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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 89,482 bioRxiv papers from 383,424 authors.

Most downloaded bioRxiv papers, since beginning of last month

87,346 results found. For more information, click each entry to expand.

86061: Identification of a novel efficient transcriptional activation domain from Chinese fir (Cunninghamia lanceolata)
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Posted to bioRxiv 20 Apr 2020

Identification of a novel efficient transcriptional activation domain from Chinese fir (Cunninghamia lanceolata)
2 downloads genetics

Tengfei Zhu, Wenyu Tang, Delan Chen, Renhua Zheng, Jian Li, Jun Su

Activation domains are used as critical components of artificial gene modification tools for genetic breeding. The high efficiency of the activation domain relies on the host plant. However, no activation domain has been identified that originates from Chinese fir ( Cunninghamia lanceolate ). In this study, a novel strong activator was identified from the whole Chinese fir cDNA library. This plant conserved activator was named TAC 3 (Transcriptional Activation domain from Chinese fir 3). C-terminal 70 amino acids of TAC (TAC3d) have a stronger ability than the commonly used strong activation domain of the virus protein VP16, or the strong plant activation domain, EDLL, in Chinese fir. Through Dual-luciferase assay, phenomic analysis and FT (Flowering Locus T [FT]) quantification, it was shown that, TAC3d can overcome the transcriptional repression of strong plant repressors (Flowering Locus C [FLC]) when fused to its C-terminal domain, thus inhibit the repression of FT expression. In conclusion, for the first time, an activation domain has been identified from Chinese fir. TAC3, which can be used for precise gene activation in Chinese fir in the future, and its function in the plant is more powerful than the commonly used strong activation domain (such as VP16 and EDLL).

86062: Rare non-coding variants are associated with plasma lipid traits in a founder population
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Posted to bioRxiv 24 May 2017

Rare non-coding variants are associated with plasma lipid traits in a founder population
2 downloads genetics

Catherine Igartua, Sahar V. Mozaffari, Dan L Nicolae, Carole Ober

Founder populations are ideally suited for studies on the clinical effects of alleles that are rare in general populations but occur at higher frequencies in these isolated populations. Whole genome sequencing in 98 South Dakota Hutterites, a founder population of European descent, and subsequent imputation to the Hutterite pedigree revealed 660,238 single nucleotide polymorphisms (SNPs; 98.9% non-coding) that are rare (<1%) or absent in European populations, but occur at frequencies greater than 1% in the Hutterites. We examined the effects of these rare in European variants on plasma levels of LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), total cholesterol and triglycerides (TG) in 828 Hutterites and applied a Bayesian hierarchical framework to prioritize potentially causal variants based on functional annotations. We identified two novel non-coding rare variants associated with LDL-C (rs17242388 in LDLR) and HDL-C (rs189679427 between GOT2 and APOOP5), and replicated previous associations of a splice variant in APOC3 (rs138326449) with TG and HDL-C. All three variants are at well-replicated loci in genome wide association study (GWAS) but are independent from and have larger effect sizes than the known common variation in these regions. We also identified variants at two novel loci (rs191020975 in EPHA6 and chr1:224811120 in CNIH3) at suggestive levels of significance with LDL-C. Candidate expression quantitative loci (eQTL) analyses in lymphoblastoid cell lines (LCLs) in the Hutterites suggest that these rare non-coding variants are likely to mediate their effects on lipid traits by regulating gene expression. Overall, we provide insights into the mechanisms regulating lipid traits and potentially new therapeutic targets.

