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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 67,039 bioRxiv papers from 295,099 authors.

Most tweeted bioRxiv papers, last 24 hours

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

21: Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia
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Posted to bioRxiv 06 Dec 2019

Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia
32 tweets neuroscience

Clara Moreau, Sebastien Urchs, Pierre Orban, Catherine Schramm, Guillaume Dumas, Aurelie Labbe, Guillaume Huguet, Elise Douard, Pierre-Olivier Quirion, Amy Lin, Leila Kushan, Stephanie Grot, David Luck, Adrianna Mendrek, Stephane Potvin, Emmanuel Stip, Thomas Bourgeron, Alan C. Evans, SimonsVIP Consortium, Carrie E Bearden, Pierre Bellec, Sebastien Jacquemont

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) networks remains unclear. We analyzed resting-state functional magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We used CNV FC-signatures to identify major dimensions contributing to complex idiopathic conditions. CNVs had large mirror effects on FC at the global and regional level, and their effect-sizes were twice as large as those of idiopathic conditions. Thalamus, somatomotor, and posterior insula regions played a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibited worse behavioral and cognitive symptoms. These seemingly distinct neuropsychiatric mutations showed similar gene co-expression patterns and converged on FC dimensions, that may represent mechanistic building blocks shared across idiopathic conditions.

22: Clair: Exploring the limit of using a deep neural network on pileup data for germline variant calling
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Posted to bioRxiv 05 Dec 2019

Clair: Exploring the limit of using a deep neural network on pileup data for germline variant calling
31 tweets bioinformatics

Ruibang Luo, Chak-Lim Wong, Yat-Sing Wong, Chi-Ian Tang, Chi-Man Liu, Henry C.M. Leung, Tak-Wah Lam

Single-molecule sequencing technologies have emerged in recent years and revolutionized structural variant calling, complex genome assembly, and epigenetic mark detection. However, the lack of a highly accurate small variant caller has limited the new technologies from being more widely used. In this study, we present Clair, the successor to Clairvoyante, a program for fast and accurate germline small variant calling, using single molecule sequencing data. For ONT data, Clair achieves the best precision, recall and speed as compared to several competing programs, including Clairvoyante, Longshot and Medaka. Through studying the missed variants and benchmarking intentionally overfitted models, we found that Clair may be approaching the limit of possible accuracy for germline small variant calling using pileup data and deep neural networks. Clair requires only a conventional CPU for variant calling and is an open source project available at https://github.com/HKU-BAL/Clair.

23: Plant Small RNA Species Direct Gene Silencing in Pathogenic Bacteria as well as Disease Protection
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Posted to bioRxiv 03 Dec 2019

Plant Small RNA Species Direct Gene Silencing in Pathogenic Bacteria as well as Disease Protection
31 tweets plant biology

Meenu SINGLA-RASTOGI, Magali CHARVIN, Odon Thiebeauld, Alvaro L Perez-Quintero, Antinea RAVET, Antonio EMIDIO-FORTUNATO, Venugopal MENDU, Lionel NAVARRO

Plant small RNAs (sRNAs) and/or double-stranded RNAs (dsRNAs) trigger RNA interference (RNAi) in interacting eukaryotic pathogens or parasites. However, it is unknown whether this phenomenon could operate in bacterial phytopathogens, which lack a eukaryoticlike RNAi machinery. Here, we first show that Arabidopsis-encoded inverted repeat transgenes trigger silencing of Pseudomonas syringae heterologous reporter and endogenous virulence-associated genes during infection. Antibacterial Gene Silencing (AGS) of the latter was associated with a reduced pathogenesis, which was also observed upon application of corresponding plant-derived RNAs onto wild-type plants prior to infection. We additionally demonstrate that sRNAs directed against virulence factor transcripts were causal for silencing and pathogenesis reduction, while cognate long dsRNAs were inactive. Overall, this study provides the first evidence that plant sRNAs can directly reprogram gene expression in a phytopathogenic bacterium and may have wider implications in the understanding of how plants regulate transcriptome, community composition and genome evolution of associated bacteria.

