456 research outputs found
Evidence for induced pseudo-vivipary in Pennisetum setaceum (Fountain grass) invading a dry river, arid Karoo, South Africa
We report the development of rootless plantlets in inflorescences of Pennisetum setaceum (Fountain grass) invasive in the Gamka River in the Karoo National Park, South Africa. The pseudo-vivipary appeared to have been induced by inundation of immature inflorescences when the river
flooded. Plantlet production may facilitate the spread of this species in seasonally flooding rivers in arid regions. To the best of our knowledge this is the first record of induced pseudo-vivipary in this grass species
Development of novel bioassays to detect soluble and aggregated Huntingtin proteins on three technology platforms
Huntington’s disease is caused by a CAG / polyglutamine repeat expansion. Mutated CAG repeats undergo somatic instability, resulting in tracts of several hundred CAGs in the brain; and genetic modifiers of Huntington’s disease have indicated that somatic instability is a major driver of age of onset and disease progression. As the CAG repeat expands, the likelihood that exon 1 does not splice to exon 2 increases, resulting in two transcripts that encode full-length huntingtin protein, as well as the highly pathogenic and aggregation-prone exon 1 huntingtin protein. Strategies that target the huntingtin gene or transcripts are a major focus of therapeutic development. It is essential that the levels of all isoforms of huntingtin protein can be tracked, to better understand the molecular pathogenesis, and to assess the impact of huntingtin protein-lowering approaches in preclinical studies and clinical trials. Huntingtin protein bioassays for soluble and aggregated forms of huntingtin protein are in widespread use on the homogeneous time-resolved fluorescence and Meso Scale Discovery platforms, but these do not distinguish between exon 1 huntingtin protein and full-length huntingtin protein. In addition, they are frequently used to quantify huntingtin protein levels in the context of highly expanded polyglutamine tracts, for which appropriate protein standards do not currently exist. Here, we set out to develop novel huntingtin protein bioassays to ensure that all soluble huntingtin protein isoforms could be distinguished. We utilized the zQ175 Huntington’s disease mouse model that has ∼190 CAGs, a CAG repeat size for which protein standards are not available. Initially, 30 combinations of six antibodies were tested on three technology platforms: homogeneous time-resolved fluorescence, amplified luminescent proximity homogeneous assay and Meso Scale Discovery, and a triage strategy was employed to select the best assays. We found that, without a polyglutamine-length-matched standard, the vast majority of soluble mutant huntingtin protein assays cannot be used for quantitative purposes, as the highly expanded polyglutamine tract decreased assay performance. The combination of our novel assays, with those already in existence, provides a tool-kit to track: total soluble mutant huntingtin protein, soluble exon 1 huntingtin protein, soluble mutant huntingtin protein (excluding the exon 1 huntingtin protein) and total soluble full-length huntingtin protein (mutant and wild type). Several novel aggregation assays were also developed that track with disease progression. These selected assays can be used to compare the levels of huntingtin protein isoforms in a wide variety of mouse models of Huntington’s disease and to determine how these change in response to genetic or therapeutic manipulations
What does the COVID-19 pandemic mean for the next decade of onchocerciasis control and elimination?
BACKGROUND: Mass drug administration (MDA) of ivermectin for onchocerciasis has been disrupted by the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modelling can help predict how missed/delayed MDA will affect short-term epidemiological trends and elimination prospects by 2030. METHODS: Two onchocerciasis transmission models (EPIONCHO-IBM and ONCHOSIM) are used to simulate microfilarial prevalence trends, elimination probabilities and age profiles of Onchocerca volvulus microfilarial prevalence and intensity for different treatment histories and transmission settings, assuming no interruption, a 1-y (2020) interruption or a 2-y (2020-2021) interruption. Biannual MDA or increased coverage upon MDA resumption are investigated as remedial strategies. RESULTS: Programmes with shorter MDA histories and settings with high pre-intervention endemicity will be the most affected. Biannual MDA is more effective than increasing coverage for mitigating COVID-19's impact on MDA. Programmes that had already switched to biannual MDA should be minimally affected. In high-transmission settings with short treatment history, a 2-y interruption could lead to increased microfilarial load in children (EPIONCHO-IBM) and adults (ONCHOSIM). CONCLUSIONS: Programmes with shorter (annual MDA) treatment histories should be prioritised for remedial biannual MDA. Increases in microfilarial load could have short- and long-term morbidity and mortality repercussions. These results can guide decision-making to mitigate the impact of COVID-19 on onchocerciasis elimination
A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients
Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al
Towards a quantum representation of the ampere using single electron pumps
Electron pumps generate a macroscopic electric current by controlled
manipulation of single electrons. Despite intensive research towards a quantum
current standard over the last 25 years, making a fast and accurate quantised
electron pump has proved extremely difficult. Here we demonstrate that the
accuracy of a semiconductor quantum dot pump can be dramatically improved by
using specially designed gate drive waveforms. Our pump can generate a current
