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179 results on '"Hilliard, Massimo"'

1. Impaired signaling for neuromuscular synaptic maintenance is a feature of Motor Neuron Disease

Author

Ding, Qiao, Kesavan, Kaamini, Lee, Kah Meng, Wimberger, Elyse, Robertson, Thomas, Gill, Melinder, Power, Dominique, Chang, Jeryn, Fard, Atefeh T., Mar, Jessica C., Henderson, Robert D., Heggie, Susan, McCombe, Pamela A., Jeffree, Rosalind L., Colditz, Michael J., Hilliard, Massimo A., Ng, Dominic C. H., Steyn, Frederik J., Phillips, William D., Wolvetang, Ernst J., Ngo, Shyuan T., and Noakes, Peter G.

Published
2022
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2. Modular transient nanoclustering of activated β2-adrenergic receptors revealed by single-molecule tracking of conformation-specific nanobodies

Author

Gormal, Rachel S., Padmanabhan, Pranesh, Kasula, Ravikiran, Bademosi, Adekunle T., Coakley, Sean, Giacomotto, Jean, Blum, Ailisa, Joensuu, Merja, Wallis, Tristan P., Lo, Harriet P., Budnar, Srikanth, Rae, James, Ferguson, Charles, Bastiani, Michele, Thomas, Walter G., Pardon, Els, Steyaert, Jan, Yap, Alpha S., Goodhill, Geoffrey J., Hilliard, Massimo A., Parton, Robert G., and Meunier, Frédéric A.

Published
2020

5. SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity

Author

Martínez-Mármol, Ramón, primary, Giordano-Santini, Rosina, additional, Kaulich, Eva, additional, Cho, Ann-Na, additional, Przybyla, Magdalena, additional, Riyadh, Md Asrafuzzaman, additional, Robinson, Emilija, additional, Chew, Keng Yih, additional, Amor, Rumelo, additional, Meunier, Frédéric A., additional, Balistreri, Giuseppe, additional, Short, Kirsty R., additional, Ke, Yazi D., additional, Ittner, Lars M., additional, and Hilliard, Massimo A., additional

Published
2023
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9. EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway

Author

Neumann, Brent, Coakley, Sean, Giordano-Santini, Rosina, Linton, Casey, Lee, Eui Seung, Nakagawa, Akihisa, Xue, Ding, and Hilliard, Massimo A.

Subjects
Neurological research, Axons -- Physiological aspects, Apoptosis -- Research, Cell hybridization -- Research, Nervous system -- Regeneration, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Functional regeneration after nervous system injury requires transected axons to reconnect with their original target tissue. Axonal fusion, a spontaneous regenerative mechanism identified in several species, provides an efficient means of achieving target reconnection as a regrowing axon is able to contact and fuse with its own separated axon fragment, thereby re-establishing the original axonal tract (1-7). Here we report a molecular characterization of this process in Caenorhabditis elegans, revealing dynamic changes in the subcellular localization of the EFF-1 fusogen after axotomy, and establishing phosphatidylserine (PS) and the PS receptor (PSR-1) as critical components for axonal fusion. PSR-1 functions cell-autonomously in the regrowing neuron and, instead of acting in its canonical signalling pathway (8), acts in a parallel phagocytic pathway that includes the transthyretin protein TTR-52, as well as CED-7, NRF-5 and CED-6 (refs 9-12). We show that TTR-52 binds to PS exposed on the injured axon, and can restore fusion several hours after injury. We propose that PS functions as a 'save-me' signal for the distal fragment, allowing conserved apoptotic cell clearance molecules to function in reestablishing axonal integrity during regeneration of the nervous system., Axonal fusion, which occurs spontaneously in several invertebrate species (1-7), is a highly efficient means to re-establish the connection between an injured neuron and its target tissue; the proximal axon [...]

Published
2015

10. A Core Metabolic Enzyme Mediates Resistance to Phosphine Gas

Author

Schlipalius, David I., Valmas, Nicholas, Tuck, Andrew G., Jagadeesan, Rajeswaran, Ma, Li, Kaur, Ramandeep, Goldinger, Anita, Anderson, Cameron, Kuang, Jujiao, Zuryn, Steven, Mau, Yosep S., Cheng, Qiang, Collins, Patrick J., Nayak, Manoj K., Schirra, Horst Joachim, Hilliard, Massimo A., and Ebert, Paul R.

