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Prion diseases are caused by prions, which are proteinaceous infectious particles that have been identified as causative factors of transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease (CJD). Prion diseases are devastating neurodegenerative disorders in humans and many animals, including sheep, cows, deer, cats, and camels. Prion diseases are classified into sporadic and genetic forms. Additionally, a third, environmentally acquired category exists. This type includes kuru, iatrogenic CJD caused by human dura mater grafts or human pituitary-derived hormones, and variant CJD transmitted through food contaminated with bovine spongiform encephalopathy prions. Bovine spongiform encephalopathy and variant CJD have nearly been controlled, but chronic wasting disease, a prion disease affecting deer, is spreading widely in North America and South Korea and recently in Northern Europe. Recently, amyloid-beta, alpha-synuclein, and other proteins related to Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases were reported to have prion features such as transmission to animals. Amyloid-beta transmission to humans has been suggested in iatrogenic CJD cases and in cerebral amyloid angiopathy cases with cerebral bleeding occurring long after childhood neurosurgery with or without cadaveric dura mater transplantation. These findings indicate that diseases caused by various prions, namely various transmissible proteins, appear to be a threat, particularly in the current longevity society. Prion disease represented by CJD has obvious transmissibility and is considered to be an "archetype of various neurodegenerative diseases". Overcoming prion diseases is a top priority currently in our society, and this strategy will certainly contribute to elucidating pathomechanism of other neurodegenerative diseases and developing new therapies for them. • Environmentally acquired category of prion diseases, including kuru, iatrogenic CJD, and variant CJD, exists. • Animal prion diseases are considered as new emerging prion diseases threatening humans. • Prion disease is considered to be an "archetype of various neurodegenerative diseases". • Overcoming prion diseases is expected to lead to developing new potential therapies for other neurodegenerative diseases. • International collaboration and cooperation are necessary in the fight against the emerging "prion threat". [ABSTRACT FROM AUTHOR]

Conformational conversion of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases. However, the conversion mechanism remains to be elucidated. Here, we generated Tg(PrPΔ91-106)-8545/Prnp0/0 mice, which overexpress mouse PrP lacking residues 91-106. We showed that none of the mice became sick after intracerebral inoculation with RML, 22L, and FK-1 prion strains nor accumulated PrPScΔ91-106 in their brains except for a small amount of PrPScΔ91-106 detected in one 22L-inoculated mouse. However, they developed disease around 85 days after inoculation with bovine spongiform encephalopathy (BSE) prions with PrPScΔ91-106 in their brains. These results suggest that residues 91-106 are important for PrPC conversion into PrPSc in infection with RML, 22L, and FK-1 prions but not BSE prions. We then narrowed down the residues 91-106 by transducing various PrP deletional mutants into RML- and 22L-infected cells and identified that PrP mutants lacking residues 97-99 failed to convert into PrPSc in these cells. Our in vitro conversion assay also showed that RML, 22L, and FK-1 prions did not convert PrPΔ97-99 into PrPScΔ97-99, but BSE prions did. We further found that PrP mutants with proline residues at positions 97 to 99 or charged residues at positions 97 and 99 completely or almost completely lost their converting activity into PrPSc in RML-and 22L-infected cells. These results suggest that the structurally flexible and noncharged residues 97-99 could be important for PrPC conversion into PrPSc following infection with RML, 22L, and FK-1 prions but not BSE prions. [ABSTRACT FROM AUTHOR]

• Mitochondria are paramount to central nervous system health and maintenance. • Mitochondrial capacity is compromised in prion diseases. • Mitochondria dysfunction exacerbates the progression and severity of prion diseases. • Mitochondria-targeted antioxidants in prion models have shown promising results. • Mitochondrial transplant may help to develop promising therapeutic options. Prion diseases encompass a group of incurable neurodegenerative disorders that occur due to the misfolding and aggregation of infectious proteins. The most well-known prion diseases are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (also known as mad cow disease), and kuru. It is estimated that around 1–2 persons per million worldwide are affected annually by prion disorders. Infectious prion proteins propagate in the brain, clustering in the cells and rapidly inducing tissue degeneration and death. Prion disease alters cell metabolism and energy production damaging mitochondrial function and dynamics leading to a fast accumulation of damage. Dysfunction of mitochondria could be considered as an early precursor and central element in the pathogenesis of prion diseases such as in sporadic CJD. Preserving mitochondria function may help to resist the rapid spread and damage of prion proteins and even clearance. In the war against prions and other degenerative diseases, studying how to preserve the function of mitochondria by using antioxidants and even replacing them with artificial mitochondrial transfer/transplant (AMT/T) may bring a new hope and lead to an increase in patients' survival. In this perspective review, we provide key insights about the relationship between the progression of prion disease and mitochondria, in which understanding how protecting mitochondria function and viability by using antioxidants or AMT/T may help to develop novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Human prion diseases, including Creutzfeldt-Jakob disease (CJD), are rapidly progressive, invariably fatal neurodegenerative conditions with no effective therapies. Their pathogenesis involves the obligate recruitment of cellular prion protein (PrPC) into self-propagating multimeric assemblies or prions. Preclinical studies have firmly validated the targeting of PrPC as a therapeutic strategy. We aimed to evaluate a first-in-human treatment programme using an anti-PrPC monoclonal antibody under a Specials Licence.Methods: We generated a fully humanised anti-PrPC monoclonal antibody (an IgG4κ isotype; PRN100) for human use. We offered treatment with PRN100 to six patients with a clinical diagnosis of probable CJD who were not in the terminal disease stages at the point of first assessment and who were able to readily travel to the University College London Hospital (UCLH) Clinical Research Facility, London, UK, for treatment. After titration (1 mg/kg and 10 mg/kg at 48-h intervals), patients were treated with 80-120 mg/kg of intravenous PRN100 every 2 weeks until death or withdrawal from the programme, or until the supply of PRN100 was exhausted, and closely monitored for evidence of adverse effects. Disease progression was assessed by use of the Medical Research Council (MRC) Prion Disease Rating Scale, Motor Scale, and Cognitive Scale, and compared with that of untreated natural history controls (matched for disease severity, subtype, and PRNP codon 129 genotype) recruited between Oct 1, 2008, and July 31, 2018, from the National Prion Monitoring Cohort study. Autopsies were done in two patients and findings were compared with those from untreated natural history controls.Findings: We treated six patients (two men; four women) with CJD for 7-260 days at UCLH between Oct 9, 2018, and July 31, 2019. Repeated intravenous dosing of PRN100 was well tolerated and reached the target CSF drug concentration (50 nM) in four patients after 22-70 days; no clinically significant adverse reactions were seen. All patients showed progressive neurological decline on serial assessments with the MRC Scales. Neuropathological examination was done in two patients (patients 2 and 3) and showed no evidence of cytotoxicity. Patient 2, who was treated for 140 days, had the longest clinical duration we have yet documented for iatrogenic CJD and showed patterns of disease-associated PrP that differed from untreated patients with CJD, consistent with drug effects. Patient 3, who had sporadic CJD and only received one therapeutic dose of 80 mg/kg, had weak PrP synaptic labelling in the periventricular regions, which was not a feature of untreated patients with sporadic CJD. Brain tissue-bound drug concentrations across multiple regions in patient 2 ranged from 9·9 μg per g of tissue (SD 0·3) in the thalamus to 27·4 μg per g of tissue (1·5) in the basal ganglia (equivalent to 66-182 nM).Interpretation: Our academic-led programme delivered what is, to our knowledge, the first rationally designed experimental treatment for human prion disease to a small number of patients with CJD. The treatment appeared to be safe and reached encouraging CSF and brain tissue concentrations. These findings justify the need for formal efficacy trials in patients with CJD at the earliest possible clinical stages and as prophylaxis in those at risk of prion disease due to PRNP mutations or prion exposure.Funding: The Cure CJD Campaign, the National Institute for Health Research UCLH Biomedical Research Centre, the Jon Moulton Charitable Trust, and the UK MRC. [ABSTRACT FROM AUTHOR]

