bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex chromosome and sex locus characterization in the goldfish, Carassius auratus
Authors: Wen Ming , Feron Romain , Pan Qiaowei , Guguin Justine , Jouanno Elodie , Herpin Amaury , Klopp Christophe , Cabau Cedric , Zahm Margot , Parrinello Hugues , Journot Laurent , Burgess Shawn M. , Omori Yoshihiro , Postlethwait John H. , Schartl Manfred , Guiguen Yann 
Published: December 2019

AbstractBackgroundGoldfish is an important model for various areas of research, including neural development and behavior and a species of significant importance in aquaculture, especially as an ornamental species. It has a male heterogametic (XX/XY) sex determination system that relies on both genetic and environmental factors, with high temperatures being able to produce female-to-male sex reversal. Little, however, is currently known on the molecular basis of genetic sex determination in this important cyprinid model. We used sequencing approaches to better characterize sex determination and sex-chromosomes in goldfish.ResultsOur results confirmed that sex determination in goldfish is a mix of environmental and genetic factors and that its sex determination system is male heterogametic (XX/XY). Using reduced representation (RAD-seq) and whole genome (pool-seq) approaches, we characterized sex-linked polymorphisms and developed male specific genetic markers. These male specific markers were used to distinguish sex-reversed XX neomales from XY males and to demonstrate that XX female-to-male sex reversal could even occur at a relatively low rearing temperature (18°C), for which sex reversal has been previously shown to be close to zero. We also characterized a relatively large non-recombining region (∼11.7 Mb) on goldfish linkage group 22 (LG22) that contained a high-density of male-biased genetic polymorphisms. This large LG22 region harbors 373 genes, including a single candidate as a potential master sex gene, i.e., the anti-Mullerian hormone gene (amh). However, no sex-linked polymorphisms were detected in the goldfish amh gene or its 5 kb proximal promoter sequence.ConclusionsThese results show that goldfish have a relatively large sex locus on LG22, which is likely the goldfish Y chromosome. The presence of a few XX males even at low temperature also suggests that other environmental factors in addition to temperature could trigger female-to-male sex reversal. Finally, we also developed sex-linked genetic markers in goldfish, which will be important for future research on sex determination and aquaculture applications in this species.
Enhancer hijacking determines intra- and extrachromosomal circularMYCNamplicon architecture in neuroblastoma
Authors: Helmsauer Konstantin , Valieva Maria , Ali Salaheddine , Gonzalez Rocio Chamorro , Schöpflin Robert , Röefzaad Claudia , Bei Yi , Garcia Heathcliff Dorado , Rodriguez-Fos Elias , Puiggròs Montserrat , Kasack Katharina , Haase Kerstin , Kuschel Luis P. , Euskirchen Philipp , Heinrich Verena , Robson Michael , Rosswog Carolina , Tödling Jörn , Szymansky Annabell , Hertwig Falk , Fischer Matthias , Torrents David , Eggert Angelika , Schulte Johannes H. , Mundlos Stefan , Henssen Anton G. , Koche Richard P. 
Published: December 2019

AbstractMYCNamplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA. The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyzed theMYCNamplicon structure and its chromatin landscape. This revealed two distinct classes of amplicons which explain the regulatory requirements forMYCNoverexpression. The first class always co-amplified a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class ofMYCNamplicons was characterized by high structural complexity, lacked key local enhancers, and instead contained distal chromosomal fragments, which harbored CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed inMYCNamplification.
Recurrent acquisition of alien ribotoxin encoding genes by insect genomes
Authors: Lapadula Walter J. , Mascotti María L. , Ayub Maximiliano Juri 
Published: December 2019

