bluuebunny/crossref_metadata_2025_split huggingface dataset:
Searching for Consistent Brain Network Topologies Across the Garden of (Shortest) Forking Paths
Authors: Luppi Andrea I. , Gellersen Helena M. , Peattie Alex R. D. , Manktelow Anne E. , Menon David K. , Dimitriadis Stavros I. , Stamatakis Emmanuel A. 
Published: July 2021

AbstractThe functional interactions between regions of the human brain can be viewed as a network, empowering neuroscientists to leverage tools such as graph theory to obtain insight about brain function. However, obtaining a brain network from functional neuroimaging data inevitably involves multiple steps of data manipulation, which can affect the organisation (topology) of the resulting network and its properties. Test-retest reliability is a gold standard for both basic research and clinical use: a suitable data-processing pipeline for brain networks should recover the same network topology across repeated scan sessions of the same individual. Analyzing resting-state functional Magnetic Resonance Imaging (rs-fMRI) recordings from two test-retest studies across short (45 minutes), medium (2-4 weeks) and long term delays (5-16 months), we investigated the reliability of network topologies constructed by applying 576 unique pipelines to the same fMRI data, obtained from considering combinations of atlas type and size, edge definition and thresholding, and use of global signal regression. We adopted the portrait divergence, an information-theoretic criterion to measure differences in network topology across all scales, enabling us to quantify the influence of different pipelines on the overall organisation of the resulting network. Remarkably, our findings reveal that the choice of pipeline plays a fundamental role in determining how reproducible an individual’s brain network topology will be across different scans: there is large and systematic variability across pipelines, such that an inappropriate choice of pipeline can distort the resulting network more than an interval of several months between scans. Across datasets and time-spans, we also identify specific combinations of data-processing steps that consistently yield networks with reproducible topology, enabling us to make recommendations about best practices to ensure high-quality brain networks.
High-throughput aminoacyl-tRNA synthetase engineering for genetic code expansion in yeast
Authors: Stieglitz Jessica T. , Van Deventer James A. 
Published: July 2021

AbstractProtein expression with genetically encoded noncanonical amino acids (ncAAs) benefits a broad range of applications, from the discovery of biological therapeutics to fundamental biological studies. A major factor limiting the use of ncAAs is the lack of orthogonal translation systems (OTSs) that support efficient genetic code expansion at repurposed stop codons. Aminoacyl-tRNA synthetases (aaRSs) have been extensively evolved in E. coli but are not always orthogonal in eukaryotes. In this work, we use a yeast display-based ncAA incorporation reporter platform with fluorescence-activated cell sorting to screen libraries of aaRSs in high throughput for 1) incorporation of ncAAs not previously encoded in yeast; 2) improvement of the performance of an existing aaRS; 3) highly selective OTSs capable of discriminating between closely related ncAA analogs; and 4) OTSs exhibiting enhanced polyspecificity to support translation with structurally diverse sets of ncAAs. The number of previously undiscovered aaRS variants we report in this work more than doubles the total number of translationally active aaRSs available for genetic code manipulation in yeast. The success of myriad screening strategies has important implications related to the fundamental properties and evolvability of aaRSs. Furthermore, access to OTSs with diverse activities and specific or polyspecific properties is invaluable for a range of applications within chemical biology, synthetic biology, and protein engineering.SynopsisA range of flow cytometry-based screens yielded diverse translational machinery for genetic code expansion in yeast, facilitating access to new chemistries and tunable specificity profiles.Abstract Figure
Cortical cell ensemble control of past experience-dependent memory updating
Authors: Suzuki Akinobu , Kosugi Sakurako , Murayama Emi , Sasakawa Eri , Ohkawa Noriaki , Konno Ayumu , Hirai Hirokazu , Inokuchi Kaoru 
Published: July 2021

SummaryWhen processing current sensory inputs, animals refer to related past experiences. Current information is then incorporated into the related neural network to update previously stored memories. However, the neuronal mechanism underlying the impact of memories of prior experiences on current learning is not well understood. Here, we found that a cellular ensemble in the posterior parietal cortex (PPC) that is activated during past experience mediates an interaction between past and current information to update memory through a PPC-anterior cingulate cortex circuit in mice. Moreover, optogenetic silencing of the PPC ensemble immediately after retrieval dissociated the interaction without affecting individual memories stored in the hippocampus and amygdala. Thus, a specific subpopulation of PPC cells represents past information and instructs downstream brain regions to update previous memories.
A Floxed exon (Flexon) approach to Cre-mediated conditional gene expression
Authors: Shaffer Justin M. , Greenwald Iva 
Published: July 2021

