scholarly journals Mutations affecting development of the notochord in zebrafish

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 117-128 ◽  
Author(s):  
D.L. Stemple ◽  
L. Solnica-Krezel ◽  
F. Zwartkruis ◽  
S.C. Neuhauss ◽  
A.F. Schier ◽  
...  
Keyword(s):  
Large Scale ◽  
Normal Development ◽  
Paraxial Mesoderm ◽  
Skeletal Element ◽  
Additional Insight ◽  
Genetic Pathway ◽  
Complementation Groups ◽  
Vertebrate Embryos ◽  
Insight Into

The notochord is critical for the normal development of vertebrate embryos. It serves both as the major skeletal element of the embryo and as a signaling source for the establishment of pattern within the neurectoderm, the paraxial mesoderm and other tissues. In a large-scale systematic screen of mutations affecting embryogenesis in zebrafish we identified 65 mutations that fall into 29 complementation groups, each leading to a defect in the formation and/or maintenance of the notochord. These mutations produce phenotypic abnormalities at numerous stages of notochord development, thereby establishing a phenotypic pathway, which in turn suggests a genetic pathway for the development of the notochord. Perturbations within adjacent tissues in mutant embryos further indicate the importance of notochord-derived signals for patterning within the embryo and suggest that these mutations will yield additional insight into the cues that regulate these patterning processes.

On the use of jerk and snap in condition monitoring of machinery – review and case studies

2021 ◽  
Vol 63 (8) ◽  
pp. 457-464
Author(s):  
S Lahdelma
Keyword(s):  
Condition Monitoring ◽  
Large Scale ◽  
Early Stage ◽  
Time Derivative ◽  
Additional Insight ◽  
Rolling Bearings ◽  
Monitoring Applications ◽  
Derivatives Of ◽  
Insight Into ◽  
Peak Value

The time derivatives of acceleration offer a great advantage in detecting impact-causing faults at an early stage in condition monitoring applications. Defective rolling bearings and gears are common faults that cause impacts. This article is based on extensive real-world measurements, through which large-scale machines have been studied. Numerous laboratory experiments provide additional insight into the matter. A practical solution for detecting faults with as few features as possible is to measure the root mean square (RMS) velocity according to the standards in the frequency range from 10 Hz to 1000 Hz and the peak value of the second time derivative of acceleration, ie snap. Measuring snap produces good results even when the upper cut-off frequency is as low as 2 kHz or slightly higher. This is valuable information when planning the mounting of accelerometers.

Electroencephalography

2016 ◽  
Author(s):  
Michael B. Gaetz ◽  
Kelly J. Jantzen
Keyword(s):  
Cognitive Deficits ◽  
Large Scale ◽  
Pyramidal Neurons ◽  
Neurological Dysfunction ◽  
Additional Insight ◽  
Physiological Basis ◽  
Sport Concussion ◽  
Neurochemical Changes ◽  
Insight Into ◽  
Behavior And Cognition

Axonal injury is currently considered to be the structural substrate behind most concussion-related neurological dysfunction. Because the principal generators of EEG fields are graded excitatory and inhibitory synaptic potentials of pyramidal neurons, the EEG is well suited for characterizing large-scale functional disruptions associated with concussion induced metabolic and neurochemical changes, and for connecting those disruptions to deficits in behavior and cognition. This essay provides an overview of the use of EEG and newly developed analytical procedures for the measurement of functional impairment related to sport concussion. Elevations in delta and theta activity can be expected in a percentage of athletes and change in asymmetry and coherence may also be present. Newer techniques are likely to be of critical importance for understanding the anatomical and physiological basis of cognitive deficits and may provide additional insight into susceptibility to future injury. Computational modeling may advance our understanding of concussion.

scholarly journals KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability

2021 ◽  
Vol 22 (10) ◽  
pp. 5408
Author(s):  
Carter Wilson ◽  
Megan Chang ◽  
Mikko Karttunen ◽  
Wing-Yiu Choy
Keyword(s):  
Molecular Dynamics ◽  
Large Scale ◽  
Md Simulations ◽  
Covalent Modification ◽  
Additional Insight ◽  
New Class ◽  
Kelch Domain ◽  
Cancer Mutations ◽  
Mutagenic Effects ◽  
Insight Into

We have performed 280 μs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise analysis of the Kelch domain points to stability as a possible target of cancer in KEAP1. Interestingly, structural analysis of the R470C ANCHOR mutant, the most prevalent missense mutation in KEAP1, revealed no significant change in structural stability or NRF2 binding site dynamics, possibly indicating an covalent modification as this mutant’s mode of action.

