2,106 research outputs found

    Free For All: Proposing Legislation to Eliminate Food Insecurity in Arkansas Public Schools

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    Schools serve millions of students daily as one of the largest food distribution sites in the United States. However, more than 13.1 million children in the United States, and almost 150,000 in Arkansas, are food insecure. Before the COVID-19 pandemic, most Arkansas schools offered free and reduced lunch to students at or below the poverty line through participation in the National School Lunch Program (“NSLP”). During COVID-19, Congress passed The Families First Coronavirus Response Act (“FFCRA”) and The Coronavirus Aid, Relief, and Economic Security Act (“CARES”) (hereinafter “The Acts”). This legislation effectively eliminated food insecurity in participating American public schools, including many in Arkansas, as it provided free lunch to all students, regardless of household income. Now, as COVID-19 has largely subsided, Congress has eliminated the funding allowed by The Acts and many states, including Arkansas, have reverted to pre-COVID-19 funding mechanisms using the NSLP. The Arkansas General Assembly must utilize its current tax surplus, or alternatively increase taxes to fund a state-wide subsidy to the NSLP

    Free For All: Proposing Legislation to Eliminate Food Insecurity in Arkansas Public Schools

    Get PDF
    Schools serve millions of students daily as one of the largest food distribution sites in the United States. However, more than 13.1 million children in the United States, and almost 150,000 in Arkansas, are food insecure. Before the COVID-19 pandemic, most Arkansas schools offered free and reduced lunch to students at or below the poverty line through participation in the National School Lunch Program (“NSLP”). During COVID-19, Congress passed The Families First Coronavirus Response Act (“FFCRA”) and The Coronavirus Aid, Relief, and Economic Security Act (“CARES”) (hereinafter “The Acts”). This legislation effectively eliminated food insecurity in participating American public schools, including many in Arkansas, as it provided free lunch to all students, regardless of household income. Now, as COVID-19 has largely subsided, Congress has eliminated the funding allowed by The Acts and many states, including Arkansas, have reverted to pre-COVID-19 funding mechanisms using the NSLP. The Arkansas General Assembly must utilize its current tax surplus, or alternatively increase taxes to fund a state-wide subsidy to the NSLP

    Examining Learning Styles and Perceived Benefits of Analogical Problem Construction on SQL Knowledge Acquisition

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    The demand for Information Systems (IS) graduates with expertise in Structured Query Language (SQL) and database management is vast and projected to increase as ‘big data’ becomes ubiquitous. To prepare students to solve complex problems in a data-driven world, educators must explore instructional strategies to help link prior knowledge to new knowledge. This study examined learning styles and the perceived benefits of analogical problem construction on SQL knowledge acquisition. The data collected from 80 participants suggests there is a perceived positive benefit to using analogical problem construction for learning introductory database concepts. The learning style of the majority of students in the sample is ‘Active-Sensing-Visual-Sequential.’ However, learning styles were not related to student perceived impact of analogical problem construction to understand database concepts. Student analogies were collected for a variety of SQL concepts; noteworthy examples are highlighted. While results related to learning styles are intriguing, the most promising path for further exploration (for both research and practice) is the use of analogy problem construction in Information Systems educational environments

    Voices of girls with disabilities in rural Iran

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    This paper investigates the interaction of gender, disability and education in rural Iran, which is a relatively unexplored field of research. The responses of 10 female students with disabilities from Isfahan indicated that the obstacles they faced included marginalization, difficulties in getting from home to school, difficulties within the school building itself, and discrimination by teachers, classmates and school authorities. The data collected for the study contain a wide range of conservative gendered discourses, and show how traditional gender beliefs interact with disability to aggravate the problems faced in education by young women with disabilities. It is hoped that the findings will raise awareness among policy-makers of the many formidable obstacles that make it difficult for young women with disabilities to achieve their full potential in education

    Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

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    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.This is the published version of the manuscript. It was published in PLOS One and can be found here: http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0105027&representation=PD

    Enhancing the efficacy of glycolytic blockade in cancer cells via RAD51 inhibition.

