Impact of maternal medication for opioid use disorder on neurodevelopmental outcomes of infants treated for neonatal opioid withdrawal syndrome.

BACKGROUND: Increasing rates of maternal opioid use disorder has led to greater number of opioid exposed newborns (OENs). Maternal enrollment in medication for opioid use disorder (MOUD) program improves short term neonatal outcomes. This study aimed at assessing neurobehavioral outcomes for OENs. METHODS: Retrospective observational cohort study of OENs between Jul 2006 and Dec 2018. Two study groups were identified as initiation of medication for opioid use disorder (MOUD) prior to diagnoses of pregnancy or after. Primary outcome variables were enrollment in and duration of EI services. Secondary outcome variable was diagnoses of a behavioral and/or developmental disorder (BDD) during the study period. RESULTS: Of 242 infants, 113 were enrolled in EI and BDD diagnoses data was available for all infants [age range 6 to 12 years], 82% infants had exposure to maternal MOUD, while 18% were exposed to either maternal prescription non-MOUD opioids or illicit opioids. Maternal MOUD initiation prior to pregnancy was associated with improved short term outcomes for OENs. Almost a third of infants were diagnosed with a BDD with no differences between the two study groups. CONCLUSION: Early initiation of maternal MOUD improved short term outcomes and discharge disposition for OENs. Prolonged in-utero exposure to opioids presents a potential for negative impact on neurodevelopmental and behavioral outcomes. These risks must be considered to increase access and adherence to EI services, as well as to focus on non-opioid based maternal MOUD. Longitudinal studies assessing the safety of MOUD on short and long-term child health outcomes are needed.

A comparative evaluation of the disulfur dinitride process for the visualisation of fingermarks on metal surfaces.

The disulfur dinitride process for fingermark visualisation was first reported a decade ago, with promising results obtained for a range of materials including metals. However, the friction sensitive nature of the material and difficulty of synthesis made routine use difficult. Many of these issues have since been addressed, making equipment and chemicals available to build an understanding of how the effectiveness of disulfur dinitride compares to other fingermark visualisation processes currently used on metal surfaces. This enables more informed advice to be given on selection of processes for treatment of metal items, an area of operational interest that encompasses weapons used in violent crime and the increasing incidence in metal theft. This paper reports a comparative study into the effectiveness of disulfur dinitride, cyanoacrylate fuming, vacuum metal deposition, gun blueing and wet powder suspensions on brass, bronze, copper and stainless steel. Experiments were conducted with the surfaces exposed to a range of environments including long term ageing, water/detergent washing, acetone washing and high temperature exposure. The results indicate that disulfur dinitride is an effective process for fingermark visualisation on metal surfaces, including those exposed to adverse environments, and may offer potential improvements over existing processes for those surfaces. Further work, including pseudo-operational trials, is recommended.

Early Head Start, Pediatric Dental Use, and Oral Health-Related Quality of Life.

The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health-related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2-percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%-3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, -13.9% to -1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. Knowledge Transfer Statement: Study results can inform policy makers that comprehensive early childhood education programs improve oral health-related quality of life (OHRQoL) for disadvantaged families with young children in pathways outside of clinical dental care. This awareness and its promotion can lead to greater resource investments in early childhood education programs. Information about the negative impacts of dental use on OHRQoL should lead to the development and testing of strategies in dentistry and Early Head Start to improve dental care experiences.

Watershed influences on the structure and function of riparian wetlands associated with headwater streams - Kenai Peninsula, Alaska.

Riparian wetlands are dynamic components of landscapes. Located between uplands and aquatic environments, riparian habitats intercept sediments and nutrients before they enter aquatic environments. They are a source of organic matter and nutrients to aquatic systems, and they provide important habitat for animals, often serving as corridors for the movement of animals between habitats in fragmented landscapes. In this project, we focused on the structure and function of riparian wetlands associated with headwater streams in Alaska that serve as nursery habitats for juvenile salmonids. We asked whether or not the structure and function of headwater wetlands differed between watersheds with and without nitrogen-fixing Alder (Alnus spp.). We found that the aboveground biomass of riparian vegetation was higher in the watershed with Alder, but the largest differences were in the litter layer and belowground where vegetation in the watershed with no Alder had significantly higher root biomass. Interstitial water chemistry also differed between the study sites with significantly higher inorganic N and significantly different characteristics of colored dissolved organic matter at the site with Alder on the watershed. The biomass of litter that hung over the creek bank was less at the site with Alder on the watershed and an in situ decomposition experiment showed significant differences between the two systems. Results of the research demonstrates that watershed characteristics can impact the ecology of headwater streams in ways that had not been previously recognized.

