bluuebunny/crossref_metadata_2025_split huggingface dataset:
The draft genome sequence of herbaceous diploid bambooRaddia distichophylla
Authors: Li Wei , Shi Cong , Li Kui , Zhang Qun-jie , Tong Yan , Zhang Yun , Wang Jun , Clark Lynn , Gao Li-zhi 
Published: April 2020

ABSTRACTBamboos are important non-timber forest plants widely distributed in the tropical and subtropical regions of Asia, Africa, America, and Pacific islands. They comprise the Bambusoideae in the grass family (Poaceae), including approximately 1,700 described species in 127 genera. In spite of the widespread uses of bamboo for food, construction and bioenergy, the gene repertoire of bamboo still remains largely unexplored.Raddia distichophylla(Schrad. ex Nees) Chase, belonging to the tribe Olyreae (Bambusoideae, Poaceae), is diploid herbaceous bamboo with only slightly lignified stems. In this study, we report a draft genome assembly of the approximately ∼589 Mb whole-genome sequence ofR. distichophyllawith a contig N50 length of 86.36 Kb. Repeated sequences account for ∼49.08% of the genome, of which LTR retrotransposons occupy ∼35.99% of whole genome. A total of 30,763 protein-coding genes were annotated in theR. distichophyllagenome with an average transcript size of 2,887 bp. Access to this herbaceous bamboo genome sequence will provide novel insights into biochemistry, molecular-assisted breeding programs and germplasm conservation for bamboo species world-wide.
A versatile system to introduce clusters of genomic double-strand breaks in large cell populations
Authors: Kolb Thorsten , Khalid Umar , Simović Milena , Ratnaparkhe Manasi , Wong John , Jauch Anna , Schmezer Peter , Rode Agata , Sebban Shulamit , Haag Daniel , Hergt Michaela , Devens Frauke , Buganim Yosef , Zapatka Marc , Lichter Peter , Ernst Aurélie 
Published: April 2020

ABSTRACTIn vitroassays for clustered DNA lesions will facilitate the analysis of the mechanisms underlying complex genome rearrangements such as chromothripsis, including the recruitment of repair factors to sites of DNA double-strand breaks. We present a novel method generating localized DNA double-strand breaks using UV-irradiation with photomasks. The size of the damage foci and the spacing between lesions are fully adjustable, making the assay suitable for different cell types and targeted areas. We validated this set-up with genomically stable epithelial cells, normal fibroblasts, pluripotent stem cells and patient-derived primary cultures. Our method does not require a specialized device such as a laser, making it accessible to a broad range of users. Sensitization by BrdU incorporation is not required, which enables analyzing the DNA damage response in post-mitotic cells. Irradiated cells can be cultivated further, followed by time-lapse imaging or used for downstream biochemical analyses, thanks to the high-throughput of the system. Importantly, we showed genome rearrangements in the irradiated cells, providing a proof of principle for the induction of structural variants by localized DNA lesions.
Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans
Authors: Hammerquist Amy M. , Curran Sean P. 
Published: April 2020

ABSTRACTThe negative regulator of RNA polymerase (pol) IIImafr-1has been shown to affect RNA pol III transcript abundance, lipid biosynthesis and storage, progeny output, and lifespan. We deletedmafr-1from theCaenorhabditis elegansgenome and found that animals lackingmafr-1replicated many phenotypes from previous RNAi-based studies, but strikingly not the oocyte-related reproductive phenotypes. Utilizing a yeast two-hybrid assay, we discovered several novel interactors of MAFR-1 that are expressed in a sperm- and germline-enriched manner. In support of a role for MAFR-1 in the male germline, we foundmafr-1null males have smaller spermatids that are less capable in competition for fertilization; a phenotype that was dependent on RNA pol III activity. Restoration of MAFR-1 expression specifically in the germline rescued the spermatid-related phenotypes, suggesting a cell autonomous role for MAFR-1 in nematode male fertility. Based on the high degree of conservation of Maf1 activity across species, our study may inform similar roles for Maf1 and RNA pol III in mammalian male fertility.
Expression ofBrassica napusGLO1 is sufficient to breakdown artificial self-incompatibility inArabidopsis thaliana
Authors: Kenney Patrick , Sankaranarayanan Subramanian , Balogh Michael , Indriolo Emily 
Published: April 2020

