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Whey protein ingestion during recovery from exercise increases myofibrillar but not muscle connective protein synthesis rates. It has been speculated that whey protein does not provide sufficient glycine to maximize postexercise muscle connective protein synthesis rates. In the present study, we assessed the impact of coingesting different amounts of collagen with whey protein as a nutritional strategy to increase plasma glycine availability during recovery from exercise. In a randomized, double-blind, crossover design, 14 recreationally active men (age: 26 ± 5 years; body mass index: 23.8 ± 2.1 kg·m−2) ingested in total 30 g protein, provided as whey protein with 0 g (WHEY), 5 g (WC05); 10 g (WC10), and 15 g (WC15) of collagen protein immediately after a single bout of resistance exercise. Blood samples were collected frequently over 6 hr of postexercise recovery to assess postprandial plasma amino acid kinetics and availability. Protein ingestion strongly increased plasma amino acid concentrations (p <.001) with no differences in plasma total amino acid availability between treatments (p >.05). The postprandial rise in plasma leucine and essential amino acid availability was greater in WHEY compared with the WC10 and WC15 treatments (p <.05). Plasma glycine and nonessential amino acid concentrations declined following whey protein ingestion but increased following collagen coingestion (p <.05). Postprandial plasma glycine availability averaged −8.9 ± 5.8, 9.2 ± 3.7, 23.1 ± 6.5, and 39.8 ± 11.0 mmol·360 min/L in WHEY, WC05, WC10, and WC15, respectively (incremental area under curve values, p <.05). Coingestion of a small amount of collagen (5 g) with whey protein (25 g) is sufficient to prevent the decline in plasma glycine availability during recovery from lower body resistance-type exercise in recreationally active men. [ABSTRACT FROM AUTHOR]

We present a detailed study on the temperature-dependent THz spectra of the polycrystalline amino acids, L-serine and L-cysteine, for wavenumbers from 20 to 120 cm−1 and temperatures from 4 to 300 K. Even though the structure of these two amino acids is very similar, with a sulfur atom in the side chain of cysteine instead of an oxygen atom in serine, the excitation spectra are drastically different. Obviously, the vibrational dynamics strongly depend on the ability of cysteine to form sulfur–hydrogen bonds. In addition, cysteine undergoes an order–disorder type phase transition close to 80 K, documented by additional specific heat experiments, with accompanying anomalies in the THz results. On increasing temperatures, well-defined vibrational excitations exhibit significant shifts in the eigenfrequencies with concomitant line-broadening yielding partly overlapping modes. Interestingly, several modes completely lose all their dipolar strength and are unobservable under ambient conditions. Comparing the recent results to the published work utilizing THz, Raman, and neutron-scattering techniques, as well as with ab initio simulations, we aim at a consistent analysis of the results ascribing certain eigenfrequencies to distinct collective lattice modes. We document that THz spectra can be used to fine-tune the parameters of model calculations and as fingerprint properties of certain amino acids. In addition, we analyzed the low-temperature heat capacity of both the compounds and detected strong excess contributions compared to the canonical Debye behavior of crystalline solids, indicating soft excitations and a strongly enhanced phonon-density of states at low frequencies. [ABSTRACT FROM AUTHOR]

Experimental and theoretical advances for understanding the temperature of maximum density (TMD) of aqueous solutions are outlined. The main equations that relate the TMD behavior to key thermodynamic properties are stated. The experimental TMD data are classified as a function of the nature of the solute (inorganic electrolytes, non-electrolytes, organic salts and ionic liquids, and amino acids and proteins). In addition, the experimental results that explore the effect of pressure are detailed. These experimental data are rationalized by making use of qualitative and semi-quantitative arguments based on the thermodynamics of aqueous systems. The main theoretical and simulation advances in TMD for aqueous solutions are also shown—including new calculations in the context of the scaled particle theory—and their ability to reproduce the experimental data is evaluated. Finally, new experiments and theoretical and simulation developments, which could give important insights into the problem of TMD for aqueous solutions, are proposed. [ABSTRACT FROM AUTHOR]

Interactions among biomacromolecules, predominantly noncovalent, underpin biological processes. However, recent advancements in biospecific chemistry have enabled the creation of specific covalent bonds between biomolecules, both in vitro and in vivo. This Review traces the evolution of biospecific chemistry in proteins, emphasizing the role of genetically encoded latent bioreactive amino acids. These amino acids react selectively with adjacent natural groups through proximity-enabled bioreactivity, enabling targeted covalent linkages. We explore various latent bioreactive amino acids designed to target different protein residues, ribonucleic acids, and carbohydrates. We then discuss how these novel covalent linkages can drive challenging protein properties and capture transient protein-protein and protein-RNA interactions in vivo. Additionally, we examine the application of covalent peptides as potential therapeutic agents and site-specific conjugates for native antibodies, highlighting their capacity to form stable linkages with target molecules. A significant focus is placed on proximity-enabled reactive therapeutics (PERx), a pioneering technology in covalent protein therapeutics. We detail its wide-ranging applications in immunotherapy, viral neutralization, and targeted radionuclide therapy. Finally, we present a perspective on the existing challenges within biospecific chemistry and discuss the potential avenues for future exploration and advancement in this rapidly evolving field.

MOTIVATION: Sidechain rotamer libraries of the common amino acids of a protein are useful for folded protein structure determination and for generating ensembles of intrinsically disordered proteins (IDPs). However, much of protein function is modulated beyond the translated sequence through the introduction of post-translational modifications (PTMs). RESULTS: In this work, we have provided a curated set of side chain rotamers for the most common PTMs derived from the RCSB PDB database, including phosphorylated, methylated, and acetylated sidechains. Our rotamer libraries improve upon existing methods such as SIDEpro, Rosetta, and AlphaFold3 in predicting the experimental structures for PTMs in folded proteins. In addition, we showcase our PTM libraries in full use by generating ensembles with the Monte Carlo Side Chain Entropy (MCSCE) for folded proteins, and combining MCSCE with the Local Disordered Region Sampling algorithms within IDPConformerGenerator for proteins with intrinsically disordered regions. AVAILABILITY AND IMPLEMENTATION: The codes for dihedral angle computations and library creation are available at https://github.com/THGLab/ptm_sc.git.