Effects of enamel fluorosis and dental caries on quality of life.

The objectives of this study were to determine the impact of enamel fluorosis and dental caries on oral health-related quality of life (OHRQoL) in North Carolina schoolchildren and their families. Students (n = 7,686) enrolled in 398 classrooms in grades K-12 were recruited for a onetime survey. Parents of students in grades K-3 and 4-12 completed the Early Childhood Oral Health Impact Scale (ECOHIS) and Family Impact Scale (FIS), respectively. Students in grades 4-12 completed the Child Perceptions Questionnaire (CPQ8-10 in grades 4-5; CPQ11-14 in grades 6-12). All students were examined for fluorosis (Dean's index) and caries experience (d2-3fs or D2-3MFS indices). OHRQoL scores (sum response codes) were analyzed for their association with fluorosis categories and sum of d2-3fs and D2-3MFS according to ordinary least squares regression with SAS procedures for multiple imputation and analysis of complex survey data. Differences in OHRQoL scores were evaluated against statistical and minimal important difference (MID) thresholds. Of 5,484 examined students, 71.8% had no fluorosis; 24.4%, questionable to very mild fluorosis; and 3.7%, mild, moderate, or severe fluorosis. Caries categories were as follows: none (43.1%), low (28.6%), and moderate to high (28.2%). No associations between fluorosis and any OHRQoL scales met statistical or MID thresholds. The difference (5.8 points) in unadjusted mean ECOHIS scores for the no-caries and moderate-to-high caries groups exceeded the MID estimate (2.7 points) for that scale. The difference in mean FIS scores (1.5 points) for the no-caries and moderate-to-high groups exceeded the MID value (1.2 points). The sum of d2-3fs and D2-3MFS scores was positively associated with CPQ11-14 (B = 0.240, p < .001), ECOHIS (B = 0.252, p ≤ .001), and FIS (B = 0.096, p ≤ .01) scores in ordinary least squares regression models. A child's caries experience negatively affects OHRQoL, while fluorosis has little impact.

Effectiveness of a school-based fluoride mouthrinse program.

The aims of this study were to estimate the caries-preventive effects of a school-based weekly fluoride mouthrinse (FMR) program and to determine whether its effectiveness varied by school-level caries risk. We used clinical and parent-reported data for 1,363 children in grades 1 through 5 from a probability sample of North Carolina (NC) schoolchildren. Children's caries experience was measured using decayed and filled primary (d(2,3)fs) and total (d(2,3)fs+D(2,3)MFS) tooth surfaces. Program participation was quantified using 'FMR years'. To estimate caries risk at program entry, children were matched with NC kindergarten-surveillance data representing school-level mean untreated decay (low-risk school: < 1 and high-risk school: ≥ 1 untreated carious teeth). Mean d(2,3)fs was 4.1 [95% confidence limits (CL) = 3.7, 4.5]. Overall, each 'FMR year' was associated with weak reduction of caries prevalence in the primary [prevalence ratio (PR) = 0.98; 95% CL = 0.90, 1.06] and the mixed dentition (PR = 0.98; 95% CL = 0.91, 1.05). We found a trend toward a larger caries-preventive benefit among children in high-risk schools compared with those in low-risk schools (i.e., 55% vs. 10% caries reduction for 5 to 6 yrs of FMR participation compared to none). Although this difference was not confirmed statistically, our results indicate that children in high-risk schools, as identified by school-level surveillance data, may experience substantial caries-preventive benefits from long-term FMR participation.

The synthesis, full characterisation and utilisation of template-free silica sodalite, a novel polymorph of silica.

Empty glass: Subjecting ethylene glycol silica sodalite to heat (680 degrees C) under a nitrogen atmosphere (i) successfully removes the templating agent to give cubic silica sodalite, which, upon consequent heating under an oxygen atmosphere (ii), transforms into a rhombohedral form of the empty sodalite, in effect a novel polymorph of silica.

Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfate.

