The Proteolipid Protein Promoter Drives Expression outside of the Oligodendrocyte Lineage during Embryonic and Early Postnatal Development

The proteolipid protein (Plp) gene promoter is responsible for driving expression of one of the major components of myelin – PLP and its splice variant DM-20. Both products are classically thought to express predominantly in oligodendrocytes. However, accumulating evidence suggests Plp expression is more widespread than previously thought. In an attempt to create a mouse model for inducing oligodendrocyte-specific gene deletions, we have generated transgenic mice expressing a Cre recombinase cDNA under control of the mouse Plp promoter. We demonstrate Plp promoter driven Cre expression is restricted predominantly to mature oligodendrocytes of the central nervous system (CNS) at postnatal day 28. However, crosses into the Rosa26LacZ and mT/mG reporter mouse lines reveal robust and widespread Cre activity in neuronal tissues at E15.5 and E10.5 that is not strictly oligodendrocyte lineage specific. By P28, all CNS tissues examined displayed high levels of reporter gene expression well outside of defined white matter zones. Importantly, our study reinforces the emerging idea that Plp promoter activity is not restricted to the myelinating cell lineage, but rather, has widespread activity both during embryonic and early postnatal development in the CNS. Specificity of the promoter to the oligodendrocyte cell lineage, as shown through the use of a tamoxifen inducible Plp-CreERt line, occurs only at later postnatal stages. Understanding the temporal shift in Plp driven expression is of consequence when designing experimental models to study oligodendrocyte biology

Development of a chemically defined medium and discovery of new mitogenic growth factors for mouse hepatocytes: Mitogenic effects of FGF1/2 and PDGF

Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes. Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are more likely to enter into spontaneous proliferation in primary culture due to activation of cell cycle pathways resulting from collagenase perfusion. These results demonstrate unanticipated fundamental differences in growth biology of hepatocytes between the two rodent species. Copyright: © 2014 Reekie et al

Study of recent and future trends in place of death in Belgium using death certificate data: a shift from hospitals to care homes

<p>Abstract</p> <p>Background</p> <p>Since most patients prefer out-of-hospital death, place of death can be considered an indicator of end-of-life care quality. The study of trends in place of death is necessary to examine causes of shifts, to evaluate efforts to alter place of death and develop future policies. This study aims to examine past trends and future projections of place of death.</p> <p>Methods</p> <p>Analysis of death certificates (decedents aged ≥ 1 year) in Belgium (Flanders and Brussels Capital region) 1998-2007. Trends in place of death were adjusted for cause of death, sociodemographic characteristics, environmental factors, numbers of hospital beds, and residential and skilled nursing beds in care homes. Future trends were based on age- and sex-specific mortality prognoses.</p> <p>Results</p> <p>Hospital deaths decreased from 55.1% to 51.7% and care home deaths rose from 18.3% to 22.6%. The percentage of home deaths remained stable. The odds of dying in a care home versus hospital increased steadily and was 1.65 (95%CI:1.53-1.78) in 2007 compared to 1998. This increase could be attributed to the replacement of residential beds by skilled nursing beds. Continuation of these trends would result in the more than doubling of deaths in care homes and a decrease in deaths at home and in hospital by 2040.</p> <p>Conclusions</p> <p>Additional end-of-life care resources in care homes largely explain the decrease in hospital deaths. Care homes will become the main locus of end-of-life care in the future. Governments should provide sufficient skilled nursing resources in care homes to fulfil the end-of-life care preferences and needs of patients.</p

Molecular Characterization of the Mouse Superior Lateral Parabrachial Nucleus through Expression of the Transcription Factor Runx1

