Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods

Autophagy is one of the well-known pathways to accelerate the clearance of protein aggregates, which contributes to the therapy of neurodegenerative diseases. Although there are numerous reports that demonstrate the induction of autophagy with small molecules including rapamycin, trehalose and lithium, however, there are few reports mentioning the clearance of aggregate-prone proteins through autophagy induction by nanoparticles. In the present article, we have demonstrated that europium hydroxide [Eu^III(OH)₃] nanorods can reduce huntingtin protein aggregation (EGFP-tagged huntingtin protein with 74 polyQ repeats), responsible for neurodegenerative diseases. Again, we have found that these nanorods induce authentic autophagy flux in different cell lines (Neuro 2a, PC12 and HeLa cells) through the expression of higher levels of characteristic autophagy marker protein LC3-II and degradation of selective autophagy substrate/cargo receptor p62/SQSTM1. Furthermore, depression of protein aggregation clearance through the autophagy blockade has also been observed by using specific inhibitors (wortmannin and chloroquine), indicating that autophagy is involved in the degradation of huntingtin protein aggregation. Since [Eu^III(OH)₃] nanorods can enhance the degradation of huntingtin protein aggregation via autophagy induction, we strongly believe that these nanorods would be useful for the development of therapeutic treatment strategies for various neurodegenerative diseases in near future using nanomedicine approach.     

Hematological and plasma biochemistry in Cirrhinus mrigala (Hamilton 1822)

Hematological and plasma chemistry indices are important parameters for the evaluation of fish physiological status. In this study, we determined the results of selected hematological and plasma biochemical profiles in Cirrhinus mrigala captured from the wild in a tropical climate of India. Blood was analyzed using standard techniques, and differences in hematological parameters including hemoglobin concentration, erythrocyte count, total leukocyte count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) of fish were compared according to sex and different seasons. Analysis of variance showed that there were significant differences (p?<?0.05) between sexes, and the results indicated that blood parameters levels between the sexes in summer were significantly different than that measure in other seasons except MCH and MCHC value. The number of total leukocyte levels was found to be higher in female fish especially in reproductive seasons (summer), but the levels of hemoglobin, hematocrit, and MCV values were high in male fish in an annual period. However, there was no difference in MCH and MCHC values between the sexes and seasons throughout the study period. These may be related to season of sampling and changing physiological cycles during these months. Differences were noted in plasma lipid, cholesterol, and glucose level in the summer season, but the higher amount of plasma protein was found in spring and winter in male and female fish, respectively. In conclusion, monitoring fish hematological and biochemical parameters essentially can be a way to evaluate the physiological and health status of their populations, which may be a useful indicator of the environmental status.     

The diabetes online community: the importance of forum use in parents of children with type 1 diabetes

Online forums for chronic health conditions emerged as early as 30 yr ago and interest in their study has blossomed. Type 1 diabetes (T1D) forums have grown exponentially since 2005. Therefore, a comprehensive evaluation of these forums is needed. This study assesses the demographics and motivations of parents who use type 1 diabetes forums and the potential impact that forum membership (FM) has on parenting stress and hypoglycemic fear. One hundred and two parents were recruited through online T1D forums and asked to complete qualitative and quantitative measures of their experience with the T1D forums. Results of this study suggest that parents who use T1D forums mirror those who participate in clinic‐based research protocols and are primarily motivated to participate in forums to increase their diabetes knowledge and gain social support. Indeed, parents who use T1D forums report high levels of trust, social support, and perceived knowledge gained. However, FM was positively related to increased self‐reported parenting stress frequency and hypoglycemic fear behaviors. Taken together, the relationships formed within these communities may have a significant impact on the experience of these caregivers. The need for future research and potential implications for physicians, including parent debriefing, are discussed.     

