scholarly journals Antivirulence Genes: Insights into Pathogen Evolution through Gene Loss

2012 ◽  
Vol 80 (12) ◽  
pp. 4061-4070 ◽  
Author(s):  
Kimberly A. Bliven ◽  
Anthony T. Maurelli
Keyword(s):  
Virulence Factors ◽  
Vaccine Development ◽  
Fine Tuning ◽  
Microbial Pathogens ◽  
Practical Application ◽  
Pathogen Evolution ◽  
Content Type ◽  
Expression Of Genes ◽  
Novel Approach ◽  
Potential Vaccine

ABSTRACTThe emergence of new pathogens and the exploitation of novel pathogenic niches by bacteria typically require the horizontal transfer of virulence factors and subsequent adaptation—a “fine-tuning” process—for the successful incorporation of these factors into the microbe's genome. The function of newly acquired virulence factors may be hindered by the expression of genes already present in the bacterium. Occasionally, certain genes must be inactivated or deleted for full expression of the pathogen phenotype to occur. These genes are known as antivirulence genes (AVGs). Originally identified inShigella, AVGs have improved our understanding of pathogen evolution and provided a novel approach to drug and vaccine development. In this review, we revisit the AVG definition and update the list of known AVGs, which now includes genes from pathogens such asSalmonella,Yersinia pestis, and the virulentFrancisella tularensissubspecies. AVGs encompass a wide variety of different roles within the microbe, including genes involved in metabolism, biofilm synthesis, lipopolysaccharide modification, and host vasoconstriction. More recently, the use of one of these AVGs (lpxL) as a potential vaccine candidate highlights the practical application of studying AVG inactivation in microbial pathogens.

scholarly journals Identification and Immunological Characterization of Three Potential Vaccinogens against Cryptosporidium Species

2011 ◽  
Vol 18 (11) ◽  
pp. 1796-1802 ◽  
Author(s):  
Patricio A. Manque ◽  
Fernando Tenjo ◽  
Ute Woehlbier ◽  
Ana M. Lara ◽  
Myrna G. Serrano ◽  
...  
Keyword(s):  
The Novel ◽  
Cryptosporidium Hominis ◽  
Content Type ◽  
Vaccine Candidates ◽  
Novel Approach ◽  
Intellectual Abilities ◽  
Significant Impairment ◽  
Life Threatening ◽  
Potential Vaccine ◽  
Cellular Immune

ABSTRACTCryptosporidiosis is a ubiquitous infectious disease, caused by the protozoan parasitesCryptosporidium hominisandCryptosporidium parvum, leading to acute, persistent, and chronic diarrhea with life-threatening consequences in immunocompromised individuals. In developing countries, cryptosporidiosis in early childhood has been associated with subsequent significant impairment in growth, physical fitness, and intellectual abilities. Currently, vaccines are unavailable and chemotherapeutics are toxic and impractical, and agents for immunoprophylaxis or treatment of cryptosporidiosis are a high priority. Availability of the genome sequences forC. hominisandC. parvumprovides new opportunities to procure and examine novel vaccine candidates. Using the novel approach of “reverse vaccinology,” we identified several new potential vaccine candidates. Three of these antigens—Cp15, profilin, and aCryptosporidiumapyrase—were delivered in heterologous prime-boost regimens as fusions with cytolysin A (ClyA) in aSalmonellalive vaccine vector and as purified recombinant antigens, and they were found to induce specific and potent humoral and cellular immune responses, suggesting their potential as new vaccinogens againstCryptosporidiuminfection.

Enhanced optimization assisted interference mitigation with vertical beamforming in 3D MIMO-OFDMA for 5G wireless communication network

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Ranjeet Yadav ◽  
Ashutosh Tripathi
Keyword(s):  
Objective Function ◽  
Spatial Diversity ◽  
Spatial Multiplexing ◽  
Fine Tuning ◽  
Dual Decomposition ◽  
Content Type ◽  
Cell Edge ◽  
Time Frequency ◽  
Novel Approach ◽  
Cell Edge User

Purpose Multiple input multiple-output (MIMO) has emerged as one among the many noteworthy technologies in recent wireless applications because of its powerful ability to improve bandwidth efficiency and performance, i.e. through developing its unique spatial multiplexing capability and spatial diversity gain. For carrying out an enhanced communication in next-generation networks, the MIMO and orthogonal frequency division multiple systems were combined that facilitate the spatial multiplexing on resource blocks (RBs) based on time-frequency. This paper aims to propose a novel approach for maximizing the throughput of cell-edge users and cell-center users. Design/methodology/approach In this work, the specified multi-objective function is defined as the single objective function, which is solved by the introduction of a new improved algorithm as well. This optimization problem can be resolved by the fine-tuning of certain parameters such as assigned power for RB, cell-center user, cell-edge user and RB allocation. The fine-tuning of parameters is attained by a new improved Lion algorithm (LA), termed as Lion with new cub generation (LA-NCG) model. Finally, the betterment of the presented approach is validated over the existing models in terms of signal to interference plus noise ratio, throughput and so on. Findings On examining the outputs, the adopted LA-NCG model for 4BS was 66.67%, 66.67% and 20% superior to existing joint processing coordinated multiple point-based dual decomposition method (JC-DDM), fractional programming (FP) and LA models. In addition, the throughput of conventional JC-DDM, FP and LA models lie at a range of 10, 45 and 35, respectively, at the 100th iteration. However, the presented LA-NCG scheme accomplishes a higher throughput of 58. Similarly, the throughput of the adopted scheme observed for 8BS was 59.68%, 44.19% and 9.68% superior to existing JC-DDM, FP and LA models. Thus, the enhancement of the adopted LA-NCG model has been validated effectively from the attained outcomes. Originality/value This paper adopts the latest optimization algorithm called LA-NCG to establish a novel approach for maximizing the throughput of cell-edge users and cell-center users. This is the first that work uses LA-NCG-based optimization that assists in fine-tuning certain parameters such as assigned power for RB, cell-center user, cell-edge user and RB allocation.

