Machine learning method for extracting elastic modulus of cells

Biomechanics and Modeling in Mechanobiology - The Hertz contact mechanics model is commonly used to extract the elastic modulus of the cell, but the basic assumptions of the model are often not met...     

Deficiency of α1,6-fucosyltransferase promotes neuroinflammation by increasing the sensitivity of glial cells to inflammatory mediators

Background

α1,6-Fucosyltransferase-deficient (Fut8^?/?) mice displayed increased locomotion and schizophrenia-like behaviors. Since neuroinflammation is a common pathological change in most brain diseases, this study was focused on investigating the effects of Fut8 in microglia and astrocytes.

Biosynthetic study of conidiation-inducing factor conidiogenone: heterologous production and cyclization mechanism of a key bifunctional diterpene synthase

Conidiogenone, a diterpene with a unique structure, is known to induce the conidiation of Penicillium cyclopium. The biosynthetic pathway of (?)-conidiogenone has been fully elucidated by the heterologous expression of biosynthetic genes in Aspergillus oryzae and by in vitro enzyme assay with ¹³C-labeled substrates. After construction of deoxyconidiogenol by the action of bifunctional terpene synthase, one cytochrome P450 catalyzes two rounds of oxidation to furnish conidiogenone. Notably, similar biosynthetic genes are conserved among more than 10 Penicillium sp., suggesting that conidiogenone is a common conidiation inducer in this genus. The cyclization mechanism catalyzed by terpene synthase, which involves successive 1,2-alkyl shifts, was fully elucidated using ¹³C-labeled geranylgeranyl pyrophosphate (GGPP) as substrate. During the structural analysis of deoxyconidiogenol, we observed broadening of some of the ¹³C signals measured at room temperature, which has not been observed with other structurally related compounds. Careful examination using techniques including ¹³C NMR studies at ?80 °C, conformational analysis and prediction of the ¹³C chemical shifts using density functional theory gave insights into this intriguing phenomenon.     

植物紫色酸性磷酸酶基因家族功能研究进展

紫色酸性磷酸酶(PAPs)是一类广泛存在于植物体内的金属磷酸酯酶, 其羧基端含有1个保守结构域, 由5个保守基序和7个氨基酸残基构成。作为一种特殊的酸性磷酸酶, PAPs在酸性环境下能够有效催化磷酸酯或酸酐的水解, 释放出植物可以利用的磷酸基团。此外, PAPs在调节植物碳代谢、细胞壁合成和抵御病菌侵染等方面也发挥重要生理作用。该文简要介绍了PAPs的结构、家族成员及其调控因子, 并着重总结了近年来对PAPs生物学功能的研究进展, 为今后系统开展PAPs功能研究提供了理论参考。     

Distributional Variations in Trabecular Architecture of the Mandibular Bone: An In Vivo Micro-CT Analysis in Rats

Purpose

To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats.

Materials and Methods

Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX) and a sham-ovariectomy group (sham). Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham) were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed.

Results

Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012), but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005). A thickness and separation map showed that trabeculae of less than 100μm increased by 46%, whereas trabeculae of more than 200μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028) and bone volume fraction (p = 0.001) were also significantly decreased in the OVX group compared to the sham group.

Conclusions

Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture.     

The Prognostic Significance of Pretreatment Serum CEA Levels in Gastric Cancer: A Meta-Analysis Including 14651 Patients

Background

Carcinoembryonic antigen (CEA) is commonly used as a serum tumor marker in clinical practice; however, its prognostic value for gastric cancer patients remains uncertain. This meta-analysis was performed to assess the prognostic value of CEA and investigate CEA as a tumor marker.

Methods

PubMed, EMBASE and other databases were searched for potentially eligible studies. Forty-one studies reporting the prognostic effect of pretreatment serum CEA expression in gastric cancer patients were selected. Data on 14651 eligible patients were retrieved for the meta-analysis. Based on the data extracted from the available literature, the hazard ratio (HR) and 95% confidence interval (CI) for an adverse prognosis were estimated for gastric cancer patients with elevated pretreatment serum levels of CEA (CEA+) relative to patients with normal pretreatment CEA levels (CEA-).

Results

The CEA+ patients had a significantly poorer prognosis than the CEA- patients in terms of overall survival (OS: HR 1.716, 95% CI 1.594 - 1.848, P< 0.001), disease-specific survival (DSS: HR 1.940, 95% CI 1.563 - 2.408, P< 0.001), and disease-free survival (DFS: HR 2.275, 95% CI 1.836 - 2.818, P< 0.001). Publication bias and an influence of different cut-off values were not observed (all P> 0.05). In the pooled analyses of multivariate-adjusted HRs, the results suggested that pretreatment serum CEA may be an independent prognostic factor in gastric cancer (OS: HR 1.681, 95% CI 1.425 - 1.982; DSS: HR 1.900, 95% CI 1.441 - 2.505; DFS: HR 2.579, 95% CI 1.935 - 3.436).

Conclusion/Significance

The meta-analysis based on the available literature supported the association of elevated pretreatment serum CEA levels with a poor prognosis for gastric cancer and a nearly doubled risk of mortality in gastric cancer patients. CEA may be an independent prognostic factor for gastric cancer patients and may aid in determining appropriate treatment which may preferentially benefit the CEA+ patients.     