24: Controlling the speed and trajectory of evolution with counterdiabatic driving
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Posted to bioRxiv 06 Dec 2019

Controlling the speed and trajectory of evolution with counterdiabatic driving
30 tweets evolutionary biology

Shamreen Iram, Emily Dolson, Joshua Chiel, Julia Pelesko, Nikhil Krishnan, Özenç Güngör, Benjamin Kuznets-Speck, Sebastian Deffner, Efe Ilker, Jacob G Scott, Michael Hinczewski

The pace and unpredictability of evolution are critically relevant in a variety of modern challenges: combating drug resistance in pathogens and cancer, understanding how species respond to environmental perturbations like climate change, and developing artificial selection approaches for agriculture. Great progress has been made in quantitative modeling of evolution using fitness landscapes, allowing a degree of prediction for future evolutionary histories. Yet fine-grained control of the speed and the distributions of these trajectories remains elusive. We propose an approach to achieve this using ideas originally developed in a completely different context: counterdiabatic driving to control the behavior of quantum states for applications like quantum computing and manipulating ultra-cold atoms. Implementing these ideas for the first time in a biological context, we show how a set of external control parameters (i.e. varying drug concentrations / types, temperature, nutrients) can guide the probability distribution of genotypes in a population along a specified path and time interval. This level of control, allowing empirical optimization of evolutionary speed and trajectories, has myriad potential applications, from enhancing adaptive therapies for diseases, to the development of thermotolerant crops in preparation for climate change, to accelerating bioengineering methods built on evolutionary models, like directed evolution of biomolecules.

25: Learning cognitive maps for vicarious evaluation
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Posted to bioRxiv 06 Dec 2019

Learning cognitive maps for vicarious evaluation
27 tweets neuroscience
26: A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila
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Posted to bioRxiv 13 May 2019

A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila
26 tweets genetics

Fillip Port, Claudia Strein, Mona Stricker, Benedikt Rauscher, Florian Heigwer, Jun Zhou, Celine Beyersdörffer, Jana Frei, Amy Hess, Katharina Kern, Roberta Malamud, Bojana Pavlovic, Kristin Rädecke, Lukas Schmitt, Lukas Voos, Erica Valentini, Michael Boutros

Genetic screens are powerful tools for the functional annotation of genomes. In the context of multicellular organisms, interrogation of gene function is greatly facilitated by methods that allow spatial and temporal control of gene abrogation. Here, we describe a large-scale transgenic short guide (sg) RNA library for efficient CRISPR-based disruption of specific target genes in a constitutive or conditional manner. The library consists currently of more than 2600 plasmids and 1600 fly lines with a focus on targeting kinases, phosphatases and transcription factors, each expressing two sgRNAs under control of the Gal4/UAS system. We show that conditional CRISPR mutagenesis is robust across many target genes and can be efficiently employed in various somatic tissues, as well as the germline. In order to prevent artefacts commonly associated with excessive amounts of Cas9 protein, we have developed a series of novel UAS-Cas9 transgenes, which allow fine tuning of Cas9 expression to achieve high gene editing activity without detectable toxicity. Functional assays, as well as direct sequencing of genomic sgRNA target sites, indicates that the vast majority of transgenic sgRNA lines mediate efficient gene disruption. Furthermore, we conducted the so far largest fully transgenic CRISPR screen in any metazoan organism, which further supported the high efficiency and accuracy of our library and revealed many so far uncharacterized genes essential for development.

27: Transposable element landscape in Drosophila populations selected for longevity
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Posted to bioRxiv 06 Dec 2019

Transposable element landscape in Drosophila populations selected for longevity
25 tweets evolutionary biology

Daniel Fabian, Handan Melike Donertas, Matias Fuentealba Valenzuela, Linda Partridge, Janet M. Thornton

Transposable elements (TEs) inflict numerous negative effects on health and fitness as they replicate by integrating into new regions of the host genome. Even though organisms utilize powerful mechanisms to demobilize TEs, transposons become increasingly derepressed during aging. The rising TE activity causes genomic instability and was suggested to be involved in age-dependent neurodegenerative diseases, inflammation and the determination of lifespan. It is therefore conceivable that long-lived individuals have improved TE silencing mechanisms and consequently fewer genomic insertions and a reduced TE expression relative to their shorter-lived counterparts. Here, we test this hypothesis by performing the first analysis of genome-wide insertions and expression of TEs in populations of Drosophila melanogaster selected for longevity through late-life reproduction for 50-170 generations from four independent studies. Surprisingly, we found that TE families were generally more abundant in long-lived populations compared to non-selected controls. Despite simulations showed that this was not expected under neutrality, we found little evidence for selection driving TE abundance differences. Additional RNA-seq analysis revealed only few differentially expressed TEs whereas reducing TE expression might be more important than regulating genomic insertions. We further find limited evidence of parallel selection on genes related to TE regulation and transposition. However, telomeric TEs were genomically and transcriptionally more abundant in long-lived flies, suggesting improved telomere maintenance as a promising TE-mediated mechanism prolonging lifespan. Our results provide a novel viewpoint proposing that reproduction at old age increases the opportunity of TEs to be passed on to the next generation with little impact on longevity.

