bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two distinct phases of chloroplast biogenesis during de-etiolation in Arabidopsis thaliana
Authors: Pipitone Rosa , Eicke Simona , Pfister Barbara , Glauser Gaetan , Falconet Denis , Uwizeye Clarisse , Pralon Thibaut , Zeeman Samuel , Kessler Felix , Demarsy Emilie 
Published: September 2020

AbstractLight triggers chloroplast differentiation whereby the etioplast transforms into a photosynthesizing chloroplast and the thylakoid rapidly emerges. However, the sequence of events during chloroplast differentiation remains poorly understood. Using Serial Block Face Scanning Electron Microscopy (SBF-SEM), we generated a series of chloroplast 3D reconstructions during differentiation, revealing chloroplast number and volume and the extent of envelope and thylakoid membrane surfaces. Furthermore, we used quantitative lipid and whole proteome data to complement the (ultra)structural data, providing a time-resolved, multi-dimensional description of chloroplast differentiation. This showed two distinct phases of chloroplast biogenesis: an initial photosynthesis-enabling ‘Structure Establishment Phase’ followed by a ‘Chloroplast Proliferation Phase’ during cell expansion. Moreover, these data detail thylakoid membrane expansion during de-etiolation at the seedling level and the relative contribution and differential regulation of proteins and lipids at each developmental stage. Altogether, we establish a roadmap for chloroplast differentiation, a critical process for plant photoautotrophic growth and survival.
DIAFree enables untargeted open-search identification for Data-Independent Acquisition data
Authors: Xu Iris 
Published: September 2020

AbstractAs a reliable and high-throughput proteomics strategy, data-independent acquisition (DIA) has shown great potential for protein analysis. However, DIA also imposes stress on the data processing algorithm by generating complex multiplexed spectra. Traditionally, DIA data is processed using spectral libraries refined from experiment histories, which requires stable experiment conditions and additional runs. Furthermore, scientists still need to use library-free tools to generate spectral libraries from additional runs. To lessen those burdens, here we present DIAFree(https://github.com/xuesu/DIAFree), a library-free, tag-index-based software suite that enables both restrict search and open search on DIA data using the information of MS1 scans in a precursor-centric and spectrum-centric style. We validate the quality of detection by publicly available data. We further evaluate the quality of spectral libraries produced by DIAFree.
On-rate modulation of cadherin interactions by chemical fragments
Authors: Senoo Akinobu , Ito Sho , Nagatoishi Satoru , Saito Yutaro , Ueno Go , Yoshida Kouhei , Tashima Takumi , Kudo Shota , Sando Shinsuke , Tsumoto Kouhei 
Published: September 2020

AbstractMany cadherin family proteins are associated with diseases such as cancer. Since cell adhesion requires homodimerization of cadherin molecules, a small-molecule regulator of dimerization would have therapeutic potential. Herein, we describe identification of a P-cadherin-specific chemical fragment that inhibits P-cadherin-mediated cell adhesion. Although the identified molecule is a fragment compound, it binds to a cavity of P-cadherin that has not previously been targeted, indirectly prevents formation of hydrogen bonds necessary for formation of an intermediate called the X dimer and thus modulates the on-rate of X dimerization. Our findings will impact on a strategy for kinetic regulation of protein-protein interactions and stepwise assembly of protein complexes using small molecules.
Effect of time delay on the synchronization of excitatory-inhibitory neural networks
Authors: Ryu Hwayeon , Campbell Sue Ann 
Published: September 2020

