Life cycle assessment and cost analysis of fly ash-rice husk ash blended alkali-activated concrete.

The utilization of industrial and agricultural by-products for the production of alkali activated concrete (AAC) has the potential to yield significant benefits towards sustainability goals. To be a viable material, the construction industry requires a construction material that achieves the requisite strength and the other property requirements as specified in codes and standards while demonstrating improved sustainability criteria. Fly ash and Rice Husk Ash (RHA) are abundantly available waste products, principally located in Asian countries. Currently, a significant proportion of these materials are disposed of in landfills, lagoons and rivers but offer potential to utilize in AAC. Hence, the identification of variables associated with fly ash and fly ah-RHA blended AAC by utilizing fly ash and RHA is vital. This study quantifies the environmental and economic factors by assessing the Greenhouse gas (GHG) emission, environmental impacts and benefits, and cost analysis of utilizing fly ash and RHA in AAC compared to Portland Cement (PC) concrete. Alkaline activator is a key component responsible for the highest GHG emission, cost and environmental impact amounts obtained for fly ash geopolymer and blended alkali-activated concrete compared with PC concrete. Alkali activators contribute to 74% of the total GHG emission, while heat curing contributed only 9% to the total GHG emission. The addition of 10% RHA to alkali-activated concrete showed a slight benefit for the analysis. Utilization of waste fly ash and RHA is responsible for providing significant benefits in terms of fresh and marine water ecotoxicity by avoiding waste disposal at the dumpsites, rivers, and storage lagoons.

CNS-derived extracellular vesicles from superoxide dismutase 1 (SOD1)G93A ALS mice originate from astrocytes and neurons and carry misfolded SOD1.

Extracellular vesicles (EVs) are secreted by myriad cells in culture and also by unicellular organisms, and their identification in mammalian fluids suggests that EV release also occurs at the organism level. However, although it is clearly important to better understand EVs' roles in organismal biology, EVs in solid tissues have received little attention. Here, we modified a protocol for EV isolation from primary neural cell culture to collect EVs from frozen whole murine and human neural tissues by serial centrifugation and purification on a sucrose gradient. Quantitative proteomics comparing brain-derived EVs from nontransgenic (NTg) and a transgenic amyotrophic lateral sclerosis (ALS) mouse model, superoxide dismutase 1 (SOD1)G93A, revealed that these EVs contain canonical exosomal markers and are enriched in synaptic and RNA-binding proteins. The compiled brain EV proteome contained numerous proteins implicated in ALS, and EVs from SOD1G93A mice were significantly depleted in myelin-oligodendrocyte glycoprotein compared with those from NTg animals. We observed that brain- and spinal cord-derived EVs, from NTg and SOD1G93A mice, are positive for the astrocyte marker GLAST and the synaptic marker SNAP25, whereas CD11b, a microglial marker, was largely absent. EVs from brains and spinal cords of the SOD1G93A ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregated SOD1. Our results indicate that CNS-derived EVs from an ALS animal model contain pathogenic disease-causing proteins and suggest that brain astrocytes and neurons, but not microglia, are the main EV source.

Disease Mechanisms in ALS: Misfolded SOD1 Transferred Through Exosome-Dependent and Exosome-Independent Pathways.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular degenerative disorder with a poorly defined etiology. ALS patients experience motor weakness, which starts focally and spreads throughout the nervous system, culminating in paralysis and death within a few years of diagnosis. While the vast majority of clinical ALS is sporadic with no known cause, mutations in human copper-zinc superoxide dismutase 1 (SOD1) cause about 20 % of inherited cases of ALS. ALS with SOD1 mutations is caused by a toxic gain of function associated with the propensity of mutant SOD1 to misfold, presenting a non-native structure. The mechanisms responsible for the progressive spreading of ALS pathology have been the focus of intense study. We have shown that misfolded SOD1 protein can seed misfolding and aggregation of endogenous wild-type SOD1 similar to amyloid-ß and prion protein seeding. Our recent observations demonstrate a transfer of the misfolded SOD1 species from cell to cell, modeling the intercellular transmission of disease through the neuroaxis. We have shown that both mutant and misfolded wild-type SOD1 can traverse cell-to-cell, either as protein aggregates that are released from dying cells and taken up by neighboring cells via macropinocytosis, or in association with vesicles which are released into the extracellular environment. Furthermore, once misfolding of wild-type SOD1 has been initiated in a human cell culture, it can induce misfolding in naïve cell cultures over multiple passages of media transfer long after the initial misfolding template is degraded. Herein we review the data on mechanisms of intercellular transmission of misfolded SOD1.

