Otx but Not Mitf Transcription Factors Are Required for Zebrafish Retinal Pigment Epithelium Development

Otx and Mitf transcription factors have been implicated in the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific roles in the development of the RPE have not been fully defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2) and two Mitf transcription factors (Mitfa and Mitfb) in the development of the zebrafish RPE was explored in these experiments. The loss of Otx activity through morpholino knockdown produced variable eye defects, ranging from delayed RPE pigmentation to severe coloboma, depending on the combination of Otx factors that were targeted. Expression analysis through in situ hybridization demonstrates that otxtranscription factors are necessary for the proper expression of mitfa and mitfb while Mitf transcription factors are not required for the expression of otx genes. Surprisingly, the loss of Mitf activity in mitfa, mitfb, or double mitf mutant zebrafish had no effect on RPE pigmentation or development. Moreover, histological analysis revealed that retinal lamination is unaffected inmitf mutants, as well as in otx morphants, even in regions lacking RPE. Otx and Mitf combined loss of function experiments suggest that mitfa and mitfb may still influence zebrafish RPE development. This is further supported by the ability of mitfa to induce pigmentation in the zebrafish retina when misexpressed. These findings suggest that one or more Otx targets in addition to mitfa and mitfb, possibly another mitf family member, are necessary for development of the RPE in zebrafish

Thin-sheet flow between coalescing bubbles

When two spherical bubbles touch, a hole is formed in the fluid sheet between them, and capillary pressure acting on its tightly curved edge drives an outward radial flow which widens the hole joining the bubbles. Recent images of the early stages of this process (Paulsen et al., Nat. Commun., vol. 5, 2014) show that the radius of the hole $r_{\!E}$ at time $t$ grows proportional to $t^{1/2}$, and that the rate is dependent on the fluid viscosity. Here, we explain this behaviour in terms of similarity solutions to a third-order system of radial extensional-flow equations for the thickness and velocity of the sheet of fluid between the bubbles, and determine the growth rate as a function of the Ohnesorge number $\mathit{Oh}$. The initially quadratic sheet profile allows the ratio of viscous and inertial effects to be independent of time. We show that the sheet is slender for $r_{\!E}\ll a$ if $\mathit{Oh}\gg 1$, where $a$ is the bubble radius, but only slender for $r_{\!E}\ll \mathit{Oh}^{2}a$ if $\mathit{Oh}\ll 1$ due to a compressional boundary layer of length $L\propto \mathit{Oh}\,r_{\!E}$, after which there is a change in the structure but not the speed of the retracting sheet. For $\mathit{Oh}\ll 1$, the detailed analysis justifies a simple momentum-balance argument, which gives the analytic prediction $r_{\!E}\sim (32a{\it\gamma}/3{\it\rho})^{1/4}t^{1/2}$, where ${\it\gamma}$ is the surface tension and ${\it\rho}$ is the density.J.P.M. acknowledges an Engineering and Physical Sciences Research Council studentship. C.R.A. and O.A.B. acknowledge the Donors of the American Chemical Society Petroleum Research Fund for partial support of this research. All data accompanying this publication are directly available within the publication.This is the accepted manuscript of a paper published in the Journal of Fluid Mechanics (Munro JP, Anthony CR, Basaran OA, Lister JR, Journal of Fluid Mechanics, 2015, 773, doi:10.1017/jfm.2015.253). The final version is available at http://dx.doi.org/10.1017/jfm.2015.25

Climate Change and Biosphere Response: Unlocking the Collections Vault

Natural history collections (NHCs) are an important source of the long-term data needed to understand how biota respond to ongoing anthropogenic climate change. These include taxon occurrence data for ecological modeling, as well as information that can be used to reconstruct mechanisms through which biota respond to changing climates. The full potential of NHCs for climate change research cannot be fully realized until high-quality data sets are conveniently accessible for research, but this requires that higher priority be placed on digitizing the holdings most useful for climate change research (e.g., whole-biota studies, time series, records of intensively sampled common taxa). Natural history collections must not neglect the proliferation of new information from efforts to understand how present-day ecosystems are responding to environmental change. These new directions require a strategic realignment for many NHC holders to complement their existing focus on taxonomy and systematics. To set these new priorities, we need strong partnerships between NHC holders and global change biologists

Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder

Patients with obsessive-compulsive disorder (OCD) show an increased error-related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder-specific.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79361/1/j.1469-8986.2010.00988.x.pd

Assessing the farm-scale impacts of cover crops and non-inversion tillage regimes on nutrient losses from an arable catchment

The efficacy of cover crops and non-inversion tillage regimes at minimising farm-scale nutrient losses were assessed across a large, commercial arable farm in Norfolk, UK. The trial area, covering 143 ha, was split into three blocks: winter fallow with mouldboard ploughing (Block J); shallow non-inversion tillage with a winter oilseed radish (Raphanus sativus) cover crop (Block P); and direct drilling with a winter oilseed radish cover crop (Block L). Soil, water and vegetation chemistry across the trial area were monitored over the 2012/13 (pre-trial), 2013/14 (cover crops and non-inversion tillage) and 2014/15 (non-inversion tillage only) farm years. Results revealed oilseed radish reduced nitrate (NO3¬¬-N) leaching losses in soil water by 75–97% relative to the fallow block, but had no impact upon phosphorus (P) losses. Corresponding reductions in riverine NO3¬¬-N concentrations were not observed, despite the trial area covering 20% of the catchment. Mean soil NO3¬¬-N concentrations were reduced by ~77% at 60–90 cm depth beneath the cover crop, highlighting the ability of deep rooting oilseed radish to scavenge nutrients from deep within the soil profile. Alone, direct drilling and shallow non-inversion tillage were ineffective at reducing soil water NO3¬¬-N and P concentrations relative to conventional ploughing. Applying starter fertiliser to the cover crop increased radish biomass and nitrogen (N) uptake, but resulted in net N accumulation within the soil. There was negligible difference between the gross margins of direct drilling (£731 ha-1) and shallow non-inversion tillage (£758 ha-1) with a cover crop and conventional ploughing with fallow (£745 ha-1), demonstrating farm productivity can be maintained whilst mitigating diffuse pollution. The results presented here support the wider adoption of winter oilseed radish cover crops to reduce NO3¬¬-N leaching losses in arable systems, but caution that it may take several years before catchment-scale impacts downstream are detected

Barley heads east: Genetic analyses reveal routes of spread through diverse Eurasian landscapes

One of the world’s most important crops, barley, was domesticated in the Near East around 11,000 years ago. Barley is a highly resilient crop, able to grown in varied and marginal environments, such as in regions of high altitude and latitude. Archaeobotanical evidence shows that barley had spread throughout Eurasia by 2,000 BC. To further elucidate the routes by which barley cultivation was spread through Eurasia, simple sequence repeat (SSR) analysis was used to determine genetic diversity and population structure in three extant barley taxa: domesticated barley (Hordeum vulgare L. subsp. vulgare), wild barley (H. vulgare subsp. spontaneum) and a six-rowed brittle rachis form (H. vulgare subsp. vulgare f. agriocrithon (Åberg) Bowd.). Analysis of data using the Bayesian clustering algorithm InStruct suggests a model with three ancestral genepools, which captures a major split in the data, with substantial additional resolution provided under a model with eight genepools. Our results indicate that H. vulgare subsp. vulgare f. agriocrithon accessions and Tibetan Plateau H. vulgare subsp. spontaneum are closely related to the H. vulgare subsp. vulgare in their vicinity, and are therefore likely to be feral derivatives of H. vulgare subsp. vulgare. Under the eight genepool model, cultivated barley is split into six ancestral genepools, each of which has a distinct distribution through Eurasia, along with distinct morphological features and flowering time phenotypes. The distribution of these genepools and their phenotypic characteristics is discussed together with archaeological evidence for the spread of barley eastwards across Eurasia

WALLABY Early Science - I. The NGC 7162 Galaxy Group

We present Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY) early science results from the Australian Square Kilometre Array Pathfinder (ASKAP) observations of the NGC 7162 galaxy group. We use archival HIPASS and Australia Telescope Compact Array (ATCA) observations of this group to validate the new ASKAP data and the data reduction pipeline ASKAPsoft. We detect six galaxies in the neutral hydrogen (HI) 21-cm line, expanding the NGC 7162 group membership from four to seven galaxies. Two of the new detections are also the first HI detections of the dwarf galaxies, AM 2159-434 and GALEXASC J220338.65-431128.7, for which we have measured velocities of $cz=2558$ and $cz=2727$ km s$^{-1}$, respectively. We confirm that there is extended HI emission around NGC 7162 possibly due to past interactions in the group as indicated by the $40^{\circ}$ offset between the kinematic and morphological major axes for NGC 7162A, and its HI richness. Taking advantage of the increased resolution (factor of $\sim1.5$) of the ASKAP data over archival ATCA observations, we fit a tilted ring model and use envelope tracing to determine the galaxies' rotation curves. Using these we estimate the dynamical masses and find, as expected, high dark matter fractions of $f_{\mathrm{DM}}\sim0.81-0.95$ for all group members. The ASKAP data are publicly available.Comment: 20 pages, 11 figures, accepted for publication in MNRA

Ethical and methodological issues in engaging young people living in poverty with participatory research methods

This paper discusses the methodological and ethical issues arising from a project that focused on conducting a qualitative study using participatory techniques with children and young people living in disadvantage. The main aim of the study was to explore the impact of poverty on children and young people's access to public and private services. The paper is based on the author's perspective of the first stage of the fieldwork from the project. It discusses the ethical implications of involving children and young people in the research process, in particular issues relating to access and recruitment, the role of young people's advisory groups, use of visual data and collection of data in young people's homes. The paper also identifies some strategies for addressing the difficulties encountered in relation to each of these aspects and it considers the benefits of adopting participatory methods when conducting research with children and young people

NQO2 is a reactive oxygen species generating off-target for acetaminophen

[Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity