bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression between African-ancestry and White patients diagnosed with Triple-Negative Breast Cancer: EGFR, Myc, Bcl2 and β-Catenin as ancestry-associated markers
Authors: Matias Ana T. , Jacinta-Fernandes Ana , Maia Ana-Teresa , Braga Sofia , Jacinto António , Cabral M. Guadalupe , Brito Patrícia H. 
Published: November 2020

AbstractPurposeTriple-negative breast cancer (TNBC) has a higher incidence, a younger age of onset, and a more aggressive behavior in African-ancestry women. Biological disparities have been suggested as an important factor influencing the ancestry-associated TNBC discrepancy. In this study, we sought to identify ancestry-associated differential gene and protein expression between African-ancestry and White TNBC patients, controlling for patients’ menopause status and pathological staging at diagnosis.MethodsDifferential gene expression analyses (DGEA) were performed using RNA-sequencing data from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) and Ingenuity Pathway Analysis (IPA), with focus on network design, were performed to highlight candidate genes for further validation through immunohistochemistry of TNBC samples from patients followed in Portugal.ResultsWith 52 African-American and 90 White TNBC patients included, TCGA’s data corroborate that African-American patients have a higher TNBC incidence (28.42% vs 11.89%, p<0.0001). Particularly, premenopausal and stage II disease African-American patients also have significantly lower survival probability, comparing with White patients (log-rank p=0.019 and 0.0038, respectively). DGEA results suggest that expression profile differences are more associated with TNBC staging than with patient’s menopause status. Hippo pathway and cellular community gene sets are downregulated, while breast cancer gene set is upregulated in African-Americans, comparing with White TNBC patients. Furthermore, MAPK pathway gene set is upregulated when controlling for stage II disease. Due to their central role in highly scored networks resulted from IPA’s network design, EGFR, Myc and Bcl2 genes were selected for further validation through immunohistochemistry. We also included β-Catenin in the validation study as it is consensually reported to be required in TNBC tumorigenesis. Although patients used in the DGEA and in the immunohistochemistry experiments are geographically and culturally distinct, both groups of African-ancestry patients are mostly of western-African ancestry and, interesting, differential gene and protein expression matched.ConclusionsWe found ancestry-associated gene expression patterns between African-ancestry and White TNBCs, particularly when controlling for menopause status or staging. EGFR, Myc, Bcl2 and β-catenin gene and protein differential expression matching results in distinct populations suggest these markers as being important indicators of TNBC’s ancestry-associated development.
A high-quality, chromosome-level genome assembly of the Black Soldier Fly (Hermetia IllucensL.)
Authors: Generalovic Tomas N. , McCarthy Shane A. , Warren Ian A. , Wood Jonathan M.D. , Torrance James , Sims Ying , Quail Michael , Howe Kerstin , Pipan Miha , Durbin Richard , Jiggins Chris D. 
Published: November 2020

AbstractBackgroundHermetia illucensL. (Diptera: Stratiomyidae), the Black Soldier Fly (BSF) is an increasingly important mass reared entomological resource for bioconversion of organic material into animal feed.ResultsWe generated a high-quality chromosome-scale genome assembly of the BSF using Pacific Bioscience, 10X Genomics linked read and high-throughput chromosome conformation capture sequencing technology. Scaffolding the final assembly with Hi-C data produced a highly contiguous 1.01 Gb genome with 99.75% of scaffolds assembled into pseudo-chromosomes representing seven chromosomes with 16.01 Mb contig and 180.46 Mb scaffold N50 values. The highly complete genome obtained a BUSCO completeness of 98.6%. We masked 67.32% of the genome as repetitive sequences and annotated a total of 17,664 protein-coding genes using the BRAKER2 pipeline. We analysed an established lab population to investigate the genomic variation and architecture of the BSF revealing six autosomes and the identification of an X chromosome. Additionally, we estimated the inbreeding coefficient (1.9%) of a lab population by assessing runs of homozygosity. This revealed a plethora of inbreeding events including recent long runs of homozygosity on chromosome five.ConclusionsRelease of this novel chromosome-scale BSF genome assembly will provide an improved platform for further genomic studies and functional characterisation of candidate regions of artificial selection. This reference sequence will provide an essential tool for future genetic modifications, functional and population genomics.
Identification of root rot resistance QTLs in pea usingFusarium solanif. sp.pisi-responsive differentially expressed genes
Authors: Williamson-Benavides Bruce A. , Sharpe Richard , Nelson Grant , Bodah Eliane T. , Porter Lyndon D. , Dhingra Amit 
Published: November 2020

