bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of NEKL-4/NEK10 and TTLL genes opposes loss of the CCPP-1 deglutamylase and prevents neuronal ciliary degeneration
Authors: Power Kade M. , Akella Jyothi S. , Gu Amanda , Walsh Jonathon D. , Bellotti Sebastian , Morash Margaret , Zhang Winne , Ross N. , Golden Andy , Smith Harold E. , Barr Maureen M. , O’Hagan Robert 
Published: May 2020

AbstractCiliary microtubules are subject to post-translational modifications that act as a “Tubulin Code” to regulate motor traffic, binding proteins and stability. In humans, loss of CCP1, acytosoliccarboxypeptidase and tubulin deglutamylating enzyme, causes infantile-onset neurodegeneration. InC. elegans,mutations inccpp-1, the homolog of CCP1, result in progressive degeneration of neuronal cilia and loss of neuronal function. To identify genes that regulate microtubule glutamylation and ciliary integrity, we performed a forward genetic screen for suppressors of ciliary degeneration inccpp-1mutants. We isolated thettll-5(my38)suppressor, a mutation in thetubulintyrosineligase-like glutamylase gene. We show that mutation inttll-4, ttll-5,orttll-11gene suppressed the hyperglutamylation-induced loss of microtubules and kinesin-2 mislocalization inccpp-1cilia. We also identified thenekl-4(my31)suppressor, an allele affecting the NIMA (Never in Mitosis A)-related kinase NEKL-4/NEK10. In humans, NEK10 mutation causes bronchiectasis, an airway and mucociliary transport disorder caused by defective motile cilia.C. elegansNEKL-4 does not localize to cilia yet plays a role in regulating axonemal microtubule stability. This work defines a pathway in which glutamylation, a component of the Tubulin Code, is written by TTLL-4, TTLL-5, and TTLL-11; is erased by CCPP-1; is read by ciliary kinesins; and its downstream effects are modulated by NEKL-4 activity. Identification of regulators of microtubule glutamylation in diverse cellular contexts is important to the development of effective therapies for disorders characterized by changes in microtubule glutamylation. By identifyingC. elegansgenes important for neuronal and ciliary stability, our work may inform research into human ciliopathies and neurodegenerative diseases.
Utilizing Temporal Measurements from UAVs to Assess Root Lodging in Maize and its Impact on Productivity
Authors: Tirado Sara B. , Hirsch Candice N. , Springer Nathan M. 
Published: May 2020

ABSTRACTBoth stalk and root lodging can cause significant yield losses in maize; however, maize plants are often able to recover from root lodging. There is potential among breeding programs for developing lines that are more tolerant and can more rapidly recover from root lodging. We assessed the incidence of root lodging utilizing end-of-season lodging scores collected among the Genomes 2 Fields (G2F) initiative trials and found a large yet variable incidence of lodging across states, years, and genotypes. Lodging in this dataset was scored manually at the end of the season, and little is known about the drivers of lodging and lodging recovery. We therefore developed an approach for utilizing temporal plant height measurements collected from unmanned aerial vehicles to capture in-season lodging and recovery in a yield trial consisting of 24 maize hybrids planted in replicate under two dates and three planting densities in St Paul, MN in the summers of 2018 and 2019. We found that growth rates during vegetative development as well as the developmental timing of plants when exposed to a storm are predictive of the amount of lodging maize plots will experience. We also found that utilizing temporal height measurements can help in not just estimating lodging and early vegetative growth rates, but that utilizing these estimates can also aid in assessing end of season yield.
Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping
Authors: Jegouic Sophie M. , Loureiro Silvia , Thom Michelle , Paliwal Deepa , Jones Ian M. 
Published: May 2020

AbstractThe newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes.
Ultra-high field (10.5 T) resting state fMRI in the macaque
Authors: Yacoub Essa , Grier Mark D. , Auerbach Edward J. , Lagore Russell L. , Harel Noam , Ugurbil Kamil , Adriany Gregor , Zilverstand Anna , Hayden Benjamin Y. , Heilbronner Sarah R. , Zimmermann Jan 
Published: May 2020

