bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Landmark-guided Bijective Brain Image Registration by Composing Region-based Locally Diffeomorphic Warpings
Authors: He Hengda , Razlighi Qolamreza R.
Published: April 2020

As the size of the neuroimaging cohorts being increased to address key questions in the field of cognitive neuroscience, cognitive aging, and neurodegenerative diseases, the accuracy of the spatial normalization as an essential pre-processing step becomes extremely important in the neuroimaging processing pipeline. Existing spatial normalization methods have poor accuracy particularly when dealing with the highly convoluted human cerebral cortex and when brain morphology is severely altered (e.g. clinical and aging populations). To address this shortcoming, we propose to implement and evaluate a novel landmark-guided region-based spatial normalization technique that takes advantage of the existing surface-based human brain parcellation to automatically identify and match regional landmarks. To simplify the non-linear whole brain registration, the identified landmarks of each region and their counterparts are registered independently with large diffeomorphic (topology preserving) deformation via geodesic shooting. The regional diffeomorphic warping fields were combined by an inverse distance weighted interpolation technique to have a smooth global warping field for the whole brain. To ensure that the final warping field is diffeomorphic, we used simultaneously forward and reverse maps with certain symmetric constraints to yield bijectivity. We have evaluated our proposed method using both simulated and real (structural and functional) human brain images. Our evaluation shows that our method can enhance structural correspondence up to around 86%, a 67% improvement compared to the existing state-of-the-art method. Such improvement also increases the sensitivity and specificity of the functional imaging studies by about 17%, reducing the required number of subjects and subsequent costs. We conclude that our proposed method can effectively substitute existing substandard spatial normalization methods to deal with the demand of large cohorts and the need for investigating clinical and aging populations.
Suppression of MicroRNA-144 Promotes CXCR4 and CXCL12 Expression and Downregulates Apoptosis in Ovarian Cancer Cells
Authors: Turut Fatma Aysun , Acidereli Hilal , Cevik Ozge
Published: April 2020

MicroRNAs are important regulators in the growth and metastasis of ovarian cancers. Many assays were established to identify the role of miR-144-3p in ovarian cancer cells and its interaction with COX-2 and chemokines (CXCR4 and CXCL12). The ovarian cancer cells (OVCAR-3 and SKOV-3) were transfected with Anti-miR-144 to downregulate the miR-144-3p and cultured for 36 h. We herein examined the cell viability, colony formation, cell migration, COX-2 reporter activity, the protein expressions of CXCR4, CXCL12, COX-2, VEGF, Caspase-3, BAX and Bcl-2. We have observed that the suppression of miR-144-3p significantly increased the cell proliferation and migration and decreased the apoptosis. Moreover, the downregulation of miR-144-3p markedly increased the COX-2, CXCR4, CXCL12 and VEGF expression in OVCAR-3 and SKOV-3 ovarian cancer cells. In conclusion, miR-144-3p may play important roles in the regulation of chemokine receptor CXCR4 and its ligand CXCL12 in the progressive ovarian tumors expressing COX2. These data suggests that miR-144 has the novel therapeutic targets for the cancer therapy and cancer prevention.
Functional properties of powders produced from either or not fermented mealworm (Tenebrio molitor) paste
Authors: Borremans A. , Bußler S. , Sagu T. S , Rawel H.M. , Schlüter O. , Van Campenhout L.
Published: April 2020

The aim of this study was to determine the effect of fermentation of mealworms (Tenebrio molitor) with commercial meat starters cultures on the functional properties of powders produced from the larvae. Full fat and defatted powder samples were prepared from non-fermented and fermented mealworm pastes. Then the crude protein, crude fat and dry matter contents, pH, bulk density, colour, water and oil binding capacity, foaming capacity and stability, emulsion capacity and stability, protein solubility, quantity of free amino groups and protein composition of the powders were evaluated. Regardless of the starter culture used, fermentation significantly (p < 0.05) reduced the crude and soluble protein content of the non-defatted mealworm powders and in general impaired their water and oil binding, foaming- and emulsifying properties. Defatting of the powders improved most functional properties studied, except the protein solubility, water binding capacity, foaming capacity and emulsion stability. The o-phthaldialdehyd assay revealed that the amount of free amino groups increased during fermentation, which may be attributed to proteolysis of mealworm proteins by the starters. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the soluble proteins of fermented powders were composed of molecules of lower molecular mass compared to non-fermented powders. As the molecular sizes of the soluble proteins decreased, it is clear that also the protein structure was modified by the fermentation process, which in turn led to changes in functional properties. It was concluded that fermentation of mealworms in general does not contribute to the functional properties studied in this work. Nevertheless, the results confirmed that the properties of non-fermented powders are comparable to other food protein sources.
linus: Conveniently explore, share, and present large-scale biological trajectory data from a web browser
Authors: Waschke Johannes , Hlawitschka Mario , Anlas Kerim , Trivedi Vikas , Roeder Ingo , Huisken Jan , Scherf Nico
Published: April 2020

