Apolipoprotein E isoform-dependent effects on the processing of Alzheimer's amyloid-β

Since the identification of the apolipoprotein E (apoE) *ε4 allele as a major genetic risk factor for late-onset Alzheimer's disease, significant efforts have been aimed at elucidating how apoE4 expression confers greater brain amyloid-β (Aβ) burden, earlier disease onset and worse clinical outcomes compared to apoE2 and apoE3. ApoE primarily functions as a lipid carrier to regulate cholesterol metabolism in circulation as well as in the brain. However, it has also been suggested to interact with hydrophobic Aβ peptides to influence their processing in an isoform-dependent manner. Here, we review evidence from in vitro and in vivo studies extricating the effects of the three apoE isoforms, on different stages of the Aβ processing pathway including synthesis, aggregation, deposition, clearance and degradation. ApoE4 consistently correlates with impaired Aβ clearance, however data regarding Aβ synthesis and aggregation are conflicting and likely reflect inconsistencies in experimental approaches across studies. We further discuss the physical and chemical properties of apoE that may explain the inherent differences in activity between the isoforms. The lipidation status and lipid transport function of apoE are intrinsically linked with its ability to interact with Aβ. Traditionally, apoE-oriented therapeutic strategies for Alzheimer's disease have been proposed to non-specifically enhance or inhibit apoE activity. However, given the wide-ranging physiological functions of apoE in the brain and periphery, a more viable approach may be to specifically target and neutralise the pathological apoE4 isoform.     

Numerical Study of an Ultra-Broadband and Wide-Angle Insensitive Perfect Metamaterial Absorber in the UV–NIR Region

Plasmonics - Developing a simple structure using low-cost material that enables both large-scale fabrication and broadband absorption response is highly desirable but very challenging for achieving...     

Targeting mesenchymal stem cell therapy for severe pneumonia patients

Pneumonia is the inflammation of the lungs and it is the world’s leading cause of death for children under 5 years of age.The latest coronavirus disease 2019(COVID-19)virus is a prominent culprit to severe pneumonia.With the pandemic running rampant for the past year,more than 1590000 deaths has occurred worldwide up to December 2020 and are substantially attributable to severe pneumonia and induced cytokine storm.Effective therapeutic approaches in addition to the vaccines and drugs under development are hence greatly sought after.Therapies harnessing stem cells and their derivatives have been established by basic research for their versatile capacity to specifically inhibit inflammation due to pneumonia and prevent alveolar/pulmonary fibrosis while enhancing antibacterial/antiviral immunity,thus significantly alleviating the severe clinical conditions of pneumonia.In recent clinical trials,mesenchymal stem cells have shown effectiveness in reducing COVID-19-associated pneumonia morbidity and mortality;positioning these cells as worthy candidates for combating one of the greatest challenges of our time and shedding light on their prospects as a nextgeneration therapy to counter future challenges.     

Linking Material Flow Analysis with Environmental Impact Potential

Technology transition can have significant implications on the evolution of environmental impact potential of disposed electronics over time. Considering technology transition, we quantify the temporal behavior of ecological and human health impact potential from select heavy metals in electronic waste (e‐waste). The case study analyzes product substitution effects in two electronic cohorts from the U.S. market: (1) computers (laptops substituting for desktops) and (2) televisions (flat‐panel liquid crystal displays [LCDs] and plasma displays substituting for cathode‐ray tubes [CRTs]). Quantities of end‐of‐life (EoL) units to year 2030 are forecasted by the unique combination of dynamic material flow analysis, logistic trend analysis, and product lifespan calibration methods. Metal content from EoL units are assessed via a pathway and effect model using USETox? characterization factors to determine the toxicity potential attributed to heavy metal releases into different media (e.g., air, water, and soil) as an indicator of environmental burden. Results show high impact materials such as lead, nickel, and zinc cause changes in human health toxicity potential and copper causes changes in ecological toxicity potential. Effects of dematerialization, such as reduced metal content in laptops over desktops, provide some positive benefits in toxicity potential per product. However, from a market perspective, emerging e‐waste quantities created by increasing per capita penetration rates of electronics and increasing population will offset gains in environmental performance at the product level. The resulting analysis provides guidance on the timing expected for emerging EoL units and an indication of high impact potential materials requiring pollution prevention as product substitution occurs.     

Purification,Characterization, and Chemical Modification of Neurotoxic Peptide from Daboia russelii Snake Venom of India

Comprehensive knowledge of venom composition is very important for effective management of snake envenomation and antivenom preparation. Daboia russelii venom from the eastern region of India is the most neurotoxic among the four venom samples investigated. From the eastern D. russelii venom sample, neurotoxic peptide has been purified by combined method of ion exchange gel permeation chromatography and reversed phase high performance liquid chromatography. Molecular weight of Daboia neurotoxin III (DNTx‐III) found to be 6,849 Da (as measured on matrix‐assisted laser desorption/ionisation‐time of flight mass spectrometer), and N‐terminal amino acid sequences is I K C F I T P D U T S Q A. Approximate LD₅₀ dosage was 0.24 mg/kg body weight. It produced concentration‐ and time‐dependent inhibition of indirectly stimulated twitches of Rana hexadactyla sciatic nerve gastrocnemius muscle preparations. Chemical modification of DNTx‐III tryptophan residue(s) reduced the twitch height inhibition property of toxin, signifying the importance of tryptophan residues for the neurotoxic function. This type of neurotoxic peptide is unique to east Indian regional D. russelii venom. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:295‐304, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21486