This study investigates the stability of chiral-molecule solution phases, with a specific focus on amino acids. The model framework is based on a two-dimensional square lattice model, where individual sites may be occupied by oriented chiral molecules or structureless solvent particles. Utilizing the Glauber dynamics and statistical mechanical formalism, as previously introduced and examined by Lombardo et al., we explore the influence of temperature, amino acid concentration, enantiomeric excess, and homochiral interaction strength on nucleation mechanisms, equilibrium phase behavior, and crystal composition. Our findings offer thermodynamic insights into the chiral amplification process of amino acids, contributing to a deeper understanding of the underlying processes. [ABSTRACT FROM AUTHOR]

Simulations of soft materials often adopt low-resolution coarse-grained (CG) models. However, the CG representation is not unique and its impact upon simulated properties is poorly understood. In this work, we investigate the space of CG representations for ubiquitin, which is a typical globular protein with 72 amino acids. We employ Monte Carlo methods to ergodically sample this space and to characterize its landscape. By adopting the Gaussian network model as an analytically tractable atomistic model for equilibrium fluctuations, we exactly assess the intrinsic quality of each CG representation without introducing any approximations in sampling configurations or in modeling interactions. We focus on two metrics, the spectral quality and the information content, that quantify the extent to which the CG representation preserves low-frequency, large-amplitude motions and configurational information, respectively. The spectral quality and information content are weakly correlated among high-resolution representations but become strongly anticorrelated among low-resolution representations. Representations with maximal spectral quality appear consistent with physical intuition, while low-resolution representations with maximal information content do not. Interestingly, quenching studies indicate that the energy landscape of mapping space is very smooth and highly connected. Moreover, our study suggests a critical resolution below which a "phase transition" qualitatively distinguishes good and bad representations. [ABSTRACT FROM AUTHOR]

We report simulation studies of 33 single intrinsically disordered proteins (IDPs) using coarse-grained bead-spring models where interactions among different amino acids are introduced through a hydropathy matrix and additional screened Coulomb interaction for the charged amino acid beads. Our simulation studies of two different hydropathy scales (HPS1, HPS2) [Dignon et al., PLoS Comput. Biol. 14, e1005941 (2018); Tesei et al. Proc. Natl. Acad. Sci. U. S. A. 118, e2111696118 (2021)] and the comparison with the existing experimental data indicate an optimal interaction parameter ϵ = 0.1 and 0.2 kcal/mol for the HPS1 and HPS2 hydropathy scales. We use these best-fit parameters to investigate both the universal aspects as well as the fine structures of the individual IDPs by introducing additional characteristics. (i) First, we investigate the polymer-specific scaling relations of the IDPs in comparison to the universal scaling relations [Bair et al., J. Chem. Phys. 158, 204902 (2023)] for the homopolymers. By studying the scaled end-to-end distances ⟨ R N 2 ⟩ / (2 L ℓ p ) and the scaled transverse fluctuations l ̃ ⊥ 2 = ⟨ l ⊥ 2 ⟩ / L , we demonstrate that IDPs are broadly characterized with a Flory exponent of ν ≃ 0.56 with the conclusion that conformations of the IDPs interpolate between Gaussian and self-avoiding random walk chains. Then, we introduce (ii) Wilson charge index (W) that captures the essential features of charge interactions and distribution in the sequence space and (iii) a skewness index (S) that captures the finer shape variation of the gyration radii distributions as a function of the net charge per residue and charge asymmetry parameter. Finally, our study of the (iv) variation of ⟨Rg⟩ as a function of salt concentration provides another important metric to bring out finer characteristics of the IDPs, which may carry relevant information for the origin of life. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. Materials and Methods: Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). Results: In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). Conclusions: The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

We present a novel approach for systematically exploring the conformational space of small molecules with multiple internal torsions. Identifying unique conformers through a systematic conformational search is important for obtaining accurate thermodynamic functions (e.g., free energy), encompassing contributions from the ensemble of all local minima. Traditional geometry optimizers focus on one structure at a time, lacking transferability from the local potential-energy surface (PES) around a specific minimum to optimize other conformers. In this work, we introduce a physics-driven meta-Gaussian processes (meta-GPs) method that not only enables efficient exploration of target PES for locating local minima but, critically, incorporates physical surrogates that can be applied universally across the optimization of all conformers of the same molecule. Meta-GPs construct surrogate PESs based on the optimization history of prior conformers, dynamically selecting the most suitable prior mean function (representing prior knowledge in Bayesian learning) as a function of the optimization progress. We systematically benchmarked the performance of multiple GP variants for brute-force conformational search of amino acids. Our findings highlight the superior performance of meta-GPs in terms of efficiency, comprehensiveness of conformer discovery, and the distribution of conformers compared to conventional non-surrogate optimizers and other non-meta-GPs. Furthermore, we demonstrate that by concurrently optimizing, training GPs on the fly, and learning PESs, meta-GPs exhibit the capacity to generate high-quality PESs in the torsional space without extensive training data. This represents a promising avenue for physics-based transfer learning via meta-GPs with adaptive priors in exploring torsional conformer space. [ABSTRACT FROM AUTHOR]

Purpose: This study was motivated by the need for better positron emission tomography (PET)-compatible tools to image bacterial infection. Our previous efforts have targeted bacteria-specific metabolism via assimilation of carbon-11 labeled d-amino acids into the bacterial cell wall. Since the chemical determinants of this incorporation are not fully understood, we sought a high-throughput method to label d-amino acid derived structures with fluorine-18. Our strategy employed a chemical biology approach, whereby an azide (-N3) bearing d-amino acid is incorporated into peptidoglycan muropeptides, with subsequent "click" cycloaddition with an 18F-labeled strained cyclooctyne partner. Procedures: A water-soluble, 18F-labeled and dibenzocyclooctyne (DBCO)-derived radiotracer ([18F]FB-sulfo-DBCO) was synthesized. This tracer was incubated with pathogenic bacteria treated with azide-bearing d-amino acids, and incorporated 18F was determined via gamma counting. In vitro uptake in bacteria previously treated with azide-modified d-amino acids was compared to that in cultures treated with amino acid controls. The biodistribution of [18F]FB-sulfo-DBCO was studied in a cohort of healthy mice with implications for future in vivo imaging. Results: The new strain-promoted azide-alkyne cycloaddition (SPAAC) radiotracer [18F]FB-sulfo-DBCO was synthesized with high radiochemical yield and purity via N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB). Accumulation of [18F]FB-sulfo-DBCO was significantly higher in several bacteria treated with azide-modified d-amino acids than in controls; for example, we observed 7 times greater [18F]FB-sulfo-DBCO ligation in Staphylococcus aureus cultures incubated with 3-azido-d-alanine versus those incubated with d-alanine. Conclusions: The SPAAC radiotracer [18F]FB-sulfo-DBCO was validated in vitro via metabolic labeling of azide-bearing peptidoglycan muropeptides. d-Amino acid-derived PET radiotracers may be more efficiently screened via [18F]FB-sulfo-DBCO modification.