The aim of this study was to identify sulfotransferase (SULT) isoform(s) responsible for the formation of indoxyl sulfate from indoxyl (3-hydroxyindole). Indoxyl was incubated together with the co-substrate 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and either human or rat liver cytosol or recombinant sulfotransferase enzymes. Formation of indoxyl sulfate from indoxyl was measured by HPLC and used for determination of sulfonation rates. Both cytosols sulfonated indoxyl with apparent Km values of 6.8 +/- 0.9 microM for human and 3.2 +/- 0.6 microM for rat cytosol. To help identify the isoform(s) of SULT responsible for indoxyl sulfate formation, indoxyl was incubated with human and rat liver cytosols and PAPS in the presence of isoform-specific SULT inhibitors. No inhibition was observed by DHEA, a specific hydroxysteroid sulfotransferase inhibitor, nor by oestrone, an inhibitor of oestrogen sulfotransferase. However, an aryl (phenol) sulfotransferase inhibitor, 2,6-dichloro-4-nitrophenol (DCNP), inhibited the formation of indoxyl sulfate with a IC50 values of 3.2 microM for human and 1.0 microM for rat cytosol indicating that human and rat aryl (phenol) sulfotransferases are responsible for the formation of indoxyl sulfate. When indoxyl was incubated with SULT1A1*2, a human recombinant aryl SULT, an apparent Km value of 5.6 +/- 1.8 microM was obtained. Kinetic studies with human and rat cytosols and human recombinant SULT1A1*2 gave similar kinetic values indicating that human and rat aryl sulfotransferases efficiently catalyze the formation of indoxyl sulfate, an important uremic toxin metabolite.

Birthdates and number of neurons in the serotonergic raphe nuclei in the rat with prenatal protein malnutrition.

The effect of prenatal protein deprivation on timing of neurogenesis and on number of neurons generated in the serotonergic dorsal (DR) and median raphe (MR) nuclei of the rat was studied. These neurons are of interest because their neurogenesis occurs during the period of malnutrition and their axonal projections participate in the earliest stages of brain development. In this study, dams were maintained on a 25% casein diet or a 6% casein diet 5 weeks prior to mating and throughout pregnancy. At birth, all pups were cross-fostered to dams on a 25% casein diet. Bromodeoxyuridine, a thymidine analog that is incorporated into nuclear deoxyribonucleic acid during the cell cycle synthetic phase, was used as a marker of neurogenesis. Bromodeoxyuridine was administered on either embryonic day 11, 12, 13 or 14. On postnatal day 30, serial sections of raphe nuclei were processed with bromodeoxyuridine immunocytochemistry to determine the number of raphe cells generated on each day and with Nissl stain to determine the total number of cells generated. There were no significant differences between the two diet groups in timing of generation or in total number of cells generated, indicating that neurogenesis of these early generated neurons appears unaffected by concomitant protein deprivation.

The Tctex1/Tctex2 class of dynein light chains. Dimerization, differential expression, and interaction with the LC8 protein family.

The Tctex1/Tctex2 family of dynein light chains associates with the intermediate chains at the base of the soluble dynein particle. These components are essential for dynein assembly and participate in specific motor-cargo interactions. To further address the role of these light chains in dynein activity, the structural and biochemical properties of several members of this polypeptide class were examined. Gel filtration chromatography and native gel electrophoresis indicate that recombinant Chlamydomonas flagellar Tctex1 exists as a dimer in solution. Furthermore, yeast two-hybrid analysis suggests that this association also occurs in vivo. In contrast, both murine and Chlamydomonas Tctex2 are monomeric. To investigate protein-protein interactions involving these light chains, outer arm dynein from Chlamydomonas flagella was cross-linked using dimethylpimelimidate. Immunoblot analysis of the resulting products revealed the interaction of LC2 (Tctex2) with LC6, which is closely related to the highly conserved LC8 protein found in many enzyme systems, including dynein. Northern dot blot analysis demonstrated that Tctex1/Tctex2 family light chains are differentially expressed both in a tissue-specific and developmentally regulated manner in humans. These data provide further support for the existence of functionally distinct populations of cytoplasmic dynein with differing light chain content.

Use of granulocyte colony-stimulating factor after high-dose chemotherapy and autologous peripheral blood stem cell transplantation: what is the optimal timing?