scholarly journals Adapting for Scalability: Automating the Video Assessment of Instructional Learning

2017 ◽  
Vol 21 (1) ◽  
Author(s):  
Amy M Roberts ◽  
Jennifer LoCasale-Crouch ◽  
Bridget K Hamre ◽  
Jordan M Buckrop
Keyword(s):  
Scoring System ◽  
Large Scale ◽  
Online Courses ◽  
Current Paper ◽  
Automated Scoring ◽  
Additional Insight ◽  
Knowledge And Skills ◽  
Video Assessment ◽  
Reliable Assessment ◽  
Insight Into

Although scalable programs, such as online courses, have the potential to reach broad audiences, they may pose challenges to evaluating learners’ knowledge and skills. Automated scoring offers a possible solution. In the current paper, we describe the process of creating and testing an automated means of scoring a validated measure of teachers’ observational skills, known as the Video Assessment of Instructional Learning (VAIL). Findings show that automated VAIL scores were consistently correlated with scores assigned by the hand scoring system. In addition, the automated VAIL replicated intervention effects found in the hand scoring system. The automated scoring technique appears to offer an efficient and reliable assessment. This study may offer additional insight into how to utilize similar techniques in other large-scale programs and interventions.

Mta3-NuRD complex is a master regulator for initiation of primitive hematopoiesis in vertebrate embryos

Blood ◽  
2009 ◽  
Vol 114 (27) ◽  
pp. 5464-5472 ◽  
Author(s):  
Xiang Li ◽  
Shunji Jia ◽  
Shaohe Wang ◽  
Yuemeng Wang ◽  
Anming Meng
Keyword(s):  
Trichostatin A ◽  
Paraxial Mesoderm ◽  
Zebrafish Embryos ◽  
Nurd Complex ◽  
Lateral Plate ◽  
Nucleosome Remodeling ◽  
Pronephric Duct ◽  
Primitive Hematopoiesis ◽  
Vertebrate Embryos ◽  
Insight Into

Abstract Metastasis-associated antigens 1/2/3 (Mta1/2/3) are components of nucleosome remodeling and deacetylase (NuRD) complexes and have been found to play roles in embryonic development and homeostasis. However, their functions in primitive hematopoiesis are unknown. In this study, we demonstrate that knockdown of mta3 by antisense morpholinos abolishes primitive hematopoietic lineages and causes abnormal angiogenesis in zebrafish embryos. However, the expression of the pronephric duct and paraxial mesoderm markers is unaltered and the specification of angioblasts is unaffected in mta3 morphants. The results suggest that mta3 is specifically required for primitive hematopoiesis. Furthermore, inhibition of deacetylase activity with the inhibitors valproic acid (VPA) or trichostatin A (TSA) in zebrafish embryos completely blocks primitive hematopoiesis, resulting in hematopoietic defects almost identical to those seen in mta3 morphants. Importantly, overexpression of scl or scl and lmo2, 2 master genes for primitive hematopoiesis, is able to overturn effects of mta3 knockdown or VPA/TSA treatment; and overexpression of mta3, and human MBD3 or HDAC1, 2 other components of NuRD complex, enhances the expression of scl and lmo2 in the posterior lateral plate mesoderm during early primitive hematopoiesis. We conclude that Mta3-NuRD complex is essential for the initiation of primitive hematopoiesis. Thus, our findings provide new insight into the regulatory hierarchy of primitive hematopoiesis in vertebrates.

scholarly journals Quantitative Phosphoproteomics Reveals System-Wide Phosphorylation Network Altered by Spry in Mouse Mammary Stromal Fibroblasts

2019 ◽  
Vol 20 (21) ◽  
pp. 5400 ◽  
Author(s):  
Tiezhu Shi ◽  
Linli Yao ◽  
Ying Han ◽  
Piliang Hao ◽  
Pengfei Lu
Keyword(s):  
Cancer Progression ◽  
Receptor Tyrosine Kinase ◽  
Normal Development ◽  
Underlying Mechanism ◽  
Phosphorylation Sites ◽  
Additional Insight ◽  
Stromal Fibroblasts ◽  
Rtk Signaling ◽  
Insight Into

