bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring Energy Landscapes of Intrinsically Disordered Proteins: Insights into Functional Mechanisms
Authors: Oliveira Antonio B. , Lin Xingcheng , Kulkarni Prakash , Onuchic José N. , Roy Susmita , Leite Vitor B.P. 
Published: January 2021

AbstractIntrinsically disordered proteins (IDPs) lack a rigid 3D structure and populate a polymorphic ensemble of conformations. Because of the lack of a reference conformation, their energy landscape representation in terms of reaction coordinates presents a daunting challenge. Here, our newly developed Energy Landscape Visualization Method (ELViM), a reaction coordinate-free approach, shows its prime application to explore frustrated energy landscapes of an intrinsically disordered protein, Prostate-Associated Gene 4 (PAGE4). PAGE4 is a transcriptional coactivator that potentiates the oncogene c-Jun. Two kinases, namely HIPK1 and CLK2, phosphorylate PAGE4 generating variants phosphorylated at different serine/threonine residues (HIPK1-PAGE4 and CLK2-PAGE4, respectively) with opposing functions. While HIPK1-PAGE4 predominantly phosphorylates Thr51 and potentiates c-Jun, CLK2-PAGE4 hyper-phosphorylates PAGE4 and attenuates transactivation. To understand the underlying mechanisms of conformational diversity among different phosphoforms, we have analyzed their atomistic trajectories simulated using AWSEM forcefield and the energy landscapes were elucidated using ELViM. This method allows us to identify and compare the population distributions of different conformational ensembles of PAGE4 phosphoforms using the same effective phase space. The results reveal a predominant conformational ensemble with an extended C-terminal segment of WT PAGE4, which exposes a functional residue Thr51, implying its potential of undertaking a fly-casting mechanism while binding to its cognate partner. In contrast, for HIPK1-PAGE4, a compact conformational ensemble enhances its population sequestering phosphorylated-Thr51. This clearly explains the experimentally observed weaker affinity of HIPK1-PAGE4 for c-Jun. ELViM appears as a powerful tool especially to analyze the highly-frustrated energy landscape representation of IDPs where appropriate reaction coordinates are hard to apprehend.
A hetero-oligomeric remorin-receptor complex regulates plant development
Authors: Abel Nikolaj B. , Buschle Corinna A. , Hernandez-Ryes Casandra , Burkart Sandy S. , Deroubaix Anne-Flore , Mergner Julia , Gronnier Julien , Jarsch Iris K. , Folgmann Jessica , Braun Karl Heinz , Bayer Emmanuelle , Germain Véronique , Derbyshire Paul , Menke Frank L.H. , Kemmerling Birgit , Zipfel Cyril , Küster Bernhard , Mongrand Sébastien , Marín Macarena , Ott Thomas 
Published: January 2021

AbstractPlant growth and development are modulated by both biotic and abiotic stress. Increasing evidence suggests that cellular integration of the corresponding signals occurs within preformed hubs at the plasma membrane called nanodomains. These membrane sub-compartments are organized by multivalent molecular scaffold proteins, such as remorins. Here, we demonstrate that Group 1 remorins form a hetero-oligomeric complex at the plasma membrane. While these remorins are functionally redundant for some pathways their multivalency also allows the recruitment of specific interaction partners. One of them, the receptor-like kinase REMORIN-INTERACTING RECEPTOR 1 (RIR1), that acts redundantly with the closely related receptor NILR2, is specifically recruited by REM1.2 in a phosphorylation-dependent manner. Overlapping developmental phenotypes suggest that the REM/RIR complex regulates key developmental pathways.
Targeting cellular metabolism to inhibit synergistic biofilm formation of multi-species isolated from a cooling water system
Authors: Kang Dingrong , Liu Wenzheng , kakahi Fatemeh Bajoul , Delvigne Frank 
Published: January 2021

