scholarly journals Prion Strains and Transmission Barrier Phenomena

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 5 ◽  
Author(s):  
◽  
◽  
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Several experimental evidences show that prions are non-conventional pathogens, which physical support consists only in proteins. This finding raised questions regarding the observed prion strain-to-strain variations and the species barrier that happened to be crossed with dramatic consequences on human health and veterinary policies during the last 3 decades. This review presents a focus on a few advances in the field of prion structure and prion strains characterization: from the historical approaches that allowed the concept of prion strains to emerge, to the last results demonstrating that a prion strain may in fact be a combination of a few quasi species with subtle biophysical specificities. Then, we will focus on the current knowledge on the factors that impact species barrier strength and species barrier crossing. Finally, we present probable scenarios on how the interaction of strain properties with host characteristics may account for differential selection of new conformer variants and eventually species barrier crossing.

2019 ◽  
Vol 116 (25) ◽  
pp. 12478-12487 ◽  
Author(s):  
Jifeng Bian ◽  
Jeffrey R. Christiansen ◽  
Julie A. Moreno ◽  
Sarah J. Kane ◽  
Vadim Khaychuk ◽  
...  

Although the unifying hallmark of prion diseases is CNS neurodegeneration caused by conformational corruption of host prion protein (PrP) to its infective counterpart, contagious transmission of chronic wasting disease (CWD) results from shedding of prions produced at high titers in the periphery of diseased cervids. While deer and elk PrP primary structures are equivalent except at residue 226, which is glutamate in elk and glutamine in deer, the effect of this difference on CWD pathogenesis is largely unknown. Using a gene-targeting approach where the mouse PrP coding sequence was replaced with elk or deer PrP, we show that the resulting GtE226 and GtQ226 mice had distinct kinetics of disease onset, prion conformations, and distributions of prions in the brains of diseased mice following intracerebral CWD challenge. These findings indicate that amino acid differences at PrP residue 226 dictate the selection and propagation of divergent strains in deer and elk with CWD. Because prion strain properties largely dictate host-range potential, our findings suggest that prion strains from elk and deer pose distinct risks to sympatric species or humans exposed to CWD. GtE226 and GtQ226 mice were also highly susceptible to CWD prions following intraperitoneal and oral exposures, a characteristic that stood in stark contrast to previously produced transgenic models. Remarkably, disease transmission was effective when infected mice were cohoused with naïve cagemates. Our findings indicate that gene-targeted mice provide unprecedented opportunities to accurately investigate CWD peripheral pathogenesis, CWD strains, and mechanisms of horizontal CWD transmission.


Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 643
Author(s):  
Angela Saviano ◽  
Mattia Brigida ◽  
Alessio Migneco ◽  
Gayani Gunawardena ◽  
Christian Zanza ◽  
...  

Background and Objectives: Lactobacillus reuteri DSM 17938 (L. reuteri) is a probiotic that can colonize different human body sites, including primarily the gastrointestinal tract, but also the urinary tract, the skin, and breast milk. Literature data showed that the administration of L. reuteri can be beneficial to human health. The aim of this review was to summarize current knowledge on the role of L. reuteri in the management of gastrointestinal symptoms, abdominal pain, diarrhea and constipation, both in adults and children, which are frequent reasons for admission to the emergency department (ED), in order to promote the best selection of probiotic type in the treatment of these uncomfortable and common symptoms. Materials and Methods: We searched articles on PubMed® from January 2011 to January 2021. Results: Numerous clinical studies suggested that L. reuteri may be helpful in modulating gut microbiota, eliminating infections, and attenuating the gastrointestinal symptoms of enteric colitis, antibiotic-associated diarrhea (also related to the treatment of Helicobacter pylori (HP) infection), irritable bowel syndrome, inflammatory bowel disease, and chronic constipation. In both children and in adults, L. reuteri shortens the duration of acute infectious diarrhea and improves abdominal pain in patients with colitis or inflammatory bowel disease. It can ameliorate dyspepsia and symptoms of gastritis in patients with HP infection. Moreover, it improves gut motility and chronic constipation. Conclusion: Currently, probiotics are widely used to prevent and treat numerous gastrointestinal disorders. In our opinion, L. reuteri meets all the requirements to be considered a safe, well-tolerated, and efficacious probiotic that is able to contribute to the beneficial effects on gut-human health, preventing and treating many gastrointestinal symptoms, and speeding up the recovery and discharge of patients accessing the emergency department.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bin Wang ◽  
Lei Zhang ◽  
Tong Dai ◽  
Ziran Qin ◽  
Huasong Lu ◽  
...  

AbstractEmerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy—but is fast-growing—it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.


Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 113
Author(s):  
Marine Remize ◽  
Yves Brunel ◽  
Joana L. Silva ◽  
Jean-Yves Berthon ◽  
Edith Filaire

N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties. After defining macro and microalgae, this review synthesizes the current knowledge on n-3 PUFAs regarding health benefits and the challenges surrounding their supply within the environmental context. Microalgae n-3 PUFA production is examined and its synthesis pathways are discussed. Finally, the use of EPA and DHA in food and feed is investigated. This work aims to define better the issues surrounding n-3 PUFA production and supply and the potential of microalgae as a sustainable source of compounds to enhance the food and feed of the future.


2021 ◽  
Vol 4 ◽  
Author(s):  
Stephan van Vliet ◽  
Frederick D. Provenza ◽  
Scott L. Kronberg

While commission reports and nutritional guidelines raise concerns about the effects of consuming red meat on human health, the impacts of how livestock are raised and finished on consumer health are generally ignored. Meat and milk, irrespective of rearing practices, provide many essential nutrients including bioavailable protein, zinc, iron, selenium, calcium, and/or B12. Emerging data indicate that when livestock are eating a diverse array of plants on pasture, additional health-promoting phytonutrients—terpenoids, phenols, carotenoids, and anti-oxidants—become concentrated in their meat and milk. Several phytochemicals found in grass-fed meat and milk are in quantities comparable to those found in plant foods known to have anti-inflammatory, anti-carcinogenic, and cardioprotective effects. As meat and milk are often not considered as sources of phytochemicals, their presence has remained largely underappreciated in discussions of nutritional differences between feedlot-fed (grain-fed) and pasture-finished (grass-fed) meat and dairy, which have predominantly centered around the ω-3 fatty acids and conjugated linoleic acid. Grazing livestock on plant-species diverse pastures concentrates a wider variety and higher amounts of phytochemicals in meat and milk compared to grazing monoculture pastures, while phytochemicals are further reduced or absent in meat and milk of grain-fed animals. The co-evolution of plants and herbivores has led to plants/crops being more productive when grazed in accordance with agroecological principles. The increased phytochemical richness of productive vegetation has potential to improve the health of animals and upscale these nutrients to also benefit human health. Several studies have found increased anti-oxidant activity in meat and milk of grass-fed vs. grain-fed animals. Only a handful of studies have investigated the effects of grass-fed meat and dairy consumption on human health and show potential for anti-inflammatory effects and improved lipoprotein profiles. However, current knowledge does not allow for direct linking of livestock production practices to human health. Future research should systematically assess linkages between the phytochemical richness of livestock diets, the nutrient density of animal foods, and subsequent effects on human metabolic health. This is important given current societal concerns about red meat consumption and human health. Addressing this research gap will require greater collaborative efforts from the fields of agriculture and medicine.


