Production of cellulolytic enzymes from theXylaria andHypoxylon species of xylariaceae

Eighteen strains of xylariaceous fungi have been screened for higher activities of cellulolytic enzymes,Trichoderma reesei QM 9414 was also examined for comparison. Strains ofXylaria anisopleura andX. regalis had higher endocellulase (CMCase) and exocellulase (Avicelase) activities after 2 weeks' incubation.Hypoxylon stygium produced the highest activity of -glucosidase 3 days after inoculation. The optimum pH for these cellulolytic enzymes was approx. 5.0 and the optimum temperatures ranged from 37 to 50°C. A mixed culture process usingT. reesei QM 9414 andH. stygium was developed to obtain enhanced synthesis of cellulase. -Glucosidase activities in the mixed culture increased within 48h whenH. stygium was introduced after 24h.     

Nucleophilic participation of reduced flavin coenzyme in mechanism of UDP-galactopyranose mutase

UDP-galactopyranose mutase (UGM) requires reduced FAD (FAD(red)) to catalyze the reversible interconversion of UDP-galactopyranose (UDP-Galp) and UDP-galactofuranose (UDP-Galf). Recent structural and mechanistic studies of UGM have provided evidence for the existence of an FAD-Galf/p adduct as an intermediate in the catalytic cycle. These findings are consistent with Lewis acid/base chemistry involving nucleophilic attack by N5 of FAD(red) at C1 of UDP-Galf/p. In this study, we employed a variety of FAD analogues to characterize the role of FAD(red) in the UGM catalytic cycle using positional isotope exchange (PIX) and linear free energy relationship studies. PIX studies indicated that UGM reconstituted with 5-deaza-FAD(red) is unable to catalyze PIX of the bridging C1-OP(β) oxygen of UDP-Galp, suggesting a direct role for the FAD(red) N5 atom in this process. In addition, analysis of kinetic linear free energy relationships of k(cat) versus the nucleophilicity of N5 of FAD(red) gave a slope of ρ = -2.4 ± 0.4. Together, these findings are most consistent with a chemical mechanism for UGM involving an S(N)2-type displacement of UDP from UDP-Galf/p by N5 of FAD(red).     

Epidemiological Characteristics of Strongyloidiasis in Inhabitants of Indigenous Communities in Borneo Island,Malaysia

Epidemiological study on strongyloidiasis in humans is currently lacking in Malaysia. Thus, a cross-sectional study was carried out to determine the prevalence of Strongyloides stercoralis infection among the inhabitants of longhouse indigenous communities in Sarawak. A single stool and blood sample were collected from each participant and subjected to microscopy, serological and molecular techniques. Five species of intestinal parasites were identified by stool microscopy. None of the stool samples were positive for S. stercoralis. However, 11% of 236 serum samples were seropositive for strongyloidiasis. Further confirmation using molecular technique on stool samples of the seropositive individuals successfully amplified 5 samples, suggesting current active infections. The prevalence was significantly higher in adult males and tended to increase with age. S. stercoralis should no longer be neglected in any intestinal parasitic survey. Combination of more than 1 diagnostic technique is necessary to increase the likelihood of estimating the ‘true’ prevalence of S. stercoralis.     

NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128

Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox-LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time-dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL-6, IL-1β, and TNF-α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells. Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox-LDL-induced inflammation and oxidative stress in AS development through sponging miR-128.     

A statistical model for the genetic origin of allometric scaling laws in biology

Many biological processes, from cellular metabolism to population dynamics, are characterized by particular allometric scaling (power-law) relationships between size and rate. Although such allometric relationships may be under genetic determination, their precise genetic mechanisms have not been clearly understood due to a lack of a statistical analytical method. In this paper, we present a basic statistical framework for mapping quantitative genes (or quantitative trait loci, QTL) responsible for universal quarter-power scaling laws of organic structure and function with the entire body size. Our model framework allows the testing of whether a single QTL affects the allometric relationship of two traits or whether more than one linked QTL is segregating. Like traditional multi-trait mapping, this new model can increase the power to detect the underlying QTL and the precision of its localization on the genome. Beyond the traditional method, this model is integrated with pervasive scaling laws to take advantage of the mechanistic relationships of biological structures and processes. Simulation studies indicate that the estimation precision of the QTL position and effect can be improved when the scaling relationship of the two traits is considered. The application of our model in a real example from forest trees leads to successful detection of a QTL governing the allometric relationship of third-year stem height with third-year stem biomass. The model proposed here has implications for genetic, evolutionary, biomedicinal and breeding research.     

Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients

In this study, we characterized the intratumoral expression of IL-17 and CD8(+) TILs in gastric adenocarcinoma patients after resection and determined the correlation between the survival probability of gastric adenocarcinoma patients and the expression of IL-17 in tumor. Expression of IL-17 and CD8 was assessed by immunohistochemistry, and the prognostic effects of intratumoral IL-17 expression and CD8(+) TILs were evaluated by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection revealed the presence of IL-17 and CD8(+) cells in gastric adenocarcinoma tissue samples (90.6%, 174 out of 192 patients and 96.9%, 186 out of 192 patients, respectively). We have also found that intratumoral IL-17 expression was significantly correlated with age (p=0.004) and that the number of CD8(+)TILs was significantly correlated with UICC staging (p=0.012) and the depth of tumor invasion (p=0.022). The five-year overall survival probability among patients intratumorally expressing higher levels of IL-17 was significantly better than those expressing lower levels of IL-17 (p=0.036). Multivariate Cox proportional hazard analyses revealed that intratumoral IL-17 expression (HR: 0.521; 95% CI: 0.329-0.823; p=0.005) was an independent factor affecting the five-year overall survival probability. We conclude that low levels of intratumoral IL-17 expression may indicate poor prognosis in gastric adenocarcinoma patients.     

Template-based modeling and ab-initio docking using CoDock in CAPRI

Integration of template-based modeling, global sampling and precise scoring is crucial for the development of molecular docking programs with improved accuracy. We combined template-based modeling and ab-initio docking protocol as hybrid docking strategy called CoDock for the docking and scoring experiments of the seventh CAPRI edition. For CAPRI rounds 38-45, we obtained acceptable or better models in the top 10 submissions for eight out of the 16 evaluated targets as predictors, nine out of the 16 targets as scorers. Especially, we submitted acceptable models for all of the evaluated protein-oligosaccharide targets. For the CASP13-CAPRI experiment (round 46), we obtained acceptable or better models in the top 5 submissions for 10 out of the 20 evaluated targets as predictors, 11 out of the 20 targets as scorers. The failed cases for our group were mainly the difficult targets and the protein-peptide systems in CAPRI and CASP13-CAPRI experiments. In summary, this CAPRI edition showed that our hybrid docking strategy can be efficiently adapted to the increasing variety of challenges in the field of molecular interactions.     

Photoacoustic Imaging of Breast Microcalcifications: A Preliminary Study with 8-Gauge Core-Biopsied Breast Specimens

Background

We presented the photoacoustic imaging (PAI) tool and to evaluate whether microcalcifications in breast tissue can be detected on photoacoustic (PA) images.

Methods

We collected 21 cores containing microcalcifications (n = 11, microcalcification group) and none (n = 10, control group) in stereotactic or ultrasound (US) guided 8-gauge vacuum-assisted biopsies. Photoacoustic (PA) images were acquired through ex vivo experiments by transmitting laser pulses with two different wavelengths (700 nm and 800 nm). The presence of microcalcifications in PA images were blindly assessed by two radiologists and compared with specimen mammography. A ratio of the signal amplitude occurring at 700 nm to that occurring at 800 nm was calculated for each PA focus and was called the PAI ratio.

Results

Based on the change of PA signal amplitude between 700 nm and 800 nm, 10 out of 11 specimens containing microcalcifications and 8 out of 10 specimens without calcifications were correctly identified on blind review; the sensitivity, specificity, accuracy, positive predictive and negative predictive values of our blind review were 90.91%, 80.0%, 85.71%, 83.33% and 88.89%. The PAI ratio in the microcalcification group was significantly higher than that in the control group (the median PAI ratio, 2.46 versus 1.11, respectively, P = .001). On subgroup analysis in the microcalcification group, neither malignant diagnosis nor the number or size of calcification-foci was proven to contribute to PAI ratios.

Conclusion

Breast microcalcifications generated distinguishable PA signals unlike breast tissue without calcifications. So, PAI, a non-ionizing and non-invasive hybrid imaging technique, can be an alternative in overcoming the limitations of conventional US imaging.     

A novel surface protein of Trichomonas vaginalis is regulated independently by low iron and contact with vaginal epithelial cells

Background  

Trichomonosis caused by Trichomonas vaginalis is the number one, non-viral sexually transmitted disease (STD) that affects more than 250 million people worldwide. Immunoglobulin A (IgA) has been implicated in resistance to mucosal infections by pathogens. No reports are available of IgA-reactive proteins and the role, if any, of this class of antibody in the control of this STD. The availability of an IgA monoclonal antibody (mAb) immunoreactive to trichomonads by whole cell (WC)-ELISA prompted us to characterize the IgA-reactive protein of T. vaginalis.