However, response in patients with NASH is variable, and improvement in liver histology is not always observed. The aim of this study was to identify genetic polymorphisms that contribute to variability Selleck BAY 80-6946 in treatment response. Methods: A total of 55 patients with NASH and prediabetes/ type 2 diabetes mellitus (T2DM) (age: 53 ± 9 years; gender: 41 males and 14 females; weight: 99 ± 17 kg; prevalence of T2DM: 60%) were treated for 18 months with pioglitazone 45 mg/day; 32 patients from

the initial randomized placebo-controlled trial and 23 patients, originally randomized to placebo, that were treated as part of the open-label phase from 18 to 36 months (NCT00994682). Patients were genotyped for 63 single nucleotide polymorphisms, which were selected based on previous association with the pathophysiology of

NAFLD or with pioglitazone response in patients with T2DM. Selected genes include: MLN0128 RETN (resistin, a hormone believed to link obesity with T2DM), PLIN1 (perilipin, a key protein that coats and protects lipid storage droplets in adipocytes), ADORA1 (ade-nosine receptor present in adipose tissue that inhibits lipoly-sis), and PPARG (PPAR-γ, pioglitazone target) among others. Results: After 18 months of pioglitazone treatment, resolution of NASH was more likely in patients with ADORA1 rs903361 G allele (OR=3.60, p=0.02). Specifically, improvement in steatosis was associated with the presence of the PPARG rs4135247 G allele

(OR=9.74, p=0.04) while improvement in necroinflammation was more frequent with RETN rs4804765 T allele (OR=3.76, p=0.03) and ADORA1 rs903361 G allele (OR=7.96, p=0.03). Improvement was defined as reduction of at least 2 grades in the histology. Overall, polymorphisms associated with change in the NAFLD activity score were: RETN rs4804765 (better reduction by 0.85 points for each T allele, p=0.003), ADORA1 rs903361 (better reduction by 0.85 points for each G allele, p=0.006), and PLIN1 rs894160 (worse reduction by 0.76 points for each T allele, p=0.01). Of note, this last variant was associated with worse response in inflammation (β=0.38, p=0.0004) and fibrosis (β=0.34, p=0.003). PNPLA3 rs738409 and rs2281135 polymorphisms were not associated with response to pioglitazone therapy. Conclusions: Genetic polymorphisms likely have significant impact medchemexpress on response to pioglitazone treatment in patients with NASH and may potentially help to identify responders and individualize therapy (i.e., RETN rs4804765, ADORA1 rs903361, PLIN1 rs894160, and PPARG rs4135247). Future studies in larger populations are warranted. Disclosures: Kenneth Cusi – Consulting: Merck, Daichi-Sankyo, Roche, Janssen; Grant/ Research Support: Takeda, Novartis, Mannkind The following people have nothing to disclose: Marina Kawaguchi-Suzuki, Fernando Bril, Taimour Langaee, Yan Gong, Reginald Frye More than 400 human genes encode proteases.

001). We could not find any relationships between OLGA gastritis stage and sex, smoking as well as a familial history of gastric cancer. The severity of EGA significantly correlated with that of OLGA gastritis stage as presented in Table 2 check details (Spearman correlation coefficient = 0.6, P < 0.001). All of the patients with high-stage OLGA gastritis had moderate-to-severe EGA (Fisher's exact test, P < 0.001). Using moderate-to-severe EGA as the diagnostic criterion for high-stage gastritis, the sensitivity, specificity, positive predictive value and negative predictive value were 100% (95% CI 75.3–100%),

57.7% (95% CI 51.5–63.7%), 10.3% (95% CI 5.6–17%), and 100% (95% CI 97.6–100%), respectively. There were 95 patients who were older than 40 years-of-age and had H. pylori infection in the present study (28 with mild EGA and 67 with moderate-to-severe EGA). In this subgroup of

