The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Microbial infectious diseases continue to be one of the leading causes of morbidity and mortality. It has been estimated that microbial species comprise about 60% of the Earth's biomass. This, together with the fact that their genetic, metabolic and physiological diversity is extraordinary, makes them a major threat to the health and development of populations across the world. Widespread antibiotic resistance, the emergence of new pathogens in addition to the resurgence of old ones, and the lack of effective new therapeutics exacerbate the problems. Thus, the need to discover and develop new antimicrobial agents is critical to improve mankind's future health. Plant secondary metabolites (PSMs) offer particular promise in this sense. Plant Kingdom could be considered a rich source of the most diverse structures (e.g. there are more than 12,000 known alkaloids, more than 8,000 phenolic compounds and over 25,000 different terpenoids), many of which were proven to possess strong antimicrobial properties (e.g. thymol, eurabienol, etc.). In many instances, PSMs can be easily isolated from the plant matrix, either in pure state or in the form of mixtures of chemically related compounds. What is also important is that the development of bacterial resistance toward natural plant products (that are generally regarded as eco-friendly) has been thus far documented in a very limited number of cases (e.g. for reserpine). Having all of the mentioned advantages of PSMs as potential antimicrobials in mind, a major question arises: why is it that there are still no commercially available or commonly used antibiotics of plant origin? This review tries to give a critical answer to this question by considering potential mechanisms of antimicrobial action of PSMs (inhibition of cell wall or protein synthesis, inducing leakage from the cells by tampering with the function of the membranes, interfering with intermediary metabolisms or DNA/RNA synthesis/function), as well as their physical and chemical properties (e.g. hydrophilicity/lipophilicity, chemical stability). To address the possible synergistic/antagonistic effects between PSMs and with standard antibiotics, special attention has been given to the antimicrobial activity of PSM-mixtures (e.g. essential oils, plant extracts). Moreover, possible ways of overcoming some of PSMs molecular limitations in respect to their usage as potential antibiotics were also discussed (e.g. derivatization that would enable fine tuning of certain molecular characteristics).
The transient nanoscale dynamics of materials on femtosecond to picosecond timescales is of great interest in the study of condensed phase dynamics such as crack formation, phase separation and nucleation, and rapid fluctuations in the liquid state or in biologically relevant environments. The ability to take images in a single shot is the key to studying non-repetitive behaviour mechanisms, a capability that is of great importance in many of these problems. Using coherent diffraction imaging with femtosecond X-ray free-electron-laser pulses we capture time-series snapshots of a solid as it evolves on the ultrafast timescale. Artificial structures imprinted on a Si 3 N 4 window are excited with an optical laser and undergo laser ablation, which is imaged with a spatial resolution of 50 nm and a temporal resolution of 10 ps. By using the shortest available free-electronlaser wavelengths 1 and proven synchronization methods 2 this technique could be extended to spatial resolutions of a few nanometres and temporal resolutions of a few tens of femtoseconds. This experiment opens the door to a new regime of time-resolved experiments in mesoscopic dynamics.To date, optical pulses have made it possible to resolve dynamics on the femtosecond timescale, but the spatial resolution of these studies has been limited to a few micrometres 3 . On the other hand, femtosecond X-ray pulses have been used to detect Å ngstrom-scale atomic motions in extended crystalline materials with long-range order through time-resolved diffraction experiments 4,5 . An entirely different methodology is needed to investigate the ultrafast dynamics of non-crystalline materials at nanometre length scales. Applications at these scales can be found in the study of fracture dynamics, shock formation, spallation, ablation, and plasma formation under extreme conditions. In the solid state it is desirable to directly image dynamic processes such as nucleation and phase growth, phase fluctuations and various forms of electronic or magnetic segregation.Electron microscopes can provide nanometre to atomic resolution, and have recently been demonstrated with ultrafast pulses 6 . However, they have limited penetrating power and struggle to obtain high-quality single-shot images due to space-charge issues 7 . Synchrotron beams from third-generation sources have comparatively long pulse lengths of 10-100 ps, as determined by the shortest electron bunch length possible in a given storage ring. Synchrotron sources can produce short-pulse ($100 fs) X-rays when operated as femtosecond slicing sources 8 , but produce comparatively weak X-ray beams of 1 Â 10 7 photons per second. Along with X-ray pulses from femtosecond laser plasma sources 9,10 and high-harmonic-generation sources 11 this limits their use to non-destructive phenomena where weak signals can be accumulated over many repeatable excitations of the sample.The intense femtosecond X-ray pulses from free-electron-laser (FEL) sources provide the penetrating power, spatial resolution and single-shot imaging c...
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