Molecular epidemiology of HIV-1 in the United Kingdom.

HIV infection is now the fastest-growing serious health hazard in the United Kingdom (UK), with an estimated 53,000 infected adults at the end of 2003. Despite a recent increase in heterosexually acquired infections, the most prevalent clade of virus within the country remains subtype B, from the main group of HIV-1, which is mainly transmitted through sex between men. To date, very little is known about how subtype B successfully invaded the British population, and how the virus has subsequently spread and evolved. Given that molecular data on HIV-1 is becoming increasingly available since the introduction of routine gene sequencing for drug-resistance monitoring, the present thesis proposes to assess the reliability of the HIV-1 pol gene for molecular analyses of epidemiological relevance. Identification of transmission networks by phylogenetic means were primarily conducted, with the further goal to investigate the dynamics of HIV-1 transmission at both individual and population level in the UK. Evolutionary and epidemiological approaches were then combined in order to assess the correlates of transmission within a population of primary HIV-1 infected individuals within a localised risk group, exploiting both molecular and clinical data. Finally, the epidemic history of HIV-1 subtype B in the UK was reconstructed from sampled HIV-1 pol gene sequences, providing new insights into the complexity of HIV- 1 epidemics that must be considered when developing monitoring and prevention initiatives. The analyses presented in these pages emphasizes the advantage of combining state-of-the-art epidemiological studies to phylogenetic frameworks when investigating the dynamics of a viral epidemic as complex as HIV-1

Seed traits and germination behaviour of kemunting (Rhodomyrtus tomentosa) populations as affected by different temperatures

To examine the variation in seed morphometric traits as well as germination performance at a range of temperatures (10-40°C), Rhodomyrtus tomentosa seeds were collected from four locations across Peninsular Malaysia (designated (C-02), (K-03), (M-01) and (T-01)). Seed source had a significant effect on seed morphometric traits with seeds from K-03 recording the highest values and seeds from C-02 the lowest values for seed length, seed width, seed thickness and 1000 seed weight. These differences in seed traits, which were attributed to maternal or environmental effects, influenced the rate of water uptake leading to variation in germination behaviour such as germination percentage (GP), days to first germination (GD) and time to 50% germination (T50) of the seeds from the four locations. Temperature significantly affected GP, GD and T50 but the effect of location was only significant for GD and T50. There were significant interaction effects of location × temperature for all the parameters tested. Generally, R. tomentosa seeds showed a slow increase in water uptake due to the presence of the operculum and the mesotesta which consists of sclerified cells, and had erratic germination behaviour

Topological Analysis of Metabolic Networks Integrating Co-Segregating Transcriptomes and Metabolomes in Type 2 Diabetic Rat Congenic Series

Background: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus is caused by complex organ-specific cellular mechanisms contributing to impaired insulin secretion and insulin resistance. Methods: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualise shortest paths between metabolites and genes significantly associated with each genomic block. Results: Despite strong genomic similarities (95-99%) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific metabotypes (mQTL) and genome-wide expression traits (eQTL). Variation in key metabolites like glucose, succinate, lactate or 3-hydroxybutyrate, and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing shortest path length drove prioritization of biological validations by gene silencing. Conclusions: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulations and to characterize novel functional roles for genes determining tissue-specific metabolism

Origins of Chevron Rollovers in Non-Two-State Protein Folding Kinetics

Chevron rollovers of some proteins imply that their logarithmic folding rates are nonlinear in native stability. This is predicted by lattice and continuum G\=o models to arise from diminished accessibilities of the ground state from transiently populated compact conformations under strongly native conditions. Despite these models' native-centric interactions, the slowdown is due partly to kinetic trapping caused by some of the folding intermediates' nonnative topologies. Notably, simple two-state folding kinetics of small single-domain proteins are not reproduced by common G\=o-like schemes.Comment: 10 pages, 4 Postscript figures (will appear on PRL

Feasibility of a Fiber Reinforced Polymer Retrofit for Non-Ductile Concrete Walls

A significant number of pre-1980’s non-ductile reinforced concrete (RC) structures in California have been identified as deficient, many of which utilize RC shear wall systems to resist earthquake lateral forces. These non-ductile wall systems are typically lightly reinforced and lack adequate boundary element detailing. Engineers suspect these walls to susceptible to brittle, compression-controlled failure modes due to damage from concrete crushing and bar buckling. As a result, one approach designers are taking is to seek fiber reinforced polymer (FRP) retrofit solutions that improve the compression capacity of high-stressed wall end zone regions based on effectiveness of these approaches with columns. This paper presents the initial results from a lightly reinforced RC shear wall test without boundary elements intended to be representative of a vintage wall. The experimental test showed that the expected compression-type damage mechanisms were not the primary contributors of wall failure. Rather the failure was attributed to the development of few, large crack planes near the base of the wall and the fracture of most longitudinal bars at the wall-foundation interface. Additionally, the drift capacity was greater than anticipated. Therefore, the original proposed fiber reinforced polymer (FRP) retrofit developed by the authors in collaboration with industry input – wrapping the wall end zones with FRP sheets and thru-wall splay anchors to improve the compression capacity of these regions – may not be a viable approach. The research findings suggest that additional investigations into FRP solutions are necessary for different classes of non-ductile walls and their respective failure types

