bluuebunny/crossref_metadata_2025 huggingface dataset:
Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft
Authors: Klein Joshua A. , Zaia Joseph
Published: June 2020

Widely-available LC-MS instruments and methods allow users to acquire glycoproteomics data. Complex glycans, however, add a dimension of complexity to the data analysis workflow. In a sense, complex glycans are post-translationally modified post-translational modifications, reflecting a series of biosynthetic reactions in the secretory pathway that are spatially and temporally regulated. One problem is that complex glycan is micro-heterogeneous, multiplying the complexity of the proteome. Another is that glycopeptide glycans undergo dissociation during tandem MS that must be considered for tandem MS interpretation algorithms and quantitative tools. Fortunately, there are a number of algorithmic tools available for analysis of glycoproteomics LC-MS data. We summarize the principles for glycopeptide data analysis and show use of our GlycReSoft tool to analyze SARS-CoV-2 spike protein site-specific glycosylation.
Ribosomal Protein Large subunit RPL6 modulates salt tolerance in rice
Authors: Moin Mazahar , Saha Anusree , Bakshi Achala , Madhav M. S. , Kirti P B
Published: June 2020

The extra-ribosomal functions of ribosomal proteins RPL6 and RPL23a in stress-responsiveness have emanated from our previous studies on activation tagged mutants of rice screened for water-use efficiency (Moinet al., 2016a). In the present study, we functionally validated theRPL6, a Ribosomal Protein Large subunit member for salt stress tolerance in rice. The overexpression ofRPL6resulted in tolerance to moderate (150 mM) to high (200 mM) levels of salt (NaCl) in rice. The transgenic rice plants expressingRPL6constitutively showed better phenotypic and physiological responses with high quantum efficiency, accumulation of more chlorophyll and proline contents, and an overall increase in seed yield compared with the wild type in salt stress treatments. An iTRAQ-based comparative proteomic analysis revealed the high expression of about 333 proteins among the 4,378 DEPs in a selected overexpression line ofRPL6treated with 200 mM of NaCl. The functional analysis showed that these highly expressed proteins (HEPs) are involved in photosynthesis, ribosome and chloroplast biogenesis, ion transportation, transcription and translation regulation, phytohormone and secondary metabolite signal transduction. Anin siliconetwork analysis of HEPs predicted that RPL6 binds with translation-related proteins and helicases, which coordinately affects the activities of a comprehensive signaling network, thereby inducing tolerance and promoting growth and yield in response to salt stress. Our overall findings identified a novel candidate, RPL6 whose characterization contributed to the existing knowledge on the complexity of salt tolerance mechanism in plants.
Neurofunctional basis underlying audiovisual integration of print and speech sound in Chinese children
Authors: Xia Zhichao , Yang Ting , Cui Xin , Hoeft Fumiko , Liu Hong , Zhang Xianglin , Shu Hua , Liu Xiangping
Published: June 2020

Effortless print-sound integration is essential to reading development, and the superior temporal cortex (STC) is the most critical brain region. However, to date, the conclusion is almost restricted to alphabetic orthographies. To examine the neural basis in non-alphabetic languages and its relationship with reading abilities, we conducted a functional magnetic resonance imaging study in typically developing Chinese children. Two neuroimaging-based indicators of audiovisual processing—additive enhancement (higher activation in the congruent than the average activation of unimodal conditions) and neural integration (different activations between the congruent versus incongruent conditions)—were used to investigate character-sounds (opaque) and pinyin-sounds (transparent) processing. We found additive enhancement in bilateral STCs processing both character and pinyin stimulations. Moreover, the neural integrations in the left STC for the two scripts were strongly correlated. In terms of differentiation, first, areas beyond the STCs showed additive enhancement in processing pinyin-sounds. Second, while the bilateral STCs, left inferior/middle frontal and parietal regions manifested a striking neural integration (incongruent > congruent) for character-sounds, no significant clusters were revealed for pinyin-sounds. Finally, the neural integration in the left middle frontal gyrus for characters was specifically associated with silent reading comprehension proficiency, indicating automatic semantic processing during implicit character-sound integration. In contrast, the neural integration in the left STC for pinyin was specifically associated with oral reading fluency that relies on grapho-phonological mapping. To summarize, this study revealed both script-universal and script-specific neurofunctional substrates of print-sound integration as well as their processing- and region-dependent associations with reading abilities in typical Chinese children.

Highlights

The bilateral superior temporal cortices display additive enhancement in processing print-sound information regardless of orthographies.

The location, direction, and strength of the neural audiovisual integration are modulated by orthographic transparency.

The neural integration in the left middle frontal gyrus in processing character-sounds is correlated to reading comprehension.

The neural integration in the left superior temporal gyrus for pinyin is correlated with oral reading fluency.

The neural integrations of character-sounds and pinyin-sounds show spatial overlap and inter-subject correlation in the left superior temporal cortex.
Bacterial influence on the maintenance of symbiotic yeast throughDrosophilametamorphosis
Authors: Guilhot Robin , Rombaut Antoine , Xuéreb Anne , Howell Kate , Fellous Simon
Published: June 2020

Interactions between microbial symbionts of metazoan hosts are emerging as key features of symbiotic systems. Little is known about the role of such interactions on the maintenance of symbiosis through host’s life cycle. We studied the influence of symbiotic bacteria on the maintenance of symbiotic yeast through metamorphosis of the flyDrosophila melanogaster. To this end we mimicked the development of larvae in natural fruit. In absence of bacteria yeast was never found in young adults. However, yeast could maintain through metamorphosis when larvae were inoculated with symbiotic bacteria isolated fromD. melanogasterfaeces. Furthermore, an Enterobacteriaceae favoured yeast transstadial maintenance. Because yeast is a critical symbiont ofD. melanogasterflies, bacterial influence on host-yeast association may have consequences for the evolution of insect-yeast-bacteria tripartite symbiosis and their cooperation.

Summary statement

Bacterial symbionts ofDrosophilainfluence yeast maintenance through fly metamorphosis, a novel observation that may have consequences for the evolution of insect-yeast-bacteria interactions.
Phenome-wide association study of a comprehensive health check-up database in a Korea population: Clinical application & trans-ethnic comparison
Authors: Choe Eun Kyung , Shivakumar Manu , Verma Anurag , Verma Shefali Setia , Choi Seung Ho , Kim Joo Sung , Kim Dokyoon
Published: June 2020

Abstracts

Background

The expanding use of the phenome-wide association study (PheWAS) faces challenges in the context of using International Classification of Diseases billing codes for phenotype definition, imbalanced study population ethnicity, and constrained application of the results to clinical practice or research.

Methods

We performed a PheWAS utilizing deep phenotypes corroborated by comprehensive health check-ups in a Korean population, along with trans-ethnic comparisons through the UK Biobank and Biobank Japan Project. Network analysis, visualization of cross-phenotype mapping, and causal inference mapping with Mendelian randomization were conducted in order to make robust, clinically applicable interpretations.

Results

Of the 136 phenotypes extracted from the health check-up database, the PheWAS associated 65 phenotypes with 14,101 significant variants (P< 4.92×10−10). In the association study for body mass index, our population showed 583 exclusive loci relative to the Japanese population and 669 exclusive loci relative to the European population. In the meta-analysis with Korean and Japanese populations, 72.5% of phenotypes had uniquely significant variants. Tumor markers and hematologic phenotypes had a high degree of phenotype-phenotype pairs. By Mendelian randomization, one skeletal muscle mass phenotype was causal and two were outcomes. Among phenotype pairs from the genotype-driven cross-phenotype associations, 71.65% also demonstrated penetrance in correlation analysis using a clinical database.

Conclusions

This comprehensive analysis of PheWAS results based on a health check-up database will provide researchers and clinicians with a panoramic overview of the networks among multiple phenotypes and genetic variants, laying groundwork for the practical application of precision medicine.
A consensus-based and readable extension ofLinearCode forReactionRules (LiCoRR)
Authors: Kellman Benjamin P. , Zhang Yujie , Logomasini Emma , Meinhardt Eric , Chiang Austin W. T. , Sorrentino James T. , Liang Chenguang , Bao Bokan , Zhou Yusen , Akase Sachiko , Sogabe Isami , Kouka Thukaa , Wilson Iain B.H. , Campbell Matthew P. , Neelamegham Sriram , Krambeck Frederick J. , Aoki-Kinoshita Kiyoko F. , Lewis Nathan E.
Published: June 2020

Systems glycobiology aims to provide models and analysis tools that account for the biosynthesis, regulation, and interactions with glycoconjugates. To facilitate these methods, there is a need for a clear glycan representation accessible to both computers and humans. Linear Code, a linearized and readily parsable glycan structure representation, is such a language. For this reason, Linear Code was adapted to represent reaction rules, but the syntax has drifted from its original description to accommodate new and originally unforeseen challenges. Here, we delineate the consensuses and inconsistencies that have arisen through this adaptation. We recommend options for a consensus-based extension of Linear Code that can be used for reaction rule specification going forward. Through this extension and specification of Linear Code to reaction rules, we aim to minimize inconsistent symbology thereby making glycan database queries easier. With a clear guide for generating reaction rule descriptions, glycan synthesis models will be more interoperable and reproducible thereby moving glycoinformatics closer to compliance with FAIR standards. Reaction rule-extended Linear Code is an unambiguous representation for describing glycosylation reactions in both literature and code.
Robust and scalable manifold learning via landmark diffusion for long-term medical signal processing
Authors: Shen Chao , Lin Yu-Ting , Wu Hau-Tieng
Published: June 2020

Motivated by analyzing long-term physiological time series, we design a robust and scalable spectral embedding algorithm, coined the algorithm RObust and Scalable Embedding via LANdmark Diffusion (ROSE-LAND). The key is designing a diffusion process on the dataset, where the diffusion is forced to interchange on a small subset called thelandmark set. In addition to demonstrating its application to spectral clustering and image segmentation, the algorithm is applied to study the long-term arterial blood pressure waveform dynamics during a liver transplant operation lasting for 12 hours long.
Mannose-binding lectin gene polymorphisms in the East Siberia and Russian Arctic populations
Authors: Tereshchenko Sergey Yu , Smolnikova Marina V , Freidin Maxim B
Published: June 2020

Background

Mannose-binding lectin (MBL) encoded byMBL2gene is a protein with the ability to form carbohydrate complexes with microbial wall promoting their subsequent elimination. Genetically determined levels of MBL can modify the risk and clinical characteristics of many infectious diseases. The frequency ofMBL2genotypes exhibits significant population differences. The data on the distribution ofMBL2genotypes among the aborigines of the Russian Arctic territories have not yet been published.

