CARAGANA FABR. PROMOTES REVEGETATION AND SOIL REHABILITATION IN SALINE-ALKALI WASTELAND

To determine how plantations of Caragana microphylla shrubs affect saline-alkali soil amelioration and revegetation, we investigated the vegetation and sampled soils from saline-alkali wasteland (SAW), perennial Caragana forestland (PCF), Caragana forest after fire disturbance (CFF). Results showed that with the development of Caragana Fabr., highly dominant species of Poaceae family, including Elymus dahuricus, Thermopsis lanceolata, Stipa tianschanica, died out in PCF. Moreover, Papilionaceae family, including Lespedeza indica, Oxytropis psammocharis, and Astragalus scaberrimus, was established both in PCF and CFF. Phytoremediation of saline-alkali wasteland (SAW) was achieved by plantation, resulting in the reduced soil pH, sodium adsorption ratio, exchangeable sodium percentage, salinity, and Na⁺ concentration around Caragana shrubs. Greater amounts of soil organic, total nitrogen, ammonium nitrogen, available phosphorus, and available potassium were observed in PCF topsoil than in SAW topsoil. The concentration of mineralized N in PCF soil was significantly lower than that in SAW soil at all sampled depths, indicating that Caragana shrubs were just using N and therefore less measured in soils. Fire disturbance resulted in decreased soil pH and salinity, but increased organic content, total nitrogen, and ammonium nitrogen. The improved soil parameters and self-recovery of shrubs indicated that Caragana shrubs were well established after burning event.     

Associations between XRCC1 and ERCC2 polymorphisms and DNA damage in peripheral blood lymphocyte among coke oven workers

A wide variety of base damages and single-strand breaks formed by reactive oxygen species during metabolic activation of polycyclic aromatic hydrocarbons (PAHs) have been recognized to be involved in PAH carcinogenesis. In this study, alkaline comet assay was used to detect the DNA damage in peripheral blood lymphocytes among 143 coke-oven workers and 50 non-coke-oven workers, and the effects of genetic polymorphisms of XRCC1 and ERCC2 genes on DNA damage were evaluated. The olive tail moment was significantly higher in coke-oven workers than in non-coke-oven workers (2.6, 95% CI=2.1–3.3 versus 1.0, 95% CI=0.8–1.2, p<0.01), and significant correlation between ln-transformed urinary 1-OHP and ln-transformed olive tail moment was found in total population (n=193, Pearson's r=0.393, p<0.001) and in coke-oven workers (n=143, Pearson's r=0.224, p=0.007). The olive tail moment was significantly higher in coke-oven workers with GA genotype of G27466A polymorphism of XRCC1 than those with GG genotype (4.6, 95% CI=2.5–8.7 versus 2.4, 95% CI=1.9–2.9, p<0.01 with adjustment for covariates). No significant associations between C26304T, G28152A and G36189A polymorphisms of XRCC1 and G23591A and A35931C polymorphisms of ERCC2 and olive tail moment were found in both groups. The study showed that the alkaline comet assay is a suitable biomarker in the detection of DNA damage among coke-oven workers and it suggested that the A allele of G27466A polymorphism of XRCC1 may be associated with decreased DNA repair capacity toward PAH-induced base damage and strand breaks.     

Net primary productivity and rain‐use efficiency as affected by warming,altered precipitation,and clipping in a mixed‐grass prairie

