Matching Items (208)
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Restoration projects can have varying goals, depending on the specific focus, rationale, and aims for restoration. When restoration projects use project-specific goals to define activities and gauge success without considering broader ecological context, determination of project implications and success can be confounding. We used case studies from the Middle Rio

Restoration projects can have varying goals, depending on the specific focus, rationale, and aims for restoration. When restoration projects use project-specific goals to define activities and gauge success without considering broader ecological context, determination of project implications and success can be confounding. We used case studies from the Middle Rio Grande (MRG), southwest USA, to demonstrate how restoration outcomes can rank inconsistently when narrowly-based goals are used. Resource managers have chosen MRG for restoration due to impacts to the natural flood regime, reduced native tree recruitment, and establishment of non-native plants. We show restoration “success” ranks differently based upon three goals: increasing biodiversity, increasing specific ecosystem functions, or restoring native communities. We monitored 12 restored and control sites for seven years. Treatments ranked higher in reducing exotic woody populations, and increasing proportions of native plants and groundwater salvage, but generally worse at removing fuels, and increasing species and habitat structural diversity. Managers cannot rely on the term “restoration” to sufficiently describe a project’s aim. Specific desired outcomes must be defined and monitored. Long-term planning should include flexibility to incorporate provisions for adaptive management to refine treatments to avoid unintended ecological consequences.

Created2012-09-19
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In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies

In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs. Specifically, we describe the emergence of technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 that can be used to edit the genome at precise locations, and discuss the strengths and weaknesses of each of these technologies. In addition, we present the current applications of these technologies in elucidating the mechanisms of human development and disease, developing novel and effective therapeutic molecules, and engineering cell-based therapies. Finally, we discuss the emerging technological advances in targeted gene editing methods.

ContributorsBrookhouser, Nicholas (Author) / Raman, Sreedevi (Author) / Potts, Chris (Author) / Brafman, David (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-02-06
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Traumatic brain injury (TBI) may result in numerous pathologies that cannot currently be mitigated by clinical interventions. Stem cell therapies are widely researched to address TBI-related pathologies with limited success in pre-clinical models due to limitations in transplant survival rates. To address this issue, the use of tissue engineered scaffolds

Traumatic brain injury (TBI) may result in numerous pathologies that cannot currently be mitigated by clinical interventions. Stem cell therapies are widely researched to address TBI-related pathologies with limited success in pre-clinical models due to limitations in transplant survival rates. To address this issue, the use of tissue engineered scaffolds as a delivery mechanism has been explored to improve survival and engraftment rates. Previous work with hyaluronic acid \u2014 laminin (HA-Lm) gels found high viability and engraftment rates of mouse fetal derived neural progenitor/stem cells (NPSCs) cultured on the gel. Furthermore, NPSCs exposed to the HA-Lm gels exhibit increased expression of CXCR4, a critical surface receptor that promotes cell migration. We hypothesized that culturing hNPCs on the HA-Lm gel would increase CXCR4 expression, and thus enhance their ability to migrate into sites of tissue damage. In order to test this hypothesis, we designed gel scaffolds with mechanical properties that were optimized to match that of the natural extracellular matrix. A live/dead assay showed that hNPCs preferred the gel with this optimized formulation, compared to a stiffer gel that was used in the CXCR4 expression experiment. We found that there may be increased CXCR4 expression of hNPCs plated on the HA-Lm gel after 24 hours, indicating that HA-Lm gels may provide a valuable scaffold to support viability and migration of hNPCs to the injury site. Future studies aimed at verifying increased CXCR4 expression of hNPCs cultured on HA-Lm gels are necessary to determine if HA-Lm gels can provide a beneficial scaffold for stem cell engraftment therapy for treating TBI.
ContributorsHemphill, Kathryn Elizabeth (Author) / Stabenfeldt, Sarah (Thesis director) / Brafman, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Visual perceptual learning (VPL) is defined as visual performance improvement after visual experiences. VPL is often highly specific for a visual feature presented during training. Such specificity is observed in behavioral tuning function changes with the highest improvement centered on the trained feature and was originally thought to be evidence

Visual perceptual learning (VPL) is defined as visual performance improvement after visual experiences. VPL is often highly specific for a visual feature presented during training. Such specificity is observed in behavioral tuning function changes with the highest improvement centered on the trained feature and was originally thought to be evidence for changes in the early visual system associated with VPL. However, results of neurophysiological studies have been highly controversial concerning whether the plasticity underlying VPL occurs within the visual cortex. The controversy may be partially due to the lack of observation of neural tuning function changes in multiple visual areas in association with VPL. Here using human subjects we systematically compared behavioral tuning function changes after global motion detection training with decoded tuning function changes for 8 visual areas using pattern classification analysis on functional magnetic resonance imaging (fMRI) signals. We found that the behavioral tuning function changes were extremely highly correlated to decoded tuning function changes only in V3A, which is known to be highly responsive to global motion with human subjects. We conclude that VPL of a global motion detection task involves plasticity in a specific visual cortical area.

