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Xanthomonas citri pv. fuscans (Xcf) and Xanthomonas phaseoli pv. phaseoli (Xpp) are responsible for the Common Bacterial Blight (CBB), a major common bean (Phaseolus vulgaris) disease. The pathogenicity of Xcf and Xpp is known to be dependent upon a functional Type III Secretion System (T3SS) allowing the injection of numerous bacterial Type III Effectors (T3Es) into plant cells. T3Es have been described as able to disrupt plant defence and manipulate plant metabolism.In this work we described the transcriptomic response of one susceptible (Flavert) and one resistant (Vezer) cultivars of P. vulgaris to the inoculation of the virulent strain Xcf CFBP4885 or its avirulent T3SS-defective hrcV mutant (CFBP13802).Leaves of both bean cultivars were infiltrated with water or bacterial suspensions. Inoculated leaves were sampled at 24 or 48 h post inoculation (hpi). The experiment was independently repeated three times for total RNA extraction and sequencing analysis. Library construction and total RNA sequencing were performed with BGISEQ-500 at Beijing Genomics Institute (BGI, Hong-Kong), generating an average of 24M of paired-end reads of 100bp per sample. FastQC was used to check reads quality. Mapping analyses were made using a quasi-mapping alignment from Salmon (version 1.2.1) against the Phaseolus vulgaris reference genome (version 2.1), revealing the expression profiles of 36,978 transcripts in leaf tissues.Fastq raw data and count files from 36 samples are available in the Gene Expression Omnibus (GEO) repository of the National Center for Biotechnology Information (NCBI) under the accession number GSE271236.This dataset is a valuable resource to investigate the role of T3Es in subverting the cellular functions of bean.

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.

In cancer biology, ETS transcription factors promote tumorigenesis by mediating transcriptional regulation of numerous genes via the conserved ETS DNA-binding domain. MicroRNAs (miRNAs) act as posttranscriptional regulators to regulate various tumor-promoting or tumor-suppressing factors. Interactions between ETS factors and miRNAs regulate complex tumor-promoting and tumor-suppressing networks. This review discusses the progress of ETS factors and miRNAs in cancer research in detail. We focused on characterizing the interaction of the miRNA/ETS axis with competing endogenous RNAs (ceRNAs) and its regulation in posttranslational modifications (PTMs) and the tumor microenvironment (TME). Finally, we explore the prospect of ETS factors and miRNAs in therapeutic intervention. Generally, interactions between ETS factors and miRNAs provide fresh perspectives into tumorigenesis and development and novel therapeutic approaches for malignant tumors.

E74-like factor 3 (ELF3) is an important member of the E-twenty-six (ETS) transcription factor family. ELF3 is expressed in various types of cells and regulates a variety of biological behaviors, such as cell proliferation, differentiation, apoptosis, migration, and invasion, by binding to DNA to regulate the expression of other genes. In recent years, studies have shown that ELF3 plays an important role in the occurrence and development of many tumors and inflammation and immune related diseases. ELF3 has different functions and expression patterns in different tumors; it can function as a tumor suppressor gene or an oncogene, highlighting its dual effects of tumor promotion and inhibition. ELF3 also affects the levels of tumor immunity-related cytokines and is involved in the regulation and expression of multiple signaling pathways. In tumor therapy, ELF3 is a complex and multifunctional gene and has become a key focus of targeted treatment research. An in-depth study of the biological function of ELF3 can help to elucidate its role in biological processes and provide ideas and a basis for the development and clinical application of ELF3-related therapeutic methods. This review introduces the structure and physiological and cellular functions of the ELF3 gene, summarizes the mechanisms of action of ELF3 in different types of malignant tumors and its role in immune regulation, inflammation, etc., and discusses treatment methods for ELF3-related diseases, providing significant reference value for scholars studying the ELF3 gene and related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

In this work level of Polycyclic Aromatic Hydrocarbon (PAHs) from indoor Environment Tobacco Smoke (ETS) of pubic bars in Nigeria was investigated. Indoor air samples were obtained from different public bars using Polyurethane foam (PUF) passive samplers. Analysis of PAHs was carried out using GC-MS operated in selected ion monitoring mode. Result showed the average concentration range of 2.71–9.69 ng/m3 while the ∑ 16 PAHs range from 43.43 to 155.11 ng/m3. The incremental lifetime cancer risk (ILCR) values from inhalation of PAHs in these bars ranged from 2.4×10−7−5.2×10−7 while non-carcinogenic risk, Hazard Quotient (HQ) ranged from 2×10−4−4.5×10−4. Although these values are lower than WHO permissible limit, nevertheless the study underscores the danger associated with the inhalation of ETS in the public bars in Nigeria.

