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Abstract Identification of potential human–virus protein–protein interactions (PPIs) contributes to the understanding of the mechanisms of viral infection and to the development of antiviral drugs. Existing computational models often have more hyperparameters that need to be adjusted manually, which limits their computational efficiency and generalization ability. Based on this, this study proposes a kernel Bayesian logistic matrix decomposition model with automatic rank determination, VKBNMF, for the prediction of human–virus PPIs. VKBNMF introduces auxiliary information into the logistic matrix decomposition and sets the prior probabilities of the latent variables to build a Bayesian framework for automatic parameter search. In addition, we construct the variational inference framework of VKBNMF to ensure the solution efficiency. The experimental results show that for the scenarios of paired PPIs, VKBNMF achieves an average AUPR of 0.9101, 0.9316, 0.8727, and 0.9517 on the four benchmark datasets, respectively, and for the scenarios of new human (viral) proteins, VKBNMF still achieves a higher hit rate. The case study also further demonstrated that VKBNMF can be used as an effective tool for the prediction of human–virus PPIs.

Identification of potential human–virus protein–protein interactions (PPIs) contributes to the understanding of the mechanisms of viral infection and to the development of antiviral drugs. Existing computational models often have more hyperparameters that need to be adjusted manually, which limits their computational efficiency and generalization ability. Based on this, this study proposes a kernel Bayesian logistic matrix decomposition model with automatic rank determination, VKBNMF, for the prediction of human–virus PPIs. VKBNMF introduces auxiliary information into the logistic matrix decomposition and sets the prior probabilities of the latent variables to build a Bayesian framework for automatic parameter search. In addition, we construct the variational inference framework of VKBNMF to ensure the solution efficiency. The experimental results show that for the scenarios of paired PPIs, VKBNMF achieves an average AUPR of 0.9101, 0.9316, 0.8727, and 0.9517 on the four benchmark datasets, respectively, and for the scenarios of new human (viral) proteins, VKBNMF still achieves a higher hit rate. The case study also further demonstrated that VKBNMF can be used as an effective tool for the prediction of human–virus PPIs. [ABSTRACT FROM AUTHOR]

Common to all biological systems and living organisms are molecular interactions, which may lead to specific physiological events. Most often, a cascade of events occurs, establishing an equilibrium between possibly competing and/or synergistic processes. Biochemical pathways that sustain life depend on multiple intrinsic and extrinsic factors contributing to aging and/or diseases. This article deals with food antioxidants and human proteins from the circulation, their interaction, their effect on the structure, properties, and function of antioxidant-bound proteins, and the possible impact of complex formation on antioxidants. An overview of studies examining interactions between individual antioxidant compounds and major blood proteins is presented with findings. Investigating antioxidant/protein interactions at the level of the human organism and determining antioxidant distribution between proteins and involvement in the particular physiological role is a very complex and challenging task. However, by knowing the role of a particular protein in certain pathology or aging, and the effect exerted by a particular antioxidant bound to it, it is possible to recommend specific food intake or resistance to it to improve the condition or slow down the process. [ABSTRACT FROM AUTHOR]

Viral infection involves a large number of protein–protein interactions (PPIs) between the virus and the host, and the identification of these PPIs plays an important role in revealing viral infection and pathogenesis. Existing computational models focus on predicting whether human proteins and viral proteins interact, and rarely take into account the types of diseases associated with these interactions. Although there are computational models based on a matrix and tensor decomposition for predicting multi-type biological interaction relationships, these methods cannot effectively model high-order nonlinear relationships of biological entities and are not suitable for integrating multiple features. To this end, we propose a novel computational framework, LTDSSL, to determine human–virus PPIs under different disease types. LTDSSL utilizes logistic functions to model nonlinear associations, sets importance levels to emphasize the importance of observed interactions and utilizes sparse subspace learning of multiple features to improve model performance. Experimental results show that LTDSSL has better predictive performance for both new disease types and new triples than the state-of-the-art methods. In addition, the case study further demonstrates that LTDSSL can effectively predict human-viral PPIs under various disease types. [ABSTRACT FROM AUTHOR]

Background/Aim: Recently, we reported that coiled-coil domain containing 25 (CCDC25) protein is elevated in the sera of patients with cholangiocarcinoma (CCA) and is suggested to be a diagnostic biomarker for CCA. This study aimed to examine whether serum CCDC25 level can be a unique biomarker for CCA. Bioinformatic analyses using Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) indicated that CCDC25 protein and mRNA are expressed not only in CCA but also in other cancers, such as colorectal cancer (CRC), breast cancer (BC), and hepatocellular carcinoma (HCC), all of which are the top 5 cancers highly prevalent in Thailand. Materials and Methods: Using a quantitative dot blot assay, serum CCDC25 levels were measured for 30 healthy controls (HC), 34 CRC, 42 BC, 43 HCC, and 83 CCA. Results: The serum CCDC25 levels of CCA patients (0.193±0.039 ng/µl) were significantly higher than those of CRC (0.019±0.006 ng/µl), BC (0.036±0.015 ng/µl), HCC (0.035±0.016 ng/µl), and higher than those of HC (0.012±0.003 ng/µl). The serum CCDC25 level can discriminate CCA from the HC, CRC, BC, and HCC with a sensitivity of 100, 99, 94, and 94%, respectively, and specificity of 100, 100, 98, and 95%, respectively. Conclusion: CCDC25 is a candidate diagnostic biomarker for CCA. [ABSTRACT FROM AUTHOR]

Common to all biological systems and living organisms are molecular interactions, which may lead to specific physiological events. Most often, a cascade of events occurs, establishing an equilibrium between possibly competing and/or synergistic processes. Biochemical pathways that sustain life depend on multiple intrinsic and extrinsic factors contributing to aging and/or diseases. This article deals with food antioxidants and human proteins from the circulation, their interaction, their effect on the structure, properties, and function of antioxidant-bound proteins, and the possible impact of complex formation on antioxidants. An overview of studies examining interactions between individual antioxidant compounds and major blood proteins is presented with findings. Investigating antioxidant/protein interactions at the level of the human organism and determining antioxidant distribution between proteins and involvement in the particular physiological role is a very complex and challenging task. However, by knowing the role of a particular protein in certain pathology or aging, and the effect exerted by a particular antioxidant bound to it, it is possible to recommend specific food intake or resistance to it to improve the condition or slow down the process.