Administration of granulocyte colony-stimulating factor to patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation accelerates neutrophil recovery and decreases hospitalization time. The optimal timing for granulocyte colony-stimulating factor infusion remains unknown. In this retrospective, case-controlled, two-armed study, we reviewed our experience at Hahnemann University Hospital to determine whether initiating granulocyte colony-stimulating factor infusions on posttransplant day 0 versus day 8 affects neutrophil recovery time, posttransplant discharge date, total hospital days after high-dose chemotherapy, and autologous peripheral blood stem cell transplantation. All patients hospitalized between 1994 and 1998 at Hahnemann University Hospital, Bone Marrow Transplantation Unit with breast cancer or non-Hodgkin's lymphoma, who underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and received granulocyte colony-stimulating factor either on posttransplant day 0 (16 patients) or day 8 (16 patients). The day 0 and day 8 groups had no statistically significant differences in age, sex, weight, height, body surface area, disease characteristics, pretransplant harvesting or conditioning regimens, or transplant CD34+ cell counts. Our main outcome measure was the mean time to reach absolute neutrophil count greater than or equal to 0.5 x 10(9)/l, the number of hospital days after transplant, and the total hospital days. The mean days to neutrophil recovery (10.56 versus 9.68, p = 0.48), posttransplant hospital days (13.62 versus 12.81, p = 0.39), and total hospital days (20.25 versus 20.25, p = 1.00) were not significantly different between day 8 and day 0 groups, respectively. No significant effects on neutrophil recovery time, posttransplant hospital days, or total hospital days were observed with the initial granulocyte colony-stimulating factor infusion on day 0 versus day 8 after transplant. Delayed administration may allow substantial cost savings (US$200 x 8 approximately equal to US $1,600 per patient) without affecting clinical outcome. More studies are needed to determine whether greater delay is feasible.

Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate.

The aim of our study was to determine which microsomal cytochrome P450 isozyme(s) were responsible for the microsomal oxidation of indole to indoxyl, an important intermediate in the information of the uremic toxin indoxyl sulfate. Indole was incubated together with an NADPH-generating system and rat liver microsomes. Formation of indigo, an auto-oxidation product of indoxyl, was used to determine the indole-3-hydroxylation activity. Apparent Km and Vmax values of 0.85 mM and 1152 pmol min(-1) mg(-1) were calculated for the formation of indoxyl from indole using rat liver microsomes. The effects of various potential inducers and inhibitors on the metabolism of indole to indoxyl by rat liver microsomes were studied to elucidate the enzymes responsible for metabolism. Studies with general and isozyme-specific P450 inhibitors demostrated that P450 enzymes and not FMO are responsible for the formation of indoxyl. In the induction studies, rate of indoxyl formation in the microsomes from untreated vs induced rats correlated nearly exactly with the CYP2E1 activity (4-nitrophenol 2-hydroxylation). These results suggests that CYP2E1 is the major isoform for the microsomal oxidation of indole to indoxyl.

Structure-function modeling of the interactions of N-alkyl-N-hydroxyanilines with rat hepatic aryl sulfotransferase IV.

Although previous investigations have clearly shown that N-hydroxy arylamines and N-hydroxy heterocyclic amines are substrates for sulfotransferases, relatively little is known about which structural features of the N-hydroxy arylamines are important for sulfation to occur. The purpose of this investigation was to determine the extent to which secondary N-alkyl-N-hydroxy arylamines interact with aryl sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase or ST1A1) and to evaluate these interactions using molecular modeling techniques. AST IV is a major cytosolic sulfotransferase in the rat, and it catalyzes the sulfation of various phenols, benzylic alcohols, arylhydroxamic acids, oximes, and primary N-hydroxy arylamines. In this study, three secondary N-hydroxy arylamines, N-hydroxy-N-methylaniline, N-ethyl-N-hydroxyaniline, and N-hydroxy-N-n-propylaniline, were found to be substrates for the purified rat hepatic AST IV. However, when the N-alkyl substituent was an n-butyl group (i.e., N-n-butyl-N-hydroxyaniline), the interaction with the enzyme changed from that of a substrate to competitive inhibition. This change in specificity was further explored through the construction and use of a model for AST IV based on mouse estrogen sulfotransferase, an enzyme whose crystal structure has been previously determined to high resolution. Molecular modeling techniques were used to dock each of the above N-hydroxy arylamines into the active site of the homology model of AST IV and determine optimum ligand geometries. The results of these experiments indicated that steric constraints on the orientation of binding of secondary N-alkyl-N-hydroxy arylamines at the active site of AST IV play a significant role in determining the nature of the interaction of the enzyme with these compounds.

