Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies

False positives in a Genome-Wide Association Study (GWAS) can be effectively controlled by a fixed effect and random effect Mixed Linear Model (MLM) that incorporates population structure and kinship among individuals to adjust association tests on markers; however, the adjustment also compromises true positives. The modified MLM method, Multiple Loci Linear Mixed Model (MLMM), incorporates multiple markers simultaneously as covariates in a stepwise MLM to partially remove the confounding between testing markers and kinship. To completely eliminate the confounding, we divided MLMM into two parts: Fixed Effect Model (FEM) and a Random Effect Model (REM) and use them iteratively. FEM contains testing markers, one at a time, and multiple associated markers as covariates to control false positives. To avoid model over-fitting problem in FEM, the associated markers are estimated in REM by using them to define kinship. The P values of testing markers and the associated markers are unified at each iteration. We named the new method as Fixed and random model Circulating Probability Unification (FarmCPU). Both real and simulated data analyses demonstrated that FarmCPU improves statistical power compared to current methods. Additional benefits include an efficient computing time that is linear to both number of individuals and number of markers. Now, a dataset with half million individuals and half million markers can be analyzed within three days.     

高温胁迫对不同热敏型辣椒同工酶及DNA甲基化的影响

分别以耐热型晚熟紫色辣椒‘7036’和热敏型早熟绿色辣椒‘9050’为材料,研究了40℃高温胁迫对其POD同工酶以及DNA甲基化表达的影响。结果显示:(1)在POD同工酶表达方面,未经高温胁迫的辣椒‘7036’比其它处理多出1条带,而同工酶活性在2种辣椒中呈现不同的变化趋势。(2)随着高温胁迫时间延长,辣椒‘7036’DNA无甲基化和全甲基化比率增加,半甲基化和总甲基化比率降低,而辣椒‘9050’只有高温处理7d(T_7)的甲基化水平变化与之类似,但半甲基化和全甲基化比率的绝对值远低于辣椒‘7036’。(3)高温处理7d的DNA甲基化模式中,辣椒‘7036’去甲基化C型条带比率较高,辣椒‘9050’以超甲基化B型条带为主。实验表明,高温胁迫下紫色辣椒‘7036’的POD同工酶活性恢复,半甲基化水平大幅下降和全甲基化水平快速上升以及去甲基化等变化可能与其耐高温胁迫特性相关。     

荒漠草原中间锦鸡儿林土壤养分效应对群落组分和多样性的影响

为系统认识荒漠草原中间锦鸡儿人工林草本植被特征及演变趋势对土壤养分的响应,采用空间代替时间的方法,以天然草地为对照,构建3个中间锦鸡儿林龄(16a、25a、37a)研究序列,调查不同中间锦鸡儿林灌丛内外土壤植被并分析二者之间的关系。结果表明:(1)随林龄增加,不同功能群植物重要值呈不同变化趋势,其中禾本科植物显著增加,豆科植物显著降低,杂草类植物先减小后增加。(2)α多样性分析显示,荒漠草原中间锦鸡儿人工林16a灌丛外物种丰富度(S)、香浓维纳指数(H)最高(P0.01);不同林龄均匀度指数(J)、优势度指数(P)未表现出明显的变化规律。(3)β多样性分析显示,Cody指数(βc)和Morisita-Horn(CMH)相似指数均表现出16a与25a、37a之间的物种差异较大、25a与37a之间物种差异相对较小、37a中间锦鸡儿林与天然草地物种组成相似,βws指数在25a中间锦鸡儿林最大。(4)人工中间锦鸡儿林存在显著的土壤碳氮"肥岛效应",其中土壤有机碳是不同林龄植物群落组成差异的显著性影响因子,土壤速效氮为不同林龄灌丛外植物多样性差异的显著性影响因子,但灌丛内植物多样性对土壤养分的响应并不显著。研究认为,中间锦鸡儿林土壤养分演替正效应提高了植物多样性,增强了植物物种的更替程度,但建植后期(37a)植物群落存在向天然草地演替趋势。     

