Energy-dispersive X-ray analysis of the extracellular cadmium sulfide crystallites of Klebsiella aerogenes

Klebsiella aerogenes forms electron-dense partieles on the cell surface in response to the presence of cadmium ions in the growth medium. These particles ranged from 20 to 200 nm in size, and quantitative energy dispersive X-ray analysis established that they comprise cadmium and sulfur in a 1:1 ratio. This observation leads to the conclusion that the particles are cadmium sulfide crystallites. A combination of atomic absorption spectroscopy, inductively coupled plasma mass spectrometry, and acid-labile sulfide analysis revealed that the total intracellular and bound extracellular cadmium:sulfur ratio is also 1:1, which suggests that the bulk of the cadmium is fixed as extracellular cadmium sulfide. The tolerance of K. acrogenes to cadmium ions and the formation of the cadmium sulfide crystallites were dependent on the buffer composition of the growth medium. The addition of cadmium ions to phosphate-buffered media resulted in cadmium phosphate precipitates that remove the potentially toxic cadmium ions from the growth medium. Electrondense particles formed on the surfaces of bacteria grown under these conditions were a combination of cadmium sulfide and cadmium phosphates. The specific bacterial growth rate in the exponential phase of batch cultures was not affected by up to 2mM cadmium in Tricine-buffered medium, but formation of cadmium sulfide crystallites was maximal during the stationary phase of batch culture. Cadmium tolerance was much lower (10 to 150 M) in growth media buffered with Tris, Bistris propane, Bes, Tes, or Hepes. These results illustrate the importance of considering medium composition when comparing levels of bacterial cadmium tolerance.Abbreviations EDXA Energy dispersive X-ray analysis - AAS Atomic absorption spectroscopy - TEM Transmission electron microscopy - SEM Scanning electron microscopy - ICP-MS Inductively coupled plasma mass spectrometry - ALSA Acid-labile sulfide analysis     

Proteomic analysis of root meristems and the effects of acetohydroxyacid synthase-inhibiting herbicides in the root of Medicago truncatula

Quantitative proteome analyses of meristematic and nonmeristematic tissues from Medicago truncatula primary and lateral roots and meristem tissues from plants treated with acetohydroxyacid synthase-inhibiting herbicides were made. The accumulation of 81 protein spots changed in meristematic and nonmeristematic tissues and 51 protein spots showed significant changes in accumulation in herbicide-treated meristems. Identified proteins indicate two trends, (i) increased accumulation of cell division and redox-mediating proteins in meristems compared to nonmeristematic tissues and (ii) increased accumulation of pathogenesis-related and decreased accumulation of metabolic proteins in herbicide-treated roots.     

Male human motor cortex stimulus-response characteristics are not altered by aging

Evidence suggests that there are aging-related changes in corticospinal stimulus-response curve characteristics in later life. However, there is also limited evidence that these changes may only be evident in postmenopausal women and not in men. This study compared corticospinal stimulus-response curves from a group of young men [19.8 ± 1.6 yr (range 17-23 yr)] and a group of old men [n = 18, aged 64.1 ± 5.0 yr (range 55-73 yr)]. Transcranial magnetic stimulation (TMS) over the contralateral motor cortex was used to evoke motor potentials at a range of stimulus intensities in the first dorsal interosseous muscle of each hand separately. There was no effect of age group or hemisphere (i.e., left vs. right motor cortex) on motor evoked potential (MEP) amplitude or any other stimulus-response characteristic. MEP variability was strongly modulated by resting motor threshold but not by age. M-wave (but not F-wave) amplitude was reduced in old men, but expressing MEP amplitude as a ratio of M-wave amplitude did not reveal any age-related differences in cortically evoked stimulus-response characteristics. We conclude that male corticospinal stimulus-response characteristics are not altered by advancing age and that previously reported age-related changes in motor cortical excitability assessed with TMS are likely due to changes inherent in the female participants only. Future studies are warranted to fully elucidate the relationship between, and functional significance of, changes in circulating neuroactive sex hormones and motor function in later life.     

Contact Heterogeneity,Rather Than Transmission Efficiency,Limits the Emergence and Spread of Canine Influenza Virus

Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R₀ = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R_e) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.     

Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration

Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-α from isolated human peripheral blood mononuclear cells with a pIC₅₀ of 11.1. GSK256066 also has a suitable profile for inhaled dosing.