12 research outputs found
α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3
Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo
PEDIA: prioritization of exome data by image analysis.
PURPOSE: Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists.
METHODS: Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds.
RESULTS: The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20-89% and the top 10 accuracy rate by more than 5-99% for the disease-causing gene.
CONCLUSION: Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis
α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3
Improving Mathematics Teachers\u27 Content Knowledge via Brief In-service: A US Case Study
This study is an evaluation on whether middleâ€level mathematics teachers\u27 participation in a weekâ€long inâ€service course on middleâ€level mathematics concepts increases their understanding of this content. A secondary purpose of this study is an exploration of teacher perceptions before and after the institute via selfâ€report surveys. Participants include 31 middleâ€level mathematics teachers who attended at least one of the two inâ€services, one emphasizing algebra concepts and the other emphasizing probability and geometry concepts. The findings indicate that teachers\u27 content knowledge significantly improved, as measured by pretest and postâ€test results. The selfâ€report survey responses did not change as a result of participation in the inâ€service, but overall patterns of responses in both the quantitative and qualitative survey data indicate how the institutes can contribute to a larger professional development strategy. Both inâ€service courses are described and implications are discussed
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NACIONAL
An Avonlea inhumation at Split-Rock Ridge, Big Dry Creek Valley, Eastern Montana High Plains
α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3
[Abstract]: Adaptive and fluid applications development methodologies such as Prototyping, RAD, FAD and Ex-treme Programming have emerged in recent years in response to organisational realities that include rapid change, uncertainty and ambiguity. These methodologies are well suited to the team-based approach that has become so important in the modern organisation. Yet, many educational programmes in the West still focus on individual learning and assessment. This paper reports on a pilot study where team-based methods are incorporated into a demanding undergraduate I.T. course. An attempt is also made to create a learning environment that incorporates elements of the ‘real world.’ It is established that a team-based approach, where there is a focus on interdependency and group learning, can lead to some dramatic improvements in the performance of IT students but a number of unexpected problems emerge