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This paper presents an in-pixel contrast enhancement circuit that performs image processing directly within the pixel circuit. The circuit leverages HyperFET, a hybrid device combining a MOSFET and a phase transition material (PTM), to enhance performance. It can be tuned for different modes of operation. In foreground enhancement mode, it suppresses low-intensity background pixels to nearly zero, isolating the foreground for better object visibility. In contrast enhancement mode, it improves overall image contrast. The contrast enhancement function is customizable both during the design phase and in real-time, allowing the circuit to adapt to specific applications and varying lighting conditions. A model of the designed pixel circuit is developed and applied to a full pixel array, demonstrating significant improvements in image quality. Simulations performed in HSPICE show a nearly 6x increase in Michelson Contrast Ratio (CR) in the foreground enhancement mode. Furthermore, process variation and Signal-to-Noise Ratio (SNR) analysis has been conducted to evaluate the robustness of the design under manufacturing variations. The simulation results indicate its potential for real-time, adaptive contrast enhancement across various imaging environments. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are essential molecular chaperones that protect cells by aiding in protein folding and preventing aggregation under stress conditions. Small heat shock proteins (sHSPs), which include members from HSPB1 to HSPB10, are particularly important for cellular stress responses. These proteins share a conserved α-crystallin domain (ACD) critical for their chaperone function, with flexible N- and C-terminal extensions that facilitate oligomer formation. Phosphorylation, a key post-translational modification (PTM), plays a dynamic role in regulating sHSP structure, oligomeric state, stability, and chaperone function. Unlike other PTMs such as deamidation, oxidation, and glycation—which are often linked to protein destabilization—phosphorylation generally induces structural transitions that enhance sHSP activity. Specifically, phosphorylation promotes the disaggregation of sHSP oligomers into smaller, more active complexes, thereby increasing their efficiency. This disaggregation mechanism is crucial for protecting cells from stress-induced damage, including apoptosis, inflammation, and other forms of cellular dysfunction. This review explores the role of phosphorylation in modulating the function of sHSPs, particularly HSPB1, HSPB4, and HSPB5, and discusses how these modifications influence their protective functions in cellular stress responses. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) are implicated in many biological processes including receptor activation, signal transduction, transcriptional regulation and protein turnover. Lysine's side chain is particularly notable, as it can undergo methylation, acetylation, SUMOylation and ubiquitination. Methylation affects not only lysine but also arginine residues, both of which are implicated in epigenetic regulation. Beyond histone-tails as substrates, dynamic methylation of transcription factors has been described. The focus of this review is on these non-histone substrates providing a detailed discussion of what is currently known about methylation of hypoxia-inducible factor (HIF), P53, nuclear receptors (NRs) and RELA. The role of methylation in regulating protein stability and function by acting as docking sites for methyl-reader proteins and via their crosstalk with other PTMs is explored. [ABSTRACT FROM AUTHOR]

Protein lactylation is a novel post-translational modification (PTM) involved in many important physiological processes such as macrophage polarization, immune regulation, and tumor cell growth. However, traditional methodologies for studying lactylation have predominantly relied on peptide enrichment from whole-cell lysates, which tend to favor the detection of high-abundance peptides, thus limiting the identification of low-abundance lactylated peptides. To address this limitation, here, we employed subcellular fractionation to separate proteins and map lactylated peptides from each isolated subcellular fraction using a model cell line. In brief, we identified 1,217 lysine lactylation (Kla) sites on 553 proteins across four subcellular fractions. Subsequent pathway enrichment analysis revealed that Kla proteins participate in distinct pathways depending on the subcellular contexts. In addition, this subcellular fractionation method enabled the discovery of 36 previously unreported Kla proteins and 223 novel Kla sites, many of which are present in low abundance. Notably, several proteins contain multiple newly identified Kla sites, exemplified by the transcriptional regulator ATRX. Furthermore, our results indicate the possibility of PTM crosstalk between Kla and other PTMs such as ubiquitination and sumoylation. In conclusion, subcellular fractionation facilitates the identification of Kla proteins that have been previously uncovered and could be overlooked by affinity enrichment of whole-cell lysates. [ABSTRACT FROM AUTHOR]

Histone lysine 2‐hydroxyisobutyrylation (Khib) was identified as a novel posttranslational modification in 2014. Significant progress has been made in understanding its roles in reproduction, development, and disease. Although 2‐hydroxyisobutyrylation shares some overlapping modification sites and regulatory factors with other lysine residue modifications, its unique structure suggests distinct functions. This review summarizes the latest advancements in Khib, including its regulatory mechanisms, roles in mammalian physiological processes, and its relationship with diseases. This provides direction for further research on Khib and offers new perspectives for developing treatment strategies for related diseases. [ABSTRACT FROM AUTHOR]

