KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13.

KCTD10 belongs to the KCTD (potassiumchannel tetramerization domain) family, many members of which are associated with neuropsychiatric disorders. However, the biological function underlying the association with brain disorders remains to be explored. Here, we reveal that Kctd10 is highly expressed in neuronal progenitors and layer V neurons throughout brain development. Kctd10 deficiency triggers abnormal proliferation and differentiation of neuronal progenitors, reduced deep-layer (especially layer V) neurons, increased upper-layer neurons, and lowered brain size. Mechanistically, we screened and identified a unique KCTD10-interacting protein, KCTD13, associated with neurodevelopmental disorders. KCTD10 mediated the ubiquitination-dependent degradation of KCTD13 and KCTD10 ablation resulted in a considerable increase of KCTD13 expression in the developing cortex. KCTD13 overexpression in neuronal progenitors led to reduced proliferation and abnormal cell distribution, mirroring KCTD10 deficiency. Notably, mice with brain-specific Kctd10 knockout exhibited obvious motor deficits. This study uncovers the physiological function of KCTD10 and provides unique insights into the pathogenesis of neurodevelopmental disorders.

Characterization of redox and salinity-tolerant alkaline protease from Bacillus halotolerans strain DS5.

Bacillus halotolerans DS5 was isolated and identified as a halophilic microbe according to 16S rRNA analysis and the physical and chemical indices of the strain. A new alkaline protease (designated as prot DS5) from Bacillus halotolerans DS5 was produced, purified, and characterized. After 12 h incubation in the medium with 1% dextrin, 0.5% NaCl, 2% soluble starch, and 1% yeast extract (pH 7.0), it could reach the maximum enzyme activity (279.74 U/ml). The prot DS5 was stable in the pH range of 6.0-12.0 and the temperature range of 40-60°C, with maximal hydrolytic activities at pH 9 and at 50°C. In the presence of Ca2+, Mn2+, Ba2+, Mg2+, and Fe3+, protease activity was enhanced. The prot DS5 was maintained highly stable in NaCl (up to 2.5 mol/L), reducing and oxidizing agents. The prot DS5 also exhibited compatibility in other detergent ingredients, such as non-ionic and anionic surfactants. These properties of prot DS5 make this enzyme suitable for various industrial applications (e.g., detergents and leather).

[Effects of Shufeng Xuanfei Jiedu formula for the inflammation-related cytokines in pneumonia mice infected with influenza virus].

OBJECTIVE: To analyze the differential gene expression of Shufeng Xuanfei Jiedu formula on whole expression profiles of the inflammation-related cytokines in mice infected with influenza virus by the gene chip technology. METHODS: Male ICR mice were divided into normal group (N group), influenza virus pneumonia model group (M group), oseltamivir control group (C group) and Shufeng Xuanfei Jiedu formula high, medium and low dose groups (SH, SM, SL groups) according to the random number table method, with 10 mice in each group. A mouse model of influenza virus pneumonia was established by nasal drip of influenza virus strain FM1 (0.05 mL); in group N, 0.05 mL normal saline was used. In SH, SM and SL groups, Shufeng Xuanfei Jiedu formula was prescribed after 2 hours of intranasal infection (drug concentration approximately 3.8, 1.9 and 1.0 kg/L), 0.2 mL once a day for 4 days; in group C, the dosage of oseltamivir was 2.5 kg/L; in group N and group M, distilled water was given. On the 5th day, the whole lung of mice was harvested, and the total RNA of lung tissue was extracted and detected after hybridization with mice whole gene expression spectrum chip. Differential expressed genes of cytokines involved in inflammatory pathways were selected. The intensity expression ratio of the chip probe signal in each group vs. M group was calculated, and P < 0.05 and log2 ratio > 1 were defined as up-regulated genes, while P < 0.05 and log2 ratio < -1 were down-regulated genes. The mRNA expressions of interleukin (IL-1, IL-8) and intercellular adhesion molecule-1 (ICAM-1) were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with group N, the differential gene expressions of IL-1, IL-8 and ICAM-1 in group M were significantly up-regulated [log2(N/M) were 2.62, 2.07, 1.41, respectively, all P < 0.05]. Compared with group M, the gene expressions of IL-1, IL-8, ICAM-1 were significantly down-regulated in SH, SM, SL and C groups [log2(SH/M) were -1.91, -1.85, -0.88; log2(SM/M) were -3.10, -1.74, -1.84; log2(SL/M) were -1.89, -1.39, -0.53; log2(C/M) were -2.46, -1.52, -1.44, respectively, all P < 0.05]. RT-PCR showed that the mRNA expressions of IL-1, IL-8 and ICAM-1 in group M were significantly higher than those in group N [IL-1 (2-ΔΔCT): 4.63±0.24 vs. 1.01±0.13, IL-8 (2-ΔΔCT): 6.28±0.13 vs. 1.02±0.09, ICAM-1 (2-ΔΔCT): 2.90±0.18 vs. 1.02±0.12, all P < 0.05]. The mRNA expressions of IL-1, IL-8, ICAM-1 in SH, SM, SL and C groups were lower than those in group M [IL-1 (2-ΔΔCT): 2.12±0.32, 1.71±0.07, 2.05±0.16, 1.66±0.13 vs. 4.63±0.24; IL-8 (2-ΔΔCT): 3.89±0.13, 2.08±0.19, 2.98±0.20, 2.02±0.12 vs. 6.28±0.13; ICAM-1 (2-ΔΔCT): 1.72±0.93, 1.34±0.14, 1.53±0.25, 1.17±0.12 vs. 2.90±0.18, all P < 0.05]. There was no significant difference among the SH, SM, SL and C groups. CONCLUSIONS: Shufeng Xuanfei Jiedu formula inhibits inflammatory damage in mice after influenza virus infection by down-regulating the expressions of IL-1, IL-8, and ICAM-1 inflammatory cytokine-related genes.