bluuebunny/crossref_metadata_2025_split huggingface dataset:
From cartoons to quantitative models in Golgi transport
Authors: Quiros D. Nicolas , Mayorga Luis S. 
Published: May 2020

ABSTRACTCell biology is evolving to become a more formal and quantitative science. In particular, several mathematical models have been proposed to address Golgi self-organization and protein and lipid transport. However, most scientific articles about the Golgi apparatus are still using static cartoons to represent their findings that miss the dynamism of this organelle. In this report, we show that schematic drawings of Golgi trafficking can be easily translated into an Agent-Based Model (ABM) using the Repast platform. The simulations generate an active interplay among cisternae and vesicles rendering quantitative predictions about Golgi stability and transport of soluble and membrane-associated cargoes. The models can incorporate complex networks of molecular interactions and chemical reactions by association with COPASI, a software that handles Ordinary Differential Equations. The strategy described provides a simple, flexible, and multiscale support to analyze Golgi transport. The simulations can be used to address issues directly linked to the mechanism of transport or as a way to incorporate the complexity of trafficking to other cellular processes that occur in dynamic organelles.
PhylSim: A New Phylogenetic Tool for Modeling Trait Evolution and Speciation
Authors: Spivakovsky P. , Lio P. , Clark M. S. 
Published: May 2020

ABSTRACTWe present a new software tool in R, the PhylSim package, which allows the user to simulate trait evolution on a phylogeny, while varying the speciation rate and evolutionary model over the course of the simulation. In particular, the user can specify any number of regimes, with a different speciation rate for each regime, or set the speciation rate to vary when the value of a trait exceeds a certain threshold. The evolutionary model can also be varied as many times as necessary over the course of the simulation, to account for traits tending toward different optima at different periods in evolutionary history. We illustrate the use of the package with an example, a simulation of the adaptive radiation of Antarctic notothenioids in the Southern Ocean.
Disease responses of hexaploid spring wheat (Triticum aestivum) culms exhibiting premature senescence (dead heads) associated withFusarium pseudograminearumcrown rot
Authors: Knight N. L. , Macdonald B. , Percy C. , Sutherland M. W. 
Published: May 2020

AbstractHexaploid spring wheat (Triticum aestivum) may exhibit significant crown rot disease responses to infection byFusarium pseudograminearum, with a range of susceptibility levels available in commercial cultivars. Dry conditions during grain-fill may lead to the expression of prematurely senescing culms, which typically fail to set grain. Assessment of hexaploid spring wheat plants exhibiting both non-senescent and prematurely senescent culms was performed using visual discolouration,Fusarium pseudograminearumbiomass, vascular colonisation and quantification of wheat DNA in culm sections sampled at three different heights above the crown and at the peduncle. A comparison of these parameters at four time points from milk development, when senescent culms are first observed, to maturity was conducted. Samples from six commercial cultivars were collected in 2014 from Narrabri and Tamworth, New South Wales and Wellcamp, Queensland. Prematurely senescent culms exhibited greater visual discolouration,Fusarium pseudograminearumbiomass and vascular colonisation than non-senescent culms in each cultivar. Colonisation of xylem and phloem tissue was extensive in the basal portions of prematurely senescent culms (36 to 99%), and suggests significant impacts on water and nutrient movement during crown rot disease. Maturation coincided with significant changes inFusarium pseudograminearumbiomass and vascular colonisation. Wheat DNA content varied among cultivars, culm conditions, culm sections and sampling times. The variation in the severity of disease states between culms of the same plant suggests that the timing of initiation of infection in individual culms may vary.
Phylogenetic origin and sequence features of MreB from the wall-less swimming bacteria Spiroplasma
Authors: Takahashi Daichi , Fujiwara Ikuko , Miyata Makoto 
Published: May 2020

