Search

XLSX file - 132K, Table S2: Effects of EPZ-6438 on Gene Expression in EZH2 Mutant Lymphoma Cells.

The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition. It has been recently reported that ovarian cancers with dual loss of the redundant SWI/SNF components SMARCA4 and SMARCA2 are characteristic of a rare rhabdoid-like subtype known as small-cell carcinoma of the ovary hypercalcemic type (SCCOHT). Here, we provide evidence that a subset of commonly used ovarian carcinoma cell lines were misdiagnosed and instead were derived from a SCCOHT tumor. We also demonstrate that tazemetostat, a potent and selective EZH2 inhibitor currently in phase II clinical trials, induces potent antiproliferative and antitumor effects in SCCOHT cell lines and xenografts deficient in both SMARCA2 and SMARCA4. These results exemplify an additional class of rhabdoid-like tumors that are dependent on EZH2 activity for survival. Mol Cancer Ther; 16(5); 850–60. ©2017 AACR.

The EZH2 small-molecule inhibitor tazemetostat (EPZ-6438) is currently being evaluated in phase II clinical trials for the treatment of non-Hodgkin lymphoma (NHL). We have previously shown that EZH2 inhibitors display an antiproliferative effect in multiple preclinical models of NHL, and that models bearing gain-of-function mutations in EZH2 were consistently more sensitive to EZH2 inhibition than lymphomas with wild-type (WT) EZH2. Here, we demonstrate that cell lines bearing EZH2 mutations show a cytotoxic response, while cell lines with WT-EZH2 show a cytostatic response and only tumor growth inhibition without regression in a xenograft model. Previous work has demonstrated that cotreatment with tazemetostat and glucocorticoid receptor agonists lead to a synergistic antiproliferative effect in both mutant and wild-type backgrounds, which may provide clues to the mechanism of action of EZH2 inhibition in WT-EZH2 models. Multiple agents that inhibit the B-cell receptor pathway (e.g., ibrutinib) were found to have synergistic benefit when combined with tazemetostat in both mutant and WT-EZH2 backgrounds of diffuse large B-cell lymphomas (DLBCL). The relationship between B-cell activation and EZH2 inhibition is consistent with the proposed role of EZH2 in B-cell maturation. To further support this, we observe that cell lines treated with tazemetostat show an increase in the B-cell maturation regulator, PRDM1/BLIMP1, and gene signatures corresponding to more advanced stages of maturation. These findings suggest that EZH2 inhibition in both mutant and wild-type backgrounds leads to increased B-cell maturation and a greater dependence on B-cell activation signaling. Mol Cancer Ther; 16(11); 2586–97. ©2017 AACR.

PDF file - 811K, Fig. S1. Effects of EPZ-6438 on Gene Promoter H3K27 Methylation, Recruitment of PRC2 Components to Gene Promoters, and Cell Cycle, in WSU-DLCL2 Cells. Fig. S2: Effects of EPZ-6438 on Gene Expression in EZH2 Mutant Lymphoma Cell Lines. Fig. S3: Pharmacokinetic Profiles of EPZ-6438 in Rats and Mice. Fig. S4: EPZ-6438 Compound Levels in Plasma and WSU-DLCL2 Xenograft Tumor Homogenates from Mice Dosed for 7 or 28 Days. Fig. S5: In vivo Effects of EPZ-6438 in Lymphoma Xenograft Models. Fig. S6: Body Weights of Mice during Xenograft Efficacy Studies.

PDF file - 25K, Table S1: LCC Values for EPZ-6438 for WSU-DLCL2 Human Lymphoma Cells Dosed Either Continuously or After Compound Washout.

Contains the mechanism footprint gene list referenced by supplemental Table S3.

