Amino Acid Pattern Research Articles

Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis

BackgroundBacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs are graspetides, so named after ATP-grasp ligases that catalyze the formation of lactam and lactone linkages in these peptides. The diversity of graspetides, the multiple proteins encoded in the respective Biosynthetic Gene Clusters (BGCs) and their evolution have not been studied in full detail. In this work, we attempt a comprehensive analysis of the graspetide-encoding BGCs and report a variety of novel graspetide groups as well as ancillary proteins implicated in graspetide biosynthesis and expression.ResultsWe compiled a comprehensive, manually curated set of graspetides that includes 174 families including 115 new families with distinct patterns of amino acids implicated in macrocyclization and further modification, roughly tripling the known graspetide diversity. We derived signature motifs for the leader regions of graspetide precursors that could be used to facilitate graspetide prediction. Graspetide biosynthetic gene clusters and specific precursors were identified in bacterial divisions not previously known to encode RiPPs, in particular, the parasitic and symbiotic bacteria of the Candidate phyla radiation. We identified Bacteroides-specific biosynthetic gene clusters (BGC) that include remarkable diversity of graspetides encoded in the same loci which predicted to be modified by the same ATP-grasp ligase. We studied in details evolution of recently characterized chryseoviridin BGCs and showed that duplication and horizonal gene exchange both contribute to the diversification of the graspetides during evolution.ConclusionsWe demonstrate previously unsuspected diversity of graspetide sequences, even those associated with closely related ATP-grasp enzymes. Several previously unnoticed families of proteins associated with graspetide biosynthetic gene clusters are identified. The results of this work substantially expand the known diversity of RiPPs and can be harnessed to further advance approaches for their identification.

A New Strategy for Multitarget Drug Discovery/Repositioning Through the Identification of Similar 3D Amino Acid Patterns Among Proteins Structures: The Case of Tafluprost and its Effects on Cardiac Ion Channels.

The identification of similar three-dimensional (3D) amino acid patterns among different proteins might be helpful to explain the polypharmacological profile of many currently used drugs. Also, it would be a reasonable first step for the design of novel multitarget compounds. Most of the current computational tools employed for this aim are limited to the comparisons among known binding sites, and do not consider several additional important 3D patterns such as allosteric sites or other conserved motifs. In the present work, we introduce Geomfinder2.0, which is a new and improved version of our previously described algorithm for the deep exploration and discovery of similar and druggable 3D patterns. As compared with the original version, substantial improvements that have been incorporated to our software allow: (i) to compare quaternary structures, (ii) to deal with a list of pairs of structures, (iii) to know how druggable is the zone where similar 3D patterns are detected and (iv) to significantly reduce the execution time. Thus, the new algorithm achieves up to 353x speedup as compared to the previous sequential version, allowing the exploration of a significant number of quaternary structures in a reasonable time. In order to illustrate the potential of the updated Geomfinder version, we show a case of use in which similar 3D patterns were detected in the cardiac ions channels NaV1.5 and TASK-1. These channels are quite different in terms of structure, sequence and function and both have been regarded as important targets for drugs aimed at treating atrial fibrillation. Finally, we describe the in vitro effects of tafluprost (a drug currently used to treat glaucoma, which was identified as a novel putative ligand of NaV1.5 and TASK-1) upon both ion channels’ activity and discuss its possible repositioning as a novel antiarrhythmic drug.

Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by HIPP-Werk Georg Hipp OHG (dossier submitted by meyer.science GmbH).

