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Accumulated mutational studies indicate that many diazotrophs have multiple pathways that mediate electron flow to nitrogenase (Figure 5). These pathways include multiple electron-transfer proteins (Fds and Flds) and multiple oxidoreductases (PFOR, FNR, the Rnf complex and other enzymes to be identified). Such redundancy, like the redundancy of Mo-nitrogenase and the alternative nitrogenase systems, might reflect the importance of N fixation for survival of bacteria. Another explanation is that, by possessing subsystems (or subengines), diazotrophs either maximize or fine-tune their capacity for N fixation to cope with various conditions.

In conclusion, the last 25 years of research has identified the basis for the “switch-off” effect at the molecular level, including the enzymes catalyzing the reversible ADP-ribosylation of dinitrogenase reductase in . However, the components of the signal transduction to DRAT and DRAG have not been identified. The recent demonstration of the role of P proteins in this pathway is, however, most likely an important contribution to future studies. It is not surprising that P proteins are involved in the signaling of the nitrogen status, but it will be crucial to show whether or not there is a direct effect of these proteins in “switch-off” by darkness. The regulatory system, which controls nitrogenase activity in and other diazotrophs, has already shown a number of new features concerning enzyme control in response to metabolic changes that are important for understanding metabolic regulation in general. Some of the possible components that have been suggested, like the role of GTP and GTP hydrolysis, may, if confirmed, add further complexity to the control cascade.

Microsoft Office is one of the world’s most used information-worker applications. This level of exposure and recognition has made these tools an enticing area for customization as developers wish to extend a tool that users are already comfortable with. Developing with Microsoft Office has traditionally meant developing in a COM-based world. This began to change with Office 2003 when Microsoft shipped primary interop assemblies (PIAs) as part of the advanced installation. These PIAs opened Office to the .NET developer community and their managed code projects. A primary interop assembly enabled a Visual Studio developer to write code against the Office applications by adding a reference in the project. This assembly took on the responsibility of translating between the COM and managed code environments. Even with the PIAs, this development was not for the faint of heart. .NET developers often struggled. Their code had to deal with the way Office maintained object lifetimes and they had to contend with lots of COM plumbing. In addition, the managed code solution was limited to running outside the process of the Office application. What was missing was a layer between the PIAs and the developer’s custom application. Microsoft Visual Studio Tools for Office (VSTO) fills that gap. Visual Studio Tools for Office extends the Visual Studio environment to support the development of managed code solutions for Microsoft Office. With VSTO, the developer can create solutions that leverage Microsoft Office applications, including the construction of add-ins, custom task panes, ribbon customizations, and smart documents.

Microsoft Office is one of the world’s most used information-worker applications. This level of exposure and recognition has made these tools an enticing area for customization as developers wish to extend a tool that users are already comfortable with. Developing with Microsoft Office has traditionally meant developing in a COM-based world. This began to change with Office 2003 when Microsoft shipped primary interop assemblies (PIAs) as part of the advanced installation. These PIAs opened Office to the .NET developer community and their managed code projects. A primary interop assembly enabled a Visual Studio developer to write code against the Office applications by adding a reference in the project. This assembly took on the responsibility of translating between the COM and managed code environments. Even with the PIAs, this development was not for the faint of heart. .NET developers often struggled. Their code had to deal with the way Office maintained object lifetimes and they had to contend with lots of COM plumbing. In addition, the managed code solution was limited to running outside the process of the Office application. What was missing was a layer between the PIAs and the developer’s custom application. Microsoft Visual Studio Tools for Office (VSTO) fills that gap. Visual Studio Tools for Office extends the Visual Studio environment to support the development of managed code solutions for Microsoft Office. With VSTO, the developer can create solutions that leverage Microsoft Office applications, including the construction of add-ins, custom task panes, ribbon customizations, and smart documents.

In conclusion, the last 25 years of research has identified the basis for the “switch-off” effect at the molecular level, including the enzymes catalyzing the reversible ADP-ribosylation of dinitrogenase reductase in . However, the components of the signal transduction to DRAT and DRAG have not been identified. The recent demonstration of the role of P proteins in this pathway is, however, most likely an important contribution to future studies. It is not surprising that P proteins are involved in the signaling of the nitrogen status, but it will be crucial to show whether or not there is a direct effect of these proteins in “switch-off” by darkness. The regulatory system, which controls nitrogenase activity in and other diazotrophs, has already shown a number of new features concerning enzyme control in response to metabolic changes that are important for understanding metabolic regulation in general. Some of the possible components that have been suggested, like the role of GTP and GTP hydrolysis, may, if confirmed, add further complexity to the control cascade.

