bluuebunny/crossref_metadata_2025_split huggingface dataset:
Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago
Authors: Morgan Andrew P , Brazeau Nicholas F , Ngasala Billy , Mhamilawa Lwidiko E. , Denton Madeline , Msellem Mwinyi , Morris Ulrika , Filer Dayne L , Aydemir Ozkan , Bailey Jeffrey A. , Parr Jonathan , Mårtensson Andreas , Bjorkman Anders , Juliano Jonathan J 
Published: December 2019

ABSTRACTBackgroundTanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.MethodsWe used whole-genome sequencing (WGS) to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. We assessed ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.ResultsWe identified significant decreases in the effective population sizes in both populations in the timeframe of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared large sections of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling,, we demonstrate a pair of isolates between the mainland and Zanzibar that are related at the expected level of half-siblings, consistent with recent importationConclusionsThese findings suggest that importation plays an increasing role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.
Gene expression pattern of vacuolar-iron transporter-like (VTL) genes in hexaploid wheat during metal stress
Authors: Sharma Shivani , Kaur Gazaldeep , Kumar Anil , Meena Varsha , Ram Hasthi , Kaur Jaspreet , Pandey Ajay Kumar 
Published: December 2019

AbstractIron is one of the important micronutrients that is not just essential for the human body, but also required for crop productivity and yield-related traits. To address the Fe homeostasis in crop plants, multiple transporters belonging to the category of Major facilitator superfamily are being explored. In this direction, Vacuolar iron transporters (VIT) are being reported and have been characterized functionally as an important candidate to address biofortification in cereal crops. In the present study, the identification and characterization of new members of Vacuolar iron transporters-like proteins (VTL) was performed. Phylogenetic analyses demonstrated distinct clustering of all the VTL genes from the previously known VIT genes. Our analysis identifies multiple VTL genes from hexaploid wheat with the highest number of this gene family localized on chromosome 2. Quantitative expression analysis suggests that most of the VTL genes are induced only during the Fe surplus condition, thereby reinforcing their role metal homeostasis. Interestingly, most of the wheat VTL genes were significantly up-regulated in a tissue-specific manner under Zn, Mn and Cu deficiency conditions. Although, no significant changes in expression of wheat VTL genes were observed in roots under heavy metals, but TaVTL2, TaVTL3 and TaVTL5 were upregulated in the presence of cobalt stress. Overall, this work deals with the characterization of wheat VTL genes that could provide an important genetic resource for addressing metal homeostasis in bread wheat.
Multiplexing information flow through dynamic signalling systems
Authors: Minas Giorgos , Woodcock Dan J. , Ashall Louise , Harper Claire V. , White Michael R. H. , Rand David A 
Published: December 2019

AbstractWe consider how a signalling system can act as an information hub by multiplexing information arising from multiple signals. We formally define multiplexing, mathematically characterise which systems can multiplex and how well they can do it. While the results of this paper are theoretical, to motivate the idea of multiplexing, we provide experimental evidence that tentatively suggests that the NF-κB transcription factor can multiplex information about changes in multiple signals. We believe that our theoretical results may resolve the apparent paradox of how a system like NF-κB that regulates cell fate and inflammatory signalling in response to diverse stimuli can appear to have the low information carrying capacity suggested by recent studies on scalar signals. In carrying out our study, we introduce new methods for the analysis of large, nonlinear stochastic dynamic models, and develop computational algorithms that facilitate the calculation of fundamental constructs of information theory such as Kullback–Leibler divergences and sensitivity matrices, and link these methods to new theory about multiplexing information. We show that many current models such as those of the NF-κB system cannot multiplex effectively and provide models that overcome this limitation using post-transcriptional modifications.
Genome resequencing, improvement of variant calling, and population genomic analyses provide insights into the seedlessness in the genusVitis
Authors: Kim Myung-Shin , Hur Youn Young , Kim Ji Hong , Jeong Soon-Chun 
Published: December 2019

