1,111 results on '"Novel protein"'
Search Results
102. Design of Novel Protein Kinase Inhibitors Using the Naturally Occurring Staurosporine Scaffold as a Lead
- Author
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Claire Shoemake and Elena Mallia
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Scaffold ,Kinase ,Novel protein ,Chemistry ,medicine ,General Engineering ,Staurosporine ,General Earth and Planetary Sciences ,medicine.drug ,Cell biology ,General Environmental Science - Published
- 2019
103. Protein conjugates and fusion proteins as ocular therapeutics
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Robert F. Kelley, Devin Tesar, and Shrenik C. Mehta
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0301 basic medicine ,medicine.medical_specialty ,Standard of care ,genetic structures ,Clinical settings ,Eye ,Macular Degeneration ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Drug Discovery ,medicine ,Humans ,Intensive care medicine ,Patient compliance ,Pharmacology ,business.industry ,Novel protein ,Treatment burden ,Proteins ,Macular degeneration ,medicine.disease ,Fusion protein ,eye diseases ,030104 developmental biology ,Delayed-Action Preparations ,030220 oncology & carcinogenesis ,cardiovascular system ,sense organs ,Ophthalmic Solutions ,business ,Healthcare providers - Abstract
Long-acting delivery (LAD) of ocular therapeutics has potential to improve the standard of care for ocular diseases, such as age-related macular degeneration (AMD), by increasing patient compliance and reducing overall treatment burden on patients and healthcare providers. Although relatively few ocular LAD technologies are currently on the market, a variety of emergent and novel protein engineering-based technologies are being investigated in both the laboratory and clinical settings. Here, we review some of the key indications and treatments that would benefit from the development of LAD for the treatment of ocular diseases and examine the current state of LAD technologies that leverage protein-engineering approaches as well as nascent technologies with potential for future impact.
- Published
- 2019
104. Characterization of ice recrystallization inhibition activity in the novel freeze-responsive protein Fr10 from freeze-tolerant wood frogs, Rana sylvatica
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Robert N. Ben, Christine L. Childers, Madeleine K. Adam, Dung Le Tri, Kenneth B. Storey, and Kyle K. Biggar
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0106 biological sciences ,Thermal shift assay ,Ranidae ,Physiology ,Acclimatization ,030310 physiology ,010603 evolutionary biology ,01 natural sciences ,Biochemistry ,Amphibian Proteins ,03 medical and health sciences ,Rana sylvatica ,Freezing ,Animals ,Thermal stability ,0303 health sciences ,biology ,Ice crystals ,Protein Stability ,Chemistry ,Novel protein ,Ice ,Recrystallization (metallurgy) ,biology.organism_classification ,Colloidal gold ,Freezing stress ,Biophysics ,Nanoparticles ,Gold ,Crystallization ,General Agricultural and Biological Sciences ,Developmental Biology - Abstract
Fr10 is a secreted freeze-responsive protein found in the wood frog (Rana sylvatica). This protein has gained notable research attention for its highly dynamic expression in response to seasonal freezing stress, while its over-expression has been documented to enhance freeze tolerance in cold-susceptible cultured cells. This study further characterizes the properties of this novel protein with regards to thermal stability and ice recrystallization inhibition (i.e. IRI) activity. Thermal stability was assessed using differential scanning fluorimetry, with an experimental Tm value of 50.8 ± 0.1 °C. Potential IRI activity of Fr10 was evaluated using a recently developed nanoparticle-based colorimetric assay, where Fr10 displayed the ability to prevent freeze-induced aggregation of gold nanoparticles. Based upon this assay, Fr10 protein appeared to have a low level of IRI activity and it was therefore predicted that one of Fr10's biological functions may be to inhibit ice crystal growth via recrystallization. A SPLAT cooling assay was then employed to directly characterize the IRI properties of Fr10 and provide further insight into this hypothesis. In the presence of 30 μM of Fr10, a 40% reduction in the mean grain size of ice crystals relative to the control samples was observed, thus introducing the possibility of Fr10 to inhibit ice recrystallization. Collectively, the results from this study provide new insight into the potential of further exploring the potential of this vertebrate freeze-responsive protein in cryoprotection.
- Published
- 2019
105. S100A4: a novel partner for heat shock protein 47 in antler stem cells and insight into the calcium ion-induced conformational changes
- Author
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Datao Wang, Yudong Shang, Chunyi Li, Zhengyao Zhang, Xiaoyan Qi, Hengxing Ba, Li, Chunyi [0000-0001-7275-4440], and Apollo - University of Cambridge Repository
- Subjects
animal structures ,antler stem cell ,030303 biophysics ,chemistry.chemical_element ,Antlers ,Calcium ,protein-protein docking ,Homology (biology) ,03 medical and health sciences ,Molecular dynamics ,Structural Biology ,S100A4 ,Animals ,S100 Calcium-Binding Protein A4 ,Binding site ,HSP47 Heat-Shock Proteins ,Molecular Biology ,Heat shock protein 47 ,chemistry.chemical_classification ,0303 health sciences ,biology ,Novel protein ,Deer ,Stem Cells ,General Medicine ,molecular dynamics ,Amino acid ,chemistry ,HSP47 ,embryonic structures ,biology.protein ,Biophysics ,Stem cell - Abstract
S100A4 is a multiple-function protein highly expressed in tumor or stem cells. We found S100A4 was a novel protein partner for heat shock protein 47 (HSP47) in deer antlerogenic periosteum cells (AP cells), indicating that S100A4 could bind with HSP47. S100A4 had both calcium-dependent and calcium-independent patterns (labeled as SCd and SCi, respectively) to execute different biological activities. Homology models of HSP47, SCd and SCi were constructed. HSP47:collagen model, HSP47:collagen I-V, HSP47:SCd and HSP47:SCi complexes were built using ZDOCK software. Together with free SCd and SCi, 200 ns molecular dynamic (MD) simulations were performed to analyze binding free energies and SCi/SCd conformational changes. The energetic results showed that SCi had the strongest affinity to HSP47, and followed by collagens. SCd had little interaction with HSP47. Decomposition energy results showed that collagen model interacted with HSP47 mainly though neutral amino acids. When SCi bound with HSP47, the majority of mediated amino acids were charged. These results indicated that SCi could compete with collagen on the binding site of HSP47. Root mean square fluctuation (RMSF) values and cross-correlation matrices of principal component analysis (PCA) were calculated to evaluate the SCi/SCd structural variation during MD simulation. Both HSP47 and Ca2+ could stabilize the conformation of SCi/SCd. The loops interacting with Ca2+s and linking the two EF-hand motifs were impacted particularly. The relative moving directions of α-helices in EF-hands were distinct by the binding effect of HSP47 and Ca2+. We found that SCi may regulate the differentiation of AP cells by disturbing the interaction between HSP47 and collagen. Communicated by Ramaswamy H. Sarma.
- Published
- 2019
106. The effect of new compounds in stabilizing downstream monoclonal antibody (mAb) process intermediates
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Madhukar Dasika, Christopher D. Maycock, Matt Dickson, Irina Ramos, M. Rita Ventura, Osvaldo S. Ascenso, and Eva C. Lourenço
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medicine.drug_class ,Chemistry, Pharmaceutical ,Ultrafiltration ,Pharmaceutical Science ,02 engineering and technology ,Protein aggregation ,Monoclonal antibody ,030226 pharmacology & pharmacy ,Virus ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Drug Stability ,law ,medicine ,Throughput (business) ,Filtration ,Chemistry ,Novel protein ,Antibodies, Monoclonal ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Immunoglobulin G ,Viruses ,Biophysics ,0210 nano-technology ,Stabilizer (chemistry) - Abstract
Determining the stability of downstream process (DSP) intermediates is an extremely important parameter used to maintain product quality attributes within their acceptance ranges. The IgG4 monoclonal antibody studied (mAb1) showed aggregation under acidic conditions, inhibiting the use of low pH treatment to inactivate endogenous retroviruses, and poor virus filtration performance. Both manufacturing steps are included in mAb DSP for viral clearance. The impact of several new compounds on the aggregation and stabilization of mAb1 in process intermediate pools encountered during these critical DSP steps was investigated. Results showed that, in the presence of a protein stabilizer at pH 3.2, 27% less aggregation was observed compared to controls, during the low pH treatment for viral inactivation. The impact of a novel protein stabilizer on virus filter throughput during mAb1 filtration was compared to L-arginine using an innovative high-throughput automation technique. Compared to control experiments without additives, conditions were found where a 70% increase in filter volumetric throughput was achieved in the presence of the novel stabilizer, and a 56% decrease in volumetric throughput observed with L-arginine. These findings present the possibility of using these novel compounds to stabilize proteins during DSP and permitting the use of platform DSP elements such as low pH treatment and high-throughput virus filtration to challenging and unstable proteins.
- Published
- 2019
107. A Novel Protein Elicitor PeBL2, from Brevibacillus laterosporus A60, Induces Systemic Resistance against Botrytis cinerea in Tobacco Plant
- Author
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Guo LiHua, Azhar Uddin Keerio, Yang XiuFen, Ghulam Hussain Jatoi, Muswar Ali Gadhi, Dewen Qiu, and Yusuf Ali Abdulle
- Subjects
0106 biological sciences ,Hypersensitive response ,Signal peptide ,Nicotiana benthamiana ,lcsh:Plant culture ,medicine.disease_cause ,01 natural sciences ,PeBL2 ,law.invention ,Microbiology ,law ,medicine ,lcsh:SB1-1110 ,protein elicitor activity ,Escherichia coli ,Botrytis cinerea ,chemistry.chemical_classification ,biology ,food and beverages ,biology.organism_classification ,Botrytis cinereal ,Amino acid ,Elicitor ,010602 entomology ,chemistry ,Recombinant DNA ,novel protein ,Brevibacillus laterosporus A60 ,Agronomy and Crop Science ,010606 plant biology & botany ,Research Article - Abstract
Here, we reported a novel secreted protein elicitor PeBL2 from Brevibacillus laterosporus A60, which can induce hypersensitive response in tobacco (Nicotiana benthamiana). The ion-exchange chromatography, high-performance liquid chromatography (HPLC) and mass spectrometry were performed for identification of protein elicitor. The 471 bp PeBL2 gene produces a 17.22 kDa protein with 156 amino acids containing an 84-residue signal peptide. Consistent with endogenous protein, the recombinant protein expressed in Escherichia coli induced the typical hypersensitive response (HR) and necrosis in tobacco leaves. Additionally, PeBL2 also triggered early defensive response of generation of reactive oxygen species (H2O2 and O2 -) and systemic resistance against of B. cinerea. Our findings shed new light on a novel strategy for biocontrol using B. laterosporus A60.