Dosage compensation in Drosophila involves upregulating male X-genes 2-fold. This process is carried out by the MSL (male-specific lethal) complex, which binds high-affinity sites and spreads to surrounding genes. Current models of MSL spreading focus on interactions between MSL3 (male-specific lethal 3) and Set2-dependent histone marks like trimethylated H3 lysine-36 (H3K36me3). However, Set2 could affect DC via another target, or there could be redundancy between canonical H3.2 and variant H3.3 histones. Furthermore, it is important to parse male-specific effects from those that are X-specific. To discriminate among these possibilities, we employed genomic approaches in H3K36 "residue" and Set2 "writer" mutants. The results confirm a role for Set2 in X-gene regulation, but show that expression trends in males are often mirrored in females. Instead of global, male-specific reduction of X-genes in Set2 or H3K36 mutants, we observe heterogeneous effects. Interestingly, we identified groups of differentially expressed genes (DEGs) whose changes were in opposite directions following loss of H3K36 or Set2, suggesting that H3K36me states have reciprocal functions. In contrast to H4K16R controls, differential expression analysis of combined H3.2K36R/H3.3K36R mutants showed neither consistent reduction in X-gene expression, nor correlation with MSL3 binding. Motif analysis of the DEGs implicated BEAF-32 and other insulator proteins in Set2/H3K36-dependent regulation. Overall, the data are inconsistent with the prevailing model wherein H3K36me3 is essential for spreading the MSL complex to genes along the male X. Rather, we propose that Set2 and H3K36 support DC indirectly, via processes that are utilized by MSL but common to both sexes. [ABSTRACT FROM AUTHOR]

This article proposes new directions to enhance spectrum resource allocation in dense cellular networks, especially during massive dissemination of public safety alerts. We are conducting a comparative study to identify the most efficient transmission mode among the following options: conventional Unicast (UC) mode, UC mode combined with beamforming, Point-To-Multipoint (PTM) single-cell broadcast mode, and multi-cell broadcast mode via a Single-Frequency Network (SFN). In the absence of standardized norms for determining the optimum mode, we are developing a model to establish a threshold for the number of users per base station, at which point each broadcast mode between SFN and PTM becomes more spectrally efficient than conventional UC and UC with beamforming. Our contribution includes an in-depth simulation study to assess the sensitivity of this threshold to the variability of system parameters under different scenarios and conditions. This analysis will support informed decisions on the optimal transmission mode, thereby improving public safety in critical circumstances.

Hydrogen deuterium‐exchange mass spectrometry (HDX‐MS) is commonly used in the study of protein dynamics and protein interactions. By measuring the isotopic exchange of backbone amide hydrogens in solution, HDX‐MS offers valuable structural insights into challenging biological systems. Traditional HDX‐MS approaches utilize bottom–up (BU) proteomics, in which deuterated proteins are digested before MS analysis. BU‐HDX enables the characterization of proteins with various sizes in simple protein mixtures or complex biological samples such as cell lysates. However, BU methods are inherently limited by the inability to resolve protein sub‐populations arising from different protein conformations, such as those arising from post‐translational modifications (PTMs). Alternatively, top–down (TD) HDX‐MS detects the global deuterium uptake at the intact proteoform level, allowing direct probing of structural changes due to protein–protein interactions, PTMs, or conformational changes. Combining TD‐HDX‐MS with electron‐based fragmentation techniques, such as electron capture dissociation (ECD) and electron transfer dissociation (ETD), has demonstrated the feasibility of studying intact protein interactions with amino acid‐level resolution. Here, we present a brief overview of methodologies, limitations, and applications of TD‐HDX‐MS using direct infusion techniques and LC‐based approaches. Furthermore, we conclude with a perspective on the future directions for TD‐HDX‐MS. [ABSTRACT FROM AUTHOR]

p57Kip2 is a member of the cyclin-dependent kinase (CDK) Interacting Protein/Kinase Inhibitory Protein (CIP/Kip) family that also includes p21Cip1/WAF1 and p27Kip1. Different from its siblings, few data are available about the p57Kip2 protein, especially in humans. Structurally, p57Kip2 is an intrinsically unstructured protein, a characteristic that confers functional flexibility with multiple transient interactions influencing the metabolism and roles of the protein. Being an IUP, its localization, stability, and binding to functional partners might be strongly modulated by post-translational modifications, especially phosphorylation. In this work, we investigated by two-dimensional analysis the phosphorylation pattern of p57Kip2 in different cellular models, revealing how the human protein appears to be extensively phosphorylated, compared to p21Cip1/WAF1 and p27Kip1. We further observed clear differences in the phosphoisoforms distributed in the cytosolic and nuclear compartments in asynchronous and synchronized cells. Particularly, the unmodified form is detectable only in the nucleus, while the more acidic forms are present in the cytoplasm. Most importantly, we found that the phosphorylation state of p57Kip2 influences the binding with some p57Kip2 partners, such as CDKs, LIMK1 and CRM1. Thus, it is necessary to completely identify the phosphorylated residues of the protein to fully unravel the roles of this CIP/Kip protein, which are still partially identified. [ABSTRACT FROM AUTHOR]