86063: Substrate channeling in oxylipin biosynthesis through a protein complex in the plastid envelope of Arabidopsis thaliana
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Posted to bioRxiv 22 Mar 2018

Substrate channeling in oxylipin biosynthesis through a protein complex in the plastid envelope of Arabidopsis thaliana
2 downloads cell biology

Stephan Pollmann, Armin Springer, Sachin Rustgi, Diter von Wettstein, ChulHee Kang, Christiane Reinbothe, Steffen Reinbothe

Oxygenated membrane fatty acid derivatives dubbed oxylipins play important roles in the plant's defense against biotic and abiotic cues. Plants challenged by insect pests, for example, synthesize a blend of different defense compounds that, amongst others, comprise volatile aldehydes and jasmonic acid (JA). Because all oxylipins are derived from the same pathway, we asked how their synthesis might be regulated and focused on two closely related, atypical cytochrome P450 enzymes designated CYP74A and CYP74B, i.e., allene oxide synthase (AOS) and hydroperoxide lyase (HPL). Both enzymes compete for the same substrate but give rise to different products. While the final product of the AOS branch is JA, those of the HPL branch comprise volatile aldehydes and alcohols. AOS and HPL are plastid envelope enzymes in Arabidopsis thaliana but accumulate at different locations. Biochemical experiments identified AOS as constituent of complexes also containing lipoxygenase 2 (LOX2) and allene oxide cyclase (AOC), which catalyze consecutive steps in JA precursor biosynthesis, while excluding the concurrent HPL reaction. Based on published X-ray data, the structure of this complex could be modelled and amino acids involved in catalysis and subunit interactions identified. Genetic studies identified the microRNA 319 (miR319)-regulated clade of TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) transcription factor genes and CORONATINE INSENSITIVE 1 (COI1) to control JA production through the AOS-LOX2-AOC2 complex. Together, our results define a molecular branch point in oxylipin bio-synthesis that allows fine-tuning the plant's defense machinery in response to biotic and abiotic stimuli.

86064: Transferrin binding protein B and Transferrin binding protein A2 expand the transferrin recognition range of Histophilus somni
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Posted to bioRxiv 09 Aug 2019

Transferrin binding protein B and Transferrin binding protein A2 expand the transferrin recognition range of Histophilus somni
2 downloads microbiology

Anastassia K Pogoutse, Trevor F. Moraes

The bacterial bipartite transferrin receptor is an iron acquisition system that is required for survival by several key human and animal pathogens. It consists of the TonB-dependent transporter Transferrin binding protein A (TbpA) and the surface lipoprotein Transferrin binding protein B (TbpB). Curiously, the Tbps are only found in host specific pathogens, and are themselves host specific, meaning that they will bind to the transferrin of their host species, but not to those of other animal species. While this phenomenon has long been established, neither the steps in the evolutionary process that led to this exquisite adaptation for the host, nor the steps that could alter it, are known. We sought to gain insight into these processes by studying Tbp specificity in Histophilus somni, a major pathogen of cattle. A past study showed that whole cells of H. somni specifically bind bovine transferrin, but not transferrin from sheep and goats, two bovids whose transferrins share 93% amino acid sequence identity with bovine transferrin. To our surprise, we found that H. somni can use sheep and goat transferrins as iron sources for growth, and that HsTbpB, but not HsTbpA, has detectable affinity for sheep and goat transferrins. Furthermore, a third transferrin binding protein, HsTbpA2, also showed affinity for sheep and goat transferrins. Our results show that H. somni TbpB and TbpA2 act to broaden the host transferrin recognition range of H. somni.

86065: An asexual flower of Silene latifolia and Microbotryum lychnidis-dioicae promoting its sexual-organ development
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Posted to bioRxiv 10 May 2019

An asexual flower of Silene latifolia and Microbotryum lychnidis-dioicae promoting its sexual-organ development
2 downloads plant biology

Hiroki Kawamoto, Kaori Yamanaka, Ayako koizumi, Kotaro Ishii, Yusuke Kazama, Tomoko Abe, Shigeyuki Kawano