AbstractThe seedlessness of grape derived from stenospermocarpy is one of the most prized traits of table or raisin grapes. It is controlled by a complex genetic system containing one major dominant gene and multiple minor recessive genes. Here, we collected dense variation data from high-depth resequencing data of seeded, seedless, and wild relative grape genomes sequenced to > 37x mean depth. Variant calls were made using a modified variant calling pipeline that was suitable for highly diverse interspecific grape accessions. The modified pipeline enabled us to call several million more variants than the commonly recommended pipeline. The quality was validated by Sanger sequencing data and subsequently supported by the genetic population structure and the phylogenetic tree constructed using the obtained variation data, results of which were generally consistent with known pedigree and taxonomic classifications. Variation data enabled us to confirm a major dominant gene and identify minor recessive loci for seedlessness. Incidentally, we found that grape cultivar Rizamat contains an ancestral chromosomal region of the major gene in Sultanina, a predominant seedlessness donor cultivar. Furthermore, we predicted new candidate causal genes includingVitvi01g00455,Vitvi08g01528, and Vitvi18g01237associated with the minor seedless-regulating loci, which showed high homology with genes that regulate seed development inArabidopsis. This study provides fundamental insights relevant to variant calling from genome resequencing data of diverse interspecific hybrid germplasms such as grape and will accelerate future efforts aimed at crop improvement.
Late life metformin treatment limits cell survival and shortens lifespan by triggering an aging-associated failure of energy metabolism
Authors: Espada Lilia , Dakhovnik Alexander , Chaudhari Prerana , Martirosyan Asya , Miek Laura , Poliezhaieva Tetiana , Schaub Yvonne , Nair Ashish , Döring Nadia , Rahnis Norman , Werz Oliver , Koeberle Andreas , Kirkpatrick Joanna , Ori Alessandro , Ermolaeva Maria A. 
Published: December 2019

SummaryThe diabetes drug metformin is to be clinically tested in aged humans to achieve health span extension, but little is known about responses of old non-diabetic individuals to this drug. Byin vitroandin vivotests we found that metformin shortens life span and limits cell survival when provided in late life, contrary to its positive early life effects. Mechanistically, metformin exacerbates aging-associated mitochondrial dysfunction towards respiratory failure, aggravated by the inability of old cells to upregulate glycolysis in response to metformin, leading to ATP exhaustion. The beneficial dietary restriction effect of metformin on lipid reserves is abrogated in old animals, contributing to metabolic failure, while ectopic stabilization of cellular ATP levels alleviates late life metformin toxicityin vitroandin vivo. The toxicity is also suspended in nematodes carrying diabetes-like insulin receptor insufficiency and showing prolonged resilience to metabolic stress induced by metformin. In sum, we uncovered an alarming metabolic decay triggered by metformin in late life which may limit its benefits for non-diabetic elderly patients. Novel regulators of life extension by metformin are also presented.HighlightsLate life metformin treatment limits cell survival and shortens lifespan.Metformin exacerbates aging-associated mitochondrial dysfunction causing fatal ATP exhaustion.Old cells fail to upregulate glycolysis as a compensatory response to metformin.The dietary restriction (DR) mimetic response to metformin is abrogated in old animals.PKA and not AMPK pathway instigates the early life DR response to metformin.Stabilization of cellular ATP levels alleviates late life metformin toxicityin vitroandin vivo.
Spike-timing-dependent plasticity rewards synchrony rather than causality
Authors: Anisimova Margarita , van Bommel Bas , Mikhaylova Marina , Wiegert J. Simon , Oertner Thomas G. , Gee Christine E. 
Published: December 2019

AbstractSpike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain, but the whole-cell recordings required for the experimental induction of STDP are typically limited to one hour. This mismatch of time scales is a long-standing weakness in synaptic theories of memory. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells. Twenty minutes after optogenetic induction of STDP (oSTDP), we observed timing-dependent depression (tLTD) and timing-dependent potentiation (tLTP), depending on the sequence of spiking. As oSTDP does not require electrodes, we could also assess the strength of these paired connections three days later. At this late time point, late tLTP was observed for both causal (CA3 before CA1) and anti-causal (CA1 before CA3) timing, but not for asynchronous activity patterns (Δt = 50 ms). Blocking activity after induction of oSTDP prevented stable potentiation. Our results confirm that neurons wire together if they fire together, but suggest that synaptic depression after anti-causal activation (tLTD) is a transient phenomenon.HighlightsOptogenetic induction of spike-timing-dependent plasticity at Schaffer collateral synapsesCausal pairing induces potentiation whereas anti-causal pairing induces depression during patch-clamp recordings.Three days after optogenetic induction, the consequence of STDP is potentiation (tLTP) irrespective of spiking order.Late tLTP requires ongoing activity in the days following oSTDP.Graphical Abstract
Extracting the GEMs: Genotype, Environment and Microbiome interactions shaping host phenotypes
Authors: Oyserman Ben O. , Cordovez Viviane , Sarango Flores Stalin W. , Nijveen Harm , Medema Marnix H. , Raaijmakers Jos M. 
Published: December 2019

AbstractOne of the fundamental tenets of biology is that the phenotype of an organism (Y) is determined by its genotype (G), the environment (E) and their interaction (GE). Quantitative phenotypes can then be modeled as Y=G+E+GE+e, where e is the biological variance. This simple and tractable model has long served as the basis for studies investigating the heritability of traits and decomposing the variability in fitness. Increasingly, the importance of microbe interactions on organismal phenotypes is being recognized, but it is currently unclear what the relative contribution of microbiomes to a given host phenotype is and how this translates into the traditional GE model. Here we address this fundamental question and propose an expansion of the original model, referred to as GEM, which explicitly incorporates the contribution of the microbiome (M) to the host phenotype, while maintaining the simplicity and tractability of the original GE model. We show that by keeping host, environment and microbiome as separate but interacting variables, the GEM model can capture the nuanced ecological interactions between these variables. Finally, we demonstrate with an in vitro experiment how the GEM model can be used to statistically disentangle the relative contributions of each component on specific host phenotypes.
CD4+T cells persist for years in the human small intestine and mediate robust TH1 immunity
Authors: Casado Raquel Bartolomé , Landsverk Ole J.B. , Chauhan Sudhir Kumar , Sætre Frank , Hagen Kjersti Thorvaldsen , Yaqub Sheraz , Øyen Ole , Horneland Rune , Aandahl Einar Martin , Aabakken Lars , Bækkevold Espen S. , Jahnsen Frode L. 
Published: December 2019

AbstractStudies in mice and humans have shown that CD8+T cell immunosurveillance in non-lymphoid tissues is dominated by resident populations. Whether CD4+T cells use the same strategies to survey peripheral tissues is less clear. Here, examining the turnover of CD4+T cells in transplanted duodenum in humans, we demonstrate that the majority of CD4+T cells were still donor-derived one year after transplantation. In contrast to memory CD4+T cells in peripheral blood, intestinal CD4+TRMcells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4+TRMcells were very potent cytokine producers; the vast majority being polyfunctional TH1 cells, whereas a minor fraction produced IL-17. Interestingly, a fraction of intestinal CD4+T cells produced granzyme-B and perforin after activation. Together, we show that the intestinal CD4+T-cell compartment is dominated by resident populations that survive for more than 1 year. This finding is of high relevance for the development of oral vaccines and therapies for diseases in the gut.
The apparent requirement for protein synthesis during G2 phase is due to checkpoint activation
Authors: Lockhead Sarah , Moskaleva Alisa , Kamenz Julia , Chen Yuxin , Kang Minjung , Reddy Anay , Santos Silvia , Ferrell James E. 
Published: December 2019