Plant-pathogenic Xanthomonas infects a wide variety of host plants and causes many devastating diseases on crops. Transcription activator-like effectors (TALEs) are delivered by a type III secretion system (T3SS) of Xanthomonas into plant nuclei to directly bind specific DNA sequences (TAL effector-binding elements, EBEs) on either strand of host target genes with an unique modular DNA-binding domain and to bidirectionally drive host gene transcription. The target genes in plants consist of host susceptibility (S) genes promoting disease (ETS) and resistance (R) genes triggering defense (ETI). Here we generally summarized the discovery of TALEs in Xanthomonas species, their functions in bacterial pathogenicity in plants and their target genes in different host plants, and then focused on the newly revealed modes of protein action in triggering or suppressing plant defense.

Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, ETV4, and ETV5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages. ATXN1L deletion, which reduces CIC protein, or ectopic expression of ETV1, ETV4, or ETV5 also modulated sensitivity to trametinib. ATXN1L expression inversely correlates with response to MAPKi inhibition in clinical studies. These observations identify the ATXN1L-CIC-ETS transcription factor axis as a mediator of resistance to MAPKi.

Background: A diverse and balanced human gut microbiota is crucial for maintaining normal human physiological functions. However, the impact of indoor microbiome and metabolites on gut microbiota is not well understood., Methods: A self-administered questionnaire was used to collect information on more than 40 personal and environmental characteristics and dietary habits from 56 children in Shanghai, China. Shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS) were used to characterize the indoor microbiome and metabolomic/chemical exposure in children's living rooms. PacBio full-length 16 S rRNA sequencing was used to characterize children's gut microbiota. Associations between environmental characteristics and gut microbiota diversity/composition were assessed using PERMANOVA and regression., Results: In total, 6247 and 318 indoor and gut microbial species and 1442 indoor metabolites were characterized. Age of children (R 2  = 0.033, p = 0.008), age start kindergarten (R 2  = 0.029, p = 0.03), living adjacent to heavy traffic (R 2  = 0.031, p = 0.01) and drinking soft drinks (R 2  = 0.028, p = 0.04) significantly impacted overall gut microbial composition, consistent with previous studies. Having pets/plants and frequent vegetable intake were positively associated with gut microbiota diversity and the Gut Microbiome Health Index (GMHI), while frequent juice and fries intake decreased gut microbiota diversity (p < 0.05). The abundance of indoor Clostridia and Bacilli was positively associated with gut microbial diversity and GMHI (p < 0.01). Total indoor indole derivatives and 6 indole metabolites (L-tryptophan, indole, 3-methylindole, indole-3-acetate, 5-hydroxy-L-tryptophan and indolelactic acid, p < 0.05) were positively associated with the abundance of total protective gut bacteria, suggesting a potential role in promoting gut health. Neural network analysis revealed that these indole derivatives were derived from indoor microorganisms., Conclusions: The study is the first to report associations between indoor microbiome/metabolites and gut microbiota, highlighting the potential role of indoor microbiome in shaping human gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Red Mud is the insoluble residue of the alumina extraction starting from the bauxite for the process Bayer. In Galicia they take place more than 400.000 annual tons of this industrial residue, constituted fundamentally by a mixture of oxides and iron hydroxides, titanium oxides, quartz, and small quantities of clays and other minerals. The present work describes the process of industrial use of the Red Mud, to obtain dense bricks used in heat accumulators, arid for highways and other ceramic products. This type of materials, up to now manufactured in an experimental way in the Institute of Ceramic of Galicia have given place to the creation of a new company and the current construction and