- Published
- 2019
108. Novel protein-lipid factors in the pathomechanism of mild preeclampsia
- Author
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Karol Charkiewicz
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carbohydrates (lipids) ,medicine.medical_specialty ,Endocrinology ,Novel protein ,Mild preeclampsia ,Internal medicine ,medicine ,lipids (amino acids, peptides, and proteins) - Abstract
The aim of this review was discussion on the new protein and lipid factors and their role in the pathomechanism of preeclampsia. Sphingolipids discussed in the review: Sph (sphingosine), S1P (sphingosine- 1-phosphate), C20-Cer (ceramides containing arachidic acid), C18-Cer (ceramides containing stearic acid), C16-Cer (ceramides containing palmitic acid), C18: 1-Cer (ceramides containing oleic acid), C22-Cer (ceramide containing behenic acid) and C24: 1-Cer (ceramides containing nervonic acid). Angiogenic factors discussed in the review: Hb-EGF (heparin-binding EGF-like growth factor), HGF (hepatocyte growth factor), LIF (leukaemia inhibitory factor), leptin, PDGF-BB (platelet-derived growth factor BB) and follistatin. Based on literature findings, it seems that protein and lipid factors may play an important role in the pathogenesis of preeclampsia, and there are many proteins and lipids that have not been studied in plasma of women with PE to date. We showed a few new pathways in pathomechanism of preeclampsia.
- Published
- 2019
109. Interchain doubly-bridged α-helical peptides for the development of protein binders
- Author
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Tao Li, Yaqi Chen, Chuanliu Wu, Jingjing Liang, Yibing Zhao, and Ping Lin
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chemistry.chemical_classification ,Bioactive peptide ,chemistry ,Novel protein ,α helical ,Cancer cell ,Biophysics ,Peptide ,General Chemistry ,Target protein ,Intracellular - Abstract
Constrained peptide scaffolds that are tolerant to extensive sequence manipulation and amenable to bioactive peptide design are of great value to the development of novel protein binders and peptide therapeutics. In this work, we reported strategies for the design and synthesis of a kind of novel interchain doubly-bridged α-helical peptides, involving mutual stabilization of two peptide α-helices linked by two interchain bisthioether crosslinkers. By taking a MDM2-binding peptide with an α-helical tendency as a model, we demonstrated that α-helical dimers with significantly improved structural and proteolytic stability and nanomolar binding affinity to the target protein can be obtained. By modulating the surface charges on the dimeric peptides, we also obtained a dimeric peptide with enhanced cell-penetrating capability, which can efficiently penetrate into cancer cells and inhibit the intracellular MDM2-p53 interactions to promote cell apoptosis. Considering that many proteins take a surface α-helical segment as the binding motif to mediate their interactions with other proteins, we believe that our interchain doubly-bridged α-helical peptides would provide a promising scaffold for the development of novel high-affinity protein binders.
- Published
- 2019
110. Contemporary approaches to site-selective protein modification
- Author
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Emily A. Hoyt, Gonçalo J. L. Bernardes, Pedro M. S. D. Cal, and Bruno L. Oliveira
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Novel protein ,Computer science ,General Chemical Engineering ,Site selective ,Posttranslational modification ,General Chemistry ,Key features ,Data science ,Large size - Abstract
Proteins constitute the majority of nature’s worker biomolecules. Designed for specific functions, complex tertiary structures make proteins ideal candidates for analysing natural systems and creating novel biological tools. Owing to both their large size and the need for proper folding, de novo synthesis of proteins has been quite a challenge, leading scientists to focus on modifying protein templates already provided by nature. Recently developed methods for protein modification fall into two broad categories: those that can modify the natural protein template directly and those that require genetic manipulation of the amino acid sequence before modification. The goal of this Review is not only to provide a window through which to view the many opportunities created by novel protein modification techniques‚ but also to act as an initial guide to help scientists find direction and form ideas in an ever-growing field. In addition to highlighting methods reported in the past 5 years, we aim to provide a broader sense of the goals and outcomes of protein modification and bioconjugation in general. While the main body of this paper comprises reactions involving the direct modification of expressed proteins, some further functionalization strategies as well as biological applications are also acknowledged. The discussion concludes by speculating which trends and discoveries will most likely come next in the field. Over the past 5 years, many novel site-selective protein modification techniques have been reported. Key features of these various strategies as well as prominent examples are discussed in this Review.
- Published
- 2019
111. Measurement of pancreatic stone protein in the identification and management of sepsis
- Author
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Yok-Ai Que, Philippe Eggimann, and Fabien Rebeaud
- Subjects
medicine.medical_specialty ,Clinical Biochemistry ,Host response ,610 Medicine & health ,030204 cardiovascular system & hematology ,Procalcitonin ,law.invention ,Biomarkers/analysis ,Biomarkers/metabolism ,Humans ,Lithostathine/analysis ,Lithostathine/metabolism ,Prognosis ,ROC Curve ,Sepsis/diagnosis ,Sepsis/metabolism ,PSP ,diagnosis ,diagnostics ,infection ,prognosis ,sepsis ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,law ,Lithostathine ,Drug Discovery ,medicine ,Intensive care medicine ,business.industry ,Novel protein ,Biochemistry (medical) ,medicine.disease ,Intensive care unit ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Identification (biology) ,Pancreatic stone protein ,business ,Biomarkers - Abstract
Sepsis is a life-threatening syndrome characterized by a dysregulated host response to an infection resulting in multiple organ dysfunctions. Early diagnosis and management of sepsis is key to improve patient outcome but remains challenging. Despite extensive research, only few biomarkers have so far proven to be helpful in the diagnosis of sepsis. A novel protein biomarker, the pancreatic stone protein (PSP), is showing great promises. Several lines of evidences suggest that PSP has a higher diagnostic performance for the identification of sepsis than procalcitonin and C-reactive protein, and a strong prognostic value to predict unfavorable outcome at admission to intensive care unit. This review summarizes the current knowledge on the molecular mechanisms of PSP function and the clinical evidences available to highlight the relevance of this protein in the diagnosis and prognosis of sepsis.
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- 2019
112. Meat alternatives: an integrative comparison
- Author
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Martinus A.J.S. van Boekel, Barbara van Mierlo, Cor van der Weele, Atze Jan van der Goot, and Peter H. Feindt
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Environmental change ,Strategic Communication ,Algae ,030309 nutrition & dietetics ,WASS ,Strategische Communicatie ,Filosofie ,03 medical and health sciences ,Human health ,Cultured meat ,Plant-based meat alternatives ,0404 agricultural biotechnology ,Framing (construction) ,Innovation ,Food Process Engineering ,Pulses ,VLAG ,0303 health sciences ,Novel protein ,food and beverages ,04 agricultural and veterinary sciences ,Environmental economics ,040401 food science ,Insects ,Philosophy ,Conceptual framework ,Sustainability ,Greenhouse gas ,Technologie and Innovatie ,Knowledge Technology and Innovation ,Kennis ,Business ,Kennis, Technologie and Innovatie ,Protein transition ,Food Science ,Biotechnology - Abstract
Background Meat, an important source of protein and other nutrients in human diets, is one of the major drivers of global environmental change in terms of greenhouse gas emissions, land and water use, animal welfare, human health and directions of breeding. Novel alternatives, including novel meat proxies (cultured meat, plant-based meat alternatives), insects and novel protein sources (like algae) receive increasing attention. But plausible socio-technological pathways for their further development have not yet been compared in an integrative, interdisciplinary perspective. Scope and approach This paper applies an integrated conceptual framework – the Reflexive Integrative Comparative Heuristic (RICH) – to comparatively assess the nutritional implications, potential sustainability gains and required technological and social-institutional change of five meat alternatives. We formulate plausible pathways for each alternative and identify their pre-conditions and implications. Key findings and conclusions High levels of transformation and processing limit the environmental sustainability gains of cultured meat, highly processed plant-based meat alternatives, algae- and insect-based food. At the same time, a high degree of societal coordination is needed to enable the potentially disruptive level of technological, organisational and institutional innovations needed to make these novel alternatives viable. Widespread expectations that solutions require break-through novelties or high-tech alternatives imply a neglect of existing and viable alternatives. Our integrative analysis suggests that the priority given to meat alternatives with limited sustainability potential does not just raise questions of technological optimisation of production systems, but is also a second-order problem of the framing of search directions.
- Published
- 2019
113. Identification of candidate neoantigens produced by fusion transcripts in human osteosarcomas
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Tracy A. Marko, Adrienne L. Watson, Susan K. Rathe, John R. Ohlfest, Flavia E. Popescu, James E. Johnson, Branden S. Moriarity, and David A. Largaespada
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0301 basic medicine ,Genome instability ,Oncogene Proteins, Fusion ,Transcription, Genetic ,Oncogene Proteins ,CLOCK Proteins ,lcsh:Medicine ,Bone Neoplasms ,Computational biology ,CD8-Positive T-Lymphocytes ,Biology ,Genome ,Antiporters ,Genomic Instability ,Article ,Transcriptome ,Epitopes ,Mice ,Open Reading Frames ,03 medical and health sciences ,0302 clinical medicine ,Antigens, Neoplasm ,Cell Line, Tumor ,Animals ,lcsh:Science ,Cation Transport Proteins ,Osteosarcoma ,Multidisciplinary ,Novel protein ,Gene Expression Profiling ,lcsh:R ,Computational Biology ,High-Throughput Nucleotide Sequencing ,Gene expression profiling ,Open reading frame ,030104 developmental biology ,Genetic Loci ,RNA splicing ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Osteosarcomas are characterized by highly disrupted genomes. Although osteosarcomas lack common fusions, we find evidence of many tumour specific gene-gene fusion transcripts, likely due to chromosomal rearrangements and expression of transcription-induced chimeras. Most of the fusions result in out-of-frame transcripts, potentially capable of producing long novel protein sequences and a plethora of neoantigens. To identify fusions, we explored RNA-sequencing data to obtain detailed knowledge of transcribed fusions, by creating a novel program to compare fusions identified by deFuse to de novo transcripts generated by Trinity. This allowed us to confirm the deFuse results and identify unusual splicing patterns associated with fusion events. Using various existing tools combined with this custom program, we developed a pipeline for the identification of fusion transcripts applicable as targets for immunotherapy. In addition to identifying candidate neoantigens associated with fusions, we were able to use the pipeline to establish a method for measuring the frequency of fusion events, which correlated to patient outcome, as well as highlight some similarities between canine and human osteosarcomas. The results of this study of osteosarcomas underscores the numerous benefits associated with conducting a thorough analysis of fusion events within cancer samples.
