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"Graham, C"
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Optical control of neuronal ion channels and receptors
Light-controllable tools provide powerful means to manipulate and interrogate brain function with relatively low invasiveness and high spatiotemporal precision. Although optogenetic approaches permit neuronal excitation or inhibition at the network level, other technologies, such as optopharmacology (also known as photopharmacology) have emerged that provide molecular-level control by endowing light sensitivity to endogenous biomolecules. In this Review, we discuss the challenges and opportunities of photocontrolling native neuronal signalling pathways, focusing on ion channels and neurotransmitter receptors. We describe existing strategies for rendering receptors and channels light sensitive and provide an overview of the neuroscientific insights gained from such approaches. At the crossroads of chemistry, protein engineering and neuroscience, optopharmacology offers great potential for understanding the molecular basis of brain function and behaviour, with promises for future therapeutics.
Journal Article
المختصر في الأمراض الجلدية
يقدم هذا الكتاب المادة العلمية في الأمراض الجلدية بصورة مختصرة يسهل على طالب الطب والطبيب الممارس والممرض أن يستفيد منه كمرجع في دراسته وممارسته، كما أن أسلوب عرضه والصور التوضيحية في الكتاب وسياقه للتاريخ الطبيعي للأمراض الجلدية وطرق تشخيصها ووسائل علاجها تعتبر مادة ثرية لكل من يهتم بتثقيف نفسه في هذا المجال حتى من المرضى وغير المتخصصين.
BOOK
Integrating the Supply Chain … 25 years on
Purpose
– Twenty-five years ago IJPDLM published “Integrating the Supply Chain” (Stevens, 1989). The purpose of that original work was to examine the state-of-the-art in supply chain management (SCM). There have been substantial changes to the landscape within which supply chains function and changes to supply chains themselves. Given these changes it is appropriate to re-visit what is the new state-of-the art and determine whether the 1989 conceptualization requires extending. The authors also attempt to assess whether the evolution of SCM is associated with improved financial performance. The paper aims to discuss these issues.
Design/methodology/approach
– The authors take a conceptual approach to suggest that SCM is undergoing a transition to devolved, collaborative supply chain clusters. In addition, the authors consider imperatives and models for supply chain change and development. In line with the 1989 work, many of the observations in this invited paper are based on the primary author’s experience. The authors use a selection of financial data from leading firms to assess whether benefits attributed to SCM and changes in supply chain operating models have affected financial performance.
Findings
– The authors formalize a model for the dynamics of SCM change. The authors also synthesize a number of models of SCM that extend the original, highly cited work. These include goal-oriented networks and devolved, collaborative supply chain clusters. The authors also find the associations between the evolution of SCM and measures of firm financial performance over time to be equivocal.
Practical implications
– This work proposes two additional operating models that firms can implement in order to improve the efficacy of their supply chains.
Originality/value
– The authors extend Stevens (1989) original work by synthesizing a number of additional models for SCI.
Journal Article
Compartmentalization of GABAergic Inhibition by Dendritic Spines
γ-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity. The precision of GABAergic control over dendritic electrical and biochemical signaling is unknown. By using cell type-specific optical stimulation in combination with two-photon calcium (Ca²⁺) imaging, we show that somatostatin-expressing interneurons exert compartmentalized control over postsynaptic Ca²⁺ signals within individual dendritic spines. This highly focal inhibitory action is mediated by a subset of GABAergic synapses that directly target spine heads. GABAergic inhibition thus participates in localized control of dendritic electrical and biochemical signaling.
Journal Article
The Ox-Bow incident
A cowboy is unable to prevent three wandering travelers from being unjustly lynched for murder.
BOOK
Vulnerability and Essential Services
This paper discusses the development of vulnerability policy in essential services in the UK, the position at present and what the future holds.
Journal Article