Autoclave treatment fails to completely inactivate DLB alpha-synuclein seeding activity.

Synucleinopathies are characterized by the deposition of alpha-synuclein (α-syn) aggregates in brain tissue. Pathological α-syn aggregates propagate in a prion-like manner and display prion-like biochemical properties. Using RT-QuIC, we measured α-syn seeding activity from brains of Dementia with Lewy body (DLB) patients post autoclave.

β-Barrel proteins tether the outer membrane in many Gram-negative bacteria.

Gram-negative bacteria have a cell envelope that comprises an outer membrane (OM), a peptidoglycan (PG) layer and an inner membrane (IM). The OM and PG are load-bearing, selectively permeable structures that are stabilized by cooperative interactions between IM and OM proteins. In Escherichia coli, Braun's lipoprotein (Lpp) forms the only covalent tether between the OM and PG and is crucial for cell envelope stability; however, most other Gram-negative bacteria lack Lpp so it has been assumed that alternative mechanisms of OM stabilization are present.

Increases in theta CSD power and coherence during a calibrated stop-signal task: implications for goal-conflict processing and the Behavioural Inhibition System.

Psychologists have identified multiple different forms of conflict, such as information processing conflict and goal conflict. As such, there is a need to examine the similarities and differences in neurology between each form of conflict. To address this, we conducted a comprehensive electroencephalogram (EEG) analysis of Shadli, Glue, McIntosh, and McNaughton's calibrated stop-signal task (SST) goal-conflict task.

Altered distribution, aggregation, and protease resistance of cellular prion protein following intracranial inoculation.

Prion protein (PrPC) is a protease-sensitive and soluble cell surface glycoprotein expressed in almost all mammalian cell types. PrPSc, a protease-resistant and insoluble form of PrPC, is the causative agent of prion diseases, fatal and transmissible neurogenerative diseases of mammals. Prion infection is initiated via either ingestion or inoculation of PrPSc or when host PrPC stochastically refolds into PrPSc.

Processing of high-titer prions for mass spectrometry inactivates prion infectivity.

Prions represent a class of universally fatal and transmissible neurodegenerative disorders that affect humans and other mammals. The prion agent contains a pathologically aggregated form of the host prion protein that can transmit infectivity without any bacterial or viral component and is thus difficult to inactivate using disinfection protocols designed for infectious microorganisms. Methods for prion inactivation include treatment with acids, bases, detergents, bleach, prolonged autoclaving and incineration.

Group and individual analyses of pre-, peri-, and post-movement related alpha and beta oscillations during a single continuous monitoring task.

Band power linked to lower and upper alpha (i.e. 8-10Hz; 10-12Hz) and lower and upper beta (i.

Mitochondrial Respiration Is Impaired during Late-Stage Hamster Prion Infection.

Mitochondria are crucial to proper neuronal function and overall brain health. Mitochondrial dysfunction within the brain has been observed in many neurodegenerative diseases, including prion disease. Several markers of decreased mitochondrial activity during prion infection have been reported, yet the bioenergetic respiratory status of mitochondria from prion-infected animals is unknown.

Complications caused by adenosine during catheter ablation of atrial fibrillation.

Adenosine is increasingly used to assess for dormant conduction following pulmonary vein isolation during atrial fibrillation ablation. While the half-life of adenosine is typically short and side effects transient, operators should be aware of more serious, lasting adverse reactions including anaphylaxis and bronchospasm.

Cellular prion protein is present in mitochondria of healthy mice.

Cellular prion protein (PrP) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. PrP misfolds to a pathogenic isoform PrP, the causative agent of neurodegenerative prion diseases. The precise function of PrP remains elusive but may depend upon its cellular localization.

Relative Abundance of apoE and Aβ1-42 Associated with Abnormal Prion Protein Differs between Creutzfeldt-Jakob Disease Subtypes.

Aggregated and protease-resistant mammalian prion protein (PrP) is the primary protein component of infectious prions. Enriched PrP preparations are often used to study the mechanisms that underly prion disease. However, most enrichment procedures are relatively nonspecific and tend to yield significant amounts of non-PrP components including various proteins that could confound functional and structural studies.

The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc). By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrP(Sc).

Proteomics applications in prion biology and structure.

Prion diseases are a heterogeneous class of fatal neurodegenerative disorders associated with misfolding of host cellular prion protein (PrP(C)) into a pathological isoform, termed PrP(Sc). Prion diseases affect various mammals, including humans, and effective treatments are not available. Prion diseases are distinguished from other protein misfolding disorders - such as Alzheimer's or Parkinson's disease - in that they are infectious.

Proteomics analysis of amyloid and nonamyloid prion disease phenotypes reveals both common and divergent mechanisms of neuropathogenesis.

Prion diseases are a heterogeneous group of neurodegenerative disorders affecting various mammals including humans. Prion diseases are characterized by a misfolding of the host-encoded prion protein (PrP(C)) into a pathological isoform termed PrP(Sc). In wild-type mice, PrP(C) is attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor and PrP(Sc) typically accumulates in diffuse nonamyloid deposits with gray matter spongiosis.

Recombinant prion protein refolded with lipid and RNA has the biochemical hallmarks of a prion but lacks in vivo infectivity.

During prion infection, the normal, protease-sensitive conformation of prion protein (PrP(C)) is converted via seeded polymerization to an abnormal, infectious conformation with greatly increased protease-resistance (PrP(Sc)). In vitro, protein misfolding cyclic amplification (PMCA) uses PrP(Sc) in prion-infected brain homogenates as an initiating seed to convert PrP(C) and trigger the self-propagation of PrP(Sc) over many cycles of amplification. While PMCA reactions produce high levels of protease-resistant PrP, the infectious titer is often lower than that of brain-derived PrP(Sc).

Activation of the innate signaling molecule MAVS by bunyavirus infection upregulates the adaptor protein SARM1, leading to neuronal death.

La Crosse virus (LACV), a zoonotic Bunyavirus, is a major cause of pediatric viral encephalitis in the United States. A hallmark of neurological diseases caused by LACV and other encephalitic viruses is the induction of neuronal cell death. Innate immune responses have been implicated in neuronal damage, but no mechanism has been elucidated.

Isolation of novel synthetic prion strains by amplification in transgenic mice coexpressing wild-type and anchorless prion proteins.

Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrP(res)]) of the cellular prion protein (PrP(C)). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrP(C). Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrP(C) and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrP(C).

Behavioural Inhibition System (BIS) sensitivity differentiates EEG theta responses during goal conflict in a continuous monitoring task.

Previous research has revealed that EEG theta oscillations are affected during goal conflict processing. This is consistent with the behavioural inhibition system (BIS) theory of anxiety (Gray & McNaughton, 2000). However, studies have not attempted to relate these BIS-related theta effects to BIS personality measures.

Dissociation of recombinant prion protein fibrils into short protofilaments: implications for the endocytic pathway and involvement of the N-terminal domain.

Fibril dissociation is necessary for efficient conversion of normal prion protein to its misfolded state and continued propagation into amyloid. Recent studies have revealed that conversion occurs along the endocytic pathway. To improve our understanding of the dissociation process, we have investigated the effect of low pH on the stability of recombinant prion fibrils.

The catalytic machinery of a key enzyme in amino Acid biosynthesis.

The aspartate pathway of amino acid biosynthesis is essential for all microbial life but is absent in mammals. Characterizing the enzyme-catalyzed reactions in this pathway can identify new protein targets for the development of antibiotics with unique modes of action. The enzyme aspartate β-semialdehyde dehydrogenase (ASADH) catalyzes an early branch point reaction in the aspartate pathway.

Role of cyclophilin A from brains of prion-infected mice in stimulation of cytokine release by microglia and astroglia in vitro.

Prion diseases or transmissible spongiform encephalopathy diseases are typically characterized by deposition of abnormally folded partially protease-resistant host-derived prion protein (PrPres), which is associated with activated glia and increased release of cytokines. This neuroinflammatory response may play a role in transmissible spongiform encephalopathy pathogenesis. We previously reported that brain homogenates from prion-infected mice induced cytokine protein release in primary astroglial and microglial cell cultures.

Identification and removal of proteins that co-purify with infectious prion protein improves the analysis of its secondary structure.

Prion diseases are neurodegenerative disorders associated with the accumulation of an abnormal isoform of the mammalian prion protein (PrP). Fourier transform infrared spectroscopy (FTIR) has previously been used to show that the conformation of aggregated, infectious PrP (PrP(Sc) ) varies between prion strains and these unique conformations may determine strain-specific disease phenotypes. However, the relative amounts of α-helix, β-sheet and other secondary structures have not always been consistent between studies, suggesting that other proteins might be confounding the analysis of PrP(Sc) secondary structure.