Depletion of SMN protein in mesenchymal progenitors impairs the development of bone and neuromuscular junction in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cell (MPC)-specific SMN-depleted mouse models, we reveal that SMN reduction in limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ). Specifically, these mice exhibited impaired growth plate homeostasis and reduced insulin-like growth factor (IGF) signaling from chondrocytes, rather than from the liver. Furthermore, the reduction of SMN in fibro-adipogenic progenitors (FAPs) resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis of SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.

Single-molecule study of the effects of temperature, pH, and RNA base on the stepwise enzyme kinetics of 10-23 deoxyribozyme.

We investigated how the stepwise enzyme kinetics of 10-23 deoxyribozyme was affected by temperature, pH, and RNA residue of the substrate at the single-molecule level. A deoxyribozyme-substrate system was employed to temporally categorize a single-turnover reaction into four distinct steps: binding, cleavage, dissociation of one of the cleaved fragments, and dissociation of the other fragment. The dwell time of each step was measured as the temperature was varied from 26 to 34 °C, to which the transition state theory was applied to obtain the enthalpy and entropy of activation for individual steps. In addition, we found that only the cleavage step was significantly affected by pH, indicating that it involves deprotonation of a single proton. We also found that different RNA residues specifically affect the cleavage step and cause the dwell time to change by as much as 5 times.

Investigating the Degradation of EUV Transmittance of an EUV Pellicle Membrane.

The extreme ultraviolet (EUV) pellicle is a freestanding membrane that protects EUV masks from particle contamination during EUV exposure. Although a high EUV transmittance of the pellicle is required to minimize the loss of throughput, the degradation of EUV transmittance during the extended exposure of the pellicle has been recently reported. This may adversely affect the throughput of the lithography process. However, the cause of this phenomenon has not yet been clarified. Therefore, we investigated the cause of the degradation in the EUV transmittance by observing the compositional change when the Ru/SiNx pellicle composite was heated in an emulated EUV scanner environment. The Ru thin film that was deposited at high pressure had more void networks but was not oxidized, whereas the SiNx thin film was oxidized after heating. This was because the void network in the Ru thin film served as a preferential diffusion path for oxygen and caused oxidation of the SiNx thin film. It was confirmed that the degradation of the EUV transmittance was due to the oxidation of SiNx. The results verified the effect of diffusivity in the thin film due to the void network on oxidation and EUV transmittance.

Microstructures of HfOx Films Prepared via Atomic Layer Deposition Using La(NO3)3·6H2O Oxidants.

Hafnium oxide (HfOx) films have a wide range of applications in solid-state devices, including metal-oxide-semiconductor field-effect transistors (MOSFETs). The growth of HfOx films from the metal precursor tetrakis(ethylmethylamino) hafnium with La(NO3)3·6H2O solution (LNS) as an oxidant was investigated. The atomic layer deposition (ALD) conditions were optimized, and the chemical state, surface morphology, and microstructure of the prepared films were characterized. Furthermore, to better understand the effects of LNS on the deposition process, HfOx films deposited using a conventional oxidant (H2O) were also prepared. The ALD process using LNS was observed to be self-limiting, with an ALD temperature window of 200-350 °C and a growth rate of 1.6 Å per cycle, two times faster than that with H2O. HfOx films deposited using the LNS oxidant had smaller crystallites than those deposited using H2O, as well as more suboxides or defects because of the higher number of grain boundaries. In addition, there was a difference in the preferred orientations of the HfOx films deposited using LNS and H2O, and consequently, a difference in surface energy. Finally, a film growth model based on the surface energy difference was proposed to explain the observed growth rate and crystallite size trends.

ZKSCAN3 Facilitates Liver Metastasis of Colorectal Cancer Associated with CEA-expressing Tumor.

AIM: Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) is overexpressed in invasive colorectal cancer (CRC) cells and regulates the expression of several genes favoring tumor progression, including vascular endothelial growth factor (VEGF) and integrin ß4. We evaluated the association of ZKSCAN3 and colorectal cancer liver metastasis (CLM) to determine whether it is related to invasive signaling pathways. MATERIALS AND METHODS: The ratios of expression by primary tumor to normal tissue and metastatic tumor to normal tissue were compared between ZKSCAN3-overexpressing and underexpressing primary tumor groups. RESULTS: In terms of CLM, the ZKSCAN3 overexpression was positively correlated with carcinoembryonic antigen (CEA), VEGF, and AKT expression. The protein-expression analysis showed that ZKSCAN-specific siRNA knockdown reduced CEA expression in LoVo and LS174T CRC cells. Matrigel invasion by ZKSCAN3-overexpressing HCT116 cells was increased when examined on CEA-coated filters compared with phosphate-buffered saline-treated controls. Additionally, matrix metalloproteinase 9 (MMP9) expression was greater in cells with reference allele (GG) than substitution allele (CC) for ZKSCAN3 rs733743 (p=0.032). ZKSCAN3 protein expression of the high serum CEA group was increased in hepatic metastatic tissue compared with the primary tumor tissue, while in the group with normal serum CEA it decreased or was similar. Reference ZKSCAN3 alleles were correlated with male dominance, a family history of malignancy, high serum CEA concentration and stage IV CRC in 450 patients with sporadic CRC. In conclusion, ZKSCAN3 appears to promote colorectal tumor progression and invasion. ZKSCAN3 may facilitate hepatic metastasis of CRC associated with CEA particularly in cases with CEA-producing tumor.

Physicochemical properties of heme iron products in the Korean market.

Since absorption efficacy of heme iron (HI) is critically dependent on its solubility in aqueous solution, we investigated the physicochemical properties of two HI products available in the Korean market. The two HI products did not differ in ingredients and color. However, HI polypeptide (HIP), produced in Korea, was fairly soluble over a wide pH range in water-based solutions, whereas HI imported from Japan was insoluble except in strong acid and base solutions. Analysis using an ultraviolet-visible spectrophotometer showed that the chromophore of HIP was shifted to the red compared with that of HI. Fourier transform-infrared analysis revealed that HIP contained mainly amide (NH) groups, while HI largely contained amine (NH(2)) groups. With regard to constituents, between HIP and HI, their major components were different from each other according to their ratio of fronts obtained by thin-layer chromatography. These results suggest that determination of solubility should be included in the quality control process of HI products.