AbstractMembers of the Brassicaceae family have the ability to regulate pollination events occurring on the stigma surface. InBrassicaspecies, self-pollination leads to an allele specific interaction between the pollen small cysteine-rich peptide ligand (SCR/SP11) and the stigmatic S-receptor kinase (SRK) that activates the E3 ubiquitin ligase ARC1 (Armadillo repeat-containing 1), resulting in proteasomal degradation of various compatibility factors including Glyoxalase I (GLO1) which is necessary for successful pollination. Suppression of GLO1 was sufficient to reduce compatibility, and overexpression of GLO1 in self-incompatibleBrassica napusstigmas resulted in partial breakdown of the self-incompatibility response. Here, we verified ifBnGLO1 could function as a compatibility factor in the artificial self-incompatibility system ofArabidopsis thalianaexpressingAlSCRb,AlSRKbandAlARC1 proteins fromA. lyrata. Overexpression ofBnGLO1 is sufficient to breakdown self-incompatibility response inA. thalianastigmas, suggesting that GLO1 functions as an inter-species compatibility factor. Therefore, GLO1 has an indisputable role as a compatibility factor in the stigma in regulating pollen attachment and pollen tube growth. Lastly, this study demonstrates the usefulness of an artificial self-incompatibility system inA. thalianafor interspecific self-incompatibility studies.
Serum levels and tumour expression of leptin and leptin receptor as promising clinical biomarkers of specific feline mammary carcinoma subtypes
Authors: Gameiro Andreia , Nascimento Catarina , Urbano Ana Catarina , Correia Jorge , Ferreira Fernando 
Published: April 2020

AbstractObesity is a risk factor for human breast cancer, being associated with increased serum levels of leptin. In cat, although obesity is a common nutritional disorder, the role of leptin and its receptor in mammary carcinoma is unknown. In this study, serum levels of leptin and leptin receptor (ObR) were evaluated in 58 cats with mammary carcinoma and compared with healthy controls by ELISA, as tumour expression by immunohistochemistry. Results showed that the free leptin index is decreased in cats with mammary carcinoma (p=0.0006), particularly for those with luminal B and HER2-positive disease that showed significantly lower serum leptin levels (p<0.0001 and p<0.005, respectively). Serum leptin levels above 4.17 pg/mL were associated with ulcerating tumours (p=0.0005) and shorter DFS (p=0.0217). Elevated serum ObR levels were found in all cats with mammary carcinoma (p<0.0001), with levels above 16.89 ng/mL being associated with smaller tumours (p=0.0118), ER-negative status in HER2-positive tumours (p=0.0291) and increased serum levels of CTLA-4 (p=0.0056), TNF-α (p=0.0025), PD-1 (p=0.0023) and PD-L1 (p=0.0002). In tumour samples, leptin was overexpressed in luminal B and triple-negative carcinomas (p=0.0046), whereas ObR was found overexpressed in luminal B samples (p=0.0425). Altogether, our results reinforce the importance of feline mammary carcinoma in comparative oncology.
Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis
Authors: Al-Amin Md. Mamun , Grandjean Joanes , Klohs Jan , Kim Jungsu 
Published: April 2020

AbstractAlthough amyloid beta (Aβ) deposition is one of the major causes of white matter (WM) alterations in Alzheimer’s disease (AD), little is known about the underlying basis of WM damage and its association with global structural connectivity and network topology. We aimed to dissect the contributions of WM microstructure to structural connectivity and network properties in the ArcAβ mice model of Aβ amyloidosis.We acquired diffusion-weighted images (DWI) of wild type (WT) and ArcAβ transgenic (TG) mice using a 9.4 T MRI scanner. Fixel-based analysis (FBA) was performed to measure fiber tract-specific properties. We also performed three complementary experiments; to identify the global differences in structural connectivity, to compute network properties and to measure cellular basis of white matter alterations.Transgenic mice displayed disrupted structural connectivity centered to the entorhinal cortex (EC) and a lower fiber density and fiber bundle cross-section. In addition, there was a reduced network efficiency and degree centrality in weighted structural connectivity in the transgenic mice. To further examine the underlying neuronal basis of connectivity and network deficits, we performed histology experiments. We found no alteration in myelination and an increased level of neurofilament light (NFL) in the brain regions with disrupted connectivity in the TG mice. Furthermore, TG mice had a reduced number of perineuronal nets (PNN) in the EC.The observed FDC reductions may indicate a decrease in axonal diameter or axon count which would explain the basis of connectivity deficits and reduced network efficiency in TG mice. The increase in NFL suggests a breakdown of axonal integrity, which would reduce WM fiber health. Considering the pivotal role of the EC in AD, Aβ deposition may primarily increase NFL release, damaging PNN in the entorhinal pathway, resulting in disrupted structural connectivity.
Oculomotor freezing reflects tactile temporal expectation and aids tactile perception
Authors: Badde Stephanie , Myers Caroline F. , Yuval-Greenberg Shlomit , Carrasco Marisa 
Published: April 2020

