Hand-Rearing Method for Infant Marmosets

The common marmoset (Callithrix jacchus) is a small and highly social New World monkey with high reproduction rates, which has been proven to be a ...

Zhejiang University

Fowl adenovirus serotype 4 (FAdV-4) strain SD1511 was isolated from chickens with severe inclusion body hepatitis and hydropericardium syndrome in Shandong Province, China. The isolate was cultured in primary chicken embryo kidney cells. A study of pathogenicity indicated that SD1511 readily infected 7-35-d-old chickens by intramuscular injection and intranasal and oral routes, causing 50%-100% mortality. The 35-d-old chickens suffered more severe infection than 7- and 21-d-old chickens with mortality highest in the intramuscular injection group. The serum from surviving chickens showed potent viral neutralizing capability. The complete genome of SD1511 was sequenced and analyzed. The strain was found to belong to the FAdV-4 cluster with more than 99% identity with the virulent FAdV-4 strains isolated in China in recent years except for some distinct variations, including deletions of open reading frame 27 (ORF27), ORF48, and part of ORF19. Our findings suggest that SD1511 might be used as a prototype strain for the study of pathogenesis and vaccine development.

Pathogenicity of an FAdV-4 isolate to chickens and its genomic analysis.

Glibenclamide protects against ischemic injury in both preclinical and clinical studies, presumably by blocking the de novo assembled sulfonylurea receptor 1-transient receptor potential M4 (Sur1-Trpm4) channel induced by ischemia. However, glibenclamide may cause unexpected serious hypoglycemia. Here, we tested whether glimepiride, another sulfonylurea with better safety, has comparable efficacy with glibenclamide and whether gene deletion of Trpm4 (Trpm4) exerts similar effect. Wild-type (WT) mice subjected to temporary middle cerebral artery occlusion (tMCAO) were randomized to receive glibenclamide (an initial dose of 10 μg/kg and additional doses of 1.2 μg every 8 h), three different doses of glimepiride (10 μg/kg, 100 μg/kg and 1 mg/kg) or vehicle after ischemia, while tMCAO-treated Trpm4 mice were randomized to receive vehicle or glimepiride. Neurological function, infarct volume, edema formation, the integrity of blood-brain barrier and inflammatory reaction were evaluated at 24 h after ischemia. In tMCAO-treated WT mice, 10 μg/kg and 100 μg/kg glimepiride had comparable efficacy with glibenclamide in improving longa score and grip test score, reducing infarct volume, mitigating brain edema, lessening extravasation of Evans blue dye and IgG, restoring tight junction protein expression as well as suppressing inflammatory cytokines. Compared with WT mice, Trpm4 mice showed less neurological deficit, smaller cerebral infarction, lighter brain edema and more integrity of blood-brain barrier. As expected, glimepiride did not provide additional neuroprotection compared with vehicle in the tMCAO-treated Trpm4 mice. Glimepiride shows comparable efficacy with glibenclamide in alleviating brain injury after ischemic stroke in mice, possibly via targeting the Sur1-Trpm4 channel.

Glimepiride and glibenclamide have comparable efficacy in treating acute ischemic stroke in mice.

Behavioral measurement and evaluation are broadly used to understand brain functions in neuroscience, especially for investigations of movement disorders, social deficits, and mental diseases. Numerous commercial software and open-source programs have been developed for tracking the movement of laboratory animals, allowing animal behavior to be analyzed digitally.  optical imaging and electrophysiological recording in freely behaving animals are now widely used to understand neural functions in circuits. However, it is always a challenge to accurately track the movement of an animal under certain complex conditions due to uneven environment illumination, variations in animal models, and interference from recording devices and experimenters. To overcome these challenges, we have developed a strategy to track the movement of an animal by combining a deep learning technique, the You Only Look Once (YOLO) algorithm, with a background subtraction algorithm, a method we label DeepBhvTracking. In our method, we first train the detector using manually labeled images and a pretrained deep-learning neural network combined with YOLO, then generate bounding boxes of the targets using the trained detector, and finally track the center of the targets by calculating their centroid in the bounding box using background subtraction. Using DeepBhvTracking, the movement of animals can be tracked accurately in complex environments and can be used in different behavior paradigms and for different animal models. Therefore, DeepBhvTracking can be broadly used in studies of neuroscience, medicine, and machine learning algorithms.

DeepBhvTracking: A Novel Behavior Tracking Method for Laboratory Animals Based on Deep Learning.

The cerebellum is involved in encoding balance, posture, speed, and gravity during locomotion. However, most studies are carried out on flat surfaces, and little is known about cerebellar activity during free ambulation on slopes. Here, it has been imaged the neuronal activity of cerebellar molecular interneurons (MLIs) and Purkinje cells (PCs) using a miniaturized microscope while a mouse is walking on a slope. It has been found that the neuronal activity of vermal MLIs specifically enhanced during uphill and downhill locomotion. In addition, a subset of MLIs is activated during entire uphill or downhill positions on the slope and is modulated by the slope inclines. In contrast, PCs showed counter-balanced neuronal activity to MLIs, which reduced activity at the ramp peak. So, PCs may represent the ramp environment at the population level. In addition, chemogenetic inactivation of lobule V of the vermis impaired uphill locomotion. These results revealed a novel micro-circuit in the vermal cerebellum that regulates ambulatory behavior in 3D terrains.

Article	Year
Pathogenicity of an FAdV-4 isolate to chickens and its genomic analysis. Journal of Zhejiang University. Science. B\| PubMed ID: 31379144	2019
Glimepiride and glibenclamide have comparable efficacy in treating acute ischemic stroke in mice. Neuropharmacology\| PubMed ID: 31704276	2020
DeepBhvTracking: A Novel Behavior Tracking Method for Laboratory Animals Based on Deep Learning. Frontiers in behavioral neuroscience\| PubMed ID: 34776893	2021
Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 36373709	2022

Chenfei Lyu

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