Conservation and flexibility in the gene regulatory landscape of heliconiine butterfly wings

Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100004440Abstract: Background: Many traits evolve by cis-regulatory modification, by which changes to noncoding sequences affect the binding affinity for available transcription factors and thus modify the expression profile of genes. Multiple examples of cis-regulatory evolution have been described at pattern switch genes responsible for butterfly wing pattern polymorphism, including in the diverse neotropical genus Heliconius, but the identities of the factors that can regulate these switch genes have not been identified. Results: We investigated the spatial transcriptomic landscape across the wings of three closely related butterfly species, two of which have a convergently evolved co-mimetic pattern and the other having a divergent pattern. We identified candidate factors for regulating the expression of wing patterning genes, including transcription factors with a conserved expression profile in all three species, and others, including both transcription factors and Wnt pathway genes, with markedly different profiles in each of the three species. We verified the conserved expression profile of the transcription factor homothorax by immunofluorescence and showed that its expression profile strongly correlates with that of the selector gene optix in butterflies with the Amazonian forewing pattern element ‘dennis.’ Conclusion: Here we show that, in addition to factors with conserved expression profiles like homothorax, there are also a variety of transcription factors and signaling pathway components that appear to vary in their expression profiles between closely related butterfly species, highlighting the importance of genome-wide regulatory evolution between species

The effect of irradiation-induced disorder on the conductivity and critical temperature of the organic superconductor κ\kappa-(BEDT-TTF)2_2Cu(SCN)2_2

We have introduced defects into clean samples of the organic superconductor $\kappa$-(BEDT-TTF)$_2$Cu(SCN)$_2$ in order to determine their effect on the temperature dependence of the conductivity and the critical temperature $T_{\rm c}$. We find a violation of Matthiessen's rule that can be explained by a model of the conductivity involving a defect-assisted interlayer channel which acts in parallel with the band-like conductivity. We observe an unusual dependence of $T_{\rm c}$ on residual resistivity which is not consistent with the generalised Abrikosov-Gor'kov theory for an order parameter with a single component, providing an important constraint on models of the superconductivity in this material

Short-term studies underestimate 30-generation changes in a butterfly metapopulation

Most studies of rare and endangered species are based on work carried out within one generation, or over one to a few generations of the study organism. We report the results of a study that spans 30 generations (years) of the entire natural range of a butterfly race that is endemic to 35 km2 of north Wales, UK. Short-term studies (surveys in single years and dynamics over 4 years) of this system led to the prediction that the regional distribution would be quite stable, and that colonization and extinction dynamics would be relatively unimportant. However, a longer-term study revealed unexpectedly high levels of population turnover (local extinction and colonization), affecting 18 out of the 20 patches that were occupied at any time during the period. Modelling the system (using the 'incidence function model' (IFM) for metapopulations) also showed higher levels of colonization and extinction with increasing duration of the study. The longer-term dynamics observed in this system can be compared, at a metapopulation level, with the increased levels of variation observed with increasing time that have been observed in single populations. Long-term changes may arise from local changes in the environment that make individual patches more or less suitable for the butterfly, or from unusual colonization or extinction events that take metapopulations into alternative states. One implication is that metapopulation and population viability analyses based on studies that cover only a few animal or plant generations may underestimate extinction threats

Late summer changes in burning conditions in the boreal regions and their implications for NO x and CO emissions from boreal fires

Copyright © 2008 American Geophysical Union. All Rights Reserved.Building emission inventories for the fires in boreal regions remains a challenging task with significant uncertainties in the methods used. In this work, we assess the impact of seasonal trends in fuel consumption and flaming/smoldering ratios on emissions of species dominated by flaming combustion (e.g., NO x ) and species dominated by smoldering combustion (e.g., CO). This is accomplished using measurements of CO and NO y at the free tropospheric Pico Mountain observatory in the central North Atlantic during the active boreal fire seasons of 2004 and 2005. ΔNO y /ΔCO enhancement ratios in aged fire plumes had higher values in June-July (7.3 × 10−3 mol mol−1) relative to the values in August-September (2.8 × 10−3 mol mol−1), indicating that NO x /CO emission ratios declined significantly as the fire season progressed. This is consistent with our understanding that an increased amount of fuel is consumed via smoldering combustion during late summer, as deeper burning of the drying organic soil layer occurs. A major growth in fuel consumption per unit area is also expected, due to deeper burning. Emissions of CO and NO x from North American boreal fires were estimated using the Boreal Wildland Fire Emissions Model, and their long-range transport to the sampling site was modeled using FLEXPART. These simulations were generally consistent with the observations, but the modeled seasonal decline in the ΔNO y /ΔCO enhancement ratio was less than observed. Comparisons using alternative fire emission injection height scenarios suggest that plumes with the highest CO levels at the observatory were lofted well above the boundary layer, likely as a result of intense crown fires

The X-ray Luminosity Function of Nearby Rich and Poor Clusters of Galaxies: A Cosmological Probe

In this letter, we present a new determination of the local (z<0.09) X-ray luminosity function (XLF) using a large, statistical sample of 294 Abell clusters and the ROSAT All-Sky-Survey. Given our large sample size, we have reduced errors by a factor of two for L(X)(0.5-2keV)>10^43 ergs/sec. We combine our data with previous work in order to explore possible constraints imposed by the shape of the XLF on cosmological models. A set of currently viable cosmologies is used to construct theoretical XLFs assuming Lx is proportional to M^p and a sigma_8-Omega_0 constraint (from Viana & Liddle 1996) based on the local X-ray temperature function. We fit these models to our observed XLF and verify that the simplest adiabatic, analytic scaling relation (e.g. Kaiser 1986) disagrees strongly with observations. If we assume that clusters can be described by the pre-heated, constant core-entropy models of Evrard & Henry (1991) then the observed XLF is consistent only with 0.1 < Omega_0 < 0.4 if the energy per unit mass in galaxies is roughly equal to the gas energy (ie if beta=1). (abridged)Comment: 4 pages, 2 figures, accepted for publication in ApJ Letters. uses emulateapj.st

Total wrist arthrodesis with and without arthrodesis of the carpoMetacarpal joint (WAWWAM):study protocol

Abstract Background It is controversial whether or not the carpometacarpal joint (CMCJ) should be included in total wrist arthrodesis (TWA). Complications commonly occur at this site and studies examining its inclusion and exclusion are conflicting. A randomised clinical trial comparing wrist arthrodesis with CMCJ arthrodesis and spanning plate to wrist arthrodesis with CMCJ preservation and non-CMCJ spanning plate has not been performed. Method A single centre randomised clinical trial including 120 adults with end-stage isolated wrist arthritis will be performed to compare TWA with and without the CMCJ included in the arthrodesis. The primary outcome is complications in the first post-operative year. Secondary outcomes are Disabilities of the Arm, Shoulder and Hand (DASH) score, Patient Rated Wrist Evaluation (PRWE) and grip strength measured at 1, 2 and 5 years. Late complications, return to work and satisfaction will also be recorded. Discussion It is unknown whether the CMCJ should be included in TWA. This trial will contribute to an improved understanding of optimal management of the CMCJ in total wrist arthrodesis. Trial registration This trial was prospectively registered with the Australia New Zealand Clinical Trials Registry with identifying number ACTRN12621000169842 on the 16th February 2021. WHO: U1111–12626523. ANZCTR: ACTRN1262100016984

Implications of leg length for metabolic health and fitness

BACKGROUND AND OBJECTIVES: Several studies have linked longer legs with favorable adult metabolic health outcomes and greater offspring birth weight. A recent Mendelian randomization study suggested a causal link between height and cardiometabolic risk; however, the underlying reasons remain poorly understood. METHODOLOGY: Using a cross-sectional design, we tested in a convenience sample of 70 healthy young women whether birth weight and tibia length as markers of early-life conditions associated more strongly with metabolically beneficial traits like organ size and skeletal muscle mass (SMM) than a statistically derived height-residual variable indexing later, more canalized growth. RESULTS: Consistent with the ‘developmental origins of health and disease’ hypothesis, we found relatively strong associations of tibia length—but not birth weight—with adult organ size, brain size, SMM and resting energy expenditure measured by magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry and indirect calorimetry, respectively. CONCLUSIONS AND IMPLICATIONS: Building on prior work, these results suggest that leg length is a sensitive marker of traits directly impacting metabolic and reproductive health. Alongside findings in the same sample relating tibia length and height-residual to MRI-measured pelvic dimensions, we suggest there may exist a degree of coordination in the development of long bone, lean mass and pelvic traits, possibly centered on early, pre-pubertal growth periods. Such phenotypic coordination has important implications for fitness, serving to benefit both adult health and the health of offspring in subsequent generations

Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

&lt;b&gt;Background:&lt;/b&gt; Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2–3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objective:&lt;/b&gt; To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Design, setting, and participants:&lt;/b&gt; RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Outcome measurements and statistical analysis:&lt;/b&gt; We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results and limitations:&lt;/b&gt; We identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions:&lt;/b&gt; RNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.&lt;p&gt;&lt;/p&gt

Hollow silicon microneedle fabrication using advanced plasma etch technologies for applications in transdermal drug delivery

A novel production process flow is presented here for the manufacture of hollow silicon microneedles using deep reactive-ion etching (DRIE) technology. The patent-pending three-step process flow has been developed to produce multiple arrays of sharp-tipped, hollow microneedles, which facilitate easy insertion and controlled fluid injection into excised skin samples. A bevelled tip and vertical sidewalls for the microneedle have been achieved with good uniformity, despite >45% open etch area. Processing steps and etch challenges are discussed, and preliminary skin testing results are presented, showing effective needle insertion and delivery of fluorescent dye into ex vivo skin from human breast tissue