Published
2012
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13. Additional file 1 of Impaired signaling for neuromuscular synaptic maintenance is a feature of Motor Neuron Disease

Author

Ding, Qiao, Kesavan, Kaamini, Lee, Kah Meng, Wimberger, Elyse, Robertson, Thomas, Gill, Melinder, Power, Dominique, Chang, Jeryn, Fard, Atefeh T., Mar, Jessica C., Henderson, Robert D., Heggie, Susan, McCombe, Pamela A., Jeffree, Rosalind L., Colditz, Michael J., Hilliard, Massimo A., Ng, Dominic C. H., Steyn, Frederik J., Phillips, William D., Wolvetang, Ernst J., Ngo, Shyuan T., and Noakes, Peter G.

Abstract

Additional file 1 Contains Online Resource 1 - Supplementary Methods, and Online Resource 2 - Supplementary Tables (S1 to S4) and Supplementary Figrues (S1 to S7).

Published
2022
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17. The Zona Pellucida domain containing proteins, CUT-1, CUT-3 and CUT-5, play essential roles in the development of the larval alae in Caenorhabditis elegans

Author

Sapio, Maria Rosaria, Hilliard, Massimo A., Cermola, Michele, Favre, Renee, and Bazzicalupo, Paolo

Subjects
Zona pellucida -- Research, Caenorhabditis elegans -- Research, Caenorhabditis elegans -- Physiological aspects, Developmental biology -- Research, Proteins -- Research, Biological sciences
Abstract

The alae, longitudinal ridges of the lateral cuticle, are the most visible specialization of the Caenorhabditis elegans surface. They are present only in L1 and dauer larvae and in adults. Little is known about the mechanisms through which at the appropriate stages secretion of cuticle components by the seam cells results in the formation of the alae. Here we show that three proteins, each containing a Zona Pellucida domain (ZP), are components of the cuticle necessary for larval alae development: CUT-1 and CUT-5 in dauer larvae and CUT-3 and CUT-5 in L1s. Transcriptional regulation of the corresponding genes contributes to the stage-specific role of these proteins. Larvae with reduced cut-1, cut-3 or cut-5 function not only lack alae but are also larger in diameter due to an increase in the width of the lateral cuticle. We propose a model in which reduction of the body diameter, which occurs in normal L1 and dauer larvae, is the result of a dorso-ventral shrinking of the internal layer of the lateral cuticle and formation of the alae results from the folding of the external layer of the lateral cuticle over the reduced, internal one. Alae of adults appear to form through a different mechanism. Keywords: Nematode; Cuticle; Alae; Dauer larvae; L1 larvae; CUT-1-like proteins; ZP domain; Extracellular matrix

Published
2005

18. Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development

Author

Rinaldo, Cinzia, Bazzicalupo, Paolo, Ederle, Sara, Hilliard, Massimo, and La Volpe, Adriana

Subjects
Genetic research -- Analysis, Caenorhabditis elegans -- Genetic aspects, Biological sciences
Abstract

We have investigated the role of Caenorhabditis elegans RAD-51 during meiotic prophase and embryogenesis, making use of the silencing effect of RNA interference (RNAi). rad-51 RNAi leads to severe defects in chromosome morphology in diakinesis oocytes. We have explored the effect of rad-51 RNAi in mutants lacking fundamental components of the recombination machinery. If double-strand breaks are prevented by spo-11 mutation, rad-51 RNAi does not affect chromosome appearance. This is consistent with a role for RAD-51 downstream of the initiation of recombination. In the absence of MRE-11, as in the absence of SPO-11, RAD-51 depletion has no effect on the chromosomes, which appear intact, thus indicating a role for MRE-11 in DSB induction. Intriguingly, rad-51 silencing in oocytes that lack MSH-5 leads to chromosome fragmentation, a novel trait that is distinct from that seen in msh-5 mutants and in rad-51 RNAi oocytes, suggesting new potential roles for the msh-5 gene. Silencing of the rad-51 gene also causes a reduction in fecundity, which is suppressed by mutation in the DNA damage checkpoint gene rad-5, but not in the cell death effector gene ced-3. Finally, RAD-51 depletion is also seen to affect the soma, resulting in hypersensitivity to ionizing radiation in late embryogenesis.