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in infant and follow‐on formula by HIPP‐Werk Georg Hipp OHG. The dossier that was submitted to the European Commission aimed at requesting an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in infant and/or follow‐on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 1.9 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to growth equivalent to a formula manufactured from intact cow’s milk protein with the same protein content. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow‐on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow‐on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow‐on formula, as long as the formula in which it is used contains a minimum of 1.9 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

Improvement of nutritional value, molecular weight patterns (soluble peptides), free amino acid patterns, total phenolics and antioxidant activity of fermented extrusion pretreatment rapeseed meal with Bacillus subtilis YY-1 and Saccharomyces cerevisiae YY-2

A study was conducted to investigate the changes of pH, total cell number, soluble peptide patterns, free amino acid patterns, total phenolics, digestibility and antioxidant activities in vitro and in vivo of fermented extruded-pretreatment rapeseed meal with selected Bacillus subtilis (YY-1) and Saccharomyces cerevisiae (YY-2) (fermented extruded-pretreatment rapeseed meal, FERSM) with fermentation time. The objective was to develop a functional food/feed ingredient to contribute to healthy improvement. The results showed that the small peptide (molecular weight<3 kDa), total phenolic contents and digestibility of FERSM at 48th h increased to the highest level, and the subunit band intensities of 2S albumin and 12S globulin had almost entirely disappeared. The DPPH radical scavenging activity of FERSM at 48th h was higher (p < .05), and the T-SOD levels in serum and liver of weaned rats fed FERSM at 48th h was higher and MDA levels were lower (p < .05). The novel approach was effective for improving antioxidant properties.

Glutamine supplementation moderately affects growth, plasma metabolite and free amino acid patterns in neonatal low birth weight piglets.

Low birth weight (LBW) neonates show impaired growth compared with normal birth weight (NBW) neonates. Glutamine (Gln) supplementation benefits growth of weaning piglets, while the effect on neonates is not sufficiently clear. We examined the effect of neonatal Gln supplementation on piglet growth, milk intake and metabolic parameters. Sow-reared pairs of newborn LBW (0·8-1·2 kg) and NBW (1·4-1·8 kg) male piglets received Gln (1 g/kg body mass (BM)/d; Gln-LBW, Gln-NBW; n 24/group) or isonitrogenous alanine (1·22 g/kg BM/d; Ala-LBW; Ala-NBW; n 24/group) supplementation at 1-5 or 1-12 d of age (daily in three equal portions at 07:00, 12:00 and 17:00 by syringe feeding). We measured piglet BM, milk intake (1, 11-12 d), plasma metabolite, insulin, amino acid (AA) and liver TAG concentrations (5, 12 d). The Gln-LBW group had higher BM (+7·5%, 10 d, P = 0·066; 11-12 d, P < 0·05) and milk intake (+14·7%, P = 0·015) than Ala-LBW. At 5 d, Ala-LBW group had higher plasma TAG (+34·7%, P < 0·1) and lower carnosine (-22·5%, P < 0·05) than Ala-NBW and Gln-LBW, and higher liver TAG (+66·9%, P = 0·029) than Ala-NBW. At 12 d, plasma urea was higher (+37·5%, P < 0·05) with Gln than Ala supplementation. Several proteinogenic AA in plasma were lower (P < 0·05) in Ala-NBW v. Gln-NBW. Plasma arginine was higher (P < 0·05) in Gln-NBW v Ala-NBW piglets (5, 12 d). Supplemental Gln moderately improved growth and milk intake and affected lipid metabolism in LBW piglets and AA metabolism in NBW piglets, suggesting effects on intestinal and liver function.

What can we learn from amino acids about oceanic organic matter cycling and degradation?

