bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the temporally flexible structure of plant-pollinator interaction networks
Authors: CaraDonna Paul J. , Waser Nickolas M. 
Published: April 2020

AbstractEcological communities consist of species that are joined in complex networks of interspecific interaction. The interactions that networks depict often form and dissolve rapidly, but this temporal variation is not well integrated into our understanding of the causes and consequences of network structure. If interspecific interactions exhibit temporal flexibility across time periods over which organisms co-occur, then the emergent structure of the corresponding network may also be temporally flexible, something that a temporally-static perspective would miss. Here, we use an empirical system to examine short-term flexibility in network structure (connectance, nestedness, and specialization), and in individual species interactions that contribute to that structure. We investigated weekly plant-pollinator networks in a subalpine ecosystem across three summer growing seasons. To link the interactions of individual species to properties of their networks, we examined weekly temporal variation in species’ contributions to network structure. As a test of the potential robustness of networks to perturbation, we also simulated the random loss of species from weekly networks. We then compared the properties of weekly networks to the properties of cumulative networks that aggregate field observations over each full season. A week-to-week view reveals considerable flexibility in the interactions of individual species and their contributions to network structure. For example, species that would be considered relatively generalized across their entire activity period may be much more specialized at certain times, and at no point as generalized as the cumulative network may suggest. Furthermore, a week-to-week view reveals corresponding temporal flexibility in network structure and potential robustness throughout each summer growing season. We conclude that short-term flexibility in species interactions leads to short-term variation in network properties, and that a season-long, cumulative perspective may miss important aspects of the way in which species interact, with implications for understanding their ecology, evolution, and conservation.
A Powerful Method for Pleiotropic Analysis under Composite Null Hypothesis Identifies Novel Shared Loci Between Type 2 Diabetes and Prostate Cancer
Authors: Ray Debashree , Chatterjee Nilanjan 
Published: April 2020

SummaryThere is increasing evidence that pleiotropy, the association of multiple traits with the same genetic variants/loci, is a very common phenomenon. Cross-phenotype association tests are often used to jointly analyze multiple traits from a GWAS. The underlying methods, however, are often designed to test the global null hypothesis that there is no association of a genetic variant with any of the traits, the rejection of which does not implicate pleiotropy. In this article, we propose a new statistical approach, PLACO, for specifically detecting pleiotropic loci between two traits by considering an underlying composite null hypothesis that a variant is associated with none or only one of the traits. We propose testing the null hypothesis based on the product of the Z-statistics of the SNPs across two studies and derive a null distribution of the test statistic in the form of a mixture distribution that allows for fractions of SNPs to be associated with none or only one of the traits. We borrow approaches from the statistical literature on mediation analysis that allow asymptotic approximation of the null distribution avoiding estimation of nuisance parameters related to mixture proportions and variance components. Simulation studies demonstrate that the proposed method can maintain type I error and can achieve major power gain over alternative simpler methods that are typically used for testing pleiotropy. PLACO allows correlation in summary statistics between studies that may arise due to sharing of controls between disease traits. Application of PLACO to publicly available summary data from two large case-control GWAS of Type 2 Diabetes and of Prostate Cancer implicated a number of novel shared genetic regions nearZBTB38(3q23),RGS17(6q25.3),HAUS6(9p22.1),UBAP2(9p13.3),RAPSN(11p11.2),AKAP6(14q12),KNL1(15q15) andZNF236(18q23).
Fonio millet genome unlocks African orphan crop diversity for agriculture in a changing climate
Authors: Abrouk Michael , Ahmed Hanin Ibrahim , Cubry Philippe , Šimoníková Denisa , Cauet Stéphane , Bettgenhaeuser Jan , Gapa Liubov , Pailles Yveline , Scarcelli Nora , Couderc Marie , Zekraoui Leila , Kathiresan Nagarajan , Čížková Jana , Hřibová Eva , Doležel Jaroslav , Arribat Sandrine , Bergès Hélène , Wieringa Jan J. , Gueye Mathieu , Kane Ndjido A. , Leclerc Christian , Causse Sandrine , Vancoppenolle Sylvie , Billot Claire , Wicker Thomas , Vigouroux Yves , Barnaud Adeline , Krattinger Simon G. 
Published: April 2020

