158 research outputs found
Teaching College Writing to High School Students: A Mixed Methods Investigation of Dual Enrollment Composition Students\u27 Writing Curriculum and Writing Self-Efficacy
The purpose of this mixed methods study was to use a quantitative survey to assess the relationships between the credit pathways students choose to earn first-year, first-semester (FYFS) university writing credit (i.e. dual enrollment, Advanced Placement, university courses, and ACT/SAT exemptions) and several writing experiences and outcomes, including writing curriculum, self-efficacy, self-regulatory strategy use, and course performance. The same survey was also used to explore relationships between these writing experiences and outcomes and preexisting student characteristics (i.e. race/ethnicity, gender, and parentsâ education). For dual enrollment (DE) students only, the following aspects of the participantsâ writing experiences were also investigated using qualitative analysis of responses to open-ended survey items and one-on-one interviews: motivation and outcomes, feedback received, curriculum experienced, and impact on academic and career choices.
Literature on this topic has focused on students at every level of education but has been typically qualitative and has not involved surveying such a large sample of undergraduates. In an effort to improve writing and general academic outcomes for students, this study advances the knowledge about DE composition studies in relation to other composition credit pathways, specifically with regard to writing self-efficacy and writing curriculum.
Key findings from the quantitative analyses include inconsistencies between curriculum in DE versus curriculum in AP and on-campus writing courses that are further supported by the qualitative findings; these differences in curriculum are related to the type and number of writing assignments and feedback received from instructors and peers. The quantitative findings also suggest a racial achievement gap between black students and non-black students taking advanced English courses. In addition, the qualitative findings related to motivation and outcomes are very similar to those discussed in the existing literature. Overall, the findings suggest that while most participants view their DE writing experiences as helpful in preparing them for subsequent college writing, program administrators and instructors must communicate and collaborate to ensure appropriate content and adequate rigor are available to all students
Preserving and Promoting Diverse Transit-Oriented Neighborhoods
This report, researched and written by staff at the Center for Neighborhood Technology, Reconnecting America, and Strategic Economics -- working together as the Center for Transit-Oriented Development -- makes a substantial new contribution to our knowledge base regarding mixed-income, mixed-race housing. We now know, via this report, that there are ample opportunities for the creation of mixed-income, mixed-race housing in transit zones. Demand for transit-oriented housing is projected to soar over the next twenty years.Locating mixed-income housing in these particular settings carries the remarkable advantage of permitting residents to stretch their budgets because transit use can lower transportation costs substantially
Multiple-Pathway Analysis of Double-Strand Break Repair Mutations in Drosophila
The analysis of double-strand break (DSB) repair is complicated by the existence of several pathways utilizing a large number of genes. Moreover, many of these genes have been shown to have multiple roles in DSB repair. To address this complexity we used a repair reporter construct designed to measure multiple repair outcomes simultaneously. This approach provides estimates of the relative usage of several DSB repair pathways in the premeiotic male germline of Drosophila. We applied this system to mutations at each of 11 repair loci plus various double mutants and altered dosage genotypes. Most of the mutants were found to suppress one of the pathways with a compensating increase in one or more of the others. Perhaps surprisingly, none of the single mutants suppressed more than one pathway, but they varied widely in how the suppression was compensated. We found several cases in which two or more loci were similar in which pathway was suppressed while differing in how this suppression was compensated. Taken as a whole, the data suggest that the choice of which repair pathway is used for a given DSB occurs by a two-stage âdecision circuitâ in which the DSB is first placed into one of two pools from which a specific pathway is then selected
Phenotypic diversity of circulating tumour cells in patients with metastatic castrationâresistant prostate cancer
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/1/bju13631_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/2/bju13631.pd
Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain
Our knowledge of the transcriptome has become much more complex since the days of
the central dogma of molecular biology. We now know that splicing takes place to
create potentially thousands of isoforms from a single gene, and we know that RNA
does not always faithfully recapitulate DNA if RNA editing occurs. Collectively, these
observations show that the transcriptome is amazingly rich with intricate regulatory
mechanisms for overall gene expression, splicing, and RNA editing.
