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Summary: Background: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome‐wide association studies (GWASs) have identified some single‐nucleotide polymorphisms (SNPs) associated with cutaneous melanoma‐specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. Objectives: To examine associations between SNPs in folate metabolic pathway genes and CMSS. Methods: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow‐up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. Results: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta‐analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32–2·32, P = 9·96 × 10–5) and 2·05 (1·39–3·01, P = 2·84 × 10–4), respectively. The genotype–phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP‐related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. Conclusions: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic?Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma‐specific prognosis.A hypothesis‐driven approach, by pooling the effects of single‐nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add?Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma‐specific survival (CMSS). What is the translational message?The identification of genetic variants will make a risk‐prediction model possible for CMSS.The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma. [ABSTRACT FROM AUTHOR]

Aims: Although comammox have been discovered in a variety of ecosystems, there are few studies in urban lakes. This paper attempted to confirm whether this ammonia‐oxidizing microbe exists in urban lakes and to determine the factors influencing its existence. Methods and Results: This study investigated the diversity and abundance of comammox bacteria in sediments of a typical urban lake in China, and their ecological relationship with other ammonia‐oxidizing micro‐organisms. The phylogenetic analysis indicated that comammox clade A existed in the sediment of Lake Donghu, and the comammox bacteria co‐existed with ammonia‐oxidizing archaea (AOA), ammonia‐oxidizing bacteria (AOB) and anaerobic ammonia‐oxidizing (anammox) bacteria in the sediment of this lake. The abundances of the ammonia monooxygenase subunit A (amoA) genes for comammox, AOA, AOB and anammox 16S rRNA were 2·43 × 108, 1·07 × 108, 3·24 × 107 and 3·21 × 1011 copies per gram dry sediment respectively. Moreover, the amoA gene abundance of comammox was positively correlated with that of AOA and AOB. The redundancy analysis showed that the abundance of the comammox amoA gene was negatively correlated with the concentration of main indicators for nitrogen status in both the sediment and the water column, indicating that eutrophication may inhibit the growth of comammox bacteria. Conclusions: Comammox bacteria play an important ecological role in the nitrogen cycle of urban lake sediments. Significance and Impact of the Study: Our results indicated comammox bacteria were widespread in urban lakes and eutrophication may inhibit their growth. [ABSTRACT FROM AUTHOR]

Objectives: To compare antibiotic susceptibility of community-acquired respiratory bacteria in China during 2009-11 and 2013-14.Methods: Susceptibility was determined by Etest(®) (bioMérieux) or disc diffusion according to CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints, except for azithromycin where Etest(®) breakpoints (in CO2 incubation) were used in place of standard CLSI breakpoints. Statistical significance of differences in susceptibility across time periods was evaluated using Fisher's exact test.Results: During 2009-11, 434 Streptococcus pneumoniae, 307 Haemophilus influenzae and 140 Moraxella catarrhalis were collected from eight centres and during 2013-14, 208 S. pneumoniae, 185 H. influenzae and 80 M. catarrhalis were collected from five centres. Penicillin-non-susceptible isolates remained stable at ∼66% over both time periods but susceptibility decreased significantly for amoxicillin/clavulanic acid (or amoxicillin) and cefaclor. For H. influenzae, the proportion of β-lactamase-positive isolates and β-lactamase-negative ampicillin-resistant strains (CLSI definition) was higher in 2013-14 (25.4% and 7.0%, respectively) than in 2009-11 (16.3% and 3.6%, respectively), with decreased ampicillin and cephalosporin susceptibility. By 2009-11 and 2013-14, only amoxicillin/clavulanic acid (amoxicillin), levofloxacin, penicillin (intravenously) and chloramphenicol inhibited >70% of S. pneumoniae. During 2013-14, M. catarrhalis showed increasing resistance, with cefaclor and levofloxacin susceptibility decreasing significantly. However, amoxicillin/clavulanic acid, cefuroxime and levofloxacin continued to inhibit >90% of isolates.Conclusions: On the whole, antimicrobial susceptibility decreased in China between 2009-11 and 2013-14. In 2013-14, amoxicillin/clavulanic acid, levofloxacin and chloramphenicol were the most active antibacterial agents tested against community-acquired respiratory pathogens when assessed by CLSI, EUCAST or PK/PD breakpoints. Resistance to other antibacterials in China was generally high. Our data demonstrate the need to harmonize breakpoints for these pathogens. [ABSTRACT FROM AUTHOR]

