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Yuan Yan Sin Laurel L. Ballantyne Kamalika Mukherjee Tim St. Amand Lianna Kyriakopoulou Andreas Schulze Colin D. Funk 《PloS one》2013,8(11)
Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing “floxed” Arg1 mice with CreERT2 mice. The resulting mice (Arg-Cre) die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency. 相似文献
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Sumit Mukherjee Wei Xu Fong‐Fu Hsu Jigesh Patel Juyang Huang Kai Zhang 《Molecular microbiology》2019,111(1):65-81
Limited knowledge on the exact functions of ergostane‐based sterols has hampered the application of sterol synthesis inhibitors against trypanosomatid parasites. Sterol methyltransferase (SMT) is directly involved in the synthesis of parasite‐specific C24‐methylated sterols, including ergosterol and 5‐dehydroepisterol. While pharmacological studies hint at its potential as a drug target against trypanosomatids, direct evidence for the cellular function and essentiality of SMT is lacking. Here, we characterized the SMT knockout mutants and their complemented strains in Leishmania major, the causative agent for cutaneous leishmaniasis. Deletion of SMT alleles led to a complete loss of C24‐methylated sterols, which were replaced by cholestane‐based sterols. SMT‐null mutants were fully viable and replicative in culture but showed increased sensitivity to sphingolipid synthesis inhibition. They were not particularly vulnerable to heat, acidic pH, nitrosative or oxidative stress, yet exhibited high mitochondrial membrane potential and increased superoxide generation indicating altered physiology of the mitochondria. Despite possessing high levels of GPI‐anchored glycoconjugates, SMT‐null mutants showed significantly attenuated virulence in mice. In total, our study reveals that the biosynthesis of ergostane‐based sterols is crucial for the proper function of mitochondria and the proliferation of Leishmania parasites in mammals. 相似文献
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Rajendra Prasad Sahu Sufia K. Kazy Himadri Bose Sunanda Mandal Avishek Dutta Anumeha Saha Sukanta Roy Srimanti Dutta Gupta Abhijit Mukherjee Pinaki Sar 《Environmental microbiology》2022,24(6):2837-2853
Deep terrestrial subsurface represents a huge repository of global prokaryotic biomass. Given its vastness and importance, microbial life within the deep subsurface continental crust remains under-represented in global studies. We characterize the microbial communities of deep, extreme and oligotrophic realm hosted by crystalline Archaean granitic rocks underneath the Deccan Traps, through sampling via 3000 m deep scientific borehole at Koyna, India through metagenomics, amplicon sequencing and cultivation-based analyses. Gene sequences 16S rRNA (7.37 × 106) show considerable bacterial diversity and the existence of a core microbiome (5724 operational taxonomic units conserved out of a total 118,064 OTUs) across the depths. Relative abundance of different taxa of core microbiome varies with depth in response to prevailing lithology and geochemistry. Co-occurrence network analysis and cultivation attempt to elucidate close interactions among autotrophic and organotrophic bacteria. Shotgun metagenomics reveals a major role of autotrophic carbon fixation via the Wood–Ljungdahl pathway and genes responsible for energy and carbon metabolism. Deeper analysis suggests the existence of an ‘acetate switch’, coordinating biosynthesis and cellular homeostasis. We conclude that the microbial life in the nutrient- and energy-limited deep granitic crust is constrained by the depth and managed by a few core members via a close interplay between autotrophy and organotrophy. 相似文献
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Hydrobiologia - Differences in habitat and diet between species are often associated with morphological differences. Habitat and trophic adaptation have therefore been proposed as important drivers... 相似文献
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The occurrence of biofouling in MFC can cause severe problems such as hindering proton transfer and increasing the ohmic and charge transfer resistance of cathodes, which results in a rapid decline in performance of MFC. This is one of the main reasons why scaling-up of MFCs has not yet been successfully accomplished. The present review article is a wide-ranging attempt to provide insights to the biofouling mechanisms on surfaces of MFC, mainly on proton exchange membranes and cathodes, and their effects on performance of MFC based on theoretical and practical evidence. Various biofouling mitigation techniques for membranes are discussed, including preparation of antifouling composite membranes, modification of the physical and chemical properties of existing membranes, and coating with antifouling agents. For cathodes of MFC, use of Ag nanoparticles, Ag-based composite nanoparticles, and antifouling chemicals is outlined in considerable detail. Finally, prospective techniques for mitigation of biofouling are discussed, which have not been given much previous attention in the field of MFC research. This article will help to enhance understanding of the severity of biofouling issues in MFCs and provides up-to-date solutions. It will be beneficial for scientific communities for further strengthening MFC research and will also help in progressing this cutting-edge technology to scale-up, using the most efficient methods as described here. 相似文献