Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition.
- 作者列表："Liu C","Ren Y","Li Z","Hu Q","Yin L","Wang H","Qiao X","Zhang Y","Xing L","Xi Y","Jiang F","Wang S","Huang C","Liu B","Liu H","Wan F","Qian W","Fan W
:Whole-genome duplication (WGD), contributing to evolutionary diversity and environmental adaptability, has been observed across a wide variety of eukaryotic groups, but not in molluscs. Molluscs are the second largest animal phylum in terms of species numbers, and among the organisms that have successfully adapted to the nonmarine realm through aquatic-terrestrial (A-T) transition. We assembled a chromosome-level reference genome for Achatina immaculata, a globally invasive species, and compared the genomes of two giant African snails (A. immaculata and Achatina fulica) to other available mollusc genomes. Macrosynteny, colinearity blocks, Ks peak and Hox gene clusters collectively suggested a WGD event in the two snails. The estimated WGD timing (~70 million years ago) was close to the speciation age of the Sigmurethra-Orthurethra (within Stylommatophora) lineage and the Cretaceous-Tertiary (K-T) mass extinction, indicating that the WGD may have been a common event shared by all Sigmurethra-Orthurethra species and conferred ecological adaptability allowing survival after the K-T extinction event. Furthermore, the adaptive mechanism of WGD in terrestrial ecosystems was confirmed by the presence of gene families related to the respiration, aestivation and immune defence. Several mucus-related gene families expanded early in the Stylommatophora lineage, and the haemocyanin and phosphoenolpyruvate carboxykinase families doubled during WGD, and zinc metalloproteinase genes were highly tandemly duplicated after WGD. This evidence suggests that although WGD may not have been the direct driver of the A-T transition, it played an important part in the terrestrial adaptation of giant African snails.
: 全基因组复制 (WGD) 有助于进化多样性和环境适应性，已在各种真核生物群体中观察到，但在软体动物中没有。就物种数量而言，软体动物是第二大动物门，也是通过水生-陆生 (a-t) 过渡成功适应非海洋领域的生物之一。我们组装了一个全球入侵物种原木虫 (Achatina immaculata) 的染色体水平参考基因组，并将两种巨大的非洲蜗牛 (a.immaculata和Achatina fulica) 的基因组与其他可用的软体动物基因组进行了比较。巨合子、共线性阻滞、Ks峰和Hox基因簇共同暗示了两种蜗牛中的WGD事件。估计的WGD时间 (~ 7000万年前) 接近于西格穆拉-正尿道 (在柱花草内) 谱系的物种形成年龄和白垩纪-第三纪 (k-t) 大灭绝，表明WGD可能是所有Sigmurethra-orthorus物种共有的共同事件，并赋予生态适应性，允许在k-t灭绝事件后存活。此外，WGD在陆地生态系统中的适应机制还被与呼吸、免疫和免疫防御相关的基因家族的存在所证实。几个粘液相关基因家族在柱花草谱系早期扩增，血蓝蛋白和磷酸烯醇式丙酮酸羧激酶家族在WGD期间加倍，锌金属蛋白酶基因在WGD后高度重复。这一证据表明，尽管WGD可能不是a-t转变的直接驱动力，但它在巨型非洲蜗牛的陆地适应中发挥了重要作用。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.