Eya1 is essential for branchial arch segmentation and branchial epithelium development through regulating Notch signaling pathway

Student Oral Presentation Session 3Craniofacial anomalies are common features of Branchio-Oto-Renal (BOR) syndrome patients. Mutations in the Eya1 gene have been found in around half of the BOR patients, but the pathogenic mechanisms mediated by Eya1 in the craniofacial malformations remain unknown. In this study, we use Eya1 mutant mice as a disease model to study the abnormal early branchial arch (BA) development. Eya1-/- mutant embryos have hypoplastic BA2. The formation of branchial cleft was severely affected. Interestingly, Notch signaling was down-regulated in the mutant branchial ...postprin

Sox10 regulates enteric neural crest cell migration in the developing gut

Concurrent Sessions 1: 1.3 - Organs to organisms: Models of Human Diseases: abstract no. 1417th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting and XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo. The Conference's web site is located at http://www.inb.unam.mx/isdb/Sox10 is a HMG-domain containing transcription factor which plays important roles in neural crest cell survival and differentiation. Mutations of Sox10 have been identified in patients with Waardenburg-Hirschsprung syndrome, who suffer from deafness, pigmentation defects and intestinal aganglionosis. Enteric neural crest cells (ENCCs) with Sox10 mutation undergo premature differentiation and fail to colonize the distal hindgut. It is unclear, however, whether Sox10 plays a role in the migration of ENCCs. To visualize the migration behaviour of mutant ENCCs, we generated a Sox10NGFP mouse model where EGFP is fused to the N-terminal domain of Sox10. Using time-lapse imaging, we found that ENCCs in Sox10NGFP/+ mutants displays lower migration speed and altered trajectories compared to normal controls. This behaviour was cell-autonomous, as shown by organotypic grafting of Sox10NGFP/+ gut segments onto control guts and vice versa. ENCCs encounter different extracellular matrix (ECM) molecules along the developing gut. We performed gut explant culture on various ECM and found that Sox10NGFP/+ ENCCs tend to form aggregates, particularly on fibronectin. Time-lapse imaging of single cells in gut explant culture indicated that the tightly-packed Sox10 mutant cells failed to exhibit contact inhibition of locomotion. We determined the expression of adhesion molecule families by qPCR analysis, and found integrin expression unaffected while L1-cam and selected cadherins were altered, suggesting that Sox10 mutation affects cell adhesion properties of ENCCs. Our findings identify a de novo role of Sox10 in regulating the migration behaviour of ENCCs, which has important implications for the treatment of Hirschsprung disease.postprin

A Novel Biphasic-Current-Pulse Calibration Technique for Electrical Neural Stimulation

One of the major challenge in neural prosthetic device design is to ensure charge-balanced stimulation. This paper presents a new calibration technique to minimize the mismatch between anodic and cathodic current amplitudes. The proposed circuit mainly consists of a digital and an analog calibration, where a successive approximation register (SAR) logic and a comparator are used in digital calibration while a source follower is adopted in analog calibration. With a 0. 18 μm high voltage CMOS process, the simulation shows that the maximum current mismatch is 45 nA (<0.05%).published_or_final_versio

Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome

Poster Session I - Morphogenesis: 205/B10117th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.Branchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.postprin

Dislocation network at InN/GaN interface revealed by scanning tunneling microscopy

For heteroepitaxy of InN on GaN(0001) by molecular-beam epitaxy, the lattice misfit strain is relieved by misfit dislocations (MDs) formed at the interface between InN and GaN. Imaging by scanning tunneling microscopy (STM) of the surfaces of thin InN epifilms reveals line feature parallel to 〈112 0〉. Their contrast becomes less apparent for thicker epifilms. From the interline spacing as well as a comparison with transmission electron microscopy studies, it is suggested that they correspond to the MDs beneath the surface. The STM contrast originates from both the surface distortion caused by the local strain at MDs and the electronic states of the defects. © 2008 American Institute of Physics.published_or_final_versio

Descriptors for Pentane-2,4-dione and Its Derivatives

We have used equations for partition coefficients of compounds from water and the gas phase to various solvents to obtain descriptors for pentane-2,4-dione and 21 of its derivatives. These descriptors can then be used to estimate further partition coefficients into a wide variety of solvents. The descriptors also yield information about the properties of pentane-2,4-dione and its derivatives. Pentane-2,4-dione and its alkyl derivatives are quite polar, with substantial hydrogen bond basicity but with no hydrogen bond acidity. In contrast 1,1,1-trifluoropentane-2,4-dione and hexafluoropentan-2,4-dione have significant hydrogen bond acidities

Cloud feedback mechanisms and their representation in global climate models

Cloud feedback – the change in top-of-atmosphere radiative flux resulting from the cloud response to warming – constitutes by far the largest source of uncertainty in the climate response to CO2 forcing simulated by global climate models (GCMs). We review the main mechanisms for cloud feedbacks, and discuss their representation in climate models and the sources of inter-model spread. Global-mean cloud feedback in GCMs results from three main effects: (1) rising free- tropospheric clouds (a positive longwave effect); (2) decreasing tropical low cloud amount (a positive shortwave effect); (3) increasing high-latitude low cloud optical depth (a negative shortwave effect). These cloud responses simulated by GCMs are qualitatively supported by theory, high-resolution modeling, and observations. Rising high clouds are consistent with the Fixed Anvil Temperature (FAT) hypothesis, whereby enhanced upper-tropospheric radiative cooling causes anvil cloud tops to remain at a nearly fixed temperature as the atmosphere warms. Tropical low cloud amount decreases are driven by a delicate balance between the effects of vertical turbulent fluxes, radiative cooling, large-scale subsidence, and lower-tropospheric stability on the boundary-layer moisture budget. High-latitude low cloud optical depth increases are dominated by phase changes in mixed- phase clouds. The causes of inter-model spread in cloud feedback are discussed, focusing particularly on the role of unresolved parameterized processes such as cloud microphysics, turbulence, and convection

A Similarity Measure for GPU Kernel Subgraph Matching

Accelerator architectures specialize in executing SIMD (single instruction, multiple data) in lockstep. Because the majority of CUDA applications are parallelized loops, control flow information can provide an in-depth characterization of a kernel. CUDAflow is a tool that statically separates CUDA binaries into basic block regions and dynamically measures instruction and basic block frequencies. CUDAflow captures this information in a control flow graph (CFG) and performs subgraph matching across various kernel's CFGs to gain insights to an application's resource requirements, based on the shape and traversal of the graph, instruction operations executed and registers allocated, among other information. The utility of CUDAflow is demonstrated with SHOC and Rodinia application case studies on a variety of GPU architectures, revealing novel thread divergence characteristics that facilitates end users, autotuners and compilers in generating high performing code

Fourier domain mode locking laser based on two-pump optical parametric amplification

We present a Fourier domain mode locked (FDML) laser scanning from 1540 to 1570 using two-pump optical parametric amplifier (OPA) as the gain medium. The sweep rate of 39.683 kHz is achieved. © 2010 IEEE.published_or_final_versionThe IEEE Photonics Society Summer Topical Meetings, Playa del Carmen, Mexico, 19-21 July 2010. In Proceedings of PHOSST, 2010, p. 186-18