Grassland productivity in response to climate change and land use is a global concern. In order to explore the effects of climate change and land use on net primary productivity (NPP), NPP partitioning [f_BNPP, defined as the fraction of belowground NPP (BNPP) to NPP], and rain‐use efficiency (RUE) of NPP, we conducted a field experiment with warming (+3 °C), altered precipitation (double and half), and annual clipping in a mixed‐grass prairie in Oklahoma, USA since July, 2009. Across the years, warming significantly increased BNPP, f_BNPP, and RUE_BNPP by an average of 11.6%, 2.8%, and 6.6%, respectively. This indicates that BNPP was more sensitive to warming than aboveground NPP (ANPP) since warming did not change ANPP and RUE_ANPP much. Double precipitation stimulated ANPP, BNPP, and NPP but suppressed RUE_ANPP, RUE_BNPP, and RUE_NPP while half precipitation decreased ANPP, BNPP, and NPP but increased RUE_ANPP, RUE_BNPP, and RUE_NPP. Clipping interacted with altered precipitation in impacting RUE_ANPP, RUE_BNPP, and RUE_NPP, suggesting land use could confound the effects of precipitation changes on ecosystem processes. Soil moisture was found to be a main factor in regulating variation in ANPP, BNPP, and NPP while soil temperature was the dominant factor influencing f_BNPP. These findings suggest that BNPP is critical point to future research. Additionally, results from single‐factor manipulative experiments should be treated with caution due to the non‐additive interactive effects of warming with altered precipitation and land use (clipping).     

CRM1 Is a Cellular Target of Curcumin: New Insights for the Myriad of Biological Effects of an Ancient Spice

Curcumin is the major constituent of turmeric plant, an ancient spice widely used in Indian cuisine and traditional herbal medicine. Recently, the potential medical use of curcumin as anti‐cancer and anti‐inflammatory agent has set off an upsurge in research into the mechanism for its broad biological effects. We showed that CRM1, an important nuclear exportin, is a cellular target of curcumin by serious experimental and theoretical investigation. Using a nuclear export functional assay, we observed a clear and rapid shift of cargo proteins from a cytoplasmic localization to the nucleus when treated with curcumin or its structural analogue dibenzylideneacetone (DBA). We demonstrated that curcumin could specifically target the conserved Cys⁵²⁸ of CRM1 through mass spectrometric analysis and in vivo experiments. Furthermore, computational modeling has revealed that curcumin could be correctly docked into the hydrophobic pocket of CRM1 judged from shape complementarity and putative molecular interactions. The Michael acceptor moiety on curcumin is within the appropriate distance to enable Michael reaction with Cys residue of CRM1. More importantly, we showed that nuclear retention of FOXO1 could be observed in the presence of Leptomycin B (LMB) or curcumin whereas in cells expressing the CRM1‐Cys⁵²⁸ mutant, only a cytoplasmic localization was observed. The inhibition of nuclear traffic by curcumin may account for its myriad of biological effects, particularly for its therapeutic properties in cancer and inflammatory diseases. Our findings may have important implications for further clinical investigation of curcumin .     

BreakTrans: uncovering the genomic architecture of gene fusions

Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTrans     

A Meta-Analysis of Anti-Vascular Endothelial Growth Factor Remedy for Macular Edema Secondary to Central Retinal Vein Occlusion

Background

Central retinal vein occlusion (CRVO) associates with severe vision outcome and no proven beneficial treatment. Our meta-analysis intended to appraise the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents in macular edema (ME) following CRVO.

Methods

Data were collected and analyzed by Review Manager 5.2.1. We employed a random-effects model to eliminate between-study heterogeneity. N_fs (called fail-safe number) was calculated to evaluate the publication bias.

Results

We included 5 trials consisting 323 cases and 281 controls. Primary outcomes showed that overall comparison of anti-VEGF agents with placebo control yielded a 374% and 136% increased tendency for a gain of 15 letters or more on Early Treatment Diabetic Retinopathy Study (ETDRS) chart (95% confidence interval [95% CI]: 2.43–9.23; P<0.00001; I² = 59%, 95% CI: 1.60–3.49; P<0.0001; I² = 0%, respectively) at 6 and 12 months. Secondary outcomes showed that a 90% and 77% decreased risk at 6 and 12 months for a loss of 15 letters or more. The overall mean difference showed a statistically significance in best-corrected visual acuity (BCVA) on each time point. However, changes of central retinal thickness (CRT) lost significance at 12 months after 6-month as-needed treatment. The incidence of adverse events (AEs) had no statistical difference between anti-VEGF and placebo groups. Subgroup analyses indicated that patients receiving Aflibercept got the highest tendency to gain 15 letters or more (OR = 9.78; 95% CI: 4.43–21.56; P<0.00001). Age controlled analysis suggested a weaken tendency of BCVA improvement in age over 50 (MD = 12.26; 95% CI: 7.55–16.98; P<0.00001). Subgroup analysis by clinical classification showed a strengthen difference of BCVA changes at 6 months in ischemic type (MD = 19.65 letters, 95% CI: 13.15 to 26.14 letters, P<0.00001).

