238 research outputs found

    Overlapping functions of the MAP4K family kinases Hppy and Msn in Hippo signaling

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    The Hippo (Hpo) tumor suppressor pathway is an evolutionarily conserved signaling pathway that controls tissue growth and organ size in species ranging from Drosophila to human, and its malfunction has been implicated in many types of human cancer. In this study, we conducted a kinome screen and identified Happyhour (Hppy)/MAP4K3 as a novel player in the Hpo pathway. Our biochemical study showed that Hppy binds and phosphorylates Wts. Our genetic experiments suggest that Hppy acts in parallel and partial redundantly with Misshapen (Msn)/MAP4K4 to regulate Yki nuclear localization and Hpo target gene expression in Drosophila wing imaginal discs. Furthermore, we showed that cytoskeleton stress restricts Yki nuclear localization through Hppy and Msn when Hpo activity is compromised, thus providing an explanation for the Wts-dependent but Hpo-independent regulation of Yki in certain contexts. Our study has unraveled an additional layer of complexity in the Hpo signaling pathway and laid down a foundation for exploring how different upstream regulators feed into the core Hpo pathway

    OsACOS12, an orthologue of Arabidopsis acyl-CoA synthetase5, plays an important role in pollen exine formation and anther development in rice

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    RT-PCR analysis of acos5/acos5 background plants using the primer pair LP/RP, LB/RP and LB/LP. (TIF 406 kb

    Altered MICOS Morphology and Mitochondrial Ion Homeostasis Contribute to Poly(GR) Toxicity Associated with C9-ALS/FTD

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    Amyotrophic lateral sclerosis (ALS) manifests pathological changes in motor neurons and various other cell types. Compared to motor neurons, the contribution of the other cell types to the ALS phenotypes is understudied. G4C2 repeat expansion in C9ORF72 is the most common genetic cause of ALS along with frontotemporal dementia (C9-ALS/FTD), with increasing evidence supporting repeat-encoded poly(GR) in disease pathogenesis. Here, we show in Drosophila muscle that poly(GR) enters mitochondria and interacts with components of the Mitochondrial Contact Site and Cristae Organizing System (MICOS), altering MICOS dynamics and intra-subunit interactions. This impairs mitochondrial inner membrane structure, ion homeostasis, mitochondrial metabolism, and muscle integrity. Similar mitochondrial defects are observed in patient fibroblasts. Genetic manipulation of MICOS components or pharmacological restoration of ion homeostasis with nigericin effectively rescue the mitochondrial pathology and disease phenotypes in both systems. These results implicate MICOS-regulated ion homeostasis in C9-ALS pathogenesis and suggest potential new therapeutic strategies

    Physicochemical property, volatile flavor quality, and microbial community composition of Jinhua fatty ham and lean ham: A comparative study

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    The physicochemical property, volatile flavor compounds, and microbial community structure of Jinhua fatty ham (FH) and lean ham (LH) were investigated and compared by high-throughput sequencing and HS-GC-IMS. Results showed that FH had higher pH and slightly lighter and yellower color than LH. Meanwhile, 33 volatile flavor compounds were identified from FH and LH, among which LH showed higher abundance of total alcohols and acids, but FH had generally richer aldehydes, ketones, esters, heterocyclic, and sulfur-containing compounds. Moreover, FH and LH did not have significant difference in α-diversity of bacterial community, but LH presented a much lower α-diversity of fungal community than FH. Besides, the dominant microorganisms (relative abundance >2%) in FH were Ruminococcaceae UCG-005, Staphylococcus, Ruminococcaceae UCG-014, Meyerozyma, and Aspergillus at the genus level, while in LH were Staphylococcus, Psychrobacter, Halomonas, Propionicicella, Ruminococcaceae UCG-005, Meyerozyma, Yamadazyma, and Aspergillus. Furthermore, the analysis of Pearson’s correlation and metabolic network confirmed that the discriminative flavor compounds of FH were mainly β-oxidation and degradation products of fatty acids, while those of LH were mostly derived from the Strecker reaction or microbial metabolism of amino acids. The present study could help understand the potential pathway of characteristic microorganisms affecting flavor formation of fat-deficient dry-cured hams and provide theoretical supports for developing healthier fermented meat products

    Long-term effects of straw and straw-derived biochar on soil aggregation and fungal community in a rice–wheat rotation system