setting in operation, of a pilot plant valued in 200.000.000 Ptas. Located in the north of the Province of Lugo, this plant will allow the production of 20 Tm/day of material for its study and commercialisation.Los Lodos Rojos son el residuo insoluble de la extracción de alúmina a partir de la bauxita por el proceso Bayer. En Galicia se producen más de 400.000 toneladas anuales de este residuo industrial, constituido fundamentalmente por una mezcla de óxidos e hidróxidos de hierro, óxidos de titanio, cuarzo, con cantidades menores de, arcillas, y otros minerales. El presente trabajo describe el proceso de aprovechamiento industrial de los Lodos Rojos, para obtener ladrillos densos para acumuladores de calor, áridos para carreteras y otros productos cerámicos. Este tipo de materiales, hasta ahora fabricados de forma experimental en el Instituto de Cerámica de Galicia han dado lugar a la creación de una nueva empresa y a la actual construcción y puesta en funcionamiento, de una planta piloto valorada en 200.000.000 Ptas. ubicada en el norte de la Provincia de Lugo. Dicha planta permitirá la fabricación de 20 Tm/día de material para su estudio y comercialización.

Undifferentiated small round cell sarcomas represent a heterogeneous group of mesenchymal neoplasms. While imprecise, this term nevertheless provides a useful framework for conceptualizing these tumors. This article highlights current trends in their classification based on morphology, immunohistochemistry, and advanced molecular techniques. As next-generation sequencing becomes commonplace in diagnostic laboratories pathologists can expect to differentiate these tumors with increasing confidence, and actively contribute to related discoveries. Ultimately, when synthesized with rigorous clinical outcome data and other investigative techniques, a more robust landscape for the molecular diagnosis and classification of undifferentiated small round cell sarcomas is expected to emerge in the future., Competing Interests: Disclosure Not applicable., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Correct vascular differentiation requires distinct patterns of gene expression in different subtypes of endothelial cells. Members of the ETS transcription factor family are essential for the transcriptional activation of arterial and angiogenesis-specific gene regulatory elements, leading to the hypothesis that they play lineage-defining roles in arterial and angiogenic differentiation directly downstream of VEGFA signalling. However, an alternative explanation is that ETS binding at enhancers and promoters is a general requirement for activation of many endothelial genes regardless of expression pattern, with subtype-specificity provided by additional factors. Here we use analysis of Ephb4 and Coup-TFII (Nr2f2) vein-specific enhancers to demonstrate that ETS factors are equally essential for vein, arterial and angiogenic-specific enhancer activity patterns. Further, we show that ETS factor binding at these vein-specific enhancers is enriched by VEGFA signalling, similar to that seen at arterial and angiogenic enhancers. However, while arterial and angiogenic enhancers can be activated by VEGFA in vivo, the Ephb4 and Coup-TFII venous enhancers are not, suggesting that the specificity of VEGFA-induced arterial and angiogenic enhancer activity occurs via non-ETS transcription factors. These results support a model in which ETS factors are not the primary regulators of specific patterns of gene expression in different endothelial subtypes., Competing Interests: Declaration of competing interest No competing interests declared., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In this work level of Polycyclic Aromatic Hydrocarbon (PAHs) from indoor Environment Tobacco Smoke (ETS) of pubic bars in Nigeria was investigated. Indoor air samples were obtained from different public bars using Polyurethane foam (PUF) passive samplers. Analysis of PAHs was carried out using GC-MS operated in selected ion monitoring mode. Result showed the average concentration range of 2.71-9.69 ng/m 3 while the ∑ 16 PAHs range from 43.43 to 155.11 ng/m 3 . The incremental lifetime cancer risk (ILCR) values from inhalation of PAHs in these bars ranged from 2.4×10 -7 -5.2×10 -7 