| 41981. |
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| 41982. |
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| 41983. |
- Kopp, J, et al.
(författare)
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Regulation of neuropeptide Y Y1 receptors by testosterone in vascular smooth muscle cells in rat testis
- 2008
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 1423-0194 .- 0028-3835. ; 88:3, s. 216-226
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Tidskriftsartikel (refereegranskat)abstract
- It is well established that testosterone and neuropeptide Y (NPY), via its Y1 receptor (Y1R), are involved in the central control of the gonadotrope axis in male rats. Here we examined if a similar interaction also occurs in the male peripheral reproductive target organ, the testes. Expression of the Y1R transcript and protein and changes in testicular microcirculation were studied in normal rats and 12 days following hypophysectomy with and without testosterone substitution (1 or 25 mg s.c.). In situ hybridization and immunohistochemistry showed strong expression of, respectively, Y1R messenger RNA (Y1R mRNA) and Y1R-like immunoreactivity (Y1R-LI) in vascular smooth muscles in the testes of control and hypophysectomized rats treated with testosterone, but was not seen without testosterone substitution. In parallel, control animals and hypophysectomized, testosterone-supplemented rats showed a strong (approximately 40%) decrease in testicular blood flow following intratesticular (i.t.) injection of the Y1-R agonists, [Leu<sup>31</sup>, Pro<sup>34</sup>]NPY, [<i>D</i>-Arg<sup>25</sup>]NPY or NPY, an effect which was completely blocked by prior intravenous administration of the Y1R antagonist, BIBP3226. No significant change in testicular blood flow following i.t. injection of NPY was seen in hypophysectomized rats without testosterone substitution. These findings suggest that the high levels of Y1R mRNA and Y1R-LI in the testes reflect expression of functional Y1Rs mediating vasoconstriction, and that testosterone regulates expression of functional Y1Rs.
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| 41984. |
- Kopparapu, Pradeep, et al.
(författare)
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Expression of cyclin d1 and its association with disease characteristics in bladder cancer
- 2013
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:12, s. 5235-4252
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Invasive urothelial carcinoma of the bladder (UCB) is characterized by alterations in cell-cycle regulatory pathways. Defects in the expression of cyclin D1, a key cell-cycle regulator, have been implicated in progression of various types of cancer. In the present study, we investigated whether cyclin D1 expression is associated with clinicopathological parameters and whether it has any potential prognostic value in determining risk of UCB recurrence.PATIENTS AND METHODS: Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder tissues (n=131) were immunostained using an antibody against cyclin D1. The association between cyclin D1 and clinicopathological parameters including stage, lymph node metastasis, and disease-free survival, were evaluated. Cyclin D1 mRNA expression data from human normal bladder (n=14) and cancer specimens (n=28) were extracted from the public Oncomine database.RESULTS: Cyclin D1 mRNA and protein expression were significantly higher in UCB compared to adjacent non-malignant bladder tissue (for mRNA p=0.003, for protein p=0.001). Cyclin D1 protein expression was significantly higher in non-invasive tumors than in muscle-invasive UCB (p=0.016). Among patients with muscle-invasive UCB, increased cyclin D1 expression in tumor cells significantly correlated with lymph node metastasis (p<0.001), and there was a trend of cyclin D1 together with lymph node positivity to be associated with disease recurrence (p=0.678). Loss of nuclear cyclin D1 expression in tumor cells was likewise significantly associated with the presence of lymph node metastasis (p<0.001).CONCLUSION: Altered expression of cyclin D1 is associated with lymph node metastasis and risk of UCB recurrence. Cyclin D1 expression may therefore have clinical value as a prognostic marker and potential therapeutic target.
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| 41985. |
- Kopparapu, Pradeep Kumar, et al.
(författare)
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Expression and localization of serotonin receptors in human breast cancer
- 2013
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:2, s. 363-370
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the expression of serotonin receptors in patients with breast cancer and to explore their utility as diagnostic and prognostic markers. Immunohistochemical analysis was performed to examine the expression of serotonin (5-HT) receptor subtypes 1A, 1B, 2B and 4 in a tissue microarray containing tumor specimens from 102 patients. Statistical analysis was performed to correlate the expression of these proteins with regard to clinical parameters. We found that all four serotonin receptors (5-HTRs) exhibited different expression patterns in breast cancer specimens. In general strong staining for 5-HTR1A was observed on the membrane of cancer cells but it was detected only in the cytoplasm of non-malignant cells. 5-HTR1B and 5-HTR2B were predominantly expressed in the cytoplasm of breast cancer cells, while 5-HTR4 was exclusively found in the nucleus of malignant and non-malignant cells. Correlation analysis revealed a significant correlation of 5-HTR2B with estrogen receptor-α (ER-α) and 5-HTR4 with ER-α and progesterone (PR). In conclusion, the different expression patterns and subcellular localization of 5-HTRs in breast cancer may reflect their role in breast cancer progression.
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| 41986. |
- Kopparapu, Pradeep Kumar, et al.
