bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualization of a Limonene Synthesis Metabolon inside Living Bacteria by Hyperspectral SRS Microscopy
Authors: Zhang Jing , Shin Jonghyeon , Tague Nathan , Lin Haonan , Zhang Meng , Ge Xiaowei , Wong Wilson , Dunlop Mary J. , Cheng Ji-Xin 
Published: July 2022

AbstractMetabolons consisting of cellular structure elements and sequential metabolic enzymes are expected to be involved in diverse biological processes. However, direct visualization of metabolons in prokaryotic cells is still challenging. In this study, we report direct visualization of concentrated subcellular regions of limonene synthesis inside single engineeredEscherichia coliby using hyperspectral stimulated Raman scattering (hSRS) microscopy. Equipped with spectral unmixing, hSRS imaging provides a reliable method to quantify intracellular limonene content. InE. colistrains with a complete limonene synthesis pathway, intracellular limonene is found locally concentrated and colocalized with proteins. Furthermore, dual-modality SRS and two-photon fluorescence imaging showed colocalization of limonene and GFP-fused limonene synthase.Significance StatementMonitoring biosynthesis activity at the single-cell level is key to metabolic engineering but is still difficult to achieve in a label-free manner. Using hyperspectral stimulated Raman scattering imaging in the 670-900 cm−1region, we visualized localized limonene synthesis inside engineeredE. coli. The colocalization of limonene and GFP-fused limonene synthase was confirmed by co-registered stimulated Raman scattering and two-photon fluorescence images. Our finding suggests a limonene synthesis metabolon with a polar distribution inside the cells. This finding expands our knowledge ofde novolimonene biosynthesis in engineered bacteria and highlights the potential of SRS chemical imaging in metabolic engineering research.
Genome-wide identification and characterization of the HSP gene superfamily in apple snails (Gastropoda: Ampullariidae) and expression analysis under temperature stress
Authors: Gao Yue , Li Jia-Nan , Pu Jia-Jia , Tao Ke-Xin , Zhao Xing-Xing , Yang Qian-Qian 
Published: July 2022

AbstractHeat shock proteins (HSPs) play important roles in the response to various stresses as molecular chaperones. Apple snails from the family Ampullariidae have become economically important due to several species mainly from the genusPomaceawere invasive. The recent release of the genomes of ampullariids (P. canaliculata, P. maculata, Lanistes nyassanus, andMarisa cornuarietis) has opened the opportunity for a comprehensive analysis of the HSP superfamily. We identified that the number of HSP fromP. canaliculata(PcaHSPs) was greater than that from the other three species. A total of 42 PcaHSPs were distributed on 12 chromosomes and were classified into the families of HSP90, HSP70, HSP60, HSP40, HSP20, and HSP10. Each family formed a monophyletic clade on the phylogenetic trees, except for the HSP40 family. We identified tandem duplication of paralogous genes in PcaHSP70 and PcaHSP20. The RNA-seq data show that the expression profiles of PcaHSPs in different tissues have similar patterns, except that several PcaHSP20 genes revealed tissue-specific expression levels. Moreover, we identified that there were more HSP genes with stronger induction levels in response to hot than cold stress. Our findings will be helpful for future studies on stress response and adaptation focusing on HSPs in apple snails.
Brain transplantation of genetically corrected Sanfilippo B Neural Stem Cells induces partial cross-correction of the disease
Authors: Pearse Yewande , Clarke Don , Kan Shih-hsin , Le Steven Q. , Sanghez Valentina , Luzzi Anna , Pham Ivy , Nih Lina R. , Cooper Jonathan D. , Dickson Patricia I. , Iacovino Michelina 
Published: July 2022