ContributorsShibata, Kazuhisa (Author) / Chang, Li-Hung (Author) / Kim, Dongho (Author) / Nanez, Jose (Author) / Kamitani, Yukiyasu (Author) / Watanabe, Takeo (Author) / Sasaki, Yuka (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2012-08-28
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Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children

Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.

Results: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phage deep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).

Conclusions: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.

ContributorsKang, Dae Wook (Author) / Adams, James (Author) / Gregory, Ann C. (Author) / Borody, Thomas (Author) / Chittick, Lauren (Author) / Fasano, Alessio (Author) / Khoruts, Alexander (Author) / Geis, Elizabeth (Author) / Maldonado Ortiz, Juan (Author) / McDonough-Means, Sharon (Author) / Pollard, Elena (Author) / Roux, Simon (Author) / Sadowsky, Michael J. (Author) / Schwarzberg Lipson, Karen (Author) / Sullivan, Matthew B. (Author) / Caporaso, J. Gregory (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2017-01-23
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High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

ContributorsKang, Dae Wook (Author) / Park, Jin (Author) / Ilhan, Zehra (Author) / Wallstrom, Garrick (Author) / LaBaer, Joshua (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2013-06-03
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Current culturing methods allow for human neural progenitor cells to be differentiated into neurons for use in diagnostic tools and disease modeling. An issue arises in the relatively low number of cells that can be successfully expanded and differentiated using these current methods, making the progress of research dependent on

Current culturing methods allow for human neural progenitor cells to be differentiated into neurons for use in diagnostic tools and disease modeling. An issue arises in the relatively low number of cells that can be successfully expanded and differentiated using these current methods, making the progress of research dependent on these cultures as a large number of cells are needed to conduct relevant assays. This project focuses on the expansion and differentiation of human neural progenitor cells cultured on microcarriers and within a rotating bioreactor system as a way to increase the total number of cells generated. Additionally, cryopreservation and the characteristics of these neurons post thaw is being investigated to create a way for long term storage, as well as, a method for standardizing cell lines between multiple experiments at different time points. The experiments covered in this study are aimed to compare the characteristics of differentiated human neurons, both demented and non-demented cell lines between pre-cryopreservation, freshly differentiated neurons and post-cryopreservation neurons. The assays conducted include immunofluorescence, calcium imaging, quantitative polymerase chain reaction, flow cytometry and ELISA data looking at Alzheimer’s disease traits. With the data collected within this study, the use of bioreactors, in addition to, cryopreservation of human neurons for long term storage can be better implemented into human neural progenitor cell research. Both of these aspects will increase the output of these cultures and potentially remove the bottleneck currently found within human neural disease modeling.
ContributorsHenson, Tanner Jay (Author) / Brafman, David (Thesis director) / Kodibagkar, Vikram (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Fumonisins are fungal metabolites found in corn and cereals. Fumonisins pose health risks, including suspected carcinogenicity, yet their mechanism of toxicity remains unclear. While modifications in the human gut microbiome can impact host health, the effects of fumonisins on the microbiome are not well understood. Thus, our study aimed to

Fumonisins are fungal metabolites found in corn and cereals. Fumonisins pose health risks, including suspected carcinogenicity, yet their mechanism of toxicity remains unclear. While modifications in the human gut microbiome can impact host health, the effects of fumonisins on the microbiome are not well understood. Thus, our study aimed to assess a possible dose-response relationship between fumonisin B1 (FB1) and the gut microbiome. We utilized in vitro anaerobic bioreactors with media simulating most of the nutrients in the human large intestine, inoculated them with fecal samples from 19 healthy adults and treated them with FB1 at concentrations of 0, 10, 100, and 1000 ppb. Analyses of bioreactor headspace revealed declining methane production over time, possibly influenced by the addition of dimethyl sulfoxide (DMSO). Significant differences in acetic acid production were observed in 10 ppb reactor (Day 2) and 100 ppb reactor (Day 8) when compared to 0 ppb control. Microbiome analysis showed minimal shifts in microbial relative abundances during FB1 treatment, except for Desulfovibrio desulfuricans C at Day 8 when compared between 0 ppb and 10 ppb as well as 10 ppb and 1000 ppb at Day 16. Alpha diversity analyses indicated significant differences in observed features within bioreactors of different treatments, with some variation in Faith’s Phylogenetic Diversity between the 0 ppb and 10 ppb bioreactors. Beta diversity analyses, however, revealed no significant differences between bioreactors. Overall, our findings suggest no clear dose-response relationship between FB1 treatment and gut microbiome composition/functions. The presence of DMSO may have obscured potential effects. This research will help contribute to our understanding of mycotoxicity influence on the human gut microbiome.
ContributorsSanchez Carreon, Aurely (Author) / Krajmalnik-Brown, Rosa (Thesis director) / Cheng, Qiwen (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05