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Bioinformatics & pathogenicity prediction

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https://www.readbyqxmd.com/read/28790983/nitrate-sensing-and-metabolism-inhibit-biofilm-formation-in-the-opportunistic-pathogen-burkholderia-pseudomallei-by-reducing-the-intracellular-concentration-of-c-di-gmp
#1
Mihnea R Mangalea, Brooke A Plumley, Bradley R Borlee
The opportunistic pathogen Burkholderia pseudomallei is a saprophytic bacterium and the causative agent of melioidosis, an emerging infectious disease associated with high morbidity and mortality. Although melioidosis is most prevalent during the rainy season in endemic areas, domestic gardens and farms can also serve as a reservoir for B. pseudomallei during the dry season, in part due to irrigation and fertilizer use. In the environment, B. pseudomallei forms biofilms and persists in soil near plant root zones...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28780406/novel-mutations-in-the-cdkl5-gene-in-complex-genotypes-associated-with-west-syndrome-with-variable-phenotype-first-description-of-somatic-mosaic-state
#2
Marwa Ben Jdila, Abir Ben Issa, Boudour Khabou, Bochra Ben Rhouma, Fatma Kamoun, Leila Ammar-Keskes, Chahnez Triki, Faiza Fakhfakh
INTRODUCTION: West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. METHODS: The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. RESULTS: The results revealed a complex genotype with more than one mutation in each patient including the known mutations c...
August 2, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28749409/host-response-comparison-of-h1n1-and-h5n1-infected-mice-identifies-two-potential-death-mechanisms
#3
Olivier Leymarie, Léa Meyer, Pierre-Louis Hervé, Bruno Da Costa, Bernard Delmas, Christophe Chevalier, Ronan Le Goffic
Highly pathogenic influenza A viruses (IAV) infections represent a serious threat to humans due to their considerable morbidity and mortality capacities. A good understanding of the molecular mechanisms responsible for the acute lung injury observed during this kind of infection is essential to design adapted therapies. In the current study, using an unbiased transcriptomic approach, we compared the host-responses of mice infected with two different subtypes of IAV: H1N1 vs. H5N1. The host-response comparison demonstrated a clear difference between the transcriptomic profiles of H1N1- and H5N1-infected mice despite identical survival kinetics and similar viral replications...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28733845/genome-wide-identification-in-silico-characterization-and-expression-analysis-of-zip-like-genes-from-trichomonas-vaginalis-in-response-to-zinc-and-iron
#4
K G Fernández-Martín, M E Alvarez-Sánchez, V E Arana-Argáez, L C Alvarez-Sánchez, J C Lara-Riegos, J C Torres-Romero
Trace elements such as Zinc and Iron are essential components of metalloproteins and serve as cofactors or structural elements for enzymes involved in several important biological processes in almost all organisms. Because either excess or insufficient levels of Zn and Fe can be harmful for the cells, the homeostatic levels of these trace minerals must be tightly regulated. The Zinc regulated transporter, Iron regulated transporter-like Proteins (ZIP) comprise a diverse family, with several paralogues in diverse organisms and are considered essential for the Zn and Fe uptake and homeostasis...
July 21, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28719833/in-silico-search-of-inhibitors-of-streptococcus-mutans-for-the-control-of-dental-plaque
#5
Rodrigo Ochoa, María Cecilia Martínez-Pabón, María Adelaida Arismendi-Echeverri, Willer Leandro Rendón-Osorio, Carlos Enrique Muskus-López
Biofilm is an extremely complex microbial community arranged in a matrix of polysaccharides and attached to a substrate. Its development is crucial in the pathophysiology of oral infections like dental caries, as well as in periodontal, pulp, and periapical diseases. Streptococcus mutans is one of the most effective microorganisms in lactic acid production of the dental biofilm. Identifying essential Streptococcus mutans proteins using bioinformatics methods helps to search for alternative therapies. To this end, the bacterial genomes of several Streptococcus mutans strains and representative strains of other cariogenic and non-cariogenic bacteria were analysed by identifying pathogenicity islands and alignments with other bacteria, and by detecting the exclusive genes of cariogenic species in comparison to the non-pathogenic ones...