Isomerized amino acid residues have been identified in many peptides extracted from tissues or excretions of humans and animals. These isomerized residues can play key roles by affecting biological activity or by exerting an influence on the process of aging. Isomerization occurs spontaneously and does not result in a mass shift. Thus, identifying and localizing isomerized residues in biological samples is challenging. Herein, we introduce a fast and efficient method using tandem mass spectrometry (MS) to locate isomerized residues in peptides. Although MS2 spectra are useful for identifying peptides that contain an isomerized residue, they cannot reliably localize isomerization sites. We show that this limitation can be overcome by utilizing MS3 experiments to further evaluate each fragment ion from the MS2 stage. Comparison at the MS3 level, utilizing statistical analyses, reveals which MS2 fragments differ between samples and, therefore, must contain the isomerized sites. The approach is similar to previous work relying on ion mobility to discriminate MS2 product ions by collision cross-section. The MS3 approach can be implemented using either ion-trap or beam-type collisional activation and is compatible with the quantification of isomer mixtures when coupled to a calibration curve. The method can also be implemented in combination with liquid chromatography in a targeted approach. Enabling the identification and localization of isomerized residues in peptides with an MS-only methodology will expand accessibility to this important information.

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.

This systematic meta-review evaluated the effects of exercise with and without protein interventions on muscle strength and function in older adults with sarcopenic obesity. PubMed, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Scopus, and SPORTDiscus databases were searched through February 2021 for relevant systematic reviews and meta-analyses with aerobic, resistance, and/or combined training interventions with and without protein supplementation in older adults ≥ 65 years with sarcopenic obesity. This meta-review showed that exercise with and without protein supplementation improved body composition (i.e., decreased percentage body fat) and functional outcomes (i.e., gait speed and grip strength). Because the current literature is limited, determining the effects of exercise and combined protein supplementation in this population requires further investigation. In the meantime, protein recommendations should align with general sarcopenia recommendations. Based upon available findings, tentative exercise recommendations to optimize health outcomes in this population are proposed. [ABSTRACT FROM AUTHOR]

Recent developments in protein design rely on large neural networks with up to 100s of millions of parameters, yet it is unclear which residue dependencies are critical for determining protein function. Here, we show that amino acid preferences at individual residues-without accounting for mutation interactions-explain much and sometimes virtually all of the combinatorial mutation effects across 8 datasets (R2 ~ 78-98%). Hence, few observations (~100 times the number of mutated residues) enable accurate prediction of held-out variant effects (Pearson r > 0.80). We hypothesized that the local structural contexts around a residue could be sufficient to predict mutation preferences, and develop an unsupervised approach termed CoVES (Combinatorial Variant Effects from Structure). Our results suggest that CoVES outperforms not just model-free methods but also similarly to complex models for creating functional and diverse protein variants. CoVES offers an effective alternative to complicated models for identifying functional protein mutations.

Foldy is a cloud-based application that allows non-computational biologists to easily utilize advanced AI-based structural biology tools, including AlphaFold and DiffDock. With many deployment options, it can be employed by individuals, labs, universities, and companies in the cloud without requiring hardware resources, but it can also be configured to utilize locally available computers. Foldy enables scientists to predict the structure of proteins and complexes up to 6000 amino acids with AlphaFold, visualize Pfam annotations, and dock ligands with AutoDock Vina and DiffDock. In our manuscript, we detail Foldys interface design, deployment strategies, and optimization for various user scenarios. We demonstrate its application through case studies including rational enzyme design and analyzing proteins with domains of unknown function. Furthermore, we compare Foldys interface and management capabilities with other open and closed source tools in the field, illustrating its practicality in managing complex data and computation tasks. Our manuscript underlines the benefits of Foldy as a day-to-day tool for life science researchers, and shows how Foldy can make modern tools more accessible and efficient.

Mutations in the BRCA2 gene are associated with sporadic and familial cancer, cause genomic instability and sensitize cancer cells to inhibition by the poly(ADP-ribose) polymerase (PARP). Here we show that human pluripotent stem cells (hPSCs) with one copy of BRCA2 deleted can be used to annotate variants of this gene and to test their sensitivities to PARP inhibition. By using Cas9 to edit the functional BRCA2 allele in the locally haploid hPSCs and in fibroblasts differentiated from them, we characterized essential regions in the gene to identify permissive and loss-of-function mutations. We also used Cas9 to directly test the function of individual amino acids, including amino acids encoded by clinical BRCA2 variants of uncertain significance, and identified alleles that are sensitive to PARP inhibitors used as a standard of care in BRCA2-deficient cancers. Locally haploid human pluripotent stem cells can facilitate detailed structure-function analyses of genes and the rapid functional evaluation of clinically observed mutations.

Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.

The clinical success of immune checkpoint inhibitors has underscored the key role of the immune system in controlling cancer. Current FDA-approved immune checkpoint inhibitors target the regulatory receptor pathways of cytotoxic T-cells to enhance their anticancer responses. Despite an abundance of evidence that natural killer (NK) cells can also mediate potent anticancer activities, there are no FDA-approved inhibitors targeting NK cell specific checkpoint pathways. Lirilumab, the most clinically advanced NK cell checkpoint inhibitor, targets inhibitory killer immunoglobulin-like receptors (KIRs), however it has yet to conclusively demonstrate clinical efficacy. Here we describe the crystal structure of lirilumab in complex with the inhibitory KIR2DL3, revealing the precise epitope of lirilumab and the molecular mechanisms underlying KIR checkpoint blockade. Notably, the epitope includes several key amino acids that vary across the human population, and binding studies demonstrate the importance of these amino acids for lirilumab binding. These studies reveal how KIR variations in patients could influence the clinical efficacy of lirilumab and reveal general concepts for the development of immune checkpoint inhibitors targeting NK cells.