patients, the positive predictive value increased to 19.4% (95% CI 10.8–30.9%). There were seven patients (2.5%) with low-grade learn more dysplasia (3 in stage I, 3 in stage III and 1 in stage IV according to the OLGA gastritis system). All the dysplastic lesions were not endoscopically visible and were detected by systemic map biopsies according to the updated Sydney system. Dysplastic lesions were frequently detected in patients with high-stage gastritis: 4/13 (30.7%) patients with high-stage gastritis versus 3/267 (1.1%) patients with low-stage gastritis (i.e. stage 0–II; Fisher’s exact test P = 0.0001; OR = 39.1; 95% CI 6.1–270.8). Dysplastic lesions were also clustered in patients with moderate-to-severe EGA: 6/126 (4.76%) with moderate-to-severe EGA versus 1/154 (0.65%) with mild EGA (Fisher’s exact test P = 0.048; OR = 7.7; 95% CI 0.9–170.9). The southern area of Vietnam, where this study was carried out, MCE公司 has

a moderate incidence of gastric cancer. The age-standardized rate per 100 000 is 16.5 in males.16 The gastritis stage of patients in the present study who were under 40 years-of-age was almost between those in the low-risk and high-risk regions.7 Therefore, the result of the present study suggests that OLGA gastritis staging parallels the gastric cancer risk in our population. However, there was a difference between our result and those from other moderate-risk regions; we found a higher proportion of patients with gastritis stage I–II and no patients with high-stage gastritis, whereas Rugge et al. reported a lower proportion of patients with stage I–II, and a few patients with high-stage gastritis in Hong Kong and Taiwan. Gastric atrophy is more severe among patients with H. pylori infection and tends to increase when the infection is prolonged.17 The present study confirmed that high-stage gastritis is significantly associated with H. pylori infection and advanced age as reported in previous studies and in other populations.8,9 It has been reported that the atrophic progression is not invariable and only appeared in a subgroup of patients with H. pylori.

001). We could not find any relationships between OLGA gastritis stage and sex, smoking as well as a familial history of gastric cancer. The severity of EGA significantly correlated with that of OLGA gastritis stage as presented in Table 2 selleck chemicals llc (Spearman correlation coefficient = 0.6, P < 0.001). All of the patients with high-stage OLGA gastritis had moderate-to-severe EGA (Fisher's exact test, P < 0.001). Using moderate-to-severe EGA as the diagnostic criterion for high-stage gastritis, the sensitivity, specificity, positive predictive value and negative predictive value were 100% (95% CI 75.3–100%),

57.7% (95% CI 51.5–63.7%), 10.3% (95% CI 5.6–17%), and 100% (95% CI 97.6–100%), respectively. There were 95 patients who were older than 40 years-of-age and had H. pylori infection in the present study (28 with mild EGA and 67 with moderate-to-severe EGA). In this subgroup of

patients, the positive predictive value increased to 19.4% (95% CI 10.8–30.9%). There were seven patients (2.5%) with low-grade SCH772984 dysplasia (3 in stage I, 3 in stage III and 1 in stage IV according to the OLGA gastritis system). All the dysplastic lesions were not endoscopically visible and were detected by systemic map biopsies according to the updated Sydney system. Dysplastic lesions were frequently detected in patients with high-stage gastritis: 4/13 (30.7%) patients with high-stage gastritis versus 3/267 (1.1%) patients with low-stage gastritis (i.e. stage 0–II; Fisher’s exact test P = 0.0001; OR = 39.1; 95% CI 6.1–270.8). Dysplastic lesions were also clustered in patients with moderate-to-severe EGA: 6/126 (4.76%) with moderate-to-severe EGA versus 1/154 (0.65%) with mild EGA (Fisher’s exact test P = 0.048; OR = 7.7; 95% CI 0.9–170.9). The southern area of Vietnam, where this study was carried out, MCE has

a moderate incidence of gastric cancer. The age-standardized rate per 100 000 is 16.5 in males.16 The gastritis stage of patients in the present study who were under 40 years-of-age was almost between those in the low-risk and high-risk regions.7 Therefore, the result of the present study suggests that OLGA gastritis staging parallels the gastric cancer risk in our population. However, there was a difference between our result and those from other moderate-risk regions; we found a higher proportion of patients with gastritis stage I–II and no patients with high-stage gastritis, whereas Rugge et al. reported a lower proportion of patients with stage I–II, and a few patients with high-stage gastritis in Hong Kong and Taiwan. Gastric atrophy is more severe among patients with H. pylori infection and tends to increase when the infection is prolonged.17 The present study confirmed that high-stage gastritis is significantly associated with H. pylori infection and advanced age as reported in previous studies and in other populations.8,9 It has been reported that the atrophic progression is not invariable and only appeared in a subgroup of patients with H. pylori.

