584 research outputs found
Gpr171, a putative P2Y-like receptor, negatively regulates myeloid differentiation in murine hematopoietic progenitors.
No full textGpr171 is an orphan G-protein-coupled receptor putatively related to the P2Y family of purinergic receptors (P2YRs) for extracellular nucleotides, a group of mediators previously shown to regulate hematopoietic progenitor cells. No information is currently available on the ligand responsible for Gpr171 activation and its biological role remains unknown. We reconstructed Gpr171 phylogenesis in mice and confirmed that Gpr171 is evolutionally related to members of a P2Y gene-cluster localized on mouse chromosome 3. As a first step toward unveiling a role for Gpr171, we investigated its expression profile in murine hematopoietic cells. As opposed to other P2YRs, we found that Gpr171 expression is down-regulated in monocytes and granulocytes, suggesting a negative role in myeloid lineage specification. To test Gpr171 functional role, we next enforced Gpr171 expression in a myeloblastic cell line (32D cells) and in primary Sca-1(+) hematopoietic progenitors, and observed a decreased expression of myeloid markers upon induction of Gpr171, as well as an increased generation of colonies in vitro. Conversely, Gpr171 silencing induced opposite results, diminishing the expression of myeloid markers and the clonogenic potential of 32D cells. In vivo, mice transplanted with hematopoietic progenitor cells overexpressing Gpr171 displayed a significant reduction in the percentage of Mac-1(+)Gr-1(-) cells. As a preliminary step in the investigation of Gpr171 role in murine hematopoiesis, our findings indicate that the orphan receptor Gpr171 negatively regulates myeloid differentiation. Together with phylogenic analyses, our data suggest that Gpr171 may have followed a separate evolutionary pathway as compared to other P2YRs belonging to the same gene cluster
Muscle-derived hematopoietic stem cells are hematopoietic in origin
No full textIt has recently been shown that mononuclear cells from murine skeletal muscle contain the potential to repopulate all major peripheral blood lineages in lethally irradiated mice, but the origin of this activity is unknown. We have fractionated muscle cells on the basis of hematopoietic markers to show that the active population exclusively expresses the hematopoietic stem cell antigens Sca-1 and CD45. Muscle cells obtained from 6- to 8-week-old C57BL/6-CD45.1 mice and enriched for cells expressing Sca-1 and CD45 were able to generate hematopoietic but not myogenic colonies in vitro and repopulated multiple hematopoietic lineages of lethally irradiated C57BL/6-CD45.2 mice. These data show that muscle-derived hematopoietic stem cells are likely derived from the hematopoietic system and are a result not of transdifferentiation of myogenic stem cells but instead of the presence of substantial numbers of hematopoietic stem cells in the muscle. Although CD45-negative cells were highly myogenic in vitro and in vivo, CD45-positive muscle-derived cells displayed only very limited myogenic activity and only in vivo
Memory Compression, Predictive Coding, and Temporal Overlap as a Computational Basis for Déjà Vu
No full textThis project develops a computational memory framework explaining déjà vu using established principles from predictive coding, memory compression, and hippocampal pattern completion. The account proposes that déjà vu arises when current perceptual input partially overlaps with compressed mnemonic representations, producing a false familiarity signal in the absence of a corresponding episodic memory. A slight predictive lead or temporal overlap in processing can amplify this effect, creating the brief but vivid impression of prior occurrence.
The attached whitepaper outlines the formal mechanism, including pattern collision and temporal compression, and provides falsifiable predictions for behavioral and neuroimaging studies. The framework avoids speculative explanations and situates déjà vu within standard models of cortical prediction and hippocampal computation.
