bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degradation of key photosynthetic genes in the critically endangered semi-aquatic flowering plantSaniculiphyllum guangxiense(Saxifragaceae)
Authors: Folk Ryan A. , Sewnath Neeka , Xiang Chun-Lei , Sinn Brandon T. , Guralnick Robert P. 
Published: December 2019

AbstractBackgroundPlastid gene loss and pseudogenization has been widely documented in parasitic and mycoheterotrophic plants, which have relaxed selective constraints on photosynthetic function. More enigmatic are sporadic reports of degradation and loss of important photosynthesis genes in lineages thought to be fully photosynthetic. Here we report the complete plastid genome ofSaniculiphyllum guangxiense, a critically endangered and phylogenetically isolated plant lineage, along with genomic evidence of reduced chloroplast function. We also report 22 additional plastid genomes representing the diversity of its containing clade Saxifragales, characterizing gene content and placing variation in a broader phylogenetic context.ResultsWe find that the plastid genome ofSaniculiphyllumhas experienced pseudogenization of five genes of the NDH complex (ndhA,ndhB, ndhD,ndhF, andndhK), previously reported in flowering plants with an aquatic habit, as well as the more surprising pseudogenization of two genes more central to photosynthesis (ccsAandcemA), contrasting with strong phylogenetic conservatism of plastid gene content in all other sampled Saxifragales. These genes participate in photooxidative protection, cytochrome synthesis, and carbon uptake. Nuclear paralogs exist for all seven plastid pseudogenes, yet these are also unlikely to be functional.ConclusionsSaniculiphyllumappears to represent the greatest degree of plastid gene loss observed to date in any fully photosynthetic lineage, yet plastid genome length, structure, and substitution rate are within the variation previously reported for photosynthetic plants. These results highlight the increasingly appreciated dynamism of plastid genomes, otherwise highly conserved across a billion years of green plant evolution, in plants with highly specialized life history traits.
Alteration of the premature tRNA landscape by gammaherpesvirus infection
Authors: Tucker Jessica , Schaller Aaron M. , Willis Ian , Glaunsinger Britt A. 
Published: December 2019

AbstractTransfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and non-canonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is largely unknown. Here, we present the first genome-wide analysis of how viral infection alters the tRNAome. Using a tRNA-specific sequencing method (DM-tRNA-seq), we find that the murine gammaherpesvirus MHV68 induces global changes in pre-tRNA expression with 14% of tRNA genes upregulated more than 3-fold, indicating that differential tRNA gene induction is a characteristic of DNA virus infection. Elevated pre-tRNA expression corresponds to increased RNAPIII occupancy for the subset of tRNA genes tested; additionally, post-transcriptional mechanisms contribute to the accumulation of pre-tRNA species. We find increased abundance of tRNA fragments derived from pre-tRNAs upregulated by viral infection, suggesting that non-canonical tRNA cleavage is also affected. Further, pre-tRNA accumulation, but not RNAPIII recruitment, requires gammaherpesvirus-induced degradation of host mRNAs by the virally encoded mRNA endonuclease muSOX. We hypothesize that depletion of pre-tRNA maturation or turnover machinery contributes to robust accumulation of full-length pre-tRNAs in infected cells. Collectively, these findings reveal pervasive changes to tRNA expression during DNA virus infection and highlight the potential of using viruses to explore tRNA biology.SignificanceViral infection can dramatically change the gene expression landscape of the host cell, yet little is known regarding changes in non-coding gene transcription by RNA polymerase III (RNAPIII). Among these are transfer RNAs (tRNAs), which are fundamental in protein translation, yet whose gene regulatory features remain largely undefined in mammalian cells. Here, we perform the first genome-wide analysis of tRNA expression changes during viral infection. We show that premature tRNAs accumulate during infection with the model gammaherpesvirus MHV68 as a consequence of increased transcription, but that transcripts do not undergo canonical maturation into mature tRNAs. These findings underscore how tRNA expression is a highly-regulated process and that cells have strategies to balance tRNA pools during conditions of elevated RNAPIII activity.
Individual head models for estimating the TMS-induced electric field in rat brain
Authors: Koponen Lari M. , Stenroos Matti , Nieminen Jaakko O. , Jokivarsi Kimmo , Gröhn Olli , Ilmoniemi Risto J. 
Published: December 2019