28: On the discovery of population-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data
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Posted to bioRxiv 26 Jul 2019

On the discovery of population-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data
23 tweets bioinformatics

Helena L Crowell, Charlotte Soneson, Pierre-Luc Germain, Daniela Calini, Ludovic Collin, Catarina Raposo, Dheeraj Malhotra, Mark D Robinson

Single-cell RNA sequencing (scRNA-seq) has quickly become an empowering technology to profile the transcriptomes of individual cells on a large scale. Many early analyses of differential expression have aimed at identifying differences between subpopulations, and thus are focused on finding markers for cell populations either in a single sample or across multiple samples. More generally, such methods can compare expression levels in multiple sets of cells, thus leading to cross-condition analyses. However, given the emergence of replicated multi-condition scRNA-seq datasets, an area of increasing focus is making sample-level inferences, termed here as differential state analysis. For example, one could investigate the condition-specific responses of cell populations measured from patients from each condition; however, it is not clear which statistical framework best handles this situation. In this work, we surveyed the methods available to perform cross-condition differential state analyses, including cell-level mixed models and methods based on aggregated pseudobulk data. We developed a flexible simulation platform that mimics both single and multi-sample scRNA-seq data and provide robust tools for multi-condition analysis within the muscat R package.

29: Tracking selective rehearsal and active inhibition of memory traces in directed forgetting
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Posted to bioRxiv 05 Dec 2019

Tracking selective rehearsal and active inhibition of memory traces in directed forgetting
22 tweets neuroscience

Marie-Christin Fellner, Gerd T. Waldhauser, Nikolai Axmacher

Selectively remembering or forgetting newly encountered information is essential for goal-directed behavior. It is still an open question, however, whether intentional forgetting is an active process based on the inhibition of unwanted memory traces or whether it occurs passively through reduced recruitment of selective rehearsal. Here we show that intentional control of memory encoding relies on both, enhanced active inhibition and decreased selective rehearsal, and that these two processes can be separated in time and space. We applied representational similarity analysis (RSA) and time-frequency analysis to EEG data during an item-method directed forgetting experiment. We identified neural signatures of both the intentional suppression and the voluntary upregulation of item-specific representations. Successful active forgetting was associated with a downregulation of item-specific representations in an early time window, 500ms after the instruction. This process was initiated by an increase in oscillatory alpha (8-13 Hz) power, a well-established signature of neural inhibition, in occipital brain areas. During a later time window, 1500ms after the cue, intentional forgetting was associated with reduced employment of active rehearsal processes, as reflected by an attenuated upregulation of item-specific representations as compared to intentionally encoded items. Our data show that active inhibition and selective rehearsal are two separate mechanisms whose consecutive employment allows for a voluntary control of memory formation.

30: Summer drought decreases the predictability of local extinctions in a butterfly metapopulation
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Posted to bioRxiv 04 Dec 2019

Summer drought decreases the predictability of local extinctions in a butterfly metapopulation
22 tweets ecology

Erik van Bergen, Tad Dallas, Michelle F DiLeo, Aapo Kahilainen, Anniina L. K. Mattila, Miska Luoto, Marjo Saastamoinen

The ecological impacts of extreme climatic events on population dynamics and/or community composition are profound and predominantly negative. Here, using extensive data of an ecological model system, we test whether predictions from ecological models remain robust when environmental conditions are outside the bounds of observation. First, we report a 10-fold demographic decline of the Glanville fritillary butterfly metapopulation on the Aland islands (Finland). Next, using climatic and satellite data we show that the summer of 2018 was an anomaly in terms of water balance and vegetation productivity indices across the habitats of the butterfly, and demonstrate that population growth rates are strongly associated with spatio-temporal variation in climatic water balance. Finally, we demonstrate that covariates that have previously been identified to impact the extinction probability of local populations in this system are less informative when populations are exposed to (severe) drought during the summer months. Our results highlight the unpredictable responses of natural populations to extreme climatic events.