Prions are transmissible protein pathogens most reliably detected by a bioassay in a suitable host, typically mice. However, the mouse bioassay is slow and cumbersome, and relatively insensitive to low titers of prion infectivity. Prions can be detected biochemically in vitro by the protein misfolding cyclic amplification (PMCA) technique, which amplifies disease-associated prion protein but does not detect bona fide prion infectivity. Here, we demonstrate that Drosophila transgenic for bovine prion protein (PrP) expression can serve as a model system for the detection of bovine prions significantly more efficiently than either the mouse prion bioassay or PMCA. Strikingly, bovine PrP transgenic Drosophila could detect bovine prion infectivity in the region of a 10-12 dilution of classical bovine spongiform encephalopathy (BSE) inoculum, which is 106-fold more sensitive than that achieved by the bovine PrP mouse bioassay. A similar level of sensitivity was observed in the detection of H-type and L-type atypical BSE and sheep-passaged BSE by bovine PrP transgenic Drosophila. Bioassays of bovine prions in Drosophila were performed within 7 weeks, whereas the mouse prion bioassay required at least a year to assess the same inoculum. In addition, bovine PrP transgenic Drosophila could detect classical BSE at a level 105-fold lower than that achieved by PMCA. These data show that PrP transgenic Drosophila represent a new tractable prion bioassay for the efficient and sensitive detection of mammalian prions, including those of known zoonotic potential. [ABSTRACT FROM AUTHOR]

Prion diseases are fatal neurodegenerative disorders caused by the deposition of abnormal prion protein aggregates (PrPSc) in the central nervous system. This study aimed to evaluate the use of iodinated pyridyl benzofuran (IPBF) derivatives as single-photon emission computed tomography (SPECT) probes for the detection of cerebral PrPSc deposits. In vitro binding assays of IPBF derivatives were carried out in the recombinant mouse prion protein (rMoPrP) and brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice. SPECT imaging of 5-(5-[123I]iodobenzofuran-2-yl)- N -methylpyridin-2-amine ([123I]IPBF-NHMe) was performed on mBSE-infected and mock-infected mice. Fluorescence microscopy results showed that fluorescence signals of IPBF derivatives corresponded to the thioflavin-T positive amyloid deposits of PrPSc in the brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice. Among the IPBF derivatives, 5-(5-iodobenzofuran-2-yl)- N -methylpyridin-2-amine (IPBF-NHMe) exhibited the highest binding affinity to the recombinant mouse prion protein (rMoPrP) aggregates with a K i of 14.3 nM. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that the [123I]IPBF-NHMe distribution in brain tissues of mBSE-infected mice co-localized with PrPSc deposits. [123I]IPBF-NHMe appears to be a prospective SPECT tracer for monitoring prion deposits in living brain tissues. [ABSTRACT FROM AUTHOR]

Gelatine is one of the components commonly used in food, cosmetics and pharmaceutical products due to its gelling properties. The most commonly used gelatines in those products are porcine and bovine gelatines. Unclear labelling and information regarding the actual sources of gelatines in products have become the main concern among societies in terms of religion and health aspects. Porcine gelatine (PG) is prohibited to be consumed by Muslim and Jewish and considered non-halal (and non-kosher) following some scholars of thought. While bovine gelatine (BG) is associated with certain diseases of bovine spongiform encephalopathy, as a consequence, there is a need to develop reliable methods for identifying gelatine sources in the products. This review highlighted some analytical methods including physico-chemical methods as well as biological methods along with advantage and disadvantage for differentiation of gelatines intended to halal authentication studies. Key Findings and Conclusions: Some analytical methods are used for screening PG and BG using physico-chemical properties including chemical precipitation, functional groups (FTIR spectroscopy), amino acid composition (liquid chromatography), detection and quantification of DNA (real-time polymerase chain reaction/RT-PCR), molecular weight distribution (electrophoresis), and protein (Enzyme-linked immunosorbent assay, ELISA). These methods are confirmed by identification of peptide markers which are specific for PG and BG using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and DNA based method using polymerase chain reaction. • Porcine gelatine is widely used in food, pharmaceutical, and cosmetics products. • Porcine gelatine is prohibited especially for Muslim because it is categorized as non-halal substance. • Physico-chemical methods for porcine gelatine detection including FTIR, high performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry. • Biological methods such as real-time PCR offer selectivity and sensitivity for porcine gelatin identification. [ABSTRACT FROM AUTHOR]

Chronic wasting disease (CWD) is caused by an unknown spectrum of prions and has become enzootic in populations of cervid species that express cellular prion protein (PrPC) molecules varying in amino acid composition. These PrPC polymorphisms can affect prion transmission, disease progression, neuropathology, and emergence of new prion strains, but the mechanistic steps in prion evolution are not understood. Here, using conformation-dependent immunoassay, conformation stability assay, and protein-misfolding cyclic amplification, we monitored the conformational and phenotypic characteristics of CWD prions passaged through deer and transgenic mice expressing different cervid PrPC polymorphisms. We observed that transmission through hosts with distinct PrPC sequences diversifies the PrPCWD conformations and causes a shift toward oligomers with defined structural organization, replication rate, and host range. When passaged in host environments that restrict prion replication, distinct co-existing PrPCWD conformers underwent competitive selection, stabilizing a new prion strain. Nonadaptive conformers exhibited unstable replication and accumulated only to low levels. These results suggest a continuously evolving diversity of CWD conformers and imply a critical interplay between CWD prion plasticity and PrPC polymorphisms during prion strain evolution. [ABSTRACT FROM AUTHOR]

• Abnormal TDP-43 aggregates have prion-like properties. • Insoluble TDP-43 accumulated in neuronal cells is propagated to other cells and Serves as seeds for further TDP-43 aggregation in them. • Suppression of propagation of pathological aggregates may be a therapeutic strategy for common neurodegenerative diseases. A neuropathological hallmark of most neurodegenerative diseases is the appearance of characteristic inclusions composed of misfolded proteins in brains of patients. Increasing evidence shows that aggregation-prone proteins such as tau, α-synuclein and TDP-43 are accumulated in a seed-dependent and self-templating manner in vitro and in vivo , suggesting that pathological protein aggregates found in these diseases function like abnormal prion protein. Indeed, insoluble tau and α-synuclein aggregates are transferred from cell to cell both in vitro and in vivo , indicating that prion-like propagation of aberrant protein aggregates may play a key role in the pathogenesis of most neurodegenerative diseases. Here, we will review the prion-like properties of TDP-43, and discuss the molecular mechanisms underlying the propagation of these accumulated proteins. The idea that aberrant protein aggregates propagate in a prion-like manner between cells opens up the possibility of novel therapeutic strategies to block the spread of these aggregates throughout the brain. [ABSTRACT FROM AUTHOR]

