Synthesis of apo-13- and apo-15-lycopenoids,cleavage products of lycopene that are retinoic acid antagonists

Consumption of the tomato carotenoid, lycopene, has been associated with favorable health benefits. Some of lycopene's biological activity may be due to metabolites resulting from cleavage of the lycopene molecule. Because of their structural similarity to the retinoic acid receptor (RAR) antagonist, β-apo-13-carotenone, the “first half” putative oxidative cleavage products of the symmetrical lycopene have been synthesized. All transformations proceed in moderate to good yield and some with high stereochemical integrity allowing ready access to these otherwise difficult to obtain terpenoids. In particular, the methods described allow ready access to the trans isomers of citral (geranial) and pseudoionone, important flavor and fragrance compounds that are not readily available isomerically pure and are building blocks for many of the longer apolycopenoids. In addition, all of the apo-11, apo-13, and apo-15 lycopenals/lycopenones/lycopenoic acids have been prepared. These compounds have been evaluated for their effect on RAR-induced genes in cultured hepatoma cells and, much like β-apo-13-carotenone, the comparable apo-13-lycopenone and the apo-15-lycopenal behave as RAR antagonists. Furthermore, molecular modeling studies demonstrate that the apo-13-lycopenone efficiently docked into the ligand binding site of RARα. Finally, isothermal titration calorimetry studies reveal that apo-13-lycopenone acts as an antagonist of RAR by inhibiting coactivator recruitment to the receptor.     

Biodiversity and the Heterogeneous Disturbance Regime on Military Training Lands

Disproportionately large numbers of threatened and endangered species and unusually high biodiversity occur on active and former military training areas. Although this may seem paradoxical given the apparently destructive nature of military training, an evaluation of the nature and extent of the disturbances is enlightening. Military training frequently produces heterogeneous landscapes. Large portions of military training areas remain virtually untouched, favoring disturbance‐averse species; other portions are heavily disturbed, favoring disturbance‐dependent species. The rich habitat mosaics include the two extremes as well as the continua of disturbance and succession between them, thus providing suitable habitat for a very large number of species with widely varying habitat requirements. To explain the phenomenon, a heterogeneous disturbance hypothesis is proposed which suggests that biodiversity is maximized where multiple kinds, frequencies, severities, periodicities, sizes, shapes, and/or durations of disturbance occur concomitantly on a landscape in a spatially and temporally distributed fashion. The enhanced biodiversity occurring on active and former military training areas illustrates the need for restoration ecologists to restore or maintain an appropriate heterogeneous disturbance regime when attempting to restore ecosystem function and biodiversity.     

Population-level cure of colorectal cancer in Malta: An analysis of patients diagnosed between 1995 and 2004

AimThe aim of this study was to estimate the population-level ‘cure’ of Maltese colorectal cancer patients diagnosed between 1995 and 2004, and to estimate the median survival time for the ‘uncured’ patients.Methods and study populationAnalysis was conducted on 1470 cases registered by the Malta National Cancer Register between 1995 and 2004 and followed up to end of 2010. The mean age of the patients was 66.4 (95%CI 65.8–67.1), and the number of men and women were equal. Background mortality for 1995–2010 was extracted from publicly available life tables. A mixture model with Weibull survival distribution and identity link was used to model ‘cure’.ResultsThe overall ‘cured’ proportion for the patients diagnosed in 1995–1999 was 45.3% (95%CI 40.2–50.5) while the ‘cured’ proportion for the patients diagnosed in 2000–2004 was 52.3% (95%CI 47.2–57.5). Median survival time for the ‘uncured’ patients increased in the second calendar period from 1.25 years (95%CI 1.04–1.45) to 1.42 years (95%CI 1.15–1.76).ConclusionIn Malta, as in the rest of Europe, improvements have been made in short- and long-term survival over the 15-year period under study. To continue this improvement, differences by age that still persist must be investigated and efforts focused to reduce any gaps between Malta and other European countries.     

A rapid altitudinal range expansion in the pine processionary moth produced by the 2003 climatic anomaly

Climatic anomalies may produce, or accelerate, geographic range expansions of species limited by temperature or other climatic variables. Most such expansions are only temporary, before the prevailing climatic conditions drive the founder populations extinct. In contrast, here, we report a recent rapid shift of the range limit during the record hot summer of 2003 in southern Europe that has the potential to be both permanent, and to have important implications on species range dynamics in general. The winter pine processionary moth (Thaumetopoea pityocampa), an important pine defoliator whose larvae feed in colonies during the winter, is limited in its distribution by winter temperatures. In the last three decades, warmer winters have led to a gradual but substantial expansion of its range both latitudinally and altitudinally. In the summer of 2003, T. pityocampa underwent an extraordinary expansion to high elevation pine stands in the Italian Alps; its altitudinal range limit increased by one third of the total altitudinal expansion over the previous three decades. In an experiment, we found flight activity of newly emerged females to increase with temperature. By determining a threshold temperature for flight take‐offs under controlled conditions, we calculated that the nights above the threshold temperature were over five times more frequent, and considerably warmer, at the range limit in 2003 than in an average year. We therefore attribute the colonization of extreme, high‐elevation sites to increased nocturnal dispersal of females during the unusually warm night temperatures in June – August 2003. Importantly, the colonies established at extreme sites survived the winter and produced offspring in 2004, although the range did not expand further because of low night temperatures that year. We discuss several life‐history characteristics of T. pityocampa that maximize the likelihood of population persistence at the new range limit. As global warming continues and climatic anomalies are predicted to become more frequent, our results draw attention to the importance of extreme climatic events in the range formation of phytophagous insects.     

