bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative whole-genome analysis of a Thar desert strainStreptomycessp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system
Authors: Harwani Dharmesh , Begani Jyotsna , Lakhani Jyoti 
Published: January 2021

AbstractWe sequenced the genome ofStreptomycessp. JB150, isolated from a unique site of the Thar desert in India. Genome mining of the JB150 genome revealed the presence of many interesting secondary metabolic biosynthetic gene clusters (BGCs). The encoded parvome of JB150 includes non-ribosomal peptides, polyketides including β-lactone, butyrolactone, ectoine, lantipeptides, lasso peptides, melanin, resorcinol, siderophores, terpenoids, thiopeptides, and other types of hybrid compounds. Among them, ~30% BGCs displayed a high degree of novelty. The genome of JB150 was enriched for a large assortment of specialized genes coding for the production of many interesting biomolecules comprising compatible solutes, multiple stress-response regulators, transport proteins, protein secretion systems, signaling molecules, chaperones and storage reserves, etc. The presence of diverse members of CAZymes enzyme families, high numbers of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), trehalose and aromatic compounds synthesis genes, putative orthologues to several of the classical fatty acid synthesis components, prototrophy for many essential amino acids exhibit metabolic versatility of JB150 to inhabit in the extreme desert environment. Besides, the genome of JB150 was observed to specifically encode thiazole-oxazole-modified thiazolemicrocin (TOMM) and ectoine. The comparison of the complete genomes ofStreptomycessp. JB150 and seven other actinomycete strains belonging to different desert ecosystems unveiled the presence of many previously undetected, distinctive, biological, and genomic signatures. We propose that these genetic traits endowed by these strains are essential for their adaptation in the highly underprivileged, extreme ecosystem of the Thar desert to cope with multiple abiotic stressors, oligotrophic nutrient conditions and to produce a huge repertoire of diverse secondary metabolites.
CrossTalkeR: Analysis and Visualisation of Ligand Receptor Networks
Authors: Nagai James S. , Leimkühler Nils B. , Schaub Michael T. , Schneider Rebekka K. , Costa Ivan G. 
Published: January 2021

ABSTRACTMotivationLigand-receptor (LR) network analysis allows the characterization of cellular crosstalk based on single cell RNA-seq data. However, current methods typically provide a list of inferred LR interactions and do not allow the researcher to focus on specific cell types, ligands or receptors. In addition, most of these methods cannot quantify changes in crosstalk between two biological phenotypes.ResultsCrossTalkeR is a framework for network analysis and visualisation of LR interactions. CrossTalkeR identifies relevant ligands, receptors and cell types contributing to changes in cell communication when contrasting two biological phenotypes, i.e. disease vs. homeostasis. A case study on scRNA-seq of human myeloproliferative neoplasms reinforces the strengths of CrossTalkeR for characterisation of changes in cellular crosstalk in disease.Availability and ImplementationCrosstalkeR is an R package available athttps://github.com/CostaLab/CrossTalkeR.
Whole-genome sequence analysis of mutations in rice plants regenerated from zygotes, mature embryos, and immature embryos
Authors: Ichikawa Masako , Kato Norio , Toda Erika , Kashihara Masakazu , Ishida Yuji , Hiei Yukoh , Isobe Sachiko N. , Shirasawa Kenta , Hirakawa Hideki , Okamoto Takashi , Komari Toshihiko 
Published: January 2021

AbstractSomaclonal variation was studied by whole-genome sequencing in rice plants (Oryza sativaL., ‘Nipponbare’) regenerated from the zygotes, mature embryos, and immature embryos of a single mother plant. The mother plant and its seed-propagated progeny were also sequenced. A total of 338 variants of the mother plant sequence were detected in the progeny, and mean values ranged from 9.0 of the seed-propagated plants to 37.4 of regenerants from mature embryos. The ratio of single nucleotide variants among the variants was 74.3%, and the natural mutation rate calculated using the variants in the seed-propagated plants was 1.2 × 10−8. The percentage and the mutation rate were consistent with the values reported previously. Plants regenerated from mature embryos had significantly more variants than different progeny types. Therefore, using zygotes and immature embryos can reduce somaclonal variation during the genetic manipulation of rice.
Transcriptome Analysis of Chloride Intracellular Channel Knockdown inDrosophilaIdentifies Oxidation-Reduction Function as Possible Mechanism of Altered Sensitivity to Ethanol Sedation
Authors: Weston Rory M. , Schmitt Rebecca E. , Grotewiel Mike , Miles Michael F. 
Published: January 2021