AbstractProtein synthesis inhibitors (e.g. cycloheximide) prevent cells from entering mitosis, suggesting that cell cycle progression requires protein synthesis until right before mitotic entry. However, cycloheximide is also known to activate p38 MAPK, which can delay mitotic entry through a G2/M checkpoint. Here we asked whether checkpoint activation or a requirement for protein synthesis is responsible for the cycloheximide effect. We found that p38 inhibitors prevent cycloheximide-treated cells from arresting in G2 phase, and that G2 duration is normal in about half of these cells. The Wee1/Myt1 inhibitor PD0166285 also prevents cycloheximide from blocking mitotic entry, raising the possibility that Wee1 and/or Myt1 mediate the cycloheximide-induced G2 arrest. Thus, the ultimate trigger for mitotic entry appears not to be the continued synthesis of mitotic cyclins or other proteins. However, M-phase progression was delayed in cycloheximide-plus-kinase-inhibitor-treated cells, emphasizing the different requirements of protein synthesis for timely entry and completion of mitosis.Impact statementCycloheximide arrests cells in G2 phase due to activation of p38 MAPK, not inhibition of protein synthesis, arguing that protein synthesis in G2 phase is not required for mitotic entry.
Evaluating the data quality of iNaturalist termite records
Authors: Hochmair Hartwig H. , Scheffrahn Rudolf H. , Basille Mathieu , Boone Matthew 
Published: December 2019

AbstractCitizen science (CS) contributes to the combined knowledge about species distributions, which is a critical foundation in the studies of invasive species, biological conservation, and response to climatic change. In this study, we assessed the value of CS for termites worldwide. First, we compared the abundance and species diversity of geo-tagged termite records in iNaturalist to that of the University of Florida termite collection (UFTC) and the Global Biodiversity Information Facility (GBIF). Second, we quantified how the combination of these data sources affected the number of genera that satisfy data requirements for ecological niche modeling. Third, we assessed the taxonomic correctness of iNaturalist termite records in the Americas at the genus and family level through expert review based on photo identification. Results showed that iNaturalist records were less abundant than those in UFTC and in GBIF, although they complemented the latter two in selected world regions. A combination of GBIF and UFTC led to a significant increase in the number of termite genera satisfying the abundance criterion for niche modeling compared to either of those two sources alone, whereas adding iNaturalist observations as a third source only had a moderate effect on the number of termite genera satisfying that criterion. Although research grade observations in iNaturalist require a community-supported and agreed upon ID below the family taxonomic rank, our results indicated that iNaturalist data do not exhibit a higher taxonomic classification accuracy when they are designated research grade. This means that non-research grade observations can be used to more completely map the presence of termite locations in certain geographic locations without significantly jeopardizing data quality. We concluded that CS termite observation records can, to some extent, complement expert termite collections in terms of geographic coverage and species diversity. Based on recent data contribution patterns in CS data, the role of CS termite contributions is expected to grow significantly in the near future.
Host targets of effectors of the lettuce downy mildew Bremia lactucae from cDNA-based yeast two-hybrid screening
Authors: Pelgrom Alexandra J.E. , Meisrimler Claudia-Nicole , Elberse Joyce , Koorman Thijs , Boxem Mike , Van den Ackerveken Guido 
Published: December 2019

AbstractPlant pathogenic bacteria, fungi and oomycetes secrete effector proteins to manipulate host cell processes to establish a successful infection. Over the last decade the genomes and transcriptomes of many agriculturally important plant pathogens have been sequenced and vast candidate effector repertoires were identified using bioinformatic analyses. Elucidating the contribution of individual effectors to pathogenicity is the next major hurdle. To advance our understanding of the molecular mechanisms underlying lettuce susceptibility to the downy mildew Bremia lactucae, we mapped a network of physical interactions between B. lactucae effectors and lettuce target proteins. Using a lettuce cDNA library-based yeast-two-hybrid system, 61 protein-protein interactions were identified, involving 21 B. lactucae effectors and 46 unique lettuce proteins. The top ten targets based on the number of independent colonies identified in the Y2H and two targets that belong to gene families involved in plant immunity, were further characterized. We determined the subcellular localization of the fluorescently tagged target proteins and their interacting effectors. Importantly, relocalization of effectors or targets to the nucleus was observed for four effector-target pairs upon their co-expression, supporting their interaction in planta.
Inferring Chromosome Radial Organization from Hi-C Data
Authors: Das Priyojit , Shen Tongye , McCord Rachel Patton 
Published: December 2019