The use of metaproteomics for studying the human gut microbiota can shed light on the taxonomic profile and the functional role of the microbial community. Nevertheless, methods for extracting proteins from stool samples continue to evolve, in the pursuit of optimal protocols for moistening and dispersing the stool sample and for disrupting microbial cells, which are two critical steps for ensuring good protein recovery. Here, we evaluated different stool sample processing (SSP) and microbial cell disruption methods (CDMs). The combination of a longer disintegration period of the stool sample in a tube rotator with sonication increased the overall number of identified peptides and proteins. Proteobacteria, Bacteroidetes, Planctomycetes, and Euryarchaeota identification was favored by mechanical cell disruption with glass beads. In contrast, the relative abundance of Firmicutes, Actinobacteria, and Fusobacteria was improved when sonication was performed before bead beating. Tenericutes and Apicomplexa identification was enhanced by moistening the stool samples during processing and by disrupting cells with medium-sized glass beads combined with or without sonication. Human protein identifications were affected by sonication. To test the reproducibility of these gut metaproteomic analyses, we examined samples from six healthy individuals using a protocol that had shown a good taxonomic diversity and identification of proteins from Proteobacteria and humans. We also detected proteins involved in microbial functions relevant to the host and related mostly to specific taxa, such as B12 biosynthesis and short chain fatty acid (SCFA) production carried out mainly by members in the Prevotella genus and the Firmicutes phylum, respectively. The taxonomic and functional profiles obtained with the different protocols described in this work provides the researcher with valuable information when choosing the most adequate protocol for the study of certain pathologies under suspicion of being related to a specific taxon from the gut microbiota.

The use of metaproteomics for studying the human gut microbiota can shed light on the taxonomic profile and the functional role of the microbial community. Nevertheless, methods for extracting proteins from stool samples continue to evolve, in the pursuit of optimal protocols for moistening and dispersing the stool sample and for disrupting microbial cells, which are two critical steps for ensuring good protein recovery. Here, we evaluated different stool sample processing (SSP) and microbial cell disruption methods (CDMs). The combination of a longer disintegration period of the stool sample in a tube rotator with sonication increased the overall number of identified peptides and proteins. Proteobacteria, Bacteroidetes, Planctomycetes, and Euryarchaeota identification was favored by mechanical cell disruption with glass beads. In contrast, the relative abundance of Firmicutes, Actinobacteria, and Fusobacteria was improved when sonication was performed before bead beating. Tenericutes and Apicomplexa identification was enhanced by moistening the stool samples during processing and by disrupting cells with medium-sized glass beads combined with or without sonication. Human protein identifications were affected by sonication. To test the reproducibility of these gut metaproteomic analyses, we examined samples from six healthy individuals using a protocol that had shown a good taxonomic diversity and identification of proteins from Proteobacteria and humans. We also detected proteins involved in microbial functions relevant to the host and related mostly to specific taxa, such as B12 biosynthesis and short chain fatty acid (SCFA) production carried out mainly by members in the Prevotella genus and the Firmicutes phylum, respectively. The taxonomic and functional profiles obtained with the different protocols described in this work provides the researcher with valuable information when choosing the most adequate protocol for the study of certain pathologies under suspicion of being related to a specific taxon from the gut microbiota. [ABSTRACT FROM AUTHOR]

Human protein subcellular localization has an important research value in biological processes, also in elucidating protein functions and identifying drug targets. Over the past decade, a number of protein subcellular localization prediction tools have been designed and made freely available online. The purpose of this paper is to summarize the progress of research on the subcellular localization of human proteins in recent years, including commonly used data sets proposed by the predecessors and the performance of all selected prediction tools against the same benchmark data set. We carry out a systematic evaluation of several publicly available subcellular localization prediction methods on various benchmark data sets. Among them, we find that mLASSO-Hum and pLoc-mHum provide a statistically significant improvement in performance, as measured by the value of accuracy, relative to the other methods. Meanwhile, we build a new data set using the latest version of Uniprot database and construct a new GO-based prediction method HumLoc-LBCI in this paper. Then, we test all selected prediction tools on the new data set. Finally, we discuss the possible development directions of human protein subcellular localization. Availability: The codes and data are available from http://www.lbci.cn/syn/. [ABSTRACT FROM AUTHOR]

• A functional segment of BAX protein can be engineered to self-assemble as fluorescent nanoparticles targeted to the tumoral marker CXCR4. • Despite their CXCR4 selectivity, BAX nanoparticles do not show a tumor biodistribution and accumulate in liver and kidney. • The cocktail administration of BAX nanoparticles with equivalent PUMA and BAK constructs results in high tumor accumulation and potent antitumoral effect. • The combined administration of BAX, PUMA and BAK nanoparticles promote potent tumor cell destruction with a profile different from that of any of the single pro-apoptotic factors. A functional 29 amino acid-segment of the helix α5 from the human BAX protein has been engineered for production in recombinant bacteria as self-assembling, GFP-containing fluorescent nanoparticles, which are targeted to the tumoral marker CXCR4. These nanoparticles, of around 34 nm in diameter, show a moderate tumor biodistribution and limited antitumoral effect when systemically administered to mouse models of human CXCR4+ colorectal cancer (at 300 μg dose). However, if such BAX nanoparticles are co-administered in cocktail with equivalent nanoparticulate versions of BAK and PUMA proteins at the same total protein dose (300 μg), protein biodistribution and stability in tumor is largely improved, as determined by fluorescence profiles. This fact leads to a potent and faster destruction of tumor tissues when compared to individual pro-apoptotic factors. The analysis and interpretation of the boosted effect, from both the structural and functional sides, offers clues for the design of more efficient nanomedicines and theragnostic agents in oncology based on precise cocktails of human proteins. Several human pro-apoptotic peptides (namely BAK, BAX and PUMA) have been engineered as self-assembling protein nanoparticles targeted to the tumoral marker CXCR4. The systemic administration of the same final amounts of those materials as single drugs, or as combinations of two or three of them, shows disparate intensities of antitumoral effects in a mouse model of human colorectal cancer, which are boosted in the triple combination on a non-additive basis. The superiority of the combined administration of pro-apoptotic agents, acting at different levels of the apoptotic cascade, opens a plethora of possibilities for the development of effective and selective cancer therapies based on the precise cocktailing of pro-apoptotic nanoparticulate agents. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Immunohistochemistry (IHC) is the accepted standard for spatial analysis of protein expression in tissues. IHC is widely used for cancer diagnostics and in basic research. The development of new antibodies to proteins with unknown expression patterns has created a demand for thorough validation. We have applied resources from the Human Protein Atlas project and the Antibody Portal at National Cancer Institute to generate protein expression data for 12 proteins across 39 cancer cell lines and 37 normal human tissue types. The outcome of IHC on consecutive sections from both cell and tissue microarrays using two independent antibodies for each protein was compared with in situ proximity ligation (isPLA), where binding by both antibodies is required to generate detection signals. Semi-quantitative scores from IHC and isPLA were compared with expression of the corresponding 12 transcripts across all cell lines and tissue types. Our results show a more consistent correlation between mRNA levels and isPLA as compared to IHC. The main benefits of isPLA include increased detection specificity and decreased unspecific staining compared to IHC. We conclude that implementing isPLA as a complement to IHC for analysis of protein expression and in antibody validation pipelines can lead to more accurate localization of proteins in tissue. [ABSTRACT FROM AUTHOR]

