Conserved but flexible modularity in the zebrafish skull: implications for craniofacial evolvability

Morphological variation is the outward manifestation of development and provides fodder for adaptive evolution. Because of this contingency, evolution is often thought to be biased by developmental processes and functional interactions among structures, which are statistically detectable through forms of covariance among traits. This can take the form of substructures of integrated traits, termed modules, which together comprise patterns of variational modularity. While modularity is essential to an understanding of evolutionary potential, biologists currently have little understanding of its genetic basis and its temporal dynamics over generations. To address these open questions, we compared patterns of craniofacial modularity among laboratory strains, defined mutant lines and a wild population of zebrafish ( ). Our findings suggest that relatively simple genetic changes can have profound effects on covariance, without greatly affecting craniofacial shape. Moreover, we show that instead of completely deconstructing the covariance structure among sets of traits, mutations cause shifts among seemingly latent patterns of modularity suggesting that the skull may be predisposed towards a limited number of phenotypes. This new insight may serve to greatly increase the evolvability of a population by providing a range of 'preset' patterns of modularity that can appear readily and allow for rapid evolution

Optimizing astrophotonic spatial reformatters using simulated on-sky performance

One of the most useful techniques in astronomical instrumentation is image slicing. It enables a spectrograph to have a more compact angular slit, whilst retaining throughput and increasing resolving power. Astrophotonic components like the photonic lanterns and photonic reformatters can be used to replace bulk optics used so far. This study investigates the performance of such devices using end-to-end simulations to approximate realistic on-sky conditions. It investigates existing components, tries to optimize their performance and aims to understand better how best to design instruments to maximize their performance. This work complements the recent work in the field and provides an estimation for the performance of the new components.Comment: Conference proceedings in SPIE 2018 Austin Texa

Achieving provider engagement: providers' perceptions of implementing and delivering integrated care

The literature on integrated care is limited with respect to practical learning and experience. Although some attention has been paid to organizational processes and structures, not enough is paid to people, relationships, and the importance of these in bringing about integration. Little is known, for example, about provider engagement in the organizational change process, how to obtain and maintain it, and how it is demonstrated in the delivery of integrated care. Based on qualitative data from the evaluation of a large-scale integrated care initiative in London, United Kingdom, we explored the role of provider engagement in effective integration of services. Using thematic analysis, we identified an evolving engagement narrative with three distinct phases: enthusiasm, antipathy, and ambivalence, and argue that health care managers need to be aware of the impact of professional engagement to succeed in advancing the integrated care agenda

Theory of paramagnetic scattering in highly frustrated magnets with long-range dipole-dipole interactions: The case of the Tb2Ti2O7, pyrochlore antiferromagnet

Highly frustrated antiferromagnets composed of magnetic rare-earth moments are currently attracting much experimental and theoretical interest. Rare-earth ions generally have small exchange interactions and large magnetic moments. This makes it necessary to understand in detail the role of long-range magnetic dipole-dipole interactions in these systems, in particular in the context of spin-spin correlations that develop in the paramagnetic phase, but are often unable to condense into a conventional long-range magnetic ordered phase. This scenario is most dramatically emphasized in the frustrated pyrochlore antiferromagnet material Tb2Ti207 which does not order down to 50 mK despite an antiferromagnetic Curie-Weiss temperature Tcw ~ -20 K. In this paper we report results from mean-field theory calculations of the paramagnetic elastic neutron-scattering in highly frustrated magnetic systems with long-range dipole-dipole interactions, focusing on the Tb2Ti207 system. Modeling Tb2Ti207 as an antiferromagnetic Ising pyrochlore, we find that the mean-field paramagnetic scattering is inconsistent with the experimentally observed results. Through simple symmetry arguments we demonstrate that the observed paramagnetic correlations in Tb2Ti207 are precluded from being generated by any spin Hamiltonian that considers only Ising spins, but are qualitatively consistent with Heisenberg-like moments. Explicit calculations of the paramagnetic scattering pattern for both Ising and Heisenberg models, which include finite single-ion anisotropy, support these claims. We offer suggestions for reconciling the need to restore spin isotropy with the Ising like structure suggested by the single-ion properties of Tb3+.Comment: Revtex4, 18 pages, 3 eps figures (2 color figures). Change in title and emphasis on Tb2Ti2O7 only. Spin-ice material removed, to appear in a later publicatio

