UFGI publications round-up week 01/16/2017
Biological responses to phenylurea herbicides in fish and amphibians: New directions for characterizing mechanisms of toxicity.
Author information: Marlatt VL1, Martyniuk CJ2.
Date of e-pub: January 2017
Abstract: Urea-based herbicides are applied in agriculture to control broadleaf and grassy weeds, acting to either inhibit photosynthesis at photosystem II (phenylureas) or to inhibit acetolactate synthase acetohydroxyacid synthase (sulfonylureas). While there are different chemical formulas for urea-based herbicides, the phenylureas are a widely used class in North America and have been detected in aquatic environments due to agricultural run-off. Here, we summarize the current state of the literature, synthesizing data on phenylureas and their biological effects in two non-target animals, fish and amphibians, with a primary focus on diuron and linuron. In fish, although the acutely lethal effects of diuron in early life stages appear to be >1mg/L, recent studies measuring sub-lethal behavioral and developmental endpoints suggest that diuron causes adverse effects at lower concentrations (i.e. <0.1mg/L). Considerably less toxicity data exist for amphibians, and this is a knowledge gap in the literature. In terms of sub-lethal effects and mode of action (MOA), linuron is well documented to have anti-androgenic effects in vertebrates, including fish. However, there are other MOAs that are not adequately assessed in toxicology studies. In order to identify additional potential MOAs, we conducted in silico analyses for linuron and diuron that were based upon transcriptome studies and chemical structure-function relationships (i.e. ToxCast™, Prediction of Activity Spectra of Substances). Based upon these analyses, we suggest that steroid biosynthesis, cholesterol metabolism and pregnane X receptor activation are common targets, and offer some new endpoints for future investigations of phenylurea herbicides in non-target animals.
Microbial siderophores and root exudates enhanced goethite dissolution and Fe/As uptake by As-hyperaccumulator Pteris vittata.
Author information: Liu X1, Fu JW1, Da Silva E2, Shi XX1, Cao Y1, Rathinasabapathi B3, Chen Y4, Ma LQ5.
Date of e-pub: January 2017
Abstract: Arsenic (As) in soils is often adsorbed on Fe-(hydro)oxides surface, rendering them more resistant to dissolution, which is undesirable for phytoremediation of As-contaminated soils. Arsenic hyperaccumulator Pteris vittata prefers to grow in calcareous soils where available Fe and As are low. To elucidate its mechanisms of acquiring Fe and As from insoluble sources in soils, we investigated dissolution of goethite with pre-adsorbed arsenate (AsV; As-goethite) in presence of four organic ligands, including two root exudates (oxalate and phytate, dominant in P. vittata) and two microbial siderophores (PG12-siderophore and desferrioxamine B). Their presence increased As solubilization from As-goethite from 0.03 to 0.27-5.33 mg L-1 compared to the control. The siderophore/phytate bi-ligand treatment released 7.42 mg L-1 soluble Fe, which was 1.2-fold that of the sum of siderophore and phytate, showing a synergy in promoting As-goethite dissolution. In the ligand-mineral-plant system, siderophore/phytate was most effective in releasing As and Fe from As-goethite. Moreover, the continuous plant uptake induced more As-goethite dissolution. The continued release of As and Fe significantly enhanced their plant uptake (from 0.01 to 0.43 mg plant-1 As and 2.7-14.8 mg plant-1 Fe) and plant growth (from 1.2 to 3.1 g plant-1 fw) in P. vittata. Since microbial siderophores and root exudates often coexist in soil rhizosphere, their synergy in enhancing dissolution of insoluble As-Fe minerals may play an important role in efficient phytoremediation of As-contaminated soils.
Seasonal Effects on the Population, Morphology and Reproductive Behavior of Narnia femorata (Hemiptera: Coreidae).
Author information: Cirino LA1, Miller CW2.