Estimating logged-over lowland rainforest aboveground biomass in Sabah, Malaysia using airborne LiDAR data

Unprecedented deforestation and forest degradation in recent decades have severely depleted the carbon storage in Borneo. Estimating aboveground biomass (AGB) with high accuracy is crucial to quantifying carbon stocks for Reducing Emissions from Deforestation and Forest Degradation-plus implementation (REDD+). Airborne Light Detection and Ranging (LiDAR) is a promising remote sensing technology that provides fine-scale forest structure variability data. This paper highlights the use of airborne LiDAR data for estimating the AGB of a logged-over tropical forest in Sabah, Malaysia. The LiDAR data was acquired using an Optech Orion C200 sensor onboard a fixed wing aircraft. The canopy height of each LiDAR point was calculated from the height difference between the first returns and the Digital Terrain Model (DTM) constructed from the ground points. Among the obtained LiDAR height metrics, the mean canopy height produced the strongest relationship with the observed AGB. This single-variable model had a root mean squared error (RMSE) of 80.02 t ha-1 or 22.31% of the mean AGB, which performed exceptionally when compared with recent tropical rainforest studies. Overall, airborne LiDAR did provide fine-scale canopy height measurements for accurately and reliably estimating the AGB in a logged-over forest in Sabah, thus supporting the state's effort in realizing the REDD+ mechanism

Saturn's Seasonal Atmosphere at Northern Summer Solstice

The incredible longevity of Cassini's orbital mission at Saturn has provided the most comprehensive exploration of a seasonal giant planet to date. This review explores Saturn's changing global temperatures, composition, and aerosol properties between northern spring and summer solstice (2015-2017), extending our previous review of Cassini's remote sensing investigations (2004-14, Fletcher et al., 2018) to the grand finale. The result is an unprecedented record of Saturn's climate that spans almost half a Saturnian year, which can be used to test the seasonal predictions of radiative climate models, neutral and ion photochemistry models, and atmospheric circulation models. Hemispheric asymmetries in tropospheric and stratospheric temperatures were observed to reverse from northern winter to northern summer; spatial distributions of hydrocarbons and para-hydrogen shifted in response to atmospheric dynamics (e.g., seasonally-reversing Hadley cells, polar stratospheric vortex formation, equatorial stratospheric oscillations, and inter-hemispheric transport); and upper tropospheric and stratospheric aerosols exhibited changes in optical thickness that modulated Saturn's visible colours (from blue hues to a golden appearance in the north near solstice), reflectivity, and near-infrared emission. Numerical simulations of radiative balance and photochemistry do a good job in reproducing the observed seasonal change and phase lags, but discrepancies between models and observations still persist, indicating a crucial role for atmospheric dynamics and the need to couple chemical and radiative schemes to the next generation of circulation models. With Cassini's demise, an extended study of Saturn's seasons, from northern summer to autumn, will require the capabilities of ground- and space-based observatories, as we eagerly await the next orbital explorer at Saturn.Comment: 24 pages, 18 figures, submitted for publication by Cambridge University Press as part of a multi-volume work edited by Kevin Baines, Michael Flasar, Norbert Krupp, and Thomas Stallard, entitled "Cassini at Saturn: The Grand Finale." The copy of the Chapter, as displayed on this website, is a draft, pre-publication copy onl

Hedonic drinking engages a supra-spinal inhibition of thermal nociception in adult rats

The taste of sucrose is commonly used to provide pain relief in newborn humans and is innately analgesic to neonatal rodents. In adulthood, sucrose remains a strong motivator to feed, even in potentially hazardous circumstances (ie, threat of tissue damage). However, the neurobiological mechanisms of this endogenous reward–pain interaction are unclear. We have developed a simple model of sucrose drinking–induced analgesia in Sprague–Dawley rats (6-10 weeks old) and have undertaken a behavioral and pharmacological characterization using the Hargreaves' test of hind-paw thermal sensitivity. Our results reveal an acute, potent, and robust inhibitory effect of sucrose drinking on thermal nociceptive behaviour that unlike the phenomenon in neonates is independent of endogenous opioid signalling and does not seem to operate through classical descending inhibition of the spinal cord circuitry. Experience of sucrose drinking had a conditioning effect whereby the apparent expectancy of sucrose enabled water alone (in euvolemic animals) to elicit a short-lasting placebo-like analgesia. Sweet taste alone, however, was insufficient to elicit analgesia in adult rats intraorally perfused with sucrose. Instead, the sucrose analgesia phenomenon only appeared after conditioning by oral perfusion in chronically cannulated animals. This sucrose analgesia was completely prevented by systemic dosing of the endocannabinoid CB1 receptor antagonist rimonabant. These results indicate the presence of an endogenous supraspinal analgesic circuit that is recruited by the context of rewarding drinking and is dependent on endocannabinoid signalling. We propose that this hedonic sucrose-drinking model may be useful for further investigation of the supraspinal control of pain by appetite and reward