interacts_with DB00391?
Modulation of antipsychotic-induced extrapyramidal side effects by medications for mood disorders . Antipsychotic drugs are widely used not only for schizophrenia , but also for mood disorders such as bipolar disorder and depression . To evaluate the interactions between antipsychotics and drugs for mood disorders in modulating extrapyramidal side effects ( EPS ) , we examined the effects of antidepressants and mood-stabilizing drugs on haloperidol ( P42357 ) -induced bradykinesia and catalepsy in mice and rats . The selective serotonin reuptake inhibitors ( SSRIs ) , fluoxetine and paroxetine , and the tricyclic antidepressant ( TCA ) clomipramine , which showed no EPS by themselves , significantly potentiated P42357 -induced bradykinesia and catalepsy in a dose-dependent manner . In contrast , the noradrenergic and specific serotonergic antidepressant ( NaSSA ) mirtazapine failed to augment , but rather attenuated P42357 -induced bradykinesia and catalepsy . DB06148 also tended to reduce the EPS induction . In addition , neither treatment with lithium , sodium valproate nor carbamazepine potentiated P42357 -induced EPS . Furthermore , treatment of animals with ritanserin ( 5- Q13049 /2C antagonist ) , ondansetron ( 5- Q9H205 antagonist ) , and SB-258585 ( P50406 antagonist ) significantly antagonized the EPS augmentation by fluoxetine . Intrastriatal injection of ritanserin or SB-258585 , but not ondansetron , also attenuated the EPS induction . The present study suggests that NaSSAs are superior to SSRIs or TCAs in combined therapy for mood disorders with antipsychotics in terms of EPS induction . In addition , 5- Q13049 /2C , 5- Q9H205 and P50406 receptors seem to be responsible for the augmentation of antipsychotic-induced EPS by serotonin reuptake inhibitors . P01236 influence on cytosol and nuclear androgen receptors in the ventral , dorsal , and lateral lobes of the rat prostate . PRL augments testosterone-mediated growth of the prostate in a permissive manner . To elucidate the mechanism of this hormonal interaction , the present study examined the effect of PRL on cytosol and nuclear androgen receptors in the three prostate lobes . Adult male Sprague-Dawley rats were castrated , given 5-mm Silastic implants of testosterone , and either grafted with two anterior pituitary glands under the kidney capsule or sham operated . Three weeks later , animals were killed , serum was collected for PRL and testosterone RIA , and the ventral , dorsal , and lateral prostate lobes were processed for either cytosol or nuclear androgen receptor quantitation . Pituitary grafts significantly elevated the serum PRL concentration and increased the weight and the content of protein and DNA of the lateral prostate lobe compared to control values . There was no effect on these parameters in the ventral or dorsal lobes . P10275 levels and apparent distributions were different in the ventral , dorsal , and lateral lobes of control animals . Unoccupied and total cytosolic androgen receptors in the three separate prostate lobes were not significantly affected by the presence of the grafts . However , an elevated PRL concentration was associated with an increase ( P less than 0.005 ) in nuclear androgen receptor content in the lateral lobe exclusively . The binding affinity was not altered by pituitary grafts in any of the lobes . These findings suggest that PRL promotes lateral prostatic growth by increasing nuclear androgen receptor levels in that tissue and , thus , optimizes its response to circulating testosterone . P61244 mutations status in Swedish patients with pheochromocytoma and paraganglioma tumours . Pheochromocytoma ( DB09058 ) and Paraganglioma are rare tumours originating from neuroendocrine cells . Up to 60 % of cases have either germline or somatic mutation in one of eleven described susceptibility loci , P31040 , P21912 , Q99643 , O14521 , Q9NX18 , P40337 , Q99814 , P07949 , P21359 , O75204 and MYC associated factor-X ( P61244 ) . Recently , germline mutations in P61244 were found to confer susceptibility to DB09058 and paraganglioma ( PGL ) . A subsequent multicentre study found about 1 % of PCCs and PGLs to have germline or somatic mutations in P61244 . However , there has been no study investigating the frequency of P61244 mutations in a Scandinavian cohort . We analysed tumour specimens from 63 patients with DB09058 and PGL treated at Uppsala University hospital , Sweden , for re-sequencing of P61244 using automated Sanger sequencing . Our results show that 0 % ( 0/63 ) of tumours had mutations in P61244 . Allele frequencies of known single nucleotide polymorphisms rs4902359 , rs45440292 , rs1957948 and rs1957949 corresponded to those available in the Single Nucleotide Polymorphism Database . We conclude that P61244 mutations remain unusual events and targeted genetic screening should be considered after more common genetic events have been excluded . Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia . AIMS : Abnormalities in dopaminergic and serotonergic transmission systems are thought to be involved in the pathophysiology of schizophrenia and the mechanisms underlying the therapeutic effects of antipsychotics . We conducted a pharmacogenetic study to evaluate whether variants in dopamine-related genes ( P21728 - P21918 , P31749 and GSK3beta ) and serotonin receptor genes ( P08908 , P28222 , P28221 , P28223 , P28335 , P50406 and P34969 ) can be used to predict the efficacy of risperidone treatment for schizophrenia . MATERIALS & METHODS : A total of 120 first-episode neuroleptic-naive schizophrenia patients were treated with risperidone monotherapy for 8 weeks and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale . RESULTS : Among the 30 variants that we examined , two SNPs in P14416 ( -241A > G [ rs1799978 ] and TaqIA [ rs1800497 ] ) and two SNPs in P31749 ( P31749 -SNP1 [ rs3803300 ] and P31749 -SNP5 [ rs2494732 ] ) were significant predictors of treatment response to risperidone . CONCLUSION : These data suggest that the SNPs in P14416 and P31749 may influence the treatment response to risperidone in schizophrenia patients . Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia : the SzGene database . In an effort to pinpoint potential genetic risk factors for schizophrenia , research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results . To facilitate the interpretation of these findings , we have created a regularly updated online database of all published genetic association studies for schizophrenia ( ' SzGene ' ) . For all polymorphisms having genotype data available in at least four independent case-control samples , we systematically carried out random-effects meta-analyses using allelic contrasts . Across 118 meta-analyses , a total of 24 genetic variants in 16 different genes ( P02649 , P21964 , DAO , P21728 , P14416 , P21917 , Q96EV8 , P47870 , Q13224 , HP , P01584 , P42898 , O75051 , P31645 , P04637 and P17752 ) showed nominally significant effects with average summary odds ratios of approximately 1.23 . Seven of these variants had not been previously meta-analyzed . According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies , four of the significant results can be characterized as showing ' strong ' epidemiological credibility . Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia . As such , it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders . Differential effects of all-trans and 13-cis-retinoic acid on mRNA levels of nuclear retinoic acid receptors in rat lung and liver . The effects of three retinoids , all-trans-retinoic acid ( all-trans-RA ) , 13- DB00982 , and etretin were examined on mRNA abundance of nuclear retinoic acid receptors ( P10276 , beta , and gamma ) in lung and liver of retinol deficient and chow fed rats . All-trans-RA increased lung P10826 mRNA levels 5 or 11-fold in chow fed and retinol deficient rats , respectively . Similarly to lung , liver P10826 mRNA levels were 3-fold higher in retinol deficient rats fed all-trans-RA than the rats fed cottonseed oil . Lung P13631 mRNA levels were also induced 2-fold by all-trans-RA . In contrast to this , 13- DB00982 and etretin at equimolar doses failed to enhance lung or liver P10826 or lung P13631 mRNA levels in retinol deficient rats . These data for the first time show that all-trans-RA is more effective than its 13-cis-isomer in regulating the expression of P10826 and gamma transcripts in adult animal . Dopamine D1 , D2 and D3 receptor genes in alcohol dependence . Hereditary factors play a substantial role in the etiology of alcohol dependence . DB00898 mediates its reinforcing effects by an activation of the mesolimbic dopamine system . These findings suggest that the genes encoding the dopamine receptor ( DR ) subtypes represent high-ranking candidates for susceptibility genes to addictive disorders . Our present population-based association study investigated whether sequence variants of the dopamine D1 , D2 and D3 receptor genes confer susceptibility to alcohol dependence in 278 alcoholics , and clinically more homogeneous subgroups ascertained through positive family history , early age at onset , delirium , withdrawal seizures and antisocial tendencies . No evidence for an allelic association was found for the PCR-based TaqA