Matching Items (8)

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Computational Analysis of Research in Mammalian Neocortical Neurogenesis

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Studies in neocortical neurogenesis have experienced an explosive growth since the early 2000s, measured by the increasing number of publications each year. I examine here the influence of Arnold Kriegstein

Studies in neocortical neurogenesis have experienced an explosive growth since the early 2000s, measured by the increasing number of publications each year. I examine here the influence of Arnold Kriegstein in the field using Topic Modeling, a set of algorithms that can be applied to a collection of texts to elucidate the central themes of said collection. Using a Java-based software called MALLET, I obtained data for his corpus, and compared it to the texts of other researchers in the field. This latter collection, which I dub "General Corpus", was separated by year from 2000 to 2014. I found that Kriegstein's most frequently discussed topic concerned highly unique terms such as GABA, glutamate, and receptor, which did not appear in any of the primary topics of the General Corpus. This was in contrast to my initial hypothesis that Kriegstein's importance stemmed from his examination of different phenomena that constitute the broader aspect of neocortical neurogenesis. I predicted that the terms in Kriegstein's primary topic would appear many times throughout the topics of the General Corpus, but it was not so, aside from the common ones such as neurons, cortical, and development. Taken in tandem with NIH Reporter data, these results suggest that Kriegstein obtains a large amount of research funding because his studies concern unique topics when compared to others in the field. The implications of these findings are especially relevant in a world where funding is becoming increasingly difficult to come by.

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  • 2015-05

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A Histological Analysis of Cell Proliferation Patterns in the Regenerating Tail of the Lizard, Anolis carolinensis

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While a number of vertebrates, including fishes, salamanders, frogs, and lizards, display regenerative capacity, the process is not necessarily the same. It has been proposed that regeneration, while evolutionarily conserved,

While a number of vertebrates, including fishes, salamanders, frogs, and lizards, display regenerative capacity, the process is not necessarily the same. It has been proposed that regeneration, while evolutionarily conserved, has diverged during evolution. However, the extent to which the mechanisms of regeneration have changed between taxa still remains elusive. In the salamander limb, cells dedifferentiate to a more plastic state and aggregate in the distal portion of the appendage to form a blastema, which is responsible for outgrowth and tissue development. In contrast, no such mechanism has been identified in lizards, and it is unclear to what extent evolutionary divergence between amniotes and anamniotes has altered this mechanism. Anolis carolinensis lizards are capable of regenerating their tails after stress-induced autotomy or self-amputation. In this investigation, the distribution of proliferating cells in early A. carolinensis tail regeneration was visualized by immunohistochemistry to examine the location and quantity of proliferating cells. An aggregate of proliferating cells at the distal region of the regenerate is considered indicative of blastema formation. Proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2) were utilized as proliferation markers. Positive cells were counted for each tail (n=9, n=8 respectively). The percent of proliferating cells at the tip and base of the regenerating tail were compared with a one-way ANOVA statistical test. Both markers showed no significant difference (P=0.585, P=0.603 respectively) indicating absence of a blastema-like structure. These results suggest an alternative mechanism of regeneration in lizards and potentially other amniotes.

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  • 2014-05

Transcriptomic and Cellular Studies of Tail Regeneration in Saurian Reptiles

Description

Traumatic injury to the central nervous or musculoskeletal system in traditional amniote models, such as mouse and chicken, is permanent with long-term physiological and functional effects. However, among amniotes, the

Traumatic injury to the central nervous or musculoskeletal system in traditional amniote models, such as mouse and chicken, is permanent with long-term physiological and functional effects. However, among amniotes, the ability to regrow complex, multi-tissue structures is unique to non-avian reptiles. Structural regeneration is extensively studied in lizards, with most species able to regrow a functional tail. The lizard regenerated tail includes the spinal cord, cartilage, de novo muscle, vasculature, and skin, and unlike mammals, these tissues can be replaced in lizards as adults. These studies focus on the events that occur before and after the tail regrowth phase, identifying conserved mechanisms that enable functional tail regeneration in the green anole lizard, Anolis carolinensis. An examination of coordinated interactions between peripheral nerves, Schwann cells, and skeletal muscle reveal that reformation of the lizard neuromuscular system is dependent upon developmental programs as well as those unique to the adult during late stages of regeneration. On the other hand, transcriptomic analysis of the early injury response identified many immunoregulatory genes that may be essential for inhibiting fibrosis and initiating regenerative programs. Lastly, an anatomical and histological study of regrown alligator tails reveal that regenerative capacity varies between different reptile groups, providing comparative opportunities within amniotes and across vertebrates. In order to identify mechanisms that limit regeneration, these cross-species analyses will be critical. Taken together, these studies serve as a foundation for future experimental work that will reveal the interplay between reparative and regenerative mechanisms in adult amniotes with translational implications for medical therapies.