Aims This study aims to explore how feuD mutation triggered the increase in nisin immunity of Lactococcus lactis L58, which was proven to be a feuD::Em-Mu mutant of Lc. lactis N8. Methods and Results The significant difference genes of Lc. lactis L58 and Lc. lactis N8 were compared at transcription and protein levels. Analysis revealed that the feuD mutation induced decrease in histidine-containing phosphocarrier protein PtsH ( HPr) and increase in thioredoxin reductase TrxB ( TR). Determination of iron concentration and cytoplasmic membrane potential ( MP) showed the iron concentration decreased around 10% and the MP decreased approx. 14% in Lc. lactis L58. Conclusions The increase in nisin immunity was dominated by TR up-expression by two main mechanisms in Lc. lactis L58. First, the TR- TRX (thioredoxin reductase) system changed the composition of cytoplasmic membrane by regulating the lipid metabolism to enhance the cells' resistance to nisin. Second, iron starvation stress induced decrease in MP; hence, the binding affinity of nisin to lipid II of Lc. lactis L58 decreased, which, in turn, increased the nisin immunity. Significance and Impact of the Study The knowledge on regulation mechanism of nisin immunity was enriched, and the theoretical basis for improving nisin production in engineering strain could be provided. [ABSTRACT FROM AUTHOR]

B memory cells remain in circulation and secrete alloantibodies without antigen exposure > 20 years after alloimmunization postpartum or by transplantation. These long-lived B cells are resistant to cytostatic drugs. Therapeutically, intravenous immunoglobulin ( IVIg) is administered to reduce allo-human leucocyte antigen ( HLA) antibodies pre- and post-transplantation, but the mechanism of reduction remains unclear. Recently, we reported that IVIg reacts with several HLA- I alleles and the HLA reactivity of IVIg is lost after its HLA- E reactivity is adsorbed out. Therefore, we have generated an anti- HLA- E monoclonal antibody that mimics the HLA-reactivity of IVIg to investigate whether this antibody suppresses IgG secretion, as does IVIg. B cells were purified from the blood of a woman in whose blood the B memory cells remained without antigen exposure > 20 years after postpartum alloimmunization. The B cells were stimulated with cytokines using a well-defined culture system. The anti- HLA- E monoclonal antibody (m Ab) significantly suppressed the allo- HLA class- II IgG produced by the B cells, and that this suppression was far superior to that by IVIg. These findings were confirmed with HLA- I antibody secreted by the immortalized B cell line, developed from the blood of another alloimmunized woman. The binding affinity of the anti- HLA- E m Ab for peptide sequences shared (i.e. shared epitopes) between HLA- E and other β2-microglobulin-free HLA heavy chains (open conformers) on the cell surface of B cells may act as a ligand and signal suppression of IgG production of activated B memory cells. We propose that anti- HLA- E monoclonal antibody may also be useful to suppress allo- HLA IgG production in vivo. [ABSTRACT FROM AUTHOR]

In wing dimorphic cricket Velarifictorus micado Saussure, group rearing could induce macropters, but rearing density had a nonlinear effect on the incidence of macroptery. Frequency of macropters increased along with rearing density under low-density conditions, but it decreased gradually under high densities, especially for the females. This result indicates that flight ability is required to escape from crowded conditions, but there is a factor that would suppress wing development under high-population density in V. micado. Investigation of body injury showed that incidence of body injury increased along with rearing density, especially for the antenna. Removal of antennas or hindlegs in the penultimate nymphal stage exerted a strong micropterizing effect. These results suggest that brachypterizing effect of high density may be related with body injury. Removed antennas at different instars, brachypterizing effect was only significant in sixth instar (penultimate instar) for males, and sixth and seventh instar (last instar) for females, which suggests that penultimate and last instars may be sensitive stages in winglength development to the effect of body injury in V. micado. [ABSTRACT FROM PUBLISHER]

