The Value of Comparative Animal Research : Krogh’s Principle Facilitates Scientific Discoveries

There are no conflicts of interest to declare. This paper developed from the 2016 Early Career Impact Award from the Federation of Associations in Behavioral & Brain Sciences to TJS. TJS has received funding from The Leverhulme Trust. FJPE is in receipt of funding from the BBSRC (BB/M001555/1). The National Institutes of Health has funded RDF (NS 034950, NS093277, NIMH 087930), AGO (HD079573, IOS-1354760) and AMK (HD081959). BAA is an Arnold O. Beckman postdoctoral fellow.Peer reviewedPostprin

Towards wafer-scale integration of high repetition rate passively mode-locked surface-emitting semiconductor lasers

One of the most application-relevant milestones that remain to be achieved in the field of passively mode-locked surface-emitting semiconductor lasers is the integration of the semiconductor absorber into the gain structure, enabling the realization of ultra-compact high-repetition-rate laser devices suitable for wafer-scale integration. We have recently succeeded in fabricating the key element in this concept, a quantum-dot-based saturable absorber with a very low saturation fluence, which for the first time allows stable mode locking of surface-emitting semiconductor lasers with the same mode areas on gain and absorber. Experimental results at high repetition rates of up to 30GHz are show

Measuring the Redshift Dependence of The Cosmic Microwave Background Monopole Temperature With Planck Data

We study the capability of Planck data to constrain deviations of the cosmic microwave background (CMB) blackbody temperature from adiabatic evolution using the thermal Sunyaev-Zeldovich anisotropy induced by clusters of galaxies. We consider two types of data sets depending on how the cosmological signal is removed: using a CMB template or using the 217 GHz map. We apply two different statistical estimators, based on the ratio of temperature anisotropies at two different frequencies and on a fit to the spectral variation of the cluster signal with frequency. The ratio method is biased if CMB residuals with amplitude approximately 1 microK or larger are present in the data, while residuals are not so critical for the fit method. To test for systematics, we construct a template from clusters drawn from a hydro-simulation included in the pre-launch Planck Sky Model. We demonstrate that, using a proprietary catalog of X-ray-selected clusters with measured redshifts, electron densities, and X-ray temperatures, we can constrain deviations of adiabatic evolution, measured by the parameter in the redshift scaling T (z) = T0(1 + z)(sup 1alpha), with an accuracy of sigma(sub alpha) = 0.011 in the most optimal case and with sigma alpha = 0.018 for a less optimal case. These results represent a factor of 2-3 improvement over similar measurements carried out using quasar spectral lines and a factor 6-20 with respect to earlier results using smaller cluster samples

Disrupted seasonal biology impacts health, food security and ecosystems

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research

The ABCD of usability testing

We introduce a methodology for tracking and auditing feedback, errors and suggestions for software packages. This short paper describes how we innovate on the evaluation mechanism, introducing an (Antecedent, Barrier, Consequence and Development) ABCD form, embedded within an eParticipation platform to enable end users to easily report on any usability issues. This methodology will be utilised to improve the STEP cloud eParticipation platform (part of the current STEP Horizon2020 project http://step4youth.eu. The platform is currently being piloted in real life contexts, with the participation of public authorities that are integrating the eParticipation platform into their regular decision-making practices. The project is involving young people, through engagement and motivation strategies and giving them a voice in Environmental decision making at the local level. The pilot evaluation aims to demonstrate how open engagement needs to be embedded within public sector processes and the usability methodology reported here will help to identify the key barriers for wide scale deployment of the platform

Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging

Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain – insights that would be difficult or impossible to extract by use of radiolabeled compounds

Conserved Expression of the Glutamate NMDA Receptor 1 Subunit Splice Variants during the Development of the Siberian Hamster Suprachiasmatic Nucleus

Glutamate neurotransmission and the N-methyl-D-aspartate receptor (NMDAR) are central to photic signaling to the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). NMDARs also play important roles in brain development including visual input circuits. The functional NMDAR is comprised of multiple subunits, but each requiring the NR1 subunit for normal activity. The NR1 can be alternatively spliced to produce isoforms that confer different functional properties on the NMDAR. The SCN undergoes extensive developmental changes during postnatal life, including synaptogenesis and acquisition of photic signaling. These changes are especially important in the highly photoperiodic Siberian hamster, in which development of sensitivity to photic cues within the SCN could impact early physiological programming. In this study we examined the expression of NR1 isoforms in the hamster at different developmental ages. Gene expression in the forebrain was quantified by in situ hybridization using oligonucleotide probes specific to alternatively spliced regions of the NR1 heteronuclear mRNA, including examination of anterior hypothalamus, piriform cortex, caudate-putamen, thalamus and hippocampus. Gene expression analysis within the SCN revealed the absence of the N1 cassette, the presence of the C2 cassette alone and the combined absence of C1 and C2 cassettes, indicating that the dominant splice variants are NR1-2a and NR1-4a. Whilst we observe changes at different developmental ages in levels of NR1 isoform probe hybridization in various forebrain structures, we find no significant changes within the SCN. This suggests that a switch in NR1 isoform does not underlie or is not produced by developmental changes within the hamster SCN. Consistency of the NR1 isoforms would ensure that the response of the SCN cells to photic signals remains stable throughout life, an important aspect of the function of the SCN as a responder to environmental changes in quality/quantity of light over the circadian day and annual cycle

Scents of Adolescence: The Maturation of the Olfactory Phenotype in a Free-Ranging Mammal

Olfaction is an important sensory modality for mate recognition in many mammal species. Odorants provide information about the health status, genotype, dominance status and/or reproductive status. How and when odor profiles change during sexual maturation is, however often unclear, particularly in free-ranging mammals. Here, we investigated whether the wing sac odorant of male greater sac-winged bats (Saccopteryx bilineata, Emballonuridae) differs between young and adults, and thus offers information about sexual maturity to potential mating partners. Using gas chromatography – mass spectrometry, we found differences in the odorants of young and adult males prior and during, but not after the mating period. The wing sac odorant of adult males consists of several substances, such as Pyrocoll, 2,6,10-trimethyl-3-oxo-6,10-dodecadienolide, and a so far unidentified substance; all being absent in the odor profiles of juveniles prior to the mating season. During the mating season, these substances are present in most of the juvenile odorants, but still at lower quantities compared to the wing sac odorants of adults. These results suggest that the wing sac odorant of males encodes information about age and/or sexual maturity. Although female S. bilineata start to reproduce at the age of half a year, most males of the same age postpone the sexual maturation of their olfactory phenotype until after the first mating season

Antibody mediated targeting of the FGFR1c isoform increases glucose uptake in white and brown adipose tissue in male mice

The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycaemia and protect from diet- and genetically-induced obesity in rodents and non-human primates. However, it is currently unknown which tissue(s) contribute to this glucose lowering effect. Thus, to elucidate this effect we treated euglycaemic mice with H7, a monoclonal antibody which selectively targets the FGFR1c isoform, and employed whole body positron emission computed tomography with a glucose tracer (18F-flurodeoxyglucose). Treatment with H7 increased basal glucose uptake in white and brown adipose tissues (WAT and BAT respectively), the brain and liver, but reduced it in the quadricep muscles. Consequentially, blood glucose was significantly reduced in response to treatment. Under insulin-stimulated conditions, the effects of H7 were maintained in WAT, BAT, liver and muscle. Treatment with H7 decreased triglyceride content and increased adipose triglyceride lipase content in white adipose tissue, whilst increasing activation of acetyl coenzyme A carboxylase, suggesting futile cycling of triglycerides, albeit favouring net hydrolysis. We demonstrated, in vitro, this is a direct effect of treatment in adipose tissue as basal cellular respiration and glucose uptake were increased in response to treatment. Taken together, these data suggest that antibody-mediated targeting of FGFR1c exerts its powerful glucose-lowering efficacy primarily due to increased glucose uptake in adipose tissue

Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake

OBJECTIVE-Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS - We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebro-ventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice. RESULTS - Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of α-melanocyte-stimulating hormone (α-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the α-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice. CONCLUSIONS - This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system. © 2010 by the American Diabetes Association