| 1. |
- Bivalacqua, Trinity J., et al.
(författare)
-
Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
- 2007
-
Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
|
|
| 2. |
- Chen, Wenbo, et al.
(författare)
-
The draft genome of whitefly Bemisia tabaci MEAM1, a global crop pest, provides novel insights into virus transmission, host adaptation, and insecticide resistance
- 2016
-
Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is among the 100 worst invasive species in the world. As one of the most important crop pests and virus vectors, B. tabaci causes substantial crop losses and poses a serious threat to global food security. Results: We report the 615-Mb high-quality genome sequence of B. tabaci Middle East-Asia Minor 1 (MEAM1), the first genome sequence in the Aleyrodidae family, which contains 15,664 protein-coding genes. The B. tabaci genome is highly divergent from other sequenced hemipteran genomes, sharing no detectable synteny. A number of known detoxification gene families, including cytochrome P450s and UDP-glucuronosyltransferases, are significantly expanded in B. tabaci. Other expanded gene families, including cathepsins, large clusters of tandemly duplicated B. tabaci-specific genes, and phosphatidylethanolamine-binding proteins (PEBPs), were found to be associated with virus acquisition and transmission and/or insecticide resistance, likely contributing to the global invasiveness and efficient virus transmission capacity of B. tabaci. The presence of 142 horizontally transferred genes from bacteria or fungi in the B. tabaci genome, including genes encoding hopanoid/sterol synthesis and xenobiotic detoxification enzymes that are not present in other insects, offers novel insights into the unique biological adaptations of this insect such as polyphagy and insecticide resistance. Interestingly, two adjacent bacterial pantothenate biosynthesis genes, panB and panC, have been co-transferred into B. tabaci and fused into a single gene that has acquired introns during its evolution. Conclusions: The B. tabaci genome contains numerous genetic novelties, including expansions in gene families associated with insecticide resistance, detoxification and virus transmission, as well as numerous horizontally transferred genes from bacteria and fungi. We believe these novelties likely have shaped B. tabaci as a highly invasive polyphagous crop pest and efficient vector of plant viruses. The genome serves as a reference for resolving the B. tabaci cryptic species complex, understanding fundamental biological novelties, and providing valuable genetic information to assist the development of novel strategies for controlling whiteflies and the viruses they transmit.
|
|
| 3. |
- Conti, David, V, et al.
(författare)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 4. |
- Hunter, Lori M., et al.
(författare)
-
Rural Outmigration, Natural Capital, and Livelihoods in South Africa
- 2014
-
Ingår i: Population, Space and Place. - : Wiley. - 1544-8444 .- 1544-8452. ; 20:5, s. 402-420
-
Tidskriftsartikel (refereegranskat)abstract
- Rural households across the globe engage in both migration and natural resource use as components of livelihood strategies designed to meet household needs. Yet, migration scholars have only recently begun to regularly integrate environmental factors into empirical modelling efforts. To examine the migration-environment association in rural South Africa, we use vegetation measures derived from satellite imagery combined with detailed demographic data from over 9000 households at the Agincourt Health and Demographic Surveillance Site. Results reveal that household-level temporary migration is associated with higher levels of local natural capital, although no such association exists for permanent migration. Further, more advantaged households exhibit a stronger association between migration-environment, in-line with the 'environmental capital' hypothesis, suggesting that natural resource availability can facilitate household income diversification. We argue that a focus on migration's environmental aspects is especially timely in the contemporary era of climate change and that natural capital availability and variability represent critical pieces of the empirical migration puzzle, especially regarding cyclical livelihood migration.
|
|
| 5. |
- Leyk, Stefan, et al.
(författare)
-
Spatially and Temporally Varying Associations between Temporary Outmigration and Natural Resource Availability in Resource-Dependent Rural Communities in South Africa : A Modeling Framework.
