HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Art assessment Policy and Practice at the High School Level: Validity, Reliability, and Resistance

National education reform policies that have increased reliance on standardized testing in subjects like reading and math as a way to judge the quality of a teacher’s performance have created challenges for educators in visual art and design when they are required to provide data about student growth. Art teachers who utilize alternate forms of assessment to judge the quality of student artwork as evidence of learning can potentially be in a precarious position because of underlying assumptions that these types of qualitative assessments lack validity. In this context, when compared to colleagues in traditionally tested disciplines, art educators face unique challenges proving their assessments are both valid and reliable. Framed in critical pedagogy, a mixed-methods study was conducted in the state of Illinois to investigate the kinds of assessment strategies high school art teachers found useful in their classrooms to measure student learning and whether their methods differed from the types of assessments their administrators expected. This study brings attention to the important aspects of assessment and how policy can shape teachers’ practice. This study provided unique insight into Illinois art teachers’ experiences with the current state teacher evaluation policy PERA (Performance Evaluation Reform Act). Participants from throughout the state were surveyed about their understanding of assessment, validity, reliability, and professional development. To elaborate and contextualize the findings, face-to- face interviews were conducted with eight participants to obtain a deeper understanding of teacher’s actual experiences in the classroom and elaborate upon the role educational policy played in assisting them to meet requirements for their performance evaluation. Assessment at the high school level can present unique challenges when compared to other disciplines because of the complexity of qualitative judgments teachers must make about their students’ work. Applying qualitative assessment methods were particularly troublesome for participants because their methods were not like traditional right-wrong answer choice tests; this created underlying mistrust of art teachers’ data that was derived from professional judgement on qualitative assessments. Deepening the challenge art teachers faced when assessing student art performance, the participants described a lack of professional development specifically for assessment in art. They also struggled with an absence of professional development to establish the validity and reliability of their assessments and sometimes received inappropriate direction about student performance data collection because of a lack of understanding by administrators or supervisors about how student artwork should be judged. In an age of test-based accountability, professional development for teachers, administrators, and pre-service educators aimed specifically for art and design assessment is essential for practitioners in public schools. Additionally, it was found the socio-economic status of teacher participants’ schools was related to the kinds of data they were asked to collect and the kinds of resources they had available within their departments thus indicating a lack of equitable access to quality art education throughout the state. In response to administrative requests that participants felt were inappropriate to their discipline, multiple forms of resistance were exhibited including covert, overt, and passive compliance as a way to help them cope with what many participants felt were overwhelming obstacles to teaching a quality visual art curriculum

The measurement of art judgment in everyday life.

Thesis (Ed.M.)--Boston Universit

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

Implications of Dam Removal: Modeling Streamflow in Lansing, Michigan Using the Soil and Water Assessment Tool

This paper uses hydrologic modeling methods to determine the effects of dam removal in Lansing, Michigan, on the streamflow of the Grand River, flooding risks, and flood mitigation strategies. In Michigan, more than one-half of the state’s dam infrastructure is more than 50 years old, and more than one-third are classified as having a moderate-to high-risk potential. Lansing, Michigan, contains two moderate-to high-risk dams along the Grand River that are a significant hazard to the surrounding community in the event of structural failure. This research utilizes the Soil and Water Assessment Tool (SWAT) to model the impacts of the Moores Park Dam and the North Lansing Dam on streamflow in the greater Lansing area. The purpose of using SWAT was to represent baseline streamflow conditions in the Grand River, compare the differences in streamflow magnitude between baseline conditions and a dam-out environment, and interpret the implications of modeling results for mitigation and management strategies in the study area. Our model exhibited similar streamflow patterns to USGS historical data, with overestimation errors during calibration and validation stemming from groundwater infiltration inaccuracies. The dams-out model for streamflow was higher than the baseline model for streamflow; however, both model iterations require further calibration and validation for the magnitude differences to be considered statistically significant. Despite issues of model calibration and validation, and ongoing model adjustments for accurately representing heavily impounded watershed, the results of this study provide a template for the City of Lansing to adapt their flood mitigation strategies in the study area and further calibrate SWAT with improved sediment, nutrient, and dam attribute data

Differential expression of sPLA2 following spinal cord injury and a functional role for sPLA2-IIA in mediating oligodendrocyte death

After the initial mechanical insult of spinal cord injury (SCI), secondary mediators propagate a massive loss of oligodendrocytes. We previously showed that following SCI both the total phospholipase activity and cytosolic PLA(2)-IV alpha protein expression increased. However, the expression of secreted isoforms of PLA(2) (sPLA(2)) and their possible roles in oligodendrocyte death following SCI remained unclear. Here we report that mRNAs extracted 15 min, 4 h, 1 day, or 1 month after cervical SCI show marked upregulation of sPLA(2)-IIA and IIE at 4 h after injury. In contrast, SCI induced down regulation of sPLA(2)-X, and no change in sPLA(2)-IB, IIC, V, and XIIA expression. At the lesion site, sPLA(2)-IIA and IIE expression were localized to oligodendrocytes. Recombinant human sPLA(2)-IIA (0.01, 0.1, or 2 microM) induced a dose-dependent cytotoxicity in differentiated adult oligodendrocyte precursor cells but not primary astrocytes or Schwann cells in vitro. Most importantly, pretreatment with S3319, a sPLA(2)-IIA inhibitor, before a 30 min H(2)O(2) injury (1 or 10 mM) significantly reduced oligodendrocyte cell death at 48 h. Similarly, pretreatment with S3319 before injury with IL-1 beta and TNFalpha prevented cell death and loss of oligodendrocyte processes at 72 h. Collectively, these findings suggest that sPLA(2)-IIA and IIE are increased following SCI, that increased sPLA(2)-IIA can be cytotoxic to oligodendrocytes, and that in vitro blockade of sPLA(2) can create sparing of oligodendrocytes in two distinct injury models. Therefore, sPLA(2)-IIA may be an important mediator of oligodendrocyte death and a novel target for therapeutic intervention following SCI

Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury. Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery