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At least 1,387 records · Page 77

Experimental Oronasal Transmission of Chronic Wasting Disease Agent from White-Tailed Deer to Suffolk Sheep

Chronic wasting disease (CWD) is a fatal prion disease of cervids. We examined host range of CWD by oronasally inoculating Suffolk sheep with brain homogenate from a CWD-positive white-tailed deer. Sixty months after inoculation, 1/7 sheep had immunoreactivity against the misfolded form of prion protein in lymphoid tissue. Results were confirmed by mouse bioassay.

59 BASIC BIOLOGICAL SCIENCES↗

Proof of Concept of Natural and Synthetic Antifouling Agents in Coatings

Marine biofouling, caused by the deposition and accumulation of marine organisms on submerged surfaces, represents a huge concern for the maritime industries and also contributes to environmental pollution and health concerns. The most effective way to prevent this phenomenon is the use of biocide-based coatings which have proven to cause serious damage to marine ecosystems. Several research groups have focused on the search for new environmentally friendly antifoulants, including marine and terrestrial natural products and synthetic analogues. Some of these compounds have been incorporated into marine coatings and display interesting antifouling activities caused by the interference with the biofilm-forming species as well as by the inhibition of the settlement of macroorganisms. This review highlights the proof-of-concept studies of emerging natural or synthetic antifouling compounds in coatings, from lab-made to commercial ones, performed between 2019 and 2023 and their results in the field or in in vivo laboratorial tests.

Pereira, Daniela↗

Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

Amyloid is a complex pathologic matrix comprised principally of para-crystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloidoses are rare (~3500 new cases per year in the US); thus, routine diagnosis is often challenging, and effective treatment options are limited, resulting in high morbidity and mortality rates. Glycosaminoglycans contribute inextricably to the formation of amyloid fibrils and foster the deposition of amyloid in tissues. Those present in amyloid deposits are biochemically and electrochemically distinct from glycosaminoglycans found in the plasma membrane and extracellular matrices of healthy tissues due to the presence of a high degree of heparin-like hypersulfation. We have exploited this unique property and evaluated heparin-reactive peptides, such as p5+14. Herein we show efficacious detection of murine systemic amyloid in vivo by using molecular imaging, and the specific targeting of the peptide to major forms of human amyloid in tissue sections. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients; thus, providing a novel technique for prognostication, patient stratification, and monitoring response to therapy.

60 APPLIED LIFE SCIENCES↗

Chloropyridinyl Esters of Nonsteroidal Anti-Inflammatory Agents and Related Derivatives as Potent SARS-CoV-2 3CL Protease Inhibitors

We report the design and synthesis of a series of new 5-chloropyridinyl esters of salicylic acid, ibuprofen, indomethacin, and related aromatic carboxylic acids for evaluation against SARS-CoV-2 3CL protease enzyme. These ester derivatives were synthesized using EDC in the presence of DMAP to provide various esters in good to excellent yields. Compounds are stable and purified by silica gel chromatography and characterized using 1 H-NMR, 13 C-NMR, and mass spectral analysis. These synthetic derivatives were evaluated in our in vitro SARS-CoV-2 3CLpro inhibition assay using authentic SARS-CoV-2 3CLpro enzyme. Compounds were also evaluated in our in vitro antiviral assay using quantitative VeroE 6 cell-based assay with RNAqPCR. A number of compounds exhibited potent SARS-CoV-2 3CLpro inhibitory activity and antiviral activity. Compound 9a was the most potent inhibitor, with an enzyme IC 50 value of 160 nM. Compound 13b exhibited an enzyme IC 50 value of 4.9 µM. However, it exhibited a potent antiviral EC 50 value of 24 µM in VeroE6 cells. Remdesivir, an RdRp inhibitor, exhibited an antiviral EC 50 value of 2.4 µM in the same assay. We assessed the mode of inhibition using mass spectral analysis which suggested the formation of a covalent bond with the enzyme. To obtain molecular insight, we have created a model of compound 9a bound to SARS-CoV-2 3CLpro in the active site.

3CLpro inhibitors↗

Virulence and Genetic Diversity of Puccinia spp., Causal Agents of Rust on Switchgrass (Panicum virgatum L.) in the USA

Switchgrass (Panicum virgatum L.) is an important cellulosic biofuel grass native to North America. Rust, caused by Puccinia spp. is the most predominant disease of switchgrass and has the potential to impact biomass conversion. In this study, virulence patterns were determined on a set of 38 switchgrass genotypes for 14 single-spore rust isolates from 14 field samples collected in seven states. Single nucleotide polymorphism (SNP) variation was also assessed in 720 sequenced cloned amplicons representing 654 base pairs of the elongation factor 1-α gene from the field samples. Five major haplotypes were identified differing by 11 out of the 39 SNP positions identified. STRUCTURE, Principal Coordinate Analysis, and phylogenetic analyses divided the rust population into two genetic clusters. Virginia and Georgia had the highest and lowest rust genetic diversity, respectively. Only nine accessions showed a differential disease response between the 14 isolates, allowing the identification of eight races, differing by 1–3 virulence factors. Overall, the results suggested clonal reproduction of the pathogen and a North–South differentiation via local adaptation. However, similar haplotypes and races were also recovered from several states, suggesting migration events, and highlighting the need to further investigate the switchgrass rust population structure and evolution in the USA.

Bahri, Bochra A. (ORCID:0000000159055880)↗

Transmission of Raccoon-Passaged Chronic Wasting Disease Agent to White-Tailed Deer

The transmission characteristics of prion diseases are influenced by host prion protein sequence and, therefore, the host species. Chronic wasting disease (CWD), a prion disease of cervids, has widespread geographical distribution throughout North America and occurs in both wild and farmed populations. CWD prions contaminate the environment through scattered excrement and decomposing carcasses. Fresh carcasses with CWD prions are accessible by free-ranging mesopredators such as raccoons and may provide a route of exposure. Previous studies demonstrated the susceptibility of raccoons to CWD from white-tailed deer. In this study, we demonstrate that white-tailed deer replicate raccoon-passaged CWD prions which results in clinical disease similar to intraspecies CWD transmission. Six white-tailed deer were oronasally inoculated with brain homogenate from a raccoon with CWD. All six deer developed clinical disease, had widespread lymphoid distribution of misfolded CWD prions (PrP Sc ), and had neuropathologic lesions with PrP Sc accumulation in the brain. The presence of PrP Sc was confirmed by immunohistochemistry, enzyme-linked immunoassay, and western blot. The western blot migration pattern of raccoon-passaged CWD was different from white-tailed deer CWD. Transmission of raccoon CWD back to white-tailed deer resulted in an interposed molecular phenotype that was measurably different from white-tailed deer CWD.

59 BASIC BIOLOGICAL SCIENCES↗