while non-carcinogenic risk, Hazard Quotient (HQ) ranged from 2×10 -4 -4.5×10 -4 . Although these values are lower than WHO permissible limit, nevertheless the study underscores the danger associated with the inhalation of ETS in the public bars in Nigeria., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Specification of the main axes of polarity of the embryo is an essential process during embryonic development. In many species, this process is achieved by the localization of maternal factors into discrete regions of the egg. However, in other animals, like in amniotes and in echinoderms, the considerable plasticity of the early blastomeres seems to preclude the existence of maternal determinants and the mechanisms by which the radial symmetry of the egg is broken remain largely enigmatic. In this chapter, we review recent progress on the identification of maternal components involved in symmetry breaking and dorsal-ventral (D/V) axis formation of the sea urchin embryo. We will first review some key experiments on D/V axis formation from classical embryologists that provided evidence for a weak maternal D/V prepattern. We will then detail more recent molecular analyses that established the critical role played by Nodal signaling in allocating cell fates along the secondary axis and led to the discovery that maternal transcription factors such as the Sry-related HMG box B1 (SoxB1), the Octamer binding factor1/2 (Oct1/2), the T-cell factor/Lymphoid enhancer-binding factor (TCF/LEF) and the Erythroblastosis virus E26 Oncogene Homolog (ETS) domain transcriptional repressor Translocation-Ets-Leukemia virus protein (Yan/Tel) as well as maternal signaling molecules like Univin are essential for the initiation of nodal expression. Finally, we will describe recent advances that uncovered a role in symmetry breaking and dorsal-ventral axis orientation for the transforming growth factor beta (TGF-beta)-like factor Panda, which appears to be both necessary and sufficient for D/V axis orientation. Therefore, even in the highly regulative sea urchin embryo, the activity of localized maternal factors provides the embryo with a blueprint of the D/V axis., (© 2020 Elsevier Inc. All rights reserved.)

Hyperandrogenism is one of the clinical and biochemical characteristics of polycystic ovary syndrome (PCOS). Our previous studies confirmed that nuclear receptor subfamily 4 group A member 1 (NR4A1), as a differentially expressed gene in the ovaries of PCOS patients, was upregulated by increased androgen. However, the potential mechanism of NR4A1 upregulation remains unknown. To elucidate the molecular mechanisms involved in NR4A1 regulation, we cloned and characterized the promoter regions of the NR4A1 gene using a series of truncated promoter plasmids in luciferase reporter assays. We identified two unique core promoters of NR4A1 located within the +1055/+1251 and +3183/+3233 regions relative to the transcription start site. TFAP2A downregulated NR4A1 expression, while five ETS transcription factors, ETS1, ELK1, ERG, FLI1 and SPI1, could upregulate NR4A1 promoter activity in HeLa cells. Of these transcription factors, ETS1 and ELK1 were the most effective ones. Moreover, all six transcription factors were confirmed to interact directly with the NR4A1 promoter. In conclusion, this study presents the first description that TFAP2A and ETS family signaling networks are involved in the androgen-mediated transcriptional regulation of NR4A1, which contributes to the understanding of the molecular mechanisms involved in the TFAP2A-NR4A1 and ETS-NR4A1 signaling networks in PCOS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Environmental hypercapnia in shallow coastal marine ecosystems can be exacerbated by increasing levels of atmospheric CO 2 . In these ecosystems organisms are expected to become increasingly subjected to pCO 2 levels several times higher than those inhabiting ocean waters (e.g.: 10,000µatm), but still our current understanding on different species capacity to respond to such levels of hypercapnia is limited. Oysters are among the most important foundation species inhabiting these coastal ecosystems, although natural oyster banks are increasingly threatened worldwide. In the present study we studied the effects of hypercapnia on two important oyster species, the pacific oyster C. gigas and the mangrove oyster C. brasiliana, to bring new insights on different species response mechanisms towards three hypercapnic levels (ca. 1,000; 4,000; 10,000 µatm), by study of a set of biomarkers related to metabolic potential (electron transport system - ETS), antioxidant capacity (SOD, CAT, GSH), cellular damage (LPO) and energetic fitness (GLY), in two life stages (juvenile and adult) after 28 days of exposure. Results showed marked differences between each species tolerance capacity to hypercapnia, with contrasting metabolic readjustment strategies (ETS), different antioxidant response capacities (SOD, CAT, GSH), which generally allowed to prevent increased cellular damage (LPO) and energetic impairment (GLY) in both species. Juveniles were more responsive to hypercapnia stress in both congeners, and are likely to be most sensitive to extreme hypercapnia in the environment. Juvenile C. gigas presented more pronounced biochemical alterations at intermediate hypercapnia (4,000µatm) than C. brasiliana. Adult C. gigas showed biochemical alterations mostly in response to high hypercapnia (10,000µatm), while adult C. brasiliana were less responsive to this environmental stressor, despite presenting decreased metabolic potential. Our data bring new insights on the biochemical performance of two important oyster species, and suggest that the duration of extreme hypercapnia events in the ecosystem may pose increased challenges for these organisms as their tolerance capacity may be time limited., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Facial blushing, associated with social phobia, may have severe negative impact on the quality of daily life. The first line of treatment should be psychological and/or pharmacologic. In severe cases not responding to nonsurgical treatment, surgical sympathetic denervation is an option. A thorough disclosure of effects, complications, and side effects is mandatory and patient selection is crucial to obtain high patient satisfaction from surgical treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Large case series and randomized trials over the past 25 years have consistently demonstrated thoracoscopic interruption of the sympathetic chain to be a safe and effective treatment of focal primary hyperhidrosis. The surgical technique has evolved toward less-invasive and less-extensive procedures in an effort to minimize perioperative morbidity and effectively balance postoperative compensatory sweating with symptomatic relief. This review summarizes available evidence regarding the surgical approach and the optimal level of interruption of the sympathetic chain based on a patient's presenting distribution of pathologic sweating., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The ascidian Ciona intestinalis is a marine invertebrate belonging to the sister group of the vertebrates, the tunicates. Its compact genome and simple, experimentally tractable embryos make Ciona well-suited for the study of cell-fate specification in chordates. Tunicate larvae possess a characteristic chordate body plan, and many developmental pathways are conserved between tunicates and vertebrates. Previous studies have shown that FGF signals are essential for neural induction and patterning at sequential steps of Ciona embryogenesis. Here we show that two different ETS family transcription factors, Ets1/2 and Elk1/3/4, have partially redundant activities in the anterior neural plate of gastrulating embryos. Whereas Ets1/2 promotes pigment cell formation in lateral lineages, both Ets1/2 and Elk1/3/4 are involved in the activation of Myt1L in medial lineages and the restriction of Six3/6 expression to the anterior-most regions of the neural tube. We also provide evidence that photoreceptor cells arise from posterior regions of the presumptive sensory vesicle, and do not depend on FGF signaling. Cells previously identified as photoreceptor progenitors instead form ependymal cells and neurons of the larval brain. Our results extend recent findings on FGF-dependent patterning of anterior-posterior compartments in the Ciona central nervous system., (Copyright © 2015. Published by Elsevier Inc.)