BACKGROUND: Untargeted high-resolution metabolomic profiling provides simultaneous measurement of thousands of metabolites. Metabolic networks based on these data can help uncover disease-related perturbations across interconnected pathways. OBJECTIVE: Identify metabolic disturbances associated with Parkinsons disease (PD) in two population-based studies using untargeted metabolomics. METHODS: We performed a metabolome-wide association study (MWAS) of PD using serum-based untargeted metabolomics data derived from liquid chromatography with high-resolution mass spectrometry (LC-HRMS) using two distinct population-based case-control populations. We also combined our results with a previous publication of 34 metabolites linked to PD in a large-scale, untargeted MWAS to assess external validation. RESULTS: LC-HRMS detected 4,762 metabolites for analysis (HILIC: 2716 metabolites; C18: 2046 metabolites). We identified 296 features associated with PD at FDR

In this study, a Gram-stain-positive, non-motile, oxidase- and catalase-negative, rod-shaped, bacterial strain (SG_E_30_P1T) that formed light yellow colonies was isolated from a groundwater sample of Sztaravoda spring, Hungary. Based on 16S rRNA phylogenetic and phylogenomic analyses, the strain was found to form a distinct linage within the family Microbacteriaceae. Its closest relatives in terms of near full-length 16S rRNA gene sequences are Salinibacterium hongtaonis MH299814 (97.72 % sequence similarity) and Leifsonia psychrotolerans GQ406810 (97.57 %). The novel strain grows optimally at 20-28 °C, at neutral pH and in the presence of NaCl (1-2 w/v%). Strain SG_E_30_P1T contains MK-7 and B-type peptidoglycan with diaminobutyrate as the diagnostic amino acid. The major cellular fatty acids are anteiso-C15 : 0, iso-C16 : 0 and iso-C14 : 0, and the polar lipid profile is composed of diphosphatidylglycerol and phosphatidylglycerol, as well as an unidentified aminoglycolipid, aminophospholipid and some unidentified phospholipids. The assembled draft genome is a contig with a total length of 2 897 968 bp and a DNA G+C content of 65.5 mol%. Amino acid identity values with it closest relatives with sequenced genomes of

Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.

Chaperonin-containing T-complex polypeptide 1 (CCT) is a molecular chaperone in the cytoplasm of eukaryotic cells involved in the correct folding and assembly of proteins, which plays an important role in cold-stress response. This study cloned two transcripts of Pinctada maxima CCT-beta composed of 1,829 bp (CCT-betal) and 2,289 bp (CCT-beta2), respectively, using rapid amplification of cDNA ends. Both transcripts possess 105 bp of 5' noncoding region and the same coding region, bul contain different 3' noncoding regions of 591 bp (CCT-betal) and 131 bp (CCT-beta2), respectively. The open reading framework (ORF) consisted of 1,593 bp that encodes 530 amino acids. The CCT-beta protein has three conserved functional domains (equatorial, apical, and intermediate domains), three CCT-family signature sequences, nine conserved ATP-binding sites, one DEAD box motif, and three protein-binding sites. The CCT-beta is highly conserved, with the cDNA homologies between P. maxima and Crassostrea gigas, Danio rerio, and Homo sapiens being 90.4%. 76.8%, and 75.8%, respectively. Real-time quantitative PCR showed that CCT-beta was differentially expressed in different organs of P. maxima, with mRNA contents declining from the gill, adductor muscle, foot, labial palps, mantle, and heart to hepatopancreas. Under cold stress, CCT-beta mRNA expression in various organs increased, but the patterns of increase varied among organs. The transcriptional level of CCT-beta peaked at 6h in the heart and hepatopancreas, and decreased significantly at 12h. In the adductor muscle, gill, and mantle, CCT-beta mRNA increased significantly at 12h and declined markedly at 24h in cold stress-exposed animals. These results indicate that CCT-beta is a cold-stress response gene, but the response pattern varies among organs. Organs with low CCT-beta basal expression may be more sensitive to cold stress than the organs with relatively high basal expression content. KEY WORDS: Pinctada maxima, CCT-beta, cDNA, cold stress, INTRODUCTION Chaperonin-containing T-complex polypeptide 1 (CCT) is a kind of type II chaperonin that is localized in the cytoplasm of eukaryotes (Frydman et al. 1992, Gao et al. 1992, Lewis [...]

BACKGROUND: Higher alcohol acetates (HAAs) are potent aroma‐active esters that impart desirable fruity and floral aromas. However, the conversion of higher alcohol precursors into HAAs is extremely low in winemaking. To investigate the underlying yeast–yeast interaction on targeted improvement of aromatic HAAs, we evaluated fermentation activity, cell viability, amino acid consumption and HAA production when Pichia kluyveri and Saccharomyces cerevisiae were inoculated concurrently or sequentially. RESULTS: Pichia kluyveri PK‐21 possessed the ability to survive and increased HAA level up to 5.2‐fold in mixed fermentation. Such an increment may benefit from the efficient conversion of higher alcohol precursors into HAAs (>27‐fold higher than S. cerevisiae). During mixed fermentation, the two yeasts exhibited crucial interactions regarding cell growth and amino acid competition. Saccharomyces cerevisiae dominated over the co‐inoculated P. kluyveri by efficient uptake of amino acids and biomass production. However, this dominance decreased in sequential fermentation, where P. kluyveri growth increased due to the consumption of preferred amino acids prior to S. cerevisiae. Pearson correlation analysis indicated that phenylalanine and aspartic acid may act as positive amino acids in boosting P. kluyveri growth and HAA production. Laboratory‐scale winemaking validated the fermentation performance of P. kluyveri in sequential inoculum, resulting in a balanced aroma profile with enhanced floral and tropical fruity characteristics in the final wines. CONCLUSION: This study proposes a microbial, non‐genetically engineered approach for targeted increase of HAA production in winemaking and the findings provide new insights into yeast–yeast interactions. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Rationale: Concerns exist over observed shifts in value and variance of nitrogen isotopes following physicochemical extraction of lipids from organic matter. The mechanisms behind these apparent changes in bulk tissue δ15N values are not fully understood yet have major implications for analytical costs and integrity of data interpretations. Methods: Changes in proximate analysis, amino acid composition, C:N ratios, bulk tissue and amino acid δ13C and δ15N values, and resulting isotope‐based food web metrics were compared between lipid‐intact and lipid‐extracted muscle tissue of fishes spanning <1% to >20% muscle fat content to identify mechanisms of nitrogen isotope fractionation associated with physicochemical lipid extraction. Results: Bulk δ13C and δ15N values increased and %N, C:N ratios and crude protein content decreased following lipid extraction. Resulting bulk isotope niche spacing and overlap varied significantly between lipid‐intact and lipid‐extracted tissues. While amino acid composition significantly changed during lipid extraction, particularly for lipid‐associated amino acids (e.g., Glu, Lys, Ser), individual amino acid δ13C and δ15N values, and their associated compound‐specific isotope analysis of amino acids (CSIA‐AA)‐based food web metrics, did not. Conclusions: Physicochemical lipid extraction caused significant tissue composition changes (e.g., leaching of amino acids and 15N‐deplete nitrogenous waste) that affected δ13C and δ15N values and tissue %C and %N beyond simply removing lipids. However, lipid extraction did not alter individual amino acid δ13C or δ15N values or their associated CSIA‐AA‐based food web metrics. [ABSTRACT FROM AUTHOR]

