المؤلفون: Grelet, C, Larsen, T, Crowe, M A, Wathes, D C, Ferris, C P, Ingvartsen, K L, Marchitelli, C, Becker, F, Vanlierde, A, Leblois, J, Schuler, U, Auer, F J, Köck, A, Dale, L, Sölkner, J, Christophe, O, Hummel, J, Mensching, A, Pierna, J A Fernández, Soyeurt, H, Calmels, M, Reding, R, Gelé, M, Chen, Y, Gengler, N, Dehareng, F

المصدر: Grelet , C , Larsen , T , Crowe , M A , Wathes , D C , Ferris , C P , Ingvartsen , K L , Marchitelli , C , Becker , F , Vanlierde , A , Leblois , J , Schuler , U , Auer , F J , Köck , A , Dale , L , Sölkner , J , Christophe , O , Hummel , J , Mensching , A , Pierna , J A F , Soyeurt , H , Calmels , M , Reding , R , Gelé , M , ....

مصطلحات موضوعية: Fourier transform mid-infrared spectrometry, fertility, ketosis, mastitis, negative energy balance, Isocitrates, Acetylglucosaminidase, Citrates, Glucose, 3-Hydroxybutyric Acid, Cattle Diseases, L-Lactate Dehydrogenase, Animals, Cattle, Biomarkers, Mastitis/veterinary, Female, Ketosis/diagnosis, Progesterone, Citric Acid, Acetone, Milk

الوصف: At the individual cow level, sub-optimum fertility, mastitis, negative energy balance and ketosis are major issues in dairy farming. These problems are widespread on dairy farms and have an important economic impact. The objectives of this study were: 1) to assess the potential of milk Mid Infrared (MIR) spectra to predict key biomarkers of energy deficit (citrate, isocitrate, glucose-6P, free glucose), ketosis (BHB and acetone), mastitis (NAGase and LDH), and fertility (progesterone); 2) to test alternative methodologies to partial least square regression (PLS) to better account for the specific asymmetric distribution of the biomarkers; and 3) to create robust models by merging large data sets from 5 international or national projects. Benefiting from this international collaboration, the data set comprised a total of 9,143 milk samples from 3,758 cows located in 589 herds across 10 countries and represented 7 breeds. The samples were analyzed by reference chemistry for biomarker contents while the MIR analyses were performed on 30 instruments from different models and brands, with spectra harmonized into a common format. Four quantitative methodologies were evaluated to address the strongly skewed distribution of some biomarkers. PLS was used as the reference basis, and compared with a random modification of distribution associated with PLS (Random-downsampling-PLS), an optimized modification of distribution associated with PLS (KennardStone-downsampling-PLS) and Support Vector Machine (SVM). When the ability of MIR to predict biomarkers was too low for quantification, different qualitative methodologies were tested to discriminate low vs high values of biomarkers. For each biomarker, 20% of the herds were randomly removed within all countries to be used as the validation data set. The remaining 80% of herds were used as the calibration data set. In calibration, the 3 alternative methodologies outperform the PLS performances for the majority of biomarkers. However, in the external herd validation, PLS ...

العلاقة: https://pure.au.dk/portal/en/publications/ff114b22-f823-48e0-9bd4-629ac0518c0cTest

الإتاحة: https://doi.org/10.3168/jds.2023-23843Test
https://pure.au.dk/portal/en/publications/ff114b22-f823-48e0-9bd4-629ac0518c0cTest
http://www.scopus.com/inward/record.url?scp=85186745391&partnerID=8YFLogxKTest

المؤلفون: Taylor, Savannah J, Winter, Maria G, Gillis, Caroline C, Silva, Laice Alves da, Dobbins, Amanda L, Muramatsu, Matthew K, Jimenez, Angel G, Chanin, Rachael B, Spiga, Luisella, Llano, Ernesto M, Rojas, Vivian K, Kim, Jiwoong, Santos, Renato L, Zhu, Wenhan, Winter, Sebastian E

المصدر: Microbiome. 10(1)

مصطلحات موضوعية: Microbiology, Biological Sciences, Infectious Diseases, Autoimmune Disease, Vaccine Related, Crohn's Disease, Digestive Diseases, Nutrition, Biodefense, Inflammatory Bowel Disease, Prevention, 2.1 Biological and endogenous factors, Aetiology, Infection, Oral and gastrointestinal, Good Health and Well Being, Mice, Animals, Dysbiosis, Gastrointestinal Microbiome, Escherichia coli, Lactic Acid, Lactate Dehydrogenase 5, Mice, Inbred C57BL, Inflammation, Colitis, Enterobacteriaceae, Host-microbe interactions, Lactate metabolism, Gut inflammation, Ecology, Medical Microbiology, Evolutionary biology