ABSTRACTRibosome inactivating proteins (RIPs) are RNAN-glycosidases that depurinate a specific adenine residue in the conserved sarcin/ricin loop of 28S rRNA. These enzymes are widely distributed among plants and bacteria. Recently, we have described RIP genes in mosquitoes belonging to the Culicinae subfamily (AediniandCulicini tribes). We have also shown that these genes are derived from a single event of horizontal gene transfer (HGT) from a prokaryotic donor. In the present work, we show the existence of two RIP encoding genes in the genome of the whiteflyBemisia tabaci(a hemiptera species belonging to the Aleyrodidae family, distantly related to mosquitoes). Contamination artifacts were ruled out analyzing three independentBemisia tabacigenome databases. In contrast to mosquitoes RIPs, the whitefly genes harbor introns and, according to transcriptomic evidence, are transcribed and spliced. Interestingly, phylogenetic inference combined with taxonomic distribution strongly supports that whitefly RIP genes are derived from an independent HGT event from a plant source. Our results suggest that RIP genes fill a functional niche in insects.
Optimization and functionalization of red-shifted rhodamine dyes
Authors: Grimm Jonathan B. , Tkachuk Ariana N. , Choi Heejun , Mohar Boaz , Falco Natalie , Patel Ronak , Lippincott-Schwartz Jennifer , Brown Timothy A. , Lavis Luke D. 
Published: December 2019

ABSTRACTExpanding the palette of fluorescent dyes is vital for pushing the frontier of biological imaging. Although rhodamine dyes remain the premier type of small-molecule fluorophore due to their bioavailability and brightness, variants excited with far-red or near-infrared light suffer from poor performance due to their propensity to adopt a lipophilic, nonfluorescent form. We report a general chemical modification for rhodamines that optimizes long-wavelength variants and enables facile functionalization with different chemical groups.
Bovine breed-specific augmented reference graphs facilitate accurate sequence read mapping and unbiased variant discovery
Authors: Crysnanto Danang , Pausch Hubert 
Published: December 2019

AbstractBackgroundThe current bovine genomic reference sequence was assembled from the DNA of a Hereford cow. The resulting linear assembly lacks diversity because it does not contain allelic variation. Lack of diversity is a drawback of linear references that causes reference allele bias. High nucleotide diversity and the separation of individuals by hundreds of breeds make cattle ideally suited to investigate the optimal composition of variation-aware references.ResultsWe augment the bovine linear reference sequence (ARS-UCD1.2) with variants filtered for allele frequency in dairy (Brown Swiss, Holstein) and dual-purpose (Fleckvieh, Original Braunvieh) cattle breeds to construct either breed-specific or pan-genome reference graphs using thevg toolkit. We find that read mapping is more accurate to variation-aware than linear references if pre-selected variants are used to construct the genome graphs. Graphs that contain random variants do not improve read mapping over the linear reference sequence. Breed-specific augmented and pan-genome graphs enable almost similar mapping accuracy improvements over the linear reference. We construct a whole-genome graph that contains the Hereford-based reference sequence and 14 million alleles that have alternate allele frequency greater than 0.03 in the Brown Swiss cattle breed. We show that our novel variation-aware reference facilitates accurate read mapping and unbiased sequence variant genotyping for SNPs and Indels.ConclusionsWe developed the first variation-aware reference graph for an agricultural animal:https://doi.org/10.5281/zenodo.3759712. Our novel reference structure improves sequence read mapping and variant genotyping over the linear reference. Our work is a first step towards the transition from linear to variation-aware reference structures in species with high genetic diversity and many sub-populations.
Mechanistic Basis for Microhomology Identification and Genome Scarring by Polymerase Theta
Authors: Carvajal-Garcia Juan , Cho Jang-Eun , Carvajal-Garcia Pablo , Feng Wanjuan , Wood Richard D. , Sekelsky Jeff , Gupta Gaorav P. , Roberts Steven A. , Ramsden Dale A. 
Published: December 2019

