Colon-Ramos DA (2009) Curr Top Dev Biol "Synapse formation in developing neural circuits."

Colon-Ramos DA

[Curr Top Dev Biol, 2009]

The nervous system consists of hundreds of billions of neurons interconnected into the functional neural networks that underlie behaviors. The capacity of a neuron to innervate and function within a network is mediated via specialized cell junctions known as synapses. Synapses are macromolecular structures that regulate intercellular communication in the nervous system, and are the main gatekeepers of information flow within neural networks. Where and when synapses form determines the connectivity and functionality of neural networks. Therefore, our knowledge of how synapse formation is regulated is critical to our understanding of the nervous system and how it goes awry in neurological disorders. Synapse formation involves pairing of the pre- and postsynaptic partners at a specific neurospatial coordinate. The specificity of synapse formation requires the precise execution of multiple developmental events, including cell fate specification, cell migration, axon guidance, dendritic growth, synaptic target selection, and synaptogenesis (Juttner and Rathjen in Cell. Mol. Life Sci. 62:2811, 2005; Salie et al., in Neuron 45:189, 2005; Waites et al., in Annu. Rev. Neurosci. 28:251, 2005). Remarkably, during the development of the vertebrate nervous system, these developmental processes occur almost simultaneously in billions of neurons, resulting in the formation of trillions of synapses. How this remarkable specificity is orchestrated during development is one of the outstanding questions in the field of neurobiology, and the focus of discussion of this chapter. We center the discussion of this chapter on the early developmental events that orchestrate the process of synaptogenesis prior to activity-dependent mechanisms. We have therefore limited the discussion of important activity-dependent synaptogenic events, which are discussed in other chapters of this book. Moreover, our discussion is biased toward lessons we have learned from invertebrate systems, in particular from C. elegans and Drosophila. We did so to complement the discussions from other chapters in this book, which focus on the important findings that have recently emerged from the vertebrate literature. The chapter begins with a brief history of the field of synaptic biology. This serves as a backdrop to introduce some of the historically outstanding questions of synaptic development that have eluded us during the past century, and which are the focus of this review. We then discuss some general features of synaptic structure as it relates to its function. In particular, we will highlight evolutionarily conserved traits shared by all synaptic structures, and how these features have helped optimize these ancient cellular junctions for interneural communication. We then discuss the regulatory signals that orchestrate the precise assembly of these conserved macromolecular structures. This discussion will be framed in the context of the neurodevelopmental process. Specifically, much of our discussion will focus on how the seemingly disparate developmental processes are intimately linked at a molecular level, and how this relationship might be crucial in the developmental orchestration of circuit assembly. We hope that the discussion of the multifunctional cues that direct circuit development provides a conceptual framework into understanding how, with a limited set of signaling molecules, precise neural wiring can be coordinated between synaptic partners.

Colon-Ramos DA et al. (2007) Science "Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans."

Margeta MA, Colon-Ramos DA, Shen K

[Science, 2007]

Neural circuits are assembled through the coordinated innervation of pre- and postsynaptic partners. We show that connectivity between two interneurons, AIY and RIA, in Caenorhabditis elegans is orchestrated by a pair of glial cells that express UNC-6 (netrin). In the postsynaptic neuron RIA, the netrin receptor UNC-40 (DCC, deleted in colorectal cancer) plays a conventional guidance role, directing outgrowth of the RIA process ventrally toward the glia. In the presynaptic neuron AIY, UNC-40 (DCC) plays an unexpected and previously uncharacterized role: It cell-autonomously promotes assembly of presynaptic terminals in the immediate vicinity of the glial cell endfeet. These results indicate that netrin can be used both for guidance and local synaptogenesis and suggest that glial cells can function as guideposts during the assembly of neural circuits in vivo.

Colon-Ramos DA et al. (2008) PLoS Biol "Cellular conductors: glial cells as guideposts during neural circuit development."

Colon-Ramos DA, Shen K

[PLoS Biol, 2008]

Sengupta, T. et al. (2017) International Worm Meeting "Neurite position and synaptogenesis in the developing AIB neuron."

Kumar, A., Colon-Ramos, D.A., Moyle, M., Sengupta, T., Shroff, H.

[International Worm Meeting, 2017]

The position of a neuronal process (neurite) within a bundle or fascicle limits contact with other neurons to restrict potential synaptic partners. The AIB neuron of C. elegans travels through two distinct fascicles, forming presynaptic specializations in the posterior fascicle and postsynaptic sites in the anterior fascicle. The mechanism by which AIB positions its neurite in these two fascicles and restricts pre- and post-synaptic contacts to the appropriate neurons is not understood. We developed fluorescent markers to visually separate the two fascicles and label pre- and postsynaptic sites within the AIB neurite. Using diSPIM (dual-view inverted selective plane illumination microscopy), we visualized the process of outgrowth and synaptic polarity establishment in AIB during embryogenesis. By performing a forward genetic screen, we isolated candidate mutations that likely disrupt fascicle position and others that affect presynaptic polarity of the AIB neurite. Uncovering the causative genetic lesions for these mutants will provide insights into mechanisms that position neurites precisely within their fascicles to enable appropriate synaptic contacts.