Abstract. Amino acids (AAs) mainly bound in proteins are major constituents of living biomass and non-living organic material in the oceanic particulate and dissolved organic matter pool. Uptake and cycling by heterotrophic organisms lead to characteristic changes in AA composition so that AA-based biogeochemical indicators are often used to elucidate processes of organic matter cycling and degradation. We analyzed particulate AA in a large sample set collected in various oceanic regions covering sinking and suspended particles in the water column, sediment samples, and dissolved AA from water column and pore water samples. The aim of this study was to test and improve the use of AA-derived biogeochemical indicators as proxies for organic matter sources and degradation and to better understand particle dynamics and interaction between the dissolved and particulate organic matter pools. A principal component analysis (PCA) of all data delineates diverging AA compositions of sinking and suspended particles with increasing water depth. A new sinking particle and sediment degradation indicator (SDI) allows a fine-tuned classification of sinking particles and sediments with respect to the intensity of degradation, which is associated with changes of stable isotopic ratios of nitrogen (δ15N). This new indicator is furthermore sensitive to sedimentary redox conditions and can be used to detect past anoxic early diagenesis. A second indicator emerges from the AA spectra of suspended particulate matter (SPM) in the epipelagic and that of the meso- and bathypelagic ocean and is a residence time indicator (RTI). The characteristic changes in AA patterns from shallow to deep SPM are recapitulated in the AA spectra of the dissolved organic matter (DOM) pool, so that deep SPM is more similar to DOM than to any of the other organic matter pools. This implies that there is equilibration between finely dispersed SPM and DOM in the deep sea, which may be driven by microbial activity combined with annealing and fragmentation of gels. As these processes strongly depend on physico-chemical conditions in the deep ocean, changes in quality and degradability of DOM may strongly affect the relatively large pool of suspended and dissolved AA in the ocean that amounts to 15 Pg amino acid carbon (AAC) and 89 ± 29 Pg AAC, respectively.

Natural selection shaped the evolution of amino acid usage in mammalian toll like receptor genes

AbstractToll-like receptors (TLRs) are important as they are able to sense diverse set of pathogens associated molecular patterns (PAMPs) as ligands. These receptors are involved in functions such as immune response, development of signaling process and cell adhesion. In the present study we are interested to analyze the influence of evolutionary selection pressure on the mutational diversity of mammalian TLR genes. We observed differential patterns of amino acid usage between primate and non-primate mammalian TLR genes. GC-content of TLR genes and hydrophobicity of the encoded proteins are the most influential factors correlated with the differential pattern of amino acid usage.The influence of the subcellular location on the amino acid usage pattern of TLRs is evident in present study. Purifying selection is uniformly present on TLR genes, positively selected sites are mostly located over the ligand binding domain. Our study clearly demonstrates that natural selection has shaped the evolution of primate and non-primate mammalian TLR genes.

Is the amino acid pattern in medical nutrition therapy crucial for successfully attenuating muscle mass loss in adult ICU patients? Secondary analysis of a RCT.

We hypothesized that in long-term immobilized intensive care unit (ICU) patients, both the quantity and quality of protein nutrition are vital in supporting muscle mass maintenance. Hence, the aim of this secondary analysis of our recently performed RCT was to calculate the intake of individual amino acids and to evaluate the potential associations of amino acid patterns with muscle mass loss during the ICU stay. Clinical and nutritional data were collected from a recent RCT conducted in long-term immobilized, critically ill patients receiving medical nutrition therapy with either 1.8g (interventional group) or 1.2g (standard group) of protein/amino acids per kg body weight per day over 4 weeks. Intake of the individual amino acids as well as the sum scores of the indispensable, conditionally indispensable, and dispensable amino acids were calculated for all patients, both group specific (n=21 in each group) and in total (n=42), based on the detailed nutrition protocols; inter-group differences were analyzed by t-tests. Linear regression models were used to test the effects of individual amino acids and the sum scores on the extent of skeletal muscle loss by measuring the quadriceps muscle layer thickness during the study period. The significance level was adjusted for multiple testing according to the Bonferroni procedure (α=0.002). In both groups, the proportion of indispensable amino acids was approximately 41% of the total exogenous protein supply, with the proportion of enteral administration slightly over 50%. The intake of conditionally indispensable amino acids (glutamine, tyrosine, cysteine, histidine, and arginine) accounted for 17% and 18% of the total amino acids in the interventional and standard groups, respectively; glutamine (5% of total amino acids) was exclusively administered enterally. The intake of dispensable amino acid varied widely, with glutamic acid, proline, and asparagine/aspartic acid representing the highest proportions (10%, 8%, and 8% of total amino acids, respectively). For all amino acids, no statistically significant association was observed between the quantitative intake and the skeletal muscle changes after terminating the intervention phase. This secondary analysis of the RCT conducted in routine clinical practice did not support our working hypothesis that the amino acid patterns of medical nutrition therapy have a statistically significant impact on the skeletal muscle loss in long-term immobilized ICU patients. Due to the limited variety of enteral/parenteral products used in this single-center study, the calculated amino acid patterns showed only small differences. Larger multi-center trials with adequate power are needed to evaluate the potential effects of the individual amino acids or defined amino acid patterns on the muscle protein metabolism in further detail. German Clinical Trials Register (http://www.drks.de); DRKS-ID: DRKS00013594.

