bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput single-cell sequencing of multiple invertible promoters reveals a strong determinant of bacterial population heterogeneity
Authors: Lan Freeman , Saba Jason , Qian Yili , Ross Tyler , Landick Robert , Venturelli Ophelia S 
Published: November 2022

ABSTRACTPopulation heterogeneity can promote bacterial fitness in response to unpredictable environmental conditions. Human gut symbiontBacteroidesspp., displays variability in single cell surface architectures by combinatorial regulation of promoter inversions that drive expression of capsular polysaccharides (CPS). Using high-throughput single-cell sequencing, we reveal population heterogeneity generated through combinatorial promoter inversion and show thatB. fragilispopulations can access diverse CPS promoter states. Combining our data with stochastic computational modeling, we demonstrate that the rates of promoter inversion regulated by a broadly conserved serine recombinase are a major mechanism shaping population heterogeneity. Exploiting control over the expression of the recombinase, we devise a method for creating phase-locked variants and show that populations with different initial compositions converge to a similar steady-state composition over time. Our approach can be used to interrogate single-cell phase variable states of diverse microbes including bacterial pathogens.Summary sentenceHigh-throughput single cell sequencing of phase variation reveals regulation as a major driver of population diversification
Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer
Authors: Shimizu Shota , Kondo Jumpei , Onuma Kunishige , Ota Kasumi , Kamada Mayumi , Harada Yohei , Tanaka Yoshihisa , Nakazawa Mai Adachi , Tamada Yoshinori , Okuno Yasushi , Kawada Kenji , Obama Kazutaka , Coffey Robert J , Fujiwara Yoshiyuki , Inoue Masahiro 
Published: November 2022

AbstractThe bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, the effect of the BMP pathway in colorectal cancer (CRC) is controversial; it can either be tumor promoting or tumor suppressing, depending on the study. In this study, we found that CRC cells reside in a BMP-rich environment based on RNA-sequencing database analysis. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of organoids in some CRC cases. CRC organoids treated with LDN193189 exhibited a decrease in epidermal growth factor receptor, which was, at least in part, mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1). Among CRC organoid panels from 18 different patients, suppression of organoid growth by BMP inhibition correlated with the induction ofLRIG1gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, simultaneous treatment with LDN192189 and trametinib, an FDA-approved MEK inhibitor, resulted in a combination effect in bothin vivoandin vitroxenograft tumor treatment in CRC organoids, which are susceptible to growth suppression by LDN193189. Taken together, the simultaneous inhibition of BMP and MEK can be a novel treatment option in CRC cases, and evaluatingin vitrogrowth suppression andLRIG1induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders.
Photocontrolled Release of Nitric Oxide for Precise Management of NO Concentration in a Solution
Authors: Zhermolenko Egor O. , Karogodina Tatyana Yu. , Vorobev Alexey Yu. , Panfilov Mikhail A. , Moskalensky Alexander E. 
Published: November 2022

AbstractNitric oxide (NO) is a unique biochemical mediator involved in the regulation of vital processes. Its short half-life and local action impede direct application in medical practice. Light-controllable NO releasers are promising for the development of smart therapies. Here we present novel aza-BODIPY derivative containingN-nitroso moiety, which shows efficient and reversible release of NO under red light. Using this molecule, we demonstrate a system for precise management of NO concentration in aqueous solutionin vitrousing the feedback loop with optical control. Our results could serve as the basis for the development of novel therapeutic methods.
HISS: Snakemake-based workflows for performing SMRT-RenSeq assembly, AgRenSeq and dRenSeq for the discovery of novel plant disease resistance genes
Authors: Adams Thomas M , Smith Moray , Wang Yuhan , Brown Lynn H , Bayer Micha M , Hein Ingo 
Published: November 2022

AbstractBackgroundIn the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of ak-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise.ResultsHere we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license.ConclusionsHISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses.
A generalizable epigenetic clock captures aging in two nonhuman primates
Authors: Goldman Elisabeth A. , Chiou Kenneth L. , Watowich Marina M. , Mercer Arianne , Sams Sierra N. , Horvath Julie E. , Anderson Jordan A. ,   Cayo Biobank Research Unit, Tung Jenny , Higham James P. , Brent Lauren J.N. , Martínez Melween I. , Montague Michael J. , Platt Michael L. , Sterner Kirstin N. , Snyder-Mackler Noah 
Published: November 2022

