scholarly journals A journey through the Corynebacterium pseudotuberculosis proteome promotes insights into its functional genome

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12456
Author(s):  
Wanderson Marques da Silva ◽  
Nubia Seyffert ◽  
Artur Silva ◽  
Vasco Azevedo
Keyword(s):  
Protein Level ◽  
Molecular Basis ◽  
Large Scale ◽  
Small Ruminants ◽  
Etiologic Agent ◽  
Corynebacterium Pseudotuberculosis ◽  
Functional Study ◽  
Functional Studies ◽  
Bioinformatics Tools ◽  
Genomic Studies

Background Corynebacterium pseudotuberculosis is a Gram-positive facultative intracellular pathogen and the etiologic agent of illnesses like caseous lymphadenitis in small ruminants, mastitis in dairy cattle, ulcerative lymphangitis in equines, and oedematous skin disease in buffalos. With the growing advance in high-throughput technologies, genomic studies have been carried out to explore the molecular basis of its virulence and pathogenicity. However, data large-scale functional genomics studies are necessary to complement genomics data and better understating the molecular basis of a given organism. Here we summarize, MS-based proteomics techniques and bioinformatics tools incorporated in genomic functional studies of C. pseudotuberculosis to discover the different patterns of protein modulation under distinct environmental conditions, and antigenic and drugs targets. Methodology In this study we performed an extensive search in Web of Science of original and relevant articles related to methods, strategy, technology, approaches, and bioinformatics tools focused on the functional study of the genome of C. pseudotuberculosis at the protein level. Results Here, we highlight the use of proteomics for understating several aspects of the physiology and pathogenesis of C. pseudotuberculosis at the protein level. The implementation and use of protocols, strategies, and proteomics approach to characterize the different subcellular fractions of the proteome of this pathogen. In addition, we have discussed the immunoproteomics, immunoinformatics and genetic tools employed to identify targets for immunoassays, drugs, and vaccines against C. pseudotuberculosis infection. Conclusion In this review, we showed that the combination of proteomics and bioinformatics studies is a suitable strategy to elucidate the functional aspects of the C. pseudotuberculosis genome. Together, all information generated from these proteomics studies allowed expanding our knowledge about factors related to the pathophysiology of this pathogen.

scholarly journals Gene Expression Imputation with Generative Adversarial Imputation Nets

2020 ◽  
Author(s):  
Ramon Viñas ◽  
Tiago Azevedo ◽  
Eric R. Gamazon ◽  
Pietro Liò
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Biological Significance ◽  
Predictive Performance ◽  
Cost Effective ◽  
Rna Seq ◽  
Comprehensive Collection ◽  
Genomic Studies ◽  
Biological Discovery ◽  
Cancer Types

AbstractA question of fundamental biological significance is to what extent the expression of a subset of genes can be used to recover the full transcriptome, with important implications for biological discovery and clinical application. To address this challenge, we present GAIN-GTEx, a method for gene expression imputation based on Generative Adversarial Imputation Networks. In order to increase the applicability of our approach, we leverage data from GTEx v8, a reference resource that has generated a comprehensive collection of transcriptomes from a diverse set of human tissues. We compare our model to several standard and state-of-the-art imputation methods and show that GAIN-GTEx is significantly superior in terms of predictive performance and runtime. Furthermore, our results indicate strong generalisation on RNA-Seq data from 3 cancer types across varying levels of missingness. Our work can facilitate a cost-effective integration of large-scale RNA biorepositories into genomic studies of disease, with high applicability across diverse tissue types.

