Dose-dependent modulation of HIF-1alpha/sima controls the rate of cell migration and invasion in Drosophila ovary border cells.

The role of the hypoxic response during metastasis was analysed in migrating border cells of the Drosophila ovary. Acute exposure to 1% O(2) delayed or blocked border cell migration (BCM), whereas prolonged exposure resulted in the first documented accelerated BCM phenotype. Similarly, manipulating the expression levels of sima, the Drosophila hypoxia-inducible factor (HIF)-1alpha ortholog, revealed that Sima can either block or restore BCM in a dose-dependent manner. In contrast, over-expression of Vhl (Drosophila von Hippel-Lindau) generated a range of phenotypes, including blocked, delayed and accelerated BCM, whereas over-expression of hph (Drosophila HIF prolyl hydroxylase) only accelerated BCM. Mosaic clone analysis of sima or tango (HIF-1beta ortholog) mutants revealed that cells lacking Hif-1 transcriptional activity were preferentially detected in the leading cell position of the cluster, resulting in either a delay or acceleration of BCM. Moreover, in sima mutant cell clones, there was reduced expression of nuclear slow border cells (Slbo) and basolateral DE-cadherin, proteins essential for proper BCM. These results show that Sima levels define the rate of BCM in part through regulation of Slbo and DE-cadherin, and suggest that dynamic regulation of Hif-1 activity is necessary to maintain invasive potential of migrating epithelial cells.

Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study.

BACKGROUND: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. METHODS: Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. RESULTS: After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. CONCLUSIONS: This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk.

NYD-SP18 is associated with obesity in the NHLBI Family Heart Study.

OBJECTIVE: The NHLBI Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q with a logarithm of odds score of 4.9 for body mass index (BMI). DESIGN: We report the results of fine mapping the linkage peak using 1020 single nucleotide polymorphisms (SNPs) to test for association to obesity in families exhibiting linkage to chromosome 7. Association observed in linked families (284 obese cases/381 controls) was examined in an independent set of unrelated FHS participants (172 obese cases/308 controls) to validate the observed association. Two dichotomous obesity phenotypes were studied based on clinical BMI cutoffs and the sex-specific distribution of both BMI and leptin levels. RESULTS: Using a P-value of 0.01 as criteria for association in the linked families, a P-value of 0.05 as criteria for association in the unrelated sample, and requiring consistency in the direction of the effect of the minor allele between the two samples, we identified two coding SNPs in the NYD-SP18 gene with minor alleles increasing the risk of obesity. Adjustment for exercise, smoking and FTO genotype did not influence the result in linked families, but improved the result in the unrelated sample. Carrying a minor allele of the nonsynonymous SNP rs6971091 conferred an odds ratio of at least 2 for obesity defined by both BMI and leptin levels. CONCLUSION: The effect of the NYD-SP18 SNP on obesity was larger than the effect of FTO in FHS families. Publicly available results from genome-wide association studies support the association between NYD-SP18 and BMI. The NYD-SP18 gene is described as testes development related, but little is known about the gene's function or the mechanism by which it may influence risk for obesity.

Deciphering the language of the genome.

The non-coding DNA in eukaryotic genomes encodes a language which programs organismal growth and development. We show that a linguistic and cryptographic approach can be used to deduce the syntax of this programming language for gene regulation and to compile a dictionary of enhancers which form its words.

The tuning of human photopigments may minimize red-green chromatic signals in natural conditions.

Humans and other Old World primates (Catarrhini) share very similar L (long-wavelength, 'red') and M (medium-wavelength, 'green') cone photopigment spectral sensitivities, with peaks at around 563 nm and 535 nm, respectively. Changes of single amino acid residues at critical sites in photopigment opsins can alter this peak tuning. Moreover, the photopigment alleles and spectral sensitivities of human populations are polymorphic, so there is potential for adaptive change or genetic drift. The manifest lack of variability suggests that the tuning of the L and M photopigments has adaptive significance, but the reason for this conservatism is unclear. To assess how natural spectral reflectances may have influenced pigment tuning, we have measured the chromatic (i.e. difference) signals available in natural scenes, and estimated how these signals would vary if spectral sensitivities of the pigments moved to longer or to shorter wavelengths. The size of the chromatic signal is, predictably, dependent principally on the spectral separation of the photopigments, but in addition we find that for a fixed separation there is a marked dependence on the specific peak tuning of the photopigments. Indeed, the naturally occurring L and M cone peaks may be set at a pair of points on the spectrum that on average minimizes the 'L-M' (i.e. red-green) chromatic signal. This somewhat paradoxical observation supports the view that red-green vision has evolved for a specific task, such as finding fruit, whilst minimizing interference by the chromatic signal in luminance vision to which both L and M cones contribute.

Thrombosis of the internal carotid artery due to soft palate injury.

Thrombosis of the internal carotid artery is a rare complication of soft palate injury, only 16 cases having been previously documented. We present the case of a 5 1/2 year-old-boy who sustained an apparently trivial laceration to the right aspect of the soft palate. However, 48 hours after injury, a right cerebral infarct occurred with subsequent left hemiparesis. On supportive and rehabilitative management he made a good recovery over a period of one year.

Mucormycosis of the trachea: an unusual cause of acute upper airway obstruction.

Mucormycosis (phycomycosis) has been reported to involve most organ systems in man. We report a young insulin-dependent diabetic who presented with acute upper airway obstruction because of isolated mucormycosis of the trachea. A combination of amphotericin B and surgical resection of the lower two thirds of the larynx and five tracheal rings with primary reanastomosis has resulted in a cure with no evidence of recurrence after nine months of follow-up. To our knowledge, this represents the first report of isolated tracheal mucormycosis and/or acute upper airway obstruction due to mucormycosis.

Ligation of patent ductus arteriosus in very low birth weight infants.

Twenty-five low birth weight, premature neonates who were refractory to aggressive medical management underwent ligation of symptomatic patent ductus arteriosus. The mean birth weight was 1,007 g and the mean gestational age 29 weeks. Six patients (24 percent) died before discharge, two from continued cardiorespiratory failure. Echocardiography showed significant improvement in left atrial and left ventricular dimensions after ligation. In the premature neonate with respiratory distress and congestive heart failure refractory to aggressive medical management, surgical ligation may be accomplished with an acceptable hospital mortality in very low birth weight infants.

Relation between cognitive and motor-oriented systems of visual position perception.

Although subjects failed to detect a target displacement if it occurred near the time of a saccadic eye movement (a cognitive visual task), they were still able to point to the center of the target with an unseen pointer (a motor visual task). Pointing performance was not affected by detecting or failing to detect a stimulus displacement. The experiments demonstrate that some information that is available to a motor-oriented visual system is unavailable to the cognitive visual system, under conditions simulating normal perception.