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School of Biological Sciences

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College of Sciences

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Center for the Study of Systems Biology

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Publication Search Results

Now showing 1 - 10 of 46

Neural Activation Patterns Arising From Gesture Recognition

(Georgia Institute of Technology, 2015-12) Basunia, Sumia

The human brain is composed of a complex network of neurons that create a representation of the world through sensation and perception. This representation facilitates interacting with the environment and is thus vital to the human experience. One aspect that is crucial to normal functioning is the ability to identify and classify the different types of gestures we see every day. Broadly, gestures are classified into three categories: transitive, intransitive and neutral. Transitive gestures involve specific hand-object actions such as tool-use; while, intransitive gestures are communicative in nature. In this experiment, we propose that the main aspect of a gesture is the context in which the gesture is performed. For example, the gesture of waving goodbye to someone, an intransitive gesture, and the gesture of wiping a window, a transitive gesture, both involve the same biomechanics and motor control; however, they differ greatly based on the context in which they were performed. To understand and differentiate such kinematically similar gestures, the cerebral cortex or deep brain structures might exhibit unique patterns of activations specific to differentiating context. Therefore, the objective in this experiment is to map patterns of neural activation that specifically encode and differentiate context when viewing kinematically similar transitive and intransitive gestures. The participants recruited were 19 young adults between the ages 20 to 30. To map the pattern of neural activation, this experiment employed the use of a neuroimaging technique called functional magnetic resonance imaging or fMRI. fMRI indirectly measures the hemodynamic response that represents the flow of blood to specific regions of the brain that are active in response to the viewing a picture such as a particular type of gesture. Each participant was placed in an MRI machine and exposed to 75 images containing gestures in either a transitive, intransitive, or neutral context. For the purposes of this experiment, we defined the neutral context as a gesture devoid of any context. Once the data was collected, a Linux based software called FSL was used to analyze the data. Analysis thus far has displayed neural activation patterns for the three types of gestures primarily in the visual cortex, along the dorsal and ventral streams and along the primary motor cortex. When contrasting transitive and intransitive gestures, there is no difference in neural activation. Data from this experiment gives insight into the basic neuroscience of how the brain effortlessly recognizes daily gestures and has clinical implications towards ideomotor apraxia, a neurological disorder that is characterized by an inability to recognize and perform transitive gestures.
Developing Tools to Monitor Vibrio cholerae Type VI Secretion During Range Expansion on Solid Surfaces

(Georgia Institute of Technology, 2015-12) Ng, Siu Lung

The waterborne bacterium Vibrio cholerae causes the fatal cholera diarrhea, and thrives in aquatic environments attached to chitinous surfaces with other bacteria. V. cholerae has been used to study natural competence, which promotes DNA uptake through horizontal gene transfer (HGT). A newly described Type VI Secretion System (T6SS) that V. cholerae employ to kill neighboring cells could increase the chance for a competent V. cholerae to take up and utilize the released DNA. The T6SS apparatus, which is similar to a bacteriophage spike, injects toxic effector proteins into prey cells causing lysis that can aid V. cholerae in acquiring DNA from its neighbors. Although previous studies have investigated the regulation and mechanism of T6SS in V. cholerae at a single cell level, the role of T6SS in the dynamics of mixed bacterial populations, such as those found in the environment, remains poorly understood. Fluorescence microscopy was used in this study to determine the effect of T6SS by growing V. cholerae predators and isogenic prey populations on agar surfaces as a model for competitors undergoing spatial expansion. These conditions may mimic conditions encountered on chitinous surfaces in marine settings. In this study, plasmids expressing green and red fluorescent proteins were constructed to visualize the predator and prey populations. Preliminary spatial expansion experiments were ultimately performed using different fluorescent protein alleles that were encoded on the chromosome of competing bacteria. Preliminary results suggest that the presence of a functional T6SS plays an important role in competition. The tools developed for this study are now being used to study interaction between diverse V. cholerae isolates, and as a platform for experimental evolution.
Knockdown of the Yes-associated Protein 1 pathway provides a basis for targeted therapy to treat infantile hemangioma

(Georgia Institute of Technology, 2015-08-18) Nord, Dianna M.

