Membrane properties of ameboid microglial cells in the corpus callosum slice from early postnatal mice

Microglial cells in culture are distinct from neurons, macroglial cells, and macrophages of tissues other than brain with respect to their membrane current pattern. To assess these cells in the intact tissue, we have applied the patch-clamp technique to study membrane currents in microglial cells from acute, whole brain slices of 6-9-d-old mice in an area of microglial cell invasion, the cingulum. As strategies to identify microglial cells prior to or after recording, we used binding and incorporation of Dil-acetylated low-density lipoproteins, binding of fluorescein isothiocyanate-coupled IgG via microglial Fc-receptors, and ultrastructural characterization. As observed previously for cultured microglial cells, depolarizing voltage steps activate only minute if any membrane currents, while hyperpolarizing voltage steps induced large inward currents. These currents exhibited properties of the inwardly rectifying K+ channel in that the reversal potential depended on the transmembrane K+ gradient, inactivation time constants decreased with hyperpolarization, and the current was blocked by tetraethylammonium (50 mM). This study represents the first attempt to assess microglial cells in situ using electrophysiological methods. It opens the possibility to address questions related to the function of microglial cells in the intact CNS

Extracellular ATP activates a cation conductance and a K+ conductance in cultured microglial cells from mouse brain

Microglial cells have important functions during regenerative processes after brain injury. It is well established that they rapidly respond to damage to the brain tissue. Stages of activation are associated with changes of cellular properties such as proliferation rate or expression of surface antigens. Yet, nothing is known about signal substances leading to the rapid changes of membrane properties, which may be required to initiate the transition from one cell stage into another. From our present study, using the patch-clamp technique, we report that cultured microglial cells obtained from mouse or rat brain respond to extracellularly applied ATP with the activation of a cation conductance. Additionally, in the majority of cells an outwardly directed K+ conductance was activated with some delay. Since ADP, AMP, and adenosine (in descending order) were less potent or ineffective in inducing the cation conductance, the involvement of a P2 purinergic receptor is proposed. The receptor activation is accompanied by an increase of cytosolic Ca2+ as determined by a fura-2-based Ca(2+)-imaging system. This ATP receptor could enable microglial cells to respond to transmitter release from nerve endings with ATP as a transmitter or cotransmitter or to the death of cells with resulting leakage of ATP

Effective conductivity of composites of graded spherical particles

We have employed the first-principles approach to compute the effective response of composites of graded spherical particles of arbitrary conductivity profiles. We solve the boundary-value problem for the polarizability of the graded particles and obtain the dipole moment as well as the multipole moments. We provide a rigorous proof of an {\em ad hoc} approximate method based on the differential effective multipole moment approximation (DEMMA) in which the differential effective dipole approximation (DEDA) is a special case. The method will be applied to an exactly solvable graded profile. We show that DEDA and DEMMA are indeed exact for graded spherical particles.Comment: submitted for publication

Containing the burden of infectious diseases is everyone’s responsibility.:A call for an integrated strategy for developing and promoting hygiene behaviour change in home and everyday life

Across the world, health agencies recognize the profound impact of infectious disease on health and prosperity. Equally, they recognize that prevention is central to fighting infection, and that hygiene in home and everyday life (HEDL) is a key part of this. A current driver is the part that hygienei plays in tackling antibiotic resistance, but it also reflects growing numbers of people at greater risk of infection being cared for in the community. Sustaining the quality of state-funded healthcare requires that the public take greater responsibility for their own health, including protecting themselves and their families against infection. Hygiene must be must be everyone’s responsibility. However, if we are to be successful in promoting hygiene as part of public health, there are barriers which need to be overcome. A key issue is the need to balance evidence of the health benefits of hygiene against possible risks, such as environmental impacts and toxicity issues. Another issue is the role of microbes in human health and whether we have become “too clean”. Lack of a unified voice advocating for hygiene means these issues have tended to take precedence. Another barrier to change is public confusion about the need for hygiene and the difference between hygiene and cleanliness. To address this, we must work together to provide the public with a clear, consistent restatement of the importance of hygiene, and to change public perceptions about hygiene and good hygiene practice. This paper is unique because it examines these issues in an integrated manner and focuses on making achievable, constructive recommendations for developing an effective and sustainable approach. The paper lays out a risk management strategy for hygiene in home and everyday life which gives hygiene appropriate priority within the context of environmental and other health concerns. This “targeted hygiene” approach needs to be placed at the heart of a multimodal prevention strategy, alongside vaccination and other interventions. Based on the findings of this paper, we issue a call to action to national and international policy makers, health agencies and health professionals to recognize the need for an integrated, family-centredii approach to hygiene, and provide effective leadership to achieve this. This paper shows that many of the components of a behaviour change strategy are already in place, but need to be integrated rather than developed independently. We also issue a call to scientists, health professionals, environmental and regulatory agencies, immunologists, microbiomists, the private sector (hygiene appliance and product manufacturers) and the media to work together, through innovative research and communication policies. A collaborative effort is vital if we are to overcome barriers to change and action integrated behaviour change programmes that really work. The report represents the consensus views of an international, interdisciplinary group of experts in the field of infection prevention and hygiene. We recognise that this paper leaves many questions unanswered and would welcome further dialogue with stakeholders on how to develop policy. The aim of this paper is to provide a sound basis for such dialogue. At the 2016 launch of the European Human Biomonitoring Initiative, the EU commissioner for food safety said the followingiii which encapsulates the aim of this report. “We must collectively recognise that risk and uncertainty are part and parcel of every decision we take. We need to engage people in a serious and rational debate. But in this world of information overload – from old media and new – information, misinformation, opinions, prejudices, truths, half-truths and un-truths all compete for public attention. We need better communication of science so that people can be better informed about risk assessment and management decisions

Structural and compositional gradients : basic idea, preparation, applications

No abstract availabl