植物病毒载体在植病互作研究中的应用

在植物与病原菌互作的研究中,植物抗性基因和病原菌无毒基因的研究是两个重要的热点。利用植物病毒沉默载体构建的VIGS(Virus Induced Gene Silencing)体系研究植物的防御机制;利用植物病毒表达载体克隆和研究病原菌的无毒基因,将使我们更深刻地理解植物和病原菌互作的分子机理,最终为培育番茄白粉病持久抗性品种打下理论基础。对植物病毒载体的研究进行了综述并就我们承担的课题进行了讨论。     

SDIR1 is a RING finger E3 ligase that positively regulates stress-responsive abscisic acid signaling in Arabidopsis

Ubiquitination plays important roles in plant hormone signal transduction. We show that the RING finger E3 ligase, Arabidopsis thaliana SALT- AND DROUGHT-INDUCED RING FINGER1 (SDIR1), is involved in abscisic acid (ABA)-related stress signal transduction. SDIR1 is expressed in all tissues of Arabidopsis and is upregulated by drought and salt stress, but not by ABA. Plants expressing the ProSDIR1-beta-glucuronidase (GUS) reporter construct confirmed strong induction of GUS expression in stomatal guard cells and leaf mesophyll cells under drought stress. The green fluorescent protein-SDIR1 fusion protein is colocalized with intracellular membranes. We demonstrate that SDIR1 is an E3 ubiquitin ligase and that the RING finger conservation region is required for its activity. Overexpression of SDIR1 leads to ABA hypersensitivity and ABA-associated phenotypes, such as salt hypersensitivity in germination, enhanced ABA-induced stomatal closing, and enhanced drought tolerance. The expression levels of a number of key ABA and stress marker genes are altered both in SDIR1 overexpression and sdir1-1 mutant plants. Cross-complementation experiments showed that the ABA-INSENSITIVE5 (ABI5), ABRE BINDING FACTOR3 (ABF3), and ABF4 genes can rescue the ABA-insensitive phenotype of the sdir1-1 mutant, whereas SDIR1 could not rescue the abi5-1 mutant. This suggests that SDIR1 acts upstream of those basic leucine zipper family genes. Our results indicate that SDIR1 is a positive regulator of ABA signaling.     

Synthesis of "reversed" methylenecyclopropane analogues of antiviral phosphonates

Synthesis of "reversed" methylenecyclopropane analogues of nucleoside phosphonates 6a,7a, 6b, and 7b is described. 1-Bromo-1-bromomethylcyclopropane 8 was converted to the bromocyclopropyl phosphonate 9 by Michaelis-Arbuzov reaction with triisopropyl phosphite. Base-catalyzed beta-elimination and deacetylation gave the key Z- and E-hydroxymethylcyclopropyl phosphonates 10 and 11 separated by chromatography. The Mitsunobu type of alkylation of 10 or 11 with adenine or 2-amino-6-chloropurine afforded phosphonates 12a, 12b, 13a, and 13b. Acid hydrolysis furnished the adenine and guanine analogues 6a, 7a, 6b, and 7b. The E and Z configuration was assigned on the basis of NOE experiments with phosphonates 6b and 7b. All Z- and E-isomers were also distinguished by different chemical shifts of CH2O or CH2N (H4 or H4'). Significant differences of the chemical shifts of the cyclopropane C3(3') carbons and coupling constants 3JP,C2(2') or 3JP,C3(3') selective for the Z- or E-isomers were also noted. Phosphonates 6a, 7a, 6b, and 7b are devoid of significant antiviral activity.     

海拔变化对凤阳山针阔混交林地土壤微生物群落的影响

风阳山自然保护区是森林生态类型自然保护区,针阔混交林是保护区内的重要森林类型。为明确海拔变化对高山针阔混交林地土壤微生物群落的影响及初步影响机理,了解气候变暖后典型林分土壤微生物群落结构的变化。以黄山松在凤阳山的分布范围800—1800 m为准,选取900、1100、1300、1500、1700 m 5个海拔梯度,在每个海拔梯度的阳坡内选取排水较好、坡度较缓、长势适中的3个标准样地(20 m×20 m),于2016年8月用蛇形法于每块样地取样,用冰盒带回实验室,测定土壤理化性质及微生物群落。采用磷脂脂肪酸(PLFA)图谱分析确定土壤微生物群落组成及其丰度,同时对土壤微生物群落组成进行非度量多维标度(NMDS)排序,对土壤微生物群落组成结构进行分析。结果表明:随着海拔升高,针阔混交林样地内植物种类组成有所变化。土壤养分含量呈先升高后降低的趋势,差异性显著(P0.05);土壤微生物群落丰度之间存在显著差异,革兰氏阴性细菌丰度在高海拔处较大;土壤微生物群落组成非度量多维标度(NMDS)排序显示,随海拔升高,土壤微生物群落组成发生明显改变,可以分为三个类群,各海拔土壤微生物群落结构在两个NMDS轴上均呈现出显著差异(P0.05)。通过对土壤微生物群落丰度与土壤理化性质的冗余分析(RDA),发现土壤p H、容重、含水量、及有效磷含量对对土壤微生物群落丰度有不同程度的影响,土壤革兰氏阳性细菌、放线菌丰度与各土壤因子之间均有显著相关关系;革兰氏阴性细菌受土壤含水量及有效磷的含量影响较大;真菌丰度与土壤p H及有机碳含量之间存在相关关系;厌氧菌及16:1ω5c丰度与土壤因子间相关性较弱。海拔变化所引起的土壤理化性质的改变,是影响土壤微生物群落丰度的因素;6个微生物群落对海拔的适应程度是不同的,革兰氏阴性细菌对高海拔的低温环境适应能力较强。