ABSTRACTSanfilippo syndrome type B (Mucopolysaccharidosis type IIIB or MPS IIIB) is a recessive genetic disorder that severely affects the brain due to a deficiency in the enzyme α-N-acetylglucosaminidase (NAGLU), leading to intralysosomal accumulation of partially degraded heparan sulfate. There are no effective treatments for this disorder. In this project, we carried out an ex vivo lentiviral correction of neural stem cells derived from Naglu-/- mice (iNSCs) using a modified enzyme in which the NAGLU is fused to an Insulin-like Growth Factor II receptor (IGFIIR) binding peptide in order to improve the cross-correction efficiency. After brain transplantation of these corrected iNSCs into Naglu-/- mice and long-term evaluation of the cross-correction, we successfully detected NAGLU-IGFII activity in all transplanted animals, as well as decreased lysosomal accumulation and reduced astrocytic and microglial activation throughout the transplanted brain. In addition, we identified a novel neuropathological phenotype in untreated brains characterized by decreased levels of MAP2 protein and accumulation of synaptophysin-positive aggregates in the brain. Following transplantation, this Naglu-/- -specific phenotype was altered with restored levels of MAP2 expression and significantly reduced formation of synaptophysin-positive aggregates. Our results demonstrate the feasibility and long-term benefit of genetically corrected iNSCs transplantation in the Sanfilippo B brain and effective cross-correction of Sanfilippo-associated pathology in Naglu-/- mice. Our findings suggest that genetically engineered iNSCs can be used to effectively deliver the missing enzyme to the brain and treat Sanfilippo type B-associated neuropathology.
NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression
Authors: Tsujimoto Goki , Ito Rin , Yoshikawa Kei , Ueki Chihiro , Okada Nobuhiro 
Published: July 2022

AbstractReprogramming of glucose metabolism occurs in many human tumor types, and one of these, gluconeogenesis, is known to exhibit anti-tumor effects in hepatocellular carcinoma (HCC). The transcription factor NFYA regulates gluconeogenesis in the normal liver tissue, but the function of the NFYA-gluconeogenesis axis in cancer and the functional differences of NFYA splicing variants in the regulation of gluconeogenesis is still unclear. Here, we demonstrate that NFYAv2, the short-form variant, upregulates the transcription of a gluconeogenic enzyme PCK1. We further reveal that its regulation induces high ROS levels and energy crisis in HCC and promotes cell death. These indicate that the NFYAv2-gluconeogenesis axis has enhanced anti-tumor effects in HCC, suggesting that the axis may be a potential therapeutic target for HCC. Furthermore, Nfyav1-deficient mice, spontaneously overexpressing Nfyav2, had no increasing gluconeogenesis in the liver. Taken together, our results reveal NFYAv2-gluconeogenesis axis has anti-tumor effects and the potential for NFYAv2 to be a safer therapeutic target for HCC.
DNA methylation is a widespread mechanism of light-induced circadian clock period plasticity
Authors: Kim Suil , McMahon Douglas G. 
Published: July 2022

AbstractThe suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, so-called period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of DNA methyltransferase inhibitors directed to the SCN. At the level of single light pulses that act as clock-resetting stimulations, pharmacologically inhibiting DNA methylation in the SCN significantly attenuates period after-effects following acute phase shifts in behavioral rhythms in vivo, and blocks period after-effects on clock gene rhythms in the isolated ex vivo SCN. Acute clock resetting shifts themselves, however, do not appear to require DNA methylation at the SCN and behavioral levels, in contrast to subsequent period plasticity. Our results indicate that DNA methylation in the SCN mediates light-induced period after-effects in response to photoperiods, and single light pulses, and together with previous studies showing that DNA methylation in the SCN is essential for period after-effects of non-24hr light cycles (T-cycles), suggest that DNA methylation in the SCN is a widespread mechanism of light-induced circadian period plasticity.
Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response
Authors: Kyunai Yuki M. , Sakamoto Mika , Koreishi Mayuko , Yoshio Tsujino , Satoh Ayano 
Published: July 2022

AbstractGlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidative response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2–antioxidative response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response.
Earl Grey: a fully automated user-friendly transposable element annotation and analysis pipeline
Authors: Baril Tobias , Galbraith James , Hayward Alex 
Published: July 2022