The potato tuber moth (PTM), Phthorimaea operculella, is one of the most economically important potato pests worldwide. In the present study, the potential of Steinernema carpocapsae for controlling PTM in infested potato tubers was evaluated and compared with S. feltiae and the pyrethroid alpha-cypermethrin. The results for efficacy percentage showed that S.carpocapsae [72.52 and 65.49% for 12.6 × 106 and 6.2 × 106 infective juveniles (IJs), respectively] and S. feltiae (69.56% for 12.6 × 106 IJs) were as efficient as alpha-cypermethrin (66.76% for10 mg ai L−1). Both concentrations of alpha-cypermethrin and S. carpocapsae showed the least tuber damage with no significant differences (33.5–39.33%), while it was as high as the control (59.26%) in both concentrations of S. feltiae. The median lethal concentration (LC50) value for S. carpocapsae [5.46 (4.41–6.55) IJs per prepupa] was significantly lower than S. feltiae [8.52 (7.12-10.20) IJs per prepupa] which confirms the superiority of S. carpocapsae. These promising findings introduce S. carpocapsae as a part of the potato tuber protection programs for treating the tubers. Accordingly, EPNs can be considered as an appropriate alternative to synthetic chemicals for PTM control. [ABSTRACT FROM AUTHOR]

Although arginine methylation (R-methylation) is one of the most important post-translational modifications (PTMs) conserved in eukaryotes, it has not been studied to the same extent as phosphorylation and ubiquitylation. Technical constraints, which are in the process of being resolved, may partly explain this lack of success. Our knowledge of R-methylation has recently evolved considerably, particularly in metazoans, where misregulation of the enzymes that deposit this PTM is implicated in several diseases and cancers. Indeed, the roles of R-methylation have been highlighted through the analyses of the main actors of this pathway: the PRMT writer enzymes, the TUDOR reader proteins, and potential "eraser" enzymes. In contrast, R-methylation has been much less studied in plants. Even so, it has been shown that R-methylation in plants, as in animals, regulates housekeeping processes such as transcription, RNA silencing, splicing, ribosome biogenesis, and DNA damage. R-methylation has recently been highlighted in the regulation of membrane-free organelles in animals, but this role has not yet been demonstrated in plants. The identified R-met targets modulate key biological processes such as flowering, shoot and root development, and responses to abiotic and biotic stresses. Finally, arginine demethylases activity has mostly been identified in vitro, so further studies are needed to unravel the mechanism of arginine demethylation. [ABSTRACT FROM AUTHOR]

Introduction: Glycosylation, the process of glycan synthesis and attachment to target molecules, is a crucial and common post-translational modification (PTM) in mammalian cells. It affects the protein's hydrophilicity, charge, solubility, structure, localization, function, and protection from proteolysis. Aberrant glycosylation in proteins can reveal new detection and therapeutic Glyco-biomarkers, which help to improve accurate early diagnosis and personalized treatment. This review underscores the pivotal role of glycans and glycoproteins as a source of biomarkers in human diseases, particularly cancer. Areas covered: This review delves into the implications of glycosylation, shedding light on its intricate roles in cancer-related cellular processes influencing biomarkers. It is underpinned by a thorough examination of literature up to June 2024 in PubMed, Scopus, and Google Scholar; concentrating on the terms: (Glycosylation[Title/Abstract]) OR (Glycan[Title/Abstract]) OR (glycoproteomics[Title/Abstract]) OR (Proteoglycans[Title/Abstract]) OR (Glycomarkers[Title/Abstract]) AND (Cancer[Title/Abstract]) AND ((Diagno*[Title/Abstract]) OR (Progno*[Title/Abstract])). Expert opinion: Glyco-biomarkers enhance early cancer detection, allow early intervention, and improve patient prognoses. However, the abundance and complex dynamic glycan structure may make their scientific and clinical application difficult. This exploration of glycosylation signatures in cancer biomarkers can provide a detailed view of cancer etiology and instill hope in the potential of glycosylation to revolutionize cancer research. [ABSTRACT FROM AUTHOR]

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This study aimed to identify the academic problems in terms of school environment among workers' welfare schools of Punjab, Pakistan. Some of the gaps regarding the environment in which Workers’ Welfare Schools have to operate in terms of curricular delivery include the far–from–real students–teacher Ratio and the lack of proper sporting facilities. A combination of quantitative and qualitative research approaches was used. Questionnaires were administered to 165 participants, including principals, teachers, students, and parents. The results were analyzed using test statistics to determine the significance of the conclusions. The problem areas observed are the student-to-teacher ratio and quantitative supplies and deficiencies to support students’ co-curricular activities (mean = 3.32 for student-to-teacher ratio and 2.66 for sports equipment). Parents-teacher meetings were also moderately received (mean = 3.92). Additional statistics supported the results of these findings with a change point location of 0.03. The cleanliness of the physical environment and its maintenance and improvement must be implemented as soon as possible. Further, measures should be undertaken to promote academic quality and foster students’ effective learning settings. [ABSTRACT FROM AUTHOR]