ABSTRACTConditional gene expression allows for genes to be manipulated and lineages to be marked during development. In the established “lox-stop-lox” approach, Cre-mediated tissue-specific gene expression is achieved by excising the stop cassette, a lox-flanked translational stop that is inserted into the 5′ untranslated region of a gene to halt its expression. Although lox-stop-lox has been successfully used in many experimental systems, the design of traditional stop cassettes also has common issues and limitations. Here, we describe the Floxed exon (Flexon), a stop cassette within an artificial exon that can be inserted flexibly into the coding region of any gene to cause premature termination of translation and nonsense-mediated decay of the mRNA. We demonstrate its efficacy in C. elegans by showing that, when promoters that cause weak and/or transient cell-specific expression are used to drive Cre in combination with a gfp(flexon) transgene, strong and sustained expression is obtained in specific lineages. We also describe several potential additional applications for using Flexon for developmental studies, including more precise control of gene expression using intersectional methods, tissue-specific protein degradation or RNAi, and generation of genetic mosaics. The Flexon approach should be feasible in any system where any site-specific recombination-based method may be applied.Summary statementThe Floxed exon (Flexon), a stop cassette that can be inserted flexibly into the coding region of any gene, facilitates Cre-mediated conditional gene expression.
Estimating dispersal rates and locating genetic ancestors with genome-wide genealogies
Authors: Osmond Matthew M , Coop Graham 
Published: July 2021

AbstractSpatial patterns in genetic diversity are shaped by individuals dispersing from their parents and larger-scale population movements. It has long been appreciated that these patterns of movement shape the underlying genealogies along the genome leading to geographic patterns of isolation by distance in contemporary population genetic data. However, extracting the enormous amount of information contained in genealogies along recombining sequences has, until recently, not been computationally feasible. Here we capitalize on important recent advances in genome-wide gene-genealogy reconstruction and develop methods to use thousands of trees to estimate per-generation dispersal rates and to locate the genetic ancestors of a sample back through time. We take a likelihood approach in continuous space using a simple approximate model (branching Brownian motion) as our prior distribution of spatial genealogies. After testing our method with simulations we apply it toArabidopsis thaliana. We estimate a dispersal rate of roughly 60km2per generation, slightly higher across latitude than across longitude, potentially reflecting a northward post-glacial expansion. Locating ancestors allows us to visualize major geographic movements, alternative geographic histories, and admixture. Our method highlights the huge amount of information about past dispersal events and population movements contained in genome-wide genealogies.
A Lethal Genetic Incompatibility between Naturally Hybridizing Species in Mitochondrial Complex I
Authors: Moran Benjamin M. , Payne Cheyenne Y. , Powell Daniel L. , Iverson Erik N. K. , Donny Alex E. , Banerjee Shreya M. , Langdon Quinn K. , Gunn Theresa R. , Rodriguez-Soto Rebecca A. , Madero Angel , Baczenas John J. , Kleczko Korbin M. , Liu Fang , Matney Rowan , Singhal Kratika , Leib Ryan D. , Hernandez-Perez Osvaldo , Corbett-Detig Russell , Frydman Judith , Gifford Casey , Schartl Manfred , Havird Justin C. , Schumer Molly 
Published: July 2021

AbstractThe evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of “hybrid incompatibilities,” where alleles derived from two different species no longer interact properly in hybrids. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes and that incompatibilities involving multiple genes should be common, but there has been sparse empirical data to evaluate these predictions. Here, we describe a mitonuclear incompatibility involving three genes in physical contact within respiratory Complex I in naturally hybridizing swordtail fish species. Individuals homozygous for specific mismatched protein combinations fail to complete embryonic development or die as juveniles, while those heterozygous for the incompatibility have reduced function of Complex I and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the impacts of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. We document the evolutionary history of the genes involved, showing for the first time that an incompatibility has been transferred between species via hybridization. This work thus provides the first glimpse into the genetic architecture, physiological impacts, and evolutionary origin of a complex incompatibility impacting naturally hybridizing species.
Nitrogen uptake and macronutrients distribution in mango trees (cv. Keitt) under three N fertigation treatments
Authors: Silber A. , Goldberg T. , Shapira O. , Hochberg U. 
Published: July 2021

AbstractWe assessed the effects of N concentration in the irrigation water on nutrient uptake and distribution in leaves and fruit of mango cv. Keitt grown in a lysimeter for four years. We applied three treatments: N1 – no N fertilization (less than 2 mg/L in the tap water); N2 – 10 mg/L N; N3 – 20 mg/L N.Deficient N conditions (N1) generated low vegetative yield, high fruit:leaf ratio, high photosynthetic activity, high leaf P and K concentrations, and high sugar content along with low acidity in the fruit. Excess N concentration (N3) induced vegetative growth, and reduced fruit yield and gas-exchange characteristics. The calculated annual nitrogen uptake heavily depended on the nitrogen supply (N1-26 g/tree; N2-196 g/tree; N3- 185 g/tree).Fruits were the major N sink being 0.82, 0.26 and 0.05 from the total annual N supplied. The N quantities accumulated in N1 fruits during the reproductive season (May-August), were above the N quantities supplied via fertigation, suggesting that N reserve in the vegetative tissues supplied the fruit’s high N demand.The finding shows the importance of adequate nitrogen supply to mango trees and the dangers of excessive fertilization.
Correlated transcriptional responses provide insights into the synergy mechanisms of the furazolidone, vancomycin and sodium deoxycholate triple combination in Escherichia coli
Authors: Olivera Catrina , Cox Murray , Rowlands Gareth J. , Rakonjac Jasna 
Published: July 2021

