scholarly journals An Irf6-Esrp1/2 regulatory axis controls midface morphogenesis in vertebrates

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev194498
Author(s):  
Shannon H. Carroll ◽  
Claudio Macias Trevino ◽  
Edward B. Li ◽  
Kenta Kawasaki ◽  
Nikita Myers ◽  
...  

ABSTRACTIrf6 and Esrp1 are important for palate development across vertebrates. In zebrafish, we found that irf6 regulates the expression of esrp1. We detailed overlapping Irf6 and Esrp1/2 expression in mouse orofacial epithelium. In zebrafish, irf6 and esrp1/2 share expression in periderm, frontonasal ectoderm and oral epithelium. Genetic disruption of irf6 and esrp1/2 in zebrafish resulted in cleft of the anterior neurocranium. The esrp1/2 mutant also developed cleft of the mouth opening. Lineage tracing of cranial neural crest cells revealed that the cleft resulted not from migration defect, but from impaired chondrogenesis. Analysis of aberrant cells within the cleft revealed expression of sox10, col1a1 and irf6, and these cells were adjacent to krt4+ and krt5+ cells. Breeding of mouse Irf6; Esrp1; Esrp2 compound mutants suggested genetic interaction, as the triple homozygote and the Irf6; Esrp1 double homozygote were not observed. Further, Irf6 heterozygosity reduced Esrp1/2 cleft severity. These studies highlight the complementary analysis of Irf6 and Esrp1/2 in mouse and zebrafish, and identify a unique aberrant cell population in zebrafish expressing sox10, col1a1 and irf6. Future work characterizing this cell population will yield additional insight into cleft pathogenesis.

2020 ◽  
Author(s):  
Shannon H. Carroll ◽  
Claudio Macias Trevino ◽  
Edward B-H Li ◽  
Kenta Kawasaki ◽  
Nora Alhazmi ◽  
...  

ABSTRACTOrofacial clefts are among the most common human congenital malformations. Irf6 and Esrp1 are two key genes important for palate development, conserved across vertebrates. In the zebrafish, we found that irf6 regulates the expression of esrp1. Using RNAscope, we detailed overlapping Irf6 and Esrp1/2 gene expression in the mouse frontonasal prominence ectoderm, lambda joint periderm, palate and lip epithelium. In the zebrafish, irf6 and esrp1/2 share expression in the pre-gastrulation periderm and the embryonic frontonasal ectoderm, oral epithelium ventral to the anterior neurocranium (ANC), and the developing stomodeum. Genetic disruption of irf6 and esrp1/2 in the zebrafish resulted in cleft of the ANC. In the esrp1/2 zebrafish mutant, cleft of the mouth opening formed and appeared to tether into the ANC cleft. Lineage tracing of the anterior cranial neural crest cells revealed that cleft of the ANC resulted not from migration defect, but from impaired chondrogenesis. Molecular analysis of the aberrant cells localized within the ANC cleft revealed that this cell population espresses sox10, col1a1 and irf6 and is adjacent to cells expressing epithelial krt4. Detailed morphogenetic analysis of mouse Irf6 mutant revealed mesenchymal defects not observed in the Esrp1/2 mutant. Analysis of breeding compound Irf6;Esrp1;Esrp2 mutant suggests that these genes interact where the triple mutant is not observed. Taken together, these studies highlight the complementary analysis of Irf6 and Esrp1/2 in mouse and zebrafish models and captured an unique aberrant embryonic cell population that contributes to cleft pathogenesis. Future work characterizing this unqiue sox10+, col1a1+, irf6+ cell population will yield additional insight into cleft pathogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin-Ze Tian ◽  
Sheng Xing ◽  
Jing-Yi Feng ◽  
Shu-Hua Yang ◽  
Yan-Fu Ding ◽  
...  

AbstractIn the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.