الوصف: BackgroundIntestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology.ResultsWe investigated microbial and host lactate metabolism in murine models of infectious and non-infectious colitis. During inflammation-associated dysbiosis, lactate levels in the gut lumen increased. The disease-associated spike in lactate availability was significantly reduced in mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells. Commensal E. coli and pathogenic Salmonella, representative Enterobacteriaceae family members, utilized lactate via the respiratory L-lactate dehydrogenase LldD to increase fitness. Furthermore, mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells exhibited lower levels of inflammation in a model of non-infectious colitis.ConclusionsThe release of lactate by intestinal epithelial cells during gut inflammation impacts the metabolism of gut-associated microbial communities. These findings suggest that during intestinal inflammation and dysbiosis, changes in metabolite availability can perpetuate colitis-associated disturbances of microbiota composition. Video Abstract.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3t65c4gpTest

المؤلفون: Kaushik, Deepak Kumar, Bhattacharya, Anindita, Mirzaei, Reza, Rawji, Khalil S, Ahn, Younghee, Rho, Jong M, Yong, V Wee

المصدر: Journal of Clinical Investigation. 129(8)

مصطلحات موضوعية: Multiple Sclerosis, Neurodegenerative, Brain Disorders, Neurosciences, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Basigin, Brain, Cell Movement, Encephalomyelitis, Autoimmune, Experimental, Female, Glycolysis, L-Lactate Dehydrogenase, Macrophages, Mice, Monocarboxylic Acid Transporters, Muscle Proteins, Autoimmune diseases, Autoimmunity, Glucose metabolism, Metabolism, Medical and Health Sciences, Immunology

الوصف: The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). This penetration likely utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of post-capillary venules are highly glycolytic as manifested by strong expression of lactate dehydrogenase A (LDHA) that converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4) specialized in secreting lactate from glycolytic cells. The functional relevance of glycolysis was confirmed by siRNA-mediated knockdown of LDHA and MCT-4, which decreased lactate secretion and macrophage transmigration. MCT-4 was in turn regulated by EMMPRIN (CD147) as determined through co-expression/co-immunoprecipitation studies, and siRNA-mediated EMMPRIN silencing. The functional relevance of MCT-4/EMMPRIN interaction was affirmed by lower macrophage transmigration in culture using the MCT-4 inhibitor, α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration and the clinical severity of EAE. Relevance to MS was corroborated by the strong expression of MCT-4, EMMPRIN and LDHA in perivascular macrophages in MS brains. These results detail the metabolism of macrophages for transmigration from perivascular cuffs into the CNS parenchyma and identifies CHCA and diet as potential modulators of neuro-inflammation in MS.

الوصول الحر: https://escholarship.org/uc/item/38b3s2kpTest

المؤلفون: Liang, Manfei, Hody, Clara, Yammine, Vanessa, Soin, Romuald, Sun, Yuqiu, Lin, Xing, Tian, Xiaoying, Meurs, Romane, Perdrau, Camille, Delacourt, Nadège, Oumalis, Marina, Andris, Fabienne, Conrard, Louise, Kruys, Véronique, Gueydan, Cyril

المصدر: EMBO reports

مصطلحات موضوعية: Sciences bio-médicales et agricoles, Animals, Drosophila melanogaster -- genetics -- metabolism, Hypoxia -- genetics, RNA, Messenger -- genetics -- metabolism, Drosophila -- genetics -- metabolism, Oxygen -- metabolism, 3' Untranslated Regions, L-Lactate Dehydrogenase -- genetics -- metabolism, Protein Biosynthesis, 3′ untranslated region, development, gene expression, lactate dehydrogenase, translation

الوصف: Hypoxia induces profound modifications in the gene expression program of eukaryotic cells due to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One significant consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. Drosophila melanogaster is strongly resistant to oxygen fluctuations; however, the mechanisms allowing specific mRNA to be translated into hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated into hypoxia by a mechanism involving a CA-rich motif present in its 3' untranslated region. Furthermore, we identified the cap-binding protein eIF4EHP as a main factor involved in 3'UTR-dependent translation under hypoxia. In accordance with this observation, we show that eIF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to LDH production and Drosophila adaptation to oxygen variations. ; SCOPUS: ar.j ; info:eu-repo/semantics/published

وصف الملف: 3 full-text file(s): application/pdf | application/pdf | application/pdf

العلاقة: uri/info:doi/10.15252/embr.202256460; uri/info:pmid/37144276; uri/info:scp/85156118367; uri/info:pmcid/PMC10328074; https://dipot.ulb.ac.be/dspace/bitstream/2013/358142/5/Liang.pdfTest; https://dipot.ulb.ac.be/dspace/bitstream/2013/358142/3/Liang.pdfTest; https://dipot.ulb.ac.be/dspace/bitstream/2013/358142/4/Liang.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/358142Test