AbstractEffective therapeutic options are urgently needed to tackle antibiotic resistance. Furazolidone (FZ), vancomycin (VAN), and sodium deoxycholate (DOC) show promise as their combination can synergistically inhibit the growth of, and kill, multidrug-resistant Gram-negative bacteria that are classified as critical priority by the World Health Organization. Here, we investigated the mechanisms of action and synergy of this drug combination using a transcriptomics approach in the model bacterium Escherichia coli. We show that FZ and DOC elicit highly similar gene perturbations indicative of iron starvation, decreased respiration and metabolism, and translational stress. In contrast, VAN induced envelope stress responses, in agreement with its known role in peptidoglycan synthesis inhibition. FZ induced the SOS response consistent with its DNA damaging effects, but we demonstrate that using FZ in combination with the other two compounds enables use of lower dosages and largely mitigates its mutagenic effects. Based on the gene expression changes identified, we propose a synergy mechanism where the combined effects of FZ, VAN, and DOC amplify damage to Gram-negative bacteria while simultaneously suppressing antibiotic resistance mechanisms.ImportanceSynergistic combinations of existing antibacterials against multidrug-resistant “superbugs” are an alternative strategy to costly and arduous development of novel antibacterial molecules. The synergistic combination of nitrofurans, vancomycin and sodium deoxycholate shows promise in inhibiting and killing multidrug-resistant Gram-negative bacteria. We examined the mechanism of action and synergy of these three antibacterials, and proposed a mechanistic basis for their synergy. Our results highlight much needed mechanistic information necessary to advance this combination as a potential therapy.
NPDS Toolbox: Neural Population (De)Synchronization toolbox for Matlab
Authors: Moayeri Mohammad Mahdi , Hemami Mohammad , Rad Jamal Amani , Parand Kourosh 
Published: July 2021

AbstractThe study of synchronous or asynchronous in (stochastic) neuronal populations is an important concept both in theory and in practice in neuroscience. The NPDS toolbox provides an interactive simulation platform for exploring such processes in Matlab looking through the lens of nonlinear dynamical systems. NPDS includes two main components: neural population (de)synchronization, and neural dynamics. One can investigate distribution controls on various neural models such as HH, FHN, RH, and Thalamic. Also, it supports many numerical approaches for simulation: finite-difference, pseudo-spectral, radial basis function, and Fourier methods. In addition, this toolbox can be used for population phase shifting and clustering.
Design of complicated all-α protein structures
Authors: Sakuma Koya , Kobayashi Naohiro , Sugiki Toshihiko , Nagashima Toshio , Fujiwara Toshimichi , Suzuki Kano , Kobayashi Naoya , Murata Takeshi , Kosugi Takahiro , Koga Rie , Koga Nobuyasu 
Published: July 2021

AbstractA wide range of de novo protein structure designs have been achieved, but the complexity of naturally occurring protein structures is still far beyond these designs. To expand the diversity and complexity of de novo designed protein structures, we sought to develop a method for designing “difficult-to-describe”α-helical protein structures composed of irregularly aligned α-helices like globins. Backbone structure libraries consisting of a myriad of α-helical structures with 5- or 6-helices were generated by combining 18 helix-loop-helix motifs and canonical α-helices, and five distinct topologies were selected for de novo design. The designs were found to be monomeric with high thermal stability in solution and fold into the target topologies with atomic accuracy. This study demonstrated that complicated α-helical proteins are created using typical building blocks. The method we developed would enable us to explore the universe of protein structures for designing novel functional proteins.
Ribocutter: Cas9-mediated rRNA depletion from multiplexed Ribo-seq libraries
Authors: Wilkins Oscar G. , Ule Jernej 
Published: July 2021