ABSTRACTEpigenetic clocks generated from DNA methylation array data provide important insights into biological aging, disease susceptibility, and mortality risk. However, these clocks cannot be applied to high-throughput, sequence-based datasets more commonly used to study nonhuman animals. Here, we built a generalizable epigenetic clock using genome-wide DNA methylation data from 493 free-ranging rhesus macaques. Using a sliding-window approach that maximizes generalizability across datasets and species, this model predicted age with high accuracy (± 1.42 years) in held-out test samples, as well as in two independent test sets: rhesus macaques from a captive population (n=43) and wild baboons in Kenya (n=271). Our model can also be used to generate insight into the factors hypothesized to alter epigenetic aging, including social status and exposure to traumatic events. Our results thus provide a flexible tool for predicting age in other populations and species and illustrate how connecting behavioral data with the epigenetic clock can uncover social influences on biological age.
Accurate identification of de novo genes in plant genomes using machine learning algorithms
Authors: Casola Claudio , Owoyemi Adekola , Pepper Alan E. , Ioerger Thomas R. 
Published: November 2022

AbstractDe novo gene birth—the evolution of new protein-coding genes from ancestrally noncoding DNA—is increasingly appreciated as an important source of genetic and phenotypic innovation. However, the frequency and overall biological impact of de novo genes (DNGs) remain controversial. Large-scale surveys of de novo genes are critical to address these issues, but DNG identification represents a persistent challenge due to the lack of standardized protocols and the laborious analyses traditionally used to detect DNGs. Here, we introduced novel approaches to identify de novo genes that rely on Machine Learning Algorithms (MLAs) and are poised to accelerate DNG discovery. We specifically investigated if MLAs developed in one species using known DNGs can accurately predict de novo genes in other genomes. To maximize the applicability of these methods across species, we relied only on DNA and protein sequence features that can be easily obtained from annotation data. Using hundreds of published and newly annotated DNGs from three angiosperms, we trained and tested both Decision Tree (DT) and Neural Network (NN) algorithms. Both MLAs showed high levels of accuracy and recall within-genomes. Although accuracies and recall decreased in cross-species analyses, they remained elevated between evolutionary closely related species. A few training features, including presence of a protein domain and coding probability, held most of the MLAs predictive power. In analyses of all genes from a genome, recall was still elevated. Although false positive rates were relatively high, MLA screenings of whole-genome datasets reduced by up to ten-fold the number of genes to be examined by conventional comparative genomic methods. Thus, a combination of MLAs and traditional strategies can significantly accelerate the accurate discovery of DNG and the annotation in angiosperm genomes.
Exploring how ecological and epidemiological processes shape multi-host disease dynamics using global sensitivity analysis
Authors: Arachchilage Kalpana Hanthanan , Hussaini Mohammed Y. , Cogan N. G. , Cortez Michael H. 
Published: November 2022

AbstractWe use global sensitivity analysis (specifically, Partial Rank Correlation Coefficients) to explore the roles of ecological and epidemiological processes in shaping the temporal dynamics of a parameterized SIR-type model of two host species and an environmentally transmitted pathogen. We compute the sensitivities of disease prevalence in each host species to model parameters. Sensitivity rankings and subsequent biological interpretations are calculated and contrasted for cases were the pathogen is introduced into a disease-free community and where a second host species is introduced into an endemic single-host community. In some cases the magnitudes and dynamics of the sensitivities can be predicted only by knowing the host species characteristics (i.e., their competitive abilities and disease competence) whereas in other cases they can be predicted by factors independent of the species characteristics (specifically, intraspecific versus interspecific processes or the species’ roles of invader versus resident). For example, when a pathogen is initially introduced into a disease-free community, disease prevalence in both hosts is more sensitive to the burst size of the first host than the second host. In comparison, disease prevalence in each host is more sensitive to its own infection rate than the infection rate of the other host species. In total, this study illustrates that global sensitivity analysis can provide useful insight into how ecological and epidemiological processes shape disease dynamics and how those effects vary across time and system conditions. Our results show that sensitivity analysis can provide quantification and direction when exploring biological hypotheses.
Tomato geranylgeranyl diphosphate synthase isoform 1 specifically interacts with phytoene synthase isoform 3 to produce strigolactones in tomato roots
Authors: Ezquerro Miguel , Li Changsheng , Barja M. Victoria , Burbano-Erazo Esteban , Pérez-Pérez Julia , Wang Yanting , Dong Lemeng , Lisón Purificación , López-Gresa M. Pilar , Bouwmeester Harro J. , Rodríguez-Concepción Manuel 
Published: November 2022