Ramos CG et al. (2014) J Bacteriol "Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia."

Feliciano JR, da Costa PJ, Ramos CG, Grilo AM, Leitao JH

[J Bacteriol, 2014]

Volume 195, no. 16, p. 35143523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitao, J. Bacteriol. 193:15151526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

(2014) J Bacteriol "Retraction for Ramos et al., The second RNA chaperone, Hfq2, is also required for survival under stress and full virulence of Burkholderia cenocepacia J2315."

[J Bacteriol, 2014]

Volume 193, no. 7, p.15151526, 2011. Problems related to images published in this paper have been brought to our attention. Figure 8 contains duplicated images as well as images previously published in articles in Microbiology and Microbial Pathogenesis, i.e., the following: S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. http://dx.doi.org/10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. http://dx.doi.org/10.1016 /j.micpath.2010.02.006. Therefore, we retract the paper.Wedeeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Otu AA (1991) Afr J Med Med Sci "Tropical surgical abdominal emergencies: acute intestinal obstruction."

Otu AA

[Afr J Med Med Sci, 1991]

In a prospective evaluation of acute intestinal obstruction in emergency surgery, 3550 consecutive patients were studied. In the vast majority of patients (75%), obstruction was due to the external hernia, the inguinal hernia being by far the commonest type. However, the ascaris worm in children, volvulus of the sigmoid colon in adults, and intussusception in both children and adults, were significant causes of the disorder, and together accounted for 18% of the patients. Obstruction by the ascaris worm is easy to diagnose (by stool microscopy), and effective treatment (with antihelminthics) is readily available and cheap. A large number (90%) of the volvulus patients required resection for gangrene of the colon, thus arguing a strong case in support of laparotomy and inspection of the colon whenever feasible. A significant (41%) proportion of intussusception cases were adult, and in 33% of this group the lesion was associated with a tumour of the small bowel. The chief reason for death (10%) was late reporting to hospital.

Bolm M et al. (2004) Science "Bacterial resistance in daf-2 mutants."

Jansen WTM, Chhatwal GS, Bolm M

[Science, 2004]

In their Brevia "Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens," D.A. Garsin et al. show that long-lived C. elegans daf-2 mutants are resistant to killing by bacterial pathogens. Partial loss-of-function mutations in daf-2, which encodes an insulin-like receptor, results in de-repression of the transcription factor daf-16, leading to life extension and increased resistance to bacterial pathogens Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa.

Bisht N et al. (2019) Biomedicines "Cystatin from Filarial Parasites Suppress the Clinical Symptoms and Pathology of Experimentally Induced Colitis in Mice by Inducing T-Regulatory Cells, B1-Cells, and Alternatively Activated Macrophages."

Khatri V, Kalyanasundaram R, Bisht N, Chauhan N

[Biomedicines, 2019]

Potential alternative therapeutic strategies for immune-mediated disorders are being increasingly recognized and are studied extensively. We previously reported the therapeutic potential of <i>Brugia malayi</i> derived recombinant cystatin (r<i>Bma</i>Cys) in attenuating clinical symptoms of experimental colitis. The aim of this study was to elucidate the mechanisms involved in the r<i>Bma</i>Cys-induced suppression of inflammation in the colon. Our results show that, the frequency of CD4⁺CD25⁺FoxP3⁺ regulatory T-cells was elevated in the colon and mesenteric lymph nodes. Similarly, the peritoneal macrophages recovered from the r<i>Bma</i>Cys-treated colitis mice were alternatively activated and displayed reduced expression of TNF- and IL-6. Another finding was significant increases in IgM⁺B1a-cells in the peritoneal cavity of mice following r<i>Bma</i>Cys-treatment. These findings suggested that the regulatory cell network promoted by the r<i>Bma</i>Cys in the colon and associated lymphoid tissues is important for its anti-inflammatory activity in the dextran sulfate sodium (DSS)-induced colitis mice.

Pena-Ramos O et al. (2023) STAR Protoc "Measuring the acidification of the phagosomal lumen in live C. elegans embryos."

Zhou Z, Pena-Ramos O

[STAR Protoc, 2023]

In metazoans, the acidification of the phagosomal lumen is essential for the efficient degradation of cargoes. Here, we present a protocol for measuring the rate of acidification inside phagosomal lumen containing apoptotic cells in living C.&#xa0;elegans embryos. We describe steps for generating a worm population, selecting embryos, and mounting embryos on agar pads. We then detail live imaging of embryos and data analysis. This protocol is applicable to any organism in which real-time fluorescence imaging can be performed. For complete details on the use and execution of this protocol, please refer to Pena-Ramos et&#xa0;al. (2022).¹.