Institution
University of Nevada, Reno
Education•Reno, Nevada, United States•
About: University of Nevada, Reno is a education organization based out in Reno, Nevada, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 13561 authors who have published 28217 publications receiving 882002 citations. The organization is also known as: University of Nevada & Nevada State University.
Papers published on a yearly basis
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TL;DR: Clinical science seems to have reached a tipping point, and a new paradigm is beginning to emerge that is questioning the validity and utility of the medical illness model, which assumes that latent disease entities are targeted with specific therapy protocols.
Abstract: Clinical science seems to have reached a tipping point. It appears that a new paradigm is beginning to emerge that is questioning the validity and utility of the medical illness model, which assumes that latent disease entities are targeted with specific therapy protocols. A new generation of evidence-based care has begun to move toward process-based therapies to target core mediators and moderators based on testable theories. This could represent a paradigm shift in clinical science with far-reaching implications. Clinical science might see a decline of named therapies defined by set technologies, a decline of broad schools, a rise of testable models, a rise of mediation and moderation studies, the emergence of new forms of diagnosis based on functional analysis, a move from nomothetic to idiographic approaches, and a move toward processes that specify modifiable elements. These changes could integrate or bridge different treatment orientations, settings, and even cultures.
403 citations
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TL;DR: Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles.
Abstract: In vivo injection of a neutralizing, monoclonal antibody (ACK2) to the receptor tyrosine kinase (c-kit) disrupts the normal motility patterns of the mouse small intestine. Immunohistochemical studies showed that cells expressing c-kit-like immunoreactivity (c-kit-LI) decreased in numbers in response to ACK2, but the identity of these cells is unknown. We investigated the identity and development of the cells that express c-kit-LI in the mouse small intestine and colon. Cells in the region of the myenteric plexus and deep muscular plexus of the small intestine and in the subserosa, in the myenteric plexus region, within the circular and longitudinal muscle layers, and along the submucosal surface of the circular muscle in the colon were labeled with ACK2. The distribution of cells that express c-kit-LI was the same as that of interstitial cells (ICs). In whole-mount preparations cells with c-kit-LI were interconnected, forming a network similar to the network formed by cells that stained with methylene blue, which has been used as a marker for ICs in the mouse gastrointestinal tract. Immunocytochemistry verified that ICs were labeled with ACK2. Multiple injections of animals with ACK2 between days 0 and 8 post partum (pp) caused a dramatic reduction in the number of ICs compared to control animals. From an ultrastructural point of view, the proliferation and development appeared to be suppressed in some classes of ICs, while others displayed an altered course of development. Functional studies showed that the decrease in ICs was accompanied by a loss of electrical rhythmicity in the small intestine and reduced neural responses in the small bowel and colon. Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles. Controlling the development of ICs provides a powerful new tool for the investigation of the physiological role of these cells.
403 citations
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TL;DR: The first high-resolution picture of the transcriptome dynamics that occur during seven stages of grape berry development is revealed and a set of previously unknown genes potentially involved in critical steps associated with fruit development can now be subjected to functional testing.