The Serum and Fecal Metabolomic Profiles of Growing Kittens Treated with Amoxicillin/Clavulanic Acid or Doxycycline.

Simple SummaryThis study investigated the impact of antibiotic treatment οn the serum and fecal metabolome (the collection of all small molecules produced by the gut bacteria and the host) of young cats. Thirty 2-month-old cats with an upper respiratory tract infection were treated with either amoxicillin/clavulanic acid for 20 days or doxycycline for 28 days. In addition, another 15 control cats that did not receive antibiotics were included. Blood was collected on days 0 (before treatment), 20/28 (last day of treatment), and 300 (10 months after the end of treatment), while feces were collected on days 0, 20/28, 60, 120, and 300. Seven serum and fecal metabolites differed between cats treated with antibiotics and control cats at the end of treatment period. Ten months after treatment, no metabolites differed from healthy cats, suggesting that amoxicillin/clavulanic acid or doxycycline treatment only temporarily affects the abundance of the serum and fecal metabolome.The long-term impact of antibiotics on the serum and fecal metabolome of kittens has not yet been investigated. Therefore, the objective of this study was to evaluate the serum and fecal metabolome of kittens with an upper respiratory tract infection (URTI) before, during, and after antibiotic treatment and compare it with that of healthy control cats. Thirty 2-month-old cats with a URTI were randomly assigned to receive either amoxicillin/clavulanic acid for 20 days or doxycycline for 28 days, and 15 cats of similar age were enrolled as controls. Fecal samples were collected on days 0, 20/28, 60, 120, and 300, while serum was collected on days 0, 20/28, and 300. Untargeted and targeted metabolomic analyses were performed on both serum and fecal samples. Seven metabolites differed significantly in antibiotic-treated cats compared to controls on day 20/28, with two differing on day 60, and two on day 120. Alterations in the pattern of serum amino acids, antioxidants, purines, and pyrimidines, as well as fecal bile acids, sterols, and fatty acids, were observed in antibiotic-treated groups that were not observed in control cats. However, the alterations caused by either amoxicillin/clavulanic acid or doxycycline of the fecal and serum metabolome were only temporary and were resolved by 10 months after their withdrawal.

The comparison of nucleotide metabolites and amino acids patterns in patients with eating disorders, with and without symptoms of depression

Purines, pyrimidines, and amino acid level have gained attention recently as potential determinants of mental disorders. However, eating disorders patients (ED) have not been yet appropriately studied, especially subjects with coexisting mood disorders. This paper examines the serum level of nucleotide catabolites and plasma amino acids in eating disorders with hyperphagia, with and without Major Depressive Disorder (MDD). Samples were taken from adult persons suffering from eating disorders (two forms: simple obesity and binge eating disorder) with MDD (n = 20) and without (n = 17). Serum nucleotides and plasma amino acids concentrations were analyzed with high-performance liquid chromatography-mass spectrometry. The nucleotides metabolite in MDD patients had a significantly (p < 0.05) lower uridine. Among MDD patients with ED significantly (p < 0.05) higher levels of asparagine, glutamine, proline, and arginine were found as compared to the control group. This study demonstrated differences in nucleotide metabolite and amino acid pattern in depression patients with eating disorders. This may be relevant to the mechanisms and may help identify biomarkers.