Hemangioma is a type of tumor commonly found in infants that is characterized by heavy vascularization and a disfiguring appearance. Hemangioma, though benign, can sometimes proliferate and be threatening to infants. Current treatments for infantile hemangioma include surgical removal as well as the use of topical and oral medication. However, current therapies are often ineffective at treating lesions and are commonly accompanied by dangerous side effects, creating the need for a new, safer treatment. This study targets the Yes-Associated Protein-1 (YAP-1), which has been described as an oncogene, by use of an interfering RNA technique in attempts to mediate tumor growth and progression. Western blotting of treatment and control BEND3 murine cells reveals that YAP-1 is knocked-down in treatment groups which have been infected with shYAP-1 siRNA genes. By successfully knocking down the YAP-1 protein, the potential for developing a novel targeted therapy for infantile hemangioma has been established.
Use of RNAi in Brachionus manjavacas to Inhibit Cold-Related Genes Implicated in Aging

(Georgia Institute of Technology, 2015-08-18) Wilson, Julie

Aging can be affected by a number of factors, including temperature; for example, organisms tend to live significantly longer when exposed to colder temperatures. Previous studies suggest that this change in life expectancy due to temperature change has a genetic component. Through the use of RNA interference, we have found that aging genes can be knocked-down in our model animal, Brachionus manjavacas (Rotifera). Using RNAi, we examined the effect of genetic knock-down on genes related to life extension at lower temperatures (16oC) compared to standard culture temperatures (22oC). This study has provided evidence that temperature-dependent changes in longevity may be largely due to changes in expression levels in select genes: Forkhead Box C (FhBC), TRP7, and S6P. Future research may show that the life extending effects of certain living conditions may be obtainable through genetic treatment.
A Study of the Relationship Between Bone Morphogenetic Proteins and Craniosynostosis

(Georgia Institute of Technology, 2015-06-30) Whitton, Alaina

INTRODUCTION: The high prevalence for craniosynostosis (1) indicates the need for genetic understanding and identification of molecular pathways involved in the premature fusion of the skull sutures. Due to the existing knowledge about bone morphogenetic proteins (BMPs) on ectopic bone formation (2), the role of the BMP family in multiple types of craniosynostosis has long been hypothesized as a key player in the early onset of suture fusion. Based on this hypothesis, the genetic expression of six bone morphogenetic proteins were examined in the four types of synostosis. METHODS: Bone collected from patients undergoing corrective craniotomies at Children’s Healthcare of Atlanta were received and cells were grown from the bone fragments. From those cells, Real-time PCR was performed to determine the mRNA levels of the predetermined genes. RESULTS: Patients expressed individual results based on several factors including suture placement, age at surgery, sex, and predisposition to syndromes known to occur in conjunction with craniosynostosis. The BMPs that were involved in extraneous bone formation and osteoblast hyperactivity were found in high levels in the fused suture bone, while the mRNA levels of the inhibitors of bone formation such as NOG were decreased in fused sutures and exhibited high levels in the patent sutures. CONCLUSION: The study further elucidates the role of BMPs in the onset of craniosynostosis and offers insight to the molecular pathways involved.
Genetics of Captive Naked Mole-Rat Populations

(Georgia Institute of Technology, 2015-06-30) Groh, Amy M

The evolution of highly social behavior (eusociality) represents one of the major transition points in evolutionary history. Naked mole-rats (NMRs), Heterocephalus glaber, are one of the few known eusocial mammals, meaning that they have a social caste system with a reproductive division of labor. In addition, NMRs show remarkable aging properties and tolerance to pain. Thus NMRs are important systems for studying life history traits. Surprisingly, however, very little is known about the mating systems and habits of NMRs. The goal of this study is to gain a better understanding of the population genetics and breeding habits of NMRs by creating a method for determining variation at microsatellite marker regions. Microsatellites are highly variable regions of the genome, which can act as identifiable markers for individuals. We have collaborated with Zoo Atlanta to study the population genetics of NMRs. We developed primer sets for examining variation at 54 microsatellite locations. Each of these loci were studied with up to 18 NMR individuals. We did this using traditional fluorescent primers and an M13-tailed fluorescent primer method that allows for cheaper and easier screening of samples. Six of these markers showed variability with two possible alleles. Thus, we have obtained the first estimates of genetic variation from the Zoo Atlanta NMR population. Our preliminary results also suggest that the population is in Hardy-Weinberg Equilibrium (HWE), which is unexpected because the population is not randomly mating. These methods and preliminary results provide insight into the breeding programs among captive NMR populations. In addition, the techniques developed will be useful for studying NMR biology in other contexts and help us understand the development of sociality and variation in health systems.
Designed Beta Hairpin Peptides as Models for Biological Metalloproteins