AbstractChloride intracellular channels (CLICs) are a unique family of evolutionarily conserved metamorphic proteins, switching between stable conformations based on redox conditions. CLICs have been implicated in a wide variety biological processes including ion channel activity, apoptosis, membrane trafficking, and enzymatic oxidoreductase activity. Understanding the molecular mechanisms by which CLICs engage in these activities is an area of active research. Here, the soleDrosophila melanogasterortholog,Clic, was targeted for RNAi knockdown to identify genes and biological processes associated withClicexpression.Clicknockdown had a substantial impact on global transcription, altering expression of over 9% of transcribedDrosophilagenes. Overrepresentation analysis of differentially expressed genes identified enrichment of 23 Gene Ontology terms including Cytoplasmic Translation, Oxidation-Reduction Process, Heme Binding, Membrane, Cell Junction, and Nucleolus. The top term, Cytoplasmic Translation, was enriched almost exclusively with downregulated genes. DrosophilaClicand vertebrate orthologClic4have previously been tied to ethanol sensitivity and ethanol-regulated expression.Clicknockdown-responsive genes from the present study were found to overlap significantly with gene sets from 4 independently published studies related to ethanol exposure and sensitivity inDrosophila. Bioinformatic analysis of genes shared between these studies revealed an enrichment of genes related to amino acid metabolism, protein processing, oxidation-reduction processes, and lipid particles among others. To determine whether the modulation of ethanol sensitivity byClicmay be related to co-regulated oxidation-reduction processes, we evaluated the effect of hyperoxia on ethanol sedation inClicknockdown flies. Consistent with previous findings,Clicknockdown reduced acute ethanol sedation sensitivity in flies housed under nomoxia. However, this effect was reversed by exposure to hyperoxia, suggesting a common set of molecular-genetic mechanism may modulate each of these processes. This study suggests thatDrosophila Clichas a major influence on regulation of oxidative stress signaling and that this function overlaps with the molecular mechanisms of acute ethanol sensitivity in the fly.
Computational analysis of GAL pathway pinpoints mechanisms underlying natural variation
Authors: Hong Jiayin , Hua Bo , Springer Michael 
Published: January 2021

AbstractQuantitative traits such as human height are measurable phenotypes that show continuous variation over a wide phenotypic range. Enormous effort has recently been put into determining the genetic influences on a variety of quantitative traits, including human genetic diseases, with mixed success. We identified a quantitative trait in a tractable model system, the GAL pathway in yeast, which controls the uptake and metabolism of the sugar galactose. GAL pathway activation depends both on galactose concentration and on the concentrations of competing, preferred sugars such as glucose. Natural yeast isolates show substantial variation in the behavior of the pathway. All studied yeast strains exhibit bimodal responses relative to external galactose concentration, i.e. a set of galactose concentrations existed at which both GAL-induced and GAL-repressed subpopulations were observed. However, these concentrations differed in different strains. We built a mechanistic model of the GAL pathway and identified parameters that are plausible candidates for capturing the phenotypic features of a set of strains including standard lab strains, natural variants, and mutants.In silicoperturbation of these parameters identified variation in the intracellular galactose sensor, Gal3p, the negative feedback node within the GAL regulatory network, Gal80p, and the hexose transporters, HXT, as the main sources of the bimodal range variation. We were able to switch the phenotype of individual yeast strainsin silicoby tuning parameters related to these three elements. Determining the basis for these behavioral differences may give insight into how the GAL pathway processes information, and into the evolution of nutrient metabolism preferences in different strains. More generally, our method of identifying the key parameters that explain phenotypic variation in this system should be generally applicable to other quantitative traits.Author summaryMicrobes adopt elaborate strategies for the preferred uptake and use of nutrients to cope with complex and fluctuating environments. As a result, yeast strains originating from different ecological niches show significant variation in the way they induce genes in the galactose metabolism (GAL) pathway in response to nutrient signals. To identify the mechanistic sources of this variation, we built a mathematical model to simulate the dynamics of the galactose metabolic regulation network, and studied how parameters with different biological implications contributed to the natural variation. We found that variations in the behavior of the galactose sensor Gal3p, the negative feedback node Gal80p, and the hexose transporters HXT were critical elements in the GAL pathway response. Tuning single parametersin silicowas sufficient to achieve phenotype switching between different yeast strains. Our computational approach should be generally useful to help pinpoint the genetic and molecular bases of natural variation in other systems.
Is Vaccination a Viable Method to Control Johne’s Disease Caused byMycobacterium aviumsubsp.paratuberculosis? Data from 12 Million Ovine Vaccinations and 7.6 Million Carcass Examinations in New South Wales, Australia from 1999-2009
Authors: Links Ian J. , Denholm Laurence J. , Evers Marilyn , Kingham Lloyd J. , Greenstein Robert J. 
Published: January 2021