• Kinetics yield mechanism and rates of aggregation of tau, PrP, Aβ and α-syn in vitro. • Animal models provide evidence for differences and similarities in mechanisms in vivo. • Mathematical models of spreading/replication can connect in vitro to human disease. • Additional detail and information from experiment is needed for a quantitative model. The formation of aggregates from a range of normally soluble peptides and proteins is the hallmark of several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. Certain such aggregates possess the ability to replicate and spread pathology, within tissues and in some case also between organisms. An understanding of which processes govern the overall rate of aggregate formation is thus of key interest. Here, we discuss the fundamental molecular processes of protein aggregation, review how their rates can be determined by kinetic measurements in the test-tube, and explore the mechanistic similarities and differences to animal models and human disease. We conclude that a quantitative mathematical model for aggregate replication and spreading in vivo requires additional information but would provide a theoretical framework to understand results from different experiments and how they connect to human disease. [ABSTRACT FROM AUTHOR]

• Preclinical biomarkers are crucial for drug study design and timing of therapy in neurodegenerative diseases. • Animal models of prion disease show a long clinically silent period prior to onset despite high prion titres. • The RT-QuIC assay is a highly sensitive and specific prion seeding assay but use is unclear in preclinical stage. • Downstream protein markers of neurodegeneration are also very useful after diagnosis. • Rate of change rather than absolute biomarker value may be a more sensitive measure. Therapeutic strategies and study designs for neurodegenerative diseases have started to explore the potential of preventive treatment in healthy people, emphasising characterisation of biomarkers capable of indicating proximity to clinical onset. This need is even more pressing for individuals at risk of prion disease given its rarity which virtually precludes the probability of recruiting enough numbers for well powered preventive trials based on clinical endpoints. Experimental mouse inoculation studies have revealed a rapid exponential rise in infectious titres followed by a relative plateau of considerable duration before clinical onset. This clinically silent incubation period represents a potential window of opportunity for the adaptation of ultrasensitive prion seeding assays to define the onset of prion infection, and for neurodegenerative biomarker discovery through similarly sensitive digital immunoassay platforms. [ABSTRACT FROM AUTHOR]

• Prion diseases are neurodegenerative disorders caused by misfolded PrP protein. • Misfolded Tau protein makes the neurofilamentous lesions found in Alzheimer's disease and tauopathies. • Tau assemblies seem to behave like prion strains. • Tau pathology seems to propagate in a similar way to prion diseases. • Several unresolved issues remain to be established for both prions diseases and tauopathies. Emerging evidences linking pathological mechanisms of prions and tauopathies are accumulating. However, Tau assemblies do not yet fulfill all the criteria of prions. Here, we review recent data pointing similarities between prions and tauopathies and discuss the still existing uncertainties. [ABSTRACT FROM AUTHOR]

In this study, we propose an extended Urban Cell Transmission Model (UCTM) that uses the agent concept to handle complex traffic behavior such as signalized intersections in urban arterial traffic. In particular, the proposed model accounts for the turning and traffic signal modeling in intersections, and the lane-changing behavior. The proposed model replicates the periodical queue generation and dissipation caused by the traffic signal at the intersection. For a realistic lane-changing behavior, we define two types of lane-changing depending whether to follow the route or to obtain additional benefits from the travel time. The model is validated with the NGSIM arterial dataset and the results show that the performance of the proposed model replicates the overall urban traffic phenomena adequately. [ABSTRACT FROM AUTHOR]

• Prion disease dementias are currently not practically treatable. • A treatment approach using dual-peptide ligand masks to stop prion diseases offers many advantages. • One treatment uses modified bacteria in gastrointestinal tracts to make dual-peptide ligand masks. • Another treatment does not introduce genetically modified bacteria. Prion disease dementias are currently not practically treatable. However, a proposed treatment approach using specifically targeted dual-peptide ligand masks can mask prion surface proteins and treat specific prion diseases. Different approaches might be used to treat these prion diseases. One treatment introduces genetically modified cells into the gastrointestinal tract or other locations to produce dual-peptide ligand masks; and another treatment introduces only the dual-peptide ligand masks into the center of prion infections to mask prion surface proteins. An independent group introduced genetically modified therapeutic bacteria into large numbers of mammals, including several human volunteers, with safe and effective experimental results, without long-term colonization by the bacteria, which experimentally supports the feasibility of the first treatment. These approaches offer several advantages compared with other potential treatments against prion diseases in humans. [ABSTRACT FROM AUTHOR]

Prion diseases are a group of incurable neurodegenerative disorders that affect humans and animals via infection with proteinaceous particles called prions. Prions are composed of PrPSc, a misfolded version of the cellular prion protein (PrPC). During disease progression, PrPSc replicates by interacting with PrPC and inducing its conversion to PrPSc. As PrPSc accumulates, cellular stress mechanisms are activated to maintain cellular proteostasis, including increased protein chaperone levels. However, the exact roles of several of these chaperones remain unclear. Here, using various methodologies to monitor prion replication (i.e. protein misfolding cyclic amplification and cellular and animal infectivity bioassays), we studied the potential role of the molecular chaperone heat shock protein 70 (HSP70) in prion replication in vitro and in vivo. Our results indicated that pharmacological induction of the heat shock response in cells chronically infected with prions significantly decreased PrPSc accumulation. We also found that HSP70 alters prion replication in vitro. More importantly, prion infection of mice lacking the genes encoding stress-induced HSP70 exhibited accelerated prion disease progression compared with WT mice. In parallel with HSP70 being known to respond to endogenous and exogenous stressors such as heat, infection, toxicants, and ischemia, our results indicate that HSP70 may also play an important role in suppressing or delaying prion disease progression, opening opportunities for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Abstract Fatal Familial Insomnia (FFI) is a hereditary prion disease caused by a mutation at codon 178 of the prion-protein gene leading to a D178N substitution in the protein determining severe and selective atrophy of mediodorsal and anteroventral thalamic nuclei. FFI is characterized by physiological sleep loss, which polygraphically appears to be a slow wave sleep loss, autonomic and motor hyperactivation with peculiar episodes of oneiric stupor. Alteration of autonomic functions is a great burden for FFI patients consisting in sympathetic overactivation, dysregulation of its physiological responses and disruption of circadian rhythms. The cardiovascular system is the most frequently and severely affected confirming the increased sympathetic drive with preserved parasympathetic responses. Sleep loss, autonomic and motor hyperactivation define Agrypnia Excitata (AE), which is not exclusive to FFI, but it has been canonically described also in Morvan Syndrome and Delirium Tremens. These three conditions present different pathophysiological mechanisms but share the same thalamo-limbic impairment of which AE is one of the possible clinical presentations. FFI, and consequently also AE, is a model for the investigation of the essential role of the thalamus in the organization of body homeostasis, integrating both sleep and autonomic function control. Highlights • Slow wave sleep loss, autonomic and motor hyperactivation characterize FFI. • Sympathetic overactivation and disruption of circadianity are the key alterations. • Agrypnia Excitata (AE) is the clinical hallmark of FFI. • AE can be a marker of disorders presenting a thalamic dysfunction. • FFI is a model for understanding the role of thalamus in body homeostasis control. [ABSTRACT FROM AUTHOR]