Methods

A total of 880 specimens of dried blood spots of the newborns were genotyped. The newborns represented four populations: Nenets, Dolgan-Nganasans, Mixed aboriginal population, and Russians (Caucasians, Krasnoyarsk). Six polymorphisms of theMBL2gene were studied: rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451.

Results

The frequency of the combined rare O allele (composed of the coding region variants rs5030737, rs1800450, and rs1800451) in the homozygous state was significantly higher in Russians: 10% vs 2% in Nenets and 1% in Dolgan-Nganosans (p<0.001 for Russians vs other populations). The frequency of the high-producing haplotype (HYPA) was 35.4% in the Russian newborns, in keeping with European populations (27-33%); 64% for Nenets and 56% for Dolgan-Nganasans, similar to the estimates obtained for Eskimos and North Amerinds (64-81%).

Conclusion

Our study results are in line with the hypothesis that human evolution has been moving in the direction of accumulation of the genotypes associated with low activity of the lectin complement activation pathway because of the prevalence of some intracellular infections such as tuberculosis, whereby low MBL activity may have a protective effect.
Direct detection of RNA modifications and structure using single molecule nanopore sequencing
Authors: Stephenson William , Razaghi Roham , Busan Steven , Weeks Kevin M. , Timp Winston , Smibert Peter
Published: June 2020

Many methods exist to detect RNA modifications by short-read sequencing, relying on either antibody enrichment of transcripts bearing modified bases or mutational profiling approaches which require conversion to cDNA. Endogenous modifications are present on several major classes of RNA including tRNA, rRNA and mRNA and can modulate diverse biological processes such as genetic recoding, mRNA export and RNA folding. In addition, exogenous modifications can be introduced to RNA molecules to reveal RNA structure and dynamics. Limitations on read length and library size inherent in short-read-based methods dissociate modifications from their native context, preventing single molecule analysis and modification phasing. Here we demonstrate direct RNA nanopore sequencing to detect endogenous and exogenous RNA modifications over long sequence distance at the single molecule level. We demonstrate comprehensive detection of endogenous modifications inE. coliandS. cerevisiaeribosomal RNA (rRNA) using current signal deviations. Notably 2’-O-methyl (Nm) modifications generated a discernible shift in current signal and event level dwell times. We show that dwell times are mediated by the RNA motor protein which sits atop the nanopore. Further, we characterize a recently described small adduct-generating 2’-O-acylation reagent, acetylimidazole (AcIm) for exogenously labeling flexible nucleotides in RNA. Finally, we demonstrate the utility of AcIm for single molecule RNA structural probing using nanopore sequencing.

Graphical abstract
Detecting copy number alterations in RNA-Seq using SuperFreq
Authors: Flensburg Christoffer , Oshlack Alicia , Majewski Ian J.
Published: June 2020

Calling copy number alterations (CNAs) from RNA-Seq is challenging, because differences in gene expression mean that read depth across genes varies by several orders of magnitude and there is a paucity of informative single nucleotide polymorphisms (SNPs). We previously developed SuperFreq to analyse exome data of tumours by combining variant calling and copy number estimation in an integrated pipeline. Here we have used the SuperFreq framework for the analysis of RNA sequencing (RNA-Seq) data, which allows for the detection of absolute and allele sensitive CNAs. SuperFreq uses an error-propagation framework to combine and maximise the information available in the read depth and B-allele frequencies of SNPs (BAFs) to make CNA calls on RNA-seq data. We used data from The Cancer Genome Atlas (TCGA) to evaluate the CNA called from RNA-Seq with those generated from SNP-arrays. When ploidy estimates were consistent, we found excellent agreement with CNAs called from DNA of over 98% of the genome for acute myeloid leukaemia (TCGA-AML, n=116) and 87% for colorectal cancer (TCGA-CRC, n=377), which has a much higher CNA burden. As expected, the sensitivity of CNA calling from RNA-Seq was dependent on gene density. Nonetheless, using RNA-Seq SuperFreq detected 78% of CNA calls covering 100 or more genes with a precision of 94%. Recall dropped markedly for focal events, but this also depended on the signal intensity. For example, in the CRC cohort SuperFreq identified 100% (7/7) of cases with high-level amplification of ERBB2, where the copy number was typically >20, but identified only 6% (1/17) of cases with moderate amplification of IGF2, typically 4 or 5 copies over a smaller region (median 5 flanking genes for IGF2, compared to 20 for ERBB2). We were able to reproduce the relationship between mutational load and CNA profile in CRC using RNA-Seq alone. SuperFreq offers an integrated platform for identification of CNAs and point mutations from RNA-seq in cancer transcriptomes.

