Pyroptosis in stroke-new insights into disease mechanisms and therapeutic strategies

Journal of Physiology and Biochemistry - Stroke is a common disease with high mortality and disability worldwide. Different forms of cell deaths, including apoptosis and necrosis, occur in ischemic...     

An apicoplast‐resident folate transporter is essential for sporogony of malaria parasites

Malaria parasites are fast replicating unicellular organisms and require substantial amounts of folate for DNA synthesis. Despite the central role of this critical co‐factor for parasite survival, only little is known about intraparasitic folate trafficking in Plasmodium. Here, we report on the expression, subcellular localisation and function of the parasite's folate transporter 2 (FT2) during life cycle progression in the murine malaria parasite Plasmodium berghei. Using live fluorescence microscopy of genetically engineered parasites, we demonstrate that FT2 localises to the apicoplast. In invasive P. berghei stages, a fraction of FT2 is also observed at the apical end. Upon genetic disruption of FT2, blood and liver infection, gametocyte production and mosquito colonisation remain unaltered. But in the Anopheles vector, FT2‐deficient parasites develop inflated oocysts with unusual pulp formation consisting of numerous single‐membrane vesicles, which ultimately fuse to form large cavities. Ultrastructural analysis suggests that this defect reflects aberrant sporoblast formation caused by abnormal vesicular traffic. Complete sporogony in FT2‐deficient oocysts is very rare, and mutant sporozoites fail to establish hepatocyte infection, resulting in a complete block of parasite transmission. Our findings reveal a previously unrecognised organellar folate transporter that exerts critical roles for pathogen maturation in the arthropod vector.     

不同剂量链脲佐菌素腹腔注射制备大鼠糖尿病心肌病模型的病理学观察

建立糖尿病性心肌病（DCM）大鼠模型,观察不同剂量链脲佐菌素（STZ）单次腹腔注射后大鼠心肌和胰腺的病理学变化。用STZ 50 mg/kg、55 mg/kg、60 mg/kg 3种剂量单次腹腔注射,制备糖尿病大鼠模型;以柠檬酸三钠-柠檬酸缓冲液腹腔注射,作为对照。72 h后,测空腹血糖及做口服葡萄糖耐量实验（OGTT）;3周后,HE染色观察各组大鼠胰腺和心肌形态学变化,Masson三色染色观察心肌纤维化改变。OGTT和空腹血糖显示3组存活大鼠糖尿病均成模;3周末,50 mg/kg和55 mg/kg剂量死亡率为25%;60 mg/kg剂量高,达到75%;HE染色显示55 mg/kg剂量组大鼠胰岛明显萎缩,轮廓不清晰,胰岛细胞数量少,心肌细胞肥大、排列紊乱,细胞间隙增大,并有炎症细胞浸润;50 mg/kg组胰岛和心肌也有变化,但无55 mg/kg组明显。心肌Masson染色显示55 mg/kg组心肌内胶原组织明显增多,排列紊乱,分布不均。55 mg/kg剂量的STZ单次注射大鼠腹腔,造模3周可以建立较明显的DCM模型,可为DCM的组织病理学和实验研究提供一个较好的动物模型。     

实践教学在植物学课程教学中的探索

《植物学》是生物学科中一门重要的基础课程,该课程与实践教学联系紧密。从课堂教学、实验教学、野外实习、科研实践等4个方面阐述了实践教学在植物学课程教学中的几点体会,试图为植物学的教学提出一些建议,以期达到提高教学质量,培养综合性人才的目的。     

人转铁蛋白偶联交联聚乙烯亚胺体外靶向转染肿瘤细胞

为了提高聚乙烯亚胺(Polythylenimine,PEI)类载体对肿瘤细胞的靶向性同时降低其细胞毒性,先用1800DaPEI制备了交联低分子量PEI,然后将人转铁蛋白与之偶联,得到了新型肿瘤靶向性人转铁蛋白偶联交联聚乙烯亚胺基因载体(TCP)。对所得的TCP的理化特性经行了表征,并检测了其细胞毒性。采用TCP介导pGL-3和pEGFP分别对293T、HepG2和Hela细胞系进行体外转染实验。结果表明:TCP是一种低毒高效的基因载体,在肿瘤细胞中的转染效率显著增强,因为其二硫键可在细胞内还原降解,而且通过偶联的转铁蛋白配体与肿瘤细胞表达的转铁蛋白受体间的相互作用,可增强该载体对肿瘤细胞的转染效率和靶向性。     

