Kinetic and structural evidence of the alkenal/one reductase specificity of human ζ-crystallin

Human ζ-crystallin is a Zn²⁺-lacking medium-chain dehydrogenase/reductase (MDR) included in the quinone oxidoreductase (QOR) family because of its activity with quinones. In the present work a novel enzymatic activity was characterized: the double bond α,β-hydrogenation of medium-chain 2-alkenals and 3-alkenones. The enzyme is especially active with lipid peroxidation products such as 4-hydroxyhexenal, and a role in their detoxification is discussed. This specificity is novel in the QOR family, and it is similar to that described in the distantly related alkenal/one reductase family. Moreover, we report the X-ray structure of ζ-crystallin, which represents the first structure solved for a tetrameric Zn²⁺-lacking MDR, and which allowed the identification of the active-site lining residues. Docking simulations suggest a role for Tyr53 and Tyr59 in catalysis. The kinetics of Tyr53Phe and Tyr59Phe mutants support the implication of Tyr53 in binding/catalysis of alkenal/one substrates, while Tyr59 is involved in the recognition of 4-OH-alkenals.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.     

A life history study of the Snake River plains endemic Lepidium papilliferum (Brassicaceae)

Lepidium papilliferum is an ephemeral species that occupies ""slick spot"" microhabitats in the matrix of sagebrush steppe vegetation of the southwestern Snake River plains, Idaho, USA. We related population demographic data collected from 1993 to 1996 to on-site precipitation data on the Orchard Training Area west of Boise. We also carried out field seed-retrieval and in situ seed bank studies. We found that L. papilliferum has a dual life history strategy. A fraction of each cohort sets seed as summer annuals, while the remaining plants remain vegetative and potentially biennial. Surviving biennials flower and set seed along with the annual cohort of the following year. The switch to flowering as an annual appears to be based on threshold rosette size. Probability of survival to flowering was much lower for biennials than for annuals of the same cohort, but surviving biennials sometimes had enhanced seed production. The summerdry environment of the Snake River plains combined with the slick spot habitat has apparently selected for a primarily summer annual life cycle for this species. Seeds were highly dormant at dispersal and were not responsive to dormancybreaking cues. Those from a given cohort of L. papilliferum remained viable in the soil for at least 11 years. This persistent seed bank provides a buffer against extinction in sequences of years when seed production is low or absent. Estimated seed bank size varied from near zero for a heavily disturbed site that formerly supported the species to 18 viable seeds · dm -2 for an extant population in high-quality habitat. Management for population preservation for L. papilliferum should focus on protecting the seed bank from destruction caused by livestock trampling and other anthropogenic disturbances.     

Systems thinking in British Telecom Training: A brief account

This paper describes how British Telecom's Training Department has been using Systems Thinking over the last few years and has started introducing Systems concepts and methodologies to a wider audience of operational managers within. The paper explores some of the reasons for British Telecom to adopt Systems Thinking and describes the application of Soft Systems Methodology (SSM) to a particular project within Training Department. The paper also describes the design and delivery of the Introduction to Systems Thinking course which is now part of British Telecom's core program of management training.     

Boulding's typology elaborated: A framework for understanding school and classroom systems

The scope of current educational reform themes is wide. Power is shifted from central governments to local, from administrative office to school site, from principal to teachers, from teacher to students. This is hopeful because traditional reform efforts have been counterproductive. These new themes parallel a worldwide paradigm shift from viewing relationships as monocausal and top-down regulating to interactive and self-regulating. The new themes are also problematic because resulting reform efforts are conflicting, proposing either control or flexibility, which increases harmful out-comes. This paper elaborates Boulding's typology of system complexity drawing from education and related disciplines. The elaboration unifies conflicting perspectives and explains why school reforms fail. Agency in change is clarified. The change model that results highlights system adjustment capacities and specifies both control and flexibility: control of morphostatic subsystems for maintaining access to resources of time, materials, equipment, and energy; and flexibility in morphogenic subsystems for learning, growth, and differentiation.     

H-Y Antigens on mouse spermatozoa

Zusammenfassung Nachweis, dass jungfräuliche weibliche C5 7BL/6 Mäuse weder beschleunigte noch verzögerte Ablehnung von syngeneischer männlicher Hautübertragung nach einer einzigen i.p. Einspritzung von 1 bis 8 Millionen syngeneischen Spermien zeigen.

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Supported by NIH Contract No. 70-2151. I thank Dr.R. E. Billingham for useful discussions on this subject.     

Acknowledgment of priority

Acknowledgment of priority     

Connecting Internal and External Representations: Spatial Transformations of Scientific Visualizations

Many scientific discoveries have depended on external diagrams or visualizations. Many scientists also report to use an internal mental representation or mental imagery to help them solve problems and reason. How do scientists connect these internal and external representations? We examined working scientists as they worked on external scientific visualizations. We coded the number and type of spatial transformations (mental operations that scientists used on internal or external representations or images) and found that there were a very large number of comparisons, either between different visualizations or between a visualization and the scientists’ internal mental representation. We found that when scientists compared visualization to visualization, the comparisons were based primarily on features. However, when scientists compared a visualization to their mental representation, they were attempting to align the two representations. We suggest that this alignment process is how scientists connect internal and external representations.