Sensors ◽  
2021 ◽  
Vol 21 (12) ◽  
pp. 4127
Author(s):  
Will Farlessyost ◽  
Kelsey-Ryan Grant ◽  
Sara R. Davis ◽  
David Feil-Seifer ◽  
Emily M. Hand

First impressions make up an integral part of our interactions with other humans by providing an instantaneous judgment of the trustworthiness, dominance and attractiveness of an individual prior to engaging in any other form of interaction. Unfortunately, this can lead to unintentional bias in situations that have serious consequences, whether it be in judicial proceedings, career advancement, or politics. The ability to automatically recognize social traits presents a number of highly useful applications: from minimizing bias in social interactions to providing insight into how our own facial attributes are interpreted by others. However, while first impressions are well-studied in the field of psychology, automated methods for predicting social traits are largely non-existent. In this work, we demonstrate the feasibility of two automated approaches—multi-label classification (MLC) and multi-output regression (MOR)—for first impression recognition from faces. We demonstrate that both approaches are able to predict social traits with better than chance accuracy, but there is still significant room for improvement. We evaluate ethical concerns and detail application areas for future work in this direction.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Asbjørn Følstad ◽  
Cameron Taylor

AbstractThe uptake of chatbots for customer service depends on the user experience. For such chatbots, user experience in particular concerns whether the user is provided relevant answers to their queries and the chatbot interaction brings them closer to resolving their problem. Dialogue data from interactions between users and chatbots represents a potentially valuable source of insight into user experience. However, there is a need for knowledge of how to make use of these data. Motivated by this, we present a framework for qualitative analysis of chatbot dialogues in the customer service domain. The framework has been developed across several studies involving two chatbots for customer service, in collaboration with the chatbot hosts. We present the framework and illustrate its application with insights from three case examples. Through the case findings, we show how the framework may provide insight into key drivers of user experience, including response relevance and dialogue helpfulness (Case 1), insight to drive chatbot improvement in practice (Case 2), and insight of theoretical and practical relevance for understanding chatbot user types and interaction patterns (Case 3). On the basis of the findings, we discuss the strengths and limitations of the framework, its theoretical and practical implications, and directions for future work.


2020 ◽  
Author(s):  
Sierra Rosiana ◽  
Liyang Zhang ◽  
Grace H. Kim ◽  
Alexey V. Revtovich ◽  
Arjun Sukumaran ◽  
...  

AbstractCandida albicans is a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role in C. albicans’ ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions in C. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, or in every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins in C. albicans virulence. We perform a comprehensive, high-throughput screen of this library, using Caenorhabditis elegans as a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilms in vitro, as well as to colonize the C. elegans host. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.SummaryCandida albicans is a human fungal pathogen and cause of life-threatening systemic infections. Cell surface-associated adhesins play a central role in this pathogen’s ability to establish infection. Here, we provide a comprehensive analysis of adhesin factors, and their role in fungal virulence. Exploiting a high-throughput workflow, we screened an adhesin mutant library using C. elegans as a simple model host, and identified mutants and genetic interactions involved in virulence. We found that adhesin mutants are impaired in in vitro pathogenicity, irrespective of their virulence. Together, this work provides new insight into the role of adhesin factors in mediating fungal virulence.


2021 ◽  
Author(s):  
Omar Khaled Ghonim ◽  
Deepti Muley ◽  
Mohamed Kharbeche ◽  
Yousef Mohamed ◽  
Ahmed Madkoor

Crashes involving pedestrians are a major concern for authorities in many developed and developing countries. To refrain pedestrians from illegal or unsafe road behavior, authorities introduced three pedestrian penalties in the State of Qatar from August 2019. This paper assesses the awareness, perception, and adaptive intentions of the new amendment to the pedestrians’ law. A questionnaire survey, designed in three languages, was distributed online using Qatar University contacts and Twitter account of the General Directorate of Traffic at the Ministry of Interior, State of Qatar. A sample of 521 complete responses was obtained and used for statistical analysis. The results indicated that only 32 % of the respondents were aware of the law amendment before taking this survey. Further, the higher score for perception, adaptive intentions and awareness showed that the respondents were aware of the risks and the law amendment will have a positive effect on their behavior on road as pedestrians. The outcomes of the analysis show the efficacy of the law amendment. However, the actual behavior changes need to be studied by analyzing the pedestrian crash data and conducting a before and after study. Moreover, the study of the effects on pedestrians’ behavior, through empirical observations, is proposed to get insight into actual behaviors after law amendment as a part of future work on the topic.


