Population genetic structure of the newly invasive Q biotype of Bemisia tabaci in Taiwan

The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is among the top 100 invasive pests in the world, and it causes serious agricultural damage and economic losses in many countries. More than 24 biotypes of the sweetpotato whitefly have been detected worldwide, of which the Q biotype has recently been reported to be a new invasive pest spreading throughout the world via trade in poinsettias, Euphorbia pulcherrima Willd. ex Klotzsch (Euphorbiaceae). In 2006, the Q biotype was first recorded in Taiwan in greenhouses, but not in the field, suggesting that the invasion of this biotype might be at an early stage in that country. The mitochondrial cytochrome oxidase I (COI) gene and 12 microsatellite loci were used to investigate the genetic structure of multiple B. tabaci Q biotype populations. The presence of only a few COI haplotypes and a low number of nucleotide differences suggest high genetic similarity among these populations. Microsatellite analyses also revealed low genetic differentiation and frequent gene flow among greenhouses. The molecular evidence supports the occurrence of a recent genetic bottleneck in the B. tabaci Q biotype. Bayesian cluster analyses indicated that at least two invasion events have occurred in Taiwan. Phylogenetic analyses of microsatellites support Q biotype migration among greenhouses, which was likely facilitated by the frequent movement of poinsettias between greenhouses. Future management strategies should focus on developing plantlet trade regulations to avoid further anthropogenic dispersal of the B. tabaci Q biotype among greenhouses in Taiwan.     

Targeting lipid droplet lysophosphatidylcholine for cisplatin chemotherapy

This study aims to explore lipidic mechanism towards low‐density lipoprotein receptor (LDLR)‐mediated platinum chemotherapy resistance. By using the lipid profiling technology, LDLR knockdown was found to increase lysosomal lipids and decrease membranous lipid levels in EOC cells. LDLR knockdown also down‐regulated ether‐linked phosphatidylethanolamine (PE‐O, lysosomes or peroxisomes) and up‐regulated lysophosphatidylcholine [LPC, lipid droplet (LD)]. This implies that the manner of using Lands cycle (conversion of lysophospholipids) for LDs might affect cisplatin sensitivity. The bioinformatics analyses illustrated that LDLR‐related lipid entry into LD, rather than an endogenous lipid resource (eg Kennedy pathway), controls the EOC prognosis of platinum chemotherapy patients. Moreover, LDLR knockdown increased the number of platinum‐DNA adducts and reduced the LD platinum amount. By using a manufactured LPC‐liposome‐cisplatin (LLC) drug, the number of platinum‐DNA adducts increased significantly in LLC‐treated insensitive cells. Moreover, the cisplatin content in LDs increased upon LLC treatment. Furthermore, lipid profiles of 22 carcinoma cells with differential cisplatin sensitivity (9 sensitive vs 13 insensitive) were acquired. These profiles revealed low storage lipid levels in insensitive cells. This result recommends that LD lipidome might be a common pathway in multiple cancers for platinum sensitivity in EOC. Finally, LLC suppressed both cisplatin‐insensitive human carcinoma cell training and testing sets. Thus, LDLR‐platinum insensitivity can be due to a defective Lands cycle that hinders LPC production in LDs. Using lipidome assessment with the newly formulated LLC can be a promising cancer chemotherapy method.     

Arabidopsis thaliana as a model system for testing the effect of Trichoderma volatile organic compounds

In ecosystems, plant and bacterial volatile organic compounds (VOCs) are known to influence plant growth but less is known about the physiological effects of fungal VOCs. We have used Arabidopsis thaliana as a model to test the effects of VOCs from the soil fungus Trichoderma viride. Mature colonies of T. viride cultured on Petri plates were placed in a growth chamber in a shared atmosphere with A. thaliana without direct physical contact. Compared to controls, plants grown in the presence of T. viride volatiles were taller, bigger, flowered earlier, and had more lateral roots. They also had increased total biomass (45 %) and chlorophyll concentration (58 %). GC–MS analysis of T. viride VOCs revealed 51 compounds of which isobutyl alcohol, isopentyl alcohol, and 3-methylbutanal were most abundant. We conclude that VOCs emitted by T. viride have growth promoting effects on A. thaliana in the absence of direct physical contact.     

