Biology subjects

Han, C.

Publications and source records attributed to Han, C..

6 recordsLinked to original sources

bioRxiv2018

Alteration of Vascular Endothelial Cadherin in Alzheimer’s Disease Patient and Mouse Model

Alzheimers disease (AD) is characterized by amyloid plaques and pathologic cerebrovascular remodeling. Cerebrovascular abnormalities may contribute to the pathology of AD, but the molecular mechanisms are not fully understood. In this study, we evaluated blood-brain barrier (BBB) disruption and the role of VE-cadherin in the progression of amyloid pathology. Here, we determined that levels of VE-cadherin are decreased in brain vessels of AD patients and mouse model of AD. In vitro experiments showed that the disappearance of VE-cadherin by beta-amyloid at the endothelial cell surface was due to cleavage of VE-cadherin. VE-cadherin cleavage was inhibited by a {gamma}-secretase and ADAM10 inhibitor. The disappearance of VE-cadherin in brain vessels was also seen in amyloid precursor protein transgenic mice. In the postmortem brain of individuals with AD, furthermore, levels of VE-cadherin were significantly reduced in vessels. Dementia patients showed a distinct blood biochemical profile characterized by high soluble VE-cadherin (sVEC). There was a strong association between plasma sVEC (adjusted odds ratio = 3.41, P < 0.001) and dementia. These results suggest that measurements of plasma VE-cadherin could have the potential for predicting the risk of progressive AD.

neuroscience↗

bioRxiv2018

Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop

Aberrant chromosomal translocations leading to tumorigenesis have been ascribed to the heterogeneously oncogenic functions. However, how fusion transcripts exporting remains to be declared. Here, we showed that the nuclear speckle-specific long non coding RNA MALAT1 controls chimeric mRNA export processes and regulates myeloid progenitor cell differentiation in malignant hematopoiesis. We demonstrated that MALAT1 regulates chimeric mRNAs export in an m6A-dependent manner and thus controls hematopoietic cell differentiation. Specifically, reducing MALAT1 or m6A methyltransferases and the reader YTHDC1 result in the universal retention of distinct oncogenic gene mRNAs in nucleus. Mechanically, MALAT1 hijacks both the chimeric mRNAs and fusion proteins in nuclear speckles during chromosomal translocations and mediates the colocalization of oncogenic fusion proteins with METTL14. MALAT1 and fusion protein complexes serve as a functional loading bridge for the interaction of chimeric mRNA and METTL14. This study demonstrated a universal mechanism of chimeric mRNA transport that involves lncRNA-fusion protein-m6A autoregulatory loop for controlling myeloid cell differentiation. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport might represent a new common paradigm for treating blood malignancies.

cancer biology↗

bioRxiv2018

Highly efficient CRISPR/Cas9-mediated tissue specific mutagenesis in Drosophila

Tissue-specific loss-of-function (LOF) analysis is an essential approach for characterizing gene function. Here we describe an efficient CRISPR-mediated tissue-restricted mutagenesis (CRISPR-TRiM) method for ablating gene function in Drosophila. This binary system consists of a tissue-specific Cas9 and a ubiquitously expressed multi-guide RNA (gRNA) transgene. To facilitate the construction of these components, we developed convenient tools for generating and evaluating enhancer-driven Cas9 lines, identified a multi-gRNA design that is highly efficient in mutagenizing somatic cells, and established an assay for testing the efficiency of multi-gRNAs in creating double-stranded breaks. We found that excision of genomic DNA induced by two gRNAs is infrequent in somatic cells, while indels more reliably cause tissue-specific LOF. Furthermore, we show that enhancer-driven Cas9 is less cytotoxic yet results in more complete gene removal than Gal4-driven Cas9 in larval neurons. Finally, we demonstrate that CRISPR-TRiM efficiently unmasks redundant gene functions in neuronal morphogenesis. Importantly, two Cas9 transgenes that turn on with different timings in the neuronal lineage revealed the extent to which gene products persist in cells after tissue-specific gene knockout. These CRISRPR tools can be applied to analyze tissue-specific gene function in many biological processes.

developmental biology↗

bioRxiv2017

No evidence for correlations between handgrip strength and sexually dimorphic acoustic properties of voices

ObjectivesRecent research on the signal value of masculine physical characteristics in men has focused on the possibility that such characteristics are valid cues of physical strength. However, evidence that sexually dimorphic vocal characteristics are correlated with physical strength is equivocal. Consequently, we undertook a further test for possible relationships between physical strength and masculine vocal characteristics.\n\nMethodsWe tested the putative relationships between White UK (N=115) and Chinese (N=106) participants handgrip strength (a widely used proxy for general upper-body strength) and five sexually dimorphic acoustic properties of voices: fundamental frequency (F0), fundamental frequencys standard deviation (F0-SD), formant dispersion (Df), formant position (Pf), and estimated vocal-tract length (VTL).\n\nResultsAnalyses revealed no clear evidence that stronger individuals had more masculine voices.\n\nConclusionsOur results do not support the hypothesis that masculine vocal characteristics are a valid cue of physical strength.

evolutionary biology↗

bioRxiv2017

Women’s preferences for facial masculinity are not related to their hormonal status

Although widely cited as strong evidence that sexual selection has shaped human facial attractiveness judgments, evidence that preferences for masculine characteristics in mens faces are related to womens hormonal status is equivocal and controversial. Consequently, we conducted the largest ever longitudinal study of the hormonal correlates of womens preferences for facial masculinity (N=584). Analyses showed no compelling evidence that preferences for facial masculinity were related to changes in womens salivary steroid hormone levels. Furthermore, both within-subject and between-subject comparisons showed no evidence that oral contraceptive use decreased masculinity preferences. However, women generally preferred masculinized over feminized versions of mens faces, particularly when assessing mens attractiveness for short-term, rather than long-term, relationships. Our results do not support the hypothesized link between womens preferences for facial masculinity and their hormonal status.

animal behavior and cognition↗

bioRxiv2017

Within-Woman Hormone-Attractiveness Correlations Are Not Simply Byproducts Of Between-Women Hormone-Attractiveness Correlations

Putative associations between sex hormones and attractive physical characteristics in women are central to many theories of human physical attractiveness and mate choice. Although such theories have become very influential, evidence that physically attractive and unattractive women have different hormonal profiles is equivocal. Consequently, we investigated hypothesized relationships between salivary estradiol and progesterone and two aspects of womens physical attractiveness that are commonly assumed to be correlated with levels of these hormones: facial attractiveness (N=249) and waist-to-hip ratio (N=247). Our analyses revealed no evidence that women with more attractive faces or lower (i.e., more attractive) waist-to-hip ratios had higher levels of estradiol or progesterone. These results do not support the influential hypothesis that between-woman differences in physical attractiveness are related to estradiol and/or progesterone.

animal behavior and cognition↗