal societies
Authors: He Peng , Klarevas-Irby James A. , Papageorgiou Danai , Christensen Charlotte , Strauss Eli D. , Farine Damien R. 
Published: January 2022

ABSTRACTGPS-based tracking is widely used for studying wild social animals. Much like traditional observational methods, using GPS devices requires making a number of decisions about sampling that can affect the robustness of a study’s conclusions. For example, sampling fewer individuals per group across more distinct social groups may not be sufficient to infer group- or subgroup-level behaviours, while sampling more individuals per group across fewer groups limits the ability to draw conclusions about populations. Here, we provide quantitative recommendations when designing GPS-based tracking studies of animal societies. We focus on the trade-offs between three fundamental axes of sampling effort: 1) sampling coverage—the number and allocation of GPS devices among individuals in one or more social groups; 2) sampling duration—the total amount of time over which devices collect data; 3) sampling frequency—the temporal resolution at which GPS devices record data. We first test GPS tags under field conditions to quantify how these aspects of sampling design can affect both GPS accuracy (error in absolute positional estimates) and GPS precision (error in the estimate relative position of two individuals), demonstrating that GPS error can have profound effects when inferring distances between individuals. We then use data from whole-group tracked vulturine guineafowl (Acryllium vulturinum) to demonstrate how the trade-off between sampling frequency and sampling duration can impact inferences of social interactions and to quantify how sampling coverage can affect common measures of social behaviour in animal groups, identifying which types of measures are more or less robust to lower coverage of individuals. Finally, we use data-informed simulations to extend insights across groups of different sizes and cohesiveness. Based on our results, we are able to offer a range of recommendations on GPS sampling strategies to address research questions across social organizational scales and social systems—from group movement to social network structure and collective decision-making. Our study provides practical advice for empiricists to navigate their decision-making processes when designing GPS-based field studies of animal social behaviours, and highlights the importance of identifying the optimal deployment decisions for drawing informative and robust conclusions.
Quantitative evaluation of warming and hemodilution as two techniques to increase the flow rate of blood during simulated massive transfusion of packed red blood cells
Authors: Shah Netra 
Published: January 2022

AbstractMassive bleeding is a leading cause of deaths in trauma, surgeries, wartime injuries, and childbirth. In these situations of ongoing blood loss, it is critical for patients to be rapidly resuscitated. Currently, patients who require major transfusions are given cold and concentrated blood from the blood bank. This blood does not flow fast due to its viscosity. Equipment for rapid resuscitation such as rapid transfusers are very costly and are not accessible everywhere. Additionally, specialized training is required to operate these machines. Therefore, it is necessary to determine simple, quick, and effective ways to increase the flow rate of blood. The flow rate can be increased by warming and hemodilution. The purpose of this study was to quantify the effects of these simple and quick methods since they can be implemented anywhere with easily accessible equipment. In this experiment, expired packed red blood cells were warmed and diluted. The time the blood took to flow through the tubing was measured and a flow rate was calculated for each trial. The research hypothesis stated that diluted blood at 39°C would have the fastest flow rate. The research hypothesis was supported and there was a 366% in flow rate by warming and diluting blood. There was a 232% increase by simply diluting the blood and a 170% increase by warming. Six t-tests were conducted for this data and they were all significant at a level of 0.001. These results indicate the significant effects of warming and diluting blood and this research could improve patient care during emergencies and massive blood loss.
Naïve Bayes Assessment of Mediterranean Basin Ecosystem Wildfires Associated With Vegetation Vigor in August 2021
Authors: Wibowo Andri 
Published: January 2022

AbstractThe Mediterranean basin, located in the Southern Mediterranean Sea in the North of Africa, is one of the ecosystems that are vulnerable to wildfire hazards. A massive wildfire occurred in this ecosystem in August 2021. Here, this study aims to detect the burnt areas and assess the ecosystem covariates related to the wildfire occurrences. Wildfire assessments were conducted using remote sensing (RS) analysis. Measured ecosystem covariates include vegetation cover, moisture, and the Normalized Difference Vegetation Index (NDVI). The RS analysis confirms at least 17090 ha of vegetation cover were damaged. The burnt vegetation cover was associated with the vegetation moisture and NDVI. The result shows 61.93% of burnt areas were observed within areas that had low vegetation moisture. While 51.75% of burnt areas occurred within areas that had low NDVI values. Naïve Bayes classifier confirms that vegetation moisture and NDVI covariates can be used to estimate the presences of wildfires with values of Kappa, accuracy, precision, recall, and F1 score are 0.7, 0.85, 0.89, 0.8, and 0.84. The area under (AUC) the receiver operating characteristic (ROC) curve values for vegetation moisture and NDVI covariates were 0.945 and 0.399. This value indicates that low vegetation moisture contributes more to the wildfire presences than low NDVI.
3D Printable High Performance Conducting Polymer Hydrogel for All-Hydrogel Bioelectronics
Authors: Zhou Tao , Yuk Hyunwoo , Hu Faqi , Wu Jingjing , Tian Fajuan , Roh Heejung , Shen Zequn , Gu Guoying , Xu Jingkun , Lu Baoyang , Zhao Xuanhe 
Published: January 2022

AbstractOwing to the unique combination of electrical conductivity and tissue-like mechanical properties, conducting polymer hydrogels have emerged as a promising candidate for bioelectronic interfacing with biological systems. However, despite the recent advances, the development of hydrogels with both excellent electrical and mechanical properties in physiological environments remains a lingering challenge. Here, we report a bi-continuous conducting polymer hydrogel (BC-CPH) that simultaneously achieves high electrical conductivity (over 11 S cm-1), stretchability (over 400%) and fracture toughness (over 3,300 J m-2) in physiological environments, and is readily applicable to advanced fabrication methods including 3D printing. Enabled by the BC-CPH, we further demonstrate multi-material 3D printing of monolithic all-hydrogel bioelectronic interfaces for long-term electrophysiological recording and stimulation of various organs. This study may offer promising materials and a platform for future bioelectronic interfacing.