Identification of stress-related characteristics of the &lt;i&gt;WRKY&lt;/i&gt; gene family: A case study of &lt;i&gt;Dendrobium catenatum&lt;/i&gt;

As one of the largest families of transcription factors (TFs) in plants, the WRKY TF family plays a key role in regulating plant responses to various biotic and abiotic stresses. However, there is no confirmed method to quickly identify stress-responsive members from the <italic>WRKY</italic> gene family. In this study, all reported functional <italic>WRKY</italic> genes were first analyzed, and the amino acid patterns in response to stress were identified in group II-c (T-R/K-S/T-E/Q/D-V/I/L-E/D-I/V/H/N-L/M-D/E-D-G/E-F/Y-K/R-WRKYG-Q/K-K-A/T-VKN-S/N-P), group II-d (VPA-I/V-S-X-K-M/L/V/I-ADIP-P/A/V-D-D/E-Y/F-S-WRKYGQKPIKGSP-H/Y-PRGYYKCS-S/T-V/M-RGCPARKVER), and group II-e (PSD-S/A/L-WAWRKYGQKPIKGSPYPR-G/S-YYRCSSSKGC). <italic>WRKY</italic> genes in<italic> Dendrobium catenatum</italic> were used to validate the accuracy of these patterns. A total of 63 <italic>DcaWRKY</italic> genes were identified, their gene structures, conserved motifs, and gene expression patterns were analyzed, and a phylogenetic tree was constructed. Gene expression patterns were then analyzed under drought stress, and seven <italic>DcaWRKY</italic> genes (<italic>Dca002550</italic>, <italic>Dca002715</italic>, <italic>Dca005648</italic>, <italic>Dca007842</italic>, <italic>Dca010430</italic>, <italic>Dca016437</italic>, and <italic>Dca006787</italic>) were randomly selected to determine their expression levels and verify their expression patterns by quantitative real-time polymerase chain reaction analysis. The identified amino acid patterns were validated by drought-responsive <italic>WRKY</italic> genes in <italic>D. catenatum</italic>, confirming the accuracy of these amino acid patterns and providing valuable insights into further research of the <italic>WRKY</italic> family in <italic>D. catenatum</italic>.

Amino acid pattern of rumen microorganisms in cattle fed mixed diets-An update.

Rumen microorganisms turn small N-containing compounds into amino acids (AA) and contribute considerably to the supply of AA absorbed from the small intestine. Previous studies summarized the literature on microbial AA patterns, most recently in 2017 (Sok et al. Journal of Dairy Science, 100, 5241-5249). The present study intended to identify the microbial AA pattern typical when feeding Central European diets and a maximum proportion of concentrate (PCO; dry matter (DM) basis) of 0.60. Data sets were created from the literature for liquid (LAB)- and particle (PAB)-associated bacteria, total bacteria and protozoa, including 16, 9, 27 and 8studies and 36, 21, 60 and 18 diets respectively. Because the only differences detected between LAB and PAB were slightly higher Phe and lower Thr percentages in PAB (p<0.05), results for bacteria were pooled. A further data set evaluated AA-N (AAN) as a proportion of total N in microbial fractions and a final data set estimated protozoal contributions to total microbial N (TMN) flow to the duodenum, which were used to calculate weighted TMN AA patterns. Protozoa showed higher Lys, Asp, Glu, Ile and Phe and lower Ala, Arg, Gly, Met, Ser, Thr and Val proportions than bacteria (p<0.05). The AAN percentage of total N in bacteria and protozoa showed large, unexplained variations, averaging 79.0% and 70.6% (p>0.05) respectively. Estimation of protozoal contribution to TMN resulted in a cattle-specific mixed model including PCO and DM intake (DMI) per unit of metabolic body size (kg0.75 ) as fixed effects (RMSE=3.77). With moderate PCO and DMI between 80 and 180g/kg0.75 , which corresponds to a DMI of approximately 10 to 25kg in a cow with 650kg body weight, protozoal contribution ranged between 9% and 26% of TMN. Within this range, the estimated protozoal contribution to TMN resulted in minor effects on the total microbial AA pattern.

