bluuebunny/crossref_metadata_2025_split huggingface dataset:
A long non-coding RNA in the let-7 complex acting as a potent and specific death effector of cancer cells
Authors: Birbaumer Tosca , Schlumpf Tommy Beat , Seimiya Makiko , Jiang Yanrui , Paro Renato 
Published: July 2021

AbstractThe let-7 complex in Drosophila encodes three evolutionarily conserved microRNAs: miR-100, let-7, and miR-125. These act as heterochronic genes in regulating developmental timing in response to the steroid hormone ecdysone and play important roles in cell differentiation. Here we identify two additional long non-coding RNAs in the let-7 complex, we named let-A and let-B. Both are transcribed in the large first intron of the primary RNA encoding the microRNAs. We show these RNAs to be sequentially expressed in early pupal stages in response to ecdysone signaling, albeit exhibiting a different expression pattern compared to the microRNA let-7. Surprisingly, ectopic expression of let-A in Drosophila cancer cells induces rapid cell death. Dead cells further release RNA molecules in the medium that is becoming toxic to other cancer cells. In vivo grown tumors lose their tumorigenicity after being incubated in the let-A induced medium. Moreover, feeding flies carrying transplanted tumor cells with such induced medium leads to reduced growth of tumors in a subset of hosts. Our results uncover a new lncRNA which can act as a potent and specific cell death effector for Drosophila tumor cells.
Long-term ecosystem nitrogen limitation from foliar δ15N data and a land surface model
Authors: Caldararu Silvia , Thum Tea , Yu Lin , Kern Melanie , Nair Richard , Zaehle Sönke 
Published: July 2021

AbstractThe effect of nutrient availability on plant growth and the terrestrial carbon sink under climate change and elevated CO2 remains one of the main uncertainties of the terrestrial carbon cycle. This is partially due to the difficulty of assessing nutrient limitation at large scales over long periods of time. Consistent declines in leaf nitrogen (N) content and leaf δ15N have been used to suggest that nitrogen limitation has increased in recent decades, most likely due to the concurrent increase in atmospheric CO2. However, such datasets are often not straightforward to interpret due to the complex factors that contribute to the spatial and temporal variation in leaf N and isotope concentration. We use the land surface model QUINCY, which has the unique capacity to represent N isotopic processes, in conjunction with two large datasets of foliar N and N isotope content. We run the model with different scenarios to test whether foliar δ15N isotopic data can be used to infer large scale nitrogen limitation and if the observed trends are caused by increasing atmospheric CO2, changes in climate or changes in sources of anthropogenic N deposition. We show that while the model can capture the observed change in leaf N content and predicts widespread increases in N limitation, it does not capture the pronounced, but very spatially heterogeneous, decrease in foliar δ15N observed in the data across the globe. The addition of an observed temporal trend in isotopic composition of N deposition leads to a more pronounced decrease in simulated leaf δ15N. Our results show that leaf δ15N observations should not, on their own, be used to assess global scale N limitation and that using such a dataset in conjunction with a land surface model can reveal the drivers behind the observed patterns.
Gut regulatory T cells mediate immunological tolerance inSalmonella-infected superspreader hosts by suppressing cytotoxic activity of T cells
Authors: Massis LM , Ruddle S , Brewer SM , Schade R , Narasimhan R , Honeycutt JD , Pham THM , McKenna JA , Brubaker SW , Chairatana P , Klein JA , Margalef-Català M , Amieva MR , Vilches-Moure JG , Monack DM 
Published: July 2021