Resonance assignments of Ca2+-bound human S100A11

The S100 family belongs to the EF-hand calcium-binding proteins regulating a wide range of important cellular processes via protein–protein interactions. Most S100 proteins adopt a conformation of non-covalent homodimer for their functions. Calcium binding to the EF-hand motifs of S100 proteins is essential for triggering the structural changes, promoting exposure of hydrophobic regions necessary for target protein interactions. S100A11 is a protein found in diverse tissues and possesses multiple functions upon binding to different target proteins. RAGE is a multiligand receptor binding to S100A11 and the interactions at molecular level have not been reported. However, the three-dimensional structure of human S100A11 containing 105 amino acids is still not available for further interaction studies. To determine the solution structure, for the first time we report the ¹H, ¹⁵N and ¹³C resonance assignments and protein secondary structure prediction of human S100A11 dimer in complex with calcium using a variety of triple resonance NMR experiments and the chemical shift index (CSI) method, respectively.     

Association Study of Polymorphisms rs4552569 and rs17095830 and the Risk of Ankylosing Spondylitis in a Taiwanese Population

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. However, the development of anklosing spondylitis is unclear. Human leukocyte antigens HLA-B27 and ERAP1 have been widely reported to be associated with AS susceptibility. A recent genome-wide association study (GWAS) showed that two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569) and within ANO6 at 12q12 (rs17095830) contribute to the risk of AS in Han Chinese. In this study, we enrolled 475 AS patients and 475 healthy subjects to assess whether these genetic variations contribute to the susceptibility and the severity of AS in the Taiwanese population. The correlation between genetic polymorphisms, AS activity indexes, (namely, BASDAI, BASFI and BAS-G) and AS complications (uveitis and inflammatory bowel disease) were tested using the markers, rs4552569 and rs17095830. Although no association between rs4552569/rs17095830 genetic polymorphisms and AS susceptibility/severity was found, a significant association between rs17095830 and inflammatory bowel disease was observed in a Taiwanese population.     

Pitavastatin and Atorvastatin Double-Blind Randomized ComPArative Study among HiGh-Risk Patients,Including ThOse with Type 2 Diabetes Mellitus,in Taiwan (PAPAGO-T Study)

Background

Evidence about the efficacy and safety of statin treatment in high-risk patients with hypercholesterolemia is available for some populations, but not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter collaborative randomized parallel-group comparative study of high-risk ethnic Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition, the effects on other lipid parameters, inflammatory markers, insulin-resistance-associated biomarkers and safety were evaluated.

Methods and Results

Between July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 ± 8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n = 112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both groups were similar, but after 12 weeks of treatment, LDL-C levels were significantly lower: pitavastatin group = −35.0 ± 14.1% and atorvastatin group = −38.4 ± 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM) (n = 125), LDL-C levels (−37.1 ± 12.9% vs. −38.0 ± 13.1%, p = 0.62) were similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62) treatment. Triglycerides, non-high density lipoprotein cholesterol, and apoprotein B were similarly and significantly lower in both treatment groups. In non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in both statin groups. Hemoglobin A₁C was significantly (p = 0.001) higher in the atorvastatin group but not in the pitavastatin group. Both statins were well tolerated, and both groups had a similar low incidence of treatment-emergent adverse events.

Conclusion

Both pitavastatin (2 mg/day) and atorvastatin (10 mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a comparable degree in high-risk Taiwanese patients with hypercholesterolemia.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01386853","term_id":"NCT01386853"}}NCT01386853 http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01386853","term_id":"NCT01386853"}}NCT01386853?term={"type":"clinical-trial","attrs":{"text":"NCT01386853","term_id":"NCT01386853"}}NCT01386853&rank=1     

"Janus" Cyclic Peptides: A New Approach to Amyloid Fibril Inhibition?