Silene latifolia is a dioecious flowering plant with sex chromosomes in the family Caryophyllaceae. Development of a gynoecium and stamens are suppressed in the male and female flowers of S. latifolia, respectively. Microbtryum lychnidis-dioicae promotes stamen development when it infects the female flower. If suppression of the stamen and gynoecium development is regulated by the same mechanism, suppression of gynoecium and stamen development is released simultaneously with the infection by M. lychnidis-dioicae. To assess this hypothesis, an asexual mutant, without gynoecium or stamen, was infected with M. lychnidis-dioicae. A filament of the stamen in the infected asexual mutant was elongated at stages 11 and 12 of the flower bud development as well as the male, but the gynoecium did not form. Instead of the gynoecium, a filamentous structure was suppressed as in the male flower. Developmental suppression of the stamen was released by M. lychnidis-dioicae, but that of gynoecium development was not released. It is thought, therefore, that the suppression of gynoecium development was not released by the infection of M. lychnidis-dioicae. M. lychnidis-dioicae would have a function similar to SPF since the elongation of the stamen that is not observed in the healthy asexual mutant was observed after stage 8 of flower bud development. Such an infection experiment also that the Y chromosome of the asexual mutant has genes related to the differentiation of archesporial cells, but none related to maturation of the tapetal cells.

86066: An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease
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Posted to bioRxiv 25 May 2018

An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease
2 downloads genetics

Suvi Makelainen, Marta Gòdia, Minas Hellsand, Agnese Viluma, Daniela Hahn, Karim Makdoumi, Caroline J Zeiss, Cathryn Mellersh, Sally L Ricketts, Kristina Narfström, Finn Hallböök, Björn Ekesten, Göran Andersson, Tomas F Bergström

Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in humans and dogs. Currently, no standard treatment is available but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs1395) was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium. The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD.

86067: Modulation of Rapid Visual Responses during Reaching by Multimodal Stimuli
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Posted to bioRxiv 09 Mar 2019

Modulation of Rapid Visual Responses during Reaching by Multimodal Stimuli
2 downloads neuroscience

Isabel S Glover, Stuart N Baker

The reticulospinal tract plays an important role in primate upper limb function, but methods for assessing its activity are limited. One promising approach is to measure rapid visual responses (RVRs) in arm muscle activity during a visually-cued reaching task; these may arise from a tecto-reticulospinal pathway. We investigated whether changes in reticulospinal excitability can be assessed non-invasively using RVRs, by pairing the visual stimuli of the reaching task with electrical stimulation of the median nerve, galvanic vestibular stimulation or loud sounds, all of which are known to activate the reticular formation. Surface electromyogram recordings were made from the right deltoid of healthy human subjects as they performed fast reaching movements towards visual targets. Stimuli were delivered up to 200ms before target appearance and RVR was quantified as the EMG amplitude in a window 75-125ms after visual target onset. Median nerve, vestibular and auditory stimuli all consistently facilitated the RVRs, as well as reducing the latency of responses. We propose that this reflects modulation of tecto-reticulospinal excitability, suggesting that the amplitude of RVRs can be used to assess changes in brainstem excitability non-invasively in humans.

86068: Does internal metabolic state determine human motor coordination strategy?
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Posted to bioRxiv 13 May 2018

Does internal metabolic state determine human motor coordination strategy?
2 downloads neuroscience

Scott V Taylor, A. Aldo Faisal

Motor coordination requires the orchestration of multiple degrees of freedom to perform actions. Humans display characteristic and predictable reaching trajectories even though multiple trajectories are possible. Computational theories of motor control can explain these reaching trajectories by assuming that subjects orchestrate their movements to minimise a cost function, such as end-point variability or movement effort. However, how internal metabolic states influence decision making and sensorimotor control is not well understood. Here we measure human behaviour during a centre out reaching task in two distinct metabolic conditions in the morning 1. after having had breakfast and 2. not. We find that humans alter their patterns of motor coordination according to their internal metabolic state and that this change in behaviour results in a 20% lower task-related energy expenditure when fasted. We suggest that movements are orchestrated according to different criteria in different metabolic states so that metabolic costs are reduced in low metabolic states. We also predict that motor coordination strategies take the metabolic costs of specific muscle groups into account when planning and executing movements. Thus, the metabolic state may alter the computational strategies of decision making between animal-based experiments (in typically low metabolic conditions) and human psychophysics experiments (in typically high metabolic conditions).

