Identification and characterization of DUSP27, a novel dual-specific protein phosphatase

A novel human dual-specific protein phosphatase (DSP), designated DUSP27, is here described. The DUSP27 gene contains three exons, rather than the predicted 4-14 exons, and encodes a 220 amino acid protein. DUSP27 is structurally similar to other small DSPs, like VHR and DUSP13. The location of DUSP27 on chromosome 10q22, 50 kb upstream of DUSP13, suggests that these two genes arose by gene duplication. DUSP27 is an active enzyme, and its kinetic parameters and were determined. DUSP27 is a cytosolic enzyme, expressed in skeletal muscle, liver and adipose tissue, suggesting its possible role in energy metabolism.     

Detection of light images by simple tissues as visualized by photosensitized magnetic resonance imaging

In this study, we show how light can be absorbed by the body of a living rat due to an injected pigment circulating in the blood stream. This process is then physiologically translated in the tissue into a chemical signature that can be perceived as an image by magnetic resonance imaging (MRI). We previously reported that illumination of an injected photosynthetic bacteriochlorophyll-derived pigment leads to a generation of reactive oxygen species, upon oxygen consumption in the blood stream. Consequently, paramagnetic deoxyhemoglobin accumulating in the illuminated area induces changes in image contrast, detectable by a Blood Oxygen Level Dependent (BOLD)-MRI protocol, termed photosensitized (ps)MRI. Here, we show that laser beam pulses synchronously trigger BOLD-contrast transients in the tissue, allowing representation of the luminous spatiotemporal profile, as a contrast map, on the MR monitor. Regions with enhanced BOLD-contrast (7-61 fold) were deduced as illuminated, and were found to overlap with the anatomical location of the incident light. Thus, we conclude that luminous information can be captured and translated by typical oxygen exchange processes in the blood of ordinary tissues, and made visible by psMRI (Fig. 1). This process represents a new channel for communicating environmental light into the body in certain analogy to light absorption by visual pigments in the retina where image perception takes place in the central nervous system. Potential applications of this finding may include: non-invasive intra-operative light guidance and follow-up of photodynamic interventions, determination of light diffusion in opaque tissues for optical imaging and possible assistance to the blind.     

The interplay of fold recognition and experimental structure determination in structural genomics

Achieving the goals of structural genomics initiatives depends on the outcomes of two groups of factors: the number and distribution of experimentally determined protein structures, and our ability to assign novel proteins to known structures (fold recognition) and use them to build models (modeling). The quality of the tools used for fold recognition defines the scope of experimental effort - the more distant the templates that can be recognized, the smaller the number of proteins that have to be solved. Recent improvements in fold recognition may have suggested that the goals of structural genomics initiatives are getting closer. However, problems that surfaced during the first few years of active work have put many of the early estimates in doubt and new ones are still slow in coming.     

Connecting the protein structure universe by using sparse recurring fragments

The quest to order and classify protein structures has lead to various classification schemes, focusing mostly on hierarchical relationships between structural domains. At the coarsest classification level, such schemes typically identify hundreds of types of fundamental units called folds. As a result, we picture protein structure space as a collection of isolated fold islands. It is obvious, however, that many protein folds share structural and functional commonalities. Locating those commonalities is important for our understanding of protein structure, function, and evolution. Here, we present an alternative view of the protein fold space, based on an interfold similarity measure that is related to the frequency of fragments shared between folds. In this view, protein structures form a complicated, crossconnected network with very interesting topology. We show that interfold similarity based on sequence/structure fragments correlates well with similarities of functions between protein populations in different folds.     

Nutritional status, cognition, and survival: a new role for leptin and AMP kinase

Although adequate nutrition is essential for optimal neural activity and survival, mild energy restriction may improve cognition and prolong longevity. Energy status is monitored by the cellular AMP-activated protein kinase (AMPK) system, whereas leptin regulates total energy balance. We investigated the roles of AMPK and leptin in cognition and survival under diet restriction (DR). Hippocampal AMPK activity increases with energy restriction. Modest activation (DR to 60%) induces neurogenesis and improves cognition. However, DR to 40% augmented AMPK activity, reduced cognition and catecholamines, and increased neural apoptosis and mortality. Leptin signaling is preserved only in DR to 60%, countering the effects of AMPK "overactivation" by preventing neuroapoptosis, restoring noradrenergic activity and behavioral performance, and increasing longevity. The balance between leptin and AMPK is crucial in determining neuronal fate, cognitive ability, and survival. Should these findings extend to Man, then controlled activation of AMPK may improve neurodegenerative diseases, and leptin may have a new role in treating stress-associated malnutrition.     

Stochastic Analysis of the Motion of DNA Nanomechanical Bipeds

In this paper, we formulate and analyze a Markov process modeling the motion of DNA nanomechanical walking devices. We consider a molecular biped restricted to a well-defined one-dimensional track and study its asymptotic behavior. Our analysis allows for the biped legs to be of different molecular composition, and thus to contribute differently to the dynamics. Our main result is a functional central limit theorem for the biped with an explicit formula for the effective diffusivity coefficient in terms of the parameters of the model. A law of large numbers, a recurrence/transience characterization and large deviations estimates are also obtained. Our approach is applicable to a variety of other biological motors such as myosin and motor proteins on polymer filaments.     

Searching for Leverage to Conserve Forests: The Industrial Ecology of Wood Products in the United States

The forest and the creatures it shelters exemplify nature, and logging exemplifies the impacts of humans. In the 1990s Americans annually removed 70% more timber from the forest than in 1900. Since I900 population rose more than three times and gross domestic product (GDP) per person almost five. Despite more people, affluence, and logging, U.S. forest area remained constant. Since mid-century, standing timber volume me nearly 30%. Consumers, millers, and foresters, responding to changes in style, ethics, and technology, have contributed to these outcomes. We examine the role of each actor in the industrial ecology of forests for their leverage for sparing forests. Consumers lessened their use of wood products per GDP (Intensity of Use) during the century by 2.5% annually to offset expanding population and GDP per person, a trend that will level or lower timber consumption if population and affluence grow as expected. Millers became highly efficient at utilizing wood and recycled fiber for their material or energy, a success that limits their fcrture leverage. Foresters have leverage to grow trees faster and thus use less forest land to grow and harvest timber. Steady or declining demand for trees coupled to productive forests could spare more US. forest land for sequestering carbon, ecosystem services, and habit for nature.