bluuebunny/crossref_metadata_2025_split huggingface dataset:
GOLDEN TANGERINE TOMATO ROOTS SHOW INCREASED ACCUMULATION OF ACYCLIC CAROTENOIDS, LESS ABSCISIC ACID, DROUGHT SENSITIVITY, AND IMPAIRED ENDOMYCORRHIZAL COLONIZATION
Authors: Nayak Jwalit J , Anwar Sidra , Krishna Priti , Chen Zhong-Hua , Plett Jonathan M. , Foo Eloise , Cazzonelli Christopher I. 
Published: December 2021

ABSTRACTHeirloom golden tomato fruit varieties are highly nutritious as they accumulate tetra-cis-lycopene, which has a higher bioavailability and recognised health benefits in treating anti-inflammatory diseases compared to all-trans-lycopene isomers found in red tomatoes. We investigated if photoisomerization of tetra-cis-lycopene occurs in roots of the goldentangerineMicro-Tom variety (tangmic), and how this affects root to shoot biomass, mycorrhizal colonization, abscisic acid accumulation, and responses to drought.tangmicplants grown in soil under glasshouse conditions displayed a reduction in height, number of flowers, fruit yield, and root length compared to wild type (WT). Soil inoculation withRhizophagus irregularisrevealed fewer arbuscules and other fungal structures in the endodermal cells of roots intangmicrelative to WT. The roots oftangmichyperaccumulated acycliccis-carotenes, while only trace levels of xanthophylls and abscisic acid were detected. In response to a water deficit, leaves from thetangmicplants displayed a rapid decline in maximum quantum yield of photosystem II compared to WT, indicating a defective root to shoot signalling response to drought. The lack of xanthophylls biosynthesis intangmicroots reduced abscisic acid levels, thereby likely impairing endomycorrhiza colonisation and drought-induced root to shoot signalling.Research HighlightsPhotoisomerization of prolycopene to lycopene is limited in root plastids.Roots oftangerinereveal an important tissue sink to store micronutrients such as prolycopene.Roots oftangerinelack ABA and show impaired mycorrhizal colonization.Thetangerineplant is drought sensitive and has a smaller biomass as well as reduced yield.
Linker histone H1FOO is required for bovine preimplantation development by regulating lineage specification and nucleosome assembly
Authors: Li Shuang , Shi Yan , Dang Yanna , Hu Bingjie , Xiao Lieying , Zhao Panpan , Wang Shaohua , Zhang Kun 
Published: December 2021

ABSTRACTLinker histone H1 binds to the nucleosome and is implicated in the regulation of the chromatin structure and function. The H1 variant H1FOO is heavily expressed in oocytes and early embryos. However, given the poor homology of H1FOO among mammals, the functional role of H1FOO during early embryonic development remains largely unknown, especially in domestic animals. Here, we find that H1FOO is not only expressed in oocytes and early embryos but granulosa cells and spermatids in cattle. We then demonstrate that the interference of H1FOO results in early embryonic developmental arrest in cattle using either RNA editing or Trim-Away approach. H1FOO depletion leads to compromised expression of critical lineage-specific genes at the morula stage and affects the establishment of cell polarity. Interestingly, H1FOO depletion causes a significant increase in expression genes encoding other linker H1 and core histones. Concurrently, there is an increase of H3K9me3 and H3K27me3, two markers of repressive chromatin and a decrease of H4K16ac, a marker of open chromatin. Importantly, overexpression of bovine H1FOO results in severe embryonic developmental defects. In sum, we propose that H1FOO controls the proper chromatin structure that is crucial for the fidelity of cell polarization and lineage specification during bovine early development.
Recut: a Concurrent Framework for Sparse Reconstruction of Neuronal Morphology
Authors: Marrett Karl , Zhu Muye , Chi Yuze , Choi Chris , Chen Zhe , Dong Hong-Wei , Park Chang Sin , Yang X. William , Cong Jason 
Published: December 2021