AbstractBiofilm is ubiquitous in natural environments, causing biofouling in industrial water systems and leading to liquidity and heat transfer efficiency decreases. In particular, multi-species coexistence in biofilms can provide the synergy needed to boost biomass production and enhance treatment resistance. In this study, a total of 37 bacterial strains were isolated from a cooling tower where acetic acid and propionic acid were used as the primary carbon sources. These isolates mainly belonged to Proteobacteria and Firmicutes, which occupied more than 80% of the total strains according to the 16S rRNA gene amplicon sequencing. Four species (Acinetobactersp. CTS3, Corynebacteriumsp. CTS5, Providenciasp. CTS12, andPseudomonassp. CTS17) were observed to co-exist in the synthetic medium, showing a synergistic effect towards biofilm formation. Three metabolic inhibitors (sulfathiazole, 3-Bromopyruvic acid, and 3-Nitropropionic acid) were employed as possible treatments against biofilm formation due to their inhibition effect on c-di-GMP biosynthesis or assimilation of volatile fatty acids. All of them displayed evident inhibition profiles to biofilm formation. Notably, the combination of these three inhibitors possessed a remarkable ability to block the development of a multi-species biofilm with lower concentrations, suggesting an enhanced effect with their simultaneous use. This study demonstrates that targeting cellular metabolism is an effective way to inhibit biofilm formation derived from multi-species.
Occasional paternal inheritance of the germline-restricted chromosome in songbirds
Authors: Pei Yifan , Forstmeier Wolfgang , Ruiz-Ruano Francisco J. , Mueller Jakob C. , Cabrero Josefa , Camacho Juan Pedro. M. , Alché Juan D. , Franke Andre , Hoeppner Marc , Börno Stefan , Gessara Ivana , Hertel Moritz , Teltscher Kim , Knief Ulrich , Suh Alexander , Kempenaers Bart 
Published: January 2021

AbstractAll songbirds have one special accessory chromosome1–4, the so-called germline-restricted chromosome (GRC)4–7, which is only present in germline cells and absent from all somatic tissues. Earlier work on the zebra finch (Taeniopygia guttata castanotis) showed that the GRC is inherited only through the female line4,6,8,9– like mitochondrial DNA7,9–12– and is eliminated from the sperm during spermatogenesis5,7,9–11. Here we show that the GRC can also be paternally inherited. Confocal microscopy using GRC-specific FISH probes indicated that a considerable fraction of sperm heads (1-19%) in zebra finch ejaculates still contained the GRC. In line with these cytogenetic data, sequencing of ejaculates revealed that individual males from two families differed strongly and consistently in the number of GRCs in their ejaculates. Examining a captive-bred population of hybrids of the two zebra finch subspecies (T. g. guttataandT. g. castanotis) revealed that the descendants inherited their mitochondria from acastanotismother but their GRC from aguttatafather. Moreover, GRC haplotypes across nine differentcastanotismatrilines showed at best a weak tendency to be co-inherited with mtDNA haplotypes. Withincastanotis, the GRC showed little variability, while the mtDNA of matrilines was highly divergent. This suggests that a single GRC haplotype has recently spread across the entirecastanotispopulation, crossing the matriline boundaries via paternal spillover. Our findings raise the possibility that certain GRC haplotypes could selfishly spread through the population, via additional paternal transmission, thereby outcompeting other GRC haplotypes that were limited to strict maternal inheritance, even if this was partly detrimental to organismal fitness.
Multisensory correlation computations in the human brain uncovered by a time-resolved encoding model
Authors: Lerousseau Jacques Pesnot , Parise Cesare , Ernst Marc O. , van Wassenhove Virginie 
Published: January 2021

ABSTRACTNeural mechanisms that arbitrate between integrating and segregating multisensory information are essential for complex scene analysis and for the resolution of the multisensory correspondence problem. However, these mechanisms and their dynamics remain largely unknown, partly because classical models of multisensory integration are static. Here, we used the Multisensory Correlation Detector, a model that provides a good explanatory power for human behavior while incorporating dynamic computations. Participants judged whether sequences of auditory and visual signals originated from the same source (causal inference) or whether one modality was leading the other (temporal order), while being recorded with magnetoencephalography. To test the match between the Multisensory Correlation Detector dynamics and the magnetoencephalographic recordings, we developed a novel dynamic encoding-model approach of electrophysiological activity, which relied on temporal response functions. First, we confirm that the Multisensory Correlation Detector explains causal inference and temporal order patterns well. Second, we found strong fits of brain activity to the two outputs of the Multisensory Correlation Detector in temporo-parietal cortices, a region with known multisensory integrative properties. Finally, we report an asymmetry in the goodness of the fits, which were more reliable during the causal inference than during the temporal order judgment task. Overall, our results suggest the plausible existence of multisensory correlation detectors in the human brain, which explain why and how causal inference is strongly driven by the temporal correlation of multisensory signals.
Two step PCR method to exchange the resistance cassette of a vector
Authors: Cremer Nils , Diehl Anne 
Published: January 2021

