Multispectral reflectance imaging of brain activation in rodents: methodological study of the differential path length estimations and first in vivo recordings in the rat olfactory bulb

International audienceDynamic maps of relative changes in blood volume and oxygenation following brain activation are obtained using multispectral reflectance imaging. The technique relies on optical absorption modifications linked to hemodynamic changes. The relative variation of hemodynamic parameters can be quantified using the modified Beer-Lambert Law if changes in reflected light intensities are recorded at two wavelengths or more and the differential path length (DP) is known. The DP is the mean path length in tissues of backscattered photons and varies with wavelength. It is usually estimated using Monte Carlo simulations in simplified semi-infinite homogeneous geometries. Here we consider the use of multilayered models of the somatosensory cortex (SsC) and olfactory bulb (OB), which are common physiological models of brain activation. Simulations demonstrate that specific DP estimation is required for SsC and OB, specifically for wavelengths above 600 nm. They validate the hypothesis of a constant path length during activation and show the need for specific DP if imaging is performed in a thinned-skull preparation. The first multispectral reflectance imaging data recorded in vivo during OB activation are presented, and the influence of DP on the hemodynamic parameters and the pattern of oxymetric changes in the activated OB are discusse

Lady Llanover and the creation of a Welsh cultural utopia

Lady Llanover (1802-1896) was one of the most important female contributors to the nineteenth century Welsh cultural revival and although historians have paid her a certain amount of attention, her life and works have never before undergone a full study. The purpose of this thesis is to analyse her place in the history of nineteenth century Wales and to consider the view that her life's actions ultimately led her to attempt to create a Welsh cultural Utopia for the Welsh tenants on her estate at Llanover in Monmouthshire. This study is not a conventional biography and therefore not every detail of Lady Llanover's life can feature, rather this thesis thematically explores her fascination with Wales, Welsh traditions and culture in order to throw light on what became a full and life long project. This thesis will focus on Lady Llanover's tenacious personality and explore her identity. It will take into account the economic, social and political changes that occurred in nineteenth century Welsh society and consider how Lady Llanover reacted and responded to such changes. Moreover, it will ask what influenced Lady Llanover's cultural ideals and reveal how her home was transformed into a centre of Welsh cultural scholarship. It will be revealed how she used her position of power to influence others and how this became an important aspect of her campaigns to safeguard her version of Welsh culture. She famously showed a special interest in the Welsh costume, triple harp and the Welsh language and therefore no work written on her could omit a discussion of those topics but what this thesis seeks to demonstrate is that even though Lady Llanover eventually came to be regarded by some, as an obsessive eccentric, she pored her energy into creating a haven for her version of Welsh culture.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Bioinformatics approaches to studying mesenchymal stem cell behaviour on artificial extracellular matrices

Stem cells have potential use in tissue engineering and regenerative medicine, and as they underlie the development and maintenance of tissues throughout life, how they function is also of interest. The extracellular matrix presents a variety of physical and chemical signals to stem cells to regulate their behaviour in vivo. Recapitulation of these signals in vitro could enable the control of explanted stem cells to facilitate their study. Biomaterials that display extracellular-matrix inspired cues are one way to do this. By combining surface chemistry and fibronectin, an extracellular matrix protein with cell binding and growth factor binding domains, the conformation of fibronectin was controlled to create artificial extracellular matrices. Adsorbed on a film of poly(ethyl acrylate), fibronectin adopted a network-like conformation which ostensibly increased the exposure of its functional domains, whereas on poly(methyl acrylate) it had an unconnected organisation with more concealed domains. The growth factors bone morphogenetic protein 2 and vascular endothelial growth factor, known to bind to fibronectin, were adsorbed to the network conformation. Prior studies have reported that these artificial extracellular matrices differentially affected cell behaviour. In this work, the growth and differentiation of human bone marrow stromal cell surface marker-1 positive mesenchymal stem cells was characterised on these substrates. It was shown that all combinations of fibronectin conformation and growth factors supported cell adhesion and growth. A high-content image processing and analysis pipeline was developed to take advantage of automated fluorescence microscopy to show that cytoskeletal, nuclei, and differentiation-associated protein features distinguished cells cultured on the artificial extracellular matrices. Those on the isolated conformation and the network conformation with vascular endothelial growth factor were particularly distinct. Further, metabolomics revealed several metabolic pathways that differed in activity between the fibronectin conformations. To analyse the metabolomics data a Quick Results web application was built, which extended the existing Polyomics integrated Metabolomics Pipeline. The application improves the visualisation and interpretation of untargeted liquid chromatography—mass spectrometry metabolomics data. This work gives insights into how these artificial extracellular matrices can control stem cell behaviour, and developed and demonstrated several tools to improve the understanding of these biomaterials and the use of metabolomics data

Lady Llanover and the creation of a Welsh cultural utopia

Lady Llanover (1802-1896) was one of the most important female contributors to the nineteenth century Welsh cultural revival and although historians have paid her a certain amount of attention, her life and works have never before undergone a full study. The purpose of this thesis is to analyse her place in the history of nineteenth century Wales and to consider the view that her life's actions ultimately led her to attempt to create a Welsh cultural Utopia for the Welsh tenants on her estate at Llanover in Monmouthshire. This study is not a conventional biography and therefore not every detail of Lady Llanover's life can feature, rather this thesis thematically explores her fascination with Wales, Welsh traditions and culture in order to throw light on what became a full and life long project. This thesis will focus on Lady Llanover's tenacious personality and explore her identity. It will take into account the economic, social and political changes that occurred in nineteenth century Welsh society and consider how Lady Llanover reacted and responded to such changes. Moreover, it will ask what influenced Lady Llanover's cultural ideals and reveal how her home was transformed into a centre of Welsh cultural scholarship. It will be revealed how she used her position of power to influence others and how this became an important aspect of her campaigns to safeguard her version of Welsh culture. She famously showed a special interest in the Welsh costume, triple harp and the Welsh language and therefore no work written on her could omit a discussion of those topics but what this thesis seeks to demonstrate is that even though Lady Llanover eventually came to be regarded by some, as an obsessive eccentric, she pored her energy into creating a haven for her version of Welsh culture

The local GLP-1 system in the olfactory bulb is required for odor-evoked cephalic phase of insulin release in mice

Objective: The olfactory bulb (OB) codes for sensory information and contributes to the control of energy metabolism by regulating foraging and cephalic phase responses. Mitral cells are the main output neurons of the OB. The glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) system in the OB (GLP-1ᴼᴮ) has been shown to be a major regulator of mitral cell activity but its function in vivo is unclear. Therefore, we investigated the role of GLP-1ᴼᴮ in foraging behavior and odor-evoked Cephalic Phase Insulin Release (CPIR)./ Methods and results: By fluorescent labeling, we confirmed the presence of GLP-1 producing neurons and the expression of GLP-1R in the mouse OB. In response to food odor presentation, we collected blood, quantified plasma insulin by ELISA and showed the existence of an odor-evoked CPIR in lean mice but its absence in obese animals. Expression of shRNA against preproglucagon mRNA in the OB resulted in blunted CPIR in lean mice. Injecting Exendin (9-39), a GLP-1R antagonist, into the OB of lean mice also resulted in decreased CPIR. Since parasympathetic cholinergic input to the pancreas is known to be partly responsible for CPIR, we systemically administered the muscarinic M3 receptor antagonist 4-DAMP which resulted in a reduced odor-evoked CPIR. Finally, local injection of Exendin (9-39) in the OB extinguished olfactory foraging in lean mice whereas the injection of the GLP-1R agonist Exendin-4 rescued the loss of foraging behavior in obese mice./ Conclusions: Our results demonstrate that GLP-1ᴼᴮ controls olfactory foraging and is required for odor-evoked CPIR. We describe a new crucial brain function for GLP-1 and GLP-1R expressed within the brain

Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice

Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning

Knockdown High Mobility Nucleosomal Binding Proteins 2 (HMGN2) Alter the Histone Modification H4K4me3 and H3K27me3 and Regulates Stem Cells Pluripotency

No abstract available

PiMP my metabolome:An integrated, web-based tool for LC-MS metabolomics data

Summary: The Polyomics integrated Metabolomics Pipeline (PiMP) fulfils an unmet need in metabolomics data analysis. PiMP offers automated and user-friendly analysis from mass spectrometry data acquisition to biological interpretation. Our key innovations are the Summary Page, which provides a simple overview of the experiment in the format of a scientific paper, containing the key findings of the experiment along with associated metadata; and the Metabolite Page, which provides a list of each metabolite accompanied by ‘evidence cards’, which provide a variety of criteria behind metabolite annotation including peak shapes, intensities in different sample groups and database information. Availability: PiMP is available at http://polyomics.mvls.gla.ac.uk, and access is freely available on request. 50 GB of space is allocated for data storage, with unrestricted number of samples and analyses per user. Source code is available at https://github.com/RonanDaly/pimp and licensed under the GPL