A magnetically separable and recyclable g-C3N4/Fe3O4/porous ruthenium nanocatalyst for the photocatalytic degradation of water-soluble aromatic amines and azo dyes

Herein, we present the development of a visible-light-driven magnetically retrievable nanophotocatalyst made of porous ruthenium nanoparticles supported on magnetic carbon nitride (g-C₃N₄/Fe₃O₄/p-RuNP) for the facile removal/degradation of aromatic amines and azo dyes from wastewater. Aromatic amines and azo-based dyes in water bodies are highly toxic and carcinogenic even at very low concentrations and are difficult to separate because of their high solubility. Our nanocatalyst can efficiently degrade/decompose the aromatic amines and azo dyes under visible light (LED/sunlight) at room temperature and in a wide pH range (pH 5.0–9.0) without using any external chemicals. The magnetic property of the nanocatalyst facilitates its efficient and facile separation from the reaction mixture for reuse in multiple photocatalytic cycles. The nanocatalyst-based degradation of azo dyes and aromatic amines presented here is simple and convenient in terms of efficiency, energy, reusability and cost. The process also does not require any external chemicals and forms gaseous/less harmful end products.

A magnetically separable and recyclable g-C₃N₄/Fe₃O₄/porous ruthenium nanocatalyst display excellent photocatalytic degradation of water-soluble aromatic amines and azo dyes at ambient condition.     

Isolation and study of insulin activated nitric oxide synthase inhibitory protein in acute myocardial infarction subjects

Insulin inhibits platelet aggregation through nitric oxide synthesis by stimulating platelet insulin activated nitric oxide synthase. Impaired platelet insulin activated nitric oxide synthase in acute myocardial infarction (AMI) patients had been reported and thus our aim was to identify and isolate the factors impairing insulin activated nitric oxide in acute myocardial infarction patients’ plasma and study its effect on platelets aggregation in vitro. The insulin activated nitric oxide synthase inhibitor was identified as a protein and was purified from the plasma of AMI subjects using DEAE cellulose and Sephadex G-50 column, molecular weight determined by SDS-PAGE, nitric oxide quantified by methaemoglobin method, inhibitor protein quantified in plasma by immunoblot and ELISA, platelet aggregation studies done using an aggregometer, thromboxane-A2 in the platelets determined by radioimmunoassay, ¹²⁵I-insulin radioligand binding studies done using normal subject platelets. The purified nitric oxide synthase inhibitor protein was ~66 kDa, concentration in AMI subjects’ plasma varied from 114 to 9,090 μM and was undetected in normal subjects’ plasma. The inhibitor protein competes with insulin for insulin receptor binding sites. The Incubation of the normal subject PRP with 5.0 μM inhibitor for 30 min followed by 0.4 μM ADP addition caused platelet aggregation in vitro, 130 μM aspirin or 400 μU insulin/ml addition was able to abrogate 0.4 μM ADP induced platelet aggregation even in the presence of 5.0 μM inhibitor. A potent inhibitory protein against insulin activated nitric oxide synthase in platelets appears in circulation of AMI subjects impairing nitric oxide production, potentiating ADP induced platelet aggregation and increasing the thromboxane-A2 level in platelets.     

An essential review of Singapore’s response to out-of-hospital cardiac arrests: improvements over a ten-year period

Care for patients who experience out-of-hospital cardiac arrest (OHCA) has rapidly evolved in the past decade. Increased sophistication of care in the community, emergency medical services (EMS) and hospital setting is associated with improved patient-centred outcomes. Notably, Utstein survival doubled from 11.6% to 23.1% between 2011 and 2016. These achievements involved collaboration between policymakers, clinicians and researchers, and were made possible by a strategic interplay of policy, research and implementation. We review the development and current state of OHCA in Singapore using primary population-based data from the Pan-Asian Resuscitation Outcomes Study and an unstructured search of research databases. We discuss the roles of important milestones in policy, community, dispatch, EMS and hospital interventions. Finally, we relate these interventions to relevant processes and outcomes, such as the relationship between the strategic implementation of bystander cardiopulmonary resuscitation and placement of automated external defibrillator with return of spontaneous circulation, survival to discharge and survival with favourable neurological outcomes.     