ABSTRACTSuperspreader hosts carry out most pathogen transmission events and are often disease tolerant since they remain asymptomatic despite high pathogen burdens. Here we describe the superspreader immune state that allows for disease tolerance. In a model ofSalmonellainfection, superspreader mice develop colitis with robust CD4+and CD8+T-cell responses, however, they remain asymptomatic. We found that superspreaders have significantly more regulatory T cells (Tregs) in the distal gut compared to non-superspreader infected hosts. Surprisingly, the depletion of Tregs did not induce pathogen clearance but rather exacerbated weight loss, increased gut inflammation, and compromised epithelial intestinal barrier. This loss of tolerance correlated with dramatic increases in cytotoxic CD4+and CD8+T cells. Interestingly, CD4 neutralization in Tregs-depleted superspreaders was sufficient to rescue tolerance. Our results indicate that Tregs play a crucial role in maintaining immunologic tolerance in the guts of superspreader mice by suppressing cytotoxic CD4+and CD8+T-cell activities.AUTHOR SUMMARYSuperspreader hosts are the main cause of disease transmission and a very important public health concern. Here, we evaluated the immunological tolerance of theSalmonellainfected superspreaders in a mouse model. By manipulating Tregs, we demonstrated the immunological mechanism from the host to maintain health status and high pathogen burden. Tregs depletion in the superspreaders led to severe disease, with damage of the intestinal epithelia, and high morbidity without having any effect on shedding and systemicSalmonellaburden. Furthermore, we demonstrated that the damage of the intestinal epithelia was related to cytotoxic activity of T cells. When Tregs were depleted, CD8+T cells produced high levels of granzyme B and perforin. CD8+T cells neutralization in Tregs depleted mice led to increased cytotoxic CD4+T cells. Interestingly, neutralization of CD4+T cells in the Tregs depleted mice led to a reduction in the CD8+T cells producing granzyme B and it was sufficient to rescue host tolerance in this model. We demonstrate for the first time that cytotoxic CD4+T cells damage the epithelial intestinal barrier and contribute to loss of tolerance in the context of a superspreader host. These findings open new perspectives to understand mechanisms of tolerance in the intestine of a superspreader host.
Non-genetic maternal effects shape individual differences in cortisol phenotypes in wild chimpanzees
Authors: Tkaczynski Patrick J. , Mafessoni Fabrizio , Girard-Buttoz Cédric , Samuni Liran , Ackermann Corinne Y. , Fedurek Pawel , Gomes Cristina , Hobaiter Catherine , Löhrich Therese , Manin Virgile , Preis Anna , Valé Prince D. , Wessling Erin G. , Wittiger Livia , Zommers Zinta , Zuberbuehler Klaus , Vigilant Linda , Deschner Tobias , Wittig Roman M. , Crockford Catherine 
Published: July 2021

AbstractGlucocorticoids, such as cortisol, mediate homeostatic processes, allowing individuals to adjust to fluctuating environments. The regulation of circadian cortisol responses, a key homeostatic function, has been shown to be heritable. However, to understand better the role of parental care in shaping physiological functioning in long-lived mammals with protracted parental care, there is a need to disentangle genetic and non-genetic parental contributions to variation in glucocorticoid phenotypes. We used a dataset of 6,123 cortisol measures from urine samples from 170 wild chimpanzees spanning 18 years of data collection. We found consistent inter-individual differences in circadian cortisol phenotypes, with differences most apparent when considering average cortisol levels given the effect of time of day. Maternal effects explained around 10% (2-18%) variation in these average cortisol levels, while variation attributable to genetic factors was not distinguishable from zero. Our results indicate, relative to genetic effects, a qualitatively stronger influence of mothers, whether via epigenetic processes or via behavioral priming for coping with stressors, in shaping cortisol phenotypes in this species. This provides novel insight into the vital role of mothers in the developmental plasticity of long-lived mammals and, more generally, the selective pressures shaping physiological plasticity.
Potentialities of biotechnological recovery of hydrogen and short- and medium-chain organic acids from the co-fermentation of cheese whey and Yerba Mate (Ilex paraguariensis) waste
Authors: Ferraz Júnior Antônio Djalma Nunes , Fuentes Laura , de la Sovera Victoria , Bovio-Winkler Patricia , Eng Felipe , Garcia Mariángeles , Etchebehere Claudia 
Published: July 2021