- Published
- 2019
114. Future Protein Supply and Demand: Strategies and Factors Influencing a Sustainable Equilibrium
- Author
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Maeve Henchion, Maria Hayes, Anne Maria Mullen, Mark Fenelon, and Brijesh Tiwari
- Subjects
protein ,novel protein ,protein demand ,in vitro meat ,algae ,insect ,dairy ,meat ,vegetal ,consumer ,Chemical technology ,TP1-1185 - Abstract
A growing global population, combined with factors such as changing socio-demographics, will place increased pressure on the world’s resources to provide not only more but also different types of food. Increased demand for animal-based protein in particular is expected to have a negative environmental impact, generating greenhouse gas emissions, requiring more water and more land. Addressing this “perfect storm” will necessitate more sustainable production of existing sources of protein as well as alternative sources for direct human consumption. This paper outlines some potential demand scenarios and provides an overview of selected existing and novel protein sources in terms of their potential to sustainably deliver protein for the future, considering drivers and challenges relating to nutritional, environmental, and technological and market/consumer domains. It concludes that different factors influence the potential of existing and novel sources. Existing protein sources are primarily hindered by their negative environmental impacts with some concerns around health. However, they offer social and economic benefits, and have a high level of consumer acceptance. Furthermore, recent research emphasizes the role of livestock as part of the solution to greenhouse gas emissions, and indicates that animal-based protein has an important role as part of a sustainable diet and as a contributor to food security. Novel proteins require the development of new value chains, and attention to issues such as production costs, food safety, scalability and consumer acceptance. Furthermore, positive environmental impacts cannot be assumed with novel protein sources and care must be taken to ensure that comparisons between novel and existing protein sources are valid. Greater alignment of political forces, and the involvement of wider stakeholders in a governance role, as well as development/commercialization role, is required to address both sources of protein and ensure food security.
- Published
- 2017
- Full Text
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115. Machine learning applied to enzyme turnover numbers reveals protein structural correlates and improves metabolic models
- Author
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Colton J. Lloyd, Zachary B. Haiman, Daniel C. Zielinski, Martin J. Lercher, Nathan Mih, Abdelmoneim Amer Desouki, David Heckmann, Yuanchi Ha, and Bernhard O. Palsson
- Subjects
0301 basic medicine ,Proteome ,Science ,1.1 Normal biological development and functioning ,Genome scale ,General Physics and Astronomy ,Context (language use) ,Biology ,Machine learning ,computer.software_genre ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Article ,Machine Learning ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Models ,Underpinning research ,Escherichia coli ,2.1 Biological and endogenous factors ,Enzyme kinetics ,Aetiology ,lcsh:Science ,chemistry.chemical_classification ,Multidisciplinary ,ComputingMilieux_THECOMPUTINGPROFESSION ,Novel protein ,business.industry ,Escherichia coli Proteins ,General Chemistry ,Biological ,Kinetics ,030104 developmental biology ,Enzyme ,chemistry ,Biocatalysis ,lcsh:Q ,Artificial intelligence ,Generic health relevance ,business ,computer ,030217 neurology & neurosurgery ,Algorithms ,Metabolic Networks and Pathways ,Biotechnology - Abstract
Knowing the catalytic turnover numbers of enzymes is essential for understanding the growth rate, proteome composition, and physiology of organisms, but experimental data on enzyme turnover numbers is sparse and noisy. Here, we demonstrate that machine learning can successfully predict catalytic turnover numbers in Escherichia coli based on integrated data on enzyme biochemistry, protein structure, and network context. We identify a diverse set of features that are consistently predictive for both in vivo and in vitro enzyme turnover rates, revealing novel protein structural correlates of catalytic turnover. We use our predictions to parameterize two mechanistic genome-scale modelling frameworks for proteome-limited metabolism, leading to significantly higher accuracy in the prediction of quantitative proteome data than previous approaches. The presented machine learning models thus provide a valuable tool for understanding metabolism and the proteome at the genome scale, and elucidate structural, biochemical, and network properties that underlie enzyme kinetics., Experimental data on enzyme turnover numbers is sparse and noisy. Here, the authors use machine learning to successfully predict enzyme turnover numbers for E. coli, and show that using these to parameterize mechanistic genome-scale models enhances their predictive accuracy.
- Published
- 2018
116. Protein deamidation to produce processable ingredients and engineered colloids for emerging food applications
- Author
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Yangchao Luo, Chun Cui, Li Liang, Inthawoot Suppavorasatit, Xing Chen, and Wenyan Fu
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Food industry ,Novel protein ,Chemistry ,Food protein ,business.industry ,010401 analytical chemistry ,04 agricultural and veterinary sciences ,Allergens ,040401 food science ,01 natural sciences ,0104 chemical sciences ,Gastrointestinal digestion ,0404 agricultural biotechnology ,Glutaminase ,Biological property ,Posttranslational modification ,Protein particles ,Biochemical engineering ,Colloids ,Deamidation ,business ,Food Science - Abstract
With the ever-increasing demands for functional and sustainable foods from the general public, there is currently a paradigm shift in the food industry toward the production of novel protein-based diet. Food scientists are therefore motivated to search for natural protein sources and innovative technologies to modify their chemical structure for desirable functionality and thus utilization. Deamidation is a viable, efficient, and attractive approach for modifying proteins owing to its ease of operating, specificity, and cost-effective processes. Over the past three decades, the knowledge of protein deamidation for food applications has evolved drastically, including the development of novel approaches for deamidation, such as protein-glutaminase and ion exchange resin, and their practices in new protein substrate. Thanks to deamidation, enhanced functionalities of food proteins from cereals, legumes, milk, oil seeds and others, and thereby their processabilities as food ingredients have been achieved. Moreover, deamidated proteins have been used to fabricate engineered food colloids, including self-assembled protein particles, protein-metallic complexes, and protein-carbohydrate complexes, which have demonstrated tailored physicochemical properties to modulate oral perception, improve gastrointestinal digestion and bioavailability, and protect and/or deliver bioactive nutrients. Novel bioactivity, altered digestibility, and varied allergenicity of deamidated proteins are increasingly recognized. Therefore, deamidated proteins with novel techno-functional and biological properties hold both promise and challenges for future food applications, and a comprehensive review on this area is critically needed to update our knowledge and provide a better understanding on the protein deamidation and its emerging applications.
- Published
- 2021
117. Novel Protein to Phosphorous Ratio Score Predicts Mortality in Hemodialysis Patients
- Author
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Dana Bielopolski, Cachet Wenziger, Benaya Rozen Zvi, Elani Streja, Tali Steinmetz, and Kamyar Kalantar-Zadeh
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Medicine (miscellaneous) ,chemistry.chemical_element ,Renal function ,Gastroenterology ,Cachexia ,Renal Dialysis ,Internal medicine ,Medicine ,Humans ,Dialysis ,Survival analysis ,Inflammation ,Nutrition and Dietetics ,business.industry ,Novel protein ,Phosphorus ,medicine.disease ,chemistry ,Nephrology ,Disease Progression ,Kidney Failure, Chronic ,Hemodialysis ,Dietary Proteins ,business ,After treatment - Abstract
Objective Lowering serum phosphorus in people on hemodialysis may improve their survival. However, prior studies have shown that restricting dietary protein intake, a major source of phosphorus, is associated with higher mortality. We hypothesized that a novel metric that incorporates both these values commensurately can improve survival prediction. Methods We used serum phosphorous and normalized protein catabolic rate (nPCR), a surrogate of dietary protein intake, to form a new metric R that was used to examine the associations with mortality in 63,016 people on hemodialysis (HD) of one year after treatment initiation. Survival models were adjusted for case-mix, malnutrition-inflammation cachexia syndrome (MICS), and residual kidney function (RKF). Results Individuals treated with hemodialysis were divided into five groups in accordance with R value. Group 1 included sick individuals with high phosphorous and low nPCR. Group 5 included individuals with low phosphorous and high nPCR. After 1-year follow-up, survival difference between the groups reflected R value, where an increase in R was associated with improved survival. The association of R with mortality was strengthened by adjustment in demographic variables and attenuated after adjustment to MICS. Mortality associations in accordance with R were not influenced by residual kidney function (RKF). Conclusion The novel protein to phosphorus ratio score R predicts mortality in people on dialysis, probably reflecting both nutrition and inflammation state independent of RKF. The metric enables better phosphorus monitoring, although adequate dietary protein intake is ensured and may improve the prediction of outcomes in the clinical setting.
- Published
- 2021
118. Functionality of Ingredients and Additives in Plant-Based Meat Analogues
- Author
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Atze Jan van der Goot, Julia K. Keppler, and Konstantina Kyriakopoulou
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Health (social science) ,vegetarian burger ,030309 nutrition & dietetics ,Computer science ,Review ,Plant Science ,lcsh:Chemical technology ,Health Professions (miscellaneous) ,Microbiology ,Plant protein ,03 medical and health sciences ,Ingredient ,0404 agricultural biotechnology ,Vegetarian steak ,plant protein ,Flavours ,Binders ,lcsh:TP1-1185 ,Food science ,Meat analogues ,vegetarian sausage ,Food Process Engineering ,VLAG ,0303 health sciences ,Novel protein ,Plant based ,04 agricultural and veterinary sciences ,040401 food science ,Colourants ,Vegetarian sausage ,meat analogues ,vegetarian steak ,Vegetarian burger ,binders ,Food Science - Abstract
Meat analogue research and development focuses on the production of sustainable products that recreate conventional meat in its physical sensations (texture, appearance, taste, etc.) and nutritional aspects. Minced products, like burger patties and nuggets, muscle-type products, like chicken or steak-like cuts, and emulsion products, like Frankfurter and Mortadella type sausages, are the major categories of meat analogues. In this review, we discuss key ingredients for the production of these novel products, with special focus on protein sources, and underline the importance of ingredient functionality. Our observation is that structuring processes are optimized based on ingredients that were not originally designed for meat analogues applications. Therefore, mixing and blending different plant materials to obtain superior functionality is for now the common practice. We observed though that an alternative approach towards the use of ingredients such as flours, is gaining more interest. The emphasis, in this case, is on functionality towards use in meat analogues, rather than classical functionality such as purity and solubility. Another trend is the exploration of novel protein sources such as seaweed, algae and proteins produced via fermentation (cellular agriculture).
