Biology subjects

Chen, C. D.

Publications and source records attributed to Chen, C. D..

3 recordsLinked to original sources

bioRxiv2022

Neuroimaging within the Dominantly Inherited Alzheimer's Network (DIAN): PET and MRI

The Dominantly Inherited Alzheimer Network (DIAN) Observational Study is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). This rare form of Alzheimer disease (AD) is caused by mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. As individuals from these families have a 50% chance of inheriting the familial mutation, this provides researchers with a well-matched cohort of carriers vs non-carriers for case-control studies. An important trait of ADAD is that the age at symptom onset is highly predictable and consistent for each specific mutation, allowing researchers to estimate an individuals point in their disease time course prior to symptom onset. Although ADAD represents only a small proportion (approximately 0.1%) of all AD cases, studying this form of AD allows researchers to investigate preclinical AD and the progression of changes that occur within the brain prior to AD symptom onset. Furthermore, the young age at symptom onset (typically 30-60 years) means age-related comorbidities are much less prevalent than in sporadic AD, thereby allowing AD pathophysiology to be studied independent of these confounds. A major goal of the DIAN Observational Study is to create a global resource for AD researchers. To that end, the current manuscript provides an overview of the DIAN magnetic resonance imaging (MRI) and positron emission tomography (PET) protocols and highlights the key imaging results of this study to date.

neuroscience↗

bioRxiv2020

Prediction of meiosis-essential genes based upon the dynamic proteomes responsive to spermatogenesis

Mammalian meiosis is a specific cell division process during sexual reproduction, whereas a comprehensive proteome of the different meiotic stages has not been systematically investigated. Here, we isolated different types of spermatocytes from the testes of spermatogenesis-synchronized mice and quantified the corresponding proteomes with high-resolution mass spectrometry. A total of 8,002 proteins were identified in nine types of germ cells, and the protein signatures of spermatogenesis were characterized using the dynamic proteomes. A supervised machine learning package, FuncProFinder, was developed to predict meiosis-essential candidate genes based on changes in their protein abundance. Of the candidates without functional annotation, four of the ten genes with the highest prediction scores, Zcwpw1, Tesmin, 1700102P08Rik, and Kctd19, were validated as meiosis-essential genes using knockout mouse models. The proteomic analysis of spermatogenic cells provides a solid foundation for studying the mechanism of mammalian meiosis.

developmental biology↗

bioRxiv2018

Novelty and surprise-timing are broadcast by the basal forebrain

The basal forebrain (BF) is a principal source of modulation of the neocortex, and is thought to regulate cognitive functions such as attention, motivation, and learning by broadcasting information about the behavioral salience of events. An event can be salient because it is novel, surprising, or associated with reward prediction errors. But to date, the type of salience-related information the BF broadcasts is unclear. Here, we report that many BF neurons display phasic excitatory bursting that rapidly conveys the magnitude, probability, and timing of primary reinforcements. The same BF neurons also discriminate fully expected novel visual objects from familiar objects and respond to object-sequence violations, regardless of their relevance for subsequent behaviors, suggesting that they are not dedicated to signaling information about primary reinforcements. A different group of BF neurons displayed ramping activations that predicted the time of novel and surprising events. Their ramping was highly sensitive to the subjects confidence in event timing. Hence, BF neurons signal statistics about time and salience. Their activity may organize cortical computations to facilitate accurate behavioral responses to a diverse set of expected and ongoing events.

neuroscience↗