47 research outputs found

    Effect of Feeding Different Types of Byproducts and Concentrations Throughout a Beef Growing System on Ground Beef Color and Lipid Oxidation

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    The objective of this trial was to evaluate the effect of feeding different concentrations of wet distillers grains during winter backgrounding and either modified wet distillers grains or Sweet BranÂź during the finishing phase on ground beef color and lipid oxidation. After a 14 day aging period, ground beef patties were made and placed in a simulated retail display for seven days. There were no overall differences in lipid oxidation between treatments but was a treatment by day interaction for discoloration. Ground beef from heifers finished with modified wet distillers grains discolored at a greater extent when compared to ground beef from heifers finished with Sweet Bran

    Application of a low cost array-based technique — TAB-Array — for quantifying and mapping both 5mC and 5hmC at single base resolution in human pluripotent stem cells

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    Abstract5-hydroxymethylcytosine (5hmC), an oxidized derivative of 5-methylcytosine (5mC), has been implicated as an important epigenetic regulator of mammalian development. Current procedures use DNA sequencing methods to discriminate 5hmC from 5mC, limiting their accessibility to the scientific community. Here we report a method that combines TET-assisted bisulfite conversion with Illumina 450K DNA methylation arrays for a low-cost high-throughput approach that distinguishes 5hmC and 5mC signals at base resolution. Implementing this approach, termed “TAB-array”, we assessed DNA methylation dynamics in the differentiation of human pluripotent stem cells into cardiovascular progenitors and neural precursor cells. With the ability to discriminate 5mC and 5hmC, we identified a large number of novel dynamically methylated genomic regions that are implicated in the development of these lineages. The increased resolution and accuracy afforded by this approach provides a powerful means to investigate the distinct contributions of 5mC and 5hmC in human development and disease

    Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression

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    Introduction: Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis. Methods: To investigate the effects of loss of p190B function on mammary tumor progression, p190B heterozygous mice were crossed with an MMTV-Neu breast cancer model. Effects of p190B deficiency on tumor latency, multiplicity, growth, preneoplastic progression and metastasis were evaluated. To investigate potential differences in tumor angiogenesis between the two groups, immunohistochemistry to detect von Willebrand factor was performed and quantified. To examine gene expression of potential mediators of the angiogenic switch, an angiogenesis PCR array was utilized and results were confirmed using immunohistochemistry. Finally, reciprocal transplantation of tumor fragments was performed to determine the impact of stromal deficiency of p190B on tumor angiogenesis. Results: P190B deficiency reduced tumor penetrance (53% of p190B+/−Neup190B^{+/-}Neu mice vs. 100% of p190B+/+Neup190B^{+/+}Neu mice formed tumors) and markedly delayed tumor onset by an average of 46 weeks. Tumor multiplicity was also decreased, but an increase in the number of preneoplastic lesions was detected indicating that p190B deficiency inhibited preneoplastic progression. Angiogenesis was decreased in the p190B heterozygous tumors, and expression of a potent angiogenic inhibitor, thrombospondin-1, was elevated in p190B+/−Neup190B^{+/-}Neu mammary glands. Transplantation of p190B+/−Neup190B^{+/-}Neu tumor fragments into wild-type recipients restored tumor angiogenesis. Strikingly, p190B+/+Neup190B^{+/+}Neu tumor fragments were unable to grow when transplanted into p190B+/−Neup190B^{+/-}Neu recipients. Conclusions: These data suggest that p190B haploinsufficiency in the epithelium inhibits MMTV-Neu tumor initiation. Furthermore, p190B deficiency in the vasculature is responsible, in part, for the inhibition of MMTV-Neu tumor progression

    Highly Parallel Genome-Wide Expression Analysis of Single Mammalian Cells

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    We have developed a high-throughput amplification method for generating robust gene expression profiles using single cell or low RNA inputs.The method uses tagged priming and template-switching, resulting in the incorporation of universal PCR priming sites at both ends of the synthesized cDNA for global PCR amplification. Coupled with a whole-genome gene expression microarray platform, we routinely obtain expression correlation values of R(2)~0.76-0.80 between individual cells and R(2)~0.69 between 50 pg total RNA replicates. Expression profiles generated from single cells or 50 pg total RNA correlate well with that generated with higher input (1 ng total RNA) (R(2)~0.80). Also, the assay is sufficiently sensitive to detect, in a single cell, approximately 63% of the number of genes detected with 1 ng input, with approximately 97% of the genes detected in the single-cell input also detected in the higher input.In summary, our method facilitates whole-genome gene expression profiling in contexts where starting material is extremely limiting, particularly in areas such as the study of progenitor cells in early development and tumor stem cell biology