Cyclic peptides are increasingly being shown as powerful inhibitors of fibril formation, and have the potential to be therapeutic agents for combating many debilitating amyloid-related diseases. One such example is a cyclic peptide derivative from the human apolipoprotein C-II, which has the ability to inhibit fibril formation by the fibrillogenic peptide apoC-II(60–70). Using classical molecular dynamics and electronic structure calculations, we were able to provide insight into the interaction between the amyloidogenic peptide apoC-II(60–70) and its cyclic derivative, cyc(60–70). Our results showed that cyc(60–70) induced increased flexibility in apoC-II(60–70), suggesting that one mechanism by which cyc(60–70) inhibits fibrillisation is by destabilising apoC-II(60–70) structure, rendering it incapable of adopting fibril favouring conformations. In contrast, cyc(60–70) shows less flexibility upon binding to apoC-II(60–70), which is predominantly mediated by hydrophobic interactions between the aromatic rings of the peptides. This effectively creates a cap around the fibril-forming region of apoC-II(60–70) and generates an outer hydrophilic shell that discourages further apoC-II(60–70) peptide self-association. We showed that apoC-II(60–70) exhibited stronger binding affinity for the hydrophobic face of cyc(60–70) and weakest binding affinity for the hydrophilic side. This suggests that cyc(60–70) can be an effective fibril inhibitor due to its amphipathic character, like that of the "Janus"-type particles. This property can be exploited in the design of specific inhibitors of amyloid fibril formation.     

Aldosterone and Mortality in Hemodialysis Patients: Role of Volume Overload

Background

Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality.

Methods

We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL).

Results

Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25–0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33−0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69–3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28−4.15) in the absence of volume overload.

Conclusions

The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.     

Peripheral Immune Cell Gene Expression Changes in Advanced Non-Small Cell Lung Cancer Patients Treated with First Line Combination Chemotherapy

Introduction

Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.

Methods

To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.

Results

Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.

Conclusions

Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.     

Routine Endoscopy for Esophageal Cancer Is Suggestive for Patients with Oral,Oropharyngeal and Hypopharyngeal Cancer

Background

This study attempted to reveal the incidence and risk of synchronous and metachronous esophageal cancer in subjects with oral, oropharyngeal and hypopharyngeal cancer based on a population-wide database in Taiwan.

Methods

We retrieved data for this cross-sectional study from the Taiwanese Longitudinal Health Insurance Database 2000. The study group included 2,965 subjects who had received their first-time diagnosis of oral/oropharyngeal/hypopharyngeal cancer in 2002∼2009. We assigned the date of their first diagnosis of oral/oropharyngeal/hypopharyngeal cancer as the index date. We also randomly retrieved 29,650 comparison subjects matched with the study subjects in terms of gender and age group. We assigned their first medical utilization that occurred in the index year as the index date for the comparison group. We further performed a conditional logistic regression to investigate the association between esophageal cancer and oral cancer.

Results

Results showed that prevalences of esophageal cancer within 3 months before and after the index date were respectively 2.19% and 0.04% for the study and comparison groups. A conditional logistic regression revealed that the odds ratio (OR) of esophageal cancer for subjects with oral/oropharyngeal/hypopharyngeal cancer was 55.33 (95% confidence interval (CI): 29.86∼102.52) compared to comparison subjects. Furthermore, compared to comparison subjects, ORs for esophageal cancer were respectively 18.41 (95% CI: 8.50–39.85), 40.49 (95% CI: 15.11∼108.64), and 240.96 (95% CI: 125.49–462.69) for study subjects with a malignancy of the oral cavity, oropharynx, and hypopharynx.

Conclusion

We concluded that there were relatively high chances for synchronous and metachronous esophageal cancers being detected through panendoscopy in patients with oral, oropharyngeal, and hypopharyngeal cancers. The routine use of panendoscopy in such patients should be encouraged with a higher priority.