The role of beta93 Cys in the inhibition of Hb S fiber formation

Recent studies have suggested that nitric oxide (NO) binding to hemoglobin (Hb) may lead to the inhibition of sickle cell fiber formation and the dissolution of sickle cell fibers. NO can react with Hb in at least 3 ways: 1) formation of Hb(II)NO, 2) formation of methemoglobin, and 3) formation of S-nitrosohemoglobin, through nitrosylation of the beta93 Cys residue. In this study, the role of beta93 Cys in the mechanism of sickle cell fiber inhibition is investigated through chemical modification with N-ethylmaleimide. UV resonance Raman, FT-IR and electrospray ionization mass spectroscopic methods in conjunction with equilibrium solubility and kinetic studies are used to characterize the effect of beta93 Cys modification on Hb S fiber formation. Both FT-IR spectroscopy and electrospray mass spectrometry results demonstrate that modification can occur at both the beta93 and alpha104 Cys residues under relatively mild reaction conditions. Equilibrium solubility measurements reveal that singly-modified Hb at the beta93 position leads to increased amounts of fiber formation relative to unmodified or doubly-modified Hb S. Kinetic studies confirm that modification of only the beta93 residue leads to a faster onset of polymerization. UV resonance Raman results indicate that modification of the alpha104 residue in addition to the beta93 residue significantly perturbs the alpha(1)beta(2) interface, while modification of only beta93 does not. These results in conjunction with the equilibrium solubility and kinetic measurements are suggestive that modification of the alpha104 Cys residue and not the beta93 Cys residue leads to T-state destabilization and inhibition of fiber formation. These findings have implications for understanding the mechanism of NO binding to Hb and NO inhibition of Hb S fiber formation.     

Integrated conservation and development project life cycles in the Annapurna Conservation Area, Nepal: Is development overpowering conservation?

The merits of integrated conservation and development projects (ICDPs), which aim to provide development incentives to citizens in return for conservation behaviors, have long been debated in the literature. Some of the most common critiques suggest that conservation activities tend to be strongly overpowered by development activities. We studied this assertion through participant observation and archival analysis of five Conservation Area Management Committees (CAMCs) in the Annapurna Conservation Area (ACA), Nepal. Committee activities were categorized as conservation activities (policy development and conservation implementation), development activities (infrastructure, health care, education, economic development, and sanitation), or activities related to institutional strengthening (administrative development and capacity building activities). Greater longevity of each ICDP was associated with greater conservation activity in relation to development activities. Project life cycles progressed from a focus on development activities in their early stages, through a transitional period of institutional strengthening, and toward a longer-term focus that roughly balanced conservation and development activities. Results suggest that the ICDP concept, as practiced in ACA, has been successful at building capacity for and interest in conservation amongst local communities. However, success has come over a period of nearly a decade, suggesting that prior conclusions about ICDP failures may have been based on unrealistic expectations of the time needed to influence behavioral changes in target populations.     

Ecological correlates of Himalayan musk deer Moschus leucogaster

Himalayan musk deer (Moschus leucogaster; hereafter musk deer) are endangered as a result of poaching and habitat loss. The species is nocturnal, crepuscular, and elusive, making direct observation of habitat use and behavior difficult. However, musk deer establish and repeatedly use the same latrines for defecation. To quantify musk deer habitat correlates, we used observational spatial data based on presence–absence of musk deer latrines, as well as a range of fine spatial‐scale ecological covariates. To determine presence–absence of musk deer, we exhaustively searched randomly selected forest trails using a 20‐m belt transect in different study sites within the Neshyang Valley in the Annapurna Conservation Area. In a subsequent way, study sites were classified as habitat or nonhabitat for musk deer. A total of 252 plots, 20 × 20 m, were systematically established every 100 m along 51 transects (each ~0.5 km long) laid out at different elevations to record a range of ecological habitat variables. We used mixed‐effect models and principal component analysis to characterize relationships between deer presence–absence data and habitat variables. We confirmed musk deer use latrines in forests located at higher elevations (3,200–4,200 m) throughout multiple seasons and years. Himalayan birch (Betula utilis) dominated forest, mixed Himalayan fir (Abies spectabilis), and birch forest were preferred over pure Himalayan fir and blue pine (Pinus wallichiana) forest. Greater crown cover and shrub diversity were associated with the presence of musk deer whereas tree height, diameter, and diversity were weakly correlated. Topographical attributes including aspect, elevation, distance to water source, and slope were also discriminated by musk deer. Over‐ and understory forest management can be used to protect forests likely to have musk deer as predicted by the models to ensure long‐term conservation of this rare deer.     

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results

Background

This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years.

Methods

Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo.

Results

DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation.

Conclusion

Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals.     

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part B - Behavioral results

Background

This study investigated the effects of oral dimercapto succinic acid (DMSA) therapy on the behavioural symptoms of children with autism spectrum disorders (ASD) ages 3-8 years.

Methods

Phase 1 involved 65 children with ASD who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo.

Results

The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures. For the seven round group, the degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione (adjusted R² of 0.28-0.75, p < 0.02 in all cases). One round of DMSA had nearly the same benefit as seven rounds. The assessment measures correlated reasonably with one another at the beginning of the study (r = 0.60-0.87) and even better at the end of the study (r = 0.63-0.94).

Conclusion

Overall, both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals, and possibly helpful in reducing some of the symptoms of autism in those children.     

Tripodal amine catechol ligands: a fascinating class of chelators for aluminium(III)

Complexation constants based on potentiometric titrations and spectrophotometric measurements in an aqueous medium of 0.1 M KCl at 25 ± 1 °C for the complexes of Al(III) with multidentate tripodal polycatechol-amine ligands, cis,cis-1,3,5-tris[(2,3-dihydroxybenzylamino)aminomethyl]cyclohexane (TMACHCAT, L¹) and N¹,N³,N⁵-tris(2-(2,3-dihydroxybenzylamino)ethyl)cyclohexane-1,3,5-tricarboxamide (CYCOENCAT, L²) have been summarized in this paper. Both the ligands released six protons to form various monomeric complexes of the types AlLH₃, AlLH₂, AlLH and AlL (L = L¹ and L²). The first species AlLH₃ depicted at low pH for which a monocapped type geometry was suggested, where the ligands were coordinated through three catecholic oxygens at ortho. Other species are formed subsequently from the species AlLH₃ in steps upon deprotonation and coordination of the catecholic oxygens at meta to give encapsulated tris(catechol) type complexes. The probable structures of the metal complexes formed in solution were proposed through molecular modeling calculations. The pAl values calculated for AlL¹ and AlL² are appreciably higher than transferrin. The ligand L² showed higher affinity towards Al(III) than L¹ and desferrioxamine (DFO), the only approved drug for the treatment of aluminium intoxication.     

Carbon source regulation of gene expression in Methylosinus trichosporium OB3b

Applied Microbiology and Biotechnology - Gene expression in methanotrophs has been shown to be affected by the availability of a variety of metals, most notably copper regulating expression of...     

晶圆盘菌属的中国新记录种(英文)

晶圆盘菌属Hyalorbilia是圆盘菌科Orbiliaceae成员,目前中国已报道8个种,报道了3个中国新记录种,其中两个建议为新组合。     

New species and records of orbiliaceous fungi from Georgia,USA

Orbilia georgiana and O. renispora are described as new species to science, in addition, O. eucalypti, O. occulta, and O. xanthoguttulata are reported based on collections taken from the state of Georgia, USA. Orbilia xanthoguttulata is a new record for North America. The morphology of all species is described based on both sexual and asexual morphs. Asexual morphs were obtained from ascospore isolates, from which also DNA was extracted and used to amplify rDNA genes (ITS and LSU) for phylogenetic comparison.