Amino acids are important for cellular metabolism. Their uptake across the plasma membrane is mediated by transport proteins. Despite the fact that the organic anion transporting polypeptide 4C1 (OATP4C1, Uniprot: Q6ZQN7) mediates transport of l‐arginine and l‐arginine derivatives, other members of the OATP family have not been characterized as amino acid transporters. The OATP family member OATP3A1 (gene symbol SLCO3A1, Uniprot: Q9UIG8) is ubiquitously expressed in human cells and highly expressed in many cancer tissues and cell lines. However, only a few substrates are known for OATP3A1. Accordingly, knowledge about its biological relevance is restricted. Our aim was to identify new substrates of OATP3A1 to gain insights into its (patho‐)physiological function. In an LC‐MS‐based untargeted metabolomics assay using untreated OATP3A1‐overexpressing HEK293 cells and control cells, we identified several amino acids as potential substrates of OATP3A1. Subsequent uptake experiments using exogenously added substrates revealed OATP3A1‐mediated transport of l‐tryptophan, l‐tyrosine, and l‐phenylalanine with 194.8 ± 28.7% (P < 0.05), 226.2 ± 18.7% (P < 0.001), and 235.2 ± 13.5% (P < 0.001), respectively, in OATP3A1‐overexpressing cells compared to control cells. Furthermore, kinetic transport parameters (Km values) were determined (Trp = 61.5 ± 14.2 μm, Tyr = 220.8 ± 54.5 μm, Phe = 234.7 ± 20.6 μm). In summary, we identified the amino acids l‐tryptophan, l‐tyrosine, and l‐phenylalanine as new substrates of OATP3A1. These findings could be used for a better understanding of (patho‐)physiological processes involving increased demand of amino acids, where OATP3A1 should be considered as an important uptake transporter of l‐tryptophan, l‐tyrosine, and l‐phenylalanine. [ABSTRACT FROM AUTHOR]

Proteinaceous matter (PrM) is a substantial component of bioaerosols. Although numerous studies have examined the characteristics and sources of PrM in the atmosphere, its interactions with atmospheric oxidants remain uncertain. A 1‐year observation of PrM characteristics in PM2.5 was performed in both urban Nanchang (eastern China) and suburban Guiyang (southwestern China), respectively. Glycine was the dominant free amino acid (FAA) species in urban Nanchang. In contrast, proline dominated both total free amino acids (FAAs) and total combined amino acids (CAAs) in suburban Guiyang. We found that oxidative degradation can significantly promote the release of FAAs, especially glycine, from CAAs in Nanchang. The controlled experiment on protein oxidation by hydroxyl radical suggested that the contribution of free glycine to the total FAA fraction tended to increase during the oxidative degradation of CAAs, supporting the predominance of glycine in FAAs in Nanchang and most previous observations. The composition of FAAs was mainly influenced by primary sources in suburban Guiyang with weak atmospheric degradation of PrM. These results suggest that the degradation of aerosol PrM by atmospheric oxidants can be responsible for the difference in FAA composition between the biosphere and the atmosphere, and also imply that the oxidative degradation of aerosol PrM may be a potential source of secondary organic nitrogen compounds in aerosols. Thus, this study can improve the current understanding of the composition characteristics of PrM in the biosphere and the atmosphere, as well as the liquid phase reactions of proteinaceous compounds with atmospheric oxidants. Plain Language Summary: Proteinaceous matter (PrM) is a ubiquitous component in both the biosphere and the atmosphere, which has seen intense research over years. This study, for the first time, combines a large amount of observational data with controlled experiments to reveal the potential atmospheric transformation of combined and free amino acids. The observed increase in the mass fraction of glycine in the total free amino acids from the biosphere to the atmosphere can be attributed to the fact that glycine has a higher release potential from the oxidative degradation of combined amino acids and is more resistant to further oxidative degradation. The overall results provide field evidence for the strong dependence of free glycine release from aerosol PrM on the hydroxyl radical, likely improving the current understanding of the composition characteristics of PrM and the multiphase reactions of proteinaceous compounds with atmospheric oxidants. Key Points: Atmospheric oxidation can cause an increase in the contribution of Gly to the aerosol TFAA fraction from the biosphere to the atmosphereThe controlled experiment suggests that the contribution of Gly to the TFAA fraction increased during the oxidative degradation of combined amino acidsThe composition profile of aerosol free amino acids depends on the oxidative degradation of proteinaceous matter after release from the biosphere to the atmosphere [ABSTRACT FROM AUTHOR]

The formulation and delivery of macromolecules through the oral route pose considerable challenges due to factors such as large molecular weight, pH sensitivity, and limited formulation approaches. This challenge is compounded if the drug is poorly permeable, necessitating innovative drug delivery strategies. Vancomycin, a widely prescribed glycopeptide antibiotic, has an oral bioavailability of less than 10%, leading to predominantly intravenous administration and potential patient discomfort. This study explores the potential of the buccal route as a non-invasive, highly vascularised alternative route of administration, offering a rapid onset of action while bypassing the first-pass metabolism. In this study, vancomycin was coated with L-glutamic acid using an isothermal dry particle coater to modulate permeation through the buccal cell line, TR146. Results confirm significant impact of both amino acid concentration and dry particle coating on the rate and extent of drug permeability. With the introduction of L-glutamic acid and utilisation of the isothermal dry particle coater, vancomycin's permeation profile increased six-fold compared to the control due to the formation of drug ion-pair complex. Imaging studies showed the presence of layered micronized glutamic acid particles on the surface of dry coated vancomycin particles which confirms the role of dry coating and amino acid concentration in modulating drug permeation. Microbiology experiments in Staphylococcus aureus, minimum inhibitory concentration and biofilm disruption studies, provided confirmatory evidence of antimicrobial activity of dry coated glutamic acid-vancomycin ion pair particulate structure. This study demonstrates, for the first-time, buccal delivery of dry coated large molecule drug, vancomycin, through controlled deposition of amino acid using innovative particle coating strategy. [ABSTRACT FROM AUTHOR]

