Genomic insights into ayurvedic and western approaches to personalized medicine

Ayurveda, an ancient Indian system of medicine documented and practised since 1500 B.C., follows a systems approach that has interesting parallels with contemporary personalized genomic medicine approaches to the understanding and management of health and disease. It is based on the trisutra, which are the three aspects of causes, features and therapeutics that are interconnected through a common organizing principle termed ‘tridosha’. Tridosha comprise three ascertainable physiological entities; vata (kinetic), pitta (metabolic) and kapha (potential) that are pervasive across systems, work in conjunction with each other, respond to the external environment and maintain homeostasis. Each individual is born with a specific proportion of tridosha that are not only genetically determined but also influenced by the environment during foetal development. Jointly they determine a person’s basic constitution, which is termed their ‘prakriti’. Development and progression of different diseases with their subtypes are thought to depend on the origin and mechanism of perturbation of the doshas, and the aim of therapeutic practice is to ensure that the doshas retain their homeostatic state. Similarly, western systems biology epitomized by translational P4 medicine envisages the integration of multiscalar genetic, cellular, physiological and environmental networks to predict phenotypic outcomes of perturbations. In this perspective article, we aim to outline the shape of a unifying scaffold that may allow the two intellectual traditions to enhance one another. Specifically, we illustrate how a unique integrative ‘Ayurgenomics’ approach can be used to integrate the trisutra concept of Ayurveda with genomics. We observe biochemical and molecular correlates of prakriti and show how these differ significantly in processes that are linked to intermediate patho-phenotypes, known to take different course in diseases. We also observe a significant enrichment of the highly connected hub genes which could explain differences in prakriti, focussing on EGLN1, a key oxygen sensor that differs between prakriti types and is linked to high altitude adaptation. Integrating our observation with the current literature, we demonstrate how EGLN1 could qualify as a molecular equivalent of tridosha that can modulate different phenotypic outcomes, where hypoxia is a cause or a consequence both during health and diseased states. Our studies affirm that integration of the trisutra framework through Ayurgenomics can guide the identification of predisposed groups of individuals and enable discovery of actionable therapeutic points in an individualized manner.     

The Effects of Modifying Sucrose Concentration on the Development of Maize Kernels Grown in vitro

Intact Zea mays L. kernels attached to cob tissue develop tomaturity when grown in vitro. This experiment was designed todetermine if it is possible to prolong kernel growth by refreshingthe culture medium. Blocks of maize kernels were grown in vitroon media containing several concentrations of sucrose. Kernels,at all concentrations of sucrose, developed to maturity at 30–35d post-pollination, indicating that it is not possible to extendthe kernel growth phase by supplying a carbohydrate source.Kernels grown on media containing 80 g 1^–1 or higher sucroseconcentration had a significantly greater percentage of kernelsthat developed to maturity, and had greater weight and starchcontent per seed. Zea mays, kernel culture, seed development, starch     

Endemic species and ecosystem sensitivity to climate change in Namibia

We present a first assessment of the potential impacts of anthropogenic climate change on the endemic flora of Namibia, and on its vegetation structure and function, for a projected climate in ～2050 and ～2080. We used both niche‐based models (NBM) to evaluate the sensitivity of 159 endemic species to climate change (of an original 1020 plant species modeled) and a dynamic global vegetation model (DGVM) to assess the impacts of climate change on vegetation structure and ecosystem functioning. Endemic species modeled by NBM are moderately sensitive to projected climate change. Fewer than 5% are predicted to experience complete range loss by 2080, although more than 47% of the species are expected to be vulnerable (range reduction >30%) by 2080 if they are assumed unable to migrate. Disaggregation of results by life‐form showed distinct patterns. Endemic species of perennial herb, geophyte and tree life‐formsare predicted to be negatively impacted in Namibia, whereas annual herb and succulent endemic species remain relatively stable by 2050 and 2080. Endemic annual herb species are even predicted to extend their range north‐eastward into the tree and shrub savanna with migration, and tolerance of novel substrates. The current protected area network is predicted to meet its mandate by protecting most of the current endemicity in Namibia into the future. Vegetation simulated by DGVM is projected to experience a reduction in cover, net primary productivity and leaf area index throughout much of the country by 2050, with important implications for the faunal component of Namibia's ecosystems, and the agricultural sector. The plant functional type (PFT) composition of the major biomes may be substantially affected by climate change and rising atmospheric CO₂– currently widespread deciduous broad leaved trees and C₄ PFTs decline, with the C₄ PFT particularly negatively affected by rising atmospheric CO₂ impacts by ～2080 and deciduous broad leaved trees more likely directly impacted by drying and warming. The C₃ PFT may increase in prominence in the northwestern quadrant of the country by ～2080 as CO₂ concentrations increase. These results suggest that substantial changes in species diversity, vegetation structure and ecosystem functioning can be expected in Namibia with anticipated climate change, although endemic plant richness may persist in the topographically diverse central escarpment region.     