AbstractSustainable food production in the context of climate change necessitates diversification of agriculture and a more efficient utilization of plant genetic resources. Fonio millet (Digitaria exilis) is an orphan African cereal crop with a great potential for dryland agriculture. Here, we established high-quality genomic resources to facilitate fonio improvement through molecular breeding. These include a chromosome-scale reference assembly and deep re-sequencing of 183 cultivated and wild Digitaria accessions, enabling insights into genetic diversity, population structure, and domestication. Fonio diversity is shaped by climatic, geographic, and ethnolinguistic factors. Two genes associated with seed size and shattering showed signatures of selection. Most known domestication genes from other cereal models however have not experienced strong selection in fonio, providing direct targets to rapidly improve this crop for agriculture in hot and dry environments.
RbAp46/48LIN-53and HAT-1 are required for initial CENP-AHCP-3deposition and de novo centromere formation inCaenorhabditis elegansembryos
Authors: Lin Zhongyang , Yee Yuen Karen Wing 
Published: April 2020

ABSTRACTForeign DNA microinjected into theCaenorhabditis elegansgermline forms episomal extra-chromosomal arrays, or artificial chromosomes (ACs), in embryos. Injected linear, short DNA fragments concatemerize into high molecular weight (HMW)-DNA arrays that are visible as punctate DAPI-stained foci in oocytes, which undergo chromatinization and centromerization in embryos. The inner centromere, inner and outer kinetochore components, including AIR-2, CENP-AHCP-3, Mis18BP1KNL-2and BUB-1, assemble onto the nascent ACs during the first mitosis. Yet, due to incomplete DNA replication of the nascent ACs, centromeric proteins are not oriented at the poleward faces of the nascent ACs in mitosis, resulting in lagging ACs. The DNA replication efficiency of ACs improves over several cell cycles. We found that a condensin subunit, SMC-4, but not the replicative helicase component, MCM-2, facilitatesde novoCENP-AHCP-3deposition on nascent ACs. Furthermore, H3K9ac, H4K5ac, and H4K12ac are highly enriched on newly chromatinized ACs. HAT-1 and RbAp46/48LIN-53, which are essential forde novocentromere formation and segregation competency of nascent ACs, also hyperacetylate histone H3 and H4. Different from centromere maintenance on endogenous chromosomes, where Mis18BP1KNL-2functions upstream of RbAp46/48LIN-53, RbAp46/48LIN-53depletion causes the loss of both CENP-AHCP-3and Mis18BP1KNL-2initial deposition atde novocentromeres on ACs.
Designing Feature-Controlled Humanoid Antibody Discovery Libraries Using Generative Adversarial Networks
Authors: Amimeur Tileli , Shaver Jeremy M. , Ketchem Randal R. , Taylor J. Alex , Clark Rutilio H. , Smith Josh , Van Citters Danielle , Siska Christine C. , Smidt Pauline , Sprague Megan , Kerwin Bruce A. , Pettit Dean 
Published: April 2020

ABSTRACTWe demonstrate the use of a Generative Adversarial Network (GAN), trained from a set of over 400,000 light and heavy chain human antibody sequences, to learn the rules of human antibody formation. The resulting model surpasses commonin silicotechniques by capturing residue diversity throughout the variable region, and is capable of generating extremely large, diverse libraries of novel antibodies that mimic somatically hypermutated human repertoire response. This method permits us to rationally designde novohumanoid antibody libraries with explicit control over various properties of our discovery library. Through transfer learning, we are able to bias the GAN to generate molecules with key properties of interest such as improved stability and developability, lower predicted MHC Class II binding, and specific complementarity-determining region (CDR) characteristics. These approaches also provide a mechanism to better study the complex relationships between antibody sequence and molecular behavior, bothin vitroandin vivo. We validate our method by successfully expressing a proof-of-concept library of nearly 100,000 GAN-generated antibodies via phage display. We present the sequences and homology-model structures of example generated antibodies expressed in stable CHO pools and evaluated across multiple biophysical properties. The creation of discovery libraries using ourin silicoapproach allows for the control of pharmaceutical properties such that these therapeutic antibodies can provide a more rapid and cost-effective response to biological threats.
Mechanistic modeling of the SARS-CoV-2 disease map
Authors: Rian Kinza , Esteban-Medina Marina , Hidalgo Marta R. , Çubuk Cankut , Falco Matias M. , Loucera Carlos , Gunyel Devrim , Ostaszewski Marek , Peña-Chilet María , Dopazo Joaquín 
Published: April 2020

AbstractHere we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map in which the detailed activity of the human signaling circuits related to the viral infection and the different antiviral responses, including immune and inflammatory activities, can be inferred from gene expression experiments. Moreover, given to the mechanistic properties of the model, the effect of potential interventions, such as knock-downs, over-expression or drug effects (currently the system models the effect of more than 8000 DrugBank drugs) can be studied in specific conditions. By providing a holistic, systems biology approach to the understanding of the complexities of the viral infection process, this tool will become an important asset in the search for efficient antiviral treatments.The tool is freely available at:http://hipathia.babelomics.org/covid19/
DenovoIdentification of Cross-linked Peptides via Isotope Coded Linkage Tags
Authors: Gunawardena Harsha P. 
Published: April 2020

ABSTRACTAn isotope labeled cross-linker (asymmetric d4-DTSSP) was developed to streamline the efforts required for the detection of cross-linked peptides. The cross-linking and mass spectrometry strategy we call Isotope Tagging of Interacting Proteins (iTIP) has improved the specificity of detecting cross-linked peptides and the accurate identification of the interacting peptide sequences via the incorporation of isotopic signatures that are readily observed in the MS/MS spectra. All tryptic peptides derived from the cross-linking reactions of a protein complex are first subjected to ETD-MS2which results in the facile cleavage of the cross-linker at the disulfide bond and the release of inter-linked polypeptide chains that are detected as a pair of peaks (doublets) in the MS2spectrum. The constituent peptide halves that are tagged by the heavy/light ends of the cross-linker are easily mass-selected from all other fragment ions, and each polypeptide half is then subjected to CID or HCD-MS3for identification. The MS3spectra are subjected to conventional database search strategies available for the sequencing of linear or non-cross-linked peptides. The confident identification of each polypeptide is further assisted by the presence of a stable isotope labeled fragment ions that localizes the cross-linked site on the polypeptide sequence.
Evolution in Sinocyclocheilus cavefish is marked by rate shifts, reversals and origin of novel traits
Authors: Mao Ting-Ru , Liu Ye-Wei , Meegaskumbura Madhava , Yang Jian , Ellepola Gajaba , Senevirathne Gayani , Fu Cheng-Hai , Gross Joshua B. , Pie Marcio R. 
Published: April 2020