Structural and functional studies of SAV1707 from Staphylococcus aureus elucidate its distinct metal-dependent activity and a crucial residue for catalysis

2021 ◽  
Vol 77 (5) ◽  
pp. 587-598
Author(s):  
Dong-Gyun Kim ◽  
Kyu-Yeon Lee ◽  
Sang Jae Lee ◽  
Seung-Ho Cheon ◽  
Yuri Choi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Metal Binding ◽  
Binding Mode ◽  
Structure And Function ◽  
Functional Study ◽  
Functional Studies ◽  
Dependent Endonuclease ◽  
Metal Selectivity ◽  
Metal Binding Domain ◽  
And Function

The metallo-β-lactamase fold is the most abundant metal-binding domain found in two major kingdoms: bacteria and archaea. Despite the rapid growth in genomic information, most of these enzymes, which may play critical roles in cellular metabolism, remain uncharacterized in terms of structure and function. In this study, X-ray crystal structures of SAV1707, a hypothetical metalloenzyme from Staphylococcus aureus, and its complex with cAMP are reported at high resolutions of 2.05 and 1.55 Å, respectively, with a detailed atomic description. Through a functional study, it was verified that SAV1707 has Ni2+-dependent phosphodiesterase activity and Mn2+-dependent endonuclease activity, revealing a different metal selectivity depending on the reaction. In addition, the crystal structure of cAMP-bound SAV1707 shows a unique snapshot of cAMP that reveals the binding mode of the intermediate, and a key residue Phe511 that forms π–π interactions with cAMP was verified as contributing to substrate recognition by functional studies of its mutant. Overall, these findings characterized the relationship between the structure and function of SAV1707 and may provide further understanding of metalloenzymes possessing the metallo-β-lactamase fold.

scholarly journals Transcriptomic Prediction of Pig Liver-Enriched Gene 1 Functions in a Liver Cell Line

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 412
Author(s):  
Zhe Zhang ◽  
Zizengchen Wang ◽  
Yanna Dang ◽  
Jinyang Wang ◽  
Sakthidasan Jayaprakash ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Liver Cells ◽  
Cellular Level ◽  
Gene Set Enrichment Analysis ◽  
Functional Study ◽  
Rna Seq ◽  
Gene Set Enrichment ◽  
Functional Studies ◽  
Er Stress Response ◽  
Domain Of Unknown Function

The newly identified liver-enriched gene 1 (LEG1) encodes a protein with a characteristic domain of unknown function 781 (DUF781/LEG1), constituting a protein family with only one member in mammals. A functional study in zebrafish suggested that LEG1 genes are involved in liver development, while the platypus LEG1 homolog, Monotreme Lactation Protein (MLP), which is enriched in the mammary gland and milk, acts as an antibacterial substance. However, no functional studies on eutherian LEG1s have been published to date. Thus, we here report the first functional prediction study at the cellular level. As previously reported, eutherian LEG1s can be classified into three paralogous groups. Pigs have all three LEG1 genes (pLEG1s), while humans and mice have retained only LEG1a. Hence, pLEG1s might represent an ideal model for studying LEG1 gene functions. RNA-seq was performed by the overexpression of pLEG1s and platypus MLP in HepG2 cells. Enrichment analysis showed that pLEG1a and pLEG1b might exhibit little function in liver cells; however, pLEG1c is probably involved in the endoplasmic reticulum (ER) stress response and protein folding. Additionally, gene set enrichment analysis revealed that platypus MLP shows antibacterial activity, confirming the functional study in platypus. Therefore, our study showed from the transcriptomic perspective that mammalian LEG1s have different functions in liver cells due to the subfunctionalization of paralogous genes.

scholarly journals Biogenic Silver Nanoparticles as a Post-surgical Treatment for Corynebacterium pseudotuberculosis Infection in Small Ruminants

