Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRβ.

Mechanisms underlying the development of idiopathic dilated cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor-β (ESRRβ), a member of the nuclear receptor family of transcription factors, as highly expressed in murine hearts and other highly oxidative striated muscle beds. Mice bearing cardiac-specific deletion of ESRRβ (MHC-ERRB KO) develop DCM and sudden death at ~10 mo of age. Isolated adult cardiomyocytes from the MHC-ERRB KO mice showed an increase in calcium sensitivity and impaired cardiomyocyte contractility, which preceded echocardiographic cardiac remodeling and dysfunction by several months. Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRβ protein is absent from the nucleus of cardiomyocytes from patients with DCM but not other forms of cardiomyopathy (ischemic, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy). Taken together these observations suggest that ESRRβ is a critical component in the onset of DCM by affecting contractility and calcium balance.NEW & NOTEWORTHY Estrogen-related receptor-β (ESRRβ) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRβ is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRβ in the pathogenesis of DCM in humans

Structure-Dynamics Relation in Physically-Plausible Multi-Chromophore Systems

We study a large number of physically-plausible arrangements of chromophores, generated via a computational method involving stochastic real-space transformations of a naturally-occurring “reference” structure, illustrating our methodology using the well-studied Fenna–Matthews–Olson complex (FMO). To explore the idea that the natural structure has been tuned for efficient energy transport, we use an atomic transition charge method to calculate the excitonic couplings of each generated structure and a Lindblad master equation to study the quantum transport of an exciton from a “source” to a “drain” chromophore. We find significant correlations between structure and transport efficiency: High-performing structures tend to be more compact and, among those, the best structures display a certain orientation of the chromophores, particularly the chromophore closest to the source-to-drain vector. We conclude that, subject to reasonable, physically motivated constraints, the FMO complex is highly attuned to the purpose of energy transport, partly by exploiting these structural motifs

The potential for land sparing to offset greenhouse gas emissions from agriculture

Greenhouse gas emissions from global agriculture are increasing at around 1% per annum, yet substantial cuts in emissions are needed across all sectors. The challenge of reducing agricultural emissions is particularly acute, because the reductions achievable by changing farming practices are limited and are hampered by rapidly rising food demand. Here we assess the technical mitigation potential offered by land sparing-increasing agricultural yields, reducing farm land area and actively restoring natural habitats on the land spared. Restored habitats can sequester carbon and can offset emissions from agriculture. Using the United Kingdom as an example, we estimate net emissions in 2050 under a range of future agricultural scenarios. We find that a land-sparing strategy has the technical potential to achieve significant reductions in net emissions from agriculture and land-use change. Coupling land sparing with demand-side strategies to reduce meat consumption and food waste can further increase the technical mitigation potential, however economic and implementation considerations might limit the degree to which this technical potential could be realised in practice.This research was funded by the Cambridge Conservation Initiative Collaborative Fund for Conservation and we thank its major sponsor Arcadia. We thank J. Bruinsma for the provision of demand data, the CEH for the provision of soil data and J. Spencer for invaluable discussions. A.L. was supported by a Gates Cambridge Scholarship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nclimate291

Extra-pair parentage and personality in a cooperatively breeding bird

Why so much variation in extra-pair parentage occurs within and among populations remains unclear. Often the fitness costs and benefits of extra-pair parentage are hypothesised to explain its occurrence; therefore, linking extra-pair parentage with traits such as personality (behavioural traits that can be heritable and affect reproductive behaviour) may help our understanding. Here, we investigate whether reproductive outcomes and success are associated with exploratory behaviour in a natural population of cooperatively breeding Seychelles warblers (Acrocephalus sechellensis) on Cousin Island. Exploratory behaviour correlates positively with traits such as risk-taking behaviour and activity in other wild bird species and might promote extra-pair mating by increasing the rate at which potential extra-pair partners are encountered. We therefore predicted that fast-exploring individuals would have more extra-pair offspring. There is also a potential trade-off between pursuing extra-pair parentage and mate guarding in males. We therefore also predicted that fast-exploring males would be more likely to pursue extra-pair parentage and that this would increase the propensity of their mate to gain extra-pair parentage. We found that neither the total number of offspring nor the number of extra-pair offspring were associated with a male’s or female’s exploratory behaviour. However, there was a small but significant propensity for females to have extra-pair fertilisations in pairs that were behaviourally disassortative. Overall, we conclude that, due to the small effect size, the association between exploratory behaviour and extra-pair paternity is unlikely to be biologically relevant. Significance statement: True genetic monogamy is rare, even in socially monogamous systems, and multiple factors, such as behaviour, social structure, morphology and physiology, determined by the biological system can cause variation in extra-pair parentage (EPP). Therefore, investigating the inherent differences in these factors among individuals could be informative. We investigated whether reproductive outcomes/success are associated with differences in the propensity to explore novel environments/objects in a promiscuous, island-dwelling cooperatively breeding bird, the Seychelles warbler. Our results showed that exploratory behaviour was not associated with the number of offspring produced by an individual, and thus the long-term fitness consequences of different exploratory tendencies did not differ. We also found that the propensity to engage in EPP in females was higher in dissimilar behavioural pairs, but due to the small effect size, we hesitate to conclude that there are personality-dependent mating outcomes in the population

