Biological & Health Sciences (BHS) Division Submission Information
Janjira Intra
Pharmaceutics Pulsatile release of biomolecules from polydimethylsiloxane (PDMS) chips with biodegradable seals.
We demonstrate, for the first time, a robust novel polydimethylsiloxane (PDMS) chip that can provide controlled pulsatile release of biomolecules without external stimuli. Poly(lactic acid-co-glycolic acid) (PLGA) films of varying composition and thickness were used as seals to the wells. The composition, molecular weight and thickness of the PLGA films were all parameters used to control the degradation rate of the seals and therefore the release profiles. Transfection experiments in a model HEK293 cell line showed that plasmid DNA loaded in the wells was functional after pulsatile release. Thicker films degraded faster than thinner films and could be used to fine-tune the release of DNA over day length periods. Finally the PDMS chip was shown to provide sequential release of CpG and a model antigen, Ovalbumin, indicating significant potential of this device for vaccinations or applications that require defined complex release patterns of a variety of chemicals, drugs and biomolecules.
Hana Itani
Molecular & Cellular Biology Regulation of Renin Gene Expression by Oxidative Stress
Angiotensin-II (AII) is involved in the pathogenesis of hypertension and mediates its effects in part by causing oxidative stress. Since AII is known to inhibit renin gene (REN) expression by a negative feedback mechanism, we hypothesized that this feedback inhibition is regulated through oxidative stress. REN mRNA levels were measured in renin expressing As4.1 cells treated with varying doses of hydrogen peroxide (HP). HP caused a dose dependent decrease in the steady state REN mRNA levels while there was no difference in cyclophilin mRNA levels. Inhibition of transcription revealed that HP effect is transcriptional yet a post-transcriptional component may be involved. Also, HP caused a dose-dependent reduction in transcriptional activity of the REN promoter. REN mRNA levels significantly decreased in cells treated with xanthine/xanthine oxidase and TNFá. Furthermore, TNFá-induced decrease in REN mRNA levels correlated with increase in reactive oxygen species (ROS) levels. These results suggest ROS downregulate REN transcription.
Christina Freisinger
Biological Sciences G-protein and Wnt/Calcium signaling in Cardiovascular Development
Cardiovascular development is a complex process requiring the coordinated differentiation of cardiomyocytes, morphogenesis and maintenance of the heart tube as well as integration into the developing vasculature. The requirement for G Protein Coupled Receptor (GPCR) signaling in cardiovascular development implicates critical roles for Regulators of G protein Signaling (RGS) proteins. In the zebrafish model, we have initiated a comprehensive analysis of the role of RGS proteins in vertebrate developmental processes. We have identified critical roles for RGS in organ formation and function, such as the heart and vascular systems. It is our goal to understand in some detail the signaling cascades that modulate cardiovascular development and function. Knowledge of these complex signaling cascades and their regulation will help us to understand the causes of congenital heart defects and systolic heart failure, thereby allowing for potential identification or treatm ent of these conditions.
Rania Hamed
Pharmaceutics Determining Key Factors that Control the Formation of Pathogenic Bioaerosols within the Upper Respiratory System
Airborne infectious diseases such as influenza and tuberculosis remain a major global health threat. The primary vector for the transmission of these airborne diseases is exhaled droplets known as bioaerosols. However, very little is known about how bioaerosols are formed in the human lungs. This lack of knowledge has hindered the development of novel strategies aimed at halting bioaerosol formation and thus the transmission of airborne pathogens. The purpose of this study was to determine the physicochemical fluid properties which control bioaerosol formation. Towards this goal, we have developed a physiologically-relevant model of the human trachea to allow quantification of bioaerosol formation. Data showed that altering the physical properties of lung mucus (bulk viscoelasticity and surface tension) results in variation in the geometric size distribution of the primary population of bioaerosols formed during cough. Future studies will focus on identifying substances that can safely halt bioaerosol formation in vivo.