Thirty-eight per cent of deaths of red foxes in European cities are due to animals being destroyed. Similar figures exist for urban areas in the US (35%), but in rural US, hunting is a minor cause of death in foxes (9%), where predation (38%) and death on roads (40%) are the major causes of mortality. Pollutants (e.g. motor oil and antifreeze) and poisons (particularly anticoagulant

rodenticides, directly poisoning the animal or where Selleckchem Fluorouracil the carnivore takes poisoned rodents) are likely to be a significant cause of mortality in urban carnivores. However, our literature review indicated that toxicity is listed as a cause of death for only a few urban and rural coyotes (Riley et al., 2003; Van Deelen & Gosselink, 2006) (Fig. 2) and for kit foxes (Cypher, 2010). The lack of reports may be related to difficulty in ascertaining poisoning as a cause of death, particularly when carcasses are located some time after death. Organochlorines (Dip et al., 2003) and lead (Dip et al., 2001) are found in higher concentrations in urban than rural red foxes in Zürich. Organochlorine levels increase in adult male foxes but not vixens, which appear see more to pass the compounds to their offspring through lactation. Protection from predators is likely to play an important role in selection of urban habitats. Predation

or aggression is responsible for the death of only 10% of urban coyotes compared with 25% for rural populations, where they conflict with wolves (Fig. 2) and it has been suggested that the massive increase in coyote numbers over recent decades is likely due to reduction in

the numbers of grey wolf across North America (Gese & Bekoff, 2004). In turn, coyotes tend to avoid landscapes with extensive human presence, and their conflict with red foxes medchemexpress means that foxes end up being relegated to areas with relatively more intense human activity (e.g. roads, farmsteads) (Gosselink et al., 2007). An estimated 38% of red foxes in rural US die due to predation/aggression, largely due to conflict with coyotes, compared with only 12% in urban US (Gosselink et al., 2007). In the UK, the absence of a natural predator for the fox results in less predation. Nevertheless, even in urban UK (London and Bristol), a high proportion of red foxes die due to wounds incurred during aggression, principally from stray dogs or conspecifics (Harris & Smith, 1987; Soulsbury et al., 2007). Recent control of stray dog numbers, however, has reduced the incidence of aggression as a cause of death (S. Harris, pers. comm. 2010). Disease has been recorded as the major cause of mortality for urban raccoons, accounting for an average of 50% of deaths in urban areas compared with only 19% of rural raccoons (Fig. 2). High levels of sarcoptic mange have been recorded in urban red foxes in Britain, causing population crashes (Baker et al., 2000; Soulsbury et al.

Thirty-eight per cent of deaths of red foxes in European cities are due to animals being destroyed. Similar figures exist for urban areas in the US (35%), but in rural US, hunting is a minor cause of death in foxes (9%), where predation (38%) and death on roads (40%) are the major causes of mortality. Pollutants (e.g. motor oil and antifreeze) and poisons (particularly anticoagulant

rodenticides, directly poisoning the animal or where check details the carnivore takes poisoned rodents) are likely to be a significant cause of mortality in urban carnivores. However, our literature review indicated that toxicity is listed as a cause of death for only a few urban and rural coyotes (Riley et al., 2003; Van Deelen & Gosselink, 2006) (Fig. 2) and for kit foxes (Cypher, 2010). The lack of reports may be related to difficulty in ascertaining poisoning as a cause of death, particularly when carcasses are located some time after death. Organochlorines (Dip et al., 2003) and lead (Dip et al., 2001) are found in higher concentrations in urban than rural red foxes in Zürich. Organochlorine levels increase in adult male foxes but not vixens, which appear INCB024360 supplier to pass the compounds to their offspring through lactation. Protection from predators is likely to play an important role in selection of urban habitats. Predation

or aggression is responsible for the death of only 10% of urban coyotes compared with 25% for rural populations, where they conflict with wolves (Fig. 2) and it has been suggested that the massive increase in coyote numbers over recent decades is likely due to reduction in

