Automatic sorting of toxicological information into the IUCLID (International Uniform Chemical Information Database) endpoint-categories making use of the semantic search engine Go3R

The knowledge-based search engine Go3R, www.Go3R.org, has been developed to assist scientists from industry and regulatory authorities in collecting comprehensive toxicological information with a special focus on identifying available alternatives to animal testing. The semantic search paradigm of Go3R makes use of expert knowledge on 3Rs methods and regulatory toxicology, laid down in the ontology, a network of concepts, terms, and synonyms, to recognize the contents of documents. Search results are automatically sorted into a dynamic table of contents presented alongside the list of documents retrieved. This table of contents allows the user to quickly filter the set of documents by topics of interest. Documents containing hazard information are automatically assigned to a user interface following the endpoint-specific IUCLID5 categorization scheme required, e.g. for REACH registration dossiers. For this purpose, complex endpoint-specific search queries were compiled and integrated into the search engine (based upon a gold standard of 310 references that had been assigned manually to the different endpoint categories). Go3R sorts 87% of the references concordantly into the respective IUCLID5 categories. Currently, Go3R searches in the 22 million documents available in the PubMed and TOXNET databases. However, it can be customized to search in other databases including in-house databanks.     

Problem Drinking’s Associations with Social Structure and Mental Health Care: Race/Ethnicity Differences

This research used a nationally representative sample of 12,756 respondents self-identified as White, Black, Hispanic, or Asian to examine problem drinking in relationship to social structure and mental healthcare factors. Associations between problem drinking and particular factors varied by racial/ethnic group. Results also indicated that Whites’ problem-drinking rates were higher than those of Hispanics, Blacks, and Asians. Americans sometimes use alcohol to manage stress stemming from social disadvantage and inadequate material resources. Across racial/ethnic groups, drinking level was associated with the type and degree of such disadvantage. Additionally, the presence of a mental health problem was associated with problem drinking.     

主要组织相容性复合体I类递呈途径抗原肽来源的研究进展

近年来,主要组织相容性复合体(MHC)-Ⅰ类递呈途径抗原肽的来源备受争议.选择性翻译产物作为抗原肽来源的模式,对经典全长蛋白降解作为抗原肽来源的模式提出了挑战,且这一模式已经被科学地实验数据证实和支持.因此,现在需要新的假说来探寻不同来源的抗原肽对MHC-I类递呈途径的生理意义.     

Matching at Human Leukocyte Antigen-C Improved the Outcomes after Double Umbilical Cord Blood Transplantation for Recipients of Two to Four of Six Human Leukocyte Antigen–Matched Grafts

We studied the effect of HLA-C matching in 515 patients after double umbilical cord blood (UCB) transplantation. After HLA matching HLA-A, -B, and -DRB1 at the allele level, we scored patients according to number of donor-recipient HLA-C matches at 4 possible loci: 2 from each donor unit, at the allele level. Given a direct interaction between HLA-A, -B, and -DRB1 matching and HLA-C score, we analyzed HLA-C matching in those receiving at least 1 2/6 to 4/6 HLA–matched unit (n?=?389) versus those receiving only 5/6 or 6/6–matched units (n?=?126). In those with at least 1 2/6 to 4/6 HLA–matched unit, a better HLA-C matching score was associated with significantly lower risk of death of any cause and nonrelapse mortality and better disease-free survival. There was no association with the risk of relapse, acute and chronic graft-versus-host disease, and hematopoietic recovery. In contrast, among patients receiving only allele-level 5/6 or 6/6 HLA–matched UCB units, HLA-C match had no demonstrable effect on any outcome. For patients receiving at least 1 allele-level 2/6 to 4/6 HLA–matched UCB unit, matching at HLA-C reduces nonrelapse mortality and improves survival.     

Expérimentation animale,peut-on s’en passer ?

Animal experiment is a subject of controversies. Some people, defenders of animals, think that it is not acceptable to use for scientific purposes at the risk of making them suffer or assert that the results obtained with animals are not transposable in the human beings. Others, in particular researchers in biology or medicine, think that the animal models are essential for the biomedical search. This confrontation of the opinions bases largely on an evolution of the place of animals in our society. The regulations authorize the use of animals for scientific purposes but oblige to make it under restrictive conditions. The application of 3Rs — replacement, reduction, and refinement — expressed in 1959 by Russel and Burch is an ethical guide to improve the welfare of animals in research. The alternative methods do not allow, in the present state of the knowledge, to answer all the scientific questions in biology and medicine research. They are, most of the time, complementary methods of the in vivo methods.     