Date of e-pub: January 2017
Abstract: Many insects are influenced by the phenology of their host plants. In North Central Florida, Narnia femorata (Hemiptera: Coreidae) spends its entire life cycle living and feeding on Opuntia mesacantha ssp. lata. This cactus begins producing flower buds in April that lead to unripe green fruit in June that ripen into red fruit through December. Many morphological and behavioral characteristics of N. femorata are known to be affected by cactus phenology in a controlled laboratory setting, including the degree of sexual dimorphism and mating behavior. Our goal with this study was to determine if similar phenotypic changes of N. femorata occurred over time in the wild, and the extent to which these changes were concordant with phenological changes in its host plant. Further, we investigate the length of the insect mouthparts (beak) over time. Ongoing work has suggested that beak length may change across cohorts of developing insects in response to feeding deep within cactus fruit where seed and pulp depth decrease as the fruit ripens. Our results revealed a drop in cactus fruit abundance between the months of July through October 2015 as cactus fruits turned red and ripened. Simultaneously, the average body size of both males and females of N. femorata declined at two sampled sites. Male hind femora (a sexually-selected weapon) decreased disproportionately in size over time so that males later in the year had relatively smaller hind femora for their body size. The sex-specific patterns of morphological change led to increased sexual-size dimorphism and decreased sexual dimorphism for hind femora later in the year. Further, we found that beak length decreased across cohorts of insects as cactus fruit ripened, suggesting phenotypic plasticity in mouthpart length. Behavioral studies revealed that female readiness to mate increased as the season progressed. In sum, we found pronounced changes in the phenotypes of these insects in the field. Although this study is far from comprehensive, it provides tantalizing patterns that suggest many directions for future research.
Returning to normal? Assessing transcriptome recovery over time in male rainbow darter (Etheostoma caeruleum) liver in response to wastewater treatment plant upgrades.
Author information: Marjan P1, Martyniuk CJ2, Fuzzen ML1, MacLatchy DL3, McMaster ME4, Servos MR1.
Date of e-pub: January 2017
Abstract: The present study measured hepatic transcriptome responses in male rainbow darter (Etheostoma caeruleum) exposed to 2 municipal wastewater treatment plants (MWWTPs) (Kitchener and Waterloo) over 4 fall seasons (2011 – 2014) in the Grand River Ontario. The overall goal was to determine if upgrades at the Kitchener MWWTP (in 2012) resulted in transcriptome responses indicative of improved effluent quality. The number of differentially expressed probes in fish downstream of the Kitchener outfall (904-1,223), remained comparable to that downstream of Waterloo (767-3,867). Noteworthy was that year, and the interaction of year and site, explained variability in more than twice the number of transcripts than site alone, suggesting that year and the interaction of year and site had a greater effect on the transcriptome than site alone. Gene Set Enrichment Analysis revealed a gradual reduction in the number of gene ontologies over time at exposure sites, which corresponded with lower contaminant load. Sub Network Enrichment Analysis revealed that there were noticeable shifts in the cell pathways differently expressed in the liver pre- and post-upgrade. The dominant pathways altered pre-upgrades were related to genetic modifications and cell division whereas, post-upgrades, they were associated with the immune system, reproduction, and biochemical responses. Molecular pathways were dynamic over time, and following the upgrades, there was little evidence that gene expression profiles in fish collected from high impact sites post-upgrade were more similar to fish collected from reference site. This article is protected by copyright. All rights reserved.
Antisense transcription of the myotonic dystrophy locus yields low-abundant RNAs with and without (CAG)n repeat.
Author information: Gudde AE1, van Heeringen SJ2, de Oude AI1, van Kessel ID1, Estabrook J3, Wang ET3, Wieringa B1, Wansink DG1.
Date of e-pub: January 2017
Abstract: The unstable (CTG·CAG)n trinucleotide repeat in the myotonic dystrophy type 1 (DM1) locus is bidirectionally transcribed from genes with terminal overlap. By transcription in the sense direction, the DMPK gene produces various alternatively spliced mRNAs with a (CUG)n repeat in their 3′ UTR. Expression in opposite orientation reportedly yields (CAG)n-repeat containing RNA, but both structure and biological significance of this antisense gene (DM1-AS) are largely unknown. Via a combinatorial approach of computational and experimental analyses of RNA from unaffected individuals and DM1 patients we discovered that DM1-AS spans >6 kb, contains alternative transcription start sites and uses alternative polyadenylation sites up- and downstream of the (CAG)n repeat. Moreover, its primary transcripts undergo alternative splicing, whereby the (CAG)n segment is removed as part of an intron. Thus, in patients a mixture of DM1-AS RNAs with and without expanded (CAG)n repeat are produced. DM1-AS expression appears upregulated in patients, but transcript abundance remains very low in all tissues analyzed. Our data suggest that DM1-AS transcripts belong to the class of long non-coding RNAs. These and other biologically relevant implications for how (CAG)n-expanded transcripts may contribute to DM1 pathology can now be explored experimentally.