31: Distinct activities of Scrib module proteins organize epithelial polarity
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Posted to bioRxiv 06 Dec 2019

Distinct activities of Scrib module proteins organize epithelial polarity
22 tweets developmental biology

Mark J Khoury, David Bilder

A polarized architecture is central to both epithelial structure and function. In many cells, polarity involves mutual antagonism between the Par complex and the Scrib module. While molecular mechanisms underlying Par-mediated apical determination are well-understood, how Scrib module proteins specify the basolateral domain remains unknown. Here, we demonstrate dependent and independent activities of Scrib, Dlg and Lgl using the Drosophila follicle epithelium. Our data support a linear hierarchy for localization, but rule out previously proposed protein-protein interactions as essential for polarization. Membrane recruitment of Scrib does not require palmitoylation or polar phospholipid binding but instead an independent cortically-stabilizing activity of Dlg. Scrib and Dlg do not directly antagonize aPKC, but may instead restrict aPKC localization by enabling the aPKC-inhibiting activity of Lgl. Importantly, while Scrib, Dlg and Lgl are each required, all three together are not sufficient to antagonize the Par complex. Our data demonstrate previously unappreciated diversity of function within the Scrib module and begin to define the elusive molecular functions of Scrib and Dlg.

32: The smfBox: an open-source platform for single-molecule FRET
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Posted to bioRxiv 05 Dec 2019

The smfBox: an open-source platform for single-molecule FRET
22 tweets biophysics

Benjamin Ambrose, James Baxter, John Cully, Matthew Willmott, Elliot Steele, Benji C. Bateman, Marisa L. Martin-Fernandez, Ashley Cadby, Jonathan Shewring, Marleen Aaldering, Timothy D Craggs

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful technique capable of resolving both relative and absolute distances within and between structurally dynamic biomolecules. High instrument costs, and a lack of open-source hardware and acquisition software have limited smFRET's broad application by non-specialists. Here, we present the smfBox, a cost-effective confocal smFRET platform, providing detailed build instructions, open-source acquisition software, and full validation, thereby democratising smFRET for the wider scientific community.

33: An updated antennal lobe atlas for the yellow fever mosquito Aedes aegypti
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Posted to bioRxiv 05 Dec 2019

An updated antennal lobe atlas for the yellow fever mosquito Aedes aegypti
20 tweets neuroscience

Shruti Shankar, Conor J. McMeniman

The yellow fever mosquito Aedes aegypti is a prolific vector of arboviral and filarial diseases that largely relies on its sense of smell to find humans. To facilitate in-depth analysis of the neural circuitry underlying Ae. aegypti olfactory-driven behaviors, we generated an updated in vitro atlas for the antennal lobe olfactory brain region of this disease vector using two independent neuronal staining methods. We performed morphological reconstructions with replicate fixed, dissected and stained brain samples from adult male and female Ae. aegypti of the LVPib12 genome reference strain and determined that the antennal lobe in both sexes is comprised of approximately 80 discrete glomeruli. Guided by landmark features in the antennal lobe, we found 63 of these glomeruli are stereotypically located in spatially invariant positions within these in vitro preparations. A posteriorly positioned, mediodorsal glomerulus denoted MD1 was identified as the largest spatially invariant glomerulus in the antennal lobe. Spatial organization of glomeruli in a recently field-derived strain of Ae. aegypti from Puerto Rico was conserved, despite differences in antennal lobe shape relative to the inbred LVPib12 strain. This model in vitro atlas will serve as a useful community guide and resource to improve antennal lobe annotation and anatomically map projection patterns of neurons expressing target genes in this olfactory center. It will also facilitate the development of chemotopic maps of odor representation in the mosquito antennal lobe to decode the molecular and cellular basis of Ae. aegypti attraction to human scent and other chemosensory cues.

34: Rootstock choice can dramatically affect grapevine growth
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Posted to bioRxiv 05 Dec 2019

Rootstock choice can dramatically affect grapevine growth
18 tweets plant biology

Zoë Migicovsky, Peter Cousins, Lindsay M. Jordan, Sean Myles, Richard Keith Striegler, Paul Verdegaal, Daniel H. Chitwood

Grape growers use rootstocks to provide protection against pests and pathogens and to modulate viticulture performance such as shoot growth. Our study examined two grapevine varieties ('Chardonnay' and 'Cabernet Sauvignon') grafted to 15 different rootstocks and determined the effect of rootstocks on eight traits important to viticulture. We assessed the vines across five years and identified both year and variety as contributing strongly to trait variation. However, the effect of rootstock was relatively consistent across years and varieties, explaining between 9% and 10% of the variation in growth-related traits including yield, pruning weight, berry weight, and Ravaz index (yield to pruning weight ratio). Increases in yield due to rootstock were generally the result of increases in berry weight, likely due to increased water uptake by vines grafted to a particular rootstock. We determined that it is possible to achieve an over 50% increase in yield, pruning weight, and Ravaz index by choosing the optimal rootstock, indicating that rootstock choice is crucial for grape growers looking to improve vine performance.