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    Background Soil aggregation is fundamental for soil functioning and agricultural productivity. Aggregate formation depends on microbial activity influencing the production of exudates and hyphae, which in turn act as binding materials. Fungi are also important for improving soil quality and promoting plant growth in a symbiotic manner. There is a scarcity of findings comparing the long-term impacts of different yearly double-crop straw return modes (e.g., straw return to the field and straw-derived biochar return to the field) on soil aggregation and fungal community structure in rice–wheat rotation systems. Methods The effects of 6-year continuous straw and straw-derived biochar amendment on soil physicochemical properties and the fungal community were evaluated in an intensively managed crop rotation system (rice–wheat). Soil samples of different aggregates (macroaggregates, microaggregates, and silt clay) from four different fertilization regimes (control, CK; traditional inorganic fertilization, CF; straw returned to field, CS; straw-derived biochar addition, CB) were obtained, and Illumina MiSeq sequencing analysis of the fungal internal transcribed spacer gene was performed. Results Compared to CF, CS and CB enhanced soil organic carbon, total nitrogen, and aggregation in 0–20 and 20–40 cm soil, with CB exhibiting a stronger effect. Additionally, agrowaste addition increased the mean weight diameter and the geometric diameter and decreased the fractal dimension (p < 0.05). Principal coordinates analysis indicated that fertilization management affected fungal community structure and aggregation distribution. In addition, CS increased fungal community richness and diversity, compared to CK, CB decreased these aspects. Ascomycota, unclassified_k_Fungi, and Basidiomycota were the dominant phyla in all soil samples. At the genus level, CB clearly increased fungi decomposing biosolids (Articulospora in macroaggregates in 0–20 cm soil and Neurospora in macroaggregates in 20–40 cm soil); decreased pathogenic fungi (Monographella in macroaggregates and Gibberella in microaggregates in 0–20 cm soil) and CO2-emission-related fungi (Pyrenochaetopsis in microaggregates and silt clay in 0–40 cm soil) (p < 0.05). Straw and biochar with inorganic fertilizer counteracted some of the adverse effects of the inorganic fertilizer with biochar showing better effects than straw

    Effects of straw returning combined with earthworm addition on nitrification and ammonia oxidizers in paddy soil

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    IntroductionSoil ammonia oxidation, which acts as the first and rate-limiting step of nitrification, is driven by ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA) and complete ammonia oxidizer (comammox, amoA gene of clade-A and clade-B). Straw returning, widely used ecological technology in China, is an effective measure for promoting straw decomposition and soil nutrient cycling when combined with earthworm addition. However, the effects of straw returning combined with earthworm addition on soil ammonia oxidizers remain poorly understood.MethodsA 2-year plot experiment was conducted with 5 treatments: no fertilizer (CK); regular fertilization (RT); straw returning (SR); earthworm addition (W); straw returning + earthworm addition (SRW). The AOA, AOB, comammox clade-A and clade-B community microbial diversities and structures were investigated by high-throughput sequencing.ResultsThe results showed that (1) compared to RT treatment, W, SR, and SRW treatments all significantly increased the richness of AOA and comammox clade-A and clade-B (p &lt; 0.05), and the richness of AOB was only significantly promoted by SRW treatment (p &lt; 0.05). However, only SRW had a higher comammox clade-B diversity index than RT. (2) The ammonia oxidizer community structures were altered by both straw returning and earthworm addition. Soil NH4+-N was the critical environmental driver for altering the ammonia oxidizer community structure. (3) Compared with RT treatment, the soil potential nitrification rate (PNR) of W and SRW treatments increased by 1.19 and 1.20 times, respectively. The PNR was significantly positively correlated with AOB abundance (path coefficient = 0.712, p &lt; 0.05) and negatively correlated with clade-B abundance (path coefficient = −0.106, p &lt; 0.05).DiscussionThis study provides scientific support for the application of straw returning combined with earthworm addition to improve soil nitrification with respect to soil ammonia-oxidizing microorganisms

    Characterization of Non-heading Mutation in Heading Chinese Cabbage (Brassica rapa L. ssp. pekinensis)

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    Heading is a key agronomic trait of Chinese cabbage. A non-heading mutant with flat growth of heading leaves (fg-1) was isolated from an EMS-induced mutant population of the heading Chinese cabbage inbred line A03. In fg-1 mutant plants, the heading leaves are flat similar to rosette leaves. The epidermal cells on the adaxial surface of these leaves are significantly smaller, while those on the abaxial surface are much larger than in A03 plants. The segregation of the heading phenotype in the F2 and BC1 population suggests that the mutant trait is controlled by a pair of recessive alleles. Phytohormone analysis at the early heading stage showed significant decreases in IAA, ABA, JA and SA, with increases in methyl IAA and trans-Zeatin levels, suggesting they may coordinate leaf adaxial-abaxial polarity, development and morphology in fg-1. RNA-sequencing analysis at the early heading stage showed a decrease in expression levels of several auxin transport (BrAUX1, BrLAXs, and BrPINs) and responsive genes. Transcript levels of important ABA responsive genes, including BrABF3, were up-regulated in mid-leaf sections suggesting that both auxin and ABA signaling pathways play important roles in regulating leaf heading. In addition, a significant reduction in BrIAMT1 transcripts in fg-1 might contribute to leaf epinastic growth. The expression profiles of 19 genes with known roles in leaf polarity were significantly different in fg-1 leaves compared to wild type, suggesting that these genes might also regulate leaf heading in Chinese cabbage. In conclusion, leaf heading in Chinese cabbage is controlled through a complex network of hormone signaling and abaxial-adaxial patterning pathways. These findings increase our understanding of the molecular basis of head formation in Chinese cabbage

    Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review

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    Copyright © 2021, The Author(s) Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. Methods: A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. Results: Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. Conclusion: Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.This study is funded by the National Institute for Health Research (NIHR) Doctoral Research Fellowship Grant (DRF-2015-08-023). JMB is partially funded by the NIHR Bristol Biomedical Research Centre and the MRC ConDUCT-II Hub for Trials Methodology Research. PRW was funded by the MRC North West Hub for Trials Methodology Research (Grant ref: MR/K025635/01).info:eu-repo/semantics/publishedVersio
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