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951.
Targeted disruption of Ing2 results in defective spermatogenesis and development of soft-tissue sarcomas 总被引:2,自引:0,他引:2
Saito M Kumamoto K Robles AI Horikawa I Furusato B Okamura S Goto A Yamashita T Nagashima M Lee TL Baxendale VJ Rennert OM Takenoshita S Yokota J Sesterhenn IA Trivers GE Hussain SP Harris CC 《PloS one》2010,5(11):e15541
ING2 (inhibitor of growth family, member 2) is a member of the plant homeodomain (PHD)-containing ING family of putative tumor suppressors. As part of mSin3A-HDAC corepressor complexes, ING2 binds to tri-methylated lysine 4 of histone H3 (H3K4me3) to regulate chromatin modification and gene expression. ING2 also functionally interacts with the tumor suppressor protein p53 to regulate cellular senescence, apoptosis and DNA damage response in vitro, and is thus expected to modulate carcinogenesis and aging. Here we investigate the developmental and physiological functions of Ing2 through targeted germline disruption. Consistent with its abundant expression in mouse and human testes, male mice deficient for Ing2 showed abnormal spermatogenesis and were infertile. Numbers of mature sperm and sperm motility were significantly reduced in Ing2(-/-) mice (~2% of wild type, P<0.0001 and ~10% of wild type, P<0.0001, respectively). Their testes showed degeneration of seminiferous tubules, meiotic arrest before pachytene stage with incomplete meiotic recombination, induction of p53, and enhanced apoptosis. This phenotype was only partially abrogated by concomitant loss of p53 in the germline. The arrested spermatocytes in Ing2(-/-) testes were characterized by lack of specific HDAC1 accumulation and deregulated chromatin acetylation. The role of Ing2 in germ cell maturation may extend to human ING2 as well. Using publicly available gene expression datasets, low expression of ING2 was found in teratozoospermic sperm (>3-fold reduction) and in testes from patients with defective spermatogenesis (>7-fold reduction in Sertoli-cell only Syndrome). This study establishes ING2 as a novel regulator of spermatogenesis functioning through both p53- and chromatin-mediated mechanisms, suggests that an HDAC1/ING2/H3K4me3-regulated, stage-specific coordination of chromatin modifications is essential to normal spermatogenesis, and provides an animal model to study idiopathic and iatrogenic infertility in men. In addition, a bona fide tumor suppressive role of Ing2 is demonstrated by increased incidence of soft-tissue sarcomas in Ing2(-/-) mice. 相似文献
952.
953.
Fang Dong Shu Yang Haimei Sun Jihong Yan Xiaoxia Guo Dandan Li 《Journal of receptor and signal transduction research》2017,37(2):141-148
Gastrointestinal (GI) distention is a common pathological characteristic in most GI motility disorders (GMDs), however, their detail mechanism remains unknown. In this study, we focused on Ca2+ overload of smooth muscle, which is an early intracellular reaction to stretch, and its downstream MAPK signaling and also reduction of SCF in vivo and in vitro. We successfully established colonic dilation mouse model by keeping incomplete colon obstruction for 8 days. The results showed that persistent colonic dilation clearly induced Ca2+ overload and activated all the three MAPK family members including JNK, ERK and p38 in smooth muscle tissues. Similar results were obtained from dilated colon of patients with Hirschsprung's disease and stretched primary mouse colonic smooth muscle cells (SMCs). Furthermore, we demonstrated that persistent stretch-induced Ca2+ overload was originated from extracellular Ca2+ influx and endoplasmic reticulum (ER) Ca2+ release identified by treating with different Ca2+ channel blockers, and was responsible for the persistent activation of MAPK signaling and SCF reduction in colonic SMCs. Our results suggested that Ca2+ overload caused by smooth muscle stretch led to persistent activation of MAPK signaling which might contribute to the decrease of SCF and development of the GMDs. 相似文献
954.