AbstractDNA Polymerase Theta mediates an end joining pathway (TMEJ) that repairs chromosome breaks. It requires resection of broken ends to generate long, 3’ single stranded DNA tails, annealing of complementary sequence segments (microhomologies) in these tails, followed by microhomology-primed synthesis sufficient to resolve broken ends. The means by which microhomologies are identified is thus a critical step in this pathway, but is not understood. Here we show microhomologies are identified by a scanning mechanism initiated from the 3’ terminus and favoring bi-directional progression into flanking DNA, typically to a maximum of 15 nucleotides into each flank. Polymerase theta is frequently insufficiently processive to complete repair of breaks in microhomology-poor, AT-rich regions. Aborted synthesis leads to one or more additional rounds of microhomology search, annealing, and synthesis; this promotes complete repair in part because earlier rounds of synthesis generate microhomologiesde novothat are sufficiently long that synthesis is more processive. Aborted rounds of synthesis are evident in characteristic genomic scars as insertions of 3-30 bp of sequence that is identical to flanking DNA (“templated” insertions). Templated insertions are present at higher levels in breast cancer genomes from patients with germlineBRCA1/2mutations, consistent with an addiction to TMEJ in these cancers. Our work thus describes the mechanism for microhomology identification, and shows both how it mitigates limitations implicit in the microhomology requirement, and generates distinctive genomic scars associated with pathogenic genome instability.
Repression of LKB1 bymiR-17∼92sensitizesMYC-dependent lymphoma to biguanide treatment
Authors: Izreig Said , Gariepy Alexandra , Donayo Ariel O. , Bridon Gaëlle , Avizonis Daina , Sheldon Ryan D. , Laister Rob , Minden Mark D. , Johnson Nathalie A. , Williams Kelsey S. , Rudoltz Marc S. , Duchaine Thomas F. , Yoo Sanghee , Pollak Michael N. , Jones Russell G. 
Published: December 2019

AbstractCancer cells display metabolic plasticity to survive metabolic and energetic stresses in the tumor microenvironment, prompting the need for tools to target tumor metabolism. Cellular adaptation to energetic stress is coordinated in part by signaling through the Liver Kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Reducing LKB1-AMPK signaling exposes metabolic vulnerabilities in tumor cells with potential for therapeutic targeting. Here we describe that miRNA-mediated silencing of LKB1 (mediated by the oncogenic miRNA clustermiR-17∼92) confers sensitivity of lymphoma cells to mitochondrial inhibition by biguanides. Using both classic (phenformin) and novel (IM156) biguanides, we demonstrate thatMyc+lymphoma cells with elevatedmiR-17∼92expression display increased sensitivity to biguanide treatment both in cell viability assaysin vitroand tumor growth assaysin vivo. This increased biguanide sensitivity is driven bymiR-17-dependent silencing of LKB1, which results in reduced AMPK activation in response to bioenergetic stress. Mechanistically, biguanide treatment inhibits TCA cycle metabolism and mitochondrial respiration inmiR-17∼92-expressing tumor cells, targeting their metabolic vulnerability. Finally, we demonstrate a direct correlation betweenmiR-17∼92expression and biguanide sensitivity in human cancer cells. Our results identifymiR-17∼92expression as a potential biomarker for biguanide sensitivity in hematological malignancies and solid tumors.One Sentence SummarymiR-17∼92 expression inMyc+tumors sensitizes cancer cells to biguanide treatment by disrupting bioenergetic stability in lymphoma cells.
Homologous laminar organization of the mouse and human subiculum
Authors: Bienkowski Michael S. , Sepehrband Farshid , Kurniawan Nyoman D. , Stanis Jim , Korobkova Laura , Khanjani Neda , Hintiryan Houri , Miller Carol A. , Dong Hong-Wei 
Published: December 2019

SummaryThe subiculum is the major output structure of the hippocampal formation and one of the brain regions most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Usingin situhybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.
Ankylosis homologue (ANKH) controls extracellular citrate and pyrophosphate homeostasis and affects bone mechanical performance
Authors: Szeri Flora , Lundkvist Stefan , Donnelly Sylvia , Engelke Udo F.H. , Rhee Kyu , Williams Charlene , Sundberg John P. , Wevers Ron A. , Tomlinson Ryan E. , Jansen Robert , van de Wetering Koen 
Published: December 2019