SummaryCarotenoids are photoprotectant pigments and precursors of the hormones abscisic acid (ABA) and strigolactones (SL). Carotenoids are produced in plastids from geranylgeranyl diphosphate (GGPP), which is diverted to the carotenoid pathway by phytoene synthase (PSY). In tomato (Solanum lycopersicum), 3 genes encode plastid-targeted GGPP synthases (SlG1 to 3) and 3 genes encode PSY isoforms (PSY1 to 3).Here we investigated the function of SlG1 by generating loss-of-function lines and combining their metabolic and physiological phenotypes with gene co-expression and co-immunoprecipitation analyses.Leaves and fruits ofslg1lines showed a wild-type phenotype in terms of isoprenoid accumulation, photosynthesis and development. Consistently,SlG1is co-expressed withPSY3and other genes involved in the production of carotenoids and SL (but not ABA) only in roots. SlG1 was also found to physically interact with the root-specific PSY3 isoform (and not with PSY1 and PSY2). Root SL (but not ABA) levels were reduced inslg1lines.Our results confirm a specific role of SlG1 in SL production in combination with PSY3. This role appears to be restricted to roots asslg1plants do not exhibit the shoot phenotype displayed by other SL-deficient mutants.
Endoplasmic reticulum calnexins participate in the primary root growth response to phosphate deficiency
Authors: Montpetit Jonatan , Clúa Joaquín , Hsieh Yi-Fang , Vogiatzaki Evangelia , Müller Jens , Abel Steffen , Strasser Richard , Poirier Yves 
Published: November 2022

AbstractAccumulation of incompletely folded proteins in the endoplasmic reticulum (ER) leads to ER stress, activates ER protein degradation pathways, and upregulates genes involved in protein folding (Unfolded Protein Response; UPR). ER stress has been associated with abiotic stress conditions that affect protein folding, including salt stress. However, the role of ER protein folding in plant responses to nutrient deficiencies is unclear. We analyzed severalArabidopsis thalianamutants affected in ER protein quality control and established that bothCALNEXIN(CNX) genes function in the primary root’s response to phosphate (Pi) deficiency. CNX and calreticulin (CRT) are homologous ER lectins that bind to N-glycosylated proteins to promote their folding. Growth ofcnx1-1andcnx2-2single mutants was similar to that of the wild type under high and low Pi conditions, but thecnx1-1 cnx2-2double mutant showed decreased primary root growth under low Pi conditions due to reduced meristematic cell division. This phenotype was specific to Pi deficiency; the double mutant responded normally to osmotic and salt stress. The root growth phenotype was Fe dependent and was associated with Fe accumulation in the root. Two genes involved in Fe-dependent inhibition of root growth under Pi deficiency, the ferroxidase geneLPR1and P5-type ATPasePDR2, are epistatic toCNX1/CNX2. OverexpressingPDR2failed to complement thecnx1-1 cnx2-2root phenotype.cnx1-1 cnx2-2showed no evidence of UPR activation, indicating a limited effect on ER protein folding. CNX might process a set of N-glycosylated proteins specifically involved in the response to Pi deficiency.One sentence summaryCalnexin, a lectin chaperone engaged in the folding of N-glycosylated proteins in the ER, participates in primary root adaptation to low phosphate conditions.
A land plant specific VPS13 mediates polarized vesicle trafficking in germinating pollen
Authors: Tangpranomkorn Surachat , Igarashi Motoko , Ishizuna Fumiko , Kato Yoshinobu , Suzuki Takamasa , Fujii Sota , Takayama Seiji 
Published: November 2022

ABSTRACTPollen has an extraordinary ability to convert from a dry state to an extremely rapidly growing state. During pollination, pollen receives water and Ca2+from the contacting pistil, which will be a directional cue for pollen tube germination. The subsequent rapid activation of directional vesicular transport must support the pollen tube growth, but the molecular mechanism leading to this process is largely unknown. Here we show that a plant-specific VPS13, AtVPS13a, mediates vesicle trafficking during the polarization process inArabidopsispollen.AtVPS13aknockout severely affected pollen germination and lipid droplet discharge, while Ca2+-dynamics after pollination was unchanged. Cellular distribution patterns of AtVPS13a and a secretory vesicle marker were synchronized, with a slight delay to the Ca2+-dynamics in polarizing pollen. The absence of AtVPS13a led to reduced cell wall deposition during pollen germination. These results suggest that AtVPS13a mediates pollen polarization, by regulating proper directional vesicular transport following Ca2+-signaling.
MORC proteins regulate transcription factor binding by mediating chromatin compaction in active chromatin regions
Authors: Zhong Zhenhui , Xue Yan , Harris C. Jake , Wang Ming , Li Zheng , Ke Yunqing , Jami-Alahmadi Yasaman , Feng Suhua , Wohlschlegel James A. , Jacobsen Steven E. 
Published: November 2022

