Isolation and characterisation of the chick orthologue of the Opitz syndrome gene, Mid1, supports a conserved role in vertebrate development

© UBC PressThe X-linked form of Opitz syndrome (OS) is caused by loss of function of the microtubule-associated MID1 protein. The phenotype of OS includes defects along the central body axis, namely hypertelorism, cleft lip and palate, hypospadias and cardiac structural anomalies. Here we describe the isolation and characterisation of full-length cDNA clones representing the chick Mid1 gene and the detailed profile of its expression in stage 7 to 28 chick embryos. Consistent with the remarkable sequence conservation of MID1 between human and chick was the good correlation of the pattern of cMid1 expression with the tissues affected in OS. In stage 10 embryos, transcripts were concentrated in the head mesenchyme which includes migratory neural crest cells. However, the incomplete overlap with a neural crest marker, Sox10, suggests that Mid1 is a marker for somitomeric mesoderm and potentially for a subset of neural crest cells. Consistent with this, cMid1 expression was also detected at later stages in neural crest-derived facial mesenchyme, in the myotome and in the condensing muscle blocks of the limb. Expression of cMid1 was observed in the neural epithelium of the forebrain beginning at stage 7 with increased signal in presumptive rhombomeres 2/3. By stage 15, expression is highest in the diencephalon. Other areas with high expression are certain facial epithelia and the midgut that will give rise to the oesophagus and trachea. These data indicate that Mid1 plays an evolutionarily conserved developmental function in vertebrates that may involve effects on cellular proliferation, tissue interactions and morphogenesis.Joy M. Richman, Katherine K. Fu, Liza L. Cox, Jane P. Sibbons and Timothy C. Co

Decision and Discovery in Defining “Disease”

This version (May 17, 2005) was published in its final form as: Schwartz PH. Decision and discovery in defining 'disease'. In: Kincaid H, McKitrick J, editors. Establishing medical reality: essays in the metaphysics and epistemology of biomedical science. Dordrecht: Springer; 2007. p. 47-63. http://dx.doi.org/10.1007/1-4020-5216-2_5The debate over how to analyze the concept of disease has often centered on the question of whether to include a reference to values, in particular the ‘disvalue’of diseases, or whether to avoid such notions. ‘Normativists,’such as King ([1954], 1981) and Culver and Gert (1982) emphasize the undesirability of diseases, while ‘Naturalists,’ most prominently Christopher Boorse (1977, 1987, 1997), instead require just the presence of biological dysfunction. The debate between normativism and naturalism often deteriorates into stalemate, with each side able to point out significant problems with the other. It starts to look as if neither approach can work. In this paper, I argue that the standoff stems from deeply questionable assumptions that have been used to formulate the opposing positions and guide the debate. In the end, I propose an alternative set of guidelines that offer a more constructive way to devise and compare theories

On eddy viscosity, energy cascades, and the horizontal resolution of gridded satellite altimeter products

Author Posting. © American Meteorological Society, 2013. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 43 (2013): 283–300, doi:10.1175/JPO-D-11-0240.1.Motivated by the recent interest in ocean energetics, the widespread use of horizontal eddy viscosity in models, and the promise of high horizontal resolution data from the planned wide-swath satellite altimeter, this paper explores the impacts of horizontal eddy viscosity and horizontal grid resolution on geostrophic turbulence, with a particular focus on spectral kinetic energy fluxes Π(K) computed in the isotropic wavenumber (K) domain. The paper utilizes idealized two-layer quasigeostrophic (QG) models, realistic high-resolution ocean general circulation models, and present-generation gridded satellite altimeter data. Adding horizontal eddy viscosity to the QG model results in a forward cascade at smaller scales, in apparent agreement with results from present-generation altimetry. Eddy viscosity is taken to roughly represent coupling of mesoscale eddies to internal waves or to submesoscale eddies. Filtering the output of either the QG or realistic models before computing Π(K) also greatly increases the forward cascade. Such filtering mimics the smoothing inherent in the construction of present-generation gridded altimeter data. It is therefore difficult to say whether the forward cascades seen in present-generation altimeter data are due to real physics (represented here by eddy viscosity) or to insufficient horizontal resolution. The inverse cascade at larger scales remains in the models even after filtering, suggesting that its existence in the models and in altimeter data is robust. However, the magnitude of the inverse cascade is affected by filtering, suggesting that the wide-swath altimeter will allow a more accurate determination of the inverse cascade at larger scales as well as providing important constraints on smaller-scale dynamics.BKA received support from Office of Naval Research Grant N00014-11-1-0487, National Science Foundation (NSF) Grants OCE-0924481 and OCE- 09607820, and University of Michigan startup funds. KLP acknowledges support from Woods Hole Oceanographic Institution bridge support funds. RBS acknowledges support from NSF grants OCE-0960834 and OCE-0851457, a contract with the National Oceanography Centre, Southampton, and a NASA subcontract to Boston University. JFS and JGR were supported by the projects ‘‘Global and remote littoral forcing in global ocean models’’ and ‘‘Agesotrophic vorticity dynamics of the ocean,’’ respectively, both sponsored by the Office of Naval Research under program element 601153N.2013-08-0

Granular Rheology in Zero Gravity

We present an experimental investigation on the rheological behavior of model granular media made of nearly elastic spherical particles. The experiments are performed in a cylindrical Couette geometry and the experimental device is placed inside an airplane undergoing parabolic flights to cancel the effect of gravity. The corresponding curves, shear stress versus shear rate, are presented and a comparison with existing theories is proposed. The quadratic dependence on the shear rate is clearly shown and the behavior as a function of the solid volume fraction of particles exhibits a power law function. It is shown that theoretical predictions overestimate the experiments. We observe, at intermediate volume fractions, the formation of rings of particles regularly spaced along the height of the cell. The differences observed between experimental results and theoretical predictions are discussed and related to the structures formed in the granular medium submitted to the external shear.Comment: 10 pages, 6 figures to be published in Journal of Physics : Condensed Matte

Instantaneous venous oxygenation estimation using the Photoplethysmograph (PPG) waveform

In this study oesophageal photoplethysmograph data from eight patients under positive pressure ventilation were analysed in order to test the hypothesis that the modulations created by the ventilation in the AC Photoplethysmograph (PPG) signal could be used to estimate venous oxygen saturation. In order to estimate the instantaneous arterial and venous oxygen saturation Smoothed-pseudo Wigner-Ville Distribution (SPWVD) was utilised. The result from this study showed that there was no significant different in the conventional (time domain) arterial saturation and the instantaneous arterial saturation. However, the instantaneous venous oxygen saturation estimated with the ventilator modulation were significantly lower then the conventional arterial saturation (P=0.008) and also from the instantaneous arterial saturation (P=0.008)

A stochastic model for heart rate fluctuations

Normal human heart rate shows complex fluctuations in time, which is natural, since heart rate is controlled by a large number of different feedback control loops. These unpredictable fluctuations have been shown to display fractal dynamics, long-term correlations, and 1/f noise. These characterizations are statistical and they have been widely studied and used, but much less is known about the detailed time evolution (dynamics) of the heart rate control mechanism. Here we show that a simple one-dimensional Langevin-type stochastic difference equation can accurately model the heart rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical to Gaussian noise, and both parts can be directly determined from the measured heart rate data. Studies of 27 healthy subjects reveal that in most cases the deterministic part has a form typically seen in bistable systems: there are two stable fixed points and one unstable one.Comment: 8 pages in PDF, Revtex style. Added more dat

Semidiurnal Internal Tide Energy Fluxes and Their Variability in a Global Ocean Model and Moored Observations

We examine the temporal means and variability of the semidiurnal internal tide energy fluxes in 1/25° global simulations of the Hybrid Coordinate Ocean Model (HYCOM) and in a global archive of 79 historical moorings. Low-frequency flows, a major cause of internal tide variability, have comparable kinetic energies at the mooring sites in model and observations. The computed root-mean-square (RMS) variability of the energy flux is large in both model and observations and correlates positively with the time-averaged flux magnitude. Outside of strong generation regions, the normalized RMS variability (the RMS variability divided by the mean) is nearly independent of the flux magnitudes in the model, and of order 23% or more in both the model and observations. The spatially averaged flux magnitudes in observations and the simulation agree to within a factor of about 1.4 and 2.4 for vertical mode-1 and mode-2, respectively. The difference in energy flux computed from the full-depth model output versus model output subsampled at mooring instrument depths is small. The global historical archive is supplemented with six high-vertical resolution moorings from the Internal Waves Across the Pacific (IWAP) experiment. The model fluxes agree more closely with the high-resolution IWAP fluxes than with the historical mooring fluxes. The high variability in internal tide energy fluxes implies that internal tide fluxes computed from short observational records should be regarded as realizations of a highly variable field, not as “means” that are indicative of conditions at the measurement sites over all time

The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms

© 2008 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3β homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases.Deutsche Forschungsgemeinschaf

Is early center-based child care associated with tantrums and unmanageable behavior over time up to school entry?

Background. Existing research suggests that there is a relationship between greater exposure to center-based child care and child behavioral problems though the mechanism for the impact is unclear. However the measure used to document child care has usually been average hours, which may be particularly unreliable in the early months when fewer children are in center care. In addition individual trajectories for behavior difficulties have not been studied. Objective. The purpose of the current study was to examine whether the extent of exposure to center-based child care before two years predicted the trajectory of children’s difficult behavior (i.e., tantrums and unmanageable behavior) from 30 to 51 months controlling for child and maternal characteristics. Method. Data were drawn from UK-based Families, Children and Child Care (FCCC) study (n=1201). Individual growth models were fitted to test the relation between early center-based child care experiences and subsequent difficult behavior. Results. Children with more exposure to center-based care before two had less difficult behavior at 30 months, but more increase over time. Initial levels were predicted by higher difficult temperament and lower verbal ability. Higher difficult temperament and lower family socio-economic status predicted its change over time. Conclusion. Findings suggest that early exposure to center-based care before two years old is a risk factor for subsequent behavior problems especially when children have a longer period of exposure. A possible explanatory process is that child coping strategies to manage frustration are less well developed in a group context, especially when they lag behind in expressive language