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Nature Communications Jun 2024Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the...
Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.
Topics: Mucopolysaccharidosis III; Humans; Lysosomes; Acetyltransferases; Cryoelectron Microscopy; Catalytic Domain; Mutation; Heparitin Sulfate; Acetyl Coenzyme A; Models, Molecular; Glucosamine; Acetylation; Intracellular Membranes
PubMed: 38918376
DOI: 10.1038/s41467-024-49614-1 -
Frontiers in Nutrition 2024The effect of Ramadan intermittent fasting (RIF) on the metabolic profile, anthropometry and blood pressure has been investigated in multiple studies. However, it is...
BACKGROUND
The effect of Ramadan intermittent fasting (RIF) on the metabolic profile, anthropometry and blood pressure has been investigated in multiple studies. However, it is still unknown to what extent changes in nutrient intakes contribute to these changes.
METHODS
This observational study was conducted in London (UK) in 2019. The study collected diverse data from a community-based sample in London before and during/after Ramadan. Collected data included a 3-day food diary (before and during Ramadan), as well as blood samples, anthropometric measurements and blood pressure (before and after Ramadan). The food diary was translated into nutritional data using nutrition software "Nutritics." The changes in nutrient intakes were investigated using a mixed-effects regression model. The impact of adjusting for nutrient intake change was investigated on the absolute difference of metabolites (Nightingale platform), systolic/diastolic blood pressure and anthropometric measures.
RESULTS
The study collected data on food intake before and during Ramadan from 56 participants; the mean age was 44.7 ± 17.3, and 51.8% ( = 29) were females. We found a change in the intake of 11 nutritional factors, glucose, fructose, betaine, sugars, sugars as monosaccharide equivalents, lutein/zeaxanthin, starch, starch as monosaccharide equivalents, proline, glutamic acid and lycopene. No changes in quantities or proportions of macronutrients, carbohydrates, protein and fat. Mainly, the changes in diet during Ramadan are characterized by more consumption of sugars (62%, < 0.001) and a lower intake of starch (-21%, = 0.012). The changes in 14 metabolite levels (two glycolysis-related metabolites, one amino acid, two ketone bodies, two triglyceride, six lipoprotein subclasses, and an inflammation marker) after Ramadan were partially associated with some changes in nutrient intakes during Ramadan, especially betaine, fructose, glucose, starches and sugars. The lutein/zeaxanthin intake change explained inversely 14% of systolic blood pressure changes. Moreover, BMI and weight changes were partially explained by changes in intake of fat (7%; 9%), monounsaturated fat (6%; 7%), starch (8%; 9%), and starch as monosaccharide equivalents (8%; 9%) intakes in a direct relationship.
CONCLUSION
Diet changes during Ramadan were associated partially with the observed changes in the metabolic profile, blood pressure and anthropometry. This confirms the changes associated with RIF in the metabolic profile, blood pressure and anthropometry are not an absolute physiological response to the diet transition occurring during Ramadan.
PubMed: 38915859
DOI: 10.3389/fnut.2024.1394673 -
Gene Jun 2024Products from stingless bees are rich reservoirs of microbial diversity, including yeasts with fermentative potential. Previously, two Saccharomyces cerevisiae strains,...
Products from stingless bees are rich reservoirs of microbial diversity, including yeasts with fermentative potential. Previously, two Saccharomyces cerevisiae strains, JP14 and IP9, were isolated from Jataí (Tetragonisca angustula) and Iraí (Nannotrigona testaceicornis) bees, respectively, aiming at mead production. Both strains presented great osmotic and sulfite tolerance, and ethanol production, although they have a high free amino nitrogen demand. Herein, their genomes were sequenced, assembled, and annotated, and the variants were compared to the S. cerevisiae S288c reference strain. The final assembly of IP9 and JP14 presented high N50 and BUSCO scores, and more than 6430 protein-coding genes. Additionally, nQuire predicted the ploidy of IP9 as diploid, but the results were not enough to determine the ploidy of JP14. The mitochondrial genomes of IP9 and JP14 presented the same gene content as S288c but the genes were rearranged and fragmented in different patterns. Meanwhile, the genes with mutations of high impact (e.g., indels, gain of stop codon) for both yeasts were enriched for transmembrane transport, electron transfer, oxidoreductase, heme binding, fructose, mannose, and glucose transport, activities related to the respiratory chain and sugar metabolism. The IP9 strain presented copy number gains in genes related to sugar transport and cell morphogenesis; in JP14, genes were enriched for disaccharide metabolism and transport, response to reactive oxygen species, and polyamine transport. On the other hand, IP9 presented copy number losses related to disaccharide, thiamine, and aldehyde metabolism, while JP14 presented depletions related to disaccharide, oligosaccharide, asparagine, and aspartate metabolism. Notably, both strains presented a killer toxin gene, annotated from the assembling of unmapped reads, representing a potential mechanism for the control of other microorganisms population in the environment. Therefore, the annotated genomes of JP14 and IP9 presented a high selective pressure for sugar and nitrogen metabolism and stress response, consistent with their isolation source and fermentative properties.