Fibroblast growth factor signaling plays a significant role in the developing eye, regulating both patterning and neurogenesis. Members of the Pea3/Etv4-subfamily of ETS-domain transcription factors (Etv1, Etv4, and Etv5) are transcriptional activators that are downstream targets of FGF/MAPK signaling, but whether they are required for eye development is unknown. We show that in the developing Xenopus laevis retina, etv1 is transiently expressed at the onset of retinal neurogenesis. We found that etv1 is not required for eye specification, but is required for the expression of atonal-related proneural bHLH transcription factors, and is also required for retinal neuron differentiation. Using transgenic reporters we show that the distal atoh7 enhancer, which is required for the initiation of atoh7 expression in the Xenopus retina, is responsive to both FGF signaling and etv1 expression. Thus, we conclude that Etv1 acts downstream of FGF signaling to regulate the initiation of neurogenesis in the Xenopus retina., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) from traffic emissions and other combustion sources, and childhood obesity, have been implicated as risk factors for developing asthma. However, the interaction between these two on asthma among young urban children has not been studied previously., Methods: Exposure to early childhood PAHs was measured by two week residential indoor monitoring at age 5-6 years in the Columbia Center for Children's Environmental Health birth cohort (n=311). Semivolatile [e.g., methylphenanthrenes] and nonvolatile [e.g., benzo(a)pyrene] PAHs were monitored. Obesity at age 5 was defined as a body mass index (BMI) greater than or equal to the 95th percentile of the year 2000 age- and sex-specific growth charts (Center for Disease Control). Current asthma and recent wheeze at ages 5 and 7 were determined by validated questionnaires. Data were analyzed using a modified Poisson regression in generalized estimating equations (GEE) to estimate relative risks (RR), after adjusting for potential covariates., Results: Neither PAH concentrations or obesity had a main effect on asthma or recent wheeze. In models stratified by presence/absence of obesity, a significant positive association was observed between an interquartile range (IQR) increase in natural log-transformed 1-methylphenanthrene (RR [95% CI]: 2.62 [1.17-5.88] with IQRln=0.76), and 9-methylphenanthrene (2.92 [1.09-7.82] with IQRln=0.73) concentrations and asthma in obese children (n=63). No association in non-obese (n=248) children was observed at age 5 (Pinteraction<0.03). Similar associations were observed for 3-methylphenanthrene, 9-methylphenanthrene, and 3,6-dimethylphenanthrene at age 7., Conclusions: Obese young children may be more likely to develop asthma in association with greater exposure to PAHs, and methylphenanthrenes in particular, than non-obese children., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Environmental tobacco smoke (ETS) is known to cause significant morbidity across a wide variety of organ systems. The purpose of this study was to examine the relationship of ETS exposure with pediatric urinary dysfunction., Patients and Methods: Participants were drawn from a university-based pediatric urology practice throughout the first half of 2011. All patients who presented with a chief complaint of urinary dysfunction were approached to participate (N = 184). Exclusion criteria eliminated all but 71 subjects. Of these, 68 subjects and their parents completed age-appropriate questionnaires on ETS exposure and symptom severity. Data were analyzed using descriptive statistics and relationship between exposure and outcome was evaluated via Spearman correlation analysis., Results: A total of 68 children with no known etiology for their urinary dysfunction were evaluated for symptom severity and ETS exposure. Participants demonstrated a significant positive correlation (rho = 0.592 for those 4-10 years; rho = 0.415 for those 11-17 years) between ETS exposure and severity of their urinary symptoms., Conclusions: These data indicate a positive relationship between ETS exposure and urinary dysfunction among children with no other obvious etiology for their symptoms. Physicians should inform parents of the potential dangers of childhood ETS exposure, including the possible relationship with urinary dysfunction., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: There is limited research examining the relationship between lead (Pb) exposure and medically diagnosed attention deficit hyperactivity disorder (ADHD) in children. The role of mercury (Hg) and cadmium (Cd) exposures in ADHD development is even less clear., Objectives: To examine the relationship between Pb, Hg, and Cd and ADHD in children living inside and outside a Lead Investigation Area (LIA) of a former lead refinery in Omaha, NE., Methods: We carried out a case-control study with 71 currently medically diagnosed ADHD cases and 58 controls from a psychiatric clinic and a pediatric clinic inside and outside of the LIA. The participants were matched on age group (5-8, 9-12 years), sex, race (African American or Caucasians and others), and location (inside or outside LIA). We measured whole blood Pb, total Hg, and Cd using inductively coupled plasma mass spectrometry., Results: Inside the LIA, the 27 cases had blood Pb geometric mean (GM) 1.89 µg/dL and the 41 controls had 1.51 µg/dL. Outside the LIA, the 44 cases had blood Pb GM 1.02 µg/dL while the 17 controls had 0.97 µg/dL. After adjustment for matching variables and maternal smoking, socioeconomic status, and environmental tobacco exposure, each natural log unit blood Pb had an odds ratio of 2.52 with 95% confidence interval of 1.07-5.92. Stratification by the LIA indicated similar point estimate but wider CIs. No associations were observed for Hg or Cd., Conclusions: Postnatal Pb exposure may be associated with higher risk of clinical ADHD, but not the postnatal exposure to Hg or Cd., (© 2013 Published by Elsevier Inc.)