Abstract Blood is an important animal by-product and an attractive source for animal feed production. However, the outspread of bovine spongiform encephalopathy led to strict regulations on the usage of animal by-products in animal feed. Although, the ban on certain processed animal proteins has been partially abolished in recent years, it is still challenging to distinguish legal from illegal protein additives in complex feed products using analytical methods. To overcome these gaps, this study aimed to develop a tissue-specific and sensitive immuno-based enrichment and mass spectrometry-based detection method to identify haemoglobin peptides of ruminant or porcine origin when mixed in a background of vegetal feed, fish meal, aquaculture feed, blood compounds, or milk powder. Here we report the first analytical method able to species-specifically detect adulterations of as little as 0.05%–1% (w/w) ruminant blood meal in various matrices on a quadrupole-time of flight instrument. Highlights • Targets for species-specific blood product detection are presented. • Immuno-enrichment of processed bovine and porcine haemoglobin is shown. • A LOD of 0.05% (w/w) for bovine haemoglobin in vegetal feed is achieved. • A protein extraction method is adapted for feed containing high amounts of fibre. [ABSTRACT FROM AUTHOR]

Abstract Progression of prion diseases is driven by the accumulation of prions in the brain. Ablation of microglia or deletion of the eat-me-signal, milk-fat globule epidermal growth factor VIII (Mfge8), accelerates prion pathogenesis, suggesting that microglia defend the brain by phagocytosing prions. Similar to Mfge8, developmental endothelial locus–1 (Del-1) is a secreted protein that acts as an opsonin bridging phagocytes and apoptotic cells to facilitate phagocytosis. We therefore asked whether Del-1 might play a role in controlling prion pathogenesis. We assessed the anti-inflammatory and phagocytosis-promoting functions of Del-1 in prion disease and determined whether Del-1 complements Mfge8 in prion clearance in mice with a C57BL/6J genetic background. We found that Del-1 deficiency did not change prion disease progression or lesion patterns. In addition, prion clearance and scrapie prion protein deposition were unaltered in Del-1–deficient mice. In addition, prion-induced neuroinflammation was not affected by Del-1 deficiency. We conclude that Del-1 is not a major determinant of prion pathogenesis in this context. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • P100 phages were immobilized on magnetic particles via chemical or physical method. • Effect of phage quantity, particle size and immobilization method on phage coupling. • Effective L. monocytogenes capture was achieved using phage-modified particles. • Prolonged stability was obtained using phage chemically-immobilized particles. • Selective isolation of L. monocytogenes was achieved from raw beef and milk. Abstract A bacteriophage-assisted magnetic separation method was developed for the isolation of Listeria monocytogenes from complex food matrices. The aim of this study is to understand the effect of phage immobilization methods and the magnetic particle sizes on the phage coupling and infectivity retention of the magnetic particles. In this study, bacteriophage P100-modified magnetic particles (PMMPs) were developed for the separation of L. monocytogenes from food matrices. Three sizes of magnetic particles (MP) (150 nm, 500 nm, and 1 μm) were used for phage immobilization via chemical and physical methods. The coupling ratio of phage was investigated, and the performance of each PMMP complex was evaluated by their L. monocytogenes capture efficiency. When compared to the chemical immobilization method, the physically immobilized PMMP complex achieved a higher capture efficiency initially, with excellent selectivity towards target bacteria. The PMMPs were further tested for selective isolation of L. monocytogenes using real food samples such as ground beef and whole milk. [ABSTRACT FROM AUTHOR]

Abstract After the Bovine Spongiform Encephalitis (BSE) crisis most processed animal proteins (PAPs) were banned from use in animal feed. For the foreseen reintroduction of pork PAPs in poultry feed, and poultry PAPs in pork feed and to comply with the species-to-species ban that prohibits cannibalism, a sensitive and specific TaqMan PCR detection method for poultry DNA has been designed and published. This poultry method is able to detect DNA of chicken, turkey, duck and geese in one PCR reaction. PAPs however, are a difficult and variable matrix. Therefore, the usability of the poultry method was investigated on a range of different poultry PAPs. It was shown that the poultry detection method is capable of detecting poultry DNA in eight out of nine different poultry PAPs mixed at a 0.1% level in chicken feed. The method can also detect at least 0.1% poultry PAPs mixed in pork PAPs. These results show that the poultry method fulfils the 0.1% detection limit requirement in the EU legislation. Highlights • Commercial poultry PAPs in chicken feeds and in real-life pork PAP were tested. • Sensitivity of the detection method for poultry PAP appeared to be sufficient. • The detection limit was shown to be at least 0.1% poultry PAP. • The method performance showed deviations for some mastermixes. • The PCR method meets the requirements of the EU legislation. [ABSTRACT FROM AUTHOR]

• Previous clinical trials in prion diseases have yielded important information. • Clinical trials in prion disease should consider prion disease-specific aspects. • Clinical trials in prion disease should consider clinically meaningful outcomes. • International collaboration will improve our ability to conduct clinical trials. Human prion diseases are usually rapid neurodegenerative illnesses that are invariably fatal. Despite several clinical trials, no effective treatment has been discovered in humans. Although prior clinical trials have not been successful, they provided information that is vital for the formation of future clinical trials. Among these findings is the realization that there are several prion disease-specific aspects that must be considered when conducting clinical trials. The rarity, rapidity, and clinical heterogeneity of prion disease affect study enrollment and the ability to measure treatment effects. In addition to affecting results, study methodology may also influence study enrollment. In this review, we explore several challenges to conducting clinical trials in prion disease and suggest some practical considerations. [ABSTRACT FROM AUTHOR]

Prion-related encephalopathies or transmissible spongiform encephalopathies (TSEs) are a group of rare progressive neurodegenerative disorders that are invariably fatal with often only six months elapsing from diagnosis to patient death. This makes the development of effective therapeutic strategies challenging. Nonetheless, compounds have been identified in animal models of TSE that prolong survival and, in some instances, eradicate the disease. These have been tested in the clinic, although with modest or negative outcomes. While little progress has been made over the last decade, new findings that include the ability to identify prion aggregates at low levels in biological fluids and cells may lead to the development of early-stage biomarkers for TSE. An increased focus on immunotherapeutic approaches to TSE may result in the development of novel preventive approaches for TSE. [ABSTRACT FROM AUTHOR]

• Cell-free prion replication assays promise to speed up the drug discovery process. • Astrocytes derived from human iPS cells are susceptible to human prions. • Prion-infected organotypic brain slices recapitulate prion neuropathology. • Drosophila melanogaster expressing ovine PrP can be infected with scrapie prions. • Transgenic PrP mice are valuable models for preclinical drug assessment. Prion diseases are devastating neurodegenerative disorders for which no drugs are available. The successful development of therapeutics depends on drug screening platforms and preclinical models that recapitulate key molecular and pathological features of the disease. Innovative experimental tools have been developed over the last few years that might facilitate drug discovery, including cell-free prion replication assays and prion-infected flies. However, there is still room for improvement. Animal models of genetic prion disease are few, and only partially recapitulate the complexity of the human disorder. Moreover, we still lack a human cell culture model suitable for high-content anti-prion drug screening. This review provides an overview of the models currently used in prion research, and discusses their promise and limitations for drug discovery. [ABSTRACT FROM AUTHOR]

