Hydrologic and atrazine simulation of the Cedar Creek Watershed using the SWAT model.

One of the major factors contributing to surface water contamination in agricultural areas is the use of pesticides. The Soil and Water Assessment Tool (SWAT) is a hydrologic model capable of simulating the fate and transport of pesticides in an agricultural watershed. The SWAT model was used in this study to estimate stream flow and atrazine (2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine) losses to surface water in the Cedar Creek Watershed (CCW) within the St. Joseph River Basin in northeastern Indiana. Model calibration and validation periods consisted of five and two year periods, respectively. The National Agricultural Statistics Survey (NASS) 2001 land cover classification and the Soil Survey Geographic (SSURGO) database were used as model input data layers. Data from the St. Joseph River Watershed Initiative and the Soil and Water Conservation Districts of Allen, Dekalb, and Noble counties were used to represent agricultural practices in the watershed which included the type of crops grown, tillage practices, fertilizer, and pesticide application rates. Model results were evaluated based on efficiency coefficient values, standard statistical measures, and visual inspection of the measured and simulated hydrographs. The Nash and Sutcliffe model efficiency coefficients (E(NS)) for monthly and daily stream flow calibration and validation ranged from 0.51 to 0.66. The E(NS) values for atrazine calibration and validation ranged from 0.43 to 0.59. All E(NS) values were within the range of acceptable model performance standards. The results of this study indicate that the model is an effective tool in capturing the dynamics of stream flow and atrazine concentrations on a large-scale agricultural watershed in the midwestern USA.

Effects of dihydrotestosterone on adipose tissue measured by serial analysis of gene expression.

Intra-abdominal fat accumulation is related to several diseases, especially diabetes and heart disease. Molecular mechanisms associated with this independent risk factor are not well established. Through the serial analysis of gene expression (SAGE) strategy, we have studied the transcriptomic effects of castration and dihydrotestosterone (DHT) in retroperitoneal adipose tissue of C57BL6 male mice. Approximately 50,000 SAGE tags were isolated in intact and gonadectomized mice, as well as 3 and 24 h after DHT administration. Transcripts involved in energy metabolism, such as glyceraldehyde-3-phosphate dehydrogenase, malic enzyme supernatant, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase and monoglyceride lipase, were upregulated by DHT. Transcripts involved in adipogenesis, and cell cycle and cell shape organization, such as DDX5, C/EBPalpha, cyclin I, procollagen types I, III, IV, V and VI, SPARC and matrix metalloproteinase 2, were upregulated by DHT. Cell defense, division and signaling, protein expression and many novel transcripts were regulated by castration and DHT. The present results provide global genomic evidence for a stimulation of glycolysis, fatty acids and triacylglycerol production, lipolysis and cell shape reorganization, as well as cell proliferation and differentiation, by DHT. The novel transcripts regulated by DHT may contribute to identify new mechanisms involved in the action of sex hormones and their potential role in obesity.

Transcriptome of mouse uterus by serial analysis of gene expression (SAGE): comparison with skeletal muscle.

The aim of this study was to identify the transcriptome of the normal mouse uterus by Serial Analysis of Gene Expression method. mRNA was extracted from the uterus and also from the gastrocnemius muscle of mice. Short sequences (tags), each one usually corresponding to a distinct transcript, were isolated and concatemerized into long DNA molecules which were cloned and sequenced. We detected 44,484 tags for the uterus and 42,518 tags for the muscle, representing 14,543 and 14,958 potential transcript species, respectively. Seventy-five and sixty-nine genes were expressed at more than 0.1%, thus corresponding to 37 and 34% of the mRNA population detected in the respective tissues. In both cases, the most highly expressed genes are especially involved in muscle contraction, energy metabolism, and protein synthesis. Compared to skeletal muscle, some differentially expressed genes in the uterus are likely to correspond to its specific reproductive functions. The majority of these genes remain to be characterized. More than 70% of the different tags detected in the uterus did not match any sequence in the public databases and can represent novel or poorly identified genes. This study is the first quantitative description of the transcriptome of the uterus.

A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence.