From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis.

Prions, self-proliferating infectious agents consisting of misfolded protein, are most often associated with aggressive neurodegenerative diseases in animals and humans. Akin to the contiguous spread of a living pathogen, the prion paradigm provides a mechanism by which a mutant or wild-type misfolded protein can dominate pathogenesis through self-propagating protein misfolding, and subsequently spread from region to region through the central nervous system. The prion diseases, along with more common neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and the tauopathies belong to a larger group of protein misfolding disorders termed proteinopathies that feature aberrant misfolding and aggregation of specific proteins. Amyotrophic lateral sclerosis (ALS), a lethal disease characterized by progressive degeneration of motor neurons is currently understood as a classical proteinopathy; the disease is typified by the formation of inclusions consisting of aggregated protein within motor neurons that contribute to neurotoxicity. It is well established that misfolded/aggregated proteins such as SOD1 and TDP-43 contribute to the toxicity of motor neurons and play a prominent role in the pathology of ALS. Recent work has identified propagated protein misfolding properties in both mutant and wild-type SOD1, and to a lesser extent TDP-43, which may provide the molecular basis for the clinically observed contiguous spread of the disease through the neuroaxis. In this review we examine the current state of knowledge regarding the prion-like properties of proteins associated with ALS pathology as well as their possible mechanisms of transmission.

Activity-dependent secretion of progranulin from synapses.

The secreted growth factor progranulin (PGRN) has been shown to be important for regulating neuronal survival and outgrowth, as well as synapse formation and function. Mutations in the PGRN gene that result in PGRN haploinsufficiency have been identified as a major cause of frontotemporal dementia (FTD). Here we demonstrate that PGRN is colocalized with dense-core vesicle markers and is co-transported with brain-derived neurotrophic factor (BDNF) within axons and dendrites of cultured hippocampal neurons in both anterograde and retrograde directions. We also show that PGRN is secreted in an activity-dependent manner from synaptic and extrasynaptic sites, and that the temporal profiles of secretion are distinct in axons and dendrites. Neuronal activity is also shown to increase the recruitment of PGRN to synapses and to enhance the density of PGRN clusters along axons. Finally, treatment of neurons with recombinant PGRN is shown to increase synapse density, while decreasing the size of the presynaptic compartment and specifically the number of synaptic vesicles per synapse. Together, this indicates that activity-dependent secretion of PGRN can regulate synapse number and structure.

Sustainable Cement Composite Integrating Waste Cellulose Fibre: A Comprehensive Review.

This review presents the research conducted to date in the field of cement-based composites reinforced with waste paper-based cellulose fibres, focusing on their composition, mechanical properties, and durability characteristics. The literature demonstrates that the properties of raw material (depending on their own chemical composition) significantly influence the formation of the cement composite binders. When considering fresh properties, the presence of silica and magnesium compounds generally lead to favourable effects on the setting of the cement composite when combined with waste paper cellulose fibre. Reduction in density values, i.e., approximately 25%, was observed with the inclusion of waste paper fibres from 20 to 80% in cement composites. The homogeneous dispersion of fibres in the matrix is one of the crucial factors to achieve in order to develop composites with well-balanced mechanical properties incorporating waste paper cellulose fibres. Hence, dispersion of fibres can be improved by increasing water quantity corresponding to the optimal value, which was a water/cement ratio of 0.64 leading to optimum strength properties of the composite. Even though the effect of fibre dispersion in the matrix improves with the addition of water, higher porosity and voids govern the strength properties beyond an optimum water-to-cement ratio. Higher porosity leads to an increase in the water absorption and a lowering of the thermal conductivity properties with the addition of paper fibre in cement binders. Paper fibre absorbs a high amount of water leading to higher water absorption. This phenomenon is related to the hydrophilic nature of cellulosic fibres absorbing some volume of water due to their microporous structure.

Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice.

Loss-of-function mutations in the progranulin (GRN) gene are a common cause of autosomal dominant frontotemporal lobar degeneration, a fatal and progressive neurodegenerative disorder common in people less than 65 years of age. In the brain, progranulin is expressed in multiple regions at varying levels, and has been hypothesized to play a neuroprotective or neurotrophic role. Four neurotoxic agents were injected in vivo into constitutive progranulin knockout (Grn(-/-)) mice and their wild-type (Grn(+/+)) counterparts to assess neuronal sensitivity to toxic stress. Administration of 3-nitropropionic acid, quinolinic acid, kainic acid, and pilocarpine induced robust and measurable neuronal cell death in affected brain regions, but no differential cell death was observed between Grn(+/+) and Grn(-/-) mice. Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study.