Conclusions

Our results showed that anti-VEGF agents were superior to placebo in CRVO-ME treatment with no statistically significant AEs, especially in younger people and for ischemic type.     

Molecular Modeling Reveals the Novel Inhibition Mechanism and Binding Mode of Three Natural Compounds to Staphylococcal α-Hemolysin

α-Hemolysin (α-HL) is a self-assembling, channel-forming toxin that is produced as a soluble monomer by Staphylococcus aureus strains. Until now, α-HL has been a significant virulence target for the treatment of S. aureus infection. In our previous report, we demonstrated that some natural compounds could bind to α-HL. Due to the binding of those compounds, the conformational transition of α-HL from the monomer to the oligomer was blocked, which resulted in inhibition of the hemolytic activity of α-HL. However, these results have not indicated how the binding of the α-HL inhibitors influence the conformational transition of the whole protein during the oligomerization process. In this study, we found that three natural compounds, Oroxylin A 7-O-glucuronide (OLG), Oroxin A (ORA), and Oroxin B (ORB), when inhibiting the hemolytic activity of α-HL, could bind to the “stem” region of α-HL. This was completed using conventional Molecular Dynamics (MD) simulations. By interacting with the novel binding sites of α-HL, the ligands could form strong interactions with both sides of the binding cavity. The results of the principal component analysis (PCA) indicated that because of the inhibitors that bind to the “stem” region of α-HL, the conformational transition of α-HL from the monomer to the oligomer was restricted. This caused the inhibition of the hemolytic activity of α-HL. This novel inhibition mechanism has been confirmed by both the steered MD simulations and the experimental data obtained from a deoxycholate-induced oligomerization assay. This study can facilitate the design of new antibacterial drugs against S. aureus.     

Confocal Comparison of Corneal Reinnervation after Small Incision Lenticule Extraction (SMILE) and Femtosecond Laser In Situ Keratomileusis (FS-LASIK)

Purpose

To evaluate corneal reinnervation, and the corresponding corneal sensitivity and keratocyte density after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK).

Methods

In this prospective, non-randomized observational study, 18 patients (32 eyes) received SMILE surgery, and 22 patients (42 eyes) received FS-LASIK surgery to correct myopia. The corneal subbasal nerve density and microscopic morphological changes in corneal architecture were evaluated by confocal microscopy prior to surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. A correlation analysis was performed between subbasal corneal nerve density and the corresponding keratocyte density and corneal sensitivity.

Results

The decrease in subbasal nerve density was less severe in SMILE-treated eyes than in FS-LASIK-treated eyes at 1 week (P = 0.0147), 1 month (P = 0.0243), and 3 months (P = 0.0498), but no difference was detected at the 6-month visit (P = 0.5277). The subbasal nerve density correlated positively with central corneal sensitivity in both groups (r = 0.416, P<0.0001, and r = 0.2567, P = 0.0038 for SMILE group and FS-LASIK group, respectively). The SMILE-treated eyes have a lower risk of developing peripheral empty space with epithelial cells filling in (P = 0.0005).

Conclusions

The decrease in subbasal nerve fiber density was less severe in the SMILE group than the FS-LASIK group in the first 3 months following the surgeries. The subbasal nerve density was correlated with central corneal sensitivity.     

High Seroprevalence of Mycoplasma pneumoniae IgM in Acute Q Fever by Enzyme-Linked Immunosorbent Assay (ELISA)

Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.