人体微生态系统与人类宏基因组计划

介绍了微生态系统的基本概念和人体基本的微生态系统,阐述了其对人类的意义;介绍了人类宏基因组计划基本知识和研究方法.     

Delineation of Interfaces on Human Alpha-Defensins Critical for Human Adenovirus and Human Papillomavirus Inhibition

Human α-defensins are potent anti-microbial peptides with the ability to neutralize bacterial and viral targets. Single alanine mutagenesis has been used to identify determinants of anti-bacterial activity and binding to bacterial proteins such as anthrax lethal factor. Similar analyses of α-defensin interactions with non-enveloped viruses are limited. We used a comprehensive set of human α-defensin 5 (HD5) and human neutrophil peptide 1 (HNP1) alanine scan mutants in a combination of binding and neutralization assays with human adenovirus (AdV) and human papillomavirus (HPV). We have identified a core of critical hydrophobic residues that are common determinants for all of the virus-defensin interactions that were analyzed, while specificity in viral recognition is conferred by specific surface-exposed charged residues. The hydrophobic residues serve multiple roles in maintaining the tertiary and quaternary structure of the defensins as well as forming an interface for virus binding. Many of the important solvent-exposed residues of HD5 group together to form a critical surface. However, a single discrete binding face was not identified for HNP1. In lieu of whole AdV, we used a recombinant capsid subunit comprised of penton base and fiber in quantitative binding studies and determined that the anti-viral potency of HD5 was a function of stoichiometry rather than affinity. Our studies support a mechanism in which α-defensins depend on hydrophobic and charge-charge interactions to bind at high copy number to these non-enveloped viruses to neutralize infection and provide insight into properties that guide α-defensin anti-viral activity.     

Human Variation and Risk Assessment: Microarray and Other Studies Utilizing Human Hepatocytes and Human Liver Subcellular Preparations

The new paradigms proposed for human health risk assessment stress the need for the use of human and human‐derived cell lines, and this review summarizes the use of primary human hepatocytes and hepatocyte subcellular preparations for the investigation of the metabolism and metabolic interactions of environmental chemicals. This includes interactions based on inhibition, induction, and activation. The role of cytotoxicity is also considered. The use of hepatocytes and hepatocyte preparations provides especially important information for the investigation of human variation and is summarized. This area is, at present, relatively neglected but will in the future be essential for accurate assessment of human health risk. A detailed summary of an initial attempt to utilize microarray technology for the study of genome‐wide effects is included.     

The Human Career: Human Biological and Cultural Origins

The Human Career: Human Biological and Cultural Origins, Richard G. Klein. 2nd edition. Chicago: University of Chicago Press, 1999. 810 pp.     

The Universal Declaration on the Human Genome and Human Rights

Since 1985, UNESCO studies ethical questions arising in genetics. In 1992, I established the International Bioethics Committee at UNESCO with the mission to draft the Universal Declaration on the Human Genome and Human Rights, which was adopted by UNESCO in 1997 and the United Nations in 1998. The Declaration relates the human genome with human dignity, deals with the rights of the persons concerned by human genome research and provides a reference legal framework for both stimulating the ethical debate and the harmonization of the law worldwide, favouring useful developments that respect human dignity.     

Archaeology and Human Evolution

Archaeology is the study of human behavior through material culture, the things we rely on for survival. Behavioral change was likely a driving factor in the evolution of our species, and archaeology therefore plays a central role in understanding human origins from the beginning of the known archaeological record some 2.5 million years ago. From its origins to subsequent diversification, the material record of human behavioral innovation provides an essential learning tool for understanding human behavioral diversity and also serves as a gateway to critical thinking in education.     

Human dispersal and divergence

Dispersal, mate exchange and behavioral innovations leading to cultural dominance and replacement have obscured some of the relationships between major linguistic groups and the biological characteristics of their speakers. Recent phylogenetic reconstructions based on nuclear and mitochondrial genes have resulted in a series of hypotheses about the spread of modern humans. These hypotheses are now being tested by linguistic reconstruction. Genes, language, archaeology and geography are sometimes congruent, but new methods to assess covariation in genetic and linguistic distances are becoming necessary.     

Human walking and running

Some of the major sources of misconceptions and learning difficulties in genetics amongst school students were examined by using in-depth recorded interviews based on genetically orientated tasks. The subsequent unstructured discussion illuminated specific areas of concern. It was found that some students' misconceptions were related to the nature of the concepts used in genetics, such as the frequent representation of meiosis by fixed inanimate stage diagrams. Other problems related to pedagogy, for example, the separation in teaching time between the presentation of meiosis and the introduction of genetics per se; and the type and extent of practical support experience available to the student.