bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal patterns of matter and energy fluxes in land and ocean ecosystems
Authors: Nefiodov A. V. 
Published: April 2020

AbstractIn work [1], the fundamental relationships for the fluxes of matter and energy in terrestrial ecosystems were obtained. Taking into account the universal characteristics of biota, these relationships permitted an estimate to be made of the vertical thickness of the live biomass layer for autotrophs and heterotrophs. The distribution of consumption of biota production as dependent on the body size of heterotrophs was also investigated. For large animals (vertebrates), the energy consumption in sustainable ecosystems was estimated to be of the order of one percent of primary production. In this comment, it is shown that the results of work [1] also hold true for ocean ecosystems and thus are universal for life as a whole. This is of paramount importance for human life on Earth.
Presence of polyadenylated 3’ tail in RNA ofPepper mild mottle virusallows the Oligo(dT)18in Priming cDNA Synthesis of its genomic RNA template
Authors: Kumari Nidhi , Sharma Vivek , Choudhary Sneha , Sharma P.N. 
Published: April 2020

AbstractThe PCR amplification of majority of the ssRNA of both genomic and non-genomic mRNA is accomplished by RT-PCR. The mRNA is subjected to cDNA synthesis using reverse transcriptase and either Oligo(dT)18, or random or gene specific reverse primers based priming strategies. The choice of primer largely depends on the nature of 3 prime terminus of mRNA and length of cDNA synthesized. In general, oligo(dT)18 is the preferred choice for mRNAs having poly(A) tail at 3 prime terminus. In general, tobamoviruses lack any poly(A) tail at their 3 prime untranslated region (UTR) which forms a tRNA like structure and upstream pseudoknot domain except tow viruses viz., Hibiscus latent Fort Pierce virus (HLFPV) and Hibiscus latent Singapore virus (HLSV) which accommodate internal poly(A) sequences of 46 and 87 nucleotides long, respectively in their 3 prime UTR. However, determination of full nucleotide sequence of Pepper mild mottle virus (PMMoV) using an oligo(dT)18 primed cDNA as template indicated the libertinism of oligo(dT)18 in priming cDNA synthesis of RNA template which are known to lack poly(A) tail. at the end or internally at its 3 prime end. Moreover, coat protein (CP) gene of PMMoV and bean common mosaic virus (BCMV) (Potyvirus with a poly(A) tract at its 3 prime end) was amplified using cDNA primed with random primer as well as oligo(dT)18 was successfully amplified but with significant variation in the intensity of the amplification band in case of PMMoV but not in BCMV. This clearly indicated the presence of PMMoV mRNA with polyadenylated 3 prime tail in total RNA isolated from PMMoV infected capsicum leaves with abundance of non-polyadenylated PMMoV genomic RNA (gRNA). Hence, we hypothesize that the generation of polyadenylated RNA population during the infection cycle of PMMoV in pepper may be possible reason for libertinism of oligo(dT)18 in priming cDNA synthesis of RNA template isolated from PMMoV infected leaves followed by amplification of entire PMMoV genome through RT-PCR. This is first study indicating the presence of polyadenylated or polyadenylated rich regions in PMMoV gRNA acquired during the infection cycle in pepper.
Subpopulations of stressedY. pseudotuberculosispreferentially survive doxycycline treatment within host tissues
Authors: Raneses Jasmine Ramirez , Ellison Alysha L. , Liu Bessie , Davis Kimberly M. 
Published: April 2020