AbstractResting state functional connectivity refers to the temporal correlations between spontaneous hemodynamic signals obtained using functional magnetic resonance imaging. This technique has demonstrated that the structure and dynamics of identifiable networks are altered in psychiatric and neurological disease states. Thus, resting state network organizations can be used as a diagnostic, or prognostic recovery indicator. However, much about the physiological basis of this technique is unknown. Thus, providing a translational bridge to an optimal animal model, the macaque, in which invasive circuit manipulations are possible, is of utmost importance. Current approaches to resting state measurements in macaques face unique challenges associated with signal-to-noise, the need for invasive contrast agents, and within-subject designs. These limitations can, in principle, be overcome through ultra-high magnetic fields. However, ultra-high field imaging has yet to be adapted for fMRI in macaques. Here, we demonstrate that the combination of high channel count transmitter and receiver arrays, optimized pulse sequences, and careful anesthesia regimens, allows for detailed within-subject resting state analysis at ultra-high resolutions. In this study, we uncover thirty spatially detailed resting state components that are highly robust across individual macaques and closely resemble the quality and findings of connectomes from large human datasets. This detailed map of the rsfMRI ‘macaque connectome’ will be the basis for future neurobiological circuit manipulation work, providing valuable biological insights into human connectomics.
Electric-field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2
Authors: Ramachandran Ashwin , Huyke Diego A. , Sharma Eesha , Sahoo Malaya K. , Banaei Niaz , Pinsky Benjamin A. , Santiago Juan G. 
Published: May 2020

AbstractThe rapid spread of COVID-19 across the world has revealed major gaps in our ability to respond to new virulent pathogens. Rapid, accurate, and easily configurable molecular diagnostic tests are imperative to prevent global spread of new diseases. CRISPR-based diagnostic approaches are proving to be useful as field-deployable solutions. In a basic form of this assay, the CRISPR-Cas12 enzyme complexes with a synthetic guide RNA (gRNA). This complex is activated when it highly specifically binds to target DNA, and the activated complex non-specifically cleaves single-stranded DNA reporter probes labeled with a fluorophore-quencher pair. We recently discovered that electric field gradients can be used to control and accelerate this CRISPR assay by co-focusing Cas12-gRNA, reporters, and target. We achieve an appropriate electric field gradient using a selective ionic focusing technique known as isotachophoresis (ITP) implemented on a microfluidic chip. Unlike previous CRISPR diagnostic assays, we also use ITP for automated purification of target RNA from raw nasopharyngeal swab sample. We here combine this ITP purification with loop-mediated isothermal amplification, and the ITP-enhanced CRISPR assay to achieve detection of SARS-CoV-2 RNA (from raw sample to result) in 30 min for both contrived and clinical nasopharyngeal swab samples. This electric field control enables a new modality for a suite of microfluidic CRISPR-based diagnostic assays.Significance statementRapid, early-stage screening is especially crucial during pandemics for early identification of infected patients and control of disease spread. CRISPR biology offers new methods for rapid and accurate pathogen detection. Despite their versatility and specificity, existing CRISPR-diagnostic methods suffer from the requirements of up-front nucleic acid extraction, large reagent volumes, and several manual steps—factors which prolong the process and impede use in low resource settings. We here combine on-chip electric-field control in combination with CRIPSR biology to directly address these limitations of current CRISPR-diagnostic methods. We apply our method to the rapid detection of SARS-CoV-2 RNA in clinical samples. Our method takes 30 min from raw sample to result, a significant improvement over existing diagnostic methods for COVID-19.
Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes
Authors: Crisp Peter A , Marand Alexandre P , Noshay Jaclyn M , Zhou Peng , Lu Zefu , Schmitz Robert J , Springer Nathan M 
Published: May 2020

AbstractThe genomic sequences of crops continue to be produced at a frenetic pace. However, it remains challenging to develop complete annotations of functional genes and regulatory elements in these genomes. Here, we explore the potential to use DNA methylation profiles to develop more complete annotations. Using leaf tissue in maize, we define ∼100,000 unmethylated regions (UMRs) that account for 5.8% of the genome; 33,375 UMRs are found greater than 2 kilobase pairs from genes. UMRs are highly stable in multiple vegetative tissues and they capture the vast majority of accessible chromatin regions from leaf tissue. However, many UMRs are not accessible in leaf (leaf-iUMRs) and these represent a set of genomic regions with potential to become accessible in specific cell types or developmental stages. Leaf-iUMRs often occur near genes that are expressed in other tissues and are enriched for transcription factor (TF) binding sites of TFs that are also not expressed in leaf tissue. The leaf-iUMRs exhibit unique chromatin modification patterns and are enriched for chromatin interactions with nearby genes. The total UMRs space in four additional monocots ranges from 80-120 megabases, which is remarkably similar considering the range in genome size of 271 megabases to 4.8 gigabases. In summary, based on the profile from a single tissue, DNA methylation signatures pinpoint both accessible regions and regions poised to become accessible or expressed in other tissues. UMRs provide powerful filters to distill large genomes down to the small fraction of putative functional genes and regulatory elements.Significance StatementCrop genomes can be very large with many repetitive elements and pseudogenes. Distilling a genome down to the relatively small fraction of regions that are functionally valuable for trait variation can be like looking for needles in a haystack. The unmethylated regions in a genome are highly stable during vegetative development and can reveal the locations of potentially expressed genes or cis-regulatory elements. This approach provides a framework towards complete annotation of genes and discovery of cis-regulatory elements using methylation profiles from only a single tissue.
Examining the bidirectional association between emotion recognition and autistic traits using observational and genetic analyses
Authors: Reed Zoe E. , Mahedy Liam , Jackson Abigail , Smith George Davey , Penton-Voak Ian , Attwood Angela S , Munafò Marcus R 
Published: May 2020