Crowding stress-related protein markers: New candidates for assessing welfare of largemouth bass reared in an in-pond raceway system

Compared to traditional pond culture, in-pond raceway system (IPRS) is an advanced model, which can reduce waste of water resources and have the characteristics of high efficiency, high yield and environmental protection. However, how to determine the appropriate stocking density has not been studied using protein markers, especially from a welfare perspective. Therefore, this study mainly evaluated the effect of stocking density on the growth, meat quality and liver proteome of largemouth bass (Micropterus salmoides). Largemouth bass (average weight, 14.29 ± 0.26 g) were randomly distributed into three in-pond raceways at three stocking densities: low stocking-density (LSD, 7000 individual/raceway), medium stocking-density (MSD, 20,000 individual/raceway) and high stocking-density (HSD, 30,000 individual/raceway). The growth performance, muscle quality and liver protein expression were analyzed after a 58-day feeding trial. The results showed that the LSD group obtained significantly higher specific growth rate compared to the HSD group. As the density increased, the survival rate of fish decreased from 92.56% to 86.33%, and the feed conversion ratio increased from 1.21 to 1.45. Different stocking densities can significantly affect the contents of essential fatty acids in muscle, but not have any obvious changes on the amino acid pattern in muscle. A total of 109, 35 and 209 differentially regulated liver proteins were detected in LSD vs. MSD, MSD vs. HSD, and HSD vs. LSD groups, respectively. Among them, Hsp70, Grp78, Erp57, Gfpt1, Pyg and Acc1 are involved in stress, glucose metabolism or lipid metabolism, which were confirmed by western blotting. Thus, these proteins could be selected as biomarkers to determine stocking density. The findings will benefit IPRS to balance the yield and welfare of fish according to the market and law changes, beyond profit-seeking in the future.

Metabolic analysis of infants with bronchopulmonary dysplasia under early nutrition therapy: An observational cohort study.

To assess the amino acid and fatty acid metabolite patterns between infants with and without bronchopulmonary dysplasia in different nutritional stages after birth and identify metabolic indicators of bronchopulmonary dysplasia. This was an observational cohort of preterm infants born at a gestational age ≤32 + 6 weeks and with a body weight ≤2000 g. Amino acid and carnitine profiles were measured in dried blood spots (DBSs) during the early nutrition transitional phase using tandem mass spectrometry. Bronchopulmonary dysplasia was defined as oxygen dependence at 36 weeks of postmenstrual age or 28 days after birth. Metabolomic analysis was employed to define metabolites with significant differences, map significant metabolites into pathways, and identify metabolic indicators of bronchopulmonary dysplasia. We evaluated 45 neonates with and 40 without bronchopulmonary dysplasia. Four amino acids and three carnitines showed differences between the groups. Three carnitines (C0, C2, and C6:1) were high in the bronchopulmonary dysplasia group mostly; conversely, all four amino acids (threonine, arginine, methionine, and glutamine (Gln)) were low in the bronchopulmonary dysplasia group. Pathway analysis of these metabolites revealed two pathways with significant changes (p < 0.05). ROC analysis showed Gln/C6:1 at total parenteral nutrition phase had both 80% sensitivity and specificity for predicting the development of bronchopulmonary dysplasia, with an area under the curve of 0.81 (95% confidence interval 0.71-0.89). Amino acid and fatty acid metabolite profiles changed in infants with bronchopulmonary dysplasia after birth during the nutrition transitional period, suggesting that metabolic dysregulation may participate in the development of bronchopulmonary dysplasia. Our findings demonstrate that metabolic indicators are promising for forecasting the occurrence of bronchopulmonary dysplasia among preterm neonates.

