Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo

AbstractZic family zinc-finger proteins play various roles in animal development. In mice, five Zic genes (Zic1–5) have been reported. Despite the partly overlapping expression profiles of these genes, mouse mutants for each Zic show distinct phenotypes. To uncover possible redundant roles, we characterized Zic2/Zic3 compound mutant mice. Zic2 and Zic3 are both expressed in presomitic mesoderm, forming and newly generated somites with differential spatiotemporal accentuation. Mice heterozygous for the hypomorphic Zic2 allele together with null Zic3 allele generally showed severe malformations of the axial skeleton, including asymmetric or rostro-caudally bridged vertebrae, and reduction of the number of caudal vertebral bones, that are not obvious in single mutants. These defects were preceded by perturbed somitic marker expression, and reduced paraxial mesoderm progenitors in the primitive streak. These results suggest that Zic2 and Zic3 cooperatively control the segmentation of paraxial mesoderm at multiple stages. In addition to the segmentation abnormality, the compound mutant also showed neural tube defects that ran the entire rostro-caudal extent (craniorachischisis), suggesting that neurulation is another developmental process where Zic2 and Zic3 have redundant functions

Production of Al-based Amorphous Alloys by a Metallic Mold Casting Method and their Thermal Stability

A mostly single Al-based amorphous phase in a sheet form with a thickness of 0.2 mm was found to be formed in the composition range of 6 to 10 at% Ni and 4 to 6 at% Ce in Al-Ni-Ce system by a metallic mold casting process. With increasing sheet thickness, the as-cast structure changes to coexistent amorphous and crystalline phases in the sheets with thicknesses of 0.3 and 0.4 mm and crystalline phases in the sheet with a thickness of 0.5 mm. The composition range in which a mostly single amorphous phase is formed by casting is located at the Al-rich side against the Al_Ni_Ce_6 alloy with the widest supercooled liquid region. No amorphous single phase is formed for the alloys which are located at the Al-poor side, though the supercooled liquid region is observed. The deviation of the glass-formation range by casting from the composition range in which the supercooled liquid region is observed is presumably because of a high growth rate or an easy heterogeneous nucleation of eutectic-type crystalline phases which appear at the Al-poor concentration side. In addition, the application of the casting process to Al_Ni_8Y_8 and Al_Ni_La_6 alloys caused the formation of coexistent amorphous and crystalline phases in the sheet with a thickness of 0.2 mm, presumably because of their lower glass-forming ability. The finding that the amorphous alloy sheet in the Al-based system is formed by the conventional casting process is quite important in the subsequent development of the amorphous alloys by utilizing the high mechanical strengths and good corrosion resistance

Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping

To identify the disease-susceptibility genes of type 2 diabetes, we performed quantitative trait loci (QTL) analysis in F2 populations generated from a BKS.Cg-m+/+Leprdb and C3H/HeJ intercross, taking advantage of genetically determined obesity and diabetes traits associated with the db gene. A genome-wide scan in the F2 populations divided by sex and db genotypes identified 14 QTLs in total and 3 major QTLs on chromosome (Chr) 3 (LOD 5.78) for fat pad weight, Chr 15 (LOD 6.64) for body weight, and Chr 16 (LOD 8.15) for blood glucose concentrations. A linear-model-based genome scan using interactive covariates allowed us to consider sex- or sex-by db-specific effects of each locus. For the most significant QTL on Chr 16, the high-resolution haplotype comparison between BKS and C3H strains reduced the critical QTL interval from 20 to 4.6 Mb by excluding shared haplotype regions and identified 11 nonsynonymous single-nucleotide polymorphisms in six candidate genes

Phospholipase Cδ4 is required for Ca2+ mobilization essential for acrosome reaction in sperm

Zona pellucida (ZP)–induced acrosome reaction in sperm is a required step for mammalian fertilization. However, the precise mechanism of the acrosome reaction remains unclear. We previously reported that PLCδ4 is involved in the ZP-induced acrosome reaction in mouse sperm. Here we have monitored Ca2+ responses in single sperm, and we report that the [Ca2+]i increase in response to ZP, which is essential for driving the acrosome reaction in vivo, is absent in PLCδ4−/− sperm. Progesterone, another physiological inducer of the acrosome reaction, failed to induce sustained [Ca2+]i increases in PLCδ4−/− sperm, and consequently the acrosome reaction was partially inhibited. In addition, we observed oscillatory [Ca2+]i increases in wild-type sperm in response to these acrosome inducers. Calcium imaging studies revealed that the [Ca2+]i increases induced by exposure to ZP and progesterone started at different sites within the sperm head, indicating that these agonists induce the acrosome reaction via different Ca2+ mechanisms. Furthermore, store-operated channel (SOC) activity was severely impaired in PLCδ4−/− sperm. These results indicate that PLCδ4 is an important enzyme for intracellular [Ca2+]i mobilization in the ZP-induced acrosome reaction and for sustained [Ca2+]i increases through SOC induced by ZP and progesterone in sperm

Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages

<p>Abstract</p> <p>Background</p> <p>Deterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice.</p> <p>Results</p> <p>Elevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice.</p> <p>Conclusion</p> <p>These results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.</p

Experimental Studies on Protective Effects of FK506 Against Hepatic Ischemia-Reperfusion Injury

Purposes ; FK506 (strong immunosuppressive agent) was investigated experimentally whether to protect the hepatic IRI. Methods ; Warm ischemic experiment using pigs and rats were performed and examined whether FK506 is effective. Results ; The results obtained are as follows. 1. Warm ischemia allowed time of the pigs without FK506 was 150 minutes, but as for that of FK506 group, the extension of 30 minutes was got in 180 minutes. 2. Biliary excretion rate of BSP after reperfusion were better in the group of 180 minutes ischemia with FK506 than in without FK506 group. 3. Chemiluminescence intensity in the peripheral neutrophils and adhered and infiltrated leukocytes in the liver were suppressed markedly by FK506. 4. The vascular endothelium with the scanning electron microscope was relatively preserved in the FK506 group comparing to the placebo group on 30 minutes after reperfusion. 5. Stress gastric ulcer was controlled and myeloperoxidase activity in the gastric mucosa was suppressed by FK506. Conclusion ; Based on the results of theses experiments, it was suggested that FK506 has a protective effect on IRI by suppressing : the impairment of sinusoidal endothelial cells ; the activation of KCs ; the disturbance of micro-circulation ; oxidative stress ; inflammation ; and the accumulation of leukocytes

HASC2011corpus: Towards the Common Ground of Human Activity Recognition

UbiComp '11 Proceedings of the 13th international conference on Ubiquitous computing, September 17-21, 2011, Beijing, ChinaHuman activity recognition through the wearable sensor will enable a next-generation human-oriented biquitous computing. However, most of research on human activity recognition so far is based on small number of subjects, and non-public data. To overcome the situation, we have gathered 4897 accelerometer data with 116 subjects and compose them as HASC2011corpus. In the field of pattern recognition, it is very important to evaluate and to improve the recognition methods by using the same dataset as a common ground. We make the HASC2011corpus into public for the research community to use it as a common ground of the Human Activity Recognition. We also show several facts and results of obtained from the corpus