bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana
Authors: Dudley Quentin M. , Jo Seohyun , Guerrero Delia Ayled Serna , Chhetry Monika , Smedley Mark A. , Harwood Wendy A. , Sherden Nathaniel H. , O’Connor Sarah E. , Caputi Lorenzo , Patron Nicola J. 
Published: August 2021

AbstractMonoterpene indole alkaloids (MIAs) are a diverse class of plant natural products that include a number of medicinally significant compounds. We set out to reconstitute the pathway for strictosidine, a key intermediate of all MIAs, from central metabolism in Nicotiana benthamiana. A disadvantage of this host is that its rich background metabolism results in the derivatization of some heterologously produced molecules. We used transcriptomic analysis to identify glycosyltransferases that were upregulated in response to biosynthetic intermediates and produced plant lines with targeted mutations in the genes encoding them. Expression of the early MIA pathway in these lines produced a more favorable product profile. Strictosidine biosynthesis was successfully reconstituted, with the best yields obtained by the co-expression of 14 enzymes, of which a major latex protein-like enzyme (MLPL) from Nepeta (catmint) was critical for improving flux through the iridoid pathway. The removal of endogenous glycosyltransferases did not impact the yields of strictosidine, highlighting that the metabolic flux of the pathway enzymes to a stable biosynthetic intermediate minimizes the need to engineer the endogenous metabolism of the host. The production of strictosidine in planta expands the range of MIA products amenable to biological synthesis.
Applying Machine Learning to Classify the Origins of Gene Duplications
Authors: McKibben Michael T.W. , Barker Michael S. 
Published: August 2021

AbstractNearly all lineages of land plants have experienced at least one whole genome duplication (WGD) in their history. The legacy of these ancient WGDs is still observable in the diploidized genomes of extant plants. Genes originating from WGD—paleologs—can be maintained in diploidized genomes for millions of years. These paleologs have the potential to shape plant evolution through sub- and neofunctionalization, increased genetic diversity, and reciprocal gene loss among lineages. Current methods for classifying paleologs often rely on only a subset of potential genomic features, have varying levels of accuracy, and often require significant data and/or computational time. Here we developed a supervised machine learning approach to classify paleologs from a target WGD in diploidized genomes across a broad range of different duplication histories. We collected empirical data on syntenic block sizes and other genomic features from 27 plant species each with a different history of paleopolyploidy. Features from these genomes were used to develop simulations of syntenic blocks and paleologs to train a gradient boosted decision tree. Using this approach, Frackify (Fractionation Classify), we were able to accurately identify and classify paleologs across a broad range of parameter space, including cases with multiple overlapping WGDs. We then compared Frackify with other paleolog inference approaches in six species with paleotetraploid and paleohexaploid ancestries. Frackify provides a way to combine multiple genomic features to quickly classify paleologs while providing a high degree of consistency with existing approaches.
Pressure for rapid and accurate mate recognition promotes avian-perceived plumage sexual dichromatism in true thrushes (genus:Turdus)
Authors: Luro Alec B. , Hauber Mark E. 
Published: August 2021

AbstractEcological conditions limiting the time to find a compatible mate or increasing the difficulty in doing so likely promote the evolution of traits used for species and mate recognition. Conspicuous traits that signal an individual’s species, sex, and breeding status reduce the challenge of identifying a compatible conspecific mate, and should be more common in migratory rather than sedentary species, species with shorter breeding seasons, and species breeding under high sympatry with many closely-related heterospecifics. Here, we tested this recognition hypothesis for promoting plumage sexual dichromatism in the true thrushes (Turdusspp.), a large and diverse genus of passerine birds. We used receptor-noise limited models of avian vision to quantify avian-perceived chromatic and achromatic visual contrasts between male and female plumage patches and tested the influence of breeding season length, spatial distribution, and sympatry with otherTurdusspecies on plumage dichromatism. As predicted, we found that 1) true thrush species with migratory behaviour have greater plumage sexual dichromatism than non-migratory species, 2) species with longer breeding seasons have less plumage sexual dichromatism, and 3) greater numbers ofTurdusthrush species breeding in sympatry is associated with more plumage sexual dichromatism. These results suggest that social recognition systems, including species and mate recognition, play a prominent role in the evolution of plumage sexual dichromatism in true thrushes.
Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction inC. elegans
Authors: Smith Hannah J. , Lanjuin Anne , Sharma Arpit , Prabhakar Aditi , Tabakovic Emina , Sehgal Rohan , Mair William B. 
Published: August 2021