AbstractSevere systemic bacterial infections result in colonization of deep tissues, which can be very difficult to eliminate with antibiotics. It remains unclear if this is because antibiotics are not reaching inhibitory concentrations within tissues, if subsets of bacteria are less susceptible to antibiotics, or if both contribute to limited treatment efficacy. To determine the concentration of doxycycline (Dox) present within deep tissues following treatment, we generated a fluorescent transcriptional reporter derived from thetetoperon to specifically detect intracellular tetracycline exposure at the single bacterial cell level. Dox exposure was detected in the spleen 2 hours after intraperitoneal injection, and by 4 hours post-injection, this treatment resulted in a significant decrease in viableYersinia pseudotuberculosisin the spleen. Nitric oxide-stressed bacteria preferentially survived treatment, suggesting stress was sufficient to alter Dox susceptibility. Many bacteria (~10%) survived a single dose of Dox, and the antibiotic accumulated at the periphery of microcolonies to growth inhibitory concentrations until 48 hours post-treatment. After this timepoint, antibiotic concentrations decreased and bacterial growth resumed. Dox-treated mice eventually succumbed to the infection, albeit with significantly prolonged survival relative to untreated mice. These results indicate that Dox delivery by intraperitoneal injection results in rapid diffusion of inhibitory concentrations of antibiotic into the spleen, but stressed cells preferentially survive drug treatment, and bacterial growth resumes once drug concentrations decrease. This fluorescent reporter strategy for antibiotic detection could easily be modified to detect the concentration of additional antimicrobial compounds within host tissues following drug administration.ImportanceBacterial infections are very difficult to treat when bacteria spread into the bloodstream and begin to replicate within deep tissues, such as the spleen. Subsets of bacteria can survive antibiotic treatment, but it remains unclear if this survival is because of limited drug diffusion into tissues, or if something has changed within the bacteria, promoting survival of some bacterial cells. Here, we have developed a fluorescent reporter to detect doxycycline (Dox) diffusion into host tissues, and show that Dox impacts the bacterial population within hours of administration, and inhibits bacterial growth for 48 hours. However, bacterial growth resumes when antibiotic concentrations decrease. Subsets of bacteria, stressed by the host response to infection, survive Dox treatment at a higher rate. These results provide critical information about the dynamics that occur within deep tissues following antibiotic administration, and suggests subsets of bacteria are predisposed to survive inhibitory concentrations of antibiotic before exposure.
Consolidated bioprocessing of lignocellulose for production of glucaric acid by an artificial microbial consortium
Authors: Li Chaofeng , Lin Xiaofeng , Ling Xing , Li Shuo , Fang Hao 
Published: April 2020

AbstractThe biomanufacturing of D-glucaric acid has been attracted increasing interest and the industrial yeast Saccharomyces cerevisiae is regarded as an excellent host for D-glucaric acid production. Here we constructed the biosynthetic pathway of D-glucaric acid in S. cerevisiae INVSc1 whose opi1 was knocked out and obtained two engineered strains, LGA-1 and LGA-C, producing record breaking titers of D-glucaric acid, 9.53 ± 0.46 g/L and 11.21 ± 0.63 g/L D-glucaric acid from 30 g/L glucose and 10.8 g/L myo-inositol in the mode of fed-batch fermentation, respectively. Due to the genetic stability and the outperformance in subsequent applications, however, LGA-1 was a preferable strain. As one of the top chemicals from biomass, there have been no reports on D-glucaric acid production from lignocellulose, which is the most abundant renewable on earth. Therefore, the biorefinery processes of lignocellulose for D-glucaric acid production including separated hydrolysis and fermentation (SHF), simultaneous saccharification and fermentation (SSF) and consolidated bioprocessing (CBP) were investigated in this work and CBP by an artificial microbial consortium composed of Trichoderma reesei Rut-C30 and S. cerevisiae LGA-1 was found to have relatively high D-glucaric acid titers and yields after 7 d fermentation, 0.54 ± 0.12 g/L D-glucaric acid from 15 g/L Avicel, and 0.45 ± 0.06 g/L D-glucaric acid from 15 g/L steam exploded corn stover (SECS), respectively. In attempts to design the microbial consortium for more efficient CBP the team consisted of the two members, T. reesei Rut-C30 and S. cerevisiae LGA-1, was found to be the best with excellent work distribution and collaboration. This desirable and promising approach for direction production of D-glucaric acid from lignocellulose deserves extensive and in-depth research.
ADrosophilanatural variation screen identifies NKCC1 as a substrate of NGLY1 deglycosylation and a modifier of NGLY1 deficiency
Authors: Talsness Dana M. , Owings Katie G. , Coelho Emily , Mercenne Gaelle , Pleinis John M. , Zuberi Aamir R. , Partha Raghavendran , Clark Nathan L. , Lutz Cathleen M. , Rodan Aylin R. , Chow Clement Y. 
Published: April 2020

