Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is an evolutionarily conserved multi-protein complex, consisting of eight subunits termed CSN1-CSN8. The main biochemical function of the CSN is the control of protein degradation via the ubiquitin-proteasome-system through regulation of cullin-RING E3-ligase (CRL) activity by deNEDDylation of cullins, but the CSN also serves as a docking platform for signaling proteins. The catalytic deNEDDylase (isopeptidase) activity of the complex is executed by CSN5, but only efficiently occurs in the three-dimensional architectural context of the complex. Due to its positioning in a central cellular pathway connected to cell responses such as cell-cycle, proliferation, and signaling, the CSN has been implicated in several human diseases, with most evidence available for a role in cancer. However, emerging evidence also suggests that the CSN is involved in inflammation and cardiovascular diseases. This is both due to its role in controlling CRLs, regulating components of key inflammatory pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), and complex-independent interactions of subunits such as CSN5 with inflammatory proteins. In this case, we summarize and discuss studies suggesting that the CSN may have a key role in cardiovascular diseases such as atherosclerosis and heart failure. We discuss the implicated molecular mechanisms ranging from inflammatory NF-kappa B signaling to proteotoxicity and necrosis, covering disease-relevant cell types such as myeloid and endothelial cells or cardiomyocytes. While the CSN is considered to be disease-exacerbating in most cancer entities, the cardiovascular studies suggest potent protective activities in the vasculature and heart. The underlying mechanisms and potential therapeutic avenues will be critically discussed

Neuropsychiatric Aspects of Healthy Aging: an Epidemiological Approach

Ageing is becoming a significant global challenge which will require economic and social adjustments. Aging causes morphological changes in the brain associated with increased prevalence and incidence of neuropsychiatric diseases, mostly depression, Alzheimer’s Disease (AD) and Parkinson’s disease (PD). Neuropsychiatric diseases impair quality of life and pose a high economic burden to individuals and society. Thus, in order to better face these challenging diseases, it is of importance to understand factors that could contribute in their pathophysiology. It is now widely accepted that there is a strong genetic component in the development of neurodegenerative diseases, whereas emerging evidence is indicating also epigenetic mechanisms such as DNA methylation and histone acetylation as key players in the development of AD and PD. Also, women due to longer lifespans and unique

Removal of organically bound sulfur from oil shale by iron(III)-ion generated-regenerated from pyrite by the action of Acidithiobacillus ferrooxidans

Oil shales are one of the alternative sources of hydrocarbon fuels ("synthetic petroleum"), characterized by the increased sulfur and nitrogen content which represent even greater ecological problem in use, compared to classical fuels. Acidithiobacillus ferrooxidans is capable of oxidizing pyrite to iron (III)-ion, providing a strong oxidation agent at low pH. We have used this oxidizing agent for oxidation of sulfur present in DBT as a substrate model to demonstrate its potential to oxidize organically bound sulfur in oil shales. An HCl-concentrate was used as the hydrocarbon matrix. Acidithiobacillus ferrooxidans is already recognized to oxidize the pyritic sulfur component, thereby potentially providing a complete sulfur removal system. By applying GC-MS we established that DBT transformation occurred by oxidation or elimination of sulfur. The products obtained are more soluble in water than parent compounds and this reduces concentration of organic sulfur.BIOHYDROMETALLURY: FROM THE SINGLE CELL TO THE ENVIRONMEN

Determinants and Predictors of Grief Severity and Persistence: The Rotterdam Study

Objective: We aimed to explore correlates and predictors of bereavement severity and persistence (triggered by “loss of a loved one”; referent group partner loss) in the Rotterdam cohort. Method: We used linear regression to examine factors associated with grief severity using a cross-sectional analysis and logistic regression to determine prospective associations. Results: Cross-sectionaly, females, child-lost, higher depressive symptoms, lower education, and difficulties in daily activities were independently associated with a higher bereavement severity. Prospectively (6 years; response rate 71%), the baseline value of the grief severity was the single predictor significantly associated with grief persistence. Discussion: Our results suggest that only grief severity is independently associated with grief persistence. Further studies are needed to confirm ou