AbstractAdvancement in modern neuroscience is bottlenecked by neural reconstruction, a process that extracts 3D neuron morphology (typically in tree structures) from image volumes at the scale of hundreds of GBs. We introduce Recut, an automated and accelerated neural reconstruction pipeline, which provides a unified, and domain specific sparse data representation with 79× reduction in the memory footprint. Recut’s reconstruction can process 111 Kneurons/day or 79 TB/day on a 24-core workstation, placing the throughput bottleneck back on microscopic imaging time. Recut allows the full brain of a mouse to be processed in memory on a single server, at 89.5× higher throughput over existing I/O-bounded methods. Recut is also the first fully parallelized end-to-end automated reconstruction pipeline for light microscopy, yielding tree morphologies closer to ground truth than the state-of-the-art while removing involved manual steps and disk I/O overheads. We also optimized pipeline stages to linear algorithmic complexity for scalability in dense settings and allow the most timing-critical stages to optionally run on accelerated hardware.
Novel Fusarium Wilt Resistance Genes Uncovered in the Wild Progenitors and Heirloom Cultivars of Strawberry
Authors: Pincot Dominique D. A. , Feldmann Mitchell J. , Hardigan Michael A. , Vachev Mishi V. , Henry Peter M. , Gordon Thomas R. , Rodriguez Alan , Cobo Nicolas , Cole Glenn S. , Coaker Gitta L. , Knapp Steven J. 
Published: December 2021

AbstractFusarium wilt, a soilborne disease caused byFusarium oxysporumf. sp.fragariae, poses a significant threat to strawberry (Fragaria×ananassa) production in many parts of the world. This pathogen causes wilting, collapse, and death in susceptible genotypes. We previously identified a dominant gene (FW1) on chromosome 2B that confers resistance to race 1 of the pathogen and hypothesized that gene-for-gene resistance to Fusarium wilt was widespread in strawberry. To explore this, a genetically diverse collection of heirloom and modern cultivars and wild octoploid ecotypes were screened for resistance to Fusarium wilt races 1 and 2. Here we show that resistance to both races is widespread and that resistance to race 1 is mediated by dominant genes (FW1, FW2, FW3, FW4, andFW5) on three non-homoeologous chromosomes (1A, 2B, and 6B). The resistance proteins encoded by these genes are not yet known; however, plausible candidates were identified that encode pattern recognition receptor or other proteins known to mediate gene-for-gene resistance in plants.High-throughput genotyping assays for SNPs in linkage disequilibrium withFW1-FW5were developed to facilitate marker-assisted selection and accelerate the development of race 1 resistant cultivars. This study laid the foundation for identifying the genes encoded byFW1-FW5, in addition to exploring the genetics of resistance to race 2 and other races of the pathogen, as a precaution to averting a Fusarium wilt pandemic.Key MessageSeveral race-specific resistance genes were identified and rapidly deployed via marker-assisted selection to develop strawberry cultivars resistant to Fusarium wilt, a devastating soil-borne disease.
Structural mechanism for bi-directional actin crosslinking by T-plastin
Authors: Mei Lin , Reynolds Matthew J. , Garbett Damien , Gong Rui , Meyer Tobias , Alushin Gregory M. 
Published: December 2021

AbstractTo fulfill the cytoskeleton’s diverse functions in cell mechanics and motility, actin networks with specialized architectures are built by crosslinking proteins, which bridge filaments to control micron-scale network geometry through nanoscale binding interactions via poorly defined structural mechanisms. Here, we introduce a machine-learning enabled cryo-EM pipeline for visualizing active crosslinkers, which we use to analyze human T-plastin, a member of the evolutionarily ancient plastin/fimbrin family of tandem calponin-homology domain (CHD) proteins. We define a sequential bundling mechanism which enables T-plastin to bridge filaments in both parallel and anti-parallel orientations. Our structural, biochemical, and cell biological data highlight inter-CHD linkers as key structural elements underlying flexible but stable crosslinking which are likely to be disrupted by mutations causing hereditary bone diseases. Beyond revealing how plastins are evolutionary optimized to crosslink dense actin networks with mixed polarity, our cryo-EM workflow will broadly enable analysis of the structural mechanisms underlying cytoskeletal network construction.One sentence summaryCryo-EM, biochemical, and cellular studies reveal how the crosslinking protein T-plastin bridges actin filaments in two opposing orientations.
The challenge of limited vaccine supplies: impact of prior infection on anti-spike IgG antibody trajectories after a single COVID-19 vaccination
Authors: Wei Jia , Matthews Philippa C. , Stoesser Nicole , Diamond Ian , Studley Ruth , Rourke Emma , Cook Duncan , Bell John I , Newton John N , Farrar Jeremy , Howarth Alison , Marsden Brian D. , Hoosdally Sarah , Jones E Yvonne , Stuart David I , Crook Derrick W. , Peto Tim E. A. , Walker A. Sarah , Eyre David W. , Pouwels Koen B. ,   the COVID-19 Infection Survey team
Published: December 2021

