A landmark-free morphometrics pipeline for high-resolution phenotyping: application to a mouse model of Down syndrome

Characterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes

Assessing the value of intangible benefits of property level flood risk adaptation (PLFRA) measures

© 2015, Springer Science+Business Media Dordrecht. Studies in the UK and elsewhere have identified that flooding can result in diverse impacts, ranging from significant financial costs (tangible) to social (intangible) impacts on households. At the same time, it is now clear that large-scale flood defence schemes are not the panacea to flood risk, and there is an increasing responsibility on property owners to protect their own properties. Hence, there is an emerging expectation for homeowners to take action in the form of investing in property level flood risk adaptation (PLFRA) measures to protect their properties. However, hitherto the level of uptake of such measures remains very low. The tangible financial benefits of investing in PLFRA measures are generally well understood and have been demonstrated to be cost beneficial for many properties at risk from frequent flooding. Importantly, these estimates tend to take little account of the value of the intangible benefits of PLFRA measures and therefore may be under estimating their full benefits. There remains a need to develop an improved understanding of these intangible benefits, and this research sets out to bridge this knowledge gap. Based on a synthesis of the literature, the contingent valuation method was selected as a means to value intangible impacts of flooding on households. A questionnaire survey of homeowners affected in the 2007 flooding was employed to elicit willingness to pay (WTP) values to avoid the intangible impacts of flooding on their households. The analysis of the questionnaire survey data revealed that the average WTP per household per year to avoid intangible flood impacts was £653. This therefore represents the value of the intangible benefits of investing in PLFRA measures and is significantly higher than previously estimated. This research builds on previous research in suggesting a higher value to the intangible impacts of flooding on households by assessing wider range of intangible impacts and focussing on more experienced individuals. Furthermore, the research indicates that factors which influence the WTP values were principally stress of flood, worrying about loss of house values, worrying about future flooding and age of respondents, with income showing a weak correlation. The establishment of a new value for the intangible impacts of flooding on households in the UK is helpful in the domain of flood risk management when evaluating the total benefits (tangible and intangible) of investing in flood protection measures, thus providing a robust assessment for decision-making on flood adaptation measures at an individual property level

Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids

Khat (Catha edulis Forsk.) is a flowering perennial shrub cultivated for its neurostimulant properties resulting mainly from the occurrence of (S)-cathinone in young leaves. The biosynthesis of (S)-cathinone and the related phenylpropylamino alkaloids (1S,2S)-cathine and (1R,2S)-norephedrine is not well characterized in plants. We prepared a cDNA library from young khat leaves and sequenced 4,896 random clones, generating an expressed sequence tag (EST) library of 3,293 unigenes. Putative functions were assigned to > 98% of the ESTs, providing a key resource for gene discovery. Candidates potentially involved at various stages of phenylpropylamino alkaloid biosynthesis from L-phenylalanine to (1S,2S)-cathine were identified

Historical sampling reveals dramatic demographic changes in western gorilla populations

Background: Today many large mammals live in small, fragmented populations, but it is often unclear whether this subdivision is the result of long-term or recent events. Demographic modeling using genetic data can estimate changes in long-term population sizes while temporal sampling provides a way to compare genetic variation present today with that sampled in the past. In order to better understand the dynamics associated with the divergences of great ape populations, these analytical approaches were applied to western gorillas (Gorilla gorilla) and in particular to the isolated and Critically Endangered Cross River gorilla subspecies (G. g. diehli).Results: We used microsatellite genotypes from museum specimens and contemporary samples of Cross River gorillas to infer both the long-term and recent population history. We find that Cross River gorillas diverged from the ancestral western gorilla population ~17,800 years ago (95% HDI: 760, 63,245 years). However, gene flow ceased only ~420 years ago (95% HDI: 200, 16,256 years), followed by a bottleneck beginning ~320 years ago (95% HDI: 200, 2,825 years) that caused a 60-fold decrease in the effective population size of Cross River gorillas. Direct comparison of heterozygosity estimates from museum and contemporary samples suggests a loss of genetic variation over the last 100 years.Conclusions: The composite history of western gorillas could plausibly be explained by climatic oscillations inducing environmental changes in western equatorial Africa that would have allowed gorilla populations to expand over time but ultimately isolate the Cross River gorillas, which thereafter exhibited a dramatic population size reduction. The recent decrease in the Cross River population is accordingly most likely attributable to increasing anthropogenic pressure over the last several hundred years. Isolation of diverging populations with prolonged concomitant gene flow, but not secondary admixture, appears to be a typical characteristic of the population histories of African great apes, including gorillas, chimpanzees and bonobos

Molar Bud-to-Cap Transition Is Proliferation Independent

Tooth germs undergo a series of dynamic morphologic changes through bud, cap, and bell stages, in which odontogenic epithelium continuously extends into the underlying mesenchyme. During the transition from the bud stage to the cap stage, the base of the bud flattens and then bends into a cap shape whose edges are referred to as "cervical loops." Although genetic mechanisms for cap formation have been well described, little is understood about the morphogenetic mechanisms. Computer modeling and cell trajectory tracking have suggested that the epithelial bending is driven purely by differential cell proliferation and adhesion in different parts of the tooth germ. Here, we show that, unexpectedly, inhibition of cell proliferation did not prevent bud-to-cap morphogenesis. We quantified cell shapes and actin and myosin distributions in different parts of the tooth epithelium at the critical stages and found that these are consistent with basal relaxation in the forming cervical loops and basal constriction around enamel knot at the center of the cap. Inhibition of focal adhesion kinase, which is required for basal constriction in other systems, arrested the molar explant morphogenesis at the bud stage. Together, these results show that the bud-to-cap transition is largely proliferation independent, and we propose that it is driven by classic actomyosin-driven cell shape-dependent mechanisms. We discuss how these results can be reconciled with the previous models and data