In biology, we are often confronted with information-rich, large-scale trajectory data, but exploring and communicating patterns in such data is often a cumbersome task. Ideally, the data should be wrapped with an interactive visualisation in one concise package that makes it straightforward to create and test hypotheses collaboratively. To address these challenges, we have developed a tool,linus, which makes the process of exploring and sharing 3D trajectories as easy as browsing a website. We provide a python script that reads trajectory data and enriches them with additional features, such as edge bundling or custom axes and generates an interactive web-based visualisation that can be shared offline and online. The goal oflinusis to facilitate the collaborative discovery of patterns in complex trajectory data.
The activity of human enhancers is modulated by the splicing of their associated lncRNAs
Authors: Tan Jennifer Y. , Marques Ana C.
Published: April 2020

Pervasive enhancer transcription is at the origin of more than half of all long noncoding RNAs in humans. Transcription of enhancer-associated long noncoding RNAs (elncRNA) contribute to their cognate enhancer activity and gene expression regulation incis.Recently, splicing of elncRNAs was shown to be associated with elevated enhancer activity. However, whether splicing of elncRNA transcripts is a mere consequence of accessibility at highly active enhancers or if elncRNA splicing directly impacts enhancer function, remains unanswered.

We analysed genetically driven changes in elncRNA expression, in humans, to address this outstanding question. We showed that splicing related motifs within multi-exonic elncRNAs evolved under selective constraints during human evolution, suggesting the processing of these transcripts is unlikely to have resulted from transcription across spurious splice sites. Using a genome-wide and unbiased approach, we used nucleotide variants as independent genetic factors to directly assess the causal relationship that underpin elncRNA splicing and their cognate enhancer activity. We found that the splicing of most elncRNAs is associated with changes in chromatin signatures at cognate enhancers and target mRNA expression.

We conclude that efficient and conserved processing of enhancer-associated elncRNAs contributes to enhancer activity.
Dense encoding of developmental regulatory information may constrain evolvability
Authors: Fuqua Timothy , Jordan Jeff , van Breugel Maria Elize , Halavatyi Aliaksandr , Tischer Christian , Polidoro Peter , Abe Namiko , Tsai Albert , Mann Richard S. , Stern David L. , Crocker Justin
Published: April 2020

Gene regulatory changes underlie much of phenotypic evolution. However, the evolutionary potential of regulatory evolution is unknown, because most evidence comes from either natural variation or limited experimental perturbations. Surveying an unbiased mutation library for a developmental enhancer inDrosophila melanogasterusing an automated robotics pipeline, we found that most mutations alter gene expression. Our results suggest that regulatory information is distributed throughout most of a developmental enhancer and that parameters of gene expression—levels, location, and state—are convolved. The widespread pleiotropic effects of most mutations and the codependency of outputs may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse drosophilids reveal mainly stasis and apparent biases in the phenotypes influenced by this enhancer. Developmental enhancers may encode a much higher density of regulatory information than has been appreciated previously, which may impose constraints on regulatory evolution.

Quote

“Rock, robot rock

Rock, robot rock

Rock, robot rock”

Daft Punk (2005)
Cloning andIn silicocharacterization of Heat shock factor (Hsf2) from Wheat (Triticum aestivum L.)
Authors: Dubey Kavita , Goswami Suneha , Kumar Narendra , Kumar Ranjeet R. , Niraj Ravi RK
Published: April 2020

A gene that encodes for Heat Shock Factor (Hsf) was characterized and designated as TaHsf2 (Gen Bank ID: KP063542) from wheat. The genomic sequence was found to be 1551bp long with open reading frame of length1123bp. The amino acid sequence so concluded showed to have HSF domain having high degree of similarity (homology) with other HSF coding gene of related species. We have reported in-silico three-dimensional model of TaHsf2 and evaluation of the predicted model, analysed with various tools. The sudden climatic variations over the years especially elevation in temperature has adversely affected the growth and productivity of winter wheat (Triticum aestivumL.). A very less number of HSFs is being reported and characterized in wheat and the data so available for wheat calls for investigation and characterization of more HSP’s coding HSFs. In our present study we have cloned one of the novel HSFs and have characterized it throughin silicotools.
Potentiating TMEM16A channel function has no effect on airway goblet cells or bronchial and pulmonary vascular smooth muscle function
Authors: Danahay Henry , Fox Roy , Lilley Sarah , Charlton Holly , Adley Kathryn , Christie Lee , Ansari Ejaz , Ehre Camille , Flen Alexis , Tuvim Michael J. , Dickey Burton F. , Williams Colin , Beaudoin Sarah , Collingwood Stephen P , Gosling Martin
Published: April 2020

The calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.

In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.

Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.

Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.
Tail-Robust Quantile Normalization
Authors: Brombacher Eva , Schad Ariane , Kreutz Clemens
Published: April 2020

High-throughput biological data – such as mass spectrometry-based proteomics data – suffer from systematic non-biological variance, which is introduced by systematic errors such as batch effects. This hinders the estimation of ‘real’ biological signals and, thus, decreases the power of statistical tests and biases the identification of differentially expressed sample classes. To remove such unintended variation, while retaining the biological signal of interest, the analysis workflows for mass spectrometry-based quantification typically comprises normalization steps prior to the statistical analysis of the data. Several normalization methods, such as quantile normalization, have originally been developed for microarray data. However, unlike microarray data, proteomics data may contain features, in the form of protein intensities, that are consistently highly abundant across experimental conditions and, hence, are encountered in the tails of the protein intensity distribution. If such proteins are present, statistical inferences of the intensity profiles of the normalized features are impeded through the increased number of false positive findings due to the biased estimation of the variance of the data. Thus, we developed a, freely available, novel approach: ‘tail-robust quantile normalization’. It extends the traditional quantile normalization to preserve the biological signals of features in the tails of the distribution over experimental conditions and to account for sample-dependent missing values.
A large effective population size for within-host influenza virus infection
Authors: Lumby Casper K , Zhao Lei , Breuer Judy , Illingworth Christopher J R
Published: April 2020

Strains of the influenza virus form coherent global populations, yet exist at the level of single infections in individual hosts. The relationship between these scales is a critical topic for understanding viral evolution. Here we investigate the within-host relationship between selection and the stochastic effects of genetic drift, estimating an effective population size of infection Nefor influenza infection. Examining whole-genome sequence data describing a chronic case of influenza B in a severely immunocompromised child we infer an Neof 2.5 × 107(95% confidence range 1.0 × 107to 9.0 × 107) suggesting the importance of genetic drift to be minimal. Our result, supported by the analysis of data from influenza A infection, suggests that positive selection during within-host infection is primarily limited by the typically short period of infection. Atypically long infections may have a disproportionate influence upon global patterns of viral evolution.
JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps
Authors: Dukart Juergen , Holiga Stefan , Rullmann Michael , Lanzenberger Rupert , Hawkins Peter C.T. , Mehta Mitul A. , Hesse Swen , Barthel Henryk , Sabri Osama , Jech Robert , Eickhoff Simon B.
Published: April 2020

Recent studies have shown that drug-induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross-modal correlation of MRI- based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma- aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson’s disease patients (PD) and risperidone-induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5-HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.
SRF is a non-histone methylation target of KDM2B and SET7 in the regulation of myogenesis
Authors: Joung Hosouk , Kang Joo-Young , Kim Ji-Young , Kwon Duk-Hwa , Jeong Anna , Min Hyun-Ki , Shin Sera , Lee Yun-Gyeong , Kim Young-Kook , Seo Sang-Beom , Kook Hyun
Published: April 2020

Demethylation of histone lysines, one of the most important modifications in transcriptional regulation, is associated with various physiological states. KDM2B is a histone H3K4, H3K36, and H3K79 demethylase associated with the repression of transcription. Here, we present a novel mechanism by which KDM2B demethylates serum response factor (SRF) K165 to negatively regulate muscle differentiation, which is counteracted by histone methyltransferase SET7. We show that KDM2B inhibited skeletal muscle differentiation by inhibiting the transcription of SRF-dependent genes. Both KDM2B and SET7 regulated the balance of SRF K165 methylation. SRF K165 methylation was required for the transcriptional activation of SRF and for the promoter occupancy of SRF-dependent genes. SET7 inhibitors blocked muscle cell differentiation. Taken together, these data indicate that SRF is a non-histone target of KDM2B and that the methylation balance of SRF maintained by KDM2B and SET7 plays an important role in muscle cell differentiation.
Lipopolysaccharide administration alters extracellular vesicles in human lung-cancer cells and mice
Authors: Jones Leandra B. , Kumar Sanjay , Bell Courtnee’ R. , Crenshaw Brennetta J. , Coats Mamie T. , Sims Brian , Matthews Qiana L.
Published: April 2020

Extracellular vesicles (EVs) play a fundamental role in cell and infection biology and have the potential to act as biomarkers for novel diagnostic tools. In this study, we explored thein vitroimpact of bacterial lipopolysaccharide administration on a cell line that represents a target for bacterial infection in the host. Administration of lipopolysaccharide at varying concentrations to this A549 cell line caused only modest changes in cell death, but EV numbers were significantly changed. After treatment with the highest concentration of lipopolysaccharide, EVs derived from A549 cells packaged significantly less interleukin-6 and lysosomal-associated membrane protein 1. We also examined the impact of lipopolysaccharide administration on exosome biogenesis and cargo composition in BALB/c mice. Serum-isolated EVs from lipopolysaccharide-treated mice showed significantly increased lysosomal-associated membrane protein 1 and toll-like receptor 4 levels compared with EVs from control mice. In summary, this study demonstrated that EV numbers and cargo were altered using thesein vitroandin vivomodels of bacterial infection.
Isoproterenol-induced Cardiac Dysfunction in Male and Female C57Bl/6 Mice
Authors: Grant Marianne K. O. , Abdelgawad Ibrahim Y. , Lewis Christine A. , Seelig Davis , Zordoky Beshay N.
Published: April 2020