新媒体时代下医学生手机依赖与人际关系的相关性研究

目的:了解新媒体背景下的医学生手机依赖与人际关系现状及两者的相关性,为相关部门制定干预策略提供依据。方法:采取方便抽样的方法抽取样本,通过手机依赖和人际关系量表开展匿名问卷调查,SPSS19.0软件进行数据处理。结果:医学生中手机依赖阳性检出率为35.81%,人际交往敏感检出率为33.78%。手机依赖组的人际关系得分明显高于非手机依赖组(P0.05);同时,手机依赖量表与人际关系量表呈正相关(P0.05)。多元线性回归分析结果显示身体锻炼频率对手机依赖有反向预测作用,人际关系中的交际与交友维度对手机依赖有正向预测作用(P0.05)。结论:医学生手机依赖与人际交往情况形势严峻、不容乐观,社会各界应关注医学生手机依赖及其引发的系列公共卫生问题,多层面、多角度进行干预。     

rSJYB1 inhibits collagen type I protein expression in hepatic stellate cells via down‐regulating activity of collagen α1 (I) promoter

YB1 is a negative regulator in liver fibrosis. We wondered whether SJYB1, a homologous protein of YB1 from Schistosoma japonicum, has an effect on liver fibrosis in vitro. Recombinant SJYB1 (rSJYB1) protein was expressed in a bacterial system and purified by Ni‐NTA His·Bind Resin. A human hepatic stellate cell line, the LX‐2 cell line, was cultured and treated with rSJYB1. The role of rSJYB1 on LX‐2 cells was then analysed by Western blot and luciferase assay. We succeeded in expressing and purifying SJYB1 in a bacterial system and the purified rSJYB1 could be recognized by S japonicum‐infected rabbit sera. Western bolt analysis showed that rSJYB1 inhibited the expression of collagen type I, but had little effect on α‐smooth muscle actin (α‐SMA). Further analysis revealed that rSJYB1 inhibited the activity of collagen α1 (I) (COL1A1) promoter and functioned at ?1592/?1176 region of COL1A1 promoter. Our data demonstrate that rSJYB1‐mediated anti‐fibrotic activity involves inhibiting the activity of COL1A1 promoter and subsequently suppressing the expression of collagen type I in hepatic stellate cells.     

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose‐dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3‐methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX‐527 suppressed melatonin‐induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1‐autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1‐autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.     

High Thermoelectric Performance in p‐type Polycrystalline Cd‐doped SnSe Achieved by a Combination of Cation Vacancies and Localized Lattice Engineering

Herein, a high figure of merit (ZT) of ≈1.7 at 823 K is reported in p‐type polycrystalline Cd‐doped SnSe by combining cation vacancies and localized‐lattice engineering. It is observed that the introduction of Cd atoms in SnSe lattice induce Sn vacancies, which act as p‐type dopants. A combination of facile solvothermal synthesis and fast spark plasma sintering technique boosts the Sn vacancy to a high level of ≈2.9%, which results in an optimum hole concentration of ≈2.6 × 10¹⁹ cm^?3 and an improved power factor of ≈6.9 µW cm^?1 K^?2. Simultaneously, a low thermal conductivity of ≈0.33 W m^?1 K^?1 is achieved by effective phonon scattering at localized crystal imperfections, as observed by detailed structural characterizations. Density functional theory calculations reveal that the role of Cd atoms in the SnSe lattice is to reduce the formation energy of Sn vacancies, which in turn lower the Fermi level down into the valence bands, generating holes. This work explores the fundamental Cd‐doping mechanisms at the nanoscale in a SnSe matrix and demonstrates vacancy and localized‐lattice engineering as an effective approach to boosting thermoelectric performance. The work provides an avenue in achieving high‐performance thermoelectric properties of materials.     

Insights into the Effects of Electrolyte Composition on the Performance and Stability of FeF2 Conversion‐Type Cathodes

As an alternative to commercial Ni‐ and Co‐based intercalation‐type cathode materials, conversion‐type metal fluoride (MF_x) cathodes are attracting more interest due to their promises to increase cell‐level energy density when coupled with lithium (Li) or silicon (Si)‐based anodes. Among metal fluorides, iron fluorides (FeF₂ and FeF₃) are regarded as some of the most promising candidates due to their high capacity, moderately high potential and the very low cost of Fe. In this study, the impacts of electrolyte composition on the performance and stability of nanostructured FeF₂ cathodes are systematically investigated. Dramatic impacts of Li salt composition, Li salt concentration, solvent composition, and cycling potential range on the cathode's most critical performance parameters—stability, capacity, rate, and voltage hysteresis are discovered. In contrast to previous beliefs, it is observed that even if the Fe²⁺ cation dissolution could be avoided, the dissolution of F^? anions may still negatively affect cathode performance. Formation of the more favorable cathode solid electrolyte interface (CEI) is found to minimize both processes.