Mechanisms of Functional and Physical Genome Reduction in Photosynthetic and Nonphotosynthetic Parasitic Plants of the Broomrape Family

Nonphotosynthetic plants possess strongly reconfigured plastomes attributable to convergent losses of photosynthesis and housekeeping genes, making them excellent systems for studying genome evolution under relaxed selective pressures. We report the complete plastomes of 10 photosynthetic and nonphotosynthetic parasites plus their nonparasitic sister from the broomrape family (Orobanchaceae). By reconstructing the history of gene losses and genome reconfigurations, we find that the establishment of obligate parasitism triggers the relaxation of selective constraints. Partly because of independent losses of one inverted repeat region, Orobanchaceae plastomes vary 3.5-fold in size, with 45 kb in American squawroot (Conopholis americana) representing the smallest plastome reported from land plants. Of the 42 to 74 retained unique genes, only 16 protein genes, 15 tRNAs, and four rRNAs are commonly found. Several holoparasites retain ATP synthase genes with intact open reading frames, suggesting a prolonged function in these plants. The loss of photosynthesis alters the chromosomal architecture in that recombinogenic factors accumulate, fostering large-scale chromosomal rearrangements as functional reduction proceeds. The retention of DNA fragments is strongly influenced by both their proximity to genes under selection and the co-occurrence with those in operons, indicating complex constraints beyond gene function that determine the evolutionary survival time of plastid regions in nonphotosynthetic plants.     

Triple Helix Binding of Oligodeoxyribonucleotides Containing 8-Oxo-2′-deoxyadenosine

Abstract

Formation of a triple helix between an oligodeoxyribonucleotide containing 8-oxo-2′-deoxyadenosine and a DNA duplex target was studied as a function of pH. Above pH 7.4, the triple helix with the 8-oxo-2′-deoxyadenosine was more stable than the complex with an analogous oligodeoxyribonucleotide containing deoxycytidine instead of 8-oxo-2′-deoxyadenosine.     

Scolecenchelys fuscogularis (Anguilliformes: Ophichthidae, Myrophinae), a new worm eel from Japan

A new species of worm eel (Ophichthidae, subfamily Myrophinae), Scolecenchelys fuscogularis, is described from two specimens collected at 90–147 m depth off the coast of Japan. The new species is characterized by its dorsal-fin origin, which is located posterior to a vertical through the anus, its high total number of vertebrae (146–149), and its uniserial dentition on jaws and vomer. The new species is similar to Scolecenchelys australis and Scolecenchelys tasmaniensis in having 148–152 total and 60–61 preanal vertebrae and its uniserial teeth, but can be distinguished from the latter two species as it has a larger head [8.5–8.8 % of total length (TL) vs. 7.8–8.3 %], a longer trunk (39 % TL vs. 34–35 %), and a shorter tail (52–53 % TL vs. 56–58 %). Although S. fuscogularis most resembles Scolecenchelys chilensis in having 146–159 total and 59–64 preanal vertebrae and uniserial teeth, as well as in the proportions of the head, trunk and tail, the new species differs from the latter in having a smaller head (8.5–8.8 % TL vs. 8.9–9.7 %), a more slender body (body depth 1.5–1.6 % TL vs. 2.3–2.9 %), a more posterior dorsal-fin origin (horizontal distance between the origin and a vertical through the anus 83 % of head length vs. 36–54 %), no groove on the ventral side of its snout, and a dark lower jaw with a patch of melanophores on the ventral side of its branchial basket.     

Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers

The fibroblast growth factor receptors (FGFRs) regulate important biological processes including cell proliferation and differentiation during development and tissue repair. Over the past decades, numerous pathological conditions and developmental syndromes have emerged as a consequence of deregulation in the FGFRs signaling network. This review aims to provide an overview of FGFR family, their complex signaling pathways in tumorigenesis, and the current development and application of therapeutics targeting the FGFRs signaling for treatment of refractory human cancers.