Jenna Armstrong
Public Health India: Golden Rice, World Hunger, and Global Food Politics
New advancements in bio-technology and genetically engineered crops (GMOs) have lead to ideas about vitamin fortification and answers to the world hunger problem (Millennium Development Goal 1). Over the past few decades, crops have become heartier, bigger, and in greater yields. Yet developing countries such as India have failed to accept the new technology as part of their hunger and disease eradication programs. Through scientific literature search and economic review, this paper seeks to understand the pros and cons of genetically modified Golden Rice and its possible introduction into the sustainable development worldwide. It seeks out an agreement between multi-national agro-chemistry corporations, researchers, and local grassroots health activism. Through strengthened local efforts and international ethics, production of profitable, nutritious crops worldwide could lead to advancements in public health--thus putting an end to poverty.
Amber Goedken
Pharmaceutical Socioeconomics Effect of cost-sharing on prescription drug use by Medicare beneficiaries after Medicare Part D and adverse selection in the Medicare drug benefit
The objectives of the study were to analyze how prescription drug cost-sharing affects prescription use by Medicare beneficiaries after the Medicare drug benefit, compare prescription drug cost-sharing and benefit structures faced by Medicare beneficiaries before and after implementation of the Medicare drug benefit, and examine the extent to which adverse selection is occurring in the Medicare drug benefit. The longitudinal study was composed of two internet-based surveys administered by Harris Interactive®. Harris Interactive® maintains a panel of individuals who have opted to be invited to participate in online surveys. A convenience sample of Medicare beneficiaries was recruited from their panel to complete each survey. An ordinary least squares regression model was used to assess the impact of cost-sharing amounts on prescription use, and a logistic regression model was used to assess adverse selection. Before and after the benefit, seniors were enrolled in plans with a variety of benefit structures.
Carlos Sanchez Marin
Occupational and Environmental Health Prevalence of Hand Symptoms and Carpal Tunnel Syndrome among Dental Students
Musculoskeletal disorders (MSDs) of the upper extremities, such as carpal tunnel syndrome (CTS), are common among dental workers. They are exposed to work-related risk factors including repetition, forceful exertions of the hand, and awkward wrist postures. As dental students learn new skills and procedures during dental school, they experience a gradually increasing exposure to these risk factors. The aims of this study are to compare the prevalence of hand and wrist musculoskeletal symptoms and nerve conduction measures across the wrist suggestive of CTS between first and fourth year dental students. Students (N=70) were asked to complete a demographic and hand questionnaires, and had nerve conduction measurements taken at the hand. Means of the nerve conduction velocity and latency will be compared with student's t-tests for statistical significance (p<0.05). The results will provide preliminary data for a more comprehensive study of MSDs among dental students and entry-level dentists.
Mi Ran Wang
Neuroscience The effects of exercise and music on the BDNF induction and episodic memory among human subjects
It is important to find preventive intervention of the Alzheimer s disease (AD) and induction of BDNF can be potential mechanism of those interventions. BDNF is necessary for neuronal survival as well as memory. BDNF levels were decreased in the hippocampus among elderly people and AD patients. BDNF has been demonstrated to be increased by exercise and listening music among animals and young human subjects. Until now there is no study to examine the effects of the exercise and listening music on the BDNF induction and the episodic memory among the middle-aged adults and subjects with mild cognitive impairment (MCI). This study will examine the effects of the exercise and music on the blood BDNF levels and the episodic memory between young adults, middle-aged adults, and the MCI. Because exercise and listening music have a variety of beneficial effects without side effects, this study may suggest effective preventive interventions of AD.
Xiaoyun Pan
Clinical and Administrative Pharmacy Effect of Reimbursement on G-CSF Treatment during First Cycle of Chemotherapy for non-Hodgkin's Lymphoma Patients
G-CSF is an expensive drug to manage febrile neutropenia with uncertain benefits. The objective was to investigate the variation in Medicare claim-paying agents (carriers) reimbursement to physicians for chemotherapy and evaluate the influence of Medicare carrier chemotherapy reimbursement on G-CSF choice. Using the national SEER-Medicare linked database, we studied patients 66 years or older diagnosed as NHL in one of the 13 SEER registry areas from 1994-2002. F test from the OLS regression model showed Medicare physician reimbursement for chemotherapy varied across Medicare carriers. Multiple logistic regressions indicated this variation affected the decision of physicians to prescribe G-CSF. At low chemotherapy reimbursement levels, increases in chemotherapy reimbursements decreased G-CSF prescribing. Physicians appear to compensate for lower reimbursements by increasing the intensity of their services.