ABSTRACTSpiroplasma are wall-less bacteria which belong to the phylum Tenericutes that evolved from Firmicutes including Bacillus subtilis. Spiroplasma swim by a mechanism unrelated to widespread bacterial motilities, such as flagellar motility, and caused by helicity switching with kinks traveling along the helical cell body. The swimming force is likely generated by five classes of bacterial actin homolog MreBs (SMreBs 1-5) involved in the helical bone structure. We analyzed sequences of SMreBs to clarify their phylogeny and sequence features. The maximum likelihood method based on around 5,000 MreB sequences showed that the phylogenetic tree was divided into several radiations. SMreBs formed a clade adjacent to the radiation of MreBH, an MreB isoform of Firmicutes. Sequence comparisons of SMreBs and Bacillus MreBs were also performed to clarify the features of SMreB. Catalytic glutamic acid and threonine were substituted to aspartic acid and lysine, respectively, in SMreB3. In SMreBs 2 and 4, amino acids involved in inter- and intra-protofilament interactions were significantly different from those in Bacillus MreBs. A membrane-binding region was not identified in most SMreBs 1 and 4 unlike many walled-bacterial MreBs. SMreB5 had a significantly longer C-terminal region than the other MreBs, which possibly forms a protein-protein interaction. These features may support the functions responsible for the unique mechanism of Spiroplasma swimming.
Loss of the conserved Alveolate kinase MAPK2 decouplesToxoplasmacell growth from the cell cycle
Authors: Hu Xiaoyu , O’Shaughnessy William J. , Beraki Tsebaot G. , Reese Michael L. 
Published: May 2020

AbstractMitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The Apicomplexan parasiteToxoplasma gondiiexpresses three MAPKs. Two of these, ERK7 and MAPKL1, have been respectively implicated in the regulation of conoid biogenesis and centrosome duplication. The third kinase, MAPK2, is specific to and conserved throughout Alveolata, though its function is unknown. We used the auxin-inducible degron system to determine phenotypes associated with MAPK2 loss-of-function inToxoplasma. We observed that parasites lacking MAPK2 failed to duplicate their centrosomes and therefore did not initiate daughter-cell budding, which ultimately led to parasite death. MAPKL2-deficient parasites initiated, but did not complete DNA replication, and arrested prior to mitosis. Surprisingly, the parasites continued to grow in size and to replicate their Golgi, mitochondria, and apicoplasts. We found that the failure in centrosome duplication is distinct from the phenotype caused by depletion of MAPKL1. As we did not observe MAPK2 localization at the centrosome at any point in the cell cycle, our data suggest MAPK2 regulates a process at a distal site that is required for completion of centrosome duplication and initiation of parasite mitosis.ImportanceToxoplasma gondiiis a ubiquitous intracellular protozoan parasite that can cause severe and fatal disease in immunocompromised patients and the developing fetus. Rapid parasite replication is critical for establishing a productive infection. Here, we demonstrate that aToxoplasmaprotein kinase called MAPK2 is conserved throughout Alveolata and essential for parasite replication. We found that parasites lacking MAPK2 protein were defective in the initiation of daughter cell budding and were rendered inviable. Specifically, TgMAPK2 appears to be required for centrosome replication at the basal end of the nucleus, and its loss causes arrest early in parasite division. MAPK2 is unique to Alveolata and not found in metazoa, and likely is a critical component of an essential parasite-specific signaling network.
Functional Connectivity of the Precuneus Reflects Effectiveness of Visual Restitution Training in Chronic Hemianopia
Authors: Halbertsma Hinke N. , Elshout Joris A. , Bergsma Douwe P. , Norris David G. , Cornelissen Frans W. , van den Berg Albert V. , Haak Koen V. 
Published: May 2020

AbstractVisual field defects in chronic hemianopia can improve through visual restitution training, yet not all patients benefit equally from this long and exhaustive process. Here, we asked if resting-state functional connectivity prior to visual restitution could predict training success. In two training sessions of eight weeks each, 20 patients with chronic hemianopia performed a visual discrimination task by directing spatial attention towards stimuli presented in either hemifield, while suppressing eye movements. We examined two effects: a sensitivity change in the attended (trained) minus the unattended (control) hemifield (i.e., a training-specific improvement), and an overall improvement (i.e., a total change in sensitivity after both sessions). We then identified five visual resting-state networks and evaluated their functional connectivity in relation to both training effects. We found that the functional connectivity strength between the anterior Precuneus and the Occipital Pole Network was positively related to the attention modulated (i.e., training-specific) improvement. No such relationship was found for the overall improvement or for the other visual networks of interest. Our finding suggests that the anterior Precuneus plays a role in training-induced visual field improvements. The resting-state functional connectivity between the anterior Precuneus and the Occipital Pole Network may thus serve as an imaging-based biomarker that quantifies a patient’s potential capacity to direct spatial attention. This may help to identify hemianopia patients that are most likely to benefit from visual restitution training.
NanoCLUST: a species-level analysis of 16S rRNA nanopore sequencing data
Authors: Rodríguez-Pérez Héctor , Ciuffreda Laura , Flores Carlos 
Published: May 2020