Sustainable drainage system site assessment method using urban ecosystem services

The United Kingdom's recently updated approach to sustainable drainage enhanced biodiversity and amenity objectives by incorporating the ecosystem approach and the ecosystem services concept. However, cost-effective and reliable methods to appraise the biodiversity and amenity values of potential sustainable drainage system (SuDS)sites and their surrounding areas are still lacking, as is a method to enable designers to distinguish and link the amenity and biodiversity benefits that SuDS schemes can offer. In this paper, therefore, the authors propose two ecosystem services- and disservices-based methods (i.e. vegetation structure cover-abundance examination and cultural ecosystem services and disservices variables appraisal) to aid SuDS designers to distinguish and link amenity and biodiversity benefits, and allow initial site assessments to be performed in a cost-effective and reliable fashion. Forty-nine representative sites within Greater Manchester were selected to test the two methods. Amenity and biodiversity were successfully assessed and habitat for species, carbon sequestration, recreation and education ecosystem services scores were produced,which will support SuDS retrofit design decision-making. Large vegetated SuDS sites with permanent aquatic features were found to be most capable of enhancing biodiversity- and amenity-related ecosystem services. Habitat for species and recreation ecosystem services were also found to be positively linked to each other. Finally, waste bins on site were found to help reduce dog faeces and litter coverage. Overall, the findings presented here enable future SuDS retrofit designs to be more wildlife friendly and socially inclusive

Cytologic features of nipple aspirate fluid using an automated non-invasive collection device: a prospective observational study

BACKGROUND: Detection of cytologic atypia in nipple aspirate fluid (NAF) has been shown to be a predictor of risk for development of breast carcinoma. Manual collection of NAF for cytologic evaluation varies widely in terms of efficacy, ease of use, and patient acceptance. We investigated a new automated device for the non-invasive collection of NAF in the office setting. METHODS: A multi-center prospective observational clinical trial involving asymptomatic women designed to assess fluid production, adequacy, safety and patient acceptance of the HALO NAF Collection System (NeoMatrix, Irvine, CA). Cytologic evaluation of all NAF samples was performed using previously described classification categories. RESULTS: 500 healthy women were successfully enrolled. Thirty-eight percent (190/500) produced fluid and 187 were available for cytologic analysis. Cytologic classification of fluid producers showed 50% (93/187) Category 0 (insufficient cellular material), 38% (71/187) Category I (benign non-hyperplastic ductal epithelial cells), 10% (18/187) Category II (benign hyperplastic ductal epithelial cells), 3% (5/187) Category III (atypical ductal epithelial cells) and none were Category IV (unequivocal malignancy). Overall, 19% of the subjects produced NAF with adequate cellularity and 1% were found to have cytologic atypia. CONCLUSION: The HALO system is a simple, safe, rapid, automated method for standardized collection of NAF which is acceptable to patients. Cytologic assessment of HALO-collected NAF showed the ability to detect benign and pre-neoplastic ductal epithelial cells from asymptomatic volunteers

Resuscitation of Severe Uncontrolled Hemorrhage 7.5% Sodium Chloride/6% Dextran 70 vs 0.9% Sodium Chloride

Objectives: Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Methods: Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. Results: One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 ± 20 mL/kg) and group III (31 ± 13 mL/kg) as compared with group I (5 ± 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. Conclusion: In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73625/1/j.1553-2712.2000.tb02060.x.pd