The software is implemented in R and is available through GitHub:https://github.com/ChristofferFlensburg/SuperFreq.
Lack of evidence for genetic association of saposins A, B, C and D with Parkinson disease
Authors: Sosero Yuri Ludwig , Bandres Ciga Sara , Hassin Sharon , Alcalay Roy N. , Gan-Or Ziv
Published: June 2020

The PSAP gene encodes prosaposin, which is later cleaved into four active saposins: saposin A, B, C and D. Mutations in these enzymes have been linked to specific lysosomal storage disorders. Recently, a genetic association between mutations in saposin D and Parkinson disease (PD) has been reported. To further examine whether variants in saposin D or the other saposins could be associated with Parkinson s disease, we performed Optimized Sequence Kernel Association Test (SKAT-O) in 4,132 Parkinson s disease patients and 4,470 controls. Furthermore, we analyzed data from a PD Genome Wide Association Study (GWAS) to examine the association of common variants in the PSAP locus with Parkinson s disease risk (analysis on 56,308 patients) and age at onset (analysis on 28,568 patients). We did not find any statistically significant associations between neither rare nor common variants in saposin D, nor any of the other saposins, and PD risk or onset. These results suggest that PSAP variants play either a very minor role, or more likely, no role, in PD.
Delirium Incidence, Duration and Severity in Critically Ill Patients with COVID-19
Authors: Khan Sikandar H , Lindroth Heidi , Perkins Anthony J. , Jamil Yasser , Wang Sophia , Roberts Scott , Farber Mark , Rahman Omar , Gao Sujuan , Marcantonio Edward R. , Boustani Malaz , Machado Roberto , Khan Babar A.
Published: June 2020

Background

Delirium incidence, duration and severity in patients admitted to the intensive care unit (ICU) due to COVID-19 is not known.

Methods

We conducted an observational study at two large urban academic Level 1 trauma centers. Consecutive patients admitted to the ICU with a positive SARS-CoV-2 nasopharyngeal swab polymerase chain reaction test from March 1st, 2020 to April 27, 2020 were included. Individuals younger than 18 years of age, without any documented delirium assessments (CAM-ICU), or without a discharge disposition were excluded. The primary outcomes were delirium rates and delirium duration and the secondary outcome was delirium severity. Outcomes were assessed for up to the first 14 days of ICU stay.

Results

Of 243 consecutive patients with confirmed COVID-19 admitted to the ICU, 144 met eligibility criteria and were included in the analysis. Delirium occurred in 73.6% (106/144) and delirium or coma occurred in 76.4% (110/144). Sixty-three percent of patients were positive for delirium on the first CAM-ICU assessment. The median duration of delirium and coma was 7 days (IQR: 3-10), and the median delirium duration was 5 days (IQR: 2-7). The median CAM-ICU-7 score was 6 (IQR: 4-7) representing severe delirium. Mechanical ventilation was associated with greater odds of developing delirium (OR: 42.1, 95%CI: 13.0-137.1). Mortality was 26.4% in patients with delirium compared to 15.8% in patients without delirium.

Conclusions

73.6% of patients admitted to the ICU with COVID-19 experience delirium that persists for approximately 1 week. Invasive mechanical ventilation is significantly associated with odds of delirium. Clinical attention to prevent and manage delirium and reduce delirium duration and severity is urgently needed for patients with COVID-19.
Changes in Reproductive Rate of SARS-CoV-2 Due to Non-pharmaceutical Interventions in 1,417 U.S. Counties
Authors: Wu Jie Ying , Killeen Benjamin D. , Nikutta Philipp , Thies Mareike , Zapaishchykova Anna , Chakraborty Shreya , Unberath Mathias
Published: June 2020

In response to the rapid spread of the novel coronavirus, SARS-CoV-2, the U.S. has largely delegated implementation of non-pharmaceutical interventions (NPIs) to local governments on the state and county level. This staggered implementation combined with the heterogeneity of the U.S. complicates quantification the effect of NPIs on the reproductive rate of SARS-CoV-2.

We describe a data-driven approach to quantify the effect of NPIs that relies on county-level similarities to specialize a Bayesian mechanistic model based on observed fatalities. Using this approach, we estimate change in reproductive rate, Rt, due to implementation of NPIs in 1,417 U.S. counties.

We estimate that as of May 28th, 2020 1,177 out of the considered 1,417 U.S. counties have reduced the reproductive rate of SARS-CoV-2 to below 1.0. The estimated effect of any individual NPI, however, is different across counties. Stay-at-home orders were estimated as the only effective NPI in metropolitan and urban counties, while advisory NPIs were estimated to be effective in more rural counties. The expected level of infection predicted by the model ranges from 0 to 28.7% and is far from herd immunity even in counties with advanced spread.

Our results suggest that local conditions are pertinent to containment and re-opening decisions.
The Association Between the Rate of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Use and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study
Authors: Johnson Kyle , Khayyat-Kholghi Maedeh , Johnson Blake , Tereshchenko Larisa G.
Published: June 2020

Background

The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of Covid-19 confirmed cases and deaths.

Methods

We conducted a geospatial study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population.

