Development of high-order harmonic focusing system based on ellipsoidal mirror.

We have developed a focusing system for extreme ultraviolet light produced by high-order harmonic generation. An ellipsoidal mirror with a precise surface shape was fabricated and installed into the focusing system. A rigid mirror manipulator and a beam profiler were employed to perform precise and stable mirror alignment. As a demonstration of the focusing performance, high-order harmonics in the wavelength range of 13.5-19.5 nm were successfully focused into a 2.4 × 2.3 µm(2) spot.

A possible connection between tumor necrosis factor alpha and adropin levels in polycystic ovary syndrome.

CONTEXT: Adropin is a peptide hormone implicated in the regulation of insulin sensitivity and energy homeostasis. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disease associated with insulin resistance. It has been demonstrated that various inflammatory markers increased in PCOS including TNF-α. TNF-α regulates the secretion of certain peptides which play a crucial role in glucose and lipid homeostasis. There is also some evidence of a link between TNF-α and adropin. OBJECTIVE: To ascertain whether there is an association between circulating adropin levels and TNF-α in PCOS. PATIENTS AND DESIGN: 152 women with PCOS and 152 age- and body mass index-matched controls without PCOS were recruited for this cross-sectional study. MAIN OUTCOME MEASURES: Adropin and TNF-α levels were measured using ELISA. RESULTS: Adropin levels were lower in the PCOS group compared with the control group (7.43 ± 0.79 vs. 9.42 ± 0.76 ng/ml, P < 0.001), whereas TNF-α levels were higher (49.93 ± 3.39 vs. 35.83 ± 2.47 pg/ml, P < 0.001). A strongly negative correlation was found between circulating adropin levels and TNF-α levels in women with PCOS (r = -0.407, P < 0.001). Binary logistic regression analysis revealed that decreased adropin levels were significantly associated with high odds of having PCOS, although, after adjustment for TNF-α, this link vanished. Additionally, multiple linear regression analysis showed that HOMA-IR and TFN-α independently predicted adropin levels. CONCLUSIONS: Serum adropin levels are significantly decreased in PCOS and are inversely associated with TNF-α. Further dissection of the nature of this association can open new therapeutic options for metabolic diseases.

Serum nesfatin-1 and leptin levels in non-obese girls with premature thelarche.

AIM: We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process. SUBJECTS-METHODS: Non-obese girls who presented with the complaint of early (2-8 years) and isolated breast development were included in the study. The control group consisted of age-matched healthy prepubertal girls. Auxological measurements were performed in all subjects. Gonadotropin-releasing hormone (GnRH) stimulation test and bone age assessment were conducted in subjects with early breast development. Girls with a bone age/chronologic age ratio <1.2 and a peak luteinizing hormone (LH) response to GnRH stimulation <5 mIU/L were included in the PT group. RESULTS: The study included 22 non-obese girls with PT and 24 healthy prepubertal controls. Body mass index (BMI), BMI-standard deviation score (SDS) and height SDS were similar between the groups (p > 0.05). Serum leptin and nesfatin-1 levels were found significantly higher in the PT group compared to controls (p < 0.05). No correlation was detected between nesfatin-1 and basal LH, basal follicle stimulating hormone (FSH), stimulated peak LH, peak FSH, leptin levels and anthropometric parameters in the PT group (p > 0.05). CONCLUSION: Results of the present study showed that serum nesfatin-1 and leptin levels are significantly higher in girls with PT than in prepubertal controls. This finding suggests that similar to leptin, nesfatin-1 may also have a central or peripheral role in the initiation of pubertal process and may be related to PT pathogenesis.

Lower cocaine- and amphetamine-regulated transcript levels pose a risk for developing PCOS.