AbstractFor co-transformation of two plasmids, both have to possess different antibiotic selection markers. If that is not the case, normally the gene of interest (GOI) is subcloned into another vector. Here we introduce a fast and easy method to exchange the antibiotic resistance cassette (ARC) in only two PCR steps.Method SummaryTo shuttle the antibiotic resistance cassette (ARC) from one vector to another, one can amplify the ARC of interest and use the resulting PCR-product as a primer pair for the next amplification step. Simply remove parental DNA template byDpnI digestion, transform PCR product directly inE. coli cells, select transformants on an appropriate agar plate and isolate target vector by plasmid preparation.
SMILE: Mutual Information Learning for Integration of Single Cell Omics Data
Authors: Xu Yang , Das Priyojit , McCord Rachel Patton 
Published: January 2021

AbstractDeep learning approaches have empowered single-cell omics data analysis in many ways, generating new insights from complex cellular systems. As there is an increasing need for single cell omics data to be integrated across sources, types, and features of data, the challenges of integrating single-cell omics data are rising. Here, we present a deep clustering algorithm that learns discriminative representation for single-cell data via maximizing mutual information, SMILE (Single-cellMutualInformationLearning). Using a unique cell-pairing design, SMILE successfully integrates multi-source single-cell transcriptome data, removing batch effects and projecting similar cell types, even from different tissues, into the same representation space. SMILE can also integrate data from two or more modalities, such as joint profiling technologies using singlecell ATAC-seq, RNA-seq, DNA methylation, Hi-C, and ChIP data. SMILE works well even when feature types are unmatched, such as genes for RNA-seq and genome wide peaks for ATAC-seq.
A unified mechanism for innate and learned visual landmark guidance in the insect central complex
Authors: Goulard Roman , Buehlmann Cornelia , Niven Jeremy E. , Graham Paul , Webb Barbara 
Published: January 2021

AbstractInsects can navigate efficiently in both novel and familiar environments, and this requires flexiblity in how they are guided by sensory cues. A prominent landmark, for example, can ellicit strong innate behaviours (attraction or menotaxis) but can also be used, after learning, as a specific directional cue as part of a navigation memory. However, the mechanisms that allow both pathways to co-exist, interact or override each other are largely unknown. Here we propose a model for the behavioural integration of innate and learned guidance based on the neuroanatomy of the central complex (CX), adapted to control landmark guided behaviours. We consider a reward signal provided either by an innate attraction to landmarks or a long-term visual memory in the mushroom bodies (MB) that modulates the formation of a local vector memory in the CX. Using an operant strategy for a simulated agent exploring a simple world containing a single visual cue, we show how the generated short-term memory can support both innate and learned steering behaviour. In addition, we show how this architecture is consistent with the observed effects of unilateral MB lesions in ants that cause a reversion to innate behaviour. We suggest the formation of a directional memory in the CX can be interpreted as transforming rewarding (positive or negative) sensory signals into a mapping of the environment that describes the geometrical attractiveness (or repulsion). We discuss how this scheme might represent an ideal way to combine multisensory information gathered during the exploration of an environment and support optimized cue integration.1Author summaryIn this paper, we modeled the neural pathway allowing insects to perform landmark guided behaviours using their internal compass. First, we observed the intrinsic property of the connectome, extracted from drosophila online database, between the internal compass neurons and the steering neurons to support an oriented behaviour towards a single landmark. Then, we proposed and evaluated an adaptation of the bees path integration neural circuit, to sustain flexible landmark guidance behaviours such as attraction or menotaxis. We showed the model ability to form a memory during the exploration of the local environment to support both innate or learned navigation behaviour using a single landmark in the environment. In addtion, we demonstrated the transformation of a simple goodness/badness signal, from innate or long-term memory pathways, into an oriented steering signal that could be applied to other sensory pathways. Furthermore, by reproducing lesion experiments in the mushroom bodies of wood ants we highlight the consistency of the model with biological observation. We then discuss the different emergent properties and the potential outcome that this local, and operant, memory supports.
Optical Tissue Clearing Enables Rapid, Precise and Comprehensive Assessment of Three-Dimensional Morphology in Experimental Nerve Regeneration Research
Authors: Daeschler Simeon C. , Zhang Jennifer , Gordon Tessa , Borschel Gregory H. 
Published: January 2021