the numbers of grey wolf across North America (Gese & Bekoff, 2004). In turn, coyotes tend to avoid landscapes with extensive human presence, and their conflict with red foxes medchemexpress means that foxes end up being relegated to areas with relatively more intense human activity (e.g. roads, farmsteads) (Gosselink et al., 2007). An estimated 38% of red foxes in rural US die due to predation/aggression, largely due to conflict with coyotes, compared with only 12% in urban US (Gosselink et al., 2007). In the UK, the absence of a natural predator for the fox results in less predation. Nevertheless, even in urban UK (London and Bristol), a high proportion of red foxes die due to wounds incurred during aggression, principally from stray dogs or conspecifics (Harris & Smith, 1987; Soulsbury et al., 2007). Recent control of stray dog numbers, however, has reduced the incidence of aggression as a cause of death (S. Harris, pers. comm. 2010). Disease has been recorded as the major cause of mortality for urban raccoons, accounting for an average of 50% of deaths in urban areas compared with only 19% of rural raccoons (Fig. 2). High levels of sarcoptic mange have been recorded in urban red foxes in Britain, causing population crashes (Baker et al., 2000; Soulsbury et al.

The occurrence of pre-copulatory

courtship in coercively mating males has not been reported before. ITF2357 In Gluvia, coercive traits suggest that forced copulation is the exclusive mating strategy. Coercive mating strategies in camel-spiders may have evolved as an anti-predation strategy, as sexual cannibalism occurred in c. 40% of all sexual interactions. “
“Sexual size dimorphism (SSD) is often explained as the differential equilibrium between stabilizing survival selection and directional sexual/fecundity selection on the body size of males and females. Provided that survival selection is similar in both sexes, female-biased SSD is thought to occur when fecundity selection on female body size is stronger than sexual selection on male body size. However, in animals with indeterminate growth, body size depends on several life-history traits, thus, to understand why SSD has evolved, one should understand how it arises. We investigate SSD in the Tyrrhenian tree frog, Hyla sarda, by describing sexual dimorphism in age and growth and by assessing how body size affects their reproductive success. Females are 16% larger than males because they mature 1 year later, live 1 year longer and reach a larger asymptotic body size. Furthermore, body size correlates positively with female fecundity, but not with male mating success. These

results suggest that SSD arises from differential optimal trade-offs between the expected number of reproductive episodes (which decreases with prolonging growth) and the expected success in each reproductive episode (which increases with prolonging growth). “
“Reproductive Selleckchem FK506 frequency is a key component of reproductive output, and has important influences on organismal fitness and population persistence. Viperid snakes, like many other ectothermic vertebrates, generally exhibit a low frequency of reproduction (LFR), as females only 上海皓元医药股份有限公司 reproduce every second year, or even less frequently. However, for small-bodied species with constrained clutch/litter sizes, and low survival, reproductive frequency cannot be too infrequent if populations are to

persist. We assessed whether Bitis schneideri, a small, arid-adapted viperid snake from southern Africa has the LFR typical of many other viperids, despite having low survival and small litters. We calculated the reproductive frequency required to sustain a population using information gathered from recent studies of the ecology of the species. The small litter size imposed by being small-bodied, and low annual survival, require B. schneideri to reproduce frequently, probably annually, for populations to persist. We also assessed the reproductive status of all available preserved adult females. A high proportion were reproductive (up to 80% during summer), with developing or mature follicles, or developing young.

, 2003). Frontal-executive functions are known to include the ability to plan ahead and to overcome impulsive behaviour. It would therefore follow that frontal-executive impairments would correlate with the occurrence of relapses. Unfortunately, no studies to date have provided convincing data to support this proposal (Bowden, Crews, Bates, Fals-Stewart, & Ambrose, 2001). A recent study by Loeber et al. (2010) demonstrated a negative effect on cognitive function and recovery in 31 patients. However, they did not show a correlation with the occurrence of relapses, and included participants with a relatively positive prognosis. In contrast, the study presented here examined

only patients with a history of being resistant to therapy, who can therefore be assumed to have a negative prognosis. Our study thus provides preliminary support for a negative check details association between frontal-executive deficits and future prognosis, although

further longitudinal data and replication with larger cohorts selleck products are required. A clinical implication may be drawn from these results based on data indicating that cognitive deficits tend to improve with abstinence (Fals-Stewart & Lam, 2010). It may hence be assumed that patients with subtle executive deficits may benefit most from long-term therapeutic options rather than from frequent detoxifications. It is also noteworthy that the cognitive deficits manifested solely in more dedicated neuropsychological tests (TMT and RWT), and would therefore probably have been missed by routine clinical tests. Similarly, while patients did not fulfil the ICD10 criteria for depressive syndrome, they reported significantly more depressive features MCE公司 in the BDI questionnaire

