Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 gene

<p>Abstract</p> <p>Background</p> <p>The <it>Fgf2 </it>gene is expressed in the brain neuroepithelium during embryonic development and in astroglial cells throughout life. Previous knockout studies suggested that FGF2 plays a role in the proliferation of neural progenitors in the embryonic cerebral cortex. These studies exclusively used knockout alleles lacking the <it>Fgf2 </it>exon 1. However, the description of putative alternative exons located downstream from the canonical exon 1 raised the possibility that alternatively spliced transcripts may compensate for the lack of the canonical exon 1 in the <it>Fgf2 </it>-/- mice.</p> <p>Results</p> <p>We generated and characterized a new line of Fgf2 knockout mice lacking the expression of exon 3, which is conserved in all <it>Fgf2 </it>transcripts and contains essential heparin and receptor binding interfaces. The expression of <it>Fgf2 </it>exon 3 was prevented by inserting a transcriptional STOP cassette in the <it>Fgf2 </it>genomic locus. These mice demonstrate a phenotype in the adult neocortex characterized by decreased density and number of cortical excitatory neurons and astrocytes, which is virtually identical to that of the <it>Fgf2 </it>-/- mice lacking exon 1. In addition, we also show that the <it>Fgf2 </it>exon 3 knockout mice have decreased proliferation of precursors in the adult cerebral cortex, which had not been previously investigated in the other mutant lines.</p> <p>Conclusion</p> <p>The results demonstrate that the phenotype of two completely different <it>Fgf2 </it>KO mouse lines, lacking exon 1 or exon 3, is remarkably similar. The combined results from these KO models clearly indicate that FGF2 plays a role in cortical cell genesis during embryonic development as well as in adulthood. Thus, FGF2 may be required for the maintenance of the pool of adult cortical progenitor cells.</p

Global Learning for Health Equity: A Literature Review

BACKGROUND: In high income countries struggling with escalating health care costs and persistent lack of equity, there is growing interest in searching for innovative solutions developed outside national borders, particularly in low- and middle-income countries (LMICs). Engaging with global ideas to apply them to local health equity challenges is becoming increasingly recognized as an approach to shift the health equity landscape in the United States (US) in a significant way. No single name or set of practices yet defines the process of identifying LMIC interventions for adaptation; implementing interventions in high-income countries (HIC) settings; or evaluating the implementation of such projects. OBJECTIVES: This paper presents a review of the literature describing the practice of adapting global ideas for use in the US, particularly in the area of health equity. Specifically, the authors sought to examine; (i) the literature that advocates for, or describes, adaption of health-related innovations from LMICs to HICs, both generally and for health equity specifically, and (ii) implementation practices, strategies, and evidence-based outcomes in this field, generally and in the area of health equity specifically. The authors also propose terminology and a definition to describe the practice. METHODS: The literature search included two main concepts: global learning and health equity (using these and related terms). The search consisted of text-words and database-specific terminology (e.g., MeSH, Emtree) using PubMed, Embase (Elsevier), CINAHL (Ebsco), and Scopus in March 2021. The authors also contacted relevant experts to identify grey literature. Identified sources were categorized according to theme to facilitate analysis. In addition, five key interviews with experts engaged with global ideas to promote health equity in the United States were conducted to develop additional data. RESULTS: The literature review yielded over ninety (n = 92) sources relating to the adaptation of global ideas from low resource to higher resource settings to promote health equity (and related concepts). Identified sources range from those providing general commentaries about the value of seeking health-related innovations outside the US border to sources describing global projects implemented in the US, most without implementation or outcome measures. Other identified sources provide frameworks or guidance to help identify and/or implement global ideas in the US, and some describe the role of the World Health Organization and other international consortia in promoting a global approach to solving domestic health equity and related challenges. CONCLUSIONS: The literature review demonstrates that there are resources and commentary describing potential benefits of identifying and adapting novel global ideas to address health equity in the US, but there is a dearth of implementation and evaluation data. Terminology is required to define and frame the field. Additional research, particularly in the area of implementation science and evidence-based frameworks to support the practice of what we define as \u27global learning\u27 for health equity, is necessary to advance the practice