AbstractThe membrane protein Ankylosis homologue (ANKH, mouse orthologue: ANK) prevents mineralization of joint-space and articular cartilage. The accepted view is that ANKH mediates cellular release of inorganic pyrophosphate (PPi), a strong physiological inhibitor of mineralization. Using global metabolite profiling, we identified citrate as the most prominent metabolite leaving HEK293 cells in an ANKH-dependent manner. Although PPi levels were increased in culture medium of HEK293-ANKH cells, PPi was formed extracellularly after release of ATP and other nucleoside triphosphates.Ankank/ankmice, which lack functional ANK, had substantially reduced concentrations of citrate in plasma and urine, while citrate was undetectable in urine of a human patient lacking functional ANKH. Bone hydroxyapatite ofAnkank/ankmice also contained markedly reduced levels of citrate and PPi and displayed diminished strength. Together, our data show that ANKH is a crucial factor in extracellular citrate and PPi homeostasis that is essential for normal bone development.
A sub+ cortical fMRI-based surface parcellation
Authors: Lewis John D. , Bezgin Gleb , Fonov Vladimir S. , Collins D. Louis , Evans Alan C. 
Published: December 2019

AbstractBoth the cortex and the subcortical structures are organized into a large number of distinct areas reflecting functional and cytoarchitectonic differences. Mapping these areas is of fundamental importance to neuroscience. A central obstacle to this task is the inaccuracy associated with mapping results from individuals into a common space. The vast individual differences in morphology pose a serious problem for volumetric registration. Surface-based approaches fare substantially better, but have thus far been used only for cortical parcellation. We extend this surface-based approach to include also the subcortical deep gray-matter structures. Using the life-span data from the Enhanced Nathan Klein Institute - Rockland Sample, comprised of data from 590 individuals from 6 to 85 years of age, we generate a functional parcellation of both the cortical and subcortical surfaces. To assess this extended parcellation, we show that our extended functional parcellation provides greater homogeneity of functional connectivity patterns than do arbitrary parcellations matching in the number and size of parcels. We also show that our subcortical parcels align with known subnuclei. Further, we show that this parcellation is appropriate for use with data from other modalities; we generate cortical and subcortical white/gray contrast measures for this same dataset, and draw on the fact that areal differences are evident in the relation of white/gray contrast to age, to sex, to brain volume, and to interactions of these terms; we show that our extended functional parcellation provides an improved fit to the complexity of the life-span changes in the white/gray contrast data compared to arbitrary parcellations matching in the number and size of parcels. We provide our extended functional parcellation for the use of the neuroimaging community.
Dnmt3aknockout in excitatory neurons impairs postnatal synapse maturation and is partly compensated by repressive histone modification H3K27me3
Authors: Li Junhao , Pinto-Duarte Antonio , Zander Mark , Lai Chi-Yu , Osteen Julia , Fang Linjing , Luo Chongyuan , Lucero Jacinta D. , Gomez-Castanon Rosa , Nery Joseph R. , Silva-Garcia Isai , Pang Yan , Sejnowski Terrence J. , Powell Susan B. , Ecker Joseph R. , Mukamel Eran A. , Behrens M. Margarita 
Published: December 2019

SummaryTwo epigenetic pathways of repression, DNA methylation and Polycomb repressive complex 2 (PRC2) mediated gene silencing, regulate neuron development and function, but their respective contributions are unknown. We found that conditional loss of thede novoDNA methyltransferaseDnmt3ain mouse excitatory neurons altered expression of synapse-related genes, stunted synapse maturation, and impaired working memory and social interest. Loss ofDnmt3aabolished postnatal accumulation of CG and non-CG DNA methylation, leaving neurons with an unmethylated, fetal-like epigenomic pattern at −140,000 genomic regions. The PRC2-associated histone modification H3K27me3 increased at many of these sites, partially compensating for the loss of DNA methylation. Our data support a dynamic interaction between two fundamental modes of epigenetic repression during postnatal maturation of excitatory neurons, which together confer robustness on neuronal regulation.
A genomic view of coral-associatedProsthecochlorisand a companion sulfate-reducing bacterium
Authors: Chen Yu-Hsiang , Yang Shan-Hua , Tandon Kshitij , Lu Chih-Ying , Chen Hsing-Ju , Shih Chao-Jen , Tang Sen-Lin 
Published: December 2019