AbstractCo-fermentation of cheese whey (CW) and thermal-alkaline pre-treated Yerba Mate (Ilex paraguariensis) waste (YMW) was performed aiming to produce biohydrogen and/or short- and medium-chain organic acids. Central Composite Designs (CCD) was chosen as the experimental design for evaluating the combinations of three independent variables namely YMW concentration, pH and inoculum concentration in hydrogen yield (H2Y; response variable). The increase of inoculum and YMW concentrations had positive effect in biohydrogen production and yield (H2Ymaxof 1.35 mMH2.g-1VSadded) whereas the initial pH had no significant effect on it. Hydrogen was produced as a coproduct to butyrate mainly. Acetate from homoacetogenesis was accounted in all conditions evaluated. The CCD also indicated operating conditions to produce moderate-to-high concentrations of short and medium-chain organic acids such as butyrate (~135 mM), caproate (~45 mM) and lactate (~140 mM). 16S rRNA gene sequences analysis revealed five groups of microorganisms related to hydrogen, lactate and caproate production, ethanol-hydrogen co-production and hydrogen consumption.HighlightsCo-fermentation improved hydrogen production in up 7.5-folds compared to the sole CW-fed system.The initial pH had no effect on hydrogen-producing batch reactors.Hydrogen was produced as a coproduct to butyrate.Design of experiment indicated operating conditions to the production of lactate and caproate.
In-situ genomic prediction using low-coverage Nanopore sequencing
Authors: Lamb Harrison J. , Hayes Ben J. , Randhawa Imtiaz A. S. , Nguyen Loan T. , Ross Elizabeth M. 
Published: July 2021

AbstractMost traits in livestock, crops and humans are polygenic, that is, a large number of loci contribute to genetic variation. Effects at these loci lie along a continuum ranging from common low-effect to rare high-effect variants that cumulatively contribute to the overall phenotype. Statistical methods to calculate the effect of these loci have been developed and can be used to predict phenotypes in new individuals. In agriculture, these methods are used to select superior individuals using genomic breeding values; in humans these methods are used to quantitatively measure an individual’s disease risk, termed polygenic risk scores. Both fields typically use SNP array genotypes for the analysis. Recently, genotyping-by-sequencing has become popular, due to lower cost and greater genome coverage (including structural variants). Oxford Nanopore Technologies’ (ONT) portable sequencers have the potential to combine the benefits genotyping-by-sequencing with portability and decreased turn-around time. This introduces the potential for in-house clinical genetic disease risk screening in humans or calculating genomic breeding values on-farm in agriculture. Here we demonstrate the potential of the later by calculating genomic breeding values for four traits in cattle using low-coverage ONT sequence data and comparing these breeding values to breeding values calculated from SNP arrays. At sequencing coverages between 2X and 4X the correlation between ONT breeding values and SNP array-based breeding values was > 0.92 when imputation was used and > 0.88 when no imputation was used. With an average sequencing coverage of 0.5x the correlation between the two methods was between 0.85 and 0.92 using imputation, depending on the trait. This demonstrates that ONT sequencing has great potential for in clinic or on-farm genomic prediction.Author SummaryGenomic prediction is a method that uses a large number of genetic markers to predict complex phenotypes in livestock, crops and humans. Currently the techniques we use to determine genotypes requires complex equipment which can only be used in laboratories. However, Oxford Nanopore Technologies’ have released a portable DNA sequencer, which can genotype a range of organisms in the field. As a result of the device’s higher error rate, it has largely only been considered for specific applications, such as characterising large mutations. Here we demonstrated that despite the devices error rate, accurate genomic prediction is also possible using this portable device. The ability to accurately predict complex phenotypes such as the predisposition to schizophrenia in humans or lifetime fertility in livestock in-situ would decrease the turnaround time and ultimately increase the utility of this method in the human clinical and on-farm settings.
Darwin’s bark spider shares a spidroin repertoire with Caerostris extrusa but achieves extraordinary silk toughness through gene expression
Authors: Kono Nobuaki , Ohtoshi Rintaro , Malay Ali D , Mori Masaru , Masunaga Hiroyasu , Yoshida Yuki , Nakamura Hiroyuki , Numata Keiji , Arakawa Kazuharu 
Published: July 2021