86069: Does circadian regulation lead to optimal gas exchange regulation?
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Posted to bioRxiv 06 Jun 2017

Does circadian regulation lead to optimal gas exchange regulation?
2 downloads ecology

Víctor Resco de Dios, Arthur Gessler, Juan Pedro Ferrio, Josu G Alday, Michael Bahn, Jorge del Castillo, Sébastien Devidal, Sonia García-Muñoz, Zachary Kayler, Damien Landais, Paula Martín-Gómez, Alexandru Milcu, Clément Piel, Karin Pirhofer-Walzl, Olivier Ravel, Serajis Salekin, David T. Tissue, Mark G. Tjoelker, Jordi Voltas, Jacques Roy

Optimal stomatal theory is an evolutionary model proposing that leaves trade-off Carbon (C) for water to maximise C assimilation (A) and minimise transpiration (E), thereby generating a marginal water cost of carbon gain (λ) that remains constant over short temporal scales. The circadian clock is a molecular timer of metabolism that controls A and stomatal conductance (gs), amongst other processes, in a broad array of plant species. Here, we test whether circadian regulation contributes towards achieving optimal stomatal behaviour. We subjected bean (Phaseolus vulgaris) and cotton (Gossypium hirsutum) canopies to fixed, continuous environmental conditions of photosynthetically active radiation, temperature and vapour pressure deficit over 48 hours. We observed a significant and self-sustained circadian oscillation in A and in stomatal conductance (gs) which also led to a circadian oscillation in λ. The lack of constant marginal water cost indicates that circadian regulation does not directly lead to optimal stomatal behaviour. However, the temporal pattern in gas exchange, indicative of either maximizing A or of minimizing E, depending upon time of day, indicates that circadian regulation could contribute towards optimizing stomatal responses. More broadly, our results add to the emerging field of plant circadian ecology and show that molecular controls may partially explain leaf-level patterns observed in the field.

86070: The Impact of Random Models on Clustering Similarity
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Posted to bioRxiv 01 Oct 2017

The Impact of Random Models on Clustering Similarity
2 downloads bioinformatics

Alexander J. Gates, Yong-Yeol Ahn

Clustering is a central approach for unsupervised learning. After clustering is applied, the most fundamental analysis is to quantitatively compare clusterings. Such comparisons are crucial for the evaluation of clustering methods as well as other tasks such as consensus clustering. It is often argued that, in order to establish a baseline, clustering similarity should be assessed in the context of a random ensemble of clusterings. The prevailing assumption for the random clustering ensemble is the permutation model in which the number and sizes of clusters are fixed. However, this assumption does not necessarily hold in practice; for example, multiple runs of K-means clustering returns clusterings with a fixed number of clusters, while the cluster size distribution varies greatly. Here, we derive corrected variants of two clustering similarity measures (the Rand index and Mutual Information) in the context of two random clustering ensembles in which the number and sizes of clusters vary. In addition, we study the impact of one-sided comparisons in the scenario with a reference clustering. The consequences of different random models are illustrated using synthetic examples, handwriting recognition, and gene expression data. We demonstrate that the choice of random model can have a drastic impact on the ranking of similar clustering pairs, and the evaluation of a clustering method with respect to a random baseline; thus, the choice of random clustering model should be carefully justified.