Sex-related differences in cardiovascular diseases are complex and context-dependent. The objective of this work was to comprehensively determine key sex differences in the response to acute and chronic adrenergic stimulation in C57Bl/6 mice. Cardiac function was assessed by trans-thoracic echocardiography before and after acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg) in male and female C57Bl/6 mice. Thereafter, chronic adrenergic stimulation was achieved by sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days in male and female mice. Cardiac function and morphometry were assessed by trans-thoracic echocardiography on the 15thday. Thereafter, the mice were euthanized and the hearts were collected. Histopathological analysis of myocardial tissue was performed after staining with hematoxylin & eosin, trichrome, and MAC-2 antibody. Gene expression of remodeling and fibrotic markers was assessed by real-time PCR. Cardiac function and morphometry were also measured before and after isoproterenol 10 mg/kg/day for 14 days in groups of gonadectomized male and female mice and sham-operated controls. In the current work, there were no statistically significant differences in key echocardiographic parameters between male and female C57Bl/6 mice in response to acute adrenergic stimulation. After chronic adrenergic stimulation, there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, chronic isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. The current work demonstrated lack of significant sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6 mice. This study suggests that female sex may not be sufficient to protect the heart against a severe pathologic stimulus and underscores the notion that sexual dimorphism in cardiovascular diseases is highly model-dependent.
Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype
Authors: Chelebian Eduard , Fuster-Garcia Elies , del Mar Álvarez-Torres María , Juan-Albarracín Javier , García-Gómez Juan M.
Published: April 2020

BACKGROUND AND PURPOSE

Genetic classifications are crucial for understanding the heterogeneity of glioblastoma. Recently, MR perfusion imaging techniques have demonstrated their ability to determine molecular alterations. In this work, we investigated whether perfusion markers within infiltrated peripheral edema were associated with proneural, mesenchymal, classical and neural subtypes.

MATERIALS AND METHODS

ONCOhabitats open web service was used to obtain the cerebral blood volume at the infiltrated peripheral edema for MRI studies of 50 glioblastoma patients from The Cancer Imaging Archive: TCGA-GBM. ANOVA and Kruskal-Wallis tests were carried out in order to assess the association between vascular features and the subtypes. For assessing specific differences, Mann-Whitney U-test was conducted. Finally, the association of overall survival with molecular and vascular features was assessed using univariate and multivariate Cox models.

RESULTS

ANOVA and Kruskal-Wallis tests for the maximum cerebral blood volume at the infiltrated peripheral edema between the four subclasses yielded false discovery rate corrected p-values of <0.001 and 0.02, respectively. This vascular feature was significantly higher (p=0.0043) in proneural patients compared to the rest of the subtypes while conducting Mann-Whitney U-test. The multivariate Cox model pointed to redundant information provided by vascular features at the peripheral edema and proneural subtype when analyzing overall survival.

CONCLUSIONS

Higher relative cerebral blood volume at infiltrated peripheral edema is associated with proneural glioblastoma subtype suggesting underlying vascular behavior related to molecular composition in that area.
Detecting turnover among complex communities using null models: A case study with sky-island haemosporidian parasites
Authors: Barrow Lisa N. , Bauernfeind Selina M. , Cruz Paxton A. , Williamson Jessie L. , Wiley Daniele L. , Ford John E. , Baumann Matthew J. , Brady Serina S. , Chavez Andrea N. , Gadek Chauncey R. , Galen Spencer C. , Johnson Andrew B. , Mapel Xena M. , Marroquin-Flores Rosario A. , Martinez Taylor E. , McCullough Jenna M. , McLaughlin Jade E. , Witt Christopher C.
Published: April 2020

