bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-serine induces distinct transcriptomes in diverse Escherichia coli pathotypes
Authors: Connolly James P. R. , Turner Natasha C. A. , Hallam Jennifer C. , Rimbi Patricia T. , Flett Tom , McCormack Mhairi J. , Roe Andrew J. , O’Boyle Nicky 
Published: May 2021

AbstractAppropriate interpretation of environmental signals facilitates niche specificity in pathogenic bacteria. However, the responses of niche-specific pathogens to common host signals are poorly understood. D-serine (D-ser) is a toxic metabolite present in highly variable concentrations at different colonisation sites within the human host that we previously found is capable of inducing changes in gene expression. In this study, we made the striking observation that the global transcriptional response of three Escherichia coli pathotypes - enterohaemorrhagic E. coli (EHEC), uropathogenic E. coli (UPEC) and neonatal meningitis associated E. coli (NMEC) - to D-ser was highly distinct. In fact, we identified no single differentially expressed gene common to all three strains. We observed the induction of ribosome-associated genes in extraintestinal pathogens UPEC and NMEC only, and the induction of purine metabolism genes in gut-restricted EHEC and UPEC indicating distinct transcriptional responses to a common signal. UPEC and NMEC encode dsdCXA – a genetic locus required for the detoxification and hence normal growth in the presence of D-ser. Specific transcriptional responses were induced in strains accumulating D-ser (WT EHEC and UPEC/NMEC mutants lacking the D-ser-responsive transcriptional activator DsdC), corroborating the notion that D-ser is an unfavourable metabolite if not metabolized. Importantly, many of the UPEC-associated transcriptome alterations correlate with published data on the urinary transcriptome, supporting the hypothesis that D-ser sensing forms a key part of urinary niche adaptation in this pathotype. Collectively, our results demonstrate distinct pleiotropic responses to a common metabolite in diverse E. coli pathotypes, with important implications for niche selectivity.ImportanceThe pathogenic Escherichia coli comprise a group of highly specialized bacteria, some of which are capable of disseminating from the intestine and causing disease at other sites within the human host. Chemicals (metabolites) derived from the host and other microorganisms shape the behaviour of E. coli in different environments. Here we investigate the changes in gene expression that occur in E. coli strains capable (UPEC and NMEC) and incapable (EHEC) of metabolizing D-ser – a metabolite specifically enriched in the urine and in regions of the brain. We show that EHEC, UPEC and NMEC – distinct pathotypes associated with disease in the gut, bladder and brain, respectively, respond in a distinct manner to D-ser. Many of the genes affected by D-ser have been shown to be important during disease, highlighting the importance of varied responses to this common signal in host infection.
Development of an STR panel for a non-native population of an endangered species
Authors: Hill Erin , Linacre Adrian , Toop Simon , Murphy Nicholas , Strugnell Jan 
Published: May 2021

AbstractThe establishment of non-native populations of threatened and legally protected species can have many implications for the areas where these species have been introduced. Non-native populations of threatened species have the potential to be exploited and therefore the subject of legal protection, while conversely, if they have become invasive in their introduced range, there is the likelihood that population control will be carried out to reduce abundance and negative impacts associated with introduced species. From both a legal and invasive species monitoring standpoint, it is important to know how many individuals are present. Short tandem repeats (STRs) were developed for the hog deer, an endangered species that was introduced following European settlement to Victoria, Australia using Illumina MiSeq sequencing technology. These markers were combined with previous STRs characterised for hog deer to create a 29-plex identification system. A total of 224 samples were genotyped across the population in Victoria, and further analyses of null allele frequencies, deviation from Hardy-Weinberg equilibrium, and the removal of monomorphic or low amplifying markers resulted in a final marker panel of 17 loci. Despite low values for number of alleles at each locus (2-4), probability of identity showed sufficient discrimination power, with an average probability of identity at 9.46 × 10−7, and a probability of sibling identity of 7.67 × 10−4 across all sites. These findings show that it is feasible to create an informative DNA profiling system that can distinguish between individuals for applications in both wildlife forensic and population control research.
Transcriptomic profiling of human orbital fat and differentiating orbital fibroblasts
Authors: Kim Dong Won , Taneja Kamil , Hoang Thanh , Santiago Clayton P. , McCulley Timothy J. , Merbs Shannath L. , Mahoney Nicholas R. , Blackshaw Seth , Rajaii Fatemeh 
Published: May 2021

