distributed sensing
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BACKGROUND/AIMS: Calcium-Sensing Receptor (CaSR) significantly affects calcium-phosphate metabolism in kidneys, and it is implicated in the pathogenesis of diabetes mellitus (DM) due to its expression in pancreatic β-cells. The role of CaSR as one of the players in pathogenesis of chronic kidney disease (CKD) has been speculated. METHODS: 158 Type 2 diabetic patients divided into three groups according to occurrence and type of kidney complications, 66 nondiabetic patients CKD, and 93 healthy subjects were enrolled into the study to analyze the role of two CaSR polymorphisms (in the codon 990 and in the intron 4) in ethiopathogenesis of DM and CKD. The Type 2 diabetic groups consisted of 48 patients without any kidney abnormalities, 58 patients with diabetic nephropathy (DN), and 52 patients with nondiabetic renal disease (NDRD). The distribution of genotype and allele frequencies was studied using PCR with the TaqMan Discrimination Assay or followed by the Restriction Fragment Length Polymorphism method, respectively. RESULTS: We have found that the intron 4 polymorphism is a risk factor for the development of DM and CKD, except DN, while the codon 990 does not show any disease association. CONCLUSION: We conclude that CaSR is a general factor in pancreas and kidney pathologies.
- MeSH
- chronická nemoc MeSH
- diabetes mellitus 2. typu diagnóza genetika MeSH
- diabetické nefropatie diagnóza genetika MeSH
- dospělí MeSH
- introny genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- komplikace diabetu diagnóza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci ledvin diagnóza genetika MeSH
- receptory "calcium-sensing" genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: High extracellular calcium concentration (Cao(2+)) acts to inhibit calcium sensing receptor (CaR) signalling on cellular surfaces in parathyroid glands. This receptor is, however, also expressed on the membranes of some non-calciotropic endocrine cells, including pituitary-derived cells. The aim of our study was to analyse relationships between the CaR gene and the circulating FSH and LH in normal post-menopausal women. METHODS: A total of 95 untreated euparathyroid post-menopausal women were investigated in the study. The serum FSH and LH levels were evaluated in relationship to allele combinations of the CaR gene (C/T polymorphism in the intron 5 and A986S polymorphism in exon 7), using an analysis of co-variance (ANCOVA) model. RESULTS: Distribution of TT, TC and CC allele combinations (intron 5 C/T polymorphism) was 51, 43 and 6 %, respectively. Higher serum FSH and LH levels were found in carriers of C allele than in women without this allele (p < 0.002 and p < 0.03, respectively). No correlations were found between A986S polymorphism and serum FSH and LH levels. CONCLUSIONS: Serum FSH and LH levels are associated with intron 5 C/T (but not A986S) polymorphism of the CaR gene in untreated post-menopausal women. The physiological role of the CaR gene in the regulation of the gonadotropic function needs to be further investigated.
- MeSH
- alely MeSH
- dospělí MeSH
- financování organizované MeSH
- folikuly stimulující hormon krev MeSH
- genotyp MeSH
- introny MeSH
- lidé MeSH
- luteinizační hormon krev MeSH
- polymorfismus genetický MeSH
- postmenopauza MeSH
- průřezové studie MeSH
- receptory "calcium-sensing" genetika metabolismus MeSH
- statistika jako téma MeSH
- vápník metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
Ultraviolet-B (UV-B) radiation is a key but under-researched environmental factor that initiates diverse responses in plants, potentially affecting their distribution. To date, only a few macroecological studies have examined adaptations of plant species to different levels of UV-B. Here, we combined herbarium specimens of Hieracium pilosella L. and Echium vulgare L. with a novel UV-B dataset to examine differences in leaf hair traits between the plants' native and alien ranges. We analysed scans of 336 herbarium specimens using standardized measurements of leaf area, hair density (both species) and hair length (H. pilosella only). While accounting for other bioclimatic variables (i.e. temperature, precipitation) and effects of herbivory, we examined whether UV-B exposure explains the variability and geographical distribution of these traits in the native (Northern Hemisphere) vs. the alien (Southern Hemisphere) range. UV-B explained the largest proportion of the variability and geographical distribution of hair length in H. pilosella (relative influence 67.1%), and hair density in E. vulgare (66.2%). Corresponding with higher UV-B, foliar hairs were 25% longer for H. pilosella and 25% denser for E. vulgare in records from the Southern as compared to those from the Northern Hemisphere. However, focusing on each hemisphere separately or controlling for its effect in a regression analysis, we found no apparent influence of UV-B radiation on hair traits. Thus, our findings did not confirm previous experimental studies which suggested that foliar hairs may respond to higher UV-B intensities, presumably offering protection against detrimental levels of radiation. We cannot rule out UV-B radiation as a possible driver because UV-B radiation was the only considered variable that differed substantially between the hemispheres, while bioclimatic conditions (e.g. temperature, precipitation) and other considered variables (herbivory damage, collection date) were at similar levels. However, given that either non-significant or inconclusive relationships were detected within hemispheres, alternative explanations of the differences in foliar hairs are more likely, including the effects of environment, genotypes or herbivory.