The earliest estimate for Great Britain (GB) as a whole to achieve negligible risk (NR) status for bovine spongiform encephalopathy (BSE) is 2021. This status allows certain tissues, such as bovine tonsils, to no longer be designated as Specified Risk Materials (SRM). The BSE control model was used to estimate what effect any additional lingual tonsillar material from harvested tongues inadvertently entering the human food chain would have on the amount of infectivity being consumed. Using the baseline model, with tonsils classed as SRM, a mean of 0.08 Bovine Oral (BO) ID 50 was estimated to enter the food chain over one year for GB. Under NR status this mean was estimated to increase to 0.83 BO ID 50 . Whilst this equates to a 10 fold increase in BO ID 50 the amount is still small due to the very low likelihood of infected animals being present in the 2017 healthy slaughter population. There are a number of assumptions made within the model, namely, the amount of lingual tonsil inadvertently entering the food chain, and the infectivity titre within this particular tonsillar material. [ABSTRACT FROM AUTHOR]

Highlights • Specified risk materials controls changing in Europe for small ruminants. • A risk assessment developed to estimate the impact for one country. • Limiting to brain and spinal cord would cause little impact in edible products. • Reducing to brain only would increase the impact to food chain to a higher degree. • Recommend other countries with different health demographics evaluate their risk. Abstract Multiple controls established during the bovine spongiform encephalopathy (BSE) epidemic were not solely applied to BSE in cattle, but were implemented for scrapie in sheep and goats due to concerns over the occurrence of BSE in sheep. In the absence of BSE in sheep being observed, control measures for prion diseases are now being evaluated to ensure they remain proportionate to risk. This risk assessment, aims to estimate, by use of stochastic simulation, the impact of reducing controls for Specified Risk Materials (SRM) from sheep at abattoir. Three scenarios have been included: 1) current list of SRM; 2) brain and spinal cord of adult sheep; and 3) the brain of adult sheep. Results indicate the total amount of infectivity passing through British abattoirs is highest for atypical scrapie with nearly 3,500,000 Ovine Oral (OO) ID 50 per year. The majority of this infectivity enters Category 1 waste for incineration, with only 13,000 OO ID 50 per year within edible products. Under Scenario 2, an additional 4000 OO ID 50 per year would be classified as edible products from the lifting of restrictions on the distal ileum of adult sheep. However, if SRM removal was limited to brain, an additional 110,000 OO ID 50 per year would be permitted into edible products with the lifting of restrictions on the spinal cord of adult sheep. For classical scrapie, there is a mean estimate of infectivity of 30,000 OO ID 50 per year at abattoir. This is lower than for atypical scrapie due to the lower occurrence of this disease in Great Britain. However, more infectivity is destined to reach the food chain as the disease is peripherally distributed in the carcase. The highest contributor to the total amount of infectivity consumed per year is the intestines (duodenum and jejunum). If SRM removal is limited to the brain and spinal cord of sheep over 12 months of age, there is an approximate mean increase from 19,000 to 21,000 OO ID 50 per year diverted to edible products. If the SRM list is restricted to brain only, this increases to over 23,000 OO ID 50 per year. For the potential of sheep-BSE, there is a very low estimate of 29 OO ID 50 per year in total from carcases entering abattoir, due to the potential very rare occurrence of this disease. Given changes in SRM regulations there is a change of an additional 4 OO ID 50 per year being diverted to edible products. [ABSTRACT FROM AUTHOR]

Strict bans on specific risk materials (SRMs) are in place to prevent the spread of bovine spongiform encephalopathy (BSE). SRMs are characterized as tissues in cattle where misfolded proteins, the potential source of BSE infection, are concentrated. As a result of these bans, SRMs must be strictly isolated and disposed of, resulting in great costs for rendering companies. The increasing yield and the landfill of SRMs also exacerbated the burden on the environment. To cope with the emergence of SRMs, novel disposal methods and feasible value-added conversion routes are needed. The focus of this review is on the valorization progress achieved in the conversion of peptides derived from SRMs via an alternative disposal method, thermal hydrolysis. Promising value-added conversion of SRM-derived peptides into tackifiers, wood adhesives, flocculants, and bioplastics, is introduced. The potential conjugation strategies that can be adapted to SRM-derived peptides for desired properties are also critically reviewed. The purpose of this review is to discover a technical platform through which other hazardous proteinaceous waste, SRMs, can be treated as a high-demand feedstock for the production of renewable materials. [Display omitted] • The increasing risks of SRM disposal led to the focus on SRM valorization. • Thermal hydrolysis converts SRM into non-infectious peptides with great potential. • Diverse conjugations strategies available for the design of SRM-based products. • Current advances offered feasible SRM conversion pathways for value-added materials. • The notability, conversion pathways, application fields of SRM are still limited. [ABSTRACT FROM AUTHOR]

Recently, traceability labels with a quick response (QR) code have been printed on product packaging to help consumers easily access traceability information through their smart phones. We analyzed consumer (n = 616) attitudes and purchase intentions towards traceable minced beef/beef steak in England, and identified psychosocial determinants of their purchase using the theory of planned behavior (TPB). Respondents held a general favorable attitude with positive behavioral beliefs and high trust towards the traceable product. In the TPB model, attitude was the main determinant of intention to purchase each traceable product, followed by subjective norm and perceived behavioral control (PBC). The predictive power of the TPB model increased marginally for each sub-group when it was extended with habits, trust, and frequency of purchase. In the TPB-extended minced beef model, PBC was no longer a significant driver, and trust replaced subjective norm as the second most important predictor. In the TPB-extended beef steak model, attitude, subjective norm and PBC were all still significant drivers of intention, however, in order of importance, production process habits and origin habits were more important than PBC. These findings have importance for those involved in the production and marketing of beef. [ABSTRACT FROM AUTHOR]

Prion (PrP) diseases are neurodegenerative diseases characterized by the formation of β-sheet rich, insoluble and protease resistant protein deposits (called PrP Sc ) that occur throughout the brain. Formation of synthetic or in vitro PrP Sc can occur through on-pathway toxic oligomers. Similarly, toxic and infectious oligomers identified in cell and animal models of prion disease indicate that soluble oligomers are likely intermediates in the formation of insoluble PrP Sc . Despite the critical role of prion oligomers in disease progression, little is known about their structure. In order, to obtain structural insight into prion oligomers, we generated oligomers by shaking-induced conversion of recombinant, monomeric prion protein PrP c (spanning residues 90–231). We then obtained two-dimensional solution NMR spectra of the PrP c monomer, a 40% converted oligomer, and a 94% converted oligomer. Heteronuclear single-quantum correlation ( 1 H– 15 N) studies revealed that, in comparison to monomeric PrP c , the oligomer has intense amide peak signals in the N-terminal (residues 90–114) and C-terminal regions (residues 226–231). Furthermore, a core region with decreased mobility is revealed from residues ~127 to 225. Within this core oligomer region with decreased mobility, there is a pocket of increased amide peak signal corresponding to the middle of α-helix 2 and the loop between α-helices 2 and 3 in the PrP c monomer structure. Using high-resolution solution-state NMR, this work reveals detailed and divergent residue-specific changes in soluble oligomeric models of PrP. [ABSTRACT FROM AUTHOR]