Structured AbstractPurposeOrbital fat hyperplasia has a central role in the manifestations of thyroid-associated orbitopathy (TAO). To better understand the pathways involved in adipogenesis in TAO, we have used transcriptomic methods to analyze gene expression in control and TAO patients, as well as in differentiating orbital fibroblasts (OFs).MethodsWe performed bulk RNA sequencing (RNA-Seq) on intraconal orbital fat to compare gene expression in control and TAO patients. We treated cultured OFs derived from TAO patients with media containing dexamethasone, insulin, rosiglitazone, and isobutylmethylxanthine (IBMX) to induce adipogenesis. We used single nuclear RNA-Seq (snRNA-Seq) profiling of treated OFs to compare gene expression over time in order to identify pathways that are involved in orbital adipogenesis in vitro and compared the dynamic patterns of gene expression identify differences in gene expression in control and TAO orbital fat.ResultsOrbital fat from TAO and control patients segregate with principal component analysis (PCA). Numerous signaling pathways are enriched in orbital fat isolated from TAO patients. SnRNA-Seq of orbital fibroblasts undergoing adipogenesis reveals differential expression of adipocyte-specific genes over the developmental time course. Furthermore, genes that are enriched in TAO orbital fat are also upregulated in orbital adipocytes that differentiate in vitro, while genes that are enriched in control orbital fat are enriched in orbital fibroblasts prior to differentiation.ConclusionsDifferentiating orbital fibroblasts serve as a model to study orbital fat hyperplasia seen in TAO. We demonstrate that the insulin-like growth factor-1 receptor (IGF-1R) and Wnt signaling pathways are differentially expressed early in orbital adipogenesis.PrécisTo understand the pathways involved in adipogenesis in TAO, we used transcriptomic methods to analyze gene expression in control and TAO patients, as well as in differentiating OFs. We demonstrate that the IGF-1R and Wnt signaling pathways are differentially expressed during orbital adipogenesis.
New cellular models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor
Authors: Bhalla Angela D. , Landers Sharon M. , Singh Anand K. , Yeagley Michelle G. , Meyerson Gabryella S.B. , Mulder Zachary A. , Delgado-Baez Cristian B. , Dunnand Stephanie , Kochat Veena , Tomczak Katarzyna J. , Nguyen Theresa , Ma Xiaoyan , Bolshakov Svetlana , Menegaz Brian A. , Lamhamedi-Cherradi Salah-Eddine , Ludwig Joseph A. , Beird Hannah C. , Mao Xizeng , Song Xingzhi , Ingram Davis R. , Wang Wei-Lien , Lazar Alexander J. , McCutcheon Ian E. , Slopis John M. , Rai Kunal , Zhang Jianhua , Lev Dina C. , Torres Keila E. 
Published: May 2021

AbstractUndifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models led us to generate additional cell lines to study these rare cancers further. Patient-derived tumors were used to establish 5 new UPS models, including one radiation-associated UPS—UPS060.1, UPS271.1, UPS511, UPS0103, and RIS620—and 3 new models of MPNST—MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of each cell line was determined by either subcutaneous injection of cells or implantation of tumor tissue into immunocompromised mice. UPS060.1, UPS271.1, and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Mutation analysis of a panel of genes frequently mutated in sarcomas showed that two of the three MPNST cell lines had NF1 mutations. Two of the three MPNST cell lines had mutations in polycomb repressive complex 2 members. These new cellular models provide the scientific community with powerful tools for detailed studies of sarcomagenesis and investigate novel therapies for UPS and MPNST.
Illuminating the plant rhabdovirus landscape through metatranscriptomics data
Authors: Bejerman Nicolás , Dietzgen Ralf G. , Debat Humberto 
Published: May 2021

