bioRxiv Science⌕ Search

Biology subjects

Chang, L.-C.

Publications and source records attributed to Chang, L.-C..

4 recordsLinked to original sources

Exploiting Four-way Phase-encoding Benefits for Robust Detection and Correction of EPI artifacts: Application to Residual Ghosts in Diffusion MRI.

PurposeTo propose and develop an image processing-based methodology for detecting and correcting echo planar imaging (EPI) artifact that employs data from 4-way phase-encoding acquisitions. ApproachPrevious studies have demonstrated that acquiring images with four different phase-encoding directions can improve the reproducibility of diffusion derived quantitative maps while retaining the same acquisition time. This improvement is achieved by averaging across phase-encoding directions (PEDs) to reduce the impact of EPI artifacts. Building on this principle, the proposed method further improves this 4-way encoding approach by leveraging the properties of signal distributions to detect artifactual regions. Additionally, the method can be tailored for specific artifact manifestations by considering their localization due to underlying acquisition parameters. The proposed method is applied to and validated using both simulated data and in-vivo diffusion MRI data affected by residual ghost artifacts. ResultsSimulations with known ground-truth images demonstrated high artifact detection accuracy, achieving a Dice score of 0.91 for reconstructions without parallel imaging. In the in-vivo dataset, the method also improved longitudinal reproducibility, reducing variability by 30% in ghost-affected regions. ConclusionThe proposed correction method effectively detected and corrected residual ghost artifacts without the need of any additional k-space data. This retrospective approach can be directly integrated into existing processing pipelines to further improve the quality of EPI images and enhancing image quality in studies that utilize 4-way PEDs acquisition.

bioengineering↗

A First-in-Class Dual Degrader of Bcl-2/Bcl-xL Reverses HIV Latency and Eliminates Ex Vivo Reservoirs

The persistence of latent HIV-1 proviruses in CD4+ T cells is a major obstacle to curing HIV. The "shock and kill" strategy involves reversing latency with latency-reversing agents (LRAs) and selectively inducing cell death in infected cells. However, current LRAs have shown limited efficacy in eliminating the ex vivo HIV reservoir. We repurposed PZ703b, a pro-apoptotic protein degrader initially developed for anti-leukemia therapy, to target HIV eradication. PZ703b induced degradation of Bcl-2 and Bcl-xL, activating the non-canonical NF-kB pathway and caspases cascade, resulting in latency reversal and selective apoptosis of infected cells. Treatment of ex vivo CD4+ T cells from ART-suppressed HIV-1 patients achieved a [~]50% reduction in the replication-competent reservoir. Our study provides proof-of-concept for using protein degraders to reverse HIV latency and induce cell death, highlighting PZ703bs potential in HIV cure strategies. This approach may pave the way for novel therapeutic interventions aimed at eliminating the HIV-inducible reservoir.

molecular biology↗

MAP kinase Slt2p attenuates cell wall mRNA decay by downregulating the RNA-binding protein Rbp1p in response to stress

The yeast cell wall integrity (CWI) MAPK pathway is a signaling cascade function in maintaining cell wall integrity under stressful environmental conditions. Recently, the activity and signaling of Slt2p (Mpk1p) MAP kinase has been shown to control assembly of the processing body (P-body) upon cell wall stresses, implicating its posttranscriptional role in decay of cell wall mRNAs. However, how Slt2p MAP kinase directly regulates the stability of cell wall transcripts during cell wall stress remains unclear. Here, we reported that the RNA-binding protein Rbp1p (Ngr1p) is a downstream effector and target of Slt2p MAP kinase during activation of the cell wall stress signaling cascade. In addition to the well-defined target mitochondrial porin mRNA, we found that Rbp1p also negatively regulates the stability of a subset of Slt2p-regulated cell wall transcripts. Deletion of RBP1 increases the level of cell wall transcripts and partially suppresses the hypersensitivity of the slt2{Delta} deletion strain to cell wall damage. Slt2p is necessary for cell wall stress-induced stabilization of cell wall transcripts. Deletion of RBP1 compromises the destabilization of cell wall transcripts in slt2{Delta} mutants under cell wall stress. Notably, C-terminal deleted Slt2p impairs its function in promoting turnover of the Rbp1p protein and fails to stabilize cell wall transcripts, although it can complement the growth defect of the slt2{Delta} strain upon cell wall stress. Altogether, our results demonstrate that MAP kinase Slt2p attenuates CWI mRNA decay in response to cell wall damage by downregulating the activity of the RNA-binding protein Rbp1p.

cell biology↗

Identification of type 2 diabetes loci in 433,540 East Asian individuals

Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.\n\nType 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic {beta} cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.

genetics↗