As major carriers of modern economy and population, cities and towns are vortex centers of pollution migration, and the environmental effects brought about by China's unprecedented urbanization can be imagined, although the specific scale is still a mystery. This paper focuses on the nonlinear response mechanism of urban PM2.5 concentration to the urbanization population scale, considering that China's urbanization development path is dominated by large- and medium-sized cities. The panel data of PM2.5 concentration of Chinese cities observed by satellite during 1998–2016 are used to capture the nonlinear characteristics of panel threshold model (PTM). The estimation results of the double-threshold PTM including the quadratic term of urbanization population show that the U-shaped relationship between urbanization population and PM2.5 concentration is nonlinear adjusted by urban GDP per capita with the two thresholds of 6777 Yuan and 10,296 Yuan at 2010 constant price. When the urban GDP per capita exceeds 10,296 Yuan, the urbanized population at the turning point of the U-shaped curve is 12.967 million people, which only appears in a few super-large cities such as Beijing, Tianjin, Shanghai and Chongqing. The size matching of urban economy and population is an important follow-up of environmental policies. [ABSTRACT FROM AUTHOR]

For the last four decades, Pakistan's northwestern Pashtun tribal areas have been in a constant state of imperialist wars. In reaction to this organized violence, a local civil rights movement, the PTM, emerged in 2014 which powerfully challenged the military's discursive regime that legitimates these US-led wars. However, the military challenged the movement's call for justice by launching a concerted discursive drive to construct an enemy image of the PTM. This study aims to discover how the military constructs the identity, as well as the cultural and political meanings of the movement. The authors found that the military strategically organizes its discourse to first build a symbolic order in which an enemy other, less than human, is created, and then its oppression is normalized and made invisible. They hope that the article contributes to the current critical scholarship on the increasing militarization of contemporary public spaces and democratic cultures, particularly in the context of South Asia. [ABSTRACT FROM AUTHOR]

ABSTRACT The microbiome plays a vital role in human health, with changes in its composition impacting various aspects of the body. Posttranslational modification (PTM) regulates protein activity by attaching chemical groups to amino acids in an enzymatic or non-enzymatic manner. PTMs offer fast and dynamic regulation of protein expression and can be influenced by specific dietary components that induce PTM events in gut microbiomes and their hosts. PTMs on microbiome proteins have been found to contribute to host-microbe interactions. For example, in Escherichia coli, S-sulfhydration of tryptophanase regulates uremic toxin production and chronic kidney disease in mice. On a broader microbial scale, the microbiomes of patients with inflammatory bowel disease exhibit distinct PTM patterns in their metaproteomes. Moreover, pathogens and commensals can alter host PTM profiles through protein secretion and diet-regulated metabolic shifts. The emerging field of metaPTMomics focuses on understanding PTM profiles in the microbiota, their association with lifestyle factors like diet, and their functional effects on host-microbe interactions.

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is a critical target for cancer immunotherapy. This review focuses on the regulation of PD-L1 through the dynamic processes of ubiquitination and deubiquitination, which are crucial for its stability and function. Here, we explored the intricate mechanisms involving various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that modulate PD-L1 expression in cancer cells. Specific ligases are discussed in detail, highlighting their roles in tagging PD-L1 for degradation. Furthermore, we discuss the actions of DUBs that stabilize PD-L1 by removing ubiquitin chains. The interplay of these enzymes not only dictates PD-L1 levels but also influences cancer progression and patient response to immunotherapies. Furthermore, we discuss the therapeutic implications of targeting these regulatory pathways and propose novel strategies to enhance the efficacy of PD-L1/PD-1-based therapies. Our review underscores the complexity of PD-L1 regulation and its significant impact on the tumor microenvironment and immunotherapy outcomes. [ABSTRACT FROM AUTHOR]

Abstract Post-translational modifications (PTMs) of proteins contribute to the occurrence and development of tumors. Previous studies have suggested that canonical PTMs such as ubiquitination, glycosylation, and phosphorylation are closely implicated in different aspects of gastrointestinal tumors. Recently, emerging evidence showed that non-canonical PTMs play an essential role in the carcinogenesis, metastasis and treatment of gastrointestinal tumors. Therefore, we summarized recent advances in sumoylation, neddylation, isoprenylation, succinylation and other non-canonical PTMs in gastrointestinal tumors, which comprehensively describe the mechanisms and functions of non-classical PTMs in gastrointestinal tumors. It is anticipated that targeting specific PTMs could benefit the treatment as well as improve the prognosis of gastrointestinal tumors.

