Improving the Timeliness and Response to an Aerosolizedanthrax Attack in the Metropolitan Washington, D.C. Region

Our research was conducted to improve the timeliness, coordination, and communication during the detection, investigation and decision-making phases of the response to an aerosolized anthrax attack in the metropolitan Washington, DC, area with the goal of reducing casualties. Our research gathered information of the current response protocols through an extensive literature review and interviews with relevant officials and experts in order to identify potential problems that may exist in various steps of the detection, investigation, and response. Interviewing officials from private and government sector agencies allowed the development of a set of models of interactions and a communication network to identify discrepancies and redundancies that would elongate the delay time in initiating a public health response. In addition, we created a computer simulation designed to model an aerosol spread using weather patterns and population density to identify an estimated population of infected individuals within a target region depending on the virulence and dimensions of the weaponized spores. We developed conceptual models in order to design recommendations that would be presented to our collaborating contacts and agencies that would use such policy and analysis interventions to improve upon the overall response to an aerosolized anthrax attack, primarily through changes to emergency protocol functions and suggestions of technological detection and monitoring response to an aerosolized anthrax attack.

Low temperature X-ray structures of two crystalline forms (I) and (II) of the pyrimidine derivative and sodium channel blocker BW1003C87: 5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine

The X-ray crystal structures of two crystalline forms of 5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine, C10H7Cl3N4 (code name BW1003C87) (I) and (II), have been carried out at liquid nitrogen temperature. A detailed comparison of the two structures is given. Both are centrosymmetric, with structure (I) in the triclinic space group P (1) over bar unit cell a = 6.4870(10), b = 9.216(2), c = 12.016(2) angstrom, alpha = 75.78(3)degrees, beta = 89.95(3)degrees, gamma = 83.45(3)degrees, V = 691.5(2) angstrom(3), Z = 2 and density (calculated) = 1.544 Mg/m(3); and (II) in the monoclinic space group P2(1)/c, unit cell a = 12.000(2), b = 7.518(2), c = 13.450(3) angstrom, beta = 97.87(3)degrees, V = 1202.0(5) angstrom(3), Z = 4, Density (calculated) = 1.600 Mg/m(3). Structure (I) includes a solvated CH3OH in the lattice. Final R indices [I > 2sigma(I)] are R1 = 0.0427, wR2 = 0.1075 for (I) and R1 = 0.0487, wR2 = 0.1222 for (II). R indices (all data) are R1 = 0.0470, wR2 = 0.1118 for (I) and R1 = 0.0623, wR2 = 0.1299 for (II). 5-Phenyl-2,4 diaminopyrimidine and 6-phenyl-1,2,4 triazine derivatives, which include lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine), have been investigated for some time for their effects on the central nervous system. Both lamotrigine and 5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine (code name BW1003C87), the subject of the present study, are anticonvulsant as well as neuroprotective in models of brain ischaemia and in a model of white matter ischaemia. BW1003C87 is a sodium channel blocker which also reduces the release of the neurotransmitter glutamate. The three dimensional structures reported here form part of a newly developed data base for the detailed investigation of members of this drug family and their biological activities.

Transcriptome analysis of sulfate deficiency response in marine microalga Emiliania huxleyi

Summary The response to sulfate deficiency of plants and freshwater green algae has been extensively analysed by system biology approaches. By contrast, seawater sulfate concentration is high and very little is known about the sulfur metabolism of marine organisms. Here, we used a combination of metabolite analysis and transcriptomics to analyse the response of the marine microalga Emiliania huxleyi as it acclimated to sulfate limitation. Lowering sulfate availability in artificial seawater from 25 to 5 mM resulted in significant reduction in growth and intracellular concentrations of dimethylsulfoniopropionate and glutathione. Sulfate-limited E. huxleyi cells showed increased sulfate uptake but sulfate reduction to sulfite did not seem to be regulated. Sulfate limitation in E. huxleyi affected expression of 1718 genes. The vast majority of these genes were upregulated, including genes involved in carbohydrate and lipid metabolism, and genes involved in the general stress response. The acclimation response of E. huxleyi to sulfate deficiency shows several similarities to the well-described responses of Arabidopsis and Chlamydomonas, but also has many unique features. This dataset shows that even though E. huxleyi is adapted to constitutively high sulfate concentration, it retains the ability to re-program its gene expression in response to reduced sulfate availability.

CYSTATIN RELATED EPIDIDYMAL SPERMATOGENIC PROTEIN RESIDES IN THE OUTER DENSE FIBRES AND LIKELY TRANSIENTLY ASSOCIATES WITH THE SURFACE OF EPIDIDYMAL MOUSE SPERMATOZOA

Cystatin Related Epididymal Spermatogenic protein (CRES) is expressed in both the testis and epididymis and found associated with spermatozoa. It appears as non-glycosylated (14 and 12 kDa) and glycosylated isoforms (19 and 17 kDa). The role of CRES is enigmatic and dependent on localization of its isoforms, which is the objective of this study. The initial approach was to investigate testicular and epididymal origins of these isoforms by immunohistochemistry and immunogold cytochemistry. To further pinpoint CRES localization we then selectively extracted and fractionated epididymal spermatozoa in order to find by immunoblotting which sperm fractions contained CRES isoforms. Immunohistochemical analysis of mouse spermatogenesis showed that CRES was expressed in the tail cytoplasm of elongating spermatids from step 9-16, with a pattern reminiscent of outer dense fibre (ODF) proteins. Ultrastructural immunocytochemistry revealed that the immunogold label was concentrated over growing ODFs and mitochondrial sheath in the testes which persisted in spermatozoa through the epididymis. Sequential extractions of isolated sperm tails with Triton X-100-dithiothreitol (DTT) to remove the mitochondrial sheath, whose extract contained an unrelated 66 kDa immunoreactive band, followed by either sodium dodecyl sulfate (SDS)-DTT or urea-DTT to solubilise accessory fibres of the tail revealed a 14 kDa immunoreactive band associated with the ODF. In addition, Western blots revealed glycosylated and non-glycosylated CRES isoforms in nonyl phenoxylpolyethoxylethanol (NP40) extracts of the caput, but not cauda, sperm. Immunohistochemical analysis of the caput and cauda epithelium showed that CRES is secreted by the Golgi apparatus of the ii initial segment, fills the proximal caput lumen, and disappears by mid caput. Western blots of caput and cauda tissue and luminal fluid revealed 14 and 19 kDa immunoreactive bands in caput tissues and luminal fluid, but not in the cauda. This study concludes that there are two origins of CRES, one arising in the testis and the other in the epididymis. Testicular CRES is ionically and covalently associated with the ODF while epididymal CRES is detergent soluble and is most likely associated temporarily with the surface of caput epididymal sperm.