Effects of iron deficiency on the growth and photosynthesis of three bloom‐forming cyanobacterial species isolated from Lake Taihu 下载免费PDF全文
Cyanobacterial blooms are found in many freshwater ecosystems around the world, but the effect of environmental factors on their growth and the proportion of species still require more investigation. In this study, the physiological responses of bloom‐forming cyanobacteria M icrocystis aeruginosa FACHB912, M icrocystis flos‐aquae FACHB1028 and P seudanabaena sp. FACHB1282 to iron deficiency were investigated. Their specific growth rates were found to decrease as the available iron concentration decreased. At low available iron concentrations of 1 × 10?7 M (pFe 21.3) and 5 × 10?8 M (pFe 21.6), M . aeruginosa had the lowest specific growth rate among three studied species. The cell sizes of M . flos‐aquae and Pseudanabaena sp. were significantly smaller under the lowest iron concentration. The chlorophyll a content of the three species decreased at the lowest iron concentration. The maximal relative electron transport rate, photosynthetic efficiency, and light‐saturation parameter of M . aeruginosa were lower than the other two cyanobacteria at pFe 21.3. Therefore, M . aeruginosa was the least able to adapt to iron deficiency. Under iron deficiency, the functional absorption cross‐section of PSII and electron transport rate on the acceptor side of PSII decreased in M . aeruginosa, while the connectivity factor between individual photosynthetic units increased in M . flos‐aquae, and the electron transport rate on the acceptor side of PSII and between PSII and PSI decreased in P seudanabaena sp. The ability to store iron was highest in M . flos‐aquae, followed by P seudanabaena sp. and M . aeruginosa. Thus, these results provide necessary information for detecting the role of iron in the succession of cyanobacterial species in Lake Taihu, the third largest freshwater lake in China, because all three species were isolated from this lake. 相似文献
955.
The plasmodial slime molds is the largest group in the phylum Amoebozoa. Its life cycle includes the plasmodial trophic stage and the spore‐bearing fruiting bodies. However, only a few species have their complete life cycle known in details so far. This study is the first reporting the morphogenesis of Didymium laxifilum and Physarum album. Spores, from field‐collected sporangia, were incubated into hanging drop cultures for viewing germination and axenic oat agar plates for viewing plasmodial development and sporulation. The spores of D. laxifilum and P. album germinated by method of V‐shape split and minute pore, respectively. The amoeboflagellates, released from spores, were observed in water film. The phaneroplasmodia of two species developed into a number of sporangia by subhypothallic type on oat agar culture. The main interspecific difference of morphogenesis was also discussed. 相似文献
956.
Shi Yang Li Wei Yu Yao Yong Jin Yuan Wen Shu Tay Nian-Lin Reena Han Rehena Sultana Pryseley N. Assam Alex Tiong-Heng Sia Ban Leong Sng 《BMC anesthesiology》2017,17(1):169
Background
The Supreme? laryngeal mask airway (SLMA) is a single-use LMA with double lumen design that allows separation of the respiratory and the alimentary tract, hence potentially reducing the gastric volume and risk of aspiration. The purpose of this prospective cohort study is to evaluate the the role of the SLMA as an airway technique for women undergoing category 2 and 3 Cesarean delivery under general anesthesia.Methods
We recruited 584 parturients who underwent category 2 or 3 Cesarean delivery under general anesthesia, in which 193 parturients underwent category 2 and 391 parturients underwent category 3 Cesarean delivery. The primary outcome was insertion success rate at 1st attempt in SLMA insertion. The secondary outcomes included anaesthetic, obstetric outcomes and maternal side effects associated with airway device.Results
The 1st attempt insertion success rate was 98.3%, while the overall insertion success rate was 100%. The mean (Standard deviation) time to effective ventilation was 15.6 (4.4) seconds. Orogastric tube insertion was successful at the 1st attempt in all parturients. There was no clinical evidence of aspiration or regurgitation. No episodes of hypoxemia, laryngospasm or bronchospasm were observed intra-operatively. The incidence of complications was low and with good maternal satisfaction reported.Conclusions
The SLMA could be an alternative effective airway in category 2 and 3 parturients emergency Cesarean Delivery under general anesthesia in a carefully-selected obstetric population.Trial registration
Clinical Trials Registration: Clinicaltrials.gov Registration NCT02026882. Registered on December 31, 2013.957.