The peopling of the Americas and the origin of the Beringian occupation model.
Author information: Mulligan CJ1, Szathmáry EJ2.
Date of e-pub: January 2017
Abstract: The current model for peopling of the Americas involves divergence from an ancestral Asian population followed by a period of population isolation and genetic diversification in Beringia, and finally, a rapid expansion into and throughout the Americas. Studies in the 1970s sought to characterize the biological relationships between different indigenous populations and first proposed an occupation of Beringia. More recent studies using molecular genetic markers often neglect to reference early works that laid the groundwork for current colonization models. We address this matter, and briefly summarize the literature and technological advances that contributed to our current understanding of the peopling of the Americas. Furthermore, we argue that describing the process of peopling of the Americas as “migrations from Asia” minimizes the significant genetic diversification that occurred outside of Asia, and offends indigenous Americans by discounting their origin narratives and land rights. Rather than referring to the indigenous peoples of the Americas as “migrants” or “immigrants,” we recommend consistency in the language used to describe all post-glacial expansions of people into Asia, Europe and the Americas.
Genome-wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions.
Author information: Mychaleckyj JC1,2, Havt A3, Nayak U4, Pinkerton R5, Farber E4, Concannon P6,7, Lima AA8, Guerrant RL5.
Date of e-pub: January 2017
Abstract: Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared to the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in 5 genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in 8 regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas.
Poor Adherence to Ketone Testing in Patients With Type 1 Diabetes.
Author information: Albanese-O’Neill A1, Wu M2, Miller KM3, Jacobsen L1, Haller MJ1, Schatz D1; T1D Exchange Clinic Network.
Date of e-pub: January 2017
Abstract: N/A
Erratum to: The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species.
Author information: Papanicolaou A1, Schetelig MF2, Arensburger P3, Atkinson PW4,5, Benoit JB6, Bourtzis K7,8, Castañera P9, Cavanaugh JP6, Chao H10, Childers C11, Curril I12, Dinh H10, Doddapaneni H10, Dolan A13, Dugan S10, Friedrich M14, Gasperi G15, Geib S16, Georgakilas G17, Gibbs RA10, Giers SD18, Gomulski LM15, González-Guzmán M9, Guillem-Amat A9, Han Y10, Hatzigeorgiou AG17, Hernández-Crespo P9, Hughes DS10, Jones JW19, Karagkouni D17, Koskinioti P20, Lee SL10, Malacrida AR15, Manni M15, Mathiopoulos K20, Meccariello A21, Munoz-Torres M22, Murali SC10, Murphy TD23, Muzny DM10, Oberhofer G12, Ortego F9, Paraskevopoulou MD17, Poelchau M11, Qu J10, Reczko M24, Robertson HM18, Rosendale AJ6, Rosselot AE6, Saccone G21, Salvemini M21, Savini G15, Schreiner P5, Scolari F15, Siciliano P15, Sim SB16, Tsiamis G8, Ureña E9, S Vlachos I17, Werren JH13, Wimmer EA12, Worley KC10, Zacharopoulou A25, Richards S10, Handler AM26.
Date of e-pub: January 2017
Abstract: N/A
Induced Pluripotent Stem Cell Research in the Era of Precision Medicine.
Author information: Hamazaki T1, El Rouby N2, Fredette NC3, Santostefano KE3, Terada N3.
Date of e-pub: January 2017
Abstract: Recent advances in DNA sequencing technologies are revealing how human genetic variations associate with differential health risks, disease susceptibilities and drug responses. Such information is now expected to help evaluate individual health risks, design personalized health plans and treat patients with precision. It is still challenging, however, to understand how such genetic variations cause the phenotypic alterations in pathobiologies and treatment response. Human induced pluripotent stem cell (iPSC) technologies are emerging as a promising strategy to fill the knowledge gaps between genetic association studies and underlying molecular mechanisms. Breakthroughs in genome editing technologies and continuous improvement in iPSC differentiation techniques are particularly making this research direction more realistic and practical. Pioneering studies have shown that iPSCs derived from a variety of monogenic diseases can faithfully recapitulate disease phenotypes in vitro when differentiated into disease-relevant cell types. It has been shown possible to partially recapitulate disease phenotypes, even with late onset and polygenic diseases. More recently, iPSCs have been shown to validate effects of disease and treatment-related SNPs identified through GWAS. In this review, we will discuss how iPSC research will further contribute to human health in the coming era of precision medicine. This article is protected by copyright. All rights reserved.