(Georgia Institute of Technology, 2015-06-30) Yohannan, Jiby

Understanding the chemistry of metalloproteins can lead to innovative solutions to major problems in fields such as energy conservation and drug development. In nature, there are numerous biological proteins that use metal cofactors as part of their function. For example, Photosystem II contains a manganese-core that assists with the oxygen evolution process. Without the metal cluster, the protein is unable to produce the final products of photosynthesis. Carbonic anhydrase is another biological protein that needs zinc to convert carbon dioxide into bicarbonate. The zinc plays a critical role in the interchangeable conversion of these two molecules. By understanding the interactions between the metal and the protein, it is possible to harness the chemistry of these biological systems for commercial purposes. This study investigates the interactions between a biologically inspired designed peptide and metals. Biomimetic peptide models, also referred to as maquettes, can be designed and used to study specific portions of complex biological proteins. This study has designed a peptide that contains the appropriate amino acid residues to facilitate metal binding. By introducing various relevant metals to the peptide system, spectroscopic methods were used to determine if the metal is binding. The results showed that the metal did indeed bind to the synthesized peptide. This study will provide a better understanding of the influence of metals in biological systems, and how these characteristics may be applied for synthetic purposes.
Cellular mechanisms of high-frequency alternating current block in peripheral nerves

(Georgia Institute of Technology, 2015-01-28) Stanford, Rachel Shizuka

High-frequency alternating currents (HFAC) can be applied to nerves to reversibly stop the conduction of signals in peripheral nerves. This can be useful in treating conditions such as chronic pain, inflammation, and neuromuscular pathologies where there is excessive neuronal activity which can cause decreased motor control or painful sensations. However, the cellular mechanisms underlying HFAC block is not well understood. In this study, tetrodotoxin (TTX), a sodium channel blocker whose cellular mechanism is known is utilized to examine the cellular mechanisms of HFAC. We expect low dosages of TTX to alter the threshold of the HFAC required for complete block. Understanding how HFAC induces block can affect how we treat neuropathologies by this technique.
Effects of biofilm production on horizontal gene transfer to Vibrio cholerae

(Georgia Institute of Technology, 2014-05-02) Wilson, Sarah

The waterborne bacterial pathogen Vibrio cholerae utilizes a cell-cell communication system called quorum sensing to coordinate group behavior in both a human host and in aquatic environments. Virulence genes like the cholera toxin, biofilm genes for sticky secreted attachment factors, and competence genes for DNA uptake are all regulated by this population density-dependent system. In a human host, both virulence and biofilm genes are repressed at high cell densities that occur late in infection, presumably to promote transmission upon exhausting the host’s resources. However, in the natural environment, regulation is more complex. Namely, at high cell densities, repression of biofilm production is coordinated with activation of competence genes that can promote horizontal gene transfer (HGT). Based on this model, it was proposed that accumulation of biofilm material on bacterial cells could hinder the uptake of extracellular DNA in aquatic settings. In support of this hypothesis, significant decreases were detected in DNA uptake by V. cholerae strains engineered to overproduce biofilm. However, reductions in DNA uptake were also observed in strains that produced no biofilms. These results suggest that proper timing of biofilm formation plays an important role in the capacity of V. cholerae to engage in HGT, one mechanism thought to allow this pathogen to rapidly evolve in changing environments.
Significant changes in microbial community composition in the Gulf of Mexico "Dead Zone" over a diel cycle

(Georgia Institute of Technology, 2014-05-02) Cartee, John C.

The structure and diversity of microbial communities associated with the oxygen minimum zone located on the Louisiana Shelf in the northern Gulf of Mexico deadzone was studied through amplicon analysis of the 16S rRNA gene. The oxygen minimum zone located on the Louisiana Shelf is a region of reduced oxygen concentrations, containing dynamic and diverse microbial communities that thrive under microaerophilic and anaerobic conditions. The Gulf of Mexico contains one of the largest zones of coastal hypoxia (region of reduced dissolved oxygen concentrations) which is dominated by complex microbial communities that contribute to marine biogeochemical cycling on a global scale. Here we used next-generation sequencing technology to track the microbial community at a single site over a day-night (diel) cycle. Two varying depths were used to collect seawater samples which were used for amplicon sequencing of the 16S rRNA gene (rDNA). By comparing our genetic data to coupled measurements of oxygen and nutrients, we determined how microbial community composition changes in response to day-night gradients and to environmental variation in oxygen and substrate availability.