PubMed: 38914244
DOI: 10.1016/j.gene.2024.148722 -
Frontiers in Microbiology 2024Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to...
Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to discern fecal and milk variations in both microbiota composition and metabolite profiles among three distinct groups of cows: healthy cows, cows with subclinical mastitis and cows with clinical mastitis. The fecal microbial community of cows with clinical mastitis was significantly less rich and diverse than the one harbored by healthy cows. In parallel, mastitis caused a strong disturbance in milk microbiota. Metabolomic profiles showed that eleven and twenty-eight molecules exhibited significant differences among the three groups in feces and milk, respectively. Similarly, to microbiota profile, milk metabolome was affected by mastitis more extensively than fecal metabolome, with particular reference to amino acids and sugars. Pathway analysis revealed that amino acids metabolism and energy metabolism could be considered as the main pathways altered by mastitis. These findings underscore the notable distinctions of fecal and milk samples among groups, from microbiome and metabolomic points of view. This observation stands to enhance our comprehension of mastitis in dairy cows.
PubMed: 38912351
DOI: 10.3389/fmicb.2024.1374911 -
Frontiers in Plant Science 2024Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when...
Metabolomics and physio-chemical analyses of mulberry plants leaves response to manganese deficiency and toxicity reveal key metabolites and their pathways in manganese tolerance.
INTRODUCTION
Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when applied in excess. is an economically significant plant, capable of adapting to a range of environmental conditions and possessing the potential for phytoremediation of contaminated soil by HMs. The mechanism by which tolerates Mn stresses remains obscure.
METHODS
In this study, Mn concentrations comprising sufficiency (0.15 mM), higher regimes (1.5 mM and 3 mM), and deficiency (0 mM and 0.03 mM), were applied to in pot treatment for 21 days to understand Mn tolerance. Mn stress effects on the net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO concentration (Ci), chlorophyll content, plant morphological traits, enzymatic and non-enzymatic parameters were analyzed as well as metabolome signatures via non-targeted LC-MS technique.
RESULTS
Mn deficiency and toxicity decrease plant biomass, Pn, Ci, Gs, Tr, and chlorophyll content. Mn stresses induced a decline in the activities of catalase (CAT) and superoxide dismutase (SOD), while peroxidase (POD) activity, and leaf Mn content, increased. Soluble sugars, soluble proteins, malondialdehyde (MDA) and proline exhibited an elevation in Mn deficiency and toxicity concentrations. Metabolomic analysis indicates that Mn concentrations induced 1031 differentially expressed metabolites (DEMs), particularly amino acids, lipids, carbohydrates, benzene and derivatives and secondary metabolites. The DEMs are significantly enriched in alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, galactose metabolism, pantothenate and CoA biosynthesis, pentose phosphate pathway, carbon metabolism, etc.
DISCUSSION AND CONCLUSION
The upregulation of Galactinol, Myo-inositol, Jasmonic acid, L-aspartic acid, Coproporphyrin I, Trigonelline, Pantothenol, and Pantothenate and their significance in the metabolic pathways makes them Mn stress tolerance metabolites in . Our findings reveal the fundamental understanding of DEMs in 's response to Mn nutrition and the metabolic mechanisms involved, which may hold potential significance for the advancement of genetic improvement initiatives and phytoremediation programs.
PubMed: 38911982
DOI: 10.3389/fpls.2024.1349456 -
Zhongguo Gu Shang = China Journal of... Jun 2024To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of...
OBJECTIVE
To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of typeⅠcollagen β special sequence(β-CTX)and risk of osteoporosis vertebral fractures (OPVFs) in elderly women.