- Published
- 2021
119. Zincbindpredict—Prediction of Zinc Binding Sites in Proteins
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Sam M. Ireland and Andrew J. Martin
- Subjects
Support Vector Machine ,Zinc binding ,Pharmaceutical Science ,chemistry.chemical_element ,Zinc ,Computational biology ,Ligands ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Drug Discovery ,Physical and Theoretical Chemistry ,Binding site ,Databases, Protein ,030304 developmental biology ,0303 health sciences ,Binding Sites ,Metal binding ,Novel protein ,030302 biochemistry & molecular biology ,Organic Chemistry ,zinc ,metal binding ,Computational Biology ,prediction ,proteins ,machine learning ,chemistry ,Chemistry (miscellaneous) ,Proteome ,Molecular Medicine ,Algorithms ,Software ,Protein Binding - Abstract
Background: Zinc binding proteins make up a significant proportion of the proteomes of most organisms and, within those proteins, zinc performs rôles in catalysis and structure stabilisation. Identifying the ability to bind zinc in a novel protein can offer insights into its functions and the mechanism by which it carries out those functions. Computational means of doing so are faster than spectroscopic means, allowing for searching at much greater speeds and scales, and thereby guiding complimentary experimental approaches. Typically, computational models of zinc binding predict zinc binding for individual residues rather than as a single binding site, and typically do not distinguish between different classes of binding site—missing crucial properties indicative of zinc binding. Methods: Previously, we created ZincBindDB, a continuously updated database of known zinc binding sites, categorised by family (the set of liganding residues). Here, we use this dataset to create ZincBindPredict, a set of machine learning methods to predict the most common zinc binding site families for both structure and sequence. Results: The models all achieve an MCC ≥ 0.88, recall ≥0.93 and precision ≥0.91 for the structural models (mean MCC = 0.97), while the sequence models have MCC ≥ 0.64, recall ≥0.80 and precision ≥0.83 (mean MCC = 0.87), with the models for binding sites containing four liganding residues performing much better than this. Conclusions: The predictors outperform competing zinc binding site predictors and are available online via a web interface and a GraphQL API.
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- 2021
120. Generating novel protein sequences using Gibbs sampling of masked language models
- Author
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Sean R. Johnson, K. Massie, Z. Sayed, and S. Monaco
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Protein therapeutics ,Process (engineering) ,Novel protein ,business.industry ,Computer science ,Pattern recognition ,Task (computing) ,symbols.namesake ,ComputingMethodologies_PATTERNRECOGNITION ,symbols ,Artificial intelligence ,Language model ,business ,Natural language ,Gibbs sampling - Abstract
Recently developed language models (LMs) based on deep neural networks have demonstrated the ability to generate fluent natural language text. LMs pre-trained on protein sequences have shown state of the art performance on a variety of downstream tasks. Protein LMs have also been used to generate novel protein sequences. In the present work we use Gibbs sampling of BERT-style LMs, pre-trained on protein sequences using the masked language modeling task, to generate novel protein sequences. We evaluate the quality of the generated sequences by comparing them to natural sequences from the same family. In particular, we focus on proteins from the chorismate mutase type II family, which has been used in previous work as an example target for protein generative models. We find that the Gibbs sampling process on BERT-style models pretrained on millions to billions of protein sequences is able to generate novel sequences that retain key features of related natural sequences. Further, we find that smaller models fine-tuned or trained from scratch on family-specific data are able to equal or surpass the generation quality of large pre-trained models by some metrics. The ability to generate novel natural-like protein sequences could contribute to the development of improved protein therapeutics and protein-catalysts for industrial chemical production.
- Published
- 2021
121. Recent applications of biotechnological approaches to elucidate the biology of plant-nematode interactions
- Author
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Sebastian Eves-van den Akker, Godelieve Gheysen, Boris Stojilković, Eves-Van Den Akker, Sebastian [0000-0002-8833-9679], and Apollo - University of Cambridge Repository
- Subjects
0106 biological sciences ,0303 health sciences ,Obligate ,Nematoda ,Effector ,Novel protein ,Biomedical Engineering ,Bioengineering ,Computational biology ,Biology ,Plants ,01 natural sciences ,Plant nematode ,03 medical and health sciences ,010608 biotechnology ,Animals ,030304 developmental biology ,Biotechnology ,Plant Diseases - Abstract
Plant-parasitic nematodes are a major threat to food security. The most economically important species have remarkable abilities to manipulate host physiology and immunity. This review highlights recent applications of biotechnological approaches to elucidate the underlying biology on both sides of the interaction. Their obligate biotrophic nature has hindered the development of simple nematode transformation protocols. Instead, transient or stable expression of the effector (native or tagged) in planta has been instrumental in elucidating the biology of plant-nematode interactions. Recent progress in the development of functional genetics tools 'in nematoda' promises further advances. Finally, we discuss how effector research has uncovered novel protein translocation routes in plant cells and may reveal additional unknown biological processes in the future.
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- 2021
122. Complexation of rice glutelin fibrils with cyanidin-3-O-glucoside at acidic condition: Thermal stability, binding mechanism and structural characterization
- Author
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Li Wang, Ting Li, Zhengxing Chen, Peibin Yu, and Xinxia Zhang
- Subjects
Glutens ,Polypeptide chain ,Fibril ,01 natural sciences ,Analytical Chemistry ,Hydrophobic effect ,Anthocyanins ,0404 agricultural biotechnology ,Glucosides ,Glutelin ,Thermal stability ,Electrostatic interaction ,biology ,Novel protein ,Chemistry ,010401 analytical chemistry ,food and beverages ,Oryza ,04 agricultural and veterinary sciences ,General Medicine ,Cyanidin 3-O-glucoside ,040401 food science ,0104 chemical sciences ,biology.protein ,Biophysics ,Food Science - Abstract
The complexation of rice glutelin fibrils (RGFs) with cyanidin-3-O-glucoside (C3G) at acidic condition was investigated. The RGFs at pH 3.5 had a greatest protective effect on the thermal stability of C3G. The binding of C3G for RGFs was exothermic and driven by hydrophobic and electrostatic interactions. The RGFs exhibited a stronger binding interaction with C3G than rice glutelin (RG), resulting from the exposure of hydrophobic groups and positive charges on the fibrils surface, and thus RGFs exhibited better protective effect on C3G. The interaction with C3G resulted in the rearrangement of polypeptide chain, thereby reducing the β-sheet content. The larger aggregates were observed in RG/RGFs-C3G complexes due to protein-polyphenols aggregation. It was noteworthy that the pre-formed RGFs were restructured into entangled aggregates due to the interaction. This study proposed a novel protein fibril to protect anthocyanins, expanding the application of anthocyanins as stable and functional ingredients in acidic food systems.
- Published
- 2021
123. A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity
- Author
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Xixi Li, Fanying Li, Xin Xia, Bo Li, Dawei Liu, Xujia Wu, Nunu Huang, Lixuan Yang, Huangkai Zhou, Songhua Xiao, Jian Zhong, Xuesong Yang, Nu Zhang, Maolei Zhang, and Feizhe Xiao
- Subjects
Patched Receptors ,Patched ,lcsh:QH426-470 ,Mice, Nude ,medicine.disease_cause ,Hedgehog pathway ,Mice ,GLI1 ,medicine ,Animals ,Humans ,Hedgehog Proteins ,Sonic hedgehog ,Receptor ,lcsh:QH301-705.5 ,Circular RNA ,Cell Proliferation ,Mice, Inbred BALB C ,Brain cancer stem cells ,biology ,Brain Neoplasms ,Stem Cells ,Research ,RNA, Circular ,Smoothened Receptor ,Hedgehog signaling pathway ,Cell biology ,lcsh:Genetics ,Disease Models, Animal ,Cell Transformation, Neoplastic ,HEK293 Cells ,lcsh:Biology (General) ,biology.protein ,Novel protein ,Female ,Stem cell ,Glioblastoma ,Smoothened ,Carcinogenesis ,Signal Transduction - Abstract
Background Aberrant activation of the Hedgehog pathway drives tumorigenesis of many cancers, including glioblastoma. However, the sensitization mechanism of the G protein-coupled-like receptor smoothened (SMO), a key component of Hedgehog signaling, remains largely unknown. Results In this study, we describe a novel protein SMO-193a.a. that is essential for Hedgehog signaling activation in glioblastoma. Encoded by circular SMO (circ-SMO), SMO-193a.a. is required for sonic hedgehog (Shh) induced SMO activation, via interacting with SMO, enhancing SMO cholesterol modification, and releasing SMO from the inhibition of patched transmembrane receptors. Deprivation of SMO-193a.a. in brain cancer stem cells attenuates Hedgehog signaling intensity and suppresses self-renewal, proliferation in vitro, and tumorigenicity in vivo. Moreover, circ-SMO/SMO-193a.a. is positively regulated by FUS, a direct transcriptional target of Gli1. Shh/Gli1/FUS/SMO-193a.a. form a positive feedback loop to sustain Hedgehog signaling activation in glioblastoma. Clinically, SMO-193a.a. is more specifically expressed in glioblastoma than SMO and is relevant to Gli1 expression. Higher expression of SMO-193a.a. predicts worse overall survival of glioblastoma patients, indicating its prognostic value. Conclusions Our study reveals that SMO-193a.a., a novel protein encoded by circular SMO, is critical for Hedgehog signaling, drives glioblastoma tumorigenesis and is a novel target for glioblastoma treatment.
- Published
- 2021
124. Self-Assembled Protein- and Peptide-Based Nanomaterials
- Author
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Jin Kim Montclare, Michael Meleties, and Priya Katyal
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chemistry.chemical_classification ,Materials science ,Novel protein ,0206 medical engineering ,Biomedical Engineering ,Nanotechnology ,Peptide ,02 engineering and technology ,Protein engineering ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Self assembled ,Nanomaterials ,Biomaterials ,chemistry ,Nanofiber ,Drug delivery ,0210 nano-technology - Abstract
Considerable effort has been devoted to generating novel protein- and peptide-based nanomaterials with their applications in a wide range of fields. Specifically, the unique property of proteins to self-assemble has been utilized to create a variety of nanoassemblies, which offer significant possibilities for next-generation biomaterials. In this minireview, we describe self-assembled protein- and peptide-based nanomaterials with focus on nanofibers and nanoparticles. Their applications in delivering therapeutic drugs and genes are discussed.
- Published
- 2021
125. A fragment-based protein interface design algorithm for symmetric assemblies
- Author
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Kyle Meador, Joshua Laniado, and Todd O. Yeates
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Computer science ,Interface (Java) ,Protein design ,Bioengineering ,Protein Engineering ,010402 general chemistry ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Fragment (logic) ,Peptide bond ,Macromolecular docking ,Molecular Biology ,Retrospective Studies ,030304 developmental biology ,Protein interface ,chemistry.chemical_classification ,0303 health sciences ,Computer program ,Novel protein ,Proteins ,Protein engineering ,Amino acid ,0104 chemical sciences ,chemistry ,Docking (molecular) ,Key (cryptography) ,Original Article ,Algorithm ,Algorithms ,Software ,Biotechnology - Abstract
Theoretical and experimental advances in protein engineering have led to the creation of precisely defined, novel protein assemblies of great size and complexity, with diverse applications. One powerful approach involves designing a new attachment or binding interface between two simpler symmetric oligomeric protein components. The required methods of design, which present both similarities and key differences compared to problems in protein docking, remain challenging, and are not yet routine. With the aim of more fully enabling this emerging area of protein material engineering, we developed a computer program, Nanohedra, to introduce two key advances. First, we encoded in the program the construction rules (i.e. the search space parameters) that underlie all possible symmetric material constructions. Second, we developed algorithms for rapidly identifying favorable docking/interface arrangements based on tabulations of empirical patterns of known protein fragment-pair associations. As a result, the candidate poses that Nanohedra generates for subsequent amino acid interface design appear highly native-like (at the protein backbone level), while simultaneously conforming to the exacting requirements for symmetry-based assembly. A retrospective computational analysis of successful vs failed experimental studies supports the expectation that this should improve the success rate for this challenging area of protein engineering.