Findings

After adjustment for confounders, the ACEI use rate did not associate with Covid-19 confirmed case rate (direct county-own effect +0.11 %; 95%CI -0.31 to 0.53; P=0.600, and indirect spillover effect -0.53 %; 95%CI -3.89 to 2.84; P=0.760). The ARB use rate was associated with increased Covid-19 confirmed case rate (direct county-owned effect +0.12 %; 95%CI 0.05-0.19; P=0.002, and indirect spillover effect -0.33 %; 95%CI -2.11 to 1.44; P=0.714). Sensitivity analysis indicated an absence of significant reverse causality bias for analyses with Covid-19 confirmed case rate, but not death rate outcome.

Interpretation

Our results highlight the safety of ACEI use for patients with clinical indications for ACEI use. However, an increase in ARB use by 1% was associated with a 0.12 % increase in Covid-19 confirmed cases. The use of ARB, due to known ACE2 upregulation, may facilitate SARS-CoV-2 entry into target cells and increase infectivity. Cluster-randomized controlled trial is warranted to answer the question of whether the replacement of ARB by ACEI may reduce the Covid-19 confirmed case rate.

Funding

LGT was supported in part by the National Institute of Health (HL118277).
Cytokinin-promoted secondary growth and nutrient storage in the perennial stem zone ofArabis alpina
Authors: Sergeeva Anna , Liu Hongjiu , Mai Hans-Jörg , Mettler-Altmann Tabea , Kiefer Christiane , Coupland George , Bauer Petra
Published: June 2020

Perennial plants maintain their life span through several growth seasons.Arabis alpinaserves as modelBrassicaceaespecies to study perennial traits.A. alpinalateral stems have a proximal vegetative zone with a dormant bud zone, and a distal senescing seed-producing inflorescence zone. We addressed the questions of how this zonation is distinguished at the anatomical level, whether it is related to nutrient storage, and which signals affect the zonation. We found that the vegetative zone exhibits secondary growth, which we termed the perennial growth zone (PZ). High-molecular weight carbon compounds accumulate there in cambium and cambium derivatives. Neither vernalization nor flowering were requirements for secondary growth and sequestration of storage compounds. The inflorescence zone with only primary growth, termed annual growth zone (AZ), or roots exhibited different storage characteristics. Following cytokinin application, cambium activity was enhanced and secondary phloem parenchyma was formed in the PZ and also in the AZ. In transcriptome analysis cytokinin-related genes represented enriched gene ontology terms and were expressed at higher level in PZ than AZ. Thus,A. alpinauses primarily the vegetative PZ for nutrient storage, coupled to cytokinin-promoted secondary growth. This finding lays a foundation for future studies addressing signals for perennial growth.

Highlight

Arabis alpinastems have a perennial zone with secondary growth, where cambium and derivatives store high-molecular weight compounds independent of vernalization. Cytokinins are signals for the perennial secondary growth zone.
Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression
Authors: Kern Fabian , Fehlmann Tobias , Violich Ivo , Alsop Eric , Hutchins Elizabeth , Kahraman Mustafa , Grammes Nadja Liddy , Guimarães Pedro , Backes Christina , Poston Kathleen , Casey Bradford , Balling Rudi , Geffers Lars , Krüger Rejko , Galasko Douglas , Mollenhauer Brit , Meese Eckart , Wyss-Coray Tony , Craig David Wesley , Van Keuren-Jensen Kendall , Keller Andreas
Published: June 2020

Coding and non-coding RNAs have diagnostic and prognostic importance in Parkinson’s diseases (PD). We studied circulating small non-coding RNAs (sncRNAs) in 7, 003 samples from two longitudinal PD cohorts (Parkinson’s Progression Marker Initiative (PPMI) and Luxembourg Parkinson’s Study (NCER-PD)) and modelled their influence on the transcriptome. First, we sequenced sncRNAs in 5, 450 blood samples of 1, 614 individuals in PPMI. The majority of 323 billion reads (59 million reads per sample) mapped to miRNAs. Other covered RNA classes include piRNAs, rRNAs, snoRNAs, tRNAs, scaRNAs, and snRNAs. De-regulated miRNAs were associated with the disease and disease progression and occur in two distinct waves in the third and seventh decade of live. Originating mostly from a characteristic set of immune cells they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. By profiling 1, 553 samples from 1, 024 individuals in the NCER-PD cohort using an independent technology, we validate relevant findings from the sequencing study. Finally, network analysis of sncRNAs and transcriptome sequencing of the original cohort identified regulatory modules emerging in progressing PD patients.
Mapping Gene-Microbe Interactions: Insights from Functional Genomics Co-culture Experiments betweenSaccharomyces cerevisiaeandPseudomonasspp
Authors: N’guyen Guillaume Quang , Jain Mani , Landry Christian R , Filteau Marie
Published: June 2020