Genetic variability can play a role in controlling gene expression, which can be
identified by examining expression quantitative trait loci (eQTLs). eQTLs are genomic
regions where genetic variants, including single nucleotide polymorphisms (SNPs)
show a statistical association with expression of mRNA transcripts. In humans, many
SNPs are also associated with disease, and have been identified using genome wide
association studies (GWAS) but the biological effects of those SNPs are usually not
known. If SNPs found in GWAS are also found in eQTLs, then one could hypothesize
that expression levels may contribute to disease risk. Performing eQTL analysis with
GWAS SNPs in both blood and brain, specifically the frontal cortex and the
cerebellum, we found both shared and tissue unique eQTLS. The identification of
tissue-unique eQTLs supports the argument that choice of tissue type is important in
eQTL studies (Paper I).
Aging is a complex process with the mechanisms underlying aging still being poorly
defined. There is evidence that the transcriptome changes with age, and hence we used
the brain dataset from our first paper as a discovery set, with an additional replication
dataset, to investigate any aging-gene expression associations. We found evidence that
many genes were associated with aging. We further found that there were more
statically significant expression changes in the frontal cortex versus the cerebellum,
indicating that brain regions may age at different rates. As the brain is a heterogeneous
tissue including both neurons and non-neuronal cells, we used LCM to capture Purkinje
cells as a representative neuronal type and repeated the age analysis. Looking at the
discovery, replication and Purkinje cell datasets we found five genes with strong,
replicated evidence of age-expression associations (Paper II).
Being able to capture and quantify the depth of the transcriptome has been a lengthy
process starting with methods that could only measure a single gene to genome-wide
techniques such as microarray. A recently developed technology, RNA-Seq, shows
promise in its ability to capture expression, splicing, and editing and with its broad
dynamic range quantification is accurate and reliable. RNA-Seq is, however, data
intensive and a great deal of computational expertise is required to fully utilize the
strengths of this method. We aimed to create a small, well-controlled, experiment in
order to test the performance of this relatively new technology in the brain. We chose
embryonic versus adult cerebral cortex, as mice are genetically homogenous and there
are many known differences in gene expression related to brain development that we
could use as benchmarks for analysis testing. We found a large number of differences
in total gene expression between embryonic and adult brain. Rigorous technical and
biological validation illustrated the accuracy and dynamic range of RNA-Seq. We were also able to interrogate differences in exon usage in the same dataset. Finally we
were able to identify and quantify both well-known and novel A-to-I edit sites. Overall
this project helped us develop the tools needed to build usable pipelines for RNA-Seq
data processing (Paper III).
Our studies in the developing brain (Paper III) illustrated that RNA-Seq was a useful
unbiased method for investigating RNA editing. To extend this further, we utilized a
genetically modified mouse model to study the transcriptomic role of the RNA editing
enzyme ADAR2. We found that ADAR2 was important for editing of the coding
region of mRNA as a large proportion of RNA editing sites in coding regions had a
statistically significant decrease in editing percentages in Adar2
-/-Gria2
R/R
mice versus
controls. However, despite indications in the literature that ADAR2 may also be
involved in splicing and expression regulatory machinery we found no changes in gene
expression or exon utilization in Adar2
-/-Gria2
R/R
mice as compared to their littermate
controls (Paper IV).
In our final study, based on the methods developed in Papers III and IV, we revisited
the idea of age related gene expression associations from Paper II. We used a subset of
human frontal cortices for RNA sequencing. Interestingly we found more gene
expression changes with aging compared to the previous data using microarrays in
Paper II. When the significant gene lists were analysed for gene ontology enrichment,
we found that there was a large number of downregulated genes involved in synaptic
function while those that were upregulated had enrichment in immune function. This
dataset illustrates that the aging brain may be predisposed to the processes found in
neurodegenerative diseases (Paper V)
Genetic risk of Parkinson disease and progression:: An analysis of 13 longitudinal cohorts.