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∌99% of the euchromatic genome and is accurate to an error rate of ∌1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

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    It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

    Modulation of Theta and Gamma Oscillations during a Place and Response Task

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    The hippocampus contributes to the formation of long term memory. However, exactly how the hippocampal neurons contribute to memory formation has yet to be fully elucidated. There is evidence that rhythmical oscillations such as theta (4-12 Hz) and gamma (25-140 Hz) are involved in mnemonic processes. Neural oscillations transiently synchronize distributed neurons processing similar information and align periods of inhibition thereby allowing precise coordination of neuronal input from behaviorally relevant stimuli. ^ Theta oscillations in the hippocampus are postulated to support various cognitive processes such as working memory, decision making, and spatial navigation in humans and rodents. Theta is thought to provide a clocking system for neuronal, support synaptic plasticity, and facilitate the encoding new information. Additionally, lesions that impair theta oscillations subsequently disrupt spatial learning. ^ Gamma oscillations support perception, sensory binding, attention, working memory, language processing, and synaptic plasticity. Gamma oscillations are also involved in non-mnemonic processes such as movement initiation and reward processing. Recent studies suggest that gamma oscillations can be segregated into low (25-55 Hz) and high (65-140 Hz) gamma frequencies, each with their own internal generators and behavioral functions. ^ There are anatomical, electrophysiological, and functional dissociations along the longitudinal (dorsal-ventral) axis of the hippocampus. Few studies have simultaneously recorded theta and gamma oscillations from dorsal and ventral hippocampus; though dissociations have been noted in theta power and in how running speed modulates theta power. ^ In the current study rats were trained to continuously switch between a hippocampal-dependent place or striatal-dependent motor-response strategy. The level of difficulty and hippocampal-dependence was varied while theta and gamma were recorded in the dorsal and ventral hippocampus during different stages of decision making and learning. ^ The most striking and consistent finding was that theta and gamma oscillations were modulated during the cognitive component of the task. Theta power increased in the dorsal, but decreased in the ventral hippocampus. Low gamma power decreased in both the dorsal and ventral hippocampus. High gamma power selectively increased in the dorsal hippocampus. Understanding what these different neural oscillations do during different cognitive processes will help elucidate how they contribute to the formation of memory.

    Modulation of Theta and Gamma Oscillations during a Place and Response Task

    No full text
    The hippocampus contributes to the formation of long term memory. However, exactly how the hippocampal neurons contribute to memory formation has yet to be fully elucidated. There is evidence that rhythmical oscillations such as theta (4-12 Hz) and gamma (25-140 Hz) are involved in mnemonic processes. Neural oscillations transiently synchronize distributed neurons processing similar information and align periods of inhibition thereby allowing precise coordination of neuronal input from behaviorally relevant stimuli. ^ Theta oscillations in the hippocampus are postulated to support various cognitive processes such as working memory, decision making, and spatial navigation in humans and rodents. Theta is thought to provide a clocking system for neuronal, support synaptic plasticity, and facilitate the encoding new information. Additionally, lesions that impair theta oscillations subsequently disrupt spatial learning. ^ Gamma oscillations support perception, sensory binding, attention, working memory, language processing, and synaptic plasticity. Gamma oscillations are also involved in non-mnemonic processes such as movement initiation and reward processing. Recent studies suggest that gamma oscillations can be segregated into low (25-55 Hz) and high (65-140 Hz) gamma frequencies, each with their own internal generators and behavioral functions. ^ There are anatomical, electrophysiological, and functional dissociations along the longitudinal (dorsal-ventral) axis of the hippocampus. Few studies have simultaneously recorded theta and gamma oscillations from dorsal and ventral hippocampus; though dissociations have been noted in theta power and in how running speed modulates theta power. ^ In the current study rats were trained to continuously switch between a hippocampal-dependent place or striatal-dependent motor-response strategy. The level of difficulty and hippocampal-dependence was varied while theta and gamma were recorded in the dorsal and ventral hippocampus during different stages of decision making and learning. ^ The most striking and consistent finding was that theta and gamma oscillations were modulated during the cognitive component of the task. Theta power increased in the dorsal, but decreased in the ventral hippocampus. Low gamma power decreased in both the dorsal and ventral hippocampus. High gamma power selectively increased in the dorsal hippocampus. Understanding what these different neural oscillations do during different cognitive processes will help elucidate how they contribute to the formation of memory.
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