受体酪氨酸激酶基因及其变异体在膀胱肿瘤组织中的表达及意义

目的 探讨RON mRNA及其变异体在膀胱肿瘤组织中的表达与临床意义。方法选择63例膀胱移行上皮癌(TCCB)、7例膀胱内翻性乳头状瘤(IPB)、9例膀胱低度恶性潜能尿路上皮瘤(PUNLMP)患者和12例外伤性膀胱破裂且经病理证实无肿瘤细胞的正常膀胱黏膜组织患者。其中,病理Ⅰ、Ⅱ和Ⅲ级患者分别为30、15和18例,临床Tis+ T1和T2 +T3 +T4期患者分别为44例和15例;用实时荧光定量RT-PCR检测其RON mRNA相对表达量,以GAPDH mRNA为内标物,用RONmRNA/GAPDH mRNA比值表示RON mRNA相对表达量;用RT-PCR检测RON mRNA选择性剪切形成的变异体;用测序检测PCR产物中可能存在的变异体,并分析变异体在不同组织间及TCCB中不同病理分级及临床分期间阳性表达率的差异。结果RON mRNA在TCCB、IPB、PUNLMP及正常膀胱黏膜组织中均见阳性表达,其RON mRNA/GAPDH mRNA比值分别为4.9×10-3(1.8×10-3 ～1.0× 10-2)、3.8×10-3（2.4×10-3～1.7×10-2）、4.9×10-3（1.7×10-3～1.1 ×10-2）、1.0×10-3(4.5×10-4 ～2.8×10-3),且不同组织间的表达差异均有统计学意义(x2K-W= 17.278,P＜0.05);RON mRNA/GAPDH mRNA比值在TCCB病理Ⅰ、Ⅱ、Ⅲ级分别为3.7×10-3(1.3×10-3 ～7.5×10-3)、4.9×10-3（1.9X10-3～1.1 ×10-2）、8.9×10-3(2.7×10-3～8.0×10-2),且差异有统计学意义(x2K-W=7.341,P＜0.05);RON mRNA/GAPDH mRNA比值在TCCB临床Tis+ T1、T2 +T3 +T4期分别为3.5×10-3（1.2×10-3 ～7.7×10-3）、9.7× 10-3（2.9×10-3～5.3 ×10-2）,差异也有统计学意义（Z= -2.306,P＜0.05）。但正常膀胱黏膜组未发现RON mRNA变异体,而在膀胱肿瘤组织中外显子11剪切缺失(E11△)的阳性表达率为70％( 55/79)。在TCCB、IPB、PUNLMP中E11△阳性表达率分别为71％ (45/63)、57％ (4/7)、67％ (6/9),而不同病理组织中的E11△阳性表达率差异无统计学意义(x2=0.620,P＞0.05);在不同TCCB病理分级和临床分期中其阳性率差异亦无统计学意义（Z值分别为0.221、0.538,P均＞0.05）。发现1种正常黏膜组织中没有的新变异体,即RON基因外显子的3 476～3 539 bp剪切缺失形成的变异体(E3 476 ～3 539△)。膀胱肿瘤组织中E3 476～3 539△的阳性表达率为56％ (44/79),在TCCB、IPB、PUNLMP中E 3 476 ～3 539△的阳性表达率分别为57％( 36/63)、43％ (3/7)、56％ (5/9),但各病理组织间的阳性率差异无统计学意义(x2=0.517,P＞0.05);在TCCB不同病理分级和临床分期中其阳性率分别为40％ (12/30)、67％ (10/15)、78％ (14/18)、48％(21/44)、80％ (12/15),差异有统计学意义（Z值分别为7.285、5.041,P均＜0.05）。结论 RONmRNA的表达与TCCB病理分级及临床分期相关,RON可能在TCCB发生发展的过程中发挥重要作用;在正常膀胱黏膜中未见RON mRNA剪切形成的变异体,而在膀胱肿瘤组织中都有不同程度的表达;E 3 476～3 539△的表达与TCCB病理分级及临床分期相关,RON mRNA变异体可能参与了膀胱肿瘤的发生。     

中西政治制度设计中的“人性假定”

任何一种制度的安排,都应该建立在特定的人性认识基础之上。中西不同的人性假定,导致了不同的治政方略和制度路径。西方政治制度理念的基本分析框架,是建立在人性恶论基础之上的权力分立和制衡思想,其基本的哲学判断是制度高于人性;中国传统政治制度理念的基本分析框架,则是建立在人性善论基础之上的崇尚德治与集权专制思想,其基本的哲学判断是人性优于制度。性善与性恶两种不同的人性假定,导致了中西德治与法治不同的政治文化与政治制度设计。德治与法治分别构成了中西政治哲学的核心理念。儒家文化中的人性本善假定从民族文化精神和心理的角度看,固然提升了人们对民族文化的自尊自豪感、民族自信心以及民族凝聚力,但却对中国政治发展也产生过一些不良影响。中国传统的德治思想必须突破和超越人治的范畴,必须在私人领域和公共领域两相区分的前提下,参照西方的宪政理念与法治经验,方可为当代中国的政治建构提供有益的借鉴。     

可变剪切事件在胰腺癌中的发生及其临床意义

目的探索胰腺癌(PAAD)中存在的差异RNA剪接模式,分析可变剪切(AS)事件与胰腺癌临床预后的关系。方法自癌症基因组图谱(TCGA)中下载RNA-seq数据、临床数据资料,提取剪接因子(SF)表达量;采用TCGA SpliceSeq工具下载提取AS事件数据,评估7种可变剪切类型在胰腺癌病例中的发生情况;采用Kaplan-Meier分析及Cox回归分析评估AS事件风险值和生存时间之间的相关性,并探索PAAD的独立危险因素;采用Cytoscape构建基于生存相关的AS事件与SF的调控关系网络。结果PAAD中与生存相关的AS事件以外显子跳跃(ES)类型多见,外显子互斥(ME)类型较少;各亚型AS事件对生存影响不同,低风险组的预后较好,且风险值可作为PAAD独立预后因素(P<0.01,AUC=0.765)。剪接网络提示PAAD患者中剪接因子的表达与AS事件之间具有相关性。结论AS事件风险值可作为PAAD的独立预后因子,且SF对AS事件的调控呈多样性,SF可能会作为PAAD治疗的潜在靶点。