Canonical BMP Signaling Is Required For Allodynia In Drosophila Melanogaster

In the United States alone over 100 million people suffer from chronic pain and unfortunately, even still, there is a lack in scientific understanding for the mechanisms of abnormal pain sensitivity. The present study utilized a candidate gene approach to identify novel components required for modulation of the tissue damage induced pain sensitization pathway in Drosophila melanogaster. We have shown that RNAi silencing of decapentaplegic (dpp), a member of the Bone Morphogenetic Protein (BMP) signaling pathway, specifically in the class IV multidendritic nociceptor neurons significantly attenuated UV-induced nociceptive sensitization. Furthermore, overexpression of dpp in nociceptor neurons was sufficient to induce sensitization in the absence of tissue damage. We then show that the dpp receptors are required on the nociceptor neuron in order to produce allodynia, demonstrating that dpp is signaling to the very neuron that produced it. Lastly, we show that this BMP pathway is utilizing the canonical signaling SMAD factors to induce allodynia. We show that the effects of BMP signaling were largely specific to the sensitization pathway and not to normal nociception or dendritic morphology. Thus, we have shown that dpp plays a crucial and novel role in sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates it seems likely that the genes we have analyzed represent potential therapeutic targets applicable to humans

Quantifying internal stress and internal resistance associated with thermal ageing and creep in a polycrystalline material

In situ neutron diffraction combined with the incremental deformation at room temperature has been used to provide a measure of the internal stress and internal resistance generated by prior inelastic deformation at high temperature in an austenitic stainless steel. Interactions between the internal stress and internal resistance are considered explicitly by using the proposed measurement technique. The magnitude of the intergranular internal stress is found to be a function of the total inelastic strain created by prior high temperature deformation. The deviation from linearity observed in the lattice strain response is used to derive the microscopic internal resistance, but a crystal plasticity model is required to infer the absolute value. The macroscopic internal resistance is shown to be consistent with Taylor hardening. A refined internal state concept is proposed based on the Kocks–Mecking model to provide a further step to predict the inelastic deformation

Numerical integration of rate-independent BCC single crystal plasticity models: comparative study of two classes of numerical algorithms

In an incremental formulation suitable to numerical implementation, the use of rate-independent theory of crystal plasticity essentially leads to four fundamental problems. The first is to determine the set of potentially active slip systems over a time increment. The second is to select the active slip systems among the potentially active ones. The third is to compute the slip rates (or the slip increments) for the active slip systems. And the last problem is the possible non-uniqueness of slip rates. The purpose of this paper is to propose satisfactory responses to the above-mentioned first three issues by presenting and comparing two novel numerical algorithms. The first algorithm is based on the usual return-mapping integration scheme, while the second follows the so-called ultimate scheme. The latter is shown to be more relevant and efficient than the former. These comparative performances are illustrated through various numerical simulations of the mechanical behavior of single crystals and polycrystalline aggregates subjected to monotonic and complex loadings. Although these algorithms are applied in this paper to Body-Centered-Cubic (BCC) crystal structures, they are quite general and suitable for integrating the constitutive equations for other crystal structures (e.g., FCC and HCP)

Feeling A Little Like An Embarrassed Jelly Fish

The focus of our research is to investigate various cellular factors that are involved in the formation of sensitization in the Drosophila melanogaster. As a key aspect of our work, it is necessary to evaluate the morphometry of the primary nociceptor neurons to understand whether the effects seen in behavior are due to changes in the morphometry, or if it is a separate cellular event. These neurons have been genetically manipulated to express red fluorescence protein (RFP), originally discovered in jellyfish. This allows us to view and quantitate this class of neurons using the confocal microscope. As an interesting note, this image was taken from a living fruit fly larva.https://dune.une.edu/confocal_student/1006/thumbnail.jp

Feeling A Little Like A Jelly Fish

The focus of our research is to investigate various cellular factors that are involved in the formation of sensitization in the Drosophila melanogaster. As a key aspect of our work, it is necessary to evaluate the morphometry of the primary nociceptor neurons to understand whether the effects seen in behavior are due to changes in the morphometry, or if it is a separate cellular event. These neurons have been genetically manipulated to express green fluorescence protein (GFP), originally discovered in jellyfish. This allows us to view and quantitate this class of neurons using the confocal microscope. As an interesting note, this image was taken from a living fruit fly larva.https://dune.une.edu/confocal_student/1005/thumbnail.jp

Targeting Transient Receptor Potential (TRP) Channels, Mas-Related G-Protein-Coupled Receptors (Mrgprs), and Protease-Activated Receptors (PARs) to Relieve Itch.

Itch (pruritus) is a sensation in the skin that provokes the desire to scratch. The sensation of itch is mediated through a subclass of primary afferent sensory neurons, termed pruriceptors, which express molecular receptors that are activated by itch-evoking ligands. Also expressed in pruriceptors are several types of Transient Receptor Potential (TRP) channels. TRP channels are a diverse class of cation channels that are responsive to various somatosensory stimuli like touch, pain, itch, and temperature. In pruriceptors, TRP channels can be activated through intracellular signaling cascades initiated by pruritogen receptors and underly neuronal activation. In this review, we discuss the role of TRP channels TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPC3/4 in acute and chronic pruritus. Since these channels often mediate itch in association with pruritogen receptors, we also discuss Mas-related G-protein-coupled receptors (Mrgprs) and protease-activated receptors (PARs). Additionally, we cover the exciting therapeutic targets amongst the TRP family, as well as Mrgprs and PARs for the treatment of pruritus