AbstractIn transcranial magnetic stimulation (TMS), the initial cortical activation due to stimulation is determined by the state of the brain and the magnitude, waveform, and direction of the induced electric field (E-field) in the cortex. The E-field distribution depends on the conductivity geometry of the head. The effects of deviations from a spherically symmetric conductivity profile have been studied in detail in humans. In small mammals, such as rats, these effects are more pronounced due to their smaller and less spherical heads. In this study, we describe a simple method for building individual realistically shaped head models for rats from high-resolution X-ray tomography images. We computed the TMS-induced E-field with the boundary element method and assessed the effect of head-model simplifications on the estimated E-field. The deviations from spherical symmetry have large, non-trivial effects on the E-field distribution: in some cases, even the direction of the E-field in the cortex cannot be reliably predicted by the coil orientation unless these deviations are properly considered.
Functional redundancy and crosstalk between flavodiiron proteins and NDH-1 inSynechocystissp. PCC 6803
Authors: Nikkanen Lauri , Sánchez Anita Santana , Ermakova Maria , Rögner Matthias , Cournac Laurent , Allahverdiyeva Yagut 
Published: December 2019

ABSTRACTIn oxygenic photosynthetic organisms excluding angiosperms, flavodiiron proteins (FDPs) catalyze light-dependent reduction of O2to H2O. This alleviates electron pressure on the photosynthetic apparatus and protects it from photodamage. InSynechocystissp. PCC 6803, four FDP isoforms function as hetero-oligomers of Flv1 and Flv3 and/or Flv2 and Flv4. An alternative electron transport pathway mediated by the NAD(P)H dehydrogenase-like complex (NDH-1) also contributes to redox hemostasis and the photoprotection of photosynthesis. Four NDH-1 types haven been characterized in cyanobacteria: NDH-11and NDH-12, which function in respiration; and NDH-13and NDH-14, which function in CO2uptake. All four types are involved in cyclic electron transport. Along with single FDP mutants (Δflv1and Δflv3) and the double NDH-1 mutants (Δd1d2, which is deficient in NDH-11,2and Δd3d4, which is deficient in NDH-13,4), we studied triple mutants lacking either one of Flv1 or Flv3, and NDH-11,2or NDH-13,4. We show that the presence of either Flv1/3 or NDH-11,2, but not NDH-13,4, is indispensable for survival during changes in growth conditions from high CO2/moderate light to low CO2/ high light. Our results suggest functional redundancy and crosstalk between FDPs and NDH-11,2under the studied conditions, and demonstrate that the functions of FDPs and NDH-11,2are dynamically coordinated for the efficient oxidation of PSI and for photoprotection under variable CO2and light availability.One sentence summaryFlavodiiron proteins and NDH-1 complex ensure survival of cyanobacterial cells by cooperatively safeguarding the photosynthetic apparatus against excessive reduction
A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis
Authors: Ahmed Chulbul M , Ildefonso Cristhian J , Johnson Howard M , Lewin Alfred S 
Published: December 2019

AbstractExperimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon α1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFNα–C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFNα–C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNFα were suppressed when IFNα–C was simultaneously present. TNF-α mediated induction of NF-kB and signaling by IL-17A were attenuated by IFNα–C. Differentiated ARPE-19 cells were treated with TNFα in the presence or absence IFNα–C and analyzed by immmunhistochemistry. IFNα–C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNFα was prevented by IFNα–C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFNα–C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFNα–C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigenspecific T cell proliferation that was inhibited in the presence of IFNα–C. IFNα–C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis.
Genome sequencing and functional characterization of aDictyopanus pusillusfungal extract offers a promising alternative for lignocellulose pretreatment of oil palm residues
Authors: Rueda Andrés M. , de los Santos Yossef López , Vincent Antony T. , Létourneau Myriam , Hernández Inés , Sánchez Clara I. , Molina V. Daniel , Ospina Sonia A. , Veyrier Frédéric J. , Doucet Nicolas 
Published: December 2019

AbstractThe pretreatment of biomass is a critical requirement of bio-renewable fuel production from lignocellulose. Although current processes primarily involve chemical and physical approaches, the biological breakdown of lignin using enzymes and microorganisms is quickly becoming an interesting eco-friendly alternative to classical processes. As a result, bioprospection of wild fungi from naturally occurring lignin-rich sources remains a suitable method to uncover and isolate new species exhibiting ligninolytic activity. In this study, wild species of white rot fungi were collected from Colombian forests based on their natural wood decay ability and high capacity to secrete oxidoreductases with high affinity for phenolic polymers such as lignin. Based on high activity obtained from solid-state fermentation using a lignocellulose source from oil palm as matrix, we describe the isolation and whole-genome sequencing ofDictyopanus pusillus, a wild basidiomycete fungus exhibiting ABTS oxidation as an indication of laccase activity. Functional characterization of a crude enzymatic extract identified laccase activity as the main enzymatic contributor to fungal extracts, an observation supported by the identification of 13 putative genes encoding for homologous laccases in the genome. To the best of our knowledge, this represents the first report of an enzymatic extract exhibiting laccase activity in theDictyopanusgenera, offering means to exploit this species and its enzymes for the delignification process of lignocellulosic by-products from oil palm.
Cross-Species Integration of Transcriptomic Effects of Tobacco and Nicotine Exposure Helps to Prioritize Genetic Effects on Human Tobacco Consumption
Authors: Palmer Rohan H C , Benca-Bachman Chelsie E. , Bubier Jason A. , McGeary John E , Ramgiri Nikhil , Srijeyanthan Jenani , Huggett Spencer , Yang Jingjing , Visscher Peter , Yang Jian , Knopik Valerie , Chesler Elissa J. 
Published: December 2019