July 1, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28715844/effects-of-pathogenic-variations-in-the-human-rhodopsin-gene-hrho-on-the-predicted-accessibility-for-a-lead-candidate-ribozyme
#6
Beau R Froebel, Alexandria J Trujillo, Jack M Sullivan
Purpose: The mutation-independent strategy for hammerhead ribozyme (hhRz) or RNA interference (RNAi)-based gene therapeutics to treat autosomal dominant diseases is predicated on the hypothesis that a single therapeutic would equivalently suppress all/most of the diverse mutant mRNAs in patients with the disease phenotype. However, the hypothesis has not been formally tested. We address this through a comprehensive bioinformatics study of how mutations affect target mRNA structure accessibility for a single lead hhRz therapeutic (725GUC↓), designed against human rod rhodopsin mRNA (hRHO), for patients with hRHO mutations that cause autosomal dominant retinitis pigmentosa...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28715501/diversity-and-distribution-of-nuclease-bacteriocins-in-bacterial-genomes-revealed-using-hidden-markov-models
#7
Connor Sharp, James Bray, Nicholas G Housden, Martin C J Maiden, Colin Kleanthous
Bacteria exploit an arsenal of antimicrobial peptides and proteins to compete with each other. Three main competition systems have been described: type six secretion systems (T6SS); contact dependent inhibition (CDI); and bacteriocins. Unlike T6SS and CDI systems, bacteriocins do not require contact between bacteria but are diffusible toxins released into the environment. Identified almost a century ago, our understanding of bacteriocin distribution and prevalence in bacterial populations remains poor. In the case of protein bacteriocins, this is because of high levels of sequence diversity and difficulties in distinguishing their killing domains from those of other competition systems...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28713344/outer-membrane-proteome-of-veillonella-parvula-a-diderm-firmicute-of-the-human-microbiome
#8
Daniel I Poppleton, Magalie Duchateau, Véronique Hourdel, Mariette Matondo, Jennifer Flechsler, Andreas Klingl, Christophe Beloin, Simonetta Gribaldo
Veillonella parvula is a biofilm-forming commensal found in the lungs, vagina, mouth, and gastro-intestinal tract of humans, yet it may develop into an opportunistic pathogen. Furthermore, the presence of Veillonella has been associated with the development of a healthy immune system in infants. Veillonella belongs to the Negativicutes, a diverse clade of bacteria that represent an evolutionary enigma: they phylogenetically belong to Gram-positive (monoderm) Firmicutes yet maintain an outer membrane (OM) with lipopolysaccharide similar to classic Gram-negative (diderm) bacteria...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28708305/a-novel-variant-of-dhh-in-a-familial-case-of-46-xy-disorder-of-sex-development-insights-from-molecular-dynamics-simulations
#9
Francoise Paris, Delphine Flatters, Sandrine Caburet, Bérangère Legois, Nadège Servant, Hervé Lefebvre, Charles Sultan, Reiner A Veitia
OBJECTIVE: Disorders of sex development (DSD) are a heterogeneous group of conditions affecting the differentiation and development of the internal and external genitalia. Here, we aimed at identifying the genetic cause of DSD in two 46,XY sisters from a consanguineous family. DESIGN: We performed a whole-exome sequencing of two 46,XY female individuals. Sanger sequencing was used to validate the most likely candidate variant, affecting the desert hedgehog (DHH) gene...
July 14, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28688561/uncovering-the-pathogenesis-of-microtia-using-bioinformatics-approach
#10
Liu Lei, Liu Zhenzhong, Lin Lin, Pan Bo
OBJECTIVE: Bioinformatics is widely used in the field of cancer research, but in the research of pathogenesis of congenital malformations the situation is different. The aim of this study was to explore the underlying mechanism using bioinformatics approach. METHODS: The data were available from Mouse Genome Informatics and Pubmed. Protein-protein interaction (PPI) network of pathogenic genes was conducted using STRING. Gene ontology and pathway enrichment analyses were also performed to pathogenic genes...
August 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28679403/identification-and-in-silico-characterization-of-p-g380r-substitution-in-fgfr3-associated-with-achondroplasia-in-a-non-consanguineous-pakistani-family
#11
Muhammad Ajmal, Asif Mir, Muhammad Shoaib, Salman Akbar Malik, Muhammad Nasir
BACKGROUND: The dimerization efficiency of FGFR3 transmembrane domain plays a critical role in the formation of a normal skeleton through the negative regulation of bone development. Recently, gain-of-function mutations in the transmembrane domain of FGFR3 has been described associated with an aberrant negative regulation, leading to the development of achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). Here, we describe a non-consanguineous Pakistani family with achondroplasia to explain hereditary basis of the disease...
July 5, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28676128/phenotype-prediction-for-mucopolysaccharidosis-type-i-by-in-silico-analysis
#12
Li Ou, Michael J Przybilla, Chester B Whitley
BACKGROUND: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease due to deficiency of α-L-iduronidase (IDUA), a lysosomal enzyme that degrades glycosaminoglycans (GAG) heparan and dermatan sulfate. To achieve optimal clinical outcomes, early and proper treatment is essential, which requires early diagnosis and phenotype severity prediction. RESULTS: To establish a genotype/phenotype correlation of MPS I disease, a combination of bioinformatics tools including SIFT, PolyPhen, I-Mutant, PROVEAN, PANTHER, SNPs&GO and PHD-SNP are utilized...
