Meteorin regulates mesendoderm development by enhancing nodal expression

During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu

Kinematic aspects of trunk motion and gender effect in normal adults

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to analyze kinematic trunk motion data in normal adults and to investigate gender effect.</p> <p>Methods</p> <p>Kinematic trunk motion data were obtained for 20 healthy subjects (11 men and 9 women; age from 21 to 40 years) during walking a 9 m long lane at a self selected speed, namely, motions in the sagittal (tilt), coronal (obliquity), and transverse (rotation) planes, which were all expressed as motions in global (relative to the ground) and those in pelvic reference frame (relative to pelvis), i.e., tilt (G), obliquity (G), rotation (G), tilt (P), obliquity (P), rotation (P).</p> <p>Results</p> <p>Range of tilt (G), obliquity (G) and rotation (G) showed smaller motion than that of tilt (P), obliquity (P) and rotation (P), respectively. When genders were compared, female trunks showed a 5 degree more extended posture during gait than male trunks (p = 0.002), which appeared to be caused by different lumbar lordosis. Ranges of coronal and transverse plane motion appeared to be correlated. In gait cycle, the trunk motion appeared to counterbalance the lower extremity during swing phase in sagittal plane, and to reduce the angular velocity toward the contralateral side immediate before the contralateral heel strike in the coronal plane.</p> <p>Conclusions</p> <p>Men and women showed different lumbar lordosis during normal gait, which might be partly responsible for the different prevalence of lumbar diseases between genders. However, this needs further investigation.</p

Mind Bomb 1-Expressing Intermediate Progenitors Generate Notch Signaling to Maintain Radial Glial Cells

SummaryNotch signaling is critical for the stemness of radial glial cells (RGCs) during embryonic neurogenesis. Although Notch-signal-receiving events in RGCs have been well characterized, the signal-sending mechanism by the adjacent cells is poorly understood. Here, we report that conditional inactivation of mind bomb-1 (mib1), an essential component for Notch ligand endocytosis, in mice using the nestin and hGFAP promoters resulted in complete loss of Notch activation, which leads to depletion of RGCs, and premature differentiation into intermediate progenitors (IPs) and finally neurons, which were reverted by the introduction of active Notch1. Interestingly, Mib1 expression is restricted in the migrating IPs and newborn neurons, but not in RGCs. Moreover, sorted Mib1+ IPs and neurons can send the Notch signal to neighboring cells. Our results reveal that not only newborn neurons but also IPs are essential Notch-ligand-presenting cells for maintaining RGC stemness during both symmetric and asymmetric divisions

The serum level of 25-hydroxyvitamin D for maximal suppression of parathyroid hormone in children: the relationship between 25-hydroxyvitamin D and parathyroid hormone

PurposeSerum level of 25-hydroxyvitamin D (25-OHD) is considered as the most appropriate marker of vitamin D status. However, only a few studies have investigated the relationship between 25-OHD and parathyroid hormone (PTH) in children. To this end, this study was aimed at evaluating the lowest 25-OHD level that suppresses the production of parathyroid hormone in children.MethodsA retrospective record review was performed for children aged 0.2 to 18 years (n=193; 106 boys and 87 girls) who underwent simultaneous measurements of serum 25-OHD and PTH levels between January 2010 and June 2014.ResultsThe inflection point of serum 25-OHD level for maximal suppression of PTH was at 18.0 ng/mL (95% confidence interval, 14.3–21.7 ng/mL). The median PTH level of the children with 25-OHD levels of <18.0 ng/mL was higher than that of children with 25-OHD levels ≥ 18.0 ng/mL (P<0.0001). The median calcium level of children with 25-OHD levels<18.0 ng/mL was lower than that of children with 25-OHD levels≥18.0 ng/mL (P=0.0001). The frequency of hyperparathyroidism was higher in the children with 25-OHD levels<18.0 ng/mL than in the children with 25-OHD levels≥18.0 ng/mL (P<0.0001). Hypocalcemia was more prevalent in the children with 25-OHD levels<18.0 ng/mL than in the children with 25-OHD levels≥18.0 ng/mL (P<0.0001).ConclusionThese data suggest that a vitamin D level of 18.0 ng/mL could be the criterion for 25-OHD deficiency in children at the inflection point of the maximal suppression of PTH

Childhood Cancer Mortality and Birth Characteristics in Korea: A National Population-based Birth Cohort Study

To examine the relationship between birth characteristics and childhood cancer mortality, a retrospective cohort study of Korean children was conducted using data collected by the national birth register between 1995 and 2006, which were then individually linked to death data. A cohort of 6,479,406 children was followed from birth until their death or until December 31, 2006. Poisson regression analyses were used to calculate rate ratios of childhood cancer deaths according to birth characteristics. A total of 1,469 cancer deaths were noted and the childhood cancer mortality rate was found to be 3.43 per 100,000 person-years in Korea during the period of 1995-2006. The birth characteristics examined in this study (i.e. , birth weight, gestational age, multiple births, parental ages, and number of siblings) were generally found to be not significantly associated with childhood cancer mortality, and the associations did not vary meaningfully with gender nor with cancer sites. However, among children aged 5-11 yr, higher birth weight was associated with elevated childhood cancer mortality (rate ratio = 1.28, 95% confidence interval 1.04-1.58). Our results offer no overall associations between childhood cancer mortality and birth characteristics, but suggest that the association may be specific to age group

Effect of Dieckol, a Component of Ecklonia cava, on the Promotion of Hair Growth

This study was conducted to evaluate the effect of Ecklonia cava, a marine alga native to Jeju Island in Korea, on the promotion of hair growth. When vibrissa follicles were cultured in the presence of E. cava enzymatic extract (which contains more than 35% of dieckol) for 21 days, E. cava enzymatic extract increased hair-fiber length. In addition, after topical application of the 0.5% E. cava enzymatic extract onto the back of C57BL/6 mice, anagen progression of the hair-shaft was induced. The treatment with E. cava enzymatic extract resulted in the proliferation of immortalized vibrissa dermal papilla cells (DPC). Especially, dieckol, among the isolated compounds from the E. cava enzymatic extract, showed activity that increased the proliferation of DPC. When NIH3T3 fibroblasts were treated with the E. cava enzymatic extract and the isolated compounds from the E. cava enzymatic extract, the E. cava enzymatic extract increased the proliferation of NIH3T3 fibroblasts, but the isolated compounds such as eckol, dieckol, phloroglucinol and triphlorethol-A did not affect the proliferation of NIH3T3 fibroblasts. On the other hand, the E. cava enzymatic extract and dieckol significantly inhibited 5α-reductase activity. These results suggest that dieckol from E. cava can stimulate hair growth by the proliferation of DPC and/or the inhibition of 5α-reductase activity

The recombination-associated protein RdgC adopts a novel toroidal architecture for DNA binding

RecA plays a central role in the nonmutagenic repair of stalled replication forks in bacteria. RdgC, a recombination-associated DNA-binding protein, is a potential negative regulator of RecA function. Here, we have determined the crystal structure of RdgC from Pseudomonas aeruginosa. The J-shaped monomer has a unique fold and can be divided into three structural domains: tip domain, center domain and base domain. Two such monomers dimerize to form a ring-shaped molecule of approximate 2-fold symmetry. Of the two inter-subunit interfaces within the dimer, one interface (‘interface A’) between tip/center domains is more nonpolar than the other (‘interface B’) between base domains. The structure allows us to propose that the RdgC dimer binds dsDNA through the central hole of ∼30 Å diameter. The proposed model is supported by our DNA-binding assays coupled with mutagenesis, which indicate that the conserved positively charged residues on the protein surface around the central hole play important roles in DNA binding. The novel ring-shaped architecture of the RdgC dimer has significant implications for its role in homologous recombination