Binding specificity of Bacillus thuringiensis Cry1Aa for purified, native Bombyx mori aminopeptidase N and cadherin-like receptors

BACKGROUND: To better understand the molecular interactions of Bt toxins with non-target insects, we have examined the real-time binding specificity and affinity of Cry1 toxins to native silkworm (Bombyx mori) midgut receptors. Previous studies on B. mori receptors utilized brush border membrane vesicles or purifed receptors in blot-type assays. RESULTS: The Bombyx mori (silkworm) aminopeptidase N (APN) and cadherin-like receptors for Bacillus thuringiensis insecticidal Cry1Aa toxin were purified and their real-time binding affinities for Cry toxins were examined by surface plasmon resonance. Cry1Ab and Cry1Ac toxins did not bind to the immobilized native receptors, correlating with their low toxicities. Cry1Aa displayed moderate affinity for B. mori APN (75 nM), and unusually tight binding to the cadherin-like receptor (2.6 nM), which results from slow dissociation rates. The binding of a hybrid toxin (Aa/Aa/Ac) was identical to Cry1Aa. CONCLUSIONS: These results indicate domain II of Cry1Aa is essential for binding to native B. mori receptors and for toxicity. Moreover, the high-affinity binding of Cry1Aa to native cadherin-like receptor emphasizes the importance of this receptor class for Bt toxin research

Absolute ion hydration enthalpies and the role of volume within hydration thermodynamics

This paper reports that various thermodynamic properties in aqueous media for certain individual ions and for compounds are linear functions of the inverse cube root of the solid respective ionic and compound solid state volumes, V m –1/3 . This is similar to the situation which has been fully exploited in solid state thermodynamics and out of which Volume–Based Thermodynamics, VBT evolved. A short resume of these various VBT applications is provided for the general reader and an improved lattice potential energy equation emerges using the state of the art data presented in this paper

Unique thermodynamic relationships for ΔfHo and ΔfGo for crystalline inorganic salts. I, Predicting the possible existence and synthesis of Na2SO2 and Na2SeO2

The concept that equates oxidation and pressure has been successfully utilized in explaining the structural changes observed in the M2S subnets of M2SOx (x = 3, 4) compounds (M = Na, K) when compared with the structures (room- and high-pressure phases) of their parent M2S 'alloy' [Martinez-Cruz et al. (1994), J. Solid State Chem. 110, 397-398; Vegas (2000), Crystallogr. Rev. 7, 189-286; Vegas et al. (2002), Solid State Sci. 4, 1077-1081]. These structural changes suggest that if M2SO2 would exist, its cation array might well have an anti-CaF2 structure. On the other hand, in an analysis of the existing thermodynamic data for M2S, M2SO3 and M2SO4 we have identified, and report, a series of unique linear relationships between the known Delta H-f(o) and Delta(f)G(o) values of the alkali metal (M) sulfide (x = 0) and their oxyanion salts M2SOx (x = 3 and 4), and the similarly between M2S2 disulfide (x = 0) and disulfur oxyanion salts M2S2Ox (x = 3, 4, 5, 6 and 7) and the number of O atoms in their anions x. These linear relationships appear to be unique to sulfur compounds and their inherent simplicity permits us to interpolate thermochemical data (Delta H-f(o)) for as yet unprepared compounds, M2SO (x = 1) and M2SO2 (x = 2). The excellent linearity indicates the reliability of the interpolated data. Making use of the volume-based thermodynamics, VBT [Jenkins et al. (1999), Inorg. Chem. 38, 3609-3620], the values of the absolute entropies were estimated and from them, the standard Delta S-f(o) values, and then the Delta(f)G(o) values of the salts. A tentative proposal is made for the synthesis of Na2SO2 which involves bubbling SO2 through a solution of sodium in liquid ammonia. For this attractive thermodynamic route, we estimate Delta G(o) to be approximately -500 kJ mol(-1). However, examination of the stability of Na2SO2 raises doubts and Na2SeO2 emerges as a more attractive target material. Its synthesis is likely to be easier and it is stable to disproportionation into Na2S and Na2SeO4. Like Na2SO2, this compound is predicted to have an anti-CaF2 Na2Se subnet