86071: Coalescence 2.0: a multiple branching of recent theoretical developments and their applications
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Posted to bioRxiv 21 Jan 2014

Coalescence 2.0: a multiple branching of recent theoretical developments and their applications
2 downloads evolutionary biology

Aurélien Tellier, Christophe Lemaire

Population genetics theory has laid the foundations for genomics analyses including the recent burst in genome scans for selection and statistical inference of past demographic events in many prokaryote, animal and plant species. Identifying SNPs under natural selection and underpinning species adaptation relies on disentangling the respective contribution of random processes (mutation, drift, migration) from that of selection on nucleotide variability. Most theory and statistical tests have been developed using the Kingman’s coalescent theory based on the Wright-Fisher population model. However, these theoretical models rely on biological and life-history assumptions which may be violated in many prokaryote, fungal, animal or plant species. Recent theoretical developments of the so called multiple merger coalescent models are reviewed here (Λ-coalescent, beta-coalescent, Bolthausen-Snitzman, Ξ-coalescent). We explicit how these new models take into account various pervasive ecological and biological characteristics, life history traits or life cycles which were not accounted in previous theories such as 1) the skew in offspring production typical of marine species, 2) fast adapting microparasites (virus, bacteria and fungi) exhibiting large variation in population sizes during epidemics, 3) the peculiar life cycles of fungi and bacteria alternating sexual and asexual cycles, and 4) the high rates of extinction-recolonization in spatially structured populations. We finally discuss the relevance of multiple merger models for the detection of SNPs under selection in these species, for population genomics of very large sample size and advocate to potentially examine the conclusion of previous population genetics studies.

86072: The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans
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Posted to bioRxiv 21 Nov 2017

The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans
2 downloads cell biology

Ye Hong, Maria Velkova, Nicola Silva, Marlène Jagut, Viktor Scheidt, Karim Labib, Verena Jantsch, A Gartner

Homologous recombination is essential for crossover (CO) formation and accurate chromosome segregation during meiosis. It is of considerable importance to work out how recombination intermediates are processed leading to CO and non-crossover (NCO) outcome. Genetic analysis in budding yeast and Caenorhabditis elegans indicates that the processing of meiotic recombination intermediates involves a combination of nucleases and DNA repair enzymes. We previously reported that in C. elegans meiotic Holiday junction resolution is mediated by two redundant pathways, conferred by the SLX-1 and MUS-81 nucleases, and by the HIM-6 Blooms helicase in conjunction with the XPF-1 endonucleases, respectively. Both pathways require the scaffold protein SLX-4. However, in the absence of all these enzymes residual processing of meiotic recombination intermediates still occurs and CO formation is reduced but not abolished. Here we show that the LEM-3 nuclease, mutation of which by itself does not have an overt meiotic phenotype, genetically interacts with slx-1 and mus-81 mutants, the respective double mutants leading to 100% embryonic lethality. LEM-3 and MUS-81 act redundantly, their combined loss leading to a reduced number of early meiotic recombination intermediates, to a delayed disassembly of foci associated with CO designated sites, and to the formation of univalents linked by SPO-11 dependent chromatin bridges (dissociated bivalents). However, LEM-3 foci do not co-localize with ZHP-3 a marker that congresses into CO designated sites. In addition, neither CO frequency nor distribution is altered in lem-3 single mutants or in combination with mus-81 or slx-4 mutations, indicating that LEM-3 drives NCO outcome. Finally, we found persistent chromatin bridges during meiotic divisions in lem-3; slx-4 double mutants. Supported by the localization of LEM-3 between dividing meiotic nuclei, this data suggests that LEM-3 is able to process erroneous recombination intermediates that persist into the second meiotic divisions.

86073: E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans
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Posted to bioRxiv 19 Dec 2014

E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans
2 downloads molecular biology

Alper Akay, Peter Sarkies, Eric A. Miska

The discovery of RNA interference (RNAi) in C. elegans has had a major impact on scientific research, led to the rapid development of RNAi tools and has inspired RNA-based therapeutics. Astonishingly, nematodes, planaria and many insects take up double-stranded RNA (dsRNA) from their environment to elicit RNAi; the biological function of this mechanism is unclear. Recently, the E. coli OxyS non-coding RNA was shown to regulate gene expression in C. elegans when E. coli is offered as food. This was surprising given that C. elegans is unlikely to encounter E. coli in nature. To directly test the hypothesis that the E. coli OxyS non-coding RNA triggers the C. elegans RNAi pathway, we sequenced small RNAs from C. elegans after feeding with bacteria. We clearly demonstrate that the OxyS non-coding RNA does not trigger an RNAi response in C. elegans. We conclude that the biology of environmental RNAi remains to be discovered.