Studies on the structures and functions of individual kinases have been used to understand the biological properties of other kinases that do not yet have experimental structures. The key factor in accurate inference by homology is an accurate sequence alignment. We present a parsimonious, structure-based multiple sequence alignment (MSA) of 497 human protein kinase domains excluding atypical kinases. The alignment is arranged in 17 blocks of conserved regions and unaligned blocks in between that contain insertions of varying lengths present in only a subset of kinases. The aligned blocks contain well-conserved elements of secondary structure and well-known functional motifs, such as the DFG and HRD motifs. From pairwise, all-against-all alignment of 272 human kinase structures, we estimate the accuracy of our MSA to be 97%. The remaining inaccuracy comes from a few structures with shifted elements of secondary structure, and from the boundaries of aligned and unaligned regions, where compromises need to be made to encompass the majority of kinases. A new phylogeny of the protein kinase domains in the human genome based on our alignment indicates that ten kinases previously labeled as "OTHER" can be confidently placed into the CAMK group. These kinases comprise the Aurora kinases, Polo kinases, and calcium/calmodulin-dependent kinase kinases. [ABSTRACT FROM AUTHOR]

Antibodies are widely used for the detection of specific molecules such as peptides, proteins, and chemical compounds. The specificity of an antibody is therefore its most important feature. However, it is very difficult to confirm antibody specificity. Recently, we made a human protein array consisting of 19,712 kinds of recombinant human proteins produced by a wheat cell-free protein production system. Here, we demonstrate a novel protein array technology for antibody validation (CF-PA2Vtech). Full-length human cDNAs were fused to N-terminal FLAG-GST and then synthesized by the wheat cell-free system. To construct a 20 K human protein array, about 10 to 14 kinds of human proteins were mixed and captured in each well by glutathione-conjugated magnetic beads in 12 plates or one plate with 384- or 1536-well format, respectively, using a strong magnetic device. Using this protein array plate, commercially available anti-HA or anti-PD-1 antibody reacted to 13 or three human proteins, respectively. The cross-reactivity of these proteins was also confirmed by immunoblotting. These proteins have a similar epitope, and alanine mutations of these epitope candidates dissolved the reactivity. These results indicated that CF-PA2Vtech is very useful for validation of antibodies against human protein. [ABSTRACT FROM AUTHOR]

This study quantitatively validates the principle that the biological properties associated with a given genotype are determined by the distribution of amino acids. In order to visualize this central law of molecular biology, each protein was represented by a point in 250-dimensional space based on its amino acid distribution. Proteins from the same family are found to cluster together, leading to the principle that the convex hull surrounding protein points from the same family do not intersect with the convex hulls of other protein families. This principle was verified computationally for all available and reliable protein kinases and human proteins. In addition, we generated 2,328,761 figures to show that the convex hulls of different families were disjoint from each other. The classification performs well with high and robust accuracy (95.75% and 97.5%) together with reasonable phylogenetic trees validate our methods further. • We use a new natural vector method to characterize protein sequences. • We propose the convex hull principle on protein families. • The convex hulls formed from the natural vectors of different families are disjoint. • We verify this principle on all reliable protein kinase domains and human proteins. • The classification results and phylogenetic trees perform well. [ABSTRACT FROM AUTHOR]

A cell contains numerous protein molecules. One of the fundamental goals in molecular cell biology is to determine their subcellular locations since this information is extremely important to both basic research and drug development. In this paper, we report a novel and very powerful predictor called "pLoc_bal-mHum" for predicting the subcellular localization of human proteins based on their sequence information alone. Cross-validation tests on exactly the same experiment-confirmed dataset have indicated that the new predictor is remarkably superior to the existing state-of-the-art predictor in identifying the subcellular localization of human proteins. To maximize the convenience for the majority of experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc%5fbal-mHum/ , by which users can easily get their desired results without the need to go through the detailed mathematics. • A very powerful method has been developed for predicting the subcellular localization of human proteins with both single location site and multiple location sites • A user-friendly web-server called "pLoc_bal-mHum" has been established for the new method by which user can easily get their desired results [ABSTRACT FROM AUTHOR]

Since 1958, cell culture media supplemented with fetal bovine serum is used, despite the well-known concerns about animal welfare, reproducibility, reliability, relevance, and safety. To obliterate these concerns and increase scientific accuracy, we recently published an open access, publicly available paper on a defined medium composition to make it possible for any lab to prepare this medium. The medium supports routine culturing and cell banking as well as investigations of growth curves, dose response testing of compounds of cells in 2D and 3D, and cell migration; all important aspects for research and toxicology. Here we give a detailed description of how to mix the defined universal cell culture medium in 14 simple steps to support any entity that wishes to make it. We also list different normal and cancer cell lines that have been cultured in the defined medium.•Open source composition of animal product free universal cell culture medium•Protocols for mixing solutions of small xeno free molecules for supplementation•Protocols for mixing solutions of human proteins for supplementation., (© 2024 The Author(s).)