Microbial interactions contribute to shape ecosystems and their functions. The interplay between microorganisms also shapes the evolutionary trajectory of each species, by imposing metabolic and physiological selective pressures. The mechanisms underlying these interactions are thus of interest to improve our understanding of microbial evolution at the genetic level. Here we applied a functional genomics approach in the model yeastSaccharomyces cerevisiaeto identify the fitness determinants of naïve biotic interactions. We used a barcoded prototroph yeast deletion collection to perform pooled fitness competitions in co-culture with sevenPseudomonasspp natural isolates. We found that co-culture had a positive impact on fitness profiles, as in general the deleterious effects of loss of function in our nutrient-poor media were mitigated. In total, 643 genes showed a fitness difference in co-culture, most of which can be explained by a media diversification procured by bacterial metabolism. However, a large fraction (36%) of gene-microbe interactions could not be recaptured in cell-free supernatant experiments, showcasing that feedback mechanisms or physical contacts modulate these interactions. Also, the gene list of some co-cultures was enriched with homologs in other eukaryote species, suggesting a variable degree of specificity underlying the mechanisms of biotic interactions and that these interactions could also exist in other organisms. Our results illustrate how microbial interactions can contribute to shape the interplay between genomes and species interactions, and thatS. cerevisiaeis a powerful model to study the impact of biotic interactions.
A method for continuously monitoring the quality of Masson pine seedlings
Authors: Wan Li , Gao Handong , Huang Zhuo , Li Chao
Published: June 2020

Root growth potential (RGP) is a popular physiological indicator used to evaluate seedling vigor. However, the time scale used in the RGP test is the order of days, which leads to poor performance of the RGP method. We propose an optical interference method, called statistical interferometry, to measure minute root elongation at a sub-nanometer scale, which can decrease the time used in measuring RGP. The time scale of this method is also 104times less than that of the RGP method. Because we can measure the length of root elongation continuously, we can compute the root elongation rate (RER), which is the variety of the length of root elongation per second. Continuous monitoring can help determine the quality of Masson pine seedling as soon as possible. To show the effectiveness of our proposed method, we designed an experiment, in which we applied different water stresses to our collected Masson pine seedlings and acquired two groups of pines, representing two different qualities: one stressed by water and one not. After measuring the RER of the groups in our experiments, we found that RER is interrelated with the quality of seedlings.

Author summary

Li Wang have worked in Nanjing Forest University. His interesting includes machine learning, computer vision and plant phenotype.
Different organic manure sources and NPK fertilizer on soil chemical properties, growth, yield and quality of okra
Authors: Adekiya Aruna Olasekan , Ejue Wutem Sunny , Olayanju Adeniyi , Dunsin Oluwagbenga , Aboyeji Christopher Muyiwa , Aremu Charity , Adegbite Kehinde , Akinpelu Olanike
Published: June 2020

Use of organic manures to meet the nutrient requirement of crop would be an inevitable practice in the years to come for sustainable agriculture since organic manures generally improve the soil physical, chemical and biological properties. Hence, field experiments were carried out in 2017 and 2018 to compare the impact of different organic manures and NPK fertilizer on soil properties, growth, yield, proximate and mineral contents of okra (Abelmoschus esculentusL.). The treatments each year 2017 and 2018 consisted of: rabbit manure, cow dung, poultry manure, green manure [Mexican sunflower (Tithonia diversifoliaAsteraceae)], pig manure, NPK 15-15-15 fertilizer applied at 120 kg N ha−1and a control (no manure/ inorganic fertilizer). The seven treatments were laid out in a randomized complete block design with three replication. Organic manures and NPK fertilizer increased the soil organic matter (OM), N, P, K, Ca and Mg (NPK fertilizer did not increase OM, Ca and Mg significantly), growth, yield, minerals, protein, ash, carbohydrate and mucilage contents of okra fruit as compared with control. Organic manures improved okra yield compared with NPK fertilizer. Okra growth and yield parameters were significantly higher in 2018 compared with 2017. Control, rabbit manure, cow dung, poultry manure, green manure, pig manure and NPK fertilizer in 2018 increased the pod yield of okra by 9.7%, 35.3%, 57.9%, 36.2%, 39.2%, 45.5% and 3.2%, respectively compare with the same treatment in 2017. Amongst various organic manures, poultry manure produced significantly higher plant growth, yield, mineral and proximate composition of okra because of its high soil chemical properties which could be related to its lowest C: N ratio, lignin and lignin: N ratio. Results also showed that okra grown during high intensity rainfall has higher yield but with reduced quality except its mucilage content. Therefore, planting of okra with poultry manure under moderate rainfall will enhance the health benefit from the fruit, however, those that desire its mucilage content planting during high rainfall is recommended.
Population estimation study reveals staggeringly high number of cattle on the streets of urban Raipur, Chhattisgarh, India
Authors: Sahu Bhupendra Kumar , Parganiha Arti , Pati Atanu Kumar
Published: June 2020