A Multi-Mitochondrial Anticancer Agent that Selectively Kills Cancer Cells and Overcomes Drug Resistance.
Author information: Peng YB1,2, Zhao ZL1,2, Liu T1,2,3, Xie GJ4, Jin C1,2, Deng TG1,2, Sun Y1,2, Li X3, Hu XX1,2, Zhang XB1,2, Ye M1,2, Tan WH1,2,5,6.
Date of e-pub: January 2017
Abstract: Mitochondria are double-membrane-bound organelles involved mainly in supplying cellular energy, but also play roles in signaling, cell differentiation, and cell death. Mitochondria are implicated in carcinogenesis, and therefore dozens of lethal signal transduction pathways converge on these organelles. Accordingly, mitochondria provide an alternative target for cancer management. In this study, F16, a drug that targets mitochondria, and chlorambucil (CBL), which is indicated for the treatment of selected human neoplastic diseases, were covalently linked, resulting in the synthesis of a multi-mitochondrial anticancer agent, FCBL. FCBL can associate with human serum albumin (HSA) to form an HSA-FCBL nanodrug, which selectively recognizes cancer cells, but not normal cells. Systematic investigations show that FCBL partially accumulates in cancer cell mitochondria to depolarize mitochondrial membrane potential (MMP), increase reactive oxygen species (ROS), and attack mitochondrial DNA (mtDNA). With this synergistic effect on multiple mitochondrial components, the nanodrug can effectively kill cancer cells and overcome multiple drug resistance. Furthermore, based on its therapeutic window, HSA-FCBL exhibits clinically significant differential cytotoxicity between normal and malignant cells. Finally, while drug dosage and drug resistance typically limit first-line mono-chemotherapy, HSA-FCBL, with its ability to compromise mitochondrial membrane integrity and damage mtDNA, is expected to overcome those limitations to become an ideal candidate for the treatment of neoplastic disease.
Hypothalamus specific re-introduction of Snord116 into otherwise Snord116 deficient mice increased energy expenditure.
Author information: Qi Y1, Purtell L2, Fu M1, Zhang L1, Zolotukhin S3, Campbell L2, Herzog H1.
Date of e-pub: January 2017
Abstract: The Snord116 gene cluster has been recognized as a critical contributor to the Prader-Willi Syndrome (PWS) with mice lacking Snord116 displaying many classical PWS phenotypes including low postnatal body weight, reduced bone mass and increased food intake. However, these mice do not develop obesity due to increased energy expenditure. To understand the physiological function of Snord116 better and potentially rescue the altered metabolism of Snord116-/- mice, we used an adeno-associated viral (AAV) approach to reintroduce the Snord116 gene product into the hypothalamus in Snord116-/- mice at different ages. Our results show that mid-hypothalamic re-introduction of Snord116 in 6-week old Snord116-/- mice leads to significantly reduced body weight and weight gain, associated with elevated energy expenditure. Importantly, when the intervention targets other areas such as the anterior region of the hypothalamus or the reintroduction occurs in older mice the positive effects on energy expenditure are diminished. These data indicate that the metabolic symptoms of PWS develop gradually and the Snord116 gene plays a critical role during this process. Furthermore, when we investigated the consequences of Snord116 re-introduction under conditions of thermo-neutrality where the mild cold stress influences are avoided, we also observed a significant increase in energy expenditure. In conclusion, the rescue of mid-hypothalamic Snord116 deficiency in young Snord116 germline deletion mice increases energy expenditure, providing fundamental information contributing to potential virus-mediated genetic therapy in PWS. This article is protected by copyright. All rights reserved.
Population dynamics of HCV subtypes in injecting drug-users on methadone maintenance treatment in China associated with economic and health reform.