ABSTRACTTransposable elements (TEs) are major components of eukaryotic genomes and are implicated in a range of evolutionary processes. Yet, TE annotation and characterisation remains challenging, particularly for non-specialists, since existing pipelines are typically complicated to install, run, and extract data from. Current methods of automated TE annotation are also subject to issues that reduce overall quality, particularly: (i) fragmented and overlapping TE annotations, leading to erroneous estimates of TE count and coverage; (ii) repeat models represented by short sections of total TE length, with poor capture of 5’ and 3’ ends. To address these issues, we present Earl Grey, a fully automated TE annotation pipeline designed for user-friendly curation and annotation of TEs in eukaryotic genome assemblies. Using nine simulated genomes and an annotation ofDrosophila melanogaster, we show that Earl Grey outperforms current widely-used TE annotation methodologies in ameliorating the issues mentioned above, whilst scoring highly in benchmarking for TE annotation and classification, and being robust across genomic contexts. Earl Grey provides a comprehensive and fully automated TE annotation toolkit that provides researchers with paper-ready summary figures and outputs in standard formats compatible with other bioinformatics tools. Earl Grey has a modular format, with great scope for the inclusion of additional modules focussed on further quality control and tailored analyses in future releases.
Early phyllosphere microbial associations impact plant reproductive success
Authors: Mehlferber Elijah C. , McCue Kent F. , Debray Reena , Kaulbach Griffin , Ferrel Jon E. , Khanna Rajnish , Koskella Britt 
Published: July 2022

SummaryThe above-ground plant microbiome (the phyllosphere) is increasingly recognized as an important component of plant health. We hypothesized that phyllosphere interactions may be disrupted in a greenhouse setting, where microbial dispersal is limited, and that adding a microbial amendment might yield important benefits to the host plant.Using a newly developed synthetic phyllosphere microbiome for Tomato, we tested this hypothesis across multiple trials by manipulating microbial colonization of leaves and measuring subsequent plant growth and reproductive success, comparing results from plants grown in both greenhouse and field settings.We confirmed that greenhouse-grown plants have a depauperate phyllosphere microbiome and that the addition of the synthetic microbial community was responsible for a clear and repeatable increase in fruit production in this setting. We further show that this effect is synergistic with the addition of micronutrient-based soil amendments, with important implications for agriculture.These results suggest that greenhouse environments have poor phyllosphere microbiome establishment, with negative impacts on the plant. The results also implicate the phyllosphere microbiome as a key component of plant fitness, emphasizing that these communities have a clear role to play in the ecology and evolution of plant communities.
Acetaminophen production in the edible, filamentous cyanobacteriumArthrospira platensis
Authors: Hilzinger Jacob M. , Friedline Skyler , Sivanandan Divya , Cheng Ya-Fang , Yamazaki Shunsuke , Clark Douglas S. , Skerker Jeffrey M. , Arkin Adam P. 
Published: July 2022

AbstractSpirulina is the common name for the edible, non-heterocystous, filamentous cyanobacteriumArthrospira platensisthat is grown industrially as a food supplement, animal feedstock, and pigment source. Although there are many applications for engineering this organism1–3, until recently no genetic tools or reproducible transformation methods have been published. While recent work showed the production of a diversity of proteins inA. platensis, including single domain antibodies for oral delivery, there remains a need for a modular, characterized genetic toolkit4. Here, we establish and characterize a genetic toolkit and reproducible method for the transformation ofA. platensisand engineer this bacterium to produce acetaminophen as proof-of-concept for small molecule production in an edible host from CO2, H2O, and light. This work opensA. platensisto the wider scientific community for future engineering as a functional food for nutritional enhancement, modification of organoleptic traits, and production of pharmaceuticals for oral delivery.
The two Gtsf paralogs in silkworms orthogonally activate their partner PIWI proteins for target cleavage
Authors: Izumi Natsuko , Shoji Keisuke , Kiuchi Takashi , Katsuma Susumu , Tomari Yukihide 
Published: July 2022