(författare)
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Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer
- 2013
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:6, s. 2381-2390
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Vascular endothelial growth factor (VEGF) signaling is frequently altered in invasive tumor cells and is associated with patient outcome. In the present study, we examined VEGF, VEGFR1, and VEGFR2 expression in non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), and evaluated the association between VEGF and its receptors with disease characteristics and bladder cancer recurrence.MATERIALS AND METHODS: Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder mucosa (n=131) were immunostained using antibodies against VEGF, VEGFR1, and VEGFR2. The association between the expression of these proteins and clinical parameters including stage, lymph node metastasis, and recurrence-free survival were statistically evaluated. VEGF mRNA expression data were extracted from the public Oncomine database.RESULTS: VEGF and VEGFR1 mRNA levels were significantly higher in bladder cancer specimens than that of normal mucosa (for VEGF, p<0.001; for VEGFR1, p=0.02). Analysis of their expression at protein levels showed that levels of VEGF and VEGFR1 were significantly higher in NMIBC than in MIBC (p<0.001), while that of VEGFR2 was significantly higher in all cancer specimens compared to benign urothelial mucosa (p=0.001). Further-more, the expression of VEGFR2 was significantly higher in MIBC, as compared to NMIBC (p<0.001). Patients with higher levels of VEGF, VEGFR1, and VEGFR2 tended to have poorer recurrence-free survival than those with lower levels, but this was not statistically significant.CONCLUSION: Our results suggest that alterations in the expression of VEGF and VEGF receptors are associated with disease stage and recurrence.
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| 41987. |
- Kopps, Anna M., et al.
(författare)
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How Well Do Molecular and Pedigree Relatedness Correspond, in Populations with Diverse Mating Systems, and Various Types and Quantities of Molecular and Demographic Data?
- 2015
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Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 5:9, s. 1815-1826
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Tidskriftsartikel (refereegranskat)abstract
- Kinship analyses are important pillars of ecological and conservation genetic studies with potentially far-reaching implications. There is a need for power analyses that address a range of possible relationships. Nevertheless, such analyses are rarely applied, and studies that use genetic-data-based-kinship inference often ignore the influence of intrinsic population characteristics. We investigated 11 questions regarding the correct classification rate of dyads to relatedness categories (relatedness category assignments; RCA) using an individual-based model with realistic life history parameters. We investigated the effects of the number of genetic markers; marker type (microsatellite, single nucleotide polymorphism SNP, or both); minor allele frequency; typing error; mating system; and the number of overlapping generations under different demographic conditions. We found that (i) an increasing number of genetic markers increased the correct classification rate of the RCA so that up to >80% first cousins can be correctly assigned; (ii) the minimum number of genetic markers required for assignments with 80 and 95% correct classifications differed between relatedness categories, mating systems, and the number of overlapping generations; (iii) the correct classification rate was improved by adding additional relatedness categories and age and mitochondrial DNA data; and (iv) a combination of microsatellite and single-nucleotide polymorphism data increased the correct classification rate if <800 SNP loci were available. This study shows how intrinsic population characteristics, such as mating system and the number of overlapping generations, life history traits, and genetic marker characteristics, can influence the correct classification rate of an RCA study. Therefore, species-specific power analyses are essential for empirical studies.
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| 41988. |
- Kopra, Jaakko J., et al.
(författare)
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Dampened Amphetamine-Stimulated Behavior and Altered Dopamine Transporter Function in the Absence of Brain GDNF
- 2017
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 37:6, s. 1581-1590
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Tidskriftsartikel (refereegranskat)abstract
- Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction and Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in various disorders with disturbed dopamine homeostasis. However, the outcomes from preclinical and clinical studies vary, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function. Nevertheless, the current lack of appropriate animal models has limited this understanding. Therefore, we have generated novel mouse models to study conditional Gdnf deletion in the CNS during embryonic development and reduction of striatal GDNF levels in adult mice via AAV-Cre delivery. We found that both of these mice have reduced amphetamine-induced locomotor response and striatal dopamine efflux. Embryonic GDNF deletion in the CNS did not affect striatal dopamine levels or dopamine release, but dopamine reuptake was increased due to increased levels of both total and synaptic membrane-associated dopamine transporters. Collectively, these results suggest that endogenous GDNF plays an important role in regulating the function of dopamine transporters in the striatum.
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| 41989. |
- Korang Adjei, Evans, et al.