AbstractGiven high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out, there is an urgent need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity at speed. We evaluate whether a single vaccination in previously infected individuals generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single dose of ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults who received at least one vaccination, 13,404 (13.3%) had serological and/or PCR evidence of prior infection. Prior infection significantly boosted antibody responses for all three vaccines, producing a higher peak level and longer half-life, and a response comparable to those without prior infection receiving two vaccinations. In those with prior infection, median time above the positivity threshold was estimated to last for >1 year after the first dose. Single-dose vaccination targeted to those previously infected may provide protection in populations with high rates of previous infection faced with limited vaccine supply, as an interim measure while vaccine campaigns are scaled up.
Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants
Authors: Blanquart François , Hozé Nathanaël , Cowling Benjamin J. , Débarre Florence , Cauchemez Simon 
Published: December 2021

AbstractEvaluating the characteristics of emerging SARS-CoV-2 variants of concern is essential to inform pandemic risk assessment. A variant may grow faster if it produces a larger number of secondary infections (transmissibility advantage) or if the timing of secondary infections (generation time) is better. So far, assessments have largely focused on deriving the transmissibility advantage assuming the generation time was unchanged. Yet, knowledge of both is needed to anticipate impact. Here we develop an analytical framework to investigate the contribution of both the transmissibility advantage and generation time to the growth advantage of a variant. We find that the growth advantage depends on the epidemiological context (level of epidemic control). More specifically, variants conferring earlier transmission are more strongly favoured when the historical strains have fast epidemic growth, while variants conferring later transmission are more strongly favoured when historical strains have slow or negative growth. We develop these conceptual insights into a statistical framework to infer both the transmissibility advantage and generation time of a variant. On simulated data, our framework correctly estimates both parameters when it covers time periods characterized by different epidemiological contexts. Applied to data for the Alpha and Delta variants in England and in Europe, we find that Alpha confers a +54% [95% CI, 45-63%] transmissibility advantage compared to previous strains, and Delta +140% [98-182%] compared to Alpha, and mean generation times are similar to historical strains for both variants. This work helps interpret variant frequency and will strengthen risk assessment for future variants of concern.
STRAIGHT-IN: A platform for high-throughput targeting of large DNA payloads into human pluripotent stem cells
Authors: Grandela Catarina , Blanch-Asensio Albert , Brandão Karina O. , de Korte Tessa , Yiangou Loukia , Mol Mervyn P.H. , van Meer Berend J. , Mummery Christine L. , Davis Richard P. 
Published: December 2021

SUMMARYInserting large DNA payloads (>10 kb) into specific genomic sites of mammalian cells remains challenging. Applications ranging from synthetic biology to evaluating the pathogenicity of disease-associated variants for precision medicine initiatives would greatly benefit from tools that facilitate this process. Here, we merge the strengths of different classes of site-specific recombinases and combine these with CRISPR/Cas9-mediated homologous recombination to develop a strategy for stringent site-specific replacement of genomic fragments at least 50 kb in size in human induced pluripotent stem cells (hiPSCs). We demonstrate the versatility of STRAIGHT-IN (Serine and Tyrosine Recombinase Assisted Integration of Genes for High-Throughput INvestigation) by: (i) inserting various combinations of fluorescent reporters into hiPSCs to assess excitation-contraction coupling cascade in derivative cardiomyocytes, and; (ii) simultaneously targeting multiple variants associated with inherited cardiac arrhythmic disorder into a pool of hiPSCs. STRAIGHT-IN offers a precise approach to generate genetically-matched panels of hiPSC lines efficiently and cost-effectively.
Genomic ancestry, diet and microbiomes of Upper Palaeolithic hunter-gatherers from San Teodoro cave (Sicily, Italy)
Authors: Scorrano Gabriele , Nielsen Sofie Holtsmark , Lo Vetro Domenico , Mackie Meaghan , Margaryan Ashot , Fotakis Anna K. , Martínez-Labarga Cristina , Fabbri Pier Francesco , Allentoft Morten E. , Carra Marialetizia , Martini Fabio , Rickards Olga , Olsen Jesper V. , Cappellini Enrico , Sikora Martin 
Published: December 2021

