Molecular control of stress transmission in the microtubule cytoskeleton

AbstractIn this article, we will summarize recent progress in understanding the mechanical origins of rigidity, strength, resiliency and stress transmission in the MT cytoskeleton using reconstituted networks formed from purified components. We focus on the role of network architecture, crosslinker compliance and dynamics, and molecular determinants of single filament elasticity, while highlighting open questions and future directions for this work

Strengthening Border Families: Frontline Practitioner Perspectives on Service Access for Immigrant Families with Young Children in Doña Ana County, NM

In recent years, federal immigration and public benefits policies with implications for immigrant families in the U.S. have been extraordinarily restrictive and punitive. These policies have exacerbated a climate of fear and vulnerability for immigrant families, while also creating significant barriers to service access and eligibility for immigrant families, particularly those services that are important for child health and wellbeing. The borderlands of New Mexico are one of the most impoverished areas of the country, where the day-to-day experiences of immigrant children and families are impacted by complex border policies and dynamics that restrict access to needed supports.

Activist Researchers:Four Cases of Affecting Change

Researchers in urban planning are frequently motivated by the desire to facilitate positive social change. In seeking better ways to effect change, the researcher becomes an activist by engaging with social and environmental issues in a meaningful way to solve a problem. It is also often at this nexus where practice and academia meet, where the researcher adopts an activist role. In this paper we argue that activist research requires researchers to place themselves in one of two dominant positionalities or engagement positions: the insider or the outsider, as they join efforts with their research participants and activities. Using four case examples from our own research, we discuss how each positionality influences the production of new knowledge in both practice and theory. We reflect on challenges faced by early-career activist researchers in adopting activist research approaches, highlighting implications for undertaking this type of research in urban planning, and the need for a rethink from current discourses to set a path for a more hopeful future

Concert recording 2022-05-19

[Track 1] Maya / Ian Clarke -- [Track 2] Souvenir Du Rigi, Op. 34 / Franz Doppler -- [Track 3] Dialogues for Flute and Trumpet. I. Allegro ; II. Largo quasi improvisando ; III. Adagio con espressione ; IV. Animato / Jindra Necasova -- [Track 4] Andante et Rondo / Franz Doppler -- [Track 5] Pavane Pour Une Infante Defunte / Maurice Ravel ; arr. Miranda Pham for Horn, Flute, and Piano -- [Track 6] Scherzo / Felix Mendelssohn

Collection Development Based on Patron Requests: Collaboration between Interlibrary Loan and Acquisitions

Libraries are exploring new models of collaboration between interlibrary loan, collection development, and acquisitions. This paper presents two models in which libraries set aside acquisitions or other funds to purchase books requested by patrons through interlibrary loan processes. Workflows, scope criteria, and departmental relationships are described. The article reports on several aspects of the effectiveness of these models, such as turnaround time (comparable to traditional ILL loans), average cost per book ($37.00), and patron satisfaction (very high). The authors also address the subsequent circulation of titles and report on the bibliographers’ analysis of the relevance of the titles to the collection of one of the libraries

Concert recording 2022-05-19

[Track 1] Maya / Ian Clarke -- [Track 2] Souvenir Du Rigi, Op. 34 / Franz Doppler -- [Track 3] Dialogues for Flute and Trumpet. I. Allegro ; II. Largo quasi improvisando ; III. Adagio con espressione ; IV. Animato / Jindra Necasova -- [Track 4] Andante et Rondo / Franz Doppler -- [Track 5] Pavane Pour Une Infante Defunte / Maurice Ravel ; arr. Miranda Pham for Horn, Flute, and Piano -- [Track 6] Scherzo / Felix Mendelssohn