AbstractRhabdoviruses infect a large number of plant species and cause significant crop diseases. They have a negative-sense, single-stranded unsegmented or bisegmented RNA genome. The number of plant-associated rhabdovirid sequences has grown in the last few years in concert with the extensive use of high-throughput sequencing platforms. Here, we report the discovery of 27 novel rhabdovirus genomes associated with 25 different host plant species and one insect, which were hidden in public databases. These viral sequences were identified through homology searches in more than 3000 plant and insect transcriptomes from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) using known plant rhabdovirus sequences as the query. The identification, assembly and curation of raw SRA reads resulted in sixteen viral genome sequences with full-length coding regions and ten partial genomes. Highlights of the obtained sequences include viruses with unique and novel genome organizations among known plant rhabdoviruses. Phylogenetic analysis showed that thirteen of the novel viruses were related to cytorhabdoviruses, one to alphanucleorhabdoviruses, five to betanucleorhabdoviruses, one to dichorhaviruses and seven to varicosaviruses. These findings resulted in the most complete phylogeny of plant rhabdoviruses to date and shed new light on the phylogenetic relationships and evolutionary landscape of this group of plant viruses. Furthermore, this study provided additional evidence for the complexity and diversity of plant rhabdovirus genomes and demonstrated that analyzing SRA public data provides an invaluable tool to accelerate virus discovery, gain evolutionary insights and refine virus taxonomy.
A single short reprogramming early in life improves fitness and increases lifespan in old age
Authors: Alle Quentin , Le Borgne Enora , Bensadoun Paul , Lemey Camille , Béchir Nelly , Gabanou Mélissa , Estermann Fanny , Bertrand-Gaday Christelle , Pessemesse Laurence , Toupet Karine , Vialaret Jérôme , Hirtz Christophe , Noël Danièle , Jorgensen Christian , Casas François , Milhavet Ollivier , Lemaitre Jean-Marc 
Published: May 2021

AbstractForced and maintained expression of four transcription factors OCT4, SOX2, KLF4 and c-MYC (OSKM), can reprogram somatic cells into induced Pluripotent Stem Cells (iPSCs) and a limited OSKM induction is able to rejuvenate the cell physiology without changing the cell identity. We therefore sought to determine if a burst of OSKM might improve tissue fitness and delay age-related pathologies in a whole animal. For this, we used a sensitive model of heterozygous premature aging mice carrying just one mutated Lamin A allele producing progerin. We briefly treated two months-young heterozygotes mice with OSKM and monitored their natural age-related deterioration by various health parameters. Surprisingly, a single two and a half weeks reprogramming was sufficient to improve body composition and functional capacities, over the entire lifespan. Mice treated early in life had improved tissue structures in bone, lung, spleen, kidney and skin, with an increased lifespan of 15%, associated to a differential DNA methylation signature. Altogether, our results indicate that a single short reprogramming early in life might initiate and propagate an epigenetically related rejuvenated cell physiology, to promote a healthy lifespan.One Sentence summaryA single short reprogramming early in life rejuvenates cell physiology, improves body composition, tissue fitness and increases lifespan in elderly.
Do soil features condition seed germination of gypsum plants? An analysis of the effect of different natural soils
Authors: Heiden Nathaniel , Cera Andreu , Palacio Sara 
Published: May 2021

