Divergent northern and southern populations and demographic history of the pearl oyster in the western Pacific revealed with genomic SNPs

In the open ocean without terrain boundaries, marine invertebrates with pelagic larvae can migrate long distances using ocean currents, suggesting reduced genetic diversification. Contrary to this assumption, however, genetic differentiation is often observed in marine invertebrates. In the present study, we sought to explain how population structure is established in the western Pacific Ocean, where the strong Kuroshio Current maintains high levels of gene flow from south to north, presumably promoting genetic homogeneity. We determined the population structure of the pearl oyster, Pinctada fucata, in the Indo-Pacific Ocean using genome-wide genotyping data from multiple sampling localities. Cluster analysis showed that the western Pacific population is distinct from that of the Indian Ocean, and that it is divided into northern (Japanese mainland) and southern (Nansei Islands, China, and Cambodia) populations. Genetic differentiation of P. fucata can be explained by geographic barriers in the Indian Ocean and a local lagoon, and by environmental gradients of sea surface temperature (SST) and oxygen concentration in the western Pacific. A genome scan showed evidence of adaptive evolution in genomic loci, possibly associated with changes in environmental factors, including SST and oxygen concentration. Furthermore, Bayesian simulation demonstrated that the past population expansion and division are congruent with ocean warming after the last glacial period. It is highly likely that the environmental gradient forms a genetic barrier that diversifies P. fucata populations in the western Pacific. This hypothesis helps to explain genetic differentiation and possible speciation of marine invertebrates

Ribonuclease H/DNA polymerase HIV-1 reverse transcriptase dual inhibitor: mechanistic studies on the allosteric mode of action of isatin-based compound RMNC6

The DNA polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) are needed for the replication of the viral genome and are validated drug targets. However, there are no approved drugs inhibiting RNase H and the efficiency of DNA polymerase inhibitors can be diminished by the presence of drug resistance mutations. In this context, drugs inhibiting both activities could represent a significant advance towards better anti-HIV therapies. We report on the mechanisms of allosteric inhibition of a newly synthesized isatin-based compound designated as RMNC6 that showed IC50 values of 1.4 and 9.8 μM on HIV-1 RT-associated RNase H and polymerase activities, respectively. Blind docking studies predict that RMNC6 could bind two different pockets in the RT: one in the DNA polymerase domain (partially overlapping the non-nucleoside RT inhibitor [NNRTI] binding pocket), and a second one close to the RNase H active site. Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI) in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6. In addition, despite being naturally resistant to NNRTIs, the polymerase activity of HIV-1 group O RT was efficiently inhibited by RMNC6. The compound was also an inhibitor of the RNase H activity of wild-type HIV-1 group O RT, although we observed a 6.5-fold increase in the IC50 in comparison with the prototypic HIV-1 group M subtype B enzyme. Mutagenesis studies showed that RT RNase H domain residues Asn474 and Tyr501, and in a lesser extent Ala502 and Ala508, are critical for RMNC6 inhibition of the endonuclease activity of the RT, without affecting its DNA polymerization activity. Our results show that RMNC6 acts as a dual inhibitor with allosteric sites in the DNA polymerase and the RNase H domains of HIV-1 R

Clinical and immunohistochemical study of eight cases with thymic carcinoma

BACKGROUND: Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the biological characteristics of thymic carcinoma, we reviewed 8 patients. METHODS: There were 2 men and 6 women: ages ranged from 19 to 67 years old (mean 54.8 years). None of these patients had concomitant myasthenia gravis and pure red cell aplasia. No patient had stage I disease, 1 stage II, 5 stage III, and 2 stage IV. The pathologic subtypes of thymic carcinoma included 5 squamous cell carcinomas, 1 adenosquamous cell carcinomas, 1 clear cell carcinoma, and 1 small cell carcinoma. Immunohistochemical study was performed using antibodies against p53, bcl-2, Ki-67, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), nm23-H1, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and factor VIII. RESULTS: Curative resection could be done in 4 patients (50%). Our data indicates a trend toward an association between complete resection and patient survival. Expression of p53, bcl-2, CEA, EMA, nm23-H1, VEGF and FGF-2 was detected in 5/8, 3/8, 4/8, 5/8, 6/8, 5/8 and 3/8, respectively. Mean Ki-67 labeling index and microvessel density was 7.01 and 34.36 (per 200× field), respectively. When compared with our previous studies, immunohistochemical staining of these proteins in thymomas, the expression rates of these proteins in thymic carcinomas were higher than those in thymomas. CONCLUSIONS: In this small series, it is suggested that a complete resection suggests a favorable result. Immunohistochemical results reveal that the expression of these proteins might indicate the aggressiveness of thymic carcinoma

