Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

Peanut proteins:Extraction,modifications,and applications:A comprehensive review

As naturally sourced proteins,peanut proteins have garnered significant attention from the food industry,owing to their numerous advantages,such as easy extraction,non-pungency,and high bioavailability.Furthermore,peanut proteins are highly digestible in the gastrointestinal tract and boast a high net protein utilization rate,making them an appealing protein source in food products and a promising alternative to animal protein.In this paper,the recent works on the extraction method,modification method,and application of peanut proteins were reviewed.Both advantages and disadvantages of current extraction and modification were discussed.Recently updated information about peanut protein research was summarized.Based on these,the prospection of peanut proteins research was presented,which may be instructive for future research in this field.Future research is still needed for accessible modification methods to develop the functional properties of peanut proteins.

Value of N-Terminal Pro B-Type Natriuretic Peptide,High-Sensitivity C-Reactive Protein,and Homocysteine Levels in Predicting Cardiovascular Events in Chronic Heart Failure Patients After Discharge

Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.

Post-translational modifications of hepatitis C viral proteins and their biological significance

Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.

The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

Impact of hot alkali modification conditions on secondary structure of peanut protein and embedding rate of curcumin

This study aimed to modify isolated and extracted peanut protein with hot alkali to study the impact of pH,heating temperature,processing time and other alkali liquor conditions on the molecular structure of the peanut.Curcumin was loaded in modified peanut protein.The results of the study are as follows:Within the alkaline range of 8<pH<12,the percentage of amino acid residue(AAR)and-turns first increased and then decreased with the increasing pH,and the percentage of AAR reached a maximum 5.21±0.33%when the pH was 11(p<0.01).The percentage of˛-helices andβ-sheets gradually decreased with increasing pH,while that of random coils gradually increased with increasing pH,reaching a maximum 11.24±0.87%when the pH was 11(p<0.05).Within the range of the heating temperature 75℃<T<95℃,the percentage of random coils andβ-sheets gradually increased with increasing heating temperature,while that of-helices and AAR gradually decreased with increasing heating temperature;they remained unchanged when the heating temperature was 90℃,and then decreased to(10.41±1.18%;p<0.01)and(4.02±2.12%;p<0.01),respectively.Within the range of 5 min<t<20 min,the percentage of random coils and AAR gradually increased with increasing heating time,while the percentage ofα-helices decreased from 11.83±1.04%to 10.75±2.34%with increased heating time(p<0.01).The optimum conditions for hot alkali modification of peanut protein as followed:heating temperature of 90℃,heating time of 20 min and a pH of alkali liquor of 11.Under these optimum conditions,the embedding rate of curcumin by the modified protein can reach 88.32±1.29%.

Lipid accumulation and protein modifications of Bruch’s membrane in age-related macular degeneration

Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.

Complex interactomes and post-translational modifications of the regulatory proteins HABP4 and SERBP1 suggest pleiotropic cellular functions

The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named CGI-55,or plasminogen activator inhibitor type-1-RNA binding protein-1,indicating that they might be paralog proteins,possibly with similar or redundant functions in human cells.Through the identification of their protein interactomes,both regulatory proteins have been functionally implicated in transcriptional regulation,mRNA metabolism,specifically RNA splicing,the regulation of mRNA stability,especially,in the context of the progesterone hormone response,and the DNA damage response.Both proteins also show a complex pattern of post-translational modifications,involving Ser/Thr phosphorylation,mainly through protein kinase C,arginine methylation and SUMOylation,suggesting that their functions and locations are highly regulated.Furthermore,they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies,upon stress,and nuclear splicing speckles.Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis.This review highlights important aspects of the structure,interactome,post-translational modifications,sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.

Characterization of physicochemical and immunogenic properties of allergenic proteins altered by food processing:a review

Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.

Aberrant post-translational protein modifications in the pathogenesis of alcohol-induced liver injury

It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.

Computer-Assisted analysis of subcellular localization signals and post-translational modifications of human prion proteins

In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determined to be in the nu-cleolus inside the nucleus by the following bio-informatics tools: Hum-PLoc, Euk-PLoc and Nuc-PLoc. Based on our results signal peptides with average of 22 base pairs in N-terminal were identified in human PrPs. This theoretical study demonstrates that PrP is post-translationally modified by: 1) attachment of two N-linked complex carbohydrate moieties (N181 and N197), 2) attachmet of glycosylphosphatidylinositol (GPI) at serine 230 and 3) formation of two di-sulfide bonds between “6–22” and “179–214” cysteines. Furthermore, ten protein kinase phosphorylation sites were predicted in human PrP. The above-noted phosphorylation was car-ried out by PKC and CK2. By using bioinfor-matics tools, we have shown that computation-ally human PrPs locate particularly into the nu-cleolus.