AbstractN-Glycanase 1 (NGLY1) is a cytoplasmic deglycosylating enzyme. Loss-of-function mutations in theNGLY1gene cause NGLY1 deficiency, which is characterized by developmental delay, seizures, and a lack of sweat and tears. To model the phenotypic variability observed among patients, we crossed aDrosophilamodel of NGLY1 deficiency onto a panel of genetically diverse strains. The resulting progeny showed a phenotypic spectrum from 0-100% lethality. Association analysis on the lethality phenotype as well as an evolutionary rate covariation analysis generated lists of modifying genes, providing insight into NGLY1 function and disease. The top association hit wasNcc69(humanNKCC1/2), a conserved ion transporter. Analyses in NGLY1 -/- mouse cells demonstrated that NKCC1 is misglycosylated and has reduced function, making it only the second confirmed NGLY1 enzymatic substrate. The misregulation of this ion transporter may explain the observed defects in secretory epithelium function in NGLY1 deficiency patients.
Altered functional connectivity of cortical networks in semantic variant Primary Progressive Aphasia
Authors: Popal Haroon , Quimby Megan , Hochberg Daisy , Dickerson Bradford C. , Collins Jessica A. 
Published: April 2020

AbstractAs their illness progresses, patients with the semantic variant of Primary Progressive Aphasia (svPPA) frequently exhibit peculiar behaviors indicative of altered visual attention or an increased interest in artistic endeavors. In the present study, we examined changes within and between large-scale functional brain networks that may explain this altered visual behavior. We first examined the connectivity of the visual association network, the dorsal attention network, and the default mode network in healthy young adults (n=89) to understand the typical architecture of these networks in the healthy brain. We then compared the large-scale functional connectivity of these networks in a group of svPPA patients (n=12) to a group of age-matched cognitively normal controls (n=30). Our results showed that the between-network connectivity of the dorsal attention and visual association networks was elevated in svPPA patients relative to controls. We further showed that this heightened between-network connectivity was associated with a decrease in the within-network connectivity of the default mode network, possibly due to progressive degeneration of the anterior temporal lobes in svPPA. These results suggest that focal neurodegeneration can lead to the reorganization of large-scale cognitive networks beyond the primarily affected network(s), possibly contributing to cognitive or behavioral changes that are commonly present as part of the clinical phenotype of svPPA.
Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogs
Authors: Chen Dongxing , Dong Cheng , Dong Guangping , Srinivasan Karthik , Min Jinrong , Noinaj Nicholas , Huang Rong 
Published: April 2020

AbstractThe interactions of a series of bisubstrate analogs with protein N-terminal methyltransferase 1 (NTMT1) were examined to probe the molecular properties of the NTMT1 active site through biochemical characterization and structural studies. Our results indicate that a 2-C to 4-C atom linker enables its respective bisubstrate analog to occupy both substrate and cofactor binding sites of NTMT1, but the bisubstrate analog with a 5-C atom linker only interacts with the substrate binding site and functions as a substrate. Furthermore, the 4-C atom linker is the optimal and produces the most potent inhibitor (Ki, app= 130 ± 40 pM) for NTMT1 to date, displaying over 100,000-fold selectivity over other methyltransferases and 3,000-fold even to its homolog NTMT2. This study reveals the molecular basis for the plasticity of the NTMT1 active site. Additionally, our study outlines a general guidance on the development of bisubstrate inhibitors for any methyltransferases.
Oncogenetic Network Estimation with Disjunctive Bayesian Networks
Authors: Nicol Phillip B. , Coombes Kevin R. , Deaver Courtney , Chkrebtii Oksana , Paul Subhadeep , Toland Amanda E. , Asiaee Amir 
Published: April 2020