RFLP fo the P14416 gene and a Bsp1286I RFLP of the P21728 gene . Without correction for multiple testing , we found a significantly increased allele frequency of a common P35462 gene variant expressing a serine at position 9 in the extracellular N-terminal part of the receptor protein in 55 alcohol-dependent individuals with delirium ( chi 2 = 4.1 , df = 1 , p = 0.042 ) . Further studies have to examine whether this amino acid substitution or a nearby mutation confers genetic susceptibility to at least a subgroup of alcohol-dependent individuals with delirium . Vitamin D analogues . The plethora of actions attributed to 1,25(OH)2D3 throughout the body have suggested potential therapeutic applications for the treatment of hyperproliferative diseases , immune dysfunction , endocrine disorders , and metabolic bone disease . However , the potent calcemic activity of the natural vitamin D hormone has precluded its use in most cases . New vitamin D analogues are under development that display greater specificity , in most cases , by retaining the therapeutic properties of 1,25(OH)2D3 , but with lower calcemic activity . Two analogues have been approved for use in patients : calcipotriol ( DB02300 from Leo Pharmaceuticals , Copenhagen , Denmark ) for the treatment of psoriasis ; and 19-nor-1,25(OH)2D2 ( DB00910 from Abbott Laboratories , Abbott Park , IL ) for secondary hyperparathyroidism . Many others analogues are currently being tested in preclinical and clinical trials for the treatment of various types of cancer and osteoporosis , and for immunosuppression . The selectivity of the analogues can be attributed to the combined interactions with four proteins : the vitamin D receptor ( P11473 ) , the serum vitamin D binding protein ( DBP ) , the vitamin D-24-hydroxylase and to a newly described membrane receptor . Low DBP affinity has been shown to be responsible for the reduced calcemic actions of calcipotriol and 22-oxacalcitriol ( O75051 ) , which is being tested for secondary hyperparathyroidism . However , the low calcemic activity of other analogues , including 19-nor-1,25(OH)2D2 , involves other , as yet undefined , mechanisms . Understanding of the molecular basis for the selectivity of the vitamin D analogues will allow the design of more effective and safer vitamin D compounds for the treatment of a wide range of clinical disorders . Defective prolactin signaling impairs pancreatic β-cell development during the perinatal period . P01236 ( PRL ) and placental lactogens stimulate β-cell replication and insulin production in pancreatic islets and insulinoma cells through binding to the PRL receptor ( P16471 ) . However , the contribution of P16471 signaling to β-cell ontogeny and function in perinatal life and the effects of the lactogens on adaptive islet growth are poorly understood . We provide evidence that expansion of β-cell mass during both embryogenesis and the postnatal period is impaired in the P16471 (-/-) mouse model . P16471 (-/-) newborns display a 30 % reduction of β-cell mass , consistent with reduced proliferation index at E18.5 . PRL stimulates leucine incorporation and S6 kinase phosphorylation in P01308 -1 cells , supporting a role for β-cell P42345 signaling in PRL action . Interestingly , a defect in the development of acini is also observed in absence of P16471 signaling , with a sharp decline in cellular size in both endocrine and exocrine compartments . Of note , a decrease in levels of P01344 , a PRL target , in the Goto-Kakizaki ( GK ) rat , a spontaneous model of type 2 diabetes , is associated with a lack of PRL-mediated β-cell proliferation in embryonic pancreatic buds . Reduced pancreatic P01344 expression in both rat and mouse models suggests that this factor may constitute a molecular link between PRL signaling and cell ontogenesis . Together , these results provide evidence that PRL signaling is essential for pancreas ontogenesis during the critical perinatal window responsible for establishing functional β-cell reserve . DB00139 dehydrogenase flavoprotein subunit expression in Saccharomyces cerevisiae -- involvement of the mitochondrial DB03147 transporter , Flx1p . The mitochondrial DB03147 transporter , Flx1p , is a member of the mitochondrial carrier family responsible for DB03147 transport in Saccharomyces cerevisiae . It has also been suggested that it has a role in maintaining the normal activity of mitochondrial DB03147 -binding enzymes , including lipoamide dehydrogenase and succinate dehydrogenase flavoprotein subunit Sdh1p . A decrease in the amount of Sdh1p in the flx1Delta mutant strain has been determined here to be due to a post-transcriptional