The structure and function of plant hemoglobins.

Plants, like humans, contain hemoglobin. Three distinct types of hemoglobin exist in plants: symbiotic, non-symbiotic, and truncated hemoglobins. Crystal structures and other structural and biophysical techniques have revealed important knowledge about ligand binding and conformational stabilization in all three types. In symbiotic hemoglobins (leghemoglobins), ligand binding regulatory mechanisms have been shown to differ dramatically from myoglobin and red blood cell hemoglobin. In the non-symbiotic hemoglobins found in all plants, crystal structures and vibrational spectroscopy have revealed the nature of the structural transition between the hexacoordinate and ligand-bound states. In truncated hemoglobins, the abbreviated globin is porous, providing tunnels that may assist in ligand binding, and the bound ligand is stabilized by more than one distal pocket residue. Research has implicated these plant hemoglobins in a number of possible functions differing among hemoglobin types, and possibly between plant species.     

Land Use,Macroalgae, and a Tumor-Forming Disease in Marine Turtles

Wildlife diseases are an increasing concern for endangered species conservation, but their occurrence, causes, and human influences are often unknown. We analyzed 3,939 records of stranded Hawaiian green sea turtles (Chelonia mydas) over 28 years to understand fibropapillomatosis, a tumor-forming disease linked to a herpesvirus. Turtle size is a consistent risk factor and size-standardized models revealed considerable spatial and temporal variability. The disease peaked in some areas in the 1990s, in some regions rates remained constant, and elsewhere rates increased. Land use, onshore of where the turtles feed, may play a role. Elevated disease rates were clustered in watersheds with high nitrogen-footprints; an index of natural and anthropogenic factors that affect coastal eutrophication. Further analysis shows strong epidemiological links between disease rates, nitrogen-footprints, and invasive macroalgae and points to foraging ecology. These turtles now forage on invasive macroalgae, which can dominate nutrient rich waters and sequester environmental N in the amino acid arginine. Arginine is known to regulate immune activity, promote herpesviruses, and contribute to tumor formation. Our results have implications for understanding diseases in aquatic organisms, eutrophication, herpesviruses, and tumor formation.     

Hydroxylamine reduction to ammonium by plant and cyanobacterial hemoglobins

Plants often face hypoxic stress as a result of flooding and waterlogged soils. During these periods, they must continue ATP production and nitrogen metabolism if they are to survive. The normal pathway of reductive nitrogen assimilation in non-legumes, nitrate, and nitrite reductase can be inhibited during low oxygen conditions that are associated with the buildup of toxic metabolites such as nitrite and nitric oxide, so the plant must also have a means of detoxifying these molecules. Compared to animal hemoglobins, plant and cyanobacterial hemoglobins are adept at reducing nitrite to nitric oxide under anaerobic conditions. Here we test their abilities to reduce hydroxylamine, a proposed intermediate of nitrite reductase, under anaerobic conditions. We find that class 1 rice nonsymbiotic hemoglobin (rice nsHb1) and the hemoglobin from the cyanobacterium Synechocystis (SynHb) catalyze the reduction of hydroxylamine to ammonium at rates 100-2500 times faster than animal hemoglobins including myoglobin, neuroglobin, cytoglobin, and blood cell hemoglobin. These results support the hypothesis that plant and cyanobacterial hemoglobins contribute to anaerobic nitrogen metabolism in support of anaerobic respiration and survival during hypoxia.     

Substrate preferences and catalytic parameters determined by structural characteristics of sterol 14alpha-demethylase (CYP51) from Leishmania infantum

Leishmaniasis is a major health problem that affects populations of ～90 countries worldwide, with no vaccine and only a few moderately effective drugs. Here we report the structure/function characterization of sterol 14α-demethylase (CYP51) from Leishmania infantum. The enzyme catalyzes removal of the 14α-methyl group from sterol precursors. The reaction is essential for membrane biogenesis and therefore has great potential to become a target for antileishmanial chemotherapy. Although L. infantum CYP51 prefers C4-monomethylated sterol substrates such as C4-norlanosterol and obtusifoliol (V(max) of ～10 and 8 min(-1), respectively), it is also found to 14α-demethylate C4-dimethylated lanosterol (V(max) = 0.9 min(-1)) and C4-desmethylated 14α-methylzymosterol (V(max) = 1.9 min(-1)). Binding parameters with six sterols were tested, with K(d) values ranging from 0.25 to 1.4 μM. Thus, L. infantum CYP51 is the first example of a plant-like sterol 14α-demethylase, where requirements toward the composition of the C4 atom substituents are not strict, indicative of possible branching in the postsqualene portion of sterol biosynthesis in the parasite. Comparative analysis of three CYP51 substrate binding cavities (Trypanosoma brucei, Trypanosoma cruzi, and L. infantum) suggests that substrate preferences of plant- and fungal-like protozoan CYP51s largely depend on the differences in the enzyme active site topology. These minor structural differences are also likely to underlie CYP51 catalytic rates and drug susceptibility and can be used to design potent and specific inhibitors.     