Table S1: Conditions and seeding densities of all cell lines used in studies; Table S2. Single agent IC50 values for agents tested for 3 days in 96-well plates as described in Materials and Methods; Figure S1. Tazemetostat dosing reduced H3K27me3 in tumor xenografts and is tolerated by SCID mice; Figure S2: CD40L has little effect on growth of DLBCL cell lines; Figure S3. SU-DHL-5 cells were treated for 4 days with TAZ (0.1 to 1 µM) followed by addition of 500 ng/mL CD40L at the indicated time points (1-60 minutes; Figure S4. An ABC-DLBCL gene signature (1) is up-regulated following tazemetostat treatment in KARPAS-422 (EZH2 mutant GCB), Farage (EZH2 WT GCB), SU-DHL-5 (EZH2 WT GCB), TMD8 (EZH2 WT ABC) and ABC vs. GCB gene signature was applied to RNAseq data from each cell line with and without tazemetostat treatment.; Figure S5: CD40L, but not IL-21 induces PRDM1 in combination with tazemetostat (TAZ); Figure S6. A CD40 responsive gene set (2) is up-regulated following tazemetostat treatment in KARPAS-422 (EZH2 mutant GCB), Farage (EZH2 WT GCB), SU-DHL-5 (EZH2 WT GCB), TMD8 (EZH2 WT ABC) and Basso_CD40¬_SIGNALING_UP gene signature was applied to RNAseq data from each cell line with and without tazemetostat treatment; Figure S7. Model for tazametostat mechanism of action in DLBCL

PDF File -1 MB, Supplemental data is to further support the statements made it the main text. Captions: Supplemental Table 1: Cell Lines used in the CRISPR pooled screen. Supplemental Table 2: Table of ovarian lines screened for tazemetostat sensitivity along with mutational and protein status for SMARCA2, SMARCA4, and ARID1A. Supplemental Table 3: p-values of COV434 SCCOHT cell line treated with tazemetostat. Supplemental Table 4: p-values of JHOC-5 clear cell ovarian cell line treated with tazemetostat. Supplemental Table 5: p-values of cell cycle analysis after tazemetostat treatment. Supplemental Table 6: p-values of apoptosis analysis after tazemetostat treatment. Supplemental Table 7: LogP scores for SWI/SNF components in ovarian lines +/- tazemetostat treatment. Supplemental Figure 1: Baseline measurement of histone 3 lysine 27 trimethyl mark and EZH2. Supplemental Figure 2a: Growth curves of SCCOHT and ovarian cancer cell lines treated with tazemetostat. Supplemental Figure 2b: Growth curves of SCCOHT and ovarian cancer cell lines treated with EPZ-007210. Supplemental Figure 3: Reduction in H3K27me3 mark after treatment. Supplemental Figure 4a: Sensitivity to PLK1 knockout as pan-essential in CRISPR pooled screen. Supplemental Figure 4b: Control sgRNAs from CRISPR pooled screen. Supplemental Figure 5: TOV112D xenograft tumor growth inhibition, tumor volume, and methyl mark. Supplemental Figure 6: body weights of mice treated with tazemetostat. Supplemental Figure 7: measured blood plasma levels of tazemetostat from xenograft mice.

Mutations within the catalytic domain of the histone methyltransferase EZH2 have been identified in subsets of patients with non-Hodgkin lymphoma (NHL). These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers. We have previously reported the discovery of EPZ005678 and EPZ-6438, potent and selective S-adenosyl-methionine-competitive small molecule inhibitors of EZH2. Although both compounds are similar with respect to their mechanism of action and selectivity, EPZ-6438 possesses superior potency and drug-like properties, including good oral bioavailability in animals. Here, we characterize the activity of EPZ-6438 in preclinical models of NHL. EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild-type and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) leads to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations. Treatment of EZH2-mutant NHL xenograft-bearing mice with EPZ-6438 causes dose-dependent tumor growth inhibition, including complete and sustained tumor regressions with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 days after stopping compound treatment in two EZH2-mutant xenograft models. These data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. Mol Cancer Ther; 13(4); 842–54. ©2014 AACR.

Contains supplemental methods, figures, and tables 1, 2, 3, and 5

Supplementary Methods and Figure Legends 1-2 from Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

Supplementary Figure 2 from Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

Supplementary Figure 1 from Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

Sport and Physical Activity (PA) Special Eurobarometer surveys may inform of the physical inactivity (PIA) levels in the European Union (EU). This study aimed to analyse the PIA levels of EU adolescents (15–17 years) in four time points, according to gender. The data were from 2002, 2005, 20013, and 2017 Special Eurobarometers. Adolescents were categorised as “Inactive” when performing less than 60 min/day of moderate to vigorous PA on average. A χ2 test was used to compare the levels of PIA between survey years. PIA levels between gender were analysed using a Z-score test for two population proportions. PIA levels ranged from 67.2% for boys (59.4% to 71.5%;) to 76.8% for girls (76.0% to 83.4) across the time points. Adjusted standardised residuals revealed a decrease in the observed levels versus the expected for 2005 (whole sample: −4.2; boys: −3.3) and an increase for 2013 (whole sample: +2.9; boys: +2.5). Boys presented lower PIA levels than girls in all years (p ≤ 0.003), but descriptively, the difference progressively decreased (from 18.4% to 11.8%). No significant reductions in PIA levels were observed between 2002 and 2017, and girls reported consistently higher levels of PIA than boys.

Palm weevils, Rhynchophorus spp. (Coleoptera: Curculionidae) double as devastating invasive pests of palms, and delicacies in many communities. This study evaluated ethyl acetate and 3-methyl-octan-4-ol for trapping palm weevils from coconut, oil and raffia palms in Kenya and Uganda; taking into account the distance of traps on oil palm from a forest or raffia palm. Eggs from the weevils from different locations were incubated and their larvae reared on sugarcane under laboratory conditions. All the 285 weevils collected were identified by morphological and molecular techniques as Rhynchophorus phoenicis, and the catch was female-biased. 3-methyl-octan-4-ol attracted more weevils than ethyl acetate. More weevils were caught at ~100 m away from the forest than within 15 m outside the forest; and on raffia palm than oil palm irrespective of distance apart. Eggs took ~4 d to develop and 95-100% of pupae developed into adults, irrespective of the collection site. Larval and pupal developmental periods for weevils from Uganda were longer than those of Kenya, resulting in egg-adult development of ~6 months and ~4 months, respectively. The sex ratio of laboratory produced males and females was similar. These results can guide in designing an integrated R. phoenicis management system with a dual benefit of protecting palms from weevil attack and utilising the weevils to improve human nutrition.

Informed by the Demand Resources and Individual Effects model (DRIVE; Mark & Smith, 2008), we assessed how work and individual characteristics were associated with perceived job stress, and psychological wellbeing outcomes (e.g., anxiety, depression, positive mood) in a cross-sectional study with two British police forces (N = 852 officers and staff). Work characteristics predicted psychological wellbeing outcomes both directly and indirectly through the perception of job stress. Work resources and individual characteristics moderated the relationships between work demands, perception of job stress and psychological wellbeing outcomes. The associations between perception of work demands, job stress and psychological wellbeing outcomes were improved in police officers and staff who reported moderate-high physical activity behavior. This study added new knowledge to the domain as it was the first to test the DRIVE model in its entirety in an occupational setting. It also provided new insight into the multi-dimensional factors associated with psychological wellbeing in policing. Practically, the findings implied a reduction of work demands, or interventions that target appraisals and/or physical activity might improve psychological wellbeing in police workers.

Background/Aim: The kisspeptin 1 (KISS1) gene encodes a precursor polypeptide which after proteolysis forms the kisspeptin-10 (KISS1) protein. KISS1, retains maximum physiological activity when it binds to its receptor (KISS1R), allowing KISS1 to effectively function as a suppressor of metastasis in melanomas and other types of cancer. The goal of this study was to evaluate the expression of KISS1 and KISS1R in breast carcinomas from African American (AA) women and correlate their association with clinicopathological features, including breast cancer subtypes, and outcomes. Materials and Methods: Tissue microarrays were constructed from formalin-fixed, paraffin-embedded surgical blocks from 216 AA patients. KISS1 and KISS1R expression was assessed using immunohistochemistry. Univariate analysis was used to determine the association between the expression of KISS1 and KISS1R, and clinicopathological characteristics. Pearson correlation was also determined between immunohistochemical H-scores, tumor size, and the number of positive lymph nodes. Kaplan–Meier estimates of overall and disease-free survival were plotted, and log-rank tests were performed to compare estimates among groups. Results: KISS1 protein expression was found to be higher in receptor-negative and triple-negative breast cancer (TNBC) compared to other subtypes (p

Capturing phylogenetic signal from a massive radiation can be daunting. The superfamily Chalcidoidea is an excellent example of a hyperdiverse group that has remained recalcitrant to phylogenetic resolution. Chalcidoidea are mostly parasitoid wasps that until now included 27 families, 87 subfamilies and as many as 500,000 estimated species. We combined 1007 exons obtained with Anchored Hybrid Enrichment with 1048 Ultra-Conserved Elements (UCEs) for 433 taxa including all extant families, over 95% of all subfamilies and 356 genera chosen to represent the vast diversity of the superfamily. Going back and forth between molecular results and our collective morphological and biological knowledge, we detected insidious bias driven by the saturation of nucleotide data and highlighted morphological convergences. Our final results are based on a concatenated analysis of the least saturated exons and UCE data sets (2054 loci, 284,106 sites). Our analyses support a sister relationship with Mymarommatoidea. Seven of the previously recognized families were not monophyletic, so foundations for a new classification are discussed. Biology appears potentially more informative than morphology, as illustrated by the elucidation of a clade of plant gall associates and a clade of taxa with planidial first-instar larvae. The phylogeny suggests a shift from smaller soft-bodied wasps to larger and more heavily sclerotized wasps. Deep divergences in Chalcidoidea coincide with an increase in insect families in the fossil record, and an early shift to phytophagy corresponds with the beginning of the “Angiosperm Terrestrial Revolution”. Our dating analyses suggest a Middle Jurassic origin of 174 Ma (167.3-180.5 Ma) and a crown age of 162.2 Ma (153.9–169.8 Ma) for Chalcidoidea. During the Cretaceous, Chalcidoidea underwent a rapid radiation in southern Gondwana with subsequent dispersals to the Northern Hemisphere. This scenario is discussed with regard to knowledge about host taxa of chalcid wasps, their fossil record, and Earth’s paleogeographic history.

DHX9 is a multifunctional DEAH-box ATP-independent RNA helicase which has been reported to play important roles in replication, transcription, translation, RNA splicing and RNA processing which contribute to DHX9’s role in maintenance of genomic stability. Functionally, DHX9’s role involves binding to as well as unwinding and/or resolving double-stranded and single-stranded DNA/RNA, DNA/RNA hybrids (R-loops), circular RNA and DNA/RNA G quadraplexes. Overexpression of DHX9 is evident in multiple cancer types, including colorectal cancer (CRC) and lung cancer. In addition, microsatellite instable (MSI) tumors exhibiting defective mismatch repair (dMMR) show a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery. Here we describe data supporting targeting DHX9 in MSI CRC as a novel therapeutic, and the first identification of potent and selective in vitro and in vivo small molecule inhibitors of DHX9. We demonstrate that DHX9 inhibition in MSI CRC, delivered either through siRNA knockdown or compound treatment, leads to an increase in RNA/DNA secondary structures such as R-loops and circRNA (i.e. circBRIP1) inducing replication stress. Cell lines that are dMMR (i.e. MSI) are unable to resolve this replication stress, resulting in prevention of DNA replication in S phase and later onset of apoptosis. We were able to confirm this selective dependency in a panel of 20 CRC cell lines; anti-proliferative effects mediated by DHX9 inhibition were dependent on cell line dMMR status in a 10-day proliferation assay. Furthermore, compound 1, an orally bioavailable DHX9 inhibitor was used to investigate in vivo efficacy in MSI CRC (LS411N) and MSS CRC (SW480) xenograft models. Compound 1 was well tolerated across the 28-day treatment period with robust and durable tumor regression (TGI = 105 %) observed in the LS411N tumor xenograft model only. In addition, following cessation of treatment, minimal tumor regrowth was observed in a 28-day post treatment window. Tumor and plasma concentrations of compound 1 and changes in pharmacodynamic markers of DHX9 inhibition, such as circBRIP1 mRNA, were measured and resulting PK and PD data were highly correlated. Together, these preclinical data validate DHX9 as a tractable new target with potential utility as a novel treatment for patients with MSI CRC. Citation Format: Jennifer Castro, Matthew H. Daniels, Chuang Lu, David Brennan, Deepali Gotur, Young-Tae Lee, Kevin Knockenhauer, April Case, Jie Wu, Shane M. Buker, Julie Liu, Brian A. Sparling, E. Allen Sickmier, Stephen J. Blakemore, P. Ann Boriack-Sjodin, Kenneth W. Duncan, Scott Ribich, Robert A. Copeland. Targeting DHX9 inhibition as a novel therapeutic modality in microsatellite instable colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1136.

Background-\ud \ud Long-COVID diagnosis is prominent, and our attention must support those experiencing debilitating and long-standing symptoms. To establish patient pathways, we must consider the societal and economic impacts of sustained COVID-19. Accordingly, we sought to determine the pertinent areas impacting quality of life (QoL) following a COVID-19 infection.\ud \ud Research methods-\ud \ud Three hundred and eighty-one participants completed a web-based survey (83% female, 17% male) consisting of 70 questions across 7 sections (demographics, COVID-19 symptoms; QoL; sleep quality; breathlessness; physical activity and mental health). Mean age, height, body mass and body mass index (BMI) were 42 ± 12 years, 167.6 ± 10.4 cm, 81.2 ± 22.2 kg, and 29.1 ± 8.4 kg.m2, respectively.\ud \ud Results-\ud \ud Participant health was reduced because of COVID-19 symptoms (‘Good health’ to ‘Poor health’ [P < 0.001]). Survey respondents who work reported ongoing issues with performing moderate (83%) and vigorous (79%) work-related activities.\ud \ud Conclusions-\ud \ud COVID-19 patients report reduced capacity to participate in activities associated with daily life, including employment activities. Bespoke COVID-19 support pathways must consider multi-disciplinary approaches that address the holistic needs of patients to restore pre-pandemic quality of life and address experienced health and wellbeing challenges.

International audience; Gall midges (Diptera: Cecidomyiidae) comprise a diverse family of small nematoceran flies. While most species are phytophagous, the family also includes predatory species, and endoparasitoids. Endoparasitic species have been reared from aphids and psyllids. We discovered parasitoid-infected weaver ant, Oecophylla longinoda (Latreille) (Hymenoptera: Formicidae) in nests on mango trees in coastal Kenya. Examination of 5 colonies revealed the presence of parasitoids in all of them, with parasitism rates ranging from 2 to 21%. Morphological examination of larval parasitoids indicated that they were gall midges, and molecular data were consistent with the identification. Attempts to rear adults were unsuccessful. This study presents to the best of our knowledge the first report of Cecidomyiidae parasitising Hymenoptera, as well as the first report of a parasitoid of weaver ants. This species should be investigated further because its damage may limit the ability of weaver ants to control pests of cultivated fruits and other insects.

The United States Army is developing and procuring their next generation of rotorcraft, called the Future Vertical Lift (FVL) program. FVL rotorcraft will fly faster and incorporate new work requirements such as command of unmanned systems and optionally piloted variants. Successful design and implementation of human automation teaming will be paramount to the mission success and safety of FVL systems, presenting both challenges and opportunities for human factors personnel supporting FVL development. The purpose of this panel is to highlight the range of human factors challenges within the FVL program. Panelists are drawn from both government and industry, and represent a diverse set of perspectives including user, researcher, and practitioner. The session will include time for panelists to introduce their work and challenges that they are addressing within the FVL program as well as interact with audience members.

There is an urgent need to address the devastating pandemic, COVID‐19, caused by SARS‐CoV‐2. The efforts to understand the details of this disease in hope of providing effective treatments is commendable. It is clear now that the virus can cause far more damage in patients with co‐morbid conditions ‐ particularly in those with respiratory, cardiovascular or immune‐compromised system ‐ than in patients without such co‐morbidities. Drug use can further exacerbate the condition. In this regard, the ill effects of smoking are amply documented, and no doubt can be a confounding factor in COVID‐19 progression. Although conflicting hypotheses on the potential role of nicotine in COVID‐19 pathology have recently been offered, we believe that nicotine itself, through its interaction with the nicotinic cholinergic system, as well as ACE2, may not only be of use in a variety of neuropsychiatric and neurodegenerative diseases, but may also be of potential use in COVID‐19. Thus, on one hand, while we strongly support smoking cessation as a means of harm reduction associated with COVID‐19, on the other hand, we support a potential therapeutic role for nicotine, nicotinic agonists or positive allosteric modulators of nicotinic cholinergic receptors in COVID‐19, owing to their varied effects including mood regulation, anti‐inflammatory as well as purported interference with SARS‐CoV‐2 entry and/or replication.

Parkinson’s disease (PD), a progressive neurodegenerative disorder, is associated with the destruction of dopamine neurons in the substantia nigra (SN) and the formation of Lewy bodies in basal ganglia. Risk factors for PD include aging, as well as environmental and genetic factors. Recent converging reports suggest a role for the gut microbiome and epigenetic factors in the onset and/or progression of PD. Of particular relevance and potential therapeutic targets in this regard, are histone deacetylases (HDACs), enzymes that are involved in chromatin remodeling. Butyrate, a short-chain fatty acid (FA) produced in the gut and presumably acting via several G protein-coupled receptors (GPCRs) including FA3 receptors (FA3Rs), is a well-known HDAC inhibitor that plays an important role in maintaining homeostasis of the gut-brain axis. Recently, its significance in regulation of some critical brain functions and usefulness in neurodegenerative diseases such as PD has been suggested. In this study we sought to determine whether butyrate may have protective effects against salsolionl (SALS)-induced toxicity in SH-SY5Y cells. SALS, an endogenous product of aldehyde and dopamine condensation, may be selectively toxic to dopaminergic neurons. SH-SY5Y cells, derived from human neuroblastoma cells are used as a model of these neurons. Exposure of SH-SY5Y cells for 24 h to 400 μM SALS resulted in approximately 60% cell death, which was concentration-dependently prevented by butyrate. The effects of butyrate in turn, were significantly attenuated by beta-hydroxy butyrate (BHB), a selective FA3R antagonist. Moreover, a selective FA3R agonist (AR 420626) also provided protective effects against SALS, which was totally blocked by BHB. These findings provide further support that butyrate or an agonist of FA3R may be of therapeutic potential in PD.

Noort, Simon van, Copeland, Robert S. (2020): First record of the genus Tanaostigma (Hymenopteraı Chalcidoideaı Tanaostigmatidae) from the Afrotropical region with description of three new species. Journal of Natural History 54 (9): 703-722, DOI: 10.1080/00222933.2020.1746426

Background: Prostate cancer (PCa) is a multifactorial disease involving complex interactions between genetic and physiological/environmental factors. Vitamin D receptor (VDR) plays a role in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to PCa. Materials and Methods: Logistic regression analysis was used to assess the association of six VDR single nucleotide polymorphisms (SNPs) and factors such as tanning potential and UV sunlight exposure with PCa risk. Results: Marginal significant interactions were found, with a 2-fold increase risk of PCa between SNP 1 (c.278-69G>A) and sunlight UV exposure [odds ratio (OR)=2.02, 95% confidence intervaI (CI)=1.036-4.36; p=0.05]; and a 4-fold increase risk of PCa between SNP 4 (c.907+75C>T) and tanning potential (OR=4.40, 95% CI=0.89-29.12; p=0.0591). In contrast, SNP 5 (rs731236, TaqI) and tanning potential interaction had a protective effect by reducing the risk of PCa by 55% (β=−0.804; OR=0.448, 95% CI=0.197-9.42; p=0.0427). SNPs 2 (rs61614328) and 6 (rs533037428) did not show any association with PCa even in the presence of UV sunlight exposure. Conclusion: The protective effect of SNP 4 from PCa is lost and modified by tanning potential in African Americans. This finding needs to be verified by larger studies in different ethnic populations.

Smicromorpha Girault (Hymenoptera: Chalcididae) is distributed in the old world tropics and subtropics from Australia through New Guinea, Southeast and South Asia. Since its original description in 1913 conclusive evidence of its host has been lacking although it has been collected in association with weaver ants (Oecophylla spp.; Formicidae: Formicinae) either in proximity to ant nests or, on one occasion, reared from one. In this paper we report the presence of Smicromorpha pupae within the gaster of Oecophylla longinoda workers from a nest collected in coastal Kenya. This discovery extends the distribution of Smicromorpha to the Afrotropical Region and demonstrates conclusively that they are koinobiont parasitoids of weaver ants.