الإتاحة: http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/358142Test
https://dipot.ulb.ac.be/dspace/bitstream/2013/358142/5/Liang.pdfTest
https://dipot.ulb.ac.be/dspace/bitstream/2013/358142/3/Liang.pdfTest
https://dipot.ulb.ac.be/dspace/bitstream/2013/358142/4/Liang.pdfTest

المؤلفون: Jelinek, David, Flores, Aimee, Uebelhoer, Melanie, Pasque, Vincent, Plath, Kathrin, Iruela-Arispe, M Luisa, Christofk, Heather R, Lowry, William E, Coller, Hilary A

المصدر: Journal of visualized experiments : JoVE. 2018(136)

مصطلحات موضوعية: Animals, Mice, L-Lactate Dehydrogenase, Biochemistry, Issue 136, Lactate dehydrogenase, in situ, enzymatic activity, mouse skin, metabolism, metabolic map, Stem Cell Research, Biochemistry and Cell Biology, Psychology, Cognitive Sciences

الوصف: Mapping enzymatic activity in space and time is critical for understanding the molecular basis of cell behavior in normal tissue and disease. In situ metabolic activity assays can provide information about the spatial distribution of metabolic activity within a tissue. We provide here a detailed protocol for monitoring the activity of the enzyme lactate dehydrogenase directly in tissue samples. Lactate dehydrogenase is an important determinant of whether consumed glucose will be converted to energy via aerobic or anaerobic glycolysis. A solution containing lactate and NAD is provided to a frozen tissue section. Cells with high lactate dehydrogenase activity will convert the provided lactate to pyruvate, while simultaneously converting provided nicotinamide adenine dinucleotide (NAD) to NADH and a proton, which can be detected based on the reduction of nitrotetrazolium blue to formazan, which is visualized as a blue precipitate. We describe a detailed protocol for monitoring lactate dehydrogenase activity in mouse skin. Applying this protocol, we found that lactate dehydrogenase activity is high in the quiescent hair follicle stem cells within the skin. Applying the protocol to cultured mouse embryonic stem cells revealed higher staining in cultured embryonic stem cells than mouse embryonic fibroblasts. Analysis of freshly isolated mouse aorta revealed staining in smooth muscle cells perpendicular to the aorta. The methodology provided can be used to spatially map the activity of enzymes that generate a proton in frozen or fresh tissue.

الوصول الحر: https://escholarship.org/uc/item/4kx9787cTest

المؤلفون: Flores, Aimee, Schell, John, Krall, Abigail S, Jelinek, David, Miranda, Matilde, Grigorian, Melina, Braas, Daniel, White, Andrew C, Zhou, Jessica L, Graham, Nicholas A, Graeber, Thomas, Seth, Pankaj, Evseenko, Denis, Coller, Hilary A, Rutter, Jared, Christofk, Heather R, Lowry, William E

المصدر: Nature Cell Biology. 19(9)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Aetiology, 2.1 Biological and endogenous factors, Acrylates, Animals, Anion Transport Proteins, Cell Proliferation, Cellular Senescence, Female, Genotype, Glycolysis, Hair Follicle, Isoenzymes, L-Lactate Dehydrogenase, Lactate Dehydrogenase 5, Lactic Acid, Male, Mice, Inbred C57BL, Mice, Knockout, Mitochondrial Membrane Transport Proteins, Monocarboxylic Acid Transporters, Phenotype, Proto-Oncogene Proteins c-myc, Signal Transduction, Stem Cells, Time Factors, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology

الوصف: Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1q76t50gTest

المؤلفون: Gillis, Caroline C, Winter, Maria G, Chanin, Rachael B, Zhu, Wenhan, Spiga, Luisella, Winter, Sebastian E

المصدر: Infection and Immunity. 87(4)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Microbiology, Clinical Sciences, Medical Microbiology, Emerging Infectious Diseases, Prevention, Genetics, Digestive Diseases, Infectious Diseases, Biodefense, Foodborne Illness, Vaccine Related, Aetiology, 2.1 Biological and endogenous factors, Infection, Animals, Bacterial Proteins, Female, Gene Expression Regulation, Bacterial, Humans, Intestinal Mucosa, L-Lactate Dehydrogenase, Lactic Acid, Male, Mice, Mice, Inbred C57BL, Oxygen, Salmonella Infections, Salmonella typhimurium, Transcription Factors, Salmonella, gut inflammation, microbiome, Agricultural and Veterinary Sciences, Medical and Health Sciences, Immunology, Medical microbiology