ABSTRACTEpitomized by the well-studied Astyanax mexicanus, cavefishes provide important model organisms to understand adaptations in response to divergent natural selection. However, the spectacular Sinocyclocheilus diversification of China, the most diverse cavefish clade in the world harboring nearly 75 species, demonstrate evolutionary convergence for many traits, yet remain poorly understood in terms of their morphological evolution. Here, using a broad sample of 49 species representative of this diversification, we analyze patterns of Sinocylocheilus evolution in a phylogenetic context. We categorized species into morphs based on eye-related condition: Blind, Micro-eyed (small-eyed), and Normal-eyed and we also considered three habitat types (Troglodytic – cave-restricted; Troglophilic – cave-associated; Surface – outside of caves). Geometric morphometric analyses show Normal-eyed morphs with fusiform shapes being segregated from Blind/Micro-eyed (Eye-regressed) morphs with deeper bodies along the first principal component (“PC”) axis. The second PC axis accounts for shape complexity related to the presence of horns. Ancestral character reconstructions of morphs suggest at least three independent origins of Blind morphs, each with different levels of modification in relation to the typical morphology of ancestral Normal-eyed morphs. Interestingly, only some Blind or Micro-eyed morphs bear horns and they are restricted to a single clade (Clade B) and arising from a Troglodytic ancestral species. Our geophylogeny shows an east-to-west diversification spanning the Pliocene and the Pleistocene, with Troglodytic species dominating karstic subterranean habitats of the plains whereas predominantly Surface species inhabit streams and pools in hills to the west (perhaps due to the scarcity of caves). Integration of morphology, phylogeny and geography suggests Sinocyclocheilus are pre-adapted for cave dwelling. Analyses of evolutionary rates suggest that lineages leading to Blind morphs were characterized by significant rate shifts, such as a slowdown in body size evolution and a 3.3 to 12.5 fold increase in the evolutionary rate of eye regression. Furthermore, body size and eye size have undergone reversals, but horns have not, a trait that seem to require substantial evolutionary time to form. These results, compared to the Astyanax model system, indicate Sinocyclocheilus fishes demonstrate extraordinary morphological diversity and variation, offering an invaluable model system to explore evolutionary novelty.
Procentriole microtubules as drivers of centriole reduplication
Authors: Vasquez-Limeta Alejandra , Sullenberger Catherine , Kong Dong , Lukasik Kimberly , Shukla Anil , Loncarek Jadranka 
Published: April 2020

ABSTRACTCentriole reduplication leads to the formation of supernumerary centrosomes, which promote cellular transformation, invasion and are a hallmark of tumors. A close association between a mother centriole and a procentriole (engagement), established during centriole duplication, intrinsically blocks reduplication. Premature loss of centriole association predisposes centrioles for reduplication and occurs during various types of cell cycle arrests in the presence of high Polo-like kinase 1 activity. Here we use nano-scale imaging and biochemistry to reveal the processes leading to the loss of centriole association and reduplication. We discover that centriole reduplication is driven by events occurring on procentriole microtubule walls. These events are mechanistically different from mitotic centriole separation driven by Pericentrin and Separase but are similar to the physiological process of centriole distancing occurring in unperturbed cycling G2 cells. We propose a concept in which centriole reduplication is a consequence of hijacked and amplified centriole maturation process.HighlightsSeparase-mediated Pericentrin reorganization is not required for centriole distancing and reduplication in interphase.Expression of active Plk1 in S phase leads to centrosomal ultrastructural changes resembling G2 phase.Procentrioles without microtubule walls cannot disengage.Centriole distancing is intrinsically regulated by the events occurring on procentriole microtubules.
Experimentally-validated correlation analysis reveals new anaerobic methane oxidation partnerships with consortium-level heterogeneity in diazotrophy
Authors: Metcalfe Kyle S. , Murali Ranjani , Mullin Sean W. , Connon Stephanie A. , Orphan Victoria J. 
Published: April 2020

AbstractArchaeal anaerobic methanotrophs (‘ANME’) and sulfate-reducing Deltaproteobacteria (‘SRB’) form symbiotic multicellular consortia capable of anaerobic methane oxidation (AOM), and in so doing modulate methane flux from marine sediments. The specificity with which ANME associate with particular SRB partnersin situ, however, is poorly understood. To characterize partnership specificity in ANME-SRB consortia, we applied the correlation inference technique SparCC to 310 16S rRNA Illumina iTag amplicon libraries prepared from Costa Rica sediment samples, uncovering a strong positive correlation between ANME-2b and members of a clade of Deltaproteobacteria we termed SEEP-SRB1g. We confirmed this association by examining 16S rRNA diversity in individual ANME-SRB consortia sorted using flow cytometry and by imaging ANME-SRB consortia with fluorescencein situhybridization (FISH) microscopy using newly-designed probes targeting the SEEP-SRB1g clade. Analysis of genome bins belonging to SEEP-SRB1g revealed the presence of a completenifHDKoperon required for diazotrophy, unusual in published genomes of ANME-associated SRB. Active expression ofnifHin SEEP-SRB1g and diazotrophic activity within ANME-2b/SEEP-SRB1g consortia was then demonstrated by microscopy using hybridization chain-reaction (HCR-) FISH targetingnifHtranscripts and by FISH-nanoSIMS experiments. NanoSIMS analysis of ANME-2b/SEEP-SRB1g consortia incubated with a headspace containing CH4and15N2revealed differences in cellular15N-enrichment between the two partners that varied between individual consortia, with SEEP-SRB1g cells enriched in15N relative to ANME-2b in one consortium and the opposite pattern observed in others, indicating both ANME-2b and SEEP-SRB1g are capable of nitrogen fixation, but with consortium-specific variation in whether the archaea or bacterial partner is the dominant diazotroph.
ERK basal and pulsatile activity are differentially regulated in mammalian epidermis to control proliferation and exit from the stem cell compartment
Authors: Hiratsuka Toru , Bordeu Ignacio , Pruessner Gunnar , Watt Fiona M. 
Published: April 2020

