scholarly journals Dynamic Hh signaling can generate temporal information during tissue patterning

2018 ◽  
Author(s):  
Diana García-Morales ◽  
Tomás Navarro ◽  
Antonella Iannini ◽  
David G. Míguez ◽  
Fernando Casares

ABSTRACTThe differentiation of tissues and organs requires that cells exchange information in space and time. Spatial information is often conveyed by morphogens, molecules that disperse across receiving cells generating signaling gradients. Cells translate such concentration gradients into space-dependent patterns of gene expression and cellular behavior [1, 2]. But could morphogen gradients also convey developmental time? Here, investigating the developmental role of Hh on a component of the Drosophila visual system, the ocellar retina, we discovered that ocellar cells use the non-linear gradient of Hh as a temporal cue, collectively performing the biological equivalent of a mathematical logarithmic transformation. In this way, a morphogen diffusing from a non-moving source is decoded as a wave of differentiating photoreceptors that travels at constant speed throughout the retinal epithelium.

Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.


2013 ◽  
Vol 62 (1) ◽  
pp. 85-95 ◽  
Author(s):  
Elzbieta Bielecka ◽  
Agnieszka Zwirowicz-Rutkowska

Abstract One of the more important elements of spatial information infrastructure is the organisational structure defining the obligations and dependencies between stakeholders that are responsible for the infrastructure. Many SDI practitioners and theoreticians emphasise that its influence on the success or failure of activities undertaken is significantly greater than that of technical aspects. Being aware of the role of the organisational structure in the creating, operating and maintenance of spatial information infrastructure (SII), Polish legislators placed appropriate regulations in the Spatial Information Infrastructure Act, being the transposition of the INSPIRE Directive into Polish Law. The principal spatial information infrastructure stakeholders are discussed in the article and also the scope of cooperation between them. The tasks and relationships between stakeholders are illustrated in UML, in both the use case and the class diagram. Mentioned also are the main problems and obstructions resulting from imprecise legal regulations.


2021 ◽  
Vol 20 ◽  
pp. 153473542110316
Author(s):  
Liang Wang ◽  
Lei Xu ◽  
Yu Wang

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.


2021 ◽  
Vol 10 (3) ◽  
pp. 166
Author(s):  
Hartmut Müller ◽  
Marije Louwsma

The Covid-19 pandemic put a heavy burden on member states in the European Union. To govern the pandemic, having access to reliable geo-information is key for monitoring the spatial distribution of the outbreak over time. This study aims to analyze the role of spatio-temporal information in governing the pandemic in the European Union and its member states. The European Nomenclature of Territorial Units for Statistics (NUTS) system and selected national dashboards from member states were assessed to analyze which spatio-temporal information was used, how the information was visualized and whether this changed over the course of the pandemic. Initially, member states focused on their own jurisdiction by creating national dashboards to monitor the pandemic. Information between member states was not aligned. Producing reliable data and timeliness reporting was problematic, just like selecting indictors to monitor the spatial distribution and intensity of the outbreak. Over the course of the pandemic, with more knowledge about the virus and its characteristics, interventions of member states to govern the outbreak were better aligned at the European level. However, further integration and alignment of public health data, statistical data and spatio-temporal data could provide even better information for governments and actors involved in managing the outbreak, both at national and supra-national level. The Infrastructure for Spatial Information in Europe (INSPIRE) initiative and the NUTS system provide a framework to guide future integration and extension of existing systems.


2013 ◽  
Vol 368 (1632) ◽  
pp. 20130018 ◽  
Author(s):  
Andrea I. Ramos ◽  
Scott Barolo

In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.


2008 ◽  
Vol 295 (4) ◽  
pp. G760-G765 ◽  
Author(s):  
Marcel C. G. van de Poll ◽  
Gerdien C. Ligthart-Melis ◽  
Steven W. M. Olde Damink ◽  
Paul A. M. van Leeuwen ◽  
Regina G. H. Beets-Tan ◽  
...  

The gut is classically seen as the main source of circulating ammonia. However, the contribution of the intestines to systemic ammonia production may be limited by hepatic extraction of portal-derived ammonia. Recent data suggest that the kidney may be more important than the gut for systemic ammonia production. The aim of this study was to quantify the role of the kidney, intestines, and liver in interorgan ammonia trafficking in humans with normal liver function. In addition, we studied changes in interorgan nitrogen metabolism caused by major hepatectomy. From 21 patients undergoing surgery, blood was sampled from the portal, hepatic, and renal veins to assess intestinal, hepatic, and renal ammonia metabolism. In seven cases, blood sampling was repeated after major hepatectomy. At steady state during surgery, intestinal ammonia release was equaled by hepatic ammonia uptake, precluding significant systemic release of intestinal-derived ammonia. In contrast, the kidneys released ammonia to the systemic circulation. Major hepatectomy led to increased concentrations of ammonia and amino acids in the systemic circulation. However, transsplanchnic concentration gradients after major hepatectomy were similar to baseline values, indicating the rapid institution of a new metabolic equilibrium. In conclusion, since hepatic ammonia uptake exactly equals intestinal ammonia release, the splanchnic area, and hence the gut, probably does not contribute significantly to systemic ammonia release. After major hepatectomy, hepatic ammonia clearance is well preserved, probably related to higher circulating ammonia concentrations.


2008 ◽  
Vol 08 (02) ◽  
pp. 153-160 ◽  
Author(s):  
BRUCE K. MILTHORPE

Cellular biomechanics is an area of study that is receiving more attention as time progresses. The response of cells to their mechanical environment, including biomechanical stimuli, has far-reaching ramifications for the area of tissue engineering, especially for tissues designed to withstand mechanical loading (e.g. bone, cartilage, tendons and ligaments, and arteries). The effects of mechanical stimuli on cells are only recently being examined, and the potential role of mechanical stimuli in tissue engineering is still one that is largely ignored in the design of tissue engineering scaffolds. The relationship of mechanical properties of scaffolds or of mechanical stimuli to cell behavior is complex, but vital to the development of the field. Also, understanding the complex interplay of form and environment on cells involves an increase in our knowledge of how cells react to their total environment including mechanical stimuli and material properties. In order to improve tissue engineering outcomes, a nexus must be developed between the mechanical, biochemical, and biological studies of cellular behavior, in the context of extremely complex systems.


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