Amino Acid
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2021 ◽  
Phillip Zhu ◽  
Rachel Franklin ◽  
Amber Vogel ◽  
Stanislau Stanisheuski ◽  
Patrick Reardon ◽  

Installing stable, functional mimics of phosphorylated amino acids into proteins offers a powerful strategy to study protein regulation. Previously, a genetic code expansion (GCE) system was developed to translationally install non-hydrolyzable phosphoserine (nhpSer), with the γ-oxygen replaced with carbon, but it has seen limited usage. Here, we achieve a 40-fold improvement in this system by engineering into Escherichia coli a biosynthetic pathway that produces nhpSer from the central metabolite phosphoenolpyruvate. Using this "PermaPhosSer" system — an autonomous 21-amino acid E. coli expression system for incorporating nhpSer into target proteins — we show that nhpSer faithfully mimics the effects of phosphoserine in three stringent test cases: promoting 14-3-3/client complexation, disrupting 14-3-3 dimers, and activating GSK3-β phosphorylation of the SARS-CoV-2 nucleocapsid protein. This facile access to nhpSer containing proteins should allow nhpSer to replace Asp and Glu as the go-to pSer phosphomimetic for proteins produced in E. coli.

Radiation ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 277-289
Shiyao Liao ◽  
Zonghuan Liu ◽  
Weijia Zhi ◽  
Lizhen Ma ◽  
Hongmei Zhou ◽  

Background: To investigate the effects of different levels of microwave radiation on learning and memory in Wistar rats and explore the underlying mechanisms of N-methyl-D-aspartate receptor (NMDAR/NR) and Brain-derived neurotropic factor (BDNF); Methods: A total of 140 Wistar rats were exposed to microwave radiation levels of 0, 10, 30 or 50 mW/cm2 for 6 min. Morris Water Maze Test, high-performance liquid chromatography, Transmission Electron Microscope and Western blotting were used; Results: The 30 and 50 mW/cm2 groups exhibited longer average escape latencies and fewer platform crossings than the 0 mW/cm2 group from 6 h to 3 d after microwave radiation. Alterations in the amino acid neurotransmitters of the hippocampi were shown at 6 h, 3 d and 7 d after exposure to 10, 30 or 50 mW/cm2 microwave radiation. The length and width of the Postsynaptic density were increased. The expression of NR1, NR2A and NR2B increased from day 1 to day 7; Postsynaptic density protein-95 and cortactin expression increased from day 3 to day 7; BDNF and Tyrosine kinase receptor B (TrkB) expression increased between 6 h and 1 d after 30 mW/cm2 microwave radiation exposure, but they decreased after 50mW/cm2 exposure. Conclusions: Microwave exposure (30 or 50 mW/cm2, for 6 min) may cause abnormalities in neurotransmitter release and synaptic structures, resulting in impaired learning and memory; BDNF and NMDAR-related signaling molecules might contribute differently to these alterations.

2021 ◽  
Vol 21 (1) ◽  
Xintong Lv ◽  
Libo Wang ◽  
Zhuang Pi ◽  
Chunyan Zhang

Abstract Background Langerhans cell histiocytosis (LCH) is a heterogeneous disease with diverse clinical manifestations. Abdominal organ involvement is rare. Early diagnosis and active treatment are needed. The purpose of this article is to enable readers to have a better knowledge of LCH and prevent misdiagnosis. Case presentation A 2-month-old boy had diarrhea, hematochezia, and a rash, and was diagnosed as having a cow milk protein allergy (CMPA). He was given an amino acid-based formula, but there was no sign of improvement in his condition. The patient then had a skin biopsy and was diagnosed as having multisystem Langerhans cell histiocytosis (MS-LCH). The general condition of the child deteriorated after the first two doses of chemotherapy, and the child died. Conclusions MS-LCH is a protracted and progressive condition with poor prognosis. Early diagnosis and treatment are essential for survival. If a child has chronic diarrhea and hematochezia in the presence of a characteristic rash, the pediatrician should consider the possibility of this disease to avoid misdiagnosis.

2021 ◽  
Vol 4 (1) ◽  
Qiupeng Peng ◽  
Bingjia Yan ◽  
Fangyi Li ◽  
Ming Lang ◽  
Bei Zhang ◽  

AbstractAlthough utilization of fluorine compounds has a long history, synthesis of chiral fluorinated amino acid derivatives with structural diversity and high stereoselectivity is still very appealing and challenging. Here, we report a biomimetic study of enantioselective [1,3]-proton shift of β,β-difluoro-α-imine amides catalyzed by chiral quinine derivatives. A wide range of corresponding β,β-difluoro-α-amino amides were achieved in good yields with high enantioselectivities. The optically pure β,β-difluoro-α-amino acid derivatives were further obtained, which have high application values in the synthesis of fluoro peptides, fluoro amino alcohols and other valuable fluorine-containing molecules.

2021 ◽  
Vol 22 (21) ◽  
pp. 11427
Chunchen Liu ◽  
Linbao Ji ◽  
Jinhua Hu ◽  
Ying Zhao ◽  
Lee J. Johnston ◽  

Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated with various diseases, such as cancer, neurodegeneration, aging, and obesity. Autophagy cannot be directly controlled and dynamic amino acid levels are sufficient to regulate autophagy. To date, arginine, leucine, glutamine, and methionine are widely reported functional amino acids that regulate autophagy. As a signal relay station, mammalian target of rapamycin complex 1 (mTORC1) turns various amino acid signals into autophagy signaling pathways for functional amino acids. Deficiency or supplementation of functional amino acids can immediately regulate autophagy and is associated with autophagy-related disease. This review summarizes the mechanisms currently involved in autophagy and amino acid sensing, diverse signal transduction among functional amino acids and autophagy, and the therapeutic appeal of amino acids to autophagy-related diseases. We aim to provide a comprehensive overview of the mechanisms of amino acid regulation of autophagy and the role of functional amino acids in clinical autophagy-related diseases and to further convert these mechanisms into feasible therapeutic applications.

2021 ◽  
Vol 4 (2) ◽  
Iryna Romash

When the structure of the connective tissue is disturbed, the probability of developing pathology of the internal organs increases. The gastrointestinal tract is one of the systems that is most often involved in the pathological process in the case of such disorders. Due to its mesenchymal origin, the esophagus is one of the first to suffer. Normalization of mineral metabolism, correction of immunological and bioenergetic status are the main tasks in the treatment of such patients. Therapy with magnesium drugs, vitamins, anabolic drugs, ?-blockers, aldosterone antagonists, and amino acid drugs should also be used for this purpose. Patients in this group should also take drugs that contain vitamin D3

Marine Drugs ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. 600
Lu-Lu Guo ◽  
Shao-Lu Wang ◽  
Fang-Chao Zhu ◽  
Feng Xue ◽  
Li-Sheng He

Crustins are widely distributed among different crustacean groups. They are characterized by a whey acidic protein (WAP) domain, and most examined Crustins show activity against Gram-positive bacteria. This study reports two Crustins, Al-crus 3 and Al-crus 7, from hydrothermal vent shrimp, Alvinocaris longirostris. Al-crus 3 and Al-crus 7 belong to Crustin Type IIa, with a similarity of about 51% at amino acid level. Antibacterial assays showed that Al-crus 3 mainly displayed activity against Gram-positive bacteria with MIC50 values of 10–25 μM. However, Al-crus 7 not only displayed activity against Gram-positive bacteria but also against Gram-negative bacteria Imipenem-resistant Acinetobacter baumannii, in a sensitive manner. Notably, in the effective antibacterial spectrum, Methicillin-sensitive Staphylococcus aureus, Escherichia coli (ESBLs) and Imipenem-resistant A. baumannii were drug-resistant pathogens. Narrowing down the sequence to the WAP domain, Al-crusWAP 3 and Al-crusWAP 7 demonstrated antibacterial activities but were weak. Additionally, the effects on bacteria did not significantly change after they were maintained at room temperature for 48 h. This indicated that Al-crus 3 and Al-crus 7 were relatively stable and convenient for transportation. Altogether, this study reported two new Crustins with specific characteristics. In particular, Al-crus 7 inhibited Gram-negative imipenem-resistant A. baumannii.

2021 ◽  
Vol 12 ◽  
Ruikai Jia ◽  
Min Huang ◽  
Lichun Qian ◽  
Xiaoye Yan ◽  
Qing Lv ◽  

Obesity, especially central obesity, is a strong risk factor for developing type 2 diabetes (T2D). However, the mechanism underlying the progression from central obesity to T2D remains unknown. Therefore, we analyzed the gut microbial profiles of central obese individuals with or without T2D from a Chinese population. Here we reported both the microbial compositional and gene functional alterations during the progression from central obesity to T2D. Several opportunistic pathogens were enriched in obese T2D patients. We also characterized thousands of genes involved in sugar and amino acid metabolism whose abundance were significantly depleted in obese T2D group. Moreover, the abundance of those genes was negatively associated with plasma glycemia level and percentage of individuals with impaired plasma glucose status. Therefore, our study indicates that the abundance of those depleted genes can be used as a potential biomarker to identify central obese individuals with high risks of developing T2D.

2021 ◽  
Ying Cui ◽  
Li Zou ◽  
Qian Ye ◽  
Dandan Li ◽  
Huiming Wu ◽  

Abstract Objective The changes of microbial community in pregnant women, let alone those of patients with recurrent spontaneous abortion (RSA), remain unclear. We analyzed the differences of gut mircobiota (GM) between RSA patients and pregnant women to find the possible mechanism of RSA. MethodsWe enrolled 30 RSA patients (RSA group) and 30 pregnant women who terminated their pregnancy and did not have a history of spontaneous abortion (NR group) in our hospital from June 2020 to August 2020, and fecal samples were obtained to analyze the GM using 16S rDNA V3–V4 sequencing.ResultsAt the phylum level, we found that there is no significant difference in composition of GM between RSA and NR. But at the genus level, compared with NR, Roseburia significantly decreased (P<0.01), and Ruminococcus significantly increased in RSA patients (P<0.05). Further analysis indicated that Klebsiella (P<0.05) was significantly increased, Prevotella.9 (P<0.05) and Roseburia (P<0.05) were significantly decreased in RSA2 group (BMI>23.9 in RSA). Moreover, Agathobacter (P<0.01) was significantly increased in NR2 group (no delivery in NR). Functional prediction indicated that GM may interfere with RSA through membrane transport, carbohydrate metabolism, amino acid metabolism and other pathways.ConclusionDecreased Roseburia in GM of pregnant women maybe related to RSA. Our results provide the basis for in-depth studies of the composition of gut microbial communities in RSA.

2021 ◽  
Yalei Cui ◽  
Hua Liu ◽  
Zimin Gao ◽  
Junying Xu ◽  
Boshuai Liu ◽  

Abstract BackgroundIn recent years, whole-plant corn silage had been widely used in China. Roughage was an important source of nutrition for ruminants and had an important effect on rumen microbiota, which plays an important role in animal growth performance and feed digestion. To better understand the effects of different silages on rumen microbiota, the effects of whole-plant corn silage or corn straw silage on growth performance, rumen fermentation products, and rumen microbiota of Simmental hybrid cattle were studied. Results60 healthy Simmental hybrid cattle were randomly divided into 2 groups with 6 repeats in each group and 5 cattle in each group. They were fed with whole-plant corn silage (WS) diet and corn straw silage (CS) diet respectively. Compared with corn straw silage, whole-plant corn silage significantly increased daily gain and decreased feed-weight ratio of beef cattle. Whole-plant corn silage also decreased the acetic acid in the rumen and the acetate to propionate (A/P) ratio compared with corn straw silage. At the genus level, the relative abundance of Prevotella_1 was significantly increased while the relative abundance of Succinivibrionaceae_UCG-002, Succiniclasticum, norank_f_Bacteroidales_RF16_group, and Ruminococcus_1 was decreased in cattle fed whole-plant corn silage compared with those fed corn straw silage. Prevotella_1 was positively correlated with acetic acid and A/P ratio, Succinivibrionaceae_UCG-002 was positively correlated with propionic acid and butyric acid, and negatively correlated with pH, Succiniclasticum was positively correlated with pH and A/P ratio, and norank_f__F082 and Rikenellaceae_RC9_gut_group were positively correlated with pH, propionic acid and butyric acid. Feeding whole-plant corn silage improved amino acid metabolism, nucleotide metabolism, and metabolism of beef cattle compared with feeding corn straw silage. Correlation analysis between rumen microbiota and metabolic pathways showed that Succinivibrionaceae_UCG-002 was negatively correlated with Carbohydrate Metabolism, Glycan Biosynthesis, and Metabolism, while Prevotellaceae_UCG-003 was positively correlated with Amino Acid Metabolism, and Carbohydrate Metabolism. ConclusionsFeeding whole-plant corn silage can improve the production performance rumen fermentation of beef cattle by altering rumen microbiota, amino acid metabolism, and nucleotide metabolism.

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