A New Cell-Based AI-2-Mediated Quorum Sensing Interference Assay in Screening of LsrK-Targeted Inhibitors

Quorum sensing (QS), a bacterial communication strategy, has been recognized as one of the control mechanisms of virulence in bacteria. Thus, targeting QS offers an interesting opportunity to impair bacterial pathogenicity and develop antivirulence agents. Aiming to enhance the discovery of QS inhibitors, we developed a bioreporter Escherichia coli JW5505 pET-Plsrlux and set up a cell-based assay for identifying inhibitors of autoinducer-2 (AI-2)-mediated QS. A comparative study on the performance of target- versus cell-based assays was performed, and 91 compounds selected with the potential to target the ATP binding pocket of LsrK, a key enzyme in AI-2 processing, were tested in an LsrK inhibition assay, providing 36 hits. The same set of compounds was tested by the AI-2-mediated QS interference assay, resulting in 24 active compounds. Among those, six were also found to be active against LsrK, whereas 18 might target other components of the pathway. Thus, this AI-2-mediated QS interference cell-based assay is an effective tool for complementing target-based assays, yet also stands as an independent assay for primary screening.     

Topological Interlocking and Geometric Stiffening as Complementary Strategies for Strong Plant Shells

Many organisms encapsulate their embryos in hard, protective shells. While birds and reptiles largely rely on mineralized shells, plants often develop highly robust lignocellulosic shells. Despite the abundance of hard plant shells, particularly nutshells, it remains unclear which fundamental properties drive their mechanical stability. This multiscale analysis of six prominent (nut)shells (pine, pistachio, walnut, pecan, hazelnut, and macadamia) reveals geometric and structural strengthening mechanisms on the cellular and macroscopic length scales. The strongest tissues, found in walnut and pistachio, exploit the topological interlocking of 3D-puzzle cells and thereby outperform the fiber-reinforced structure of macadamia under tensile and compressive loading. On the macroscopic scale, strengthening occurs via an increased shell thickness, spherical shape, small size, and a lack of extended sutures. These functional interrelations suggest that simple geometric modifications are a powerful and resource-efficient strategy for plants to enhance the fracture resistance of entire shells and their tissues. Understanding the interplay between structure, geometry, and mechanics in hard plant shells provides new perspectives on the evolutionary diversification of hard seed coats, as well as insights for nutshell-based material applications.     

Properties of Wave Propagation in a Gel-type Belousov–Zhabothinsky Reaction under Micro-gravity

The Belousov–Zhabothinsky (BZ) reaction is a chemical reaction which exhibits spatial as well as temporal pattern formation. Being an excitable medium, it can be influenced by even small external forces. One of these small forces which under ground conditions permanently is given is gravity. The gravity dependence of the BZ-reaction has been investigated in some detail up to now, and it has been found that especially the propagation velocity of waves in thin layers of fluid BZ-medium depends significantly on gravity-amplitude and -orientation. This finding has been mainly assigned to an interaction of gravity with diffusion and convection in the medium at the wave front, and consequently it has been stated that the propagation of waves in gels of BZ-medium is not significantly gravity dependent. We have now done more detailed experiments and have been able to show that also in gels the propagation velocity of BZ-waves is altered by gravity, but less than in fluid systems. Experiments have been performed in a lab centrifuge, a sounding rocket experiment and a parabolic flight mission.     

Fast growing IB-IIB cancer of the uterine cervix. Apropos of 20 cases

Twenty cases of fast growing cancer of the uterine cervix (14 IB, three IIA, three IIB FIGO), the definition of which is specified, have been reviewed and compared to a cohort of 160 cases not having this feature, to assess their outcomes. In regard to fast growing carcinomas, the median age was 41 (25-50) years and the median follow-up 22 months (8-213) as compared to 54 years (27-79) and 80 months (5-199) for the reference cohort. The comparison of the two cohorts shows only a difference of breakdown which concerns the pelvic lymph nodes status (P < 0.05, chi 2). Thirteen deaths are reported in the fast growing series instead of 54 in the other series. The 5-year overall survival is respectively 34% (13-55) versus 74% (68-82), the loco-regional free survival 58% (33-84) versus 85% (79-81) (P < 0.001), the 5-year metastasis free survival 61% (38-84) versus 84% (78-90) (P = 0.004). This particular form needs a multidisciplinary approach, and the local regional treatment has to be intensified.     