AbstractBackgroundMycobacterium aviumsubsp.paratuberculosis(MAP) causes Johne’s disease (or paratuberculosis), a chronic wasting disease of ruminants and other animals resulting from granulomatous enteritis. There are increasing concerns that MAP is zoonotic. The prevalence of Johne’s disease is increasing worldwide. In an attempt to control an epidemic of ovine Johne’s disease (OJD) in New South Wales (NSW), a government/industry sponsored voluntary vaccination/on-farm management program commenced in 2000. We report herein an observational study of changes in disease prevalence as vaccination progressed, based on abattoir surveillance data for OJD from 1999 to 2009. We also discuss the epidemiological, policy, regulatory, research, economic and sociological elements that contributed to the development of a mature control program, whose aim was to halt the epidemic spread of OJD in a naïve sheep population.MethodsNSW was divided into areas of “High” (HPA), “Medium” (MPA) and “Low” (LPA) OJD prevalence. A killed whole cell vaccine (Gudair®) was administered to sheep from 2000 to 2009. Trained examiners evaluated the viscera of adult sheep carcasses at slaughter for gross evidence of OJD. MAP infection was confirmed by histopathology.Principal findingsFrom 2000-2009, 12 million vaccine doses were administered in NSW (91%; 10.9 million in the HPA). Many of the vaccinated flocks were suffering > 5% annual mortality in adult sheep, with some individual flocks with 10-15% losses attributable to OJD. A total of 7.6 million carcasses were examined (38%; 2.9 million from the HPA). Overall, 16% of slaughter consignments (sheep consigned to the abattoir from a single vendor) were positive for OJD, of which 94% were from the HPA. In the HPA, the percentage of animals with lesions attributable to OJD at slaughter fell progressively from 2.4% (10,406/432,860) at commencement of vaccination in 2000 to 0.8% (1,573/189,564) by 2009. Herd immunity from vaccination in the HPA was estimated at 70% by 2009. This coincided with a progressive decrease in reports of clinical disease and mortalities in vaccinated flocks.SignificanceWe show a decrease in the prevalence of lesions attributable to OJD in NSW concomitant with initiation of voluntary vaccination, on-farm management plans, abattoir monitoring and feedback of animal prevalence data to sheep producers. We conclude that a target of ≤ 1% regional prevalence of OJD affected sheep at slaughter is achievable using these interventions.
Stress and corticotropin releasing factor (CRF) promote necrotizing enterocolitis in a formula-fed neonatal rat model
Authors: Bell Robert L. , Withers Ginger S. , Kuypers Frans A. , Stehr Wolfgang , Bhargava Aditi 
Published: January 2021

AbstractThe etiology of necrotizing enterocolitis (NEC) is not known. Alterations in gut microbiome, mucosal barrier function, immune cell activation, and blood flow are characterized events in its development, with stress as a contributing factor. The hormone corticotropin-releasing factor (CRF) is a key mediator of stress responses and influences these aforementioned processes. CRF signaling is modulated by NEC’s main risk factors of prematurity and formula feeding. Using an established neonatal rat model of NEC, we tested hypotheses that: (i) increased CRF levels—as seen during stress—promote NEC in formula-fed newborn rats, and (ii) antagonism of CRF action ameliorates NEC. Newborn pups were formula-fed to initiate gut inflammation and randomized to: no stress, no stress with subcutaneous CRF administration, stress (acute hypoxia followed by cold exposure—NEC model), or stress after pretreatment with the CRF peptide antagonist Astressin. Dam-fed unstressed and stressed littermates served as controls. NEC incidence and severity in the terminal ileum were determined using a histologic scoring system. Changes in CRF, CRF receptor (CRFRs), and toll-like receptor 4 (TLR4) expression levels were determined by immunofluorescence and immunoblotting, respectively. Stress exposure in FF neonates resulted in 40.0% NEC incidence, whereas exogenous CRF administration resulted in 51.7% NEC incidence compared to 8.7% in FF non-stressed neonates (p<0.001). Astressin prevented development of NEC in FF-stressed neonates (7.7% vs. 40.0%; p=0.003). CRF and CRFR immunoreactivity increased in the ileum of neonates with NEC compared to dam-fed controls or FF unstressed pups. Immunoblotting confirmed increased TLR4 protein levels in FF stressed (NEC model) animals vs. controls, and Astressin treatment restored TLR4 to control levels. Peripheral CRF may serve as specific pharmacologic target for the prevention and treatment of NEC.
Ribosomal DNA revealed an extensive role of allopolyploidy in the radiation ofUlexL
Authors: Fonseca João P. , Pereira Ana , Robalo Joana I. , Neto Carlos , Costa José C. 
Published: January 2021