86074: TraRECo: A Greedy Approach based de novo Transcriptome Assembler with Read Error Correction using Consensus Matrix
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Posted to bioRxiv 08 Nov 2017

TraRECo: A Greedy Approach based de novo Transcriptome Assembler with Read Error Correction using Consensus Matrix
2 downloads bioinformatics

Seokhyun Yoon, Daeseung Kim, Keunsoo Kang, Woong June Park

Background: Challenges in developing a good de novo transcriptome assembler include how to deal with read errors and sequence repeats. Almost all de novo assemblers utilize de Bruijn graph, which has a complexity linearly growing with data size while suffers from errors and repeat. Although one can correct errors by inspecting topological structure of the graph, it is an uneasy task when there are too many branches. There are two research directions: improving either graph reliability or path search precision. We focused on improving the reliability. Results: We present TraRECo, a greedy approach to de novo assembly employing error-aware graph construction. The idea is similar to overlap-layout-consensus approach used for genome assembly, but is different in that consensus is made through the entire graph construction step. Basically, we built contigs by direct read alignment within a distance margin and performed junction search to construct splicing graphs. While doing so, however, a contig of length l was represented by 4xl matrix (called consensus matrix), of which each element was the base count of aligned reads so far. A representative sequence is obtained, by taking majority in each column of the consensus matrix, to be used for further read alignment. Once splicing graphs were obtained, we used IsoLasso to find paths with noticeable read depth. The experiments using real and simulated reads showed that the method provides considerable improvements in sensitivity and reasonably better performances when comparing both sensitivity and precision. This could be achieved by making more erroneous reads to be participated in graph construction, which, in turn, improved the depth information quality used for the subsequent path search step. The results for simulated reads showed also challenges are still remaining since non-negligible percentage of transcripts with high abundance were not recovered by the assemblers we considered. Conclusion: de novo assembly is mainly to explore not-yet-discovered isoforms and must be able to represent as much reads as possible in an efficient way. In this sense, TraRECo provides us a potential alternative to improve graph reliability, even though the computational burden can be much higher than single k-mer de Bruijn graph approach.

86075: The LDB1 complex co-opts CTCF for erythroid lineage specific long-range enhancer interactions
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Posted to bioRxiv 17 Apr 2017

The LDB1 complex co-opts CTCF for erythroid lineage specific long-range enhancer interactions
2 downloads molecular biology

Jongjoo Lee, Ivan Krivega, Ryan K. Dale, Ann Dean

Lineage-specific transcription factors are critical for long-range enhancer interactions but direct or indirect contributions of architectural proteins such as CTCF to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that a novel LDB1-bound enhancer upstream of carbonic anhydrase 2 (Car2) activates its expression by interacting directly with CTCF at the gene promoter. Both LDB1 and CTCF are required for enhancer-Car2 looping and the domain of LDB1 contacted by CTCF is necessary to rescue Car2 transcription in LDB1 deficient cells. Genome wide studies and CRISPR/Cas9 genome editing indicate that LDB1-CTCF enhancer looping underlies activation of a substantial fraction of erythroid genes. Our results provide a mechanism by which long-range interactions of architectural protein CTCF can be tailored to achieve a tissue-restricted pattern of chromatin loops and gene expression.