To facilitate analysis and sharing of mass spectrometry (MS)-based proteomics data, we created online tools called CURTAIN (https://curtain.proteo.info) and CURTAIN-PTM (https://curtainptm.proteo.info) with an accompanying series of video tutorials (https://www.youtube.com/@CURTAIN-me6hl). These are designed to enable non-MS experts to interactively peruse volcano plots and deconvolute primary experimental data so that replicates can be visualized in bar charts or violin plots and exported in publication-ready format. They also allow assessment of overall experimental quality by correlation matrix and profile plot analysis. After making a selection of protein "hits", the user can analyze known domain structure, AlphaFold predicted structure, reported interactors, relative expression as well as disease links. CURTAIN-PTM permits analysis of all identified PTM sites on protein(s) of interest with selected databases. CURTAIN-PTM also links with the Kinase Library to predict upstream kinases that may phosphorylate sites of interest. We provide examples of the utility of CURTAIN and CURTAIN-PTM in analyzing how targeted degradation of the PPM1H Rab phosphatase that counteracts the Parkinson's LRRK2 kinase impacts cellular protein levels and phosphorylation sites. We also reanalyzed a ubiquitylation dataset, characterizing the PINK1-Parkin pathway activation in primary neurons, revealing data of interest not highlighted previously. CURTAIN and CURTAIN-PTM are free to use and open source, enabling researchers to share and maximize the impact of their proteomics data. We advocate that MS data published in volcano plot format be reported containing a shareable CURTAIN weblink, thereby allowing readers to better analyze and exploit the data. [ABSTRACT FROM AUTHOR]

Aggregation prone molecules, such as tau, form both historically well characterized fibrillar deposits (neurofibrillary tangles) and recently identified phosphate-buffered saline (PBS) extract species called proteopathic seeds. Both can cause normal endogenous tau to undergo templated misfolding. The relationship of these seeds to the fibrils that define tau-related diseases is unknown. We characterized the aqueous extractable and sarkosyl insoluble fibrillar tau species derived from human Alzheimer brain using mass spectrometry and in vitro bioassays. Post-translational modifications (PTMs) including phosphorylation, acetylation and ubiquitination are identified in both preparations. PBS extract seed competent tau can be distinguished from sarkosyl insoluble tau by the presence of overlapping, but less abundant, PTMs and an absence of some PTMs unique to the latter. The presence of ubiquitin and other PTMs on the PBS-extracted tau species correlates with the amount of tau in the seed competent size exclusion fractions, with the bioactivity and with the aggressiveness of clinical disease. These results demonstrate that the PTMs present on bioactive, seed competent PBS extract tau species are closely related to, but distinct from, the PTMs of mature paired helical filaments, consistent with the idea that they are a forme fruste of tau species that ultimately form fibrils. [ABSTRACT FROM AUTHOR]

Cellular homeostasis is constantly challenged by a myriad of extrinsic and intrinsic stressors. To mitigate the stress-induced damage, cells activate transient survival programs. The heat shock response (HSR) is an evolutionarily well-conserved survival program that is activated in response to proteotoxic stress. The HSR encompasses a dual regulation of transcription, characterized by rapid activation of genes encoding molecular chaperones and concomitant global attenuation of non-chaperone genes. Recent genome-wide approaches have delineated the molecular depth of stress-induced transcriptional reprogramming. The dramatic rewiring of gene and enhancer networks is driven by key transcription factors, including heat shock factors (HSFs), that together with chromatin-modifying enzymes remodel the 3D chromatin architecture, determining the selection of either gene activation or repression. Here, we highlight the current advancements of molecular mechanisms driving transcriptional reprogramming during acute heat stress. We also discuss the emerging implications of HSF-mediated stress signaling in the context of physiological and pathological conditions. Protein-damaging stress endangers cellular and organismal homeostasis. Cell survival depends on transcriptional rewiring, which is coordinated by chromatin-modifying enzymes and stress-responsive transcription factors. Apart from acute stress, proteostasis is also challenged in a variety of physiological and pathological conditions. Pessa et al. discuss the diversity of mechanisms regulating these processes. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and Huntington's disease, are identified and characterized by the progressive loss of neurons and neuronal dysfunction, resulting in cognitive and motor impairment. Recent research has shown the importance of PTMs, such as phosphorylation, acetylation, methylation, ubiquitination, sumoylation, nitration, truncation, O-GlcNAcylation, and hydroxylation, in the progression of neurodegenerative disorders. PTMs can alter protein structure and function, affecting protein stability, localization, interactions, and enzymatic activity. Aberrant PTMs can lead to protein misfolding and aggregation, impaired degradation, and clearance, and ultimately, to neuronal dysfunction and death. The main objective of this review is to provide an overview of the PTMs involved in neurodegeneration, their underlying mechanisms, methods to isolate PTMs, and the potential therapeutic targets for these disorders. The PTMs discussed in this article include tau phosphorylation, α-synuclein and Huntingtin ubiquitination, histone acetylation and methylation, and RNA modifications. Understanding the role of PTMs in neurodegenerative diseases may provide new therapeutic strategies for these devastating disorders. [ABSTRACT FROM AUTHOR]