AbstractSummaryNanoCLUST is an analysis pipeline for classification of amplicon-based full-length 16S rRNA nanopore reads. It is characterized by an unsupervised read clustering step, based on Uniform Manifold Approximation and Projection (UMAP), followed by the construction of a polished read and subsequent Blast classification. Here we demonstrate that NanoCLUST performs better than other state-of-the-art software in the characterization of two commercial mock communities, enabling accurate bacterial identification and abundance profile estimation at species level resolution.Availability and implementationSource code, test data and documentation of NanoCLUST is freely available athttps://github.com/genomicsITER/NanoCLUSTunder MIT License.Contactcflores@ull.edu.es
Probing the ionotropic activity of the orphan glutamate delta 2 receptor with genetically-engineered photopharmacology
Authors: Lemoine Damien , Mondoloni Sarah , Tange Jérôme , Lambolez Bertrand , Faure Philippe , Taly Antoine , Tricoire Ludovic , Mourot Alexandre 
Published: May 2020

AbstractGlutamate delta (GluD) receptors belong to the ionotropic glutamate receptor family, yet whether they actually form functional and physiologically-relevant ion channels in neurons remains a debated question. Here we used a chemo-genetic approach to engineer specific and photo-reversible pharmacology in the orphan GluD2 receptor. We incorporated a cysteine mutation in the cavity located above the putative ion channel pore, for site-specific conjugation with a photoswitchable ligand. We first showed that, in the constitutively-open GluD2 Lurcher mutant, current could be rapidly and reversibly decreased with light. We then transposed the cysteine mutation to the native receptor, to demonstrate with absolute pharmacological specificity that metabotropic glutamate receptor signaling opens the GluD2 ion channel in heterologous expression system. Our results assess the functional relevance of GluD2 ion channel and introduce an optogenetic tool that will provide a novel and powerful means for probing GluD2 ionotropic contribution to neuronal physiology.
Cingulin unfolds ZO-1 and organizes myosin-2B and γ-actin to mechanoregulate apical and tight junction membranes
Authors: Vasileva Ekaterina , Rouaud Florian , Spadaro Domenica , Huang Wenmao , Colom Adai , Flinois Arielle , Shah Jimit , Dugina Vera , Chaponnier Christine , Sluysmans Sophie , Méan Isabelle , Jond Lionel , Roux Aurélien , Yan Jie , Citi Sandra 
Published: May 2020

SUMMARYHow junctional proteins regulate the mechanics of the plasma membrane and how actin and myosin isoforms are selectively localized at epithelial cell-cell junctions is poorly understood. Here we show by atomic force indentation microscopy, immunofluorescence analysis and FLIM membrane tension imaging that the tight junction (TJ) protein cingulin maintains apical surface stiffness and TJ membrane tortuosity and down-regulates apico-lateral membrane tension in MDCK cells. KO of cingulin in MDCK, mCCD and Eph4 cells results in a decrease in the juxta-membrane accumulation of labeling for cytoplasmic myosin-2B (NM2B), γ-actin, phalloidin and ARHGEF18, but no detectable effect on myosin-2A (NM2A) and β-actin. Loss of paracingulin leads to weaker mechanical phenotypes in MDCK cells, correlating with no detectable effect on the junctional accumulation of myosins and actins. Cingulin and paracingulin form biomolecular condensates, bind to the ZU5 domain of ZO-1, and are recruited as clients into ZO-1 condensates in a ZU5-dependent manner. Cingulin binding to ZO-1 promotes the unfolding of ZO-1, as determined by interaction with DbpA in cells lacking ZO-2 and in vitro. Cingulin promotes the accumulation of a pool of ZO-1 at the TJ and is required in a ZU5-dependent manner for the recruitment of phalloidin-labelled actin filaments into ZO-1 condensates, suggesting that ZU5-cingulin interaction promotes ZO-1 interaction with actin filaments. Our results indicate that cingulin tethers the juxta-membrane and apical branched γ-actin-NM2B network to TJ to modulate ZO-1 conformation and the TJ assembly of a pool of ZO-1 and fine-tune the distribution of forces to apical and TJ membranes.
Need for speed: Examining protein behaviour during cryoEM grid preparation at different timescales
Authors: Klebl David P. , Gravett Molly S. C. , Kontziampasis Dimitrios , Wright David J. , Bon Robin S. , Monteiro Diana , Trebbin Martin , Sobott Frank , White Howard D. , Darrow Michele , Thompson Rebecca F. , Muench Stephen P. 
Published: May 2020