AbstractWe study a model for a network of synaptically coupled, excitable neurons to identify the role of coupling delays in generating different network behaviors. The network consists of two distinct populations, each of which contains one excitatory-inhibitory neuron pair. The two pairs are coupled via delayed synaptic coupling between the excitatory neurons, while each inhibitory neuron is connected only to the corresponding excitatory neuron in the same population. We show that multiple equilibria can exist depending on the strength of the excitatory coupling between the populations. We conduct linear stability analysis of the equilibria and derive necessary conditions for delay-induced Hopf bifurcation. We show that these can induce two qualitatively different phase-locked behaviors, with the type of behavior determined by the sizes of the coupling delays. Numerical bifurcation analysis and simulations supplement and confirm our analytical results. Our work shows that the resting equilibrium point is unaffected by the coupling, thus the network exhibits bistability between a rest state and an oscillatory state. This may help understand how rhythms spontaneously arise neuronal networks.
Ecological specialization promotes diversity and diversification in the East Mediterranean genusRicotia(Brassicaceae)
Authors: Özüdoğru Barış , Karacaoğlu Çağaşan , Akaydın Galip , Erik Sadık , Mummenhoff Klaus , Sağlam İsmail Kudret 
Published: September 2020

AbstractDespite its amazing biodiversity, the Eastern Mediterranean remains a highly understudied region especially when compared to the Western Mediterranean. Scarcity of such studies restrict our understanding of the processes shaping diversity across the entire Mediterranean. To this end we used a combination of molecular markers and presence/absence data from all species of the Eastern Mediterrranean genusRicotiacollected across its full geographic range to determine historical, ecological and evolutionary factors responsible for lineage-specific diversification in this genus. Network analysis based on nuclear ribosomal and chloroplast DNA revealed high genetic structure within all lineages and phylogenetic reconstructions based on the multispecies coalescent showed that within lineage diversification corresponded to the onset of the Mediterranean climate. Reconstruction of ancestral histories indicate the genus originated within Anatolia and slowly spread across the Eastern Mediterranean and Levant using the Taurus mountains. Ecological niche models based on climatic and environmental variables suggest local populations did not go through any major distributional shifts and have persisted in present day habitats since the LGM. Furthermore, niche differentiation tests revealed significant niche differences between closely related species and showed the main variables predicting species limits to be different for each species. Our results give crucial information on the patterns and processes shaping diversity in the Eastern Mediterranean and show the main factor promoting diversification to be local environmental dynamics and ecological specialization and not large scale latitudinal movements as often reported for southern Europe. By determining regional and global patterns of diversification in an eastern Mediterranean genus we further our understanding of the major trends influencing plant diversity in the Mediterranean basin as a whole.
Population Structure Discovery in Meta-Analyzed Microbial Communities and Inflammatory Bowel Disease
Authors: Ma Siyuan , Shungin Dmitry , Mallick Himel , Schirmer Melanie , Nguyen Long H. , Kolde Raivo , Franzosa Eric , Vlamakis Hera , Xavier Ramnik , Huttenhower Curtis 
Published: September 2020

AbstractMicrobial community studies in general, and of the human microbiome in inflammatory bowel disease (IBD) in particular, have now achieved a scale at which it is practical to associate features of the microbiome with environmental exposures and health outcomes across multiple large-scale populations. This permits the development of rigorous meta-analysis methods, of particular importance in IBD as a means by which the heterogeneity of disease etiology and treatment response might be explained. We have thus developed MMUPHin (Meta-analysis Methods with a Uniform Pipeline for Heterogeneity in microbiome studies) for joint normalization, meta-analysis, and population structure discovery using microbial community taxonomic and functional profiles. Applying this method to ten IBD cohorts (5,151 total samples), we identified a single consistent axis of microbial associations among studies, including newly associated taxa such asAcinetobacterandTuricibacterdetected due to the sensitivity of meta-analysis. Linear random effects models further revealed associations with medications, disease location, and interaction effects consistent within and between studies. Finally, multiple unsupervised clustering metrics and dissimilarity measures agreed on a lack of discrete microbiome “types” in the IBD gut microbiome. These results thus provide a benchmark for consistent characterization of the IBD gut microbiome and a general framework applicable to meta-analysis of any microbial community types.
Database and deep learning toolbox for noise-optimized, generalized spike inference from calcium imaging
Authors: Rupprecht Peter , Carta Stefano , Hoffmann Adrian , Echizen Mayumi , Blot Antonin , Kwan Alex C. , Dan Yang , Hofer Sonja B. , Kitamura Kazuo , Helmchen Fritjof , Friedrich Rainer W. 
Published: September 2020

