Buckling without bending: a new paradigm in morphogenesis

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out-of-phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in-phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2d morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluid-like film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential". Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale-invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bio-inspired applications, and address how our model is and is not unique to the developing nervous system.Comment: version accepted by Physical Review

Identifying Untapped Potential: A Geospatial Analysis of Florida and California’s 2009 Recycled Water Production

Increased water demand attributed to population expansion and reduced freshwater availability caused by saltwater intrusion and drought, may lead to water shortages. These may be addressed, in part, by use of recycled water. Spatial patterns of recycled water use in Florida and California during 2009 were analyzed to detect gaps in distribution and identify potential areas for expansion. Databases of recycled water products and distribution centers for both states were developed by combining the 2008 Clean Water Needs Survey database with Florida’s 2009 Reuse Inventory and California’s 2009 Recycling Survey, respectively. Florida had over twice the number of distribution centers (n 1/4 426) than California (n 1/4 228) and produced a larger volume of recycled water (674.85 vs. 597.48 mgd (3.78 mL/d1/4 1 mgd), respectively). Kernel Density Estimation shows the majority of distribution in central Florida (Orlando and Tampa), California’s Central Valley region (Fresno and Bakersfield), and around major cities in California. Areas for growth were identified in the panhandle and southern regions of Florida, and northern, southwestern, and coastal California. Recycled water is an essential component of integrated water management and broader adoption of recycled water will increase water conservation in water-stressed coastal communities by allocating the recycled water for purposes that once used potable freshwater

Robust Chauvenet Outlier Rejection

Sigma clipping is commonly used in astronomy for outlier rejection, but the number of standard deviations beyond which one should clip data from a sample ultimately depends on the size of the sample. Chauvenet rejection is one of the oldest, and simplest, ways to account for this, but, like sigma clipping, depends on the sample's mean and standard deviation, neither of which are robust quantities: Both are easily contaminated by the very outliers they are being used to reject. Many, more robust measures of central tendency, and of sample deviation, exist, but each has a tradeoff with precision. Here, we demonstrate that outlier rejection can be both very robust and very precise if decreasingly robust but increasingly precise techniques are applied in sequence. To this end, we present a variation on Chauvenet rejection that we call "robust" Chauvenet rejection (RCR), which uses three decreasingly robust/increasingly precise measures of central tendency, and four decreasingly robust/increasingly precise measures of sample deviation. We show this sequential approach to be very effective for a wide variety of contaminant types, even when a significant -- even dominant -- fraction of the sample is contaminated, and especially when the contaminants are strong. Furthermore, we have developed a bulk-rejection variant, to significantly decrease computing times, and RCR can be applied both to weighted data, and when fitting parameterized models to data. We present aperture photometry in a contaminated, crowded field as an example. RCR may be used by anyone at https://skynet.unc.edu/rcr, and source code is available there as well.Comment: 62 pages, 48 figures, 7 tables, accepted for publication in ApJ

Semiclassical approach to discrete symmetries in quantum chaos

We use semiclassical methods to evaluate the spectral two-point correlation function of quantum chaotic systems with discrete geometrical symmetries. The energy spectra of these systems can be divided into subspectra that are associated to irreducible representations of the corresponding symmetry group. We show that for (spinless) time reversal invariant systems the statistics inside these subspectra depend on the type of irreducible representation. For real representations the spectral statistics agree with those of the Gaussian Orthogonal Ensemble (GOE) of Random Matrix Theory (RMT), whereas complex representations correspond to the Gaussian Unitary Ensemble (GUE). For systems without time reversal invariance all subspectra show GUE statistics. There are no correlations between non-degenerate subspectra. Our techniques generalize recent developments in the semiclassical approach to quantum chaos allowing one to obtain full agreement with the two-point correlation function predicted by RMT, including oscillatory contributions.Comment: 26 pages, 8 Figure

Study of Nitrate Stress in Desulfovibrio vulgaris Hildenborough Using iTRAQ Proteomics

The response of Desulfovibrio vulgaris Hildenborough (DvH),a sulphate-reducing bacterium, to nitrate stress was examined usingquantitative proteomic analysis. DvH was stressed with 105 m M sodiumnitrate(NaNO3), a level that caused a 50 percent inhibition in growth.The protein profile of stressed cells was compared with that of cellsgrown in the absence of nitrate using the iTRAQ peptide labellingstrategy and tandem liquid chromatography separation coupled with massspectrometry (quadrupoletime-of-flight) detection. A total of 737 uniqueproteins were identified by two or more peptides, representing 22 percentof the total DvH proteome and spanning every functional category. Theresults indicate that this was a mild stress, as proteins involved incentral metabolism and the sulphate reduction pathway were unperturbed.Proteins involved in the nitrate reduction pathway increased. Increasesseen in transport systems for proline, glycine^ betaineandglutamateindicate that the NaNO3 exposure led to both salt stress and nitratestress.Up-regulation observed in oxidative stress response proteins (Rbr,RbO, etc.) and a large number of ABC transport systems as well as in iron^ sulphur -cluster-containing proteins, however, appear to be specific tonitrate exposure. Finally, a number of hypothetical proteins were amongthe most significant changers, indicating that there may be unknownmechanisms initiated upon nitrate stress in DvH

Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Aerobic capacity, activity levels and daily energy expenditure in male and female adolescents of the kenyan nandi sub-group

The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text]) was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(.) kg(-1.) min(-1) and 61.5±6.3 ml(.) kg(-1.) min(-1), respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(.) day(-1), 5.4±3.0 MJ(.) day(-1) and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2) = 54.7%) and body mass index (partial R(2) = 15.9%). Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success

Spatial heterogeneity of habitat suitability for Rift Valley fever occurrence in Tanzania: an ecological niche modelling approach

Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics