Role of Adiponectin‐Notch pathway in cognitive dysfunction associated with depression and in the therapeutic effect of physical exercise

A substantial percentage of late‐life depression patients also have an cognitive impairment, which severely affects the life quality, while the co‐occurring mechanisms are still unclear. Physical exercise can ameliorate both depressive behaviors and cognitive dysfunction, but the molecular mechanisms underlying its beneficial effects remain elusive. In this study, we uncover a novel adipose tissue to hippocampus crosstalk mediated by Adiponectin‐Notch pathway, with an impact on hippocampal neurogenesis and cognitive function. Adiponectin, an adipocyte‐derived hormone, could activate Notch signaling in the hippocampus through upregulating ADAM10 and Notch1, two key molecules in the Notch signaling. Chronic stress inhibits the Adiponectin‐Notch pathway and induces impaired hippocampal neurogenesis and cognitive dysfunction, which can be rescued by AdipoRon and running. Inhibition Notch signaling by DAPT mimics the adverse effects of chronic stress on hippocampal neurogenesis and cognitive function. Adiponectin knockout mice display depressive‐like behaviors, associated with inhibited Notch signaling, impaired hippocampal neurogenesis and cognitive dysfunction. Physical exercise could activate Adiponectin‐Notch pathway, and improve hippocampal neurogenesis and cognitive function, while deleting adiponectin gene or inhibiting Notch signaling blocks its beneficial effects. Together, our data not only suggest that Adiponectin‐Notch pathway is involved in the pathogenesis of cognitive dysfunction associated with depression, but also contributes to the therapeutic effect of physical exercise. This work helps to decipher the etiology of cognitive impairment associated with depression and hence will provide a potential innovative therapeutic target for these patients.     

Analysis of trichloroethylene-induced global DNA hypomethylation in hepatic L-02 cells by liquid chromatography–electrospray ionization tandem mass spectrometry

Trichloroethylene (TCE), a major occupational and environmental pollutant, has been recently associated with aberrant epigenetic changes in experimental animals and cultured cells. TCE is known to cause severe hepatotoxicity; however, the association between epigenetic alterations and TCE-induced hepatotoxicity are not yet well explored. DNA methylation, catalyzed by enzymes known as DNA methyltransferases (DNMT), is a major epigenetic modification that plays a critical role in regulating many cellular processes. In this study, we analyzed the TCE-induced effect on global DNA methylation and DNMT enzymatic activity in human hepatic L-02 cells. A sensitive and quantitative method combined with liquid chromatography and electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) was validated and utilized for assessing the altered DNA methylation in TCE-induced L-02 cells. Quantification was accomplished in multiple reaction monitoring (MRM) mode by monitoring a transition pair of m/z 242.1 (molecular ion)/126.3 (fragment ion) for 5-mdC and m/z 268.1/152.3 for dG. The correlation coefficient of calibration curves between 5-mdC and dG was higher than 0.9990. The intra-day and inter-day relative standard derivation values (RSD) were on the range of 0.53–7.09% and 0.40–2.83%, respectively. We found that TCE exposure was able to significantly decrease the DNA methylation and inhibit DNMT activity in L-02 cells. Our results not only reveal the association between TCE exposure and epigenetic alterations, but also provide an alternative mass spectrometry-based method for rapid and accurate assessment of chemical-induced altered DNA methylation in mammal cells.     

大鼠肠癌中Ⅳ型胶原酶及ras P21表达的研究

用二甲肼诱发Ｗｉｓｔａｒ大鼠肠癌,并应用免疫组化双标记方法对肠道良、恶性病变中Ⅳ型胶原酶的表达及基底膜的改变作了研究,同时观察Ｐ２１的表达情况。结果显示,肠道良性病变及良性肿瘤中Ⅳ型胶原酶反应阳性率为２１．７４％,在肠癌中阳性率为７９．４１％,两者差异极显著（Ｐ＜０．０１）。Ⅳ型胶原染色显示,良性病变及良性肿瘤基底膜完整,而肠癌中基底膜出现断裂或缺失。表明Ⅳ型胶原酶对基底膜的破坏及肠癌浸润转移起重要作用。Ｐ２１在肠良性病变及良性肿瘤中阳性率为３０．４３％,而在肠癌中为６７．６５％,两者差异也有极显著意义（Ｐ＜０．０１）。肠癌中Ⅳ型胶原酶的表达与Ｐ２１的表达之间呈正相关（ｒ＝０．８１３,Ｐ＜０．０５）。     

Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing,China

Coxsackievirus A24 variant (CVA24v) is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC). In China, the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988, followed by another two significant outbreaks respectively in 1994 and 2007, which coincides with the three-stage dynamic distribution of AHC in the world after 1970s. To illustrate the genetic characteristics of CVA24v in different periods, a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed. Compared with the prototype strain, the 23 strains shared four nucleotide deletions in the 5' UTR except the 0744 strain isolated in 2007. And at the 98th site, one nucleotide insertion was found in all the strains collected from 2007. From 1994 to 2007, amino acid polarity in the VP1 region at the 25th and the 32nd site were changed. Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III (GIII), and 2007 strains to Genotype IV (GIV). According to the Bayesian analysis based on complete genome sequence, the most recent common ancestors for the isolates in 1988, 1994 and 2007 were respectively estimated around October 1987, February 1993 and December 2004. The evolutionary rate of the CVA24v was estimated to be 7.45×10^-3 substitutions/site/year. Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII. Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak. CVA24v has been evolving constantly with a relatively rapid rate.     

iWRAP: An interface threading approach with application to prediction of cancer-related protein-protein interactions

Current homology modeling methods for predicting protein-protein interactions (PPIs) have difficulty in the “twilight zone” (< 40%) of sequence identities. Threading methods extend coverage further into the twilight zone by aligning primary sequences for a pair of proteins to a best-fit template complex to predict an entire three-dimensional structure. We introduce a threading approach, iWRAP, which focuses only on the protein interface. Our approach combines a novel linear programming formulation for interface alignment with a boosting classifier for interaction prediction. We demonstrate its efficacy on SCOPPI, a classification of PPIs in the Protein Databank, and on the entire yeast genome. iWRAP provides significantly improved prediction of PPIs and their interfaces in stringent cross-validation on SCOPPI. Furthermore, by combining our predictions with a full-complex threader, we achieve a coverage of 13% for the yeast PPIs, which is close to a 50% increase over previous methods at a higher sensitivity. As an application, we effectively combine iWRAP with genomic data to identify novel cancer-related genes involved in chromatin remodeling, nucleosome organization, and ribonuclear complex assembly. iWRAP is available at http://iwrap.csail.mit.edu.     

Length of Acupuncture Training and Structural Plastic Brain Changes in Professional Acupuncturists

Background

The research on brain plasticity has fascinated researchers for decades. Use/training serves as an instrumental factor to influence brain neuroplasticity. Parallel to acquisition of behavioral expertise, extensive use/training is concomitant with substantial changes of cortical structure. Acupuncturists, serving as a model par excellence to study tactile-motor and emotional regulation plasticity, receive intensive training in national medical schools following standardized training protocol. Moreover, their behavioral expertise is corroborated during long-term clinical practice. Although our previous study reported functional plastic brain changes in the acupuncturists, whether or not structural plastic changes occurred in acupuncturists is yet elusive.

Methodology/Principal Findings

Cohorts of acupuncturists (N = 22) and non-acupuncturists (N = 22) were recruited. Behavioral tests were delivered to assess the acupuncturists’ behavioral expertise. The results confirmed acupuncturists’ tactile-motor skills and emotion regulation proficiency compared to non-acupuncturists. Using the voxel-based morphometry technique, we revealed larger grey matter volumes in acupuncturists in the hand representation of the contralateral primary somatosensory cortex (SI), the right lobule V/VI and the bilateral ventral anterior cingulate cortex/ventral medial prefrontal cortex. Grey matter volumes of the SI and Lobule V/VI positively correlated with the duration of acupuncture practice.

Conclusions

To our best knowledge, this study provides first evidence for the anatomical alterations in acupuncturists, which would possibly be the neural correlates underlying acupuncturists’ exceptional skills. On one hand, we suggest our findings may have ramifications for tactile-motor rehabilitation. On the other hand, our results in emotion regulation domain may serve as a target for our future studies, from which we can understand how modulations of aversive emotions elicited by empathic pain develop in the context of expertise. Future longitudinal study is necessary to establish the presence and direction of a causal link between practice/use and brain anatomy.     

Anatomical structure of <Emphasis Type="Italic">Camellia oleifera</Emphasis> shell

The main product of Camellia oleifera is edible oil made from the seeds, but huge quantities of agro-waste are produced in the form of shells. The primary components of C. oleifera fruit shell are cellulose, hemicellulose, and lignin, which probably make it a good eco-friendly non-wood material. Understanding the structure of the shell is however a prerequisite to making full use of it. The anatomical structure of C. oleifera fruit shells was investigated from macroscopic to ultrastructural scale by stereoscopic, optical, and scanning electron microscopy. The main cell morphology in the different parts of the shell was observed and measured using the tissue segregation method. The density of the cross section of the shell was also obtained using an X-ray CT scanner to check the change in texture. The C. oleifera fruit pericarp was made up of exocarp, mesocarp, and endocarp. The main types of exocarp cells were stone cells, spiral vessels, and parenchyma cells. The mesocarp accounted for most of the shell and consisted of parenchyma, tracheids, and some stone cells. The endocarp was basically made up of cells with a thickened cell wall that were modified tracheid or parenchyma cells with secondary wall thickening. The most important ultrastructure in these cells was the pits in the cell wall of stone and vessel cells that give the shell a conducting, mechanical, and protective role. The density of the shell gradually decreased from exocarp to endocarp. Tracheid cells are one of the main cell types in the shell, but their low slenderness (length to width) ratio makes them unsuitable for the manufacture of paper. Further research should be conducted on composite shell-plastic panels (or other reinforced materials) to make better use of this agro-waste.     

A robust approach for electronic health record–based case-control studies with contaminated case pools

We consider analyses of case-control studies assembled from electronic health records (EHRs) where the pool of cases is contaminated by patients who are ineligible for the study. These ineligible patients, referred to as “false cases,” should be excluded from the analyses if known. However, the true outcome status of a patient in the case pool is unknown except in a subset whose size may be arbitrarily small compared to the entire pool. To effectively remove the influence of the false cases on estimating odds ratio parameters defined by a working association model of the logistic form, we propose a general strategy to adaptively impute the unknown case status without requiring a correct phenotyping model to help discern the true and false case statuses. Our method estimates the target parameters as the solution to a set of unbiased estimating equations constructed using all available data. It outperforms existing methods by achieving robustness to mismodeling the relationship between the outcome status and covariates of interest, as well as improved estimation efficiency. We further show that our estimator is root-n-consistent and asymptotically normal. Through extensive simulation studies and analysis of real EHR data, we demonstrate that our method has desirable robustness to possible misspecification of both the association and phenotyping models, along with statistical efficiency superior to the competitors.     

模拟边坡条件下常见护坡植物苗期根系构型特征

植物根系对提高边坡稳定性具有重要作用。采用喷播的方式在侵蚀槽中制备模拟石质边坡,植物生长6个月后采用全根挖掘和Win-RHIZO根系分析仪扫描相结合的方法,研究了模拟边坡条件下11种常见护坡植物苗期的根系构型特征。结果表明：紫花苜蓿根系生物量最大,柠条根系生物量最小,二者主根发达,仅分布在下坡方向。沙打旺、胡枝子、紫穗槐和欧李根系生物量、总根数、总基根数、总根长、总根表面积、总根体积均较大,在上坡方向和下坡方向分布均匀,拓扑指数介于0.53—0.61之间,为叉状分枝结构,根系固土护坡能力较强,可作为边坡生态修复工程的优选植物。根系生物量与根系表面积、根体积呈现显著的线性正相关关系(R²分别为0.68和0.80),拓扑指数与根系长度、根系表面积、总根数、总基根数呈现显著的指数负相关关系(R²分别为0.82、0.68、0.87、0.86),可为植物根系构型研究提供科学依据及理论支撑。