Table_1_Efficacy of lure mixtures in baited traps to attract different fruit fly species in guava and vegetable fields.docx

Fruit flies (Diptera: Tephritidae) are major pests of fruits and vegetables worldwide. We measured the efficacy of attractive lure mixtures in baited traps on naturally-occurring fruit flies in commercial mosaic guava and vegetables fields in Pakistan. We tested three mixtures (methyl-eugenol [ME] and cue lure [CL]; GF-120 and methyl eugenol; and GF-120 and cue lure) in eleven ratios: 0:100, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, and 100:0. We recorded three fruit fly species: Bactrocera zonata was the most abundant in baited traps, followed by Bactrocera dorsalis, while Zeugodacus cucurbitae was significantly less attracted to baited traps. We also found that the most attractive mixture and ratio varied among species: B. dorsalis was most attracted by 40CL:60ME, while B. zonata was most and equally attracted by 100ME, 10CL:90ME, 20CL:80ME, 30CL:70ME, and 40CL:60ME. Finally, Z. cucurbitae was most attracted by 10CL:90ME, which resulted in the highest total number of flies counted in 10CL:90ME-baited traps. Mixtures with GF-120 were less attractive to all three species. Our results suggest that lure mixtures in baited traps influence the attraction of fruit flies in a species-specific way. This needs to be considered in the integrated pest management of multiple species of fruit flies simultaneously. If Bactrocera species are most damaging and abundant, a 40CL:60ME mixture in baited traps will likely be most effective to reduce pest abundance and crop damage. However, if Z. cucurbitae is the main pest target causing most crop damage and yield loss, 10CL:90ME-baited traps will be a more effective in their monitoring and management. </p

Promoter Methylation Status Modulate the Expression of Tumor Suppressor (RbL2/p130) Gene in Breast Cancer

<div><p>Background</p><p>Aberrant expression of tumor suppressor genes may correspond to the abnormal cell development and tumorigenesis. Rbl2/p130, a member of retinoblastoma family of proteins, has growth suppressive properties. Numerous studies reported de-regulation of Rbl2/p130 in various types of cancer as a consequence of a number of genetic alterations. However, role of epigenetic mechanisms like DNA methylation in Rbl2/p130 expression remains elusive.</p><p>Methods</p><p>In the current study, 76 breast cancer tumors along with normal tissues (n = 76), blood (n = 76) of respective individuals and control blood (n = 50) were analyzed. Rbl2/p130 expression was analyzed by quantitative real time PCR (syber green method). Promoter methylation status was studied through methylation specific PCR of bisulfite converted genomic DNA. Data was analyzed using various statistical tests.</p><p>Results</p><p>We report significantly reduced Rbl2/p130 expression (P = 0.001) in tumors tissues as compared to control samples. Similarly, Rbl2/p130 expression varies with age and disease stages (P = 0.022), which suggest its involvement in tumor progression. Aberrant promoter methylation (Δmeth) was found in almost all the diseased samples and that was significantly different (P<0.001) with control samples. Similarly, methylation status varies significantly with tumor progression stages (P = 0.022). Hyper-methylation was observed at -1, +3, +15 and +75 of Rbl2/p130 promoter flanking around the TSS. Statistical analysis revealed that Rbl2/p130 expression negatively correlates to its promoter methylation (r = -0.412) in tumor tissues. Our results reflect an epigenetic regulation of Rbl2/p130 expression in breast cancer. This highlights the importance of Rbl2/p130 promoter methylation in breast cancer pathogenesis.</p></div

Map of Rbl2/p130 promoter showing methylated and un-methylated CpG’s cytosine ranging from −10 to +80 with reference to TSS (transcription start site).

<p>Map of Rbl2/p130 promoter showing methylated and un-methylated CpG’s cytosine ranging from −10 to +80 with reference to TSS (transcription start site).</p

Statistical relation of Rbl2/p130 expression and its promoter methylation.

<p>(<b>A)</b> Differences in Rbl2/p130 promoter methylation status of tumor and normal tissues in study cohort I (<45 years) and study cohort II (≥45 years); (<b>B)</b> Observed differences in Rbl2/p130 promoter methylation status of various tumor tissues at different disease stages; (<b>C & D)</b> Correlation of relative expression (ΔCT values) and promoter methylation status as observed. Unmeth (C panel) and Meth (D panel) values are plotted separately. Adjusted R-values are shown in respective panels.</p

Relative expression profiling of Rbl2/p130 gene in different age groups and tumor stages.

<p>(<b>A)</b> Changes in relative Rbl2/p130 expression (ΔCT values) with age, both in normal and tumor tissues; (<b>B)</b> Observed changes in Rbl2/p130 in tumor and control tissues; (<b>C)</b> Differences in relative expression of Rbl2/p130 transcript as observed among control and different disease stages (<b>D)</b> Showing Rbl2 expression in control and disease samples, in both the study cohort (<45 and ≥45 years).</p

Rbl2/p130 promoter methylation and transcript expression analysis among various histological types of breast cancer.

<p><b>(A)</b> Relative expression of Rbl2/p130 in control and tumor tissues among various histological types of breast cancer. <b>(B)</b> Change in promoter methylation (ΔMeth) status in control and diseased tissues among different histological different types of breast cancer. <b>DCI;</b> ductal carcinoma in situ. <b>IDC;</b> invasive ductal carcinoma. <b>ILC;</b> invasive lobular carcinoma.</p

Mean comparison of Rbl2/p130 promoter methylation status using tukey test.

<p>Mean comparison of Rbl2/p130 promoter methylation status using tukey test.</p

Promoter methylation analysis of Rbl2/p130 gene in normal individuals and breast cancer patients.

<p><b>(A)</b> 2% agarose gel showing amplified products of methyl specific PCR (MSP). “M” represents methylation, “UM” represents un-methylation and L represents DNA size ladder. (<b>B)</b> Upper panel shows methylation of CpG “C” in tumors, whereas lower panel highlights un-methylation in control individuals. <u><b>T</b></u> shows position of non CpG “C” converted into <b>T</b> as a results of bisulfite conversion while arrows indicates the position of methylated cytosine at CpGs sites.</p

Synthesis of a Unique Isoindoline/Tetrahydroisoquinoline-based Tricyclic Sultam Library Utilizing a Heck-aza-Michael Strategy

The synthesis of a unique isoindoline- and tetrahydroisoquinoline (THIQ)-containing tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy is reported. Both isoindoline and THIQ rings are installed through a Heck reaction on a vinylsulfonamide, followed by one-pot deprotection and intramolecular aza-Michael reaction. Subsequent cyclization with either paraformaldehyde condensation or 1,1′-carbonyldiimidazole coupling generates a variety of tricyclic sultams. Overall, a 160-member library of these sultams, together with their isoindolines/THIQ and secondary sulfonamides precursors, were constructed using this strategy

Automated Synthesis of a Library of Triazolated 1,2,5-Thiadiazepane 1,1-Dioxides via a Double Aza-Michael Strategy

The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products