47 research outputs found
Alginate-regulating genes are identified in the clinical cystic fibrosis isolate of Pseudomonas aeruginosa PA2192
The natural history and genotypeâphenotype correlations of TMPRSS3 hearing loss:an international, multi-center, cohort analysis
TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3Â dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotypeâphenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.</p
The role of leadership in salespeopleâs price negotiation behavior
Salespeople assume a key role in defending firmsâ price levels in price negotiations with customers. The degree to which salespeople defend prices should critically depend upon their leadersâ influence. However, the influence of leadership on salespeopleâs price defense behavior is barely understood, conceptually or empirically. Therefore, building on social learning theory, the authors propose that salespeople might adopt their leadersâ price defense behavior given a transformational leadership style. Furthermore, drawing on the contingency leadership perspective, the authors argue that this adoption fundamentally depends on three variables deduced from the motivationâabilityâopportunity (MAO) framework, that is, salespeopleâs learning motivation, negotiation efficacy, and perceived customer lenience. Results of a multi-level model using data from 92 salespeople and 264 salespersonâcustomer interactions confirm these predictions. The first to explore contingencies of salespeopleâs adoption of their transformational leadersâ price negotiation behaviors, this study extends marketing theory and provides actionable guidance to practitioners
Nociceptors: a phylogenetic view
The ability to react to environmental change is crucial for the survival of an organism and an essential prerequisite is the capacity to detect and respond to aversive stimuli. The importance of having an inbuilt âdetect and protectâ system is illustrated by the fact that most animals have dedicated sensory afferents which respond to noxious stimuli called nociceptors. Should injury occur there is often sensitization, whereby increased nociceptor sensitivity and/or plasticity of nociceptor-related neural circuits acts as a protection mechanism for the afflicted body part. Studying nociception and nociceptors in different model organisms has demonstrated that there are similarities from invertebrates right through to humans. The development of technology to genetically manipulate organisms, especially mice, has led to an understanding of some of the key molecular players in nociceptor function. This review will focus on what is known about nociceptors throughout the Animalia kingdom and what similarities exist across phyla; especially at the molecular level of ion channels
Identification of Alginate-regulating Genes in the Clinical Cystic Fibrosis Isolate of Pseudomonas aeruginosa PA2192
Cystic fibrosis (CF) is a genetic disorder that leads to a buildup of mucus in the lungs ideal for bacterial colonization. When Pseudomonas aeruginosa enters the CF lung, it undergoes a conversion from nonmucoid to mucoid; colonization by a mucoid strain of P. aeruginosa greatly increases mortality. The mucoid phenotype is due to the production of alginate. The regulator of alginate production is the AlgT/U sigma factor which directs RNA polymerase to transcribe the alg regulon, thereby initiating alginate biosynthesis. The observed phenotypic conversion is due to a mutation in the mucA gene coding for an anti-sigma factor, MucA, which sequesters AlgT/U. This mucoid phenotype is unstable when the strains are removed from the lung as they acquire second-site mutations. This in vitro reversion phenomenon is utilized to identify novel genes regulating alginate production. Previously, second-site mutations were mapped to algT/U, algO, and mucP, demonstrating their role in alginate regulation. Most of these studies were performed using a non-CF isolate. It was hypothesized that second site mutations in a clinical strain would be mapped to the same genes. In this study, a clinical, hyper-mucoid P. aeruginosa strain PA2192 was used to study the reversion phenomenon. This study found that PA2192 has a novel mucA mutation which was named them mucA180 allele. Twelve colonies were sub-cultured for two weeks without aeration at room temperature and plated daily for single colonies in order to obtain nonmucoid suppressors of alginate production (sap). Only 41 sap mutants were stable for more than 48 hours â a reversion frequency of 3.9% as compared to ~90% in laboratory strains showing that PA2192 has a stable mucoid phenotype. This phenotype was restored in 28 of the 41 sap mutants when complimented with plasmids harboring algT/U. Four of the sap mutants are complemented by algO. Sequence analyses of the algT/U mutants have found a novel mutation in the promoter region
Teaching Natural Resources Courses Online
This panel will focus on the components and âbest practicesâ of an online lesson âmoduleâ in a Natural Resources course. The presenters will address common assumptions about online courses, including the idea that online lessons are simply repositories of readings and assignments, or pre-recorded lectures. While online courses certainly include these elements, instructors may choose from a wealth of activities (including fieldwork and in-service assignments) and materials (video, interactive Flash animations) that encourage student engagement, concept application and synthesis, time-on-task, and critical thinking. This panel will be comprised of four parts: 1. A short presentation covering the elements of a lesson module for an online natural resources course; 2. A discussion of âbest practicesâ and pedagogical research; 3. Informal comments by a Natural Resources faculty member who is currently teaching online; and, 4. An open forum for audience questions and comments
Alginate-regulating genes are identified in the clinical cystic fibrosis isolate of Pseudomonas aeruginosa PA2192
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Generation of hiPSC line UMi030-A from an individual with the hearing loss-related GJB2 mutation c.109GÂ >Â A
Genetic variants in the GJB2 gene which encodes for the Connexin 26 protein account for âŒÂ 60% of cases of genetic hearing loss. A novel hiPSC line was generated from an individual with the hearing loss-related variant c.109G > A in GJB2 leading to the p.V37I alteration in the Connexin26 protein. These cells will help to delineate the role of GJB2 in hearing loss pathogenesis and serve as a platform for drug discovery and development