In vitro bioactivation of N-hydroxy-2-amino-alpha-carboline.

2-Amino-alpha-carboline (A alpha C) is a mutagenic and carcinogenic heterocyclic amine present in foods cooked at high temperature and in cigarette smoke. The mutagenic activity of A alpha C is dependent upon metabolic activation to N-hydroxy-A alpha C (N-OH-A alpha C); however, the metabolism of N-OH-A alpha C has not been studied. We have synthesized 2-nitro-alpha-carboline and N-OH-A alpha C and have examined in vitro bioactivation of N-OH-A alpha C by human and rodent liver cytosolic sulfotransferase(s) and acetyltransferase(s) and by recombinant human N-acetyltransferases, NAT1 and NAT2. The sulfotransferase-dependent bioactivation of N-OH-A alpha C by human liver cytosol exhibited large inter-individual variation (0.5-75, n = 14) and was significantly higher than bioactivation of N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP). Correlation and inhibition studies suggested that the isoform of sulfotransferase primarily responsible for bioactivation of N-OH-A alpha C in human liver cytosol is SULT1A1. O-Acetyltransferase-dependent bioactivation of N-OH-A alpha C by human liver cytosol also exhibited large inter-individual variation (16-192, n = 18). In contrast to other N-hydroxy heterocyclic amines, which are primarily substrates only for NAT2, both NAT1 and NAT2 catalyzed bioactivation of N-OH-A alpha C. The rate of bioactivation of N-OH-A alpha C by both NAT1 and NAT2 was significantly higher than that for N-OH-PhIP. In rat and mouse liver cytosols, the level of sulfotransferase-dependent bioactivation of N-OH-A alpha C was similar to the level in the high sulfotransferase activity human liver cytosol. The level of O-acetyltransferase-dependent bioactivation of N-OH-A alpha C in rat liver cytosol was also comparable with that in the high acetyltransferase activity human liver cytosol. However, the level of O-acetyltransferase-dependent bioactivation of N-OH-A alpha C in mouse liver cytosol was comparable with that in the low acetyltransferase activity human liver cytosol. In contrast to N-OH-PhIP, bioactivation of N-OH-A alpha C was not inhibited by glutathione S-transferase activity; however, DNA binding of N-acetoxy-A alpha C was inhibited 20% in the presence of GSH. These results suggest that bioactivation of N-OH-A alpha C may be a significant source of DNA damage in human tissues after dietary exposure to AalphaC and that the relative contribution of each pathway to bioactivation or detoxification of N-OH-A alpha C differs significantly from other N-hydroxy heterocyclic or aromatic amines.

Concentrations of suspended particulate organic carbon in the tidal Yorkshire Ouse River and Humber Estuary.

Data are presented for particulate organic carbon (POC) and particulate nitrogen (PN) concentrations in the Humber Estuary and tidal River Ouse Estuary. The POC data were derived from approximately monthly surveys and are consistent with data reported for suspended particulate matter (SPM) in the non-tidal River Ouse (the freshwater river) and with SPM, or bed sediments, in estuarine ecosystems such as the Mississippi, Delaware, San Francisco Bay, Tolo Harbour, the Vellar Estuary and Cochin Backwater, as well as the Loire, Gironde, Ems and Tamar Estuaries. Relative to the dry weight of SPM, the Humber-averaged organic carbon and nitrogen percentages during the year February 1995-March 1996 were 2.6 +/- 0.6% (mean and S.D.) and 0.21 +/- 0.04%, respectively. The ratio of Humber-averaged POC to Humber-averaged PN was 13 +/- 3. Higher POC levels were observed near the Humber's mouth and in the adjacent coastal zone during 'bloom' conditions, and in the upper estuarine reaches during large, winter and springtime freshwater inflows. At these times of high runoff, the POC content of SPM increased progressively up-estuary from the coastal zone to the tidal River Ouse. When inflows became very low, during late spring to early autumn of 1995, both the freshwater-saltwater interface (FSI) and the strengthening turbidity maximum (TM) moved further up-estuary and the POC content of SPM in the upper reaches of the Ouse became lower compared with that immediately down-estuary. This led to a poorly defined POC maximum near the confluence of the Humber, Ouse and Trent, before POC eventually decreased again towards the coastal zone. The lower POC contents in the upper estuarine reaches of the tidal Ouse may have been partly due to POC respiration by heterotrophic bacteria attached to SPM within the TM, consistent with the severe oxygen depletion observed there during high turbidity, summertime spring tides.