AbstractPisum sativum(pea) yields have declined significantly over the last decades, predominantly due to susceptibility to root rot diseases. One of the main causal agents of root rot is the fungusFusarium solanif. sp.pisi(Fsp), leading to yield losses ranging from 15 to 60%. Determining and subsequently incorporating the genetic basis for resistance in new cultivars offers one of the best solutions to control this pathogen; however, no green-seeded pea cultivars with complete resistance toFsphave been identified. To date, only partial levels of resistance toFsphas been identified among pea genotypes. SNPs mined fromFsp-responsive differentially expressed genes (DEGs) identified in a preceding study were utilized to identify QTLs associated withFspresistance using composite interval mapping in two recombinant inbred line (RIL) populations segregating for partial root rot resistance. A total of 769 DEGs with single nucleotide polymorphisms (SNPs) were identified, and the putative SNPs were evaluated for being polymorphic across four partially resistant and four susceptibleP. sativumgenotypes. The SNPs with validated polymorphisms were used to screen two RIL populations using two phenotypic criteria: root disease severity and plant height. One QTL,WB.Fsp-Ps5.1 that mapped to chromosome V explained 14.76 % of the variance with a confidence interval of 10.36 cM. The other four QTLs located on chromosomes II, III, and V, explained 5.26–8.05 % of the variance. The use of SNPs derived fromFsp-responsive DEGs for QTL mapping proved to be an efficient way to identify molecular markers associated withFspresistance in pea. These QTLs are potential candidates for marker-assisted selection and gene pyramiding to obtain high levels of partial resistance in pea cultivars to combat root rot caused byFsp.
Andean uplift, drainage basin formation, and the evolution of riverweeds(Marathrum,Podostemaceae)in northern South America
Authors: Bedoya Ana M. , Leaché Adam D. , Olmstead Richard G. 
Published: November 2020

SummaryNorthern South America is a geologically dynamic and species-rich region. While fossil and stratigraphic data show that reconfiguration of river drainages resulted from mountain uplift in the tropical Andes, investigations of the impact of landscape change on the evolution of the flora in the region have been restricted to terrestrial taxa.We explore the role of landscape change on the evolution of plants living strictly in rivers across drainage basins in northern South America by conducting population structure, phylogenomic, phylogenetic networks, and divergence-dating analyses for populations of riverweeds (Marathrum, Podostemaceae).We show that mountain uplift and drainage basin formation isolated populations ofMarathrumand created barriers to gene flow across rivers drainages. Sympatric species hybridize and the hybrids show the phenotype of one parental line. We propose that the pattern of divergence of populations reflect the formation of river drainages, which was not complete until <4 MaOur study provides a clear picture of the role of landscape change in shaping the evolution of riverweeds in northern South America, advances our understanding of the reproductive biology of this remarkable group of plants, and spotlights the impact of hybridization in phylogenetic inference.
The primary cilium is required for MC4R control of food intake and body weight
Authors: Wang Yi , Bernard Adelaide , Comblain Fanny , Yue Xinyu , Paillart Christophe , Zhang Sumei , Reiter Jeremy F. , Vaisse Christian 
Published: November 2020

AbstractThe Melanocortin-4 Receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis and mutations in MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R expressing neurons are unknown. We recently reported that MC4R localizes to primary cilia, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether MC4R functions there. Here, using mouse genetic approaches, we found that cilia are required specifically on MC4R-expressing neurons to restrain feeding behavior. Moreover, these cilia were critical for pharmacological activators of MC4R to exert an anorexigenic effect. MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus (PVN) of the hypothalamus are essential to restrict food intake. MC4R activation increases adenylyl cyclase activity. Like removing cilia, inhibiting adenylyl cyclase activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, MC4R signals via cilia of PVN neurons to control food intake and body weight. We propose that defects in ciliary localization of MC4R cause obesity in human inherited obesity syndromes and ciliopathies.
Directional phyllotactic bias in calatheas (Goeppertia, Marantaceae): a citizen science approach
Authors: Durrington Benjamin , Chong Fiona , Chitwood Daniel H. ,   Twitter Calathea Poll Participants
Published: November 2020

