101 research outputs found

    GnRHR signaling in neuronal cells: in vitro and in vivo data

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    Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary gonadotrope cells. While GnRHR signaling in gonadotropes is well described, knowledge of GnRHR activation-related events at extrapituitary sites including neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct changes in hippocampal gene expression, emotional processes, and cognitive functions. To explore neuronal GnRHR signaling we used the human neuroblastoma cell line SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and investigated the expression of several relevant genes in the hippocampus and preoptic area of peripubertal male rats treated with GnRHa. GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after adding GnRHa in the incubation media. Electrophysiological recordings confirmed that GnRHa induced membrane depolarization but could not evoke action potentials. In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala, and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal rats with GnRHa had no effect on the expression of genes in the hippocampus previously shown to be affected in the sheep model of delayed puberty. These results imply that neuronal GnRHR is either differently coupled (not coupled with Gq/11 protein), or that its membrane density is too low to induce transcriptional events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR signaling in the brain.kategorija M6

    Silicon Differently Affects Apoplastic Binding of Excess Boron in Wheat and Sunflower Leaves

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    Monocots and dicots differ in their boron (B) requirement, but also in their capacity to accumulate silicon (Si). Although an ameliorative effect of Si on B toxicity has been reported in various crops, differences among monocots and dicots are not clear, in particular in light of their ability to retain B in the leaf apoplast. In hydroponic experiments under controlled conditions, we studied the role of Si in the compartmentation of B within the leaves of wheat (Triticum vulgare L.) as a model of a high-Si monocot and sunflower (Helianthus annuus L.) as a model of a low-Si dicot, with the focus on the leaf apoplast. The stable isotopes 10B and 11B were used to investigate the dynamics of cell wall B binding capacity. In both crops, the application of Si did not affect B concentration in the root, but significantly decreased the B concentration in the leaves. However, the application of Si differently influenced the binding capacity of the leaf apoplast for excess B in wheat and sunflower. In wheat, whose capacity to retain B in the leaf cell walls is lower than in sunflower, the continuous supply of Si is crucial for an enhancement of high B tolerance in the shoot. On the other hand, the supply of Si did not contribute significantly in the extension of the B binding sites in sunflower leaves. © 2023 by the authors

    The Importance of Artificial Intelligence in Upper Gastrointestinal Endoscopy

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    Recently, there has been a growing interest in the application of artificial intelligence (AI) in medicine, especially in specialties where visualization methods are applied. AI is defined as a computer’s ability to achieve human cognitive performance, which is accomplished through enabling computer “learning”. This can be conducted in two ways, as machine learning and deep learning. Deep learning is a complex learning system involving the application of artificial neural networks, whose algorithms imitate the human form of learning. Upper gastrointestinal endoscopy allows examination of the esophagus, stomach and duodenum. In addition to the quality of endoscopic equipment and patient preparation, the performance of upper endoscopy depends on the experience and knowledge of the endoscopist. The application of artificial intelligence in endoscopy refers to computer-aided detection and the more complex computer-aided diagnosis. The application of AI in upper endoscopy is aimed at improving the detection of premalignant and malignant lesions, with special attention on the early detection of dysplasia in Barrett’s esophagus, the early detection of esophageal and stomach cancer and the detection of H. pylori infection. Artificial intelligence reduces the workload of endoscopists, is not influenced by human factors and increases the diagnostic accuracy and quality of endoscopic methods

    Silicon Differently Affects Apoplastic Binding of Excess Boron in Wheat and Sunflower Leaves

    Get PDF
    Monocots and dicots differ in their boron (B) requirement, but also in their capacity to accumulate silicon (Si). Although an ameliorative effect of Si on B toxicity has been reported in various crops, differences among monocots and dicots are not clear, in particular in light of their ability to retain B in the leaf apoplast. In hydroponic experiments under controlled conditions, we studied the role of Si in the compartmentation of B within the leaves of wheat (Triticum vulgare L.) as a model of a high-Si monocot and sunflower (Helianthus annuus L.) as a model of a low-Si dicot, with the focus on the leaf apoplast. The stable isotopes 10B and 11B were used to investigate the dynamics of cell wall B binding capacity. In both crops, the application of Si did not affect B concentration in the root, but significantly decreased the B concentration in the leaves. However, the application of Si differently influenced the binding capacity of the leaf apoplast for excess B in wheat and sunflower. In wheat, whose capacity to retain B in the leaf cell walls is lower than in sunflower, the continuous supply of Si is crucial for an enhancement of high B tolerance in the shoot. On the other hand, the supply of Si did not contribute significantly in the extension of the B binding sites in sunflower leaves

    Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis

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    Multiple sclerosis (MS) is an autoimmune disease affecting the CNS and occurring far more prevalently in women than in men. In both MS and its animal models, sex hormones play important immunomodulatory roles. We have previously shown that experimental autoimmune encephalomyelitis (EAE) affects the hypothalamic–pituitary–gonadal axis in rats of both sexes and induces an arrest in the estrous cycle in females. To investigate the gonadal status in female rats with EAE, we explored ovarian morphometric parameters, circulating and intraovarian sex steroid levels, and the expression of steroidogenic machinery components in the ovarian tissue. A prolonged state of diestrus was recorded during the peak of EAE, with maintenance of the corpora lutea, elevated intraovarian progesterone levels, and increased gene and protein expression of StAR, similar to the state of pseudopregnancy. The decrease in CYP17A1 protein expression was followed by a decrease in ovarian testosterone and estradiol levels. On the contrary, serum testosterone levels were slightly increased. With unchanged serum estradiol levels, these results point at extra-gonadal sites of sex steroid biosynthesis and catabolism as important regulators of their circulating levels. Our study suggests alterations in the function of the female reproductive system during central autoimmunity and highlights the bidirectional relationships between hormonal status and EAE

    <i>GPX3</i> rs8177412 Polymorphism Modifies Risk of Upper Urothelial Tumors in Patients with Balkan Endemic Nephropathy

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    Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16–9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27–11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75–3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development

    Nitrogen and Phosphorus Concentrations and Their Ratios as Indicators of Water Quality and Eutrophication of the Hydro-System Danube–Tisza–Danube

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    Conserving clean and safe freshwater is a global challenge, with nitrogen (N) and phosphorus (P) as frequent limiting factors affecting water quality due to eutrophication. This paper provides a critical overview of the spatiotemporal variability in both nutrient concentrations and their total mass ratio (TN:TP) in the canal network of the Hydro system Danube–Tisza–Danube at 21 measuring locations monitored by the Environmental Protection Agency of the Republic of Serbia over a length of almost 1000 km, collected once a month during the last decade. A spatiotemporal variation in nutrient concentrations in the tested surface water samples was confirmed by correlations and cluster analyses. The highest TN concentrations were found in winter and early spring (non-vegetation season), and the highest TP concentrations in the middle of the year (vegetation season). The TN:TP mass ratio as an indicator of the eutrophication pointed out N and P co-limitation (TN:TP 8–24) in 64% of samples, N limitation (TN:TP 24) in the remaining 9% of water samples. Such observations indicate slow-flowing, lowland water courses exposed to the effects of non-point and point contamination sources as nutrient runoff from the surrounding farmlands and/or urban and industrial zones, but further investigation is needed for clarification. These results are an important starting point for reducing N and P runoff loads and controlling source pollution to improve water quality and underpin recovery from eutrophication in the studied watershed

    Phenotypic and genetic heterogeneity of adult patients with hereditary spastic paraplegia from Serbia

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    Hereditary spastic paraplegia (HSP) is among the most genetically diverse of all monogenic diseases. The aim was to analyze the genetic causes of HSP among adult Serbian patients. The study comprised 74 patients from 65 families clinically diagnosed with HSP during a nine-year prospective period. A panel of thirteen genes was analyzed: L1CAM (SPG1), PLP1 (SPG2), ATL1 (SPG3A), SPAST (SPG4), CYP7B1 (SPG5A), SPG7 (SPG7), KIF5A (SPG10), SPG11 (SPG11), ZYFVE26 (SPG15), REEP1 (SPG31), ATP13A2 (SPG78), DYNC1H1, and BICD2 using a next generation sequencing-based technique. A copy number variation (CNV) test for SPAST, SPG7, and SPG11 was also performed. Twenty-three patients from 19 families (29.2%) had conclusive genetic findings, including 75.0% of families with autosomal dominant and 25.0% with autosomal recessive inheritance, and 15.7% of sporadic cases. Twelve families had mutations in the SPAST gene, usually with a pure HSP phenotype. Three sporadic patients had conclusive findings in the SPG11 gene. Two unrelated patients carried a homozygous pathogenic mutation c.233T>A (p.L78*) in SPG7 that is a founder Roma mutation. One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. The combined genetic yield of our gene panel and CNV analysis for HSP was around 30%. Our findings broaden the knowledge on the genetic epidemiology of HSP, with implications for molecular diagnostics in this region

    Framtagning av testmetod för utvärdering av sorptionslänsor

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    En vanlig metod vid sanering av olja är olika typer av länsor för avgränsning och upptagning av miljöfarliga ämnen. I detta projekt fokuserar vi på sorptionslänsor som suger upp farliga ämnen med hjälp av sorberande material. Tekniken används av merparten av de organisationer som jobbar med oljebekämpning.Det finns många typer av sorptionsmaterial med olika egenskaper vad avser sorberingsförmåga, vikt, volym, miljöpåverkan mm. Konstruktionen av en sorptionslänsa påverkar hur slittålig den är, hur den kan skarvas, delbarhet mm. Hur bra länsor sorberar ämnen beskrivs ofta av tillverkaren men då uppgifterna inte är verifierade för verklig förmåga vid skarp användning blir det ofta missvisande värden. Rapporten beskriver framtagandet av en testmetod i syfte att skapa erfarenheter kring olika länsors egenskaper, effektivitet och miljöpåverkan inför nyanskaffningar.
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