AbstractSpider silk is a protein-based material whose toughness suggests possible novel applications. A particularly fascinating example of silk toughness is provided by Darwin’s bark spider (Caerostris darwini) found in Madagascar. This spider produces extraordinarily tough silk, with an average toughness of 350 MJ/m and over 50% extensibility, and can build river-bridging webs with a size of 2.8 m2. Recent studies have suggested that specific spidroins expressed in C. darwini are responsible for the mechanical properties of its silk. Therefore, a more comprehensive investigation of spidroin sequences, silk thread protein contents, and phylogenetic conservation among closely related species is required. Here, we conducted genomic, transcriptomic, and proteomic analyses of C. darwini and its close relative Caerostris extrusa. A variety of spidroins and low-molecular-weight proteins were found in the dragline silk of these species; all of the genes encoding these proteins were conserved in both genomes, but their genes were more expressed in C. darwini. The potential to produce very tough silk is common in the genus Caerostris, and our results may suggest the existence of plasticity allowing silk mechanical properties to be changed by optimizing related gene expression in response to the environment.
Histone H3 deacetylation promotes host cell viability for efficient infection byListeria monocytogenes
Authors: Eldridge Matthew J.G. , Hamon Mélanie A. 
Published: July 2021

ABSTRACTFor many intracellular bacterial pathogens manipulating host cell survival is essential for maintaining a replicative niche, and is a common strategy used to promote infection. The bacterial pathogenListeria monocytogenesis well known to hijack host machinery for its own benefit, such as targeting the host histone H3 for modification by SIRT2. However, in what way this modification benefits infection, as well as the molecular players involved, remain unknown. Here we show that SIRT2 activity supportsListeriaintracellular survival by maintaining genome integrity and host cell viability. This protective effect is dependent on H3K18 deacetylation, which safeguards the host genome by counteracting infection-induced DNA damage. Mechanistically, infection causes SIRT2 to interact with the nucleic acid binding protein TDP-43 and localise to genomic R-loops, where H3K18 deacetylation occurs. This work highlights novel functions of TDP-43 and R-loops during bacterial infection and identifies the mechanism through whichL. monocytogenesco-opts SIRT2 to allow efficient infection.
Significant Variability exists in the Toxicity of Global Methicillin-resistant Staphylococcus aureus Lineages
Authors: Laabei Maisem , Peacock Sharon J. , Blane Beth , Baines Sarah L. , Howden Benjamin P. , Stinear Timothy P. , Massey Ruth C. 
Published: July 2021

AbstractStaphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily toxin driven, leading to the suggestion that hyper-virulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the toxic activity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced toxicity. Interestingly, the majority of isolates that were attenuated in toxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.
Combining ancestral reconstruction with folding-landscape simulations to engineer heterologous protein expression
Authors: Gamiz-Arco Gloria , Risso Valeria A. , Gaucher Eric A. , Gavira Jose A. , Naganathan Athi N. , Ibarra-Molero Beatriz , Sanchez-Ruiz Jose M. 
Published: July 2021