Clock feedthrough compensation with phase slope control in SCcircuits

A clock feedthrough compensation technique for SC circuits is presented. The principle is based on the control of the switch turn-off slope. A single control block can drive a large number of identical SC structures, thus minimising area overhead. Experimental results from an integrated prototype show that the injected charge is reduced by a factor as high as 13     

Natural killer cell receptors specific for MHC class I molecules

The aim of this study was to describe serum GH, IGF-I, and IGF binding protein (BP) 3 levels at birth and during the first 2 y of life in intrauterine growth-retarded (IUGR) children and to correlate these hormonal values with auxologic parameters noted during this period to investigate their predictive value on the postnatal growth pattern. Three hundred and seventeen children were included at birth and studied for auxologic and biologic parameters at birth, 3 and 30 d, and 3, 6, 12, 18, and 24 mo of age. At birth, when analyzed according to gestational age, serum GH levels were increased (p = 0.0001) and serum IGF-I and IGFBP3 levels were decreased (p = 0.0001) in IUGR as compared with normal neonates. When two cohorts were established at birth as a function of the ponderal index (PI) (< or = or > 3rd percentile), serum IGF-I and IGFBP3 levels were found to be significantly reduced in the case of low PI. All parameters were within normal limits at 1 mo of age and remained normal thereafter. During the first 3 mo of life, a positive correlation was found between IGF-I increment and weight gain (r = 0.28, p = 0.002). None of the biologic parameters at birth were predictive either of later growth or of short stature at 2 y of age. In conclusion, low serum IGF-I and IGFBP3 levels at birth were related to fetal malnutrition and were not predictive parameters for later growth.     

Reduction by indobufen of neutrophil activation in peripheral arterial occlusive disease

We evaluated the effectiveness of indobufen administration in reducing neutrophil activation in a clinical model of ischemia-reperfusion. Thirty stable patients with intermittent claudication due to occlusive peripheral arterial disease of the leg were randomly assigned to two groups. Patients in group I were treated with indobufen [200 mg orally twice daily (p.o. b.i.d.) for a week]; patients in group II received a placebo. Both groups of patients were submitted to standardized treadmill exercise until onset of claudication. Plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha(6-k-PGF1alpha) neutrophil filterability, and neutrophil activation (by nitro-blue tetrazolium test) were assessed in blood samples from the femoral vein draining the ischemic leg. The values were obtained at rest and 5, 30, and 60 min after onset of claudication. Urinary albumin excretion was measured at rest and 1 h after onset of claudication. Plasma levels of TxB2 and 6-k-PGF1alpha increased significantly in the placebo group 5 min after onset of claudication, whereas only a slight nonsignificant increase was observed in the indobufen-treated group at the same timepoint.     

Banana: cultivars,biotechnological approaches and genetic transformation

Genetic modification of banana has been considered as a path towards increasing the value of this crop according to health and nutrition in developing countries. Banana as a crop is one of the most important and widely consumed fruits as a weaning food by children and as a starchy staple for all other consumers. As well as providing a low cost and easily produced source of energy, bananas are also rich in certain minerals and in vitamins A, C and B6. Growing urbanisation in many developing countries upgraded the crop importance as a source of revenue, occasionally providing the main source of income for rural communities. Genetically modified organism bananas have been advocated as carrier for vaccines and as a source of carotenoids that can counteract debilitating vitamin A deficiency. The rather high vulnerability of banana to pests and diseases triggered biotechnological applications in an attempt to produce new, more resistant banana cultivars. However, the potential biosafety of genetically modified banana and its applications should be taken into account prior to its extensive usage. The current survey summarises the most important biotechnological techniques (in vitro culture, DNA fingerprinting, somatic emrbyogenesis, DNA flow cytometry, etc.) and applications (micropropagation, in vitro selection, somaclonal variation, protoplast fusion, haploid production, etc.) in banana and emphasises on genetic transformation in conjunction with the expressed gene and modified trait aiming at a further improvement of this crop.     

Are autostereograms useful for computer graphics and scientific visualization

Autostereograms are images that can be observed as “flat” 2D pictures or as a display of 3D objects without any extra apparatus. More than one million copies of books on this subject have been sold recently, but are autostereograms useful for computer graphics and scientific visualization? This short note provides some assistance for easily designing still and animated autostereograms, and tries to encourage reader involvement in finding new scientific applications.     

Flexibility plot of proteins

The flexibility plot of a protein lies on the observation thatamino acid residues with the highest turn potential, i.e. locatedin highly mobile regions of protein surface, also possess thesmallest volumes as well as the lowest hydrophobicities. Theplot is generated by shifting a five residue window along theprotein sequence and calculating the value of the hydrophobicity–volumeproduct for consecutive quintuplets of amino acid residues.The concomitant occurrence of small volumes and low hydrophobicitiesresults in very deep minima. A threshold value has also beenintroduced in order to discriminate significant minima. To substantiatethe interpretation that the selected minima actually indicatevery flexible segments of a protein (loops, turns, etc.), wehave compared plots obtained for model proteins (lysozyme, myoglobin,ribonuclease, trypsin, thermolysin and T4 lysozyme) with X-raythermal factors profiles available for the same proteins. Whencompared to thermal profiles, the majority of flexible segmentsevidenced by our plots have been found to be in agreement withregions characterized by high thermal factors. Results havealso been discussed in the light of local organization possessedby examined proteins.