Genomic analysis of Alteromonas sp. M12 isolated from the Mariana Trench reveals its role in dimethylsulfoniopropionate cycling.

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of bio­sulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria.

The peroxins BcPex8, BcPex10, and BcPex12 are required for the development and pathogenicity of Botrytis cinerea.

Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea. The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δbcpex8, Δbcpex10, and Δbcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δbcpex8, Δbcpex10, and Δbcpex12 strains. The mycelial growth rates of Δbcpex8, Δbcpex10, and Δbcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δbcpex8, Δbcpex10, and Δbcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8, BcPEX10, and BcPEX12 are indispensable for the development and pathogenicity of B. cinerea.

[Analysis of clinical features of chronic periaortitis].

OBJECTIVE: Understand the clinical features of chronic periaortitis. METHODS: The medical records of 28 cases with definite diagnosis of chronic periaortitis were reviewed retrospectively. RESULTS: Among these 28 cases, 20 (71.4%) fulfilled the diagnostic criteria of idiopathic retroperitoneal fibrosis (IPF), 5 (17.8%) were inflammatory abdominal aortic aneurysm (IAAA) and 3 (10.7%) were perianeurysmal retroperitoneal fibrosis (PARF). The common symptoms were abdominal blunt pain (35.7%), lumbago (25%), loss of body weight (25%), abdominal distension (17.8%) and lower extremities pitting edema (17.8%). Hydronephrosis was found by B ultrasonography in 17 (85%) patients with IPF. Dilated abdominal aorta were found in 7 patients. One case was complicated with ankylosing spondylitis and another one was diagnosed to have undifferentiated connective diseases. All 5 IAAA patients were treated by aneurysm segregation or stent implantation, but none had medical therapy. The 3 perianeurysmal retroperitoneal fibrosis patients were mis-diagnosed as with either IPF or AAA. Seventeen patients in this group were treated with corticosteroid combined with immunosuppressive agents or tamoxifen. Four cases were followed up and their conditions were improved which were demonstrated by repeated CT or MRI. CONCLUSION: Chronic periaortitis is a rare autoimmune rheumatic disease. IPF is the most common one compared to IAAA and PARF. It can be complicated with autoimmune disorders or serum auto-antibodies. No case with other organ fibrosis disorder wis observed in this study. Radiological examination and pathological examination are necessary for confirming the diagnosis. Corticosteroid combined with immunosuppressive agents or tamoxifen is the effective treatment.

[BAY11-7082 and Lactacystein in CD154-induced NF-kappaB activation].

OBJECTIVE: To investigate the inhibition mechanisms of BAY11-7082 (IkappaB-alpha phosphorylation inhibitor) and Lactacystein (proteosome inhibitor) in CD154-induced NF-kappaB activation. METHODS: We used recombinant CD154 to stimulate EBV/LMP1 negative Ramos B cell and observed the effects of BAY11-7082 and Lactacystein in CD154-induced NF-kappaB luciferase activation, phosphorylation and degradation of IkappaB-alpha, phosphorylation of p65, and nuclear translocation of NF-kappaB subunits upon CD154 stimulation. RESULTS: Both BAY11-7082 and Lactacystein abrogated CD154-induced NF-kappaB luciferase activation in Ramos cells. While CD154-induced phosphorylation of p65, phosphorylation and degradation of IkappaB-alpha, and nuclear translocation of p50, p65, and c-Rel were all blocked by BAY11-7082; Lactacystein only inhibited degradation of IkappaB-alpha and p65 nuclear translocation. CONCLUSION: BAY11-7082 and Lactacystein inhibit CD154-induced NF-kappaB activation through different mechanisms.

EDM1: a novel point mutation in cartilage oligomeric matrix protein gene in a Chinese family with multiple epiphyseal dysplasia.

BACKGROUND: Multiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP). METHODS: Five patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members. RESULTS: We have identified a novel mutation in axon 14 of COMP gene in the family. CONCLUSIONS: This mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Genetic analysis and serum level of cartilage oligomeric matrix protein in patients with pseudoachondroplasia.

BACKGROUND: Pseudoachondroplasia (PSACH) is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation. There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH. Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH. METHODS: A family with three patients and a sporadic case were recruited. Genomic and phenotypic data were recorded. The diagnosis of PSACH was made on the base of clinical evaluation. The genomic DNA was extracted from peripheral blood leukocytes. The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein. RESULTS: A deletion (c.1447-1455del) was identified in exon 13 in the sporadic case. The mean serum COMP concentrations of four patients (3.12+/-2.28) were significantly lower than those of control group (10.86+/-2.21, P<0.05). There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls. CONCLUSIONS: Mutations in COMP gene are responsible for the PSACH. Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.

Expression of programmed death 1 and its ligands in the liver of autoimmune hepatitis C57BL/6 mice.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with unknown etiology. Programmed death 1 (PD-1) and its ligands (PD-L1 and PD-L2), B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that are involved in the regulation of immune responses. Previous observation suggests that PD-1 system plays an inhibitory role in regulating peripheral blood T cells, B cells and myeloid cells, thus their abnormality may be related to autoimmune diseases. This study aimed to explore the role of PD-1/PD-L1, L2 system in the pathogenesis of AIH. METHODS: The mice model of experimental autoimmune hepatitis (EAH) was established in C57BL/6 mice and the expression levels of PD-1 and PD-L1, L2 in the murine liver and the cytokines, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-4 in the spleen were detected using reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with those of normal controls. RESULTS: The expression levels of PD-1, PD-L1, PD-L2 mRNA were higher in EAH compared with normal controls (P < 0.05), the PD-L2/PD-1 ratio was relatively lower in EAH (EAH -0.08 +/- 0.35, normal controls 0.52 +/- 0.07, P = 0.009). In the EAH, the expression of the three cytokines were all upregulated compared with normal controls. PD-L1 had a positive correlation with the expression of IFN-gamma (r = 0.289, P < 0.05), while PD-L2 showed a positive correlation with both expressions of IL-4 (r = 0.378, P< 0.01) and IFN-gamma (r = 0.261, P < 0.05). While TNF-alpha showed no correlation with PD-L1 (r = 0.044, P = 0.736) or PD-L2 (r = 0.127, P = 0.335). CONCLUSIONS: The expression of PD-1/PD-L1, L2 is upregulated in EAH and regulated by IFN-gamma and IL-4. PD-1 system may play an important role in the pathogenesis of AIH.