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    Targeting the early steps of the glycolysis pathway in cancers is a well-established therapeutic strategy; however, the doses required to elicit a therapeutic effect on the cancer can be toxic to the patient. Consequently, numerous preclinical and clinical studies have combined glycolytic blockade with other therapies. However, most of these other therapies do not specifically target cancer cells, and thus adversely affect normal tissue. Here we first show that a diverse number of cancer models - spontaneous, patient-derived xenografted tumor samples, and xenografted human cancer cells - can be efficiently targeted by 2-deoxy-D-Glucose (2DG), a well-known glycolytic inhibitor. Next, we tested the cancer-cell specificity of a therapeutic compound using the MEC1 cell line, a chronic lymphocytic leukemia (CLL) cell line that expresses activation induced cytidine deaminase (AID). We show that MEC1 cells, are susceptible to 4,4\u27-Diisothiocyano-2,2\u27-stilbenedisulfonic acid (DIDS), a specific RAD51 inhibitor. We then combine 2DG and DIDS, each at a lower dose and demonstrate that this combination is more efficacious than fludarabine, the current standard- of- care treatment for CLL. This suggests that the therapeutic blockade of glycolysis together with the therapeutic inhibition of RAD51-dependent homologous recombination can be a potentially beneficial combination for targeting AID positive cancer cells with minimal adverse effects on normal tissue. IMPLICATIONS: Combination therapy targeting glycolysis and specific RAD51 function shows increased efficacy as compared to standard of care treatments in leukemias

    Onset of common mental disorders and suicidal behavior following women's first exposure to gender based violence: a retrospective, population-based study

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    Published: 18 November 2014BACKGROUND: Women exposed to gender-based violence (GBV) experience a high rate of common mental disorders and suicidal behaviour ("mental disturbance"). Little is known however about the timing of onset of mental disturbance following first exposure to GBV amongst women with no prior mental disorder. METHODS: The analysis was undertaken on the Australian National Mental Health and Wellbeing Survey dataset (N = 8841). We assessed lifetime prevalence and first onset of common mental disorder and suicidal behaviour (mental disturbance) and exposure to GBV and its first occurrence based on the Composite International Diagnostic Interview Version 3 (WMH-CIDI 3.0). We used the Kaplan-Meier method to derive cumulative incident curves for first onset mental disturbance. The two derived subgroups were women who experienced GBV without prior mental disturbance; and women never exposed to GBV stratified to match the former group on age and socio-economic status. RESULTS: For women with no prior mental disorder, the cumulative incidence curves showed a high incidence of all mental disturbances following first GBV, compared to women without exposure to GBV (all log rank tests <0.0001). Nearly two fifths (37%) of any lifetime mental disturbance had onset in the year following first GBV in women exposed to abuse. For these women, over half (57%) of cases of lifetime PTSD had onset in the same time interval. For GBV exposed women, half of all cases of mental disturbance (54%) and two thirds of cases of PTSD (66.9%) had onset in the five years following first abuse. In contrast, there was a low prevalence of onset of mental disturbance in the comparable imputed time to event period for women never exposed to GBV (for any mental disturbance, 1% in the first year, 12% in five years; for PTSD 3% in the first year, 7% in five years). CONCLUSIONS: Amongst women without prior mental disturbance, common mental disorders and suicidal behaviour have a high rate of onset in the one and five year intervals following exposure to GBV. There is a particularly high incidence of PTSD in the first year following GBV.Susan Rees, Zachary Steel, Mark Creamer, Maree Teesson, Richard Bryant, Alexander C McFarlane, Katherine L Mills, Tim Slade, Natacha Carragher, Meaghan O, Donnell, David Forbes and Derrick Silov

    Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.