BACKGROUND: The melanocortin system includes five receptors (MC1R to MC5R), and mouse and human MC4R has been shown to be involved in the regulation of feeding, and mouse MC3R in body composition. To verify a possible similar effect of MC3R in humans, we analyzed one insertion and one single nucleotide polymorphism by restriction fragment length polymorphisms (RFLP), and a microsatellite (D20S32e) in relation to body composition and glucose metabolism. METHODS: Eight hundred twelve subjects of the Québec Family Study (QFS) cohort were analyzed for body composition, food intake, and energy metabolism phenotypes. Southern Blot with the complete MC3R cDNA was used to detect a new +2138InsCAGACC variant by Pst1 restriction. PCR-RFLP with BsaJ1 was used to type amino acid polymorphism V81I arising from a G241A nucleotide change. PCR and automatic DNA sequencers were used for the analysis of the TG dinucleotide repeat D20S32e located between -1933/-1892 of MC3R. In a covariance analysis among genotypes, phenotypes were adjusted for age and sex as covariates. Food intake and energy metabolism phenotypes were also adjusted for body mass index (BMI), and leptin and abdominal fat, as assessed by a computed tomography scan, for fatness using six skinfold thicknesses. RESULTS: An association between the +2138InsCAGACC MC3R polymorphism was observed with fat mass (FM), percent body fat (%FAT), and total abdominal fat (ATF). Homozygote subjects for the +2138 insertion variant allele in normal weight (BMI < 25 kg/m(2)) and overweight (25 < or = BMI < 30 kg/m(2)) subjects showed a similar level of fatness despite the overall difference in BMI. In normal weight, homozygotes for the insertion allele showed higher mean values than heterozygotes and homozygotes for wild-type allele without insertion (%FAT: 24.0 +/- 1.1 versus 19.3 +/- 0.9 and 20.5 +/- 0.8, p = 0.0005; FM: 15.7 +/- 0.9 kg versus 11.7 +/- 0.7 kg and 12.6 +/- 0.6 kg, p = 0.0003). In contrast, overweight subjects homozygote for the variant allele showed lower mean values (%FAT: 27.0 +/- 1.2 versus 31.4 +/- 0.8 and 30.9 +/- 0.7, p = 0.002; FM: 18.3 +/- 1.0 kg versus 22.8 +/- 0.8 kg and 22.0 +/- 0.6 kg, p = 0.0001). This resulted in a similar level of body fat between both BMI groups for subjects homozygote for the insertion allele versus wild-type allele carriers (%FAT: +/-2-3% versus +/-10-12%; FM: +/-2 kg versus +/-9-11 kg). In obese subjects (BMI > or = 30 kg/m(2) ), a lower level of ATF was seen (-15%, p = 0.002). Other polymorphisms and phenotypes tested showed no association. CONCLUSION: A new 12138InsCAGACC MC3R polymorphism is associated with the level of adiposity and with body fat partitioning in interaction with corpulence in humans.

A new gene related to human obesity identified by suppression subtractive hybridization.

OBJECTIVE: The aim of the research was to identify genes specially expressed in the obese state and potentially involved in the pathogenesis of obesity. DESIGN AND SUBJECTS: We used the technique of suppression subtractive hybridization (SSH), which combines subtractive hybridization with PCR, to generate a population of PCR fragments enriched for transcripts of high or low abundance from differentially expressed genes. PolyA+ mRNA was isolated from subcutaneous abdominal adipose tissue of five massively obese (>35 kg/m(2)) and five normal-weight (<25 kg/m(2)) women. cDNA generated from RNA pooled from the obese subjects was contrasted by SSH with an excess of pooled cDNA from the normal-weight women. RESULTS: Seventy-nine clones were obtained among which one showed by RT-PCR a higher expression in obese than in normal-weight subjects. This gene was shown to be predominantly expressed in adipose tissue in contrast to brain, liver, kidney, heart and skeletal muscle, and was called "Adipogene". No expression was detected in lung, pancreas and placenta. The cDNA was 1.5 kb long with an open reading frame of 1004 nucleotides encoding a protein of 334 amino acids (37 kDa). No significant sequence similarity was found in databanks, except for weak amino acid homologies with prokaryotic AraC/XylS transcriptional regulator family. Adipogene is encoded on chromosome 8, less than 1 centiMorgan (cM) from the beta3 adrenergic receptor (ADRB3) locus. Weak linkages were observed with body mass index (BMI) and three microsatellite markers located within 10 cM of Adipogene, whereas no linkage was observed with Trp64Arg ADRB3 polymorphism using the Québec Family Study database. CONCLUSION: Using the SSH technique, we have identified a new gene, called Adipogene, which is overexpressed in the adipose tissue of the obese individuals and could be involved in obesity.

Endocrine regulation of uncoupling proteins and energy expenditure.

Regulatory thermogenesis occurs upon exposure to the cold or during food intake. Among a variety of mechanisms leading to heat production, uncoupling of respiration in brown adipocyte mitochondria appears to be a major contributor to resistance to the cold in rodents. This uncoupling mechanism is due to the activity of uncoupling protein-1 (UCP-1), a specific carrier present in the inner membrane of mitochondria. The recent identification of UCP-2 and UCP-3, two homologues of the brown fat UCP, suggested that respiration uncoupling could contribute to thermogenesis in most tissues. Activity and expression of the three UCP's are stimulated by several neuromediators and hormones such as noradrenaline, tri-iodothyronine and leptin.