- 2012
-
Ingår i: Applied Geography. - : Elsevier. - 0143-6228 .- 1873-7730. ; 34, s. 559-568
-
Tidskriftsartikel (refereegranskat)abstract
- Migration-environment models tend to be aspatial within chosen study regions, although associations between temporary outmigration and environmental explanatory variables likely vary across the study space. This research extends current approaches by developing migration models considering spatial non-stationarity and temporal variation - through examination of the migration-environment association at nested geographic scales (i.e. whole-population, village, and subvillage) within a specific study site. Demographic survey data from rural South Africa, combined with indicators of natural resource availability from satellite imagery, are employed in a nested modeling approach that brings out distinct patterns of spatial variation in model associations derived at finer geographic scales. Given recent heightened public and policy concern with the human migratory implications of climate change, we argue that consideration of spatial variability adds important nuance to scientific understanding of the migration-environment association.
|
|
| 6. |
- Mandt, Kathleen E., et al.
(författare)
-
Ion densities and composition of Titan's upper atmosphere derived from the Cassini Ion Neutral Mass Spectrometer : Analysis methods and comparison of measured ion densities to photochemical model simulations
- 2012
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. E10006-
-
Tidskriftsartikel (refereegranskat)abstract
- The Cassini Ion Neutral Mass Spectrometer (INMS) has measured both neutral and ion species in Titan's upper atmosphere and ionosphere and the Enceladus plumes. Ion densities derived from INMS measurements are essential data for constraining photochemical models of Titan's ionosphere. The objective of this paper is to present an optimized method for converting raw data measured by INMS to ion densities. To do this, we conduct a detailed analysis of ground and in-flight calibration to constrain the instrument response to ion energy, the critical parameter on which the calibration is based. Data taken by the Cassini Radio Plasma Wave Science Langmuir Probe and the Cassini Plasma Spectrometer Ion Beam Spectrometer are used as independent measurement constraints in this analysis. Total ion densities derived with this method show good agreement with these data sets in the altitude region (similar to 1100-1400 km) where ion drift velocities are low and the mass of the ions is within the measurement range of the INMS (1-99 Daltons). Although ion densities calculated by the method presented here differ slightly from those presented in previous INMS publications, we find that the implications for the science presented in previous publications is mostly negligible. We demonstrate the role of the INMS ion densities in constraining photochemical models and find that (1) cross sections having high resolution as a function of wavelength are necessary for calculating the initial photoionization products and (2) there are disagreements between the measured ion densities representative of the initial steps in Titan photochemistry that require further investigation.
|
|
| 7. |
- Mbiba, Monicah, et al.
(författare)
-
Social capital is subordinate to natural capital in buffering rural livelihoods from negative shocks : Insights from rural South Africa
- 2019
-
Ingår i: Journal of Rural Studies. - : Elsevier. - 0743-0167 .- 1873-1392. ; 65, s. 12-21
-
Tidskriftsartikel (refereegranskat)abstract
- Rural livelihoods in developing countries are disproportionately vulnerable to multiple shocks and stresses that exacerbate vulnerability, which can result in increased dependence on natural resources. Several studies have been conducted on the safety net role of natural resources, which lower the impact of negative shocks on rural livelihoods. However, the role of social capital as a safety net that can potentially lower natural resource use when households experience negative shocks has been less studied. We examined the role of natural resources and social capital as buffers against negative shocks to reduce vulnerability in rural livelihoods. Using five years of panel data from a rural population in South Africa, multilevel models were constructed to quantify the influence of shocks, social capital and household socio-demographic characterization on three dimensions of natural resource use, namely the number of types of natural resources used, the frequency of natural resource use, and the quantities of natural resources used. Results show that household experience of negative shocks was consistently associated with a significant increase in all dimensions of natural resource use. However, and unexpectedly, social capital did not significantly reduce natural resource use when households experienced shocks. This in no way discounts the role social capital plays in cushioning households post experience of shocks, but rather indicates that reliance on social and natural capital could be complementary rather than substitutable coping strategies post experience of shocks. Efforts to secure rural livelihoods and achieve sustainability should thus focus on building household physical capital to reduce dependency on natural resources in rural households.
|
|
| 8. |
- Richards, Stephen, et al.
(författare)
-
Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
-
Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
-
Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
|
|
| 9. |
- Wang, Anqi, et al.
(författare)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
|
|
| 10. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