2019 ◽  
Vol 10 ◽  
Author(s):  
Laerte Marlon Santos ◽  
Danijela Stanisic ◽  
Ulisses José Menezes ◽  
Marcos Antônio Mendonça ◽  
Thiago Doria Barral ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Surgical Treatment ◽  
Small Ruminants ◽  
Corynebacterium Pseudotuberculosis ◽  
Biogenic Silver Nanoparticles

scholarly journals Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sophie Tandonnet ◽  
Gisele Antoniazzi Cardoso ◽  
Pedro Mariano-Martins ◽  
Raquel Dietsche Monfardini ◽  
Vanessa A. S. Cunha ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Molecular Basis ◽  
Pyrethroid Resistance ◽  
Management Strategies ◽  
Evolutionary Process ◽  
Specific Expression ◽  
Altered Expression ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Starting Point

Abstract Background The emergence of insecticide resistance is a fast-paced example of the evolutionary process of natural selection. In this study, we investigated the molecular basis of resistance in the myiasis-causing fly Cochliomyia hominivorax (Diptera: Calliphoridae) to dimethyl-organophosphate (OP) insecticides. Methods By sequencing the RNA from surviving larvae treated with dimethyl-OP (resistant condition) and non-treated larvae (control condition), we identified genes displaying condition-specific polymorphisms, as well as those differentially expressed. Results Both analyses revealed that resistant individuals have altered expression and allele-specific expression of genes involved in proteolysis (specifically serine-endopeptidase), olfactory perception and cuticle metabolism, among others. We also confirmed that resistant individuals carry almost invariably the Trp251Ser mutation in the esterase E3, known to confer OP and Pyrethroid resistance. Interestingly, genes involved in metabolic and detoxifying processes (notably cytochrome P450s) were found under-expressed in resistant individuals. An exception to this were esterases, which were found up-regulated. Conclusions These observations suggest that reduced penetration and aversion to dimethyl-OP contaminated food may be important complementary strategies of resistant individuals. The specific genes and processes found are an important starting point for future functional studies. Their role in insecticide resistance merits consideration to better the current pest management strategies.

scholarly journals Sheep Brucellosis in Kuwait: A Large-Scale Serosurvey, Identification of Brucella Species and Zoonotic Significance

2020 ◽  
Vol 7 (3) ◽  
pp. 132 ◽  
Author(s):  
Yousef Al-Sherida ◽  
Adel H. El-Gohary ◽  
Amro Mohamed ◽  
Mohamed El-Diasty ◽  
Gamal Wareth ◽  
...  
Keyword(s):  
Large Scale ◽  
Small Ruminants ◽  
Health Impact ◽  
Control Measures ◽  
Economic Losses ◽  
Serum Samples ◽  
Tissue Samples ◽  
High Prevalence ◽  
History Of ◽  
Combined Action

Brucellosis is a common zoonotic disease of major concern in humans of Kuwait, and B. melitensis causes most human cases. The disease is endemic in small ruminants, cattle, and camels for decades, causing substantial economic losses in livestock production. However, a nationwide large-scale investigation of brucellosis in the small ruminant population has not been done in the past two decades. A serosurvey of sheep brucellosis in the five districts of Kuwait with most animal production farms was done between 2016 and 2019. In total, 67,054 serum samples from 233 sheep herds were collected and tested. Additionally, milk and tissue samples were collected from 46 seropositive cases for bacteriology. Thirty persons from seven seropositive farms were tested by serology. The incidence of seropositive cases was 7% in districts devoid of vaccination, while it was 4.7% in farms with history of vaccination. The serosurvey revealed that 89% of non-vaccinated herds (n = 181) were seropositive by Rose Bengal test (RBT), buffered acidified plate antigen test (BAPAT), and complement fixation test (CFT). Prevalence of 100% was reported for non-vaccinated sheep herds from Al-Wafrah and Al-Jahra districts, followed by those from Al-Salmi (88.24%), Al-Abdali (86.7%) and Kabd (75.6%). Implementation of vaccination with B. melitensis Rev.1 vaccine and test-and-slaughters in 20 herds reduced the seroprevalence to 33.3% and 25% in herds from Al-Jahra and AL-Wafrah, respectively. B. melitensis was isolated from 20 samples (43.5%). More than half of the examined animal owners (56.6%) tested positive for Brucella using RBT, BAPAT and CFT. The high numbers of infected herds and high prevalence in herdsmen are alarming. Thus, control measures have to be ensured immediately. The epidemiological situation in Kuwait is similar to those of the neighboring countries and the combined action of these states is needed. The understanding of the economic and public health impact of brucellosis in Kuwait needs to grow.