METHODS
The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed. According to whether or not fracture, patients were divided into non-fracture group (186 patients) and fracture group(260 patients). Univariate analysis was performed to analysis age, body mass index(BMI), N-terminal mioldle molecular fragment of osteocalcin, N-MID OC), t-PINP, β-CTX, 25-hydroxyvitamin D[25-(OH) VitD], blood sugar (Glu), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Ca, P, Mg, urea (UREA), creatinine (Cr) and Cystatin C(CysC), and correlation between OPVFs and the above indexes and lipid, bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL, t-PINP/β-CTX. Logistic regression was used to analyze risk factors and stratification relationship between OPVFs and HDL/LDL, t-PINP/β-CTX.
RESULTS
There were no significant difference in age and BMI between non-fracture group and fracture group (>0.05). Compared with non-fracture group, contents of HDL, t-PINP/β-CTX and HDL/LDL in fracture group were decreased, and contents of β-CTX were increased (<0.05). OPVFs was positively correlated with β-CTX (=0.110, <0.05), and negatively correlated with HDL, HDL/LDL and t-PINP/β-CTX (=-0.157, -0.175, -0.181, <0.05). HDL and HDL/LDL were negatively correlated with β-CTX (=-0.22, -0.12, <0.05) and t-PINP (=-0.13, -0.10, <0.05). 25-(OH) VitD was positively correlated with TC and HDL (=0.11, 0.18, <0.05). HDL/LDL was positively correlated with t-PINP/β-CTX(=0.11, =0.02). t-PINP/β-CTX[=0.998, 95%(0.997, 1.000), <0.05], HDL/LDL[=0.228, 95%(0.104, 0.499), <0.01] were risk factors for vertebral fracture. The lower levels between two tristratified indicators, the higher the vertebral fracture rate. The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum, with an adjusted OR was[2.112, 95%(1.310, 3.404)] and [2.331, 95%(1.453, 3.739)], respectively.
CONCLUSION
Serum low HDL/LDL and t-PINP /β-CTX are independent risk factors for OPVF in elderly women, and have good predictive value for OPVF risk.
Topics: Humans; Female; Aged; Osteoporotic Fractures; Spinal Fractures; Lipoproteins, LDL; Middle Aged; Retrospective Studies; Lipoproteins, HDL; Procollagen; Peptide Fragments; Collagen Type I; Aged, 80 and over; Peptides; Osteocalcin
PubMed: 38910378
DOI: 10.12200/j.issn.1003-0034.20221194 -
Journal of Dairy Science Jun 2024Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery...
Changes in Rumen Epithelial Morphology and Transcriptome, Rumen Metabolome, and Blood Biochemical Parameters in Lactating Dairy Cows with Subacute Rumen Acidosis Following Rumen Content Transplantation.
Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of subacute ruminal acidosis (SARA) remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum/basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEGs) were identified between the 2 groups. Enrichment analysis showed that the DEGs were significantly enriched in 11 Gene Ontology biological processes and 14 KEGG pathways. The DEGs corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino sugar and nucleotide metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino sugar and nucleotide sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.
PubMed: 38908691
DOI: 10.3168/jds.2024-24694 -
Plant Physiology and Biochemistry : PPB Jun 2024Low-temperature events are one of the leading environmental cues that considerably reduce plant growth and shift species biodiversity. Hydrogen peroxide (HO) is a...
Physiological and molecular analysis of pitaya (Hylocereus polyrhizus) reveal up-regulation of secondary metabolites, nitric oxide, antioxidant defense system, and expression of responsive genes under low-temperature stress by the pre-treatment of hydrogen peroxide.