Targeted specific inhibition of bacterial and Candida species by mesoporous Ag/Sn–SnO2 composite nanoparticles: in silico and in vitro investigation

Invasive bacterial and fungal infections have notably increased the burden on the health care system and especially in immune compromised patients. These invasive bacterial and fungal species mimic and interact with the host extracellular matrix and increase the adhesion and internalization into the host system. Further, increased resistance of traditional antibiotics/antifungal drugs led to the demand for other therapeutics and preventive measures. Presently, metallic nanoparticles have wide applications in health care sectors. The present study has been designed to evaluate the advantage of Ag/Sn–SnO₂ composite nanoparticles over the single oxide/metallic nanoparticles. By using in silico molecular docking approaches, herein we have evaluated the effects of Ag/Sn–SnO₂ nanoparticles on adhesion and invasion responsible molecular targets such as LpfD (E. coli), Als3 (C. albicans) and on virulence/resistance causing PqsR (P. aeruginosa), RstA (Bmfr) (A. baumannii), FoxA (K. pneumonia), Hsp90 and Cyp51 (C. albicans). These Ag/Sn–SnO₂ nanoparticles exhibited higher antimicrobial activities, especially against the C. albicans, which are the highest ever reported results. Further, Ag/Sn–SnO₂ NPs exhibited interaction with the heme proionate residues such as Lys143, His468, Tyr132, Arg381, Phe105, Gly465, Gly464, Ile471 and Ile304 by forming hydrogen bonds with the Arg 381 residue of lanosterol 1 4α-demethylase and increased the inhibition of the Candida strains. Additionally, the Ag/Sn–SnO₂ nanoparticles exhibited extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species followed by several molecular pathways which indicated that it can be used to eliminate the resistance to traditional antibiotics.

Mesoporous Ag/Sn–SnO₂ composite nanoparticles exhibits extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species which can be used to eliminate the resistance of traditional antibiotics.     

Achieving highly efficient and selective cesium extraction using 1,3-di-octyloxycalix[4]arene-crown-6 in n-octanol based solvent system: experimental and DFT investigation

Due to the long half-life of ¹³⁷Cs (t_1/2 ∼ 30 years), the selective extraction of cesium (Cs) from high level liquid waste is of paramount importance in the back end of the nuclear fuel cycle to avoid long term surveillance of high radiotoxic waste. As 1,3-di-octyloxycalix[4]arene-crown-6 (CC6) is suggested to be a promising candidate for selective Cs extraction, the improvement in the Cs extraction efficiency by CC6 has been investigated through the optimization of the effect of dielectric media on the extraction process. The effects of the feed acid (HNO₃, HCl, and HClO₄) and the composition of the diluents for the ligand in the organic phase on the extraction efficiency of Cs have been investigated systematically. In 100% n-octanol medium, Cs is found to form a 1 : 1 ion-pair complex with CC6 (0.03 M) providing a very high distribution ratio of D_Cs ∼ 22, suggesting n-octanol as the most suitable diluent for Cs extraction. No significant interference of other relevant cations such as Na, Mg and Sr was observed on the D_Cs value in the optimized solvent system. Density functional theory (DFT) based calculations have been carried out to elucidate the reason of ionic selectivity and enhanced Cs extraction efficiency of CC6 in the studied diluent systems. In addition to the ionic size-based selectivity of the crown-6 cavity, the polarity of the organic solvent system, the hydration energy of the ion, and the relative reorganization of CC6 upon complexation with Cs are understood to have roles in achieving the enhanced efficiency for the extraction of Cs by the CC6 extractant in nitrobenzene medium.

Separation scheme was developed for selective extraction of long-lived fission product ¹³⁷Cs using substituted calix crown 6 ether from aqueous acidic solution.     

Writing for publication

Writing for publication is rewarding; it requires specific skills which are identified and explored in this article. Intending authors are encouraged to be systematic in targeting the audience, prepararing the text, and presenting it to a publisher. The differing styles needed for academic articles, book reviews and letters are explored as are the stages in publication.