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Adipocyte NR1D1 dictates adipose tissue expansion during obesity
No full textThe circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (Nr1d1Flox2-6:AdipoqCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of NR1D1 regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, Nr1d1Flox2-6:AdipoqCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT NR1D1 cistrome with differential gene expression reveals broad control of metabolic processes by NR1D1 which is unmasked in the obese state. Adipocyte NR1D1 does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, NR1D1 action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance
A Ray-Knight representation of up-down Chinese restaurants
No full textWe study composition-valued continuous-time Markov chains that appear naturally in the framework of Chinese Restaurant Processes (CRPs). As time evolves, new customers arrive (up-step) and existing customers leave (down-step) at suitable rates derived from the ordered CRP of Pitman and Winkel (Ann. Probab. 37 (2009) 1999–2041). We relate such up-down CRPs to the splitting trees of Lambert (Ann. Probab. 38 (2010) 348–395) inducing spectrally positive Lévy processes. Conversely, we develop theorems of Ray–Knight type to recover more general up-down CRPs from the heights of Lévy processes with jumps marked by integer-valued paths. We further establish limit theorems for the Lévy process and the integer-valued paths to connect to work by Forman, Pal, Rizzolo, Shi and Winkel on interval partition diffusions and hence to some long-standing conjectures
Secukinumab provides sustained improvements in clinical and imaging outcomes in patients with psoriatic arthritis and axial manifestations: results from the MAXIMISE trial
No full textEffects of land-use change on avian taxonomic, functional and phylogenetic diversity in a tropical montane rainforest
No full textAim: Although land-use change is a leading cause of biodiversity loss worldwide, there is scant information on the extent to which it has affected the structure and composition of bird communities in the Afrotropical region. This study aimed to quantify the effects of habitat transformation on taxonomic, functional, and phylogenetic diversity in Afrotropical bird communities.
Location: Nyungwe landscape, a montane rainforest with adjoining farmland in south-west Rwanda.
Methods: Data on bird occurrence, abundance, and functional traits were collected in 2017/18 using point-counts. We also collected data on habitat and morphological traits for all bird species recorded. We quantified bird diversity using a range of metrics, including the Inverse Simpson index, functional dispersion and the standardized effect size of mean nearest taxon distance.
Results: In comparison to primary forest areas, even low levels of land-use change altered species composition, and reduced species diversity. Although overall functional and phylogenetic diversity were similar across land-use types, we found a significant contraction of trophic and locomotory trait structures of bird communities in restored areas and cultivated areas, respectively. Soil moisture, elevation, and lower vegetation height were major factors influencing taxonomic, functional and phylogenetic dimensions of bird communities, although their effects varied across these dimensions.
Main conclusions: The sensitivity of forest species to minor habitat disturbance emphasises the value of conserving primary vegetation. Long-term conservation of bird communities in Afromontane ecosystems requires halting wide-scale destruction of primary forest, promoting vegetation heterogeneity in the ecological restoration of degraded habitats, and adopting wildlife-friendly agricultural practices. Our results suggest that monitoring and conservation in these landscapes can be refined using taxonomic, functional and phylogenetic diversity metrics to provide complementary information about the current and likely future impacts of land-use change
Finntopia: A long read
No full textFinland is rarely mentioned as an example by leftists and Greens who want to build a better future. Yet this little-noticed country is one of the most equal, peaceful and happiest on the planet. Danny Dorling and Annika Koljonen explain how Finland came to demonstrate the benefits of investing in people – and suggest what its model might have to offer the rest of the world
In situ solid-state nanopore fabrication
No full textNanopores in solid-state membranes are promising for a wide range of applications including DNA sequencing, ultra-dilute analyte detection, protein analysis, and polymer data storage. Techniques to fabricate solid-state nanopores have typically been time consuming or lacked the resolution to create pores with diameters down to a few nanometres, as required for the above applications. In recent years, several methods to fabricate nanopores in electrolyte environments have been demonstrated. These in situ methods include controlled breakdown (CBD), electrochemical reactions (ECR), laser etching and laser-assisted controlled breakdown (la-CBD). These techniques are democratising solid-state nanopores by providing the ability to fabricate pores with diameters down to a few nanometres (i.e. comparable to the size of many analytes) in a matter of minutes using relatively simple equipment. Here we review these in situ solid-state nanopore fabrication techniques and highlight the challenges and advantages of each method. Furthermore we compare these techniques by their desired application and provide insights into future research directions for in situ nanopore fabrication methods
Memory effects, arches and polar defect ordering at the cross-over from wet to dry active nematics
No full textWe use analytic arguments and numerical solutions of the continuum, active nematohydrodynamic equations to study how friction alters the behaviour of active nematics. Concentrating on the case where there is nematic ordering in the passive limit, we show that, as the friction is increased, memory effects become more prominent and +1/2 topological defects leave increasingly persistent trails in the director field as they pass. The trails are preferential sites for defect formation and they tend to impose polar order on any new +1/2 defects. In the absence of noise and for high friction, it becomes very difficult to create defects, but trails formed by any defects present at the beginning of the simulations persist and organise into parallel arch-like patterns in the director field. We show aligned arches of equal width are approximate steady state solutions of the equations of motion which co-exist with the nematic state. We compare our results to other models in the literature, in particular dry systems with no hydrodynamics, where trails, arches and polar defect ordering have also been observed
Hypothesis-driven science in large-scale studies: the case of GWAS
No full textIt is now well-appreciated by philosophers that contemporary large-scale ‘-omics’
studies in biology stand in non-trivial relationships to more orthodox hypothesisdriven approaches. These relationships have been clarified substantially by Ratti
(2015); however, there remains much more to be said regarding how an important
field of genomics cited in that work—‘genome-wide association studies’ (GWAS)—
fits into this framework. In the present article, we propose a revision to Ratti’s framework more suited to studies such as GWAS. In the process of doing so, we introduce
to the philosophical literature novel exploratory experiments in (phospho)proteomics,
and demonstrate how these experiments interplay with the above considerations
Long-term trends in population-based hospitalisation rates for myocardial infarction in England: a national database study of 3.5 million admissions, 1968–2016
No full textAim To analyse the timing and scale of temporal changes in rates of hospitalised myocardial infarction (MI) in England by age and sex from 1968 to 2016.
Methods MI admissions for adults aged 15–84 years were identified from electronic hospital data. We calculated age-standardised and age-specific rates, and examined trends using joinpoint.
Results From 1968 to 2016, there were 3.5 million admissions for MI in England (68% men). Rates increased in the early years of the study in both men and women, peaked in the mid-1980s (355 per 100 000 population in men; 127 in women) and declined by 38.8% in men and 37.4% in women from 1990 to 2011. From 2012, however, modest increases were observed in both sexes. Long-term trends in rates over the study period varied by age and sex, with those aged 70 years and older having the greatest and most sustained increases in the early years (1968–1985). During subsequent years, rates decreased in most age groups until 2010–2011. The exception was younger women (35–49 years) and men (15–34 years) who experienced significant increases from the mid-1990s to 2007 (range +2.1%/year to 4.7%/year). From 2012 onwards, rates increased in all age groups except the oldest, with the most marked increases in men aged 15–34 years (7.2%/year) and women aged 40–49 (6.9%–7.3%/year) .
Conclusion Despite substantial declines in hospital admission rates for MI in England since 1990, the burden of annual admissions remains high. Continued surveillance of trends and coronary disease preventive strategies are warranted
International primate neuroscience research regulation, public engagement and transparency opportunities
No full textScientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care (“culture of care”) and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research