AbstractThe oculomotor system keeps the eyes steady in expectation of visual events. Here, recording microsaccades while people performed a tactile, frequency discrimination task enabled us to test whether the oculomotor system shows an analogous preparatory response for unrelated tactile events. We manipulated the temporal predictability of tactile targets using tactile cues, which preceded the target by either constant (high predictability) or variable (low predictability) time intervals. We find that microsaccades are inhibited prior to tactile targets and more so for constant than variable intervals, revealing a tight crossmodal link between tactile temporal expectation and oculomotor action. These findings portray oculomotor freezing as a marker of crossmodal temporal expectation. Moreover, microsaccades occurring around the tactile target presentation are associated with reduced task performance, suggesting that oculomotor freezing mitigates potential detrimental, concomitant effects of microsaccades and revealing a crossmodal coupling between tactile perception and oculomotor action.
Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the RVM
Authors: Sluka KA , Kolker SJ , Danielson J , Rasmussen L 
Published: April 2020

AbstractRegular physical activity/exercise is an effective non-pharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The RVM sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia. The goal of these studies was to examine if regular physical activity modifies RVM-spinal cord circuitry. Male and female mice received Fluoro-Gold placed on the spinal cord to identify spinally projecting neurons from the rostral ventromedial medulla (RVM) and the nucleus raphe obscuris/nucleus raphe pallidus (NRO/NRP), dermorphin-488 into caudal medulla to identify mu-opioid receptors, and were immunohistochemically stained for either phosphorylated-N-methyl-D-aspartate subunit NR1 (p-NR1) to identify excitatory neurons or tryptophan hydroxylase (TPH) to identify serotonin neurons. The percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH), and the percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH) and Fluoro-Gold was calculated.Physically active animals were provided running wheels in their cages for 8 weeks and compared to sedentary animals without running wheels. Animals with chronic muscle pain, induced by two intramuscular injections of pH 4.0, were compared to sham controls (pH 7.2). Physically active animals had less mu-opioid expressing neurons projecting to the spinal cord when compared to sedentary animals in the RVM, but not the NRO/NRP. No changes were observed for TPH. These data suggest that regular exercise alters central facilitation so that there is less descending facilitation to result in a net increase in inhibition.Summary StatementPhysically active animals has less mu-opioid expressing neurons projecting to the spinal cord in the RVM, but not the NRO/NRP, when compared to sedentary animals.
The complete mitochondrial genome sequence ofOryctes rhinoceros(Coleoptera: Scarabaeidae) based on long-read nanopore sequencing
Authors: Filipović Igor , Hereward James P. , Rašić Gordana , Devine Gregor J. , Furlong Michael J. , Etebari Kayvan 
Published: April 2020