Dynamic, but Not Necessarily Disordered, Human-Virus Interactions Mediated through SLiMs in Viral Proteins

Most viruses have small genomes that encode proteins needed to perform essential enzymatic functions. Across virus families, primary enzyme functions are under functional constraint; however, secondary functions mediated by exposed protein surfaces that promote interactions with the host proteins may be less constrained. Viruses often form transient interactions with host proteins through conformationally flexible interfaces. Exposed flexible amino acid residues are known to evolve rapidly suggesting that secondary functions may generate diverse interaction potentials between viruses within the same viral family. One mechanism of interaction is viral mimicry through short linear motifs (SLiMs) that act as functional signatures in host proteins. Viral SLiMs display specific patterns of adjacent amino acids that resemble their host SLiMs and may occur by chance numerous times in viral proteins due to mutational and selective processes. Through mimicry of SLiMs in the host cell proteome, viruses can interfere with the protein interaction network of the host and utilize the host-cell machinery to their benefit. The overlap between rapidly evolving protein regions and the location of functionally critical SLiMs suggest that these motifs and their functional potential may be rapidly rewired causing variation in pathogenicity, infectivity, and virulence of related viruses. The following review provides an overview of known viral SLiMs with select examples of their role in the life cycle of a virus, and a discussion of the structural properties of experimentally validated SLiMs highlighting that a large portion of known viral SLiMs are devoid of predicted intrinsic disorder based on the viral SLiMs from the ELM database.

Estimation of the ideal dietary essential amino acid pattern for pacu (Piaractus mesopotamicus) in the later-juvenile growth phase

This study aimed to estimate the ideal pattern of dietary essential amino acids (EAAs) for pacu ( Piaractus mesopotamicus ) in the later-juvenile growth phase (weighing 460–560 g) by the amino acid (AA) deletion method. A total of 231 pacu in the later-juvenile growth phase (with initial average body weight of 460 ± 4.65 g) were equally distributed in a completely randomized design among 33 fiber tanks of 1000-L (7 fish per tank) in a closed water recirculation system. The trial consisted of 11 treatments including a control diet (CD) and 10 EAA-deficient diets (DDs), with three replicates (tanks) per treatment. The CD consisted of 45% synthetic amino acids and purified feed ingredients and 55% non-purified conventional feed ingredients. The 10 DDs represented the same nutritional composition of the CD but each DD was maintained deficient in 45% of the respective test EAA. During the 60-day experimental duration, fish were fed with extruded diets three times a day until apparent satiation. The present results revealed that fish fed with CD showed better growth performance, feed utilization and body N deposition as compared to DDs. The ideal pattern of dietary EAAs was estimated through the relationship between body nitrogen retention and the amount of amino acid deleted from the control diet. Based on the deletion method, the ideal pattern of dietary EAAs for pacu in the later-juvenile growth phase (expressed relative to lysine requirement of 100%) was estimated as: arginine (84.33%); phenylalanine (55.21%); histidine (29.52%); isoleucine (55.06%); leucine (73.82%); methionine (24.86%); threonine (46.08%); tryptophan (10.42%); and valine (57.00%). • Deletion method can efficiently estimate the ideal EAA pattern for pacu in the later-juvenile • growth phase • 2: Estimation of ideal ratios of EAAs is required for obtaining maximum performance of fish • 3: Diets with ideal EAA ratios may optimize the feed utilization efficiency of fish • 4: Estimation of ideal EAA profiles could help to economize the protein content of feed

Codon usage signatures in Sabia and Chapare for host adaptation.

