Separation and Detection of Tyrosine and Phenylalanine-derived Oxidative Stress Biomarkers Using Microchip Electrophoresis with Electrochemical Detection

This is the peer reviewed version of the following article: D. B. Weerasekara, S. M. Lunte, Electroanalysis 2022, 34, 1913, which has been published in final form at https://doi.org/10.1002/elan.202100580. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.A method for the determination of selected aromatic amino acid biomarkers of oxidative stress using microchip electrophoresis with electrochemical detection is described. The separation of the major reaction products of phenylalanine and tyrosine with reactive nitrogen and oxygen species was accomplished using ligand exchange micellar electrokinetic chromatography with a PDMS/glass hybrid chip. Electrochemical detection was achieved using a pyrolyzed photoresist film working electrode. The system was evaluated for the analysis of the products of the Fenton reaction with tyrosine and phenylalanine, and the reaction of peroxynitrite with tyrosine

CURRENT STATUS OF AMBEWELA RESERVOIR OF SRI LANKA WITH SPECIALREFERENCE TO WATER POLLUTION

The water pollution trends in the Ambewela reservoir at the uppermost catchment of Kotmale River was assessed through a study on chemical and bio monitoring programme that carried out from March to October 2008.The mean average value (mean ± SD) of the nitrate, nitrite, phosphate and ammonia concentrations in Ambewela reservoir were 0.780 ± 1.386 mg/l, 0.103 ± 0.223mg/l, 0.051 ± 0.061mg/l and 0.218± 0.261 mg/l whereas values for the streams selected from Dambagasthalawa Oya were 0.985 ± 0.902 mg/l, 0.099  ± 0.207mg/l, 0.038 ± 0.026 mg/l and 0.085± 0.077 mg/l respectively. Average Chlorophyll- a values of the reservoir were 17.85 ± 17.858 mg/m3 and 8.30 ± 4.686 mg/m3for other two streams accordingly. Average BOD values of the reservoir were 8.06 ± 3.494 and 4.25 ± 2.251 for other two streams correspondingly.The bio monitoring studies also clearly showed sudden records of huge colonies of  Hydra(approximately 258/cm3) in the reservoir from time to time. This phenomenon was found in relatively dry period that directly coincided with intensified use of agro chemicals. Moreover, steady population of Chironomid (average population density 208/cm3) that is commonly accepted pollution indicator was reported at Ambewela reservoir throughout the study period.Therefore, both chemical and bio monitoring studies indicate eutrophic condition in Ambewela reservoir in which long run might affect on the ecology of the entire ecosystem. Hence prompt mitigatory action should be implemented to avoid further depletion.Key Words: Ambewela Reservoir, Water Pollution, Physico-Chemical Parameters, Chlorophyll –

Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.molpharmaceut.8b00887.Contemporary approaches to treating autoimmune diseases like multiple sclerosis broadly modulate the immune system and leave patients susceptible to severe adverse effects. Antigen-specific immunotherapies (ASIT) offer a unique opportunity to selectively suppress autoreactive cell populations but have suffered from marginal efficacy even when employing traditional adjuvants to improve delivery. The development of immunologically active antigen delivery vehicles could potentially increase the clinical success of antigen-specific immunotherapies. An emulsion of the antioxidant tocopherol delivering an epitope of proteolipid protein autoantigen (PLP139–151) yielded significant efficacy in mice with experimental autoimmune encephalomyelitis (EAE). In vitro studies indicated tocopherol emulsions reduced oxidative stress in antigen-presenting cells. Ex vivo analysis revealed that tocopherol emulsions shifted cytokine responses in EAE splenocytes. In addition, IgG responses against PLP139–151 were increased in mice treated with tocopherol emulsions delivering the antigen, suggesting a possible skew in immunity. Overall, tocopherol emulsions provide a functional delivery vehicle for ASIT capable of ameliorating autoimmunity in a murine model

STUDY THE EFFECT OF SALINITY AND NUTRIENTS FOR THE GROWTH OF Najas marina AND ITS IMPACT TO AQUATIC BIODIVERSITY IN MADU GANGA RAMSAR WETLAND IN SRI LANKA

Madu Ganga is the latest addition to the Ramsar International Convention of Wetlands. Najas marinais an alien aquatic plant and 0.5 m long that are often branched toward the upward portion of the plant. The objective of the study was to study the impact of salinity and nutrients for the growth of Najas marina. Samples were collected for analysed water quality parameters from March, 2006 to January 2007 in the lagoon. Mapping was done using Garmin GPS map 76CS and Arc GIS used to developed maps.Mean nutrient such as, nitrate nitrogen, ammonia nitrogen and orthophosphate concentrations were observed 0.26 ± 0.3 mg/l, 0.057 ± 0.04 mg/l, and 0.354 ± 0.77 mg/l subsequently. Mean salinity variation in bottom and surface are 6.38 ± 6.65 ppt and 4.31 ±  4.68 ppt. Higher bottom salinity was observed in location number 02 (near to sea mouth) and  Najas marinawas not present in the area. Najas marina was also not recorded in upper part of the lagoon and fresh water streams studied. High density of Najas marina plants were observed in sampling location 07, 08 and 09, because of the high nutrient concentration flowing through feeding tributaries. More than 25 % of lagoon area was covered by Najas marina.

