Publications by authors named "James Ashley"

One of the challenges of studying synaptic structure and function is accessibility. Some of the earliest readily identifiable and accessible synapses were from the frog and various arthropods. To address questions regarding mechanisms that underlie synaptic development and function, genetically tractable systems were required, and researchers turned to the embryonic/larval neuromuscular preparation.

View Article and Find Full Text PDF

For decades, the larval neuromuscular junction (NMJ) has been a go-to model for synaptic development. This simple, accessible system is composed of a repeating pattern of 33 distinct neurons that stereotypically innervate 30 muscles. Fundamental mechanisms that underlie diverse aspects of axon pathfinding, synaptic form, and function have been uncovered at the NMJ, and new pathways continue to be uncovered.

View Article and Find Full Text PDF

In the nearly 50 years since the neuromuscular junction (NMJ) was first established as a model synapse, its molecular composition has been extensively characterized. Early work relied on fluorescent signals to determine whether proteins localized to the pre- and postsynaptic regions. As more synaptic molecules were identified, determining the localization of these proteins relative to each other became important.

View Article and Find Full Text PDF

The neuromuscular junction (NMJ) is an excellent model for studying vertebrate glutamatergic synapses. Researchers have uncovered fundamental mechanisms at the fly NMJ that are conserved in higher-order organisms. To gain molecular and structural insight into these and other structures, immunolabeling is invaluable.

View Article and Find Full Text PDF

Tissue development requires local and long-distance communication between cells. Cell ablation experiments have provided critical insights into the functions of specific cell types and the tissue surrounding the dead cells. In the neuromuscular system, ablation of motor neurons and muscles has revealed the roles of the ablated cells in axon pathfinding and circuit wiring.

View Article and Find Full Text PDF

Determining the precise localization of interacting proteins provides fundamental insight into their putative function. Classically, immunolabeling of endogenous proteins or generating tagged versions of proteins has been used to localize interacting proteins. However, in many cases, the interacting partner of a protein of interest is unknown.

View Article and Find Full Text PDF

The Dpr and DIP proteins belong to the immunoglobulin superfamily of cell surface proteins (CSPs). Their hetero- and homophilic interactions have been implicated in a variety of neuronal functions, including synaptic connectivity, cell survival, and axon fasciculation. However, the signaling pathways underlying these diverse functions are unknown.

View Article and Find Full Text PDF

Mental health is an important factor for children's overall wellbeing. National health statistics show that millions of children are diagnosed with mental health disorders every year, and evidence from studies on chemical pollutants like lead and bisphenols indicate that environmental exposures are linked to mental health illnesses in youth. However, the relationship between children's mental health and the environment is not well understood.

View Article and Find Full Text PDF

In situ methods are valuable in all fields of research. In toxicology, the importance of dose is well known, elevating the need for in situ techniques to measure levels of toxicants and their byproducts in precise anatomically identifiable locations. More recently, additional emphasis has been placed on the value of techniques which can detect chemical form or speciation, which is equally important in the toxicology of a chemical compound.

View Article and Find Full Text PDF

Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their terminal bouton number and activity. We term this compensation as cross-neuron plasticity, and in this study, we demonstrate that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required for cross-neuron plasticity.

View Article and Find Full Text PDF

Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the cell death of their neighbors is not fully understood. In the larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their axon terminal size and activity. We termed this compensation as cross-neuron plasticity, and in this study, we demonstrated that the engulfment receptor, Draper, and the associated kinase, Shark, are required in glial cells.

View Article and Find Full Text PDF

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial.

View Article and Find Full Text PDF

In complex nervous systems, neurons must identify their correct partners to form synaptic connections. The prevailing model to ensure correct recognition posits that cell-surface proteins (CSPs) in individual neurons act as identification tags. Thus, knowing what cells express which CSPs would provide insights into neural development, synaptic connectivity, and nervous system evolution.

View Article and Find Full Text PDF

Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies.

View Article and Find Full Text PDF

Selenium is in many ways an enigmatic element. It is essential for health but toxic in excess, with the difference between the two doses being narrower than for any other element. Environmentally, selenium is of concern due to its toxicity.

View Article and Find Full Text PDF

A central problem in evolutionary biology is to identify the forces that maintain genetic variation for fitness in natural populations. Sexual antagonism, in which selection favours different variants in males and females, can slow the transit of a polymorphism through a population or can actively maintain fitness variation. The amount of sexually antagonistic variation to be expected depends in part on the genetic architecture of sexual dimorphism, about which we know relatively little.

View Article and Find Full Text PDF

Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other's structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs.

View Article and Find Full Text PDF

8-Hydroxyquinolines (8HQs) comprise a family of metal-binding compounds that have been used or tested for use in numerous medicinal applications, including as treatments for bacterial infection, Alzheimer's disease, and cancer. Two key 8HQs, CQ (5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (2-(dimethylamino)methyl-5,7-dichloro-8-hydroxyquinoline), have drawn considerable interest and have been the focus of many studies investigating their in vivo properties. These drugs have been described as copper and zinc ionophores because they do not cause metal depletion, as would be expected for a chelation mechanism, but rather cellular accumulation of these ions.

View Article and Find Full Text PDF

8-Hydroxyquinolines (8HQs) are a family of lipophilic metal ion chelators that have been used in a range of analytical and pharmaceutical applications over the last 100 years. More recently, CQ (clioquinol; 5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) have undergone clinical trials for the treatment of Alzheimer's disease and Huntington's disease. Because CQ and PBT2 appear to redistribute metals into cells, these compounds have been redefined as copper and zinc ionophores.

View Article and Find Full Text PDF

Industrial release of mercury into the local Minamata environment with consequent poisoning of local communities through contaminated fish and shellfish consumption is considered the classic case of environmental mercury poisoning. However, the mercury species in the factory effluent has proved controversial, originally suggested as inorganic, and more recently as methylmercury species. We used newly available methods to re-examine the cerebellum of historic Cat 717, which was fed factory effluent mixed with food to confirm the source.

View Article and Find Full Text PDF

Elotuzumab (Elo) is an IgG monoclonal antibody targeting SLAMF7 (CS1, CRACC, and CD319), which is highly expressed on multiple myeloma (MM) cells, natural killer (NK) cells, and subsets of other leukocytes. By engaging with FcγRIIIA (CD16), Elo promotes potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) toward SLAMF7 MM tumor cells. Relapsed/refractory MM patients treated with the combination of Elo, lenalidomide, and dexamethasone have improved progression-free survival.

View Article and Find Full Text PDF