ABSTRACTOne of the most robust and reproducible methods to prolong lifespan in a variety of organisms is inhibition of the mTORC1 (mechanistic target of rapamycin complex 1) pathway. mTORC1 is a metabolic sensor that promotes anabolic growth when nutrients are abundant. Inhibition of mTORC1 extends lifespan, but also frequently has other effects such as stunted growth, slowed development, reduced fertility, and disrupted metabolism. It has long been assumed that suppression of anabolism and resulting phenotypes such as impaired growth and reproduction may be causal to mTORC1 longevity, but this hypothesis has not been directly tested. RAGA-1 is an upstream activator of TORC1. Previous work from our lab using aC. elegansmodel of mTORC1 longevity, the long-livedraga-1null mutant, found that the presence ofraga-1only in the neurons suppresses longevity of the null mutant. Here, we use the auxin-inducible degradation (AID) system to test whether neuronal mTORC1 inhibition is sufficient for longevity, and whether any changes in lifespan are also linked to stunted growth or fertility. We find that life-long AID of RAGA-1 either in all somatic tissue or only in the neurons ofC. elegansis sufficient to extend lifespan. We also find that AID of RAGA-1 or LET-363/mTOR beginning at day 1 of adulthood extends lifespan to a similar extent. Unlike somatic degradation of RAGA-1, neuronal degradation of RAGA-1 doesn’t impair growth, slow development, or decrease the reproductive capacity of the worms. Lastly, while AID of LET-363/mTOR in all somatic cells shortens lifespan, neuronal AID of LET-363/mTOR slows aging. This work demonstrates that targeting mTORC1 specifically in the neurons uncouples longevity from growth and reproductive impairments, challenging previously held ideas about the mechanisms of mTORC1 longevity and elucidating the promise of tissue-specific aging therapeutics.
Effects of land-use and landscape drivers in the species richness and distribution of carnivores in Faragosa-Fura Landscape of Southern Rift Valley, Ethiopia
Authors: Gebo Berhanu , Takele Serekebirhan , Shibru Simon 
Published: August 2021

AbstractUnderstanding the species richness and distribution of carnivores across anthropogenic land-use types in an area is an essential first step for biodiversity conservation and human-carnivore coexistence. However, quantitative data on carnivore species coexisting with humans in different land-use types remain largely missing. Thus, this paper investigated the effect of anthropogenic land-use and landscape drivers on carnivore species richness and distribution in the Faragosa-Fura Landscape, Gamo Zone, southern Ethiopia. To collect data, we employed the line transect method using three complementary field surveys techniques: sign survey, camera-trapping, and opportunistic sighting survey during wet and dry seasons in 2020 and 2021. We stratified the study landscape into five land-use types-forest, wetland, grassland, agricultural land, and settlement. The result proved the occurrence of 12 carnivore species belonging to six families, including vulnerable Felidae species -Panthera pardus. Family Felidae and Herpestidae were composed of a greater number of species, while Hyaenidae and Mustelidae were each represented by single species. Out of identified species, only two species (Panthera pardusandCrocuta crocuta) were large-sized, while the rest were medium and small-sized carnivores. Overall, the mean richness of the study area was 5.73±0.284(SE). The species richness was highest in the wetland (n = 12, mean = 7.67±0.494(SE)) and lowest in the settlement (n = 5, mean = 4.25±0.479(SE)). The regression analysis showed that most of the carnivores displayed a strong negative relationship with agriculture, roads, and settlement while displayed a strong positive relationship with wetland and forest. In general, out of 32 species recorded in Ethiopia, this study quantified 12 carnivore species that signify the area is an important area for wildlife conservation in Ethiopia. Further, the study concluded that the wetland is the most important habitat, particularly for larger-sized and habitat specialists while anthropogenic land-uses types adversely affecting species richness. Thus, a generic paradigm to reconcile land management and biodiversity conservation is highly important.
SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact
Authors: Pang Yui Tik , Acharya Atanu , Lynch Diane L. , Pavlova Anna , Gumbart James C. 
Published: August 2021