35: On deleterious mutations in perennials: inbreeding depression, mutation load and life-history evolution
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Posted to bioRxiv 05 Dec 2019

On deleterious mutations in perennials: inbreeding depression, mutation load and life-history evolution
18 tweets evolutionary biology

Thomas Lesaffre, Sylvain Billiard

In Angiosperms, perennials typically present much higher levels of inbreeding depression than annuals. The mechanisms leading to this pattern are poorly understood. In fact, despite the potential significance of this pattern for important evolutionary questions, only two hypotheses have been proposed to explain it. Based on the fact that mutations occurring in somatic tissues may be passed onto the offspring in plants, because they do not have a segregated germline, the first hypothesis states that more long-lived species may accumulate more somatic mutations as they grow, thereby generating higher inbreeding depression. The second hypothesis, which is not in contradiction with the first, stems from the observation that inbreeding depression is typically expressed across multiple life stages in Angiosperms. It posits that increased inbreeding depression in more long-lived species could also be explained by the fact that mutations, regardless of whether they are produced during mitosis or meiosis, may differ in the way they affect fitness in annual and perennial populations, through the life stages at which they are expressed. In this study, we aim to investigate the second hypothesis, setting aside somatic mutations accumulation. We combine a physiological growth model and multilocus population genetics approaches in order to describe a full genotype-to-phenotype-to-fitness map, where the phenotype relates to fitness through biological assumptions, so that the fitness landscape emerges from biological assumptions instead of being assumed a priori. We study the behaviour of different types of mutations affecting growth or survival, and explore their consequences in terms of inbreeding depression and mutation load. Then, we discuss the role deleterious mutations maintained at mutation-selection balance may play in the coevolution between growth and survival strategies.

36: Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning
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Posted to bioRxiv 04 Dec 2019

Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning
17 tweets genomics

Martin Smith, Tansel Ersavas, James M. Ferguson, Huanle Liu, Morghan C Lucas, Oguzhan Begik, Lilly Bojarski, Kirston Barton, Eva Maria Novoa

Nanopore sequencing has enabled sequencing of native RNA molecules without conversion to cDNA, thus opening the gates to a new era for the unbiased study of RNA biology. However, a formal barcoding protocol for direct sequencing of native RNA molecules is currently lacking, limiting the efficient processing of multiple samples in the same flowcell. A major limitation for the development of barcoding protocols for direct RNA sequencing is the error rate introduced during the base-calling process, especially towards the 5' and 3' ends of reads, which complicates sequence-based barcode demultiplexing. Here, we propose a novel strategy to barcode and demultiplex direct RNA sequencing nanopore data, which does not rely on base-calling or additional library preparation steps. Specifically, custom DNA oligonucleotides are ligated to RNA transcripts during library preparation. Then, raw current signal corresponding to the DNA barcode is extracted and transformed into an array of pixels, which is used to determine the underlying barcode using a deep convolutional neural network classifier. Our method, DeePlexiCon, implements a 20-layer residual neural network model that can demultiplex 93% of the reads with 95.1% specificity, or 60% of reads with 99.9% specificity. The availability of an efficient and simple barcoding strategy for native RNA sequencing will enhance the use of direct RNA sequencing by making it more cost-effective to the entire community. Moreover, it will facilitate the applicability of direct RNA sequencing to samples where the RNA amounts are limited, such as patient-derived samples.