- Published
- 2021
126. Black Soldier Fly Larval Meal in Feed Enhances Growth Performance, Carcass Yield and Meat Quality of Finishing Pigs
- Author
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Chrysantus M. Tanga, Isaac M. Osuga, Macdonald Githinji, Thomas Dubois, David Miano Mwangi, J.J.A. van Loon, A.O. Alaru, Shaphan Y. Chia, Marcel Dicke, and Sunday Ekesi
- Subjects
Hermetia illucens ,Biology ,Soldier fly ,03 medical and health sciences ,Fish meal ,Animal science ,crude protein ,Laboratory of Entomology ,030304 developmental biology ,insect larval meal ,0303 health sciences ,Larva ,Meal ,finisher pig diet ,Novel protein ,0402 animal and dairy science ,food and beverages ,04 agricultural and veterinary sciences ,biology.organism_classification ,PE&RC ,Laboratorium voor Entomologie ,040201 dairy & animal science ,carcass quality ,market weight ,Insect Science ,EPS ,Food Science - Abstract
Using black soldier fly (BSF, Hermetia illucens) larvae as a novel protein source substituting fishmeal (FM) in animal feeds is globally gaining momentum. BSF can be reared on agro-industrial residues. However, incorporating BSF larval meal (BSFLM) into finisher pig diets has received inadequate attention. This study evaluated the effects of replacing dietary FM with BSFLM on growth, carcass traits and meat quality of finisher pigs. A control diet (including FM: 0% BSFLM) was compared with four dietary levels of replacement of FM with BSFLM at 25, 50, 75 or 100%. Forty hybrid pigs (crossbreeds of purebred Large White and Landrace) were randomly allocated to the five different dietary treatments. Feed intake, body weight gain and feed conversion ratio were measured. After 98 days of feeding, all pigs were slaughtered for the evaluation of carcass and nutritional content of the organ and muscle tissues. Diet significantly affected pig growth performance. Carcass weight of pigs fed diets with BSFLM replacing FM by 50, 75 or 100% (w/w) was higher than for pigs fed control diet with 100% FM as protein source. Crude protein content of pork tissues was high (65-93% on dry-matter basis) across all dietary groups. Therefore, BSFLM can replace FM in pig feed. This is relevant for commercial pig feed production and provides for the first time a nutritional analysis of pork derived from pigs raised on BSFLM.
- Published
- 2021
127. Structural mechanism for modulation of functional amyloid and biofilm formation by Staphylococcal Bap protein switch
- Author
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Xiaobing Zuo, Junfeng Ma, Xianyang Fang, Shilong Fan, Jaione Valle, Xiang Cheng, Iñigo Lasa, Zhonghe Xu, Yikan Zhang, Universidad Pública de Navarra. Departamento de Ciencias de la Salud, and Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
- Subjects
Amyloid ,Staphylococcus aureus ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Bacterial Proteins ,Calcium-binding protein ,Sense (molecular biology) ,medicine ,Molecular Biology ,Cell Aggregation ,030304 developmental biology ,0303 health sciences ,General Immunology and Microbiology ,Novel protein ,General Neuroscience ,Biofilm ,Biofilm associated protein ,Structural integrity ,Articles ,Liquid-liquid phase separation ,Biofilms ,Amyloid aggregation ,Functional amyloid ,Biophysics ,Order-disorder conformational switches ,Calcium ,030217 neurology & neurosurgery - Abstract
The Staphylococcal Bap proteins sense environmental signals (such as pH, [Ca2+]) to build amyloid scaffold biofilm matrices via unknown mechanisms. We here report the crystal structure of the aggregation-prone region of Staphylococcus aureus Bap which adopts a dumbbell-shaped fold. The middle module (MM) connecting the N-terminal and C-terminal lobes consists of a tandem of novel double-Ca2+-binding motifs involved in cooperative interaction networks, which undergoes Ca2+-dependent order–disorder conformational switches. The N-terminal lobe is sufficient to mediate amyloid aggregation through liquid–liquid phase separation and maturation, and subsequent biofilm formation under acidic conditions. Such processes are promoted by disordered MM at low [Ca2+] but inhibited by ordered MM stabilized by Ca2+ binding, with inhibition efficiency depending on structural integrity of the interaction networks. These studies illustrate a novel protein switch in pathogenic bacteria and provide insights into the mechanistic understanding of Bap proteins in modulation of functional amyloid and biofilm formation, which could be implemented in the anti-biofilm drug design. This work was supported by grants from the National Natural Science Foundation of China (No. 31872712), the National Key Research and Development Project of China (2016YFA0500700), the Beijing Advanced Innovation Center for Structural Biology, the Tsinghua-Peking Joint Center for Life Sciences, to X.F.
- Published
- 2021
128. Interfacial behavior of plant proteins — novel sources and extraction methods
- Author
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Leonard M.C. Sagis and Jack Yang
- Subjects
Physics and Physical Chemistry of Foods ,Polymers and Plastics ,Globulin ,biology ,Oil-water interface ,Air water interface ,Chemistry ,Novel protein ,Biobased Chemistry and Technology ,Albumin ,Interfacial rheology ,food and beverages ,Surfaces and Interfaces ,Colloid and Surface Chemistry ,Protein purification ,biology.protein ,Extraction methods ,Plant proteins ,Physical and Theoretical Chemistry ,Biological system ,Air-water interface ,VLAG - Abstract
Understanding the air-water and oil-water interfacial behavior of plant proteins is crucial for developing stable emulsions and foams in food systems. Plant crops are often processed into protein extracts with high purity, which primarily consist of globulins. These globulins are often unable to form stiff interfacial layers owing to their compact and highly aggregated state and have inferior functionality compared with animal-derived proteins from milk or eggs. Much of the current focus is on modifying these proteins, whereas better interface stabilizing functionality can also be obtained by choosing more targeted protein extraction methods. This review will highlight the benefits and drawbacks of current and novel protein sources and protein extraction methods with respect to interfacial properties.
- Published
- 2021
129. Mdeepred: Novel Multi-Channel Protein Featurization For Deep Learning-Based Binding Affinity Prediction In Drug Discovery
- Author
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R Cetin Atalay, Maria Jesus Martin, Ahmet Sureyya Rifaioglu, D Cansen Kahraman, Volkan Atalay, Tunca Doğan, Mühendislik ve Doğa Bilimleri Fakültesi -- Elektrik-Elektronik Mühendisliği Bölümü, and Rifaioğlu, Ahmet Süreyya
- Subjects
Statistics and Probability ,Adverse Drug Reactions ,Polypharmacology ,Computer science ,Statistics & Probability ,Computational biology ,Biochemistry ,Biochemical Research Methods ,Protein–protein interaction ,03 medical and health sciences ,Deep Learning ,0302 clinical medicine ,Drug Discovery ,Humans ,Interdisciplinary Applications ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Drug discovery ,Novel protein ,business.industry ,Deep learning ,Drug Repositioning ,Proteins ,Ligand (biochemistry) ,Small molecule ,Chemical space ,In vitro ,Computer Science Applications ,Computational Mathematics ,Drug repositioning ,Biotechnology & Applied Microbiology ,Computational Theory and Mathematics ,030220 oncology & carcinogenesis ,Computer Science ,Neural-networks ,Benchmark (computing) ,Neural Networks, Computer ,Mathematical & Computational Biology ,Target protein ,Artificial intelligence ,business ,Software ,Protein Binding - Abstract
Motivation Identification of interactions between bioactive small molecules and target proteins is crucial for novel drug discovery, drug repurposing and uncovering off-target effects. Due to the tremendous size of the chemical space, experimental bioactivity screening efforts require the aid of computational approaches. Although deep learning models have been successful in predicting bioactive compounds, effective and comprehensive featurization of proteins, to be given as input to deep neural networks, remains a challenge. Results Here, we present a novel protein featurization approach to be used in deep learning-based compound–target protein binding affinity prediction. In the proposed method, multiple types of protein features such as sequence, structural, evolutionary and physicochemical properties are incorporated within multiple 2D vectors, which is then fed to state-of-the-art pairwise input hybrid deep neural networks to predict the real-valued compound–target protein interactions. The method adopts the proteochemometric approach, where both the compound and target protein features are used at the input level to model their interaction. The whole system is called MDeePred and it is a new method to be used for the purposes of computational drug discovery and repositioning. We evaluated MDeePred on well-known benchmark datasets and compared its performance with the state-of-the-art methods. We also performed in vitro comparative analysis of MDeePred predictions with selected kinase inhibitors’ action on cancer cells. MDeePred is a scalable method with sufficiently high predictive performance. The featurization approach proposed here can also be utilized for other protein-related predictive tasks. Availability and implementation The source code, datasets, additional information and user instructions of MDeePred are available at https://github.com/cansyl/MDeePred. Supplementary information Supplementary data are available at Bioinformatics online.
- Published
- 2021
130. Affinity Proteomics Assays for Cardiovascular and Atherosclerotic Disease Biomarkers
- Author
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Maria Jesus Iglesias, Jochen M. Schwenk, and Jacob Odeberg
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0301 basic medicine ,Vascular inflammation ,business.industry ,Novel protein ,Atherosclerotic disease ,Disease ,Computational biology ,Proteomics ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Proteome ,Medicine ,Biomarker (medicine) ,Bead array ,business - Abstract
Systematic exploration of the dynamic human plasma proteome enables the discovery of novel protein biomarkers. Using state-of-the-art technologies holds the promise to facilitate a better diagnosis and risk prediction of diseases. Cardiovascular disease (CVD) pathophysiology is characterized for unbalancing of processes such as vascular inflammation, endothelial dysfunction, or lipid profiles among others. Such processes have a direct impact on the dynamic and complex composition of blood and hence the plasma proteome. Therefore, the study of the plasma proteome comprises an excellent exploratory source of biomarker research particularly for CVD. We describe the protocol for performing the discovery of protein biomarker candidates using the suspension bead array technology. The process does not require depletion steps to remove abundant proteins and consumes only a few microliters of sample from the body fluid of interest. The approach is scalable to measure many analytes as well as large numbers of samples. Moreover, we describe a bead-assisted antibody-labeling process that helps to develop quantitative assays for validation purposes and facilitate the translation of the identified candidates into clinical studies.