of up to 150 pA, corresponding to almost a billion electrons per second, with
an experimentally demonstrated current accuracy better than 1.2 parts per
million (ppm) and strong evidence, based on fitting data to a model, that the
true accuracy is approaching 0.01 ppm. This type of pump is a promising
candidate for further development as a realisation of the SI base unit ampere,
following a re-definition of the ampere in terms of a fixed value of the
elementary charge.Comment: 8 pages, 7 figure
Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK
The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de HistologÃa y EmbriologÃa de Mendoza Dr. Mario H. Burgos; Argentin
Modeling the airborne survival of influenza virus in a residential setting: the impacts of home humidification
Prediction of catalytic residues using Support Vector Machine with selected protein sequence and structural properties
BACKGROUND: The number of protein sequences deriving from genome sequencing projects is outpacing our knowledge about the function of these proteins. With the gap between experimentally characterized and uncharacterized proteins continuing to widen, it is necessary to develop new computational methods and tools for functional prediction. Knowledge of catalytic sites provides a valuable insight into protein function. Although many computational methods have been developed to predict catalytic residues and active sites, their accuracy remains low, with a significant number of false positives. In this paper, we present a novel method for the prediction of catalytic sites, using a carefully selected, supervised machine learning algorithm coupled with an optimal discriminative set of protein sequence conservation and structural properties. RESULTS: To determine the best machine learning algorithm, 26 classifiers in the WEKA software package were compared using a benchmarking dataset of 79 enzymes with 254 catalytic residues in a 10-fold cross-validation analysis. Each residue of the dataset was represented by a set of 24 residue properties previously shown to be of functional relevance, as well as a label {+1/-1} to indicate catalytic/non-catalytic residue. The best-performing algorithm was the Sequential Minimal Optimization (SMO) algorithm, which is a Support Vector Machine (SVM). The Wrapper Subset Selection algorithm further selected seven of the 24 attributes as an optimal subset of residue properties, with sequence conservation, catalytic propensities of amino acids, and relative position on protein surface being the most important features. CONCLUSION: The SMO algorithm with 7 selected attributes correctly predicted 228 of the 254 catalytic residues, with an overall predictive accuracy of more than 86%. Missing only 10.2% of the catalytic residues, the method captures the fundamental features of catalytic residues and can be used as a "catalytic residue filter" to facilitate experimental identification of catalytic residues for proteins with known structure but unknown function
Human and Chimpanzee Gene Expression Differences Replicated in Mice Fed Different Diets
Although the human diet is markedly different from the diets of closely related primate species, the influence of diet on phenotypic and genetic differences between humans and other primates is unknown. In this study, we analyzed gene expression in laboratory mice fed diets typical of humans and of chimpanzees. The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain. Importantly, 10% of the genes that differ in their expression between humans and chimpanzee livers differed also between the livers of mice fed the human and chimpanzee diets. Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes. Our results suggest that the mouse can be used to study at least some aspects of human-specific traits
Cross-sectional interactions between quality of the physical and social environment and self-reported physical activity in adults living in income-deprived communities
Background: Understanding the environmental determinants of physical activity in populations at high risk of inactivity could contribute to the development of effective interventions. Socioecological models of activity propose that environmental factors have independent and interactive effects of physical activity but there is a lack of research into interactive effects.
Objectives:
This study aimed to explore independent and interactive effects of social and physical environmental factors on self-reported physical activity in income-deprived communities.
Methods:
Participants were 5,923 adults in Glasgow, United Kingdom. Features of the social environment were self-reported. Quality of the physical environment was objectively-measured. Neighbourhood walking and participation in moderate physical activity [MPA] on ≥5 days/week was self-reported. Multilevel multivariate logistic regression models tested independent and interactive effects of environmental factors on activity.
Results:
‘Social support’ (walking: OR:1.22,95%CI=1.06-1.41,p<0.01; MPA: OR:0.79,95%CI=0.67-0.94,p<0.01), ‘social interaction’ (walking: OR:1.25,95%CI=1.10-1.42,p<0.01; MPA: OR:6.16,95%CI=5.14-7.37,p<0.001) and ‘cohesion and safety’ (walking: OR:1.78,95%CI=1.56-2.03,p<0.001; MPA: OR:1.93,95%CI=1.65-2.27,p<0.001), but not ‘trust and empowerment’, had independent effects on physical activity. ‘Aesthetics of built form’ (OR:1.47,95%CI=1.22-1.77,p<0.001) and ‘aesthetics and maintenance of open space’ (OR:1.32, 95%CI=1.13-1.54,p<0.01) were related to walking. ‘Physical disorder’ (OR:1.63,95%CI=1.31-2.03,p<0.001) had an independent effect on MPA. Interactive effects of social and physical factors on walking and MPA were revealed.
Conclusions:
Findings suggest that intervening to create activity-supportive environments in deprived communities may be most effective when simultaneously targeting the social and physical neighbourhood environment
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