scholarly journals Tools, Strains, and Strategies To Effectively Conduct Anaerobic and Aerobic Transcriptional Reporter Screens and Assays in Staphylococcus aureus

2021 ◽  
Vol 87 (21) ◽  
Author(s):  
Erin E. Price ◽  
Paulami Rudra ◽  
Javiera Norambuena ◽  
Franklin Román-Rodríguez ◽  
Jeffrey M. Boyd
Keyword(s):  
Infectious Disease ◽  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Human Pathogen ◽  
Content Type ◽  
Transcriptional Reporter ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Host Tissues

Staphylococcus aureus is a human pathogen and a leading cause of infectious disease-related illness and death worldwide. For S. aureus to successfully colonize and invade host tissues, it must tightly control the expression of genes encoding virulence factors.

scholarly journals Molecular Engineering of Ghfp, the Gonococcal Orthologue of Neisseria meningitidis Factor H Binding Protein

2015 ◽  
Vol 22 (7) ◽  
pp. 769-777 ◽  
Author(s):  
Valentina Rippa ◽  
Laura Santini ◽  
Paola Lo Surdo ◽  
Francesca Cantini ◽  
Daniele Veggi ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Rational Design ◽  
Vaccine Development ◽  
Structural Information ◽  
Binding Protein ◽  
Molecular Engineering ◽  
Factor H ◽  
Microbial Pathogens ◽  
Content Type ◽  
Content Factor

ABSTRACTKnowledge of the sequences and structures of proteins produced by microbial pathogens is continuously increasing. Besides offering the possibility of unraveling the mechanisms of pathogenesis at the molecular level, structural information provides new tools for vaccine development, such as the opportunity to improve viral and bacterial vaccine candidates by rational design. Structure-based rational design of antigens can optimize the epitope repertoire in terms of accessibility, stability, and variability. In the present study, we used epitope mapping information on the well-characterized antigen ofNeisseria meningitidisfactor H binding protein (fHbp) to engineer its gonococcal homologue, Ghfp. Meningococcal fHbp is typically classified in three distinct antigenic variants. We introduced epitopes of fHbp variant 1 onto the surface of Ghfp, which is naturally able to protect against meningococcal strains expressing fHbp of variants 2 and 3. Heterologous epitopes were successfully transplanted, as engineered Ghfp induced functional antibodies against all three fHbp variants. These results confirm that structural vaccinology represents a successful strategy for modulating immune responses, and it is a powerful tool for investigating the extension and localization of immunodominant epitopes.

A cell-based smoothed point interpolation method (CS-PIM) for 2D thermoelastic problems

2017 ◽  
Vol 27 (6) ◽  
pp. 1249-1265 ◽  
Author(s):  
Yijun Liu ◽  
Guiyong Zhang ◽  
Huan Lu ◽  
Zhi Zong
Keyword(s):  
Thermal Stresses ◽  
Interpolation Method ◽  
Content Type ◽  
Novel Approach ◽  
Convergence Results ◽  
Point Interpolation Method ◽  
Point Interpolation ◽  
Thermoelastic Problems ◽  
Gradient Smoothing ◽  
Practical Implications

Purpose Due to the strong reliance on element quality, there exist some inherent shortcomings of the traditional finite element method (FEM). The model of FEM behaves overly stiff, and the solutions of automated generated linear elements are generally of poor accuracy about especially gradient results. The proposed cell-based smoothed point interpolation method (CS-PIM) aims to improve the results accuracy of the thermoelastic problems via properly softening the overly-stiff stiffness. Design/methodology/approach This novel approach is based on the newly developed G space and weakened weak (w2) formulation, and of which shape functions are created using the point interpolation method and the cell-based gradient smoothing operation is conducted based on the linear triangular background cells. Findings Owing to the property of softened stiffness, the present method can generally achieve better accuracy and higher convergence results (especially for the temperature gradient and thermal stress solutions) than the FEM does by using the simplest linear triangular background cells, which has been examined by extensive numerical studies. Practical implications The CS-PIM is capable of producing more accurate results of temperature gradients as well as thermal stresses with the automated generated and unstructured background cells, which make it a better candidate for solving practical thermoelastic problems. Originality/value It is the first time that the novel CS-PIM was further developed for solving thermoelastic problems, which shows its tremendous potential for practical implications.