ABSTRACTThe trimeric spike (S) glycoprotein, which protrudes from the SARS-CoV-2 viral envelope, binds to human ACE2, initiated by at least one protomer’s receptor binding domain (RBD) switching from a “down” (closed) to an “up” (open) state. Here, we used large-scale molecular dynamics simulations and two-dimensional replica exchange umbrella sampling calculations with more than a thousand windows and an aggregate total of 160 µs of simulation to investigate this transition with and without glycans. We find that the glycosylated spike has a higher barrier to opening and also energetically favors the down state over the up state. Analysis of the S-protein opening pathway reveals that glycans at N165 and N122 interfere with hydrogen bonds between the RBD and the N-terminal domain in the up state, while glycans at N165 and N343 can stabilize both the down and up states. Finally we estimate how epitope exposure for several known antibodies changes along the opening path. We find that the BD-368-2 antibody’s epitope is continuously exposed, explaining its high efficacy.
Quantifying microbial associations of dissolved organic matter under global change
Authors: Hu Ang , Choi Mira , Tanentzap Andrew J. , Liu Jinfu , Jang Kyoung-Soon , Lennon Jay T. , Liu Yongqin , Soininen Janne , Lu Xiancai , Zhang Yunlin , Shen Ji , Wang Jianjun 
Published: August 2021

AbstractMicrobes play a critical role in regulating the size, composition, and turnover of dissolved organic matter (DOM), which is one of the largest pools of carbon in aquatic ecosystems. Global change may alter DOM-microbe associations with implications for biogeochemical cycles, although disentangling these complex interactions remains a major challenge. Here we develop a framework called Energy-Diversity-Trait integrative Analysis (EDTiA) to examine the associations between DOM and bacteria along temperature and nutrient gradients in a manipulative field experiment on mountainsides in contrasting subarctic and subtropical climates. In both study regions, the chemical composition of DOM correlated with bacterial communities, and was primarily controlled by nutrients and to a lesser degree by temperature. At a molecular-level, DOM-bacteria associations depended strongly on the molecular traits of DOM, with negative associations indicative of decomposition as molecules are more biolabile. Using bipartite networks, we further demonstrated that negative associations were more specialized than positive associations indicative of DOM production. Nutrient enrichment promoted specialization of positive associations, but decreased specialization of negative associations particularly at warmer temperatures in subtropical climate. These global change drivers influenced specialization of negative associations most strongly via molecular traits, while both molecular traits and bacterial diversity similarly affected positive associations. Together, our framework provides a quantitative approach to understand DOM-microbe associations and wider carbon cycling across scales under global change.
Conserved T-cell epitopes predicted by bioinformatics in SARS-COV-2 variants
Authors: Lu Feiyu , Wang Shengnan , Wang Ying , Yao Yunpeng , Wang Yangeng , Liu Shujun , Wang Yangyang , Yu Yongli , Wang Liying 
Published: August 2021