ABSTRACTCalcium imaging is a key method to record patterns of neuronal activity across populations of identified neurons. Inference of temporal patterns of action potentials (‘spikes’) from calcium signals is, however, challenging and often limited by the scarcity of ground truth data containing simultaneous measurements of action potentials and calcium signals. To overcome this problem, we compiled a large and diverse ground truth database from publicly available and newly performed recordings. This database covers various types of calcium indicators, cell types, and signal-to-noise ratios and comprises a total of >35 hours from 298 neurons. We then developed a novel algorithm for spike inference (CASCADE) that is based on supervised deep networks, takes advantage of the ground truth database, infers absolute spike rates, and outperforms existing model-based algorithms. To optimize performance for unseen imaging data, CASCADE retrains itself by resampling ground truth data to match the respective sampling rate and noise level. As a consequence, no parameters need to be adjusted by the user. To facilitate routine application of CASCADE we developed systematic performance assessments for unseen data, we openly release all resources, and we provide a user-friendly cloud-based implementation.
In silico Drosophila Patient ModelReveals Optimal Combinatorial Therapies for Colorectal Cancer
Authors: Gondal Mahnoor Naseer , Butt Rida Nasir , Shah Osama Shiraz , Nasir Zainab , Hussain Risham , Khawar Huma , Tariq Muhammad , Faisal Amir , Chaudhary Safee Ullah 
Published: September 2020

AbstractIn silicomodels of biomolecular regulation in cancer, annotated with patient-specific gene expression data can aid in the development of novel personalized cancer therapeutics strategies.Drosophila melanogasteris a well-established animal model that is increasingly being employed to evaluate preclinical personalized cancer therapies. Here, we report five Boolean network models of biomolecular regulation in cells lining theDrosophilamidgut epithelium and annotate them with patient-specific mutation data to develop anin silico Drosophila Patient Model(DPM). The network models were validated against cell-type-specific RNA-seq gene expression data from the FlyGut-seqdatabase and through three literature-based case studies on colorectal cancer. The results obtained from the study help elucidate cell fate evolution in colorectal tumorigenesis, validate cytotoxicity of nine FDA-approved cancer drugs, and devise optimal personalized drug treatment combinations. The proposed personalized therapeutics approach also helped identify synergistic combinations of chemotherapy (paclitaxel) with targeted therapies (pazopanib, or ruxolitinib) for treating colorectal cancer. In conclusion, this work provides a novel roadmap for decoding colorectal tumorigenesis and in the development of personalized cancer therapeutics through a DPM.
Activation of the Cpx-envelope stress response system promotes tolerance to antibacterials delivered by arginine-rich peptides and aminoglycosides inEscherichia coli
Authors: Frimodt-Møller Jakob , Koulouktsis Andreas , Charbon Godefroid , Otterlei Marit , Nielsen Peter E. , Løbner-Olesen Anders 
Published: September 2020

