Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

致倦库蚊主要组织结构的石蜡切片观察

【目的】蚊虫是传播人类多种疾病的重要媒介害虫, 对其组织形态学的认识是开展众多领域研究的基础。本文通过研究致倦库蚊Culex pipiens quinquefasciatus成虫组织结构及形态, 为媒介蚊虫的抗药性研究及有效防治提供基础材料。【方法】采用改进的石蜡切片法和HE染色, 结合活体内脏器官解剖及光学显微镜观察, 从形态学和组织学水平对致倦库蚊组织结构做详尽展示。【结果】获得结构完整、 染色清晰、 定位准确的消化排泄系统、 生殖系统、 神经系统、 呼吸系统等HE染色石蜡切片。【结论】探讨了改进制片和染色过程中一些步骤及注意事项。研究结果为利用原位杂交、 免疫组化等方法研究蚊虫体内抗药性基因的准确定位及基因功能分析提供了可靠的基础。     

In Defense of Some `Cartesian' Assumptions Concerning the Brain and Its Operation

I argue against a growing radical trend in current theoretical cognitive science that moves from the premises of embedded cognition, embodied cognition, dynamical systems theory and/or situated robotics to conclusions either to the effect that the mind is not in the brain or that cognition does not require representation, or both. I unearth the considerations at the foundation of this view: Haugeland's bandwidth-component argument to the effect that the brain is not a component in cognitive activity, and arguments inspired by dynamical systems theory and situated robotics to the effect that cognitive activity does not involve representations. Both of these strands depend not only on a shift of emphasis from higher cognitive functions to things like sensorimotor processes, but also depend on a certain understanding of how sensorimotor processes are implemented - as closed-loop control systems. I describe a much more sophisticated model of sensorimotor processing that is not only more powerful and robust than simple closed-loop control, but for which there is great evidence that it is implemented in the nervous system. The is the emulation theory of representation, according to which the brain constructs inner dynamical models, or emulators, of the body and environment which are used in parallel with the body and environment to enhance motor control and perception and to provide faster feedback during motor processes, and can be run off-line to produce imagery and evaluate sensorimotor counterfactuals. I then show that the emulation framework is immune to the radical arguments, and makes apparent why the brain is a component in the cognitive activity, and exactly what the representations are in sensorimotor control.     

黄脸油葫芦与短额负蝗马氏管组织结构比较

采用组织学方法对直翅目剑尾亚目和锥尾亚目的两个物种--黄脸油葫芦Teleogryllus emma和短额负蝗Atractomorpha sinensis成虫的马氏管进行了观察,发现两者在着生位置、方式和细胞结构上存在明显不同.着生位置上,黄脸油葫芦的马氏管着生在后肠前端与后肠后端的交界处,短额负蝗的马氏管着生在中肠与后肠的交界处.着生方式上,黄脸油葫芦的马氏管是通过一根无色透明的公共管与肠道相通的,而短额负蝗的马氏管分为12丛,每一丛直接与肠道相连.细胞结构上,黄脸油葫芦的管壁由8个细胞构成,且集中在管的中央,与管壁有空隙;而短额负蝗的管壁由3～4个细胞组成,分散在管壁外围,有马氏管凸.     

Serum biomarkers of Burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses

Background

The bacterium Burkholderia mallei is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. Clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. However, progress in developing sensitive assays for monitoring B. mallei infection is hampered by a shortage of useful biomarkers.

Results

Reasoning that there should be a strong correlation between the proteomes of infected tissues and circulating serum, we employed imaging mass spectrometry (IMS) of thin-sectioned tissues from Chlorocebus aethiops (African green) monkeys infected with B. mallei to localize host and pathogen proteins that were associated with abscesses. Using laser-capture microdissection of specific regions identified by IMS and histology within the tissue sections, a more extensive proteomic analysis was performed by a technique that combined the physical separation capabilities of liquid chromatography (LC) with the sensitive mass analysis capabilities of mass spectrometry (LC-MS/MS). By examining standard formalin-fixed, paraffin-embedded tissue sections, this strategy resulted in the identification of several proteins that were associated with lung and skin abscesses, including the host protein calprotectin and the pathogen protein GroEL. Elevated levels of calprotectin detected by ELISA and antibody responses to GroEL, measured by a microarray of the bacterial proteome, were subsequently detected in the sera of C. aethiops, Macaca mulatta, and Macaca fascicularis primates infected with B. mallei.