Sabia and Chapare viruses in the Arenavirus family cause viral hemorrhagic fever among humans with a fatality rate of 30% with no treatment models. Therefore, it is of interest to document the codon usage, amino acid patterns and associated factors influencing the observed variations in Sabia and Chapare viruses for host adaptation. Multivariate statistical analysis revealed compositional constraint and host selection pressure influencing the viral codon usage patterns. These data suggests the codon usage signatures in Sabia and Chapare viruses for host adaptation in the human host implying its role in the rapid progression of the infection. Dinucleotides UpG and CpA were noted to be over-represented among the Sabia, Chapare viruses and human genomes. Strong restraint from the usage of CpG dinucleotides among viruses is linked with the molecular mimicry of the human immune system. Thus, the data reported from this study help in understanding the mechanism of viral adaptation inside the host genome for further consideration in drug discovery.

Predicted Functional and Structural Diversity of Receiver Domains in Fungal Two-Component Regulatory Systems

ABSTRACTFungal two-component regulatory systems incorporate receiver domains into hybrid histidine kinases (HHKs) and response regulators. We constructed a nonredundant database of 670 fungal receiver domain sequences from 51 species sampled from nine fungal phyla. A much greater proportion (21%) of predicted fungal response regulators did not belong to known groups than previously appreciated. Receiver domains in Rim15 response regulators from Ascomycota and other phyla are very different from one another, as are the duplicate receiver domains in group XII HHKs. Fungal receiver domains from five known types of response regulators and 20 known types of HHKs exhibit distinct patterns of amino acids at conserved and variable positions known to be structurally and functionally important in bacterial receiver domains. We inferred structure/activity relationships from the patterns and propose multiple experimentally testable hypotheses about the mechanisms of signal transduction mediated by fungal receiver domains.

Effect of nitrate reduction and storage time on the antioxidative properties, biogenic amines and amino acid profile of dry fermented loins

SummaryThe aim of this work was to evaluate the effect of nitrate reduction and storage time on the content of amino acids and biogenic amines (BAs), total antioxidant capacity (TAC) and antioxidative properties of peptides isolated from dry fermented loins. The results showed that reducing the addition of nitrates increased the amount of BAs formed during storage of dry fermented loins. The lowest TAC value (tested by ABTS assay) was recorded for the sample with the highest nitrate addition (150 mg kg‐1) at beginning, while the highest value was noted for the sample without nitrate addition at 180 days of storage. The amino acid profile showed that dry fermented loin with the highest addition of nitrate was characterised by a significantly lower content of amino acids, which are precursors of key aroma compounds compared with loin samples with a lower amount of added sodium nitrate. The sum of ranking differences (SRD) indicated that loin sample with traditional addition of nitrate (150 mg kg‐1) after 120 days of storage was characterised by the lowest SRD result, which means that they are the closest to the assumed values, that is the lowest content of BAs, the highest antioxidant activity and amino acid patterns recommended by WHO/FAO/UNU Experts.

Differential barcoding of opioid receptors trafficking.

Over the past several years, studies have highlighted the δ-opioid receptor (DOPr) as a promising therapeutic target for chronic pain management. While exhibiting milder undesired effects than most currently prescribed opioids, its specific agonists elicit effective analgesic responses in numerous animal models of chronic pain, including inflammatory, neuropathic, diabetic, and cancer-related pain. However, as compared with the extensively studied μ-opioid receptor, the molecular mechanisms governing its trafficking remain elusive. Recent advances have denoted several significant particularities in the regulation of DOPr intracellular routing, setting it apart from the other members of the opioid receptor family. Although they share high homology, each opioid receptor subtype displays specific amino acid patterns potentially involved in the regulation of its trafficking. These precise motifs or "barcodes" are selectively recognized by regulatory proteins and therefore dictate several aspects of the itinerary of a receptor, including its anterograde transport, internalization, recycling, and degradation. With a specific focus on the regulation of DOPr trafficking, this review will discuss previously reported, as well as potential novel trafficking barcodes within the opioid and nociceptin/orphanin FQ opioid peptide receptors, and their impact in determining distinct interactomes and physiological responses.