Turnover in species composition between sites, or beta diversity, is a critical component of species diversity that is typically influenced by geography, environment, and biotic interactions. Quantifying turnover is particularly challenging, however, in multi-host, multi-parasite assemblages where undersampling is unavoidable, resulting in inflated estimates of turnover and uncertainty about its spatial scale. We developed and implemented a framework using null models to test for community turnover in avian haemosporidian communities of three sky islands in the southwestern United States. We screened 776 birds for haemosporidian parasites from three genera (Parahaemoproteus, Plasmodium, andLeucocytozoon) by amplifying and sequencing a mitochondrial DNA barcode. We detected infections in 280 birds (36.1%), sequenced 357 infections, and found a total of 99 parasite haplotypes. When compared to communities simulated from a regional pool, we observed more unique, single-mountain haplotypes and fewer haplotypes shared among three mountain ranges than expected, indicating that haemosporidian communities differ to some degree among adjacent mountain ranges. These results were robust even after pruning datasets to include only identical sets of host species, and they were consistent for two of the three haemosporidian genera. The two more distant mountain ranges were more similar to each other than the one located centrally, suggesting that the differences we detected were due to stochastic colonization-extirpation dynamics. These results demonstrate that avian haemosporidian communities of temperate-zone forests differ on relatively fine spatial scales associated with adjacent sky-islands. Null models are essential tools for detecting turnover in complex, undersampled, and poorly known systems.
Exploiting Electrophysiological Measures of Semantic Processing for Auditory Attention Decoding
Authors: Dijkstra Karen , Desain Peter , Farquhar Jason
Published: April 2020

In Auditory Attention Decoding, a user’s electrophysiological brain responses to certain features of speech are modelled and subsequently used to distinguish attended from unattended speech in multi-speaker contexts. Such approaches are frequently based on acoustic features of speech, such as the auditory envelope. A recent paper shows that the brain’s response to a semantic description (i.e., semantic dissimilarity) of narrative speech can also be modelled using such an approach. Here we use the (publicly available) data accompanying that study, in order to investigate whether combining this semantic dissimilarity feature with an auditory envelope approach improves decoding performance over using the envelope alone. We analyse data from their ‘Cocktail Party’ experiment in which 33 subjects attended to one of two simultaneously presented audiobook narrations, for 30 1-minute fragments. We find that the addition of the dissimilarity feature to an envelope-based approach significantly increases accuracy, though the increase is marginal (85.4% to 86.6%). However, we subsequently show that this dissimilarity feature, in which the degree of dissimilarity of the current word with regard to the previous context is tagged to the onsets of each content word, can be replaced with a binary content-word-onset feature, without significantly affecting the results (i.e., modelled responses or accuracy), putting in question the added value of the dissimilarity information for the approach introduced in this recent paper.
Genotypic characterization of the U.S. peanut core collection
Authors: Otyama Paul I. , Kulkarni Roshan , Chamberlin Kelly , Ozias-Akins Peggy , Chu Ye , Lincoln Lori M. , MacDonald Gregory E. , Anglin Noelle L. , Dash Sudhansu , Bertioli David J. , Fernández-Baca David , Graham Michelle A. , Cannon Steven B. , Cannon Ethalinda K.S.
Published: April 2020

Cultivated peanut (Arachis hypogaea) is an important oil, food, and feed crop worldwide. The USDA peanut germplasm collection currently contains 8,982 accessions. In the 1990s, 812 accessions were selected as a core collection on the basis of phenotype and country of origin. The present study reports genotyping results for the entire available core collection. Each accession was genotyped with the Arachis_Axiom2 SNP array, yielding 14,430 high-quality, informative SNPs across the collection. Additionally, a subset of 253 accessions was replicated, using between two and five seeds per accession, to assess heterogeneity within these accessions. the genotypic diversity of the core is mostly captured in five genotypic clusters, which have some correspondence with botanical variety and market type. There is little genetic clustering by country of origin, reflecting peanut’s rapid global dispersion in the 18th and 19th centuries. A genetic cluster associated with thehypogaea/aequatoriana/peruvianavarieties, with accessions coming primarily from Bolivia, Peru, and Ecuador, is consistent with these having been the earliest landraces. The genetics, phenotypic characteristics, and biogeography are all consistent with previous reports of tetraploid peanut originating in Southeast Bolivia. Analysis of the genotype data indicates an early genetic radiation, followed by regional distribution of major genetic classes through South America, and then a global dissemination that retains much of the early genetic diversity in peanut. Comparison of the genotypic data relative to alleles from the diploid progenitors also indicates that subgenome exchanges, both large and small, have been major contributors to the genetic diversity in peanut.

All data is available at the National Ag Library:https://doi.org/10.15482/USDA.ADC/1518508and at PeanutBase:https://peanutbase.org/data/public/Arachis_hypogaea/mixed.esm.KNWV
Local climate and habitat continuity interact to alter contemporary dispersal potential
Authors: Sullivan Lauren L. , Portlas Zoe M. , Hamilton Jill A.
Published: April 2020

Understanding the evolution of dispersal under changing global environments is essential to predicting a species ability to track shifting ecological niches. Two important, but anthropogenically altered, sources of selection on dispersal are climate and habitat continuity. Despite the likelihood these global drivers of selection act simultaneously on plant populations, their combined effects on dispersal are rarely examined. To understand the interactive effect of climate and habitat continuity on dispersal potential, we study Geum triflorum - a perennial grassland species that spans a wide range of environments, including both continuous prairie and isolated alvar habitats. We explore how the local climate of the growing season and habitat continuity (continuous vs isolated) interact to alter dispersal potential. We find a consistent interactive effect of local climate and habitat continuity on dispersal potential. Across continuous prairie populations, an increased number of growing degree days favors traits that increase dispersal potential. However, for isolated alvar populations, dispersal potential tends to decrease as the number of growing degree days increase. Our findings suggest that under continued warming, populations in continuous habitats will benefit from increased gene flow, while isolated populations will become increasingly segregated, with reduced potential to track shifting fitness optima.
Integration host factor bends and bridges DNA in a multiplicity of binding modes with varying specificity
Authors: Yoshua Samuel B. , Watson George D. , Howard Jamieson A. L. , Velasco-Berrelleza Victor , Leake Mark C. , Noy Agnes
Published: April 2020

Nucleoid-associated proteins (NAPs) are crucial in organizing prokaryotic DNA and regulating genes. Vital to these activities are complex nucleoprotein structures, however, how these form remains unclear. Integration host factor (IHF) is an Escherichia coli NAP that creates very sharp bends in DNA at sequences relevant to several functions including transcription and recombination, and is also responsible for general DNA compaction when bound non-specifically. We show that IHF–DNA structural multimodality is more elaborate than previously thought, and provide insights into how this drives mechanical switching towards strongly bent DNA. Using single-molecule atomic force microscopy and atomic molecular dynamics simulations we find three binding modes in roughly equal proportions: “associated” (73° of DNA bend), “half-wrapped” (107°) and “fully-wrapped” (147°), only the latter occurring with sequence specificity. We show IHF bridges two DNA double helices through non-specific recognition that gives IHF a stoichiometry greater than one and enables DNA mesh assembly. We observe that IHF-DNA structural multiplicity is driven through non-specific electrostatic interactions that we anticipate to be a general NAP feature for physical organization of chromosomes.
The beginning of the end: a chromosomal assembly of the New World malaria mosquito ends with a novel telomere
Authors: Compton Austin , Liang Jiangtao , Chen Chujia , Lukyanchikova Varvara , Qi Yumin , Potters Mark , Settlage Robert , Miller Dustin , Deschamps Stephane , Mao Chunhong , Llaca Victor , Sharakhov Igor V. , Tu Zhijian
Published: April 2020

Chromosome level assemblies are accumulating in various taxonomic groups including mosquitoes. However, even in the few reference-quality mosquito assemblies, a significant portion of the heterochromatic regions including telomeres remain unresolved. Here we produce ade novoassembly of the New World malaria mosquito,Anopheles albimanusby integrating Oxford Nanopore sequencing, Illumina, Hi-C and optical mapping. This 172.6 Mbps female assembly, which we call AalbS3, is obtained by scaffolding polished large contigs (contig N50=13.7 Mbps) into three chromosomes. All chromosome arms end with telomeric repeats, which is the first in mosquito assemblies and represents a significant step towards the completion of a genome assembly. These telomeres consist of tandem repeats of a novel 30-32 bp telomericrepeatunit (TRU) and are confirmed by analysing the termini of long reads and through both chromosomalin situhybridization and a Bal31 sensitivity assay. The AalbS3 assembly included previously uncharacterized centromeric and rDNA clusters and more than doubled the content of transposable elements and other repetitive sequences. This telomere-to-telomere assembly, although still containing gaps, represents a significant step towards resolving biologically important but previously hidden genomic components. The comparison of different scaffolding methods will also inform future efforts to obtain reference-quality genomes for other mosquito species.

100-word Article Summary

We report AalbS3, a telomere-to-telomere assembly of theAnopheles albimanusgenome produced by integrating advancing technologies including Oxford Nanopore and Bionano optical mapping. AalbS3 features much of the difficult-to-assemble genomic ‘dark matters’ including previously missed transposons, centromeres and rDNA clusters. We describe novel telomeric repeats that are confirmed by analysis of long reads and by telomere hybridization assays. This reference-quality assembly represents a significant step towards completing the genomic puzzle pieces and informs efforts to improve the assembly of other mosquito species. Future research into the relationship between telomere and mosquito life span may have significant implications to disease control.
Structured sampling of olfactory input by the fly mushroom body
Authors: Zheng Zhihao , Li Feng , Fisher Corey , Ali Iqbal J. , Sharifi Nadiya , Calle-Schuler Steven , Hsu Joseph , Masoodpanah Najla , Kmecova Lucia , Kazimiers Tom , Perlman Eric , Nichols Matthew , Li Peter H. , Jain Viren , Bock Davi D.
Published: April 2020