Conclusions

Our results demonstrate that a combination of multidimensional MS analysis of traditional histology specimens with high-content protein microarrays can be used to discover lead pairs of host-pathogen biomarkers of infection that are identifiable in biological fluids.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9079-4) contains supplementary material, which is available to authorized users.     

Proteins from formalin-fixed paraffin-embedded prostate cancer sections that predict the risk of metastatic disease

Background

Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer related deaths among men living in developed countries. Biomarkers that predict disease outcome at the time of initial diagnosis would substantially aid disease management.

Results

Proteins extracted from formalin-fixed paraffin-embedded tissue were identified using nanoflow liquid chromatography-MALDI MS/MS or after separation by one- or two-dimensional electrophoresis. The proteomics data have been deposited to the ProteomeXchange with identifier PXD000963. A list of potential biomarker candidates, based on proposed associations with prostate cancer, was derived from the 320 identified proteins. Candidate biomarkers were then examined by multiplexed Western blotting of archival specimens from men with premetastatic disease and subsequent disease outcome data. Annexin A2 provided the best prediction of risk of metastatic disease (log-rank Chi squared p = 0. 025). A tumor/control tissue >2-fold relative abundance increase predicted early biochemical failure, while <2-fold change predicted late or no biochemical failure.

Conclusions

This study confirms the potential for use of archival FFPE specimens in the search for prognostic biomarkers for prostate cancer and suggests that annexin A2 abundance in diagnostic biopsies is predictive for metastatic potential. Protein profiling each cancer may lead to an overall reduction in mortality from metastatic prostate cancer as well as reduced treatment associated morbidity.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9096-3) contains supplementary material, which is available to authorized users.     

桦树松萝的石蜡切片方法改良及形态学研究

以传统石蜡切片方法为基础,在固定、软化、包埋、染色等具体方法上进行了适合松萝属植物特点的改良。结果表明:采用改良制片方法获得了染色清晰、组织完整的桦树松萝切片。桦树松萝地衣体横切面结构从外到内依次划分为皮层、藻层、髓层和中轴;皮层是由横向分裂的菌丝交织成类似于高等植物的假厚壁组织,藻层由大量共生藻的藻细胞和菌丝所组成;髓层由疏松的菌丝体组成;中轴由致密的菌丝体组成。     

红托鬼笔黄水病病原鬼笔复膜孢酵母侵染过程的组织学观察

红托鬼笔黄水病是一种由鬼笔复膜孢酵母引起的致灾性土传病害,极难防治。本研究通过探索获得高质量红托鬼笔组织石蜡切片技术的基础上,对幼担子果生长期病原接种后第8、16、24、32、40、48和72h进行组织取样,利用Van-clear透明剂制备石蜡切片,观察病原的侵染过程,以健康的幼担子果做对照。结果表明：健康的红托鬼笔包被表面菌丝呈管状,与包被中部菌丝结构无明显差异。而接种病原后第8h时,即可观察到病原细胞和假丝形成,包被表面菌丝萎缩、褐变,病原细胞通过菌丝间隙向内扩散和侵染,侵染速度18.14μm/h。接种后32 h包被表面菌丝大量降解,主要是病原细胞和假丝存在,此时病原可以侵染至包被中部菌丝组织。接种后40 h幼担子果表面分泌黄色渗出物液滴,包被表面开始溃烂,病原侵染至幼担子果包被胶质层,并不断向内侵染。本研究采用石蜡切片法对黄水病病原的侵染过程进行了组织学观察,为其致病机制和病害综合防治研究提供借鉴。