AbstractRecent improvements in the analysis of ancient biomolecules from human remains and associated dental calculus have provided new insights into the prehistoric diet and past genetic diversity of our species. Here we present a “multi-omics” study, integrating genomic and proteomic analyses of two post-Last Glacial Maximum (LGM) individuals from San Teodoro cave (Italy), to reconstruct their lifestyle and the post-LGM resettlement of Europe. Our analyses show genetic homogeneity in Sicily during the Palaeolithic, representing a hitherto unknown Italian genetic lineage within the previously identified “Villabruna cluster”. We argue that this lineage took refuge in Italy during the LGM, followed by a subsequent spread to central-western Europe. Multi-omics analysis of dental calculus showed a diet rich of animal proteins which is also reflected on the oral microbiome composition. Our results demonstrate the power of using a multi-omics approach in the study of prehistoric human populations.
iMUT-seq: high-resolution mapping of DSB mutational landscapes reveals new insights into the mutagenic mechanisms of DSB repair
Authors: Bader Aldo S. , Bushell Martin 
Published: December 2021

SUMMARYDNA double-strand breaks (DSBs) are the most mutagenic form of DNA damage, and play a significant role in cancer biology, neurodegeneration and aging. However, studying DSB-induced mutagenesis is currently limited by the tools available for mapping these mutations. Here, we describe iMUT-seq, a technique that profiles DSB-induced mutations at high-sensitivity and single-nucleotide resolution around endogenous DSBs spread across the genome. By depleting 20 different DSB-repair factors we defined their mutational signatures in detail, revealing remarkable insights into the mechanisms of DSB-induced mutagenesis. We find that homologous-recombination (HR) is mutagenic in nature, displaying high levels of base substitutions and mononucleotide deletions due to DNA-polymerase errors, but simultaneously reduced translocation events, suggesting the primary role of HR is the specific suppression of genomic rearrangements. The results presented here offer new fundamental insights into DSB-induced mutagenesis and have significant implications for our understanding of cancer biology and the development of DDR-targeting chemotherapeutics.
The structural basis of mRNA recognition and binding by eukaryotic pseudouridine synthase PUS1
Authors: Grünberg Sebastian , Doyle Lindsey A. , Wolf Eric J. , Dai Nan , Corrêa Ivan R. , Yigit Erbay , Stoddard Barry L. 
Published: December 2021

ABSTRACTThe chemical modification of RNA bases represents a ubiquitous activity that spans all domains of life. Pseudouridylation is the most common RNA modification and is observed within tRNA, rRNA, ncRNA and mRNAs. Pseudouridine synthase or ‘PUS’ enzymes include those that rely on guide RNA molecules and others that function as ‘stand-alone’ enzymes. Among the latter, several have been shown to modify mRNA transcripts. Although recent studies have defined the structural requirements for RNA to act as a PUS target, the mechanisms by which PUS1 recognizes these target sequences in mRNA are not well understood. Here we describe the crystal structure of yeast PUS1 bound to an RNA target that we identified as being a hot spot for PUS1-interaction within a model mRNA at 2.4 Å resolution. The enzyme recognizes and binds both strands in a helical base-paired RNA duplex, and thus guides the RNA containing the target uridine to the active site for subsequent modification of the transcript. The study also allows us to show the divergence of related PUS1 enzymes and their corresponding RNA target specificities, and to speculate on the basis by which PUS1 binds and modifies mRNA or tRNA substrates.
Allosteric regulation of the proteasome’s catalytic sites by the proteasome activator PA28γ /REGγ
Authors: Thomas Taylor A , Smith David M. 
Published: December 2021