Protein–protein interactions (PPIs) have been widely used to understand different biological processes and cellular functions associated with several diseases like cancer. Although some cancer‐related protein interaction databases are available, lack of experimental data and conflicting PPI data among different available databases have slowed down the cancer research. Therefore, in this study, the authors have focused on various proteins that are directly related to different types of cancer disease. They have prepared a PPI database between cancer‐associated proteins with the rest of the human proteins. They have also incorporated the annotation type and direction of each interaction. Subsequently, a biclustering‐based association rule mining algorithm is applied to predict new interactions with type and direction. This study shows the prediction power of association rule mining algorithm over the traditional classifier model without choosing a negative data set. The time complexity of the biclustering‐based association rule mining is also analysed and compared to traditional association rule mining. The authors are able to discover 38 new PPIs which are not present in the cancer database. The biological relevance of these newly predicted interactions is analysed by published literature. Recognition of such interactions may accelerate a way of developing new drugs to prevent different cancer‐related diseases. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) negatively affects steroid production in human luteinized granulosa cells (GC). This study was designed to address two important questions: (1) whether BPA exerts the same disruptive effect in human cumulus granulosa cells (hCGC) and (2) to reveal the molecular mechanism underlying the BPA's action on steroidogenesis. We used cultured hCGC since these cells exert the properties of GC from early antral follicles. Results showed that BPA at 100 μM decreased estradiol level and CYP19A1 mRNA, but increased progesterone production, steroidogenic acute regulatory protein (STAR) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression after 48 h. Shorter (6 h) exposure to BPA elevated PPAR γ mRNA level in hCGC. Addition of ERK1/2 (U0126), EGFR (AG1478) and PPARγ (GW9662) inhibitors prevented the BPA-induced STAR and PPAR γ mRNA expression. Western blot analysis showed that BPA induced a rapid EGFR and ERK1/2 activation. The BPA-induced EGFR phosphorylation was prevented by addition of the PPARγ inhibitor, whereas the BPA-induced ERK1/2 activation was prevented by addition of the EGFR or PPARγ inhibitor. These data show that BPA increases the progesterone and decreases the estradiol biosynthetic pathway in hCGC. Augmentation of the progesterone biosynthetic pathway is mediated through the PPARγ-dependent activation of EGFR and ERK1/2, leading to increased expression of STAR mRNA. • BPA increases STAR mRNA expression in human cumulus granulosa cells. • BPA increases progesterone production in human cumulus granulosa cells. • BPA increases STAR mRNA through the PPARγ dependent activation of EGFR and ERK1/2. [ABSTRACT FROM AUTHOR]

The early control and prevention of cancer contributes effectively interventions and cancer therapies. Secretory protein, one of the richest biomarkers, is proved important as molecular signposts of the physiological state of a cell. In this work, we aim to propose a proteomic high-throughput technology platform to facilitate detection of early cancer by means of biomarkers that secreted into the bloodstream. We compile a new benchmark dataset of human secretory proteins in plasma. A series of sequence-derived features, which have been proved involved in the structure and function of the secretory proteins, are collected to mathematically encode these proteins. Considering the influence of potential irrelevant or redundant features, we introduce discrete firefly optimization algorithm to perform feature selection. We evaluate and compare the proposed method SCRIP (Secretory proteins in plasma) with state-of-the-art approaches on benchmark datasets and independent testing datasets. SCRIP achieves the average AUC values of 0.876 and 0.844 in five-fold the cross-validation and independent test, respectively. Besides that, we also test SCRIP on proteins in four types of cancer tissues and successfully detect 66∼77% potential cancer biomarkers. [ABSTRACT FROM AUTHOR]

Abstract Next-generation sequencing (NGS) technology is highly expected to help researchers disclose the complexity of alternative splicing and understand its association with carcinogenesis. Alternative splicing alterations are firmly associated with multiple malignancies, in terms of functional roles in malignant transformation, motility, and/or metastasis of cancer cells. One perfect example illustrating the connection between alternative splicing and cancer is the human protein arginine methyltransferase 1 (PRMT1) gene, previously cloned from members of our research group and involved in a variety of processes including transcription, DNA repair, and signal transduction. Two splice variants of PRMT1 (variants v.1 and v.2) are downregulated in breast cancer. In addition, PRMT1 v.2 promotes the survival and invasiveness of breast cancer cells, while it could serve as a biomarker of unfavorable prognosis in colon cancer patients. The aim of this study was the molecular cloning of novel alternative splice variants of PRMT1 with the use of 3′ RACE coupled with NGS technology. Extensive bioinformatics and computational analysis revealed a significant number of 19 novel alternative splicing events between annotated exons of PRMT1 as well as one novel exon, resulting in the discovery of multiple PRMT1 transcripts. In order to validate the full sequence of the novel transcripts, RT-PCR was carried out with the use of variant-specific primers. As a result, 58 novel PRMT1 transcripts were identified, 34 of which are mRNAs encoding new protein isoforms, whereas the rest 24 transcripts are candidates for nonsense-mediated mRNA decay (NMD). Highlights • We used NGS technology to identify novel splice variants of the PRMT1 gene. • 58 novel and 5′-partial splice variants of the PRMT1 gene were identified. • 34 novel splice variants of PRMT1 are predicted to encode new protein isoforms. • The rest 24 transcripts are probably nonsense-mediated mRNA decay (NMD) candidates. [ABSTRACT FROM AUTHOR]