AbstractCell penetrating peptides (CPP) are increasingly used for cellular drug delivery in both pro- and eukaryotic cells, and oligoarginines have attracted special attention. However; their mechanism of action, particularly for prokaryotes is still unknown. Arginine-rich CPPs (R-CPP) efficiently delivers the antimicrobial peptide nucleic acid (PNA) into bacteria. Here, we show that resistance to an R-CPP PNA conjugate inEscherichia colirequires multiple genetic modifications and is specific to R-CPP and not to the PNA-part. An integral part of the resistance was the constitutively activated Cpx-envelope stress response system (cpx*), which decreased the cytoplasmic membrane potential and thereby indicates an indirectly energy dependent uptake mechanism. Interestingly,cpx* mutants also showed increased tolerance to aminoglycosides and R-CPP conjugated to a peptide targeting the DNA sliding clamp; i.e., similar uptake inE. colifor these antimicrobial compounds. We speculate that thecpx* phenotype could create an evolutionary opportunity to adapt and evolve in the presence of either compounds.Author summaryThe emergence of multidrug resistant bacteria is raising the need for new classes of antibiotics. Peptide nucleic acids (PNAs) may fill this requirement by their ability to block translation of essential mRNAs and hence inhibit growth. PNA needs conjugation to a delivery peptide (cell penetrating peptide; CPP) to enter the bacteria. Arginine-rich CPPs (CPPR) are receiving a lot of attention for use as delivery vessels. Here, we show, for the first time, CPPR-PNA resistance inEscherichia colidirected towards the delivery peptide. Consequently, resistance also applies to other antimicrobial compounds delivered by the same carrier. An integral part of CPPRresistance is due to a constitutive active Cpx-response system, which leads to a decreased electric potential (ΔΨ) across the inner membrane. The decreased ΔΨis a result of down-regulation of two aerobic respiratory operons, namely NADH:ubiquinone oxidoreductase complex I and cytochrome bo3ubiquinol oxidase. The decreased ΔΨalso led to increased tolerance to aminoglycosides. This shows that a (large) negative ΔΨis important for providing sufficient free energy for membrane translocation of both CPPRand that the inner membrane is the main barrier for entry of both arginine-rich delivery peptides and aminoglycosides.
Head-direction coding in the hippocampal formation of birds
Authors: Ben-Yishay Elhanan , Krivoruchko Ksenia , Ron Shaked , Ulanovsky Nachum , Derdikman Dori , Gutfreund Yoram 
Published: September 2020

AbstractBirds strongly rely on spatial memory and navigation. Therefore, it is of utmost interest to reveal how space is represented in the avian brain. Here we used tetrodes to record neurons from the hippocampal formation of Japanese quails – a ground-dwelling species – while the quails roamed a 1×1-meter arena (>2,100 neurons from 23 birds). Whereas spatially-modulated cells (place-cells, border-cells, etc.) were generally not encountered, the firing-rate of 12% of the neurons was unimodally and significantly modulated by the head-azimuth – i.e. these were head-direction cells (HD cells). Typically, HD cells were maximally active at one preferred-direction and minimally at the opposite null-direction, with preferred-directions spanning all 360°. The HD tuning was relatively broad (mean width ∼130°), independent of the animal’s position and speed, and was stable during the recording-session. Similarly to findings in rodents, the HD tuning usually rotated with the rotation of a salient visual cue in the arena. These findings support the existence of an allocentric head-direction representation in the quail hippocampal formation, and provide the first demonstration of head-direction cells in birds.
Pervasive compartment-specific regulation of gene expression during homeostatic synaptic scaling
Authors: Colameo David , Rajman Marek , Soutschek Michael , Bicker Silvia , von Ziegler Lukas , Bohacek Johannes , Germain Pierre-Luc , Dieterich Christoph , Schratt Gerhard 
Published: September 2020

AbstractSynaptic scaling is a form of homeostatic plasticity which allows neurons to adjust their action potential firing rate in response to chronic alterations in neural activity. Synaptic scaling requires profound changes in gene expression, but the relative contribution of local and cell-wide mechanisms is controversial. Here we performed a comprehensive multi-omics characterization of the somatic and process compartments of primary rat hippocampal neurons during synaptic scaling. Thereby, we uncovered both highly compartment-specific and correlated changes in the neuronal transcriptome and proteome. Whereas downregulation of crucial regulators of neuronal excitability occurred primarily in the somatic compartment, structural components of excitatory postsynapses were mostly downregulated in processes. Motif analysis further suggests an important role for trans-acting post-transcriptional regulators, including RNA-binding proteins and microRNAs, in the local regulation of the corresponding mRNAs. Altogether, our study indicates that compartmentalized gene expression changes are widespread in synaptic scaling and might co-exist with neuron-wide mechanisms to allow synaptic computation and homeostasis.
Selection favors adaptive plasticity in a long-term reciprocal transplant experiment
Authors: Anderson Jill , Jameel M. Inam , Geber Monica A. 
Published: September 2020

