scholarly journals Exploiting Sparse Statistics for a Sequence-Based Prediction of the Effect of Mutations

Algorithms ◽  
2019 ◽  
Vol 12 (10) ◽  
pp. 214 ◽  
Author(s):  
Mihaly Mezei

Recent work showed that there is a significant difference between the statistics of amino acid triplets and quadruplets in sequences of folded proteins and randomly generated sequences. These statistics were used to assign a score to each sequence and make a prediction whether a sequence is likely to fold. The present paper extends the statistics to higher multiplets and suggests a way to handle the treatment of multiplets that were not found in the set of folded proteins. In particular, foldability predictions were done along the line of the previous work using pentuplet statistics and a way was found to combine the quadruplet and pentuplets statistics to improve the foldability predictions. A different, simpler, score was defined for hextuplets and heptuplets and were used to predict the direction of stability change of a protein upon mutation. With the best score combination the accuracy of the prediction was 73.4%.

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1543 ◽  
Author(s):  
Naomi Yoshii ◽  
Koji Sato ◽  
Riki Ogasawara ◽  
Yusuke Nishimura ◽  
Yasushi Shinohara ◽  
...  

Dietary protein intake is critical for the maintenance of skeletal muscle mass. Plasma amino acid concentrations increase with protein intake and increases in muscle protein synthesis are dependent on leucine concentrations. We aimed to investigate the effect of a mixed meal and free amino acids intake on plasma leucine concentrations. In this randomized crossover study, 10 healthy young men (age 25 ± 1 years, height 1.73 ± 0.02 m, weight 65.8 ± 1.5 kg) underwent tests under different conditions—intake of 2 g of leucine (LEU), intake of a mixed meal (protein 27.5 g, including 2.15 g of leucine, protein: fat: carbohydrate ratio—22:25:53) only (MEAL), intake of 2 g of leucine immediately after a mixed meal (MEAL-LEU) and intake of 2 g of leucine 180 min after a mixed meal (MEAL-LEU180). Blood samples were collected within 420 min (240 min for LEU only) after intake and changes in amino acid concentrations were evaluated. Although the maximum plasma leucine concentration increased to 442 ± 24 µM for LEU, it was lower at 347 ± 16 µM (p < 0.05 vs. LEU) for MEAL-LEU, 205 ± 8 µM (p < 0.05 vs. LEU) for MEAL. The maximum plasma leucine concentration for MEAL-LEU180 increased to 481 ± 27 µM and compared to LEU there was no significant difference (p > 0.1). The observation that rapid elevations in plasma leucine concentrations are suppressed when leucine is ingested at the same time as a meal suggests that the timing of its intake must be considered to maximize the anabolic response.


The models on view in the ante-room show a way of folding a polypeptide chain which is consistent with some observations we have recently made with polarized infra-red radiation (Ambrose & Hanby 1949; Ambrose, Elliott & Temple 1949). The α -folded proteins, keratin, myosin and tropomyosin, have been found when oriented to show greater absorption of the N-H frequency when the electric vector of the absorbed radiation is in the direction of the fibre axis, hence the N-H bond must be preferentially oriented in this direction. A study of models has suggested that the only likely folding of the polypeptide chain consistent with this fact involves a seven-membered ring containing two amino-acid residues; the ring is completed by hydrogen bonds: A new type of atomic model which has been developed in our laboratories has been used. The scale is 0·8 in. to the Angstrom unit. The valency links, while allowing free rotation about single co-valent bonds, also allow some distortion of the bond angles when strains occur but are strong enough to allow long polymer chains to be built. The molecular model exhibited shows twenty-four amino-acid residues, with side chains on one side of the back-bone, representative of those occurring in myosin; the side chains on the other side have been removed for clearness and their positions indicated by single carbon atoms.


Agronomy ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1637
Author(s):  
Quintino Reis de Araujo ◽  
Guilherme Amorim Homem de Abreu Loureiro ◽  
Cid Edson Mendonça Póvoas ◽  
Douglas Steinmacher ◽  
Stephane Sacramento de Almeida ◽  
...  

Free amino acids in cacao beans are important precursors to the aroma and flavor of chocolate. In this research, we used inferential and explanatory statistical techniques to verify the effect of different edaphic crop conditions on the free amino acid profile of PH-16 dry cacao beans. The decreasing order of free amino acids in PH-16 dry cacao beans is leucine, phenylalanine, glutamic acid, alanine, asparagine, tyrosine, gamma-aminobutyric acid, valine, isoleucine, glutamine, lysine, aspartic acid, serine, tryptophan, threonine, glycine. With the exception of lysine, no other free amino acid showed a significant difference between means of different edaphic conditions under the ANOVA F-test. The hydrophobic free amino acids provided the largest contribution to the explained variance with 58.01% of the first dimension of the principal component analysis. Glutamic acid stands out in the second dimension with 13.09%. Due to the stability of the biochemical profile of free amino acids in this clonal variety, it is recommended that cacao producers consider the genotype as the primary source of variation in the quality of cacao beans and ultimately the chocolate to be produced.


2021 ◽  
Author(s):  
Lijuan Wang ◽  
Chen Sun ◽  
Suyun Qian ◽  
Yingchao Liu ◽  
Kaihu Yao ◽  
...  

Abstract Background. Methicillin-resistant Staphylococcus aureus (MRSA) Clonal Complex 59 (CC59) clone has spread among Chinese children, resulting in many Staphylococcus aureus infections. α-hemolysin (Hlα) is an important virulence factor of Staphylococcus aureus, but little research has been done on CC59 isolates with negative α-hemolysis. Results. During the 4 periods (2009-2011, 2012-2013, 2016, 2017), 291 MRSA isolates were collected. Isolates with β and δ hemolysis accounted for 60.47% among the MRSA isolates in 2009-2011; 56.41% in 2012-2013; 77.14% in 2016; and 56.25% in 2017. most ST59 isolates (94.38%), 9 ST338 isolates (100%) showed β and δ hemolysis, both ST59 and ST338 clone belong to CC59 clone. Twenty-two ST239 isolates (73.33%), 8 ST88 isolates (80%), 4 ST5 isolates (100%), 13 ST22 isolates (92.86%) and 6 ST398 isolates (85.71%) showed α and δ hemolysis. α hemolysin in most clinical isolates is highly conservative, each showed one amino acid locus variation, the most common mutation was threonine at position 275 instead of isoleucine, then glutamic acid replaced aspartic acid at 208. Seventeen ST59 and 2 ST338 isolates had no mutation, 3 ST59 isolates showed single mutation (C448G), and only one ST59 isolate showed multilocus mutation. Other ST typing, such as ST1, ST5, ST88, ST20, ST239 and ST398, all had multilocus mutations, sites were from 3 to 8, no conservative sequence was found among isolates with the same ST typing. The carrying rates of RNA III, Rot, agrA, SarR, SarU and SigB were all over 93%, the carrying rates of SarZ and SarA genes were 41.86% and 34.88% respectively. Trancriptional levels of hlα in isolates showed α and δ hemolysis and β and δ hemolysis were equal. USA300 and R23 produced Hlα, R23 didn’t showed α hemolysis phenotype.Conclusions. Most clinical CC59 isolates from children in China were α hemolysis negative. There was no statistically significant difference in hlα gene and RNA expression, they produced the protein. The reason for the phenotypic deletion probably related to β hemolysin (Hlβ).


2021 ◽  
Author(s):  
Binhan Hao ◽  
Wenjie Zhou ◽  
Steven M Theg

The twin-arginine translocation (Tat) pathway utilizes the proton-motive force (PMF) to transport folded proteins across cytoplasmic membranes in bacteria and archaea, as well as across the thylakoid membrane in plants and the inner membrane in mitochondria. In most species, the minimal components required for Tat activity consist of three subunits, TatA, TatB, and TatC. Previous studies have shown that a polar amino acid is present at the N-terminus of the TatA transmembrane helix (TMH) across many different species. In order to systematically assess the functional importance of this polar amino acid in the TatA TMH in Escherichia coli, a complete set of 19-amino-acid substitutions was examined. Unexpectedly, although being preferred overall, our experiments suggest that the polar amino acid is not necessary for a functional TatA. Hydrophobicity and helix stabilizing properties of this polar amino acid were found to be highly correlated with the Tat activity. Specifically, change in charge status of the amino acid side chain due to pH resulted in a shift in hydrophobicity, which was demonstrated to impact the Tat transport activity. Furthermore, a four-residue motif at the N-terminus of the TatA TMH was identified by sequence alignment. Using a biochemical approach, the N-terminal motif was found to be functionally significant, with evidence indicating a potential role in the preference for utilizing different PMF components. Taken together, these findings yield new insights into the functionality of TatA and its potential role in the Tat transport mechanism.