Author information: Zhou S1,2, Cella E3,4,5, Zhou W2, Kong WH2, Liu MQ2, Liu PL2, Ciccozzi M3,6, Salemi M5,7, Chen XG2,8.
Date of e-pub: January 2017
Abstract: The extensive genetic heterogeneity of hepatitis C virus (HCV) requires in-depth understanding of the population dynamics of different viral subtypes for more effective control of epidemic outbreaks. We analyzed HCV sequences data from 125 participants in Wuhan, China. These participants were newly infected by subtype 1b (n=13), 3a (n=15), 3b (n=50), and 6a (n=39) while on methadone maintenance treatment (MMT). Bayesian phylogenies and demographic histories were inferred for these subtypes. Participants infected with HCV-1b and 3a were clustered in well-supported monophyletic clades, indicating local sub-epidemics. Subtypes 3b and 6a strains were intermixed with other Chinese isolates, as well as isolates from other Asian countries, reflecting ongoing across geographic boundary transmissions. Subtypes 1b and 3a declined continuously during the past ten years, consistent with the health and economic reform in China, while subtype 3b showed ongoing exponential growth and 6a was characterized by several epidemic waves, possibly related to the recently growing number of travelers between China and other Asian countries. In conclusion, results of this study suggest that HCV subtype 3b and 6a sub-epidemics in China are currently not under control, and new epidemic waves may emerge given the rapid increase in international traveling following substantial economic growth. This article is protected by copyright. All rights reserved.
“The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Outcomes and Metrics of Pharmacogenetic Implementations Across Diverse Healthcare Systems”.
Author information: Luzum JA1,2, Pakyz RE3, Elsey AR4, Haidar CE5, Peterson JF6,7, Whirl-Carrillo M8, Handelman SK2, Palmer K3, Pulley JM9, Beller M10, Schildcrout JS11, Field JR9, Weitzel KW4, Cooper-DeHoff RM4, Cavallari LH4, O’Donnell PH12, Altman RB8, Pereira N13, Ratain MJ12, Roden DM6, Embi PJ14, Sadee W2,15, Klein TE8, Johnson JA4, Relling MV5, Wang L16, Weinshilboum RM16, Shuldiner AR3, Freimuth RR17; Pharmacogenomics Research Network Translational Pharmacogenetics Program.
Date of e-pub: January 2017
Abstract: Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the NIH Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real-world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene-drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs. This article is protected by copyright. All rights reserved.
Influence of the Gastrointestinal Environment on the Bioavailability of Ethinyl Estradiol Sorbed to Single-Walled Carbon Nanotubes.
Author information: Bisesi JH Jr1,2, Robinson SE1,2, Lavelle CM1,2, Ngo T1,2, Castillo B1,2, Crosby H1,2, Liu K3,4,5, Das D6, Plazas-Tuttle J6, Saleh NB6, Ferguson PL3,4,5, Denslow ND2,7, Sabo-Attwood T1,2.
Date of e-pub: January 2017
Abstract: Recent evidence suggests that, because of their sorptive nature, if single-walled carbon nanotubes (SWCNTs) make their way into aquatic environments, they may reduce the toxicity of other waterborne contaminants. However, few studies have examined whether contaminants remain adsorbed following ingestion by aquatic organisms. The objective of this study was to examine the bioavailability and bioactivity of ethinyl estradiol (EE2) sorbed onto SWCNTs in a fish gastrointestinal (GI) tract. Sorption experiments indicated that SWCNTs effectively adsorbed EE2, but the chemical was still able to bind and activate soluble estrogen receptors (ERs) in vitro. However, centrifugation to remove SWCNTs and adsorbed EE2 significantly reduced ER activity compared to that of EE2 alone. Additionally, the presence of SWCNTs did not reduce the extent of EE2-driven induction of vitellogenin 1 in vivo compared to the levels in organisms exposed to EE2 alone. These results suggest that while SWCNTs adsorb EE2 from aqueous solutions, under biological conditions EE2 can desorb and retain bioactivity. Additional results indicate that interactions with gastrointestinal proteins may decrease the level of adsorption of estrogen to SWCNTs by 5%. This study presents valuable data for elucidating how SWCNTs interact with chemicals that are already present in our aquatic environments, which is essential for determining their potential health risk.
NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine