Mitochondrial dysfunction in glaucoma: understanding genetic influences

Glaucoma is the leading cause of irreversible blindness worldwide. This review aims to provide a greater understanding of the complex genetic influences that may lead to mitochondrial dysfunction and increase susceptibility to retinal ganglion cell (RGC) loss in primary open angle glaucoma (POAG), and thus elucidate potentially important pathophysiological pathways amenable to therapeutic intervention. Emerging evidence from genome wide association and other genetic studies suggests that changes in the mitochondrial DNA (mtDNA) and in nuclear DNA genes that encode mitochondrial proteins may influence mitochondrial structure and function and, therefore, contribute to the pathogenesis of POAG. We propose that a variety of genes (OPA1, MFN1, MFN2, CYP1B1, PARL, SOD2, SRBD1, GST, NOS3, TNFa and TP53) may each confer a background susceptibility to POAG in different populations having one common link: mitochondrial dysfunction. The relationship between polymorphisms in these genes and increasing risk for POAG is presented and the limitations of the available current knowledge are discussed.     

Lignin genetic engineering

Although lignins play important roles in plants, they often represent an obstacle to the utilization of plant biomass in different areas: pulp industry, forage digestibility. The recent characterization of different lignification genes has stimulated research programmes aimed at modifying the lignin profiles of plants through genetic engineering (antisense and sense suppression of gene expression). The first transgenic plants with a modification of monomeric composition of lignins and lignin content have been recently obtained. Down regulation of the OMT gene induces dramatic reduction of syringyl units. CAD down regulated plants exhibit a unusual red phenotype associated with the developing xylem and several chemical modifications of their lignins including an increase in cinnamaldehydes in the polymer structure. Interestingly this novel lignin is removed more easily during the pulping process. In both OMT and CAD down regulated plants no changes in phenotypic characteristics such as growth architecture and morphology were observed. More recent experiments have shown that a reduction of CCR activity determines specific changes in the coloration of the xylem area suggesting significant chemical modifications which are currently being studied.These different results show that it is possible to manipulate lignins through targeted genetic transformation of plants and that lignins exhibit a relative flexibility of their chemical structure. Future developments should probe the impact of down regulating the expression of other recently characterized lignification genes such as F5H and CCoAOMT and also of a combination of genes in order to tailor lignins more adapted to specific purposes. In addition to biotechnological applications which should provide important economical benefits for utilization of wood in the pulp industry, genetic engineering of lignins offer very promising perspectives for the understanding of lignin synthesis, structure and properties.     

Cell genetic engineering: Transmission genetics of plants

Achievements of cell and genetic engineering that led to formation of a new genetics chapter— transmission genetics—have been described. Results have been analyzed and new opportunities in the field of transgenomic somatic hybrids and cybrid obtaining, production of transgenic plants with agronomic pharmaceutical application, development of transplastomic plants, and accumulation of recombinant proteins by using the transient expression of foreign genes in plants have been shown.     

Introduction: Making Human Rights Claims Public

This introduction explores some of the broader themes in this special section on the technologies of witnessing. In today's globally mediated world, visual images play a central role in determining which violences are redeemed and which get recognized. Northern human rights activists understand this fact and in recent years have built a transnational communications infrastructure through which "local" actors' claims are formatted into human rights "issues." I discuss the axiom that underpins this infrastructure, the notion that "seeing is believing," and then go on to briefly analyze some of the models (mobilization of shame) and forms (testimony) through which activists mediate their claims.     

Journalists and genetic engineering

Mass media coverage of genetic engineering is considered as an essential cause of the public image which this technology has. Because most people have only few experiences with this technology, the influence of journalists, who report on genetic engineering, seems to be obviously high. Which attitudes do these journalists have? How do they inform themselves? These and other questions are to be answered by a standardized survey among German journalists. For the first time the results of this study reveal the methods of investigation and source selection of 'genetic engineering journalists' and afford an insight into the journalistic climate of opinion on genetic engineering and its applications. There is clear evidence of an altogether positive global judgement of journalists reporting on this technology, which finds support in their immediate professional social environment.     

Inverse metabolic engineering: A strategy for directed genetic engineering of useful phenotypes

The classical method of metabolic engineering, identifying a rate-determining step in a pathway and alleviating the bottleneck by enzyme overexpression, has motivated much research but has enjoyed only limited practical success. Intervention of other limiting steps, of counterbalancing regulation, and of unknown coupled pathways often confounds this direct approach. Here the concept of inverse metabolic engineering is codified and its application is illustrated with several examples. Inverse metabolic engineering means the elucidation of a metabolic engineering strategy by: first, identifying, constructing, or calculating a desired phenotype; second, determining the genetic or the particular environmental factors conferring that phenotype; and third, endowing that phenotype on another strain or organism by directed genetic or environmental manipulation. This paradigm has been successfully applied in several contexts, including elimination of growth factor requirements in mammalian cell culture and increasing the energetic efficiency of microaerobic bacterial respiration. (c) 1996 John Wiley & Sons, Inc.     

Inverse metabolic engineering: a strategy for directed genetic engineering of useful phenotypes

The classical method of metabolic engineering, identifying a rate-determining step in a pathway and alleviating the bottleneck by enzyme overexpression, has motivated much research but has enjoyed only limited practical success. Intervention of other limiting steps, of counter-balancing regulation, and of unknown coupled pathways often confounds this direct approach. Here the concept of inverse metabolic engineering is codified and its application is illustrated with several examples. Inverse metabolic engineering means the elucidation of a metabolic engineering strategy by: first, identifying, constructing, or calculating a desired phenotype; second, determining the genetic or the particular environmental factors conferring that phenotype; and third, endowing that phenotype on another strain or organism by directed genetic or environmental manipulation. This paradigm has been successfully applied in several contexts, including elimination of growth factor requirements in mammalian cell culture and increasing the energetic efficiency of microaerobic bacterial respiration.     

Actinomycetes--the test-organisms of genetic engineering

The paper contains a short review of the data on using the methods of genetic engineering in studies of genetics and molecular biology in Streptomyces. The techniques of DNA introduction into actinomycetes and wide-spread vectors are briefly described. The origin of the actinomycete plasmids as chromosomal segments capable of autonomous replication is discussed. In this view, it is suggested that genetic instability in actinomycetes is connected with excision of specific DNA sequences from the chromosome at frequencies characteristic of recombination events. Also, amplification of short DNA segments within the chromosome resulting in tandem repeats is a consequence of unequal crossing over between direct repeats flanking the amplifying DNA and, possibly, of induction of replication of this DNA. The data on molecular cloning of actinomycete genes for primary metabolism and those for resistance to and biosynthesis of antibiotics, on using actinomycetes as the hosts for foreign genes to be expressed, as well as on analysis of nucleotide sequences of actinomycete DNA, are presented.