(författare)
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Kompetensförsörjning i Skellefteå : Studie av yrkesstruktur och flyttmönster
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten syftar till att analysera Skellefteå kommuns kompetensstruktur under perioden 2002-2013 samt de övergripande strukturerna i flyttmönster till och från Skellefteå.När det gäller den befintliga kompetensstrukturen, definierat som de yrken som finns i regionen idag, återfinns de tydligaste yrkesspecialiseringarna inom de huvudsakliga kategorierna anläggning och maskinoperatör (8) samt bygg och konstruktion (7). Jämfört med övriga regioner i Sverige är det alltså inom ett relativt tydligt industriellt kompetensområde som Skellefteå har en hög specialisering. Storleksmässigt (utan hänsyn till sammansättningen i övriga regioner) är det dock inom restaurang och handel som både många arbetar samt där många inflyttare har sina kompetenser. Dock är det tydligt att en relativt hög andel av inflyttarna till Skellefteå sedan 2002 jämfört med den befintliga arbetskraften antingen har yrken som inte kräver någon specialistkompetens, eller består av tjänstemän och personaladministration. De yrken regionen i huvudsak är specialiserad inom verkar inte utgöra ett typiskt yrke bland inflyttare. Med andra ord har den kompetensförsörjningen en tydligt lokal dimension.Vad gäller inflyttare kommer en klar majoritet från övriga norra Sverige, framförallt från övriga Västerbotten. Utöver detta skiljer sig också inflyttarna utifrån vilka yrkesgrupper som kommer från olika regioner. Personer med yrken som kräver universitetsexamen (inklusive chefer) kommer framförallt från Stockholmsregionen. Detta är särskilt tydligt vad gäller tjänstemän och olika former av administratörer. Mer industriellt kopplade yrken (tex anläggning-, process- och maskinoperatörer) kommer i högre utsträckning från norra Sverige. Detta är särskilt tydligt bland hemvändare som i högre utsträckning har mer industriellt kopplade yrken, särskilt om de kommer från norra Sverige. Från södra Sverige (framförallt Stockholm och Västsverige) dominerar hemvändare som jobbat inom service och handel. Beroende på vilka kompetenser som eftersöks kan därmed olika områden vara lämpliga källor för ny kompetens och det är en viss variation mellan inflyttare generellt och hemvändare.När vi slutligen följt utflyttare från Skellefteå sedan början av 1990-talet finner vi att ungefär en fjärdedel flyttar ut från Skellefteå och sedan blir kvar i den regionen de flyttat till under kommande 10 år. Det gäller framförallt personer som flyttat till övriga Västerbotten, men också Stockholm, övriga övre Norrland samt Västsverige och östra Mellansverige. Det går inte att se några tydliga skillnader mellan mäns och kvinnors fortsatta flyttmönster. Däremot är det tydligt att högutbildade och utlandsfödda i mindre utsträckning återvänder till Skellefteå när de väl flyttat. Drygt en tredjedel av de som flyttat från Skellefteå återvänder någon gång under kommande tioårsperiod. Det gäller främst personer som flyttat till övriga Västerbotten eller till Västsverige. Dock är graden av återkommande flytt bland dessa personer relativt hög (ungefär en tredjedel) och av de som stannar kvar i Skellefteå efter att ha flyttat tillbaka är det framförallt personer som bott i övriga Västerbotten men också i övriga övre Norrland eller Stockholm (totalt 69% av alla återvändande stannare). Det är en marginell överrepresentation av kvinnor, svenskfödda och personer under 35 år bland de återvändande stannarna även om andelen män ökar kraftigt under de senaste åren. Bland återvändarna som igen lämnar för en annan region, sjunker andelen migranter till övriga Västerbotten och det är framförallt storstadsregionerna (främst Stockholm) som ökar sin mottagarandel.
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| 41990. |
- Korch, C, et al.
(författare)
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Cloning, nucleotide sequence, and regulation of MET14, the gene encoding the APS kinase of Saccharomyces cerevisiae
- 1991
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Ingår i: Molecular General Genetics. - : Springer. - 0026-8925 .- 1432-1874. ; 229:1, s. 96-108
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Tidskriftsartikel (refereegranskat)abstract
- The MET14 gene of Saccharomyces cerevisiae, encoding APS kinase (ATP:adenylylsulfate-3'-phosphotransferase, EC 2.7.1.25), has been cloned. The nucleotide sequence predicts a protein of 202 amino acids with a molecular mass of 23,060 dalton. Translational fusions of MET14 with the beta-galactosidase gene (lacZ) of Escherichia coli confirmed the results of primer extension and Northern blot analyses indicating that the ca. 0.7 kb mRNA is transcriptionally repressed by the presence of methionine in the growth medium. By primer extension the MET14 transcripts were found to start between positions -25 and -45 upstream of the initiator codon. Located upstream of the MET14 gene is a perfect match (positions -222 to -229) with the previously proposed methionine-specific upstream activating sequence (UASMet). This is the same as the consensus sequence of the Centromere DNA Element I (CDEI) that binds the Centromere Promoter Factor I (CPFI) and of two regulatory elements of the PHO5 gene to which the yeast protein PHO4 binds. The human oncogenic protein c-Myc also has the same recognition sequence. Furthermore, in the 270 bp upstream of the MET14 coding region there are several matches with a methionine-specific upstream negative (URSMet) control element. The significance of these sequences was investigated using different upstream deletion mutations of the MET14 gene which were fused to the lacZ gene of E. coli and chromosomally integrated. We find that the methionine-specific UASMet and one of the URSMet lie in regions necessary for strong activation and weak repression of MET14 transcription, respectively. We propose that both types of control are exerted on MET14.
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