الوصف: During Salmonella enterica serovar Typhimurium infection, host inflammation alters the metabolic environment of the gut lumen to favor the outgrowth of the pathogen at the expense of the microbiota. Inflammation-driven changes in host cell metabolism lead to the release of l-lactate and molecular oxygen from the tissue into the gut lumen. Salmonella utilizes lactate as an electron donor in conjunction with oxygen as the terminal electron acceptor to support gut colonization. Here, we investigated transcriptional regulation of the respiratory l-lactate dehydrogenase LldD in vitro and in mouse models of Salmonella infection. The two-component system ArcAB repressed transcription of l-lactate utilization genes under anaerobic conditions in vitro The ArcAB-mediated repression of lldD transcription was relieved under microaerobic conditions. Transcription of lldD was induced by l-lactate but not d-lactate. A mutant lacking the regulatory protein LldR failed to induce lldD transcription in response to l-lactate. Furthermore, the lldR mutant exhibited reduced transcription of l-lactate utilization genes and impaired fitness in murine models of infection. These data provide evidence that the host-derived metabolites oxygen and l-lactate serve as cues for Salmonella to regulate lactate oxidation metabolism on a transcriptional level.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/78f1w7dhTest

المؤلفون: Flores, A, Sandoval-Gonzalez, S, Takahashi, R, Krall, A, Sathe, L, Wei, L, Radu, C, Joly, JH, Graham, NA, Christofk, HR, Lowry, WE

المصدر: Nature communications. 10(1)

مصطلحات موضوعية: Animals, Mice, Transgenic, Mice, Carcinoma, Squamous Cell, Neoplasms, Experimental, L-Lactate Dehydrogenase, Enzyme Induction, Female, Male, Transgenic, Carcinoma, Squamous Cell, Neoplasms, Experimental

الوصف: Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/69h6t8v9Test

المؤلفون: Leal, Michaiah J, Clark, Brigitte E, Van Eenennaam, Joel P, Schreier, Andrea D, Todgham, Anne E

مصطلحات موضوعية: Acclimatization, Animals, Blood Glucose, Citrate (si)-Synthase, Female, Fish Proteins, Fishes, Gills, Hydrocortisone, Immunity, Innate, L-Lactate Dehydrogenase, Lactic Acid, Male, Ploidies, Principal Component Analysis, Stress, Physiological, Temperature, Sturgeon, Polyploidy, Generalized stress response, Immunity, Temperature acclimation, Metabolism, Biochemistry and Cell Biology, Physiology, Zoology

الوصف: Previous studies suggest fish with additional copies of their genome (polyploids) underperform in suboptimal conditions and may be more susceptible to stress and disease. The objective of this study was to determine the role ploidy plays in the physiological response of white sturgeon to chronically elevated water temperatures. White sturgeon of two ploidies (8 N and 10 N) were acclimated to ambient (18 °C) and warm (22 °C) water. Bioindices of stress (plasma cortisol, glucose and lactate, total erythrocyte count, hematocrit, hemoglobin, mean erythrocyte volume, mean erythrocyte hemoglobin, and mean erythrocyte hemoglobin concentration), immunity (respiratory burst, plasma lysozyme, and total leukocyte count), and cellular metabolic capacity (lactate dehydrogenase and citrate synthase activity) were measured before and after a 6-week acclimation period. Both ploidies appear comparable in their constitutive immune and stress parameters and respond similarly to warming. Hematological indices suggest 8 N and 10 N sturgeon are similar in oxygen carrying capacity; however, differences in enzyme activity between ploidies indicate that 10 N sturgeon may have a lower cellular aerobic capacity. Our results have implications for the screening and management of ploidy on white sturgeon farms and hatcheries, as the differences between ploidies may affect 10 N sturgeon performance at elevated water temperatures. Further research is needed to elucidate the differences in inducible stress and immune responses and metabolism of white sturgeon of different ploidies.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5gw0f8wvTest

المؤلفون: Guo, Gang, Zhu, Yongjie, Wu, Zhenru, Ji, Hongjie, Lu, Xufeng, Zhou, Yongjie, Li, Yuanmin, Cao, Xiaoyue, Lu, Yanrong, Talbot, Prue, Liao, Jiayu, Shi, Yujun, Bu, Hong

المصدر: Journal of cellular and molecular medicine. 22(9)

مصطلحات موضوعية: Monocytes, Animals, Macaca mulatta, Mice, Hepatic Encephalopathy, Liver Failure, Acute, Disease Progression, Amanitins, L-Lactate Dehydrogenase, Alanine Transaminase, Aspartate Aminotransferases, Lipopolysaccharides, Interleukin-6, Cytokines, Liver Function Tests, Gene Expression, acute liver failure, interleukin-6, monocyte, non-human primate, Liver Failure, Acute, Biochemistry & Molecular Biology, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Clinical Sciences

الوصف: Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin-induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL-6 increase was the most rapid and drastic. Interestingly, we found that IL-6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte-derived IL-6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6xb2b7qrTest