Mercury chloride-induced oxidative stress in human erythrocytes and the effect of vitamins C and E in vitro

Mercury can exist in the environment as metal, as monovalent and divalent salts and as organomercurials, one of the most important of which is mercuric chloride (HgCl2). It has been shown to induce oxidative stress in erythrocytes through the generation of free radicals and alteration of thecellular antioxidant defense system. The effect of simultaneous pretreatment with vitamins C and E on the toxicity of HgCl2 in human erythrocytes was evaluated. We examined the effect of several differentdoses of HgCl2 (1.052, 5.262, 10.524 M), or HgCl2 in combination with vitamin C (VC; 10 M) and vitamin E (VE; 30 M), on the levels of malondialdehyde (MDA) and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in human erythrocytes in vitro. Erythrocytes were incubated under various treatment conditions (HgCl2 alone, vitamins alone, or HgCl2 plus vitamin) at 37°C for 60 min and the levels of MDA and SOD, CAT and GPx activities, were determined. Treatment with HgCl2 alone increased the levels of MDA and decreased SOD, CAT and GPx activities in erythrocytes (P < 0.05). VC and VE-pretreated erythrocytes showed a significant protection aganist thecytotoxic effects induced by HgCl2 on the studied parameters. There were no statistical differences among VC+VE-treated erythrocytes, as compared to non-treated control cells. These results indicated that the presence of vitamins at concentrations that are similar to the levels found in plasma could be able to ameliorate HgCl2-induced oxidative stress by decreasing lipid peroxidation and altering antioxidant defense system in erythrocytes

Impact of Lighting Arrangements and Illuminances on Different Impressions of a Room

Cataloged from PDF version of article.This study explores whether different lighting arrangements (general lighting, wall washing and cove lighting) and different illuminances (500 and 320 lux) could affect the perception of the same space. An experimental study was conducted to investigate how the qualitative aspects of space (the impressions of a space) could be enhanced with lighting. Hundred participants were first asked to choose the most suitable lighting arrangement for each impression (clarity, spaciousness, relaxation, privacy, pleasantness and order) under the 500 lux illuminance. In the second stage, they were asked to compare the two illuminances (500 and 320 lux) for the lighting arrangement they selected in the first stage. There was a statistically significant relation between impressions and lighting arrangements, also between impressions and lighting levels. Thus, different lighting arrangements and lighting levels could be used to enhance the clarity, spaciousness, relaxation, privacy, pleasantness and order of a room. The results of this study found most suitable lighting arrangements with their illuminances for each impression, which is reported in the paper

Ascaroside Expression in Caenorhabditis elegans Is Strongly Dependent on Diet and Developmental Stage

Background: The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as “dauer pheromones” because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development. Methodology/Principal Findings: Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions. Conclusions/Significance: Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies

Quantifying methane point sources from fine-scale satellite observations of atmospheric methane plumes

Anthropogenic methane emissions originate from a large number of relatively small point sources. The planned GHGSat satellite fleet aims to quantify emissions from individual point sources by measuring methane column plumes over selected ∼ 10×10&thinsp;km2 domains with  ≤ 50×50&thinsp;m2 pixel resolution and 1&thinsp;%–5&thinsp;% measurement precision. Here we develop algorithms for retrieving point source rates from such measurements. We simulate a large ensemble of instantaneous methane column plumes at 50×50&thinsp;m2 pixel resolution for a range of atmospheric conditions using the Weather Research and Forecasting model (WRF) in large eddy simulation (LES) mode and adding instrument noise. We show that standard methods to infer source rates by Gaussian plume inversion or source pixel mass balance are prone to large errors because the turbulence cannot be properly parameterized on the small scale of instantaneous methane plumes. The integrated mass enhancement (IME) method, which relates total plume mass to source rate, and the cross-sectional flux method, which infers source rate from fluxes across plume transects, are better adapted to the problem. We show that the IME method with local measurements of the 10&thinsp;m wind speed can infer source rates with an error of 0.07–0.17&thinsp;t&thinsp;h−1 + 5&thinsp;%–12&thinsp;% depending on instrument precision (1&thinsp;%–5&thinsp;%). The cross-sectional flux method has slightly larger errors (0.07–0.26&thinsp;t&thinsp;h−1 + 8&thinsp;%–12&thinsp;%) but a simpler physical basis. For comparison, point sources larger than 0.3&thinsp;t&thinsp;h−1 contribute more than 75&thinsp;% of methane emissions reported to the US Greenhouse Gas Reporting Program. Additional error applies if local wind speed measurements are not available and may dominate the overall error at low wind speeds. Low winds are beneficial for source detection but detrimental for source quantification.</p

Relativistic K shell decay rates and fluorescence yields for Zn, Cd and Hg

In this work we use the multiconfiguration Dirac-Fock method to calculate the transition probabilities for all possible decay channels, radiative and radiationless, of a K shell vacancy in Zn, Cd and Hg atoms. The obtained transition probabilities are then used to calculate the corresponding fluorescence yields which are compared to existing theoretical, semi-empirical and experimental results