37: Nanopore direct RNA sequencing maps an Arabidopsis N6 methyladenosine epitranscriptome
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Posted to bioRxiv 17 Jul 2019

Nanopore direct RNA sequencing maps an Arabidopsis N6 methyladenosine epitranscriptome
16 tweets molecular biology

Matthew T Parker, Katarzyna Knop, Anna V Sherwood, Nicholas J Schurch, Katarzyna Mackinnon, Peter D. Gould, Anthony Hall, Geoffrey J Barton, Gordon G Simpson

Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant Arabidopsis thaliana and a mutant defective in mRNA methylation (m6A). Here we show that m6A can be mapped in full-length mRNAs transcriptome-wide and reveal the combinatorial diversity of cap-associated transcription start sites, splicing events, poly(A) site choice and poly(A) tail length. Loss of m6A from 3′ untranslated regions is associated with decreased relative transcript abundance and defective RNA 3′ end formation. A functional consequence of disrupted m6A is a lengthening of the circadian period. We conclude that nanopore direct RNA sequencing can reveal the complexity of mRNA processing and modification in full-length single molecule reads. These findings can refine Arabidopsis genome annotation. Further, applying this approach to less well-studied species could transform our understanding of what their genomes encode.

38: d-Lysergic acid diethylamide has major potential as a cognitive enhancer
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Posted to bioRxiv 06 Dec 2019

d-Lysergic acid diethylamide has major potential as a cognitive enhancer
16 tweets neuroscience

Felipe A Cini, Isis Ornelas, Encarni Marcos, Livia Goto-Silva, Juliana Nascimento, Sergio Ruschi, Jose Salerno, Karina Karmirian, Marcelo Costa, Eduardo Sequerra, Draulio B de Araujo, Luis Fernando Tofoli, Cesar Renno-Costa, Daniel Martins-de-Souza, Amanda Feilding, Stevens Rehen, Sidarta Ribeiro

Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains uncharted. Here we show that a single dose of d-LSD, a potent serotonergic agonist, increased novel object preference in young and adult rats several days after treatment. d-LSD alone did not increase preference in old animals, but could rescue it to young levels when followed by a 6-day exposure to enriched environment (EE). Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions, with alterations of long-range synapses. Better pattern separation within EE explained its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.

39: Combining high-resolution AFM with MD simulations shows that DNA supercoiling induces kinks and defects that enhance flexibility and recognition.
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Posted to bioRxiv 05 Dec 2019

Combining high-resolution AFM with MD simulations shows that DNA supercoiling induces kinks and defects that enhance flexibility and recognition.
15 tweets biophysics

Alice L B Pyne, Agnes Noy, Kavit Main, Victor Velasco-Berrelleza, Michael M. Piperakis, Lesley A. Mitchenhall, Fiorella M. Cugliandolo, Joseph G. Beton, Clare E M Stevenson, Bart W Hoogenboom, Andrew D. Bates, Anthony Maxwell, Sarah A. Harris

In the cell, DNA is arranged into highly organised and topologically constrained (supercoiled) structures. It remains unclear how this supercoiling affects the double-helix structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations by a combination of atomic force microscopy (AFM) and atomistic molecular dynamics (MD) simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. We observe that negative superhelical stress induces local variation in the canonical B-form DNA structure by introducing kinks and defects that affect global minicircle structure and flexibility. We probe how these local and global conformational changes affect DNA interactions through the binding of triplex-forming oligonucleotides to DNA minicircles. We show that the energetics of triplex formation is governed by a delicate balance between electrostatics and bonding interactions. Our results provide mechanistic insight into how DNA supercoiling can affect molecular recognition of diverse conformational substrates.

40: Local axonal conduction delays underlie precise timing of a neural sequence
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Posted to bioRxiv 05 Dec 2019

Local axonal conduction delays underlie precise timing of a neural sequence
15 tweets neuroscience

Robert Egger, Yevhen Tupikov, Kalman A Katlowitz, Sam E Benezra, Michel A Picardo, Felix Moll, Joergen Kornfeld, Dezhe Z. Jin, Michael A Long

Sequential activation of neurons has been observed during various behavioral and cognitive processes and is thought to play a critical role in their generation. Here, we studied a circuit in the songbird forebrain that drives the performance of adult courtship song. In this region, known as HVC, neurons are sequentially active with millisecond precision in relation to behavior. Using large-scale network models, we found that HVC sequences could only be accurately produced if sequentially active neurons were linked with long and heterogeneous axonal conduction delays. Although such latencies are often thought to be negligible in local microcircuits, we empirically determined that HVC interconnections were surprisingly slow, generating delays up to 22 ms. An analysis of anatomical reconstructions suggests that similar processes may also occur in rat neocortex, supporting the notion that axonal conduction delays can sculpt the dynamical repertoire of a range of local circuits.

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