Showing papers by "Emyr Lloyd-Evans published in 2023"
TL;DR: In this article , the authors identify pathological hallmarks of TRPML1 dysregulation in LOAD neurons, including increased perinuclear clustering and vacuolation of endolysosomes.
Abstract: Abnormalities in the endosomal-autophagic-lysosomal (EAL) system are an early event in Alzheimer's disease (AD) pathogenesis. However, the mechanisms underlying these abnormalities are unclear. The transient receptor potential channel mucolipin 1(TRPML1), a vital endosomal-lysosomal Ca2+ channel whose loss of function leads to neurodegeneration, has not been investigated with respect to EAL pathogenesis in late onset AD (LOAD). Here, we identify pathological hallmarks of TRPML1 dysregulation in LOAD neurons, including increased perinuclear clustering and vacuolation of endolysosomes. We reveal that iPSC human cortical neurons expressing APOE e4, the strongest genetic risk factor for LOAD, have significantly diminished TRPML1-induced endolysosomal Ca2+ release. Furthermore, we found that blocking TRPML1 function in primary neurons by depleting the TRPML1 agonist PI(3,5)P2. via PIKfyve inhibition, recreated multiple features of EAL neuropathology evident in LOAD. This included increased endolysosomal Ca2+ content, enlargement and perinuclear clustering of endolysosomes, autophagic vesicle accumulation, and early endosomal enlargement. Strikingly, these AD-like neuronal EAL defects were rescued by TRPML1 reactivation using its synthetic agonist ML-SA1. These findings implicate defects in TRPML1 in LOAD EAL pathogenesis and present TRPML1 as a potential therapeutic target.
1 citations
TL;DR: In this paper , the authors reviewed clinical conditions and medications leading to an imbalance between thrombosis and hemostatic capacity, including anticoagulation monitoring strategies, in patients on mechanical support.
TL;DR: In this article , a whey protein isolate and native phosphocaseins (PC) were processed with retinyl acetate (RAC) using pressure-assisted technological tools to improve RAC embedding through processing-induced protein structural changes.
TL;DR: For example, unrelated cord blood (UCB) is now the preferred donor source when hematopoietic stem cell transplantation (HSCT) is used to treat patients with lysosomal storage disorders (LSD) as mentioned in this paper .
TL;DR: For example, unrelated cord blood (UCB) is now the preferred donor source when hematopoietic stem cell transplantation (HSCT) is used to treat patients with lysosomal storage disorders (LSD) as discussed by the authors .
TL;DR: In this article , a whey protein isolate and native phosphocaseins (PC) were processed with retinyl acetate (RAC) using pressure-assisted technological tools to improve RAC embedding through processing-induced protein structural changes.
TL;DR: In this article , a subset of frontotemporal dementia cases are neuropathologically defined by tau-negative, TAR DNA-binding protein-43 and ubiquitin-positive inclusions in the brain and are associated with mutations in the progranulin gene (GRN).
TL;DR: In this paper , the role of carbohydrate binding in the toxicity of the most utilized group of Bt pesticidal proteins, three domain Cry (3D-Cry) toxins, is discussed.
Abstract: Abstract Bacillus thuringiensis (Bt) proteins are an environmentally safe and effective alternative to chemical pesticides and have been used as biopesticides, with great commercial success, for over 50 years. Global agricultural production is predicted to require a 70% increase until 2050 to provide for an increasing population. In addition to agriculture, Bt proteins are utilized to control human vectors of disease—namely mosquitoes—which account for >700 000 deaths annually. The evolution of resistance to Bt pesticial toxins threatens the progression of sustainable agriculture. Whilst Bt protein toxins are heavily utilized, the exact mechanisms behind receptor binding and toxicity are unknown. It is critical to gain a better understanding of these mechanisms in order to engineer novel toxin variants and to predict, and prevent, future resistance evolution. This review focuses on the role of carbohydrate binding in the toxicity of the most utilized group of Bt pesticidal proteins—three domain Cry (3D-Cry) toxins.
TL;DR: In this article , the authors conducted a state-of-the-art search of the best evidence available to date, in terms of diagnostic methods and emerging therapies, to offer the clinician a practical vision for a comprehensive approach.
TL;DR: In this paper , a recent study has questioned the mechanism of action of GPN and concluded that, acutely, it does not permeabilize lysosomes but releases Ca2+ directly from the ER instead.
TL;DR: In this article , a small molecule scavenger was synthesized for the detection and quantification of copper in serum and systemically in vivo in vitro diagnostics, the developed technique involves only a routine capillary blood sampling or venipuncture, removing the need for invasive biopsies.
TL;DR: In this paper , the authors investigated the amount of Bradysia odoriphaga larval feeding at each developmental stage and the related morphology of salivary glands, and they concluded that the decrease of daily feeding amount in the last instar was related to the structural change of saliva gland closely.
TL;DR: In this paper , a whey protein isolate and native phosphocaseins (PC) were processed with retinyl acetate (RAC) using pressure-assisted technological tools to improve RAC embedding through processing-induced protein structural changes.