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Recent advances in nonequilibrium statistical physics have provided unprecedented insight into the thermodynamics of dynamic processes. The author recently used these advances to extend Landauer’s semi-formal reasoning concerning the thermodynamics of bit erasure, to derive the minimal free energy required to implement an arbitrary computation. Here, I extend this analysis,

Recent advances in nonequilibrium statistical physics have provided unprecedented insight into the thermodynamics of dynamic processes. The author recently used these advances to extend Landauer’s semi-formal reasoning concerning the thermodynamics of bit erasure, to derive the minimal free energy required to implement an arbitrary computation. Here, I extend this analysis, deriving the minimal free energy required by an organism to run a given (stochastic) map π from its sensor inputs to its actuator outputs. I use this result to calculate the input-output map π of an organism that optimally trades off the free energy needed to run π with the phenotypic fitness that results from implementing π. I end with a general discussion of the limits imposed on the rate of the terrestrial biosphere’s information processing by the flux of sunlight on the Earth.

Created2016-04-13
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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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Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and

Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.

Results:
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.

Conclusions:
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.

ContributorsKostelich, Eric (Author) / Kuang, Yang (Author) / McDaniel, Joshua (Author) / Moore, Nina Z. (Author) / Martirosyan, Nikolay L. (Author) / Preul, Mark C. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2011-12-21
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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
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