scholarly journals Changes in the epidemiological characteristics of human brucellosis in Shaanxi Province from 2008 to 2020

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cui-hong An ◽  
Zhi-guo Liu ◽  
Shou-min Nie ◽  
Yang-xin Sun ◽  
Suo-ping Fan ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Large Scale ◽  
Small Ruminants ◽  
Raw Milk ◽  
Shaanxi Province ◽  
Significant Feature ◽  
Human Brucellosis ◽  
Northern Shaanxi ◽  
Southern Shaanxi ◽  
Epidemiological Characteristics

AbstractIn the present study, surveys of case numbers, constituent ratios, conventional biotyping, and multilocus sequence typing (MLST) were applied to characterize the incidence rate and epidemiological characteristics of human brucellosis in Shaanxi Province, China. A total of 12,215 human brucellosis cases were reported during 2008–2020, for an annual average incidence rate of 2.48/100,000. The most significant change was that the county numbers of reported cases increased from 36 in 2008 to 84 in 2020, with a geographic expansion trend from northern Shaanxi to Guanzhong, and southern Shaanxi regions; the incidence rate declined in previous epidemic northern Shaanxi regions while increasing each year in Guanzhong and southern Shaanxi regions such as Hancheng and Xianyang. The increased incidence was closely related to the development of large-scale small ruminants (goats and sheep) farms in Guanzhong and some southern Shaanxi regions. Another significant feature was that student cases (n = 261) were ranked second among all occupations, accounting for 2.14% of the total number of cases, with the majority due to drinking unsterilized goat milk. Three Brucella species were detected (B. melitensis (bv. 1, 2, 3 and variant), B. abortus bv. 3/6, and B. suis bv. 1) and were mainly distributed in the northern Shaanxi and Guanzhong regions. Three known STs (ST8, ST2, and ST14) were identified based on MLST analysis. The characteristics that had not changed were that B. melitensis strains belonging to the ST8 population were the dominant species and were observed in all nine regions during the examined periods. Strengthened human and animal brucellosis surveillance and restriction of the transfer of infected sheep (goats) as well as students avoiding drinking raw milk are suggested as optimal control strategies.

scholarly journals Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy

2020 ◽  
Vol 4 (1) ◽  
pp. 299-313
Author(s):  
Gemma L. Kelly ◽  
Andreas Strasser
Keyword(s):  
Cell Death ◽  
Structural Analysis ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Large Scale ◽  
Tissue Homeostasis ◽  
Clinical Testing ◽  
Malignant Cells ◽  
Functional Studies ◽  
Genome Analyses

Apoptosis is critical for embryonic development, tissue homeostasis, and the removal of infected or otherwise dangerous cells. It is controlled by three subgroups of the BCL-2 protein family—the BH3-only proteins that initiate cell death; the effectors of cell killing, BAX and BAK; and the antiapoptotic guardians, including MCL-1 and BCL-2. Defects in apoptosis can promote tumorigenesis and render malignant cells refractory to anticancer therapeutics. Activation of cell death by inhibiting antiapoptotic BCL-2 family members has emerged as an attractive strategy for cancer therapy, with the BCL-2 inhibitor venetoclax leading the way. Large-scale cancer genome analyses have revealed frequent amplification of the locus encoding antiapoptotic MCL-1 in human cancers, and functional studies have shown that MCL-1 is essential for the sustained survival and expansion of many types of tumor cells. Structural analysis and medicinal chemistry have led to the development of three distinct small-molecule inhibitors of MCL-1 that are currently undergoing clinical testing.

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