Impact!: Improving Student Learning through an Inquiry Crater Investigation

The fight against student compartmentalization of science concepts is an ongoing battle for all science educators. When an inquiry-based investigation of natural phenomena, like that presented here, is integrated into curricula new links between science concepts are created. These new connections promote a deep and robust understanding of science content. This cratering activity has students applying prior knowledge of gravitational forces, momentum, conservation of energy, and density while exploring the intricate relationships between these fundamental concepts. This activity also provides abundant opportunities for explicit connections to the nature of science. Impact cratering is a phenomena which can be easily modeled within a classroom, and deeply understanding it requires application of several fundamental science concepts. This article addresses National Science Education Standards A, B, D, and G and Iowa Teaching Standards 1, 2, 3, 4, and 5

Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to altered dysbindin-1 gene expression

DTNBP1 (dystrobrevin binding protein 1) remains one of the top candidate genes in schizophrenia. Reduced expression of this gene and the protein it encodes, dysbindin-1, has been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia cases. It has not been established, however, if all dysbindin-1 isoforms are reduced in the DLPFC or if the reduction is associated with reduced DTNBP1 gene expression. Using Western blotting of whole-tissue lysates of the DLPFC with antibodies differentially sensitive to the three major isoforms of this protein (dysbindin-1A, -1B, and -1C), we found no significant differences between our schizophrenia cases and matched controls in dysbindin-1A or -1B, but did find a mean 46% reduction in dysbindin-1C in 71% of 28 case-control pairs (p = 0.022). This occurred in the absence of the one DTNBP1 risk haplotype for schizophrenia reported in the US and without alteration in levels of dysbindin-1C transcripts. Conversely, the absence of changes in the dysbindin-1A and -1B isoforms was accompanied by increased levels of their transcripts. We thus found no correspondence between alterations in dysbindin-1 gene and protein expression, the latter of which might be due to posttranslational modifications such as ubiquitination. Reduced DLPFC dysbindin-1C in schizophrenia probably occurs in PSDs, where we find dysbindin-1C to be heavily concentrated in the human brain. Given known postsynaptic effects of dysbindin-1 reductions in the rodent homolog of the prefrontal cortex, these findings suggest that reduced dysbindin-1C in the DLPFC may contribute to cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction

Source gases: Concentrations, emissions, and trends

Source gases are defined as those gases that influence levels of stratospheric ozone (O3) by transporting species containing halogen, hydrogen, and nitrogen to the stratosphere. Examples are the CFC's, methane (CH4), and nitrous oxide (N2O). Other source gases that also come under consideration in an atmospheric O3 context are those that are involved in the O3 or hydroxyl (OH) radical chemistry of the troposphere. Examples are CH4, carbon monoxide (CO), and nonmethane hydrocarbons (NMHC's). Most of the source gases, along with carbon dioxide (CO2) and water vapor (H2O), are climatically significant and thus affect stratospheric O3 levels by their influence on stratospheric temperatures. Carbonyl sulphide (COS) could affect stratospheric O3 through maintenance of the stratospheric sulphate aerosol layer, which may be involved in heterogeneous chlorine-catalyzed O3 destruction. The previous reviews of trends and emissions of source gases, either from the context of their influence on atmospheric O3 or global climate change, are updated. The current global abundances and concentration trends of the trace gases are given in tabular format

Transcriptional changes following cellular knockdown of the schizophrenia risk gene SETD1A are enriched for common variant association with the disorder

Loss of function mutations in SETD1A are the first experiment-wide significant findings to emerge from exome sequencing studies of schizophrenia. Although SETD1A is known to encode a histone methyltransferase, the consequences of reduced SETD1A activity on gene expression in neural cells have, to date, been unknown. To explore transcriptional changes through which genetic perturbation of SETD1A could confer risk for schizophrenia, we have performed genome-wide gene expression profiling of a commonly used human neuroblastoma cell line in which SETD1A expression has been experimentally reduced using RNA interference (RNAi). We identified 1,031 gene expression changes that were significant in two separate RNAi conditions compared with control, including effects on genes of known neurodevelopmental importance such as DCX and DLX5. Genes that were differentially expressed following SETD1A knockdown were enriched for annotation to metabolic pathways, peptidase regulator activity and integrin-mediated regulation of cell adhesion. Moreover, differentially expressed genes were enriched for common variant association with schizophrenia, suggesting a degree of molecular convergence between this rare schizophrenia risk factor and susceptibility variants for the disorder operating more generally

Adjustable Prone Trolley Design for People Suffering from Spinal Cord Injuries in Nepal