July 4, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28670130/four-novel-arsa-gene-mutations-with-pathogenic-impacts-on-metachromatic-leukodystrophy-a-bioinformatics-approach-to-predict-pathogenic-mutations
#13
Masoumeh Dehghan Manshadi, Behnam Kamalidehghan, Omid Aryani, Elham Khalili, Sepideh Dadgar, Mahdi Tondar, Fatemeh Ahmadipour, Goh Yong Meng, Massoud Houshmand
Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the ARSA gene in 12 non-consanguineous MLD patients and 40 healthy individuals was examined using polymerase chain reaction sequencing. Furthermore, the structural and functional effects of new mutations on ARSA were analyzed using SIFT (sorting intolerant from tolerant), I-Mutant 2, and PolyPhen bioinformatics software...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28668253/expression-and-secretion-of-the-giardia-duodenalis-variant-surface-protein-9b10a-by-transfected-trophozoites-causes-damage-to-epithelial-cell-monolayers-mediated-by-protease-activity
#14
Ariana Cabrera-Licona, Eduardo Solano-González, Rocío Fonseca-Liñán, Ma Luisa Bazán-Tejeda, Raúl Argüello-García, Rosa Ma Bermúdez-Cruz, Guadalupe Ortega-Pierres
Giardia duodenalis is the protozoan parasite responsible for most cases of parasitic diarrhea worldwide. The pathogenic mechanisms of giardiasis have not yet been fully characterized. In this context parasite's excretory/secretory products have been related to the damage induced by the parasite on enterocytes. Among these is the Variable Surface Proteins (VSPs) family involved in antigenic variation and in the induction of protective response. In proteomic analyses carried out to identify the proteases with high molecular weight secreted by Giardia trophozoites during the initial phase of interaction with IEC-6 cell monolayers we identified the VSP9B10A protein...
August 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28659964/transcription-factor-repertoire-of-necrotrophic-fungal-phytopathogen-ascochyta-rabiei-predominance-of-myb-transcription-factors-as-potential-regulators-of-secretome
#15
Sandhya Verma, Rajesh K Gazara, Praveen K Verma
Transcription factors (TFs) are the key players in gene expression and their study is highly significant for shedding light on the molecular mechanisms and evolutionary history of organisms. During host-pathogen interaction, extensive reprogramming of gene expression facilitated by TFs is likely to occur in both host and pathogen. To date, the knowledge about TF repertoire in filamentous fungi is in infancy. The necrotrophic fungus Ascochyta rabiei, that causes destructive Ascochyta blight (AB) disease of chickpea (Cicer arietinum), demands more comprehensive study for better understanding of Ascochyta-legume pathosystem...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#16
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28637420/bioinformatics-insights-on-targets-receptors-of-amiodarone-in-human-and-acanthamoeba-castellanii
#17
Abdul Baig, Zohaib Rana, H R Ahmad
BACKGROUND: Amiodarone is prescribed for certain cardiac arrhythmias in medical practice. The drug targets and inhibits voltage dependent sodium (Na+v), calcium (Ca+2v), potassium (K+v) channels, and enzymes like cytochrome P450 and oxidosqualene cyclase. Past studies have shown that amiodarone exerts anti-amoebic effects against Trypanosoma cruzi and Acanthamoeba castellanii. OBJECTIVES: The presence of aforementioned targets and the type of cell death induced by amiodarone in these pathogenic eukaryotes like Acanthamoeba castellanii remain to be verified...
June 21, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28630199/genome-wide-analysis-of-the-antimicrobial-peptides-in-python-bivittatus-and-characterization-of-cathelicidins-with-potent-antimicrobial-activity-and-low-cytotoxicity
#18
Dayeong Kim, Nagasundarapandian Soundrarajan, Juyeon Lee, Hye-Sun Cho, Minkyeung Choi, Se-Yeoun Cha, Byeongyong Ahn, Hyoim Jeon, Minh Thong Le, Hyuk Song, Jin-Hoi Kim, Chankyu Park
In this study, we sought to identify novel antimicrobial peptides (AMPs) in Python bivittatus through bioinformatic analyses of publicly available genome information and experimental validation. In our analysis of the python genome, we identified 29 AMP-related candidate sequences. Of these, we selected five cathelicidin-like sequences and subjected them to further in silico analyses. The results showed that these sequences likely have antimicrobial activity. The sequences were named Pb-CATH1-Pb-CATH5 according to their sequence similarity to previously reported snake cathelicidins...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28625995/novel-antibiotic-resistance-determinants-from-agricultural-soil-exposed-to-antibiotics-widely-used-in-human-medicine-and-animal-farming
#19
Calvin Ho-Fung Lau, Kalene van Engelen, Stephen Gordon, Justin Renaud, Edward Topp
Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized for accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are "hotspots" for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28622862/identification-of-lawsonia-intracellularis-putative-hemolysin-protein-a-and-characterization-of-its-immunoreactivity
#20
Jehyung Kim, Gayeon Won, Suyeon Park, John Hwa Lee
Despite the recent global increase in fatal endemic outbreaks of proliferative enteropathy (PE) caused by the obligate intracellular bacterium Lawsonia intracelluralis (LI) in the swine industry, development of effective prevention strategies or immunodiagnostic tests has been delayed due to the difficulty of cultivating this pathogen in vitro. Although several genetic analyses have been performed at the level of gene transcription after the complete genome sequence of LI was made available, the mechanism of LI infection and virulence genes remain unidentified...
June 2017: Veterinary Microbiology
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