control that involves regulatory sequences located upstream of the P21912 coding sequence . The P21912 coding sequence and the regulatory sequences located downstream of the P21912 coding region , as well as protein import and cofactor attachment , seem to be not involved in the decrease in the amount of protein . Dopamine receptors and psychiatric drug treatment . The established antipsychotic drugs act mainly by antagonizing dopamine mediated synaptic transmission in the brain . Increase in the rate of production of dopamine metabolites as well as the firing rate of dopamine-containing neurons can be interpreted as compensatory responses to an interruption of synaptic transmission at dopamine nerve terminals . The demonstration of involvement of limbic and cortical mechanisms in the antipsychotic activity of neuroleptic drugs is far more difficult than the involvement of nigro-striatal and tubero-infundibular mechanisms in the neurological and neuroendocrine effects of these drugs . Application of radioreceptor techniques to dopamine research has supported the findings obtained by other neuropsychopharmacological research techniques , providing more direct evidence of dopamine receptor blockade by neuroleptic drugs . Further research is needed especially in studying the nature of the time-dependent adaptive changes at the receptor sites as well as the differences between the different dopamine projections and neural systems in the brain . The different subtypes of dopamine receptors in the brain , currently called D1 and D2 dopamine receptors , seem to be parallel , although in many respects independently-acting regulatory systems . P14416 -selective antagonists such as sulpiride seem to cause selective D2 receptor up-regulation . P01236 secretion seems to be regulated by D2 dopamine receptors . The exact physiological role of D1 dopamine receptors as well as the clinical consequences of selective D1 antagonism is not known . DB00391 and clozapine are examples of atypical neuroleptic compounds that have quite different profile of action , the former having strong and selective antidopaminergic action , the latter combining a number of non- dopaminergic mechanisms with rather slight effects on dopamine receptors. ( ABSTRACT TRUNCATED AT 250 WORDS ) P01236 exerts a prosurvival effect on human spermatozoa via mechanisms that involve the stimulation of Akt phosphorylation and suppression of caspase activation and capacitation . The purpose of this study was to examine the impact of prolactin ( PRL ) on human sperm function , in light of a recent proteomic analysis indicating that these cells express the PRL receptor ( P16471 ) . Immunocytochemical analyses confirmed the presence of P16471 in human spermatozoa and localized this receptor to the postacrosomal region of the sperm head as well as the neck , midpiece , and principal piece of the sperm tail . Nested PCR analysis indicated that these cells possess four splice variants of the P16471 : the long form and three short isoforms , one of which is reported for the first time . A combination of Western blot analyses and immunocytochemistry demonstrated that PRL inhibited sperm capacitation in a dose-dependent manner , suppressing P12931 kinase activation and phosphotyrosine expression , two hallmarks of this process . The suppression of sperm capacitation was accompanied by a powerful prosurvival effect , supporting the prolonged motility of these cells and preventing the formation of spontaneous DNA strand breaks via mechanisms that involved the concomitant suppression of caspase activation . Western blot analyses indicated that the prosurvival effect of PRL on human spermatozoa involved the stimulation of Akt phosphorylation , whereas inhibitors of phosphatidylinositol-3-OH kinase and Akt negated this effect , as did the direct induction of sperm capacitation with DB02527 analogues . We conclude that PRL is a prosurvival factor for human spermatozoa that prevents these cells from defaulting to an intrinsic apoptotic pathway associated with cell senescence . These findings have implications for preservation of sperm integrity in vivo and in vitro . Analyses of cross species polymerase chain reaction products to infer the ancestral state of human polymorphisms . In numerous population genetic and disease association studies decisions about the ancestry of polymorphic alleles are often made based on the relative frequency of the alleles in the extant populations with the most frequent allele being deemed as ancestral . However , the frequency of an allele in a population is generally not a perfect indicator of its ancestral status . A more