Exosome TDP-43 profile in canine model of ALS: A preliminary study in developing surrogate biomarker

Blood-based biomarkers are much-needed diagnostic and prognostic tools for ALS. Canine degenerative myelopathy (DM) is recognized animal disease model to study the biology of human ALS. Serum derived exosomes are potential carrier that transport intercellular hormone-like messengers, together with their stability as carrier of proteins and RNA, make them ideal as biomarkers for a variety of diseases and biological processes. We study exosomal TDP-43 pattern as a surrogate biomarker that reflects biochemical changes in central nervous system. We isolated exosomes from canine serum using commercial exosome isolation reagents. TDP-43 and SOD1 profile in spinal cord homogenate lysate and that of serum-derived exosomes were found elevated in dogs with DM. We conclude levels of spinal cord TDP-43 and serum-derived exomes were similar in TDP-43 profiling, which warrant further investigation of disease sensitivity and specificity for establishing as a blood-based biomarker in canine DM.

Exosome TDP-43 Profile in Canine Model of ALS: A Preliminary Study in Developing Surrogate Biomarker

Blood-based biomarkers are much-needed diagnostic and prognostic tools for ALS. Canine degenerative myelopathy (DM) is recognized animal disease model to study the biology of human ALS. Serum derived exosomes are potential carrier that transport intercellular hormone-like messengers, together with their stability as carrier of proteins and RNA, make them ideal as biomarkers for a variety of diseases and biological processes. We study exosomal TDP-43 pattern as a surrogate biomarker that reflects biochemical changes in central nervous system. We isolated exosomes from canine serum using commercial exosome isolation reagents. TDP-43 and SOD1 profile in spinal cord homogenate lysate and that of serum-derived exosomes were found elevated in dogs with DM. We conclude levels of spinal cord TDP-43 and serum-derived exomes were similar in TDP-43 profiling, which warrant further investigation of disease sensitivity and specificity for establishing as a blood-based biomarker in canine DM.

A hierarchical 3D-motion learning framework for animal spontaneous behavior mapping

Animal behavior usually has a hierarchical structure and dynamics. Therefore, to understand how the neural system coordinates with behaviors, neuroscientists need a quantitative description of the hierarchical dynamics of different behaviors. However, the recent end-to-end machine-learning-based methods for behavior analysis mostly focus on recognizing behavioral identities on a static timescale or based on limited observations. These approaches usually lose rich dynamic information on cross-scale behaviors. Here, inspired by the natural structure of animal behaviors, we address this challenge by proposing a parallel and multi-layered framework to learn the hierarchical dynamics and generate an objective metric to map the behavior into the feature space. In addition, we characterize the animal 3D kinematics with our low-cost and efficient multi-view 3D animal motion-capture system. Finally, we demonstrate that this framework can monitor spontaneous behavior and automatically identify the behavioral phenotypes of the transgenic animal disease model. The extensive experiment results suggest that our framework has a wide range of applications, including animal disease model phenotyping and the relationships modeling between the neural circuits and behavior.

Candidate Animal Disease Model of Elizabethkingia Spp. Infection in Humans, Based on the Systematic Pathology and Oxidative Damage Caused by E. miricola in Pelophylax nigromaculatus

Most species of the genus Elizabethkingia are pathogenic to humans and animals, most commonly causing meningitis. However, our understanding of the pathogenic mechanisms involved is poor and there have been few pathological studies of Elizabethkingia spp. in animals. To understand the host injury induced by Elizabethkingia spp., we established a model of E. miricola infection in the black-spotted frog (Pelophylax nigromaculatus). The systematic pathology in and oxidative damage in the infection model were investigated. Our results show that recently isolated E. miricola is a bacterium that mainly parasitizes the host brain and that neurogenic organs are the predominant sites of damage. Infection mainly manifested as severe brain abscesses, meningoencephalitis, necrotic spondylitis, and necrotic retinitis. The liver, spleen, kidney, gastrointestinal tract, and lung were also affected to varying degrees, with bacterial necrotic inflammation. P. nigromaculatus also suffered enormous damage to its oxidative system during E. miricola infection, which may have further aggravated its disease state. Our results provide a preliminary reference for the study and treatment of Elizabethkingia spp.-induced neurological diseases in animals.

The Triphenylethylenes, a Novel Class of Antifungals

ABSTRACT New antifungals are needed, particularly in the developing world, to treat life-threatening fungal infections, such as cryptococcosis. Drug repurposing is one strategy to identify new drug-like compounds, but it is often difficult to identify a mechanism of action. Here we discuss the outstanding effort by Butts et al. to identify calmodulin as an antifungal target of repurposed estrogen receptor antagonists [A. Butts, K. Koselny, Y. Chabrier-Roselló, C. P. Semighini, Y. C. S. Brown, et al., mBio 5(1):e00765-13, 2014, doi:10.1128/mBio.00765-13]. The authors show that these compounds bind to and directly inhibit fungal calmodulin and also reduce fungal burden in an animal disease model. These studies thus establish both the key preclinical efficacy and the antifungal mechanism of action, which will allow these compounds to progress toward development of novel antifungal therapies.