Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome

Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.     

Genome-wide identification of simple sequence repeats and development of polymorphic SSR markers for genetic studies in tea plant (<Emphasis Type="Italic">Camellia sinensis</Emphasis>)

The tea plant (Camellia sinensis (L.) O. Kuntze) is one of the most popular non-alcoholic beverage crops worldwide. The availability of complete genome sequences for the Camellia sinensis var. ‘Shuchazao’ has provided the opportunity to identify all types of simple sequence repeat (SSR) markers by genome-wide scan. In this study, a total of 667,980 SSRs were identified in the ~?3.08 Gb genome, with an overall density of 216.88 SSRs/Mb. Dinucleotide repeats were predominant among microsatellites (72.25%), followed by trinucleotide repeats (15.35%), while the remaining SSRs accounted for less than 13%. The motif AG/CT (49.96%) and AT/TA (40.14%) were the most and the second most abundant among all identified SSR motifs, respectively; meanwhile, AAT/ATT (41.29%) and AAAT/ATTT (67.47%) were the most common among trinucleotides and tetranucleotides, respectively. A total of 300 primer pairs were designed to screen six tea cultivars for polymorphisms of SSR markers using the five selected repeat types of microsatellite sequences. The resulting 96 SSR markers that yielded polymorphic and unambiguous bands were further deployed on 47 tea cultivars for genetic diversity assessment, demonstrating high polymorphism of these SSR markers. Remarkably, the dendrogram revealed that the phylogenetic relationships among these tea cultivars are highly consistent with their genetic backgrounds or places of origin. The identified genome-wide SSRs and newly developed SSR markers will provide a powerful means for genetic researches in tea plant, including genetic diversity and evolutionary origin analysis, fingerprinting, QTL mapping, and marker-assisted selection for breeding.     

海洋酸化和铜离子胁迫对海月水母碟状幼体的影响

海洋酸化和重金属污染作为全球性海洋环境问题,均影响海洋生物的生存和生态系统的健康。海月水母是近岸海域常见的胶质性浮游动物,其生长发育和种群数量易受到海洋环境变化的影响。研究海月水母碟状幼体对海洋酸化（pH 8.1和pH 7.6）和Cu²⁺（0、10 μg/L和25 μg/L）胁迫的生理响应,从氧化应激酶和酸碱平衡相关酶活性、呼吸、运动和生长等方面探究海洋酸化和铜污染对海月水母碟状幼体的综合影响。研究发现,经过16 d的暴露期后Cu²⁺对海月水母碟状幼体产生较强的毒性效应,抑制Ca²⁺-ATP酶和过氧化氢酶活性,造成超氧化物歧化酶活性和呼吸代谢速率异常升高、收缩频率降低、生长速度减慢。正常pH,25 μg/L铜暴露处理的超氧化物歧化酶活性和呼吸率最高,收缩频率和伞部直径最小。随着铜暴露浓度的增加,海洋酸化可以缓解Cu²⁺对海月水母呼吸率和生长的影响,但对Ca²⁺-ATP酶和过氧化氢酶活性具有协同抑制作用。确定了海洋酸化和Cu²⁺对海月水母的不同生理影响,这种差异影响可能会导致未来海洋生物多样性和生态系统的改变。     

New glimpses of caveolin-1 functions in embryonic development and human diseases

Caveolin-1 (Cav-1) isoforms, including Cav-1α and Cav-1β, were identified as integral membrane proteins and the major components of caveolae. Cav-1 proteins are highly conserved during evolution from {itCaenorhabditis elegans} to human and are capable of interacting with many signaling molecules through their caveolin scaffolding domains to regulate the activities of multiple signaling pathways. Thus, Cav-1 plays crucial roles in the regulation of cellular proliferation, differentiation and apoptosis in a cell-specific and contextual manner. In addition, Cav-1 is essential for embryonic development of vertebrates owing to its regulation of BMP, Wnt, TGF-β and other key signaling molecules. Moreover, Cav-1 is mainly expressed in terminally differentiated cells and its abnormal expression is often associated with human diseases, such as tumor progression, cardiovascular diseases, fibrosis, lung regeneration, and diseases related to virus. In this review, we will further discuss the potential of Cav-1 as a target for disease therapy and multiple drug resistance.