Development ◽  
1965 ◽  
Vol 13 (3) ◽  
pp. 275-283
Author(s):  
E. M. Deuchar ◽  
A. M. L. Dryland

In an earlier publication (Deuchar & Dryland, 1964) it was reported that α-methyl-norvaline, an amino acid described by Ross et al. (1961), whose structure resembles that of both valine and leucine (see below), caused a visible reduction in the quantity of haemoglobin formed by explants of the area vasculosa of the 48-hr, chick embryo, as compared with controls explanted without the analogue present. The structure of the haemoglobin molecule in birds has not yet been fully worked out, but according to recent work (reviewed by Gratzer & Allison, 1960) there are at least four N-terminal valine groups, two of which have leucine adjacent to them. The inhibition of haemoglobin synthesis by α-methyl-norvaline might, therefore, be due to competition with valine or leucine for uptake into these terminal sites on the peptide chains of the globin. The analogue might itself be taken up in their place, forming an abnormal haemoglobin.


Fermentation ◽  
2019 ◽  
Vol 5 (3) ◽  
pp. 52 ◽  
Author(s):  
Yong Xing Tan ◽  
Wai Kit Mok ◽  
Jaslyn Lee ◽  
Jaejung Kim ◽  
Wei Ning Chen

Brewers’ spent grains (BSG) are underutilized food waste materials produced in large quantities from the brewing industry. In this study, solid state fermentation of BSG using Bacillus subtilis WX-17 was carried out to improve the nutritional value of BSG. Fermenting BSG with the strain WX-17, isolated from commercial natto, significantly enhanced the nutritional content in BSG compared to unfermented BSG, as determined by the marked difference in the level of metabolites. In total, 35 metabolites showed significant difference, which could be categorized into amino acids, fatty acids, carbohydrates, and tricarboxylic acid cycle intermediates. Pathway analysis revealed that glycolysis was upregulated, as indicated by the drop in the level of carbohydrate compounds. This shifted the metabolic flux particularly towards the amino acid pathway, leading to a 2-fold increase in the total amount of amino acid from 0.859 ± 0.05 to 1.894 ± 0.1 mg per g of BSG after fermentation. Also, the total amount of unsaturated fatty acid increased by 1.7 times and the total antioxidant quantity remarkably increased by 5.8 times after fermentation. This study demonstrates that novel fermentation processes can value-add food by-products, and valorized food waste could potentially be used for food-related applications. In addition, the study revealed the metabolic changes and mechanisms behind the microbial solid state fermentation of BSG.


1999 ◽  
Vol 277 (6) ◽  
pp. R1605-R1611 ◽  
Author(s):  
Yuqi Wang ◽  
Kenneth R. Olson ◽  
Michael P. Smith ◽  
Michael J. Russell ◽  
J. Michael Conlon

Endothelin (ET) from a nontetrapod species has never been characterized, either structurally or biologically. A single molecular form of trout ET with 21-amino-acid residues was isolated in pure form from an extract of the kidney of the steelhead trout, Oncorhynchus mykissand its primary structure established as Cys-Ser-Cys-Ala-Thr-Phe-Leu-Asp-Lys-Glu10-Cys-Val-Tyr-Phe-Cys-His-Leu-Asp-Ile-Ile20-Trp. This amino acid sequence shows only three substitutions (Ala4→Ser, Thr5→Ser, and Phe6→Trp) compared with human ET-2, demonstrating that the structure of the peptide has been well conserved during evolution and that the pathway of posttranslational processing of preproendothelin in the trout is probably similar to that in mammals. Synthetic trout ET produced concentration-dependent constrictions of isolated rings of vascular tissue from trout efferent branchial artery (EBA; pD2 = 7.90 ± 0.06, n = 5), caeliacomesenteric artery (pD2 = 8.03 ± 0.04, n = 4), anterior cardinal vein (ACV; pD2 = 8.57 ± 0.25, n = 4), and rat abdominal aorta (AO; pD2 = 8.86 ± 0.08, n = 7). Trout and rat vessels were more sensitive to mammalian ET-1 than to trout ET (pD2 for human ET-1 in: EBA = 9.12 ± 0.14; ACV = 9.90 ± 0.15; AO = 8.86 ± 0.08), but there was no significant difference in the maximum tension produced by either peptide in these vessels.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1654-1654
Author(s):  
Qian Li ◽  
Yuxiao Zou ◽  
Sentai Liao

