Cholecystokinin (CCK) - induced anxiety in rats: influence of environmental stimuli and involvement of endopioid mechanisms and serotonin

http://www.ester.ee/record=b1183069~S1*es

Algamas on uuring „Epidemioloogiline ja geneetiline tõendus tervishoiutöötajate suitsetamiskäitumise ja nikotiinisõltuvuse kohta”

Eesti Arst 2014; 93(7):42

RNA-sequencing of WFS1-deficient pancreatic islets.

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in theWFS1gene.WFS1encodes an endoplasmic reticulum resident transmembrane protein. TheWfs1-null mice exhibit progressive insulin deficiency and diabetes. The aim of this study was to describe the insulin secretion and transcriptome of pancreatic islets inWFS1-deficient mice.WFS1-deficient (Wfs1KO) mice had considerably less pancreatic islets than heterozygous (Wfs1HZ) or wild-type (WT) mice. Wfs1KOpancreatic islets secreted less insulin after incubation in 2 and 10 mmol/L glucose and with tolbutamide solution compared toWTand Wfs1HZislets, but not after stimulation with 20 mmol/L glucose. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KOhad an increased level of proinsulin. After incubation in 2 mmol/L glucose solution the proinsulin/insulin ratio in Wfs1KOwas significantly higher than that ofWTand Wfs1HZRNA-seq from pancreatic islets found melastatin-related transient receptor potential subfamily member 5 protein gene (Trpm5) to be downregulated inWFS1-deficient mice. Functional annotation ofRNAsequencing results showed thatWFS1 deficiency influenced significantly the pathways related to tissue morphology, endocrine system development and function, molecular transport network

Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease

Unfolded stress response (UPR) is a conserved cellular pathway involved in protein quality control to maintain homeostasis under different conditions and disease states characterized by cell stress. Although three general schemes of and genes induced by UPR are rather well-established, open questions remain including the precise role of UPR in human diseases and the interactions between different sensor systems during cell stress signaling. Particularly, the issue how the normally adaptive and pro-survival UPR pathway turns into a deleterious process causing sustained endoplasmic reticulum (ER) stress and cell death requires more studies. UPR is also named a friend with multiple personalities that we need to understand better to fully recognize its role in normal physiology and in disease pathology. UPR interacts with other organelles including mitochondria, and with cell stress signals and degradation pathways such as autophagy and the ubiquitin proteasome system. Here we review current concepts and mechanisms of UPR as studied in different cells and model systems and highlight the relevance of UPR and related stress signals in various human diseases

Peripheral Blood RNA Expression Profiling in Illicit Methcathinone Users Reveals Effect on Immune System

Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modeling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative real-time PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement, and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of subjects. A similar functional activation of the “immunological disease” category was evident when we compared subjects according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the subjects. Mn–methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections

Humaniin – väike peptiid, suured ülesanded? Ülevaateartikkel humaniini-nimelisest peptiidist

Aastal 2001 kirjeldati esimest korda humaniini-nimelist peptiidi, mis võib olla esimene nn mitokondriaalne signaalmolekul. Praeguseks on kõnealusel peptiidil kirjeldatud mitmeid positiivseid omadusi: antiapoptootiline toime, tsütoprotektsioon mitmete mehhanismide kaudu. Peptiidi seostatakse vanusega seotud haigustega, näiteks diabeedi ja ateroskleroosiga. Artiklis on tutvustatud humaniini kui peptiidi, millest loodetakse potentsiaalset siirdemeditsiinilist läbimurret.Eesti Arst 2017; 96(6):328–33

Longitudinal intronic RNA-Seq analysis of Parkinson’s Disease patients reveals disease-specific nascent transcription