AbstractThe coconut rhinoceros beetle (CRB,Oryctes rhinoceros) is a severe and invasive pest of coconut and other palms throughout Asia and the Pacific. The biocontrol agent, Oryctes rhinoceros nudivirus (OrNV), has successfully suppressedO. rhinocerospopulations for decades but new CRB invasions started appearing after 2007. A single-SNP variant within the mitochondrialcox1gene is used to distinguish the recently-invading CRB-G lineage from other haplotypes, but the lack of mitogenome sequence for this species hinders further development of a molecular toolset for biosecurity and management programmes against CRB. Here we report the complete circular sequence and annotation for CRB mitogenome, generated to support such efforts.Sequencing data were generated using long-read Nanopore technology from genomic DNA isolated from a CRB-G female. The mitochondrial genome was assembled with Flye v.2.5, using the short-read Illumina sequences to remove homopolymers with Pilon, and annotated with MITOS. Independently-generated transcriptome data were used to assess theO. rhinocerosmitogenome annotation and transcription. The aligned sequences of 13 protein-coding genes (PCGs) (with degenerate third codon position) fromO. rhinoceros, 13 other Scarabaeidae taxa and two outgroup taxa were used for the phylogenetic reconstruction with the Maximum likelihood (ML) approach in IQ-TREE and Bayesian (BI) approach in MrBayes.The complete circular mitochondrial genome ofO. rhinocerosis 20,898 bp-long, with a gene content canonical for insects (13 PCGs, 2 rRNA genes, and 22 tRNA genes), as well as one structural variation (rearrangement oftrnQandtrnI) and a long control region (6,204 bp). Transcription was detected across all 37 genes, and interestingly, within three domains in the control region. ML and BI phylogenies had the same topology, correctly groupingO. rhinoceroswith one other Dynastinae taxon, and recovering the previously reported relationship among lineages in the Scarabaeidae.In silicoPCR-RFLP analysis recovered the correct fragment set that is diagnostic for the CRB-G haplogroup. These results validate the high-quality of the CRB mitogenome sequence and annotation.
A rare mutation in an infant derived HIV-1 envelope glycoprotein alters interprotomer stability and susceptibility to broadly neutralizing antibodies targeting the trimer apex
Authors: Mishra Nitesh , Sharma Shaifali , Dobhal Ayushman , Kumar Sanjeev , Chawla Himanshi , Singh Ravinder , Das Bimal Kumar , Kabra Sushil Kumar , Lodha Rakesh , Luthra Kalpana 
Published: April 2020

AbstractThe envelope glycoprotein (Env) of human immunodeficiency virus-1 (HIV-1) is the sole target of broadly neutralizing antibodies (bnAbs). Several mechanisms, such as acquisition of mutations due to the error prone reverse transcriptase, variability of loop length and alterations in glycan pattern are employed by the virus to shield neutralizing epitopes on the env, to sustain survival and infectivity within the host. Identification of mutations that can lead to viral evasion from host immune response is essential for optimization and engineering of Env based trimeric immunogens. Herein, we report a rare leucine to phenylalanine escape mutation (L184F) at the base of hypervariable loop 2 (population frequency of 0.0045%) in a nine-month-old perinatally HIV-1 infected infant broad neutralizer. The L184F mutation disrupted the intramolecular interaction, stabilizing the trimer apex thereby leading to viral escape from autologous plasma bnAbs and known bnAbs, targeting exclusively the N160 glycan at trimer apex and not any other known epitope. The L184F amino acid change led to acquisition of a relatively open trimeric configuration, often associated with tier 1 HIV-1 isolates and an increased susceptibility to neutralization by polyclonal plasma antibodies of weak neutralizers. While there was no impact of the L184F mutation on free virus transmission, a reduction in cell-to-cell transmission was observed. In conclusion, we report a viral escape mutation that plausibly destabilized the trimer apex and favoured evasion from broadly neutralizing antibodies. Such mutations, though rare, should be taken into consideration while designing an immunogen, based on a stable correctly-folded HIV-1 Env trimer.ImportanceDesign of HIV-1 envelope-based immunogens, capable of eliciting broadly neutralizing antibodies (bnAbs), are currently under active research. Some of the most potent bnAbs target the quaternary epitope at the V2 apex of HIV-1 Env trimer. By studying naturally circulating viruses from an HIV-1 perinatally infected infant, with plasma neutralizing antibodies targeted to the V2-apex, we identified a rare leucine to phenylalanine substitution in two out of six functional viral clones, that destabilized the trimer apex. This single amino acid alteration impaired the interprotomeric interactions that stabilize the trimer apex, resulting in an open trimer conformation, and escape from broadly neutralizing autologous plasma antibodies and known V2-apex directed bnAbs, thereby favouring viral evasion of the early bnAb response of the infected host. Defining the mechanisms by which viral mutations influence the sensitivity of HIV-1 to bnAbs is crucial for the development of effective vaccines against HIV-1 infection.
Copy number signature analyses in prostate cancer reveal distinct etiologies and clinical outcomes
Authors: Wang Shixiang , Li Huimin , Song Minfang , He Zaoke , Wu Tao , Wang Xuan , Tao Ziyu , Wu Kai , Liu Xue-Song 
Published: April 2020