What do stroke survivors' value about participating in research and what are the most important research problems related to stroke or transient ischemic attack (TIA)? A survey

Background: Recruitment to stroke clinical trials is challenging, but consumer registers can facilitate participation. Researchers need to understand the key factors that facilitate trial involvement and improve consumer partnerships to identify what research topics important to stroke and transient ischemic attack (TIA) survivors and their carers. We aimed to examine i) the experience of being involved in a stroke research register, and ii) the priorities for stroke research from the perspective of stroke survivors. Methods: Online and paper-based surveys were sent directly to members of a stroke register and disseminated online. Multiple choice questions were reported as counts and percentages and open-ended questions were thematically analysed using Braun and Clarke’s 6-stage process. Results: Of 445 survey respondents, 154 (38%) were a member of the Stroke Research Register. The most frequently reported reason for research participation was to help others in the future. Respondents reported they were less likely to take part in research if the research question was not relevant to them, if transport was an issue, or because they lacked time. The most important research problems reported were targeting specific impairments including recovery of movement, fatigue, and aphasia, improvement of mental health services, and increased support for carers. Conclusions: Recruitment to trials may be improved by research registers if an inclusive research culture is fostered, in which consumers feel valued as members of a community, have direct and timely access to research findings and the opportunity to be meaningfully involved in research around the problems that consumers find most important.Ishanka Weerasekara, Jasmine Baye, Meredith Burke, Gary Crowfoot, Gillian Mason, Rachael Peak, Dawn Simpson, Frederick Rohan Walker, Michael Nilsson, Michael Pollack, and Coralie Englis

Rheology of moist food powders as affected by moisture content

Dynamic testing to determine rheological characteristics of moist food powders (semolina, coarse wheat flour, potato starch) was carried out using a powder rheometer of a new construction. The unique feature of the rheometer is that scale of shearing was confined to the thickness of shearing band of powder bed only. It was found that flow pattern of moistened samples was noticeably and diversely affected by both moisture content (varying in the range of 0–15% w/w) and shear rate. The observed changes showed statistical significance p < 0.01 in all trials carried out. What is noteworthy about the conducted research is that at some shear rate values, the shear stress of the bed reached the maximum for specific moisture content levels, irrespective of particle size of the bed. Such behavior may provide an indication of complex interference of different powder shearing mechanisms in the presence of moisture. For beds consisted of larger particles, shear stress values decreased considerably with increasing moisture content. To explain this, modeling of the shearing process with Discrete Element Method (DEM) was performed. The results obtained supported the idea that friction coefficients of particulate material were significantly reduced at higher moisture content of the powder bed in the whole range of shear rates applied

Human stomach microbiota: Effects on health and disease

The gut microbiota is a complex ecological community, consisting of trillions of microbes which include bacteria, viruses, fungi and protozoa. The stomach was previously considered as a sterile site uninhabited by microbes due to its hostile environmental conditions. Breaking this concept, Helicobacter pylori was the first pathogen reported to inhabit the stomach. Recent studies have suggested that the stomach harbours transient as well as certain commensal bacterial and fungal species. The five major microbial phyla in the stomach have been identified as Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Proteobacteria. The composition of gastric microbiota is dynamic and is affected by several factors.  These include age group, dietary habits, medication use, inflammation of gastric mucosa and H. pylori colonization.  Further, the role of host genetics has recently been studied in maintaining the stomach microbiota. Mutations in host genes may affect the host’s immune response towards commensal bacteria and reduce their number and diversity. The essential multiple roles of gut microorganisms include maintaining homeostasis in the gut, contributing to immune function and extraction of nutrients and energy from our diets.  Loss of the normal balance between the gut microbiota and host has been associated with several abnormal conditions and disorders such as obesity, malnutrition, inflammatory bowel diseases (IBD), neurological disorders, and cancer. In the stomach, the interaction between H. pylori and the gastric microbiota can also influence gastric dis­ease progression. Further studies should focus on addressing the role of gastric dysbiosis in health and disease. Identifying gastric microbiota is essential to understand how the gut microbiota and H. pylori affect health and disease.</p

Rogue wave generation by inelastic quasi-soliton collisions in optical fibres

Optical “rogue” waves are rare and very high intensity pulses of light that occur in optical devices such as communication fibers. They appear suddenly and can cause transmission errors and damage in optical communication systems. Indeed, the physics governing their dynamics is very similar to “monster” or “freak” waves on the Earth’s oceans, which are known to harm shipping. It is therefore important to characterize rogue wave generation, dynamics and, if possible, predictability. Here we demonstrate a simple cascade mechanism that drives the formation and emergence of rogue waves in the generalized non-linear Schrödinger equation with third-order dispersion. This generation mechanism is based on inelastic collisions of quasi-solitons and is well described by a resonant-like scattering behaviour for the energy transfer in pair-wise quasi-soliton collisions. Our theoretical and numerical results demonstrate a threshold for rogue wave emergence and the existence of a period of reduced amplitudes — a “calm before the storm” — preceding the arrival of a rogue wave event. Comparing with ultra-long time window simulations of 3.865 × 106ps we observe the statistics of rogue waves in optical fibres with an unprecedented level of detail and accuracy, unambiguously establishing the long-ranged character of the rogue wave power-distribution function over seven orders of magnitude

Structure-Based Exploration and Exploitation of the S4 Subsite of Norovirus 3CL Protease in the Design of Potent and Permeable Inhibitors

Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents. We hypothesized that the S4 subsite of the enzyme may provide an effective means of designing potent and cell permeable inhibitors of the enzyme. We report herein the structure-guided exploration and exploitation of the S4 subsite of norovirus 3CL protease in the design and synthesis of effective inhibitors of the protease