compared with controls. These depressive tendencies may have aggravated executive impairments, but also would not have been detected in routine clinical tests. In summary, the study presented here found that severely alcohol-dependent subjects who have experienced recurrent withdrawals display subtle cognitive deficits. These deficits occurred primarily in the frontal-executive domain, while memory functions and visuospatial capacities were largely spared. Our pilot study therefore suggests that extensive cognitive testing might be a helpful additional tool in assessing therapy-resistant heavy drinkers. Future trials will elucidate the influence these cognitive deficits have on prognosis and quality of life. “
“Impulse control disorders (ICDs) and apathy are recognized as two important neuropsychiatric syndromes associated with Parkinson’s disease (PD), but as yet we understand very little about the cognitive mechanisms underlying them. Here, we review emerging findings, from both human and animal studies, that suggest that impulsivity and apathy are opposite extremes of a dopamine-dependent spectrum of motivated decision making.

6). A model with separate parameters for each of the seven subpopulations failed to converge, however, such a model did converge when the length data from French Frigate Shoals was excluded. This model was a much better fit than one with shared parameters for the six remaining subpopulations after French Frigate Shoals was excluded (▵AICc = −53.624 for the full data set, ▵AICc = −34.857 for the reduced data set). A French Frigate Shoals length curve was fitted by iteratively fixing the asymptote at varying values as described in the Methods. Resulting curves for each subpopulation exhibit marked variability. To demonstrate differences in the

growth trajectories, we chose an arbitrary reference length (180 cm) and calculated the Selleckchem Ku0059436 expected age when this length would be attained at

each site. This ranged from just over age 3 yr at sites with relatively rapid growth to between age 6 and 7 yr at French Frigate Shoals and Lisianski Island (Fig. 3). As with length, we found no support for sex differences in axillary girth growth. A sex effect model of pooled data was not an improvement compared to equal parameters for males and females (AICc increased by 0.485). Testing for subpopulation differences in girth growth patterns within a model comparison framework was hampered by difficulties in achieving convergence. Efforts to fit the three-parameter model to data from three (French Frigate Shoals, Laysan Island, and Pearl and Hermes Reef) Rucaparib medchemexpress of the seven subpopulations failed. Therefore, two-parameter (with the asymptote estimated iteratively) models were fitted to these sites. Site-specific girth growth curves varied similarly to growth in length. The age when seals were expected to reach an arbitrary reference (120 cm) girth varied from just over 3 yr in the main Hawaiian Islands to 9 and 12 yr at French Frigate Shoals and Lisianski Island, respectively (Fig. 4). Table 2 presents estimated parameters for length and girth models. Kenyon and Rice (1959) reported that adult female Hawaiian monk seals

appeared to be larger than males. This was apparently based only on visual assessment, and in the context of the authors’ landmark comprehensive description of the species’ natural history, was likely offered as a tentative observation. Yet, adult female monk seals exceeding males in size has been oft-repeated in publications and has seemingly taken on a certainty that the original authors likely did not intend. Here we find no evidence of sexual dimorphism in growth or body size. Antonelis et al. (2003) likewise found no sex differences in the size of pups at weaning. There were striking differences in growth curves among the various monk seal subpopulations. The fitted parameters (Table 2) for each site are provided for reference, though when considered individually, they provide limited insight into growth patterns.

6). A model with separate parameters for each of the seven subpopulations failed to converge, however, such a model did converge when the length data from French Frigate Shoals was excluded. This model was a much better fit than one with shared parameters for the six remaining subpopulations after French Frigate Shoals was excluded (▵AICc = −53.624 for the full data set, ▵AICc = −34.857 for the reduced data set). A French Frigate Shoals length curve was fitted by iteratively fixing the asymptote at varying values as described in the Methods. Resulting curves for each subpopulation exhibit marked variability. To demonstrate differences in the

growth trajectories, we chose an arbitrary reference length (180 cm) and calculated the click here expected age when this length would be attained at