Associative memory formation and recall in the adult fruit flyDrosophila melanogasteris subserved by the mushroom body (MB). Upon arrival in the MB, sensory information undergoes a profound transformation. Olfactory projection neurons (PNs), the main MB input, exhibit broadly tuned, sustained, and stereotyped responses to odorants; in contrast, their postsynaptic targets in the MB, the Kenyon cells (KCs), are nonstereotyped, narrowly tuned, and only briefly responsive to odorants. Theory and experiment have suggested that this transformation is implemented by random connectivity between KCs and PNs. However, this hypothesis has been challenging to test, given the difficulty of mapping synaptic connections between large numbers of neurons to achieve a unified view of neuronal network structure. Here we used a recent whole-brain electron microscopy (EM) volume of the adult fruit fly to map large numbers of PN- to-KC connections at synaptic resolution. Comparison of the observed connectome to precisely defined null models revealed unexpected network structure, in which a subset of food-responsive PN types converge on individual downstream KCs more frequently than expected. The connectivity bias is consistent with the neurogeometry: axons of the overconvergent PNs tend to arborize near one another in the MB main calyx, making local KC dendrites more likely to receive input from those types. Computational modeling of the observed PN-to-KC network showed that input from the overconvergent PN types is better discriminated than input from other types. These results suggest an ‘associative fovea’ for olfaction, in that the MB is wired to better discriminate more frequently occurring and ethologically relevant combinations of food-related odors.
Metabolism modulates network synchrony in the aging brain
Authors: Weistuch Corey , Mujica-Parodi Lilianne R , Amgalan Anar , Dill Ken A
Published: April 2020

Brain aging is associated with hypometabolism and associated global changes in functional connectivity. Using fMRI, we show that network synchrony, a collective property of brain activity, decreases with age. Applying quantitative methods from statistical physics, we provide a generative (Ising) model for these changes as a function of the average communication strength between brain regions. In particular, we find healthy brains to be poised at a critical point of this communication strength, enabling a balance between segregated (to functional domains) and integrated (between domains) patterns of synchrony. However, one characteristic of criticality is a high sensitivity to small changes. Thus, minute weakening of pairwise communication between regions, as seen in the aging brain, gives rise to qualitatively abrupt changes in synchrony. Finally, by experimentally modulating metabolic activity in younger adults, we show how metabolism alone–independent of other changes associated with aging–can provide a mechanism for global changes in synchrony.
Genomic convergence of locus-based GWAS meta-analysis identifies DDX11 as a novel Systemic Lupus Erythematosus gene
Authors: Saeed Mohammad , Ibáñez-Costa Alejandro , Patiño-Trives Alejandra María , Estevez Eduardo Collantes , Aguirre María Ángeles , López-Pedrera Chary
Published: April 2020

Genome-wide association studies (GWAS) of systemic lupus erythematosus (SLE) explain only ∼15% of genetic risk, indicating genes of modest effect remain to be discovered. Association clustering methods such as OASIS are more apt at identifying modest genetic effects. 410 genes were mapped to previously identified OASIS GWAS SLE loci and investigated for expression in SLE GEO datasets. GSE50395 dataset from Cordoba was used for validation. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes was used. Confirmatory qPCR on monocytes of 12 SLE patients and controls was performed. We identified 55 genes that were differentially expressed in at least 2 SLE GEO datasets with all probes directionally aligned.DDX11was downregulated in both GEO (P=3.60E-02) and Cordoba (P=8.02E-03) datasets and confirmed by qPCR (P=0.001). The most significant SNP, rs3741869 (P=3.2E-05) in OASIS locus 12p11.21, containingDDX11, was a cis-eQTL regulatingDDX11expression (P=8.62E-05).DDX11interacted with multiple genes includingSTAT1/STAT4. Genomic convergence with OASIS and multiple expression datasets identifies novel genes.DDX11, RNA helicase involved in genome stability, is repressed in SLE.

Summary Statement

More than 100 genes for SLE have been identified but they explain only ∼15% of heritability. GWAS are challenged by risk genes of modest effect. Using locus-based GWAS mapping and multiple gene expression replications,DDX11was identified as a novel SLE gene.DDX11, repressed in SLE, may be used as a clinical diagnostic tool.
Light effects on circadian and homeostatic regulation: alertness increases independent of time awake
Authors: Lok R. , Woelders T. , van Koningsveld M.J. , Oberman K. , Fuhler S.G. , Beersma D.G.M. , Hut R.A.
Published: April 2020