Abstract: Grape berry development is a dynamic process that involves a complex series of molecular genetic and biochemical changes divided into three major phases. During initial berry growth (Phase I), berry size increases along a sigmoidal growth curve due to cell division and subsequent cell expansion, and organic acids (mainly malate and tartrate), tannins, and hydroxycinnamates accumulate to peak levels. The second major phase (Phase II) is defined as a lag phase in which cell expansion ceases and sugars begin to accumulate. Veraison (the onset of ripening) marks the beginning of the third major phase (Phase III) in which berries undergo a second period of sigmoidal growth due to additional mesocarp cell expansion, accumulation of anthocyanin pigments for berry color, accumulation of volatile compounds for aroma, softening, peak accumulation of sugars (mainly glucose and fructose), and a decline in organic acid accumulation. In order to understand the transcriptional network responsible for controlling berry development, mRNA expression profiling was conducted on berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0 spanning seven stages of berry development from small pea size berries (E-L stages 31 to 33 as defined by the modified E-L system), through veraison (E-L stages 34 and 35), to mature berries (E-L stages 36 and 38). Selected metabolites were profiled in parallel with mRNA expression profiling to understand the effect of transcriptional regulatory processes on specific metabolite production that ultimately influence the organoleptic properties of wine. Over the course of berry development whole fruit tissues were found to express an average of 74.5% of probes represented on the Vitis microarray, which has 14,470 Unigenes. Approximately 60% of the expressed transcripts were differentially expressed between at least two out of the seven stages of berry development (28% of transcripts, 4,151 Unigenes, had pronounced (≥2 fold) differences in mRNA expression) illustrating the dynamic nature of the developmental process. The subset of 4,151 Unigenes was split into twenty well-correlated expression profiles. Expression profile patterns included those with declining or increasing mRNA expression over the course of berry development as well as transient peak or trough patterns across various developmental stages as defined by the modified E-L system. These detailed surveys revealed the expression patterns for genes that play key functional roles in phytohormone biosynthesis and response, calcium sequestration, transport and signaling, cell wall metabolism mediating expansion, ripening, and softening, flavonoid metabolism and transport, organic and amino acid metabolism, hexose sugar and triose phosphate metabolism and transport, starch metabolism, photosynthesis, circadian cycles and pathogen resistance. In particular, mRNA expression patterns of transcription factors, abscisic acid (ABA) biosynthesis, and calcium signaling genes identified candidate factors likely to participate in the progression of key developmental events such as veraison and potential candidate genes associated with such processes as auxin partitioning within berry cells, aroma compound production, and pathway regulation and sequestration of flavonoid compounds. Finally, analysis of sugar metabolism gene expression patterns indicated the existence of an alternative pathway for glucose and triose phosphate production that is invoked from veraison to mature berries. These results reveal the first high-resolution picture of the transcriptome dynamics that occur during seven stages of grape berry development. This work also establishes an extensive catalog of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern berry development in a widely grown cultivar of wine grape. More importantly, this analysis identified a set of previously unknown genes potentially involved in critical steps associated with fruit development that can now be subjected to functional testing.
401 citations
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TL;DR: In this article, a practical alternating directions implicit method to solve a class of two-dimensional initial-boundary value fractional partial differential equations with variable coefficients on a finite domain is discussed.
399 citations
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TL;DR: A primary focus of this review is why more than one RyR is required for this purpose, particularly in a tissue, such as vertebrate fast-twitch skeletal muscles, where a relatively simple and straightforward change in calcium would appear to be required to elicit contraction.
Abstract: Complexities in calcium signaling in eukaryotic cells require diversity in the proteins involved in generating these signals. In this review, we consider the ryanodine receptor (RyR) family of intracellular calcium release channels. This includes species, tissue, and cellular distributions of the RyRs and mechanisms of activation, deactivation, and inactivation of RyR calcium release events. In addition, as first observed in nonmammalian vertebrate skeletal muscles, it is now clear that more than one RyR isoform is frequently coexpressed within many cell types. How multiple ryanodine receptor release channels are used to generate intracellular calcium transients is unknown. Therefore, a primary focus of this review is why more than one RyR is required for this purpose, particularly in a tissue, such as vertebrate fast-twitch skeletal muscles, where a relatively simple and straightforward change in calcium would appear to be required to elicit contraction. Finally, the roles of the RyR isoforms and the calcium release events they mediate in the development of embryonic skeletal muscle are considered.
399 citations
Authors
Showing all 13726 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert Langer | 281 | 2324 | 326306 |
Thomas C. Südhof | 191 | 653 | 118007 |
David W. Johnson | 160 | 2714 | 140778 |
Menachem Elimelech | 157 | 547 | 95285 |
Jeffrey L. Cummings | 148 | 833 | 116067 |
Bing Zhang | 121 | 1194 | 56980 |
Arturo Casadevall | 120 | 980 | 55001 |
Mark H. Ellisman | 117 | 637 | 55289 |
Thomas G. Ksiazek | 113 | 398 | 46108 |
Anthony G. Fane | 112 | 565 | 40904 |
Leonardo M. Fabbri | 109 | 566 | 60838 |
Gary H. Lyman | 108 | 694 | 52469 |
Steven C. Hayes | 106 | 450 | 51556 |
Stephen P. Long | 103 | 384 | 46119 |
Gary Cutter | 103 | 737 | 40507 |