The ability to precisely identify separate neuronal populations is essential to the understanding of the development and function of different brain structures. This necessity is particularly evident in regions such as the brainstem, where the anatomy is quite complex and little is known about the identity, origin, and function of a number of distinct nuclei due to the lack of specific cellular markers. In this regard, the gene encoding the transcription factor Runx1 has emerged as a specific marker of restricted neuronal populations in the murine central and peripheral nervous systems. The aim of this study was to precisely characterize the expression of Runx1 in the developing and postnatal mouse brainstem.Anatomical and immunohistochemical studies were used to characterize mouse Runx1 expression in the brainstem. It is shown here that Runx1 is expressed in a restricted population of neurons located in the dorsolateral rostral hindbrain. These neurons define a structure that is ventromedial to the dorsal nucleus of the lateral lemniscus, dorsocaudal to the medial paralemniscal nucleus and rostral to the cerebellum. Runx1 expression in these cells is first observed at approximately gestational day 12.5, persists into the adult brain, and is lost in knockout mice lacking the transcription factor Atoh1, an important regulator of the development of neuronal lineages of the rhombic lip. Runx1-expressing neurons in the rostral hindbrain produce cholecystokinin and also co-express members of the Groucho/Transducin-like Enhancer of split protein family.Based on the anatomical and molecular characteristics of the Runx1-expressing cells in the rostral hindbrain, we propose that Runx1 expression in this region of the mouse brain defines the superior lateral parabrachial nucleus

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science

Acetaminophen (Paracetamol) Induces Hypothermia During Acute Cold Stress.

BACKGROUND Acetaminophen is an over-the-counter drug used to treat pain and fever, but it has also been shown to reduce core temperature (T c) in the absence of fever. However, this side effect is not well examined in humans, and it is unknown if the hypothermic response to acetaminophen is exacerbated with cold exposure. OBJECTIVE To address this question, we mapped the thermoregulatory responses to acetaminophen and placebo administration during exposure to acute cold (10 °C) and thermal neutrality (25 °C). METHODS Nine healthy Caucasian males (aged 20-24 years) participated in the experiment. In a double-blind, randomised, repeated measures design, participants were passively exposed to a thermo-neutral or cold environment for 120 min, with administration of 20 mg/kg lean body mass acetaminophen or a placebo 5 min prior to exposure. T c, skin temperature (T sk), heart rate, and thermal sensation were measured every 10 min, and mean arterial pressure was recorded every 30 min. Data were analysed using linear mixed effects models. Differences in thermal sensation were analysed using a cumulative link mixed model. RESULTS Acetaminophen had no effect on T c in a thermo-neutral environment, but significantly reduced T c during cold exposure, compared with a placebo. T c was lower in the acetaminophen compared with the placebo condition at each 10-min interval from 80 to 120 min into the trial (all p  0.05). CONCLUSION This preliminary trial suggests that acetaminophen-induced hypothermia is exacerbated during cold stress. Larger scale trials seem warranted to determine if acetaminophen administration is associated with an increased risk of accidental hypothermia, particularly in vulnerable populations such as frail elderly individuals

A review of a decade of lessons from one of the world’s largest MPAs: conservation gains and key challenges

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordtribute to global conservation targets, we review outcomes of the last decade of marine conservation research in the British Indian Ocean Territory (BIOT), one of the largest MPAs in the world. The BIOT MPA consists of the atolls of the Chagos Archipelago, interspersed with and surrounded by deep oceanic waters. Islands around the atoll rims serve as nesting grounds for sea birds. Extensive and diverse shallow and mesophotic reef habitats provide essential habitat and feeding grounds for all marine life, and the absence of local human impacts may improve recovery after coral bleaching events. Census data have shown recent increases in the abundance of sea turtles, high numbers of nesting seabirds and high fsh abundance, at least some of which is linked to the lack of recent harvesting. For example, across the archipelago the annual number of green turtle clutches (Chelonia mydas) is~20,500 and increasing and the number of seabirds is ~1 million. Animal tracking studies have shown that some taxa breed and/or forage consistently within the MPA (e.g. some reef fshes, elasmobranchs and seabirds), suggesting the MPA has the potential to provide long-term protection. In contrast, post-nesting green turtles travel up to 4000 km to distant foraging sites, so the protected beaches in the Chagos Archipelago provide a nesting sanctuary for individuals that forage across an ocean basin and several geopolitical borders. Surveys using divers and underwater video systems show high habitat diversity and abundant marine life on all trophic levels. For example, coral cover can be as high as 40–50%. Ecological studies are shedding light on how remote ecosystems function, connect to each other and respond to climate-driven stressors compared to other locations that are more locally impacted. However, important threats to this MPA have been identifed, particularly global heating events, and Illegal, Unreported and Unregulated (IUU) fshing activity, which considerably impact both reef and pelagic fshes.Bertarelli Foundatio