Chk1 dynamics in G2 phase upon replication stress predict daughter cell outcome

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Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity^1-5. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions.Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures^1,6,7. We developed a new model¹ which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (K_d) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections.     

The Structure of Detoxin D1

The structure of detoxin D₁, one of the main active principles of detoxio complex, has been established on the basis of the degradative studies and spectral evidences as depicted in formula (I).

Detoxin D₁ has been demonstrated to belong to a new class of the depsipeptide contained an amino acid designated detoxinine which was newly isolated as a natural product.     

Isolation and Identification of the Female Sex Pheromone of the Potato Tuberworm Moth,Phthorimaea operculella (Zeller)

The sex pheromone produced by adult females of the potato tuberworm moth was isolated from unmated female moths reared in the laboratory. The gas Chromatographic and mass spectrometric data suggested the pheromone to be a tridecatrienyl acetate. The isolated pheromone was subjected to partial hydrogenation with hydrazine and hydrogen peroxide and subsequent ozonolysis to produce a mixture of ω-acetoxy-alkanals. They were identified by mass Chromatographic technique as 4-acetoxy-butanal, 7-acetoxy-heptanal, and 10-acetoxy-decanal respectively. Consequently, the pheromone was identified as 4,7,10-tridecatrienyl acetate except the geometric configuration.     

A comparison of mechanisms of desiccation tolerance among three angiosperm resurrection plant species

The mechanisms of protection against mechanical and oxidative stress were identified and compared in the angiosperm resurrection plants Craterostigma wilmsii, Myrothamnus flabellifolius and Xerophyta humilis. Drying-induced ultrastructural changes within mesophyll cells were followed to gain an understanding of the mechanisms of mechanical stabilisation. In all three species, water filled vacuoles present in hydrated cells were replaced by several smaller vacuoles filled with non-aqueous substances. In X. humilis, these occupied a large proportion of the cytoplasm, preventing plasmalemma withdrawal and cell wall collapse. In C. wilmsii, vacuoles were small but extensive cell wall folding occurred to prevent plasmalemma withdrawal. In M. flabellifolius, some degree of vacuolation and wall folding occurred, but neither were sufficient to prevent plasmalemma withdrawal. This membrane was not ruptured, possibly due to membrane repair at plasmodesmata junctions where tearing might have occurred. In addition, the extra-cytoplasmic compartment appeared to contain material (possibly similar to that in vacuoles) which could facilitate stabilisation of dry cells.Photosynthesis and respiration are particularly susceptible to oxidative stress during drying. Photosynthesis ceased at high water contents and it is proposed that a controlled shut down of this metabolism occurred in order to minimise the potential for photo-oxidation. The mechanisms whereby this was achieved varied among the species. In X. humilis, chlorophyll was degraded and thylakoid membranes dismantled during drying. In both C. wilmsii and M. flabellifolius, chlorophyll was retained, but photosynthesis was stopped due to chlorophyll shading from leaf folding and anthocyanin accumulation. Furthermore, in M. flabellifolius thylakoid membranes became unstacked during drying. All species continued respiration during drying to 10% relative water content, which is proposed to be necessary for energy to establish protection mechanisms. Activity of antioxidant enzymes increased during drying and remained high at low water contents in all species, ameliorating free radical damage from both photosynthesis and respiration. The nature and extent of antioxidant upregulation varied among the species. In C. wilmsii, only ascorbate peroxidise activity increased, but in M. flabellifolius and X. humilis ascorbate peroxidise, glutathione reductase and superoxide dismutase activity increased, to various extents, during drying. Anthocyanins accumulated in all species but this was more extensive in the homoiochlorophyllous types, possibly for protection against photo-oxidation.     

Isolation of a heat-stable maize endosperm ADP-glucose pyrophosphorylase variant

Heat stress reduces maize yield and several lines of evidence suggest that the heat lability of maize endosperm ADP-glucose pyrophosphorylase (AGPase) contributes to this yield loss. AGPase catalyzes a rate-limiting step in starch synthesis. Herein, we present a novel maize endosperm AGPase small subunit variant, termed BT2-TI that harbors a single amino acid change of residue 462 from threonine to isoleucine. The mutant was isolated by random mutagenesis and heterologous expression in a bacterial system. BT2-TI exhibits enhanced heat stability compared to wildtype maize endosperm AGPase.The TI mutation was placed into another heat-stable small subunit variant, MP. MP is composed of sequences from the maize endosperm and the potato tuber small subunit. The MP-TI small subunit variant exhibited greater heat stability than did MP. Characterization of heat stability as well as kinetic and allosteric properties suggests that MP-TI may lead to increased starch yield when expressed in monocot endosperms.     

Effect of different larval rearing temperatures on the productivity (Ro) and morphology of the malaria vector Anopheles superpictus Grassi (Diptera: Culicidae) using geometric morphometrics

Temperature affects both the biology and morphology of mosquito vectors. Geometric morphometrics is a useful new tool for capturing and analyzing differences in shape and size in many morphological parameters, including wings. We have used this technique for capturing the differences in the wings of the malaria vector Anopheles superpictus, using cohorts reared at six different constant temperatures (15°, 20°, 25°, 27°, 30°, and 35° C) and also searched for potential correlations with the life tables of the species. We studied wing shape in both male and female adults, using 22 landmarks on the wing in relation to ecological parameters, including the development rate. The ecological zero was calculated as 9.93° C and the thermal constant as 296.34 day‐degrees. The rearing temperature affects egg, larval, and pupal development and also the total time from egg to adult. As rearing temperatures increased, longevity decreased in both sexes. In An. superpictus, R_o value and productivity correlated with the statistically significant gradual deformations in the wing shape related to size in both sexes. These deformations directly linked to differences in immature rearing temperatures. Analysis using PCA and UPGMA phenograms showed that although wings of females became narrower dorsoventrally as the temperature increased, they became broader in males. Comparisons of the wing landmarks indicated the medial part of the wing was most affected by larval rearing temperatures, showing relatively more deformations. Algorithmic values of the life tables were determined in correlation with the results of geometric morphometrics. Comparisons of centroid sizes in the cohorts showed that overall wing size became smaller in both sexes in response to higher rearing temperatures.