Prediction of recidivism in extrafamilial child molesters based on court-related assessments.

One hundred ninety-two convicted extrafamilial child molesters were followed for an average of 7.8 years after their conviction. The percentage of men who had committed a sexual, a violent, or any criminal offense by the 12th year was 15.1, 20.3, and 41.6, respectively. The sexual recidivists, compared with the nonrecidivists; demonstrated more problems with alcohol and showed greater sexual arousal to assaultive stimuli involving children than to mutually consenting stimuli with children. The violent recidivists, compared with the nonrecidivists, were more likely to have a history of violence in the families in which they were raised and were rated significantly more psychopathic on the Psychopathy Checklist--Revised (PCL-R). They also showed more sexual arousal to stimuli depicting mutually consenting sexual interactions with children than to adult stimuli. In terms of any criminal recidivism, recidivists were younger, had completed fewer years of school, and were raised in psychologically more harmful family environments compared with nonrecidivists. They also reported that, before 16 years of age, they were more likely to have been physically abused and were more likely to have been removed from their homes compared to those that did not recidivate. In addition, recidivists demonstrated more general hostility on the Buss-Durkee Hostility Inventory and were rated significantly more psychopathic on the PCL-R. The phallometric assessments revealed, that the criminal recidivists, compared to the nonrecidivists, showed more sexual arousal to stimuli depicting coercive sexual activity with children than consenting sexual activities with children. In addition, they showed more sexual arousal to scenes depicting adult rape then adult mutually consenting sex. Finally, the recidivists also had more charges or convictions for violence and any criminal acts. The small number of significant differences between recidivists and nonrecidivists in the sexual and violent categories precluded an attempt to determine which combination of factors meaningfully predicted reoffending. However, for criminal recidivism, a stepwise discriminant function analysis to assess the combination of factors that most successfully distinguished between groups in terms of criminal recidivism was significant, with subjects' age, total number of criminal convictions, and pedophile assault index being retained for optimal prediction. The procedure correctly classified 70.6% of the original group, 82.8% of the nonrecidivists, and 52.6% of the recidivists. PCL-R Total Score alone was equally successful in a similar discriminant function.

Contributions of studies on uncoupling proteins to research on metabolic diseases.

The coupling of O2 consumption to ADP phosphorylation in mitochondria is partial. This is particularly obvious in brown adipocyte mitochondria which use a regulated uncoupling mechanism generating heat production from substrate oxidation, and catalysing thermogenesis in rodents or infants in response to cold, and arousing hibernators. In the case of brown adipose tissue, the uncoupling mechanism is related to a specific protein in the inner mitochondrial membrane referred to as UCP1. Although the biological importance of UCP1 in human adults is not demonstrated, genetic analysis of various human cohorts suggested a participation of UCP1 to control of fat content and body weight. Very recently, the cloning of UCP2 and UCP3, two homologues of UCP1, has renewed the field of research on the importance of respiration control in metabolic processes and metabolic diseases. UCP2 is widely expressed in organs, whereas UCP3 is mainly present in muscles. These proteins may explain why the coupling of respiration to ADP phosphorylation is less than perfect. Their biological importance should be studied. They also represent new putative targets for drugs against metabolic diseases such as obesity.

Recidivism in convicted rapists.

Factors associated with recidivism in 86 men convicted of rape were studied. These men had been out of prison for up to 12 years (mean, 7.6 years). The majority of the men had been assessed in a sexual behaviors clinic of a general psychiatric hospital at the time of their conviction. Almost 50 percent of the group had committed some offense by the fifth year out of prison. The recidivism rates for sexual, violent, and any criminal recidivism were 16 percent, 26 percent, and 53 percent, respectively. The ability to predict sexual and violent recidivism in this population of rapists was rather poor. More sexual recidivists, compared with nonrecidivists, had been removed from their family home prior to age 16. Violent recidivists compared with nonrecidivists were also more frequently removed from their homes prior to 16 years of age, and they showed significantly more problems with alcohol. In terms of any criminal recidivism, recidivists compared with nonrecidivists were younger and scored higher on the Michigan Alcohol Screening Test (MAST). They also had more previous charges and/or convictions for violent offenses and more charges and/or convictions for any criminal acts. The combination of age and MAST scores was able to predict 92.6 percent of the nonrecidivists and 53.3 percent of the recidivists. The outstanding feature of the total group of rapists was their poor sexual adjustment as indicated on the Derogatis Sexual Functioning Inventory, on which they scored at approximately the seventh percentile of the population at large. There was also an indication that rapists have problems with hostility, as measured by the Buss-Durkee Hostility Inventory. Furthermore, the range of scores on the MAST indicated that the total group of rapists has serious problems with alcohol. The inability of phallometric assessments and psychopathy as measured by the Psychopathy Checklist-R to predict recidivism are discussed.

Homicidal sex offenders: psychological, phallometric, and diagnostic features.

Homicidal sex offenders represent an understudied population in the forensic literature. Forty-eight homicidal sex offenders assessed between 1982 and 1992 were studied in relation to a comparison group of incest offenders. Historical features, commonly used psychological inventories, criminal histories, phallometric assessments, and DSM diagnoses were collected on each group. The homicidal sex offenders, compared with the incest offenders, self-reported that they had more frequently been removed from their homes during childhood and had more violence and forensic psychiatric contact in their histories. On the self-report psychological inventories, the homicidal sex offenders portrayed themselves as functioning significantly better in the areas of sexuality (Derogatis Sexual Functioning Inventory) and aggression/hostility (Buss-Durkee Hostility Inventory). However, on the Psychopathy Checklist-Revised (PCL-R), researchers rated the homiciders significantly more psychopathic than the incest offenders on Factor 1 (personality traits) and Factor 2 (antisocial history). Police records revealed the homicidal subjects also had been charged or convicted of more violent and nonviolent nonsexual offenses. The phallometric assessments indicated that the homicidal sex offenders demonstrated higher levels of response to pedophilic stimuli and were significantly more aroused to stimuli depicting assaultive acts to children, relative to the incest offenders. Despite the homiciders' self-reports of fairly good psychological functioning, DSM-III diagnoses reliably discriminated between the groups. A large number of homicidal sex offenders were diagnosed as suffering from psychosis, antisocial personality disorder, paraphilias, sexual sadism, sexual sadism with pedophilia, and substance abuse. Seventy-five percent of the homicidal sex offenders had three or more diagnoses compared with six percent of the incest offenders. The article addresses the role of "hard" versus "soft" measures in the assessment and treatment of violent sex offenders. In addition, the usefulness of phallometric assessments and the PCL-R and its subscales are considered.

Specific IgE-dependent sensitization, atopy, and bronchial hyperresponsiveness in apprentices starting exposure to protein-derived agents.

Atopy, specific IgE sensitization, and bronchial hyperresponsiveness (BHR) were examined in a cohort of 769 apprentices starting career programs in animal health or veterinary medicine (Group 1), pastry making (Group 2), and dental hygiene (Group 3). The hypothesis were that: (1) a proportion of subjects can be "sensitized" although no significant specific occupational exposure has occurred; and (2) there is a relationship between baseline specific sensitization to work-related antigens and host characteristics. Skin tests were administered using 11 common inhalants and specific allergens, including six laboratory animal extracts, three cereal antigens, alpha-amylase, and latex. Methacholine challenge tests were performed. The prevalence of atopy was 54.4% in Group 1, 58.1% in Group 2, and 52.5% in Group 3. Skin reactivity to work-specific proteins was as follows: laboratory animal proteins, 13.8% in Group 1, 14.0% in Group 2, and 15.6% in Group 3. No subject was sensitized to alpha-amylase, whereas 1.2% in Group 1, 5% in Group 2, and 4.1% in Group 3 were sensitized to flour. Five subjects reacted to latex. BHR (PC20 < or = 8 mg/ml) was present in 17.6%, 21.2%, and 14.8% of subjects in Groups 1, 2, and 3, respectively. Specific sensitization was associated with positive skin reactions to common allergens, work-related symptoms, and BHR. These results suggest that students starting career programs with exposure to high-molecular-weight allergens have a low but substantial frequency of specific sensitization to work-related allergens that is related to atopy and BHR.

Essential cis-acting elements in rat uncoupling protein gene are in an enhancer containing a complex retinoic acid response domain.

