68 research outputs found

    Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian

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    Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases

    Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis

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    BACKGROUND: Human trichomoniasis caused by Trichomonas vaginalis is one of the most common sexually transmitted diseases with more than 200 million cases worldwide. It has caused a series of health problems to patients. For prevention and control of infectious diseases, vaccines are usually considered as one of the most cost-efficient tools. However, until now, work on the development of T. vaginalis vaccines is still mainly focused on the screening of potential immunogens. Alpha-actinin characterized by high immunogenicity in T. vaginalis was suggested as a promising candidate. Therefore, the purpose of this study was to evaluate the protective potency of recombinant α-actinin against T. vaginalis infection in a mouse intraperitoneal model. METHODS: Two selected coding regions of α-actinin (ACT-F, 14-469 aa and ACT-T, 462-844 aa) amplified from cDNA were cloned into pET-32a (+) expression vector and transfected into BL21 cells. After induction with IPTG and purification with electroelution, the two recombinant fusion proteins were emulsified in Freund's adjuvant (FA) and used to immunize BALB/C mice. Following intraperitoneal inoculation with T. vaginalis, the survival rate of mice was monitored for the assessment of protective potency. After immunization, the antibody level in mouse serum was assessed by ELISA, splenocyte proliferation response was detected with CCK8 and cytokines in the supernatant of splenocytes were quantified with a cytometric bead-based assay. RESULTS: We successfully obtained purified ACT-F (70.33 kDa) and ACT-T (61.7kDa). Both recombinant proteins could provide significant protection against T. vaginalis challenge, especially ACT-T (with 100% protection within one month). Meanwhile, high levels of specific total IgG and subtypes (IgG1 > IgG2a) were detected in sera from the immunized mice. Our results also revealed a statistically significant increase in splenocyte proliferation and related cytokine (IFN-γ, IL-6, IL-17A and IL-10) production after repeated stimulation with the corresponding antigens in vitro. CONCLUSIONS: Immunization with both ACT-F and ACT-T could confer partial to complete protection and trigger strong Th1/Th2 mixed humoral and cellular immune responses in the mouse host. This suggested that recombinant α-actinin subunit antigens may be promising vaccine candidates against trichomoniasis

    Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC)

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    Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer

    Investigation of Dyslexia and SLI Risk Variants in Reading- and Language-Impaired Subjects

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    Dyslexia (or reading disability) and specific language impairment (or SLI) are common childhood disorders that show considerable co-morbidity and diagnostic overlaps and have been suggested to share some genetic aetiology. Recently, genetic risk variants have been identified for SLI and dyslexia enabling the direct evaluation of possible shared genetic influences between these disorders. In this study we investigate the role of variants in these genes (namely MRPL19/C20RF3,ROBO1,DCDC2, KIAA0319, DYX1C1, CNTNAP2, ATP2C2 and CMIP) in the aetiology of SLI and dyslexia. We perform case–control and quantitative association analyses using measures of oral and written language skills in samples of SLI and dyslexic families and cases. We replicate association between KIAA0319 and DCDC2 and dyslexia and provide evidence to support a role for KIAA0319 in oral language ability. In addition, we find association between reading-related measures and variants in CNTNAP2 and CMIP in the SLI families

    Neural Network Development in Late Adolescents during Observation of Risk-Taking Action

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    Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n = 25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed

    Near-IR Laser and Raman Spectroscopy of Colon Mucosal Tissues: A Comparative Study on Metabolite Characterisations for Early Diagnosis of Inflammation and Ulceration

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    Mucosal tissues exhibit extended near-IR transparency in the 900 - 1300 nm window, which overlaps nicely with the technologies developed for optical communication systems operating in the 800 - 1700 nm range. In this work, we have demonstrated a laser, based on an ytterbium-ion (Yb 3+ )-doped tellurium oxide glass gain medium, emitting in a narrow window of 1050 - 1055 nm, for use in the first instance as a histopathological microscopic application for bowel tissue examination. The light scattering properties of tumorous and healthy human bowel tissues were characterised using this laser. It was found that both types of tissue were highly transparent at this wavelength and that the laser scattering was significantly lower in the tumorous than that in the healthy tissue.Raman spectra were obtained for inflamed (ulcerative colitis) and healthy bowel tissues. A clear difference was identified in the concentrations of carotenoids, which were twice as strong in the inflamed, and in the phospholipids, which were lower in the inflamed. Myoglobin was another metabolite which was also identified. Using multivariate statistical analysis, we show that the intensities of five peaks (three carotenoid peaks at Raman shifts of 1003, 1155 and 1518 cm -1 and two phospholipid peaks at 1440 and 2762 cm -1 ) are significantly different between healthy and inflamed tissues. Both the near-IR scattering and Raman data allow differentiation between the healthy and inflamed or tumorous tissues and show a potential methodology for early diagnosis tools for ascertaining the presence of inflammation

    Near-IR mode-locked laser assisted sintering and morphological engineering of biomaterials - A new approach for integrative manufacturing of hard-soft tissues for in-theatre use!

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    The emergence of mode-locked near-IR (NIR) lasers has opened novel and exciting opportunities in dental and orthopaedic medicine. In a mode-locked laser cavity the pulse duration and repetition rates may be controlled between 10-100s of femtosecond (fs) and kHz-GHz ranges, respectively. This unique capability for controlling the incident laser power in a near-IR mode-locked laser has been explored for studying the materials phase transformation, sintering and bonding mechanisms in calcium phosphate and chitosan/calcium phosphate suspensions as biomaterials. The investigation primarily focusses on interaction of such a laser in a linear regime, resulting in a plethora of phase combinations and morphologically controlled structures, which are well suited for in-theatre processing of hard-soft tissues for personalized therapy. In this article, the engineered medical device which combines the materials and laser power delivery at the point of tissue restoration is also discussed. The article exemplifies the case for enamel restoration using such a medical device, which then sets the scene for much wider use in tissue engineering
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