Adaptive Mantel Test for AssociationTesting in Imaging Genetics Data

Mantel's test (MT) for association is conducted by testing the linear relationship of similarity of all pairs of subjects between two observational domains. Motivated by applications to neuroimaging and genetics data, and following the succes of shrinkage and kernel methods for prediction with high-dimensional data, we here introduce the adaptive Mantel test as an extension of the MT. By utilizing kernels and penalized similarity measures, the adaptive Mantel test is able to achieve higher statistical power relative to the classical MT in many settings. Furthermore, the adaptive Mantel test is designed to simultaneously test over multiple similarity measures such that the correct type I error rate under the null hypothesis is maintained without the need to directly adjust the significance threshold for multiple testing. The performance of the adaptive Mantel test is evaluated on simulated data, and is used to investigate associations between genetics markers related to Alzheimer's Disease and heatlhy brain physiology with data from a working memory study of 350 college students from Beijing Normal University

To Deconvolve, or Not to Deconvolve: Inferences of Neuronal Activities using Calcium Imaging Data

With the increasing popularity of calcium imaging data in neuroscience research, methods for analyzing calcium trace data are critical to address various questions. The observed calcium traces are either analyzed directly or deconvolved to spike trains to infer neuronal activities. When both approaches are applicable, it is unclear whether deconvolving calcium traces is a necessary step. In this article, we compare the performance of using calcium traces or their deconvolved spike trains for three common analyses: clustering, principal component analysis (PCA), and population decoding. Our simulations and applications to real data suggest that the estimated spike data outperform calcium trace data for both clustering and PCA. Although calcium trace data show higher predictability than spike data at each time point, spike history or cumulative spike counts is comparable to or better than calcium traces in population decoding

Effects of Xinwei granule on expression levels of cyclin D1 and its upstream genes in gastric intraepithelial neoplasia tissues

Purpose: To explore the effects of Xinwei granule (XWG) on low-grade gastric intraepithelial neoplasia (LGIN) and the underlying mechanisms. Methods: To establish LGIN model, Wistar rats were treated with N-methyl-N'-nitrosoguanidine for 3 months. LGIN model rats were randomly grouped into five groups (n = 15), viz, negative control (NC), normal saline (NS) group, Xinwei granule (XWG) group, Weifuchun tablet (WFCT) group, and vatacoenayme tablet (VT) group. Normal rats (n = 17) served as negative control. Histological evaluation of gastric mucosa was undertaken using hematoxylin and eosin staining. Quantitative realtime polymerase chain reaction (qRT-PCR), western blot, and immunohistochemical assays were performed to determine mRNA expressions, protein expression, and the distribution of cyclin D1, kruppel-like factor 4 (KLF4), and p21-WAF1-CIP1, respectively. Results: Compared with LGIN group, the body weight of the rats increased in XWG, WFCT, and VT groups. The pathological characteristics of LGIN group were alleviated by XWG, WFCT and VT treatments. The positive expression of cyclin D1 was enhanced in LGIN group, but reduced in XWG, WFCT and VT groups. The expression levels of KLF4 and p21-WAF1-CIP1, upstream regulators of cyclin D1 reduced in LGIN groups. However, administration of XWG, WFCT and VT strengthened the expressions of KLF4 and p21-WAF1-CIP1. More importantly, the protective effects of XWG against LGIN were superior to those of WFCT and VT. Conclusion: Xinwei granules alleviate LGIN in vivo by inhibiting cyclin D1 expression and enhancing KLF4 and p21-WAF1-CIP1 expression

Complex I deficiency in m.3243A>G fibroblasts is alleviated by reducing NADH accumulation

Introduction: Mitochondrial disease is a spectrum of debilitating disorders caused by mutations in the mitochondrial DNA (mtDNA) or nuclear DNA that compromises the respiratory chain. Mitochondrial 3243A>G (m.3243 A>G) is the most common mutation showing great heterogeneity in phenotype. Previous studies have indicated that NADH: ubiquinone oxidoreductase (complex I) deficiency accompanied by a decreased nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) ratio may play a pivotal role in the pathogenesis of m.3243A>G mutation.Methods: To evaluate the potential effects of strategies targeting the imbalanced NAD+/NADH ratio in m.3243A>G mutation, we treated fibroblasts derived from patients with the m.3243 A>G mutation using nicotinamide riboside (NR) or mitochondria-targeted H2O-forming NADH oxidase (mitoLbNOX).Results: M.3243 A>G fibroblasts showed a significant reduction in complex I core subunit 6, complex I enzymatic activity, complex I-dependent oxygen consumption rate (OCR), and adenosine triphosphate (ATP) production compared to the controls. The NAD+/NADH ratio was also significantly reduced in m.3243 A>G fibroblasts, and, using fluorescence lifetime imaging microscopy, we also found that the NADH level was elevated in m.3243 A>G fibroblasts. After NR treatment, the NAD+/NADH ratio, complex I-dependent OCR, and ATP levels increased, whereas NADH levels remained unchanged. More excitingly, after treatment with mitoLbNOX, the NAD+/NADH ratio, complex I-independent OCR, and ATP levels increased more pronouncedly compared with the NR treatment group, accompanied by significantly reduced NADH levels.Discussion: The present study suggests that compared with repletion of NAD+ alone, the combination of this therapeutic modality with alleviation of NADH overload may amplify the treatment effect of restoring NAD+/NADH balance in m.3243A>G fibroblasts