AbstractMotivationCancer is the process of accumulating genetic alterations that confer selective advantages to tumor cells. The order in which aberrations occur is not arbitrary, and inferring the order of events is challenging due to the lack of longitudinal samples from tumors. Moreover, a network model of oncogenesis should capture biological facts such as distinct progression trajectories of cancer subtypes and patterns of mutual exclusivity of alterations in the same pathways. In this paper, we present the Disjunctive Bayesian Network (DBN), a novel oncogenetic model with a phylogenetic interpretation. DBN is expressive enough to capture cancer subtypes’ trajectories and mutually exclusive relations between alterations from unstratified data.ResultsIn cases where the number of studied alterations is small (<30), we provide an efficient dynamic programming implementation of an exact structure learning method that finds a best DBN in the super-exponential search space of networks. In rare cases that the number of alterations is large, we provided an efficient genetic algorithm in our software package, OncoBN. Through numerous synthetic and real data experiments, we show OncoBN’s ability in inferring ground truth networks and recovering biologically meaningful progression networks.AvailabilityOncoBN is implemented in R and is available athttps://github.com/phillipnicol/OncoBN.
Discovery of potential epigenetic inhibitors against histone methyltransferases through molecular docking and molecular dynamics simulations
Authors: Babu Tirumalasetty Muni Chandra , Zhang Zaiping , Qin Danian , Huang Chengyang 
Published: April 2020

AbstractHistone methyltransferases (HMTases) catalyze histone methylations that are the important epigenetic marks regulating gene expression, cell fate, and disease progression. In this study, we investigated potential epigenetic inhibitors against HMTases through in silico approaches, including ensembled molecular docking and molecular dynamics simulations (MDS).We identified three candidate compounds, including echinomycin, emetine, and streptonigrin, which showed interactions with HMTases. Echinomycin showed similar binding affinity with H3K4-HMTase NSD3 and H3K9-HMTase SETDB1 but streptonigrin and emetine had preferential binding affinity with NSD3 and SETDB1, respectively. The binding of NSD3 to streptonigrin and echinomycin and binding of SETDB1 to emetine and echinomycin were further confirmed by the results of hydrogen bonding profile and MM/PBSA calculations. Together, our results uncover the binding affinities of echinomycin, emetine, and streptonigrin with histone methyltransferases, and suggest that these compounds are potential epigenetic inhibitors regulating cell activities.
White matter fascicles and cortical microstructure predict reading-related responses in human ventral temporal cortex
Authors: Grotheer Mareike , Yeatman Jason , Grill-Spector Kalanit 
Published: April 2020

AbstractReading-related responses in the lateral ventral temporal cortex (VTC) show a consistent spatial layout across individuals, which is puzzling, since reading skills are acquired during childhood. Here, we tested the hypothesis that white matter fascicles and gray matter microstructure predict the location of reading-related responses in lateral VTC. We obtained functional (fMRI), diffusion (dMRI), and quantitative (qMRI) magnetic resonance imaging data in 30 adults. fMRI was used to map reading-related responses by contrasting responses in a reading task with those in adding and color tasks; dMRI was used to identify the brain’s fascicles and to map their endpoints density in lateral VTC; qMRI was used to measure proton relaxation time (T1), which depends on cortical tissue microstructure. We fit linear models that predict reading-related responses in lateral VTC from endpoint density and T1and used leave-one-subject-out cross-validation to assess prediction accuracy. Using a subset of our participants (N=10, feature selection set), we find that i) endpoint density of the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), and vertical occipital fasciculus (VOF) are significant predictors of reading-related responses, and ii) cortical T1of lateral VTC further improves the predictions of the fascicle model. Next, in the remaining 20 participants (validation set), we showed that a linear model that includes T1, AF, ILF and VOF significantly predicts i) the map of reading-related responses across lateral VTC and ii) the location of the visual word form area, a region critical for reading. Overall, our data-driven approach reveals that the AF, ILF, VOF and cortical microstructure have a consistent spatial relationship with an individual’s reading-related responses in lateral VTC.HighlightsThe ILF, AF, and VOF predict the spatial layout of reading-related responses in VTCGray matter microstructure improves the prediction of reading-related responsesFascicles and gray matter structure together predict the location of the VWFA
RNA matchmaking remodels lncRNA structure and promotes PRC2 activity
Authors: Balas Maggie M. , Hartwick Erik W. , Barrington Chloe , Roberts Justin T. , Wu Stephen K. , Bettcher Ryan , Griffin April M. , Kieft Jeffrey S. , Johnson Aaron M. 
Published: April 2020