2019 ◽  
Author(s):  
Lauren Marie Ackerman

This paper presents a framework for how the multifaceted nature of "gender" (human and linguistic) interacts with grammatical operations such as coreference dependency formation. It frames the question through the lens of English, in which it focuses on how personal names and referents who identify as nonbinary can provide insight into the conceptual representations of gender. Additional data from a variety of modern languages supports a model of how gender might be cognitively represented such that the observed linguistic patterns are available. A three-tiered model of gender is proposed that unites grammatical, cognitive, social, and biological aspects and describes how implications of this model might be tested in future work.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ramón Fuentes ◽  
Alain Arias ◽  
María Florencia Lezcano ◽  
Diego Saravia ◽  
Gisaku Kuramochi ◽  
...  

The aim of this study was to analyze the general, geometric, and kinematic characteristics of the masticatory cycle’s movements in a tridimensional way, using a method developed by our study group to provide a new insight into the analysis of mandibular movements due to advancement in the potential of computational analysis. Ten individuals (20.1 ± 2.69 years), molar class I, without mandibular movement problems participated in this study. The movements of the masticatory cycles, frontal and sagittal mandibular border movements, were recorded using 3D electromagnetic articulography and processed with computational scripts developed by our research group. The number of chewing cycles, frequency (cycles/s), chewing cycle areas/mandibular border movements areas ratios, and the mouth opening and closing speeds on the 3D trajectory of the chewing cycle were compared. The cycles were divided and analyzed in thirds. The masticatory cycles showed high variation among the individuals (21.6 ± 9.4 cycles); the frequency (1.46 ± 0.21 cycles/s) revealed a moderate positive correlation (R = 0.52) with the number of cycles. The frontal area ratios between the cycle area and the mandibular border movement presented higher values in the first third (6.65%) of the masticatory cycles, and the ratios of sagittal areas were higher and more variable (first, 7.67%; second, 8.06%; and third, 10.04%) than the frontal view. The opening and closing mouth speeds were greater in the second third of the masticatory cycles (OS, 57.82 mm/s; CS, 58.34 mm/s) without a significant difference between the opening and closing movements when the same thirds were evaluated. Further studies are necessary to improve the understanding of the masticatory cycles regarding the standardization of parameters and their values.


2017 ◽  
Vol 114 (31) ◽  
pp. E6447-E6456 ◽  
Author(s):  
Inbal Eizenberg-Magar ◽  
Jacob Rimer ◽  
Irina Zaretsky ◽  
David Lara-Astiaso ◽  
Shlomit Reich-Zeliger ◽  
...  

During cell differentiation, progenitor cells integrate signals from their environment that guide their development into specialized phenotypes. The ways by which cells respond to complex signal combinations remain difficult to analyze and model. To gain additional insight into signal integration, we systematically mapped the response of CD4+ T cells to a large number of input cytokine combinations that drive their differentiation. We find that, in response to varied input combinations, cells differentiate into a continuum of cell fates as opposed to a limited number of discrete phenotypes. Input cytokines hierarchically influence the cell population, with TGFβ being most dominant followed by IL-6 and IL-4. Mathematical modeling explains these results using additive signal integration within hierarchical groups of input cytokine combinations and correctly predicts cell population response to new input conditions. These findings suggest that complex cellular responses can be effectively described using a segmented linear approach, providing a framework for prediction of cellular responses to new cytokine combinations and doses, with implications to fine-tuned immunotherapies.


2013 ◽  
Vol 9 (S297) ◽  
pp. 226-228 ◽  
Author(s):  
N. Wehres ◽  
B. Ochsendorf ◽  
J. Bally ◽  
T Snow ◽  
V. Bierbaum ◽  
...  

AbstractThis work focusses on MWC 922, the central object in the Red Square Nebula. We obtained low and medium resolution spectra of both, the central object and the surrounding nebula, using the DIS and TSpec spectrograph. The spectra show the whole spectral range between ~3 500 Å up to ~25 000 Å. The central object shows a plethora of emission lines, including many Fe II and forbidden Fe [II] lines. Here, we present the inventory of the emission lines of the central object, MWC 922. Future work will comprise the identification of the nebula emission lines by using newly obtained X-Shooter spectra. That way we want to gain further insight into the physical and chemical conditions in this environment. A comparison of the Red Square to the Red Rectangle Nebula is anticipated and will guide our search for DIBs in emission.


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