OBJECTIVE: To determine if any association between previously identified alleles that confer risk for Parkinson disease and variables measuring disease progression. METHODS: We evaluated the association between 31 risk variants and variables measuring disease progression. A total of 23,423 visits by 4,307 patients of European ancestry from 13 longitudinal cohorts in Europe, North America, and Australia were analyzed. RESULTS: We confirmed the importance of GBA on phenotypes. GBA variants were associated with the development of daytime sleepiness (p.N370S: hazard ratio [HR] 3.28 [1.69-6.34]) and possible REM sleep behavior (p.T408M: odds ratio 6.48 [2.04-20.60]). We also replicated previously reported associations of GBA variants with motor/cognitive declines. The other genotype-phenotype associations include an intergenic variant near LRRK2 and the faster development of motor symptom (Hoehn and Yahr scale 3.0 HR 1.33 [1.16-1.52] for the C allele of rs76904798) and an intronic variant in PMVK and the development of wearing-off effects (HR 1.66 [1.19-2.31] for the C allele of rs114138760). Age at onset was associated with TMEM175 variant p.M393T (-0.72 [-1.21 to -0.23] in years), the C allele of rs199347 (intronic region of GPNMB, 0.70 [0.27-1.14]), and G allele of rs1106180 (intronic region of CCDC62, 0.62 [0.21-1.03]). CONCLUSIONS: This study provides evidence that alleles associated with Parkinson disease risk, in particular GBA variants, also contribute to the heterogeneity of multiple motor and nonmotor aspects. Accounting for genetic variability will be a useful factor in understanding disease course and in minimizing heterogeneity in clinical trials.The Intramural Research Program the National Institute on Aging (NIA, Z01-AG000949-02), Biogen Idec, and the Michael J Fox Foundation for Parkinsonâs Researc
Differences in the Presentation and Progression of Parkinson's Disease by Sex.
BACKGROUND: Previous studies reported various symptoms of Parkinson's disease (PD) associated with sex. Some were conflicting or confirmed in only one study. OBJECTIVES: We examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data. METHODS: We tested 40 clinical phenotypes, using longitudinal, clinic-based patient cohorts, consisting of 5946 patients, with a median follow-up of 3.1âyears. For continuous outcomes, we used linear regressions at baseline to test sex-associated differences in presentation, and linear mixed-effects models to test sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox regression models for survival analyses. We adjusted for age, disease duration, and medication use. In the secondary analyses, data from 17â719 PD patients and 7588 non-PD participants from an online-only, self-assessment PD cohort were cross-sectionally evaluated to determine whether the sex-associated differences identified in the primary analyses were consistent and unique to PD. RESULTS: Female PD patients had a higher risk of developing dyskinesia early during the follow-up period, with a slower progression in activities of daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings in the longitudinal, clinic-based cohorts were mostly consistent with the results of the online-only cohort. CONCLUSIONS: We observed sex-associated contributions to PD heterogeneity. These results highlight the necessity of future research to determine the underlying mechanisms and importance of personalized clinical management. © 2020 International Parkinson and Movement Disorder Society.This study was supported by the Intramural Research Program the National
Institute on Aging (NIA, Z01-AG000949-02), Biogen Idec, and the Michael J Fox Foundation for Parkinsonâs Research
The Cysteine Protease α-Clostripain is Not Essential for the Pathogenesis of Clostridium perfringens-Mediated Myonecrosis
Clostridium perfringens is the causative agent of clostridial myonecrosis or gas gangrene and produces many different extracellular toxins and enzymes, including the cysteine protease α-clostripain. Mutation of the α-clostripain structural gene, ccp, alters the turnover of secreted extracellular proteins in C. perfringens, but the role of α-clostripain in disease pathogenesis is not known. We insertionally inactivated the ccp gene C. perfringens strain 13 using TargeTron technology, constructing a strain that was no longer proteolytic on skim milk agar. Quantitative protease assays confirmed the absence of extracellular protease activity, which was restored by complementation with the wild-type ccp gene. The role of α-clostripain in virulence was assessed by analysing the isogenic wild-type, mutant and complemented strains in a mouse myonecrosis model. The results showed that although α-clostripain was the major extracellular protease, mutation of the ccp gene did not alter either the progression or the development of disease. These results do not rule out the possibility that this extracellular enzyme may still have a role in the early stages of the disease process
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.
Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 Ă 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease
How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property
The modern concept of âdynastyâ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegelâs references to âdynastyâ, read with Marxâs critique, further show how âdynastyâ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about âdynastyâ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of âdynastyâ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/âtribalâ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ârajavamshiâ and âKshatriyaâ. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe
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