- MeSH
- Asteraceae anatomie a histologie účinky záření MeSH
- Echium anatomie a histologie účinky záření MeSH
- ekosystém MeSH
- listy rostlin anatomie a histologie účinky záření MeSH
- podnebí MeSH
- technologie dálkového snímání MeSH
- ultrafialové záření MeSH
- zavlečené druhy MeSH
- Publikační typ
- časopisecké články MeSH
In the body, the brain is the most cholesterol-rich organ. Despite this, remarkably little is known about the mechanisms in the brain that regulate cholesterol homeostasis. Due to the blood-brain barrier, plasma lipoproteins are unable to traverse, and instead cholesterol must be synthesized de novo from within the central nervous system. Thyroid hormone receptors, activated in response to thyroid hormone (T(3)), are known to modulate the level of serum cholesterol via complex regulatory pathways. By screening for T(3)-regulated genes we have identified Disp3, a sterol-sensing domain-containing protein that is related to the Dispatched family of proteins. Analysis by RT-PCR and immunohistochemistry demonstrated that DISP3 is predominately expressed in specific cell types of the brain, retina, and testis. Using the model of hyperthyroidism in vivo, we observed the modulation of Disp3 expression in the retina. Furthermore, in vitro analysis of Disp3 expression in cells treated with T(3) revealed both positive and negative regulation. DISP3 localizes within the endoplasmic reticulum and was further found to colocalize with cholesterol. Ectopic expression of DISP3 in fibroblasts resulted in elevated cholesterol levels combined with an altered cholesterol distribution. Given that DISP3 is highly expressed in Purkinje cells, hippocampal neurons, and retinal ganglion cells and that its overexpression results in increased cholesterol levels, it is tempting to postulate that DISP3 may contribute to cholesterol homeostasis in neural cell types. Taken together, we propose that DISP3 represents a new molecular link between thyroid hormone and cholesterol metabolism.
- MeSH
- buněčné linie MeSH
- cholesterol metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- financování organizované MeSH
- fylogeneze MeSH
- hormony štítné žlázy metabolismus MeSH
- kuřecí embryo MeSH
- lidé MeSH
- membránové proteiny genetika klasifikace metabolismus MeSH
- molekulární sekvence - údaje MeSH
- receptory thyreoidních hormonů genetika metabolismus MeSH
- regulace genové exprese MeSH
- rekombinantní fúzní proteiny genetika metabolismus MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- lidé MeSH
- zvířata MeSH
Termites are among the few animals that themselves can digest the most abundant organic polymer, cellulose, into glucose. In mice and Drosophila, glucose can activate genes via the transcription factor carbohydrate-responsive element-binding protein (ChREBP) to induce glucose utilization and de novo lipogenesis. Here, we identify a termite orthologue of ChREBP and its downstream lipogenic targets, including acetyl-CoA carboxylase and fatty acid synthase. We show that all of these genes, including ChREBP, are upregulated in mature queens compared with kings, sterile workers and soldiers in eight different termite species. ChREBP is expressed in several tissues, including ovaries and fat bodies, and increases in expression in totipotent workers during their differentiation into neotenic mature queens. We further show that ChREBP is regulated by a carbohydrate diet in termite queens. Suppression of the lipogenic pathway by a pharmacological agent in queens elicits the same behavioural alterations in sterile workers as observed in queenless colonies, supporting that the ChREBP pathway partakes in the biosynthesis of semiochemicals that convey the signal of the presence of a fertile queen. Our results highlight ChREBP as a likely key factor for the regulation and signalling of queen fertility.