- Published
- 2021
131. Detecting Sequentially Novel Classes with Stable Generalization Ability
- Author
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De-Chuan Zhan, Yang Yang, and Da-Wei Zhou
- Subjects
Structure (mathematical logic) ,Generalization ,Novel protein ,business.industry ,Computer science ,Data stream mining ,Pattern recognition ,02 engineering and technology ,Object (computer science) ,Class (biology) ,Robustness (computer science) ,020204 information systems ,Model learning ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,Artificial intelligence ,business - Abstract
Recognizing object of unseen novel classes is of great importance in real-world incremental data scenarios. Additionally, novel classes arise frequently in data stream mining, e.g., new topics in opinion monitoring, and novel protein families in protein sequence classification. Conducting streaming novel class detection is a complex problem composed of detection and model update. However, when updating the model solely with detected novel instances, it concentrates more on the novel patterns than known ones; thus the detection ability of the model may degrade consequently. This would exert harmful affections to further classification as the data evolving. To this end, in this paper, we consider the accuracy of the detection along with the robustness of model updating, and propose DEtecting Sequentially Novel clAsses with Stable generalization Ability (DesNasa). Specifically, DesNasa utilizes a prototypical network to reflect the structure information between scattered prototypes for novel class detection. Furthermore, the well-designed data augmentation method can help the model learning novel patterns robustly without degrading detection ability. Experiments on various datasets successfully validate the effectiveness of our proposed method.
- Published
- 2021
132. Adaptation of livestock to new diets using feed components without competition with human edible protein sources—a review of the possibilities and recommendations
- Author
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Marinus F.W. te Pas, Teun Veldkamp, André Bannink, Yvette de Haas, and Esther D. Ellen
- Subjects
0301 basic medicine ,Animal Nutrition ,Physiology ,Veterinary medicine ,media_common.quotation_subject ,Review ,Biology ,Breeding ,Competition (biology) ,Nutrigenetics ,Alternative protein ,03 medical and health sciences ,SF600-1100 ,Protein efficiency ,Fokkerij & Genomica ,Adaptation (computer science) ,media_common ,General Veterinary ,business.industry ,Novel protein ,0402 animal and dairy science ,Human inedible protein sources ,04 agricultural and veterinary sciences ,040201 dairy & animal science ,Diervoeding ,Biotechnology ,030104 developmental biology ,Nutrigenomics ,QL1-991 ,WIAS ,Animal Science and Zoology ,Livestock ,business ,Zoology ,Human edible protein sources ,Animal Breeding & Genomics - Abstract
Simple Summary Livestock feed contains components that can also be consumed by humans, which may become less available for livestock. Proteins are such components that may become less available for livestock feed. This review focuses on using alternative protein sources in feed. We may expect protein efficiency problems and we discuss how these could be solved using a combination of alternative protein sources and animal breeding. We make recommendations for the use and optimization of novel protein sources. Abstract Livestock feed encompasses both human edible and human inedible components. Human edible feed components may become less available for livestock. Especially for proteins, this calls for action. This review focuses on using alternative protein sources in feed and protein efficiency, the expected problems, and how these problems could be solved. Breeding for higher protein efficiency leading to less use of the protein sources may be one strategy. Replacing (part of) the human edible feed components with human inedible components may be another strategy, which could be combined with breeding for livestock that can efficiently digest novel protein feed sources. The potential use of novel protein sources is discussed. We discuss the present knowledge on novel protein sources, including the consequences for animal performance and production costs, and make recommendations for the use and optimization of novel protein sources (1) to improve our knowledge on the inclusion of human inedible protein into the diet of livestock, (2) because cooperation between animal breeders and nutritionists is needed to share knowledge and combine expertise, and (3) to investigate the effect of animal-specific digestibility of protein sources for selective breeding for each protein source and for precision feeding. Nutrigenetics and nutrigenomics will be important tools.
- Published
- 2021
133. Effect of sterilization and storage on a model meat analogue pet food
- Author
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Atze Jan van der Goot, Ariane Wehrmaker, and Guido Bosch
- Subjects
Plant-based ,Salt content ,Moisture ,Animal Nutrition ,Novel protein ,Chemistry ,Vegan ,food and beverages ,Sterilization ,Plant based ,Sterilization (microbiology) ,Proximate composition ,Texture profile analysis ,Diervoeding ,Pet food technology ,Pet food ,WIAS ,Animal Science and Zoology ,Food science ,Food Process Engineering ,VLAG - Abstract
Recently, it was demonstrated that it is possible to create highly fibrous meat analogues, using simple shear structuring. We investigated how the model meat analogue responds to sterilization and storage in media (water, jelly, or gravy) with pet food and beef chunks as reference. Chunks were analysed before and after sterilization, and after storage for textural properties and proximate composition. The fibrous appearance of the model meat analogue was retained after sterilization and storage. Moisture uptake of the model meat analogue was about twice the amount of that in pet food, resulting in textural properties approaching pet food after sterilization. Proximate composition and texture of the model meat analogue remained stable during storage, except for in gravy, which was probably caused by the salt content in the gravy. Due to the fibrousness and pet food-like texture after sterilization, the model meat analogue can be considered promising for the development of plant-based pet foods.
- Published
- 2021
134. A systematic meta-analysis based review on black soldier fly (Hermetia illucens) as a novel protein source for salmonids
- Author
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Margareth Øverland, Jon Øvrum Hansen, Pabodha Weththasinghe, and Liv Torunn Mydland
- Subjects
Hermetia illucens ,Ecology ,biology ,Novel protein ,Computational biology ,Management, Monitoring, Policy and Law ,Aquatic Science ,biology.organism_classification ,Soldier fly - Published
- 2021
135. MRX8, the conserved mitochondrial YihA GTPase family member, is required for de novo Cox1 synthesis at suboptimal temperatures in Saccharomyces cerevisiae
- Author
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Kaustuv Datta, Yash Verma, Upasana Mehra, Dharmendra Kumar Pandey, Joy Kar, Xochitl Pérez-Martínez, and Siddhartha S. Jana
- Subjects
Family member ,Cellular respiration ,Novel protein ,Saccharomyces cerevisiae ,Translation (biology) ,Cell Biology ,GTPase ,Articles ,Biology ,biology.organism_classification ,Molecular Biology ,Cold stress ,Cell biology - Abstract
The synthesis of Cox1, the conserved catalytic-core subunit of Complex IV, a multisubunit machinery of the mitochondrial oxidative phosphorylation (OXPHOS) system under environmental stress, has not been sufficiently addressed. In this study, we show that the putative YihA superfamily GTPase, Mrx8, is a bona fide mitochondrial protein required for Cox1 translation initiation and elongation during suboptimal growth condition at 16°C. Mrx8 was found in a complex with mitochondrial ribosomes, consistent with a role in protein synthesis. Cells expressing mutant Mrx8 predicted to be defective in guanine nucleotide binding and hydrolysis were compromised for robust cellular respiration. We show that the requirement of Pet309 and Mss51 for cellular respiration is not bypassed by overexpression of Mrx8 and vice versa. Consistently the ribosomal association of Mss51 is independent of Mrx8. Significantly, we find that GTPBP8, the human orthologue, complements the loss of cellular respiration in Δmrx8 cells and GTPBP8 localizes to the mitochondria in mammalian cells. This strongly suggests a universal role of the MRX8 family of proteins in regulating mitochondrial function.
- Published
- 2021
136. Estimating Change in Foldability Due to Multipoint Deletions in Protein Structures
- Author
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Pralay Mitra, Kushal Kanti Ghosh, Amit Kumar, and Anupam Banerjee
- Subjects
Protein Folding ,Computer science ,Novel protein ,General Chemical Engineering ,Proteins ,General Chemistry ,Computational biology ,Library and Information Sciences ,Prediction system ,Protein Engineering ,Computer Science Applications ,Protein structure ,Posttranslational modification ,Amino Acids - Abstract
Insertions/deletions of amino acids in the protein backbone potentially result in altered structural/functional specifications. They can either contribute positively to the evolutionary process or can result in disease conditions. Despite being the second most prevalent form of protein modification, there are no databases or computational frameworks that delineate harmful multipoint deletions (MPD) from beneficial ones. We introduce a positive unlabeled learning-based prediction framework (PROFOUND) that utilizes fold-level attributes, environment-specific properties, and deletion site-specific properties to predict the change in foldability arising from such MPDs, both in the non-loop and loop regions of protein structures. In the absence of any protein structure dataset to study MPDs, we introduce a dataset with 153 MPD instances that lead to native-like folded structures and 7650 unlabeled MPD instances whose effect on the foldability of the corresponding proteins is unknown. PROFOUND on 10-fold cross-validation on our newly introduced dataset reports a recall of 82.2% (86.6%) and a fall out rate (FR) of 14.2% (20.6%), corresponding to MPDs in the protein loop (non-loop) region. The low FR suggests that the foldability in proteins subject to MPDs is not random and necessitates unique specifications of the deleted region. In addition, we find that additional evolutionary attributes contribute to higher recall and lower FR. The first of a kind foldability prediction system owing to MPD instances and the newly introduced dataset will potentially aid in novel protein engineering endeavors.
- Published
- 2020
137. The Linguistics of Bacterial Conflict Systems Reveal Ancient Origins of Eukaryotic Innate Immunity
- Author
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Emily Kibby and Aaron T. Whiteley
- Subjects
0303 health sciences ,Innate immune system ,Bacteria ,030306 microbiology ,Novel protein ,Nucleotides ,Eukaryota ,Genomics ,Biology ,biology.organism_classification ,Microbiology ,03 medical and health sciences ,Bacterial Proteins ,Evolutionary biology ,Immune System ,Horizontal gene transfer ,Bacteriology ,Commentary ,Amino Acid Sequence ,Molecular Biology ,Gene ,Sequence Alignment ,030304 developmental biology - Abstract
Nucleotide-activated effector deployment, prototyped by interferon-dependent immunity, is a common mechanistic theme shared by immune systems of several animals and prokaryotes. Prokaryotic versions include CRISPR-Cas with the CRISPR polymerase domain, their minimal variants, and systems with second messenger oligonucleotide or dinucleotide synthetase (SMODS). Cyclic or linear oligonucleotide signals in these systems help set a threshold for the activation of potentially deleterious downstream effectors in response to invader detection. We establish such a regulatory mechanism to be a more general principle of immune systems, which can also operate independently of such messengers. Using sensitive sequence analysis and comparative genomics, we identify 12 new prokaryotic immune systems, which we unify by this principle of threshold-dependent effector activation. These display regulatory mechanisms paralleling physiological signaling based on 3'-5' cyclic mononucleotides, NAD
- Published
- 2020
138. Recent advances in CHO cell line development for recombinant protein production
- Author
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László Nyitray and Borbála Tihanyi
- Subjects
Computer science ,medicine.drug_class ,Industrial production ,Computational biology ,CHO Cells ,Monoclonal antibody ,01 natural sciences ,03 medical and health sciences ,Cricetulus ,Cricetinae ,Drug Discovery ,Screening method ,medicine ,Animals ,030304 developmental biology ,Pharmaceutical industry ,0303 health sciences ,010405 organic chemistry ,business.industry ,Novel protein ,Chinese hamster ovary cell ,Antibodies, Monoclonal ,Cell Differentiation ,Recombinant Proteins ,0104 chemical sciences ,Cell culture ,Recombinant protein production ,Molecular Medicine ,business - Abstract
Recombinant proteins used in biomedical research, diagnostics and different therapies are mostly produced in Chinese hamster ovary cells in the pharmaceutical industry. These biotherapeutics, monoclonal antibodies in particular, have shown remarkable market growth in the past few decades. The increasing demand for high amounts of biologics requires continuous optimization and improvement of production technologies. Research aims at discovering better means and methods for reaching higher volumetric capacity, while maintaining stable product quality. An increasing number of complex novel protein therapeutics, such as viral antigens, vaccines, bi- and tri-specific monoclonal antibodies, are currently entering industrial production pipelines. These biomolecules are, in many cases, difficult to express and require tailored product-specific solutions to improve their transient or stable production. All these requirements boost the development of more efficient expression optimization systems and high-throughput screening platforms to facilitate the design of product-specific cell line engineering and production strategies. In this minireview, we provide an overview on recent advances in CHO cell line development, targeted genome manipulation techniques, selection systems and screening methods currently used in recombinant protein production.