ABSTRACTHuman Polycomb Repressive Complex 2 (PRC2) catalysis of histone H3 lysine 27 methylation at certain loci depends on long noncoding RNAs (lncRNAs). Yet, in apparent contradiction, RNA is a potent catalytic inhibitor of PRC2. Here we show that intermolecular RNA-RNA interactions between the lncRNA HOTAIR and its target genes can relieve RNA inhibition of PRC2. RNA matchmaking is promoted by heterogenous nuclear ribonucleoprotein (hnRNP) B1, which uses multiple protein domains to bind regions of HOTAIR via multi-valent protein-RNA interactions. Chemical probing demonstrates that RNA matchmaking changes HOTAIR RNA structure. Genome-wide HOTAIR/PRC2 activity occurs at genes whose transcripts can make favorable RNA-RNA interactions with HOTAIR. We demonstrate that RNA-RNA matches of HOTAIR with target gene RNAs can relieve the inhibitory effect of a single lncRNA for PRC2 activity. Our work highlights an intrinsic switch that allows PRC2 activity in specific RNA contexts, which could explain how many lncRNAs work with PRC2.
rcs5-mediated spot blotch resistance in barley is conferred by wall-associated kinases that resist pathogen manipulation
Authors: Ameen Gazala , Solanki Shyam , Drader Thomas , Sager-Bittara Lauren , Steffenson Brian , Kleinhofs Andris , Vogiatzis Chrysafis , Brueggeman Robert S. 
Published: April 2020

ABSTRACTPlant biotrophic pathogen disease resistances rely on immunity receptor-mediated programmed cell death (PCD) responses, but specialized necrotrophic/hemi-biotrophic pathogens hijack these mechanisms to colonize the resulting dead tissue in their necrotrophic phase. Thus, immunity receptors can become necrotrophic pathogen dominant susceptibility targets but resistance mechanisms that resist necrotroph manipulation are recessive resistance genes. The barleyrcs5QTL imparts recessive resistance against the disease spot blotch caused by the hemi-biotrophic fungal pathogenBipolaris sorokiniana. Thercs5genetic interval was delimited to ~0.23 cM, representing an ~234 kb genomic region containing four wall-associated kinase (WAK) genes, designatedHvWak2, Sbs1, Sbs2(susceptibility toBipolarissorokiniana1&2), andHvWak5. Post-transcriptional gene silencing ofSbs1&2in susceptible barley cultivars resulted in resistance showing dominant susceptibility function. Allele analysis ofSbs1&2from resistant and susceptible barley cultivars identified sequence polymorphisms associated with phenotypes in their primary coding sequence and promoter regions, suggesting differential transcriptional regulation may contribute to susceptibility. Transcript analysis ofSbs1&2showed nearly undetectable expression in resistant and susceptible cultivars prior to pathogen challenge; however, upregulation of both genes occurred specifically in susceptible cultivars post-inoculation with a virulent isolate. Apoplastic wash fluids collected from barley infected with a virulent isolate inducedSbs1, suggesting regulation by an apoplastic-secreted effector. Thus,Sbs1&2 function asB. sorokinianasusceptibility targets and non-functional alleles or alleles that resist induction by the pathogen mediatercs5-recessive resistance. Thesbs1&2alleles underlying thercs5QTL that the pathogen is unable to manipulate are the first resistance genes identified against spot blotch.SIGNIFICANCE STATEMENTThercs5locus in barley confers a high level of seedling resistance and a moderate level of adult plant resistance to spot blotch. It is part of a complex that has provided durable spot blotch resistance in many North American barley cultivars (cv) for more than 50 years. Genetic characterization and positional cloning ofrcs5identified the dominant susceptibility genes,Sbs1andSbs2(susceptibility toBipolaris sorokiniana1 and 2) as wall-associated kinases. These genes are hijacked by the hemibiotrophic pathogen in its necrotrophic phase to induce programmed cell death, facilitating disease development. We report the first spot blotch resistance/susceptibility genes cloned that function via alleles that cannot be specifically induced and hijacked by virulent isolates of the pathogen.