AbstractGypseous soils are widespread across arid and semiarid environments worldwide. They present remarkable challenges to plants and host a unique flora. We aimed to assess up to what point the specificity and distribution of species on gypsum might be driven by species-specific germination responses to soil gypsum availability. We analyzed the germination of six gypsum specialists and four closely related generalist plant species from the Iberian Peninsula and the Chihuahuan Desert in four different field soils with contrasting concentrations of gypsum, pH and soil texture. Plant restriction to gypsum was unrelated to the germinating ability of seeds on different substrates. Irrespective of their affinity for gypsum, most species germinated better on mixed gypsum-calcareous soil and worse in the acidic soil treatment. Our data suggest soil pH was the main soil feature driving seed germination, while the effect of gypsum content was generally not significant. The main exception was the Iberian gypsum specialist Helianthemum squamatum (L.) Dum. Cours., which showed increased germination on gypseous soils and higher germination in response to increased soil gypsum content. Except for this species, our findings indicate alkaline soils favor the germination of most of the species analyzed, irrespectively of their gypsum content.HighlightsGypsum soils are one of the most widespread special substrates of the worldWe evaluated the effects of natural soils on the germination of gypsum plantsSoil pH was the main soil feature driving seed germinationThe effect of gypsum content was not significantWe suggest a potential origin of gypsophiles from plants adapted to alkaline soils
Stomatal CO2-responses at sub- and above-ambient CO2levels employ different pathways in Arabidopsis
Authors: Koolmeister Kaspar , Merilo Ebe , Hõrak Hanna , Kollist Hannes 
Published: May 2021

AbstractStomatal pores that control plant CO2uptake and water loss affect global carbon and water cycles. In the era of increasing atmospheric CO2levels and vapor pressure deficit (VPD), it is essential to understand how these stimuli affect stomatal behavior. It is unknown whether stomatal responses to sub-ambient and above-ambient CO2levels are governed by the same regulators and whether these responses depend on VPD. We studied stomatal conductance responses in Arabidopsis stomatal signaling mutants under conditions where CO2levels were either increased from sub-ambient to ambient (400 ppm) or from ambient to above-ambient levels under normal or elevated VPD. We found that guard cell signaling components involved in CO2-induced stomatal closure have different roles in the sub-ambient and above-ambient CO2levels. The CO2-specific regulators prominently affected sub-ambient CO2responses, whereas the lack of guard cell slow-type anion channel SLAC1 more strongly affected the speed of above-ambient CO2-induced stomatal closure. Elevated VPD caused lower stomatal conductance in all and faster CO2-responsiveness in some studied genotypes and CO2-transitions. Our results highlight the importance of experimental set-ups in interpreting stomatal CO2- responsiveness, as stomatal movements under different CO2concentration ranges are controlled by distinct mechanisms. Sometimes elevated CO2and VPD responses also interact. Hence, multi-factor treatments are needed to understand plant behavior under future climate conditions.
Partial response electromyography as a marker of action stopping
Authors: Raud Liisa , Thunberg Christina , Huster René J. 
Published: May 2021

AbstractResponse inhibition is among the core constructs of cognitive control. It is notoriously difficult to quantify from overt behavior, since the outcome of successful inhibition is the lack of a behavioral response. Currently, the most common measure of action stopping, and by proxy response inhibition, is the model-based stop signal reaction time (SSRT) derived from the stop signal task. Recently, partial response electromyography (prEMG) has been introduced as a complementary physiological measure to capture individual stopping latencies. PrEMG refers to muscle activity initiated by the go signal that plummets after the stop signal before its accumulation to a full response. Whereas neither the SSRT nor the prEMG is an unambiguous marker for neural processes underlying response inhibition, our analysis indicates that the prEMG peak latency is better suited to investigate brain mechanisms of action stopping. This study is a methodological resource with a comprehensive overview of the psychometric properties of the prEMG in a stop signal task, and further provides practical tips for data collection and analysis.
Lack of food intake during shift work alters the heart transcriptome and leads to cardiac fibrosis and inflammation in rats
Authors: Trott Alexandra J. , Greenwell Ben J , Karhadkar Tejas R. , Guerrero-Vargas Natali N. , Escobar Carolina , Buijs Ruud M , Menet Jerome S 
Published: May 2021