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- 2020
139. Decorating proteins with LACE
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Maximilian Fottner and Kathrin Lang
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Chemistry ,Novel protein ,General Chemical Engineering ,Acylation ,Lysine ,Ubiquitination ,Chemical modification ,General Chemistry ,Recombinant Proteins ,law.invention ,Biochemistry ,law ,Labelling ,Recombinant DNA - Abstract
Labelling proteins at internal sites holds promise for generating novel protein conjugates in a programmable fashion. Now, a chemoenzymatic approach, dubbed LACE, enables the site-specific modification of recombinant proteins that contain a short genetically encoded tag.
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- 2020
140. COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding
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Opelopejesu Owolabi, Surajit Debnath, Eva Akurut, Folagbade Muyiwa Abitogun, Lawrence Macalalad, Nirvana Munir, Siddhant Sharma, Olawale Ojo-Rowland, Abayomi Giwa, Rajvee Srivastava, and Viktoria Komarysta
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Immune system ,Antigen ,Novel protein ,Protein subunit ,Immunogenicity ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Subunit vaccines ,Computational biology ,Biology ,Epitope - Abstract
The COVID19 pandemic has resulted in 1,092,342 deaths as of 14thOctober 2020, indicating the urgent need for a vaccine. This study highlights novel protein sequences generated by shot gun sequencing protocols that could serve as potential antigens in the development of novel subunit vaccines and through a stringent inclusion criterion, we characterized these protein sequences and predicted their 3D structures. We found distinctly antigenic sequences from the SARS-CoV-2 that have led to identification of 4 proteins that demonstrate an advantageous binding with Human leukocyte antigen-1 molecules. Results show how previously unexplored proteins may serve as better candidates for subunit vaccine development due to their high stability and immunogenicity, reinforce by their HLA-1 binding propensities and low global binding energies. This study thus takes a unique approach towards furthering the development of vaccines by employing multiple consensus strategies involved in immuno-informatics technique.
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- 2020
141. The golgin family exhibits a propensity to form condensates in living cells
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Morven Graham, Pascal Ziltener, Andreas M. Ernst, Aleksander A. Rebane, and James E. Rothman
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Membrane Trafficking, Vesicles, Organelles ,Biochemistry & Molecular Biology ,Cell Survival ,Biophysics ,Golgi Apparatus ,Matrix (biology) ,Biochemistry ,Autoantigens ,Time-Lapse Imaging ,03 medical and health sciences ,symbols.namesake ,Medicinal and Biomolecular Chemistry ,Structural Biology ,Genetics ,Humans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Evolutionary Biology ,Chemistry ,Novel protein ,Vesicle ,030302 biochemistry & molecular biology ,Golgi organization ,Golgi Matrix Proteins ,Cell Biology ,Golgi apparatus ,Editor's Choice ,Hela Cells ,symbols ,Generic health relevance ,Biochemistry and Cell Biology ,Internal organization ,HeLa Cells ,trans-Golgi Network - Abstract
The Golgi is surrounded by a ribosome‐excluding matrix. Recently, we reported that the cis‐Golgi‐localized golgin GM130 can phase‐separate to form dynamic, liquid‐like condensates in vitro and in vivo. Here, we show that the overexpression of each of the remaining cis (golgin160, GMAP210)‐ and trans (golgin97, golgin245, GCC88, GCC185)‐golgins results in novel protein condensates. Focused ion beam scanning electron microscopy (FIB‐SEM) images of GM130 condensates reveal a complex internal organization with branching aqueous channels. Pairs of golgins overexpressed in the same cell form distinct juxtaposed condensates. These findings support the hypothesis that, in addition to their established roles as vesicle tethers, phase separation may be a common feature of the golgin family that contributes to Golgi organization.
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- 2020
142. Structure and function of naturally evolved de novo proteins
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Klára Hlouchová, Andreas Lange, and Erich Bornberg-Bauer
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0303 health sciences ,Novel protein ,Protein design ,Proteins ,Computational biology ,Genomics ,Biology ,Protein evolution ,Structure and function ,Evolution, Molecular ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Structural Biology ,Regulatory sequence ,Molecular Biology ,Gene ,030217 neurology & neurosurgery ,DNA ,030304 developmental biology ,Sequence (medicine) - Abstract
Comparative evolutionary genomics has revealed that novel protein coding genes can emerge randomly from non-coding DNA. While most of the myriad of transcripts which continuously emerge vanish rapidly, some attain regulatory regions, become translated and survive. More surprisingly, sequence properties of de novo proteins are almost indistinguishable from randomly obtained sequences, yet de novo proteins may gain functions and integrate into eukaryotic cellular networks quite easily. We here discuss current knowledge on de novo proteins, their structures, functions and evolution. Since the existence of de novo proteins seems at odds with decade-long attempts to construct proteins with novel structures and functions from scratch, we suggest that a better understanding of de novo protein evolution may fuel new strategies for protein design.
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- 2020
143. Prostaglandin E2 EP receptors in cardiovascular disease: An update
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Pamela Harding and Timothy D. Bryson
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Prostaglandin E receptor 3 ,Prostaglandin E2 receptor ,Disease ,Bioinformatics ,Biochemistry ,Dinoprostone ,Cardiac regeneration ,Animals ,Humans ,Regeneration ,Medicine ,Prostaglandin E2 ,Receptor ,Pharmacology ,Novel protein ,business.industry ,Models, Cardiovascular ,Receptors, Prostaglandin E, EP2 Subtype ,Receptors, Prostaglandin E, EP1 Subtype ,Review article ,Cardiovascular Diseases ,Receptors, Prostaglandin E, EP3 Subtype ,lipids (amino acids, peptides, and proteins) ,business ,Receptors, Prostaglandin E, EP4 Subtype ,medicine.drug - Abstract
This review article provides an update for the role of prostaglandin E2 receptors (EP1, EP2, EP3 and EP4) in cardiovascular disease. Where possible we have reported citations from the last decade although this was not possible for all of the topics covered due to the paucity of publications. The authors have attempted to cover the subjects of ischemia–reperfusion injury, arrhythmias, hypertension, novel protein binding partners of the EP receptors and their pathophysiological significance, and cardiac regeneration. These latter two topics bring studies of the EP receptors into new and exciting areas of research that are just beginning to be explored. Where there is peer-reviewed literature, the authors have placed particular emphasis on clinical studies although these are limited in number.
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- 2022
144. Effect of diets containing full-fat Hermetia illucens on rainbow trout microbiota: A dual cultivation-independent approach with DGGE and NGS.
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Bruni, Leonardo, Milanović, Vesna, Tulli, Francesca, Aquilanti, Lucia, and Parisi, Giuliana
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HERMETIA illucens , *RAINBOW trout , *SATURATED fatty acids , *INTESTINAL mucosa , *GUT microbiome , *DIETARY proteins - Abstract
Given the drift to improve economic and ecological sustainability of the aquaculture sector, novel ingredients fulfilling these requirements are sought. Hermetia illucens , commonly called black soldier fly, (Diptera: Stratiomydae; H) is a promising dietary protein source but its effect on fish gut microbiota is still to be clarified. The aim of the present study was to increase the knowledge of the effect of dietary full-fat H meal on rainbow trout (Oncorhynchus mykiss) microbiota and, in particular, on intestinal mucosa-adherent microbiota by applying a dual approach based on polymerase chain reaction-denaturing gradient gel electrophoresis and high-throughput sequencing of the 16S rRNA gene. Rainbow trout (initial body weight of 137.3 ± 10.5 g) was fed for 98 days with a control diet (H0) containing fishmeal and protein-rich vegetable ingredients and an experimental diet (H50) where 50% of the fishmeal had been replaced by full-fat H meal rich in saturated fatty acids. Proteobacteria, Firmicutes and Actinobacteria were generally present in all samples, although the core microbiota (relative prevalence higher than or equal to 80% in all samples) only consisted of the proteobacteria Caulobacter , Delftia , Agrobacterium and Ochrobactrum. In addition, Streptococcus infantis and a member of the Cytophagaceae family were part of the core taxa of mucosa samples. Tenericutes were abundant in pyloric caeca samples and, among them, Mycoplasmataceae seemed to increase in the group fed the high saturated fatty acid diet containing H meal; a consideration about the connection between this bacterial group and the dietary lipid content must be considered. Dietary treatment did not clearly affect alpha-diversity metrics, but mucosa samples tended to be more resilient to dietary changes than content samples. Permutational analysis of variance showed significantly different β-diversities between diets (p < 0.05) but principal coordinates analysis did not confirm this result. Diets for rainbow trout containing full-fat H meal determined interesting modifications in the gut microbiota with patterns similar to the ones found in the literature. The dietary lipids can exert an effect on microbiota. Nonetheless, research data on this topic are still scarce and further studies are highly encouraged. • Rainbow trout were fed diets containing full-fat Hermetia illucens larvae meal. • Gut content and mucosa microbiota of fish fed full-fat H. illucens analysed separately. • Mycoplasmataceae seemed to increase in the high saturated fatty acid-fed group. • Recurring patterns between literature and the study. • No clear hypothesis on the microbiota structure and diversity. [ABSTRACT FROM AUTHOR]
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- 2022
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- View/download PDF
145. Effect of charged polysaccharides on the techno-functional properties of fractions obtained from algae soluble protein isolate.