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  • 2020

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Insights towards developing regenerative therapies: the lizard, Anolis carolinensis, as a genetic model for regeneration in amniotes

Description

Damage to the central nervous system due to spinal cord or traumatic brain injury, as well as degenerative musculoskeletal disorders such as arthritis, drastically impact the quality of life. Regeneration

Damage to the central nervous system due to spinal cord or traumatic brain injury, as well as degenerative musculoskeletal disorders such as arthritis, drastically impact the quality of life. Regeneration of complex structures is quite limited in mammals, though other vertebrates possess this ability. Lizards are the most closely related organism to humans that can regenerate de novo skeletal muscle, hyaline cartilage, spinal cord, vasculature, and skin. Progress in studying the cellular and molecular mechanisms of lizard regeneration has previously been limited by a lack of genomic resources. Building on the release of the genome of the green anole, Anolis carolinensis, we developed a second generation, robust RNA-Seq-based genome annotation, and performed the first transcriptomic analysis of tail regeneration in this species. In order to investigate gene expression in regenerating tissue, we performed whole transcriptome and microRNA transcriptome analysis of regenerating tail tip and base and associated tissues, identifying key genetic targets in the regenerative process. These studies have identified components of a genetic program for regeneration in the lizard that includes both developmental and adult repair mechanisms shared with mammals, indicating value in the translation of these findings to future regenerative therapies.

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Date Created
  • 2015

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Using Molecular, Cellular and Bioengineering Approaches Towards Understanding Muscle Stem Cell Biology

Description

Satellite cells are adult muscle stem cells that activate, proliferate, and differentiate into myofibers upon muscle damage. Satellite cells can be cultured and manipulated in vitro, and thus represent an

Satellite cells are adult muscle stem cells that activate, proliferate, and differentiate into myofibers upon muscle damage. Satellite cells can be cultured and manipulated in vitro, and thus represent an accessible model for studying skeletal muscle biology, and a potential source of autologous stem cells for regenerative medicine. This work summarizes efforts to further understanding of satellite cell biology, using novel model organisms, bioengineering, and molecular and cellular approaches. Lizards are evolutionarily the closest vertebrates to humans that regenerate entire appendages. An analysis of lizard myoprogenitor cell transcriptome determined they were most transcriptionally similar to mammalian satellite cells. Further examination showed that among genes with the highest level of expression in lizard satellite cells were an increased number of regulators of chondrogenesis. In micromass culture, lizard satellite cells formed nodules that expressed chondrogenic regulatory genes, thus demonstrating increased musculoskeletal plasticity. However, to exploit satellite cells for therapeutics, development of an ex vivo culture is necessary. This work investigates whether substrates composed of extracellular matrix (ECM) proteins, as either coatings or hydrogels, can support expansion of this population whilst maintaining their myogenic potency. Stiffer substrates are necessary for in vitro proliferation and differentiation of satellite cells, while the ECM composition was not significantly important. Additionally, satellite cells on hydrogels entered a quiescent state that could be reversed when the cells were subsequently cultured on Matrigel. Proliferation and gene expression data further indicated that C2C12 cells are not a good proxy for satellite cells. To further understand how different signaling pathways control satellite cell behavior, an investigation of the Notch inhibitor protein Numb was carried out. Numb deficient satellite cells fail to activate, proliferate and participate in muscle repair. Examination of Numb isoform expression in satellite cells and embryonic tissues revealed that while developing limb bud, neural tube, and heart express the long and short isoforms of NUMB, satellite cells predominantly express the short isoforms. A preliminary immunoprecipitation- proteomics experiment suggested that the roles of NUMB in satellite cells are related to cell cycle modulation, cytoskeleton dynamics, and regulation of transcription factors necessary for satellite cell function.

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Date Created
  • 2020

Advancing the lizard, Anolis carolinensis, as a model system for genomic studies of evolution, development and regeneration