AbstractGenome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer, however, signatures of cancer genome copy number alteration (CNA) are still elusive in most cancer types, especially in prostate cancer (PC), which is particularly driven by complex genome alterations. Here, a user-friendly open source bioinformatics tool “sigminer” has been constructed for copy number signature extraction, analysis and visualization. Five copy number signatures are identified from human PC genome with this tool. The underlying driving forces for each signature have been illustrated. Sample clustering based on copy number signature exposure revealed considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. Copy number signature analyses provide distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.
Genetic determinism of spontaneous masculinisation in XX female rainbow trout: new insights using medium throughput genotyping and whole-genome sequencing
Authors: Fraslin Clémence , Phocas Florence , Bestin Anastasia , Charles Mathieu , Bernard Maria , Krieg Francine , Dechamp Nicolas , Ciobotaru Céline , Hozé Chris , Petitprez Florent , Milhes Marine , Lluch Jérôme , Bouchez Olivier , Poncet Charles , Hocdé Philippe , Haffray Pierrick , Guiguen Yann , Quillet Edwige 
Published: April 2020

AbstractRainbow trout has a male heterogametic (XY) sex determination system controlled by a major sex-determining gene,sdY. Unexpectedly, a few phenotypically masculinised fish are regularly observed in all-female farmed trout stocks. To better understand the genetic determinism underlying spontaneous maleness in XX-rainbow trout, we recorded the phenotypic sex of 20,210 XX-rainbow trout from a French farm at 10 and 15 months post-hatching. The masculinisation rate was 1.45%. We performed two genome-wide association studies (GWAS) using both medium-throughput genotyping (31,811 SNPs) and whole-genome sequencing (WGS, 8.7 million SNPs) on a subsample of 1,139 individuals classified as females, intersex or males. The genomic heritability of maleness ranged between 0.48 and 0.62 depending on the method and number of SNPs used for estimation. At the 31K SNPs level, we detected four QTLs on three chromosomes (Omy1, Omy12 and Omy20). Using WGS information, we narrowed down the positions of the two QTLs detected on Omy1 to 96 kb and 347 kb respectively, with the second QTL explaining up to 14% of the total genetic variance of maleness. Within this QTL, we detected three putative candidate genes,fgfa8, cyp17a1and an uncharacterised protein (LOC110527930), which might be involved in spontaneous maleness of XX-female rainbow trout.
Adversarial Deconfounding Autoencoder for Learning Robust Gene Expression Embeddings
Authors: Dincer Ayse B. , Janizek Joseph D. , Lee Su-In 
Published: April 2020

AbstractMotivationIncreasing number of gene expression profiles has enabled the use of complex models, such as deep unsupervised neural networks, to extract a latent space from these profiles. However, expression profiles, especially when collected in large numbers, inherently contain variations introduced by technical artifacts (e.g., batch effects) and uninteresting biological variables (e.g., age) in addition to the true signals of interest. These sources of variations, called confounders, produce embeddings that fail to transfer to different domains, i.e., an embedding learned from one dataset with a specific confounder distribution does not generalize to different distributions. To remedy this problem, we attempt to disentangle confounders from true signals to generate biologically informative embeddings.ResultsIn this paper, we introduce the AD-AE (AdversarialDeconfoundingAutoEncoder) approach to deconfounding gene expression latent spaces. The AD-AE model consists of two neural networks: (i) an autoencoder to generate an embedding that can reconstruct original measurements, and (ii) an adversary trained to predict the confounder from that embedding. We jointly train the networks to generate embeddings that can encode as much information as possible without encoding any confounding signal. By applying AD-AE to two distinct gene expression datasets, we show that our model can (1) generate embeddings that do not encode confounder information, (2) conserve the biological signals present in the original space, and (3) generalize successfully across different confounder domains. We demonstrate that AD-AE outperforms standard autoencoder and other deconfounding approaches.AvailabilityOur code and data are available athttps://gitlab.cs.washington.edu/abdincer/ad-ae.Contactabdincer@cs.washington.edu;suinlee@cs.washington.edu