Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer

The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration. Augmented NK activity peaks by 24 h after FAA injection and returns to normal after 6 days. Combined treatment of established murine renal cancer with FAA and rIL-2 results in up to 80% long term survival whereas FAA or rIL-2 alone were unable to induce any long term survivors. The optimal dose of rIL-2 required for use with FAA was in the range of 10,000 to 30,000 U/day. Further studies demonstrated that the regimen of FAA plus rIL-2 administration that was effective in treating established murine renal cancer also induced a more potent augmentation of NK activity than did either FAA or rIL-2 alone. Subsequent studies revealed that the therapeutic effectiveness of FAA plus rIL-2 was significantly reduced when tumor-bearing mice were treated with anti-asialo GM1 serum. These results are consistent with a role for augmented NK activity in the therapeutic effects of FAA plus rIL-2 murine renal cancer. In addition, these studies demonstrate that FAA and rIL-2 is a useful approach for cancer treatment in that subtoxic doses of rIL-2 can be used and significant anti-tumor efficacy occurs even without accompanying adoptive immunotherapy.     

Microcin C: Biosynthesis,Mode of Action,and Potential as a Lead in Antibiotics Development

The natural compound Microcin C (McC) is a Trojan horse inhibitor of aspartyl tRNA synthetases endowed with strong antibacterial properties, in which a heptapeptide moiety is responsible for active transport of the inhibitory metabolite part into the bacterial cell. The intracellularly formed aspartyl AMP analogue carries a chemically more stable phosphoramidate linkage, in comparison to the labile aspartyl-adenylate, and in addition is esterified with a 3-aminopropyl moiety. Therefore, this compound can target aspartyl-tRNA synthetase. The biochemical production and secretion of McC, and the possibilities to develop new classes of antibiotics using the McC Trojan horse concept in combination with sulfamoylated adenosine analogues will be discussed briefly.     

Morphological Parameters Associated with Ruptured Posterior Communicating Aneurysms

The rupture risk of unruptured intracranial aneurysms is known to be dependent on the size of the aneurysm. However, the association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations. We evaluated posterior communicating artery (PCoA) aneurysms for morphological parameters associated with aneurysm rupture in that location. CT angiograms were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005–2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. We found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms.     

When corridors collide: Road-related disturbance in commuting bats

As an increasingly dominant feature in the landscape, transportation corridors are becoming a major concern for bats. Although wildlife–vehicle collisions are considered to be a major source of mortality, other negative implications of roads on bat populations are just now being realized. Recent studies have revealed that bats, like many other wildlife species, will avoid roads rather than cross them. The consequence is that roads act as barriers or filters to movement, restricting bats from accessing critical resources. Our objective was to assess specific features along the commuting route, road, or surrounding landscape (alone or in combination) that exacerbated or alleviated the likelihood of a commuting bat exhibiting an avoidance behavior in response to an approaching vehicle. At 5 frequently used commuting routes bisected by roads, we collected data on vehicles travelling along the roads (such as visibility and audibility), commuting bats (such as height), and composition of the commuting route. We revealed that commuting route structure dictated the frequency at which bats turned back along their commuting routes and avoided the road. We found that gaps (>2 m) in commuting routes, such as the road itself, caused bats to turn away just before they reached the road. Furthermore, we found that turning frequencies of bats increased with vehicle noise levels and the locations at which bats responded to vehicles corresponded with areas where noise levels were greatest, including gaps <2 m. This suggested that bats had a disturbance threshold, and only reacted to vehicles when associated noise reached a certain level. We found that threshold levels for our study species were approximately 88 dB, but this value was likely to vary among species. Thus, our findings indicate that restoring (e.g., replanting native trees and shrubs in gaps) and establishing commuting routes (such as planting tree-lines and wooded hedgerows), as well as creating road-crossing opportunities (such as interlinking canopies) will improve the permeability of a road-dominated landscape to bats. Furthermore, our study highlights the influence of the soundscape. We recommend that effective management and mitigation strategies should take into account the ecological design of the acoustic environment. © 2012 The Wildlife Society.