Insulin-releasing and cytotoxic properties of the frog skin peptide,tigerinin-1R: a structure–activity study

The frog skin host-defense peptide tigerinin-1R (RVCSAIPLPICH.NH₂) is insulinotropic both in vitro and in vivo. This study investigates the effects on insulin release and cytotoxicity of changes in cationicity and hydrophobicity produced by selected substitutions of amino acids by l-arginine, l-lysine and l-tryptophan. The [A5W], [L8W] and [I10W] analogs produced a significant (P < 0.01) increase in the rate of insulin release from BRIN-BD11 rat clonal β cells at concentration of 0.01 nM compared with 0.1 nM for tigerinin-1R. The increase in the rate of insulin release produced by a 3 μM concentration of the [S4R], [H12K], and [I10W] analogs from both BRIN-BD11 cells and mouse islets was significantly greater (P < 0.05) than that produced by tigerinin-1R. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM indicating that plasma membrane integrity had been preserved. [A5W] tigerinin-1R was the only analog tested that showed cytotoxic activity against human erythrocytes (LC₅₀ = 265 ± 16 μM) and inhibited growth of Escherichia coli (MIC = 500 μM) and Staphylococcus aureus (MIC = 250 μM). The circular dichroism spectra of tigerinin-1R and [A5W] tigerinin-1R indicate that the peptides adopt a mixture of β-sheet, random coil and reverse β-turn conformations in 50% trifluoroethanol/water and methanol/water. Administration of [S4R] tigerinin-1R (75 nmol/kg body weight) to high-fat fed mice with insulin resistance significantly (P < 0.05) enhanced insulin release and improved glucose tolerance over a 60 min period following an intraperitoneal glucose load. The study supports the claim that tigerinin-1R shows potential for development into novel therapeutic agents for treatment of type 2 diabetes mellitus.     

Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover

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Single-molecule studies reveal branched pathways for activator-dependent assembly of RNA polymerase II pre-initiation complexes

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COMPARISON OF VERTICAL AERIAL PHOTOGRAPHIC AND GROUND CENSUSES OF STELLER SEA LIONS AT AÑO NUEVO ISLAND, JULY 1990-1993

Counts of Steller sea lion ( Eumetopias jubatus ) pups and non-pups (adults and juveniles) from aerial photographs of rookeries at Año Nuevo Island between 1990 and 1993 were significantly higher than those made on the ground. Based on regression of natural logs of photographic counts versus year, the number of pups declined at a rate of −0.099yr while non-pup numbers declined at −0.315/yr. Examination of ground count data for the same period revealed a significant decline in non-pups (−0.139/yr), but no trend was detected in the ground counts of pups. The regression coefficients from photographic and ground counts of non-pups did not differ significantly. Power analyses using the program TRENDS indicated that detectable rates of change in abundance from four annual surveys were much lower for counts of pups than counts of non-pups where sampling precision was based on fits to linear models.     

Angiotensin III and IV activation of the brain AT1 receptor subtype in cardiovascular function

The present investigation determined that native angiotensins II and III (ANG II and III) were equipotent as pressor agents when ICV infused in alert rats, whereas native angiotensin IV (ANG IV) was less potent. An analogue of each of these angiotensins was prepared with a hydroxyethylamine (HEA) amide bond replacement at the N-terminus, yielding additional resistance to degradation. These three angiotensin analogues, HEA-ANG II, HEA-ANG III, and HEA-ANG IV, were equivalent with respect to maximum elevation in pressor responses when ICV infused; and each evidenced significantly extended durations of effect compared with their respective native angiotensin. Comparing analogues, HEA-ANG II had a significantly longer effect compared with HEA-ANG III, and HEA-ANG IV, whereas the latter were equivalent. Pretreatment with the AT₁ receptor subtype antagonist, Losartan (DuP753), blocked subsequent pressor responses to each of these analogues, suggesting that these responses were mediated by the AT₁ receptor subtype. Pretreatment with the specific AT₄ receptor subtype antagonist, Divalinal (HED 1291), failed to influence pressor responses induced by the subsequent infusion of these analogues. These results suggest an important role for Ang III, and perhaps ANG IV, in brain angiotensin pressor responses mediated by the AT₁ receptor subtype.     