Low-temperature events are one of the leading environmental cues that considerably reduce plant growth and shift species biodiversity. Hydrogen peroxide (HO) is a signaling molecule that has a distinguished role during unfavorable conditions and shows outstanding perspectives in low-temperature stress. Herein, we elucidated the protective role and regulatory mechanism of HO in alleviating the deleterious effects of low-temperature stress in pitaya plants. Micropropagated pitaya plants were cultured in Murashige and Skoog media supplemented with different levels of HO (0, 5, 10, and 20 mM) and then exposed to low-temperature stress (5 °C for 24 h). HO at 10 mM, improved low-temperature stress tolerance by relieving oxidative injuries and ameliorating growth parameters in terms of fresh weight (66.7%), plant length (16.7%), and pigments content viz., chlorophyll a (157.4%), chlorophyll b (209.1%), and carotenoids (225.9%). HO counteracted the low-temperature stress by increasing amino acids (224.7%), soluble proteins (190.5%), and sugars (126.6%). Simultaneously, secondary metabolites like ascorbic acid (ASA), anthocyanins, phenolics, flavonoids, total antioxidant (TOA), and proline were also up-regulated by HO (104.9%, 128.8%, 166.3%, 141.4%, and 436.4%, respectively). These results corresponded to the stimulative role triggered by HO in boosting the activities of catalase (22.4%), ascorbate peroxidase (20.7%), superoxide dismutase (88.4%), polyphenol oxidase (60.7%), soluble peroxidase (23.8%), and phenylalanine ammonia-lyase (57.1%) as well as the expression level of HpCAT, HpAPX, HpSOD, HpPPO, and HpPAL genes, which may help to moderate low-temperature stress. In conclusion, our findings stipulate new insights into the mechanisms by which HO regulates low-temperature stress tolerance in pitaya plants.
PubMed: 38908352
DOI: 10.1016/j.plaphy.2024.108840 -
Water Research Jun 2024Various pretreatments are commonly adopted to facilitate dissolved organic matter (DOM) release from waste activated sludge (WAS) for high-valued volatile fatty acids...
Various pretreatments are commonly adopted to facilitate dissolved organic matter (DOM) release from waste activated sludge (WAS) for high-valued volatile fatty acids (VFAs) promotion, while the interplay impact of DOM dynamics transformation on microbial population and metabolic function traits is poorly understood. This work constructed "DOM-microorganisms-metabolism-VFAs" symbiotic ecologic networks to disclose how DOM dynamics variation intricately interacts with bacterial community networks, assembly processes, and microbial traits during WAS fermentation. The distribution of DOM was altered by different pretreatments, triggering the release of easily biodegradable compounds (O/C ratio > 0.3) and protein-like substance. This alteration greatly improved the substrates biodegradability (higher biological index) and upregulated microbial metabolism capacity (e.g., hydrolysis and fatty acid synthesis). In turn, microbial activity modifications augment substance metabolism level and expedite the conversion of highly reactive compounds (proteins-like DOM) to VFAs, leading to 1.6-4.2 fold rise in VFAs generation. Strong correlations were found between proteins-like DOM and topological properties of DOM-bacteria associations, suggesting that high DOM availability leads to more intricate ecological networks. A change in the way communities assemble, shifting from stronger uniform selection in pH10 and USp reactors to increased randomness in heat reactor, was linked to DOM composition alterations. The ecologic networks further revealed metabolic synergy between hydrolytic-acidogenic bacteria (e.g., Bacteroidota and Firmicutes) and biodegradable DOM (e.g., proteins and amino sugars) leading to higher VFAs generation. This study provides a deeper knowledge of the inherent connections between DOM and microbial traits for efficient VFAs biosynthesis during WAS anaerobic fermentation, offering valuable insights for effective WAS pretreatment strategies.
PubMed: 38908316
DOI: 10.1016/j.watres.2024.121930 -
Carbohydrate Research Jun 2024Non-enzymatic cascade reactions between amines and reducing sugars are known as Maillard reaction. The late phase of these reactions consists of advanced glycation end...
Non-enzymatic cascade reactions between amines and reducing sugars are known as Maillard reaction. The late phase of these reactions consists of advanced glycation end products (AGEs), which have been implicated in the pathogenesis of numerous human diseases. Recent evidence suggests that galectin-3 acts as a receptor for AGEs and some early products of the Maillard reaction. The early phase of the Maillard reaction, which consists of 1-amino-1-deoxyketoses (Amadori compounds) and 2-amino-2-deoxyaldoses (Heyns compounds), was the subject of our study. The binding interactions between galectin-3 and the Amadori and Heyns compounds of leucine-enkephalin (YGGFL), leucine-enkephalin methyl ester (YGGFL-OMe), truncated enkephalin (YGG and Y) and tetrapeptide (LSKL) were measured using the AlphaScreen competitive binding assay. The affinity of galectin-3 for Amadori and Heyns compounds depends on both the sugar moiety and the amino acid sequence of the model compounds. The best results were obtained with Leu-enkephalin derivatives of Amadori (IC = 6.06 μm) and Heyns (IC = 8.6 μm) compound, respectively.
PubMed: 38908217
DOI: 10.1016/j.carres.2024.109195