| 1. |
- Deng, Min, et al.
(author)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Journal article (peer-reviewed)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 2. |
- Long, Chang, et al.
(author)
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Regulating reconstruction of oxide-derived Cu for electrochemical CO2 reduction toward n-propanol
- 2023
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In: Science Advances. - 2375-2548. ; 9:43
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Journal article (peer-reviewed)abstract
- Oxide-derived copper (OD-Cu) is the most efficient and likely practical electrocatalyst for CO2 reduction toward multicarbon products. However, the inevitable but poorly understood reconstruction from the pristine state to the working state of OD-Cu under strong reduction conditions largely hinders the rational construction of catalysts toward multicarbon products, especially C-3 products like n-propanol. Here, we simulate the reconstruction of CuO and Cu2O into their derived Cu by molecular dynamics, revealing that CuO-derived Cu (CuOD-Cu) intrinsically has a richer population of undercoordinated Cu sites and higher surficial Cu atom density than the counterpart Cu2O-derived Cu (Cu2OD-Cu) because of the vigorous oxygen removal. In situ spectroscopes disclose that the coordination number of CuOD-Cu is considerably lower than that of Cu2OD-Cu, enabling the fast kinetics of CO2 reaction and strengthened binding of *C-2 intermediate(s). Benefiting from the rich undercoordinated Cu sites, CuOD-Cu achieves remarkable n-propanol faradaic efficiency up to similar to 17.9%, whereas the Cu2OD-Cu dominantly generates formate.
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| 3. |
- Yin, Chunhua, et al.
(author)
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Role of Host-Guest Charge Transfer in Cyclodextrin Complexation : A Computational Study
- 2019
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In: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 123:29, s. 17745-17756
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Journal article (peer-reviewed)abstract
- Charge transfer (CT) was proposed to play a role in the cyclodextrin (CD) complexation with guest molecules. To elucidate the importance of CT interactions, here we used computational methods of quantum mechanics, docking, and molecular dynamics (MD) to investigate alpha-CD complexes with aromatic guest molecules of nitrobenzene, carboxybenzene, benzoate, 4-nitrophenol, and 4-nitrophenolate. Considering host guest CT in the docking has more of a chance to search reasonable guest orientations relative to alpha-CD matching the experiment, compared to that without CT. The CT interaction enlarges the difference in binding affinities of varied guests, as evidenced from potential of mean force (PMF) MD calculations. Energy decomposition of the total enthalpy and entropy shows the CT influence on the binding reactions in detail and indicates that there are considerable compensating effects of individual contributions from the binding partners and surrounding water. Charge transfer reduces the total dipole of alpha-CD by 9% on average and alters its dipole direction thereby affecting guest association. Gas-phase zeroth-order symmetry-adapted perturbation theory calculations show host guest CT amounts to approximately 6% of the total binding energy. The continuum solvation model based on the quantum mechanical charge density predicts binding energies comparable with the well depth of PMF profiles in explicit water. The abnormal binding strength of alpha-CD with the similar guests can be rationalized in terms of hydrogen bonding, extent of host guest CT, and dipole arrangement of guest relative to host.
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| 4. |
- Zhou, Yutong, et al.
(author)
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The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment
- 2023
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 22:9, s. 2936-2949
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Journal article (peer-reviewed)abstract
- Sleep loss is associated with cognitive dysfunction. However, the detailed mechanisms remain unclear. In this study, we established a para-chlorophenylalanine (PCPA)-induced insomniac mouse model with impaired cognitive function. Mass-spectrometry-based proteomics showed that the expression of 164 proteins was significantly altered in the hippocampus of the PCPA mice. To identify critical regulators among the potential markers, a transcriptome-wide association screening was performed in the BXD mice panel. Among the candidates, the expression of pleiotrophin (Ptn) was significantly associated with cognitive functions, indicating that Ptn-mediates sleep-loss-induced cognitive impairment. Gene co-expression analysis further revealed the potential mechanism by which Ptn mediates insomnia-induced cognitive impairment via the MAPK signaling pathway; that is, the decreased secretion of Ptn induced by insomnia leads to reduced binding to Ptprz1 on the postsynaptic membrane with the activation of the MAPK pathway via Fos and Nr4a1, further leading to the apoptosis of neurons. In addition, Ptn is genetically trans-regulated in the mouse hippocampus and implicated in neurodegenerative diseases in human genome-wide association studies. Our study provides a novel biomarker for insomnia-induced cognitive impairment and a new strategy for seeking neurological biomarkers by the integration of proteomics and systems genetics.
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