The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer's Disease Reveals New Insights for AD Study.

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment, and its pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second compared carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in the pre-symptom stages. Finally, we analyzed the differentially expressed proteins (DEPs) for biological and functional enrichment. These proteins showed impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways, in line with previous AD reports. Our study is the first to conduct a proteomic analysis of MSCs from the Jalisco FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

PSEN1 c.1292C<A Variant and Early-Onset Alzheimer's Disease: A Scoping Review.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive loss of cognitive function, with ß-amyloid plaques and neurofibrillary tangles being its major pathological findings. Although the disease mainly affects the elderly, c. 5-10% of the cases are due to PSEN1, PSEN2, and APP mutations, principally associated with an early onset of the disease. The A413E (rs63750083) PSEN1 variant, identified in 2001, is associated with early-onset Alzheimer's disease (EOAD). Although there is scant knowledge about the disease's clinical manifestations and particular features, significant clinical heterogeneity was reported, with a high incidence of spastic paraparesis (SP), language impairments, and psychiatric and motor manifestations. This scoping review aims to synthesize findings related to the A431E variant of PSEN1. In the search, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the guidelines proposed by Arksey and O'Malley. We searched and identified 247 studies including the A431E variant of PSEN1 from 2001 to 2021 in five databases and one search engine. After the removal of duplicates, and apply inclusion criteria, 42 studies were finally included. We considered a narrative synthesis with a qualitative approach for the analysis of the data. Given the study sample conformation, we divided the results into those carried out only with participants carrying A431E (seven studies), subjects with PSEN variants (11 studies), and variants associated with EOAD in PSEN1, PSEN2, and APP (24 studies). The resulting synthesis indicates most studies involve Mexican and Mexican-American participants in preclinical stages. The articles analyzed included carrier characteristics in categories such as genetics, clinical, imaging techniques, neuropsychology, neuropathology, and biomarkers. Some studies also considered family members' beliefs and caregivers' experiences. Heterogeneity in both the studies found and carrier samples of EOAD-related gene variants does not allow for the generalization of the findings. Future research should focus on reporting data on the progression of carrier characteristics through time and reporting results independently or comparing them across variants.

Novel Thermal and Microscopic Techniques To Determine the Causes of Suboptimal Combustion Performance at Colombian Stoker Furnaces.

This study presents the application of a novel approach, using thermal and optical techniques, to identify the causes of poor burnout performance of Colombian stoker furnaces in the Cauca Valley State. The four coals used in these furnaces were characterized to obtain particle size distribution, particle and tapped density, elemental and proximate composition, mineral composition, and maceral content. Up to 80% incomplete combustion was noted in macro-TGA tests compared to complete combustion in a micro-TGA. Reflectance and intrinsic reactivity measurements were for chars prepared in three different particle sizes (<6, 6-19, and 19 mm), three temperatures (700, 900, and 1050 °C), and three residence times (10, 30, and 120 min). Two of the coals produced char samples with reflectance values above 6%, which matched those seen in the stoker, indicating that the furnace temperature was not the cause of poor combustion and that only two of the four coals were likely to be present in the furnace bottom ash. These tests were also able to prove that oxygen diffusion limitation was the root cause of the poor burnout where the carbon inside the furnace bottom ash was shielded from oxygen ingress through the formation of a nonpermeable slag layer. Thus, this study demonstrates the potential of both thermal profiling and optical reflectance as a tool for forensically evaluating the thermal history and operational performance of furnaces.

Upgrading of Low-Grade Colombian Coals via Low-Cost and Sustainable Calcium Nitrate Dense Media Separation.

Wet coal beneficiation in Colombia is prohibitive due to the high cost and scarcity of commonly used dense media. The practical value of this study is that it demonstrates for the first time that a common fertilizer, calcium nitrate, can be used in the beneficiation of low-grade Colombian coals. Three high-ash low-grade Colombian coals (Valle, Cundinamarca, and Antioquia) commonly used in Colombian sugar mill stoker furnaces were tested. Coal mineralogy and prevalence were analyzed before and after washing using mineral liberation analysis. The swelling potential of the coals was assessed using a novel application of thermal mechanical analysis (TMA) and an ash fusion oven (AFO). Calcium nitrate reduced ash levels across all size fractions, even for high-ash coals like Valle (29% to below 7%) to acceptable levels for coke manufacturing or pulverized fuel combustion. The novel use of TMA and AFO to analyze coal swelling demonstrated that swelling varies under constrained and unconstrained conditions and the small sample size allows for rapid testing of coal swelling. This study has demonstrated that the use of common fertilizers can allow beneficiation to become a processing option for low-grade coals in Official Development Assistance countries where conventional dense media is prohibitively expensive.