Initiating and regulating humoral immunity, Fc gamma receptors (FcγRs) have been identified both as therapeutics and as drug targets, and thus production of biologically active FcγRs is highly demanded for biopharmaceutical development. Focusing on low‐affinity FcγRs IIA (131H/R allotypes), IIB, and IIIA (176F/V), this study used human 293‐F cells to achieve correct post‐translational modifications (PTMs) including biotinylation, N‐glycosylation, and disulfides. Approaches involving co‐expression of FcγR‐AviTag and Escherichia coli biotin ligase BirA, endoplasmic reticulum retention, stable and transient transfections, and optimization of transgene ratio were investigated. Protein electrophoresis under reducing and non‐reducing conditions, enzymatic deglycosylation, streptavidin pull‐down assays, and binding kinetic analysis collectively indicated that the produced FcγR ectodomains were fully biotinylated, N‐glycosylated, had formed disulfide bond, and exhibited expected binding affinities toward IgG1 trastuzumab and its Fc mutants. A clear trade‐off between production yield and PTM quality was also observed. Achieving multiple types of PTMs completely by one‐step cell culture should have applications for the production of a variety of complex proteins of biomedical importance. [ABSTRACT FROM AUTHOR]

Penyakit Tidak Menular merupakan suatu penyakit kronis yang sangat berbahaya karena tidak memberikan gejala atau keluhan. Capain Standar Pelayanan Minimal skrinning PTM Puskesmas Ngaglik I belum mencapai target karena rendahnya pemanfaatan posbindu PTM. Penelitian ini bertujuan untuk menganalisis determinan pemanfaatan posbindu PTM oleh masyarakat di RW 36 Padukuhan Ngabean Kulon Sinduharjo Ngaglik Sleman. Penelitian ini dilakukan di Posbindu Ngudi Waras RW 36 Padukuhan Ngabean Kulon Sinduharjo Ngaglik Sleman. Jenis penelitian menggunakan metode kuantitatif dengan pendekatan cross sectional. Sampel diambil dengan metode proportional random sampling dengan jumlah sampel sebanyak 88 responden. Analisis data menggunakan analisis bivariat dengan uji fisher’s dan analisis multivariat dengan regresi logistik. Hasil analisis bivariat menunjukkan bahwa pengetahuan (p=0,000), motivasi (p=0,000), persepsi manfaat (p=0,000), fasilitas kesehatan (p=0,000), dukungan keluarga (p=0,000) dan dukungan kader (p=0,020). Faktor yang mempengaruhi pemanfaatan Posbindu PTM adalah fasilitas kesehatan (p=0,004) dan dukungan keluarga (p=0,029). Faktor yang paling dominan dalam pemanfaatan Posbindu PTM adalah fasilitas kesehatan (p=0,004) dengan nilai OR = 60,079 yang artinya fasilitas kesehatan memiliki peluang 60,079 kali dalam mempengaruhi masayarakat dalam memanfaatakan posbindu PTM. Perlunya memberikan pendampingan kepada kader, meningkatkan sumber daya yang ada untuk melengkapi fasilitas kesehatan yang kurang dan membuat inovasi kegiatan untuk menarik masyarakat agar memanfaatkan posbindu penyakit tidak menular.

Recent advances have rekindled the interest in ion mobility as an additional dimension of separation in mass spectrometry (MS)-based proteomics. Ion mobility separates ions according to their size and shape in the gas phase. Here, we set out to investigate the effect of 22 different post-translational modifications (PTMs) on the collision cross section (CCS) of peptides. In total, we analyzed ~4300 pairs of matching modified and unmodified peptide ion species by trapped ion mobility spectrometry (TIMS). Linear alignment based on spike-in reference peptides resulted in highly reproducible CCS values with a median coefficient of variation of 0.26%. On a global level, we observed a redistribution in the m/z vs. ion mobility space for modified peptides upon changes in their charge state. Pairwise comparison between modified and unmodified peptides of the same charge state revealed median shifts in CCS between −1.4% (arginine citrullination) and +4.5% (O-GlcNAcylation). In general, increasing modified peptide masses were correlated with higher CCS values, in particular within homologous PTM series. However, investigating the ion populations in more detail, we found that the change in CCS can vary substantially for a given PTM and is partially correlated with the gas phase structure of its unmodified counterpart. In conclusion, our study shows PTM- and sequence-specific effects on the cross section of peptides, which could be further leveraged for proteome-wide PTM analysis. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) of proteins contribute to the occurrence and development of tumors. Previous studies have suggested that canonical PTMs such as ubiquitination, glycosylation, and phosphorylation are closely implicated in different aspects of gastrointestinal tumors. Recently, emerging evidence showed that non-canonical PTMs play an essential role in the carcinogenesis, metastasis and treatment of gastrointestinal tumors. Therefore, we summarized recent advances in sumoylation, neddylation, isoprenylation, succinylation and other non-canonical PTMs in gastrointestinal tumors, which comprehensively describe the mechanisms and functions of non-classical PTMs in gastrointestinal tumors. It is anticipated that targeting specific PTMs could benefit the treatment as well as improve the prognosis of gastrointestinal tumors. [ABSTRACT FROM AUTHOR]