Studying gene-environment interactions may elucidate the complex origins of atopic diseases. The aim of this study was to evaluate the association of CD14 polymorphisms and atopy in Egyptian children and to study whether atopy is influenced by CD14 interaction with tobacco smoke exposure. CD14 -159 C/T and CD14 -550 C/T were genotyped in 500 asthmaic children, 150 allergic rhinitis children and 150 controls. We found that CD14 -159T allele, CD14 -550T allele and CD14 -159T/-550T haplotype were significantly associated with atopic asthma and allergic rhinitis groups. CD14 -159 TT and CD14 -550 TT genotypes associated with elevated IgE levels in children exposed to tobacco smoke. The TT genotype of CD14 -159 C/T and CD14 -550 C/T was associated with higher serum levels of sCD14. The present study indicated that CD14 gene polymorphisms may contribute to susceptibility to atopy in Egyptian children and influenced with tobacco smoke exposure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Cigarette smoke causes direct oxidative DNA damage as well as indirect damage through inflammation. Epidemiological studies show a strong relationship between secondhand smoke and cancer; however, the mechanisms of secondhand smoke-induced cancer are not well understood. Animal models with either (i) deficient oxidative DNA damage repair, or (ii) a decreased capacity to combat oxidative stress may help determine the pathways important in mitigating damage caused by smoke. In this study, we used mice lacking Ogg1 and Myh, both of which are involved in base excision repair by removing oxidatively damaged DNA bases. Gclm-deficient mice, which have decreased levels of glutathione (GSH), were used to look at the role of smoke-induced oxidative damage. Ex vivo experiments show significantly elevated levels of DNA single-strand breaks and chromosomal aberrations in peripheral blood lymphocytes from Ogg1(-/-)Myh(-/-) double knockout mice compared to wild type (WT) mice after 24h of exposure to cigarette smoke extract (CSE). The average γH2AX foci per cell was significantly elevated 3h after exposure to CSE in cells from Ogg1(-/-)Myh(-/-) double knockout mice compared to wildtype mice. In vivo we found that all mice had increased markers of DNA damage after exposure to side-stream tobacco smoke (SSTS). Ogg1(-/-)Myh(-/-) and Gclm(-/-) mice had altered levels of peripheral blood glutathione after SSTS exposure whereas wild type mice did not. This may be due to differential regulation of glutathione synthesis in the lung. We also found that Ogg1(-/-)Myh(-/-) mice had a decreased lifespan after oral gavage with benzo[a]pyrene compared to wildtype mice and sham-exposed Ogg1(-/-)Myh(-/-) mice. Our results are important in investigating the roles of oxidative stress and oxidative DNA damage repair in cigarette smoke-induced cancers and characterizing the role of genetic polymorphisms in smoke-related disease susceptibility., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Ets factors are members of one of the largest families of evolutionarily conserved transcription factors, regulating critical functions in normal cell homeostasis, which when perturbed contribute to tumor progression. The well-documented alterations in ETS factor expression and function during cancer progression result in pleiotropic effects manifested by the downstream effect on their target genes. Multiple ETS factors bind to the same regulatory sites present on target genes, suggesting redundant or competitive functions. The anti- and prometastatic signatures obtained by examining specific ETS regulatory networks will significantly improve our ability to accurately predict tumor progression and advance our understanding of gene regulation in cancer. Coordination of multiple ETS gene functions also mediates interactions between tumor and stromal cells and thus contributes to the cancer phenotype. As such, these new insights may provide a novel view of the ETS gene family as well as a focal point for studying the complex biological control involved in tumor progression. One of the goals of molecular biology is to elucidate the mechanisms that contribute to the development and progression of cancer. Such an understanding of the molecular basis of cancer will provide new possibilities for: (1) earlier detection, as well as better diagnosis and staging of disease; (2) detection of minimal residual disease recurrences and evaluation of response to therapy; (3) prevention; and (4) novel treatment strategies. Increased understanding of ETS-regulated biological pathways will directly impact these areas., (Copyright © 2013 Elsevier Inc. All rights reserved.)