Pay-offs and penalties of competing migratory schedules

We relate variation in the timing of arrival by migrating birds breeding at northerly latitudes to individual differences in the prior accumulation of energy stores. Balancing starvation risks early in the season against the almost universal declining trend in reproductive prospects with advancing date is seen as an individual decision with fitness consequences. We review three studies implicating events at the staging sites or in winter in setting the individual migratory schedule. Climate change influences the timetable of a pied flycatcher (Ficedula hypoleuca) population breeding in The Netherlands and wintering in West Africa, followed since 1960. Mean air temperature in the period mid April‐mid May (arrival and laying) increased and laying date advanced by 10 days. Still, in recent years most birds did not lay early enough to maximise fitness (determined by recruitment and parental survival) whereas many parents achieved this goal in 1980–1985. As the flycatchers have not started to arrive earlier, some ecological constraint further upstream is postulated (possibly the hurdle of the crossing of Sahara and Mediterranean). The ability to follow individual migrants provides a second avenue to assess the fitness implications of migratory schedules. Thus, brightly coloured male bar‐tailed godwits (Limosa lapponica) captured in the Dutch Wadden Sea (the intermediate staging site linking a West African wintering area with breeding sites in arctic Russia) and traced with miniature radio‐transmitters did not depart early. The ‘best’ males (with bright breeding plumage) were picked up by the listening stations in Sweden 650 km further along the migratory route ten days later than the paler individuals. If early arrival confers the competitive advantage of prior occupancy but increases mortality, the ‘best’ males may be able to afford arriving later and thus avoid some of the survival costs. Return rate of the ‘bright’ males to the staging site in later seasons was indeed higher than for the ‘pale’, early males. Intensive observation of pink‐footed geese (Anser brachyrhynchus) fitted with coded neck‐collars substantiate the tight relationship between energy stores (fat) accumulated up to final departure from the final staging site (Vesterålen, N. Norway) en route to the nesting grounds (Spitsbergen) and subsequent success. The breeding outcome of individual parents (accompanied by juveniles or not) could be related to observations of body condition before departure (visual ‘abdominal profile index’). Recently, perceived conflicts with agriculture have resulted in widespread harassment by humans. The geese have: drastically shortened their stay on the Vesterålen, fail to achieve the body condition usual a decade ago and reproductive output has fallen. Although the geese are currently pioneering new staging sites, an adequate alternative has not materialised, underlining the critical role of the final take‐off site.     

An Observational Study of Slimming Behavior in Denmark in 1992 and 1998

Objective: To elucidate how frequent weight‐loss attempts are made, the methods used to achieve weight loss, and the extent to which the outcome is positive. Research Methods and Procedures: Two independent interviews were conducted in 1992 and in 1998, each with 1200 randomly selected adult subjects. Each survey was designed to ensure an equal distribution of age, gender, and geographical regions in Denmark. Results: The proportion of subjects having attempted weight loss did not change from 1992 to 1998, although the prevalence of overweight and obesity increased from 1992 (overweight, 30%; obesity, 6%) to 1998 (overweight, 35%; obesity, 8%). Almost twice as many women (61%) than men (32%) had attempted weight loss (p < 0.0001). Slimming occurred more often in subjects <50 years (51%) than >50 years (39%) (p < 0.0001), although overweight and obesity were more frequent in the elderly. Over‐the‐counter diet pills or meal replacements were associated with a negative outcome of slimming treatment (p < 0.0001). Discussion: Approximately half of all adult Danes have attempted weight loss, particularly women and individuals <50 years. This finding is inconsistent with the fact that overweight and obesity are more prevalent in men and in individuals >50 years. Changes in habitual diet and increased physical activity are the most prevalent modes of slimming, whereas the use of over‐the‐counter diet pills or meal replacements has decreased from 1992 to 1998. This development may have a positive impact on future body‐ weight‐management strategies.     

Conference and workshop on modelling global land use implications in the environmental assessment of biofuels

Background, Aims and Scope  On 4–5 June 2007, an international conference was held in Copenhagen. It provided an interdisciplinary forum where economists and geographers met with LCA experts to discuss the challenges of modelling the ultimate land use changes caused by an increased demand for biofuels. Main Features  The main feature of the conference was the cross-breeding of experience from the different approaches to land use modelling: The field of LCA could especially benefit from economic modelling in the identification of marginal crop production and the resulting expansion of the global agricultural area. Furthermore, the field of geography offers insights in the complexity behind new land cultivation and practical examples of where this is seen to occur on a regional scale. Results  Results presented at the conference showed that the magnitude and location of land use changes caused by biofuels demand depend on where the demand arises. For instance, mandatory blending in the EU will increase land use both within and outside of Europe, especially in South America. A key learning for the LCA society was that the response to a change in demand for a given crop is not presented by a single crop supplier or a single country, but rather by responses from a variety of suppliers of several different crops in several countries. Discussion  The intensification potential of current and future crop and biomass production was widely discussed. It was generally agreed that some parts of the third world hold large potentials for intensification, which are not realised due to a number of barriers resulting in so-called yield gaps. Conclusions  Modelling the global land use implications of biofuels requires an interdisciplinary approach optimally integrating economic, geographical, biophysical, social and possibly other aspects in the modelling. This interdisciplinary approach is necessary but also difficult due to different perspectives and mindsets in the different disciplines. Recommendations and Perspectives  The concept of a location dependent marginal land use composite should be introduced in LCA of biofuels and it should be acknowledged that the typical LCA assumption of linear substitution is not necessarily valid. Moreover, fertiliser restrictions/accessibility should be included in land use modelling and the relation between crop demand and intensification should be further explored. In addition, environmental impacts of land use intensification should be included in LCA, the powerful concept of land use curves should be further improved, and so should the modelling of diminishing returns in crop production.     

Antimutator role of DNA glycosylase MutY in pathogenic Neisseria species

Genome alterations due to horizontal gene transfer and stress constantly generate strain on the gene pool of Neisseria meningitidis, the causative agent of meningococcal (MC) disease. The DNA glycosylase MutY of the base excision repair pathway is involved in the protection against oxidative stress. MC MutY expressed in Escherichia coli exhibited base excision activity towards DNA substrates containing A:7,8-dihydro-8-oxo-2'-deoxyguanosine and A:C mismatches. Expression in E. coli fully suppressed the elevated spontaneous mutation rate found in the E. coli mutY mutant. An assessment of MutY activity in lysates of neisserial wild-type and mutY mutant strains showed that both MC and gonococcal (GC) MutY is expressed and active in vivo. Strikingly, MC and GC mutY mutants exhibited 60- to 140-fold and 20-fold increases in mutation rates, respectively, compared to the wild-type strains. Moreover, the differences in transitions and transversions in rpoB conferring rifampin resistance observed with the wild type and mutants demonstrated that the neisserial MutY enzyme works in preventing GC-->AT transversions. These findings are important in the context of models linking mutator phenotypes of disease isolates to microbial fitness.     

Soil–atmosphere exchange of N2O, CO2 and CH4 along a slope of an evergreen broad-leaved forest in southern China

At most sites the magnitude of soil-atmosphere exchange of nitrous dioxide (N₂O), carbon dioxide (CO₂) and methane (CH₄) was estimated based on a few chambers located in a limited area. Topography has been demonstrated to influence the production and consumption of these gases in temperate ecosystems, but this aspect has often been ignored in tropical areas. In this study, we investigated spatial variability of the net fluxes of these gases along a 100 m long slope of a evergreen broadleaved forest in southern China over a whole year. We expected that the lower part of slope would release more N₂O and CO₂, but take up less atmospheric CH₄ than the upper part due to different availability of water and nutrients. Our results showed that the soil moisture (Water Filled Pore Space, WFPS) decreased along the slope from bottom to top as we expected, but among the three gases only N₂O emissions followed this pattern. Annual means of WFPS ranged from 27.7% to 52.7% within the slope, and annual emissions of N₂O ranged from 2.0 to 4.4 kg N ha^?1 year^?1, respectively. These two variables were highly and positively correlated across the slope. Neither potential rates of net N mineralization and nitrification, nor N₂O emissions in the laboratory incubated soils varied with slope positions. Soil CO₂ release and CH₄ uptake appeared to be independent on slope position in this study. Our results suggested that soil water content and associated N₂O emissions are likely to be influenced by topography even in a short slope, which may need to be taken into account in field measurements and modelling.     

Ubiquitin-specific Protease 11 (USP11) Deubiquitinates Hybrid Small Ubiquitin-like Modifier (SUMO)-Ubiquitin Chains to Counteract RING Finger Protein 4 (RNF4)

Ring finger protein 4 (RNF4) is a SUMO-targeted ubiquitin E3 ligase with a pivotal function in the DNA damage response (DDR). SUMO interaction motifs (SIMs) in the N-terminal part of RNF4 tightly bind to SUMO polymers, and RNF4 can ubiquitinate these polymers in vitro. Using a proteomic approach, we identified the deubiquitinating enzyme ubiquitin-specific protease 11 (USP11), a known DDR-component, as a functional interactor of RNF4. USP11 can deubiquitinate hybrid SUMO-ubiquitin chains to counteract RNF4. SUMO-enriched nuclear bodies are stabilized by USP11, which functions downstream of RNF4 as a counterbalancing factor. In response to DNA damage induced by methyl methanesulfonate, USP11 could counteract RNF4 to inhibit the dissolution of nuclear bodies. Thus, we provide novel insight into cross-talk between ubiquitin and SUMO and uncover USP11 and RNF4 as a balanced SUMO-targeted ubiquitin ligase/protease pair with a role in the DDR.     

Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation.     

Use of low‐dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator‐controlled cohort study

At standard doses used for schizophrenia or bipolar disorder, quetiapine has been associated with weight gain and increased levels of triglycerides, to­tal cholesterol and low‐density lipoprotein (LDL) cholesterol, which are risk factors for cardiovascular morbidity and mortality. However, this drug is also commonly used off‐label at low doses for anxiolytic or hypnotic purposes, and its cardiovascular safety at these doses is unknown. We aimed to assess the risk of major adverse cardiovascular events with use of low‐dose quetiapine compared to use of Z‐drug hypnotics in a nationwide, active comparator‐controlled cohort study. The cohort included new users of either drugs in Denmark from 2003 to 2017, aged 18‐85 years, without history of ischemic stroke, myocardial infarction, cancer, and severe mental illness. The main outcome was the occurrence of major adverse cardiovascular events, defined as non‐fatal myocardial infarction or ischemic stroke, or death from cardiovascular causes. Selective serotonin reuptake inhibitors (SSRIs) were used as an alternative comparator in sensitivity analyses. Altogether, we compared 60,566 low‐dose quetiapine users with 454,567 Z‐drug users, followed for 890,198 person‐years in intent‐to‐treat analysis, and 330,334 person‐years in as‐treated analysis. In intention‐to‐treat analysis, low‐dose quetiapine was associated with an increased risk of major adverse cardiovascular events (adjusted hazard ratio, aHR=1.13, 95% CI: 1.02‐1.24, p=0.014) and cardiovascular death (aHR=1.26, 95% CI: 1.11‐1.43, p<0.001). In as‐treated analysis, continuous low‐dose quetiapine use was associated with increased risk of major adverse cardiovascular events (aHR=1.52, 95% CI: 1.35‐1.70, p<0.001), non‐fatal ischemic stroke (aHR=1.37, 95% CI: 1.13‐1.68, p=0.002) and cardiovascular death (aHR=1.90, 95% CI: 1.64‐2.19, p<0.001). The risk of major adverse cardiovascular events was greater in women (aHR=1.28, p=0.02) and those aged ≥65 years at initiation (aHR=1.24, p<0.001). Compared to SSRIs, low‐dose quetiapine use was associated with an increased risk of major adverse cardiovascular events (aHR=1.42, p<0.001), non‐fatal ischemic stroke (aHR=1.27, p=0.0028) and cardiovascular death (aHR=1.72, p<0.001). So, we conclude that the use of low‐dose quetiapine is associated with an increased risk of major adverse cardiovascular events, especially in women and the elderly. On the basis of these findings, we suggest that use of off‐label low‐dose quetiapine for sedative or hypnotic purposes should be discouraged.