UNLABELLED: Cocaine- and amphetamine-regulated transcript (CART) is an anorectic neuropeptide abundantly expressed in the central, peripheral, and enteric nervous systems, as well as in several different endocrine cell types. Besides regulating food intake and endocrine function, it is also proposed to modulate ovarian function during follicular waves in cattle and has potent inhibitory effects on follicular development. Polycystic ovary syndrome (PCOS), presenting itself with multiple follicular ovarian cysts, is the most common endocrinological disorder among women of reproductive age. Here we aimed to investigate the association of this peptide with PCOS. Our research was designed as a case-control study, in which a total of 148 subjects (73 with PCOS and 75 age- and BMI-matched CONTROLS) were consecutively recruited. Fasting blood glucose (FBG), insulin, high-sensitivity C-reactive protein, lipids, follicle stimulating hormone, luteinizing hormone, estradiol, CART, and free testosterone levels were measured in all participants. Homeostasis model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) were calculated. CART levels were found to be significantly lower in patients with PCOS (PCOS: 90.77 ± 5.98 pg/ml, CONTROLS: 93.24 ± 8.17 pg/ml, p=0.038). Pearson's correlation analysis showed that CART was significantly and negatively correlated with BMI and waist circumference in both (PCOS and control) groups. In CONTROLS only, CART was positively correlated with insulin and HOMA-IR, and negatively correlated with FBG. Logistic regression analysis results are suggestive of a possible protective effect of CART against PCOS (OR: 0.94, 95% CI=0.888-0.997, p=0.038).

Experimental validation of a novel compact focusing scheme for future energy-frontier linear lepton colliders.

A novel scheme for the focusing of high-energy leptons in future linear colliders was proposed in 2001 [P. Raimondi and A. Seryi, Phys. Rev. Lett. 86, 3779 (2001)]. This scheme has many advantageous properties over previously studied focusing schemes, including being significantly shorter for a given energy and having a significantly better energy bandwidth. Experimental results from the ATF2 accelerator at KEK are presented that validate the operating principle of such a scheme by demonstrating the demagnification of a 1.3 GeV electron beam down to below 65 nm in height using an energy-scaled version of the compact focusing optics designed for the ILC collider.

Low omentin-1 levels are related with clinical and metabolic parameters in obese children.

This is the first clinical study evaluating the relation of serum omentin 1 levels with anthropometric and metabolic parameters in obese children with a particular interest to identify the possible role of omentin 1 in childhood obesity and related metabolic disturbances.The study included obese children with a body mass index (BMI)>95th percentile and healthy children with a BMI<85th percentile. The healthy and obese subjects had similar age and gender distribution. Glucose, insulin, lipid profile, and omentin 1 levels were measured to evaluate the metabolic parameters.49 obese children who applied to our department with complaint of weight gain and 30 healthy age and sex matched subjects were enrolled. In obese children BMI, body mass index-standard deviation score (BMI-SDS), systolic blood pressure (SBP), diastolic blood pressure (DBP), mid-arm circumference (MAC), triceps skin fold (TSF), waist circumference (WC), homeostasis model assessment-insulin resistance (HOMA-IR), serum insulin, and triglyceride levels were higher whereas omentin-1 levels were lower than control subjects (p<0.05). In the obese group, omentin 1 level was negatively correlated with BMI, insulin, HOMA-IR, and WC, while no significant correlation was observed with other parameters (p>0.05). Additionally, although statistically insignificant, patients with IR (n=31) had lower omentin-1 levels compared to obese children without IR (n=18).Our data indicates that serum omentin 1 levels are i) lower in obese children and ii) negatively correlated with BMI, WC, HOMA-IR and insulin levels suggesting that omentin 1 might be a biomarker for metabolic dysfunction also in childhood and adolescence. Lower omentin 1 levels tended to be associated with insulin resistance however this association failed to reach statistical significance. Further studies in larger populations are needed to better-define the relation of omentin 1 and insulin resistance in obese children.

Seasonal changes of fertilizer impacts on agricultural drainage in a salinized area in Adana, Turkey.