Light induced improvements in alertness are more prominent during night-time than during the day, indicating circadian regulation or wake duration related dependence. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. Here we investigate alerting effects of light in a novel 4×18 hours FD protocol (5h sleep, 13h wake) under dim (6 mlux) and bright light (1159 mlux) conditions. Hourly saliva samples (melatonin and cortisol assessment) and 2-hourly test-sessions were used to assess effects of bright light on subjective and objective alertness (electroencephalography and performance). Results reveal (1) stable free-running cortisol rhythms with uniform phase progression under both light conditions, indicating that FD designs can be conducted under high intensity lighting, (2) subjective alerting effects of light depend on elapsed time awake, while (3) light consistently improves objective alertness independent of time awake. Three dimensional graphs reflecting light induced alertness improvements depending on wake duration related variation and circadian clock phase suggest that performance is improved during daytime, while subjective alertness remains unchanged. This suggests that light during office hours might be beneficial for performance, even though this may not be perceived as such.
Visible light optical coherence tomography angiography (vis-OCTA) and local microvascular retinal oximetry in human retina
Authors: Song Weiye , Shao Wenjun , Yi Wei , Liu Rongrong , Desai Manishi , Ness Steven , Yi Ji
Published: April 2020

We report herein the first visible light optical coherence tomography angiography (vis-OCTA) for human retinal imaging. Compared to the existing vis-OCT systems, we devised a spectrometer with a narrower bandwidth to increase the spectral power density for OCTA imaging, while retaining the major spectral contrast in the blood. We achieved a 100 kHz A-line rate, the fastest acquisition speed reported so far for human retinal vis-OCT. We rigorously optimized the imaging protocol such that a single acquisition takes <6 seconds with a field of view (FOV) of 3×7.8 mm2. The angiography enables accurate localization of microvasculature down to the capillary level and thus enables oximetry at vessels < 100 μm in diameter. We demonstrated microvascular hemoglobin oxygen saturation (sO2) at the feeding and draining vessels at the perifoveal region. The longitudinal repeatability was assessed by <5% coefficient of variation (CV). The unique capabilities of our vis-OCTA system may allow studies on the role of microvascular oxygen in various retinal pathologies.
Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR
Authors: Smyrlaki Ioanna , Ekman Martin , Lentini Antonio , Sousa Nuno Rufino de , Papanicolaou Natali , Vondracek Martin , Aarum Johan , Safari Hamzah , Muradrasoli Shaman , Rothfuchs Antonio Gigliotti , Albert Jan , Högberg Björn , Reinius Björn
Published: April 2020

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method of COVID-19 diagnostics is a reverse transcription polymerase chain reaction (RT-PCR) assay, to detect the presence of SARS-CoV-2 RNA in patient samples, typically from nasopharyngeal swabs. RNA extraction is a major bottleneck in current COVID-19 testing, in terms of turn-around, logistics, component availability and cost, which delays or completely precludes COVID-19 diagnostics in many settings. Efforts to simplify the current methods are critical, as increased diagnostic availability and efficiency would benefit patient care and infection control. Here, we describe methods to circumvent RNA extraction in COVID-19 testing by performing RT-PCR directly on heat-inactivated subject samples as well as samples lysed with readily available detergents. Our data, including benchmarking with 597 clinically diagnosed patient samples against a standardised and sensitive diagnostic system, show that direct RT-PCR is a viable option to extraction-based COVID-19 diagnostics. Furthermore, using controlled amounts of active SARS-CoV-2, we evaluated performance of generic buffers as sample medium for the direct RT-PCR assay, identifying several suitable formulations. We also confirmed the effectiveness of heat inactivation of SARS-CoV-2 by plaque assay. Significant savings in terms of time and cost can be achieved by embracing RNA-extraction-free protocols, that feed directly into the established PCR-based testing pipeline. This could aid the expansion of COVID-19 testing.
Ratio of the interferon-γsignature to the immunosuppression signature predicts anti-PD-1 therapy response in melanoma
Authors: Kong Yan , Xu Canqiang , Cui Chuanliang , Yang Wenxian , Yang Shuang , Chi Zhihong , Sheng Xinan , Si Lu , Xie Yihong , Yu Jinyu , Chen Xuejun , Wang Shun , Hu Jing , Zheng Frank , Zhou Wengang , Yu Rongshan , Guo Jun
Published: April 2020

Immune checkpoint inhibitor (ICI) treatments produce clinical benefit in many patients. However, better pretreatment predictive biomarkers for ICI are still needed to help match individual patients to the treatment most likely to be of benefit. Existing gene expression profiling (GEP)-based biomarkers for ICI are primarily focused on measuring a T cell-inflamed tumour microenvironment that contributes positively to the response to ICI. Here, we identified an immunosuppression signature (IMS) through analysing RNA sequencing data from a combined discovery cohort (n= 120) consisting of three publicly available melanoma datasets. Using the ratio of an established IFN-γsignature and IMS led to consistently better prediction of the ICI therapy outcome compared to a collection of nine published GEP signatures from the literature on a newly generated internal validation cohort (n= 55) and three published datasets of metastatic melanoma treated with anti-PD-1 (n= 48) and anti-CTLA-4 (n= 42) as well as in patients with gastric cancer treated with antiPD-1 (n= 45), demonstrating the potential utility of IMS as a predictive/prognostic biomarker that complements existing GEP signatures for immunotherapy.