AbstractMorphological analyses are key outcome assessments for nerve regeneration studies but are historically limited to tissue sections. Novel optical tissue clearing techniques enabling three-dimensional imaging of entire organs at a subcellular resolution have revolutionized morphological studies of the brain. To extend their applicability to experimental nerve repair studies we adapted these techniques to nerves and their motor and sensory targets in rats. The solvent-based protocols rendered harvested peripheral nerves and their target organs transparent within 24 h while preserving tissue architecture and fluorescence. Optical clearing is compatible with conventional laboratory techniques, including retrograde labelling studies, and computational image segmentation, providing fast and precise cell quantitation. Further, optically cleared organs enable three-dimensional morphometry at an unprecedented scale including dermatome-wide innervation studies, tracing of intramuscular nerve branches and mapping of neurovascular networks. Given their wide-ranging applicability, rapid processing times and low costs, tissue clearing techniques are likely to be a key technology for next-generation nerve repair studies.
Amplicon sequencing of variable 16S rRNA and ITS2 regions reveal honeybee susceptibility to diseases resulted of their dietary preferences under anthropogenic landforms
Authors: Ptaszyńska Aneta A. , Latoch Przemysław , Hurd Paul J. , Polaszek Andrew , Michalska-Madej Joanna , Grochowalski Łukasz , Strapagiel Dominik , Gnat Sebastian , Załuski Daniel , Gancarz Marek , Rusinek Robert , Krutmuang Patcharin , Martín Hernández Raquel , Pascual Mariano Higes , Starosta Agata L. 
Published: January 2021

AbstractEuropeanApis melliferaand AsianApis ceranahoneybees, are essential crop pollinators. Microbiome studies can provide complex information on health and fitness of these insects in relation to environmental changes, and plant availability. Amplicon sequencing of variable regions of 16S rRNA and internally transcribed spacers (ITSs) allow identification of the metabiome. These methods provide a tool for monitoring otherwise uncultured microbes isolated from the gut of the honeybees. They also help monitor the composition of the gut fungi and, intriguingly, pollens collected by the insect. Here, we present data from amplicon sequencing of the 16S rRNA and ITS2 regions from honeybees collected at various time points from anthropogenic landforms as urban areas in Poland, UK, Spain, Greece, and Thailand. We have analysed microbial composition of honeybee intestine as well as fungi and pollens. We conclude that differences between samples were mainly influenced by the bacteria, plant pollens and fungi, respectively. Moreover, honeybees feeding on a honeydew diet, mainly based on sugars, were more prone to fungal pathogens (Nosema ceranae) and neogregarines. Finally, the period when honeybees switch to the winter generation (longer-lived forager honeybees) is the most sensitive to diet perturbations and hence pathogens attack, for the whole beekeeping season. It is possible that evolutionary adaptation of bees fails to benefit them in the modern anthropomorphised environment.
TRIPLE-NEGATIVE BREAST CANCER CELLS RECRUIT NEUTROPHILS BY SECRETING TGF-β AND CXCR2 LIGANDS
Authors: SenGupta Shuvasree , Hein Lauren E. , Xu Yang , Zhang Jason , Konwerski Jamie , Li Ye , Johnson Craig , Cai Dawen , Smith Janet , Parent Carole A. 
Published: January 2021