Background: Amino acids are crucial for nutrition and metabolism, regulating metabolic pathways and activities vital to organismal health and stability. Glycine and histidine act as potent antioxidants and anti-inflammatory agents; however, limited knowledge exists regarding the associations between these amino acids and hyperlipidemia and hypertension. The purpose of this study is to investigate the relationship between dietary glycine and histidine, and hyperlipidemia and hypertension. Methods: This population-based cross-sectional study evaluated the influence of dietary glycine and histidine, as well as their combined effect, on hyperlipidemia and hypertension in Chinese adults participating in the Nutrition Health Atlas Project (NHAP). General characteristics were acquired using a verified Internet-based Dietary Questionnaire for the Chinese. Binary logistic regression, along with gender, age groups, and median energy intake subgroup analyses, was employed to investigate the associations between dietary glycine and histidine and hyperlipidemia and hypertension. A sensitivity analysis was conducted to assess the impact of excluding individuals who smoke and consume alcohol on the results. Results: Based on the study's findings, 418 out of 1091 cases had hyperlipidemia, whereas 673 had hypertension. A significant inverse relationship was found between dietary glycine, histidine, and glycine + histidine and hyperlipidemia and hypertension. Compared with the 1st and 2nd tertiles, the multivariable-adjusted odd ratios (ORs) (95% confidence intervals) (CIs) of the 3rd tertile of dietary glycine for hyperlipidemia and hypertension were 0.64 (0.49–0.84) (p < 0.01) and 0.70 (0.56–0.88) (p < 0.001); histidine was 0.63 (0.49–0.82) (p < 0.01) and 0.80 (0.64–0.99) (p < 0.01); and glycine + histidine was 0.64 (0.49–0.83) (p < 0.01) and 0.74 (0.59–0.92) (p < 0.001), respectively. High glycine and high histidine (HGHH) intake were negatively associated with hyperlipidemia and hypertension OR (95% CIs) were: 0.71 (0.58–0.88) (p < 0.01) and 0.73 (0.61–0.87) (p < 0.01), respectively. Conclusions: Dietary glycine and histidine, as well as their HGHH group, revealed an inverse relationship with hyperlipidemia and hypertension. Further investigations are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. Methods: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. Results: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. Conclusions: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.). [ABSTRACT FROM AUTHOR]

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins. [ABSTRACT FROM AUTHOR]

Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof‐of‐concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p and interacts with Ago2. Trp/Ago2/miR‐193a increases miR‐193a‐3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR‐103 and miR‐107 in the Trp complex enhance miR‐193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR‐193a complex interacts with Trp‐binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR‐193a‐3p complex is more efficient than miR‐193a‐3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA‐induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy. [ABSTRACT FROM AUTHOR]

An efficient synthesis of spiro[2.3]hexane‐ and spiro[3.3]heptane‐derived α‐amino acids is reported. The used methods are divided on two different approaches. First of them involves modification of commercially available spirocyclic diesters via monohydrolysis, Curtius rearrangement and functional groups deprotection sequence. Alternative approach was based on Bucherer ‐ Bergs hydantoine synthesis with its subsequent cleavage to the target amino acid fragment. The proposed synthetic schemes offer the desired product in 31–52 % overall yield on up to 22.5 g scale. Acid‐base titration of the obtained spirocyclic amino acids revealed lowered pI values compared to the parent 1‐amino‐cyclohexane‐ and ‐cycloheptanecarboxylic acids. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Traditional fish sauce products rely on relatively long fermentation time and high salt concentration, resulting in inconsistent quality and health risks. Branched‐chain fatty acids (BCFAs) are associated with nutritional benefits and health‐care effects, mainly derived from food fermentation. This study aimed to screen BCFAs‐producing bacteria with high protease and aminotransferase activity as starter cultures for fish sauce fermentation.The low‐salt fish sauce products were obtained by co‐fermentation with three chosen strains. Trichloroacetic acid (TCA)‐soluble peptides and amino acid nitrogen concentrations were higher in the co‐fermentation group (FH group). The organoleptic evaluation showed co‐fermentation optimized flavor composition and endured with rich taste. The levels of BCFAs and branched‐chain amino acids (BCAAs) significantly increased by co‐fermentation. Volatile metabolomics analysis indicated that BCFAs, branched‐chain esters, and pyrazines were the key flavor compounds in the co‐fermented group.The co‐fermentation system with selected strains to ferment low‐salt fish sauce has the potential to increase BCFA content and improve flavor and nutrition. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The current evaluation was conducted to investigate the chemical composition and functional properties of protein hydrolysates from different Satureja species. The major amino acids (mg/100 g protein) in the protein from different Satureja species were arginine (6.06–14.37), asparagine (1.39–17.06), glutamine (2.42–11.60), glutamic acid (6.34–9.32), beta‐aminoisobutyric acid (3.31–10.29), alanine (4.64–9.59), aspartic acid (5.73–9.54), proline (4.25–8.14), leucine (3.63–5.69), serine (2.64–4.83), lysine (1.89–4.56), glycine (0.96–5.27), valine (2.76–4.83), and phenylalanine (2.86–3.75). Protein hydrolysates from Satureja species exhibited comparable antioxidant activity (IC50 = 0.270–0.328 mg/mL), anti‐linoleic acid oxidation (IC50 = 0.231–0.301 mg/mL), anti‐lecithin oxidation (IC50 = 0.198–0.258 mg/mL), anti‐starch oxidation (IC50 = 0.201–0.277 mg/mL), anti‐amylase activity (IC50 = 0.314–0.337 mg/mL), and anti‐lipase activity (IC50 = 0.309–0.369 mg/mL). The physico‐chemical properties of gelatin dispersion were electrical conductivity (1197 microsiemens/cm), osmolarity (190 milliosmol/kg), surface tension (45 mN/m), particle size (179 nm), zeta potential (−48 mV), and viscosity (4.92 mPa.s). Techno‐functional characteristics of freeze‐dried gelatin particles were as follows: water content (7.68%), water solubility (84.57%), water swelling (151.33%), hygroscopicity (38.20%), hydrophobicity (6.50 μg/g), emulsification activity (68.54%), emulsification stability (57.86%), foam expansion activity (56.08%), foam stability (41.84%), oil‐holding capacity (1.96 g/g), and water‐holding capacity (4.45 g/g). Protein hydrolysate causes minor changes in the physico‐chemical and techno‐functional properties of gelatin. The current investigation introduces Satureja protein hydrolysate as a possible functional and techno‐functional ingredient for bioactive food products for treating diabetes and oxidative stress and as a natural preservative for the food industry. [ABSTRACT FROM AUTHOR]