The thermodynamics of uranium salts and their hydrates - Estimating thermodynamic properties for nuclear and other actinoid materials using the Thermodynamic Difference Rule (TDR)

A comprehensive thermodynamic database of experimental standard enthalpy of formation, Δ f H o values, standard free energies of formation, Δ f G o and standard entropies, S o 298 for uranium salts and their hydrates at 298 K and 1 bar pressure is assembled. For many of these materials there exist experimental uncertainties or else multiple values (often considerably different) are listed for the same material. The aim of this paper is to showcase the ability of the Thermodynamic Difference Rule (TDR) to provide quite accurate estimates of such data (usually errors are less than 1%) and to provide guidance as to the most trusted value to adopt. In addition, where possible the TDR has been used to estimate missing literature values. New thermochemical data values are predicted and TDR is not reliant on possession of knowledge of crystal structures

Blocking binding of Bacillus thuringiensis Cry1Aa to Bombyx mori cadherin receptor results in only a minor reduction of toxicity

<p>Abstract</p> <p>Background</p> <p><it>Bacillus thuringiensis </it>Cry1Aa insecticidal protein is the most active known <it>B. thuringiensis </it>toxin against the forest insect pest <it>Lymantria dispar </it>(gypsy moth), unfortunately it is also highly toxic against the non-target insect <it>Bombyx mori </it>(silk worm).</p> <p>Results</p> <p>Surface exposed hydrophobic residues over domains II and III were targeted for site-directed mutagenesis. Substitution of a phenylalanine residue (F328) by alanine reduced binding to the <it>Bombyx mori </it>cadherin by 23-fold, reduced biological activity against <it>B. mori </it>by 4-fold, while retaining activity against <it>Lymantria dispar</it>.</p> <p>Conclusion</p> <p>The results identify a novel receptor-binding epitope and demonstrate that virtual elimination of binding to cadherin BR-175 does not completely remove toxicity in the case of <it>B. mori</it>.</p

Tuberculous meningitis in children: a forgotten public health emergency

Tuberculous meningitis (TBM) remains a major cause of morbidity and mortality in children with tuberculosis (TB), yet there are currently no estimates of the global burden of paediatric TBM. Due to frequent non-specific clinical presentation and limited and inadequate diagnostic tests, children with TBM are often diagnosed late or die undiagnosed. Even when diagnosed and treated, 20% of children with TBM die. Of survivors, the majority have substantial neurological disability with significant negative impact on children and their families. Surveillance data on this devastating form of TB can help to quantify the contribution of TBM to the overall burden, morbidity and mortality of TB in children and the epidemiology of TB more broadly. Paediatric TBM usually occurs shortly after primary infection with Mycobacterium tuberculosis and reflects ongoing TB transmission to children. In this article we explain the public health importance of paediatric TBM, discuss the epidemiology within the context of overall TB control and health system functioning and the limitations of current surveillance strategies. We provide a clear rationale for the benefit of improved surveillance of paediatric TBM using a TB care cascade framework to support monitoring and evaluation of paediatric TB, and TB control more broadly. Considering the public health implications of a diagnosis of TBM in children, we provide recommendations to strengthen paediatric TBM surveillance and outline how improved surveillance can help us identify opportunities for prevention, earlier diagnosis and improved care to minimize the impact of TBM on children globally

Enthalpies of Formation of Gas-Phase N3, N3-, N5+, and N5- from Ab Initio Molecular Orbital Theory, Stability Predictions for N5+N3- and N5+N5-, and Experimental Evidence for the Instability of N5+N3-