accurate method to assess ancestral/derived status of polymorphic alleles involves identification of shared alleles between species . We used this strategy to examine genomic regions homologous to several human polymorphisms in four species of non-human primates . Cross species polymerase chain reaction ( CS-PCR ) , with primers designed from human sequence , was used to investigate regions of interest . Nineteen polymorphisms at six loci ( P14416 , HOXB@ , PAH , D4S10 , P10745 , and P07949 ) were examined either by restriction fragment length analysis of PCR products ( PCR-RFLP ) or by direct sequencing . At seventeen of the eighteen PCR-RFLPs , non-human primates were monomorphic and identical to each other for either lack of restriction enzyme site or presence of the site . Thus , at these seventeen polymorphic sites the shared alleles are most likely to be the ancestral ones in humans . In several cases we have used sequence data to further demonstrate that the nucleotide at the site of the polymorphism is conserved between species confirming the hypothesis of a single ancestral allele . However , not all human alleles can be simply resolved into ancestral and derived ; sequence data from one PCR-RFLP ( in an intron of the PAH locus ) and a single strand conformational polymorphism ( SSCP ) in the 3' untranslated region ( UTR ) of the P14416 gene illustrate this point . [ P62158 -dependent regulation of Ca,Mg-ATPase activity in plasma membranes of the swine myometrium ] . Highly purified plasma membrane ( PM ) preparations of pig myometrium were found to contain 0.91 +/- 0.22 microgram calmodulin per mg of PM protein . Treatment of membranes with 1 mM EGTA in the presence of 0.2 M NaCl causes the diminution of the calmodulin content down to 3 % of the original level . The activity of Ca , Mg-ATPase is thereby decreased by 40 % . Exogenous calmodulin restores the enzyme activity up to 1.94 +/- +/- 0.30 mumol Pi/mg protein/hour . The maximal activation of Ca , Mg-ATPase is observed with 10(-7) M calmodulin . P62158 increases the total ATPase activity of myometrium PM without affecting the Mg-ATPase activity . DB00831 ( 20 microM ) diminishes the activating effect of exogenous calmodulin on Ca , Mg-ATPase . P62158 stimulates Ca , Mg-ATPase at low concentrations of Ca2+ ( 10(-8)-10(-6) M ) by decreasing Km for Ca2+ from 0.4.10(-6) M to 2.10(-8) M as well as by increasing Vmax -- from 0,8 to 1.42 mumol Pl/mg protein/hour . It is supposed that the activating effect of calmodulin on Ca , Mg-ATPase is based on electrostatic interactions of Ca2+-free calmodulin with the enzyme . Evaluation of the endogenous cannabinoid system in mediating the behavioral effects of dipyrone ( metamizol ) in mice . DB04817 is a common nonopioid analgesic and antipyretic , which , in many countries , is available over the counter and is more widely used than paracetamol or aspirin . However , the exact mechanisms by which dipyrone acts remain inconclusive . Two novel arachidonoyl-conjugated metabolites are formed in mice following the administration of dipyrone that are dependent on the activity of fatty acid amide hydrolase ( FAAH ) , which also represents the major catabolic enzyme of the endogenous cannabinoid ligand anandamide . These arachidonoyl metabolites not only inhibit cyclooxygenase ( P23219 / P35354 ) but also bind to cannabinoid receptors at low micromolar concentrations . The relative contributions of cannabinoid receptors and FAAH in the overall behavioral response to dipyrone remain untested . Accordingly , the two primary objectives of the present study were to determine whether the behavioral effects of dipyrone would ( a ) be blocked by cannabinoid receptor antagonists and ( b ) occur in FAAH mice . Here , we report that thermal antinociceptive , hypothermic , and locomotor suppressive actions of dipyrone are mediated by a noncannabinoid receptor mechanism of action and occurred after acute or repeated administration irrespective of FAAH . These findings indicate that FAAH-dependent arachidonoyl metabolites and cannabinoid receptors are not requisites by which dipyrone exerts these pharmacological effects under noninflammatory conditions . Topical rapamycin ( sirolimus ) for facial angiofibromas . DB00877 ( sirolimus ) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin , or P42345 . DB00877 is a novel class of anticancer and immunosuppressant drugs targeting the proteins at molecular level . DB00877 ( sirolimus ) is routinely incorporated in drug-eluting stents used for cardiac angioplasty . In recent years , rapamycin was found to be efficacious in managing the symptom complex of tuberous