AbstractWe studied the phylogeny ofUlexL., a genus of spiny legumes, which its center of diversity in the Iberian Peninsula, using ribosomal DNA markers (rDNA), namely ETS, 5.8S and ITS (45S), and 5S intergenic spacer regions. One of the main findings was the presence of very different haplotypes in 5S-IGS genes and, to a less extent, in ETS and ITS, in seven polyploidtaxa.We interpreted these results as an indication of hybrid origins and proposed allopolyploidy forU. argenteusssp.subsericeus, U. australis ssp. australis, U. australisssp. welwitschianus, U. densus, U. europaeusssp.europaeus, U. europaeusssp.latebracteatus,andU. jussiaei.These results reinforce an early hypothesis which stated that the radiation ofUlexoccurred mainly by polyplodization.Phylograms showed two main clades, one grouping the hydrophilicU. gallii,U. breoganiiandU. minor, and the other grouping the southern, xerophytic,taxa. The putative allopolyploids showed haplotypes, which grouped in both clades, indicating that allopolyploidy, occurred through hybridization from these hydrophilic and xerophytic lineages.The phylogenetic position ofU. micranthusis not certain and it is discussed. The 5S-IGS showed to retain more polymorphisms than ETS gene or ITS markers. This result is compatible with the hypothesis that 5S rDNA region is less vulnerable to inter-loci concerted evolution than 45S, providing a more suitable marker for reconstructing histories of allopolyploid species. We discuss the taxonomic consequences of these results.
Ecological outcomes of hybridization vary extensively inCatostomusfishes
Authors: Mandeville Elizabeth G. , Hall Robert O. , Buerkle C. Alex 
Published: January 2021

AbstractHybridization has been studied extensively to learn about speciation and mechanisms of reproductive isolation, but increasingly we recognize that hybridization outcomes vary geo-graphically and can depend on the environment. At the same time, hybridization can reshape biotic interactions in an ecosystem, leading to ecological shifts where hybridization occurs. Identifying how hybrid individuals function ecologically would link evolutionary outcomes of hybridization to ecological consequences, but relatively few studies have focused on ecological traits of hybrids. We described the feeding ecology of severalCatostomusfish species and their hybrids by using stable isotopes (δ13C andδ15N) as a proxy for diet and habitat use, and compared two native species, an introduced species, and three interspecific hybrid crosses. We replicated this comparison spatially, including hybrids and parental species from seven rivers in the Upper Colorado River basin where parental species co-occur and the opportunity for hybridization exists. Although relationships between native species in isotopic space varied, individual native species did not fully overlap in isotopic space in any river sampled, suggesting little overlap of resource use between these historically sympatric species. The introduced species overlapped with one or both native species in every river, suggesting similar resource use and potential for competition. Hybrids occupied intermediate, matching, or more extreme (transgressive) isotopic space relative to parental species, and were isotopically variable within and among rivers. We suggest that ecological outcomes of hybridization, like genomic outcomes of hybridization, are likely to vary across locations where a pair of species hybridizes. This variation implies that hybridization might have large unpredictable, idiosyncratic ecological effects on fish assemblages where hybrids occur. Although we found little evidence that hybrids are at a disadvantage ecologically—there were no significant declines in body condition relative to parental species—it is nevertheless possible that abiotic or biotic attributes of a river might constrain the range of interspecific hybrids that are successful, thus contributing to variation in hybridization outcomes across rivers.
Regeneration of spinal motor axons: Negative regulation by Celsr2 implicating Cdc42/Rac1 and JNK/c-Jun signaling
Authors: Wen Quan , Weng Huandi , Liu Tao , Yu Lingtai , Zhao Tainyun , Qin Jingwen , Fadel Tissir , Qu Yibo , Zhou Libing 
Published: January 2021

