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The polypeptide fold of NAP and the arrangement of the cofactors is related to that of Escherichia coli formate dehydrogenase (FDH) and distantly resembles dimethylsulphoxide reductase. The close structural homology of NAP and FDH shows how small changes in the vicinity of the molybdenum catalytic site are sufficient for the substrate specificity.

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Bloodsucking parasites such as ticks have evolved a wide variety of immunomodulatory proteins that are secreted in their saliva, allowing them to feed for long periods of time without being detected by the host immune system. One possible strategy used by ticks to evade the host immune response is to produce proteins that selectively bind and neutralize the chemokines that normally recruit cells of the innate immune system that protect the host from parasites. We have identified distinct cDNAs encoding novel chemokine binding proteins (CHPBs), which we have termed Evasins, using an expression cloning approach. These CHBPs have unusually stringent chemokine selectivity, differentiating them from broader spectrum viral CHBPs. Evasin-1 binds to CCL3, CCL4, and CCL18; Evasin-3 binds to CXCL8 and CXCL1; and Evasin-4 binds to CCL5 and CCL11. We report the characterization of Evasin-1 and -3, which are unrelated in primary sequence and tertiary structure, and reveal novel folds. Administration of recombinant Evasin-1 and -3 in animal models of disease demonstrates that they have potent antiinflammatory properties. These novel CHBPs designed by nature are even smaller than the recently described single-domain antibodies (Hollinger, P., and P.J. Hudson. 2005. Nat. Biotechnol. 23:1126–1136), and may be therapeutically useful as novel antiinflammatory agents in the future.

An intense laser pulse in a plasma can accelerate electrons [1][2][3][4] to GeV energies in centimetres [5][6][7] . Transverse betatron motion 8,9 in the plasma wake results in X-ray photons with an energy that depends on the electron energy, oscillation amplitude and frequency of the betatron motion [10][11][12] . Betatron X-rays from laser-accelerator electrons have hitherto been limited to spectra peaking between 1 and 10 keV (ref. 13). Here we show that the betatron amplitude is resonantly enhanced when electrons interact with the rear of the laser pulse 14,15 . At high electron energy, resonance occurs when the laser frequency is a harmonic of the betatron frequency, leading to a significant increase in the photon energy. 10 X-ray pulses from synchrotron sources have become immensely useful tools for investigating the structure of matter 17 , which has led to a huge international effort to construct light sources for many different scientific and technological applications. Synchrotrons are usually based on radio-frequency (RF) accelerating cavities that are limited to fields of 10-100 MV m −1 because of electrical breakdown, which results in very large and expensive devices.High-power lasers, on the other hand, have led to the development of many new areas of science, as diverse as inertial confinement fusion and laboratory astrophysics to the study of warm dense matter. However, they now have the potential to transform accelerator and light source technology. In the late 1970s, Tajima and Dawson 1 proposed harnessing the ponderomotive force associated with intense laser fields to excite plasma waves and form wake-like structures 18 (as behind a boat) that travel with a velocity close to the speed of light, c. The electrostatic forces of these charge density structures can rapidly accelerate particles to very high energies 6 ; where momentum is gained analogous to a surfer riding an ocean wave. Recent progress in the development of laser wakefield accelerators (LWFAs) has enabled electron beams to be accelerated with unprecedented acceleration gradients 2-4 , three orders of magnitude higher than in RF cavities, thus reducing a 100 m long GeV accelerator to centimetres in length 6 . The LWFA can now produce high-quality electron beams with low emittance, ε n , of the order 1π mm mrad 19 , small energy spread 20 , δγ /γ 1%, where γ is the Lorenz factor, and high charge 4 , Q = 10-100 pC. At high laser intensities, in the so-called blowout regime 21 , the LWFA structure has an approximately spherical bubble shape with a radius of R ≈ 2 √ a 0 c/ω p , which is primarily determined by the normalized laser vector potential, a 0 = eA/m e c 2 and the plasma frequency, ω p = √ 4π n p e 2 /m e , where n p is the plasma density, e, the electron charge and m e , the electron mass 22 . The plasma wave is efficiently driven when the laser pulse duration is approximately a plasma period. Micrometre-long electron bunches that extend only a fraction of the plasma wavelength, λ p = 2πc/ω p , are self-injected and accelerate...

Sudan virus (genus ebolavirus) is lethal, yet no monoclonal antibody is known to neutralize it. Here we describe antibody 16F6 that neutralizes Sudan virus and present its structure bound to the trimeric viral glycoprotein. Unexpectedly, the 16F6 epitope overlaps that of KZ52, the only other antibody against the GP1,2 core to be visualized. Further, both antibodies against this key GP1–GP2-bridging epitope neutralize at a post-internalization step, likely fusion.

Mutational signatures are patterns of mutations that arise during tumorigenesis. We present an enhanced, practical framework for mutational signature analyses. Applying these methods on 3,107 whole genome sequenced (WGS) primary cancers of 21 organs reveals known signatures and nine previously undescribed rearrangement signatures. We highlight inter-organ variability of

and Venezuela have the domestic, peridomicile and sylvatic cycles, with high prevalence of human infection and prevalence of chronic Chagas' cardiomyopathy (CCC).Group II -Colombia, Costa Rica and Mexico, characterized by domestic and peridomicile cycles with presence of CCC.Group III -El Salvador, Guatemala, Nicaragua and Panama have domestic, peridomicile and sylvatic cycles with poor clinical information. AbstractMuch has been achieved in one century after Carlos Chagas' discovery. However, there is surely much to be done in the next decades. At present, we are witnessing many remarkable efforts to monitor the epidemiology of the disease, to better understand the biology of the T. cruzi and its interaction with human beings as well as the pathogenesis and pathophysiology of the complications in the chronic phase, and deal more appropriately and effectively with late cardiac and digestive manifestations.