Herein, we present the first metal-free decarboxylative C(sp3)–C(sp3) cross-coupling of glycine derivatives with redox-active esters through highly atom and energy economical convergent paired electrolysis enabled radical–radical cross-coupling. Under mild and scalable conditions, various α-alkylated unnatural α-amino acids were prepared efficiently from readily available starting materials. The key point for the successful implementation of this strategy is minimizing the interelectrode distance to permit the rapid diffusion of radical species and outpace radical decomposition. Mechanistic investigations showed a radical–radical coupling pathway generated from anode and cathode simultaneously in the same electrolysis system. This novel protocol was successfully applied for the late-stage modification of pharmaceuticals, amino acids and peptides. [ABSTRACT FROM AUTHOR]

The 1D homochiral coordination polymer (CP-1) {[Co(dTMP)(bpe)2(H2O)3]·9H2O}n was constructed by using 2′-deoxy thymidine 5′-monophosphate disodium salt (dTMP·2Na), and auxiliary ligand bpe (1,2-bis(4-pyridyl)ethene) and characterized by single-crystal XRD, PXRD, IR, UV-visible, CD and TGA analyses. Molecular simulations revealed the selective chiral behaviour of CP-1 towards phenylalanine and histidine, as indicated by their higher binding free energies compared to other amino acids. Theoretical parameters were also compared with experimental UV-visible verdicts. Notably, the D -enantiomers of phenylalanine and histidine demonstrated strong bonding abilities and optimal configurations for probing and distinguishing them from their L -counterparts. These findings led to propositions suggesting that the dissimilarities between these D and L amino acid forms and their binding orientations with CP-1 may contribute to alterations in the CD signal. CP-1 exhibited a robust inherent circular dichroism (CD) signal in aqueous solutions, modulated by the presence of specific amino acids, namely D / L phenylalanine and D / L histidine. Leveraging the measurement of CD signal intensity, a sensor capable of detecting unmodified amino acids has been developed. Unlike previously reported approaches that relied on complex chemical reactions between initially CD-silent molecules and probed amino acids, this new method offers a more straightforward means of amplifying the CD signal. Consequently, this change facilitates a more accurate differentiation between the enantiomers of these specific amino acids compared to others. [ABSTRACT FROM AUTHOR]

Fluorescence indicators capable of binding to human immunodeficiency virus-1 (HIV-1) trans-activation responsive (TAR) RNA are powerful tools for the exploratory studies of the identification of anti-HIV drug candidates. This work presents a new design strategy for fluorogenic indicators with a transactivator of transcription (Tat)-derived peptide based on the forced intercalation of thiazole orange (TO) dyes (FIT). The developed 9-mer FIT peptide (RKKRR-TO-RRR: named FiLuP) features the TO unit integrated onto a Dap (2,3-diaminopropionic acid) residue in the middle of the Tat peptide sequence; the Q (glutamic acid) residue in the Tat peptide (RKKRR-Q-RRR) is replaced with TO as if it were an amino acid surrogate. This facilitates a significant light-up response (450-fold at λem = 541 nm, Φfree = 0.0057, and Φbound = 0.61) upon binding to TAR RNA. The response of FiLuP is highly selective to TAR RNA over other non-cognate RNAs, and FiLuP maintains strong binding affinity (Kd = 1.0 ± 0.6 nM). Significantly, in contrast to previously developed Tat peptide-based FRET probes, FiLuP is able to discriminate between "competitive" and "noncompetitive" inhibitors when used in the fluorescence indicator displacement (FID) assay. The FID assay under stringent screening conditions is also possible, enabling super-strong competitive binders toward TAR RNA to be sieved out. [ABSTRACT FROM AUTHOR]

In this study, we explored the effects of chronic stress on lumpfish (Cyclopterus lumpus) physiological, immune response, health, and plasma free amino acids. 3 groups of lumpfish were exposed to 1-minute air exposure. 1 group was exposed to stress once per week, a second group exposed 2 times per week, and a third group exposed 4 times per week. The present study revealed significant alterations in immunity and increased nutritional demands, particularly the branched chain amino acids and lysine. Cortisol levels fluctuated, with significantly higher levels halfway through the experiment on the groups that were stressed more often. Though, by the end of the experiment, there were no significant differences in cortisol levels between groups. Regardless of stress exposure, cataract developed in virtually all sampled fish, pointing toward a potential dietary imbalance. A transient immunomodulation of stress was visible. While in early stages stress had an immune enhancing effect, as seen by the increase in plasma nitric oxide and peroxidase in the group most frequently exposed to stress, these differences were not apparent by the end of the experiment. Additionally, the worst health condition was found in this group. Our results underscore the complex interplay between stress, immunity and nutrition, highlighting the need for tailored dietary strategies and improved rearing practices. [ABSTRACT FROM AUTHOR]