An occasional diagnosis of myasthenia gravis - a focus on thymus during cardiac surgery: a case report

<p>Abstract</p> <p>Background</p> <p>Myasthenia gravis, an uncommon autoimmune syndrome, is commonly associated with thymus abnormalities. Thymomatous myasthenia gravis is considered to have worst prognosis and thymectomy can reverse symptoms if precociously performed.</p> <p>Case report</p> <p>We describe a case of a patient who underwent mitral valve repair and was found to have an occasional thymomatous mass during the surgery. A total thymectomy was performed concomitantly to the mitral valve repair.</p> <p>Conclusion</p> <p>The diagnosis of thymomatous myasthenia gravis was confirmed postoperatively. Following the surgery this patient was strictly monitored and at 1-year follow-up a complete stable remission had been successfully achieved.</p

Unique presentation of a giant mediastinal tumor as kyphosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although posture distortion is a common problem in elderly patients, spinal deformity caused by a thymoma has not been previously reported. Thymomas are slowly growing tumors that predominantly cause respiratory symptoms.</p> <p>Case presentation</p> <p>We report the case of an 83-year-old woman who was admitted with a giant mediastinal mass that had caused progressive spinal distortion and weight loss to our department. The clinical and laboratory investigations that followed revealed one of the largest thymomas ever reported in the medical literature, presenting as a mass lesion placed at the left hemithorax. She underwent complete surgical excision of the tumor via a median sternotomy. Two years after the operation, she showed significant improvement in her posture, no pulmonary discomfort, and a gain of 20 kg; she remains disease free based on radiographic investigations.</p> <p>Conclusions</p> <p>In this case, a chronic asymmetric load on the spine resulted in an abnormal vertebral curvature deformity that presented as kyphosis.</p

Comparative Genome Analysis of Lactobacillus reuteri and Lactobacillus fermentum Reveal a Genomic Island for Reuterin and Cobalamin Production

Lactobacillus reuteri is a heterofermentative lactic acid bacterium that naturally inhabits the gut of humans and other animals. The probiotic effects of L. reuteri have been proposed to be largely associated with the production of the broad-spectrum antimicrobial compound reuterin during anaerobic metabolism of glycerol. We determined the complete genome sequences of the reuterin-producing L. reuteri JCM 1112T and its closely related species Lactobacillus fermentum IFO 3956. Both are in the same phylogenetic group within the genus Lactobacillus. Comparative genome analysis revealed that L. reuteri JCM 1112T has a unique cluster of 58 genes for the biosynthesis of reuterin and cobalamin (vitamin B12). The 58-gene cluster has a lower GC content and is apparently inserted into the conserved region, suggesting that the cluster represents a genomic island acquired from an anomalous source. Two-dimensional nuclear magnetic resonance (2D-NMR) with 13C3-glycerol demonstrated that L. reuteri JCM 1112T could convert glycerol to reuterin in vivo, substantiating the potential of L. reuteri JCM 1112T to produce reuterin in the intestine. Given that glycerol is shown to be naturally present in feces, the acquired ability to produce reuterin and cobalamin is an adaptive evolutionary response that likely contributes to the probiotic properties of L. reuteri

DNA Fingerprinting of Pearls to Determine Their Origins

We report the first successful extraction of oyster DNA from a pearl and use it to identify the source oyster species for the three major pearl-producing oyster species Pinctada margaritifera, P. maxima and P. radiata. Both mitochondrial and nuclear gene fragments could be PCR-amplified and sequenced. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in the internal transcribed spacer (ITS) region was developed and used to identify 18 pearls of unknown origin. A micro-drilling technique was developed to obtain small amounts of DNA while maintaining the commercial value of the pearls. This DNA fingerprinting method could be used to document the source of historic pearls and will provide more transparency for traders and consumers within the pearl industry