In herds with typical moderate to low within-herd prevalence, testing for Mycobacterium avium ssp. paratuberculosis (MAP), the infectious agent of Johne's disease, will be more cost-effective if individual fecal samples are cultured in composite pools. However, sensitivity to classify a pool containing 1 or more positive individual samples as positive may depend on pool size and number of individual positive samples within a pool. Fecal samples collected from 994 dairy cows sampled at slaughter were cultured to detect MAP. Culturing was done both individually and as composite pooled samples using the TREK ESP Culture System II broth medium (Thermo Fisher Scientific, Trek Diagnostic Systems Inc., Cleveland, OH). Composite samples consisted of pools containing feces from 3, 5, 8, 10, or 15 cows. The number of individual fecal culture-positive cows within each pool ranged from 0 to 4. Culture of individual fecal samples detected MAP in 36 (3.6%) of the 994 cows. Individual samples that were detected within the first 50 d by TREK ESP Culture System II were more likely to lead to a positive pool result. In total, 840 pooled fecal samples were examined for presence of MAP, and of those, 272 pools actually contained feces from fecal culture-positive cows. The crude sensitivity (proportion of pools that contained at least 1 fecal-positive cow that tested positive) for pools of 3, 5, 8, 10, and 15 was 47, 67, 44, 59, and 39%, respectively. Across pools, an increase of the number of fecal culture-positive samples from 1 to 2 enhanced overall crude sensitivity from 44 to 71%. However, sensitivity did not further increase for pools with 3 or 4 fecal culture-positive samples (63 and 60%, respectively). Additionally, a simulation analysis assessing probability of pooled fecal samples being positive in herds of 50 and 100 cows was conducted. The simulation assumed that 1, 2, or 5 cows per herd were MAP fecal culture-positive and that pools of 5 and 10 were used. This low-prevalence herd simulation indicated that weighted mean herd probabilities of detecting a positive herd ranged between 52 and 99.3%, with the lowest probability for pools of 10 with 1 positive cow in the herd and the highest probability for pools of 5 with 5 positive cows in the herd. However, overall, pools of 5 and 10 had similar diagnostic capabilities, enabling cost savings by utilizing pools of 10. [ABSTRACT FROM AUTHOR]

Several studies have indicated that certain misfolded amyloids composed of tau, β-amyloid or α-synuclein can be transferred from cell to cell, suggesting the contribution of mechanisms reminiscent of those by which infective prions spread through the brain. This process of a ‘prion-like’ spreading between cells is also relevant as a novel putative therapeutic target that could block the spreading of proteinaceous aggregates throughout the brain which may underlie the progressive nature of neurodegenerative diseases. The relevance of β-amyloid oligomers and cellular prion protein (PrP C ) binding has been a focus of interest in Alzheimer’s disease (AD). At the molecular level, β-amyloid/PrP C interaction takes place in two differently charged clusters of PrP C . In addition to β-amyloid, participation of PrP C in α-synuclein binding and brain spreading also appears to be relevant in α-synucleopathies. This review summarizes current knowledge about PrP C as a putative receptor for amyloid proteins and the physiological consequences of these interactions. [ABSTRACT FROM AUTHOR]

Bacillus cereus is the causative agent of two gastrointestinal diseases that cause emesis and diarrhea. As evidenced by the reviewed literature published between 2002 and 2016, the contribution of the catering industry to the spread of B. cereus foodborne intoxications is evident. The reported settings included banquettes, a prison facility, clinics, a wedding, pubs and clubs, a take-away restaurant, a kindergarten, and a hotel restaurant. Many of the reported outbreaks were related to the consumption of rice-based products and starchy foods, together with vegetable-based dishes, with an attack rate that varied between 22.2% and 95.0%. Epidemiological and microbiological investigations allowed the common risk factors to be identified, including incorrect temperature maintenance of the foods and improper cleaning of food production equipment. Hence, to prevent microbial growth and toxin formation, appropriate training of the staff involved in food production and management must be pursued. [ABSTRACT FROM AUTHOR]

Anaerobic digestion was investigated as a potential method for on-farm disposal of fallen stock (pig carcases), degrading the carcase material to produce biogas and digestate. The effects of feedstock (sugar beet pulp or pig carcase material or a 50:50 mix) and organic loading rate (50 g-TS L −1 or 100 g-TS L −1 ), during mesophilic (35 °C) anaerobic digestion were investigated. Anaerobic digestion was achieved for all experimental treatments, however the pig carcase material at the higher organic loading rate produced the second highest methane yield (0.56 Nm 3 kg-VS −1 versus a range of 0.14–0.58 Nm 3 kg-VS −1 for other treatments), with the highest percentage of methane in total biogas (61.6% versus a range of 36.1–55.2% for all other treatments). Satisfactory pathogen reduction is a legislative requirement for disposal of carcase material. Pathogens were quantified throughout the anaerobic digestion process. Enterococcus faecalis concentrations decreased to negligible levels (2.8 log 10 CFU g-TS −1 ), whilst Clostridium perfringens levels remained unaffected by treatment throughout the digestion process (5.3 ± 0.2 log 10 CFU g-TS −1 ). [ABSTRACT FROM AUTHOR]

Feed sustainability is one of the biggest challenges for the next few years. Solutions have to be found that take feed quality and safety into account. Animal by-products are one valuable source of proteins. However, since the bovine spongiform encephalopathy (BSE) crisis, their use has been strictly regulated. The objective of this study was to propose a routine, sensitive and specific method using ultra-high performance liquid chromatography coupled to tandem mass spectrometry for the detection of blood-derived products and milk powder in feed. Contaminated aquafeeds were analysed in order to evaluate the sensitivity and specificity of the method. This new method meets both selectivity and sensitivity (0.1% (w/w)) requirements imposed by the European Commission for animal proteins detection methods. It offers an innovative and complementary solution for the simultaneously identification of authorised and unauthorised animal by-products such as processed animal proteins (PAPs). [ABSTRACT FROM AUTHOR]

Political boundaries may represent ecological barriers due to differences in wildlife management policies. In the European Union, it might be expected that these differences should be highly diluted, because all countries have to comply with common directives issued by the European Commission. However, the subsidiarity principle may lead to the uneven uptake of European Union regulations, which can impact on biodiversity conservation due to unequal legislation in neighboring countries, particularly in the case of highly mobile organisms. Here we address this issue, by analyzing how EU regulations issued in response to the Bovine Spongiform Encephalopathy (BSE) crisis differentially affected vulture conservation in Portugal and Spain. Taking advantage of the intensive GPS-tracking of 60 griffon ( Gyps fulvus ) and 11 cinereous vultures ( Aegypius monachus ) from Spain, we found that the Spanish-Portuguese border acts as a quasi-impermeable barrier. In fact, there was an abrupt decline in the number of vulture locations across the Spanish-Portuguese border, with modelling showing that this was unlikely to be related to differences in land cover or topography. Instead, the pattern found was likely due to differences in trophic resource availability, namely carcasses from extensive livestock husbandry, resulting from the differential application of European sanitary legislation regarding the mandatory removal of dead livestock from the field. Overall, our results should be seen as a warning signal to policy makers and conservation managers, highlighting the need for a stronger integration of sanitary and environmental policies at the European level. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine the effects of 1) the extraction temperature (65, 75, 85, and 95°C) of chicken feet gelatin (CFG) and 2) CFG extracted at different temperatures and wheat fiber (WF) with different particle sizes (80, 250, and 500 µm) on the physicochemical properties of the resultant gels. Raw chicken feet (CF) were swelled by treatment of an acidic solution [i.e., 0.1 N HCl (pH 2)]. The CFG was extracted from the swelled CF at different temperatures. Samples of 4% CFG or a mixture of 3% CFG and 3% WF were prepared using distilled water at 42 ± 1°C and then cooled to form gels. The physicochemical properties of the prepared CFG or the gel with CFG and WF were then investigated. The results indicate that the extraction yield, protein content, and L* values for the CFG samples significantly increased as the extraction temperature increased, whereas the viscosity, melting point, and a* values decreased. For the gel with CFG and WF, the gel strength, melting point, viscosity, and L* and b* values were significantly affected (P < 0.05) by the extraction temperature of CFG, but they partially were not affected (P > 0.05) by the particle size of WF. The gel with WF and extracted CFG at 65°C had the highest (P < 0.05) gel strength, melting point, viscosity, and a* values. In conclusion, CFG or the gel with CFG and WF could be utilized to prepare gelatins or gel with different physicochemical properties by controlling the extraction temperature or particle size of WF, depending on the specific application. Moreover, with its distinct physicochemical properties, the gel with CFG and WF could possibly be used as a non-meat ingredient for fat replacement. [ABSTRACT FROM AUTHOR]

