d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75079/1/ACEL_504_sm_FigS1_TableS1-S2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75079/2/j.1474-9726.2009.00504.x.pd

A novel systems biology approach to evaluate mouse models of late-onset Alzheimer\u27s disease.

BACKGROUND: Late-onset Alzheimer\u27s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer\u27s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes. RESULTS: This resource enables precise gene-based alignment between new animal models and human molecular signatures of disease. Here, we describe a new resource to efficiently screen mouse models for LOAD relevance. A new NanoString nCounter® Mouse AD panel was designed to correlate key human disease processes and pathways with mRNA from mouse brains. Analysis of the 5xFAD mouse, a widely used amyloid pathology model, and three mouse models based on LOAD genetics carrying APOE4 and TREM2*R47H alleles demonstrated overlaps with distinct human AD modules that, in turn, were functionally enriched in key disease-associated pathways. Comprehensive comparison with full transcriptome data from same-sample RNA-Seq showed strong correlation between gene expression changes independent of experimental platform. CONCLUSIONS: Taken together, we show that the nCounter Mouse AD panel offers a rapid, cost-effective and highly reproducible approach to assess disease relevance of potential LOAD mouse models

Cryogenic Orbital Test Bed 3 (CRYOTE3) Overview and Status

CRYOTE3 is a grassroots CFM test effort with contributing government and industry partners focused on developing and testing hardware to produce needed data for model validation and implementation into flight systems

Teacher perceptions of bullying and ASD (Plumb et al., 2022)

Purpose: The purpose of this study was to investigate teachers’ perceptions of bullying of students with autism spectrum disorder (ASD) and their views of the speech-language pathologist (SLP) as a source of support regarding bullying management. Method: A web-based survey was created and distributed through e-mail and Facebook. One hundred twenty-six general and special education teachers completed the survey. The majority of teachers indicated teaching elementary grades (n = 81, 64%). The remainder indicated teaching middle school, high school, or specialized school. The teachers’ experience ranged from less than 1 year to greater than 10 years. All teachers reported teaching at least one student with ASD within the past 5 years. Results: The majority of participants acknowledged bullying of children with ASD as a problem and witnessed bullying at their schools. Teachers were least likely to select SLPs as school professionals who could play a valuable role in the management of bullying. Conclusions: SLPs’ training in social communication places them in a unique position to contribute to bullying management. School-based SLPs should therefore educate school personnel on the unique and necessary role they can play to help foster a safe and inclusive school culture for students with disabilities, including those with ASD. Supplemental Material S1. Collaborative flyer for teachers.  Plumb, A. M., Moates, A. E., Piazza, L. I., & Mauldin, E. O. (2022). Bullying and autism spectrum disorder: Teacher perspectives and the role of the speech-language pathologist. Perspectives of the ASHA Special Interest Groups. Advance online publication. https://doi.org/10.1044/2022_PERSP-22-00046</p

Saccharomyces cerevisiae Mus81-Mms4 prevents accelerated senescence in telomerase-deficient cells

International audienceAlternative lengthening of telomeres (ALT) in human cells is a conserved process that is often activated in telomerase-deficient human cancers. This process exploits components of the recombination machinery to extend telomere ends, thus allowing for increased prolif-erative potential. Human MUS81 (Mus81 in Saccharomyces cerevisiae) is the catalytic sub-unit of structure-selective endonucleases involved in recombination and has been implicated in the ALT mechanism. However, it is unclear whether MUS81 activity at the telo-mere is specific to ALT cells or if it is required for more general aspects of telomere stability. In this study, we use S. cerevisiae to evaluate the contribution of the conserved Mus81-Mms4 endonuclease in telomerase-deficient yeast cells that maintain their telomeres by mechanisms akin to human ALT. Similar to human cells, we find that yeast Mus81 readily localizes to telomeres and its activity is important for viability after initial loss of telomerase. Interestingly, our analysis reveals that yeast Mus81 is not required for the survival of cells undergoing recombination-mediated telomere lengthening, i.e. for ALT itself. Rather we infer from genetic analysis that Mus81-Mms4 facilitates telomere replication during times of telomere instability. Furthermore, combining mus81 mutants with mutants of a yeast telo-mere replication factor, Rrm3, reveals that the two proteins function in parallel to promote normal growth during times of telomere stress. Combined with previous reports, our data can be interpreted in a consistent model in which both yeast and human MUS81-dependent nucleases participate in the recovery of stalled replication forks within telomeric DNA. Furthermore , this process becomes crucial under conditions of additional replication stress, such as telomere replication in telomerase-deficient cells

Saccharomyces cerevisiae Mus81-Mms4 prevents accelerated senescence in telomerase-deficient cells.

Alternative lengthening of telomeres (ALT) in human cells is a conserved process that is often activated in telomerase-deficient human cancers. This process exploits components of the recombination machinery to extend telomere ends, thus allowing for increased proliferative potential. Human MUS81 (Mus81 in Saccharomyces cerevisiae) is the catalytic subunit of structure-selective endonucleases involved in recombination and has been implicated in the ALT mechanism. However, it is unclear whether MUS81 activity at the telomere is specific to ALT cells or if it is required for more general aspects of telomere stability. In this study, we use S. cerevisiae to evaluate the contribution of the conserved Mus81-Mms4 endonuclease in telomerase-deficient yeast cells that maintain their telomeres by mechanisms akin to human ALT. Similar to human cells, we find that yeast Mus81 readily localizes to telomeres and its activity is important for viability after initial loss of telomerase. Interestingly, our analysis reveals that yeast Mus81 is not required for the survival of cells undergoing recombination-mediated telomere lengthening, i.e. for ALT itself. Rather we infer from genetic analysis that Mus81-Mms4 facilitates telomere replication during times of telomere instability. Furthermore, combining mus81 mutants with mutants of a yeast telomere replication factor, Rrm3, reveals that the two proteins function in parallel to promote normal growth during times of telomere stress. Combined with previous reports, our data can be interpreted in a consistent model in which both yeast and human MUS81-dependent nucleases participate in the recovery of stalled replication forks within telomeric DNA. Furthermore, this process becomes crucial under conditions of additional replication stress, such as telomere replication in telomerase-deficient cells