AbstractBackgroundThe nonrandom radial organization of eukaryotic chromosome territories (CTs) inside the nucleus plays an important role in nuclear functional compartmentalization. Increasingly, chromosome conformation capture (Hi-C) based approaches are being used to characterize the genome structure of many cell types and conditions. Computational methods to extract 3D arrangements of CTs from this type of pairwise contact data will thus increase our ability to analyze CT organization in a wider variety of biological situations.ResultsA number of full-scale polymer models have successfully reconstructed the 3D structure of chromosome territories from Hi-C. To supplement such methods, we explore alternative, direct, and less computationally intensive approaches to capture radial CT organization from Hi-C data. We show that we can infer relative chromo-some ordering using PCA on a thresholded inter-chromosomal contact matrix. We simulate an ensemble of possible CT arrangements using a force-directed network layout algorithm and propose an approach to integrate additional chromosome properties into our predictions. Our CT radial organization predictions have a high correlation with microscopy imaging data for various cell nucleus geometries (lymphoblastoid, skin fibroblast, and breast epithelial cells), and we can capture previously documented changes in senescent and progeria cells.ConclusionsOur analysis approaches provide rapid and modular approaches to screen for alterations in CT organization across widely available Hi-C data. We demon-strate which stages of the approach can extract meaningful information, and also de-scribe limitations of pairwise contacts alone to predict absolute 3D positions.
Polynuclear ruthenium amines inhibit K2P channels via a ‘finger in the dam’ mechanism
Authors: Pope Lianne , Lolicato Marco , Minor Daniel L. 
Published: December 2019

ABSTRACTThe trinuclear ruthenium amine Ruthenium Red (RuR) inhibits diverse ion channels including K2P potassium channels, TRPs, the mitochondrial calcium uniporter, CALHMs, ryanodine receptors, and Piezos. Despite this extraordinary array, there is very limited information for how RuR engages its targets. Here, using X-ray crystallographic and electrophysiological studies of an RuR-sensitive K2P, K2P2.1 (TREK-1) I110D, we show that RuR acts by binding an acidic residue pair comprising the ‘Keystone inhibitor site’ under the K2P CAP domain archway above the channel pore. We further establish that Ru360, a dinuclear ruthenium amine not known to affect K2Ps, inhibits RuR-sensitive K2Ps using the same mechanism. Structural knowledge enabled a generalizable RuR ‘super-responder’ design strategy for creating K2Ps having nanomolar sensitivity. Together, the data define a ‘finger in the dam’ inhibition mechanism acting at a novel K2P inhibitor binding site. These findings highlight the polysite nature of K2P pharmacology and provide a new framework for K2P inhibitor development.
MicroRNA function transitions from regulating developmental genes to transposable elements during the maturation of pollen
Authors: Oliver Cecilia , Annacondia Maria Luz , Wang Zhenxing , Slotkin R Keith , Köhler Claudia , Martinez German 
Published: December 2019

AbstractmicroRNAs play important roles to control the development of eukaryotic organisms. Both animal and plant microRNAs are essential for the spatio-temporal regulation of development but together with this role, plant microRNAs also control transposable elements and stimulate the production of epigenetically-active small interfering RNAs. This last role is evident in the plant male gamete containing structure, the male gametophyte or pollen grain, but how the dual role of plant microRNAs is integrated during its development is unknown. Here, we provide a detailed analysis of microRNA dynamics during pollen development and their genic and transposable element targets using small RNA and mRNA cleavage (PARE) high-throughput sequencing. Furthermore we uncover the microRNAs loaded in the two main Argonaute proteins in the mature pollen grain, AGO1 and AGO5. Our results indicate that the developmental progression from microspore to mature pollen grain is characterized by a reprogramming from microRNAs focused on the control of development to microRNAs regulating transposable element control.