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Scientific Reports May 2024Intramuscular fat (IMF) in pork holds significant importance for economic performance within the pig industry and dietary calcium supplementation enhances the...
Intramuscular fat (IMF) in pork holds significant importance for economic performance within the pig industry and dietary calcium supplementation enhances the accumulation of intramuscular fat. Additionally, calcium ions inhibit translation and reduce protein synthesis. However, the mechanism by which calcium regulates IMF deposition in muscle through translation remains largely unknown. In this study, we compared the ribosome profiles of the longissimus dorsi muscles of Duroc Landrace Large white pigs from the normal calcium (NC) group or calcium supplement (HC) group by Ribo-seq, and RNA-seq. By integrating multiple-omics analysis, we further discovered 437 genes that were transcriptionally unchanged but translationally altered and these genes were significantly enriched in the oxidative phosphorylation signaling pathway. Furthermore, experimental data showed that inhibiting the expression of COX10 and mtND4L increased triglyceride accumulation in C2C12 cells, providing new targets for intramuscular fat deposition. Finally, this work links dietary calcium, translation regulation and IMF deposition, providing a new strategy for both meat quality and economic performance within the pig industry.
Topics: Animals; Muscle, Skeletal; Swine; Calcium, Dietary; Adipose Tissue; Dietary Supplements; Mice; Protein Biosynthesis; Triglycerides; Calcium
PubMed: 38811812
DOI: 10.1038/s41598-024-62986-0 -
Scientific Reports May 2024In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in...
In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in this process. Ribosome-bound nascent chains (RNCs) of intrinsically disordered proteins and RNCs bearing a signal/arrest sequence are known to interact with ribosomal proteins. However, in the case of RNCs bearing foldable protein sequences, not much information is available on these interactions. Here, via a combination of chemical crosslinking and time-resolved fluorescence-anisotropy, we find that nascent chains of the foldable globin apoHmp interact with ribosomal protein L23 and have a freely-tumbling non-interacting N-terminal compact region comprising 63-94 residues. Longer RNCs (apoHmp) also interact with an additional yet unidentified ribosomal protein, as well as with chaperones. Surprisingly, the apparent strength of RNC/r-protein interactions does not depend on nascent-chain sequence. Overall, foldable nascent chains establish and expand interactions with selected ribosomal proteins and chaperones, as they get longer. These data are significant because they reveal the interplay between independent conformational sampling and nascent-protein interactions with the ribosomal surface.
Topics: Ribosomes; Ribosomal Proteins; Protein Folding; Protein Binding; Molecular Chaperones; Intrinsically Disordered Proteins; Protein Biosynthesis; Models, Molecular; Protein Conformation; Humans
PubMed: 38811604
DOI: 10.1038/s41598-024-61274-1 -
Biological & Pharmaceutical Bulletin 2024Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating...
Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating properties. However, whether the alteration of intestinal microbiota is associated with the antidiabetic effect of mogroside remains poorly understood. This study investigated the mechanism underlying the hypoglycemic effect of mogroside in regulating intestinal flora and attenuating metabolic endotoxemia. Kunming mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet and intraperitoneal injection of streptozotocin were randomly divided into model, pioglitazone (2.57 mg/kg) and mogroside (200, 100, and 50 mg/kg) groups. After 28 d of administration, molecular changes related to glucose metabolism and metabolic endotoxemia in mice were evaluated. The levels of insulin receptor substrate-1 (IRS-1), cluster of differentiation 14 (CD14) and toll-like receptor 4 (TLR4) mRNAs were measured, and the composition of intestinal microflora was determined by 16s ribosomal DNA (rDNA) sequencing. The results showed that mogroside treatment significantly improved hepatic glucose metabolism in T2DM mice. More importantly, mogroside treatment considerably reduced plasma endotoxin (inhibition rate 65.93%, high-dose group) and inflammatory factor levels, with a concomitant decrease in CD14 and TLR4 mRNA levels. Moreover, mogroside treatment reduced the relative abundance of Firmicutes and Proteobacteria (the inhibition rate of Proteobacteria was 85.17% in the low-dose group) and increased the relative abundance of Bacteroidetes (growth rate up to 40.57%, high-dose group) in the intestines of diabetic mice. This study reveals that mogroside can relieve T2DM, regulating intestinal flora and improving intestinal mucosal barrier, indicating that mogroside can be a potential therapeutic agent or intestinal microbiota regulator in the treatment of T2DM.