AbstractThe PIWI-interacting RNA (piRNA) pathway is a protection mechanism against transposons in animal germ cells. Most PIWI proteins possess piRNA-guided endonuclease activity, which is critical for silencing transposons and producing new piRNAs. Gametocyte-specific factor 1 (Gtsf1), an evolutionarily conserved zinc finger protein, promotes catalysis by PIWI proteins. Many animals have multiple Gtsf1 paralogs; however, their respective roles in the piRNA pathway are not fully understood. Here, we dissected the roles of Gtsf1 and its paralog Gtsf1-like (Gtsf1L) in the silkworm piRNA pathway. We found that Gtsf1 and Gtsf1L preferentially bind the two silkworm PIWI paralogs, Siwi and BmAgo3, respectively, and facilitate the endonuclease activity of each PIWI protein. This orthogonal activation effect was further supported by specific reduction of BmAgo3-boundMasculinizerpiRNA and Siwi-boundFeminizerpiRNA, the unique piRNA pair required for silkworm feminization, upon depletion of Gtsf1 and Gtsf1L, respectively. Our results indicate that the two Gtsf paralogs in silkworms activate their respective PIWI partners, thereby facilitating the amplification of piRNAs.
Croton caudatus Geiseler Induces Differentiation of the Acute Myeloid Leukemia cell lines
Authors: Machathoibi Takhellambam Chanu , Singh Lisam Shanjukumar 
Published: July 2022

AbstractCroton caudatus Geiseler (CCG) is a traditional medicinal plant and it has also been reported as having anticancer activity. However, most of the studies of the anticancer activity of CGG based only on cytotoxicity and antioxidant properties. The present study investigates the anticancer activity of leaf crude extract of CCG on an acute myeloid leukemia cell line, HL60. The results showed that CCG promotes the monocyte macrophage-like morphology of HL60 cells but it does not cause cytotoxicity on HL60.The results also showed that CCG increased the expression of a marker for monocyte/macrophage differentiation, CD11b, and induced arrest of cell cycle at S phase. Further, the results indicate that leaf the crude extract of CCG has a very high ROS activity. The present study is the first report of CCG inducing cell differentiation. The overall results suggest that CCG is a promising agent for differentiation induction chemotherapy (DIC) for leukemia.
Microbiome response in an urban river system is dominated by seasonality over wastewater treatment upgrades
Authors: Kodera Sho M. , Sharma Anukriti , Martino Cameron , Dsouza Melissa , Grippo Mark , Lutz Holly L. , Knight Rob , Gilbert Jack A. , Negri Cristina , Allard Sarah M. 
Published: July 2022

AbstractMicroorganisms such as coliform-forming bacteria are commonly used to assess freshwater quality for drinking and recreational use. However, such organisms do not exist in isolation; they exist within the context of dynamic, interactive microbial communities which vary through space and time. Elucidating spatiotemporal microbial dynamics is imperative for discriminating robust community changes from ephemeral ecological trends, and for improving our overall understanding of the relationship between microbial communities and ecosystem health. We conducted a seven-year (2013-2019) microbial time-series investigation in the Chicago Area Waterways (CAWS): an urban river system which, in 2016, experienced substantial upgrades to disinfection processes at two wastewater reclamation plants (WRPs) that discharge into the CAWS and improved stormwater capture, to improve river water quality and reduce flooding. Using culture-independent and culture-dependent approaches, we compared CAWS microbial ecology before and after the intervention. Examinations of time-resolved beta distances between WRP-adjacent sites showed that community similarity measures were often consistent with the spatial orientation of site locations to one another and to the WRP outfalls. Fecal coliform results suggested that upgrades reduced coliform-associated bacteria in the effluent and the downstream river community. However, examinations of whole community changes through time suggest that the upgrades did little to affect overall riverine community dynamics, which instead were overwhelmingly driven by yearly patterns consistent with seasonality. Such results emphasize the dynamic nature of microbiomes in open environmental systems such as the CAWS, but also suggest that the seasonal oscillations remain consistent even when perturbed.ImportanceThis study presents a systematic effort to combine 16S rRNA gene amplicon sequencing with traditional culture-based methods to evaluate the influence of treatment innovations and systems upgrades on the microbiome of the Chicago Area Waterway System, representing the longest and most comprehensive characterization of the microbiome of an urban waterway yet attempted. We found that the systems upgrades were successful in improving specific water quality measures immediately downstream of wastewater outflows. Additionally, we found that the implementation of the water quality improvement measures to the river system did not disrupt the overall dynamics of the downstream microbial community, which remained heavily influenced by seasonal trends.
Proton magnetic resonance spectroscopy of N-acetyl aspartate in first depressive episode and chronic major depressive disorder: a systematic review and meta-analysis
Authors: Saccaro Luigi F. , Tassone Matteo , Tozzi Francesca , Rutigliano Grazia 
Published: July 2022