LC2, the chlamydomonas homologue of the t complex-encoded protein Tctex2, is essential for outer dynein arm assembly.

Tctex2 is thought to be one of the distorter genes of the mouse t haplotype. This complex greatly biases the segregation of the chromosome that carries it such that in heterozygous +/t males, the t haplotype is transmitted to >95% of the offspring, a phenomenon known as transmission ratio distortion. The LC2 outer dynein arm light chain of Chlamydomonas reinhardtii is a homologue of the mouse protein Tctex2. We have identified Chlamydomonas insertional mutants with deletions in the gene encoding LC2 and demonstrate that the LC2 gene is the same as the ODA12 gene, the product of which had not been identified previously. Complete deletion of the LC2/ODA12 gene causes loss of all outer arms and a slow jerky swimming phenotype. Transformation of the deletion mutant with the cloned LC2/ODA12 gene restores the outer arms and rescues the motility phenotype. Therefore, LC2 is required for outer arm assembly. The fact that LC2 is an essential subunit of flagellar outer dynein arms allows us to propose a detailed mechanism whereby transmission ratio distortion is explained by the differential binding of mutant (t haplotype encoded) and wild-type dyneins to the axonemal microtubules of t-bearing or wild-type sperm, with resulting differences in their motility.

Detoxification of carcinogenic aromatic and heterocyclic amines by enzymatic reduction of the N-hydroxy derivative.

The metabolic activation pathways associated with carcinogenic aromatic and heterocyclic amines have long been known to involve N-oxidation, catalyzed primarily by cytochrome P4501A2, and subsequent O-esterification, often catalyzed by acetyltransferases (NATs) and sulfotransferases (SULTs). We have found a new enzymatic mechanism of carcinogen detoxification: a microsomal NADH-dependent reductase that rapidly converts the N-hydroxy arylamine back to the parent amine. The following N-OH-arylamines and N-OH-heterocyclic amines were rapidly reduced by both human and rat liver microsomes: NOH-4-aminoazobenzene, N-OH-4-aminobiphenyl (N-OH-ABP), N-OH-aniline, N-OH-2-naphthylamine, N-OH-2-aminofluorene, N-OH-4,4'-methylenebis(2-chloroaniline) (N-OH-MOCA), N-OH-1-naphthyamine, N-OH-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), N-OH-2-amino-alpha-carboline (N-OH-AalphaC), N-OH-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx), and N-OH-2-amino-3-methylimidazo[4,5-f]quinoline (N-OH-IQ). In addition, primary rat hepatocytes and human HepG2 cells efficiently reduced N-OH-PhIP to PhIP. This previously unrecognized detoxification pathway may limit the bioavailability of carcinogenic N-OH heterocyclic and aromatic amines for further activation, DNA adduct formation, and carcinogenesis.

Drosophila roadblock and Chlamydomonas LC7: a conserved family of dynein-associated proteins involved in axonal transport, flagellar motility, and mitosis.

Eukaryotic organisms utilize microtubule-dependent motors of the kinesin and dynein superfamilies to generate intracellular movement. To identify new genes involved in the regulation of axonal transport in Drosophila melanogaster, we undertook a screen based upon the sluggish larval phenotype of known motor mutants. One of the mutants identified in this screen, roadblock (robl), exhibits diverse defects in intracellular transport including axonal transport and mitosis. These defects include intra-axonal accumulations of cargoes, severe axonal degeneration, and aberrant chromosome segregation. The gene identified by robl encodes a 97-amino acid polypeptide that is 57% identical (70% similar) to the 105-amino acid Chlamydomonas outer arm dynein-associated protein LC7, also reported here. Both robl and LC7 have homology to several other genes from fruit fly, nematode, and mammals, but not Saccharomyces cerevisiae. Furthermore, we demonstrate that members of this family of proteins are associated with both flagellar outer arm dynein and Drosophila and rat brain cytoplasmic dynein. We propose that roadblock/LC7 family members may modulate specific dynein functions.