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Fu, C.

Publications and source records attributed to Fu, C..

3 recordsLinked to original sources
bioRxiv2019

Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset. MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain predicted age difference (brain-PAD). FindingsOn average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohens d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004). InterpretationThis highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates. FundingThis work was supported, in part, by NIH grants U54 EB020403 and R01 MH116147.

neuroscience↗
bioRxiv2019

Unisexual reproduction promotes foraging for mating partners in the global human fungal pathogen Cryptococcus deneoformans

Courtship is pivotal for successful mating. However, courtship is challenging for the Cryptococcus neoformans species complex, comprised of opportunistic fungal pathogens, as the majority of isolates are mating type. In the absence of mating partners of the opposite mating type, C. deneoformans can undergo unisexual reproduction, during which a yeast-to-hyphal morphological transition occurs. Hyphal growth during unisexual reproduction is a quantitative trait, which reflects a strains ability to undergo unisexual reproduction. In this study, we determined whether unisexual reproduction confers an ecological benefit by promoting foraging for mating partners. Through competitive mating assays using strains with different abilities to produce hyphae, we showed that unisexual reproduction potential did not enhance competition for mating partners of the same mating type, but when cells of the opposite mating type were present, cells with enhanced hyphal growth were more competitive for mating partners of either the same or opposite mating type. Enhanced mating competition was also observed in a strain with increased hyphal production that lacks the mating repressor gene GPA3, which contributes to the pheromone response. Hyphal growth in unisexual strains also enables contact between adjacent colonies and enhances mating efficiency during mating confrontation assays. The pheromone response pathway activation positively correlated with unisexual reproduction hyphal growth during bisexual mating and exogenous pheromone promoted bisexual cell fusion. Despite the benefit in competing for mating partners, unisexual reproduction conferred a fitness cost. Taken together, these findings suggest C. deneoformans employs hyphal growth to facilitate contact between colonies at long distances and utilizes pheromone sensing to enhance mating competition.\n\nAuthor SummarySexual reproduction plays a pivotal role in shaping fungal population structure and diversity in nature. The global human fungal pathogen Cryptococcus neoformans species complex evolved distinct sexual cycles: bisexual reproduction between mating partners of the opposite mating types, and unisexual reproduction with only one mating type. During both sexual cycles, cells undergo a yeast-to-hyphal morphological transition and nuclei diploidize through either cell-cell fusion followed by nuclear fusion during bisexual reproduction or endoreplication during unisexual reproduction. Despite the complex sexual life cycle, the majority of Cryptococcal isolates are mating type. Albeit the scarcity of MATa cells in the environment, meiotic recombination is prevalent. To decipher this conundrum, we ask whether there is an underlying mechanism in which Cryptococcus species increase their mating opportunities. In this study, we showed that the undirected hyphal growth during unisexual reproduction enables MAT cells to forage for mating partners over a larger surface area, and when MAT hyphae come into close proximity of rare MATa cells, pheromone response pathway activation in both MAT and MATa cells can further enhance mating. This mating enhancement could promote outcrossing and facilitate genome reshuffling via meiotic recombination.

microbiology↗
bioRxiv2018

Mitochondrial cristae biogenesis coordinates with ETC complex IV assembly during Drosophila maturation

Mitochondrial cristae contain electron transport chain (ETC) complexes and are distinct from the inner boundary membrane (IBM) in both protein composition and function. While many details of mitochondrial membrane structure are known, the processes governing cristae biogenesis, including the organization of lipid membranes and assembly of proteins encoded by both nuclear and mitochondrial DNA, remain obscure. We followed cristae biogenesis in situ upon Drosophila eclosion using serial-section electron tomography and revealed that the morphogenesis of lamellar cristae coordinates with ETC complex IV assembly. The membrane morphogenesis and gain-of-function were intricately co-evolved during cristae biogenesis. Marf-knockdown flies formed lamellar cristae containing ATP synthase and functional COX. However, OPA1-knockdown flies showed impaired cristae biogenesis. Overall, this study revealed the multilevel coordination of protein-coupled membrane morphogenesis in building functional cristae.

cell biology↗