scholarly journals Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable Consequences of Tankyrase Inhibition in Human Cells

2015 ◽  
Vol 35 (14) ◽  
pp. 2425-2435 ◽  
Author(s):  
Ozlem Kulak ◽  
Hua Chen ◽  
Brody Holohan ◽  
Xiaofeng Wu ◽  
Huawei He ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Telomere Length ◽  
Experimental Approach ◽  
Cultured Cells ◽  
Transcriptional Response ◽  
Chemical Exposure ◽  
Telomere Protection ◽  
Chemical Inhibitors ◽  
Cell Immortalization

Maintenance of chromosomal ends (telomeres) directly contributes to cancer cell immortalization. The telomere protection enzymes belonging to the tankyrase (Tnks) subfamily of poly(ADP-ribose) polymerases (PARPs) have recently been shown to also control transcriptional response to secreted Wnt signaling molecules. Whereas Tnks inhibitors are currently being developed as therapeutic agents for targeting Wnt-related cancers and as modulators of Wnt signaling in tissue-engineering agendas, their impact on telomere length maintenance remains unclear. Here, we leveraged a collection of Wnt pathway inhibitors with previously unassigned mechanisms of action to identify novel pharmacophores supporting Tnks inhibition. A multifaceted experimental approach that included structural, biochemical, and cell biological analyses revealed two distinct chemotypes with selectivity for Tnks enzymes. Using these reagents, we revealed that Tnks inhibition rapidly induces DNA damage at telomeres and telomeric shortening upon long-term chemical exposure in cultured cells. On the other hand, inhibitors of the Wnt acyltransferase Porcupine (Porcn) elicited neither effect. Thus, Tnks inhibitors impact telomere length maintenance independently of their affects on Wnt/β-catenin signaling. We discuss the implications of these findings for anticancer and regenerative medicine agendas dependent upon chemical inhibitors of Wnt/β-catenin signaling.

Registered Report: Transcriptional Analysis of Savings Memory Suggests Forgetting Is Due to Retrieval Failure

2020 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman ◽  
Tania Rosiles ◽  
Melissa Nguyen ◽  
Annette Garcia ◽  
...  
Keyword(s):  
Memory Trace ◽  
Aplysia Californica ◽  
Transcriptional Response ◽  
Transcriptional Analysis ◽  
Retrieval Failure ◽  
Initial Learning ◽  
Rigorous Test ◽  
Stage 1 ◽  
Induced Changes

[[This is a Stage 2 Registered Report manuscript now accepted for publication at eNeuro. The accepted Stage 1 manuscript is posted here: https://psyarxiv.com/s7dft, and the pre-registration for the project is available here (https://osf.io/fqh8j, 9/11/2019). A link to the final Stage 2 manuscript will be posted after peer review and publication.]] There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting lead to different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay, then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval failure, then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day after training), a forgotten memory (8 days after training), and a savings memory (8 days after training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We found that the re-activation of sensitization during savings does not involve a substantial transcriptional response. Thus, savings is transcriptionally distinct relative to a newer (1-day old) memory, with no co-regulated transcripts, negligible similarity in regulation-ranked ordering of transcripts, and a negligible correlation in training-induced changes in gene expression (r = .04 95% CI [-.12, .20]). Overall, our results suggest that forgetting of sensitization memory represents retrieval failure.

scholarly journals Transcriptional Response of Soybean Suspension-cultured Cells Induced by Nod Factors Obtained from Bradyrhizobium japonicum USDA110

2002 ◽  
Vol 43 (11) ◽  
pp. 1314-1322
Author(s):  
Tsuneo Hakoyama ◽  
Tadashi Yokoyama ◽  
Hiroshi Kouchi ◽  
Ken-ichi Tsuchiya ◽  
Hisatoshi Kaku ◽  
...  
Keyword(s):  
Bradyrhizobium Japonicum ◽  
Cultured Cells ◽  
Transcriptional Response ◽  
Nod Factors ◽  
Suspension Cultured Cells

scholarly journals Wnt Signaling Is Required for Long-Term Memory Formation

Cell Reports ◽  
2013 ◽  
Vol 4 (6) ◽  
pp. 1082-1089 ◽  
Author(s):  
Ying Tan ◽  
Dinghui Yu ◽  
Germain U. Busto ◽  
Curtis Wilson ◽  
Ronald L. Davis
Keyword(s):  
Wnt Signaling ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory

scholarly journals Nestling telomere shortening, but not telomere length, reflects developmental stress and predicts survival in wild birds

2014 ◽  
Vol 281 (1785) ◽  
pp. 20133287 ◽  
Author(s):  
Jelle J. Boonekamp ◽  
G. A. Mulder ◽  
H. Martijn Salomons ◽  
Cor Dijkstra ◽  
Simon Verhulst
Keyword(s):  
Telomere Length ◽  
Brood Size ◽  
Developmental Stress ◽  
Free Living ◽  
Telomere Shortening ◽  
Developmental Effects ◽  
Fitness Consequences ◽  
Developmental Conditions ◽  
Fledgling Mass

Developmental stressors often have long-term fitness consequences, but linking offspring traits to fitness prospects has remained a challenge. Telomere length predicts mortality in adult birds, and may provide a link between developmental conditions and fitness prospects. Here, we examine the effects of manipulated brood size on growth, telomere dynamics and post-fledging survival in free-living jackdaws. Nestlings in enlarged broods achieved lower mass and lost 21% more telomere repeats relative to nestlings in reduced broods, showing that developmental stress accelerates telomere shortening. Adult telomere length was positively correlated with their telomere length as nestling ( r = 0.83). Thus, an advantage of long telomeres in nestlings is carried through to adulthood. Nestling telomere shortening predicted post-fledging survival and recruitment independent of manipulation and fledgling mass. This effect was strong, with a threefold difference in recruitment probability over the telomere shortening range. By contrast, absolute telomere length was neither affected by brood size manipulation nor related to survival. We conclude that telomere loss, but not absolute telomere length, links developmental conditions to subsequent survival and suggest that telomere shortening may provide a key to unravelling the physiological causes of developmental effects on fitness.