A Simple ERP Method for Quantitative Analysis of Cognitive Workload in Myoelectric Prosthesis Control and Human-Machine Interaction

Common goals in the development of human-machine interface (HMI) technology are to reduce cognitive workload and increase function. However, objective and quantitative outcome measures assessing cognitive workload have not been standardized for HMI research. The present study examines the efficacy of a simple event-related potential (ERP) measure of cortical effort during myoelectric control of a virtual limb for use as an outcome tool. Participants trained and tested on two methods of control, direct control (DC) and pattern recognition control (PRC), while electroencephalographic (EEG) activity was recorded. Eighteen healthy participants with intact limbs were tested using DC and PRC under three conditions: passive viewing, easy, and hard. Novel auditory probes were presented at random intervals during testing, and significant task-difficulty effects were observed in the P200, P300, and a late positive potential (LPP), supporting the efficacy of ERPs as a cognitive workload measure in HMI tasks. LPP amplitude distinguished DC from PRC in the hard condition with higher amplitude in PRC, consistent with lower cognitive workload in PRC relative to DC for complex movements. Participants completed trials faster in the easy condition using DC relative to PRC, but completed trials more slowly using DC relative to PRC in the hard condition. The results provide promising support for ERPs as an outcome measure for cognitive workload in HMI research such as prosthetics, exoskeletons, and other assistive devices, and can be used to evaluate and guide new technologies for more intuitive HMI control.     

Breeding success at the range margin of a desert species: implications for a climate‐induced elevational shift

If the breeding range of a species is limited by biotic or abiotic environmental factors that depress breeding success at the range margin, then range expansion is expected when those limiting factors are alleviated. Over a three‐year period, we measured breeding success of a desert species, black‐throated sparrow Amphispiza bilineata, along a steep elevation gradient between the Peninsular Mountains and Colorado Desert (San Diego County, California) that is undergoing a warming trend. We compared breeding success at geographically marginal locations (higher‐elevation chaparral sites) to more central locations (lower‐elevation desert scrub sites) only a short distance apart. Breeding success was measured at the nest level, territory level, and population level. At each level measured, breeding success tended to be greater at higher‐elevation chaparral sites at the distribution margin compared to lower‐elevation sites where the bird was more common. Black‐throated sparrows had 100% reproductive failure at lower‐elevation sites during the two driest years of our study (2006–2007), but did relatively well at higher‐elevation sites. Only in a wetter year (2008) was breeding success improved at lower‐elevation sites. Surprisingly, there was no evidence of an upward elevational shift in distribution over a 26‐year period despite a clear warming trend and drier conditions. Greater territory density at lower‐elevation sites with reproductive failure during dry years suggests the possibility of an ecological trap in this system, which could prevent or delay climate‐induced range shifts. A common presumption has been that desert species will undergo relatively mild negative impacts due to a warming climate, but it is possible that some desert species are already at or near their temperature and aridity tolerance limits within their current range and shifts may not always be possible.     

Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition

CYP51 (sterol 14α-demethylase) is an efficient target for clinical and agricultural antifungals and an emerging target for treatment of Chagas disease, the infection that is caused by multiple strains of a protozoan pathogen Trypanosoma cruzi. Here, we analyze CYP51A from the Y strain T. cruzi. In this protein, proline 355, a residue highly conserved across the CYP51 family, is replaced with serine. The purified enzyme retains its catalytic activity, yet has been found less susceptible to inhibition. These biochemical data are consistent with cellular experiments, both in insect and human stages of the pathogen. Comparative structural analysis of CYP51 complexes with VNI and two derivatives suggests that broad-spectrum CYP51 inhibitors are likely to be preferable as antichagasic drug candidates.     

Artificial Warthog Burrows Used to Sample Adult and Immature Tsetse (Glossina spp) in the Zambezi Valley of Zimbabwe

BackgroundThe biology of adult tsetse (Glossina spp), vectors of trypanosomiasis in Africa, has been extensively studied – but little is known about larviposition in the field.Conclusions/SignificanceArtificial warthog burrows provide a novel method for collecting tsetse pupae, studying tsetse behaviour at larviposition, assessing the physiological status of female tsetse and their larvae, and of improving understanding of the physiological dynamics of terminal pregnancy, and population dynamics generally, with a view to improving methods of trypanosomiasis control.     

Bioprospecting the African Renaissance: The new value of <Emphasis Type="Italic">muthi</Emphasis> in South Africa

This article gives an overview of anthropological research on bioprospecting in general and of available literature related to bioprospecting particularly in South Africa. It points out how new insights on value regimes concerning plant-based medicines may be gained through further research and is meant to contribute to a critical discussion about the ethics of Access and Benefit Sharing (ABS). In South Africa, traditional healers, plant gatherers, petty traders, researchers and private investors are assembled around the issues of standardization and commercialization of knowledge about plants. This coincides with a nation-building project which promotes the revitalization of local knowledge within the so called African Renaissance. A social science analysis of the transformation of so called Traditional Medicine (TM) may shed light onto this renaissance by tracing social arenas in which different regimes of value are brought into conflict. When medicinal plants turn into assets in a national and global economy, they seem to be manipulated and transformed in relation to their capacity to promote health, their market value, and their potential to construct new ethics of development. In this context, the translation of socially and culturally situated local knowledge about muthi into global pharmaceuticals creates new forms of agency as well as new power differentials between the different actors involved.