AbstractTranscriptomic studies usually focus on either gene or exon-based annotations, and only limited experiments have reported changes in reads mapping to introns. The analysis of intronic reads allows the detection of nascent transcription that is not influenced by steady - state RNA levels and provides information on actively transcribed genes. Here we describe substantial intronic transcriptional changes in Parkinson’s Disease (PD) patients compared to healthy controls (CO) at two different timepoints; at the time of diagnosis (BL) and three years later (V08). We used blood RNA-Seq data from the Parkinson’s Progression Markers Initiative (PPMI) cohort and identified significantly changed transcription of intronic reads only in PD patients during this follow up period. In CO subjects, only nine transcripts demonstrated differentially expressed introns between visits. However, in PD patients 4,873 transcripts had differentially expressed introns at visit V08 compared to BL, many of them in genes previously associated with neurodegenerative diseases, such as LRRK2, C9orf72, LGALS3, KANSL1AS1 and ALS2. In addition, at the time of diagnosis (BL visit) we identified 836 transcripts (e.g. SNCA, DNAJC19, PRRG4) and at visit V08 2,184 transcripts (e.g. PINK1, GBA, ALS2, PLEKHM1) with differential intronic expression specific to PD patients. In contrast, reads mapping to exonic regions demonstrated little variation indicating highly specific changes only in intronic transcription. Our study demonstrated that Parkinson’s disease is characterized by substantial changes in the nascent transcription and description of these changes could help to understand the molecular pathology underpinning this disease.Impact statementTranscriptomic studies in most cases describe the steady state changes of the cellular RNA combined with signals from newly synthesised RNA or nascent RNA. Nascent RNA reflects dynamic alterations in the cellular transcriptome and improves the resolution of RNA-Seq analysis. In the present study, we describe the changes in nascent RNA transcription in Parkinson’s disease by using intronic RNA-Seq analysis. We compared transcriptome changes at the time of diagnosis and 3 years after the initial diagnosis. As a result, we were able to describe disease-specific time-dependent alterations in the nascent transcription in the blood of Parkinson’s patients illustrating another layer of the blood-based biomarkers that could be diagnostic of both risk and progression of Parkinson’s disease.</jats:sec

Genetic Interaction Between Two VNTRs in the SLC6A4 Gene Regulates Nicotine Dependence in Vietnamese Men

Nicotine dependence is an addiction to tobacco products and a global public health concern. Association between the SLC6A4 polymorphisms and nicotine dependence is controversial. Two variable number tandem repeat (VNTR) domains, termed HTTLPR and STin2, in the SLC6A4 gene are well characterized transcriptional regulatory elements. Their polymorphism in the copy number of the repeat correlates with the particular personality and psychiatric traits. We analyzed nicotine dependence in 1,804 participants from Central Vietnam. The Fagerström Test (FTND) was used to evaluate the nicotine dependence and PCR was used to determine the SLC6A4 HTTLPR and STin2 VNTRs. The HTTLPR VNTR was associated with difficulties to refrain from smoking in a prohibiting environment. The STIn2 10/10 genotype was associated with (1) years of smoking, (2) difficulties to quit the first cigarette, and (3) higher number of cigarettes smoked per day (CPD). Stratification analysis was used to find the genetic interaction between these two VNTRs in nicotine dependence as they may synergistically regulate the SLC6A4 expression. Smokers with the S/S HTTLPR genotypes showed a much stronger association between STin2 10/10 variant and CPD. This finding is consistent with the molecular evidence for the functional interaction between HTTLPR and STin2 in cell line models, where STin2 has described as a stronger expressional regulator. Similarly, we found that STin2 is a much stronger modifier of smoking with 10/10 genotype related to higher nicotine dependence. The present study supports genetic interaction between HTTLPR and STin2 VNTRs in the regulation of nicotine dependence with the dominance of the STin2 effects. This finding could be explained by their differential effect on the SLC6A4 expression

Veise sigimine: kõrgkooliõpik

Eestis on veisekasvatusest lugu peetud juba kiviajast peale. Meil on heade tõuomadustega ja suure toodanguga piimakari ja kiiresti kasvav lihakari ning me suudame toota kvaliteetset piima ja veiseliha nii kohalikele tarbijatele kui ka ekspordiks. Veiste sigimisprobleemid on oluliseks veisekasvatuse kasumlikkust mõjutavaks teguriks. Selleks, et sigimisprobleemide olemust mõista ja nende teket ennetada või neid ravida, on vajalikud põhjalikud teadmised veise sigimise erinevatest aspektidest. Seni puudub üks terviklik veise sigimise alast teavet koondav eestikeelne õppevahend. Käesoleva õpiku abil soovime seda lünka täita. Oleme õpikusse kokku kogunud teadmised suguorganite morfoloogiast ja füsioloogiast, tiinusest ja sünnitusest ning poegimisjärgsetest haigustest. Suguorganite anatoomiat käsitletakse õpikus mitte klassikalise, vaid funktsionaalse anatoomia seisukohast. Veise tiinuse ja sünnituse