AbstractN-acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in the pathophysiology of Major Depressive Disorder (MDD). To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a meta-analysis of Proton Magnetic Resonance Spectroscopy (1H-MRS) studies comparing NAA concentrations in chronic MDD (cMDD) and first episode of depression (FED) to healthy controls. We searched Scopus® and Web of Knowledge □ using search terms related to depression and NAA. Hedges’ g was used as effect size measure, together with heterogeneity analyses, test of moderators and publication bias and quality assessment. The protocol is registered in PROSPERO (CRD42020221050). Sixty-two studies were included and meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in cMDD compared to healthy controls within the frontal lobe (n=26, Hedges’ g= -0.330, 95% CI -0.598 to -0.062; p= 0.018), the occipital lobe (n = 4, Hedges’ g= -0.677, 95% CI -1.013 to -0.341; p = 0.007), the thalamus (n= 4, Hedges’ g= -0.673, 95% CI -1.108 to -0.238; p = 0.016) and the frontal (n = 6, Hedges’ g= -0.471, 95% CI -0.891 to -0.052; p= 0.034) and periventricular white matter (n= 3, Hedges’ g= -0.478, 95% CI -0.938 to -0.018; p= 0.047). We highlighted a gap of knowledge regarding NAA levels in FED. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. Our findings are in line with previous evidence showing alterations in the aforementioned brain areas in MDD. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression, also considering our preliminary results on the modifying effect of antidepressant treatment.
Uncertainty and error in SARS-CoV-2 epidemiological parameters inferred from population-level epidemic models
Authors: Whittaker Dominic G. , Herrera-Reyes Alejandra D. , Hendrix Maurice , Owen Markus R. , Band Leah R. , Mirams Gary R. , Bolton Kirsty J. , Preston Simon P. 
Published: July 2022

AbstractDuring the SARS-CoV2 pandemic, epidemic models have been central to policy-making. Public health responses have been shaped by model-based projections and inferences, especially related to the impact of various non-pharmaceutical interventions. Accompanying this has been increased scrutiny over model performance, model assumptions, and the way that uncertainty is incorporated and presented. Here we consider a population-level model, focusing on how distributions representing host infectiousness and the infection-to-death times are modelled, and particularly on the impact of inferred epidemic characteristics if these distributions are misspecified. We introduce an SIR-type model with the infected population structured by ‘infected age’, i.e. the number of days since first being infected, a formulation that enables distributions to be incorporated that are consistent with clinical data. We show that inference based on simpler models without infected age, which implicitly misspecify these distributions, leads to substantial errors in inferred quantities relevant to policy-making, such as the reproduction number and the impact of interventions. We consider uncertainty quantification via a Bayesian approach, implementing this for both synthetic and real data focusing on UK data in the period 15 Feb–14 Jul 2020, and emphasising circumstances where it is misleading to neglect uncertainty.