The phylogenetic relationships among infraorders and superfamilies of Diptera based on morphological evidence

Members of the megadiverse insect order Diptera (flies) have successfully colonized all continents and nearly all habitats. There are more than 154 000 described fly species, representing 10–12% of animal species. Elucidating the phylogenetic relationships of such a large component of global biodiversity is challenging, but significant advances have been made in the last few decades. Since Hennig first discussed the monophyly of major groupings, Diptera has attracted much study, but most researchers have used non‐numerical qualitative methods to assess morphological data. More recently, quantitative phylogenetic methods have been used on both morphological and molecular data. All previous quantitative morphological studies addressed narrower phylogenetic problems, often below the suborder or infraorder level. Here we present the first numerical analysis of phylogenetic relationships of the entire order using a comprehensive morphological character matrix. We scored 371 external and internal morphological characters from larvae, pupae and adults for 42 species, representing all infraorders selected from 42 families. Almost all characters were obtained from previous studies but required revision for this ordinal‐level study, with homology assessed beyond their original formulation and across all infraorders. We found significant support for many major clades (including the Diptera, Culicomorpha, Bibionomorpha, Brachycera, Eremoneura, Cyclorrhapha, Schizophora, Calyptratae and Oestroidea) and we summarize the character evidence for these groups. We found low levels of support for relationships between the infraorders of lower Diptera, lower Brachycera and major lineages of lower Cyclorrhapha, and this is consistent with findings from molecular studies. These poorly supported areas of the tree may be due to periods of rapid radiation that left few synapomorphies in surviving lineages.     

BEYOND SUN,SAND, AND STITCHES: ASSIGNING RESPONSIBILITY FOR THE HARMS OF MEDICAL TOURISM

Medical tourism (MT) can be conceptualized as the intentional pursuit of non‐emergency surgical interventions by patients outside their nation of residence. Despite increasing popular interest in MT, the ethical issues associated with the practice have thus far been under‐examined. MT has been associated with a range of both positive and negative effects for medical tourists' home and host countries, and for the medical tourists themselves. Absent from previous explorations of MT is a clear argument of how responsibility for the harms of this practice should be assigned. This paper addresses this gap by describing both backward looking liability and forward looking political responsibility for stakeholders in MT. We use a political responsibility model to develop a decision‐making process for individual medical tourists and conclude that more information on the effects of MT must be developed to help patients engage in ethical MT.     

Wildlife and climate change: assessing the sensitivity of selected species to simulated doubling of atmospheric CO2

We explored, using computer simulations, the sensitivity of four mammal species (elk, Cervus canadensis ; white-tailed deer, Odocoileus virginianus ; Columbian ground squirrel, Spermophilus columbianus ; and chipmunk, Tamias striatus ) within the continental USA to the effect of anticipated levels of global climate change brought about by a doubling of atmospheric CO₂. Sensitivity to the direct effects of climate change were evaluated using a climate-space approach to delineate the range of thermal conditions tolerable by each species. Sensitivity to indirect effects were evaluated by quantifying the association of each species to the current vegetation distribution within the continental USA and using this association to assess whether wildlife species distributions might shift in response to vegetation shifts under climate change. Results indicate that altered thermal conditions alone should have little or no effect on the wildlife species' distributions as physiological tolerance to heat load would allow them to survive. Analyses of the effects of vegetation change indicate that deer and chipmunks should retain their current distributions and possibly expand westward in the USA. For Elk and ground squirrels, there is a possibility that their current distributions would shrink and there is little possibility that each species would spread to new regions. This work emphasizes that the distributions of the four mammalian species are likely to be influenced more by vegetation changes than by thermal conditions. Future efforts to understand the effects of global change on wildlife species should focus on animal–habitat and climate–vegetation linkages.     

OLFACTORY RESPONSIVENESS TO DIACETYL

Odor thresholds in the headspace over aqueous solutions of diacetyl (butane-2,3-dione) were measured in quadruplicate by a forced-choice procedure in 53 individuals. Mean individual thresholds varied over a factor of 256, with the group average at .005 μg/ml. Thresholds showed a modest negative correlation with suprathreshold intensity ratings. Intensity ratings were distributed bimodally, consistent with the existence of insensitive and sensitive groups and suggesting the possibility of a specific anosmia for this compound.     

Habitat use by five sympatric Australian freshwater crayfish species (Parastacidae)

1. The Grampians National Park in Victoria is a ‘hot spot’ for freshwater crayfish diversity, with seven species from six genera occurring in sympatry. Few studies have examined how multiple species of freshwater crayfish co‐exist across landscapes consisting of a mosaic of perennial and seasonal habitats. Despite their endemicity and likely key role in freshwaters, the ecology and biology of these crayfish remains unknown. 2. This study determined the distribution and habitat use of five crayfish species (Euastacus bispinosus, Cherax destructor, Geocharax falcata, Gramastacus insolitus and Engaeus lyelli). Seasonal sampling surveys ascertained whether crayfish distribution was related to habitat type, environmental or physicochemical variables, catchment or season. 3. Distribution was directly related to habitat type and the environmental and physicochemical variables that characterised habitats. Engaeus lyelli, G. falcata and G. insolitus occurred predominantly in floodplain wetlands and flooded vegetation habitats, E. bispinosus occurred only in flowing soft‐sediment channels and C. destructor was found in all catchments and habitat types studied. Gramastacus insolitus co‐occurred with G. falcata at all sites except two, so no distinct habitat separations were apparent for these two species. 4. A high percentage cover of boulders was the best indicator of crayfish absence, and discriminated between habitat types and crayfish species: it was probably a surrogate for a larger range of environmental and physicochemical variables. Catchment and season did not affect crayfish distribution. 5. These crayfish species varied in their degree of habitat specialisation from strongly generalist (C. destructor) to occupying only a specific habitat type (E. bispinosus). Some species appeared specialised for seasonal wetlands (G. insolitus and G. falcata). Overlap in site occupancy also varied: G. insolitus and G. falcata distributions were strongly associated, whereas C. destructor appeared to occur opportunistically across habitats, both alone and co‐occurring with all the other species. 6. Management strategies to conserve multiple species of crayfish co‐existing within landscapes will need to incorporate a range of perennial and seasonal habitat types to ensure sufficient space is available for species to maintain different occupancy patterns. Given that water resources are under increasing pressure and are strongly regulated within the Grampians National Park, this may present a conservation challenge to water managers in this location.