scholarly journals Automated Confirmation of Protein Annotation Using NLP and the UniProtKB Database

2020 ◽  
Vol 11 (1) ◽  
pp. 24
Author(s):  
Jin Tao ◽  
Kelly Brayton ◽  
Shira Broschat
Keyword(s):  
Language Processing ◽  
Fine Tuning ◽  
Support Vector ◽  
Protein Annotation ◽  
Computing Power ◽  
Journal Publication ◽  
Novel Approach ◽  
Uniprotkb Database ◽  
Public Repositories ◽  
Annotation Errors

Advances in genome sequencing technology and computing power have brought about the explosive growth of sequenced genomes in public repositories with a concomitant increase in annotation errors. Many protein sequences are annotated using computational analysis rather than experimental verification, leading to inaccuracies in annotation. Confirmation of existing protein annotations is urgently needed before misannotation becomes even more prevalent due to error propagation. In this work we present a novel approach for automatically confirming the existence of manually curated information with experimental evidence of protein annotation. Our ensemble learning method uses a combination of recurrent convolutional neural network, logistic regression, and support vector machine models. Natural language processing in the form of word embeddings is used with journal publication titles retrieved from the UniProtKB database. Importantly, we use recall as our most significant metric to ensure the maximum number of verifications possible; results are reported to a human curator for confirmation. Our ensemble model achieves 91.25% recall, 71.26% accuracy, 65.19% precision, and an F1 score of 76.05% and outperforms the Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT) model with fine-tuning using the same data.

scholarly journals Synthesis of 4-Substituted-1,2-Dihydroquinolines by Means of Gold-Catalyzed Intramolecular Hydroarylation Reaction of N-Ethoxycarbonyl-N-Propargylanilines

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3366
Author(s):  
Antonio Arcadi ◽  
Andrea Calcaterra ◽  
Giancarlo Fabrizi ◽  
Andrea Fochetti ◽  
Antonella Goggiamani ◽  
...  
Keyword(s):  
Building Blocks ◽  
Fine Tuning ◽  
Para Position ◽  
Cyclization Product ◽  
Synthetic Route ◽  
Substituted Anilines ◽  
Novel Approach ◽  
High Yields

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of N-ethoxycarbonyl protected-N-propargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6-endo cyclization product in good to high yields. In the presence of N-ethoxycarbonyl-N-propargyl-meta-substituted anilines, the regiodivergent cyclization at the ortho-/para-position is achieved by the means of catalyst fine tuning.

scholarly journals Identification of the conserved long non-coding RNAs in myogenesis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anupam Bhattacharya ◽  
Simang Champramary ◽  
Tanya Tripathi ◽  
Debajit Thakur ◽  
Ilya Ioshikhes ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Muscle Development ◽  
Three Dimensional ◽  
C2c12 Cells ◽  
Mouse Muscle ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Topologically Associated Domains

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

scholarly journals Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jasmine Martinez ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Robert Courville ◽  
Camila Pimentel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Atp Synthesis ◽  
Bloodstream Infections ◽  
Model Systems ◽  
Phenotypic Traits ◽  
Virulence Determinants ◽  
Expression Of Genes

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.

The 4Cs of mass customization in service industries: a customer lens

2020 ◽  
Vol 34 (4) ◽  
pp. 499-511 ◽  
Author(s):  
Jessica L. Pallant ◽  
Sean Sands ◽  
Ingo Oswald Karpen
Keyword(s):  
Boundary Conditions ◽  
Mass Customization ◽  
Design Methodology ◽  
Service Industries ◽  
Future Research ◽  
Practical Application ◽  
Theoretical Understanding ◽  
Content Type ◽  
Priority Areas ◽  
Research Priority

Purpose Increasingly, customers are demanding products that fit their individual needs. Many firms respond by cultivating product individualization via mass customization, often integrating this capability via interactive platforms that connect them with customers. Despite such customization, research to date has lacked cohesion, often taking the organizational, rather than customer, view. The purpose of this paper is to provide inconclusive theorizing in regard to customization from the consumers’ perspective. Design/methodology/approach The review and synthesis of the literature revealed that co-configuration is an underexplored domain of mass customization. Consequently, an initial conceptualization of co-configuration is developed and compared with current customization strategies. Specifically, the definition and boundary conditions of co-configuration are compared with three domains of mass customization, namely, co-production, co-construction and co-design. This led to the development of research priority areas to establish an agenda for future research on mass customization and its role in customer’ firm relationships. Findings This paper provides the delineation of four distinct consumer customization strategies, conceptualized in a matrix, and proposes separate customer journey visualizations. In advancing the theoretical understanding by means of a unifying typology, this paper identifies three existing Cs of mass customization (co-production, co-construction and co-design) and focuses specifically on a fourth (co-configuration), identified as an understudied mass customization strategy. Originality/value This paper extends the previous conceptualizations of mass customization comprising co-production, co-design and co-construction. The proposed typology establishes a foundation for four research priority areas that can improve both academic rigor and practical application.

Sign in / Sign up

Export Citation Format

Share Document