A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. In this phase I study, SAM486A was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled with advanced/refractory disease not amenable to established treatments, PS ≤ 2, adequate marrow, liver, renal and cardiac function. Doses were escalated in 100% increments without toxicity in 24 pts from 3 mg m–2cycle–1up to 400 mg m–2cycle–1. At 550 and 700 mg m–2cycle–1reversible dose-limiting neutropenia occurred. Other toxicities included mild fatigue, nausea and vomiting. No objective remission was seen. Pharmakokinetic analysis showed a terminal half-life of approximately 2 days. AUC and Cmax were related to dose; neutropenia correlated with AUC. The recommended dose for further phase II studies on this schedule is 400 mg m–2cycle–1. © 2000 Cancer Research Campaig

Summer eczema in exported Icelandic horses: influence of environmental and genetic factors

A cross sectional study was designed to estimate the prevalence of summer eczema (a chronic, recurrent seasonal dermatitis) in exported Icelandic horses and the influence of environmental and genetic factors on the development of the disease. Among 330 horses, which had been exported to Germany, Denmark and Sweden, 114 (34.5%) were found to have clinical signs of summer eczema. The prevalence was highest 2 years after export and the exposure to the biting midges Culicoides spp., was found to be the main risk factor for developing the disease. Genetic influence on the sensitivity for the disease was not established. It was concluded that exported Icelandic horses are predisposed for summer dermatitis and the fact that they are not introduced to the antigens of the biting midges early in live, due to it's absence in Iceland, is likely to explain the high prevalence of the disease after export

Differing views - can chimpanzees do level 2 perspective-taking?

We gratefully acknowledge financial support by the German National Academic Foundation.Although chimpanzees understand what others may see, it is unclear if they understand how others see things (Level 2 perspective-taking). We investigated whether chimpanzees can predict the behavior of a conspecific which is holding a mistaken perspective that differs from their own. The subject competed with a conspecific over two food sticks. While the subject could see that both were the same size, to the competitor one appeared bigger than the other. In a previously established game, the competitor chose one stick in private first and the subject chose thereafter, without knowing which of the sticks was gone. Chimpanzees and 6-year-old children chose the ‘riskier’ stick (that looked bigger to the competitor) significantly less in the game than in a nonsocial control. Children chose randomly in the control, thus showing Level 2 perspective-taking skills; in contrast, chimpanzees had a preference for the ‘riskier’ stick here, rendering it possible that they attributed their own preference to the competitor to predict her choice. We thus run a follow-up in which chimpanzees did not have a preference in the control. Now they also chose randomly in the game. We conclude that chimpanzees solved the task by attributing their own preference to the other, while children truly understood the other’s mistaken perspective.Publisher PDFPeer reviewe

Relating Habitat and Climatic Niches in Birds

Predicting species' responses to the combined effects of habitat and climate changes has become a major challenge in ecology and conservation biology. However, the effects of climatic and habitat gradients on species distributions have generally been considered separately. Here, we explore the relationships between the habitat and thermal dimensions of the ecological niche in European common birds. Using data from the French Breeding Bird Survey, a large-scale bird monitoring program, we correlated the habitat and thermal positions and breadths of 74 bird species, controlling for life history traits and phylogeny. We found that cold climate species tend to have niche positions in closed habitats, as expected by the conjunction of the biogeographic history of birds' habitats, and their current continent-scale gradients. We also report a positive correlation between thermal and habitat niche breadths, a pattern consistent with macroecological predictions concerning the processes shaping species' distributions. Our results suggest that the relationships between the climatic and habitat components of the niche have to be taken into account to understand and predict changes in species' distributions

Sensitivity of the Advanced LIGO detectors at the beginning of gravitational wave astronomy

The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10-23/Hz was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30 M could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914

Long‐Distance Natal Dispersal Is Relatively Frequent and Correlated with Environmental Factors in a Widespread Raptor

Dispersal is a critical process influencing population dynamics and responses to global change. Long‐distance dispersal (LDD) can be especially important for gene flow and adaptability, although little is known about the factors influencing LDD because studying large‐scale movements is challenging and LDD tends to be observed less frequently than shorter‐distance dispersal (SDD). We sought to understand patterns of natal dispersal at a large scale, specifically aiming to understand the relative frequency of LDD compared to SDD and correlates of dispersal distances. We used bird banding and encounter data for American kestrels (Falco sparverius) to investigate the effects of sex, migration strategy, population density, weather, year and agricultural land cover on LDD frequency, LDD distance and SDD distance in North America from 1961 to 2015. Nearly half of all natal dispersal (48.9%) was LDD (classified as \u3e30 km), and the likelihood of LDD was positively associated with the proportion of agricultural land cover around natal sites. Correlates of distance differed between LDD and SDD movements. LDD distance was positively correlated with latitude, a proxy for migration strategy, suggesting that migratory individuals disperse farther than residents. Distance of LDD in males was positively associated with maximum summer temperature. We did not find sex‐bias or an effect of population density in LDD distance or frequency. Within SDD, females tended to disperse farther than males, and distance was positively correlated with density. Sampling affected all responses, likely because local studies more frequently capture SDD within study areas. Our findings that LDD occurs at a relatively high frequency and is related to different proximate factors from SDD, including a lack of sex‐bias in LDD, suggest that LDD may be more common than previously reported, and LDD and SDD may be distinct processes rather than two outcomes originating from a single dispersal distribution. To our knowledge, this is the first evidence that LDD and SDD may be separate processes in an avian species, and suggests that environmental change may have different outcomes on the two processes

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study

The integrin αvβ3, whose αv subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population