Topics: Animals; Gastrointestinal Microbiome; Male; Diabetes Mellitus, Type 2; Diabetes Mellitus, Experimental; Mice; Hypoglycemic Agents; Diet, High-Fat; Blood Glucose; Triterpenes; Toll-Like Receptor 4; Endotoxemia; Liver
PubMed: 38811190
DOI: 10.1248/bpb.b24-00124 -
Science Advances May 2024Transporting and translating mRNAs in axons is crucial for neuronal viability. Local synthesis of nuclear-encoded mitochondrial proteins protects long-lived axonal...
Transporting and translating mRNAs in axons is crucial for neuronal viability. Local synthesis of nuclear-encoded mitochondrial proteins protects long-lived axonal mitochondria from damage; however, the regulatory factors involved are largely unknown. We show that CLUH, which binds mRNAs encoding mitochondrial proteins, prevents peripheral neuropathy and motor deficits in the mouse. CLUH is enriched in the growth cone of developing spinal motoneurons and is required for their growth. The lack of CLUH affects the abundance of target mRNAs and the corresponding mitochondrial proteins more prominently in axons, leading to ATP deficits in the growth cone. CLUH interacts with ribosomal subunits, translation initiation, and ribosome recycling components and preserves axonal translation. Overexpression of the ribosome recycling factor ABCE1 rescues the mRNA and translation defects, as well as the growth cone size, in CLUH-deficient motoneurons. Thus, we demonstrate a role for CLUH in mitochondrial quality control and translational regulation in axons, which is essential for their development and long-term integrity and function.
Topics: Animals; Motor Neurons; Mitochondria; Axons; Protein Biosynthesis; Mice; Peripheral Nervous System Diseases; Growth Cones; RNA, Messenger; Mitochondrial Proteins; Mice, Knockout
PubMed: 38809982
DOI: 10.1126/sciadv.adn2050 -
ISME Communications Jan 2024The genome of a microorganism encodes its potential functions that can be implemented through expressed proteins. It remains elusive how a protein's selective expression...
The genome of a microorganism encodes its potential functions that can be implemented through expressed proteins. It remains elusive how a protein's selective expression depends on its metabolic essentiality to microbial growth or its ability to claim resources as ecological niches. To reveal a protein's metabolic or ecological role, we developed a computational pipeline, which pairs metagenomics and metaproteomics data to quantify each protein's gene-level and protein-level functional redundancy simultaneously. We first illustrated the idea behind the pipeline using simulated data of a consumer-resource model. We then validated it using real data from human and mouse gut microbiome samples. In particular, we analyzed ABC-type transporters and ribosomal proteins, confirming that the metabolic and ecological roles predicted by our pipeline agree well with prior knowledge. Finally, we performed cultures of a human gut microbiome sample and investigated how oversupplying various sugars involved in ecological niches influences the community structure and protein abundance. The presented results demonstrate the performance of our pipeline in identifying proteins' metabolic and ecological roles, as well as its potential to help us design nutrient interventions to modulate the human microbiome.
PubMed: 38808120
DOI: 10.1093/ismeco/ycae063 -
Frontiers in Plant Science 2024F. E. Brown ex Miellez var. viridulum Baker (Longya lily) is a variety of F.E. Br. ex Miellez. We used HS-SPME and GC-MS to screened the tissues of roots, stems,...