RimJ-Catalyzed Sequence-Specific Protein N-Terminal Acetylation in <i>Escherichia coli</i>

In order to establish the sequence dependence of RimJ-mediated protein N-terminal acetylation in E. coli, the Z-domain variants differing by the second or third amino acid residue were expressed and analyzed by mass spectrometry. Only subsequent to the initiating methionine residue cleavage, the RimJ-catalyzed N-terminal acetylation mainly occurred at the N-terminal serine and threonine residues and was significantly enhanced by hydrophobic or negatively charged residues in the penultimate position.

2007 International Symposium on Protein Modification and Degradation in Beijing(SPMDB2007)

Presidents of Symposium Depei Liu,President of Chinese Academy of Medical Sciences Zhu Chen,Vice President of Chinese Academy ofSciences.

Effect of Electrode Surface Modification by Sulfide on QCM Based Protein Biosensor

The rapid development of surface sensitive biosensor technologies requires optimum control of surface modification to provide reliable and reproducible results. With the aim to assemble a quartz crystal microbalance (QCM)-based protein biosensor, we focus our attention on sulfide receptor and its integration with the surface of the electrode. Here, we present different surface modification processing time to allow sulfide molecules to be immobilized to gold coated sensor for QCM sensing. The optimum surface modification processing time is also obtained by bovine serum albumin (BSA) binding measurement.

Chemical Modification of Food Proteins

Acylation has been shown to be an effective toolfor improving surface functional properties of plant proteins.Soy bean protein has been extensively modified throughchemical and enzvmatic treatments.Their effectiveness lies intheir high nutritional value and low cost,which promotetheir use as ingredients for the formulation of food products.This paper reports a complete review of chemical modificationof various proteins from plant and animal sources,The nutri-tive and toxicological aspects through in vitro and in vivotests are also described.

Evaluation of laboratory and environmental exposure systems for protein modification upon gas pollutants and environmental factors

Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere.Using bovine serum albumin(BSA)as a model protein,we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study.In the laboratory simulation system,the generated gaseous pollutants showed negligible losses.Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%.For environmental exposure experiment,quartz fiber filter was selected as the upper filter with low gaseous O_(3)(8.0%)and NO_(2)(1.7%)losses,and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%.The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions,while environmental factors(e.g.,molecular oxygen and ultraviolet)may cause greater protein monomer losses.Based on the evaluation,the study exemplarily applied the two systems to protein modification and both showed that O_(3) promotes the protein oligomerization and nitration,while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples.The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions.A combination of the two will further reveal the actual mechanism of protein modifications.

Protein post-translational modifications in auxin signaling

Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.

Cold Plasma Surface Modification of NiTi for Biomedical Applications

Surface-grafted poly(ethylene glycol) (PEG) molecules are known to prevent protein adsorption to the surface. Nitinol samples were coated under tetraglyme ECR cold plasma conditions to enhance its biocompatibility. The modified Nitinol surfaces were characterized by high resolution ESCA and contact angle, it was demonstrated that the deposited PEG-like coatings were built up mainly of-CH2-CH2-O- linkages in surfaces. The surface wettability of the modified Nitinol was increased compared with the control surface. Human plasma protein was adsorbed on Nitinol evaluated by SEM, the protein adsorption on modified surfaces decreased rapidly. Thus, the potential benefits of cold plasma technique will be of use to the biomedical industries improving the biocompatibility of metals.

Combined molecular docking, homology modeling and DFTmethod for the modification of bovine serum albumin (BSA) toimprove fluorescence spectroscopy for phthalate acid esterschelated with BSA

While phthalate acid esters(PAEs)cannot fluoresce alone,they can be detected by fluorescence spectroscopy after chelation with bovine serum albumin(BSA).In this study,the types of amino acid residues at the active site of PAEs chelated with BSA were determined using molecular docking technology.A modification scheme of BSA with higher detection sensitivity fluorescence spectroscopy for PAEs was proposed based on the docking results and constructed for a novel BSA structure with a higher detection sensitivity of fluorescence spectroscopy using a homologous modeling method.Density functional theory(DFT)was employed to explore the influence before and after BSA modification on PAEs’detection through fluorescence spectroscopy.The results showed that the docking scores between BSAs and dimethyl phthalate(DMP),dibutyl phthalate(DBP)and di-n-octyl phthalate(DNOP)were increased up to 26.45%,16.82%and 16.30%,respectively,indicating that the active site modification of BSA could enhance the binding affinity between BSA and PAEs.The fluorescence intensity of PAEs chelated with modified BSAs were calculated.The fluorescence intensity of fluorescence spectroscopy for DMP,DBP and DNOP chelated with BSAs after modification was increased up to 2.8-,104.51-and 62.43-fold,respectively,which achieved the purpose of theoretically modifying BSA to improve the detection sensitivity of fluorescence spectroscopy for PAEs.