We quantify effects of disease outbreaks on agricultural trade with a gravity model of impacts of foot and mouth disease (FMD) and bovine spongiform encephalopathy (BSE) on beef trade. We account for official FMD status and for the impact of recent disease outbreaks. During and after a FMD outbreak, exporting countries substitute away from markets recognized as FMD-free toward lower value markets not recognized as FMD-free. Similarly, a country that has experienced BSE will export less to markets that have not experienced BSE and more to markets that have. Regaining official recognition of FMD-free status may aid recovery but does not negate the effects of a recent FMD outbreak. Models of FMD impacts should incorporate these market-switching effects, while analysis of FMD outbreaks should not focus solely on the loss of markets but rather should incorporate our finding that these loses are somewhat mitigated by market substitution. For countries not free of FMD, if the disease were to be eradicated an exporter should eventually be able to substitute towards higher value FMD-free markets. The value of this change in export market profile should be counted when considering the benefits of FMD eradication programs. [ABSTRACT FROM AUTHOR]

The present study is based on the quantitative structure-activity relationship (QSAR) analysis of binding affinity toward human prion protein ( huPrP C ) of quinacrine, pyridine dicarbonitrile, diphenylthiazole and diphenyloxazole analogs applying different linear and non-linear chemometric regression techniques, including univariate linear regression, multiple linear regression, partial least squares regression and artificial neural networks. The QSAR analysis distinguished molecular lipophilicity as an important factor that contributes to the binding affinity. Principal component analysis was used in order to reveal similarities or dissimilarities among the studied compounds. The analysis of in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters was conducted. The ranking of the studied analogs on the basis of their ADMET parameters was done applying the sum of ranking differences, as a relatively new chemometric method. The main aim of the study was to reveal the most important molecular features whose changes lead to the changes in the binding affinities of the studied compounds. Another point of view on the binding affinity of the most promising analogs was established by application of molecular docking analysis. The results of the molecular docking were proven to be in agreement with the experimental outcome. [ABSTRACT FROM AUTHOR]

Prions are infectious proteins that cause fatal neurodegenerative disorders including Creutzfeldt-Jakob and bovine spongiform encephalopathy (mad cow) diseases. The yeast [PSI+] prion is formed by the translation-termination factor Sup35, is the best-studied prion, and provides a useful model system for studying such diseases. However, despite recent progress in the understanding of prion diseases, the cellular defense mechanism against prions has not been elucidated. Here, we report that proteolytic cleavage of Sup35 suppresses spontaneous de novo generation of the [PSI+] prion. We found that during yeast growth in glucose media, a maximum of 40% of Sup35 is cleaved at its N-terminal prion domain. This cleavage requires the vacuolar proteases PrA-PrB. Cleavage occurs in a manner dependent on translation but independently of autophagy between the glutamine/asparagine-rich (Q/N-rich) stretch critical for prion formation and the oligopeptide-repeat region required for prion maintenance, resulting in the removal of the Q/N-rich stretch from the Sup35 N terminus. The complete inhibition of Sup35 cleavage, by knocking out either PrA (pep4∆) or PrB (prb1∆), increased the rate of de novo formation of [PSI+] prion up to +5-fold, whereas the activation of Sup35 cleavage, by overproducing PrB, inhibited [PSI+] formation. On the other hand, activation of the PrB pathway neither cleaved the amyloid conformers of Sup35 in [PSI+] strains nor eliminated preexisting [PSI+]. These findings point to a mechanism antagonizing prion generation in yeast. Our results underscore the usefulness of the yeast [PSI+] prion as a model system to investigate defense mechanisms against prion diseases and other amyloidoses. [ABSTRACT FROM AUTHOR]

The increased interest in fish collagen is a consequence of the risk of exposure to Creutzfeld-Jacob disease (CJD) and the bovine spongiform encephalopathy (BSE), whose occurrence is associated with prions carried by bovine collagen. Collagen is the main biopolymer in living organisms and the main component of the skin and bones. Until the discovery of the BSE, bovine collagen had been widely used. The BSE epidemic increased the interest in new sources of collagen such as fish skin collagen (FSC) and its properties. Although the thermal properties of collagen originating from mammals have been well described, less attention has been paid to the thermal properties of FSC. Denaturation temperature is a particularly important parameter, depending on the collagen origin and hydration level. In the reported experiment, the free water and bound water release processes along with thermal denaturation process were studied by means of the differential scanning calorimetry (DSC). Measurements were carried out using a DSC 7 instrument (Elmer-Perkin), in the temperature range 298–670 K. The study material was FSC derived by acidic hydration method. The bovine Achilles tendon (BAT) collagen type I was used as the control material. The thermograms recorded revealed both, exothermic and endothermic peaks. For both materials, the peaks in the temperature range of 330–360 K were assigned to the release of free water and bound water. The denaturation temperatures of FSC and BAT collagen were determined as 420 K and 493 K, respectively. Thermal decomposition process was observed at about 500 K for FSC and at about 510 K for BAT collagen. These results show that FSC is less resistant to high temperature than BAT collagen. [ABSTRACT FROM AUTHOR]

The knowledge and experiences obtained with oral phospholipid excipients is increasing continuously. Nevertheless the present number of oral products using these excipients as essential excipient is very limited. This is remarkable to note, since phospholipids play a significant role in the food uptake mechanisms of the GI tract and these mechanisms could be translated into suitable dosage forms and corresponding drug delivery strategies. In addition, phospholipid excipients are multifunctional biodegradable, non-toxic excipients, which can be used in oral dosage forms as wetting agents, emulsifier, solubilizer and matrix forming excipients. Especially natural phospholipid excipients, made from renewable sources, may be considered as environmentally friendly excipients and as a viable alternative to synthetic phospholipid and non-phospholipid analogues. This review describes 1) essential physico-chemical properties of oral phospholipid excipients 2) the fate of orally administered phospholipids with respect to absorption and metabolism in the GI tract 3) the main dosage forms used for oral administration containing phospholipids. These elements are critically assessed and areas of future research of interest for the use of oral phospholipid excipients are summarized. [ABSTRACT FROM AUTHOR]