Accumulated mutational studies indicate that many diazotrophs have multiple pathways that mediate electron flow to nitrogenase (Figure 5). These pathways include multiple electron-transfer proteins (Fds and Flds) and multiple oxidoreductases (PFOR, FNR, the Rnf complex and other enzymes to be identified). Such redundancy, like the redundancy of Mo-nitrogenase and the alternative nitrogenase systems, might reflect the importance of N fixation for survival of bacteria. Another explanation is that, by possessing subsystems (or subengines), diazotrophs either maximize or fine-tune their capacity for N fixation to cope with various conditions.

In conclusion, the last 25 years of research has identified the basis for the “switch-off” effect at the molecular level, including the enzymes catalyzing the reversible ADP-ribosylation of dinitrogenase reductase in . However, the components of the signal transduction to DRAT and DRAG have not been identified. The recent demonstration of the role of P proteins in this pathway is, however, most likely an important contribution to future studies. It is not surprising that P proteins are involved in the signaling of the nitrogen status, but it will be crucial to show whether or not there is a direct effect of these proteins in “switch-off” by darkness. The regulatory system, which controls nitrogenase activity in and other diazotrophs, has already shown a number of new features concerning enzyme control in response to metabolic changes that are important for understanding metabolic regulation in general. Some of the possible components that have been suggested, like the role of GTP and GTP hydrolysis, may, if confirmed, add further complexity to the control cascade.

In conclusion, the last 25 years of research has identified the basis for the “switch-off” effect at the molecular level, including the enzymes catalyzing the reversible ADP-ribosylation of dinitrogenase reductase in . However, the components of the signal transduction to DRAT and DRAG have not been identified. The recent demonstration of the role of P proteins in this pathway is, however, most likely an important contribution to future studies. It is not surprising that P proteins are involved in the signaling of the nitrogen status, but it will be crucial to show whether or not there is a direct effect of these proteins in “switch-off” by darkness. The regulatory system, which controls nitrogenase activity in and other diazotrophs, has already shown a number of new features concerning enzyme control in response to metabolic changes that are important for understanding metabolic regulation in general. Some of the possible components that have been suggested, like the role of GTP and GTP hydrolysis, may, if confirmed, add further complexity to the control cascade.

Our understanding of the regulation of the nitrogen-fixation process in free-living diazotrophs has advanced considerably in the last decade with information coming from a wide range of model systems. These advances have led to a much more global view of the mechanisms, which facilitate the very stringent control that is necessary to maximise the physiological benefits from diazotrophy. With regard to nitrogen control, members of the P protein family, , the GlnB, GlnK, NifI, etc. proteins, clearly play a pivotal role in nearly all organisms and P is now being recognised as the critical signal-transduction protein in a wide variety of aspects of bacterial nitrogen metabolism (Arcondéguy , 2001).

At the molecular level, our understanding of the regulatory processes is advancing considerably in those organims that have a NifA-dependent mode of control, although the ability to purify active NifA proteins (particularly of the O-sensitive group) is still a major hurdle.

The heterocystous cyanobacteria are particularly complex owing to the integration of the regulation of both nitrogenase expression and activity with that of heterocyst development. Nevertheless, considerable information is now emerging and a broad outline of the major signal-transduction pathways may be achieved fairly soon. The groups of organisms where there is still much to be learnt are the Archaea and the Gram-positive diazotrophs. In the Archaea, the advent of genome sequences and good genetic systems in model organisms, and , shows considerable promise for the future but similar opportunities are not yet apparent in the Gram-positive diazotrophs.

In summary, the challenge in the future is to begin to integrate our current knowledge into a whole-cell perspective of the genetic, biochemical and physiological processes that contribute to successful diazotrophy.

Microsoft Office is one of the world’s most used information-worker applications. This level of exposure and recognition has made these tools an enticing area for customization as developers wish to extend a tool that users are already comfortable with. Developing with Microsoft Office has traditionally meant developing in a COM-based world. This began to change with Office 2003 when Microsoft shipped primary interop assemblies (PIAs) as part of the advanced installation. These PIAs opened Office to the .NET developer community and their managed code projects. A primary interop assembly enabled a Visual Studio developer to write code against the Office applications by adding a reference in the project. This assembly took on the responsibility of translating between the COM and managed code environments. Even with the PIAs, this development was not for the faint of heart. .NET developers often struggled. Their code had to deal with the way Office maintained object lifetimes and they had to contend with lots of COM plumbing. In addition, the managed code solution was limited to running outside the process of the Office application. What was missing was a layer between the PIAs and the developer’s custom application. Microsoft Visual Studio Tools for Office (VSTO) fills that gap. Visual Studio Tools for Office extends the Visual Studio environment to support the development of managed code solutions for Microsoft Office. With VSTO, the developer can create solutions that leverage Microsoft Office applications, including the construction of add-ins, custom task panes, ribbon customizations, and smart documents.