Approaches to diagnose DNA mismatch repair gene defects in cancer

The DNA repair pathway mismatch repair (MMR) is responsible for the recognition and correction of DNA biosynthetic errors caused by inaccurate nucleotide incorporation during replication. Faulty MMR leads to failure to address the mispairs or insertion deletion loops (IDLs) left behind by the replicative polymerases and results in increased mutation load at the genome. The realization that defective MMR leads to a hypermutation phenotype and increased risk of tumorigenesis highlights the relevance of this pathway for human disease. The association of MMR defects with increased risk of cancer development was first observed in colorectal cancer patients that carried inactivating germline mutations in MMR genes and the disease was named as hereditary non-polyposis colorectal cancer (HNPCC). Currently, a growing list of cancers is found to be MMR defective and HNPCC has been renamed Lynch syndrome (LS) partly to include the associated risk of developing extra-colonic cancers. In addition, a number of non-hereditary, mostly epigenetic, alterations of MMR genes have been described in sporadic tumors. Besides conferring a strong cancer predisposition, genetic or epigenetic inactivation of MMR genes also renders cells resistant to some chemotherapeutic agents. Therefore, diagnosis of MMR deficiency has important implications for the management of the patients, the surveillance of their relatives in the case of LS and for the choice of treatment. Some of the alterations found in MMR genes have already been well defined and their pathogenicity assessed. Despite this substantial wealth of knowledge, the effects of a large number of alterations remain uncharacterized (variants of uncertain significance, VUSs). The advent of personalized genomics is likely to increase the list of VUSs found in MMR genes and anticipates the need of diagnostic tools for rapid assessment of their pathogenicity. This review describes current tools and future strategies for addressing the relevance of MMR gene alterations in human disease.     

Individual Intelligence in the Context of Modern Psycholinguistic Studies

The article reports a comparative study on university students’ linguistic consciousness and world-view. An attempt is made to integrate psycholinguistics with the study of intelligence. Psycholinguistic tools are combined to diagnose indicators of intelligence. A special focus is on linguistic tools for reflection, generalization, and transformation of reality.     

Apps can help bridge restoration science and restoration practice

Scientists need to find innovative ways to communicate their findings with restoration practitioners in an era of global change. Apps are a promising bridge between restoration science and practice because they apply broad scientific concepts to specific situations. For example, habitat connectivity promotes ecological function, but practitioners lack ways to incorporate connectivity into decision‐making. We created an app where users calculate how habitat restoration or loss affects connectivity. By providing our app as an example and discussing the benefits and challenges in creating apps for practitioners, we encourage other restoration ecologists to similarly create apps that bridge science with practice.     

石灰岩石器使用功效的模拟实验——以重庆巫山玉米洞遗址为例

本文以巫山玉米洞遗址为例,对石灰岩石器进行复制与使用功效的模拟实验,结果表明有些石灰岩在石器打制层面表现出较好的适用性,石灰岩石器在常规的砍砸、切割、挖掘等行为活动中表现出良好的功能实用性和效率。通过实验标本与遗址出土石器的对比分析,我们认为该遗址应存在优选天然毛坯直接使用而形成的“使用石器”,类型主要集中在砍砸器和手镐等重型工具,但二次加工的石器比“使用石器”更为有效耐用;有尖类石器在作用于硬性对象或结构不稳定、受力不均时容易产生残损,与出土有尖类石器较高的残损率相吻合;把手修理在石器使用过程中显得非常必要,为遗址出土石器普遍存在把手修理现象提供了合理解释。     

Lipid mimetics: A versatile toolbox for lipid biology and beyond

Being the principal component of biological membranes lipids are essential building blocks of life. Given their huge biological importance, the investigation of lipids, their properties, interactions and metabolic pathways is of prime importance for the fundamental understanding of living cells and organisms as well as the emergence of diseases. Different strategies have been applied to investigate lipid-mediated biological processes, one of them being the use of lipid mimetics. They structurally resemble their natural counterparts but are equipped with functionality that can be used to probe or manipulate lipid-mediated biological processes and biomembranes. Lipid mimetics therefore constitute an indispensable toolbox for lipid biology and membrane research but also beyond for potential applications in medicine or synthetic biology. Herein, we highlight recent advances in the development and application of lipid-mimicking compounds.     

Comparative Map and Trait Viewer (CMTV): an integrated bioinformatic tool to construct consensus maps and compare QTL and functional genomics data across genomes and experiments

In the past few decades, a wealth of genomic data has been produced in a wide variety of species using a diverse array of functional and molecular marker approaches. In order to unlock the full potential of the information contained in these independent experiments, researchers need efficient and intuitive means to identify common genomic regions and genes involved in the expression of target phenotypic traits across diverse conditions. To address this need, we have developed a Comparative Map and Trait Viewer (CMTV) tool that can be used to construct dynamic aggregations of a variety of types of genomic datasets. By algorithmically determining correspondences between sets of objects on multiple genomic maps, the CMTV can display syntenic regions across taxa, combine maps from separate experiments into a consensus map, or project data from different maps into a common coordinate framework using dynamic coordinate translations between source and target maps. We present a case study that illustrates the utility of the tool for managing large and varied datasets by integrating data collected by CIMMYT in maize drought tolerance research with data from public sources. This example will focus on one of the visualization features for Quantitative Trait Locus (QTL) data, using likelihood ratio (LR) files produced by generic QTL analysis software and displaying the data in a unique visual manner across different combinations of traits, environments and crosses. Once a genomic region of interest has been identified, the CMTV can search and display additional QTLs meeting a particular threshold for that region, or other functional data such as sets of differentially expressed genes located in the region; it thus provides an easily used means for organizing and manipulating data sets that have been dynamically integrated under the focus of the researchers specific hypothesis.     

关于周口店第15地点石器类型和加工技术的研究

在周口店第 15地点经过加工的石器中 ,刮削器占近 93%。其它石器类型包括砍砸器、尖刃器、石锥、凹缺器、雕刻器和薄刃斧。石器由锤击加工。绝大多数标本向一面加工。石片石器多为正向加工。大多数石器个体很小 ,形态不规则 ,修疤呈鳞状 ,深浅、大小不一。少数标本的修疤浅平、规则而平行。统计分析显示在各类器型之间存在着明显的大小与加工上的区别。单边刃刮削器的各亚型之间在大小、加工长度和深度以及刃角和刃形诸方面不存在明显的差异 ,说明这些刮削器在刃口形态 (直、凸与凹 )方面的的变异主要取决于毛坯的原始形态 ,而非代表类型与功能的不同。变量相关分析揭示石器的大小与加工程度和原坯的大小与形态紧密相关。     

A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78

Neuroleukin (NLK) is a multifunctional protein involved in neuronal growth and survival, cell motility and differentiation, and glucose metabolism. We report herein that hippocampal expression of NLK and its receptor gp78 is associated with maze learning in rats. First, mRNA levels of NLK and gp78 were significantly increased in hippocampi of male Fischer-344 rats following training in the Stone T-maze and the Morris water maze. Second, a parallel increase was found in hippocampal NLK and gp78 proteins after maze learning. Third, NLK and gp78 mRNA and protein expression in hippocampus was reduced in a group of aged rats that showed more errors during the acquisition of the Stone maze task as compared with young rats. Finally, application of recombinant NLK to hippocampal neurons significantly enhanced glutamate-induced ion currents, functional molecular changes that have been correlated with learning in vivo. Taken together, our results identify a novel association of hippocampal expression of NLK and its receptor gp78 with rat maze learning. Interaction of NLK with gp78 and subsequent signaling may strengthen synaptic mechanisms underlying learning and memory formation.