AbstractDuring development, cadherins Celsr2 and Celsr3 control axon navigation. Unlike Celsr3, Celsr2 remains expressed in the adult, suggesting unexplored roles in maintenance and repair. Here we show thatCelsr2knockdown promotes motor axon regeneration in mouse and human spinal cord explants and cultured motor neurons.Celsr2downregulation is accompanied by increased levels of GTP-bound Rac1 and Cdc42, and of JNK and c-Jun proteins. Using a branchial plexus injury model, we show that forelimb functional recovery is improved inCelsr2mutant versus control mice. Compared to controls, in mutant mice, reinnervated biceps muscles are less atrophic, contain more newly formed neuromuscular junctions, and generate larger electromyographic potentials, while motor neuron survival and axon regeneration are improved. GTP-bound Rac1 and Cdc42, JNK and c-Jun are upregulated in injured mutant versus control spinal cord. In conclusion, Celsr2 negatively regulates motor axon regeneration via Cdc42/Rac1/JNK/c-Jun signaling and is a target for neural repair.
Two contrasting mediodorsal thalamic circuits target the medial prefrontal cortex
Authors: Lyuboslavsky Polina , Kizimenko Alena , Brumback Audrey C. 
Published: January 2021

ABSTRACTAt the heart of the prefrontal executive and limbic networks is the mediodorsal thalamus (MD). Despite the importance of MD in a broad range of behaviors and neuropsychiatric disorders, virtually nothing is known about the physiology of neurons in MD. Here, we injected the retrograde tracer cholera toxin subunit B (CTB) into the medial prefrontal cortex (mPFC) of adult (8 – 12 week old) male and female wildtype mice. We prepared acute brain slices and used current clamp electrophysiology to measure and compare the intrinsic properties of the neurons in MD that project to mPFC (MD→mPFC neurons). MD→mPFC neurons are located predominantly in the medial (MD-M) and lateral (MD-L) subnuclei of MD. We found that that MD-M→mPFC neurons have longer membrane time constants, higher membrane resistance, less Hyperpolarization and Cyclic Nucleotide gated (HCN) channel activity, and more readily generate action potentials compared to MD-L→mPFC neurons. Additionally, MD-M→mPFC neurons have larger and more complex dendritic arbors compared to MD-L→mPFC neurons. These data demonstrating that the two populations of MD→mPFC neurons have distinct physiologies and morphologies suggests a differential role in thalamocortical information processing and potentially behavior.
Low photorespiratory capacity is sufficient to block the induction of photosynthetic capacity in high light
Authors: Baker Christopher R. , Cocurrun Jean Christophe , Alonso Ana Paula , Niyogi Krishna K. 
Published: January 2021

AbstractThe induction of high photosynthetic capacity in high light (HL) is a common response among many herbaceous dicot plants, however, the signals that control this response remain largely unknown. Here, multiple independent lines of evidence are presented in support of the conclusion that low photorespiratory capacity acts a negative signal to limit photosynthetic capacity acclimation in HL inArabidopsis thaliana. Using a panel of natural accessions, primary nitrogen (N) assimilation and photorespiration rates early after a shift to growth in HL, as well as activities for key enzymes in these pathways, were shown to positively correlate with the magnitude of the subsequent induction of photosynthetic capacity, which occurred several days later. Time-resolved metabolomic data during acclimation to HL were collected using a strongly acclimating ecotype and a weakly acclimating ecotype, revealing in greater detail the differences in N assimilation, photorespiration, and triose-phosphate utilization pathways underlying efficient photosynthetic capacity acclimation. When shifted into HL growth conditions under non-photorespiratory conditions, weakly acclimating ecotypes and even photorespiratory mutants gained the ability to strongly induce high photosynthetic capacity in HL. Thus, a negative, photorespiration-dependent signal early in the HL shift appears to block photosynthetic capacity acclimation in accessions with low photorespiratory capacity, whereas accessions with high photorespiratory capacity are licensed to increase photosynthetic capacity.