Cattle (bovine species) are economically and ecologically very important and are cosmopolitan in distribution. Increasing number of cattle on the urban streets of developing and underdeveloped countries has become an unmanageable menace in recent time. Consequently numbers of road accidents have increased in the urban areas of most of the developing countries, like India. In the present study, we estimated the population of street cattle wandering on the street/road/highway of Raipur city of India using direct head count method and advanced Photographic Capture Recapture Method (PCRCM). We compared these two scientific methods of population estimation to check their adequacy. We prepared grid (1.0 x 1.0 km) on the map of Raipur city using Quantum Geographic Information System (QGIS) software and randomly selected 20 grids for the estimation of street cattle population. We used line transects and block count methods for data sampling. Results of direct head count method indicated an estimation of 11808.45 cattle (using line transects sampling method) and 11198.30 cattle (using block counting sampling method) visibly roaming on the street of Raipur city. Further, advanced PCRCM indicated an estimation of 35149.61 cattle using line transects sampling method and 34623.20 cattle using block counting sampling method. We observed female biased sex ratio in both mature and immature cattle. Frequency of mature cattle was significantly higher than that of immature cattle followed by calves. Further, the frequency of cattle in a grid was found in the following order: cow > bull > heifer > immature male > female calve > male calve. We concluded that the estimated population of street cattle in Raipur city is about 34623. Results of both the techniques, i.e., direct head count method and PCRCM for population estimation are consistent. The direct head count method yields the number of cattle visibly roaming on the street in a particular time; whereas advanced PCRCM gives the total population of street cattle in the city. Results of this study might be helpful in the management of street cattle menace in urban habitat and landscape.
A microRNA Signature of Metastatic Colorectal Cancer
Authors: Høye Eirik , Fromm Bastian , Böttger Paul Heinrich Michael , Domanska Diana , Torgunrud Annette , Lund-Andersen Christin , Abrahamsen Torveig Weum , Fretland Åsmund Avdem , Dagenborg Vegar Johansen , Lorenz Susanne , Edwin Bjørn , Hovig Eivind , Flatmark Kjersti
Published: June 2020

Although microRNAs (miRNA) are involved in all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood and contradictory results have been published. The aim of this work was to identify miRNAs associated with metastatic progression of colorectal cancer (CRC). Novel and previously published next generation sequencing (NGS) datasets generated from 268 samples with primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues were analyzed. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, utilizing miRNA-tailored quality control and processing, and applying a physiologically meaningful cut-off value (100 reads per million). The results were adjusted for host tissue background expression and samples from the different metastatic sites were independently analyzed. A metastatic signature containing five miRNAs up-regulated at multiple metastatic sites was identified (Mir-210_3p, Mir-191_5p, Mir-8-P1b_3p(mir-141-3p), Mir-1307_5p, and Mir-155_5p) along with a number of miRNAs that were differentially expressed at individual metastatic sites. Several of these have previously been implicated in metastasis through involvement in epithelial-to-mesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The identified differentially expressed miRNAs confirm known associations and contribute novel insights into miRNA involvement in the metastatic process. The use of open science practices facilitates reproducibility, and new datasets may easily be added to the publicly available pipeline to continuously improve the knowledge in the field. The identified set of miRNAs provides a reliable starting-point for further research into the role of miRNAs in metastatic progression.
Complement factor C4a does not activate protease activated receptor 1 (PAR1) or PAR4 on human platelets
Authors: Han Xu , de la Fuente Maria , Nieman Marvin T.
Published: June 2020

Background

Protease activated receptor 1 (PAR1) and PAR4 are key thrombin signal mediators for human platelet activation and aggregation in response to vascular injury. They are primarily activated by thrombin cleavage of the N-terminus to expose a tethered ligand. In addition to the canonical activation by thrombin, a growing panel of proteases can also elicit PAR1- or PAR4-mediate signal transduction. Recently, complement factor C4a was reported as the first endogenous agonist for both PAR1 and PAR4. Further, it is the first endogenous non-tethered ligand that activates PAR1 and PAR4. These studies were conducted with human microvascular cells; the impact of C4a on platelet PARs is unknown.

Objectives

The goal of this study was to interrogate PAR1 and PAR4 activation by C4a on human platelets.

Methods

Platelet rich plasma (PRP) were isolated from healthy donors. PRP was stimulated with C4a and the platelet aggregation was measured. HEK293 Flp-In T-rex cells were used to further test if C4a stimulation can initiate PAR1- or PAR4-mediated Gαqsignaling, which was measured by intracellular calcium mobilization.

Results

C4a failed to elicit platelet aggregation via PAR1- or PAR4-mediated manner. In addition, no PAR1- or PAR4-mediated calcium mobilization was observed upon C4a stimulation on HEK293 cells.

Conclusions

Complement factor C4a does not activate PAR1 or PAR4 on human platelets. These data show that PAR1 and PAR4 activation by C4a on microvascular cells likely requires a cofactor, which re-enforces the concept of cell-type specific regulation of protease signaling.

Essentials

C4a is an agonist for both PAR1 and PAR4 on human microvascular cells.

We sought to determine if C4a activates human platelets through PAR1 or PAR4.

C4a does not activate PAR1 and PAR4 on human platelets.

This re-enforces the concept of cell-type specific regulation of PAR signaling.
Switchgrass metabolomics reveals striking genotypic and developmental differences in specialized metabolic phenotypes
Authors: Li Xingxing , Sarma Saurav J. , Sumner Lloyd W. , Jones A. Daniel , Last Robert L.
Published: June 2020

Switchgrass (Panicum virgatumL.) is a bioenergy crop that grows productively on lands not suitable for food production, and is an excellent target for low-pesticide input biomass production. We hypothesize that resistance to insect pests and microbial pathogens is influenced by low molecular weight compounds known as specialized metabolites. We employed untargeted liquid chromatography-mass spectrometry (LC-MS), quantitative gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy to identify differences in switchgrass ecotype metabolomes. This analysis revealed striking differences between upland and lowland switchgrass metabolomes as well as distinct developmental profiles. Terpenoid and polyphenol derived specialized metabolites were identified, including steroidal saponins, di- and sesqui-terpenoids and flavonoids. The saponins are especially abundant in switchgrass extracts and have diverse aglycone cores and sugar moieties. We report seven structurally distinct steroidal saponin classes with unique steroidal cores and glycosylated at one or two positions. Quantitative GC-MS revealed differences in total saponin concentrations in leaf blade, leaf sheath, stem, rhizome and root. The quantitative data also demonstrated that saponin concentrations is higher in roots of lowland than upland ecotype plants, suggesting ecotypic specific biosynthesis and/or biological functions. These results enable future testing of these specialized metabolites on biotic and abiotic stress tolerance and can inform development of low-input bioenergy crops.

