DLX6 (distal-less homeobox 6)

DLX6 belongs to the six-member family of DLX genes characterized by a homeobox related to that found in the insect Distal-less (Dll) gene. The six DLX genes are organized as three bigenic pairs with a tail-to-tail orientation (Zerucha et al., 2000), and located on chromosomes where HOX clusters are also found (DLX5/DLX6; 7q21.3, syntenic to the HOXA cluster), (DLX1/DLX2; 2q32 syntenic to the HOXD cluster) and (DLX3/DLX4; 17q21.33 syntenic to the HOXB cluster). During embryonic development DLX genes are involved in the control of appendage and craniofacial morphogenesis and in the differentiation of reproductive organs; in the adult they play a role in bone homeostasis and in the maintenance of tissue integrity

DLX5 (distal-less homeobox 5)

DLX5 belongs to the six-member family of DLX genes characterized by a homeobox related to that found in the insect Distal-less (Dll) gene. The six DLX genes are organized as three bigenic pairs with a tail-to-tail orientation (Zerucha et al., 2000) and located on chromosomes where HOX clusters are also found (DLX5/DLX6; 7q21.3, syntenic to the HOXA cluster), (DLX1/DLX2; 2q32, syntenic to the HOXD cluster; Simeone et al., 1994) and (DLX3/DLX4; 17q21.33, syntenic to the HOXB cluster). During embryonic development DLX genes are involved in the control of appendage and craniofacial morphogenesis and in the differentiation of reproductive organs; in the adult they play a role in bone homeostasis and in the maintenance of tissue integrity

PIONIER: a visitor instrument for the VLTI

PIONIER is a 4-telescope visitor instrument for the VLTI, planned to see its first fringes in 2010. It combines four ATs or four UTs using a pairwise ABCD integrated optics combiner that can also be used in scanning mode. It provides low spectral resolution in H and K band. PIONIER is designed for imaging with a specific emphasis on fast fringe recording to allow closure-phases and visibilities to be precisely measured. In this work we provide the detailed description of the instrument and present its updated status.Comment: Proceedings of SPIE conference Optical and Infrared Interferometry II (Conference 7734) San Diego 201

Movement of the external ear in human embryo

Introduction: External ears, one of the major face components, show an interesting movement during craniofacial morphogenesis in human embryo. The present study was performed to see if movement of the external ears in a human embryo could be explained by differential growth. Methods: In all, 171 samples between Carnegie stage (CS) 17 and CS 23 were selected from MR image datasets of human embryos obtained from the Kyoto Collection of Human Embryos. The three-dimensional absolute positio

Apoptosis screening of human chromosome 21 proteins reveals novel cell death regulators

The functional analysis of chromosome 21 (Chr21) proteins is of great medical relevance. This refers, in particular, to the trisomy of human Chr21, which results in Down’s syndrome, a complex developmental and neurodegenerative disease. In a previous study we analyzed 89 human Chr21 genes for the subcellular localization of their encoded proteins using a transfected-cell array technique. In the present study, the results of the follow-up investigation are presented in which 52 human Chr21 genes were over-expressed in HEK cells using the transfected-cell array platform, and the effect of this protein over-expression on the induction of apoptosis has been analyzed. We found that the over-expression of two Chr21 proteins (claudin-14 and -8) induced cell death independent of the classic caspase-mediated apoptosis. Our results strongly suggest the functional involvement of claudins in the control of the cell cycle and regulation of the cell death induction mechanism

Two prospective, multicenter studies for the identification of biomarker signatures for early detection of pulmonary hypertension (PH): the CIPHER and CIPHER‐MRI studies

A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study aimed to develop a microRNA-based signature for detecting PH in breathless patients and enrolled adults with a high suspicion of PH who had undergone right heart catheterization (RHC). The CIPHER-MRI study was added to assess the performance of this CIPHER signature in a population with low probability of having PH who underwent cardiac magnetic resonance imaging (cMRI) instead of RHC. The microRNA signature was developed using a penalized linear regression (LASSO) model. Data were modeled both with and without N-terminal pro-brain natriuretic peptide (NT-proBNP). Signature performance was assessed against predefined thresholds (lower 98.7% CI bound of ≥0.73 for sensitivity and ≥0.53 for specificity, based on a meta-analysis of echocardiographic data), using RHC as the true diagnosis. Overall, 926 CIPHER participants were screened and 888 were included in the analysis. Of 688 RHC-confirmed PH cases, approximately 40% were already receiving PH treatment. Fifty microRNA (from 311 investigated) were algorithmically selected to be included in the signature. Sensitivity [97.5% CI] of the signature was 0.85 [0.80–0.89] for microRNA-alone and 0.90 [0.86–0.93] for microRNA+NT-proBNP, and the corresponding specificities were 0.33 [0.24–0.44] and 0.28 [0.20–0.39]. Of 80 CIPHER-MRI participants with evaluable data, 7 were considered PH-positive by cMRI whereas 52 were considered PH-positive by the microRNA signature. Due to low specificity, the CIPHER miRNA-based signature for PH (either with or without NT-proBNP in model) did not meet the prespecified diagnostic threshold for the primary analysis

Transcriptome and Proteome Exploration to Model Translation Efficiency and Protein Stability in Lactococcus lactis

This genome-scale study analysed the various parameters influencing protein levels in cells. To achieve this goal, the model bacterium Lactococcus lactis was grown at steady state in continuous cultures at different growth rates, and proteomic and transcriptomic data were thoroughly compared. Ratios of mRNA to protein were highly variable among proteins but also, for a given gene, between the different growth conditions. The modeling of cellular processes combined with a data fitting modeling approach allowed both translation efficiencies and degradation rates to be estimated for each protein in each growth condition. Estimated translational efficiencies and degradation rates strongly differed between proteins and were tested for their biological significance through statistical correlations with relevant parameters such as codon or amino acid bias. These efficiencies and degradation rates were not constant in all growth conditions and were inversely proportional to the growth rate, indicating a more efficient translation at low growth rate but an antagonistic higher rate of protein degradation. Estimated protein median half-lives ranged from 23 to 224 min, underlying the importance of protein degradation notably at low growth rates. The regulation of intracellular protein level was analysed through regulatory coefficient calculations, revealing a complex control depending on protein and growth conditions. The modeling approach enabled translational efficiencies and protein degradation rates to be estimated, two biological parameters extremely difficult to determine experimentally and generally lacking in bacteria. This method is generic and can now be extended to other environments and/or other micro-organisms

Hand use predicts the structure of representations in sensorimotor cortex.

Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than by correlated muscle activity. This also generalized to an experiment using complex multi-finger movements. Finally, the organizational structure correlated with patterns of involuntary co-contracted finger movements for high-force presses. Together, our results suggest that hand use shapes the relative arrangement of finger-specific activity patterns in sensory-motor cortex

Phenothiourea Sensitizes Zebrafish Cranial Neural Crest and Extraocular Muscle Development to Changes in Retinoic Acid and IGF Signaling

1-phenyl 2-thiourea (PTU) is a tyrosinase inhibitor commonly used to block pigmentation and aid visualization of zebrafish development. At the standard concentration of 0.003% (200 µM), PTU inhibits melanogenesis and reportedly has minimal other effects on zebrafish embryogenesis. We found that 0.003% PTU altered retinoic acid and insulin-like growth factor (IGF) regulation of neural crest and mesodermal components of craniofacial development. Reduction of retinoic acid synthesis by the pan-aldehyde dehydrogenase inhibitor diethylbenzaldehyde, only when combined with 0.003% PTU, resulted in extraocular muscle disorganization. PTU also decreased retinoic acid-induced teratogenic effects on pharyngeal arch and jaw cartilage despite morphologically normal appearing PTU-treated controls. Furthermore, 0.003% PTU in combination with inhibition of IGF signaling through either morpholino knockdown or pharmacologic inhibition of tyrosine kinase receptor phosphorylation, disrupted jaw development and extraocular muscle organization. PTU in and of itself inhibited neural crest development at higher concentrations (0.03%) and had the greatest inhibitory effect when added prior to 22 hours post fertilization (hpf). Addition of 0.003% PTU between 4 and 20 hpf decreased thyroxine (T4) in thyroid follicles in the nasopharynx of 96 hpf embryos. Treatment with exogenous triiodothyronine (T3) and T4 improved, but did not completely rescue, PTU-induced neural crest defects. Thus, PTU should be used with caution when studying zebrafish embryogenesis as it alters the threshold of different signaling pathways important during craniofacial development. The effects of PTU on neural crest development are partially caused by thyroid hormone signaling