The FOXO1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells

Basal-like breast cancer (BBC) and glioblastoma multiforme (GBM) are poor-prognosis cancers that lack effective targeted therapies and harbor embryonic stem gene expression signatures. Recently, our group and others found that forkhead box transcription factor FOXO1 promotes stem gene expression in BBC and GBM cell lines. Given the critical role of cancer stem cells in promoting cancer progression, we examined the impact of FOXO1 inhibition with AS1842856 (a cell-permeable small molecule that directly binds to unphosphorylated FOXO1 protein to block transcriptional regulation) on BBC and GBM cell viability. We treated a set of BBC and GBM cancer cell lines with increasing concentrations of AS1842856 and found reduced colony formation. Treatment of BBC and GBM cancer cells with AS1842856 led to increases in FAS (FAS cell surface death receptor) and BIM (BCL2L11) gene expression, as well as increased positivity for markers for apoptosis such as annexin V and propidium iodide. Treatment with another FOXO1 inhibitor AS1708727 or FOXO1 RNAi also led to FAS induction. This work is the first to show that targeting BBC and GBM with FOXO1 inhibition leads to apoptosis. These novel findings may ultimately expand the repertoire of therapies for poor-prognosis cancers

Fall Protection Training: A Case Study Using Cbt for Latino Construction Workers

Latino construction workers are at an increased risk of worksite injuries and fatalities due to language, cultural barriers, and ineffective training. This case-study investigated computer-based video training (CBT) for scaffold safety. The CBT training was developed using a participatory approach involving direct input from Latino roofers and framers. This paper focuses on evaluation-improvement of training that combined workers’ ideas of a safe work environment with OSHA standards. Researchers investigated the appropriateness and effectiveness of a brief CBT presentation addressing fall protection and scaffold use among Latino roofers. The results indicated that Latino construction workers at a roofing company in Colorado gained knowledge (p-value \u3c0.05) and liked the use of a culturally appropriate educational video as a method of training. The positive reactions to the training intervention are encouraging and support information and communication technologies (ICTs) for training Latino construction workers with lessons learned for follow-up training and evaluation

Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells

Objective: To explore the impact of oxidative insults on mitochondrial dynamics. In mammalian cells, oxidative insults activate stress response pathways including inflammation, cytokine secretion, and apoptosis. Intriguingly, mitochondria are emerging as a sensitive network that may function as an early indicator of subsequent cellular stress responses. Mitochondria form a dynamic network, balancing fusion, mediated by optic atrophy-1 (OPA1), and fission events, mediated by dynamin-related protein-1 (DRP1), to maintain homeostasis. Methods: Here, we examine the impact of oxidative insults on mitochondrial dynamics in 143B osteosarcoma and H9c2 cardiomyoblast cell lines via confocal microscopy, flow cytometry, and protein-based analyses. Results: When challenged with hydrogen peroxide (H2O2), a ROS donor, both cell lines display fragmentation of the mitochondrial network and loss of fusion-active OPA1 isoforms, indicating that OPA1-mediated mitochondrial fusion is disrupted by oxidative damage in mammalian cells. Consistent with this, cells lacking OMA1, a key protease responsible for cleavage of OPA1, are protected against OPA1 cleavage and mitochondrial fragmentation in response to H2O2 challenge. Discussion: Taken together, these findings indicate that oxidative insults damage OPA1-mediated mitochondrial dynamics in mammalian cells via activation of OMA1, consistent with an emerging role for mitochondrial dynamics as an early indicator of cellular stress signaling

PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

Glioblastoma (GBM) is the most lethal primary brain cancer that lacks effective molecular targeted therapies. The PI3K/AKT/mTOR pathway is activated in 90% of all Glioblastoma multiforme (GBM) tumors. To gain insight into the impact of the PI3K pathway on GBM metabolism, we treated U87MG GBM cells with NVP-BEZ235 (PI3K and mTOR a dual inhibitor) and identified differentially expressed genes with RNA-seq analysis. RNA-seq identified 7803 differentially regulated genes in response to NVP-BEZ235. Gene Set Enrichment Analysis (GSEA) identified two glycolysis-related gene sets that were significantly enriched (p \u3c 0.05) in control samples compared to NVP-BEZ235-treated samples. We validated the inhibition of glycolytic genes by NVP-BEZ235 and examined the impact of the FOXO1 inhibitor (AS1842856) on these genes in a set of GBM cell lines. FOXO1 inhibition alone was associated with reduced LDHA expression, but not ENO1 or PKM2. Bioinformatics analyses revealed that PI3K-impacted glycolytic genes were over-expressed and co-expressed in GBM clinical samples. The elevated expression of PI3K-impacted glycolytic genes was associated with poor prognosis in GBM based on Kaplan–Meier survival analyses. Our results suggest novel insights into hallmark metabolic reprogramming associated with the PI3K-mTOR dual inhibition