AbstractLateral organs arranged in spiral phyllotaxy are separated by the golden angle, ≈137.5°, leading to handedness: either clockwise or counter-clockwise. In some species, leaves are asymmetric such that they are smaller and curved towards the side ascending the phyllotactic spiral. As such, these asymmetries lead to mirroring of leaf shapes in plants of opposite phyllotactic handedness. Previous reports had suggested that the pin-stripe calathea (Goeppertia ornata) may be exclusively of one phyllotactic direction, counter-clockwise, but had limited sampling to a single population. Here, we use a citizen science approach leveraging a social media poll, internet image searches, and in-person verification at nurseries in four countries and two continents to demonstrate that calatheas (Goeppertia spp.) around the world are biased towards counter-clockwise phyllotaxy. The possibility that this bias is genetic and its implications for models of phyllotaxy that assume handedness is stochastically specified in equal proportions is discussed.
Hidden cell diversity in Placozoa: Ultrastructural Insights fromHoilungia hongkongensis
Authors: Romanova Daria Y. , Varoqueaux Frederique , Daraspe Jean , Nikitin Mikhail A. , Eitel Michael , Fasshauer Dirk , Moroz Leonid L. 
Published: November 2020

AbstractFrom a morphological point of view, placozoans are among the most simple free-living animals. This enigmatic phylum is critical for our understanding of the evolution of animals and their cell types. Their millimeter-sized, disc-like bodies consist of only three cell layers that are shaped by roughly six major cell types. Placozoans lack muscle cells and neurons but are able to move using their ciliated lower surface and take up food in a highly coordinated manner. Intriguingly, the genome ofTrichoplax adhaerens, the founding member of the enigmatic phylum, has disclosed a surprising level of genetic complexity. Moreover, recent molecular and functional investigations have uncovered a much larger, so-far hidden cell-type diversity. Here, we have extended the microanatomical characterization of a recently described placozoan species –Hoilungia hongkongensis. InH. hongkongensis, we recognized the established canonical three-layered placozoan body plan but also came across several morphologically distinct and potentially novel cell types, among them novel gland cells and “shiny spheres”-bearing cells at the upper epithelium. Thus, the diversity of cell types in placozoans is indeed higher than anticipated.
Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution
Authors: Roberts Kingman Garrett A , Vyas Deven N , Jones Felicity C , Brady Shannon D , Chen Heidi I , Reid Kerry , Milhaven Mark , Bertino Thomas S , Aguirre Windsor E , Heins David C , von Hippel Frank A , Park Peter J , Kirch Melanie , Absher Devin M , Myers Richard M , Di Palma Federica , Bell Michael A , Kingsley David M , Veeramah Krishna R 
Published: November 2020

AbstractSimilar forms often evolve repeatedly in nature, raising longstanding questions about the underlying mechanisms. Here we use repeated evolution in sticklebacks to identify a large set of genomic loci that change recurrently during colonization of new freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Dramatic genotypic and phenotypic changes arise within 5-7 years, facilitated by standing genetic variation and linkage between adaptive regions. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwin’s finches, suggesting similar features are important for evolution across diverse taxa.
Degradation ofboscalid, pyraclostrobin, fenbuconazole, andglyphosateresidues by an advanced oxidative process utilizing ultraviolet light and hydrogen peroxide
Authors: Skanes Blake , Ho Jordan , Warriner Keith , Prosser Ryan S. 
Published: November 2020

AbstractRecently an advanced oxidative process (AOP) combining H2O2and UV-C light was observed to be effective at controllingListeria monocytogens(Murray et al., 2018) andEscherichia coliO157:H7 and degrading chlorpyrifos residues on the surface of apples (Ho et al., 2020). Little is known about the application of AOP for the degradation of other pesticide residues. This study examined degradation of boscalid, pyraclostrobin, fenbuconazole and glyphosate by 3% (w/v) H2O2, UV-C (254 nm) irradiation and their combination on apple skin and glass. The extent of degradation was not significantly different between the AOP and optimal individual treatment. However, treatment susceptibility was different with glyphosate most effectively degraded by H2O2exposure (up to 98% on apple, 3% (w/v) H2O2at 30□C for 15 min) while boscalid, pyraclostrobin and fenbuconazole were more effectively degraded by UV-C (up to 88%, 100% and 70% degradation after ~11,000 mJ/cm2). Suggestions for possible causes of degradation are proposed.
Can a nick promote partial genome re-replication?
Authors: Johansson Erik , Diffley John F.X 
Published: November 2020

AbstractSingle-stranded DNA breaks, including simple nicks, are amongst the most common forms of DNA damage in cells. They can be readily repaired by ligation; however, if a nick occurs just ahead of an approaching replisome, the outcome is a ‘collapsed’ replication fork in which the nick is converted into a single-ended double-strand DNA break. Attention has largely focused on the processes by which this broken end is used to prime replication restart. We realized that in eukaryotic cells, where replication initiates from multiple replication origins, a second fork converging on the collapsed fork offers additional opportunities for repair, but also generates a substrate that can promote localized re-replication. We have modelled this with purified proteinsin vitroand have found that there is, indeed, an additional hazard that eukaryotic replisomes face. We discuss how this problem might be mitigated.
GABAergic signaling promotes early-life seizures in epileptic SYNGAP1+/-mice
Authors: Sullivan Brennan J. , Kipnis Pavel A. , Ammanuel Simon G. , Kadam Shilpa D. 
Published: November 2020

AbstractObjectiveSYNGAP1encephalopathy is a developmental and epileptic encephalopathy caused by pathogenic loss of function variants.Syngap1-heterozygous (Het+/-) mice demonstrate progressive epilepsy with multiple seizure phenotypes in adulthood. Here, we investigate early-life seizures in Het+/-pups and explore ofSyngap1encephalopathy during development.MethodsPost-natal day 7 (P7) and P12 mice were investigated by tethered video-electroencephalographic (vEEG). The effects of GABAergic drugs phenobarbital (PB) and pentylenetetrazol (PTZ) were investigated at P7 and P12, respectively. 24h tethered vEEG was performed at P24, and telemetric 24h vEEG with 6h sleep deprivation was performed at P35. The effect of perampanel (PMP), an AMPA receptor antagonist, was investigated at P24.ResultsHet+/-mice have spontaneous early-life seizures that lack an overt behavioral phenotype. These subclinical seizures are refractory to PB, but the GABAAreceptor (GABAAR) antagonist PTZ significantly reduced seizure frequency suggesting that GABAergic signaling may promote seizure generation in Het+/-pups. At juvenile ages, Het+/-pups recapitulated the early emergence of high gamma (35-50Hz) during NREM and disruption of behavioral-state gamma homeostasis. This biomarker was significantly exacerbated in Het+/-pups after increasing sleep pressure with sleep deprivation.SignificanceSeizures during development have adverse effects on cognitive function. Therefore, an improved understanding of theSYNGAP1epilepsy during developmental ages is necessary to delineate the deleterious interactions between aberrant synaptic function and recurrent seizures. The development of evidence-based therapies for early-life intervention will benefit from these insights.
Preferred auditory temporal processing regimes and auditory-motor interactions
Authors: Kern Pius , Assaneo M. Florencia , Endres Dominik , Poeppel David , Rimmele Johanna M. 
Published: November 2020

