scholarly journals Multimodal transcriptional control of pattern formation in embryonic development

2018 ◽  
Author(s):  
Nicholas C Lammers ◽  
Vahe Galstyan ◽  
Armando Reimer ◽  
Sean A Medin ◽  
Chris H Wiggins ◽  
...  

AbstractPredicting developmental outcomes from regulatory DNA sequence and transcription factor patterns remains an open challenge in physical biology. Using stripe 2 of theeven-skippedgene inDrosophilaembryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe, and that control of thewindow of timeover which each nucleus transcribeseven-skippedplays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies—bursting and the time window—obey different kinds of regulatory logic, suggesting that the stripe is shaped by the interplay of two distinct underlying molecular processes.

2019 ◽  
Vol 117 (2) ◽  
pp. 836-847 ◽  
Author(s):  
Nicholas C. Lammers ◽  
Vahe Galstyan ◽  
Armando Reimer ◽  
Sean A. Medin ◽  
Chris H. Wiggins ◽  
...  

Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes.


2021 ◽  
Vol 22 (8) ◽  
pp. 4236
Author(s):  
Amelia Eva Aránega ◽  
Estefanía Lozano-Velasco ◽  
Lara Rodriguez-Outeiriño ◽  
Felicitas Ramírez de Acuña ◽  
Diego Franco ◽  
...  

microRNAs (miRNAs) are small non-coding RNAs required for the post-transcriptional control of gene expression. MicroRNAs play a critical role in modulating muscle regeneration and stem cell behavior. Muscle regeneration is affected in muscular dystrophies, and a critical point for the development of effective strategies for treating muscle disorders is optimizing approaches to target muscle stem cells in order to increase the ability to regenerate lost tissue. Within this framework, miRNAs are emerging as implicated in muscle stem cell response in neuromuscular disorders and new methodologies to regulate the expression of key microRNAs are coming up. In this review, we summarize recent advances highlighting the potential of miRNAs to be used in conjunction with gene replacement therapies, in order to improve muscle regeneration in the context of Duchenne Muscular Dystrophy (DMD).


2018 ◽  
Vol 95 (3) ◽  
pp. 2-20 ◽  
Author(s):  
Andrew Wiese

Place-based activism has played a critical role in the history of urban and environmental politics in California. This article explores the continuing significance of environmental place making to grassroots politics through a case study of Friends of Rose Canyon, an environmental group in San Diego. Based in the fast-growing University City neighborhood, Friends of Rose Canyon waged a long, successful campaign between 2002 and 2018 to prevent construction of a bridge in the Rose Canyon Open Space Park in their community. Using historical and participant observer methodologies, this study reveals how twenty-first-century California urbanites claimed and created meaningful local places and mobilized effective politics around them. It illuminates the critical role of individual activists; suggests practical, replicable strategies for community mobilization; and demonstrates the significant impact of local activism at the urban and metropolitan scales.


2015 ◽  
Vol 21 (6) ◽  
pp. 741-754 ◽  
Author(s):  
Llandis Barratt-Pugh ◽  
Susanne Bahn

AbstractThis paper explores the role played by a Human Resources (HR) department orchestrating culture change during the merger of two large State departments with dissimilar cultures. A 2-year case study determined what HR strategies were having the greatest impact on embedding new organisational values to produce a more flexible culture and how these practices could be accelerated. This paper indicates how a more strategic approach by HR departments can support and develop relational managing capability that accelerates cultures change towards a more flexible work environment.This paper describes the context of the change process, the relevant literature, and outlines the research process. The findings from the phases of the data collection are summarised revealing the traumatic perceptions of the change process, but also the instrumental actions of some managers, working creatively with their teams to tackle new tasks and projects. The evidence suggests that these informal practices of task allocation were at the core of change agency in this case study and put the new flexible organisational values into action. The findings illustrate how the organisation moves from valuing managers for their technical competence to valuing managers for their relational competence.The paper then discusses what strategic HR actions were accelerating this process and illuminates the critical role of building managers as change agents. The paper concludes by confirming the need for a strategic approach by HR during organisational change. Building manager capability and supporting informal change agency practices is presented as a core focus for HR during such organisational cultural change programmes.


2021 ◽  
Vol 13 (14) ◽  
pp. 7600
Author(s):  
Wenting Ma ◽  
Rui Mu ◽  
Martin de Jong

Co-production is a solution by which the government provides public services. Co-production theory is built upon Western experience and currently focuses on the types of co-production in different policy stages, the barriers and governance strategies for co-production. However, little attention is paid to how political background will influence the co-production process. To fill the gap, we analyzed a case of co-production that occurred in China, and we characterized the political background as consisting of three main political features: political mobility, central–local relations, and performance measurement. Based on an in-depth case study of a government project in a medium-sized Chinese city, the impact and the changes of political features affecting governmental projects in different co-production stages are analyzed and assessed. We find that political features play a critical role in the co-production of China’s large government projects and may separately and jointly affect co-production. Government performance measurement affects the co-design and co-implementation of projects. Political mobility and changes in local government and performance measurement also affect the co-implementation continuity of the project. Political focus affects the co-design of projects. Central-local relations influence the support from higher government and the actual practices of lower government in the co-implementation stage.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Ana Clara Carvalho Tourinho ◽  
Sabrina Andrade Barbosa ◽  
Özgür Göçer ◽  
Klaus Chaves Alberto