AbstractBackgroundThere is mixed evidence for an association between autism spectrum disorder (ASD) and emotion recognition deficits. We sought to assess the bidirectionality of this association using phenotypic and genetic data in a large community sample.MethodsAnalyses were conducted in three stages. First, we examined the bidirectional association between autistic traits at age 8 years and emotion recognition task (ERT) responses at age 24 years (Study 1; N=3,562); and between Diagnostic Analysis of Non-Verbal Accuracy (DANVA) emotion recognition responses at age 8 years and autistic traits at age 10 years (Study 2; N=9,071). Next, we used genetic analyses (Study 3) to examine the association between polygenic risk scores for ASD and these phenotypes. The genetic correlation between ASD and ERT responses at age 24 was also estimated. Analyses were conducted in the Avon Longitudinal Study of Parents and Children.ResultsAutistic traits at age 8 years were negatively associated with later total correct responses on ERT in Study 1 (b=-0.18; 95% CI: −0.27 to −0.09). We also found evidence of an association in Study 2 (b=-0.04; 95% CI: −0.05 to −0.03). We found the opposite association i.e., positive, between the ASD polygenic risk score and ERT (b=0.40; 95% CI: 0.10 to 0.70); however, this association varied across different p-value thresholds so should be interpreted with caution. We did not find evidence of a genetic correlation between ASD and ERT.ConclusionWe found an observational association between poorer emotion recognition and increased autistic traits. Our genetic analyses revealed an association between ASD polygenic risk and the ERT outcome, which may suggest a shared genetic aetiology between these or a potential causal pathway. Our results may inform interventions targeting emotion recognition.
Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States
Authors: Goldstein Joshua R. , Atherwood Serge 
Published: May 2020

AbstractDifferent estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The CDC’s decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside re-weighted racial/ethnic population distributions—in effect, a geographic adjustment—makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per-capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and more than 50% higher for Hispanics, relative to Whites, on a national level, while there is almost no disparity for Asians. State-specific estimates show wide variation in mortality disparities. Comparison with non-epidemic mortality reveals potential roles for pre-existing health disparities and differential rates of infection and care.
Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses
Authors: Yu Xi , Zhang Liming , Tong Liangqin , Zhang Nana , Wang Han , Yang Yun , Shi Mingyu , Xiao Xiaoping , Zhu Yibin , Wang Penghua , Ding Qiang , Zhang Linqi , Qin Chengfeng , Cheng Gong 
Published: May 2020

AbstractViruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from aChromobacteriumbacterium, namedChromobacteriumantiviral effector-1 (CbAE-1) andCbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). TheCbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation ofCbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore,CbAE-2 presented low toxicityin vivoandin vitro, highlighting its potential as a broad-spectrum antiviral drug.
A clinically validated human capillary blood transcriptome test for global systems biology studies
Authors: Toma Ryan , Pelle Ben , Duval Nathan , Parks Matthew M , Gopu Vishakh , Tily Hal , Hatch Andrew , Perlina Ally , Banavar Guruduth , Vuyisich Momchilo 
Published: May 2020

AbstractChronic diseases are the leading cause of morbidity and mortality globally. Yet, the majority of them have unknown etiologies, and genetic contribution is weak. In addition, many of the chronic diseases go through the cycles of relapse and remission, during which the genomic DNA does not change. This strongly suggests that human gene expression is the main driver of chronic disease onset and relapses. To identify the etiology of chronic diseases and develop more effective preventative measures, a comprehensive gene expression analysis of the human body is needed. Blood tissue is easy to access and contains a large number of expressed genes involved in many fundamental aspects of our physiology.We report here the development of a whole blood transcriptome clinical test that is high throughput, automated, inexpensive, and clinically validated. The test requires only 50 microliters of blood from a finger prick, enabling access by diverse populations that have been traditionally under-represented in clinical research. The transcripts in the samples are preserved at the time of collection and can be stored and/or transported at ambient temperatures for up to 28 days. The sample preservative protects integrity, while also inactivating all pathogens (bacteria, fungi, and viruses), enabling safe transportation globally. Given its unique set of usability features and clinical performance, this test should be integrated into longitudinal, population-scale, systems biology studies.
Effect of nanocarbon molecules on theArabidopsis thalianatranscriptome
Authors: Nakamichi Norihito , Sato Ayato , Aihara Yusuke , Kinoshita Toshinori , Segawa Yasutomo , Amaike Kazuma , Itami Kenichiro 
Published: May 2020