Author: Tyler J. Goodell
Independent Researcher in Memory & Perceptio
Public assistance in redevelopment of historic Goodell Mill in Antrim, New Hampshire
No full textThis project spearheaded the local community's involvement in redeveloping the privately owned Goodell Mill and attempted to secure funding for a renovation that addresses the needs of small businesses and residents in the neighborhood, town, and region. It was initiated by the Downtown Antrim Tax Increment Finance (TIF) District, with labor and input from neighborhood and town residents. To provide meaningful and necessary assistance to the private redevelopment project, the TIF District Administrator applied for a feasibility study and identified construction funding sources. The administrator and board, serving as the town's agent, will now seek funding from regional, state, federal, non-profit, and private business-development and historic preservation organizations while continuing to work in close partnership with the owner. The TIF district also investigated whether to recommend purchase by the town or a nonprofit. The project would be deemed successful if the feasibility study, ownership recommendation, and funding for redevelopment were delivered by April 2004. (Author abstract)Essex, D. (2004). Public assistance in redevelopment of historic Goodell Mill in Antrim, New Hampshire. Retrieved from http://academicarchive.snhu.eduMaster of Science (M.S.)School of Community Economic Developmen
Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity
No full textPolycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU)-induced mutation in Suppressor of Zeste 12 (Suz12), a core component of Polycomb Repressive Complex 2 (PRC2), we show here that loss of Suz12 function enhances hematopoietic stem cell (HSC) activity. In addition to these effects on a wild-type genetic background, mutations in Suz12 are sufficient to ameliorate the stem cell defect and thrombocytopenia present in mice that lack the thrombopoietin receptor (c-Mpl). To investigate the molecular targets of the PRC2 complex in the HSC compartment, we examined changes in global patterns of gene expression in cells deficient in Suz12. We identified a distinct set of genes that are regulated by Suz12 in hematopoietic cells, including eight genes that appear to be highly responsive to PRC2 function within this compartment. These data suggest that PRC2 is required to maintain a specific gene expression pattern in hematopoiesis that is indispensable to normal stem cell function
'Crisis in Ohio' article
No full textArticle titled "The Crisis in Ohio" by Maria G. Frost, which calls for a revision of the Ohio Constitution in favor of women's suffrage. Frost couches her argument in religious and patriotic terms in support of "self government" for women. Maria Goodell Frost (1826-1899) was the daughter of William Goodell, a noted abolitionist and temperance advocate from New York. She supported both of these reform movements, and was active in support of women's suffrage.
This item comes from the Frances Jennings Casement Papers, a manuscript collection comprised of letters and association records related to the founding and leadership of the Ohio Woman Suffrage Association. Casement (1840-1928) was born in Painesville, Ohio, and graduated from Painesville Academy and Willoughby Female Seminary. Her father, Charles Casement, supported abolition and women's suffrage and encouraged Frances to be active in social causes. Frances Casement established the Painesville Equal Rights Association in 1883, and shortly after became involved in the Ohio Woman Suffrage Association, serving as its president from 1885 to 1888
A history of the town of Keene from 1732, when the township was granted by Massachusetts, to 1874, when it became a city. With events of interest in the history of the city from 1874 to 1904, by Frank H. Whitcomb. And an introductory sketch of the author by O. Applegate, Jr.
No full textCompleted and published by authority of the city councils, after the death of the author
Plantation medicine in Hawaii 1840 to 1964: a patient's perspective.
No full textThe first contract laborers arrived from China in 1852, but little attention was paid to their medical needs. In 1886 a physician from Japan arrived to minister to the health and medical needs of the Japanese immigrants. After 1900 most physicians caring for immigrant plantation workers were Western trained from the Mainland. Many advances in medicine were started on plantations such as the second x-ray machine in Hawaii. The 1950s brought rapid changes in plantation medicine with the closing of plantation facilities on Oahu. The author describes her personal experience as a patient in the plantation medical system
Chapter Introduction
No full textThis introduction to the book provides a conceptual and historical overview of learning engineering. Although its formal definition is still evolving, learning engineering aims to optimize specific learning solutions--from the learning sciences to human-centered design methodologies to data-informed decision-making--in order to understand under what conditions and with what learners a current design is optimal or not, and to develop and test alternative more robust, or more refined, solutions that are more scalable. The author makes the case for learning engineering as a multidisciplinary approach that complements related professional practices and fields of study such as instructional design, learning sciences, data analytics, instructional systems design, and more. After a brief exploration of the differences between science from engineering, this introduction goes on to address the theoretical and professional origins of learning engineering as well as its inherently team-based process, using as examples the language-learning platform Duolingo and the Carnegie Mellon University spinoff Carnegie Learning, Inc. to discuss effective techniques
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