PurposeUsing the campus of a Brazilian university as case study, this research aims to identify which aspects of the outdoor spaces are the most significant in attracting people.Design/methodology/approachThis research relies on the application of different post-occupancy evaluation (POE) methods, including user tracking, behavioural mapping and questionnaires, on one plateau of the campus.FindingsThree group of aspects (socialization, proximity and infrastructure) were identified as key elements in explaining the impact of the campus physical characteristics on users’ behaviour. The results indicate that having characteristics of at least one group of aspects in those spaces can guarantee their vitality and, if there is presence of attributes of more than one group, liveliness can be increased.Research limitations/implicationsFurther studies should be conducted on an entire campus to identify other spatial elements in the three groups.Practical implicationsThis research contributes to the planning of future campuses and to solutions to the existed ones, indicating the most relevant spatial characteristics to be considered. Additionally, the combination of different methods may be useful to future research.Originality/valueMost of the investigations on the university campuses focus on the buildings, and little research has investigated the outdoor spaces, although they play a critical role in learning and academic life, where people establish social, cultural and personal relationships. In addition, studies using several POE allowed a consistent and complete diagnostic about the aspects of the campus, giving recommendations for future projects.


2019 ◽  
Vol 20 (5) ◽  
pp. 897-919
Author(s):  
Hung-Lung Lin ◽  
Cheng-Chung Cho ◽  
Yu-Yu Ma ◽  
Ying-Qing Hu ◽  
Ze-Hui Yang

The rapid development of e-commerce in China has played a critical role in the development of the national economy and ongoing modernization. The plant industry is unique among industries that employ e-commerce sales models because its products exhibit special characteristics such as high death and damage rates. Therefore, its e-commerce and logistical requirements are stricter than in other industries and, as a result, excess warehouse storage can be extremely difficult for e-commerce–based plant shops to manage. Numerous studies have indicated the need to identify a product’s most up-to-date market conditions, as well as the type, function, and size of warehouses. Therefore, based on a case study, this study proposes an optimization plan for solving excess warehouse storage in e-commerce–based plant shops. First, sales volume data of the case company, Enterprise A, were analyzed to predict future sales. Then, entropy and the technique for order preference by similarity to an ideal solution were used to construct the decision-making model. Finally, a cloud warehouse–based optimization plan was proposed to solve excess warehouse storage in e-commerce–based plant shops. This plan can serve as a reference for decision-makers or executives in e-commerce–based plant shops when handling excess warehouse storage.


Author(s):  
Carmen Lopez ◽  
Mingfeng Cao ◽  
Zhanyi Yao ◽  
Zengyi Shao

Production of industrially relevant compounds in microbial cell factories can employ either genomes or plasmids as an expression platform. Selection of plasmids as pathway carriers is advantageous for rapid demonstration but poses a challenge of stability. Yarrowia lipolytica has attracted great attention in the past decade for the biosynthesis of chemicals related to fatty acids at titers attractive to industry, and many genetic tools have been developed to explore its oleaginous potential. Our recent studies on the autonomously replicating sequences (ARSs) of nonconventional yeasts revealed that the ARSs from Y. lipolytica showcase a unique structure that includes a previously unannotated sequence (spacer) linking the origin of replication (ORI) and the centromeric (CEN) element and plays a critical role in modulating plasmid behavior. Maintaining a native 645-bp spacer yielded a 4.5-fold increase in gene expression and higher plasmid stability compared to a more universally employed minimized ARS. Testing the modularity of the ARS sub-elements indicated that plasmid stability exhibits a pronounced cargo dependency. Instability caused both plasmid loss and intramolecular rearrangements. Altogether, our work clarifies the appropriate application of various ARSs for the scientific community and sheds light on a previously unexplored DNA element as a potential target for engineering Y. lipolytica.


Author(s):  
Richard Rosch ◽  
Michelle Heys ◽  
Hannah Kuper

Worldwide, many children do not meet their developmental potential. This is particularly the case in LMICs and especially affects children living with disability. Thus, improving developmental attainment and reducing the impact of disability has now become an integral part of many of the sustainable development goals. This chapter introduces several tools currently available to measure both childhood development, and the effects of disability. Using examples from current research in global health this chapter introduces both known effective intervention strategies that improve developmental outcomes, and highlights challenges and future priorities for further research. These points are further illustrated using epilepsy as a case study, highlighting how the interaction of biomedical, psychosocial, and socioeconomic factors impacts on childhood development.


Author(s):  
Patriarca Riccardo ◽  
Del Pinto Gianluca ◽  
Di Gravio Giulio ◽  
Costantino Francesco

Due to the inherent complexity of nowadays Air Traffic Management (ATM) system, standard methods looking at an event as a linear sequence of failures might become inappropriate. For this purpose, adopting a systemic perspective, the Functional Resonance Analysis Method (FRAM) originally developed by Hollnagel, helps in identifying nonlinear combinations of events and interrelationships. This paper aims to enhance the strength of FRAM-based accident analyses, discussing the Resilience Analysis Matrix (RAM), a user-friendly tool that supports the analyst during the analysis, in order to reduce the complexity of representation of FRAM. The RAM offers a two-dimensional representation which systematically highlights the connections among couplings, and thus even the highly connected group of couplings. As an illustrative case study, this paper develops a systemic accident analysis for the runway incursion happened in February 1991 at LAX airport, involving SkyWest Flight 5569 and USAir Flight 1493. FRAM confirms itself a powerful method to characterize the variability of the operational scenario, identifying the dynamic couplings with a critical role during the event and helping in discussing the systemic effects of variability at different level of analysis.


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