Bioresorbable Microspheres as Injectable Cell Carrier: FRom Preparation to in Vitro Evaluation

1998 ◽  
Vol 550 ◽  
Author(s):  
Y. Senuma ◽  
S. Franceschin ◽  
J. G. Hilborn ◽  
P. Tissiéres ◽  
P. Frey
Keyword(s):  
Cultured Cells ◽  
Urothelial Cells ◽  
New Approach ◽  
Muscular Structure ◽  
Cell Carrier ◽  
Support Matrix ◽  
Vesico Ureteral Reflux

AbstractA new approach to the vesico-ureteral reflux could be a local regeneration of the defective vesicoureteral junction by transplanting living cells to the target site. The aim of this work is to provide a long-term effective treatment by producing bioresorbable microspheres which can act as support matrix for those cells, with the goal of an in vivo transfer of the in vitro cultured cells with a minimal surgical procedure. After microsphere degradation, the cells should be integrated into the muscular structure of the junction. Most innovative is that these are cultured muscle and urothelial cells from the bladder of the same patient.

scholarly journals Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation

2017 ◽  
Vol 29 (5) ◽  
pp. 1539-1551 ◽  
Author(s):  
Stacy S. Drury ◽  
Brittany R. Howell ◽  
Christopher Jones ◽  
Kyle Esteves ◽  
Elyse Morin ◽  
...  
Keyword(s):  
Telomere Length ◽  
Nonhuman Primate ◽  
Social Rank ◽  
Juvenile Period ◽  
Primate Model ◽  
Causal Pathways ◽  
Biological Mother ◽  
Physiologic Regulation ◽  
Negative Health Outcomes

AbstractThe molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.

Frequency selectivity, multistability, and oscillations emerge from models of genetic regulatory systems

1998 ◽  
Vol 274 (2) ◽  
pp. C531-C542 ◽  
Author(s):  
Paul Smolen ◽  
Douglas A. Baxter ◽  
John H. Byrne
Keyword(s):  
Cellular Response ◽  
Cultured Cells ◽  
Computational Approach ◽  
Long Term Memory ◽  
Mrna Levels ◽  
Complex Dynamic ◽  
Dynamic Activity ◽  
Regulatory Systems ◽  
Complex Models

To examine the capability of genetic regulatory systems for complex dynamic activity, we developed simple kinetic models that incorporate known features of these systems. These include autoregulation and stimulus-dependent phosphorylation of transcription factors (TFs), dimerization of TFs, crosstalk, and feedback. The simplest model manifested multiple stable steady states, and brief perturbations could switch the model between these states. Such transitions might explain, for example, how a brief pulse of hormone or neurotransmitter could elicit a long-lasting cellular response. In slightly more complex models, oscillatory regimes were identified. The addition of competition between activating and repressing TFs provided a plausible explanation for optimal stimulus frequencies that give maximal transcription. Such optimal frequencies are suggested by recent experiments comparing training paradigms for long-term memory formation and examining changes in mRNA levels in repetitively stimulated cultured cells. In general, the computational approach illustrated here, combined with appropriate experiments, provides a conceptual framework for investigating the function of genetic regulatory systems.

An Experimental Approach to the Function of Classic Maya Chultuns

1971 ◽  
Vol 36 (3) ◽  
pp. 322-335 ◽  
Author(s):  
Dennis E. Puleston
Keyword(s):  
Experimental Approach ◽  
Experimental Studies ◽  
Water Storage ◽  
Food Storage ◽  
Food Crop ◽  
Traditional Foods ◽  
Long Term Storage ◽  
Brosimum Alicastrum ◽  
Term Storage

AbstractExperimental techniques have provided an exciting breakthrough for the functional analysis of Maya chultuns. While deep cistern-like chultuns, common at certain sites in the northern lowlands, have been shown to be functional for water storage, smaller lateral-chambered chultuns characteristic of certain parts of the southern lowlands probably had a very different function. Excavation and examination of the latter features, in light of a whole range of possibilities, suggest that they were constructed to be used for food storage. Experimental studies, however, reveal them to be unsuitable for the storage of most traditional foods, including maize. At least one local food crop, the seed of the ramon (Brosimum alicastrum, Moraceae), appears to be ideally suited for long-term storage under these conditions. Chambers constructed beneath platforms in the northern lowlands may have been used for the storage of maize. A need for more experimental work is indicated.

Adaptation of greater plantain, Plantago major L., to long-term radiation and chemical exposure

2016 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
V. N. Pozolotina ◽  
E. V. Antonova ◽  
N. S. Shimalina
Keyword(s):  
Chemical Exposure ◽  
Plantago Major
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