An asymmetric image encryption algorithm based on integer wavelet transformation (IWT) and Rivest-Shamir-Adleman (RSA) algorithm is proposed. Firstly, two plain characteristic parameters (PCP) of the plain image are extracted and two random numbers are chosen. Then, a new parameter transformation model (PTM) is constructed to do nonlinear processing for them, and three cipher characteristic parameters (CCP) are got. After applying RSA operation for CCP (seen as plain messages), three cipher messages are obtained. Secondly, a new initial value obtaining model (IOM) for all plain messages and cipher messages is established, by which initial values of 3D chaotic system are produced. Then, three chaotic sequences can be generated. Thirdly, chaotic sequences are used to confuse the plain image by a way of row-column cycle. Then, IWT operation is carried out and the above chaotic sequences are employed to confuse again the wavelet coefficients. Thereafter, inverse IWT is applied to get the confused image, realizing double confusion operations on both spatial domain and frequency domain. Finally, the confused image is diffused as a whole to get the cipher image. Experiment results explain that the proposed algorithm can realize the encryption in short time, and resist effectively against brute-force attack and noise attack.

Circulating uremic toxin indoxyl sulfate (IS), endothelial cell (EC) dysfunction, and decreased nitric oxide (NO) bioavailability are found in chronic kidney disease patients. NO nitrosylates/denitrosylates a specific protein's cysteine residue(s), forming S-nitrosothios (SNOs), and the decreased NO bioavailability could interfere with NO-mediated signaling events. We were interested in investigating the underlying mechanism(s) of the reduced NO and how it would regulate the S-nitrosylation of tissue transglutaminase (TG2) and its substrates on glycolytic, redox and inflammatory responses in normal and IS-induced EC injury. TG2, a therapeutic target for fibrosis, has a Ca2+-dependent transamidase (TGase) that is modulated by S-nitrosylation. We found IS increased oxidative stress, reduced NADPH and GSH levels, and uncoupled eNOS to generate NO. Immunoblot analysis demonstrated the upregulation of an angiotensin-converting enzyme (ACE) and significant downregulation of the beneficial ACE2 isoform that could contribute to oxidative stress in IS-induced injury. An in situ TGase assay demonstrated IS-activated TG2/TGase aminylated eNOS, NFkB, IkBα, PKM2, G6PD, GAPDH, and fibronectin (FN), leading to caspases activation. Except for FN, TGase substrates were all differentially S-nitrosylated either with or without IS but were denitrosylated in the presence of a specific, irreversible TG2/TGase inhibitor ZDON, suggesting ZDON-bound TG2 was not effectively transnitrosylating to TG2/TGase substrates. The data suggest novel roles of TG2 in the aminylation of its substrates and could also potentially function as a Cys-to-Cys S-nitrosylase to exert NO's bioactivity to its substrates and modulate glycolysis, redox, and inflammation in normal and IS-induced EC injury. [ABSTRACT FROM AUTHOR]

Abstract—The implementation of computational approaches for protein glycosylation site prediction is becoming popular since the experimental-validated glycosylation data became more abundant. Some of the data were found to be wrong after the experiment was again carried out with more sophisticated technology. To solve this issue, the latest state-of-the-art model trained the model based on a positive-unlabelled algorithm. The aim of this research is to explore the possibility of an approach applying a simple neural network algorithm and still achieve high classification performance. The model proposed in this research gave competitive results with fewer preprocessing steps. Increasing the accuracy of glycosylation site prediction can complement laboratory-based methods and is very useful for understanding the role of glycosylation. [ABSTRACT FROM AUTHOR]

In terms of its relative frequency, lysine is a common amino acid in the human proteome. However, by bioinformatics we find hundreds of proteins that contain long and evolutionarily conserved stretches completely devoid of lysine residues. These so-called lysine deserts show a high prevalence in intrinsically disordered proteins with known or predicted functions within the ubiquitin-proteasome system (UPS), including many E3 ubiquitin-protein ligases and UBL domain proteasome substrate shuttles, such as BAG6, RAD23A, UBQLN1 and UBQLN2. We show that introduction of lysine residues into the deserts leads to a striking increase in ubiquitylation of some of these proteins. In case of BAG6, we show that ubiquitylation is catalyzed by the E3 RNF126, while RAD23A is ubiquitylated by E6AP. Despite the elevated ubiquitylation, mutant RAD23A appears stable, but displays a partial loss of function phenotype in fission yeast. In case of UBQLN1 and BAG6, introducing lysine leads to a reduced abundance due to proteasomal degradation of the proteins. For UBQLN1 we show that arginine residues within the lysine depleted region are critical for its ability to form cytosolic speckles/inclusions. We propose that selective pressure to avoid lysine residues may be a common evolutionary mechanism to prevent unwarranted ubiquitylation and/or perhaps other lysine post-translational modifications. This may be particularly relevant for UPS components as they closely and frequently encounter the ubiquitylation machinery and are thus more susceptible to nonspecific ubiquitylation. [ABSTRACT FROM AUTHOR]