sclerosis , i.e. renal angiomyolipoma , giant cell astrocytoma and pulmonary lymphangiomyomatosis . Various investigators have also proved that topically applied rapamycin causes regression of facial angiofibromas , giving better cosmetic results . P10275 in human placental villi . In studies with a synthetic androgen , R 1881 , an androgen-binding component was found in the cytosol of human placental villi . Kinetic analysis indicated that the Kd value of this component was 1.4 nM at 0-4 degrees C and that binding of R 1881 amounted to 277 +/- 73 fmol/mg protein. glycerol density gradient ultracentrifugation showed a peak of binding activity in the 8S region in a medium of low ionic strength , but in the 4.5S region in a medium containing 9.5 M DB00761 . The R 1881-binding component was inactivated by mild heat- or trypsin-treatment , but not by treatment with DNase or RNase . Most of the R 1881-binding activity was sedimented at 20 to 40 % saturation of ammonium sulfate . These findings indicate that the R 1881-binding component in human placental cytosol is quite similar in its characteristics to androgen receptors , which are present in various androgen-responsive organs . DB00624 was a more potent competitor of R 1881-binding than DB02901 or cyproterone acetate . Scatchard plots indicated that the binding site of testosterone was identical with that of R 1881 . These findings suggest that the androgen receptor in placental cytosol is specific for testosterone . The Kd value for testosterone was calculated to be 3.2 nM . miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro . Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells , which is critical for embryo implantation and pregnancy establishment . The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels , however very little is known about the post-transcriptional regulation of this process . miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia . In this study we profile the miRNAs expression throughout human endometrial stromal ( hESCs ) decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process . A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs . Three miRNAs families , miR-181 , miR-183 and miR-200 , are down-regulated during the decidualization process . Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs . The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization . We have analyzed a battery of decidualization markers such as cell morphology , P01236 , P08833 , P55773 and P35625 secretion as well as P31260 , P35354 , SP1 , C/EBPß and Q12778 expression in decidualized hESCs with decreased Dicer function . We found decreased levels of P31260 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control . Our results provide the miRNA signature of hESC during the decidualization process in vitro . We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human endometrial decidualization . Human chromosome 3 and pig chromosome 13 show complete synteny conservation but extensive gene-order differences . A comparative map of human chromosome 3 ( HSA 3 ) and pig chromosome 13 ( SSC 13 ) was constructed using physically assigned pig sequence-tagged sites ( STSs ) . Pig STSs representing 11 HSA 3 genes , including v- P04049 murine leukemia viral oncogene homolog 1 ( P04049 ) , retinoic acid beta receptor ( P10826 ) , cholecystokinin ( CCK ) , pituitary transcription factor 1 ( P28069 ) , ceruloplasmin ( CP ) , guanine nucleotide binding protein , alpha-inhibiting polypeptide 2 ( P04899 ) , sucrase-isomaltase ( SI ) , rhodopsin ( P08100 ) , dopamine receptor D3 ( P35462 ) , growth-associated protein 43 ( P17677 ) , and somatostatin ( P61278 ) , were developed . Ten pig STSs were regionally mapped using a somatic cell hybrid panel ( SCHP ) to SSC 13 with 80-100 % concordance . Large-insert probes were obtained by screening a pig yeast artificial chromosome ( YAC ) library with primers for each STS . Several YACs were identified for P35462 , P17677 , P28069 , P08100 , SI , and P61278 for fluorescence in situ hybridization ( Q5TCZ1 ) mapping . Single gene and bi-color Q5TCZ1 with each pairwise combination were used to further define the gene order on SSC 13 . While these data confirm chromosome painting results showing that HSA 3 probes hybridize to a major portion of SSC 13 , they also demonstrate extensive gene-order differences between man and pig within this large conserved synteny group . Interestingly , several conserved chromosomal regions have been detected between pig and mouse that are not conserved between man and mouse , suggesting that the SSC 13 gene arrangement may be the closest to that of the ancestral