Zebrafish eda and edar Mutants Reveal Conserved and Ancestral Roles of Ectodysplasin Signaling in Vertebrates

The genetic basis of the development and variation of adult form of vertebrates is not well understood. To address this problem, we performed a mutant screen to identify genes essential for the formation of adult skeletal structures of the zebrafish. Here, we describe the phenotypic and molecular characterization of a set of mutants showing loss of adult structures of the dermal skeleton, such as the rays of the fins and the scales, as well as the pharyngeal teeth. The mutations represent adult-viable, loss of function alleles in the ectodysplasin (eda) and ectodysplasin receptor (edar) genes. These genes are frequently mutated in the human hereditary disease hypohidrotic ectodermal dysplasia (HED; OMIM 224900, 305100) that affects the development of integumentary appendages such as hair and teeth. We find mutations in zebrafish edar that affect similar residues as mutated in human cases of HED and show similar phenotypic consequences. eda and edar are not required for early zebrafish development, but are rather specific for the development of adult skeletal and dental structures. We find that the defects of the fins and scales are due to the role of Eda signaling in organizing epidermal cells into discrete signaling centers of the scale epidermal placode and fin fold. Our genetic analysis demonstrates dose-sensitive and organ-specific response to alteration in levels of Eda signaling. In addition, we show substantial buffering of the effect of loss of edar function in different genetic backgrounds, suggesting canalization of this developmental system. We uncover a previously unknown role of Eda signaling in teleosts and show conservation of the developmental mechanisms involved in the formation and variation of both integumentary appendages and limbs. Lastly, our findings point to the utility of adult genetic screens in the zebrafish in identifying essential developmental processes involved in human disease and in morphological evolution

The Effects of Physical Activity on Markers of Hepatic Lipid Metabolism during Weight Cycling

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of liver disease and develops when the rate of hepatic triglyceride formation exceeds the rate of disposal. Weight loss is often prescribed to treat NAFLD; however, only one in six obese or overweight individuals who lose weight through diet are successful at maintaining weight loss resulting in weight regain (i.e., weight cycling). Purpose: To determine the effect of physical activity on the prevention of hepatic steatosis and expression of lipogenic genes during weight cycling. Methods: To induce obesity, male C57BL/6 mice were fed a 60% fat diet for 10-weeks. Following weight gain, mice were randomly assigned to a 10% fat diet either with (Diet+PA) or without (Diet) physical activity to induce weight loss for 8 weeks. Physical activity consisted of unrestricted access to running wheels. Following weight loss, the Diet and Diet+PA groups were switched back to a 60% fat diet for 10 weeks to cause weight regain. The Diet+PA had continued access to physical activity during weight regain. Age-matched lean and obese control mice were fed either a 10% fat diet (LF) or 60% fat diet (HF) for the entire 28 weeks of the study. Significant differences (P\u3c0.05) between groups were identified by one-way ANOVA. Results: Following weight regain, body mass of the Diet+PA was significantly lower than the HF (47.8 vs. 55.3 g) and Diet (47.8 vs. 53.9 g). No significant difference in body mass was observed between Diet and HF groups. The Diet+PA had significantly lower plasma cholesterol levels compared to HF (230.5 vs. 254.5 mg/dL) and Diet (230.5 vs. 271.9 mg/dL). In addition, the Diet+PA group had significantly lower total hepatic lipid (23.2 vs. 26.5%) when compared with Diet, which was associated with 60%, 50%, and 40% lower expression of lipogenic genes Fasn, Srebp1c, and Chrebp, respectively. No difference was noted between Diet and Diet+PA for the expression of lipogenic genes Scd1 and Acc1. Conclusions: These data suggests that the continued physical activity during weight cycling resulted in lower weight regain and reduced the accumulation of hepatic lipid by decreased de novo lipogenesis. Overall, the reduced expression of lipogenic related genes might point to a potential protective mechanism that physical activity has on the development of NAFLD during weight cycling

The Effect of a Western Diet on Hepatic Autophagy in Age Accelerated SAMP8 Mice

Non-alcoholic steatohepatitis (NASH) is characterized as a dysregulation of hepatic lipid metabolism and a chronic inflammatory state. It is hypothesized the link between lipid dysregulation and inflammation may be due in part to defective hepatic autophagy and reduced mitochondrial capacity to oxidize fatty acids. It remains to be determined; however, the effects of a Western diet on hepatic autophagy and mitochondrial function during aging. PURPOSE: The purpose of this study was to determine the effect of a high-fat high fructose diet (HFF) on markers of hepatic autophagy and mitochondrial function in an age accelerated mouse model. METHODS: Twenty week old, male and female, SAMP8 mice (n=49) were randomly assigned, matching for gender, to either a standard chow (SC) or HFF (45% fat, 24% fructose) diet for 32 weeks. Liver tissue was analyzed for mRNA expression of autophagic (BNIP3, Beclin 1, p62, and Atg7) and mitochondrial (PGC1α and COXIV) genes. Differences between gender and dietary groups were identified by a 2 x 2 ANOVA and statistical significance was set at p\u3c0.05. RESULTS: Following 32 weeks of feeding, male mice fed the HFF diet were significantly heavier than male mice in the SC group (31.6 g vs 26.5 g; p=0.001); however, no difference was observed between diet groups for female mice. The HFF diet resulted in higher autophagic activity as observed by Beclin 1 (+36%; p=0.001) and BNIP3 (+40%; P=0.003) expression. Despite the higher autophagic activity, p62 was higher (+31%; p\u3c0.001) in the HFF compared to the SC group, suggesting impaired autophagic flux. In addition, mitochondrial COXIV expression was elevated (+43%; P\u3c0.001) in the HFF group compared to the SC group suggesting increased β-oxidation. Overall, the expression of all autophagic and mitochondrial markers was higher in male compared to female mice; however, both sexes responded similarly to the HFF diet. CONCLUSION: Despite the higher expression of autophagic and mitochondrial genes, elevated expression of p62 suggests an impaired autophagic flux in age accelerated mice following a Western diet

Dicarbonyl­dichloridobis(trimethyl­phosphane)iron(II)–carbonyl­dichlorido­tris(trimethyl­phosphane)iron(II)–tetra­hydro­furan (1/1/2)

The asymmetric unit of the title crystal, [FeCl2(C3H9P)3(CO)]·[FeCl2(C3H9P)2(CO)2]·2C4H8O, contains half mol­ecules of the two closely related FeII complexes lying on mirror planes and a tetra­hydro­furan solvent mol­ecule, one C atom of which is disordered over two sets of sites with site occupancy factors 0.633 (9) and 0.367 (9). In both FeII complex mol­ecules, a distorted octa­hedral coordination geometry has been observed around the Fe atoms. Weak intermolecular C—H⋯O inter­actions are observed in the crystal structure

Optical Polarization and Spectral Variability in the M87 Jet

During the last decade, M87's jet has been the site of an extraordinary variability event, with one knot (HST-1) increasing by over a factor 100 in brightness. Variability was also seen on timescales of months in the nuclear flux. Here we discuss the optical-UV polarization and spectral variability of these components, which show vastly different behavior. HST-1 shows a highly significant correlation between flux and polarization, with P increasing from $\sim 20$ at minimum to >40% at maximum, while the orientation of its electric vector stayed constant. HST-1's optical-UV spectrum is very hard ($\alpha_{UV-O}\sim0.5$, $F_\nu\propto\nu^{-\alpha}$), and displays "hard lags" during epochs 2004.9-2005.5, including the peak of the flare, with soft lags at later epochs. We interpret the behavior of HST-1 as enhanced particle acceleration in a shock, with cooling from both particle aging and the relaxation of the compression. We set 2$\sigma$ upper limits of $0.5 \delta$ parsecs and 1.02$c$ on the size and advance speed of the flaring region. The slight deviation of the electric vector orientation from the jet PA, makes it likely that on smaller scales the flaring region has either a double or twisted structure. By contrast, the nucleus displays much more rapid variability, with a highly variable electric vector orientation and 'looping' in the $(I,P)$ plane. The nucleus has a much steeper spectrum ($\alpha_{UV-O} \sim 1.5$) but does not show UV-optical spectral variability. Its behavior can be interpreted as either a helical distortion to a steady jet or a shock propagating through a helical jet.Comment: 14 pages, 7 figures, ApJ, in pres