Protein phosphorylation is a ubiquitous post-translational modification controlled by the opposing activities of protein kinases and phosphatases, which regulate diverse biological processes in all kingdoms of life. One of the key challenges to a complete understanding of phosphoregulatory networks is the unambiguous identification of kinase and phosphatase substrates. Liquid chromatography-coupled mass spectrometry (LC-MS/MS) and associated phosphoproteomic tools enable global surveys of phosphoproteome changes in response to signaling events or perturbation of phosphoregulatory network components. Despite the power of LC-MS/MS, it is still challenging to directly link kinases and phosphatases to specific substrate phosphorylation sites in many experiments. Here, we survey common LC-MS/MS-based phosphoproteomic workflows for identifying protein kinase and phosphatase substrates, noting key advantages and limitations of each. We conclude by discussing the value of inducible degradation technologies coupled with phosphoproteomics as a new approach that overcomes some limitations of current methods for substrate identification of kinases, phosphatases, and other regulatory enzymes. [ABSTRACT FROM AUTHOR]

Ongole Crossbreed (PO) cattle are a kind of indigenous cattle that are bred in the area and eaten by the people. Through the use of reproductive technology, namely artificial insemination, there is the potential to increase the availability of high-quality beef. One of the many considerations that go into the process of producing cow semen is the animals' ages. This study's goal was to perform a macroscopical and microscopical examination of the motility of spermatozoa in ongole crossbreed cattle both before and after they had been frozen. A fully randomized design (CRD) was used, and there were a total of six replications conducted at the ages of 4, 6, and 8 years. The data analysis procedure included the One Way ANOVA test and Duncan's follow-up test. Age had a statistically significant effect on the quality of fresh sperm and individual motility, according to the study's findings, with the maximum value being created at 4 years of age (82.22%), while the lowest score being achieved at 8 years of age (60.27%). The motility measured before freezing did not indicate a significant difference between the ages of 6 years (57.17%) and 8 years (56.17%), and the motility measured after thawing also did not reveal a significant difference. The value was at its lowest point at the age of 6, which was 42.23%. As can be seen from the above, age variations have an impact on individual motility but have no effect on the values measured before freezing or after PTM. [ABSTRACT FROM AUTHOR]

Methylmalonic acidemia (MMA) is a severe inborn error of metabolism that is characterized by pleiotropic metabolic perturbations and multiorgan pathology. Treatment options are limited and non‐curative as the underlying causative molecular mechanisms remain unknown. While earlier studies have focused on the potential direct toxicity of metabolites such as methylmalonic and propionic acid as a mechanism to explain disease pathophysiology, new observations have revealed that aberrant acylation, specifically methylmalonylation, is a characteristic feature of MMA. The mitochondrial sirtuin enzyme SIRT5 is capable of recognizing and removing this PTM, however, reduced protein levels of SIRT5 along with other mitochondrial SIRTs 3 and 4 in MMA and potentially reduced function of all three indicates aberrant acylation may require clinical intervention. Therefore, targeting posttranslational modifications may represent a new therapeutic approach to treat MMA and related organic acidemias. [ABSTRACT FROM AUTHOR]

Recently, lysine lactylation (Kla), a novel post-translational modification (PTM), which can be stimulated by lactate, has been found to regulate gene expression and life activities. Therefore, it is imperative to accurately identify Kla sites. Currently, mass spectrometry is the fundamental method for identifying PTM sites. However, it is expensive and time-consuming to achieve this through experiments alone. Herein, we proposed a novel computational model, Auto-Kla, to quickly and accurately predict Kla sites in gastric cancer cells based on automated machine learning (AutoML). With stable and reliable performance, our model outperforms the recently published model in the 10-fold cross-validation. To investigate the generalizability and transferability of our approach, we evaluated the performance of our models trained on two other widely studied types of PTM, including phosphorylation sites in host cells infected with SARS-CoV-2 and lysine crotonylation sites in HeLa cells. The results show that our models achieve comparable or better performance than current outstanding models. We believe that this method will become a useful analytical tool for PTM prediction and provide a reference for the future development of related models. The web server and source code are available at http://tubic.org/Kla and https://github.com/tubic/Auto-Kla , respectively. [ABSTRACT FROM AUTHOR]

α-Synuclein is a protein linked to various synuclein-associated diseases ('synucleinopathies'), including Parkinson's disease, dementia with Lewy Bodies and multiple system atrophy, and is highly expressed in the central nervous system and in erythrocytes. Moreover, α-synuclein-containing erythrocyte-derived extracellular vesicles may be involved in the pathogenesis of synucleinopathies and their progression across the blood–brain barrier. Several post-translational modifications of α-synuclein have been reported in brain inclusions, including S129 phosphorylation, but fewer have been found in erythrocytes. In this study, we analysed the post-translational modifications of erythrocyte α-synuclein using liquid chromatography–mass spectrometry. We found that all lysine residues in the α-synuclein protein could be modified by acetylation, glycation, ubiquitination or SUMOylation but that phosphorylation, nitration and acylation were uncommon minor post-translational modifications in erythrocytes. Since the post-translational modification of lysine residues has been implicated in both membrane association and protein clearance, our findings provide new insight into how synucleinopathies may progress and suggest possible therapeutic strategies designed to target α-synuclein. [ABSTRACT FROM AUTHOR]