Venomous marine cone snails produce peptide toxins (conotoxins) that bind ion channels and receptors with high specificity and therefore are important pharmacological tools. Conotoxins contain conserved cysteine residues that form disulfide bonds that stabilize their structures. To gain structural insight into the large, yet poorly characterized conotoxin H-superfamily, we used NMR and CD spectroscopy along with MS-based analyses to investigate H-Vc7.2 from Conus victoriae, a peptide with a VI/VII cysteine framework. This framework has CysI-CysIV/CysII-CysV/CysIII-CysVI connectivities, which have invariably been associated with the inhibitor cystine knot (ICK) fold. However, the solution structure of recombinantly expressed and purified H-Vc7.2 revealed that although it displays the expected cysteine connectivities, H-Vc7.2 adopts a different fold consisting of two stacked β-hairpins with opposing β-strands connected by two parallel disulfide bonds, a structure homologous to the N-terminal region of the human granulin protein. Using structural comparisons, we subsequently identified several toxins and nontoxin proteins with this "mini-granulin" fold. These findings raise fundamental questions concerning sequence-structure relationships within peptides and proteins and the key determinants that specify a given fold. [ABSTRACT FROM AUTHOR]

Multisubunit tethering complexes (MTCs) are multitasking hubs that form a link between membrane fusion, organelle motility and signaling. CORVET, CHEVI and HOPS are MTCs of the endo-lysosomal system. They regulate the major membrane flows required for endocytosis, lysosome biogenesis, autophagy and phagocytosis. In addition, individual subunits control complex-independent transport of specific cargoes and exert functions beyond tethering, such as attachment to microtubules and SNARE activation. Mutations in CHEVI subunits lead to arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome, while defects in CORVET and, particularly, HOPS are associated with neurodegeneration, pigmentation disorders, liver malfunction and various forms of cancer. Diseases and phenotypes, however, vary per affected subunit and a concise overview of MTC protein function and associated human pathologies is currently lacking. Here, we provide an integrated overview on the cellular functions and pathological defects associated with CORVET, CHEVI or HOPS proteins, both with regard to their complexes and as individual subunits. The combination of these data provides novel insights into how mutations in endo-lysosomal proteins lead to human pathologies. [ABSTRACT FROM AUTHOR]

Membrane tethering is a highly regulated event occurring during the initial physical contact between membrane-bounded transport carriers and their target subcellular membrane compartments, thereby ensuring the spatiotemporal specificity of intracellular membrane trafficking. Although Rab-family small GTPases and specific Rab-interacting effectors, such as coiled-coil tethering proteins and multisubunit tethering complexes, are known to be involved in membrane tethering, how these protein components directly act upon the tethering event remains enigmatic. Here, using a chemically defined reconstitution system, we investigated the molecular basis of membrane tethering by comprehensively and quantitatively evaluating the intrinsic capacities of 10 representative human Rab-family proteins (Rab1a, -3a, -4a, -5a, -6a, -7a, -9a, -11a, -27a, and -33b) to physically tether two distinct membranes via homotypic and heterotypic Rab-Rab assembly. All of the Rabs tested, except Rab27a, specifically caused homotypic membrane tethering at physiologically relevant Rab densities on membrane surfaces (e.g., Rab-to-lipid molar ratios of 1:100-1:3000). Notably, endosomal Rab5a retained its intrinsic potency to drive efficient homotypic tethering even at concentrations below the Rab-to-lipid ratio of 1:3000. Comprehensive reconstitution experiments further uncovered that heterotypic combinations of human Rab-family isoforms, including Rab1a/6a, Rab1a/9a, and Rab1a/33b, can directly and selectively mediate membrane tethering. Rab1a and Rab9a in particular synergistically triggered very rapid and efficient membrane tethering reactions through their heterotypic trans-assembly on two opposing membranes. In conclusion, our findings establish that, in the physiological context, homotypic and heterotypic trans-assemblies of Rab-family small GTPases can provide the essential molecular machinery necessary to drive membrane tethering in eukaryotic endomembrane systems. [ABSTRACT FROM AUTHOR]

Highlights • E. dentata and A. nidulans have been identified with robust growth at 37 °C, and strong PAD productivity. • Purified E. dentata and A. nidulans PADs have molecular mass 41 and 48 kDa, respectively. • PADs peptide fingerprints of E. dentata and A. nidulans displayed 18% and 31% similarity to human PAD4. • The orientation of surface trypsinolytic sites on PADs from both fungal isolates were similar. • PADs from both isolates are calcium dependent with participation of serine and cysteine residues on their catalytic sites. Abstract Peptidylarginine deiminases (PADs) are a group of hydrolases, mediating the deimination of peptidylarginine residues into peptidyl-citrulline. Equivocal protein citrullination by PADs of fungal pathogens has a strong relation to the progression of multiple human diseases, however, the biochemical properties of fungal PADs remain ambiguous. Thus, this is the first report exploring the molecular properties of PAD from thermotolerant fungi, to imitate the human temperature. The teleomorph Emericella dentata and anamorph Aspergillus nidulans have been morphologically and molecularly identified, with observed robust growth at 37–40 °C, and strong PAD productivity. The physiological profiles of E. dentata and A. nidulans for PADs production in response to carbon, nitrogen sources, initial medium pH and incubation temperature were relatively identical, emphasizing the taxonomical proximity of these fungal isolates. PADs were purified from E. dentata and A. nidulans with apparent molecular masses 41 and 48 kDa, respectively. The peptide fingerprints of PADs from E. dentata and A. nidulans have been analyzed by MALDI-TOF/MS, displaying a higher sequence similarity to human PAD4 by 18% and 31%, respectively. The conserved peptide sequences of E. dentata and A. nidulans PADs displayed a higher similarity to human PAD than A. fumigatus PADs clade. PADs from both fungal isolates have an optimum pH and pH stability at 7.0–8.0, with putative p I 5.0–5.5, higher structural denaturation at pH 4.0–5.5 and 9.5–12 as revealed from absorbance at λ 280 nm. E. dentata PAD had a higher conformationally thermal stability than A. nidulans PAD as revealed from its lower K r value. From the proteolytic mapping, the orientation of trypsinolytic recognition sites on the PADs surface from both fungal isolates was very similar. PADs from both isolates are calcium dependent, with participation of serine and cysteine residues on their catalytic sites. PADs displayed a higher affinity to deiminate the peptidylarginine residues with a feeble affinity to work as ADI. So, PADs from E. dentata and A. nidulans had a relatively similar conformational and kinetic properties. Further molecular modeling analysis are ongoing to explore the role of PADs in citrullination of human proteins in Aspergillosis, that will open a new avenue for unraveling the vague of protein-protein interaction of human A. nidulans pathogen. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common and highly lethal form of cancer. Although the etiologic role of Fusobacterium nucleatum (F. nucleatum) in the development of CRC has been elucidated, the specific tumor molecules involved in the progression of CRC induced by F. nucleatum have not been identified. This study investigated several miRNAs and genes involved in the progression of F. nucleatum-induced CRC by Affymetrix miRNA microarray technology and GeneChip Human Transcriptome Array 2.0. The results suggest that miR-4474 and miR-4717 are up-regulated in CRC tissues in response to F. nucleatum infection, compared with the control group (paracancerous tissues), while other genes associated with signaling pathways in cancer, including CREB-binding protein (CREBBP), STAT1, PRKACB, CAMK2B, JUN, TP53 and EWSR1, were dysregulated. Bioinformatic analysis identified CREBBP as the primary aberrantly expressed gene in F. nucleatum-induced CRC. Consistent with the microarray analysis results, real-time RT-PCR analysis demonstrated that the expression of miR-4474/4717 was upregulated while that of CREBBP mRNA was downregulated in CRC patients infected with F. nucleatum. Additionally, CREBBP was identified as a novel target of miR-4474/4717. The results of this study suggest that miR-4474 and miR-4717 are involved in the progression of F. nucleatum-induced CRC by posttranscriptionally regulating the target gene CREBBP. [ABSTRACT FROM AUTHOR]