AbstractBackgroundFinding conservative T cell epitopes in the proteome of numerous variants of SARS-COV-2 is required to develop T cell activating SARS-COV-2 capable of inducing T cell responses against SARS-COV-2 variants.MethodsA computational workflow was performed to find HLA restricted CD8+ and CD4+ T cell epitopes among conserved amino acid sequences across the proteome of 474727 SARS-CoV-2 strains.ResultsA batch of covserved regions in the amino acid sequences were found in the proteome of the SARS-COV-2 strains. 2852 and 847 peptides were predicted to have high binding affinity to distint HLA class I and class II molecules. Among them, 1456 and 484 peptides are antigenic. 392 and 111 of the antigenic peptides were found in the conseved amino acid sequences. Among the antigenic-conserved peptides, 6 CD8+ T cell epitopes and 7 CD4+ T cell epitopes were identifed. The T cell epitopes could be presented to T cells by high-affinity HLA molecules which are encoded by the HLA alleles with high population coverage.ConclusionsThe T cell epitopes are conservative, antigenic and HLA presentable, and could be constructed into SARS-COV-2 vaccines for inducing protective T cell immunity against SARS-COV-2 and their variants.
Factors influencing wellbeing in young people during COVID-19: A survey with 6291 young people in Wales
Authors: James Michaela , Jones Hope , Baig Amana , Marchant Emily , Waites Tegan , Todd Charlotte , Hughes Karen , Brophy Sinead 
Published: August 2021

AbstractCOVID-19 infection and the resultant restrictions has impacted all aspects of life across the world. This study explores factors that promote or support wellbeing for young people during the pandemic, how they differ by age, using a self-reported online survey with those aged 8 - 25 in Wales between September 2020 and February 2021. Open-ended responses were analysed via thematic analysis to provide further context. A total of 6,291 responses were obtained from 81 education settings across Wales (including primary and secondary schools as well as sixth form, colleges and universities). Wellbeing was highest in primary school children and boys and lowest in those who were at secondary school children, who were girls and, those who preferred not to give a gender. Among primary school children, higher wellbeing was seen for those who played with others (rather than alone), were of Asian ethnicity (OR 2.3, 95% CI: 1.26 to 4.3), lived in a safe area (OR: 2.0, 95% CI: 1.67 to 2.5) and had more sleep. To support their wellbeing young people reported they would like to be able to play with their friends more. Among secondary school children those who were of mixed ethnicity reported lower wellbeing (OR: 5.10, 95% CI: 1.70 to 15.80). To support their wellbeing they reported they would like more support with mental health (due to anxiety and pressure to achieve when learning online). This study found self-reported wellbeing differed by gender, ethnicity and deprivation and found younger children report the need for play and to see friends to support wellbeing but older children/young people wanted more support with anxiety and educational pressures.
Infectious SARS-CoV-2 in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection
Authors: Adenaiye Oluwasanmi O. , Lai Jianyu , de Mesquita P. Jacob Bueno , Hong Filbert , Youssefi Somayeh , German Jennifer , Tai S.-H. Sheldon , Albert Barbara , Schanz Maria , Weston Stuart , Hang Jun , Fung Christian , Chung Hye Kyung , Coleman Kristen K. , Sapoval Nicolae , Treangen Todd , Berry Irina Maljkovic , Mullins Kristin , Frieman Matthew , Ma Tianzhou , Milton Donald K. ,   for the University of Maryland StopCOVID Research Group
Published: August 2021

AbstractBackgroundSARS-CoV-2 epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood.MethodsWe recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies.ResultsWe enrolled 49 seronegative cases (mean days post onset 3.8 ±2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 45% of fine (≤5 µm), 31% of coarse (>5 µm) aerosols, and 65% of fomite samples overall and in all samples from four alpha-variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive.ConclusionSARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.Key PointsCases exhale infectious viral aerosolsSARS-CoV-2 evolution favors more efficient aerosol generation.Loose-fitting masks moderately reduce viral RNA aerosol.Ventilation, filtration, UV air sanitation, and tight-fitting masks are needed to protect vulnerable people in public-facing jobs and indoor spaces.
Unravelling the binding mode of a methamphetamine aptamer: a spectroscopic and calorimetric investigation
Authors: Sester Clement , McCone Jordan AJ , Vorster Ian , Harvey Joanne E , Hodgkiss Justin M 
Published: August 2021

