Language Assessment in a Snap: Monitoring Progress Up to 36 Months

This article describes the development and validation of the Developmental Snapshot, a 52-item parent questionnaire on child language and vocal communication development that can be administered monthly and scored automatically. The Snapshot was created to provide an easily administered monthly progress monitoring tool that enables parents to better recognize language milestones and offers professionals prompt information to fine-tune intervention strategies. Initial items were piloted by 15 families; refinement and further development of the instrument was conducted with parents of 308 typically developing children. Reliability and criterion validity metrics were examined on subsets of approximately 60 children who completed the Snapshot on a monthly basis and who were evaluated on standard assessments administered by speech language pathologists (SLPs). Divergent validity was also examined for samples of children diagnosed with language delays related to autism spectrum disorder (ASD) (n = 77) or not (n = 49). Results supported the criterion validity (r = .67–.97) and test–retest reliability claims of the Snapshot (r = .95). Sensitivity and specificity for language delay detection also were good at 87%. Potential applications for progress monitoring, fidelity of intervention, and enhancing parents’ awareness of their child’s language and vocal communication changes are discussed

Cysteine-rich protein 1 (CRP1) regulates actin filament bundling

BACKGROUND: Cysteine-rich protein 1 (CRP1) is a LIM domain containing protein localized to the nucleus and the actin cytoskeleton. CRP1 has been demonstrated to bind the actin-bundling protein α-actinin and proposed to modulate the actin cytoskeleton; however, specific regulatory mechanisms have not been identified. RESULTS: CRP1 expression increased actin bundling in rat embryonic fibroblasts. Although CRP1 did not affect the bundling activity of α-actinin, CRP1 was found to stabilize the interaction of α-actinin with actin bundles and to directly bundle actin microfilaments. Using confocal and photobleaching fluorescence resonance energy transfer (FRET) microscopy, we demonstrate that there are two populations of CRP1 localized along actin stress fibers, one associated through interaction with α-actinin and one that appears to bind the actin filaments directly. Consistent with a role in regulating actin filament cross-linking, CRP1 also localized to the membrane ruffles of spreading and PDGF treated fibroblasts. CONCLUSION: CRP1 regulates actin filament bundling by directly cross-linking actin filaments and stabilizing the interaction of α-actinin with actin filament bundles

CRP1, a Protein Localized in Filopodia of Growth Cones, Is Involved in Dendritic Growth

The cysteine-rich protein (CRP) family is a subgroup of LIM domain proteins. CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells. Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons. Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons. Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity. Expression of CRP1 with a constitutively active form of Cdc42, a GTPase involved in filopodia formation, increases filopodia formation in COS-7 cells, suggesting cooperation between the two proteins. Moreover, we demonstrate that neuronal activity upregulates CRP1 expression in hippocampal neurons via Ca²⁺ influx after depolarization. Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein mediate the Ca²⁺-induced upregulation of CRP1 expression. Furthermore, CRP1 is required for the dendritic growth induced by Ca²⁺ influx or CaMKIV. Together, these data are the first to demonstrate a role for CRP1 in dendritic growth.Keywords: Kinase-IV, Hippocampal neurons, Crysteine-rich protein-1, Muscle differentiation, Actin cytoskeleton, binding protein, TRPC6 channels, Spine morphology, Lim domain, Gene expressionThis is the publisher’s final pdf. The published article is copyrighted by Society for Neuroscience and can be found at: http://www.jneurosci.org/

Impact of Lumacaftor/Ivacaftor on Pulmonary Exacerbation Rates in Members with Cystic Fibrosis in a Medicaid Population

This poster gives an overview of pulmonary exacerbation rates pre- and post-initiation of Lumacaftor/Ivacaftor (LUM/IVA) in Massachusetts\u27 Medicaid program. Pulmonary disease is one of the leading causes of morbidity and mortality among patients with cystic fibrosis. LUM/IVA has been effective in improving pulmonary outcomes in two observational studies, but before this study, there had been no published data evaluating real-world outcomes for Medicaid patients receiving this therapy. This poster on the impact of a drug for patients with cystic fibrosis was shared during the 2018 Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting and awarded a gold ribbon. The poster abstracts were evaluated on relevance, originality, quality, bias and clarity. Only 20 percent of submitted abstracts were honored with awards

Coibamide A Induces mTOR-Independent Autophagy and Cell Death in Human Glioblastoma Cells

Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative of a unique mechanism of action. We report that coibamide A is a more potent and efficacious cytotoxin than was previously appreciated, inducing concentration-and time-dependent cytotoxicity (EC₅₀<100 nM) in human U87-MG and SF-295 glioblastoma cells and mouse embryonic fibroblasts (MEFs). This activity was lost upon linearization of the molecule, highlighting the importance of the cyclized structure for both anti-proliferative and cytotoxic responses. We show that coibamide A induces autophagosome accumulation in human glioblastoma cell types and MEFs via an mTOR-independent mechanism; no change was observed in the phosphorylation state of ULK1 (Ser-757), p70 S6K1 (Thr-389), S6 ribosomal protein (Ser-235/236) and 4EBP-1 (Thr-37/46). Coibamide A also induces morphologically and biochemically distinct forms of cell death according to cell type. SF-295 glioblastoma cells showed caspase-3 activation and evidence of apoptotic cell death in a pattern that was also seen in wild-type and autophagy-deficient (ATG5-null) MEFs. In contrast, cell death in U87-MG glioblastoma cells was characterized by extensive cytoplasmic vacuolization and lacked clear apoptotic features. Cell death was attenuated, but still triggered, in Apaf-1-null MEFs lacking a functional mitochondria-mediated apoptotic pathway. From the study of ATG5-null MEFs we conclude that a conventional autophagy response is not required for coibamide A-induced cell death, but likely occurs in dying cells in response to treatment. Coibamide A represents a natural product scaffold with potential for the study of mTOR-independent signaling and cell death mechanisms in apoptotic-resistant cancer cells

Identification of gold nanoparticle-resistant mutants of Saccharomyces cerevisiae suggests a role for respiratory metabolism in mediating toxicity

Positively-charged gold nanoparticles (0.8-nm core diameter) reduced yeast survival, but not growth, at a concentration of 10 to 100 μg/ml. Among 17 resistant deletion mutants isolated in a genome-wide screen, highly significant enrichment was observed for respiration-deficient mutants lacking genes encoding proteins associated with the mitochondrion