Strategies for signal amplification in nucleic acid detection

Many aspects of molecular genetics necessitate the detection of nucleic acid sequences. Current approaches involving target amplification (in situ PCR, Primed in situ Labeling, Self-Sustained Sequence Replication, Strand Displacement Amplification), probe amplification (Ligase Chain Reaction, Padlock Probes, Rolling Circle Amplification) and signal amplification (Tyramide Signal Amplification, Branched DNA Amplification) are summarized in the present review, together with their advantages and limitations.     

Attachment styles impact on pet visitation effectiveness

Abstract

This paper describes a field study on the effects of attachment styles on the subjective well-being of institutionalized older persons after participating in a pet visitation program. We compared how attachment style (i.e., secure, anxious ambivalent, dismissive avoidant, and fearful avoidant) moderated the impact of a dog visitation program in 52 elderly residents of an assisted-living facility. Controlling for pre-visitation mood, the results revealed that the secure style related to increases in positive mood after interacting with the dogs. The anxious ambivalent style related to increases in positive mood and decreases in ratings of depression. Most importantly, the fearful avoidant style related to increases in depression after interacting with the dogs. The results highlight the notion that not all participants benefit from taking part in pet visitation programs. Theoretically, this study presents preliminary evidence for the relevance of attachment styles in understanding human–pet interactions.     

Understanding the true burden of “Naegleria fowleri” (Vahlkampfiidae) in patients from Northern states of India: Source tracking and significance

The present study is an attempt to investigate the presence of Naegleria fowleri in Indian population. A total of 307 patients were enrolled and water samples were collected from both residential and surrounding areas of patients found positive for N. fowleri. The different species of Naegleria from both clinical and water samples were identified taxonomically. Recommended microbiological conventional techniques were used to identify different Naegleria stages and other free-living amoebae from the samples. PCR assays, using both genus and species specific primers were also optimized. None of the samples were positive by conventional microbiological examinations. However, PCR assays detected only three samples positive for N. fowleri. A total of 10 water bodies (ponds), that were used by Naegleria positive patients were examined. The pH and temperature of the water samples collected from water bodies ranged between 5.6–7.2 and 25–32 °C respectively. Among all the 10 water samples tested, four samples were positive for genus Naegleria by PCR assay, of which only two samples, showed positive amplification for N. fowleri. The sequence analysis of N. fowleri strain belonged to genotype II.     

Confronting the challenges of discovery of novel antibacterial agents

Bacterial resistance is inevitable and is a growing concern. It can be addressed only by discovery and development of new agents. However the discovery and development of new antibacterial agents are at an all time low. This article broadly examines the historical as well as current status of antibacterial discovery and provides some perspective as how to address some of the challenges.     

Effect of nutrient level on competition intensity in the field for three coexisting grass species

A field experiment encompassing both neighbour- and nutrient-manipulations was conducted in a nutrient-impoverished old-field habitat to investigate how the intensity of plant competition was affected by soil nutrient level. Three perennial grasses were used as target species: Agropyron repens, Poa pratensis and Phleum pratense. Neighbour manipulations involved the removal (through herbicide application) of all neighbouring vegetation within a 20 cm or 40 cm radius around target plants. Target performance was measured under five levels of added nutrients (N-P-K) in both the neighbour-removal plots and in non-removal (control) plots. Both neighbour and nutrient manipulations had a highly significant effect on both biomass and tiller production but the interaction between these treatments was generally insignificant. Below-ground/above-ground biomass quotient was affected only by neighbour manipulations and was greatest in the control plots (with no neighbours removed) for all three species. The suppressive effect of neighbours was not markedly affected by nutrient level. However, yield suppression showed a significant decreasing trend with increasing nutrient level for biomass production in Agropyron and an increasing trend for tiller production in Phleum. For Poa, there was no trend in the intensity of competition across nutrient level. The results suggest that the general intensity of competition within this community neither increases nor decreases with increasing nutrient level. Rather, coexisting species appear to respond individually in terms of the intensity of competition that they experience. These results conflict with predictions from the triangular C-S-R model of plant strategies. However, they are consistent with a recently modified ‘habitat templet’ model for vegetation.