Antimicrobial activity in the skin of the channel catfish Ictalurus punctatus: characterization of broad-spectrum histone-like antimicrobial proteins

Three antibacterial proteins were isolated from acid extracts of channel catfish (Ictalurus punctatus) skin by cation exchange chromatography and reverse-phase high-pressure liquid chromatography. The molecular masses of the proteins were 15.5, 15.5 and 30 kD as determined by SDS-polyacrylamide gel electrophoresis. Mass spectrometry, amino acid composition and amino acid sequence data suggest that the most abundant protein is closely related to histone H2B. The H2B-like protein was inhibitory to Aeromonas hydrophila and Saprolegnia spp., which are important bacterial and fungal pathogens of fish. These findings suggest that histones may be important defensive molecules in fish. Received 22 December 1997; received after revision 5 March 1998; accepted 5 March 1998     

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.     

Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models

Using transgenic mice expressing human cystatin C (encoded by CST3), we show that cystatin C binds soluble amyloid-beta peptide and inhibits cerebral amyloid deposition in amyloid-beta precursor protein (APP) transgenic mice. Cystatin C expression twice that of the endogenous mouse cystatin C was sufficient to substantially diminish amyloid-beta deposition. Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease.     

Quantification, Mandated Science and Judgment

In his Trust in Numbers: The Pursuit of Objectivity in Science and Public Life, Ted Porter asks how to account for the prestige and power of quantitative methods in the modern world. His answer involves two theses. One reverses a standard claim by asserting that quantification in basic sciences can often be driven by quantification in more applied areas such as government and business. The second thesis, which I call judgment replacement, asserts that quantification overcomes lack of trust in humans by replacing human judgment in scientific communities and public life. Some aspects of the latter thesis are insightful and convincing. However, as a general claim, the judgment replacement thesis says that quantification and objectivity imply shallowness, superficiality and lack of subtlety. I examine one of Porter's key examples and show that as a general proposition the judgment replacement thesis gives a warped account of governmental decisions that involve a great deal of scientific input, an activity that colleagues and I have called mandated science. I show that Porter obfuscates the very features of mandated science that need the most clarification. The quantitative mentality can be superficial but it can also be complex and profound, and quantification can actually increase human judgment. The virtues of quantitative methods help account for their prestige and power.     

A CASE FOR SUSTAINABLE SECURITY SYSTEMS ENGINEERING： INTEGRATING NATIONAL, HUMAN, ENERGY AND ENVIRONMENTAL SECURITY

In the wake of the September 11, 2001 terrorist attacks, there is a growing sense of insecurity felt by many citizens around the world. Sustainable security, with roots in the sustainable development and human security literature, seeks positive transformations for the co-evolving and mutually dependent human-environmental condition by integrating (and subsuming) national, human, environmental, and energy security concerns and capitalizing on opportunities provided by human creativity, diplomatic openings, modernization and environmental change. The field of Sustainable Security Systems Engineering is proposed for protecting, restoring, designing, and implementing a set of integrated natural and man-made processes that equitably and responsibly meet the biophysical needs of human communities, while maintaining long-term security, respecting financial constraints, meeting ecological limits, and improving institutional arrangements for transparent and effective governance. Scenario planning is shown to help promote sustainable security by identifying the preconditions of instability and helping to proactively address them in an increasingly complex and uncertain world. The six papers published in this featured collection cross policy domains, geographic, political, and sectoral boundaries and were discussed at forums sponsored by the Systems Engineering and Global Policy group. Collectively, they demonstrate the quality, breadth and depth of systems engineering methodologies that are used to promote sustainable security.     

Multi-Disciplinary North-South Collaboration in Participatory Action Research on Food Value Chains: a German-Tanzanian Case Study on Perceptions,Experiences and Challenges

Systemic Practice and Action Research - Upgrading local food value chains is a promising approach to invigorating African food systems. This endeavour warrants multi-disciplinary North-South...     

Cannabidiol and its pharmacokinetic interaction with delta1-tetrahydrocannabinol.

Co-administration of cannabidiol with delta1-tetrahydrocannabinol was found to have no effect on the rate of disappearance of delta1-tetrahydrocannabinol from the blood of rats. The implications of this finding are discussed.