The halophile Vibrio vulnificus is an etiologic agent of human mortality from seafood-borne infections. We applied whole-genome sequencing and comparative analysis to investigate the evolution of this pathogen. The genome of biotype 1 strain, V. vulnificus YJ016, was sequenced and includes two chromosomes of estimated 3377 kbp and 1857 kbp in size, and a plasmid of 48,508 bp. A super-integron (SI) was identified, and the SI region spans 139 kbp and contains 188 gene cassettes. In contrast to non-SI sequences, the captured gene cassettes are unique for any given Vibrio species and are highly variable among V. vulnificus strains. Multiple rearrangements were found when comparing the 5.3-Mbp V. vulnificus YJ016 genome and the 4.0-Mbp V. cholerae El Tor N16961 genome. The organization of gene clusters of capsular polysaccharide, iron metabolism, and RTX toxin showed distinct genetic features of V. vulnificus and V. cholerae. The content of the V. vulnificus genome contained gene duplications and evidence of horizontal transfer, allowing for genetic diversity and function in the marine environment. The genomic information obtained in this study can be applied to monitoring vibrio infections and identifying virulence genes in V. vulnificus.[Supplemental material is available online at www.genome.org and at http://genome.nhri.org.tw/vv/. The nucleotide sequence data from this study have been submitted to DDBJ/EMBL/GenBank under accession nos. BA000037, BA000038, and AP005352.]Vibrio vulnificus is an etiologic agent for severe human infection acquired through wounds or contaminated seafood. This organism is divided into three biotypes according to their different biochemical and biological properties (Linkous and Oliver 1999). Among them the biotype 1 strains are most frequently isolated from the clinical specimens. Opportunistic infection in susceptible individuals typically causes mortality within 24 to 48 h of the exposure. The bacterium is halophilic, and it is abundantly present in estuarine ecosystems throughout the world. Isolated incidents of V. vulnificus infection have been reported in the U.S.A., Europe, Korea, Taiwan (Park et al. 1991;Chuang et al. 1992;Dalsgaard et al. 1996;Hlady and Klontz 1996), and many other countries. According to CDC statistics, V. vulnificus is a major bacterial cause of mortality associated with food-borne diseases, and it results in the highest death rate of any causative agent (Todd 1989).V. vulnificus belongs to the ␥-group of Proteobacteria, and it shares morphological and biochemical characteristics with other human vibrio pathogens, including Vibrio cholerae and Vibrio parahaemolyticus. Bacteria of the Vibrionaceae family, which show a comma-shape microscopic appearance and a polar flagellum appendage, are mostly aquatic inhabitants that require NaCl for optimal growth. On the basis of clinical and epidemiology studies, diseases associated with V. vulnificus infection have been found to present in two patterns (Blake et al. 1979). In one, primary septicemia occurred in individ...
Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multichanneled (MC) scaffolds, cross-linked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts.
Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. However, its impact on breast cancer subtypes remains unclear. Here, we performed a comprehensive and quantitative analysis of WGD and its influence on breast cancer subtypes in patients from Taiwan and consequently highlight the genomic association between WGD and homologous recombination deficiency (HRD). A higher manifestation of WGD was reported in triple-negative breast cancer, conferring high chromosomal instability (CIN), while HER2 + tumors exhibited early WGD events, with widely varied CIN levels, compared to luminal-type tumors. An association of higher activity of de novo indel signature 2 with WGD and HRD in Taiwanese breast cancer patients was reported. A control test between WGD and pseudo non-WGD samples was further employed to support this finding. The study provides a better comprehension of tumorigenesis in breast cancer subtypes, thus assisting in personalized treatment.
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