AbstractEndolithic microbial symbionts in the coral skeleton may play a pivotal role in maintaining coral health. However, compared to aerobic microorganisms, research on the roles of endolithic anaerobic microorganisms and microbe-microbe interactions in the coral skeleton are still in their infancy. In our previous study, we showed that a group of coral-associatedProsthecochloris(CAP), a genus of anaerobic green sulfur bacteria, was dominant in the skeleton of the coralIsopora palifera. Though CAP is diverse, the 16S rRNA phylogeny presents it as a distinct clade separate from other free-livingProsthecochloris. In this study, we build on previous research and further characterize the genomic and metabolic traits of CAP by recovering two new near-complete CAP genomes—CandidatusProsthecochloris isoporaea andCandidatusProsthecochloris sp. N1—from coralIsopora paliferaendolithic cultures. Genomic analysis revealed that these two CAP genomes have high genomic similarities compared with otherProsthecochlorisand harbor several CAP-unique genes. Interestingly, different CAP species harbor various pigment synthesis and sulfur metabolism genes, indicating that individual CAPs can adapt to a diversity of coral microenvironments. A novel near-complete SRB genome—CandidatusHalodesulfovibrio lyudaonia—was also recovered from the same culture. The fact that CAP and various sulfate-reducing bacteria (SRB) co-exist in coral endolithic cultures and coral skeleton highlights the importance of SRB in the coral endolithic community. Based on functional genomic analysis ofCa. P. sp. N1 andCa. H. lyudaonia, we also propose a syntrophic relationship between the SRB and CAP in the coral skeleton.ImportanceLittle is known about the ecological roles of endolithic microbes in the coral skeleton; one potential role is as a nutrient source for their coral hosts. Here, we identified a close ecological relationship between CAP and SRB. Recovering novel near-complete CAP and SRB genomes from endolithic cultures in this study enabled us to understand the genomic and metabolic features of anaerobic endolithic bacteria in coral skeletons. These results demonstrate that CAP members with similar functions in carbon, sulfur, and nitrogen metabolisms harbor different light-harvesting components, suggesting that CAP in the skeleton adapts to niches with different light intensities. Our study highlights the potential ecological roles of CAP and SRB in coral skeletons and paves the way for future investigations into how coral endolithic communities will respond to environmental changes.
Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood
Authors: Marquardt Nicole , Scharenberg Marlena , Mold Jeffrey E. , Hård Joanna , Kekäläinen Eliisa , Buggert Marcus , Nguyen Son , Wilson Jennifer N. , Al-Ameri Mamdoh , Ljunggren Hans-Gustaf , Michaëlsson Jakob 
Published: December 2019

AbstractHuman adaptive-like “memory” CD56dimCD16+ NK cells in peripheral blood from cytomegalovirus-seropositive individuals have been extensively investigated in recent years and are currently explored as a treatment strategy for hematological cancers. However, treatment of solid tumors remains limited due to insufficient NK cell tumor infiltration, and it is unknown whether large expansions of adaptive-like NK cells that are equipped for tissue-residency and tumor-homing exist in peripheral tissues. Here, we show that human lung and blood contains adaptive-like CD56brightCD16− NK cells with hallmarks of tissue-residency, including expression of CD49a. Expansions of adaptive-like lung tissue-resident (tr)NK cells were found to be present independently of adaptive-like CD56dimCD16+ NK cells and to be hyperresponsive towards target cells. Together, our data demonstrate that phenotypically, functionally, and developmentally distinct subsets of adaptive-like NK cells exist in human lung and blood. Given their tissue-related character and hyperresponsiveness, human lung adaptive-like trNK cells might represent a suitable alternative for therapies targeting solid tumors.