AbstractBackgroundThe Microrchidia (MORC) proteins are a family of evolutionarily conserved GHKL-type ATPases involved in chromatin compaction and gene silencing. Arabidopsis MORC proteins act in the RNA-directed DNA methylation (RdDM) pathway, where they act as molecular tethers to ensure the efficient establishment of RdDM andde novogene silencing. However, MORC proteins also have RdDM-independent functions; although, their underlying mechanisms are unknown.ResultsIn this study, we examined regions of MORC binding where RdDM does not occur in order to shed light on the RdDM-independent functions of MORC proteins. We found that MORC proteins compact chromatin and reduce DNA accessibility to transcription factors (TFs), thereby repressing gene expression. We also found that MORC-mediated repression of gene expression was particularly important under conditions of stress. We showed that MORC proteins regulate TFs through either direct or indirect interactions, and these TFs can in some cases regulate their own transcription, resulting in feedforward loops.ConclusionsOur findings provide insights into the molecular mechanisms of MORC-mediated chromatin compaction and transcription regulation.
Transcriptome profiles of eggplant (Solanum melongena) and its wild relativeS. dasyphyllumunder different levels of osmotic stress provide insights into response mechanisms to drought
Authors: Villanueva Gloria , Vilanova Santiago , Plazas Mariola , Prohens Jaime , Gramazio Pietro 
Published: November 2022

AbstractDefence mechanisms to abiotic stresses, like drought, are very broad and RNA sequencing (RNA-Seq) can help in understanding the complex responses triggered. In this study, we performed RNA-Seq of the transcriptomes of eggplant (Solanum melongena) and its related wild species (S. dasyphyllum) under two PEG concentrations (20% and 30%), two different times (after 0.5 h and 2 h of osmotic stress) and at two plant phenological stages (three and five true fully developed leaves).Solanum dasyphyllumwas more tolerant to osmotic stress, and a differential expression pattern of drought-related genes was identified between the two species. Plants subjected to a higher osmotic potential, at a more adult stage and at a higher stress exposure time displayed a higher number of DEGs (differential expressed genes). Gene ontology (GO) enrichment analysis revealed that, compared toS. melongena, S. dasyphyllumtriggered the regulation of a wide range of transcription factors (AP2/ERF, DREB, bZIP, WRKY and bHLH). In both species, the abscisic acid (ABA) signaling response pathway played a crucial role leading to stomatal closure. Other important pathways involved in abiotic stresses tolerance including flavonoid, carotenoid and phenylpropanoid biosynthesis, chlorophyll metabolism and photosynthesis pathway among others were found to have a relevant role under both moderate and severe osmotic stresses. Our results reveal thatS. dasyphyllumis a potential source of genes for breeding resilient eggplant varieties.
Metals and metal isotopes in insect wings: Implications for diet, geolocation and pollution exposure
Authors: Reich Megan S. , Kindra Mira , Dargent Felipe , Hu Lihai , Tyler Flockhart D.T. , Norris D. Ryan , Kharouba Heather , Talavera Gerard , Bataille Clément P. 
Published: November 2022

AbstractAnthropogenic activities are exposing insects to abnormal levels of toxic metals, with unknown implications for migratory insects. Simultaneously, metals and metal isotopes have become promising tools for the geolocation of migratory insects. Furthering our understanding of metal cycling in insect tissues is essential, both for the development of metals and metal isotopes as geolocation tools, and for assessing the toxicity risks of metals to insects. We conducted a diet-switching experiment on monarch butterflies (Danaus plexippus) with controlled larval and adult diets to evaluate the dietary and environmental sources of 23 metals and metalloids, strontium isotopes, and lead isotopes to insect wing tissues over a period of 8 weeks. Concentrations of Ca, Co, and Sb differed between the sexes. Ni and Zn bioaccumulated in the insect wing tissues over time, likely from the adult diet, while increases in Al, Cr, Cd, Cu, Fe, and Pb were likely from external sources (i.e., dust aerosols). Bioaccumulation of Pb in the monarch wings was confirmed by Pb isotopes to be from external anthropogenic sources, revealing the potential of Pb isotopes to become an indicator and tracer of metal pollution exposure along migratory paths. Concentrations of Ba, Cs, Mg, Na, Rb, Sr, Ti, Tl, and U appeared to be unaffected by dietary or environmental contamination and should be further developed for geolocation purposes. Strontium isotope ratios remained indicative of the larval diet, at least in males, supporting its potential as a geolocation tool. However, the difference in strontium isotope ratios between sexes, as well as the possibility of external contamination by wetting, requires further investigation. Our results demonstrate the complexity of metal cycling in insects and the need for further investigations, as well as the value of studying metals to develop new tools to quantify pollution exposure, metal toxicity and insect mobility.