Published
2002

22. Mutations in Caenorhabditis elegans neuroligin-like glit-1, the apoptosis pathway and the calcium chaperone crt-1 increase dopaminergic neurodegeneration after 6-OHDA treatment

Author

Offenburger, Sarah-Lena, Ho, Xue Yan, Tachie-Menson, Theresa, Coakley, Sean, Hilliard, Massimo A., and Gartner, Anton

Subjects
Life Cycles, Cell signaling, Nematoda, Apoptosis, Signal transduction, Biochemistry, Animals, Genetically Modified, Larvae, Nerve Fibers, Animal Cells, Neurons, Cell Death, Eukaryota, Signaling cascades, Neurochemistry, Animal Models, Oxidants, Experimental Organism Systems, Caenorhabditis Elegans, Cell Processes, Intercellular Signaling Peptides and Proteins, Neurochemicals, Cellular Types, Research Article, Paraquat, endocrine system, MAPK signaling cascades, lcsh:QH426-470, Research and Analysis Methods, Model Organisms, Animals, Caenorhabditis elegans Proteins, Oxidopamine, Dopaminergic Neurons, Organisms, JNK Mitogen-Activated Protein Kinases, nutritional and metabolic diseases, Biology and Life Sciences, Cell Biology, Hydrogen Peroxide, Invertebrates, Axons, lcsh:Genetics, Oxidative Stress, Cellular Neuroscience, Mutation, Nerve Degeneration, Caenorhabditis, Carrier Proteins, Dopaminergics, Neuroscience, Developmental Biology
Abstract

Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson’s disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting Caenorhabditis elegans dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the transthyretin-related gene ttr-33. The only described C. elegans transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair. We demonstrate that TTR-52 and TTR-33 have distinct roles. TTR-33 is likely produced in the posterior arcade cells in the head of C. elegans larvae and is predicted to be a secreted protein. TTR-33 protects C. elegans from oxidative stress induced by paraquat or H2O2 at an organismal level. The increased oxidative stress sensitivity of ttr-33 mutants is alleviated by mutations affecting the KGB-1 MAPK kinase pathway, whereas it is enhanced by mutation of the JNK-1 MAPK kinase. Finally, we provide genetic evidence that the C. elegans cell corpse engulfment pathway is required for the degeneration of dopaminergic neurons after exposure to 6-OHDA. In summary, we describe a new neuroprotective mechanism and demonstrate that TTR-33 normally functions to protect dopaminergic neurons from oxidative stress-induced degeneration, potentially by acting as a secreted sensor or scavenger of oxidative stress., Author summary Animals employ multiple mechanisms to prevent their cells from damage by reactive oxygen species, chemically reactive molecules containing oxygen. Oxidative stress, caused by the overabundance of reactive oxygen species or a decreased cellular defence against these chemicals, is linked to a variety of neurodegenerative conditions, including the loss of dopaminergic neurons in Parkinson’s disease. In this study, we discovered a novel protective molecule that functions to prevent dopaminergic neurodegeneration caused by oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA). We used the nematode C. elegans, a well-characterised model in which mechanisms can be studied on an organismal level. When C. elegans is exposed to 6-OHDA, its dopaminergic neurons gradually die. Our major findings include (i) mutations of the transthyretin-related gene ttr-33 causes highly increased dopaminergic neurodegeneration after 6-OHDA exposure; (ii) TTR-33 is likely produced and secreted by several cells in the head of the animal; (iii) TTR-33 protects against oxidative stress induced by other compounds; (iv) mutations in the KGB-1 MAP kinase stress pathway alleviate dopaminergic neuron loss in the ttr-33 mutant; and (v) the cell corpse engulfment pathway is required for dopaminergic neurodegeneration. We hypothesise that TTR-33 protects dopaminergic neurons against 6-OHDA-induced oxidative stress by acting as an oxygen sensor or scavenger.

Published
2018

26. How the Australian Functional Genomics Network (AFGN) contributes to improved patient care

Author

Scott, Hamish S., Matotek, Ebony, Mattiske, Tessa, Bryson-Richardson, Robert J., Smyth, Ian, Gecz, Jozef, Christodoulou, John, Palpant, Nathan, Smith, Kelly, Warr, Coral, Bennetts, Bruce, Thomas, Paul, Bowles, Josephine, Hilliard, Massimo, Hime, Gary, Hool, Livia, Quinn, Leonie, Wolvetang, Ernst, Jamieson, Robyn, Baynam, Gareth, Dudding-Byth, Tracy, Tan, Tiong Yang, Milnes, Di, Wallis, Mathew, Palmer, Elizabeth, Patel, Chirag, Jones, Kristi, Tam, Patrick, Stark, Zornitza, Dunwoodie, Sally, and Sinclair, Andrew