S,N co‐doped carbon quantum dots (N,S‐CQDs) with super high quantum yield (79%) were prepared by the hydrothermal method and characterized by transmission electron microscopy, photoluminescence, UV–Vis spectroscopy and Fourier transformed infrared spectroscopy. N,S‐CQDs can enhance the chemiluminescence intensity of a luminol–H2O2 system. The possible mechanism of the luminol–H2O2–(N,S‐CQDs) was illustrated by using chemiluminescence, photoluminescence and ultraviolet analysis. Ranitidine can quench the chemiluminescence intensity of a luminol–H2O2–N,S‐CQDs system. So, a novel flow‐injection chemiluminescence method was designed to determine ranitidine within a linear range of 0.5–50 μg ml?1 and a detection limit of 0.12 μg ml?1. The method shows promising application prospects. 相似文献
958.
Silver nanoclusters stabilized with denatured fish sperm DNA and the application on trace mercury ions detection 下载免费PDF全文
Yangfang Kuang Sheng Liang Fangfang Ma Shu Chen Yunfei Long Rongjin Zeng 《Luminescence》2017,32(4):674-679
In this study, fluorescent silver nanoclusters (Ag NCs) were synthesized using denatured fish sperm DNA as the template. In contrast to other methods, this method did not use artificial DNA as the template. After their reaction with denatured fish sperm DNA, Ag+ ions were reduced by NaBH4 to form Ag NCs. The Ag NCs showed a strong fluorescence emission at 650 nm when excited at 585 nm. The fluorescence intensity increased fourfold at pH 3.78, controlled with Britton–Robinson buffer solution. The fluorescence of the Ag NCs was quenched in the presence of trace mercury ions (Hg2+) in a weakly acidic medium and nitrogen atmosphere. The extent of the fluorescence quenching of Ag NCs strongly depends on the Hg2+ ion concentration over a linear range from 2.0 nmol L?1 to 3.0 μmol L?1. The detection limit (3σ/k) for Hg2+ was 0.7 nmol L?1. Thus, a sensitive and rapid method was developed for the detection of Hg2+ ions. 相似文献
959.
960.
理性设计盐桥构建伯克霍尔德菌脂肪酶热稳定突变体 总被引:1,自引:1,他引:0
【目的】借助蛋白质工程技术提高伯克霍尔德菌ZYB002脂肪酶LipA的热稳定性,以期更好地将其应用于工业生产中。【方法】利用YASARA、Fold X、Rosetta、Gromacs等生物信息学软件,构建1个脂肪酶Lip A的热稳定性提高的微型突变体电子文库;通过对突变体的结构信息和自由能变化进行评估,筛选出潜在的有价值的突变体。继而利用基因定点突变技术,构建上述候选突变体的突变基因文库,通过实验筛选出热稳定性提高的脂肪酶LipA突变体。【结果】利用上述方法,从构建的20个脂肪酶LipA突变体中,筛选到热稳定性有显著提高的3个突变体LipA-Asn~(125)Asp、LipA-Asn~(125)Glu和LipA-Gln~(262)Glu。经55°C处理12 min后,上述3个突变体的T1250值较野生型分别提高4.0°C、5.5°C和4.4°C;在55°C下的半衰期较野生型分别提高了2.2倍、3.8倍和2.6倍。【结论】利用生物信息学软件,构建脂肪酶LipA突变体电子文库,结合蛋白质的结构信息,可以快速筛选到热稳定性提高的脂肪酶LipA突变体。 相似文献