ABSTRACTComputational advances have fostered the development of new methods and tools to integrate gene expression and functional evidence into human-genetic association analyses. Integrative functional genomics analysis for altered response to alcohol in mice provided the first evidence that multi-species analysis tools, such as GeneWeaver, can identify or confirm novel alcohol-related loci. The present study describes an integrative framework to investigate how highly-connected genes linked by their association to tobacco-related behaviors, contribute to individual differences in tobacco consumption. Data from individuals of European ancestry in the UKBiobank (N=139,043) were used to examine the relative contribution of orthologs of a set of genes that are transcriptionally co-regulated by tobacco or nicotine exposure in model organism experiments to human tobacco consumption. Multi-component mixed linear models using genotyped and imputed single nucleotide variants indicated that: (1) variation within human orthologs of these genes accounted for 2-5% of the observed heritability (meta h2SNP-Total=0.08 [95% CI: 0.07, 0.09]) of tobacco/nicotine consumption across three independent folds of unrelated individuals (enrichment ranging from 0.85 - 2.98), and (2) variation around (5, 10, 15, 25, and 50 Kb regions) the set of co-transcriptionally regulated genes accounted for 5-36% of the observed SNP-heritability (enrichment ranging from 1.60 – 31.45). Notably, the effects of variants in co-transcriptionally regulated genes were enriched in tobacco GWAS. These findings highlight the advantages of using multiple species evidence to isolate genetic factors to better understand the etiological complexity of tobacco and other nicotine consumption.
A Metric Space of Ranked Tree Shapes and Ranked Genealogies
Authors: Kim Jaehee , Rosenberg Noah A. , Palacios Julia A. 
Published: December 2019

AbstractGenealogical tree modeling is essential for estimating evolutionary parameters in population genetics and phylogenetics. Recent mathematical results concerning ranked genealogies without leaf labels enable new opportunities in the analysis of evolutionary trees. In particular, comparisons between ranked genealogies facilitate the study of evolutionary processes for organisms sampled in multiple time periods. We propose a metric space on ranked genealogies for lineages sampled from both isochronous and time-stamped heterochronous sampling. Our new tree metrics make it possible to conduct statistical analyses of ranked tree shapes and timed ranked tree shapes, or ranked genealogies. Such analyses allow us to assess differences in tree distributions, quantify estimation uncertainty, and summarize tree distributions. We show the utility of our metrics via simulations and an application in infectious diseases.
A single cell transcriptional atlas of early synovial joint development
Authors: Bian Qin , Cheng Yu-Hao , Wilson Jordan P , Kim Dong Won , Wang Hong , Blackshaw Seth , Cahan Patrick 
Published: December 2019

SUMMARYSynovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 6,202 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics,in situhybridization, and functional analysis of prospectively isolated populations, we have inferred the underlying transcriptional networks of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.
A cellular stress response induced by the CRISPR/dCas9 activation system is not heritable through cell divisions
Authors: Johnston Andrew D. , Abdulrazak Alali , Sato Hanae , Maqbool Shahina B. , Suzuki Masako , Greally John M. , Simões-Pires Claudia A. 
Published: December 2019

ABSTRACTThe CRISPR/Cas9 system can be modified to perform ‘epigenetic editing’ by utilizing the catalytically-inactive (dead) Cas9 (dCas9) to recruit regulatory proteins to specific genomic locations. In prior studies, epigenetic editing with multimers of the transactivator VP16 and guide RNAs (gRNAs) was found to cause adverse cellular responses. These side effects may confound studies inducing new cellular properties, especially if the cellular responses are maintained through cell divisions - an epigenetic regulatory property. Here we show how distinct components of this CRISPR/dCas9 activation system, particularly untargeted gRNAs, upregulate genes associated with transcriptional stress, defense response, and regulation of cell death. Our results highlight a previously undetected acute stress response to CRISPR/dCas9 components in human cells, which is transient and not maintained through cell divisions.
A Genetic Screen Links the Disease-Associated Nab2 RNA-Binding Protein to the Planar Cell Polarity Pathway inDrosophila melanogaster
Authors: Lee Wei-Hsuan , Corgiat Edwin , Rounds J. Christopher , Shepherd Zenyth , Corbett Anita H. , Moberg Kenneth H. 
Published: December 2019