ABSTRACTObligate symbionts exhibit high evolutionary rates and extensive sequence divergence. Here, we use the thioredoxin from Candidatus Photodesmus katoptron, an uncultured symbiont of flashlight fish, to explore evolutionary and engineering aspects of protein folding in heterologous hosts. The symbiont protein is a standard thioredoxin in terms of 3D-structure, stability and redox activity. However, its refolding in vitro is very slow and its expression in E. coli leads to insoluble protein. By contrast, resurrected Precambrian thioredoxins express efficiently in E. coli, plausibly reflecting an ancient adaptation to unassisted folding. We have used a statistical-mechanical model of the folding landscape to guide back-to-ancestor engineering of the symbiont protein. Remarkably, we find that the efficiency of heterologous expression correlates with the in vitro refolding rate and that the ancestral expression efficiency can be achieved with only 1-2 back-to-ancestor replacements. These results demonstrate a sequence-engineering approach to rescue inefficient heterologous expression, a major biotechnological bottleneck.
Creating detailed metadata for an R Shiny analysis of circadian behavior sequence data
Authors: Colomb Julien , Winter York 
Published: July 2021

ABSTRACTAutomated mouse phenotyping through the high-throughput analysis of home cage behavior has brought hope of a more effective and efficient method for testing rodent models of diseases. Advanced video analysis software is able to derive behavioral sequence data sets from multiple-day recordings. However, no dedicated mechanisms exist for sharing or analyzing these types of data. In this article, we present a free, open-source software actionable through a web browser (an R Shiny application), which can perform state-of-the-art multidimensional analysis of home cage behavioral sequence data. The software aligns time-series data to the light/dark cycle, and then uses different time windows to produce up to 162 behavior variables per animal. It prevents p-hacking by providing an analysis that uses a principal component analysis strategy, while also representing the behavior graphically for further explorative analysis. A machine-learning approach was implemented, but it proved ineffective at separating the experimental groups.The software requires spreadsheets that provide information about the experiment (i.e., metadata), thus promoting a data management strategy that leads to FAIR data production. This encourages the publication of some metadata even when the data are kept private. We tested our software by comparing the behavior of female mice in videos recorded twice at 3 and 7 months in a home cage monitoring system. This study demonstrated that combining data management with data analysis leads to a more efficient and effective research process.
Lower cognitive set shifting ability is associated with stiffer balance recovery behavior and larger perturbation-evoked cortical responses in older adults
Authors: Payne Aiden M. , Palmer Jacqueline A. , McKay J. Lucas , Ting Lena H. 
Published: July 2021

1.AbstractThe mechanisms underlying associations between cognitive set shifting impairments and balance dysfunction are unclear. Cognitive set shifting refers to the ability to flexibly adjust behavior to changes in task rules or contexts, which could be involved in flexibly adjusting balance recovery behavior to different contexts, such as the direction the body is falling. Prior studies found associations between cognitive set shifting impairments and severe balance dysfunction in populations experiencing frequent falls. The objective of this study was to test whether cognitive set shifting ability is expressed in successful balance recovery behavior in older adults with high clinical balance ability (N=19, 71 ± 7 years, 6 female). We measured cognitive set shifting ability using the Trail Making Test and clinical balance ability using the miniBESTest. For most participants, cognitive set shifting performance (Trail Making Test B-A = 37 ± 20s) was faster than normative averages (46s for comparable age and education levels), and balance ability scores (miniBESTest = 25 ± 2 / 28) were above the threshold for fall risk (23 for people between 70-80 years). Reactive balance recovery in response to support-surface translations in anterior and posterior directions was assessed in terms of body motion, muscle activity, and brain activity. Across participants, lower cognitive set shifting ability was associated with smaller peak center of mass displacement during balance recovery, lower directional specificity of late phase balance-correcting muscle activity (i.e., greater antagonist muscle activity 200-300ms after perturbation onset), and larger cortical N1 responses (100-200ms). None of these measures were associated with clinical balance ability. Our results suggest that cognitive set shifting ability is expressed in balance recovery behavior even in the absence of profound clinical balance disability. Specifically, our results suggest that lower flexibility in cognitive task performance is associated with lower ability to incorporate the directional context into the cortically-mediated later phase of the motor response. The resulting antagonist activity and stiffer balance behavior may help explain associations between cognitive set shifting impairments and frequent falls.