AbstractFluctuation in signal transduction pathways is frequently observed during mammalian development. However, its role in regulating stem cells has not been explored. Here we tracked spatiotemporal ERK MAPK dynamics in human epidermal stem cells. While stem cells and differentiated cells were distinguished by high and low stable basal ERK activity, respectively, we also found cells with pulsatile ERK activity. Transitions from Basalhi-Pulselo(stem) to Basalhi-Pulsehi, Basalmid-Pulsehi, and Basallo-Pulselo(differentiated) cells occurred in expanding keratinocyte colonies and in response to a range of differentiation stimuli. Pharmacological inhibition of ERK induced differentiation only when cells were in the Basalmid-Pulsehistate. Basal ERK activity and pulses were differentially regulated by DUSP10 and DUSP6, leading us to speculate that DUSP6-mediated ERK pulse downregulation promotes initiation of differentiation whereas DUSP10-mediated downregulation of mean ERK activity promotes and stabilizes post-commitment differentiation. Quantification of MAPK1/3, DUSP6 and DUSP10 transcripts in individual cells demonstrated that ERK activity is controlled both transcriptionally and post-transcriptionally. When cells were cultured on a topography that mimics the epidermal-dermal interface, spatial segregation of mean ERK activity and pulses was observed. In vivo imaging of mouse epidermis revealed a patterned distribution of basal cells with pulsatile ERK activity and downregulation was linked to the onset of differentiation. Our findings demonstrate that ERK MAPK signal fluctuations link kinase activity to stem cell dynamics.SignificanceUnderstanding how intracellular signaling cascades control cell fate is a key issue in stem cell biology. Here we show that exit from the stem cell compartment in mammalian epidermis is characterised by pulsatile ERK MAPK activity. Basal activity and pulses are differentially regulated by DUSP10 and DUSP6, two phosphatases that have been shown previously to regulate differentiation commitment in the epidermis. ERK activity is controlled both transcriptionally and post-transcriptionally. Spatial segregation of mean ERK activity and pulses is observed both in reconstituted human epidermis and in mouse epidermis. Our findings demonstrate the tight spatial and temporal regulation of ERK MAPK expression and activity in mammalian epidermis.
High performance intensiometric direct- and inverse-response genetically encoded biosensors for citrate
Authors: Zhao Yufeng , Shen Yi , Wen Yurong , Campbell Robert E. 
Published: April 2020

AbstractMotivated by the growing recognition of citrate as a central metabolite in a variety of biological processes associated with healthy and diseased cellular states, we have developed a series of high-performance genetically encoded citrate biosensors suitable for imaging of citrate concentrations in mammalian cells. The design of these biosensors was guided by structural studies of the citrate-responsive sensor histidine kinase, and took advantage of the same conformational changes proposed to propagate from the binding domain to the catalytic domain. Following extensive engineering based on a combination of structure guided mutagenesis and directed evolution, we produced an inverse-response biosensor (ΔF/Fmin~ 18) designated Citroff1 and a direct-response biosensor (ΔF/Fmin~ 9) designated Citron1. We report the x-ray crystal structure of Citron1 and demonstrate the utility of both biosensors for qualitative and quantitative imaging of steady-state and pharmacologically-perturbed citrate concentrations in live cells.