AbstractMany epidemiological studies revealed that shift work is associated with increased risk of cardiovascular diseases. However, the underlying mechanisms remain poorly understood. An experimental model of shift work in rats has been shown to recapitulate the metabolic disorders observed in human shift workers, and used to demonstrate that restricting food consumption outside working hours prevents shift work-associated obesity and metabolic disturbance. Here we used this model to characterize the effects of shift work in the heart. We show that experimental shift work reprograms the heart cycling transcriptome independently of food consumption. While phases of rhythmic gene expression are distributed across the 24-hour day in control rats, they are clustered towards discrete times in shift workers. Additionally, preventing food intake during shift work affects the expression level of hundreds of genes in the heart. Many of them are found in transcriptional signatures associated with pressure overload and cardiac hypertrophy, and encode for components of the extracellular matrix and inflammatory markers. Consistent with this, the heart of shift worker rats not eating during work exhibits fibrosis and is colonized by immune cells. While maintaining food access during shift work has less effects on gene expression, genes found in transcriptional signatures of cardiac hypertrophy remain affected, and the heart of shift worker rats exhibits fibrosis without inflammation. Together, our findings provide insights into how shift work affects cardiac function, and suggest that some interventions aiming at mitigating metabolic disorders in shift workers may have adverse effects on cardiovascular diseases.
Scalable mapping of myelin and neuron density in the human brain with micrometer resolution
Authors: Chang Shuaibin , Varadarajan Divya , Yang Jiarui , Chen Ichun Anderson , Kura Sreekanth , Magnain Caroline , Augustinack Jean C. , Fischl Bruce , Greve Douglas N. , Boas David A. , Wang Hui 
Published: May 2021

AbstractOptical Coherence Tomography (OCT) is an emerging 3D imaging technique that allows quantification of intrinsic optical properties such as scattering coefficient and back-scattering coefficient, and has proved useful in distinguishing delicate microstructures in the human brain. The origins of scattering in brain tissues are contributed by the myelin content, neuron size and density primarily; however, no quantitative relationships between them have been reported, which hampers the use of OCT in fundamental studies of architectonic areas in the human brain and the pathological evaluations of diseases. To date, histology remains the golden standard, which is prone to errors and can only work on a small number of subjects. Here, we demonstrate a novel method that uses serial sectioning OCT to quantitatively measure myelin content and neuron density in the human brain. We found that the scattering coefficient possesses a strong linear relationship with the myelin content across different regions of the human brain, while the neuron density serves as a secondary contribution that only slightly modulates the overall tissue scattering.
Scale-dependent tipping points of bacterial colonization resistance
Authors: Karita Yuya , Limmer David T. , Hallatschek Oskar 
Published: May 2021

ABSTRACTBacteria are efficient colonizers of a wide range of secluded micro-habitats, such as soil pores, skin follicles, or intestinal crypts. How the structural diversity of these habitats modulates microbial self-organization remains poorly understood, in part because of the challenge to specifically manipulate the physical structure of microbial environments. Using a microfluidic device to grow bacteria in crypt-like incubation chambers of systematically varied lengths, we show that small variations in the physical structure of the micro-habitat can drastically alter bacterial colonization success and resistance against invaders. Small crypts are un-colonizable, intermediately sized crypts can stably support dilute populations, while beyond a second critical lengthscale, populations phase-separate into a dilute and a jammed region. The jammed state is characterized by extreme colonization resistance, even if the resident strain is suppressed by an antibiotic. Combined with a flexible biophysical model, we demonstrate that colonization resistance and associated priority effects can be explained by a crowding-induced phase transition, which results from a competition between proliferation and density-dependent cell leakage. The emerging sensitivity to scale underscores the need to control for scale in microbial ecology experiments. Systematic flow-adjustable lengthscale variations may serve as a promising strategy to elucidate further scale-sensitive tipping points and to rationally modulate the stability and resilience of microbial colonizers.