scholarly journals The Dachsous/Fat/Four-jointed pathway implements axial long-range cell orientation

2016 ◽  
Author(s):  
Federica Mangione ◽  
Enrique Martín-Blanco

SUMMARYDespite a cumulative body of knowledge describing short-range cell interactions in morphogenetic processes, relatively little is known on the mechanism involved in the long-range spatial and temporal coordination of cells to build functional and structurally organized tissues. In particular, the attainment of a functionally optimized epithelia must require directional cues to instruct cell movements and cell orientations throughout the tissue field. In Drosophila, the adult epidermis of the abdominal segments is created de novo by the replacement of obsolete larval epidermal cells (LECs) by histoblasts (imaginal founder cells). As these proliferate, expand and fuse, they uniformly organize orienting on the surface along the antero-posterior axis. We found that the coordinated, axially oriented changes in shape of histoblasts respond to a dynamic, yet stereotyped redesign of the epithelial field mediated by the Dachsous/Fat/Four-jointed (Ds/Ft/Fj) pathway. The establishment and refinement of the expression gradients of the atypical cadherins Ds and Ft result in their axial polarization across cell interfaces and differential adhesiveness. We suggest that the role of Ds/Ft/Fj in long-range axially oriented planar cell alignment is a general function and that the regulation of the expression of its components would be crucial in the achievement of tissue uniformity in many other morphogenetic models or during tissue repair.

Nano LIFE ◽  
2014 ◽  
Vol 04 (01) ◽  
pp. 1450002 ◽  
Author(s):  
Qingsu Cheng ◽  
Greg M. Harris ◽  
Marc-Olivier Blais ◽  
Katy Rutledge ◽  
Ehsan Jabbarzadeh

Stem cells offer a promising tool in tissue engineering strategies, as their differentiated derivatives can be used to reconstruct most biological tissues. These approaches rely on controlling the biophysical cues that tune the ultimate fate of cells. In this context, significant effort has gone to parse out the role of conflicting matrix-elicited signals (e.g., topography and elasticity) in regulation of macroscopic characteristics of cells (e.g., shape and polarity). A critical hurdle, however, lies in our inability to recapitulate the nanoscale spatiotemporal pattern of these signals. The study presented in this manuscript took an initial step to overcome this challenge by developing a carbon nanotube (CNT)-based substrate for nanoresolution control of focal adhesion formation and cell alignment. The utility of this system was studied using human umbilical vascular endothelial cells (HUVECs) and human embryonic stem cells (hESCs) at a single cell level. Our results demonstrated the ability to control cell orientation by merely controlling the alignment of focal adhesions at a nanoscale size. Our long-term vision is to use these nanoengineered substrates to mimic cell orientation in earlier development and explore the role of polarity in asymmetric division and lineage specification of dividing cells.


2021 ◽  
Author(s):  
Metztli Cisneros-Aguirre ◽  
Felicia Wednesday Lopezcolorado ◽  
Linda Jillianne Tsai ◽  
Ragini Bhargava ◽  
Jeremy M Stark

Canonical non-homologous end joining (C-NHEJ) factors can assemble into a long-range (LR) complex with DNA ends relatively far apart that contains DNAPKcs, XLF, XRCC4, LIG4, and the KU heterodimer and a short-range (SR) complex lacking DNAPKcs that has the ends positioned for ligation. Since the SR complex can form de novo, the role of the LR complex (i.e., DNAPKcs) for chromosomal EJ is unclear. We have examined EJ of chromosomal blunt DNA double-strand breaks (DSBs), and found that DNAPKcs is significantly less important than XLF and XRCC4 for such EJ. However, weakening XLF via disrupting interaction interfaces (e.g., disrupting the XLF homodimer interface) causes a marked requirement for DNAPKcs, its kinase activity, and its ABCDE-cluster autophosphorylation sites for blunt DSB EJ. In contrast, other aspects of genome maintenance are sensitive to DNAPKcs kinase inhibition in a manner that is not further enhanced by XLF loss (i.e., suppression of homology-directed repair and structural variants, and IR-resistance). We suggest that DNAPKcs is required to position a weakened XLF in an LR complex that can transition into a functional SR complex for blunt DSB EJ, but also has distinct functions for other aspects of genome maintenance.