For people suffering from spinal cord injuries, it is important to stay active. However, with spinal cord injuries, the use of a wheelchair isn’t feasible. These patients require a prone trolley. A prone trolley is a horizontal pad with four wheels that a patient can maneuver and control while lying in a prone position. Our partner, International Nepal Fellowship (INF), deals directly with patients who suffer from spinal cord injuries on a daily basis. INF, a Christian, medical organization, manages a hospital in Pokhara, Nepal which specializes in treating patients with spinal cord injuries. The Nepal Prone Trolley Team’s goal is to provide our partner with a sustainable prone trolley design and create the required manufacturing documentation to enable them to produce the prone trolleys in country at their Green Pastures hospital. The team began our work by researching what a prone trolley is, how it functions and what is currently available. During the research, the team discovered that there weren’t many examples of a manually powered prone trolley or critical dimensions for ergonomics for manually powered trolleys. This drove the team to develop testing methods and preliminary designs specifically for INF. Various basic designs were considered, but, through communication with INF, a single design was chosen. Computer modeling of this design was used to decrease the overall weight of the trolley and simplify the frame. With most of the design finalized, the team is ready to begin prototyping next semester.https://mosaic.messiah.edu/engr2021/1012/thumbnail.jp

Meta-analysis of cell therapy studies in heart failure and acute myocardial infarction

Heart failure (HF) is one of the leading causes of death worldwide and has reached epidemic proportions in most industrialized nations. Despite major improvements in the treatment and management of the disease, the prognosis for patients with HF remains poor with approximately only half of patients surviving for 5 years or longer after diagnosis. The poor prognosis of HF patients is in part because of irreparable damage to cardiac tissue and concomitant maladaptive changes associated with the disease. Cell-based therapies may have the potential to transform the treatment and prognosis of HF through regeneration or repair of damaged cardiac tissue. Accordingly, numerous phase I and II randomized clinical trials have tested the clinical benefits of cell transplant, mostly autologous bone marrow–derived mononuclear cells, in patients with HF, ischemic heart disease, and acute myocardial infarction. Although many of these trials were relatively small, meta-analyses of cell-based therapies have attempted to apply rigorous statistical methodology to assess the potential clinical benefits of the intervention. As a prelude to larger phase III trials, meta-analyses, therefore, remain the obvious means of evaluating the available clinical evidence. Here, we review the different meta-analyses of randomized clinical trials that evaluate the safety and potential beneficial effect of cell therapies in HF and acute myocardial infarction spanning nearly 2 decades since the first pioneering trials were conducted

Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy

The dystrophin-associated protein complex (DPC), comprising sarcoglycans, dystroglycans, dystrobrevins, and syntrophins, is a component of synapses both in muscle and brain. Dysbindin is a novel component of the DPC, which binds to β-dystrobrevin and may serve as an adaptor protein that links the DPC to an intracellular signaling cascade. Disruption of the DPC results in muscular dystrophy, and mutations in the human ortholog of dysbindin have been implicated in the pathogenesis of schizophrenia. In both cases, patients also present with neurological symptoms reminiscent of cerebellar problems. In the mouse cerebellum, dysbindin immunoreactivity is expressed at high levels in a subset of mossy fiber synaptic glomeruli in the granular layer. Lower levels of dysbindin immunoreactivity are also detected in Purkinje cell dendrites. In the cerebellar vermis, dysbindin-immunoreactive glomeruli are restricted to an array of parasagittal stripes that bears a consistent relationship to Purkinje cell parasagittal band boundaries as defined by the expression of the respiratory isoenzyme zebrin II/aldolase c. In a mouse model of Duchenne muscular dystrophy, the mdx mutant, in which dystrophin is not expressed, there is a dramatic increase in the number of dysbindin-immunoreactive glomeruli in the posterior cerebellar vermis. Moreover, the topography of the terminal fields is disrupted, replacing the stripes by a homogeneous distribution. Abnormal synaptic organization in the cerebellum may contribute to the neurological problems associated with muscular dystrophy and schizophrenia

Isoform-Specific Reduction of the Basic Helix-Loop-Helix Transcription Factor TCF4 Levels in Huntington's Disease

Huntington's disease (HD) is an inherited neurodegenerative disorder with onset of characteristic motor symptoms at midlife, preceded by subtle cognitive and behavioral disturbances. Transcriptional dysregulation emerges early in the disease course and is considered central to HD pathogenesis. Using wild-type (wt) and HD knock-in mouse striatal cell lines we observed a HD genotype-dependent reduction in the protein levels of transcription factor 4 (TCF4), a member of the basic helix-loop-helix (bHLH) family with critical roles in brain development and function. We characterized mouse Tcf4 gene structure and expression of alternative mRNAs and protein isoforms in cell-based models of HD, and in four different brain regions of male transgenic HD mice (R6/1) from young to mature adulthood. The largest decrease in the levels of TCF4 at mRNA and specific protein isoforms were detected in the R6/1 mouse hippocampus. Translating this finding to human disease, we found reduced expression of long TCF4 isoforms in the postmortem hippocampal CA1 area and in the cerebral cortex of HD patients. Additionally, TCF4 protein isoforms showed differential synergism with the proneural transcription factor ASCL1 in activating reporter gene transcription in hippocampal and cortical cultured neurons. Induction of neuronal activity increased these synergistic effects in hippocampal but not in cortical neurons, suggesting brain region-dependent differences in TCF4 functions. Collectively, this study demonstrates isoform-specific changes in TCF4 expression in HD that could contribute to the progressive impairment of transcriptional regulation and neuronal function in this disease