Combined Methylmalonic Aciduria and Homocystinuria cblC Type of a Taiwanese Infant With c.609G>A and c.567dupT Mutations in the MMACHC Gene

Combined methylmalonic aciduria and homocystinuria, cobalamin (cbl)C type (cblC disease), the most common inborn error of vitamin B12, is a rare disorder of intracellular cbl metabolism because of mutations in the MMACHC gene located in chromosome region 1p34.1. It has become possible to establish phenotype–genotype correlations and to observe ethnicity-related trends. This article provides detailed clinical manifestations and outcomes of a Taiwanese infant boy with early-onset cblC disease, heterozygous for c.609G>A and c.567dupT mutations, although there is limited information about cases with c.609G>A or c.567dupT mutation in the literature. He had no significant clinical abnormality during his neonatal period, whereas elevated C3 level was noted at newborn screening. He presented later with life-threatening manifestations and failure to thrive, which resolved through our treatment, although delayed development was still noted at 6 months of age. To date, all reported cblC patients with the c.609G>A mutation have been East Asians. Therefore, we suggest that c.609G>A should be included in the initial mutation screening tests for a cblC patient in East Asian populations

The (+)-Brevipolide H Displays Anticancer Activity against Human Castration-Resistant Prostate Cancer: The Role of Oxidative Stress and Akt/mTOR/p70S6K-Dependent Pathways in G1 Checkpoint Arrest and Apoptosis

Because conventional chemotherapy is not sufficiently effective against prostate cancer, various examinations have been performed to identify anticancer activity of naturally occurring components and their mechanisms of action. The (+)-brevipolide H, an α-pyrone-based natural compound, induced potent and long-term anticancer effects in human castration-resistant prostate cancer (CRPC) PC-3 cells. Flow cytofluorometric analysis with propidium iodide staining showed (+)-brevipolide H-induced G1 arrest of cell cycle and subsequent apoptosis through induction of caspase cascades. Since Akt/mTOR pathway has been well substantiated in participating in cell cycle progression in G1 phase, its signaling and downstream regulators were examined. Consequently, (+)-brevipolide H inhibited the signaling pathway of Akt/mTOR/p70S6K. The c-Myc inhibition and downregulation of G1 phase cyclins were also attributed to (+)-brevipolide H action. Overexpression of myristoylated Akt significantly rescued mTOR/p70S6K and downstream signaling under (+)-brevipolide H treatment. ROS and Ca2+, two key mediators in regulating intracellular signaling, were determined, showing that (+)-brevipolide H interactively induced ROS production and an increase of intracellular Ca2+ levels. The (+)-Brevipolide H also induced the downregulation of anti-apoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL) and loss of mitochondrial membrane potential, indicating the contribution of mitochondrial dysfunction to apoptosis. In conclusion, the data suggest that (+)-brevipolide H displays anticancer activity through crosstalk between ROS production and intracellular Ca2+ mobilization. In addition, suppression of Akt/mTOR/p70S6K pathway associated with downregulation of G1 phase cyclins contributes to (+)-brevipolide H-mediated anticancer activity, which ultimately causes mitochondrial dysfunction and cell apoptosis. The data also support the biological significance and, possibly, clinically important development of natural product-based anticancer approaches

Chamaecyparis montane cloud forest in Taiwan: ecology and vegetation classification

Montane cloud forest is one of the most endangered ecosystems. However, there are few comprehensive studies on the distribution of subtropical montane cloud forest (SMCF). Chamaecyparis forest is one type of SMCF in Taiwan, distributed across the whole island. This study describes eleven types of this forest in Taiwan based on the Braun-Blanquet approach. Plots were selected from the National Vegetation Database of Taiwan. Two alliances were defined, both of which belong to the order Fagetalia hayatae. Topography and altitude explain the contrasting habitat requirements of these two alliances, whereas seasonality of moisture, soil properties and altitude explain differences in floristic composition at the association level. The alliance of Chamaecyparidion formosanae on slopes and ridges includes coniferous or mixed coniferous and evergreen broad-leaved forests; it is found at higher altitudes and is more influenced by the summer monsoon than the other alliance. Five associations are defined within this alliance. The alliance of Pasanio kawakamii - Machilion japonicae growing on slopes and in valleys contains evergreen broad-leaved forests or forests with a mixture of coniferous and evergreen broad-leaved species. Six associations can be determined under the alliance of Pasanio kawakamii-Machilion japonicae. Classification of each syntaxon was formalized using Cocktail Determination Key

Chamaecyparis montane cloud forest in Taiwan: ecology and vegetation classification

Montane cloud forest is one of the most endangered ecosystems. However, there are few comprehensive studies on the distribution of subtropical montane cloud forest (SMCF). Chamaecyparis forest is one type of SMCF in Taiwan, distributed across the whole island. This study describes eleven types of this forest in Taiwan based on the Braun-Blanquet approach. Plots were selected from the National Vegetation Database of Taiwan. Two alliances were defined, both of which belong to the order Fagetalia hayatae. Topography and altitude explain the contrasting habitat requirements of these two alliances, whereas seasonality of moisture, soil properties and altitude explain differences in floristic composition at the association level. The alliance of Chamaecyparidion formosanae on slopes and ridges includes coniferous or mixed coniferous and evergreen broad-leaved forests; it is found at higher altitudes and is more influenced by the summer monsoon than the other alliance. Five associations are defined within this alliance. The alliance of Pasanio kawakamii - Machilion japonicae growing on slopes and in valleys contains evergreen broad-leaved forests or forests with a mixture of coniferous and evergreen broad-leaved species. Six associations can be determined under the alliance of Pasanio kawakamii-Machilion japonicae. Classification of each syntaxon was formalized using Cocktail Determination Key

A Complete High-to-Low spin state Transition of Trivalent Cobalt Ion in Octahedral Symmetry in SrCo_0.5Ru_0.5O_3‑δ

The complex metal oxide SrCo_0.5Ru_0.5O_3‑δ possesses a slightly distorted perovskite crystal structure. Its insulating nature infers a well-defined charge distribution, and the six-fold coordinated transition metals have the oxidation states +5 for ruthenium and +3 for cobalt as observed by X-ray spectroscopy. We have discovered that Co³⁺ ion is purely high-spin at room temperature, which is unique for a Co³⁺ in an octahedral oxygen surrounding. We attribute this to the crystal field interaction being weaker than the Hund’s-rule exchange due to a relatively large mean Co–O distances of 1.98(2) Å, as obtained by EXAFS and X-ray diffraction experiments. A gradual high-to-low spin state transition is completed by applying high hydrostatic pressure of up to 40 GPa. Across this spin state transition, the Co Kβ emission spectra can be fully explained by a weighted sum of the high-spin and low-spin spectra. Thereby is the much debated intermediate spin state of Co³⁺ absent in this material. These results allow us to draw an energy diagram depicting relative stabilities of the high-, intermediate-, and low-spin states as functions of the metal–oxygen bond length for a Co³⁺ ion in an octahedral coordination

Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, with their human orthologs being categorized as VUR. Using UK Biobank data, we validate the importance of the DNAJC18 gene for cardiac homeostasis by showing that its loss of function is associated with altered left ventricular systolic function. Our results identify hundreds of previously unappreciated genes with potential function in congenital heart disease and suggest causal function of five VUR in congenital heart disease