In microbial engineering, heat stress is an important environmental factor modulating cell growth, metabolic flux distribution and the synthesis of target products.Yarrowia lipolytica, as a GARS (generally recognized as safe) nonconventional yeast, has been widely used in the food industry, especially as the host of erythritol production. Biomanufacturing economics is limited by the high operational cost of cooling energy in large-scale fermentation. It is of great significance to select thermotolerant Y. lipolytica to reduce the cooling cost and elucidate the heatresistant mechanism at molecular level. For this purpose, we performed adaptive evolution and obtained a thermotolerant strain named Y. lipolytica BBE-18. Transcriptome analysis allows us to identify four genes in thiamine metabolism pathway that are responsible for the complicated thermotolerant phenotype. The heatresistant phenotype was validated with the model strain Y. lipolytica Po1f by overexpression of single and combined genes. Then, conferring the thermotolerant phenotype to the wild-type Y. lipolytica BBE-17 enable the strain to produce threetimes more erythritol of the control strain with 3°C higher than optimal cultivation temperature. To our knowledge, this is the first report on engineering heat-resistant phenotype to improve the erythritol production in Y. lipolytica. However, due to the increase of culture temperature, a large amount of adenosine triphosphate is consumed to ensure the life activities of Y. lipolytica which limits the potential of cell synthetic products to a certain extent. Even so, this study provides a reference for Y. lipolytica to produce other products under high temperature.
LAMP2 (lysosomal associated membrane protein 2) is one of the major protein components of the lysosomal membrane. There currently exist three LAMP2 isoforms, LAMP2A, LAMP2B and LAMP2C, and they vary in distribution and function. LAMP2A serves as a receptor and channel for transporting cytosolic proteins in a process called chaperone-mediated autophagy (CMA). LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and is one of the components of exosome membranes. LAMP2C is primarily implicated in a novel type of autophagy in which nucleic acids are taken up into lysosomes for degradation. In this review, the current evidence for the function of each LAMP2 isoform in various pathophysiological processes and human diseases, as well as their possible mechanisms, are comprehensively summarized. We discuss the evolutionary patterns of the three isoforms in vertebrates and provide technical guidance on investigating these isoforms. We are also concerned with the newly arising questions in this particular research area that remain unanswered. Advances in the functions of the three LAMP2 isoforms will uncover new links between lysosomal dysfunction, autophagy and human diseases.
Abbreviation:
ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: autophagy related 14; AVSF: autophagic vacuoles with unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: chaperone-mediated autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript 4; ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem cells; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/β-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma stem cells; HCC: hepatocellular carcinoma; HD: Huntington disease; HSCs: hematopoietic stem cells; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; IL3: interleukin 3; IR: ischemia-reperfusion; LAMP2: lysosomal associated membrane protein 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase 2; MA: macroautophagy; MHC: major histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver disease; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NLRP3: NLR family pyrin domain containing 3; PARK7: Parkinsonism associated deglycase; PD: Parkinson disease; PEA15/PED: proliferation and apoptosis adaptor protein 15; PKM/PKM2: pyruvate kinase M1/2; RA: rheumatoid arthritis; RARA: retinoic acid receptor alpha; RCAN1: regulator of calcineurin 1; RCC: renal cell carcinoma; RDA: RNautophagy and DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase 3; SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin C-terminal hydrolase L1; VAMP8: vesicle associated membrane protein 8
This paper is about study to increase the γ-PGA yield by developing new methods. The effect of various amino acids on production of γ-PGA by Bacillus subtilis Z15 was investigated. The γ-PGA yield was increased 23.18%, 12.15% and 31.46%, respectively, with 3 g/L aspartic acid (0 h), 1.5 g/L phenylalanine (0 h) and 7 g/L glutamic acid (24 h). Additonally, crude extract of glutamic acid after isoelectric crystallization (CEGA)could be a replacement for glutamate for γ-PGA production. Then, response surface methodology (RSM) was used for further optimization. The final media ingredient of amino acids were obtained as follow: CEGA 9 g/L, aspartic acid 4 g/L, phenylalanine 1.55 g/L. By applying this receipt in 5-L bioreactor, the γ-PGA yield reached 42.92 ± 0.23 g/L after 44 h, which is 63.1% higher than the control without amino acids for production. In addition, amino acids could shorten the lag phase and the average fermentation time (44 h versus 48 h). Fermentation with amino acids addition can be an positive option for γ-PGA production.
Objective: The potential correlation between the ε2/ε3/ε4 variants of the ApoE (Apolipoprotein E) gene and the odds of mesial temporal lobe epilepsy was investigated.
Methods: The database searching for eligible studies was performed in October 2020. A series of pooling analyses were conducted.
Results: We enrolled a total of twelve case-control studies for pooling. Within the pooling analysis of ε4, there was an in- creased risk of mesial temporal lobe epilepsy in cases under the models of carrier ε4 vs. ε3, ε3ε4 vs. ε3ε3, and ε3ε4+ε4ε4 vs. ε3ε3 [P < 0.05, odds ratio (OR) > 1], compared with controls. Moreover, we observed similar positive results in the subgroup analyses of “China” and “Population-based control” under the genetic models of ε4 (P < 0.05, OR > 1). Nevertheless, we did not detect the significant difference between the mesial temporal lobe epilepsy cases and controls in the pooling analyses of ε2 (all P > 0.05).
Conclusion: The ε3ε4 genotype of ApoE seems to be linked to the risk of mesial temporal lobe epilepsy for patients in China. More sample sizes are required to confirm the potential role of ApoE isoforms in the susceptibility to diverse types of epilepsy from different origins.
Keywords: Epilepsy; ApoE; isoforms; susceptibility.
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