AbstractA host of new technologies are under development to improve the quality and reproducibility of cryoEM grid preparation. Here we have systematically investigated the preparation of three macromolecular complexes using three different vitrification devices (Vitrobot™, chameleon and a time-resolved cryoEM device) on various timescales, including grids made within 6 ms, (the fastest reported to date), to interrogate particle behaviour at the air-water interface for different timepoints. Results demonstrate that different macromolecular complexes can respond to the thin film environment formed during cryoEM sample preparation in highly variable ways, shedding light on why cryoEM sample preparation can be difficult to optimise. We demonstrate that reducing time between sample application and vitrification is just one tool to improve cryoEM grid quality, but that it is unlikely to be a generic ‘silver bullet’ for improving the quality of every cryoEM sample preparation.
Conservation and host-specific expression of non-tandemly repeated heterogenous ribosome RNA gene in arbuscular mycorrhizal fungi
Authors: Maeda Taro , Kobayashi Yuuki , Nakagawa Tomomi , Ezawa Tatsuhiro , Yamaguchi Katsushi , Bino Takahiro , Nishimoto Yuki , Shigenobu Shuji , Kawaguchi Masayoshi 
Published: May 2020

AbstractThe ribosomal RNA-encoding gene (rDNA) has a characteristic genomic nature: tens to thousands of copies in a genome, tandemly repeated structure, and intragenomic sequence homogeneity. These features contribute to ribosome productivity via physiological and evolutionary processes. We reported previously the exceptional absence of these features in the model arbuscular mycorrhizal (AM) fungusRhizophagus irregularis.Here we examine the phylogenetic distribution of the exceptional rDNA features in the genusRhizophagusvia improving the genome sequence ofR. clarus.Cross-species comparison indicated similarity of their rDNAs not only in the genomic features but also in the distribution of intragenomic polymorphic sites on the paralogs. Ribosomal RNA comprises multiple domains with different functions. The twoRhizophagusspecies commonly exhibited a variation enrichment site, ES27L, which is related to translational fidelity and antibiotic sensitivity. Variation enrichment on ES27L has not been observed in other organisms lacking the three rDNA features such as malaria parasites andCyanidioschyzon merolae.Expression profiling of rDNAs inR. irregularisrevealed that rDNA paralogs are expressed differently in association with host plant species. Our results suggest a broad distribution of the disarranged rDNA across AM fungi and its involvement in the successful association with the broad range of host species.
Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis
Authors: O’Neill John S. , Hoyle Nathaniel P. , Robertson J. Brian , Edgar Rachel S. , Beale Andrew D. , Peak-Chew Sew Y. , Day Jason , Costa Ana S. H. , Frezza Christian , Causton Helen C. 
Published: May 2020

AbstractEvery aspect of yeast physiology is subject to robust temporal regulation, this becomes apparent under nutrient-limiting conditions1-6and results in biological oscillations whose function and mechanism is poorly resolved7. These yeast metabolic oscillations share features with circadian rhythms and typically interact with, but are independent of, the cell division cycle. Here we show that these cellular rhythms act to minimise energy expenditure by temporally restricting protein synthesis until sufficient cellular resources are present, whilst maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells initially ‘sequester and store’ metabolic resources such as carbohydrates, amino acids, K+and other osmolytes; which accumulateviaincreased synthesis, transport, autophagy and biomolecular condensation that is stimulated by low glucose and cytosolic acidification. Replete stores trigger increased H+export to elevate cytosolic pH, thereby stimulating TORC1 and liberating proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates a burst of increased protein synthesis, the liquidation of storage carbohydrates to sustain higher respiration rates and increased ATP turnover, and the export of osmolytes to maintain osmotic potential. As the duration of translational bursting is determined by cell-intrinsic factors, the period of oscillation is determined by the time cells take to store sufficient resources to license passage through the pH-dependent metabolic checkpoint that initiates translational bursting. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints have selected for temporal organisation that promotes oscillatory behaviour.
BAP31 regulated polarization of macrophages through C/EBP β in cutaneous wound healing
Authors: Yuan Qing , Zhao Bo , Cao Yu-hua , Yan Jia-cheng , Sun Li-jun , Liu Xia , Xu Yang , Wang Xiao-yu , Wang Bing 
Published: May 2020