eutherian chromosome . Agonism of human pregnane X receptor by rilpivirine and etravirine : comparison with first generation non-nucleoside reverse transcriptase inhibitors . DB08864 and etravirine are second generation non-nucleoside reverse transcriptase inhibitors approved recently by the United States Food and Drug Administration for the treatment of human immunodeficiency virus-1 infection . O75469 ( O75469 ) is a member of the superfamily of nuclear receptors that regulate the expression of various genes controlling diverse biological functions . The present study investigated the effects of rilpivirine and etravirine on the activity of human O75469 ( hPXR ) , including the mode of activation , and compared them to those of efavirenz , nevirapine , and delavirdine , which are first generation non-nucleoside reverse transcriptase inhibitors . In transiently transfected HepG2 cells , rilpivirine , etravirine , and efavirenz , but not nevirapine or delavirdine , activated human , mouse , and rat O75469 . Results from mechanistic studies indicated that rilpivirine , etravirine , and efavirenz , but not nevirapine or delavirdine , bound to the ligand-binding domain of hPXR , as assessed by a transactivation assay and by a competitive ligand-binding assay using time-resolved fluorescence resonance energy transfer ; triggered nuclear translocation of a green fluorescence protein-tagged hPXR , as visualized by confocal imaging ; and recruited steroid receptor coactivator-1 ( Q15788 ) , P12931 -2 , and Q9Y6Q9 to hPXR , as demonstrated by mammalian two-hybrid assays . DB08864 , etravirine , and efavirenz , but not nevirapine or delavirdine , increased hPXR target gene ( P08684 ) expression in primary cultures of human hepatocytes . In summary , select non-nucleoside reverse transcriptase inhibitors activated human and rodent O75469 . DB08864 , etravirine , and efavirenz , but not nevirapine or delavirdine , were identified as agonists of hPXR , as assessed in mechanistic experiments , and inducers of P08684 , as determined in primary cultures of human hepatocytes . Gene expression profiles of adipose tissue of obese rats after central administration of neuropeptide Y- Q15761 antisense oligodeoxynucleotides by cDNA microarrays . To investigate the gene expression profiles of adipose tissue of obese rats after central administration of neuropeptide Y- Q15761 antisense oligodeoxynucleotides ( ODNs ) , Q15761 antisense , mismatched ODNs or vehicle was intracerebroventricularly injected and cDNA microarrays were undertaken . Central administration of Q15761 antisense ODNs decreased food intake , body weight and serum insulin compared with both vehicle and mismatched ODNs . The average area of adipocytes both at retroperitoneal and epididymal adipose tissue were fall in antisense group while only the weight of the retroperitoneal fat pats was reduced in antisense group . cDNA microarrays containing 18,000 genes/Ests were used to investigate gene expression of adipose tissue . Autoradiographic analysis showed that 404 , 81 , and 34 genes were differently expressed over twofold , threefold , and fivefold , respectively . The analysis of gene expression profiles indicated that 332 genes were up-regulated and 187 genes were down-regulated in response to Q15761 antisense ODNs treatment . Different clusters of genes associated with apoptosis , signal transduction , energy metabolism , lipid metabolism , etc. , such as P51114 , Q8WV24 , Q7L5Y9 , P27986 , P13598 , Q00169 , P62158 , Q13557 , P61925 , P14416 , O95258 , CKB , P22760 , P38571 , O15254 , O60427 , were concerned . Analysis of differentially expressed genes will help to understand the effects of Q15761 antisense ODNs therapy . [ DB00391 in the management of functional dyspepsia and delayed gastric emptying ] . DB00391 is a sulpiride isomer that exerts its prokinetic action through a dual mechanism : 1 ) as a P14416 antagonist and 2 ) as a serotonin 5HT(4) receptor agonist , conferring this drug with a cholinergic effect . At a dosage of 25mg three times daily , levosulpiride accelerates gastric and gallbladder emptying . Clinical trials have shown that this agent is more effective than placebo in reducing the symptoms of dyspepsia , while comparative studies have demonstrated that its effect is similar or superior to that of other dopamine antagonists . The safety profile of levosulpiride is good and the frequency of adverse events is similar to that of other D(2) dopamine antagonists . Therefore , this drug is a useful therapeutic option in the management of patients with functional dyspepsia , as well as in those with delayed gastric emptying .