Synthesis, structure, and antimycobacterial activity of 6-[1(3H)-isobenzofuranylidenemethyl]purines and analogs

6-Benzofuryl-, styryl, benzyl, and furfurylpurines as well as 6-[1(3H)-isobenzofuranylidenemethyl]purines have been synthesized and their activities against Mycobacterium tuberculosis (Mtb) determined. Several compounds displayed profound antimycobacterial activity in combination with low toxicity towards mammalian cells. NMR and X-ray crystallography were employed to determine the detailed structures and the results were supported by quantum chemical calculations.     

From climate change to population change: the need to consider annual life cycles

Detailed studies of organisms' life cycles are important for understanding population response to climate change. However, in general one cannot make strong inference about the overall population response from such studies, unless the full annual cycle of the species in question is covered. Here, we present a theoretical framework for the understanding of population response to climate change. Owing to the combined effects of demography, intraspecific feedback, and a possible use of environmental cues, environmentally induced changes in survival and/or reproduction do not necessarily lead to a straightforward change in population size. This framework can guide our thinking about how abiotic conditions work their way to the population level. More specifically, it can help us to identify mechanisms that need to be examined when predicting population change in response to expected climate change.     

Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts

In migrating fibroblasts, rearward movement of the nucleus orients the centrosome toward the leading edge. Nuclear movement results from coupling rearward-moving, dorsal actin cables to the nucleus by linear arrays of nesprin-2G and SUN2, termed transmembrane actin-associated nuclear (TAN) lines. A-type lamins anchor TAN lines, prompting us to test whether emerin, a nuclear membrane protein that interacts with lamins and TAN line proteins, contributes to nuclear movement. In fibroblasts depleted of emerin, nuclei moved nondirectionally or completely failed to move. Consistent with these nuclear movement defects, dorsal actin cable flow was nondirectional in cells lacking emerin. TAN lines formed normally in cells lacking emerin and were coordinated with the erratic nuclear movements, although in 20% of the cases, TAN lines slipped over immobile nuclei. Myosin II drives actin flow, and depletion of myosin IIB, but not myosin IIA, showed similar nondirectional nuclear movement and actin flow as in emerin-depleted cells. Myosin IIB specifically coimmunoprecipitated with emerin, and emerin depletion prevented myosin IIB localization near nuclei. These results show that emerin functions with myosin IIB to polarize actin flow and nuclear movement in fibroblasts, suggesting a novel function for the nuclear envelope in organizing directional actin flow and cytoplasmic polarity.     

Weed performance in crop rotations with and without leys and at different nitrogen levels

Weed populations were studied from a 26-year-old field experiment in southern Sweden with three different 6-year crop rotations, each with four rates of nitrogen application. The rotations differed in that one had a two-year legume-grass ley, another had a two-year grass ley, and that the third had spring wheat followed by a repeatedly harrowed fallow. The leys and the fallow were followed by turnip rape, winter wheat, oats and barley which was undersown in the two ley rotations. Data on weed biomass, collected in one season, were subjected to multivariate analysis.
Winter turnip rape had the highest weed biomass. However, of the several weed species, only Matricaria perforata Merat was important in wheat (the crop following turnip rape in the rotation). The weed flora did not differ consistently between rotations. We conclude that none of the three rotations had developed any major weed problems under the past weed management regime (herbicides applied to cereal crops).
There was no consistent effect of nitrogen fertilisation on total weed biomass in any of the three rotations. However, when comparing the weed floras in winter wheat, turnip rape and oats, the unfertilised plots differed from the plots receiving nitrogen. In the two latter crops, the abundant, low-growing annual Stellaria media (L.) Vil. performed best in fertilised plots with dense stands. Equisetum arvense L., the most abundant perennial weed, was important only in unfertilised plots.     

Activated Galpha subunits can inhibit multiple signal transduction pathways during Dictyostelium development.

Mutations impairing the GTPase activity of G protein Galpha subunits can result in activated Galpha subunits that affect signal transduction and cellular responses and, in some cases, promote tumor formation. An analogous mutation in the Dictyostelium Galpha4 subunit gene (Q200L substitution) was constructed and found to inhibit Galpha4-mediated responses to folic acid, including the accumulation of cyclic nucleotides and chemotactic cell movement. The Galpha4-Q200L subunit also severely inhibited responses to cAMP, including cyclic nucleotide accumulation, cAMP chemotaxis, and cellular aggregation. An analogous mutation in the Galpha2 subunit (Q208L substitution), previously reported to inhibit cAMP responses (K. Okaichi et al., 1992, Mol. Biol. Cell 3, 735-747), was also found to partially inhibit folic acid chemotaxis. Chemotactic responses to folic acid and cAMP and developmental aggregation were also inhibited by a mutant Galpha5 subunit with the analogous alteration (Q199L substitution). All aggregation-defective Galpha mutants were capable of multicellular development after a temporary incubation at 4 degrees C and this development was found to be dependent on wild-type Galpha4 function. This study indicates that mutant Galpha subunits can inhibit signal transduction pathways mediated by other Galpha subunits.     

UV effects on stoichiometry and PUFAs of Selenastrum capricornutum and their consequences for the grazer Daphnia magna

1. The effect of ultraviolet (UV) radiation (280–400 nm) on fatty acid composition and elemental ratios of carbon (C), nitrogen (N) and phosphorus (P) of a unialgal culture of the chlorophyte Selenastrum capricornutum was investigated. Algae were cultured in the presence or absence of UV radiation and were subsequently fed to Daphnia magna to assess potential effects of UV on zooplankton fatty acid composition, growth and reproduction. 2. Algal growth rate was substantially reduced by UV radiation, probably because of a severe inhibition of photosynthetic efficiency (measured as optimal quantum yield). 3. Algae exposed to UV radiation had a significantly reduced content of 18 : 1 n‐9, while C18 polyunsaturated fatty acids (PUFAs) were higher under UV radiation. These observations point at an increased demand for and synthesis of PUFAs under UV stress. 4. The C : P and N : P ratios showed a remarkable decrease in UV‐exposed cells primarily owing to an increased uptake of P. The nutritional quality in terms of both fatty acid composition and stoichiometry was therefore higher in the UV treatment relative to the control. 5. Despite the UV‐induced changes in nutritional quality of S. capricornutum, no significant effects on D. magna growth or reproduction were detected. The fatty acid composition of Daphnia fed on UV irradiated algae showed a significantly lower content of 18 : 1 n‐9, but no changes in the essential PUFAs.     

THE DESIGN OF REPLICATED DIFFERENCE TESTS

We show that adding replications in replicated difference tests results in larger power and smaller variance when the number of assessors is fixed. On the other hand, when the number of total assessments is fixed, the power usually decreases and the variability increases whenever replications are considered instead of different assessors. The appropriate numbers of assessor needed to gain the same power and variability, respectively, when replications are used will be given. It is shown that the number of assessors might indeed be reduced, but this has to be paid for by an increasing total number of assessments. We show that two key models, namely the mixture binomial and a corrected version of the Beta-binomial model, are quite similar with respect to the properties of interest. We provide tables from which, according to her/his requirements, the investigator might find an appropriate setting with respect to the number of assessors and replications.     

The antagonism between botulinum toxin and calcium in motor nerve terminals

The effects of tetraethylammonium and manganese, which modify calcium entry into motor nerve terminals, have been studied during advanced stages of botulinum paralysis. Evidence has been obtained that the voltage-activated calcium current in the nerve endings is not significantly reduced by botulinum toxin. The depression of transmitter release that the toxin produces must arise at a later stage, at an intracellular site of the release mechanism.