Technical Adequacy of Curriculum-Based Measures in Writing in Grades 1–3

The purpose of this study was to investigate evidence of reliability, criterion validity, and grade-level differences of curriculum-based measures of writing (CBM-W) with 612 students in grades 1–3. Four scoring procedures (words written, words spelled correctly, correct word sequences, and correct minus incorrect word sequences) were used with two CBM-W tasks (picture–word and story prompt) during fall, winter, and spring of one academic year. A subsample of participants (n = 244) were given a criterion measure in spring of the academic year. Pearson’s r coefficients were calculated to determine evidence of alternate form reliability and criterion validity, and a MANOVA was used to detect significant growth within and across grade levels. Results indicated that scores on both CBM-W tasks had adequate reliability and validity coefficients in grades 2–3 and mixed results in grade 1. Significant growth was detected within and across all grades at each time point on each task. Implications for research and practice are discussed

Murine esBAF chromatin remodeling complex subunits BAF250a and Brg1 are necessary to maintain and reprogram pluripotency-specific replication timing of select replication domains

Background: Cellular differentiation and reprogramming are accompanied by changes in replication timing and 3D organization of large-scale (400 to 800 Kb) chromosomal domains (‘replication domains’), but few gene products have been identified whose disruption affects these properties. Results: Here we show that deletion of esBAF chromatin-remodeling complex components BAF250a and Brg1, but not BAF53a, disrupts replication timing at specific replication domains. Also, BAF250a-deficient fibroblasts reprogrammed to a pluripotency-like state failed to reprogram replication timing in many of these same domains. About half of the replication domains affected by Brg1 loss were also affected by BAF250a loss, but a much larger set of domains was affected by BAF250a loss. esBAF binding in the affected replication domains was dependent upon BAF250a but, most affected domains did not contain genes whose transcription was affected by loss of esBAF. Conclusions: Loss of specific esBAF complex subunits alters replication timing of select replication domains in pluripotent cells

CT of unusual mediastinal vascular abnormalities

The previously unreported CT findings of supracardiac anomalous pulmonary venous return and Takayasu arteritis are presented. CT demonstration of a left vertical vein and an enlarged superior vena cava strongly suggests a diagnosis of supracardiac anomalous venous return. Dynamic scanning of the mediastinum following bolus injection of urographic contrast with close attention to vascular enhancement patterns is required to suggest a diagnosis of Takayasu arteritis. CT is not the preferred diagnostic modality for either entity, but may prove definitive in some patients and may serve to triage other patients to the appropriate diagnostic modalities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24654/1/0000067.pd

The Distinct Metabolic Phenotype of Lung Squamous Cell Carcinoma Defines Selective Vulnerability to Glycolytic Inhibition

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient

A Consensus Genetic Map for Pinus taeda and Pinus elliottii and Extent of Linkage Disequilibrium in Two Genotype-Phenotype Discovery Populations of Pinus taeda

A consensus genetic map for Pinus taeda (loblolly pine) and Pinus elliottii (slash pine) was constructed by merging three previously published P. taeda maps with a map from a pseudo-backcross between P. elliottii and P. taeda. The consensus map positioned 3856 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.6 cM and total map length was 2305 cM. Functional predictions of mapped genes were improved by aligning expressed sequence tags used for marker discovery to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 3305 scaffold sequences onto 12 linkage groups. The consensus genetic map was used to compare the genome-wide linkage disequilibrium in a population of distantly related P. taeda individuals (ADEPT2) used for association genetic studies and a multiple-family pedigree used for genomic selection (CCLONES). The prevalence and extent of LD was greater in CCLONES as compared to ADEPT2; however, extended LD with LGs or between LGs was rare in both populations. The average squared correlations, r2, between SNP alleles less than 1 cM apart were less than 0.05 in both populations and r2 did not decay substantially with genetic distance. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association mapping and genomic selection in P. taeda and P. elliottii.J.W.W. was supported by a USDA CSREES Food and Agricultural Sciences National Needs Graduate Fellowship. V.E.C. was supported by USDA NIFA Award #2011-68002-30185 (PINEMAP) and the USDA Forest Service. L.S.W. was supported by the National Science Foundation under grant no. ABI-1062432 to Indiana University. P.M.G., D.N., and K.M. were supported in part by USDA NIFA Award #2011-67009-30030 (PineRefSeq) to University of California, Davis.Peer reviewe