AbstractRNA sequencing libraries produced from fragmented RNA, especially Ribo-seq libraries, contain high proportions of reads from abundant non-coding RNAs. Here, we describe a streamlined Cas9-based protocol for removing abundant rRNA/ncRNA contaminants from Ribo-seq (or other small RNA-seq) libraries and an easy-to-use software tool, ribocutter, for designing ready-to-order sgRNA templates. Following sgRNA template design, the pool of templates is in vitro transcribed using a 1-step commercial kit, which produces enough sgRNAs for multiple treatments. A single multiplexed sequencing library is then treated with Cas9/sgRNAs, followed by a short PCR program, which can increase the fraction of useful reads by more than 3-fold. Comparison of samples before and after depletion demonstrates that Cas9 produces minimal off-target effects and preserves key features (eg. footprint length, periodicity) of Ribo-seq libraries. The method is thus highly effective, costs <£0.50 per sample, and minimises non-specific depletion and technical variation between samples.
Lightning Fast and Highly Sensitive Full-Length Single-cell sequencing using FLASH-Seq
Authors: Hahaut Vincent , Pavlinic Dinko , Cowan Cameron , Picelli Simone 
Published: July 2021

AbstractIn the last 10 years, single-cell RNA-sequencing (scRNA-seq) has undergone exponential growth. Emulsion droplets methods1–3, such as those commercialized by 10x Genomics, have allowed researchers to analyze tens of thousands of cells in parallel in a robust and reproducible way. However, in contrast to SMART-based full-length sequencing protocols4,5, these methods interrogate only the outer portion of the transcripts and still lack the required sensitivity for analyzing comprehensively the transcriptome of individual cells. Building upon the existing SMART-seq forerunners protocols4,5, we developed FLASH-Seq (FS), a new scRNA-seq method which displays greater sensitivity while decreasing incubation times and reducing the number of processing steps compared to its predecessors. The entire FS protocol - from lysed cells to pooled cDNA libraries - can be performed in ~4.5 hours, is automation-friendly and can be easily miniaturized to decrease costs.
cylcop: An R Package for Circular-Linear Copulae with Angular Symmetry
Authors: Hodel Florian H. , Fieberg John R. 
Published: July 2021

AbstractThe R packagecylcopextends thecopulapackage to allow modeling of correlated circular-linear random variables using copulae that are symmetric in the circular dimension. We present and derive several new circular-linear copulae with this property and demonstrate how they can be implemented in thecylcoppackage to model animal movements in discrete time. The package contains methods for estimating copulae parameters, plotting probability density and cumulative distribution functions, and simulating data.
The haplotype-resolved reference genome of lemon (Citrus limon L. Burm f.)
Authors: Guardo M. Di , Moretto M. , Moser M. , Catalano C. , Troggio M. , Deng Z. , Cestaro A. , Caruso M. , Distefano G. , La Malfa S. , Bianco L. , Gentile A. 
Published: July 2021

AbstractLemon (Citrus limon (L.) Burm. f.) is an evergreen tree belonging to the genus Citrus. The fruits are particularly prized for their organoleptic and nutraceutical properties of the juice.Herein we report, for the first time, the release of a high-quality reference genome of the two haplotypes of lemon. The sequencing has been carried out coupling Illumina short reads and Oxford Nanopore data leading to the definition of a primary and an alternative assembly characterized by a genome size of 312.8 Mb and 324.74 Mb respectively. The analysis of the long terminal repeat (LTR) allowed the identification of 1921 regions on the primary and 1911 on the alternative assembly distributed across the nine chromosomes. Furthermore, an in-silico analysis of the microRNA genes was carried out using 246 mature miRNA and the respective pre-miRNA hairpin sequences of C. sinensis. Such analysis highlighted a high conservation between the two species with 233 mature miRNAs and 51 pre-miRNA stem-loops aligning with perfect match on the lemon genome.In parallel, total RNA was extracted from fruit, flower, leaf and root enabling the detection of 38,205 and 37,753 predicted transcripts on primary and alternative assemblies respectively. Among those, the highest and lowest number of tissue-specific transcripts were detected in flower (2.73% and 2.71% in primary and alternative assemblies respectively) and leaf (0.7% and 0.68%) while gene ontology analysis enables a more precise characterization of the expressed genes based on their function.The availability of a reference genome is an important prerequisite both for the set-up of high-throughput genotyping analysis and for functional genomic approaches toward the characterization of the genetic determinism of traits of agronomic interest.
Autocrine signaling explains the emergence of Allee effects in cancer cell populations
Authors: Gerlee Philip , Altrock Philipp M. , Krona Cecilia , Nelander Sven 
Published: July 2021

AbstractIn many human cancers, the rate of cell growth depends crucially on the size of the tumour cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer cells themselves. We show, analytically and by simulation, that autocrine signaling suffices to cause both strong and weak Allee effects. Whether low cell densities lead to negative (strong effect) or reduced (weak effect) growth rate depends directly on the ratio of cell death to proliferation, and indirectly on cellular dispersal. Our model is consistent with experimental observations of brain tumor cells grown at different densities. We propose that further studying and quantifying population-wide feedback, impacting cell growth, will be central for advancing our understanding of cancer dynamics and treatment, potentially exploiting Allee effects for therapy.