ABSTRACTMutations in the gene encoding the ubiquitously expressed RNA-binding protein ZC3H14 result in a non-syndromic form of autosomal recessive intellectual disability. Studies inDrosophilahave defined roles for the ZC3H14 ortholog, Nab2 (akaDrosophilaNab2 or dNab2), in axon guidance and memory due in part to interaction with a second RNA-binding protein, the fly Fragile X homolog Fmr1, and coregulation of shared Nab2-Fmr1 target mRNAs. Despite these advances, neurodevelopmental pathways regulated by Nab2 remain poorly defined. Structural defects inNab2null brains resemble defects observed upon disruption of the planar cell polarity (PCP) pathway, which regulates planar orientation of static and motile cells. A kinked bristle phenotype in survivingNab2mutant adults additionally suggests a defect in F-actin polymerization and bundling, which is also a PCP-regulated processes. To test for Nab2-PCP genetic interactions, a collection of PCP loss-of-function alleles was screened for modification of a rough-eye phenotype produced by Nab2 overexpression in the eye (GMR-Nab2) and subsequently for modification ofNab2null phenotypes. Multiple PCP alleles dominantly modifyGMR-Nab2eye roughening and a subset of these alleles also rescue low survival and thoracic bristle kinking inNab2zygotic nulls. Moreover, alleles of two X-linked PCP factors,dishevelled(dsh) and βamyloid protein precursor-like(Appl), rescueGMR-Nab2eye roughening in male progeny derived from hemizygousdshorApplmutant fathers, suggesting an additional effect inherited through the male germline. These findings demonstrate a consistent pattern of Nab2-PCP genetic interactions that suggest molecular links between Nab2 and the PCP pathway in the developing eye, wing and germline.
Transfer from number to size reveals abstract coding of magnitude in honeybees
Authors: Bortot Maria , Stancher Gionata , Vallortigara Giorgio 
Published: December 2019

AbstractNumber discrimination has been documented in honeybees. It is not known, however, whether it reflects, as in vertebrates, the operating of an underlying general magnitude system that estimates quantities irrespective of dimensions (e.g., number, space, time) and format (discrete, continuous). We investigated whether bees spontaneously transfer discrete discrimination of number to continuous discrimination of size. Bees were trained to discriminate between different numerical comparisons having either a 0.5 (2vs.4 and 4vs.8) or 0.67 ratio (2vs.3 and 4vs.6). Half of the subjects learnt to choose the smaller quantity and the other half the larger quantity. Bees were then tested for spontaneous choice (in the absence of reward) using comparisons with identical numbers but different sizes. Irrespective of the ratio of the stimuli, bees trained to select the smaller numerical quantity chose the congruent smaller size; bees trained to choose the larger numerical quantity chose the congruent larger size. This finding provides the first evidence for a cross-dimensional transfer between discrete (numerical) and continuous (spatial) dimensions in an invertebrate species and supports the hypothesis of a cognitive universality of a coding for general magnitude.
Endogenous and exogenous control of visuospatial selective attention in freely behaving mice
Authors: You Wen-Kai , Mysore Shreesh P. 
Published: December 2019

SUMMARYSelective spatial attention, the ability to dynamically prioritize the most important spatial location, is essential for adaptive behavior. It has been studied primarily in head-fixed animals, and almost exclusively in primates. Here, we report the development of two human-inspired, discrimination-based behavioral paradigms for studying selective visuospatial attention in the freely behaving mouse: the spatial probability task, and the flanker task. In the spatial probability task, we found enhanced response accuracy, perceptual discriminability, and rates of sensory evidence accumulation at the location with higher probability of target occurrence, and opposite effects at the lower probability location. In the absence of systematic differences in sensory input, motor biases, and trial structure, these results demonstrated endogenous expectation-driven shifts of spatial attention. In the flanker task, we found that a second, ‘flanker’ stimulus presented with the target, but with incongruent information, caused switch-like decrements in response accuracy and perceptual discriminability as a function of flanker contrast, as well as a reduced rate of evidence accumulation. These results demonstrated exogenous capture of spatial attention. The innovation of behavioral tasks for selective visuospatial attention in unrestrained mice opens up a rich avenue for future research dissecting the neural circuit mechanisms underlying this critical executive function.