Abstract Objectives In this study we compared the antiobesity effects of mulberry leaf powder, dietary fiber, polyphenols, and a fiber/polyphenols mixture.Combining intestinal community modulation and metabolite analysis, we investigated the antiobesity effects and mechanisms of mulberry leaf components, detecting the interaction between mulberry leaf dietary fiber and polyphenol. Methods An obesity model was established by feeding rats with a high-calorie diet. Rats were divided into seven groups: the obesity model control (MC), positive control (PC), mulberry leaf powder (MLP), mulberry leaf fiber (MLF), mulberry leaf polyphenols (MLPS), mulberry leaf fiber and polyphenols mixture (MLM), and normal control (NC), and fed daily for 6 consecutive weeks.the 16S rRNA gene was sequenced using Illumina MiSeq.UPLC Triple TOF MS/MS system and Agilent 6890 N GC-MS were used to profile the urinary/fecal metabolites. Results The synergistic interaction between mulberry dietary fiber and polyphenols (MLM) in antiobesity was reported for the first time. The content of Firmicutes in the MC group was increased significantly. Except for the MLPS group, other test groups regulated the Firmicutes content to a normal level. Our study demonstrated that different components of mulberry leaves might achieve weight loss by reducing the amount of Lachnespiraceae. At the same time, the reduction Lactobacillus_vaginalis and Lactobacillus_gasseri species was closely related to the improvement of lipid metabolism profiles. In addition, the high energy diet induced feces and urine metabolic disorders in MC group with significant difference. The amino acid and oligopeptide metabolites were regulated to the NC level under the regulation of mulberry leaf components. Conclusions MLM group had the best efficiency on weight loss, indicating synergistic interactions between MLPS and MLF. The reduction of Firmicutes abundance, and the downstream Clostridiales, Lachnespiraceae, was a key pathway for the antiobesity effects. The increased abundances of Lactobacillus vaginalis and Lactobacillus gasseri might result in lipid metabolism disorder. The test groups regulated the amino acid and oligopeptides metabolic disorder tents to normal levels compared with the MC and NC groups. Funding Sources The Science & Technology Projects of Guangdong Province No.2017A050501022/No.2017A030310416.


2009 ◽  
Vol 54 (No. 8) ◽  
pp. 359-364 ◽  
Author(s):  
Z. Vykoukalová ◽  
A. Knoll ◽  
S. Čepica

Perilipin, encoded by the <I>PLIN</I> gene, is a lipid droplet-associated phosphoprotein that functions as a key regulator of triacylglycerol storage and hydrolysis in adipocytes. In this study, structure and variability of the porcine <I>PLIN</I> gene were characterised. PCR fragments encompassing exons 1 to 9 and interspersed introns were sequenced and the obtained sequence was deposited in EMBL/GenBank/DDBJ databases (AM931171). Seven silent polymorphisms and one nonsynonymous polymorphism were detected in the coding sequence. The nonsynonymous polymorphism g.627G>A causing an amino acid substitution p.Val3Ile was found only in Meishan and Meishan × Piétrain cross. Associations were studied between loci g.4119A>G and g.7966T>C, and average daily gain (ADG), backfat thickness (BFT) or lean meat content (LMC) in 166 gilts from two herds. Due to supposed complete linkage disequilibrium between loci g.4119A>G and g.7966T>C only genotype combinations <I>AA-TT, AG-TC</I> and <I>GG-CC</I> were detected. A significant difference (<I>P</I> = 0.0290) between <I>GG-CC</I> and <I>AG-TC</I> genotype combinations for BFT in herd 2 and a suggestive difference (<I>P</I> = 0.0516) between <I>GG-CC</I> and <I>AA-TT</I> genotypes for ADG in herd 1 were detected.


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