AbstractSpatial and temporal environmental variation can favor the evolution of adaptive phenotypic plasticity, such that genotypes alter their phenotypes in response to local conditions to maintain fitness across heterogeneous landscapes. When individuals show greater fitness in one habitat than another, asymmetric migration can restrict adaptive responses to selection in the lower quality environment. In these cases, selection is predicted to favor traits that enhance fitness in the higher-quality source habitat at the expense of fitness in the marginal habitat, resulting in specialization to the high-quality environment. Here, we test whether plasticity is adaptive in a system regulated by demographic source-sink dynamics.Vaccinium elliottii(Ericaceae) occurs in dry upland and flood-prone bottomland forests throughout the southeastern United States, and shows patterns consistent with source-sink dynamics. We conducted a multi-year field experiment to evaluate whether plasticity in foliar morphology is advantageous. Both across habitats and within the high-quality upland environment, selection favored plasticity in specific leaf area and stomatal density. Stabilizing selection acted on plasticity in these traits, suggesting that extreme levels of plasticity are disadvantageous. We conclude that even in systems driven by source-sink dynamics, temporal and spatial variation in conditions can favor the evolution of plasticity.
Oleic acid protectsCaenorhabditismothers from mating-induced death
Authors: Choi Leo S. , Shi Cheng , Murphy Coleen T. 
Published: September 2020

AbstractReproduction comes at a cost, including death. Previous studies of the interconnections between reproduction, lifespan, and fat metabolism inC. eleganswere predominantly performed in low-reproduction conditions. To understand how increased reproduction affects lifespan and fat metabolism, we examined mated worms; we find that a Δ9 desaturase, FAT-7, is significantly up-regulated. Dietary supplementation of oleic acid (OA), the immediate downstream product of FAT-7 activity, restores fat storage and completely rescues mating-induced death, while other fatty acids cannot. OA-mediated lifespan restoration is also observed inC. elegansmutants suffering increased death from short-term mating, and in matedC. remaneifemales, indicating a conserved role of oleic acid in post-mating lifespan regulation. Because OA supplementation does not further increase the reproductive span or the brood size of matedC. elegansmothers, our results suggest that altering specific fat metabolism uncouples reproduction and somatic lifespan regulation, providing potent targets to ameliorate the cost of reproduction.
DNA methylation signatures of duplicate gene evolution in angiosperms
Authors: Kenchanmane Raju Sunil K. , Ledford S. Marshall , Niederhuth Chad E. 
Published: September 2020

ABSTRACTGene duplication is a source of evolutionary novelty. DNA methylation may play a role in the evolution of duplicate genes through its association with gene expression. While this relationship is examined to varying extent in a few individual species, the generalizability of these results at either a broad phylogenetic scale with species of differing duplication histories or across a population, remains unknown. We apply a comparative epigenomics approach to 43 angiosperm species across the phylogeny and a population of 928Arabidopsis thalianaaccessions, examining the association of DNA methylation with paralog evolution. Genic DNA methylation is differentially associated with duplication type, the age of duplication, sequence evolution, and gene expression. Whole genome duplicates are typically enriched for CG-only gene-body methylated or unmethylated genes, while single-gene duplications are typically enriched for non-CG methylated or unmethylated genes. Non-CG methylation, in particular, was characteristic of more recent single-gene duplicates. Core angiosperm gene families are differentiated into those which preferentially retain paralogs and ‘duplication-resistant’ families, which convergently revert to singletons following duplication. Duplication-resistant families which still have paralogous copies are, uncharacteristically for core angiosperm genes, enriched for non-CG methylation. Non-CG methylated paralogs have higher rates of sequence evolution, higher frequency of presence-absence variation, and more limited expression. This suggests that silencing by non-CG methylation may be important to maintaining dosage following duplication and be a precursor to fractionation. Our results indicate that genic methylation marks differing evolutionary trajectories and fates between paralogous genes and have a role in maintaining dosage following duplication.