The emergence and epidemic of classical Bovine Spongiform Encephalopathy (cBSE) represents one of the most important and unique episodes in disease control of a zoonotic disease due to its novelty and its impact. Since its detection in 1986 in the United Kingdom, it has also been detected in 25 countries. The novel nature of its infectious agent and the discovery of its zoonotic potential (causing the new variant of Creutzfeldt-Jakob disease in humans) caught the food industry, policy makers, scientific community and consumers off guard, with concerns over massive human exposure and health impact. Thirty-five years later, and following the feed bans of mammalian protein to livestock in 1996, the epidemic is now in its final stages, with expectations of occasional cases emerging until the year 2026. In the last six years, two cBSE cases from animals Born After the Reinforced feed Ban (BARB) have been identified in Scotland and England, delaying their application for BSE Negligible status. This paper provides a current and historical analysis of the cBSE epidemic situation in Great Britain and review the policies implemented, its impact and the possible factors explaining the occurrence of new cases. The analysis and review reinforce the hypothesis that cBSE BARB cases occurrence may not be spontaneous, yet there remains much uncertainty of their aetiology. To date, 181,122 cBSE cases have been detected in Great Britain, of which 178 are BARB cases; and 178 human cases of the new variant of Creutzfeldt-Jakob have been diagnosed. The disease triggered major policy responses in the country, and worldwide, that have transformed the industry and our approach to animal health. Almost all its impact originated from societal reactions to the disease, from disposal of animals and products, to reduction of the national herd and its production efficiency, losses through trade restrictions and reduction in market prices and consumers' confidence, hardening of cleaning and control procedures in farms and hospitals, generation of heavy government investment plans through numerous support, surveillance and research schemes, and political and societal changes. BSE is an example of major system shock to a food industry, but which experience has resulted in better traceability systems of animals, increased capacity to develop robust diagnostic methods, numerous lessons learnt on policy coordination, implementation and communication, increased society awareness on food systems and overall improved the country's preparedness to future epidemics. [ABSTRACT FROM AUTHOR]

The utilization of industrial waste streams as input materials for bio-mediated production processes constitutes a current R&D objective not only to reduce process costs at the input side but in parallel, to minimize hazardous environmental emissions. In this context, the EU-funded project ANIMPOL elaborated a process for the production of polyhydroxyalkanoate (PHA) biopolymers starting from diverse waste streams of the animal processing industry. This article provides a detailed economic analysis of PHA production from this waste biorefinery concept, encompassing the utilization of low-quality biodiesel, offal material and meat and bone meal (MBM). Techno-economic analysis reveals that PHA production cost varies from 1.41 €/kg to 1.64 €/kg when considering offal on the one hand as waste, or, on the other hand, accounting its market price, while calculating with fixed costs for the co-products biodiesel (0.97 €/L) and MBM (350 €/t), respectively. The effect of fluctuating market prices for offal materials, biodiesel, and MBM on the final PHA production cost as well as the investment payback time have been evaluated. Depending on the current market situation, the calculated investment payback time varies from 3.25 to 4.5 years. [ABSTRACT FROM AUTHOR]

Policy decisions have the potential to affect biodiversity conservation and modify, among other factors, animal demography, behavior and ecological processes. This became manifest in Europe in the past decade in light of the appearance of bovine spongiform encephalopathy (BSE). However, the obvious effects of policy decisions on foraging behavior are lacking. Here, we use data from a long-term study (1992–2015) of the ecology of the bearded vulture Gypaetus barbatus in the Pyrenees to assess whether or not the implementation of health policies in the period 2006–2011 really did affect this vulture's foraging behavior and breeding success. To test this, we used the frequency of nest changeovers (between 1992 and 2015) as a surrogate for the time invested in searching for and obtaining food. Additionally, between 2006 and 2015 we monitored the movements of 20 bearded vultures with GPS satellite transmitters. Our findings show no differences between annual home range sizes and/or the time used to search for food either before, during or after the imposition of health regulations. No differences between periods (during or after health regulations) were found in the use of supplementary feeding sites (SFS). An analysis of food available indicates that this similarity of use in different periods could be explained by the high habitat quality in the Pyrenees and the good availability of trophic resources. Our results suggest that diet plasticity and habitat quality compensate for the sudden effects of food shortages and so question the true usefulness of SFS in buffering a quantitative food deficit. We discuss the implications of these results from both ecological and conservation perspectives. [ABSTRACT FROM AUTHOR]

The existing European Regulation (EC n° 51/2013) prohibits the use of animals meals in feedstuffs in order to prevent Bovine Spongiform Encephalopathy infection and diffusion, however the legislation is rapidly moving towards a partial lifting of the “feed ban” and the competent control organisms are urged to develop suitable analytical methods able to avoid food safety incidents related to animal origin products. The limitations of the official methods (i.e. light microscopy and Polymerase Chain Reaction) suggest exploring new analytic ways to get reliable results in a short time. The combination of spectroscopic techniques with optical microscopy allows the development of an individual particle method able to meet both selectivity and sensitivity requirements (0.1% w/w). A spectroscopic method based on Fourier Transform micro-Raman spectroscopy coupled with Discriminant Analysis is here presented. This approach could be very useful for in-situ applications, such as customs inspections, since it drastically reduces time and costs of analysis. [ABSTRACT FROM AUTHOR]

Much attention has recently been paid to natural bioactive compounds from marine organisms as functional ingredients due to their various beneficial health effects. Marine bioactive compounds have numerous applications in food packaging, animal feeding, biodiesel/biogas, natural pigments, cosmetics, and enzyme isolation, among others. In addition, many studies have reported that marine bioactive compounds can be used as antioxidative, antihypertensive, antitumor, anticoagulant, and antimicrobial components in functional foods or nutraceuticals and pharmaceuticals due to their health benefits and therapeutic potentials. This review focuses on the utilization of marine bioactive by-products and their potential application in food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP res ). In this study, we report and analyze yet another PrP res type (PrP res-2011 ), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP res profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP res-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP res-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP res-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease. [ABSTRACT FROM AUTHOR]

During the bovine spongiform encephalopathy (BSE) epidemic in July 2001 the European Commission established a surveillance scheme for the comprehensive sampling of all BSE clinical suspects, healthy slaughter (HS) animals >30 months, and all emergency slaughter and fallen stock animals tested when >24 months. With the exponential decline in classical BSE cases, this comprehensive surveillance system has been successively modified to become risk-based, targeting those exit streams and ages where cases from the original epidemic are most likely to be detected. Such reductions in testing are not without losses in the information subsequently collected, which could affect the sensitivity of the surveillance system to relatively small changes in the underlying prevalence of BSE across the European Union (EU). Here we report on a cohort-based approach to estimate the time taken for EU surveillance to observe a theoretical re-emergence of BSE in cattle. A number of surveillance schemes were compared. The baseline scheme considered detection being triggered by at least one case in the ‘age window’ 48–72 months in the fallen stock or emergency slaughter exit streams. Alternative schemes changed the start and end of this age window as well as considering testing for HS cattle. Under the baseline scheme, an estimated 15 years would lapse ([2.5th, 97.5th] percentiles = [10,24]) prior to detection, during which time 2867 infected animals ([2.5th, 97.5th] = [1722,6967]) would enter the slaughter population. These animals would be predominantly young animals (majority <24 months) showing no clinical signs. This baseline scheme reduced the time to detection by 2 years, compared to a scheme where only clinical suspects were tested assuming BSE symptoms are recognised to the same degree by veterinary surgeons. Additional testing of younger animals did not improve detection as young infected animals were unlikely to test positive, but testing of older animals reduced the time to detection. Testing of HS animals >72 months reduced the time to detection by one year compared to the baseline model, but would incur a high financial cost, e.g. testing HS animals >72 months of age for 14 years would entail approximately 50.4 million additional tests. A limitation of the results is that there is no guarantee that current detection methods, optimised for detection of classical BSE, would identify a novel prion disease in cattle and it is currently difficult to envisage plausible routes by which a re-emergence of classical BSE could occur in Europe. [ABSTRACT FROM AUTHOR]