Understanding the fundamental role of the stroma in normal development and cancer progression has been an emerging focus in recent years. The receptor tyrosine kinase (RTK) signaling pathway has been reported playing critical roles in regulating the normal and cancer microenvironment, but the underlying mechanism is still not very clear. By applying the quantitative phosphoproteomic analysis of Sprouty proteins (SPRYs), generic modulators of RTK signaling and deleted mouse mammary fibroblasts, we quantified a total of 11,215 unique phosphorylation sites. By contrast, 554 phosphorylation sites on 425 proteins had SPRY-responsive perturbations. Of these, 554 phosphosites, 362 sites on 277 proteins, were significantly increased, whereas 192 sites on 167 proteins were decreased. Among the regulated proteins, we identified 31 kinases, 7 phosphatases, and one phosphatase inhibitor that were not systematically characterized before. Furthermore, we reconstructed a phosphorylation network centered on RTK signaling regulated by SPRY. Collectively, this study uncovered a system-wide phosphorylation network regulated by SPRY, providing an additional insight into the complicated RTK signaling pathways involved in the mammary gland microenvironment.

Predictive Numerical Modeling of Artificial Tracers Migration in the Large-Scale Heating and Hydration Experiments of the FEBEX Project

1997 ◽  
Vol 506 ◽  
Author(s):  
J. Samper ◽  
J. Delgado ◽  
J. Molinero ◽  
R. Juncosa
Keyword(s):  
Numerical Modeling ◽  
Large Scale ◽  
The Novel ◽  
Additional Insight ◽  
Bentonite Buffer ◽  
Waste Repository ◽  
Engineered Barrier ◽  
High Level ◽  
Insight Into ◽  
Artificial Tracers

ABSTRACTFEBEX (Full-scale Engineered Barrier EXperiment) is a demonstration and research project dealing with the bentonite engineered barrier designed for sealing and containment of waste in a high level radioactive waste repository. In the FEBEX experiment the bentonite barrier will be subject to heating and hydration during at least three years. One of the novel aspects of FEBEX is the use of artificial tracers, which are intended to provide additional insight into the hydrodynamic and geochemical behavior of the bentonite buffer. Here the results of the numerical prediction of tracers migration are presented. Numerical modeling of the experiments has allowed the identification of the most relevant parameters and will be useful for the design of post-morten analyses.

Classification of Infant Vocalizations by Untrained Listeners

2019 ◽  
Vol 62 (9) ◽  
pp. 3265-3275
Author(s):  
Heather L. Ramsdell-Hudock ◽  
Anne S. Warlaumont ◽  
Lindsey E. Foss ◽  
Candice Perry
Keyword(s):  
Formal Education ◽  
Additional Insight ◽  
Listener Responses ◽  
Infant Vocalization ◽  
Early Infant ◽  
Infant Vocalizations ◽  
Audio Recordings ◽  
Speech And Language Development ◽  
Insight Into

Purpose To better enable communication among researchers, clinicians, and caregivers, we aimed to assess how untrained listeners classify early infant vocalization types in comparison to terms currently used by researchers and clinicians. Method Listeners were caregivers with no prior formal education in speech and language development. A 1st group of listeners reported on clinician/researcher-classified vowel, squeal, growl, raspberry, whisper, laugh, and cry vocalizations obtained from archived video/audio recordings of 10 infants from 4 through 12 months of age. A list of commonly used terms was generated based on listener responses and the standard research terminology. A 2nd group of listeners was presented with the same vocalizations and asked to select terms from the list that they thought best described the sounds. Results Classifications of the vocalizations by listeners largely overlapped with published categorical descriptors and yielded additional insight into alternate terms commonly used. The biggest discrepancies were found for the vowel category. Conclusion Prior research has shown that caregivers are accurate in identifying canonical babbling, a major prelinguistic vocalization milestone occurring at about 6–7 months of age. This indicates that caregivers are also well attuned to even earlier emerging vocalization types. This supports the value of continuing basic and clinical research on the vocal types infants produce in the 1st months of life and on their potential diagnostic utility, and may also help improve communication between speech-language pathologists and families.

Diversity, Rationality, and the Division of Cognitive Labor

2017 ◽  
Author(s):  
Ryan Muldoon
Keyword(s):  
Social Structure ◽  
Division Of Labor ◽  
Additional Insight ◽  
Division Of Cognitive Labor ◽  
Social Structure Of Science ◽  
The Social ◽  
Insight Into

Existing models of the division of cognitive labor in science assume that scientists have a particular problem they want to solve and can choose between different approaches to solving the problem. In this essay I invert the approach, supposing that scientists have fixed skills and seek problems to solve. This allows for a better explanation of increasing rates of cooperation in science, as well as flows of scientists between fields of inquiry. By increasing the realism of the model, we gain additional insight into the social structure of science and gain the ability to ask new questions about the optimal division of labor.

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