Compliance and approach to voluntary HIV testing in a high-risk region for HIV transmission in Europe

Background: The Kosovo province is being considered as a high-risk region for the spread of HIV. Objective: To estimate the prevalence and factors associated with HIV testing in a sample of university students from the Serbian northern Kosovo province. Material and Methods: A questionnaire examining socio-demographic characteristics, HIV–related knowledge, attitudes towards people living with HIV (PLHIV) and HIV testing was used in data collection. A total of 1,017 students from the University of Priština temporarily seated in Kosovska Mitrovica completed the questionnaire. Results: Only 5.4% of students have previously been tested for HIV, even though the majority (70.9%) had a positive approach to HIV testing. Factors associated with having been tested for HIV were being male and younger, having interest in HIV testing and having previous contact with PLHIV. Being more knowledgeable about HIV and having stronger positive attitude towards PLHIV, being older, receiving information about HIV through friends and special educational programs, using condom at last sexual intercourse, having positive opinion on gays/lesbians and previous contact with PLHIV were associated with positive approach to HIV testing. Conclusion: Having a positive approach to HIV testing does not suggest that students would take the HIV test. However, students who have low HIV-related knowledge, negative approach or lack of interest in HIV testing (believing that there is no need to take it) would likely never take the HIV test. Increasing HIV-related knowledge, acceptance of PLHIV and access to testing facilities should be public health priorities to raise HIV testing rates. Keywords: HIV testing; attitude; knowledge; University students

Molecular and Morphological Inference of Three Cryptic Species within the Merodon aureus Species Group (Diptera:Syrphidae)

The Merodon aureus species group (Diptera: Syrphidae: Eristalinae) comprises a number of different sub-groups and species complexes. In this study we focus on resolving the taxonomic status of the entity previously identified as M. cinereus B, here identified as M. atratus species complex. We used an integrative approach based on morphological descriptions, combined with supporting characters that were obtained from molecular analyses of the mitochondrial cytochrome c oxidase I gene as well as from geometric morphometry of wing and surstylus shapes and environmental niche comparisons. All applied data and methods distinguished and supported three morphologically cryptic species: M. atratus stat. nov., M. virgatus sp. nov. and M. balkanicus sp. nov., which constitute the M. atratus species complex. We present an identification key for the sub-groups and species complexes of the M. aureus species group occurring in Europe, describe the taxa and discuss the utility of the applied methods for species delimitation. The estimated divergence times for the species splits of these taxa coincide with the Pleistocene Gunz-Mindel interglaciation and the Great interglaciation (between the Ris and Mindel glacial periods).Peer reviewe

Promena izoprenoidne, steranske i terpanske frakcije tokom ex situ bioremedijacije mazuta na industrijskom nivou