F. E. Brown ex Miellez var. viridulum Baker (Longya lily) is a variety of F.E. Br. ex Miellez. We used HS-SPME and GC-MS to screened the tissues of roots, stems, bulbs, and leaves and obtained 2,4-DTBP as an autotoxic substance for subsequent analysis. 2,4-DTBP was highly autotoxic in some treatment groups. Based on changes in physiological indicators, we carried out transcriptomic analysis to investigate the mechanisms of autotoxicity of substances on and obtained 188,505 Unigenes. GO and KEGG enrichment analyses showed that responded differently to different concentrations and treatment times of 2,4-DTBP. We observed significant changes in genes associated with ROS, phytohormones, and MAPK signaling cascades. 2,4-DTBP affects chloroplasts, the integrity of the respiratory electron transport chain, and ribosomes, causing autotoxicity. Our findings provide a practical genomic resource for future research on autotoxicity and evidence for the mechanism of action of autotoxic substances.
PubMed: 38807780
DOI: 10.3389/fpls.2024.1330061 -
BMC Oral Health May 2024Patients with cleft lip and palate (CLP) have an oronasal communication differed from the closed state in healthy individuals, leading to a unique oral microbiome. This... (Comparative Study)
Comparative Study
BACKGROUND
Patients with cleft lip and palate (CLP) have an oronasal communication differed from the closed state in healthy individuals, leading to a unique oral microbiome. This study aimed to determine if variances in the oral microbiota persist among CLP patients who have received treatments for the closure of these fistulas compared to the microbiota of healthy individuals.
METHODS
Saliva samples were collected from a cohort comprising 28 CLP patients (CLP group) and 30 healthy controls (HC group). Utilizing 16S rRNA sequencing on the Illumina NovaSeq platform, we conducted a comprehensive analysis of the diversity and composition of the oral microbiota.
RESULTS
The analysis of the microbiota in the saliva samples revealed a total of 23 microbial phyla, 38 classes, 111 orders, 184 families, 327 genera and 612 species. The alpha diversity with microbial abundance and evenness indicated the significant difference between the CLP and HC groups. Principal coordinate analysis (PCoA) and the ADONIS test further supported the presence of distinct microorganisms between the two groups. The CLP group displayed elevated abundances of Neisseria, Haemophilus, Porphyromonas, and Granulicatella, as indicated by LefSe analysis. Conversely, Rothia, Veillonella, and Pauljensenia exhibited significant reductions in abundance in the CLP group. The results of the PICRUSt analysis indicated significant differences in the relative abundance of 25 KEGG pathways within the CLP group. Through Spearman correlation analysis, strong associations between Rothia, Veillonella, and Pauljensenia and 25 functional pathways linked to CLP were identified.
CONCLUSION
Findings of this study offer a thorough comprehension of the microbiome profiles of CLP patients after the restoration of oronasal structure and are anticipated to present innovative concepts for the treatment of CLP.
Topics: Humans; Cleft Palate; Cleft Lip; Microbiota; Male; Female; Saliva; Case-Control Studies; RNA, Ribosomal, 16S; Adolescent; Adult; Mouth; Child; Young Adult
PubMed: 38807164
DOI: 10.1186/s12903-024-04387-3 -
Microbial Ecology May 2024Fungi contribute to different important ecological processes, including decomposition of organic matter and nutrient cycling, but in the marine environment the main...
Fungi contribute to different important ecological processes, including decomposition of organic matter and nutrient cycling, but in the marine environment the main factors influencing their diversity and dynamics at the spatial and temporal levels are still largely unclear. In this study, we performed DNA metabarcoding on seawater sampled monthly over a year and a half in the Gulf of Trieste (northern Adriatic Sea), targeting the internal transcribed spacer (ITS) and the 18S rRNA gene regions. The fungal communities were diverse, very dynamic, and belonged predominantly to marine taxa. Samples could be clustered in two groups, mainly based on the high (> 30%) or low relative proportion of the ascomycetes Parengyodontium album, which emerged as a key taxon in this area. Dissolved and particulate organic C:N ratio played important roles in shaping the mycoplankton assemblages, suggesting that differently bioavailable organic matter pools may be utilized by different consortia. The proportion of fungal over total reads was 31% for ITS and 0.7% for 18S. ITS had the highest taxonomic resolution but low power to detect early divergent fungal lineages. Our results on composition, distribution, and environmental drivers extended our knowledge of the structure and function of the mycobiome of coastal waters.