each site. This ranged from just over age 3 yr at sites with relatively rapid growth to between age 6 and 7 yr at French Frigate Shoals and Lisianski Island (Fig. 3). As with length, we found no support for sex differences in axillary girth growth. A sex effect model of pooled data was not an improvement compared to equal parameters for males and females (AICc increased by 0.485). Testing for subpopulation differences in girth growth patterns within a model comparison framework was hampered by difficulties in achieving convergence. Efforts to fit the three-parameter model to data from three (French Frigate Shoals, Laysan Island, and Pearl and Hermes Reef) Small molecule library cell line medchemexpress of the seven subpopulations failed. Therefore, two-parameter (with the asymptote estimated iteratively) models were fitted to these sites. Site-specific girth growth curves varied similarly to growth in length. The age when seals were expected to reach an arbitrary reference (120 cm) girth varied from just over 3 yr in the main Hawaiian Islands to 9 and 12 yr at French Frigate Shoals and Lisianski Island, respectively (Fig. 4). Table 2 presents estimated parameters for length and girth models. Kenyon and Rice (1959) reported that adult female Hawaiian monk seals

appeared to be larger than males. This was apparently based only on visual assessment, and in the context of the authors’ landmark comprehensive description of the species’ natural history, was likely offered as a tentative observation. Yet, adult female monk seals exceeding males in size has been oft-repeated in publications and has seemingly taken on a certainty that the original authors likely did not intend. Here we find no evidence of sexual dimorphism in growth or body size. Antonelis et al. (2003) likewise found no sex differences in the size of pups at weaning. There were striking differences in growth curves among the various monk seal subpopulations. The fitted parameters (Table 2) for each site are provided for reference, though when considered individually, they provide limited insight into growth patterns.

Activation of AhR mediates the expression of LGK-974 datasheet target genes (e.g., CYP1A1) by binding to dioxin response element (DRE) sequences in their promoter region. To understand the multiple mechanisms of AhR-mediated gene regulation, a microarray analysis on liver isolated from ligand-treated transgenic mice expressing a wild-type (WT) Ahr or a DRE-binding mutant Ahr (A78D) on an ahr-null background was performed. Results revealed that AhR DRE binding is not required for the suppression of genes involved in cholesterol synthesis. Quantitative reverse-transcription

polymerase chain reaction performed on both mouse liver and primary human hepatocyte RNA demonstrated a coordinated repression of genes involved in cholesterol biosynthesis, namely, HMGCR, FDFT1, SQLE, and LSS after receptor activation. An additional transgenic mouse line was established expressing a liver-specific Ahr-A78D

on a CreAlb/Ahrflox/flox background. These mice displayed a similar repression of cholesterol biosynthetic genes, compared to Ahrflox/flox MLN0128 manufacturer mice, further indicating that the observed modulation is AhR specific and occurs in a DRE-independent manner. Elevated hepatic transcriptional levels of the genes of interest were noted in congenic C57BL/6J-Ahd allele mice, when compared to the WT C57BL/6J mice, which carry the Ahb allele. Down-regulation of AhR nuclear translocator levels using short interfering RNA in a human cell line MCE revealed no effect on the expression of cholesterol biosynthetic genes. Finally, cholesterol secretion was shown to be significantly decreased in human cells after AhR activation. Conclusion: These data firmly establish an endogenous role for AhR as a regulator of the cholesterol biosynthesis pathway independent of its DRE-binding ability, and suggest that AhR may be a previously unrecognized therapeutic target. (HEPATOLOGY 2012;55:1994–2004) The aryl hydrocarbon

receptor (AhR) is a ligand-activated transcription factor belonging to the basic helix-loop-helix (bHLH)/Per ARNT Sim (PAS) family of transcription factors. Ligands for the AhR include the planar, hydrophobic halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons, many of which are environmental contaminants. Activation of AhR by xenobiotic agonists, such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a prototypic potent ligand, is known to have toxic consequences, illustrating its role as an exogenous chemical sensor. Atypical ligands include bilirubin and indirubin.1, 2 The presence of potent endogenous ligands for the human AhR exhibiting agonistic activities, such as kynurenic acid3 and 3-indoxyl sulfate,4 have been identified. Upon ligand binding, the AhR heterodimerizes with the AhR nuclear translocator protein (ARNT), another bHLH-PAS family member.5 The AhR/ARNT heterodimer represents a fully competent transcription factor capable of binding a consensus sequence known as dioxin response element (DRE) or xenobiotic response element.