scholarly journals V(D)J recombination: signal and coding joint resolution are uncoupled and depend on parallel synapsis of the sites.

1993 ◽  
Vol 13 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
K M Sheehan ◽  
M R Lieber

V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations.

1993 ◽  
Vol 13 (3) ◽  
pp. 1363-1370
Author(s):  
K M Sheehan ◽  
M R Lieber

V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations.


Biochemistry ◽  
1989 ◽  
Vol 28 (19) ◽  
pp. 7913-7918 ◽  
Author(s):  
Chingkuang Tu ◽  
David N. Silverman ◽  
Cecilia Forsman ◽  
Bengt Harald Jonsson ◽  
Sven Lindskog

2018 ◽  
Author(s):  
Veronica L. Flores ◽  
Tamar Parmet ◽  
Narendra Mukherjee ◽  
Sacha Nelson ◽  
Donald B. Katz ◽  
...  

ABSTRACTThe strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with incidental stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste pre-exposure—TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (c-Fos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change c-Fos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA-related c-Fos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.


2021 ◽  
Vol 17 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Julie Poitras Santos

Walking the forest imaginary: a breath between us is a site-specific audio artwork that invites the audience to walk into the forest imaginary populated by things magical and unseen. Crafted uniquely in response to Alingsås Nolhaga Park, and using cues in the landscape as guides to research and poetic inscription, the artwork consists of an approximately one-hour walk with audio listening points throughout the park. Audio is accessed digitally through QR codes posted on pre-existing pathways and listened to with individual headphones. Wandering pathways through the woods, participants listen to a hybrid essay that explores the alternate spaces and time scales of the miniature worlds of moss. Focusing on the ancient and present role of bryophytes in creating oxygen and storing carbon, and helping to keep our ecosystem in balance, the work considers this ancient exchange as a form of dialogue.


2021 ◽  
pp. 102154
Author(s):  
Xin Wang ◽  
Baolong Zheng ◽  
Kehang Yu ◽  
Sen Jiang ◽  
Enrique J. Lavernia ◽  
...  

2011 ◽  
Vol 16 (3) ◽  
pp. 154-157 ◽  
Author(s):  
Charlotte Bates

This paper describes a site-specific sociological experiment and looks back at the history of British sociology from the Outlook Tower in Edinburgh. It considers the role of technological innovation in observation, and explores how attention is guided through two exercises in sensory attunement; augmented listening and telescopic looking. Reconfiguring the observer through different technologies and devices, the paper questions what it means to listen and to look, and highlights how our sociological outlook is deeply ethical and historical.


2016 ◽  
Vol 18 (4) ◽  
pp. 336-350 ◽  
Author(s):  
Larissa Hjorth

This article explores the unofficial role of camera phone practices in visualizing everyday forms of play as part of emergent urban cartographies. I argue that camera phone practices—especially in an age of timestamping—are creating their own cartographies of place that overlay the visual with the ambient, social with the geographic, emotional with the electronic, in new ways. By focusing upon the playful qualities of camera phone practices, we can begin to understand places as sites for ambient meandering and co-presence. Having outlined the notion of performative cartography as part of what has been defined as “critical cartography,” I consider how camera phone practices can be understood through ambient, co-present play. I turn to a site-specific mobile game, keitai mizu (mobile water), made for a post-Tokyo tsunami and Fukushima disaster context (known as 3/11), to explore the ways in which cartography can be performed.


Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4278-4286 ◽  
Author(s):  
Hiroyuki Kawagoe ◽  
Gerard C. Grosveld

The MN1-TEL (meningioma 1-translocation-ETS-leukemia) fusion oncoprotein is the product of the t(12;22)(p13;q11) in human myeloid leukemia consisting of N-terminal MN1 sequences, a transcriptional coactivator, fused to C-terminal TEL sequences, an E26-transformation–specific (ETS) transcription factor. To analyze the role of MN1-TEL in leukemogenesis, we created a site-directed transgenic (knock-in) mouse model carrying a conditional MN1-TEL transgene under the control of the Aml1 regulatory sequences. After induction, MN1-TEL expression was detected in both myeloid and lymphoid cells. Activation of MN1-TEL expression enhanced the repopulation ability of myeloid progenitors in vitro as well as partially inhibited their differentiation in vivo. MN1-TEL also promoted the proliferation of thymocytes while it blocked their differentiation from CD4-/CD8- to CD4+/CD8+ in vivo. After long latency, 30% of the MN1-TEL–positive mice developed T-lymphoid tumors. This process was accelerated by N-ethyl-N-nitrosourea–induced mutations. MN1-TEL–positive T-lymphoid tumors showed elevated expression of the Notch-1, Hes-1, c-Myc, and Lmo-2 genes while their Ink4a/pRB and Arf/p53 pathways were impaired, suggesting that these alterations cooperatively transform T progenitors. We conclude that MN1-TEL exerts its nonlineage-specific leukemogenic effects by promoting the growth of primitive progenitors and blocking their differentiation, but cooperative mutations are necessary to fully induce leukemic transformation.


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