2016 ◽  
Vol 04 (01) ◽  
pp. 4-10

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.


2013 ◽  
pp. 97-116 ◽  
Author(s):  
A. Apokin

The author compares several quantitative and qualitative approaches to forecasting to find appropriate methods to incorporate technological change in long-range forecasts of the world economy. A?number of long-run forecasts (with horizons over 10 years) for the world economy and national economies is reviewed to outline advantages and drawbacks for different ways to account for technological change. Various approaches based on their sensitivity to data quality and robustness to model misspecifications are compared and recommendations are offered on the choice of appropriate technique in long-run forecasts of the world economy in the presence of technological change.


2013 ◽  
Vol 1 (1) ◽  
pp. 125-142 ◽  
Author(s):  
Susanne Durst ◽  
Ingi Runar Edvardsson ◽  
Guido Bruns

Studies on knowledge creation are limited in general, and there is a particular shortage of research on the topic in small and medium-sized enterprises (SMEs). Given the importance of SMEs for the economy and the vital role of knowledge creation in innovation, this situation is unsatisfactory. Accordingly, the purpose of our study is to increase our understanding of how SMEs create new knowledge. Data are obtained through semi-structured interviews with ten managing directors of German SMEs operating in the building and construction industry. The findings demonstrate the influence of external knowledge sources on knowledge creation activities. Even though the managing directors take advantage of different external knowledge sources, they seem to put an emphasis on informed knowledge sources. The study´s findings advance the limited body of knowledge regarding knowledge creation in SMEs.


2004 ◽  
Vol 52 (Suppl 1) ◽  
pp. S122.6-S123
Author(s):  
M. Garg ◽  
C. Bell ◽  
L. Rogers ◽  
S. Bassilian ◽  
W. N.P. Lee

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.


2021 ◽  
pp. 002188632110330
Author(s):  
Teresa Beste

This paper investigates the role of microlearning on cost-efficiency on knowledge transfer in a project-based organization. As part of an action research study in a Norwegian public sector organization working with construction projects, a microlearning series was initiated to increase knowledge transfer on cost-efficiency. Seven microlearning lessons were distributed to 334 employees, including short questionnaires after the first and last lesson. The study reflects on the design process of the lessons, on the participation rate, and on how it contributes to an increase of knowledge. Microlearning was perceived as relevant by the participants. It makes knowledge transfer less arbitrary by providing a common body of knowledge to all project teams. For the organizational practice, this implies that microlearning also has potential for knowledge sharing on other topics in the project-based organization. Updating the microlearning series with further examples and new lessons is expected to contribute to continuous learning on cost-efficiency.


2020 ◽  
Vol 13 (1) ◽  
pp. 96
Author(s):  
Carmen Bălan

The academic literature on consumer engagement and sustainable consumption has developed gradually over the last two decades. The body of knowledge related to the role of food and non-food retailers in this context, however, is only beginning to develop. The purpose of this systematic review is to analyse the existing literature on how retailers fulfil their role in engaging consumers in sustainable consumption. The need for a study with this purpose is proven by the fact that academic literature lacks a systematic review on this topic, despite the ascending trend in the number of published articles in the field. This systematic review is based on a five-step process to ensure quality, replicability, transparency, and reliable conclusions. The reviewed articles were published relatively recently in academic journals from different domains. This review identified seven distinct types of retail marketing interventions (involvement of retailers in marketing actions with the aim to engage consumers in sustainable consumption), 30 types of retail marketing mechanisms (consisting in marketing strategies, techniques, tools, and channels used by retailers), and 14 distinct types of consumer engagement in sustainable consumption patterns. The review suggests an agenda for further research and identifies practical implications for retail management.


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