Rationale Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. Objective To determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis. Methods Crocidolite asbestos (100 μg/50 μL), TiO2 (negative control), bleomycin (0.025 units/50 μL), or PBS was instilled intratracheally in 8–10 week-old wild-type (WT - C57Bl/6 J) or MCAT mice. The lungs were harvested at 21 d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3)/Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay. Results Compared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced. Conclusions Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role for AEC mitochondrial H2O2-induced mtDNA damage in promoting lung fibrosis. We reason that strategies aimed at limiting AEC mtDNA damage arising from excess mitochondrial H2O2 production may be a novel therapeutic target for mitigating pulmonary fibrosis.

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The adoption and sustainability of evidence-based Tier 1 literacy practices in secondary content-area classes is important to improve the reading success among students with learning disabilities. We conducted an exploratory multiple-case study investigating teachers’ adoption and sustained use of evidence-based Tier 1 literacy practices that benefit students with learning disabilities. The study was conducted within the context of an adolescent literacy model demonstration project funded by the Office of Special Education Programs (i.e., Promoting Adolescents’ Comprehension of Text [PACT] Plus). Interviews were conducted with two administrators and seven teachers who sustained implementation of the PACT practices beyond 1 year of researcher support. Analyses revealed practice and school-level factors that influenced teachers’ sustained use of the practices. We used findings from this study to propose a model of sustainability of Tier 1 evidence-based literacy practices used to improve outcomes for students with learning disabilities. Limitations and implications for future research are provided.

The Project CALI (Content Area Literacy Instruction) instructional framework is designed to enhance reading comprehension for all students, those with disabilities as well as their typically developing peers, in inclusive co-taught middle school content-area classrooms. For students with and at-risk for disabilities, even well-designed, research-based, and whole-class instruction often leads to inadequate improvement in reading comprehension and thus learning of content material. In CALI, teachers use student data to determine which students need more support and targeted, individualized instruction, and by contrast, which students may benefit from opportunities to extend their learning with more challenging texts and student-managed work. This article provides guidance for designing and implementing customizable lessons using station-teaching to individualize instruction. The Project CALI student support model is the final instructional piece of the CALI instructional framework.