Ab initio molecular orbital theory has been used to calculate accurate enthalpies of formation and adiabatic electron affinities or ionization potentials for N3, N3-, N5+, and N5- from total atomization energies. The calculated heats of formation of the gas-phase molecules/ions at 0 K are ΔHf(N3(2Π)) = 109.2, ΔHf(N3-(1∑+)) = 47.4, ΔHf(N5-(1A1‘)) = 62.3, and ΔHf(N5+(1A1)) = 353.3 kcal/mol with an estimated error bar of ±1 kcal/mol. For comparison purposes, the error in the calculated bond energy for N2 is 0.72 kcal/mol. Born−Haber cycle calculations, using estimated lattice energies and the adiabatic ionization potentials of the anions and electron affinities of the cations, enable reliable stability predictions for the hypothetical N5+N3- and N5+N5- salts. The calculations show that neither salt can be stabilized and that both should decompose spontaneously into N3 radicals and N2. This conclusion was experimentally confirmed for the N5+N3- salt by low-temperature metathetical reactions between N5SbF6 and alkali metal azides in different solvents, resulting in violent reactions with spontaneous nitrogen evolution. It is emphasized that one needs to use adiabatic ionization potentials and electron affinities instead of vertical potentials and affinities for salt stability predictions when the formed radicals are not vibrationally stable. This is the case for the N5 radicals where the energy difference between vertical and adiabatic potentials amounts to about 100 kcal/mol per N5

Size Segregation and Convection of Granular Mixtures Almost Completely Packed in the Rotating Thin Box

Size segregation of granular mixtures which are almost completely packed in a rotating drum is discussed with an effective simulation and a brief analysis. Instead of a 3D drum, we simulate 2D rotating thin box which is almost completely packed with granular mixtures. The phase inversion of radially segregated pattern which was found in a 3D experiment are qualitatively reproduced with this simulation, and a brief analysis is followed. Moreover in our simulation, a global convection appears after radial segregation pattern is formed, and this convection induces axially segregated pattern.Comment: 9 pages, 5 figures, PACS number(s): 45.70.-n, 45.70.M

The complete management of extremity vascular injury in a local population: A wartime report from the 332nd Expeditionary Medical Group/Air Force Theater Hospital, Balad Air Base, Iraq

Background: Although the management of vascular injury in coalition forces during Operation Iraqi Freedom has been described, there are no reports on the in-theater treatment of wartime vascular injury in the local population. This study reports the complete management of extremity vascular injury in a local wartime population and illustrates the unique aspects of this cohort and management strategy. Methods: From September 1, 2004, to August 31, 2006, all vascular injuries treated at the Air Force Theater Hospital (AFTH) in Balad, Iraq, were registered. Those in non-coalition troops were identified and retrospectively reviewed. Results: During the study period, 192 major vascular injuries were treated in the local population in the following distribution: extremity 70% (n = 134), neck and great vessel 17% (n = 33), and thoracoabdominal 13% (n = 25). For the extremity cohort, the age range was 4 to 68 years and included 12 pediatric injuries. Autologous vein was the conduit of choice for these vascular reconstructions. A strict wound management strategy providing repeat operative washout and application of the closed negative pressure adjunct was used. Delayed primary closure or secondary coverage with a split-thickness skin graft was required in 57% of extremity wounds. All patients in this cohort remained at the theater hospital through definitive wound healing, with an average length of stay of 15 days (median 11 days). Patients required an average of 3.3 operations (median 3) from the initial injury to definitive wound closure. Major complications in extremity vascular patients, including mortality, were present in 15.7% (n = 21). Surgical wound infection occurred in 3.7% (n = 5), and acute anastomotic disruption in 3% (n = 4). Graft thrombosis occurred in 4.5% (n = 6), and early amputation and mortality rates during the study period were 3.0% (n = 4) and 1.5% (n = 2), respectively. Conclusions: To our knowledge, this study represents the first large report of wartime extremity vascular injury management in a local population. These injuries present unique challenges related to complex wounds that require their complete management to occur in-theater. Vascular reconstruction using vein, combined with a strict wound management strategy, results in successful limb salvage with remarkably low infection, amputation and mortality rates