Description

Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian

Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian model organism for comparative studies between the vertebrates and for studies of biological processes unique to reptiles. To help fill in this gap the green anole lizard, Anolis carolinensis, is being adapted as a model organism. Despite the recent release of the complete genomic sequence of the A. carolinensis, the lizard lacks some resources to aid researchers in their studies. Particularly, the lack of transcriptomic resources for lizard has made it difficult to identify genes complete with alternative splice forms and untranslated regions (UTRs). As part of this work the genome annotation for A. carolinensis was improved through next generation sequencing and assembly of the transcriptomes from 14 different adult and embryonic tissues. This revised annotation of the lizard will improve comparative studies between vertebrates, as well as studies within A. carolinensis itself, by providing more accurate gene models, which provide the bases for molecular studies. To demonstrate the utility of the improved annotations and reptilian model organism, the developmental process of somitogenesis in the lizard was analyzed and compared with other vertebrates. This study identified several key features both divergent and convergent between the vertebrates, which was not previously known before analysis of a reptilian model organism. The improved genome annotations have also allowed for molecular studies of tail regeneration in the lizard. With the annotation of 3' UTR sequences and next generation sequencing, it is now possible to do expressional studies of miRNA and predict their mRNA target transcripts at genomic scale. Through next generation small RNA sequencing and subsequent analysis, several differentially expressed miRNAs were identified in the regenerating tail, suggesting miRNA may play a key role in regulating this process in lizards. Through miRNA target prediction several key biological pathways were identified as potentially under the regulation of miRNAs during tail regeneration. In total, this work has both helped advance A. carolinensis as model system and displayed the utility of a reptilian model system.

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Date Created
  • 2012

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Using mechanical strain as a vehicle to direct fibroblasts-mediated myoblast differentiation and myotube function

Description

Skeletal muscle injury may occur from repetitive short bursts of biomechanical strain that impair muscle function. Alternatively, variations of biomechanical strain such as those held for long-duration are used by

Skeletal muscle injury may occur from repetitive short bursts of biomechanical strain that impair muscle function. Alternatively, variations of biomechanical strain such as those held for long-duration are used by clinicians to repair muscle and restore its function. Fibroblasts embedded within the unifying connective tissue of skeletal muscle experience these multiple and diverse mechanical stimuli and respond by secreting cytokines. Cytokines direct all stages of muscle regeneration including myoblasts differentiation, fusion to form myotubes, and myotube functionality. To examine how fibroblasts respond to variations in mechanical strain that may affect juxtapose muscle, a myofascial junction was bioengineered that examined the interaction between the two cell types. Fibroblasts were experimentally shown to increase myoblast differentiation, and fibroblast biomechanical strain mediated the extent to which differentiation occurred. Intereleukin-6 is a strain-regulated cytokine secreted by fibroblasts was determined to be necessary for fibroblast-mediated myoblast differentiation. Myotubes differentiated in the presence of strained fibroblasts express greater number of acetylcholine receptors, greater acetylcholine receptor sizes, and modified to be more or less sensitive to acetylcholine-induced contraction. This study provides direct evidence that strained and non-strained fibroblasts can serve as a vehicle to modify myoblast differentiation and myotube functionality. Further understanding the mechanisms regulating these processes may lead to clinical interventions that include strain-activated cellular therapies and bioengineered cell engraftment for mediating the regeneration and function of muscle in vivo.

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Created

Date Created
  • 2014

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Analyzing the opportunities for NIPAAm dehumidification in air conditioning systems

Description

When air is supplied to a conditioned space, the temperature and humidity of the air often contribute to the comfort and health of the occupants within the space. However, the

When air is supplied to a conditioned space, the temperature and humidity of the air often contribute to the comfort and health of the occupants within the space. However, the vapor compression system, which is the standard air conditioning configuration, requires air to reach the dew point for dehumidification to occur, which can decrease system efficiency and longevity in low temperature applications.

To improve performance, some systems dehumidify the air before cooling. One common dehumidifier is the desiccant wheel, in which solid desiccant absorbs moisture out of the air while rotating through circular housing. This system improves performance, especially when the desiccant is regenerated with waste or solar heat; however, the heat of regeneration is very large, as the water absorbed during dehumidification must be evaporated. N-isopropylacrylamide (NIPAAm), a sorbent that oozes water when raised above a certain temperature, could potentially replace traditional desiccants in dehumidifiers. The heat of regeneration for NIPAAm consists of some sensible heat to bring the sorbent to the regeneration temperature, plus some latent heat to offset any liquid water that is evaporated as it is exuded from the NIPAAm. This means the NIPAAm regeneration heat has the potential to be much lower than that of a traditional desiccant.

Models were created for a standard vapor compression air conditioning system, two desiccant systems, and two theoretical NIPAAm systems. All components were modeled for simplified steady state operation. For a moderate percent of water evaporated during regeneration, it was found that the NIPAAm systems perform better than standard vapor compression. When compared to the desiccant systems, the NIPAAm systems performed better at almost all percent evaporation values. The regeneration heat was modeled as if supplied by an electric heater. If a cheaper heat source were utilized, the case for NIPAAm would be even stronger.

Future work on NIPAAm dehumidification should focus on lowering the percent evaporation from the 67% value found in literature. Additionally, the NIPAAm cannot exceed the lower critical solution temperature during dehumidification, indicating that a NIPAAm dehumidification system should be carefully designed such that the sorbent temperature is kept sufficiently low during dehumidification.

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Created

Date Created
  • 2019