AbstractThe functions carried out by macrophages are essential in the processes of repairing skin injury. However, the mechanism of the M2 macrophage and its role in cutaneous wound healing remain elusive. B cell receptor associated protein 31 (BAP31) plays an important role in the immune system, and its function in connection with macrophages has yet to be determined. The present study demonstrates that the process of cutaneous wound healing slowed down in bone marrow-specific BAP31 knock down Lyz2-cre-BAP31flox/floxmice. In addition, further studies show that various kinds of macrophage M2 polarization related factors were regulated by BAP31. Among these molecules C/EBP β was significantly affected. However, IL-4 but not IFN-γ, is able to recover the expression levels of C/EBP β and its downstream transcript factors induced by BAP31. Then, we demonstrated that BAP31 regulated macrophage M2 polarization by negative regulation of IL-4Rα and positive influence on Egr-2 to affect C/EBP β. Our findings reveal a novel mechanism of BAP31 in regulating M2 macrophage, and provide novel targets for the prevention and treatment of chronic wounds.
When effort matters: Expectations of reward and efficacy guide cognitive control allocation
Authors: Frömer R. , Lin H. , Dean Wolf C. K. , Inzlicht M. , Shenhav A. 
Published: May 2020

AbstractThe amount of mental effort we invest in a task is influenced by the reward we can expect if we perform that task well. However, some of the rewards that have the greatest potential for driving these efforts (e.g., jobs, grants) are partly determined by factors beyond one’s control. In such cases, effort has more limitedefficacyfor obtaining rewards. We have proposed that people integrate information about the expected reward and efficacy for effort to determine the expected value of control, and then adjust their control allocation (i.e. mental effort) accordingly. Here we test this theory’s key behavioral and neural predictions. We show that participants invest more control when this control is more rewarding and more efficacious, and that these incentive components separately modulate EEG signatures of incentive evaluation and proactive control allocation. Our findings support the prediction that people combine worth and worthwhileness to determine how much effort to invest.
RIPK2 Stabilizes c-Myc and is an Actionable Target for Inhibiting Prostate Cancer Metastasis
Authors: Yan Yiwu , Zhou Bo , Qian Chen , Vasquez Alex , Chatterjee Avradip , Yuan Xiaopu , Posadas Edwin , Kyprianou Natasha , Knudsen Beatrice S. , Murali Ramachandran , Gertych Arkadiusz , You Sungyong , Freeman Michael R. , Yang Wei 
Published: May 2020

AbstractDespite advances in diagnosis and treatment, metastatic prostate cancer remains incurable and is associated with high mortality rates. Thus, novel actionable drug targets are urgently needed for therapeutic interventions in advanced prostate cancer. Here we report receptor-interacting protein kinase 2 (RIPK2) as an actionable drug target for suppressing prostate cancer metastasis. RIPK2 is frequently amplified in lethal prostate cancers and its overexpression is associated with disease progression and aggressiveness. Genetic and pharmacological inhibition of RIPK2 significantly suppressed prostate cancer progressionin vitroand metastasisin vivo.Multi-level proteomic analysis revealed that RIPK2 strongly regulates c-Myc protein stability and activity, largely by activating the MKK7/JNK/c-Myc phosphorylation pathway—a novel, non-canonical RIPK2 signaling pathway. Targeting RIPK2 inhibits this phosphorylation pathway, and thus promotes the degradation of c-Myc—a potent oncoprotein for which no drugs have been approved for clinical use yet. These results support targeting RIPK2 for personalized therapy in prostate cancer patients towards improving survival.