One sentence summary

Integrated mass-spectrometry and nuclear magnetic resonance spectroscopy based metabolomics reveal that switchgrass accumulates structurally diverse terpenoids and phenolics, which vary in abundance and structure in a tissue- and ecotype-specific manner.
A heuristic underlies the search for relief in fruit flies
Authors: Meda Nicola , Menti Giulio Maria , Megighian Aram , Zordan Mauro Agostino
Published: June 2020

Humans rely on multiple systems of sensory information to make decisions. However, strategies that shorten decision-making time by taking into account fewer but more essential elements of information are preferred to strategies involving complex analyses. These “shortcuts to decision” are also termed “heuristics”. The identification of heuristic principles in species phylogenetically distant to humans would shed light on the evolutionary origin of speed-accuracy trade-offs and offer the possibility to investigate the brain representations of such trade-offs, urgency, and uncertainty. During experiments on spatial learning, we acknowledged that the search strategies of the invertebrateDrosophila melanogaster, the common fruit fly, resembled a spatial heuristic. Here we show that the fruit fly applies a heuristic termed the “Nearest Neighbour Rule” to avoid bitter taste (a negative stimulation). That is, the fly visits the salient location closest to its current position to hopefully stop the negative stimulation. Only if this strategy proves unsuccessful, the animal uses other learned associations to avoid bitter taste. The acknowledgement of a heuristic inD. melanogastersupports the view that invertebrates can leverage on ‘economic’ principles when making choices and that the existence of heuristics in evolution dates to at least 600 million years ago.
BARD1 links histone H2A Lysine-15 ubiquitination to initiation of BRCA1-dependent homologous recombination
Authors: Becker Jordan R. , Bonnet Clara , Clifford Gillian , Groth Anja , Wilson Marcus D. , Chapman J. Ross
Published: June 2020

Protein ubiquitination at sites of DNA double-strand breaks (DSBs) by RNF168 recruits BRCA1 and 53BP1, mediators of the homologous recombination (HR) and non-homologous end joining (NHEJ) DSB repair pathways, respectively. While NHEJ relies on 53BP1 binding to ubiquitinated Lysine 15 on H2A-type histones (H2AK15ub), an RNF168-dependent modification, the mechanism linking RNF168 to BRCA1 recruitment during HR has remained unclear. Here, we identify a tandem BRCT domain ubiquitin-dependent recruitment motif (BUDR) in BARD1 – BRCA1’s obligate partner protein – that binds H2AK15ub directly, thereby recruiting BRCA1 to DSBs. BARD1 BUDR mutations compromise HR, and render cells hypersensitive to PARP inhibition and cisplatin treatment. We find that BARD1-nucleosome interactions require BUDR binding to H2AK15ub and ankyrin repeat domain-mediated binding of the histone H4 tail, specifically when unmethylated on Lysine-20 (H4K20me0), a state limited to post replicative chromatin. Finally, we demonstrate that by integrating DNA damagedependent H2AK15ub and DNA replication-dependent H4K20me0 signals at sites of DNA damage, BARD1 coordinates BRCA1-dependent HR with 53BP1 pathway antagonization, establishing a simple paradigm for the governance of DSB repair pathway choice.
Cell-type-specific promoters forC. elegansglia
Authors: Fung Wendy , Wexler Leigh , Heiman Maxwell G.
Published: June 2020

Glia shape the development and function of theC. elegansnervous system, especially its sense organs and central neuropil (nerve ring). Cell-type-specific promoters allow investigators to label or manipulate individual glial cell types, and therefore provide a key tool for deciphering glial function. In this technical resource, we compare the specificity, brightness, and consistency of cell-type-specific promoters forC. elegansglia. We identify a set of promoters for the study of seven glial cell types (F16F9.3, amphid and phasmid sheath glia;F11C7.2, amphid sheath glia only;grl-2, amphid and phasmid socket glia;hlh-17, cephalic (CEP) sheath glia; andgrl-18, inner labial (IL) socket glia) as well as a pan-glial promoter (mir-228). We compare these promoters to promoters that are expressed more variably in combinations of glial cell types (delm-1anditx-1). We note that the expression of some promoters depends on external conditions or the internal state of the organism, such as developmental stage, suggesting glial plasticity. Finally, we demonstrate an approach for prospectively identifying cell-type-specific glial promoters using existing single-cell sequencing data, and we use this approach to identify two novel promoters specific to IL socket glia (col-53andcol-177).