Transgenic mice were generated with a transgene containing the 211-base pair (bp) enhancer and 0.4 kilobase pairs of 5'-flanking DNA of the uncoupling protein (ucp) gene. Expression of this transgene was restricted to brown adipose tissue and was inducible by cold exposure or treatment of transgenic mice by norepinephrine, retinoic acid (RA), or CL-316,243 beta3-adrenoreceptor agonist. A search for retinoic acid response elements in the ucp gene enhancer was undertaken using mutagenesis and transfection of cultured cells with chloramphenicol acetyltransferase constructs. Deletion or mutations of several putative retinoic acid response elements were ineffective. Mutations of a TGAATCA region dramatically decreased the transcriptional activity in the presence of RA. In vitro this region was able to bind a complex containing proteins recognized by antibodies against Jun or Fos. Mutations of an adjacent region related to an inverted repeat of type 2 also markedly decreased RA effect. This region was able to bind in vitro retinoid X receptor alpha and retinoic acid receptor beta. The two regions form an activating region between bp -2421 and -2402 (referred to as the ucp gene-activating region), which has an enhancer activity but cannot confer RA response to a promoter. This response was obtained with a larger DNA fragment (bp -2489 to -2398) constituting a complex RA response domain.

Activation of STAT factors by prolactin, interferon-gamma, growth hormones, and a tyrosine phosphatase inhibitor in rabbit primary mammary epithelial cells.

In numerous studies on mammary epithelial cell lines multiple factors, added to the medium or contained in the serum, were required for casein gene expression. It has been shown in these systems that the mammary gland factor (MGF) is implicated in the activation of the beta-casein gene promoter. In the present study, we determined the relationship between known agents that affect casein gene expression and MGF activity using the properties of rabbit primary mammary epithelial cells to respond to PRL alone, when cultured in chemically defined medium. We demonstrate that MGF is rapidly activated by PRL alone or by human growth hormone, a natural ligand of many PRL receptors (PRL-Rs), in the cytoplasm and accumulated in the nucleus. The MGF activation by PRL occurred in the absence of endogenous extracellular matrix, a condition where casein synthesis is known to be markedly reduced. Different inhibitors of protein-tyrosine kinases, which have been shown to reduce casein mRNA synthesis, but not of protein kinase C, decrease the MGF activity. A tyrosine phosphatase inhibitor, sodium pervanadate, induced two GAS-binding complexes related to MGF and STAT1. Our data show that MGF is a latent cytoplasmic factor rapidly activated in mammary epithelial cells, by a mechanism involving a tyrosine kinase and a tyrosine phosphatase.

The treatment of depression with group behavioural-cognitive therapy and imipramine.

Twenty-four outpatients meeting DSM-III-R criteria for major depression were assigned to group behavioral-cognitive therapy either with or without antidepressant medication (imipramine). Eighteen patients completed 15 weekly sessions of treatment. Equivalent improvement was observed in both regimens after treatment. The results essentially maintained at six months follow-up. This suggests that a group format of behavioural-cognitive therapy is a viable therapeutic intervention for outpatients diagnosed as suffering from major depression. However, the addition of imipramine to group behavioural-cognitive therapy did not enhance the outcome.

In vitro interactions between nuclear proteins and uncoupling protein gene promoter reveal several putative transactivating factors including Ets1, retinoid X receptor, thyroid hormone receptor, and a CACCC box-binding protein.

Previous studies of rat ucp (uncoupling protein) gene organization carried out in this laboratory identified regulatory sequences located in the 5'-flanking region. In this work, DNase I footprint analysis of the enhancer revealed two domains at base pairs (bp) -2444 to -2423 and bp -2352 to -2319. The former domain can bind in vitro, in a cooperative manner, factors related to nuclear factor 1 and Ets1; the latter domain contains a type 3 directly repeated sequence that was shown to be able to bind the retinoid X and triiodothyronine receptors. Moreover, a positive effect of retinoic acid on ucp mRNA levels in immortalized brown adipocytes was observed. DNase I footprint analysis identified two hypersensitive regions, A and B, at bp -509 to -472 and bp -403 to -350, respectively; region A contains a repeated CACCC box, and region B can bind protein related to Ets1. The A box differentially binds liver and brown adipose tissue nuclear proteins and could be involved in uncoupling protein induction. Further analysis showed three foot-printed boxes, C-E, at bp -182 to -159, -147 to -120, and -111 to -85, able to bind in vitro proteins related to nuclear factor 1, cAMP response element-binding protein, and Sp1, respectively.

Canadian experience with a copper-covered intrauterine contraceptive device.

PIP: 518 patients were inserted with T-Cu120sq. mm(168), T-Cu200sq. mm(250), and Lippes Loop (60) for a 20-month comparative study of the devices. Events of spotting, dysmenorrhea, metrorrhagia, and secondary side effects were less in the T-Cu devices. The expulsion rate was higher for the T-Cu200sq. mm than T-Cu120sq. mm, but for all other types of termination the T-Cu120sq. mm was highest. Termination rate for Lippes Loops was 19.66; T-Cu120sq. mm 32.03; and T-Cu200sq. mm, 24.17. Insertion was easier with T devices.^ieng