A study to determine the pharmacodynamics of digitalis which the nursing student understands at the end of thirty months in a three year diploma program.

Thesis (M.S.)--Boston Universit

An Investigation into Noxious Mechanosensation, and the Role of Peripheral Neuron Subpopulations in Pain

This thesis uses transgenic mice to explore the role of candidate and known mechanotransducers in acute mechanical pain. It also utilises transgenics to ablate whole populations of sensory neurons in mice to establish what role these also have in pain, both under normal and inflammatory conditions. The water and ion channel Aquaporin 1 (Aqp1) is preferentially expressed in the small diameter neurons of the peripheral nervous system (PNS). These are responsible for nociception, and Aqp1 has previously been implicated in pain sensation. Its role in acute mechanical pain has not fully been explored. By using global Aqp1 knockout (Aqp1KO) mice and mechano-clamp electrophysiology I am the first to demonstrate that Aqp1 contributes to the mechanically activated (MA) currents associated with pain sensing in nociceptors. However, it does not produce MA currents when expressed in naïve cells. Aqp1 is necessary for normal mechanical pain in vivo as Aqp1KO animals have an increased mechanical pain threshold. Thus, it is unlikely that Aqp1 is a pore-forming component of a noxious mechanotransducer but may form part of a membrane complex essential to mechanical pain sensation. Piezo2 is a known mammalian mechanotransducer and is responsible for light touch sensation and proprioception. It’s contribution to mechanical pain under pathological conditions is established but it’s role in acute mechanical pain remains controversial. I generate mice with a nociceptor-specific Piezo2 deletion and again use a combination of electrophysiological and behavioural assays to demonstrate that Piezo2 is not required for acute noxious mechanosensation. Thus, my data confirms that the mechanotransducer responsible for mechanical pain remains ambiguous. Finally I study the role of the cutaneous population of Parvalbumin-positive (PV+) sensory neurons in pain. This population is required for innocuous mechanical sensation including vibration sensing. By genetically ablating PV+ neurons to generate ‘PVDTA’ mice, I provide evidence that these neurons are necessary for negatively regulating the thermal, mechanical, and inflammatory pain response, as behaving animals are hypersensitive to these insults. I am the first to propose that cutaneous PV+ neurons are responsible for closing the so-called ‘pain gate’ in the dorsal horn of the spinal cord. Further evidence for this comes from an in vivo electrophysiological study of dorsal horn neurons in PVDTA mice, which exhibit increased excitability as a consequence of noxious stimulation. In vivo DRG neuron imaging in animals expressing a reporter protein in PV+ sensory neurons show that these neurons are capable of responding to noxious stimuli, thus solidifying this hypothesis

Alice E. Modes Correspondence

Entries include a conflicting, typed bibliographic letter on National Bureau of Casualty and Surety Underwriters stationery

Theology, News and Notes - Vol. 19, No. 04

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1044/thumbnail.jp

Protein S‐palmitoylation: advances and challenges in studying a therapeutically important lipid modification

The lipid post‐translational modification S‐palmitoylation is a vast developing field, with the modification itself and the enzymes that catalyse the reversible reaction implicated in a number of diseases. In this review we discuss the past and recent advances in the experiment tools used in this field, including pharmacological tools, animal models and techniques to understand how palmitoylation controls protein localisation and function. Additionally, we discuss the obstacles to overcome in order to advance the field, particularly to the point at which modulating palmitoylation may be achieved as a therapeutic strategy

Cyclophilin D palmitoylation and permeability transition: a new twist in the tale of myocardial ischaemia-reperfusion injury

No abstract available

Post-translational regulation of cardiac myosin binding protein-C: a graphical review

Cardiac myosin binding protein-C (cMyBP-C) is a fundamental component of the cardiac sarcomere involved in regulating systolic and diastolic activity, processes which must be tightly maintained to preserve cardiac function. Importantly, as a non-enzymatic protein, cMyBP-C relies solely on post-translational modifications and protein-protein interactions in order to modulate its function, and does so through phosphorylation, glutathionylation and acetylation amongst others. Although some are better understood than others, these modifications may represent novel therapeutic routes to modulate cMyBP-C function in the treatment of cardiac disease

Editorial: Advances in ecoacoustics

Presentation of a Special Issue on ecoacoustics with analysis of the contributions and of the current knowledge gaps