86076: Tree diversity effects on forest productivity increase through time because of spatial partitioning
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Posted to bioRxiv 23 Feb 2020

Tree diversity effects on forest productivity increase through time because of spatial partitioning
2 downloads ecology

Shinichi Tatsumi

Background: Experimental manipulations of tree diversity have often found overyielding in mixed-species plantations. While most experiments are still in the early stages of stand development, the impacts of tree diversity are expected to accumulate over time. Here, I present findings from a 31-year-old tree diversity experiment (as of 2018) in Japan. Results: I find that the net diversity effect on stand biomass increased linearly through time. The species mixture achieved 64% greater biomass than the average monoculture biomass 31 years after planting. The complementarity effect was positive and increased exponentially with time. The selection effect was negative and decreased exponentially with time. In the early stages (≤3 years), the positive complementarity effect was explained by enhanced growths of early- and mid-successional species in the mixture. Later on (≥15 years), it was explained by their increased survival rates owing to vertical spatial partitioning; i.e., alleviation of self-thinning via canopy stratification. The negative selection effect resulted from suppressed growths of late-successional species in the bottom layer. Conclusions: The experiment provides pioneering evidence that the positive impacts of diversity-driven spatial partitioning on forest biomass can accumulate over multiple decades. The results indicate that forest biomass production and carbon sequestration can be enhanced by multispecies afforestation strategies.

86077: Causally investigating cortical dynamics and signal processing by targeting natural system attractors with precisely timed stimulation.
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Posted to bioRxiv 26 Oct 2018

Causally investigating cortical dynamics and signal processing by targeting natural system attractors with precisely timed stimulation.
2 downloads neuroscience

Dmitriy Lisitsyn, Udo A. Ernst

Electrical stimulation is a promising tool for interacting with neuronal dynamics to identify neural mechanisms that underlie cognitive function. Since effects of a single short stimulation pulse typically vary greatly and depend on the current network state, many experimental paradigms have rather resorted to continuous or periodic stimulation in order to establish and maintain a desired effect. However, such an approach explicitly leads to forced and 'unnatural' brain activity. Further, continuous stimulation can make it hard to parse the recorded activity and separate neural signal from stimulation artifacts. In this study we propose an alternate strategy: by monitoring a system in realtime, we use the existing preferred states or attractors of the network and to apply short and precise pulses in order to switch between its preferred states. When pushed into one of its attractors, one can use the natural tendency of the system to remain in such a state to prolong the effect of a stimulation pulse, opening a larger window of opportunity to observe the consequences on cognitive processing. To elaborate on this idea, we consider flexible information routing in the visual cortex as a prototypical example. When processing a stimulus, neural populations in the visual cortex have been found to engage in synchronized gamma activity. In this context, selective signal routing is achieved by changing the relative phase between oscillatory activity in sending and receiving populations (communication through coherence, CTC). In order to explore how perturbations interact with CTC, we investigate a biophysically realistic network exhibiting similar synchronization and signal routing phenomena. We develop a closed-loop stimulation paradigm based on the phase-response characteristics of the network and demonstrate its ability to establish desired synchronization states. By measuring information content throughout the model, we evaluate the effect of signal contamination caused by the stimulation in relation to the magnitude of the injected pulses and intrinsic noise in the system. Finally, we demonstrate that, up to a critical noise level, precisely timed perturbations can be used to artificially induce the effect of attention by selectively routing visual signals to higher cortical areas.

86078: Dense And Accurate Whole-Chromosome Haplotyping Of Individual Genomes
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Posted to bioRxiv 10 Apr 2017

Dense And Accurate Whole-Chromosome Haplotyping Of Individual Genomes
2 downloads bioinformatics

David Porubsky, Shilpa Garg, Ashley D. Sanders, Jan O. Korbel, Victor Guryev, Peter M. Lansdorp, Tobias Marschall