AbstractProteasome Activator 28γ (PA28γ) is a member of the 11S family of proteasomal regulators that is constitutively expressed in the nucleus and is implicated in certain cancers, lupus, rheumatoid arthritis, and Poly-glutamine neurodegenerative diseases. However, how PA28γ functions in protein degradation remains unclear. Though PA28γ’s mechanism has been investigated for some time, many alternative hypotheses have not been tested: e.g. 1) substrate selection, 2) allosteric upregulation of the Trypsin-like catalytic site, 3) allosteric inhibition of the Chymotrypsin- and Caspase-like catalytic sites, 4) conversion of the Chymotrypsin- or Caspase-like sites to new Trypsin-like catalytic sites, and 5) gate-opening in combination with these. The purpose of this study was to conclusively determine how PA28γ regulates proteasome function. Here, we rigorously and definitively show that PA28γ uses an allosteric mechanism to upregulate the proteolytic activity of the 20S proteasome’s Trypsin-like catalytic site. Using a constitutively open channel proteasome, we were able to dissociate gating affects from catalytic affects demonstrating that the PA28γ-increases the affinity (Km) and Vmax for Trypsin-like peptide substrates. Mutagenesis of PA28γ also reveals that it does not select for (i.e. filter) peptide substrates, and does not change the specificity of the other active sites to trypsin-like. Further, using Cryo-EM we were able to visualize the C7 symmetric PA28γ-20S proteasome complex at 4.4Å validating it’s expected 11S-like quaternary structure and proteasome binding mode. The results of this study provide unambiguous evidence that PA28γ functions by allosterically upregulating the T-L like site in the 20S proteasome.Significance StatementThis study rigorously demonstrates that PA28g allosterically activates the b-2 proteolytic site of the 20S proteasome directly without affecting 20S gating. Further, we generated the first human 11S-human 20S proteasome cryo-EM structure of the PA28g-20S complex showing that, despite it’s different affects on 20S activity, it has a similar quaternary structure as the other 11S family members. The significance of these findings is paramount as the b-2 site is responsible for post-basic cleavage and suggests that PA28g is specialized to degrade positively charged DNA binding proteins. Further, b-2 upregulation via PA28g could provide a protective effect against poly-glutamine expanded proteins, like Huntingtin. This work provides a framework for PA28g drug development to treat PA28g addicted cancers and Huntington’s Disease.
Effect of inulin and oat flour on viability of probiotics and physicochemical properties of reduced fat synbiotic ice cream
Authors: Mabrouk Ahmed Moawad , Abd-Elgawad Ahmed Rabea , Abd El-Montaleb Hani S. 
Published: December 2021

PurposeThe purpose of this study is to investigate the viability of probiotics, physicochemical and sensory properties of reduced fat synbiotic ice cream.Design/methodology/approachThe treatments were as follows: control was made by the addition of Lactobacillus salivarius NBIMCC 1589 and Lactobacillus crispatus NBIMCC 2451 (1:1). The treatments (T1, T2 and T3) were made with the addition of L. salivarius NBIMCC 1589 and L. crispatus NBIMCC 2451 (1:1) + 2% oat flour, 2% inulin and 4% oat flour + inulin (1:1). Physiochemical parameters (pH, moisture, fat, protein, fibre, ash, overrun, first dripping time and melting rate) were determined.FindingsThe ice cream with inulin and oat flour had lower moisture content, which was recorded 70.41, 69.88 and 68.82% for T1, T2 and T3, respectively. While the protein, fat and ash content of treated samples increased. The highest acidity (0.43%) was recorded in T3. The overrun increased by around 43% in T3 compared with control. The viable counts of probiotics were significantly (p = 0.05) decreased by two or three log cycles. Finally, T3 received the highest sensory score, which could be due to the combination between oat flour and inulin.Originality/valueA novel ice cream was produced using a combination of inulin and oat flour, which enhanced the viability of added probiotics. Reduced fat synbiotic ice cream was a good carrier for probiotics, which facilitates the production of healthy dairy products.