Seasonal changes in the impacts of fertilizer on the composition of agricultural drainage water were examined by analyzing the (87)Sr/(86)Sr isotope ratio and chemical composition of drainage water samples. Samples of drainage water were taken from the main drainage canals of the Lower Seyhan Irrigation Project, at sites designated as D10, D11, and D12. Plots of (87)Sr/(86)Sr vs. 1/Sr indicated that the (87)Sr/(86)Sr ratio of drainage water was positively related to those of fertilizer and irrigation water. The origins of Sr in two of the end-components were fertilizer and irrigation water. The data from the end-drain in winter suggested that the origin of Sr in the third end-component was fossil seawater. Analysis of a mixing model incorporating these three end-components showed that the origins of Sr in drainage differed markedly between summer and winter. Fertilizer made the greatest contribution to Sr in drainage water both in summer and winter, contributing 38-72% of total Sr in summer and 64-87% of total Sr in winter. In summer, fertilizer contributed 72% of total Sr in drainage water in D12, 44% in D10, and 38% in D11. This result implies that fertilizer was applied excessively at the D12 site. In winter, seawater accounted for 10% of Sr in drainage water in D12, whereas it accounted for 19-27% of Sr in drainage water in D10 and D11. Therefore, at least 70% of the salt in drainage water originates from fertilizer and irrigation water. At this study site, the salt originating from seawater is replaced by that from fertilizer and irrigation water, due to intensive agricultural management. The study site is a delta that lay on the ocean subsurface at least 3000years ago, and therefore, was originally a primary salinization area. This result suggests that anthropogenic secondary salinization progressed over time via fertilizer and irrigation applications.

Cocktail-substrate assay system for mechanism-based inhibition of CYP2C9, CYP2D6, and CYP3A using human liver microsomes at an early stage of drug development.

We established a mechanism-based inhibition cocktail-substrate assay system using human liver microsomes and drug-probe substrates that enabled simultaneous estimation of the inactivation of main cytochrome P450 (CYP) enzymes, CYP2C9, CYP2D6, and CYP3A, in drug metabolism. The inactivation kinetic parameters of typical mechanism-based inhibitors, tienilic acid, paroxetine, and erythromycin, for each enzyme in the cocktail-substrate assay were almost in agreement with the values obtained in the single-substrate assay. Using this system, we confirmed that multiple CYP inactivation caused by mechanism-based inhibitors such as isoniazid and amiodarone could be detected simultaneously. Mechanism-based inhibition potency can be estimated by the determination of the observed inactivation rate constants (k(obs)) at a single concentration of test compounds because the k(obs) of eleven CYP3A inactivators at 10 microM in the assay system nearly corresponded to k(inact)/K(I) values, an indicator of a compound's propensity to alter the activity of a CYP in vivo (R(2) = 0.97). Therefore, this cocktail-substrate assay is considered to be a powerful tool for evaluating mechanism-based inhibition at an early stage of drug development.

Optical coherence tomography evaluation of zotarolimus-eluting stents at 9-month follow-up: comparison with sirolimus-eluting stents.

OBJECTIVE: To evaluate the vascular response at 9 months after zotarolimus-eluting stent (ZES; Endeavor) implantation using optical coherence tomography (OCT). These findings were compared with those after implantation of a sirolimus-eluting stent (SES; Cypher Select). DESIGN: Cross-sectional observational study with prospective OCT registry. SETTING: Nine months after ZES or SES implantation. PATIENTS AND METHODS: A total of 68 patients (32 ZES and 36 SES) underwent OCT at 9 months after stent implantation. The neointima hyperplasia (NIH) thickness inside each strut and percentage of NIH area at every 1 mm cross section were measured. MAIN OUTCOME MEASUREMENT: The degree of neointimal coverage and the prevalence of malapposition at 9 months after ZES and SES implantation using OCT. RESULTS: The mean (SD) NIH thickness (251.2 (110.0) mum vs 85.5 (53.3) mum, p<0.001) and percentage of NIH area (27.9 (9.1)% vs 11.2 (7.1)%, p<0.001) were significantly greater in ZES than in SES. The prevalence of uncovered strut as well as malapposed strut was significantly lower in ZES than in SES (0.3% vs 12.3%, p<0.001 and 0.08% vs 2.6%, p<0.001). Thrombus was not observed in ZES (0.0% in ZES vs 27.8% in SES, p = 0.001). CONCLUSIONS: Neointimal coverage in ZES was almost complete and malapposition was very rare at 9-months' follow-up.

Altered activity of lysophospholipase D, which produces bioactive lysophosphatidic acid and choline, in serum from women with pathological pregnancy.

Altered lipid metabolism is associated with human abnormal pregnancy, such as pre-eclampsia and preterm labor, and potentially leads to fetus loss. A causative factor for the onset and progress of the systemic multifactorial syndromes associated with the pathological pregnancy is oxidized low-density lipoprotein, an active identity of which was postulated to be lysophosphatidic acid (LPA). We previously found that LPA is produced extracellularly by plasma lysophospholipase D (lysoPLD) activity of autotaxin, a tumor cell motility-stimulating protein. In this study, a convenient assay based on the choline released from endogenous substrate or exogenous lysophosphatidylcholine (LPC) was used for comparison of serum lysoPLD activity among patients with normal and abnormal pregnancy. The serum choline-producing activity was found to be mainly due to autotaxin, and dependent on its dilution rate. There was some association between low dilution dependency of serum lysoPLD activity toward an exogenous LPC and high lysoPLD activity toward endogenous substrates in cases of patients with preterm labor and pre-eclampsia. However, there was no difference in the serum level of LPC between women with normal pregnancy and those with pathological pregnancy. These results indicate that production of bioactive LPA by lysoPLD activity is elevated by an unknown mechanism that may be related to increased availability of endogenous substrates LPC, but not its concentration in human serum. If the level of LPA in blood circulation is elevated in the pathological pregnancies in vivo, it may play a role in induction and/or progression of systemic vascular dysfunction seen patients with preterm labor or pre-eclampsia.

Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo.

Intracerebral hemorrhage represents stroke characterized by formation and expansion of hematoma within brain parenchyma. Blood-derived factors released from hematoma are considered to be involved in poor prognosis of this disorder. We previously reported that thrombin, a blood-derived serine protease, induced cytotoxicity in the cerebral cortex and the striatum in organotypic slice cultures, which depended on mitogen-activated protein kinase (MAPK) pathways. Here we investigated the mechanisms of thrombin cytotoxicity in the striatum in vivo. Thrombin microinjected into the striatum of adult rats induced neuronal death and microglial activation around the injection site. Neuronal loss without any sign of nuclear fragmentation was observed as early as 4 h after thrombin injection, which was followed by gradual neuronal death exhibiting nuclear fragmentation. Thrombin-induced damage assessed at 72 h after injection was partially but significantly reduced by concomitant administration of inhibitors of MAPK pathways. Activation of extracellular signal-regulated kinase (ERK) and p38 MAPK in response to thrombin was verified by Western blot analysis. Moreover, phosphorylated ERK and p38 MAPK were localized prominently in reactive microglia, and inhibition of microglial activation by minocycline attenuated thrombin-induced damage, suggesting that reactive microglia were responsible for thrombin-induced neuronal death. Thus, MAPK pathways and microglial activation may serve as therapeutic targets of pathogenic conditions associated with hemorrhagic stroke.

Pharmacokinetics and metabolism of TR-14035, a novel antagonist of a4ss1/a4ss7 integrin mediated cell adhesion, in rat and dog.

The pharmacokinetics and disposition of N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine (TR-14035), a novel a4ss1/a4ss7 antagonist, were investigated in the rat and dog. Results indicate extensive clearance of TR-14035 and low oral bioavailability, 17% and 13% in the rat and dog, respectively, at an oral dose of 10 mg/kg. At least 63% of the oral dose was absorbed from the gastrointestinal tract in the rat, and about one-third of the intravenous dose was excreted into bile as unchanged drug in the rat and dog. These data indicate that the oral bioavailability of TR-14035 was limited due to significant first-pass metabolism and biliary excretion in the liver. A species-dependent difference in metabolism was observed. The principal metabolite, O-desmethyl TR-14035, observed in rat, dog and probably human, was further conjugated with sulfate in the rat, but never in dog and human, based on in vitro metabolism and in vivo metabolite profile studies. Urinary excretion was a minor elimination route, but an interesting species difference was recognized. TR-14035 was reabsorbed from the rat renal proximal tubules, and by contrast, secreted into the tubules in the dog, probably via active transport systems.

Decreased activity of hepatic P-glycoprotein in the isolated perfused liver of the adjuvant arthritis rat.

1. We investigated the hepatobiliary transport of doxorubicin in the isolated perfused liver prepared from the adjuvant arthritis rat, an animal model for rheumatoid arthritis, to examine the hepatic P-glycoprotein activity in the adjuvant arthritis rat. 2. Liver was isolated from the normal and the adjuvant arthritis rat and perfused for 60 min with recirculating buffer and the perfusate and bile samples were collected at timed interval. 3. The elimination of doxorubicin in the adjuvant arthritis rat tended to be reduced, but it was not significantly different from the normal rat. Biliary clearance (CL(bile)) in the normal rat was 1.93 +/- 0.48 ml min(-1), whereas, CL(bile) in the adjuvant arthritis rat was significantly decreased to 0.40 +/- 0.13 ml min(-1). 4. CL(bile) was markedly decreased to about 0.15 ml min(-1) in the presence of 100 microM verapamil in both types of rat. Methotrexate treatment had no effect on CL(bile) in both the normal and adjuvant arthritis rat (2.18 +/- 0.22 and 0.47 +/- 0.22 ml min(-1), respectively). 5. The results suggest that the hepatic P-glycoprotein activity was markedly decreased in the adjuvant arthritis rat and the effect of methotrexate on the hepatic P-glycoprotein activity did not corresponded to its anti-inflammatory effect.

[Thrombus entrapped in a patent foramen ovale of the atrial septum].

A 59-year-old women was referred to our hospital due to severe dyspnea and shock status 12 days after intracranial hematoma evacuation for the hypertensive right putaminal hemorrhage. Transthoracic echocardiography revealed right ventricular dilatation and floating structures in the right atrium. Transesophageal echocardiography demonstrated a large, snake-like structure crossing her foramen ovale of the interatrial septum, and impending paradoxical embolism was diagnosed. She did not receive any anticoagulation and surgery due to recent cerebral hemorrhage. Follow-up TEE showed complete disappearance of the thrombus in the atrium two weeks after the onset. Phlebogram of deep vein demonstrated several thrombus in her leg. She underwent placement of inferior vena cava filter and was discharged from our hospital without any symptom of paradoxical embolism.

Differences in pharmacokinetics and hepatobiliary transport of a novel anti-inflammatory agent between normal and adjuvant arthritis rats.

1. The pharmacokinetics, particularly the hepatobiliary transport of T-5557 ((3-methyl-2-oxo-piperadin-3-yl)-acetic acid N'-(3-thieophen-2-yl-8-methoxy-quinazolin-1-yl)-hydrazide), a novel anti-inflammatory agent, has been examined in normal and adjuvant arthritis (AA) rats. 2. Following oral administration of T-5557, the absolute bioavailability in AA rats was increased by sixfold compared with normal rats. The extent of binding T-5557 to plasma proteins obtained from AA rats was markedly greater than in normal rats (97.0 versus 88.2%). The biliary clearance in AA rats was significantly lower than that in normal rats (1.186 versus 5.621 ml min(-1) kg(-1)), and lower intrinsic biliary clearance was also observed in AA rats (40.33 versus 69.83 ml min(-1) kg(-1)). 3. Concomitant administration of T-5557 with quinidine, a potent P-glycoprotein inhibitor, to normal rats caused a significant decrease in the biliary clearance of T-5557 by 37.9%. Moreover, the transport of T-5557 for the apical-to-basal compartment in a Caco-2 cells' monolayer was fourfold lower than that for the opposite direction, and was increased in the presence of quinidine and verapamil. 4. These results suggest that P-glycoprotein is involved in the biliary excretion of T-5557 and the decrease in the transport activity as well as the increase in plasma protein binding caused the elevated plasma concentration and bioavailability of T-5557 in AA rats.

Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats.

1. We investigated the difference in hepatobiliary transport of methotrexate in normal and adjuvant arthritis (AA) rats and substantiated the expression level of multidrug resistance-associated protein 2 (MRP2) in the liver. 2. Biliary clearance of methotrexate in normal and AA rats was calculated from plasma concentrations and biliary excretion following intravenous infusion and hepatic uptake clearance was estimated from an integration plot using methotrexate concentrations in plasma and liver. 3. Biliary clearance of methotrexate in AA rats was 2.30 +/- 0.23 ml min(-1) kg(-1) (mean SD) and significantly lower than in normal rats (8.42 +/- 0.81 ml min(-1) kg(-1)). The uptake clearance of methotrexate in AA rats was also lower than in normal rats (0.138 versus 0.278 ml min(-1) g liver(-1)). 4. MRP2 in the liver was detected by fluorescein isothiocyanate-labelled antibody and visualized using a confocal laser microscope system. The expression level of MRP2 in AA rats was very low compared with normal rats, indicating a down-regulation in AA rats. 5. In conclusion, biliary clearance of methotrexate was decreased due to the lower activities in both uptake and canalicular secretion, suggesting that several active transporters in the liver, including MRP2, are down-regulated in AA rats.

Real-time [11C]methionine translocation in barley in relation to mugineic acid phytosiderophore biosynthesis.

[11C]Methionine was supplied through barley roots and the 11C signal was followed for 90 min using a real-time imaging system (PETIS), with subsequent development of autoradiographic images of the whole plant. In all cases, [11C]methionine was first translocated to the 'discrimination center', the basal part of the shoot, and this part was most strongly labeled. Methionine absorbed by the roots of the plants was subsequently translocated to other parts of the plant. In Fe-deficient barley plants, a drastic reduction in [11C]methionine translocation from the roots to the shoot was observed, while a greater amount of 11C was found in the leaves of Fe-sufficient or methionine-pretreated Fe-deficient plants. Treatment of Fe-deficient plants with aminooxyacetic acid, an inhibitor of nicotianamine aminotransferase, increased the translocation of [11C]methionine to the shoot. The retention of exogenously supplied [11C]methionine in the roots of Fe-deficient barley indicates that the methionine is used in the biosynthesis of mugineic acid phytosiderophores in barley roots. This and the absence of methionine movement from shoots to the roots suggest that the mugineic acid precursor methionine originates in the roots of plants.

The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis.

The murine Foxc1/Mf1 and Foxc2/Mfh1 genes encode closely related forkhead/winged helix transcription factors with overlapping expression in the forming somites and head mesoderm and endothelial and mesenchymal cells of the developing heart and blood vessels. Embryos lacking either Foxc1 or Foxc2, and most compound heterozygotes, die pre- or perinatally with similar abnormal phenotypes, including defects in the axial skeleton and cardiovascular system. However, somites and major blood vessels do form. This suggested that the genes have similar, dose-dependent functions, and compensate for each other in the early development of the heart, blood vessels, and somites. In support of this hypothesis, we show here that compound Foxc1; Foxc2 homozygotes die earlier and with much more severe defects than single homozygotes alone. Significantly, they have profound abnormalities in the first and second branchial arches, and the early remodeling of blood vessels. Moreover, they show a complete absence of segmented paraxial mesoderm, including anterior somites. Analysis of compound homozygotes shows that Foxc1 and Foxc2 are both required for transcription in the anterior presomitic mesoderm of paraxis, Mesp1, Mesp2, Hes5, and Notch1, and for the formation of sharp boundaries of Dll1, Lfng, and ephrinB2 expression. We propose that the two genes interact with the Notch signaling pathway and are required for the prepatterning of anterior and posterior domains in the presumptive somites through a putative Notch/Delta/Mesp regulatory loop.

The winged helix transcription factor Foxc1a is essential for somitogenesis in zebrafish.

Previous studies identified zebrafish foxc1a and foxc1b as homologs of the mouse forkhead gene, Foxc1. Both genes are transcribed in the unsegmented presomitic mesoderm (PSM), newly formed somites, adaxial cells, and head mesoderm. Here, we show that inhibiting synthesis of Foxc1a (but not Foxc1b) protein with two different morpholino antisense oligonucleotides blocks formation of morphological somites, segment boundaries, and segmented expression of genes normally transcribed in anterior and posterior somites and expression of paraxis implicated in somite epithelialization. Patterning of the anterior PSM is also affected, as judged by the absence of mesp-b, ephrinB2, and ephA4 expression, and the down-regulation of notch5 and notch6. In contrast, the expression of other genes, including mesp-a and papc, in the anterior of somite primordia, and the oscillating expression of deltaC and deltaD in the PSM appear normal. Nevertheless, this expression is apparently insufficient for the maturation of the presumptive somites to proceed to the stage when boundary formation occurs or for the maintenance of anterior/posterior patterning. Mouse embryos that are compound null mutants for Foxc1 and the closely related Foxc2 have no morphological somites and show abnormal expression of Notch signaling pathway genes in the anterior PSM. Therefore, zebrafish foxc1a plays an essential and conserved role in somite formation, regulating both the expression of paraxis and the A/P patterning of somite primordia.