This paper presents the results of an ex situ bioremediation of soil contaminated by mazut (heavy residual fuel oil) in the field scale (600 m(3)). The treatment-bed (thickness 0.4 m) consisted of mechanically mixed mazut-contaminated soil, softwood sawdust as an additional carbon source and crude river sand, as a bulking and porosity increasing material. The inoculation/reinoculation was conducted periodically using a biomass of a consortium of zymogenous microorganisms isolated from a bioremediation substrate. The biostimulation was performed through addition of nutritious substances (N, P and K). The aeration was improved by systematic mixing of the bioremediation system. After 50 days, the number of hydrocarbon degraders had increased a 100 fold. Based on the changes in the group composition, the average biodegradation rate during bioremediation was 24 mg kg(-1) day(-1) for the aliphatic fraction, 6 mg kg(-1) day(-1) for the aromatic fraction and 3 mg kg(-1) day(-1) for the nitrogen-sulphur-oxygen compounds (NSO)-asphaltene fraction. In the saturated hydrocarbon fraction, gas chromatography-mass spectrometry (GC-MS) in the single ion-monitoring mode (SIM) was applied to analyse isoprenoids pristane and phytane and polycyclic molecules of sterane and triterpane type. Biodegradation occurred during the bioremediation process, as well as a reduction of the relative quantities of isoprenoids, steranes, tri- and tetracyclic terpanes and pentacyclic terpanes of the hopane type.Prikazani su rezultati ex situ bioremedijacije zemljišta kontaminiranog mazutom na industrijskom nivou (600 m3). Bioremedijacioni materijal (debljine 0,4 m) se sastojao od mehanički pomešanih mazutom zagađenog zemljišta, čamove piljevine kao dodatnog izvora ugljenika i neprečišćenog rečnog peska, dodatog u cilju mešanja i povećanja poroznosti. Inokulacija/reinokulacija (bioaugmentacija) je periodično rađena sa biomasom konzorcijuma zimogenih mikrooorganizama izolovanih iz supstrata za bioremedijaciju. Biostimulacija je realizovana dodatkom hranljivih supstanci (N, P i K). Aeracija je poboljšavana sistematskim mešanjem bioremedijacionog sistema. Nakon 50 dana broj mikroorganizama koji degradiraju ugljovodonike povećan je 100 puta. Na osnovu promena u grupnom sastavu prosečna stopa biodegradacije tokom bioremedijacije je bila za alifatičnu frakciju 24 mg kg-1 po danu, za aromatičnu 6 mg kg-1 po danu i 3 mg kg-1 po danu za NSO-asfaltensku frakciju. U zasićenoj ugljovodoničnoj frakciji metodom GC-MS (SIM metod) analizirani su izoprenoidi pristan i fitan i policiklični molekuli steranskog i triterpanskog tipa. Tokom bioremedijacionog procesa došlo je do biodegradacije i smanjenja relativnih količina izoprenoida, sterana, tri- i tetracikličnih terpana i pentacikličnih terpana hopanskog tipa

Phytoestrogen supplementation and body composition in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials

Phytoestrogen-based medications are commonly used by menopausal women, and especially by obese postmenopausal women, to relieve menopausal symptoms. Substitution of animal with soy protein is often used in weight loss regimens, yet the effect of phytoestrogens, the main constituent of soy foods, on body composition is not completely understood. We conducted a systematic review and meta-analysis to investigate the associations between phytoestrogen supplementation and body weight and the main parameters of body composition in postmenopausal women. A literature search was done using 5 electronic databases from inception to April 2018. Randomized controlled trials (RCTs) with postmenopausal women comparing phytoestrogen supplementation followed by usual diet and placebo were included in the present meta-analysis. From 5932 references, we identified 23 RCTs that met our inclusion criteria, with a total of 1880 postmenopausal women. No association was observed between phytoestrogen supplementation and body weight, body mass index, waist and hip circumference, total fat mass or percentage of body fat. However, the use of phytoestrogens supplementation was associated with a slight decrease in waist-hip ratio; the pooled mean difference was −0.01 cm (95%CI: −0.01 to −0.006). In subgroup analysis, we found a modest decrease in body weight with phytoestrogens supplementation compared with placebo in healthy postmenopausal women [pooled mean difference of changes −0.28 kg (95%CI: −0.52 to −0.04)] and in RCTs with a median number of participants of 66 or less [pooled mean difference of changes −0.49 kg (95%CI: −0.87 to −0.11)]. In contrast, phytoestrogen supplementation was associated with increased body weight in postmenopausal women with preexisting metabolic disorders (prediabetes, type 2 diabetes, prehypertension and hyperlipidemia) [pooled mean difference of changes: 0.78 kg(95%CI: 0.53–1.03)]. In addition, there were some indications that some types of phytoestrogens, such as daidzein, but not soy products or isoflavone mix, could lead to modest adverse changes in body composition in menopausal women. Therefore, future studies should investigate the potential adverse effects of phytoestrogen supplementation on body composition among postmenopausal women