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Schwenzfeier, Anja, Wierenga, Peter A., Eppink, Michel H.M., and Gruppen, Harry
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POLYSACCHARIDES , *ALGAL proteins , *PROTEIN solubility , *SURFACE active agents , *URONIC acids , *GLYCOPROTEINS - Abstract
Abstract: It has been suggested previously that charged polysaccharides present in algae soluble protein isolate (ASPI) contribute to its foaming and emulsifying properties. In this study ASPI was fractioned into one fraction enriched in uronic acids (the building blocks of charged polysaccharides, [ASPI-UA]), one enriched in protein (ASPI-P) and one containing small, dissociated (glyco-)proteins (ASPI-S). Emulsions prepared using ASPI-UA were stable against flocculation between pH 3–7, while ASPI-P and ASPI-S showed decreased emulsion stabilities around pH 5. This indicates the importance of the charged polysaccharides present in ASPI for emulsion stability at pH 5. For the foaming properties of ASPI no effect of charged polysaccharides was observed. Instead, ASPI-S showed considerably higher foam stabilities at pH 5–7 than the other fractions. These results suggest that dependent on the application charged polysaccharides or dissociated (glyco-) proteins can contribute to ASPI's techno-functional properties. Its further fractionation yields a fraction with improved emulsion stability and a fraction with improved foaming properties. [Copyright &y& Elsevier]
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- 2014
- Full Text
- View/download PDF
146. AutoCoEv – a high-throughput in silico pipeline for predicting inter-protein co-evolution
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Petar Petrov, Vid Šuštar, Martti Tolvanen, Luqman O Awoniyi, and Pieta K. Mattila
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Protein family ,Computer science ,Novel protein ,In silico ,Computational biology ,Pipeline (software) ,Coevolution ,Protein–protein interaction - Abstract
Protein-protein communications govern cellular processes via complex regulatory networks, that are still far from being understood. Thus, identifying novel interactions between proteins can significantly facilitate our comprehension of the mechanistic principles of protein functions. Co-evolution between proteins is a sign of functional communication and, as such, provides a powerful approach to search for novel direct or indirect molecular partners. However, evolutionary analysis of large arrays of proteins, in silico, is a highly time-consuming effort, which has limited the usage of this method to protein pairs or small protein groups. Here, we developed AutoCoEv, a user-friendly computational pipeline for the search of co-evolution between a large number of proteins. By driving 15 individual programs, culminating in CAPS2 as the software for detecting co-evolution, AutoCoEv achieves seamless automation and parallelization of the workflow. Importantly, we provide a patch to CAPS2 source code to strengthen its statistical output, allowing for multiple comparisons correction and enhanced analysis of the results. We apply the pipeline to inspect co-evolution among 324 proteins identified to locate at the vicinity of the lipid rafts of B lymphocytes. We successfully detected multiple strong coevolutionary relations between the proteins, predicting many novel partners and previously unidentified clusters of functionally related molecules. We conclude that AutoCoEv, available at https://github.com/mattilalab/autocoev, can be used to predict functional interactions from large datasets in a time and cost-efficient manner.
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- 2020
147. A set of rhamnosylation-specific antibodies enables detection of novel protein glycosylations in bacteria
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Franziska Koller, Anja Hoffmann-Röder, Jürgen Lassak, Ralph Krafczyk, Lukas Bauer, Swetlana Wunder, and Daniel Gast
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0301 basic medicine ,biology ,Bacteria ,Novel protein ,Chemistry ,030106 microbiology ,Organic Chemistry ,biology.organism_classification ,Biochemistry ,Bacterial cell structure ,03 medical and health sciences ,Specific antibody ,Cytosol ,030104 developmental biology ,Bacterial virulence ,biology.protein ,Physical and Theoretical Chemistry ,Antibody - Abstract
Despite its potential importance for bacterial virulence, protein rhamnosylation has not yet been sufficiently studied. Specific anti-SerRha, anti-ThrRha and anti-AsnRha antibodies allowed the identification of previously unknown monorhamnosylated proteins in cytosol and membrane fractions of bacterial cell lysates. Mapping of the complete rhamnoproteome in pathogens should facilitate development of targeted therapies against bacterial infections.
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- 2020
148. Cyberlindnera jadinii Yeast as a Protein Source for Weaned Piglets—Impact on Immune Response and Gut Microbiota
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Alexander Kashulin Bekkelund, Leidy Lagos, Caroline Piercey Åkesson, Adrijana Skugor, Charles McLean Press, Margareth Øverland, and Ragnhild Ånestad
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Population ,Immunology ,Ileum ,Gut flora ,yeast ,post-weaning pig ,Microbiology ,03 medical and health sciences ,Cecum ,0302 clinical medicine ,medicine ,microbiota ,Immunology and Allergy ,Large intestine ,Microbiome ,education ,chemistry.chemical_classification ,education.field_of_study ,biology ,Fatty acid ,health ,biology.organism_classification ,Yeast ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,novel protein ,lcsh:RC581-607 ,030215 immunology - Abstract
Supplying novel feed ingredients for pig production is crucial to enhance food security and decrease the environmental impact of meat production. Several studies have focused on evaluating the beneficial health effects of yeast in pigs. However, its use as a protein source has been partially addressed. Previously, we have shown that yeast at high inclusion levels maintains growth performance and digestibility, while nutrient digestibility, intestinal villi height and fecal consistency were improved. The present study combined microbiome, short-chain fatty acid, and immune parameter analysis to investigate the effect of high inclusion of yeast in diets for post-weaning piglets. Our results showed that yeast did not have a significant impact on the hematological or biochemical parameters in blood. The different immune cell subpopulations isolated from blood and distal jejunal lymph nodes (DJLN) were analyzed by flow cytometry and showed that yeast diet induced an increased number of the subtype of leukocytes CD45+/CD3-/CD8+, a special type of Natural Killer (NK) cells. Also, a very mild to moderate infiltration of neutrophilic granulocytes and lower IgA level were observed in the colon of yeast fed piglets. The microbiome profiling in different compartments of the gastrointestinal tract of piglets was performed using 16S rRNA metabarcoding. The results showed that 40% replacement of dietary protein had a statistically significant effect on the microbial communities in cecum and colon, while the microbial population in ileum and jejunum were not affected. Analysis of predicted microbial metabolic pathways analysis revealed significant upregulation of short-chain fatty acids, ether lipid metabolisms, secondary bile acids, and several other important biosynthesis pathways in cecum and colon of pigs fed yeast. In conclusion, the results showed that diet containing 40% of yeast protein positively shaped microbial community in the large intestine and increased the number of a specific subpopulation of NK cells in the DJLN. These results showed that yeast modulates the microbiome and decreases the secretion of IgA in the colon of post-weaning pigs.
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- 2020
149. Genome-wide Prediction of Small Molecule Binding to Remote Orphan Proteins Using Distilled Sequence Alignment Embedding
- Author
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Ruth Nussinov, Lei Xie, Tian Cai, Hansaim Lim, Yue Qiu, and Kyra Alyssa Abbu
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Computer science ,Drug discovery ,Novel protein ,business.industry ,Ligand ,Deep learning ,Supervised learning ,Sequence alignment ,Endogeny ,Computational biology ,Genome ,Small molecule ,Margin (machine learning) ,Artificial intelligence ,Small molecule binding ,business ,G protein-coupled receptor - Abstract
Endogenous or surrogate ligands of a vast number of proteins remain unknown. Identification of small molecules that bind to these orphan proteins will not only shed new light into their biological functions but also provide new opportunities for drug discovery. Deep learning plays an increasing role in the prediction of chemical-protein interactions, but it faces several challenges in protein deorphanization. Bioassay data are highly biased to certain proteins, making it difficult to train a generalizable machine learning model for the proteins that are dissimilar from the ones in the training data set. Pre-training offers a general solution to improving the model generalization, but needs incorporation of domain knowledge and customization of task-specific supervised learning. To address these challenges, we develop a novel protein pre-training method, DIstilled Sequence Alignment Embedding (DISAE), and a module-based fine-tuning strategy for the protein deorphanization. In the benchmark studies, DISAE significantly improves the generalizability and outperforms the state-of-the-art methods with a large margin. The interpretability analysis of pre-trained model suggests that it learns biologically meaningful information. We further use DISAE to assign ligands to 649 human orphan G-Protein Coupled Receptors (GPCRs) and to cluster the human GPCRome by integrating their phylogenetic and ligand relationships. The promising results of DISAE open an avenue for exploring the chemical landscape of entire sequenced genomes.
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- 2020
150. The biology of unconventional invasion of Duffy-negative reticulocytes by Plasmodium vivax and its implication in malaria epidemiology and public health
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Eugenia Lo, Lucas Amenga-Etego, Alfred Amambua-Ngwa, and Lemu Golassa
- Subjects
medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Reticulocytes ,lcsh:RC955-962 ,030231 tropical medicine ,Plasmodium vivax ,Protozoan Proteins ,Ligand ,Antigens, Protozoan ,Receptors, Cell Surface ,Review ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,parasitic diseases ,medicine ,Malaria, Vivax ,Humans ,lcsh:RC109-216 ,030212 general & internal medicine ,Malaria epidemiology ,Reticulocyte ,biology ,Novel protein ,Transmission (medicine) ,Public health ,biology.organism_classification ,Virology ,Infectious Diseases ,Parasitology ,Duffy antigens ,Vivax malaria ,Public Health ,Duffy Blood-Group System ,Receptor - Abstract
Plasmodium vivaxhas been largely neglected over the past century, despite a widespread recognition of its burden across region where it is endemic. The parasite invades reticulocytes, employing the interaction betweenPlasmodium vivaxDuffy binding protein (PvDBP) and human Duffy antigen receptor for chemokines (DARC). However,P. vivaxhas now been observed in Duffy-negative individuals, presenting a potentially serious public health problem as the majority of African populations are Duffy-negative. Invasion of Duffy-negative reticulocytes is suggested to be through duplication of the PvDBP and a novel protein encoded byP. vivaxerythrocyte binding protein (EBP) genes. The emergence and spread of specificP. vivaxstrains with ability to invade Duffy-negative reticulocytes has, therefore, drawn substantial attention and further complicated the epidemiology and public health implication of vivax malaria. Given the right environment and vectorial capacity for transmission coupled with the parasite’s ability to invade Duffy-negative individuals,P. vivaxcould increase its epidemiological significance in Africa. In this review, authors present accruing knowledge on the paradigm shift inP. vivaxinvasion of Duffy-negative reticulocytes against the established mechanism of invading only Duffy-positive individuals and offer a perspective on the epidemiological diagnostic and public health implication in Africa.
- Published
- 2020
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