Egyptian tortoise conservation: A community‐based,field research program developed from a study on a captive population

Local community participation and ex situ conservation has the potential to assist the recovery of the endangered Egyptian tortoise, Testudo kleinmanni. We initiated an in situ community‐based conservation and research program from a captive population of T. kleinmanni. We used a captive population of the Egyptian tortoise to train a member of the local community as a research technician and used his indigenous tracking skills and knowledge of the area to collect activity and dietary data on 28 captive tortoises. We overcame problems with illiteracy by creating a data sheet based on symbols and numbers. This data sheet allowed us to use the indigenous knowledge of various people from the community, and employ them in the future. Our local community approach to data collection, in conjunction with a craft program, made the conservation of the Egyptian tortoise more rewarding to the local community by providing a more sustainable form of income than collecting animals for the pet trade. Our multidimensional approach (local community participation as research technicians, craft program, and trust building) for gaining local support eventually led to the rediscovery of wild Egyptian tortoises in North Sinai, which was significant, as this species was presumed extinct in Egypt. We have now shifted our focus to in situ conservation, using the research and local capacity building template developed from this captive population study. Our template can be used by zoos and conservation organizations with small budgets and collections of native species in natural habitats to create similar captive research programs that can be applied to in situ conservation. Zoo Biol 26:397–406, 2007. © 2007 Wiley‐Liss, Inc.     

A genetic and spatial Bayesian analysis of mastitis resistance

A nationwide health card recording system for dairy cattle was introduced in Norway in 1975 (the Norwegian Cattle Health Services). The data base holds information on mastitis occurrences on an individual cow basis. A reduction in mastitis frequency across the population is desired, and for this purpose risk factors are investigated. In this paper a Bayesian proportional hazards model is used for modelling the time to first veterinary treatment of clinical mastitis, including both genetic and environmental covariates. Sire effects were modelled as shared random components, and veterinary district was included as an environmental effect with prior spatial smoothing. A non-informative smoothing prior was assumed for the baseline hazard, and Markov chain Monte Carlo methods (MCMC) were used for inference. We propose a new measure of quality for sires, in terms of their posterior probability of being among the, say 10% best sires. The probability is an easily interpretable measure that can be directly used to rank sires. Estimating these complex probabilities is straightforward in an MCMC setting. The results indicate considerable differences between sires with regards to their daughters disease resistance. A regional effect was also discovered with the lowest risk of disease in the south-eastern parts of Norway.     

Temporal and spatial trends in heavy metal concentrations in the marine mussel Mytilus edulis from the Western Scheldt estuary (The Netherlands)

Since the first North Sea Conference (1984, Bremen), all countries bordering the North Sea made commitments to reduce discharge of hazardous substances into the North Sea. From Belgium and The Netherlands, large reductions (upto 90) in heavy metal emissions from land-based sources have been reported between 1985 and 2000. Recently, some studies in the Western Scheldt estuary (WS) have shown that total metal concentration in the water, sediments and suspended particles have decreased compared to levels in the 70s. However, data on aquatic organisms is still very limited and it is therefore difficult to confirm whether the reductions in pollution input and generally improving water quality in the WS have a corresponding impact on the levels of heavy metals in aquatic organisms. The current study measured metal concentrations in the soft tissues of mussels, Mytilus edulis (known to be good indicators of environmental metal pollution) during the period 1996–2002. Spatial (salinity and pollution gradients), temporal and seasonal variations were also studied. Results showed a down-stream decreasing trend for the metals studied (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn) during all sampling campaigns. There was also a significant seasonal effect on tissue metal concentrations, with a peak observed around spring in both WS and the nearby less polluted Eastern Scheldt (ES). On temporal trends, a clear drop of metals in mussels was observed in the early 80s coinciding with the start of the efforts to reduce chemical pollution input into the North Sea. Since those early reductions, metal concentrations in mussels generally remained unchanged upto mid 90s. However, in recent times metal concentration in mussels have increased significantly, for example Cd in 2002 was almost 10 times the values in 1983 and similar to levels seen during the peak in the 70s. Other metals also increased in the 90s also reaching levels seen in the 70s. As there is no indication of recent increase in metal input into the estuary, we suggest that increased metal concentrations observed in mussels in recent years especially in the upper estuary are most likely a result of changes in physical and chemical speciation and metal bioavailability. Such changes may be caused by changes in some water quality parameters in the estuary (i.e. increased dissolved oxygen, concentration of organic matter), resulting in conditions that favour releases of sediment-bound metals into the water column. The relationship between metal content and season showed very similar annual profiles in the polluted WS and less polluted ES. Thus, seasonal variations in metal concentrations appear to be largely controlled by biological processes, while total body burdens are dependent on environmental levels and bioavailability.     

Prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano

The prevalence of neuropathic pain is difficult to estimate as most studies evaluating chronic pain do not differentiate neuropathic from nociceptive pain. There are only a few studies of neuropathic pain in the elderly, specifically in the oncology population. This article is a non-systematic review of the relevant evidence on the prevalence and aetiopathogenesis of neuropathic cancer pain in the elderly.