Published
2024
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27. Defects in synaptic transmission at the neuromuscular junction precede motor deficits in a TDP-43Q331K transgenic mouse model of amyotrophic lateral sclerosis

Author

Chand, Kirat, Lee, Kah Meng, Lee, John D, Qiu, Hao, Willis, Emily F, Lavidis, Nickolas A., Hilliard, Massimo Antonio, Noakes, Peter Gerrard, Chand, Kirat, Lee, Kah Meng, Lee, John D, Qiu, Hao, Willis, Emily F, Lavidis, Nickolas A., Hilliard, Massimo Antonio, and Noakes, Peter Gerrard

Abstract

Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 is a major protein component of ubiquinated inclusions that are found in amyotrophic lateral sclerosis (ALS); however, the function of TDP-43 at the neuromuscular junction (NMJ) and its role in ALS pathogenesis is largely unknown. Here, we show that TDP-43Q331K mutation in mice resulted in impaired neurotransmission by age 3 mo, preceding deficits in motor function and motor neuron loss, which were observed from age 10 mo. These defects were in the effective fusion and release of synaptic vesicles within the motor nerve terminal and manifested in decreased quantal content and reduced probability of quantal release. We observed morphologic alterations that were associated with the TDP-43Q331K mutation, such as aberrant innervation patterns and the distribution of synaptic vesicle-related proteins, which is indicative of a failing NMJ undergoing synaptic remodeling. These findings support a growing acceptance that dysregulation of the NMJ function is a key early event in the pathology of ALS.—Chand, K. K., Lee, K. M., Lee, J. D, Qiu, H., Willis, E. F., Lavidis, N. A., Hilliard, M. A., Noakes, P. G. Defects in synaptic transmission at the neuromuscular junction precede motor deficits in a TDP-43Q331K transgenic mouse model of amyotrophic lateral sclerosis.

Published
2018

37. Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis

Author

Fogarty, Matthew, Klenowski, Paul, Lee, John, Drieberg-Thompson, Joy, Bartlett, Selena, Ngo, Shyuan, Hilliard, Massimo, Bellingham, Mark, Noakes, Peter, Fogarty, Matthew, Klenowski, Paul, Lee, John, Drieberg-Thompson, Joy, Bartlett, Selena, Ngo, Shyuan, Hilliard, Massimo, Bellingham, Mark, and Noakes, Peter

Abstract

Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43Q331K mutation. These findings demonstrate substantive alterations in the motor cortex neural network, long before an overt degenerative phenotype has been reported. We conclude that increased excitatory neurotransmission is a common pathophysiology amongst differing genetic cases of ALS and may be of relevance to the 95% of sporadic ALS cases that exhibit TDP-43 inclusions.

Published
2016

39. Neuron-specific knock-down of SMN1 causes neuron degeneration and death through an apoptotic mechanism

Author

Gallotta, Ivan, primary, Mazzarella, Nadia, additional, Donato, Alessandra, additional, Esposito, Alessandro, additional, Chaplin, Justin C., additional, Castro, Silvana, additional, Zampi, Giuseppina, additional, Battaglia, Giorgio S., additional, Hilliard, Massimo A., additional, Bazzicalupo, Paolo, additional, and Di Schiavi, Elia, additional

Published
2016
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47. The Heterochronic Gene lin-14Controls Axonal Degeneration in C. elegansNeurons

Author

Ritchie, Fiona K., Knable, Rhianna, Chaplin, Justin, Gursanscky, Rhiannon, Gallegos, Maria, Neumann, Brent, and Hilliard, Massimo A.

Abstract

The disproportionate length of an axon makes its structural and functional maintenance a major task for a neuron. The heterochronic gene lin-14has previously been implicated in regulating the timing of key developmental events in the nematode C. elegans. Here, we report that LIN-14 is critical for maintaining neuronal integrity. Animals lacking lin-14display axonal degeneration and guidance errors in both sensory and motor neurons. We demonstrate that LIN-14 functions both cell autonomously within the neuron and non-cell autonomously in the surrounding tissue, and we show that interaction between the axon and its surrounding tissue is essential for the preservation of axonal structure. Furthermore, we demonstrate that lin-14expression is only required during a short period early in development in order to promote axonal maintenance throughout the animal’s life. Our results identify a crucial role for LIN-14 in preventing axonal degeneration and in maintaining correct interaction between an axon and its surrounding tissue.

Published
2017
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