The diploid nature of the genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. Many important biological phenomena such as compound heterozygosity and epistatic effects between enhancers and target genes, however, can only be studied when haplotype-resolved genomes are available. This lack of haplotype-level analyses can be explained by a dearth of methods to produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy that combines global, but sparse haplotypes obtained from strand-specific single cell sequencing (Strand-seq) with dense, yet local, haplotype information available through long-read or linked-read sequencing. Our experiments provide comprehensive guidance on favorable combinations of Strand-seq libraries and sequencing coverages to obtain complete and genome-wide haplotypes of a single individual genome (NA12878) at manageable costs. We were able to reliably assign > 95% of alleles to their parental haplotypes using as few as 10 Strand-seq libraries in combination with 10-fold coverage PacBio data or, alternatively, 10X Genomics linked-read sequencing data. We conclude that the combination of Strand-seq with different sequencing technologies represents an attractive solution to chart the unique genetic variation of diploid genomes.

86079: Demultiplexing overlapping signaling scaffold functions to probe lipid messenger coupling to cytoskeletal dynamics.
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Posted to bioRxiv 14 Jun 2019

Demultiplexing overlapping signaling scaffold functions to probe lipid messenger coupling to cytoskeletal dynamics.
2 downloads biophysics

Nicholaus J. Trenton, R. Tyler McLaughlin, Satya K. Bellamkonda, David S. Tsao, Emily M. Mace, Jordan S. Orange, Volker Schweikhard, Michael R Diehl

The coordination of lipid messenger signaling with cytoskeletal regulation is central to many organelle-specific signaling and regulatory processes. While central to many aspects of cell physiology, this coupling often depends on the function of multi-domain scaffolds that orchestrate transient interactions and dynamic feedback among a spectrum of signaling intermediates and regulatory proteins on organelles. Understanding scaffold protein functions has remained challenging given this complexity. This work employs live-cell imaging and statistical analyses to deconvolve (demultiplex) how the multi-domain scaffold IQGAP1 coordinates phosphoinositide signaling with organelle-specific actin regulation and membrane processing events. Using actin-ensconced endosomes that localize to the basal cortex of polarized epithelial cells as a model system, we demonstrate abilities to dissect how IQGAP1 transitions between different actin and endosomal-membrane tethered states. We provide evidence IQGAP1 functions as a transient inhibitor of actin growth around the endosomes in at least one of these states. While not easily distilled via standard (static) colocalization analyses or traditional pathway perturbations methods, this negative regulation was revealed via a series of dynamic correlation and multiple regression analyses. These methods also uncovered that the negative actin regulation is linked to GTPase-dependent tethering to the endosomal membrane. Moreover, the scaffold transitions underlying this control are shown to depend on the production of PIP3 lipid messengers by the lipid kinase PI3K. Overall, these methods and results provide new insights in to how IQGAP1 act as a signaling hub by orchestrating time-dependent membrane and cytoskeletal protein interactions and provide new routes to dissect scaffold-mediated pathway regulation in a variety of settings.

86080: A Hierarchical Anti-Hebbian Network Model for the Formation of Spatial Cells in Three-Dimensional Space
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Posted to bioRxiv 13 Feb 2018

A Hierarchical Anti-Hebbian Network Model for the Formation of Spatial Cells in Three-Dimensional Space
2 downloads neuroscience

Karthik Soman, Srinivasa Chakravarthy, Michael M Yartsev

Three dimensional (3D) spatial cells in the mammalian hippocampal formation are believed to support the existence of 3D cognitive maps. Modeling studies are crucial to comprehend the neural principles governing the formation of these maps, yet to date very few have addressed this topic in 3D space. Here, we present a hierarchical network model for the formation of 3D spatial cells using anti-hebbian network. Built on empirical data, the model accounts for the natural emergence of 3D place, border and grid-cells as well as a new type of previously undescribed spatial cell type which we call plane cells. It further explains the plausible reason behind the place and grid-cell anisotropic coding that has been observed in rodents and the potential discrepancy with the predicted periodic coding during 3D volumetric navigation. Lastly, it provides evidence for the importance of unsupervised learning rules in guiding the formation of higher dimensional cognitive maps.

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