Viral protein 2C plays a critical role in EV-A71 replication. The discovery of 2C binding proteins will likely provide potential targets to treat EV-A71 infection. Here, we provide a global proteomic analysis of the human proteins that interact with the EV-A71 2C protein. TRIM4, exportin2, and ARFGAP1 were validated as 2C binding partners. Further functional studies revealed that TRIM4, exportin2, and ARFGAP1 were novel host dependency factors for EV-A71. Moreover, enteroviruses' 2C family proteins interacted with exportin2 and ARFGAP1. In conclusion, our study provides a cellular interactome of the EV-A71 2C and identifies the proviral roles of TRIM4, exportin2, and ARFGAP1 in EV-A71 infection. [ABSTRACT FROM AUTHOR]

Microrchidia 3 (MORC3) is a human protein linked to autoimmune disorders, Down syndrome, and cancer. It is a member of a newly identified family of human ATPases with an uncharacterized mechanism of action. Here, we elucidate the molecular basis for inhibition and activation of MORC3. The crystal structure of the MORC3 region encompassing the ATPase and CW domains in complex with a nonhydrolyzable ATP analog demonstrates that the two domains are directly coupled. The extensive ATPase:CW interface stabilizes the protein fold but inhibits the catalytic activity of MORC3. Enzymatic, NMR, mutational, and biochemical analyses show that in the autoinhibited, off state, the CW domain sterically impedes binding of the ATPase domain to DNA, which in turn is required for the catalytic activity. MORC3 autoinhibition is released by disrupting the intramolecular ATPase:CW coupling through the competitive interaction of CW with histone H3 tail or by mutating the interfacial residues. Binding of CW to H3 leads to a marked rearrangement in the ATPase-CW cassette, which frees the DNA-binding site in active MORC3 (on state). We show that ATP-induced dimerization of the ATPase domain is strictly required for the catalytic activity and that the dimeric form of ATPase-CW might cooperatively bind to dsDNA. Together, our findings uncovered a mechanism underlying the fine-tuned regulation of the catalytic domain of MORC3 by the epigenetic reader, CW. [ABSTRACT FROM AUTHOR]

Abstract Background We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy. Methods In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6 months after commencement of ivacaftor , and were correlated with FEV 1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI). Results After 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV 1 (r = −0.5376; P <.001 and r = −0.3285; P <.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV 1 by multiple regression analysis (β = −0.57, P =.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV 1 (0.722 [95% CI 0.581–0.863]; P =.029) were used as classifier, especially in the first 2 months of treatment (0.806 [95% CI 0.665–0.947]; P <.001). Conclusions This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. [ABSTRACT FROM AUTHOR]

The nutritional regulation of protein and amino acid balance in human skeletal muscle carried out by the authors with Mike Rennie is reviewed in the context of a simple physiological model for the regulation of the maintenance and growth of skeletal muscle, the "Bag Theory". Beginning in London in the late 1970s the work has involved the use of stable isotopes to probe muscle protein synthesis and breakdown with two basic experimental models, primed‐dose continuous tracer infusions combined with muscle biopsies and arterio‐venous (A‐V) studies across a limb, most often the leg, allowing both protein synthesis and breakdown as well as net balance to be measured. In this way, over a 30 year period, the way in which amino acids and insulin mediate the anabolic effect of a meal has been elaborated in great detail confirming the original concepts of bag filling within the muscle endomysial "bag", which is limited by the "bag" size unless bag enlargement occurs requiring new collagen synthesis. Finally we briefly review some new developments involving 2H2O labelling of muscle proteins. Skeletal muscle intracellular protein is contained within an inelastic connective‐tissue framework, in effect collagen "bags", which define the myofibre volume, and the maximum protein content. A "bag full" signal to the two processes of protein synthesis (MPS), and protein breakdown (MPB) controls maximum protein content.In the fasted state protein is lost through a reduction in MPS below the rate of MPB, but food intake reverses this response by an insulin‐mediated inhibition of MPB and an essential amino acid, (EAA), mediated stimulation of MPS. This restores muscle protein to a "muscle full" level at which point the "bag full" signal switches off the anabolic response usually after 1.5‐2h. In a healthy adult the EAA stimulation of MPS shows a dose response from 2 to 20g of EAAs with the insulin inhibition of MPB maximal at low insulin levels (5 mU). The elderly exhibit anabolic blunting with reduced stimulation of MPS and reduced inhibition of MPB by feeding. Resistance exercise induces increased collagen synthesis and connective tissue remodellingallowing "bag" enlargement and increased muscle mass which is observed as an extended "bag full" point to 3‐4h after feeding. [ABSTRACT FROM AUTHOR]

While circulating autoantibodies have been detected in patients with several cardiovascular diseases, such studies have not been performed for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Here we investigated the production of certain auto-antibodies in CTEPH patients. Initial screening was performed in 5 CTEPH patients and 5 healthy donors (HDs) using a ProtoArray Human Protein Microarray v5.1 containing 9,375 human proteins, and we selected 34 antigens recognized by IgG antibodies more strongly in the sera of CTEPH patients than in the sera of HDs. In subsequent second/third analyses, we validated the auto-antibody level using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 96 CTEPH patients and 96 HDs as follows: At the second screening, we used 63 crude peptides derived from those selected 34 antigens and found that the serum levels of autoantibodies for 4 peptides seemed higher in CTEPH patients than in HDs. In third analysis, we used the purified peptides of those selected in second screening and found that serum antibodies against peptides derived from exonuclease 3'-5' domain-containing 2 (EXD2) and phosphorylated adaptor for RNA export (PHAX) were significantly higher in CTEPH patients than in HDs. The serum antibody levels to these antigens were also elevated in PAH patients. The titers against EXD2 peptide decreased after surgical treatment in CTEPH patients. These autoantibodies may be useful as biomarkers of CTEPH and PAH, and further investigations may provide novel insight into the etiology. [ABSTRACT FROM AUTHOR]

PURPOSE: Cervical cancer (CC) is the most common cancer affecting women worldwide. Human papillomavirus (HPV) infection is a major contributing factor for the development of CC. The development of CC occurs progressively from precancer stages to cancerous stages (ie, invasive squamous cell carcinoma [ISCC] and adenocarcinoma [ADC]). ADC is a rare form of CC that develops from the mucinous endocervical epithelium. It is believed that the downstream targets of Notch signaling contribute to the etiology of CC. One such target is HES1, whose role in the modulation of ADC is unknown. The purpose of this study is to determine the role of HES1 protein in HPV-associated ADC subtype of CC and also to compare its expression in histologic subtypes of precancer and ISCC. PATIENTS AND METHODS: A total of 148 patients (30 with precancers, 98 with ISCC, and 20 with ADC) and 40 normal control participants were analyzed for the expression of HES1 via immunohistochemistry, with results validated by immunoblotting. RESULTS: The comparison between HPV-16 and HES1 expression was significant in precancer (cervical intraepithelial neoplasia grades 1 to 3; P =.013), ISCC (International Federation of Gynecology and Obstetrics stages I to IV; P =.001), and ADC (P =.007). An overall significant mean difference was observed between HES1, JAG1, and Notch-3 proteins in precancer (P =.001), ISCC (P =.001), and ADC (P =.001). Pairwise comparisons between HES1 and JAG1 and HES1 and Notch-3 were also found to be significant. CONCLUSION: This study showed that among all HPV-16–positive precancers, the major HES1 positivity signal arises from cervical intraepithelial neoplasia grades 2 and 3 that develops into ISCC. Moreover, HPV-16–positive ADC also showed an association with HES1. The HES1, JAG1, and Notch-3 proteins showed their synergistic role in modulating HPV associated ADC along with histologic subtypes of precancer and ISCC of CC. [ABSTRACT FROM AUTHOR]

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The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins. In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation. Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins. From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process. However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition. The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.

Background: Benchmark datasets are essential for both method development and performance assessment. These datasets have numerous requirements, representativeness being one. In the case of variant tolerance/pathogenicity prediction, representativeness means that the dataset covers the space of variations and their effects. Results: We performed the first analysis of the representativeness of variation benchmark datasets. We used statistical approaches to investigate how proteins in the benchmark datasets were representative for the entire human protein universe. We investigated the distributions of variants in chromosomes, protein structures, CATH domains and classes, Pfam protein families, Enzyme Commission (EC) classifications and Gene Ontology annotations in 24 datasets that have been used for training and testing variant tolerance prediction methods. All the datasets were available in VariBench or VariSNP databases. We tested also whether the pathogenic variant datasets contained neutral variants defined as those that have high minor allele frequency in the ExAC database. The distributions of variants over the chromosomes and proteins varied greatly between the datasets. Conclusions: None of the datasets was found to be well representative. Many of the tested datasets had quite good coverage of the different protein characteristics. Dataset size correlates to representativeness but only weakly to the performance of methods trained on them. The results imply that dataset representativeness is an important factor and should be taken into account in predictor development and testing. [ABSTRACT FROM AUTHOR]

Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts. Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values < 0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values < 10−14) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values < 0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria. Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis. [ABSTRACT FROM AUTHOR]

The present study aimed to identify key pathways and genes in the pathogenesis of lung cancer. The GSE10072 dataset was downloaded from the Gene Expression Omnibus database. Protein‑protein interaction data were collected from Human Protein Reference Database, and 201 pathways were downloaded from the Kyoto Encyclopedia of Genes and Genomes database. Signaling network impact analysis was performed to identify enriched pathways, followed by the construction of a pathway‑pathway crosstalk network. Benzopyrene was used to treat normal human lung cells at concentrations of 0.01, 0.1, 1 and 10 μM, and cell viability was measured. Furthermore, growth arrest and DNA damage inducible β (GADD45B), p53, cyclin B, Akt and nuclear factor (NF)‑κB protein levels were also measured via western blotting. Impact analysis identified 11 enriched lung cancer‑associated KEGG pathways, including ‘complement and coagulation cascades’, ‘ECM‑receptor interaction’, ‘P53 signaling pathway’, ‘cell adhesion molecules’ and ‘focal adhesion’. In addition, cell cycle, ‘drug metabolism‑cytochrome P450’, ‘metabolic pathways’, ‘pathways in cancer’, ‘focal adhesion’ and ‘antigen processing and presentation’ were central in the pathway‑pathway cross‑talk network. Furthermore, the upregulated gene GADD45B was associated with three of the pathways, including an activated pathway (‘MAPK signaling pathway’) and two repressed pathways (‘cell cycle’ and ‘P53 pathway’). Western blotting demonstrated that the expression of NF‑κB, Akt and GADD45B increased over time in lung cells treated with benzopyrene, whereas the expression levels of cyclin B and P53 decreased. In conclusion, GADD45B may contribute to lung carcinogenesis via affecting the MAPK, P53 signaling and cell cycle pathways. [ABSTRACT FROM AUTHOR]