Topics: Seawater; Fungi; Biodiversity; RNA, Ribosomal, 18S; Mycobiome; DNA, Fungal; DNA Barcoding, Taxonomic; Phylogeny; DNA, Ribosomal Spacer; Ascomycota
PubMed: 38806848
DOI: 10.1007/s00248-024-02394-z -
Microbial Ecology May 2024Water-filled sinkholes known locally as cenotes, found on the Yucatán Peninsula, have remarkable biodiversity. The primary objective of this study was to explore the...
Water-filled sinkholes known locally as cenotes, found on the Yucatán Peninsula, have remarkable biodiversity. The primary objective of this study was to explore the biotechnological potential of Gram-positive cultivable bacteria obtained from sediment samples collected at the coastal cenote Pol-Ac in Yucatán, Mexico. Specifically, the investigation aimed to assess production of hydrolytic enzymes and antimicrobial compounds. 16 S rRNA gene sequencing led to the identification of 49 Gram-positive bacterial isolates belonging to the phyla Bacillota (n = 29) and Actinomycetota (n = 20) divided into the common genera Bacillus and Streptomyces, as well as the genera Virgibacillus, Halobacillus, Metabacillus, Solibacillus, Neobacillus, Rossellomorea, Nocardiopsis and Corynebacterium. With growth at 55ºC, 21 of the 49 strains were classified as moderately thermotolerant. All strains were classified as halotolerant and 24 were dependent on marine water for growth. Screening for six extracellular hydrolytic enzymes revealed gelatinase, amylase, lipase, cellulase, protease and chitinase activities in 93.9%, 67.3%, 63.3%, 59.2%, 59.2% and 38.8%, of isolated strains, respectively. The genes for polyketide synthases type I, were detected in 24 of the strains. Of 18 strains that achieved > 25% inhibition of growth in the bacterial pathogen Staphylococcus aureus ATCC 6538, 4 also inhibited growth in Escherichia coli ATCC 35,218. Isolates Streptomyces sp. NCA_378 and Bacillus sp. NCA_374 demonstrated 50-75% growth inhibition against at least one of the two pathogens tested, along with significant enzymatic activity across all six extracellular enzymes. This is the first comprehensive report on the biotechnological potential of Gram-positive bacteria isolated from sediments in the cenotes of the Yucatán Peninsula.
Topics: Geologic Sediments; Mexico; Biodiversity; Gram-Positive Bacteria; RNA, Ribosomal, 16S; Bioprospecting; Phylogeny; Anti-Bacterial Agents; Seawater
PubMed: 38806738
DOI: 10.1007/s00248-024-02392-1 -
Communications Biology May 2024The gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host...
The gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host interactions at the molecular level is still in its infancy. To gain further insights into the hidden gut metabolome and its impact, we identified a cryptic non-ribosomal peptide BGC in the genome of Bacillus cereus DSM 28590 from the mouse intestine ( www.dsmz.de/miBC ), which was predicted to encode a thiazol(in)e substructure. Cloning and heterologous expression of this BGC revealed that it produces bacillamide D. In-depth functional evaluation showed potent cytotoxicity and inhibition of cell migration using the human cell lines HCT116 and HEK293, which was validated using primary mouse organoids. This work establishes the bacillamides as selective cytotoxins from a bacterial gut isolate that affect mammalian cells. Our targeted structure-function-predictive approach is demonstrated to be a streamlined method to discover deleterious gut microbial metabolites with potential effects on human health.
Topics: Bacillus cereus; Animals; Mice; Humans; HEK293 Cells; Gastrointestinal Microbiome; Cytotoxins; HCT116 Cells; Intestines; Cell Movement; Organoids
PubMed: 38806706
DOI: 10.1038/s42003-024-06208-3