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    Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro-inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state

    PubChem3D: Similar conformers

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    <p>Abstract</p> <p>Background</p> <p>PubChem is a free and open public resource for the biological activities of small molecules. With many tens of millions of both chemical structures and biological test results, PubChem is a sizeable system with an uneven degree of available information. Some chemical structures in PubChem include a great deal of biological annotation, while others have little to none. To help users, PubChem pre-computes "neighboring" relationships to relate similar chemical structures, which may have similar biological function. In this work, we introduce a "Similar Conformers" neighboring relationship to identify compounds with similar 3-D shape and similar 3-D orientation of functional groups typically used to define pharmacophore features.</p> <p>Results</p> <p>The first two diverse 3-D conformers of 26.1 million PubChem Compound records were compared to each other, using a shape Tanimoto (ST) of 0.8 or greater and a color Tanimoto (CT) of 0.5 or greater, yielding 8.16 billion conformer neighbor pairs and 6.62 billion compound neighbor pairs, with an average of 253 "Similar Conformers" compound neighbors per compound. Comparing the 3-D neighboring relationship to the corresponding 2-D neighboring relationship ("Similar Compounds") for molecules such as caffeine, aspirin, and morphine, one finds unique sets of related chemical structures, providing additional significant biological annotation. The PubChem 3-D neighboring relationship is also shown to be able to group a set of non-steroidal anti-inflammatory drugs (NSAIDs), despite limited PubChem 2-D similarity.</p> <p>In a study of 4,218 chemical structures of biomedical interest, consisting of many known drugs, using more diverse conformers per compound results in more 3-D compound neighbors per compound; however, the overlap of the compound neighbor lists per conformer also increasingly resemble each other, being 38% identical at three conformers and 68% at ten conformers. Perhaps surprising is that the average count of conformer neighbors per conformer increases rather slowly as a function of diverse conformers considered, with only a 70% increase for a ten times growth in conformers per compound (a 68-fold increase in the conformer pairs considered).</p> <p>Neighboring 3-D conformers on the scale performed, if implemented naively, is an intractable problem using a modest sized compute cluster. Methodology developed in this work relies on a series of filters to prevent performing 3-D superposition optimization, when it can be determined that two conformers cannot possibly be a neighbor. Most filters are based on Tanimoto equation volume constraints, avoiding incompatible conformers; however, others consider preliminary superposition between conformers using reference shapes.</p> <p>Conclusion</p> <p>The "Similar Conformers" 3-D neighboring relationship locates similar small molecules of biological interest that may go unnoticed when using traditional 2-D chemical structure graph-based methods, making it complementary to such methodologies. The computational cost of 3-D similarity methodology on a wide scale, such as PubChem contents, is a considerable issue to overcome. Using a series of efficient filters, an effective throughput rate of more than 150,000 conformers per second per processor core was achieved, more than two orders of magnitude faster than without filtering.</p

    A non-coding RNA balancing act: miR-346-induced DNA damage is limited by the long non-coding RNA NORAD in prostate cancer

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    Background: miR‑346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)‑linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR‑346 on DNA damage, and its potential as a therapeutic agent. Methods: RNA‑IP, RNA‑seq, RNA‑ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification‑free, single nucleotide‑resolution genome‑wide mapping of DNA breaks (INDUCE‑seq). Results: miR‑346 induces rapid and extensive DNA damage in PC cells ‑ the first report of microRNA‑induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R‑loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR‑346 also interacts with genome‑protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA‑seq studies. In contrast, miR‑346 is associated with improved PC survival. INDUCE‑seq reveals that miR‑346‑induced DSBs occur preferentially at binding sites of the most highly‑transcriptionally active transcription factors in PC cells, including c‑Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA‑seq reveals widespread miR‑346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target‑directed miR decay (TDMD) of miR‑346 as a novel genome protection mechanism: NORAD silencing increases mature miR‑346 levels by several thousand‑fold, and WT but not TDMD‑mutant NORAD rescues miR‑346‑induced DNA damage. Importantly, miR‑346 sensitises PC cells to DNA‑damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR‑346:NORAD balance is a valid therapeutic strategy
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