Aims: To characterize and identify a novel Huperzine A (HupA)-producing fungal strain Slf14 isolated from Huperzia serrata (Thunb. ex Murray) Trev. in China. Methods and Results: The isolation, identification and characterization of a novel endophytic fungus producing HupA specifically and consistently from the leaves of H. serrata were investigated. The fungus was identified as Shiraia sp. Slf14 by molecular and morphological methods. The HupA produced by this endophytic fungus was shown to be identical to authentic HupA analysed by thin layer chromatographic, High-performance liquid chromatography (HPLC), LC-MS, 1H NMR and acetylcholinesterase (AChE) inhibition activity in vitro. The amount of HupA produced by Shiraia sp. Slf14 was quantified to be 327·8 μg l−1 by HPLC, which was far higher than that of the reported endophytic fungi, Acremonium sp., Blastomyces sp. and Botrytis sp. Conclusions: The production of HupA by endophyte Shiraia sp. Slf14 is an enigmatic observation. It would be interesting to further study the HupA production and regulation by the cultured endophyte in H. serrata and in axenic cultures. Significance and Impact of the Study: Although the current accumulation of HupA by the endophyte is not very high, it could provide a promising alterative approach for large-scale production of HupA. However, further strain improvement and the fermentation process optimization are required to result in the consistent and dependable production. [ABSTRACT FROM AUTHOR]

Objective: Pneumocystis is an opportunistic pathogen that often causes fatal pneumonia in immunocompromised patients. It remains an important cause of morbidity and mortality in immunocompromised hosts. Therefore, the development of a vaccine is needed. Kexin is a furin-like protease which may be involved in the proteolytic processing of other proteins of Pneumocystis. We focused on the cellular and humoral responses to the kexin antigen fragment of Pneumocystis in our study. Methods: The full-length DNA sequence of the kexin gene was amplified from rat Pneumocystis carinii (P. carinii). The recombinant plasmid pET-kexin was constructed, and the recombinant antigen His-kexin was purified, respectively. Then the mice were immunized with His-kexin. To ensure the isolated protein used in the next experiments was purified and of the right molecular weight, Western blotting analysis was performed. Then the specific humoral immunity was measured by ELISA. The specific cellular immunity was measured by the proliferation response of spleen lymphocytes. Results: The full-length Pneumocystis kexin gene was cloned successfully. The sera could recognize another recombinant antigen GST-kexin containing the identical amino acid sequence of kexin fragment with His-kexin, as identified by Western blotting and ELISA. The splenocytes collected from the mice immunized with His-kexin had significantly proliferative responses to GST-kexin compared to the control animals. Conclusions: These findings showed that kexin was the potential antigen to induce immune defense against P. carinii infection. The result would provide basis for the further vaccine study in the development of immunoprophylaxis and immunotherapy against P. carinii infection. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to develop endurance to copper stress in Potamogeton crispus L. by inoculation with the anti-copper strain ACU – a novel Enterobacteriaceae bacterium isolated from the rhizosphere of Eichhornia crassipes with high copper-removal ability. Methods and Results: A spherical copper-resistant bacterium, namely ACU, was isolated from the rhizosphere of E. crassipes. It was demonstrated to have substantial copper-removing capability, even at copper concentrations as high as 69 mg l−1. The 16S rRNA gene sequence of ACU suggested it to be a novel Enterobacteriaceae bacterium most closely related to Providencia sp. With increasing copper concentrations, the growth rate of ACU gradually decreased with a delay in the logarithmic growth phase. ACU demonstrated high copper-removal ability at the lag phase when cultivated in media with high copper concentrations. A 48-kDa extracellular copper-binding protein was detected in ACU. When P. crispus was inoculated with ACU, the growth ability of P. crispus significantly improved at all the tested copper concentrations, and the lethal time for 10 mg l−1 was delayed. Further study revealed that while ACU cells were rarely detected in the culture solution, they were associated with the surface of P. crispus. These findings indicated that ACU grew by anchoring itself on the surface of P. crispus and could increase the ability of P. crispus to resist copper toxicity. Conclusion: To the best of our knowledge, the Enterobacteriaceae bacterium ACU is a novel nonpathogenic bacterium with high copper-removing ability from water. Significance and Impact of the Study: This study demonstrated that the Enterobacteriaceae bacterium ACU has potential applicability for use in copper removal and in the protection of aquatic plants in copper-polluted water. [ABSTRACT FROM AUTHOR]