AbstractNanocarbons, such as fullerenes, carbon nanotubes, and graphene have attracted a great deal of attention as next-generation materials because of their unprecedented structures and unique physicochemical properties; however, almost all nanocarbons reported previously were used as mixtures. Thus, there are still many unsolved issues about their biological functions at the molecular level. Our synthetic campaign in the last decade has synthesized structurally uniform and atomically precise nanocarbons, leading to the preparation of a library consisting of eighty structurally diverse nanocarbon molecules. This resource motivated us to explore the as yet uncovered biological functions of these nanocarbon molecules in organisms. Recently, nanotubes were used to deliver genes to plants; however, the effects of the molecules on plants are not well known. To monitor the effects of nanocarbon molecules on plants, we analyzed the transcriptome ofArabidopsis thalianaseedlings treated with [9]cycloparaphenylene (CPP), decaborylated warped nanographene (WNG), and dimethoxyhexabenzotetracene (HBT). Clustering analysis indicated few effects of nanocarbon molecules on the transcriptome, perhaps suggesting a low toxicity of nanocarbon molecules on plants. We found thatAT1G05880(ARIADNE 12) gene, categorized into ‘response to hypoxia’ genes, was up-regulated by nanocarbon molecules, suggesting that this gene is usable as maker for treatment of nanocarbon molecules.
Integrated cross-study datasets of genetic dependencies in cancer
Authors: Pacini Clare , Dempster Joshua M. , Boyle Isabella , Gonçalves Emanuel , Najgebauer Hanna , Karakoc Emre , van der Meer Dieudonne , Barthorpe Andrew , Lightfoot Howard , Jaaks Patricia , McFarland James M. , Garnett Mathew J. , Tsherniak Aviad , Iorio Francesco 
Published: May 2020

AbstractCRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary to adequately represent the heterogeneity of human cancers and to assemble a comprehensive map of cancer genetic vulnerabilities. Here, we integrated the two largest public independent CRISPR-Cas9 screens performed to date (at the Broad and Sanger institutes) by assessing, comparing, and selecting methods for correcting biases due to heterogeneous single guide RNA efficiency, gene-independent responses to CRISPR-Cas9 targeting originated from copy number alterations, and experimental batch effects. Our integrated datasets recapitulate findings from the individual datasets, provide greater statistical power to cancer- and subtype-specific analyses, unveil additional biomarkers of gene dependency, and improve the detection of common essential genes. We provide the largest integrated resources of CRISPR-Cas9 screens to date and the basis for harmonizing existing and future functional genetics datasets.
Discovery of multiple anti-CRISPRs uncovers anti-defense gene clustering in mobile genetic elements
Authors: Pinilla-Redondo Rafael , Shehreen Saadlee , Marino Nicole D. , Fagerlund Robert D. , Brown Chris M. , Sørensen Søren J. , Fineran Peter C. , Bondy-Denomy Joseph 
Published: May 2020

AbstractMany prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have evolved Anti-CRISPR (Acr) proteins to bypass this immunity, yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we uncover 11 new type I anti-CRISPR genes encoded on numerous chromosomal and extrachromosomal mobile genetic elements withinEnterobacteriaceaeandPseudomonas. Candidate genes were identified adjacent to anti-CRISPR associated gene 5 (aca5)and assayed against a panel of six type I systems: I-F (Pseudomonas,Pectobacterium, andSerratia), I-E (PseudomonasandSerratia), and I-C (Pseudomonas), revealing the type I-F and/or I-Eacrgenes and a newaca(aca9). We find thatacrgenes not only associate with otheracrgenes, but also with inhibitors of distinct bacterial defense systems. These genomic regions appear to be “anti-defense islands”, reminiscent of the clustered arrangement of “defense islands” in prokaryotic genomes. Our findings expand on the diversity of CRISPR-Cas inhibitors and reveal the potential exploitation ofacrloci neighborhoods for identifying new anti-defense systems.