AbstractTumor associated neutrophils (TANs) are frequently detected in triple-negative breast cancer (TNBC). Recent studies also reveal the importance of neutrophils in promoting tumor progression and metastasis during breast cancer. However, the mechanisms regulating neutrophil trafficking to breast tumors are less clear. We sought to determine whether neutrophil trafficking to breast tumors is determined directly by the malignant potential of cancer cells. We found that tumor conditioned media (TCM) harvested from highly aggressive, metastatic TNBC cells induced a polarized morphology and robust neutrophil migration, while TCM derived from poorly aggressive estrogen receptor positive (ER+) breast cancer cells had no activity. In a three-dimensional (3D) type-I collagen matrix, neutrophils migrated toward TCM from aggressive breast cancer cells with increased velocity and directionality. Moreover, in a neutrophil-tumor spheroid co-culture system, neutrophils migrated with increased directionality towards spheroids generated from TNBC cells compared to ER+ cells. Based on these findings, we next sought to characterize the active factors secreted by TNBC cell lines. We found that TCM-induced neutrophil migration is dependent on tumor-derived chemokines, and screening TCM elution fractions based on their ability to induce polarized neutrophil morphology revealed the molecular weight of the active factors to be around 12 kDa. TCM from TNBC cell lines contained copious amounts of GRO (CXCL1/2/3) chemokines and TGF-β cytokines compared to ER+ cell-derived TCM. TCM activity was inhibited by simultaneously blocking receptors specific to GRO chemokines and TGF-β, while the activity remained intact in the presence of either single receptor inhibitor. Together, our findings establish a direct link between the malignant potential of breast cancer cells and their ability to induce neutrophil migration. Our study also uncovers a novel coordinated function of TGF-β and GRO chemokines responsible for guiding neutrophil trafficking to the breast tumor.
A novel allele in theArabidopsis thalianaMACPF protein CAD1 results in deregulated immune signaling
Authors: Holmes Danalyn R. , Bredow Melissa , Thor Kathrin , Pascetta Sydney A. , Sementchoukova Irina , Siegel Kristen R. , Zipfel Cyril , Monaghan Jacqueline 
Published: January 2021

AbstractImmune recognition in plants is governed by two major classes of receptors: pattern recognition receptors (PRRs) and nucleotide-binding leucine-rich repeat receptors (NLRs). Located at the cell surface, PRRs bind extracellular ligands originating from microbes (indicative of ‘non-self’) or damaged plant cells (indicative of ‘infected-self’), and trigger signaling cascades to protect against infection. Located intracellularly, NLRs sense pathogen-induced physiological changes and trigger localized cell death and systemic resistance. Immune responses are under tight regulation in order to maintain homeostasis and promote plant health. In a forward-genetic screen to identify regulators of PRR-mediated immune signaling, we identified a novel allele of the membrane-attack complex and perforin (MACPF)-motif containing protein CONSTITUTIVE ACTIVE DEFENSE 1 (CAD1) resulting from a missense mutation in a conserved N-terminal cysteine. We show thatcad1-5mutants display deregulated immune signaling and symptoms of autoimmunity dependent on the lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), suggesting that CAD1 integrity is monitored by the plant immune system. We further demonstrate that CAD1 localizes to both the cytosol and plasma membrane using confocal microscopy and subcellular fractionation. Our results offer new insights into immune homeostasis and provide tools to further decipher the intriguing role of MACPF proteins in plants.
Methylation of histone H3 lysine 4 is required for maintenance of beta cell function in adult mice
Authors: Vanderkruk Ben , Maeshima Nina , Pasula Daniel J. , An Meilin , McDonald Cassandra L. , Lynn Francis C. , Luciani Dan S. , Hoffman Brad G. 
Published: January 2021

AbstractPancreatic β-cells control glucose homeostasis via regulated production and secretion of insulin. This function arises from a highly specialized gene expression program which is established during development and then sustained, with limited flexibility, in terminally differentiated β-cells. Dysregulation of this program is seen in type 2 diabetes (T2D) but mechanisms that preserve gene expression or underlie its dysregulation in mature β-cells are not well resolved. Here we show that trithorax group-dependent histone H3 lysine 4 trimethylation (H3K4me3) maintains expression of genes important for insulin biosynthesis and glucose-responsiveness in β-cells. Transcriptional changes in H3K4me3-deficient β-cells lead to severe hyperglycemia in adult mice. We show that H3K4me3 deficiency leads to a less active and more repressed epigenome profile, which locally correlates with gene expression deficits but does not globally reduce gene expression. Instead, developmentally regulated genes and genes in weakly active or suppressed states particularly rely on H3K4 methylation. We then show that H3K4me3 is re-organized in diabeticLeprdb/dbmouse islets in favour of weakly active and disallowed genes at the expense of terminal β-cell markers with broad H3K4me3 peaks. Our results point to key roles of H3K4me3 in maintaining mature β-cell function and establishing a dysfunctional transcriptome in diabetic islets.