Towards improving classification of Canadian dark-cutting beef carcasses: Consumer sensory evaluation.

This study evaluated whether different colour intensities of ribeye steaks from dark-cutting (B4 grade) beef carcasses (Dark-B4DK/Moderate-B4MD) were similar in appearance and eating quality to steaks from normal (N) carcasses of lower marbling grades (AA or A) as assessed by consumers. The B4MDAAA and B4DK/MDAA had similar raw appearance and eating quality to N carcasses with a one quality downgrade for marbling (P > 0.1), potentially supporting a B4MDAAA and B4DK/MDAA re-class to NAA and NA grades, respectively.

Amyloid-β precursor protein mutant zebrafish exhibit seizure susceptibility that depends on prion protein.

It has been proposed that Amyloid β Precursor Protein (APP) might act as a rheostat controlling neuronal excitability, but mechanisms have remained untested. APP and its catabolite Aβ are known to impact upon synapse function and dysfunction via their interaction with the prion protein (PrP), suggesting a candidate pathway. Here we test if PrP is required for this APP function in vivo, perhaps via modulating mGluR5 ion channels.

Prion gene paralogs are dispensable for early zebrafish development and have nonadditive roles in seizure susceptibility.

Normally folded prion protein (PrP) and its functions in healthy brains remain underappreciated compared with the intense study of its misfolded forms ("prions," PrP) during the pathobiology of prion diseases. This impedes the development of therapeutic strategies in Alzheimer's and prion diseases. Disrupting the zebrafish homologs of PrP has provided novel insights; however, mutagenesis of the zebrafish paralog did not recapitulate previous dramatic developmental phenotypes, suggesting redundancy with the paralog.

An ancient conserved role for prion protein in learning and memory.

The misfolding of cellular prion protein (PrP) to form PrP Scrapie (PrP) is an exemplar of toxic gain-of-function mechanisms inducing propagated protein misfolding and progressive devastating neurodegeneration. Despite this, PrP function in the brain is also reduced and subverted during prion disease progression; thus understanding the normal function of PrP in healthy brains is key. Disrupting PrP in mice has led to a myriad of controversial functions that sometimes map onto disease symptoms, including a proposed role in memory or learning.

Reduced Abundance and Subverted Functions of Proteins in Prion-Like Diseases: Gained Functions Fascinate but Lost Functions Affect Aetiology.

Prions have served as pathfinders that reveal many aspects of proteostasis in neurons. The recent realization that several prominent neurodegenerative diseases spread via a prion-like mechanism illuminates new possibilities for diagnostics and therapeutics. Thus, key proteins in Alzheimer Disease and Amyotrophic lateral sclerosis (ALS), including amyloid-β precursor protein, Tau and superoxide dismutase 1 (SOD1), spread to adjacent cells in their misfolded aggregated forms and exhibit template-directed misfolding to induce further misfolding, disruptions to proteostasis and toxicity.

Protein Misfolding in Prion and Prion-Like Diseases: Reconsidering a Required Role for Protein Loss-of-Function.

Prion disease research has contributed much toward understanding other neurodegenerative diseases, including recent demonstrations that Alzheimer's disease (AD) and other neurodegenerative diseases are prion-like. Prion-like diseases involve the spread of degeneration between individuals and/or among cells or tissues via template directed misfolding, wherein misfolded protein conformers propagate disease by causing normal proteins to misfold. Here we use the premise that AD, amyotrophic lateral sclerosis, Huntington's disease, and other similar diseases are prion-like and ask: Can we apply knowledge gained from studies of these prion-like diseases to resolve debates about classical prion diseases? We focus on controversies about what role(s) protein loss-of-function might have in prion diseases because this has therapeutic implications, including for AD.

Zebrafish prion protein PrP2 controls collective migration process during lateral line sensory system development.

Prion protein is involved in severe neurodegenerative disorders but its physiological role is still in debate due to an absence of major developmental defects in knockout mice. Previous reports in zebrafish indicate that the two prion genes, PrP1 and PrP2, are both involved in several steps of embryonic development thus providing a unique route to discover prion protein function. Here we investigate the role of PrP2 during development of a mechano-sensory system, the posterior lateral line, using morpholino knockdown and PrP2 targeted inactivation.

Evaluating the mutagenic activity of targeted endonucleases containing a Sharkey FokI cleavage domain variant in zebrafish.

Synthetic targeted endonucleases such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have recently emerged as powerful tools for targeted mutagenesis, especially in organisms that are not amenable to embryonic stem cell manipulation. Both ZFNs and TALENs consist of DNA-binding arrays that are fused to the nonspecific FokI nuclease domain. In an effort to improve targeted endonuclease mutagenesis efficiency, we enhanced their catalytic activity using the Sharkey FokI nuclease domain variant.

Targeted mutation of the gene encoding prion protein in zebrafish reveals a conserved role in neuron excitability.

The function of the cellular prion protein (PrP(C)) in healthy brains remains poorly understood, in part because Prnp knockout mice are viable. On the other hand, transient knockdown of Prnp homologs in zebrafish (including two paralogs, prp1 and prp2) has suggested that PrP(C) is required for CNS development, cell adhesion, and neuroprotection. It has been argued that zebrafish Prp2 is most similar to mammalian PrP(C), yet it has remained intransigent to the most thorough confirmations of reagent specificity during knockdown.

Amyloid beta precursor protein and prion protein have a conserved interaction affecting cell adhesion and CNS development.

Genetic and biochemical mechanisms linking onset or progression of Alzheimer Disease and prion diseases have been lacking and/or controversial, and their etiologies are often considered independent. Here we document a novel, conserved and specific genetic interaction between the proteins that underlie these diseases, amyloid-β precursor protein and prion protein, APP and PRP, respectively. Knockdown of APP and/or PRNP homologs in the zebrafish (appa, appb, prp1, and prp2) produces a dose-dependent phenotype characterized by systemic morphological defects, reduced cell adhesion and CNS cell death.