Inositol 1,4,5- Trisphosphate Receptor Function in Drosophila Insulin Producing Cells

The Inositol 1,4,5- trisphosphate receptor (InsP3R) is an intracellular ligand gated channel that releases calcium from intracellular stores in response to extracellular signals. To identify and understand physiological processes and behavior that depends on the InsP3 signaling pathway at a systemic level, we are studying Drosophila mutants for the InsP3R (itpr) gene. Here, we show that growth defects precede larval lethality and both are a consequence of the inability to feed normally. Moreover, restoring InsP3R function in insulin producing cells (IPCs) in the larval brain rescues the feeding deficit, growth and lethality in the itpr mutants to a significant extent. We have previously demonstrated a critical requirement for InsP3R activity in neuronal cells, specifically in aminergic interneurons, for larval viability. Processes from the IPCs and aminergic domain are closely apposed in the third instar larval brain with no visible cellular overlap. Ubiquitous depletion of itpr by dsRNA results in feeding deficits leading to larval lethality similar to the itpr mutant phenotype. However, when itpr is depleted specifically in IPCs or aminergic neurons, the larvae are viable. These data support a model where InsP3R activity in non-overlapping neuronal domains independently rescues larval itpr phenotypes by non-cell autonomous mechanisms

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

A STUDY OF THE USE OF COMPENSATION MOTIONS WHEN USING PROSTHETIC WRISTS

It is well known that the functional capability of a prosthetic hand is less than that of the natural hand and thus it cannot perform the majority of the tasks a natural hand does, as well or as easily. Of the many consequences from this circumstance is that the prosthetic hand is generally used in a support role when there is a contralateral natural hand available. This is because the prosthesis is unable to grasp objects as flexibly as the natural hand. It is known, from splinting studies of the wrists of unimpaired volunteers, that if the person is not able to present the hand in the correct orientation, even the most flexible hand cannot perform prehensile tasks easily, [1,2]. In the prosthetic circumstance, without a wrist to orientate the hand relative to the object, conventional terminal devices do not grasp as effectively. The user must move their arm in a different way, that allows the prosthesis to be presented to the target in an orientation that will facilitate a secure grasp. A result from this is that there is a very real risk that these compensatory motions use greater ranges of motion, larger forces, or occur more often than necessary with a natural hand. Kidd et al [3], observed that these are three of the conditions likely to induce the changes in the musculoskeletal system that are referred to as injuries of overuse. There are few long term studies of the effect of overuse in prosthesis wearers. It is a well known observation amongst the clinicians that users who do not use their prostheses tend to suffer from the sort of degenerative changes associated with overuse. Less still is known about the effect of the compensatory actions of the contralateral limb