- MeSH
- fertilita MeSH
- fylogeneze MeSH
- glukosa metabolismus MeSH
- hmyzí proteiny metabolismus MeSH
- Isoptera klasifikace fyziologie MeSH
- lipogeneze MeSH
- mapy interakcí proteinů MeSH
- signální transdukce MeSH
- tkáňová distribuce MeSH
- transkripční faktory metabolismus MeSH
- upregulace * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Resistance development and exhaustion of the arsenal of existing antibacterial agents urgently require an alternative approach toward drug discovery. Herein, we report the screening of Medicines for Malaria Venture (MMV) Pandemic Response Box (PRB) through a cascade developed to streamline the potential compounds with antivirulent properties to combat an opportunistic pathogen, Pseudomonas aeruginosa. To find an agent suppressing the production of P. aeruginosa virulence factors, we assessed the potential of the compounds in PRB with quorum sensing inhibitory activity. Our approach led us to identify four compounds with significant inhibition of extracellular virulence factor production and biofilm formation. This provides an opportunity to expand and redirect the application of these data sets toward the development of a drug with unexplored target-based activity. IMPORTANCE The rise of drug-resistant pathogens as well as overuse and misuse of antibiotics threatens modern medicine as the number of effective antimicrobial drugs steadily decreases. Given the nature of antimicrobial resistance development under intense selective pressure such as the one posed by pathogen-eliminating antibiotics, new treatment options which could slow down the emergence of resistance are urgently needed. Antivirulence therapy aims at suppressing a pathogen's ability to cause disease rather than eliminating it, generating significantly lower selective pressure. Quorum sensing inhibitors are thought to be able to downregulate the production of virulence factors, allowing for smaller amounts of antimicrobials to be used and thus preventing the emergence of resistance. The PRB constitutes an unprecedented opportunity to repurpose new as well as known compounds with cytotoxicity and in vitro absorption, distribution, metabolism and excretion (ADME) profile available, thus shortening the time between compound discovery and medicinal use.
Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.
- Publikační typ
- časopisecké články MeSH
Stripping voltammetric determination of purine bases in the presence of copper ions at mercury, amalgam, or carbon-based electrodes has recently been utilized in analysis of DNA or synthetic oligodeoxynucleotides (ODNs). Here we report on copper-enhanced label-free anodic stripping detection of guanine and adenine bases in acid-hydrolyzed DNA at anodically oxidized boron-doped diamond electrode (AO-BDDE). The AO-BDDE was successfully applied in a three-electrode microcell in which an approximately 50 microL drop of the analyte solution can be efficiently stirred during the accumulation step by streaming of an inert gas. Accelerated mass transport due to the solution motion in the presence of copper resulted in enhancement of the guanine oxidation signal by about 2 orders of magnitude (compared to accumulation of the analyte from still solution not containing copper), allowing an easy detection of approximately 25 fmol of the ODNs. The proposed technique is shown to be suitable for a determination of purine (particularly guanine) content in DNA samples. Applications of the technique in magnetic bead-based DNA assays (such as hybridization with DNA sequences exhibiting asymmetrical distribution of purine/pyrimidine nucleotides between the complementary strands or monitoring of amplification of specific DNA fragments in a duplex polymerase chain reaction) are demonstrated.
- MeSH
- bor chemie MeSH
- diamant chemie MeSH
- DNA-dependentní DNA-polymerasy metabolismus MeSH
- DNA MeSH
- elektrochemie MeSH
- elektrody MeSH
- financování organizované MeSH
- hydrolýza MeSH
- kationty chemie MeSH
- kyseliny chemie MeSH
- měď chemie MeSH
- oligonukleotidy chemie MeSH
- oxidace-redukce MeSH
- puriny chemie MeSH
- sekvence nukleotidů MeSH
BACKGROUND: Survival reflects the accumulation of multiple influences experienced over the life course. Given the amount of time usually spent at work, the influence of work may be particularly important. We examined the association between work-related stress in midlife and subsequent mortality, investigating whether sense of coherence modified the association. METHODS: Self-reported work-related stress was assessed in 1393 Swedish workers aged 42-65 who participated in the nationally representative Level of Living Survey in 1991. An established psychosocial job exposure matrix was applied to measure occupation-based stress. Sense of coherence was measured as meaningfulness, manageability and comprehensibility. Mortality data were collected from the Swedish National Cause of Death Register. Data were analyzed with hazard regression with Gompertz distributed baseline intensity. RESULTS: After adjustment for socioeconomic position, occupation-based high job strain was associated with higher mortality in the presence of a weak sense of coherence (HR, 3.15; 1.62-6.13), a result that was stronger in women (HR, 4.48; 1.64-12.26) than in men (HR, 2.90; 1.12-7.49). Self-reported passive jobs were associated with higher mortality in the presence of a weak sense of coherence in men (HR, 2.76; 1.16-6.59). The link between work stress and mortality was not significant in the presence of a strong sense of coherence, indicating that a strong sense of coherence buffered the negative effects of work-related stress on mortality. CONCLUSIONS: Modifications to work environments that reduce work-related stress may contribute to better health and longer lives, especially in combination with promoting a sense of coherence among workers.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mortalita * MeSH
- pracovní stres epidemiologie psychologie MeSH
- rizikové faktory MeSH
- senioři MeSH
- sexuální faktory MeSH
- socioekonomické faktory MeSH
- věkové faktory MeSH
- životní smysluplnost * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Švédsko epidemiologie MeSH