ABSTRACTNucleic acid aptamers are bio-molecular recognition agents that bind to their targets with high specificity and affinity, and hold promise in a range of biosensor and therapeutic applications. In the case of small molecule targets, their small size and limited number of functional groups constitute challenges for their detection by aptamer-based biosensors because bio-recognition events may both be weak and produce poorly transduced signals. The binding affinity is principally used to characterize aptamer-ligand interactions; however a structural understanding of bio-recognition is arguably more valuable in order to design a strong response in biosensor applications. Using a combination of nuclear magnetic resonance, circular dichroism, and isothermal titration calorimetry, we propose a binding model for a new methamphetamine aptamer and determine the main interactions driving complex formation. These measurements reveal only modest structural changes to the aptamer upon binding and are consistent with a conformational selection binding model. The aptamer-methamphetamine complex formation was observed to be entropically driven, apparently involving hydrophobic and electrostatic interactions. Taken together, our results establish a means of elucidating small molecule-aptamer binding interactions, which may be decisive in the development of aptasensors and therapeutics, and may contribute to a deeper understanding of interactions driving aptamer selection.
The small and large intestine contain transcriptionally related mesenchymal stromal cell subsets that derive from embryonic Gli1+ mesothelial cells
Authors: Pærregaard Simone Isling , Schussek Sophie , Wulff Line , Niss Kristoffer , Mörbe Urs , Jendholm Johan , Wendland Kerstin , Andrusaite Anna T. , Brulois Kevin F. , Nibbs Robert J. B. , Sitnik Katarzyna , Mowat Allan McI , Butcher Eugene C. , Brunak Søren , Agace William W. 
Published: August 2021

SummaryIntestinal fibroblasts (FB) play essential roles in intestinal homeostasis. Here we show that the small and large intestinal lamina propria (LP) contain similar FB subsets that locate in specific anatomical niches and express distinct arrays of epithelial support genes. However, there were tissue specific differences in the transcriptional profile of intestinal FB subsets in the two sites. All adult intestinal LP mesenchymal stromal cells (MSC), including FB, smooth muscle cells (SMC) and pericytes derive from Gli1-expressing embryonic precursors which we identify as mesothelial cells. Trajectory analysis suggested that adult SMC and FB derive from distinct embryonic intermediates, and that adult FB subsets develop in a linear trajectory from CD81+ FB. Finally, we show that colonic subepithelial PDGFRαhi FB comprise several functionally and anatomically distinct populations that originate from an Fgfr2-expressing FB intermediate. Collectively our results provide novel insights into MSC diversity, location, function and ontogeny, with implications for our understanding of intestinal development, homeostasis and disease.
Automated Design of Robust Genetic Circuits: Structural Variants and Parameter Uncertainty
Authors: Schladt Tobias , Engelmann Nicolai , Kubaczka Erik , Hochberger Christian , Koeppl Heinz 
Published: August 2021

AbstractGenetic design automation methods for combinational circuits often rely on standard algorithms from electronic design automation in their circuit synthesis and technology mapping. However, those algorithms are domain-specific and are hence often not directly suitable for the biological context. In this work we identify aspects of those algorithms that require domain-adaptation. We first demonstrate that enumerating structural variants for a given Boolean specification allows us to find better performing circuits and that stochastic gate assignment methods need to be properly adjusted in order to find the best assignment. Second, we present a general circuit scoring scheme that accounts for the limited accuracy of biological device models including the variability across cells and show that circuits selected according to this score exhibit higher robustness with respect to parametric variations. If gate characteristics in a library are just given in terms of intervals, we provide means to efficiently propagate signals through such a circuit and compute corresponding scores. We demonstrate the novel design approach using the Cello gate library and 33 logic functions that were synthesized and implementedin vivorecently (1). We show that an average 1.3-fold and a peak 6.5-fold performance increase can be achieved by simply considering structural variants and that an average 1.8-fold and a peak 30-fold gain in the novel robustness score can be obtained when selecting circuits according to it.Graphical TOC Entry