This paper is an attempt to generalize the nitrogen isotope information of the molecules that make up the cell from our point of view. Nitrogen in the cell exists as 20 proteinaceous amino acids, nucleobases, hemes, chlorophylls, and others, and their composition is similar among organisms. Based on a physiologically simple autonomous system that maintains a balance between inputs and outputs, it is theoretically predicted that 15N is distributed to each cellular compound with a certain regularity, and thus a specific relationship in nitrogen isotopic ratios among compounds. Previous studies essentially confirm this. The nitrogen isotopic ratio of compound i constituting the cell can be generalized as δ15Ni = δ15Nplant + Δi (TP − 1) + γi, where TP represents the trophic position, and Δi and γi are the trophic discrimination factor and the intracellular 15N distribution of compound i, respectively. Knowing reliable values of Δi and γi will help us to better understand nitrogen dynamics in the biosphere and advance our understanding of the picture of the Earth's environment through biogeochemistry. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA), a ubiquitous non-protein 4-carbon amino acid present in both prokaryotic and eukaryotic organisms. It is conventionally recognized as a neurotransmitter in mammals and plays a crucial role in plants. The context of this review centers on the impact of GABA in mitigating abiotic stresses induced by climate change, such as drought, salinity, heat, and heavy metal exposure. Beyond its neurotransmitter role, GABA emerges as a key player in diverse metabolic processes, safeguarding plants against multifaceted abiotic as well as biotic challenges. This comprehensive exploration delves into the GABA biosynthetic pathway, its transport mechanisms, and its intricate interplay with various abiotic stresses. The discussion extends to the nuanced relationship between GABA and phytohormones during abiotic stress acclimation, offering insights into the strategic development of mitigation strategies against these stresses. The delineation of GABA's crosstalk with phytohormones underscores its pivotal role in formulating crucial strategies for abiotic stress alleviation in plants. [ABSTRACT FROM AUTHOR]

More than a century after the first description of Alzheimer's disease (AD), the road to a cure for this complex and heterogeneous neurodegenerative disorder has been paved by countless descriptive hypotheses and successive clinical trial failures. Auspiciously, the era of genome-wide association studies revolutionized the classical "neurocentric" view of AD by providing clues that brain-resident immune cells (i.e., microglia and astrocytes) are also key players in the pathological and clinical trajectory of this neurodegenerative disorder. Considering that the intercommunication among neurons, astrocytes, and microglia is fundamental for the functional organization of the brain, it is evident that the disruption of the proper functioning of this "triad" could contribute to the neuroinflammatory and neurodegenerative events that occur in the AD brain. Importantly, recent scientific progress in the burgeoning field of immunometabolism, a crossroad between metabolism and immune response, shed light on the importance of metabolic reprogramming of brain-resident immune cells in AD pathology. In this sense, the present review is aimed to summarize and discuss the current knowledge on the metabolic patterns of brain-resident immune cells during the AD continuum, putting a special focus on glucose, amino acids, and lipid metabolism. Changing the "old" picture of AD pathological basis by integrating the role of brain-resident immune cells it is imperative to establish new and feasible therapeutic interventions able to curb neuroinflammatory and neurodegenerative processes, and consequently cognitive deterioration. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSThe ornithine-urea cycle (OUC) in fungal cells has biotechnological importance and many physiological functions and is closely related to the acetyl glutamate cycle (AGC). Fumarate can be released from argininosuccinate under the catalysis of argininosuccinate lyase in OUC which is regulated by the Ca2+ signaling pathway and over 93.9 ± 0.8 g/L fumarate can be yielded by the engineered strain of Aureobasidium pullulans var. aubasidani in the presence of CaCO3. Furthermore, 2.1 ± 0.02 mg of L-ornithine (L-Orn)/mg of the protein also can be synthesized via OUC by the engineered strains of Aureobasidum melanogenum. Fumarate can be transformed into many drugs and amino acids and L-Orn can be converted into siderophores (1.7 g/L), putrescine (33.4 g/L) and L-piperazic acid (L-Piz) (3.0 g/L), by different recombinant strains of A. melanogenum. All the fumarate, L-Orn, siderophore, putrescine and L-Piz have many applications. As the yeast-like fungi and the promising chassis, Aureobasidium spp, have many advantages over any other fungal strains. Further genetic manipulation and bioengineering will enhance the biosynthesis of fumarate and L-Orn and their derivates.OUC in fungal cells has biotechnological importance and many physiological functions; OUC is closely related to acetyl glutamate cycle (AGC). Fumarate, L-Orn, siderophore, putrescine and L-Piz produced from OUC have many applications. [ABSTRACT FROM AUTHOR]

The objective was to conduct a systematic review to clarify the effects of l‐arginine supplementation in pregnant and lactating sows on plasma hormone levels, milk production and composition, the body condition of sows and piglet performance. In April 2023, an online search and a systematic search were performed in the following databases: Embase, Scopus, SciELO, Web of Science, PubMed and Science Direct. The combinations of keywords used were sow and arginine and lactation; sow and arginine and lactating; sow and arginine and gestation; sow and arginine and gestating; sow and arginine and pregnancy; sow and arginine and reproduction; piglet and arginine; and sow and arginine and mammary gland. In total, 21 scientific articles with original data were selected according to preestablished criteria. Among the 21 articles, seven (33%) reported measurements of some plasma hormones, and among these, six reported an increase in the levels of at least one hormone, namely, estradiol, insulin‐like growth factor 1 (IGF‐1), insulin, follicle stimulating hormone, growth hormone or prolactin, with l‐arginine supplementation. The parameters of milk were evaluated in 11 studies (52%), one reported an increase in protein content, and one reported an increase in IGF‐1 content in milk with supplementation of this amino acid. Of the 14 studies that evaluated the performance parameters of piglets, only four reported improvements in some parameters of piglets from sows that received supplementation. Dietary supplementation of arginine for sows in the final third of gestation and/or lactation may alter the plasma levels of some hormones, which may reflect in greater development of the mammary gland tissue and, consequently, promote benefits on the performance of piglets. However, more studies are needed to evaluate the real impact of this amino acid supplementation on the physiology of the sows, in general, and the performance of suckling piglets. [ABSTRACT FROM AUTHOR]

Summary The present study investigated the phenolic profile, sugar composition and amino acid profile of lyophilised 10‐day‐old wheatgrass cultivated under varying temperature and photoperiod conditions. The targeted phenolic profile showed the abundant presence of chlorogenic, caffeic, ferulic and p‐coumaric acid. The phenolic content varied with temperature and photoperiod conditions. The comprehensive sugar profile indicated the variation in the concentration of glucose with different growing conditions altered carbohydrate metabolism in wheatgrass. Similarly, the concentration of amino acids also varied with growing conditions. Notably, the concentration of proline, arginine and GABA in wheatgrass from all wheat varieties increased more prominently in photoperiod of 22 h and growth temperature of 22 °C in light and 17 °C in dark as a response of defence mechanism. [ABSTRACT FROM AUTHOR]