AbstractDecoding the rich temporal dynamics of complex sounds such as speech is constrained by the underlying neuronal processing mechanisms. Oscillatory theories suggest the existence of one optimal perceptual performance regime at auditory stimulation rates in the delta to theta range (<10 Hz), but reduced performance in the alpha range (10-14 Hz) is controversial. Additionally, the widely discussed motor system contribution to timing remains unclear. We measured rate discrimination thresholds between 4-15 Hz, and auditory-motor coupling strength was estimated through auditory-motor synchronization. In a Bayesian model comparison, high auditory-motor synchronizers showed a larger range of constant optimal temporal judgments than low synchronizers, with performance decreasing in the alpha range. This evidence for optimal auditory processing in the theta range is consistent with preferred oscillatory regimes in auditory cortex that compartmentalize stimulus encoding and processing. The findings suggest, remarkably, that increased auditory-motor interaction might extend such an optimal range towards faster rates.
Genome-wide Identification of the Genetic Basis of Amyotrophic Lateral Sclerosis
Authors: Zhang Sai , Cooper-Knock Johnathan , Weimer Annika K. , Shi Minyi , Moll Tobias , Harvey Calum , Nezhad Helia Ghahremani , Franklin John , dos Santos Souza Cleide , Wang Cheng , Li Jingjing , Elhaik Eran , Eitan Chen , Hornstein Eran , Kenna Kevin P. ,   Project MinE Sequencing Consortium, Veldink Jan , Ferraiuolo Laura , Shaw Pamela J. , Snyder Michael P. 
Published: November 2020

ABSTRACTAmyotrophic lateral sclerosis (ALS) is an archetypal complex disease centered on progressive death of motor neurons. Despite heritability estimates of 52%, GWAS studies have discovered only seven genome-wide significant hits, which are relevant to <10% of ALS patients. To increase the power of gene discovery, we integrated motor neuron functional genomics with ALS genetics in a hierarchical Bayesian model called RefMap. Comprehensive transcriptomic and epigenetic profiling of iPSC-derived motor neurons enabled RefMap to systematically fine-map genes and pathways associated with ALS. As a significant extension of the known genetic architecture of ALS, we identified a group of 690 candidate ALS genes, which is enriched with previously discovered risk genes. Extensive conservation, transcriptome and network analyses demonstrated the functional significance of these candidate genes in motor neurons and disease progression. In particular, we observed a genetic convergence on the distal axon, which supports the prevailing view of ALS as a distal axonopathy. Of the new ALS genes we discovered, we further characterizedKANK1that is enriched with coding and noncoding, common and rare ALS-associated genetic variation. Modelling patient mutations in human neurons reducedKANK1expression and produced neurotoxicity with disruption of the distal axon. RefMap can be applied broadly to increase the discovery power in genetic association studies of human complex traits and diseases.
Insulin Resistance Mediates Crosstalk between Skeletal Muscle and the Heart to Prevent Cardiac Dysfunction
Authors: Jia Dandan , Zhang Jun , Liu Xueling , Anderson John-Paul , Tian Zhenjun , Nie Jia , Shi Yuguang 
Published: November 2020

AbstractObesity and type 2 diabetes milieus (T2DM) are the leading causes of cardiovascular morbidity and mortality. Although insulin resistance is believed to underlie these disorders, a paradox exists that obese patients with cardiovascular diseases have better prognoses relative to leaner patients with the same diagnoses, whereas improvement of insulin sensitivity by thiazolidines significantly increases the risk of heart failure in T2DM patients. Using mice with skeletal muscle-specific deletion of the insulin receptor gene (MIRKO), we resolved this dilemma by demonstrating that insulin resistance in the skeletal muscle prevents myocardial hypertrophy and dysfunction in response to diet-induced obesity. In spite of aggregating obesity, insulin resistance selectively protected the heart, but not other metabolic tissues, from mitochondrial dysfunction and insulin resistance in MIRKO mice, leading to significant attenuation of inflammation and apoptosis of cardiomyocytes. Together, our findings revealed an unexpected role of insulin resistance as a double edge sword, calling for reevaluation of ongoing efforts for targeting insulin resistance for the treatment of metabolic diseases.Significance statementInsulin resistance is commonly recognized as one of the major causes of T2DM and other aging-related chronic diseases. However, cumulative efforts in targeting insulin resistance for the treatment of T2DM and other metabolic disorders have not met with great success due to unwanted side effects on heart failure. Here we report that insulin resistance in skeletal muscle is a double edge sword. On one hand, insulin resistance in skeletal muscle aggregates obesity and its related metabolic syndromes, and on the other it protects the heart from the development of myocardial hypertrophy, dysfunction, and apoptosis in response to DIO. Our findings call for reevaluation of the ongoing strategies in targeting insulin resistance as a novel treatment for T2DM and other metabolic diseases.