Investigating the biology of consciousness.

The fact that consciousness is a private, first-person phenomenon makes it more difficult to study than other cognitive phenomena that, although being equally private, also have characteristic behavioural signatures. Nonetheless, by combining cognitive and neurobiological methods, it is possible to approach consciousness, to describe its cognitive nature, its behavioural correlates, its possible evolutionary origin and functional role; last but not least, it is possible to investigate its neuroanatomical and neurophysiological underpinnings. In this brief essay I distinguish between two kinds of consciousness: core consciousness and extended consciousness. Core consciousness corresponds to the transient process that is incessantly generated relative to any object with which an organism interacts, and during which a transient core self and transient sense of knowing are automatically generated. Core consciousness requires neither language nor working memory, and needs only a brief short-term memory. Extended consciousness is a more complex process. It depends on the gradual build-up of an autobiographical self, a set of conceptual memories pertaining to both past and anticipated experiences of an individual, and it requires conventional memory. Extended consciousness is enhanced by language.     

Heparan sulfate structure in mice with genetically modified heparan sulfate production

Using a high throughput heparan sulfate (HS) isolation and characterization protocol, we have analyzed HS structure in several tissues from mice/mouse embryos deficient in HS biosynthesis enzymes (N-deacetylase/N-sulfotransferase (NDST)-1, NDST-2, and C5-epimerase, respectively) and in mice lacking syndecan-1. The results have given us new information regarding HS biosynthesis with implications on the role of HS in embryonic development. Our main conclusions are as follows. 1) The HS content, disaccharide composition, and the overall degree of N- and O-sulfation as well as domain organization are characteristic for each individual mouse tissue. 2) Removal of a key biosynthesis enzyme (NDST-1 or C5-epimerase) results in similar structural alterations in all of the tissues analyzed. 3) Essentially no variation in HS tissue structure is detected when individuals of the same genotype are compared. 4) NDST-2, although generally expressed, does not contribute significantly to tissue-specific HS structures. 5) No change in HS structure could be detected in syndecan-1-deficient mice.     

Specific arrests of spermatogenesis in genetically modified and mutant mice

In naturally occurring mutant mice but also in mice genetically modified for the study of other organs, relatively often a spermatogenic arrest is seen. In a number of cases the arrests appear to be very specific causing apoptosis of germ cells at a particular step in their development, while before this step cells progress normally. These steps include: proliferation/migration of primordial germ cells, the production of differentiating spermatogonia by gonocytes, the regulation of stem cell renewal/differentiation, the differentiation of A(al) into A1 spermatogonia, proliferation of A1-A4 spermatogonia, germ cell density regulation, start of meiosis, epithelial stage IV checkpoint of pachytene spermatocytes, the first meiotic division, the formation of the acrosomic vesicle in spermatids and several other steps in spermatid development. In addition, there are many mice that have not been studied in enough detail for a proper categorization. In this review an overview is given of the various mutations and genetically modified mice showing a direct effect on specific spermatogenic cell types. In addition, the relevance of these models to our understanding of the spermatogenic process is discussed.     

Novel insights into the genetic background of genetically modified mice

Unclear or misclassified genetic background of laboratory rodents or a lack of strain awareness causes a number of difficulties in performing or reproducing scientific experiments. Until now, genetic differentiation between strains and substrains of inbred mice has been a challenge. We have developed a screening method for analyzing inbred strains regarding their genetic background. It is based on 240 highly informative short tandem repeat (STR) markers covering the 19 autosomes as well as X and Y chromosomes. Combination of analysis results for presence of known C57BL/6 substrain-specific mutations together with autosomal STR markers and the Y-chromosomal STR-haplotype provides a comprehensive snapshot of the genetic background of mice. In this study, the genetic background of 72 mouse lines obtained from 18 scientific institutions in Germany and Austria was determined. By analyzing only 3 individuals per genetically modified line it was possible to detect mixed genetic backgrounds frequently. In several lines presence of a mispairing Y chromosome was detected. At least every second genetically modified line displayed a mixed genetic background which could lead to unexpected and non-reproducible results, irrespective of the investigated gene of interest.     

转基因食品的安全性探讨

转基因食品近几年成了大众关注的一个热点问题,但普遍存在一些错误观点。从转基因食品常用的基因,如抗生素抗性基因、Bt基因、抗除草剂抗性基因、人或动物基因等,分析其食用安全性, 排除对转基因食品的疑惑。     

Intrathymic implants of genetically modified fibroblasts.

Implantation of autologous rodent fibroblasts genetically altered to express human growth hormone has recently been shown to be a feasible approach to the delivery of new gene products in somatic gene therapy. However, the novel gene product elicited in its recipients an intense antibody response that would have curtailed the effectiveness of such therapy. The possibility of inducing tolerance to foreign gene product was explored by implanting allogeneic fibroblasts transfected with the human growth hormone gene into rat thymus, a site recently shown to be immunologically privileged and able to induce donor-specific tolerance to transplanted tissues. In the circulation of the implanted rats, human growth hormone was detected at 4-15 ng/ml serum within the first day and subsided to 0.6-9 ng/ml within the first wk in all animals implanted either thymically or intraperitoneally. Within 2-3 wk, high titers of anti-human growth hormone were detected in all animals regardless of the site of implantation. The failure of the thymus to offer immune protection for the foreign antigen was further confirmed when the animals were subsequently challenged with purified human growth hormone. An immediate twofold increase in titer within the first week of challenge was detected in animals previously implanted thymically. In contrast, animals implanted intraperitoneally but treated with short-term daily injection of cyclosporine A (28-41 days) did not mount any significant antibody response to human growth hormone throughout the experiment or even when challenged subsequently at weeks 8-10 with purified growth hormone. In conclusion, implantation of genetically modified fibroblasts in the thymus does not lead to tolerization toward soluble novel gene product secreted by these cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

The molecular biology computer research resource.

Described is a new National Institutes of Health supported Molecular Biology Computer Research Resource located at the Dana-Farber Cancer Institute in association with Harvard University, Boston, Massachusetts.     

Metabolic phenotyping of genetically modified mice: An NMR metabonomic approach

Monocyte chemoattractant protein-1 (MCP-1) plays a relevant role in macrophage migration but recent findings suggest an additional role in lipid and glucose metabolism. We report the use of ¹H NMR spectroscopy as a useful complementary method to assess the metabolic function of this gene in a comparative strategy. This metabonomic analysis was rapid, simple, quantitative and reproducible, and revealed a suggestive relationship between the expression of the MCP-1 gene and hepatic glucose and taurine concentrations. This approach should be considered in genetically modified mice when a metabolic alteration is suspected, or in routine assessment of metabolic phenotype.     

Ultrastructural analysis of testes from mice fed on genetically modified soybean

We have considered the possible effects of a diet containing genetically modified (GM) soybean on mouse testis. This organ, in fact, is a well known bioindicator and it has already been utilized, for instance, to monitor pollution by heavy metals. In this preliminary study, we have focussed our attention on Sertoli cells, spermatogonia and spermatocytes by means of immunoelectron microscopy. Our results point out that the immunolabelling for Sm antigen, hnRNPs, SC35 and RNA Polymerase II is decreased in 2 and 5 month-old GM-fed mice, and is restored to normal at 8 months. In GM-fed mice of all ages considered, the number of perichromatin granules is higher and the nuclear pore density lower. Moreover, we found enlargements in the smooth endoplasmic reticulum in GM-fed mice Sertoli cells. A possible role played by traces of the herbicide to which the soybean is resistant is discussed.     

The molecular biology of K+ channels.

It is now clear that voltage-gated K+ channels are encoded by a set of multigene subfamilies. Expression of different members of these subfamilies, coupled with mutational analysis, has advanced our knowledge of the structure and function of voltage-dependent K+ channels.     

The case for genetically modified crops with a poverty focus

Recently seven National Academies of Science produced a report on transgenic plants and world agriculture. The report provides scientific perspectives to the ongoing public debate about the potential role for transgenic technology in world agriculture. In this article, we develop the themes of the report and emphasize the potential for future genetically modified (GM) crops with a poverty focus, emphasizing the potential of GM resistance to plant parasitic nematodes for subsistence potato farmers in Bolivia. We judge that a range of incremental gains to crop yields from many transgenes are valuable for future world security. We advocate the establishment of a standard that GM crops must achieve before they are both biosafe and appropriate for resource-poor farmers and we believe that the best interests of the poor require biotechnologists to work towards that objective.     

The impact of genetically modified crops on soil microbial communities.

Genetically modified (GM) plants represent a potential benefit for environmentally friendly agriculture and human health. Though, poor knowledge is available on potential hazards posed by unintended modifications occurring during genetic manipulation. The increasing amount of reports on ecological risks and benefits of GM plants stresses the need for experimental works aimed at evaluating the impact of GM crops on natural and agro-ecosystems. Major environmental risks associated with GM crops include their potential impact on non-target soil microorganisms playing a fundamental role in crop residues degradation and in biogeochemical cycles. Recent works assessed the effects of GM crops on soil microbial communities on the basis of case-by-case studies, using multimodal experimental approaches involving different target and non-target organisms. Experimental evidences discussed in this review confirm that a precautionary approach should be adopted, by taking into account the risks associated with the unpredictability of transformation events, of their pleiotropic effects and of the fate of transgenes in natural and agro-ecosystems, weighing benefits against costs.