An acetylsalicylic acid-sensitive aggregation phenomenon in Dipodascopsis uninucleata

Aggregation of ascospores has been discovered in the yeast Dipodascopsis uninucleata. When this yeast is cultivated to reach the sexual reproductive stage, small ascospores are individually released from the tip of a sac-like ascus which then aggregate in orderly clusters. Acetylsalicylic acid (ASA) inhibited ascospore release and subsequent ordered aggregation process. We suggest that novel ASA-sensitive oxidised fatty acids (3 R-hydroxy-oxylipins) and small hooks located on the surface of these ascospores, are involved.     

A quantitative analysis of behavioral selectivity for pulse rise-time in the gray treefrog, Hyla versicolor

The selectivity of female phonotactic responses to synthetic advertisement calls was tested in choice situations. Preferences based on differences in the linear rise-time of synthetic pulses depended on intensity and carrier frequency. When the carrier frequency was 1.1 kHz, simulating the low-frequency peak in the advertisement call, females preferred alternatives with slower rise-time pulses that differed by 5 ms at playback levels of 75 dB SPL and higher. A rise-time difference of 10 ms was discriminated at 65 dB SPL. When the carrier frequency was 2.2 kHz, simulating the high-frequency peak in the call, females discriminated a 5-ms difference in rise-time only at 85 dB SPL. Females showed no preference when the difference was 10 ms at lower playback levels. The difference in the thresholds (about 15–20 dB) for discriminating differences in rise-time at the two carrier frequencies was greater than the difference in behavioral thresholds for these two frequencies (about 10 dB). This result suggests that rise-time discrimination can be mediated solely by the neural channel mainly tuned to the low-frequency peak in the call. Females probably assess differences in rise-time by comparing the first few pulses of each call rather than by averaging over the entire call. Accepted: 30 March 1999     

New records of Acari from the sub-Antarctic Prince Edward Islands

Sixty species of Acari are recorded from the sub-Antarctic Marion and Prince Edward Islands (the Prince Edward archipelago). Twenty of the 45 species collected on recent expeditions are new and currently undescribed. Other new taxa include a family of Mesostigmata, four new genera, and the first sub-Antarctic records of Cillibidae (Mesostigmata) and Eryngiopus (Prostigmata). Fifteen of the 31 species previously reported from the islands are confirmed, although eight of the previous accounts remain doubtful. The fauna, which shows a distinction between the shoreline and terrestrial components, comprises endemic, South Indian Ocean Province and sub-Antarctic mite species. Accepted: 18 July 1998     

New antiprotozoal agents: Synthesis and biological evaluation of different 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives

In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5–14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC₅₀ values (0.14–1.26 μM) lower than the standard drug metronidazole (IC₅₀ 1.80 μM). All nine compounds exhibited antimalarial activity (IC₅₀ range: 1.42–19.62 μM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC₅₀ range: 14.67–81.24 μM) than quinine (IC₅₀: 275.6 ± 16.46 μM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae.     

The abundance of an invasive freshwater snail Tarebia granifera (Lamarck, 1822) in the Nseleni River,South Africa

The invasive freshwater snail Tarebia granifera (Lamarck, 1822) was first reported in South Africa in 1999 and it has become widespread across the country, with some evidence to suggest that it reduces benthic macroinvertebrate biodiversity. The current study aimed to identify the primary abiotic drivers behind abundance patterns of T. granifera, by comparing the current abundance of the snail in three different regions, and at three depths, of the highly modified Nseleni River in KwaZulu-Natal, South Africa. Tarebia granifera was well established throughout the Nseleni River system, with an overall preference for shallow waters and seasonal temporal patterns of abundance. Although it is uncertain what the ecological impacts of the snail in this system are, its high abundances suggest that it should be controlled where possible and prevented from invading other systems in the region.     

Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability

The angiogenic sprout has been compared to the growing axon, and indeed, many proteins direct pathfinding by both structures. The Roundabout (Robo) proteins are guidance receptors with well-established functions in the nervous system; however, their role in the mammalian vasculature remains ill defined. Here we show that an endothelial-specific Robo, Robo4, maintains vascular integrity. Activation of Robo4 by Slit2 inhibits vascular endothelial growth factor (VEGF)-165-induced migration, tube formation and permeability in vitro and VEGF-165-stimulated vascular leak in vivo by blocking Src family kinase activation. In mouse models of retinal and choroidal vascular disease, Slit2 inhibited angiogenesis and vascular leak, whereas deletion of Robo4 enhanced these pathologic processes. Our results define a previously unknown function for Robo receptors in stabilizing the vasculature and suggest that activating Robo4 may have broad therapeutic application in diseases characterized by excessive angiogenesis and/or vascular leak.     

Hormonal modulation of phonotaxis and advertisement-call preferences in the gray treefrog (Hyla versicolor)

Hormonal levels fluctuate during the breeding season in many anurans, but the identity of the hormones that modulate breeding behavior and their effects remain unclear. We tested the influence of a combined treatment of progesterone and prostaglandin on phonotaxis, the key proceptive reproductive behavior of female anurans. First, we found that female gray treefrogs (Hyla versicolor) treated with progesterone and prostaglandin exhibited phonotaxis to synthetic male advertisement signals significantly more often than animals treated with ringers vehicle or uninjected controls. Responsive females had greater levels of plasma progesterone and estradiol compared to both control groups, suggesting that these steroids may be promoting phonotaxis. Second, we found that the selectivity of hormonally-induced phonotaxis in H.versicolor was similar to that observed in freshly captured breeding animals. Females made the same choices between acoustic signals after hormone treatments in tests of frequency, call rate and pulse rate, compared to their responses without treatment immediately after collection from the breeding chorus. The preference for a longer call was, however, significantly weaker after hormonal induction of phonotaxis. Hormonally primed females were also less likely to respond in any test and took longer to respond than did freshly collected females. Consequently, our study shows how progesterone-prostaglandin induced phonotaxis in female treefrogs influences both the quality and quantity of phonotaxis, relative to that exhibited by naturally breeding females.     

Dipeptidyl nitrile inhibitors of Cathepsin L

A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.     

Microwave‐assisted solid‐phase peptide synthesis at 60 °C: alternative conditions with low enantiomerization

Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS‐ET), but we have elected the following as our first choice: 2.5‐fold molar excess of 0.04–0.08 M Boc or Fmoc‐amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 °C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave‐SPPS, peptides containing L ‐Ser, L ‐His, L ‐Cys and/or L ‐Met were manually synthesized traditionally, at 60 °C using conventional heating and at 60 °C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave‐assisted coupling of L ‐Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 °C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave‐assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS‐ET and suggests alternative conditions for microwave‐assisted SPPS. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Specificity of the myotubularin family of phosphatidylinositol-3-phosphatase is determined by the PH/GRAM domain

Myotubularins (MTM) are a large subfamily of lipid phosphatases that specifically dephosphorylate at the D3 position of phosphatidylinositol 3-phosphate (PI(3)P) in PI(3)P and PI(3,5)P2. We recently found that MTMR6 specifically inhibits the Ca2+-activated K+ channel, KCa3.1, by dephosphorylating PI(3)P. We now show that inhibition is specific for MTMR6 and other MTMs do not inhibit KCa3.1. By replacing either or both of the coiled-coil (CC) and pleckstrin homology/GRAM (PH/G) domains of MTMs that failed to inhibit KCa3.1 with the CC and PH/G domains of MTMR6, we found that chimeric MTMs containing both the MTMR6 CC and PH/G domains functioned like MTMR6 to inhibit KCa3.1 channel activity, whereas chimeric MTMs containing either domain alone did not. Immunofluorescent microscopy demonstrated that both the MTMR6 CC and PH/G domains are required to co-localize MTMR6 to the plasma membrane with KCa3.1. These findings support a model in which two specific low affinity interactions are required to co-localize MTMR6 with KCa3.1: 1) between the CC domains on MTMR6 and KCa3.1 and (2) between the PH/G domain and a component of the plasma membrane. Our inability to detect significant interaction of the MTMR6 G/PH domain with phosphoinositides suggests that this domain may bind a protein. Identifying the specific binding partners of the CC and PH/G domains on other MTMs will provide important clues to the specific functions regulated by other MTMs as well as the mechanism(s) whereby loss of some MTMs lead to disease.