Biology subjects

Turck, C. W.

Publications and source records attributed to Turck, C. W..

4 recordsLinked to original sources

bioRxiv2024

PyINETA: Open-source platform for INADEQUATE-JRES integration in NMR metabolomics

Annotating compounds with high confidence is a critical element in metabolomics. 13C-detection NMR experiment INADEQUATE (incredible natural abundance double-quantum transfer experiment) stands out as a powerful tool for structural elucidation, whereas this valuable experiment is not often included in metabolomics studies. This is partly due to the lack of community platform that provides structural information based INADEQUATE. Also, it is often the case that a single study uses various NMR experiments synergistically to improve the quality of information or balance total NMR experiment time, but there is no public platform that can integrate the outputs of INADEQUATE and other NMR experiments either. Here, we introduce PyINETA, Python-based INADEQUATE network analysis. PyINETA is an open-source platform that provides structural information of molecules using INADEQUATE, conducts database search, and integrates information of INADEQUATE and a complementary NMR experiment 13C J-resolved experiment (13C-JRES). Those steps are carried out automatically, and PyINETA keeps track of all the pipeline parameters and outputs, ensuring the transparency of annotation in metabolomics. Our evaluation of PyINETA using a model mouse study showed that our pipeline successfully integrated INADEQUATE and 13C-JRES. The results showed that 13C-labeled amino acids that were fed to mice were transferred to different tissues, and, also, they were transformed to other metabolites. The distribution of those compounds was tissue-specific, showing enrichment of particular metabolites in liver, spleen, pancreas, muscle, or lung. The value of PyINETA was not limited to those known compounds; PyINETA also provided fragment information for unknown compounds. PyINETA is available on NMRbox.

systems biology↗

bioRxiv2023

New tree shrew Parkinson's model: a cost-effective alternative to monkey models

The surge in demand for experimental monkeys has led to a rapid increase in their associated costs. Consequently, there is a growing need for the development of a cost-effective model for Parkinsons disease (PD) that exhibits all core clinical and pathological phenotypes of PD. Evolutionarily, tree shrews (Tupaia belangeri) are much closer to primates in comparison to rodents and share more similar PD-related brain structures and movement ability with monkeys. As such, tree shrews represent an ideal small animal species for modeling PD. To develop a tree shrew PD model, we used the 1-Methyl-4-phenylpyridinium (MPP+) metabolite, derived from the well-established PD modeling drug 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to induce lesions in the dopaminergic neurons of the unilateral substantia nigra. After determining the optimal modeling dosage, the tree shrews consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms closely resembled the ones observed in PD monkeys and included bradykinesia, rest tremor, postural instability, and apomorphine-induced rotations, a classic phenotype of unilateral PD models. Immunostaining showed a significant loss of dopaminergic neurons (approximately 95%) in the substantia nigra on the lesioned side of the brain, a crucial pathological marker of PD. Further cytomorphological analysis revealed that the size of nigral dopaminergic neurons in tree shrews exceeded that of rodents and more closely approximated that of macaques. Based on the principle that structure determines function, the morphological similarity between tree shrews and monkeys may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, this study successfully developed a PD model in a small animal species that faithfully recapitulated the classical clinical symptoms and key pathological indicators of PD monkeys. In addition to the well-recognized monkey models, the tree shrew model provides a novel avenue for the evaluation of PD treatments and underlying mechanisms.

neuroscience↗

bioRxiv2022

Naturally occurring Alzheimer's disease in rhesus monkeys

Alzheimers disease (AD) is the most common neurodegenerative disease. To date, its cause is unclear and there are no effective treatments or preventive measures. Despite there are accumulating evidences for the existence of AD pathological hallmarks in the brain of aging rhesus monkeys, it remains a mainstream notion that monkeys do not develop AD naturally. This is an important issue because it will determine how we use monkeys in AD studies. To settle down this issue, a group (n=10) of aged rhesus monkeys 26 years old or above went through a systematic AD screening procedure in this study. Three of these monkeys showed severe memory impairments (SMI) after evaluated with a classic working memory test. Further behavioral testing revealed that the SMI monkeys also exhibited apathy-like behavior, which is another core AD clinical symptom. In addition to the cognitive deficits, two of the three SMI monkeys developed all of the three AD pathological hallmarks, including neurofibrillary tangles, senile plaques and neuronal loss. According to the diagnostic criteria of human AD, the two SMI monkeys were clearly naturally occurring AD monkeys. These results suggest that AD is not a uniquely human disease and monkeys have great potential for the development of much needed etiological AD models, which are vital for better understanding of developmental process of AD and the base of identification of early diagnostic biomarkers and effective therapeutic targets of AD.

neuroscience↗

bioRxiv2020

Stress-primed secretory autophagy drives extracellular BDNF maturation

The stress response is an essential mechanism that strives to maintain homeostasis, and its disruption is implicated in several psychiatric disorders. As a cellular response to stressors, autophagy is activated to regulate homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway where autophagosomes fuse with the plasma membrane rather than lysosomes. In this study, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy, via the stress-responsive co-chaperone FK506-binding protein 51. We identified the matrix metalloproteinase 9 (MMP9) as one of the stress-induced secreted proteins. Using cellular assays and in vivo microdialysis, we further found that stress-enhanced MMP9 secretion increases the cleavage of pro-brain derived neurotrophic factor (proBDNF) to its mature form. BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a novel mechanistic link between stress, stress adaptation and the development of psychiatric disorders, with possible therapeutic implications.

molecular biology↗