2010 ◽  
Vol 84 (11) ◽  
pp. 5706-5714 ◽  
Author(s):  
Ronald A. Shikiya ◽  
Jacob I. Ayers ◽  
Charles R. Schutt ◽  
Anthony E. Kincaid ◽  
Jason C. Bartz

ABSTRACT Prion strain interference can influence the emergence of a dominant strain from a mixture; however, the mechanisms underlying prion strain interference are poorly understood. In our model of strain interference, inoculation of the sciatic nerve with the drowsy (DY) strain of the transmissible mink encephalopathy (TME) agent prior to superinfection with the hyper (HY) strain of TME can completely block HY TME from causing disease. We show here that the deposition of PrPSc, in the absence of neuronal loss or spongiform change, in the central nervous system corresponds with the ability of DY TME to block HY TME infection. This suggests that DY TME agent-induced damage is not responsible for strain interference but rather prions compete for a cellular resource. We show that protein misfolding cyclic amplification (PMCA) of DY and HY TME maintains the strain-specific properties of PrPSc and replicates infectious agent and that DY TME can interfere, or completely block, the emergence of HY TME. DY PrPSc does not convert all of the available PrPC to PrPSc in PMCA, suggesting the mechanism of prion strain interference is due to the sequestering of PrPC and/or other cellular components required for prion conversion. The emergence of HY TME in PMCA was controlled by the initial ratio of the TME agents. A higher ratio of DY to HY TME agent is required for complete blockage of HY TME in PMCA compared to several previous in vivo studies, suggesting that HY TME persists in animals coinfected with the two strains. This was confirmed by PMCA detection of HY PrPSc in animals where DY TME had completely blocked HY TME from causing disease.


2020 ◽  
Vol 22 (8) ◽  
Author(s):  
Barbara De Berardis ◽  
Magda Marchetti ◽  
Anna Risuglia ◽  
Federica Ietto ◽  
Carla Fanizza ◽  
...  

AbstractIn recent years, the introduction of innovative low-cost and large-scale processes for the synthesis of engineered nanoparticles with at least one dimension less than 100 nm has led to countless useful and extensive applications. In this context, gold nanoparticles stimulated a growing interest, due to their peculiar characteristics such as ease of synthesis, chemical stability and optical properties. This stirred the development of numerous applications especially in the biomedical field. Exposure of manufacturers and consumers to industrial products containing nanoparticles poses a potential risk to human health and the environment. Despite this, the precise mechanisms of nanomaterial toxicity have not yet been fully elucidated. It is well known that the three main routes of exposure to nanomaterials are by inhalation, ingestion and through the skin, with inhalation being the most common route of exposure to NPs in the workplace. To provide a complete picture of the impact of inhaled gold nanoparticles on human health, in this article, we review the current knowledge about the physico-chemical characteristics of this nanomaterial, in the size range of 1–100 nm, and its toxicity for pulmonary structures both in vitro and in vivo. Studies comparing the toxic effect of NPs larger than 100 nm (up to 250 nm) are also discussed.


2020 ◽  
Vol 22 (6) ◽  
pp. 1315-1346 ◽  
Author(s):  
Darrin A. Thompson ◽  
Hans-Joachim Lehmler ◽  
Dana W. Kolpin ◽  
Michelle L. Hladik ◽  
John D. Vargo ◽  
...  

The review examines literature relevant to environmental fate, transformation, and toxicity, and human exposure and health risks of neonicotinoid insecticides.


2018 ◽  
Vol 182 ◽  
pp. 01007
Author(s):  
Vladimir Boykov ◽  
Aleksandr Povarecho

This paper presents selected problems connected with automation of procedures involved in assessment of machine degradation degree using vibration method with special emphasis on the machine state prognosis. The current knowledge of these problems is not sufficient and needs further research on data processing, analysis of efficiency of diagnostic and prognostic procedures, collection and selection of diagnostic parameters and development of automatic procedures for recognition and prognosis of a machine state. New solutions and different aspects of diagnostic prognosis based on the proposed partial procedures focus on factors determining automation of procedures for identification of technical systems states. New automated procedures for acquisition and processing of symptoms indicating the machine state provide better possibilities of control and supervision of technical systems operation and maintenance through identification of their current states, and its good prognosis.


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