The therapeutic potential of mesenchymal stromal cells (MSCs) from various tissue origins have extensively been explored in both experimental and clinical studies, and peritoneal dialysis effluent-derived MSC (pMSC) may be an easily obtainable MSC source for clinical applications. In this study, we expanded and characterized the pMSCs after expansion in a human protein culture medium. The pMSCs were expanded in plastic dishes with the human protein medium. MSC marker expression was examined by flow cytometry. Spherical formation was tested by hanging drop method, and osteogenic, adipogenic, and chondrogenic differentiation capacities were confirmed by positive staining with Alizarin red, Oil red O, and Alcian blue, respectively. Here, we showed that after four passages of culturing in plastic dishes, pMSCs in the human protein medium displayed a homogeneous pattern of classical MSC markers (positive: CD29, CD44, CD73, CD90, and CD166; negative: CD14, CD34, CD45, CD79a, CD105, CD146, CD271, HLA-DR, SSEA-4, and Stro-1), while in the standard medium, pMSCs from some donors were CD45 or HLA-DR positive. For nonclassical MSC markers, pMSCs were CD200 positive from all the donors, negative for CD163, CD271, CD36, and CD248, and either positive or negative for CD274 and CD140b. Further, pMSCs from the human protein medium had the spherical formation capacity and multipotent differentiation capacity in vitro. In conclusion, upon expansion in a human protein medium, pMSCs showed a differential MSC marker expression profile from those of bone marrow or adipose tissue-derived MSCs and could maintain the multipotency. The therapeutic potential of the pMSCs requires further investigation. [ABSTRACT FROM AUTHOR]

A model was developed to estimate beef's contribution toward meeting human protein requirements using a summative model of net protein contribution (NPC) and methane production. NPC was calculated by multiplying the ratio of human-edible protein (HeP) in beef to the HeP in feedstuffs by the protein quality ratio (PQR). PQR describes the change in biological value of HeP that occurs when plant-derived HeP is converted to beef. An NPC > 1 indicates that the production system is positively contributing to meeting human requirements; systems with NPC < 1 reduce the net protein available to meet human requirements. Scenarios were arranged as a 2 × 2 factorial with two sets of dietary inputs and two sets of production parameters. Dietary inputs represented either inputs used in a previous report estimating HeP (previous diet; PD) or inputs more representative of conventional beef production systems (current diet; CD). Production parameters were either drawn from previous reports (previous parameters; PP) or chosen to characterize current industry standards (current parameters; CP). The HeP conversion efficiency (HePCE) for current industry diets and production parameters (CDCP) (kg HeP yield/kg HeP input) was greatest in the cow-calf sector (2,640.83) compared with stocker (5.22) and feedlot (0.34), and other scenarios followed a similar trend. In addition, the entire production system had an HePCE of 0.99 for CDCP; the previous model diets and production parameters (PDPP) scenario estimated HePCE to be 0.46, and other scenarios were in between. For the CDCP scenario, 56%, 10%, and 34% of the HeP were produced in the cow-calf, stocker, and feedlot sectors; PDPP was similar (59%, 13%, and 28%, respectively). PQR averaged 3.04, 3.04, and 2.64 for cow-calf, stocker, and feedlot sectors, respectively, indicating each sector enhances the biological value of the HeP fed. The NPC was greatest for the cow-calf sector (8,794), followed by the stocker and feedlot sectors (8.85 and 0.23, respectively). The entire beef value chain had a PQR of 2.68 and NPC ranged from 1.01 to 3.11, which correspond to PDPP and CDCP, respectively. Overall, 3.05 kg of CH4 were produced per kilogram HeP for CDCP and 2.58 for PDPP, with the cow-calf sector being greater than the feedlot sector (4.53 vs. 0.94 kg CH4/kg HeP, CDCP). Our results suggest that each individual beef sector and the entire value chain produce more high-quality HeP than is consumed in production. Accordingly, beef is a net contributor to meeting human protein requirements. [ABSTRACT FROM AUTHOR]

Background: Protein complexes are one of the keys to deciphering the behavior of a cell system. During the past decade, most computational approaches used to identify protein complexes have been based on discovering densely connected subgraphs in protein-protein interaction (PPI) networks. However, many true complexes are not dense subgraphs and these approaches show limited performances for detecting protein complexes from PPI networks. Results: To solve these problems, in this paper we propose a supervised learning method based on network node embeddings which utilizes the informative properties of known complexes to guide the search process for new protein complexes. First, node embeddings are obtained from human protein interaction network. Then the protein interactions are weighted through the similarities between node embeddings. After that, the supervised learning method is used to detect protein complexes. Then the random forest model is used to filter the candidate complexes in order to obtain the final predicted complexes. Experimental results on real human and yeast protein interaction networks show that our method effectively improves the performance for protein complex detection. Conclusions: We provided a new method for identifying protein complexes from human and yeast protein interaction networks, which has great potential to benefit the field of protein complex detection. [ABSTRACT FROM AUTHOR]

Blood products laboratory is a Central Drug Testing Laboratory for testing quality standards of plasmaderived products in India. Blood products laboratory received 243 batches of human normal albumin during the financial year 2015-16 from indigenous and international manufacturers for testing. As per Indian Pharmacopoeia, the biuret method is different from European and British Pharmacopoeia for protein estimation, therefore, harmonisation of such method is necessary as per World Health Organization's recommendation. In this context, blood products laboratory conducted a comparative study between the methods of Indian, European and British Pharmacopoeia for protein estimation in biologicals, especially for human albumin preparation to prevent any bias regarding protein content between indigenous samples and imported products. Results showed that both the methods were significantly not different (p=0.05), and also showed that Indian Pharmacopoeial biuret method was more sensitive although reagent stability was lower than that of European and British Pharmacopoeial methods. [ABSTRACT FROM AUTHOR]