Security Analysis and Improvements for the IETF MLS Standard for Group Messaging

Secure messaging (SM) protocols allow users to communicate securely over untrusted infrastructure. In contrast to most other secure communication protocols (such as TLS, SSH, or Wireguard), SM sessions may be long-lived (e.g., years) and highly asynchronous. In order to deal with likely state compromises of users during the lifetime of a session, SM protocols do not only protect authenticity and privacy, but they also guarantee forward secrecy (FS) and post-compromise security (PCS). The former ensures that messages sent and received before a state compromise remain secure, while the latter ensures that users can recover from state compromise as a consequence of normal protocol usage. SM has received considerable attention in the two-party case, where prior work has studied the well-known double-ratchet paradigm in particular and SM as a cryptographic primitive in general. Unfortunately, this paradigm does not scale well to the problem of secure group messaging (SGM). In order to address the lack of satisfactory SGM protocols, the IETF has launched the message-layer security (MLS) working group, which aims to standardize an eponymous SGM protocol. In this work we analyze the TreeKEM protocol, which is at the core of the SGM protocol proposed by the MLS working group. On a positive note, we show that TreeKEM achieves PCS in isolation (and slightly more). However, we observe that the current version of TreeKEM does not provide an adequate form of FS. More precisely, our work proceeds by formally capturing the exact security of TreeKEM as a so-called continuous group key agreement (CGKA) protocol, which we believe to be a primitive of independent interest. To address the insecurity of TreeKEM, we propose a simple modification to TreeKEM inspired by recent work of Jost et al. (EUROCRYPT \u2719) and an idea due to Kohbrok (MLS Mailing List). We then show that the modified version of TreeKEM comes with almost no efficiency degradation but achieves optimal (according to MLS specification) CGKA security, including FS and PCS. Our work also lays out how a CGKA protocol can be used to design a full SGM protocol. Finally, we propose and motivate an extensive list of potential future research directions for the area

Enhancer of Zeste Homolog 2 Induces Pulmonary Artery Smooth Muscle Cell Proliferation

Pulmonary Arterial Hypertension (PAH) is a progressively devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. The proliferation of cancer cells is mediated by increased expression of Enhancer of Zeste Homolog 2 (EZH2), a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes. However, the role of EZH2 in PAH has not been studied. In this study, it is hypothesized that EZH2 could play a role in the proliferation of PASMCs.In the present study, the expression patterns of EZH2 were investigated in normal and hypertensive mouse PASMCs. The effects of EZH2 overexpression on the proliferation of human PASMCs were tested. PASMCs were transfected with EZH2 or GFP using nucleofector system. After transfection, the cells were incubated for 48 hours at 37°C. Proliferation and cell cycle analysis were performed using flow cytometry. Apoptosis of PASMCs was determined using annexin V staining and cell migration was tested by wound healing assay.EZH2 protein expression in mouse PASMCs were correlated with an increase in right ventricular systolic pressure and Right Ventricular Hypertrophy (RVH). The overexpression of EZH2 in human PASMCs enhances proliferation, migration, and decrease in the rate of apoptosis when compared to GFP-transfected cells. In the G2/M phase of the EZH2 transfected cells, there was a 3.5 fold increase in proliferation, while there was a significant decrease in the rate of apoptosis of PASMCs, when compared to control.These findings suggest that EZH2 plays a role in the migration and proliferation of PASMCs, which is a major hallmark in PAH. It also suggests that EZH2 could play a role in the development of PAH and can serve as a potential target for new therapies for PAH

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C–Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living culture

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

De novo mutations in CHD8 are strongly associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural-specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8.National Institutes of Health (U.S.) (Grant UH1-MH106018-03

Perceived efficacy of herbal remedies by users accessing primary healthcare in Trinidad

BACKGROUND: The increasing global popularity of herbal remedies requires further investigation to determine the probable factors driving this burgeoning phenomenon. We propose that the users' perception of efficacy is an important factor and assessed the perceived efficacy of herbal remedies by users accessing primary health facilities throughout Trinidad. Additionally, we determined how these users rated herbal remedies compared to conventional allopathic medicines as being less, equally or more efficacious. METHODS: A descriptive cross-sectional study was undertaken at 16 randomly selected primary healthcare facilities throughout Trinidad during June-August 2005. A de novo, pilot-tested questionnaire was interviewer-administered to confirmed herbal users (previous or current). Stepwise multiple regression analysis was done to determine the influence of predictor variables on perceived efficacy and comparative efficacy with conventional medicines. RESULTS: 265 herbal users entered the study and cited over 100 herbs for the promotion of health/wellness and the management of specific health concerns. Garlic was the most popular herb (in 48.3% of the sample) and was used for the common cold, cough, fever, as 'blood cleansers' and carminatives. It was also used in 20% of hypertension patients. 230 users (86.8%) indicated that herbs were efficacious and perceived that they had equal or greater efficacy than conventional allopathic medicines. Gender, ethnicity, income and years of formal education did not influence patients' perception of herb efficacy; however, age did (p = 0.036). Concomitant use of herbs and allopathic medicines was relatively high at 30%; and most users did not inform their attending physician. CONCLUSION: Most users perceived that herbs were efficacious, and in some instances, more efficacious than conventional medicines. We suggest that this perception may be a major contributing factor influencing the sustained and increasing popularity of herbs. Evidence-based research in the form of randomized controlled clinical trials should direct the proper use of herbs to validate (or otherwise) efficacy and determine safety. In the Caribbean, most indigenous herbs are not well investigated and this points to the urgent need for biomedical investigations to assess the safety profile and efficacy of our popular medicinal herbs