Carissa Philippi
Neuroscience The inferior fronto-occipital fasciculus mediates recognition of the facial expression of emotion
Lesion and neuroimaging studies have implicated multiple visual and emotion-related brain regions in the recognition of emotion from facial expressions. However, the mechanism by which visual representations of the face can be efficiently conveyed to emotion-related brain regions that associate the face with its emotional content remains unknown. To test the hypothesis that long-range association fiber tracts are critical for this process, we used a novel approach incorporating fiber tract information into lesion mapping. Disconnection of the right inferior fronto-occipital fasciculus (IFOF) significantly predicted an overall impairment in emotion recognition as well as disproportionate impairments for fear and anger. We found one subject with a white matter lesion virtually restricted to the IFOF with an emotion recognition impairment that supported the group level results. Our findings strongly implicate the right IFOF as a critical component of the large-scale neural system supporting the recognition of the facial expression of emotion.
Matthew Dickson
Genetics and Medicine Functional Regulation of Human Angiotensinogen Expression via Naturally Occurring Polymorphisms
Hypertension is a common disorder with a strong genetic component. Perhaps the strongest candidate gene for hypertension is angiotensinogen (AGT). Among naturally-occurring polymorphisms in human AGT, -20 and -217 have the strongest effects on expression and may affect transcription factor binding. The risk alleles (-20C and -217A) are common and support higher transactivation. We show that upstream stimulatory factor (USF) preferentially binds the -20C allele in vitro. In vivo assays confirm preferential association of USF1 with -20C and show that FOS-related antigen 2 (FRA2) preferentially associates with -20C. Cell culture experiments confirm that FRA2 preferentially activates -20C expression while shRNA-mediated knockdown of USF causes allele-specific attenuation of AGT expression. Knockdown of USF within transgenic mice results in markedly attenuated expression from -20C. We conclude that USF and perhaps FRA proteins functionally and differentially regulate AGT expression via the -20 polymorphism and that this may play an important role in hypertension.
Nicholas Ettinger
Molecular and Cellular Biology Genetic Admixture in Brazilians Exposed to Infection with Leishmania chagasi
Visceral leishmaniasis (VL) is a vector-borne infectious disease caused by the protozoa Leishmania chagasi, L. donovani or L. infantum. Infection leads to variable clinical outcomes ranging from asymptomatic infection to fatal disease. Prior studies suggest that the genetic background of the host contributes to the development of different outcomes. There has been a peri-urban endemic focus of VL surrounding the city of Natal, Brazil since the mid-1980s. The population of northeast Brazil is a mixture of distinct racial and ethnic groups. Therefore, we hypothesized that some sub-populations may be more susceptible than others to develop different clinical outcomes after L. chagasi infection. Analysis of 289 microsatellite markers across the genome demonstrated that there was no apparent genome-wide significant difference in population admixture proportions among clinical phenotype groups. However, several markers displayed Excess Ancestry in particular ethnic backgrounds, suggesting regions that may contribute to susceptibility to L. chagasi infection.
James D. Lewis
Speech Pathology & Audiology Measurement of Hearing Aid Internal Noise Using Synchronous Averaging
The current industrial and clinical standard for quantifying the internal noise of a hearing aid (HA) is the equivalent input noise (EIN), as specified in ANSI S3.22. We question the value of the EIN because 1) it assumes the measured noise is dependent upon the gain of the hearing aid, 2) it is highly variable in clinical measurement, and 3) it does not predict a user s perception of a HA s internal noise. Our study proposes a new method for measuring the internal noise of a HA. Using a synchronous measurement paradigm, we calculated the variance of HA output across repeated presentations of a speech-like stimulus at various intensities. Results demonstrated that for the majority of HAs tested, measured noise was not dependent upon gain contrary to the EIN assumption. Our proposed method provides an accurate measurement of HA internal noise and reliably predicts a user s perception of that noise.
Lea Davis
Genetics/Psychiatry Using copy number variants to identify genes involved in autism
Autism is a neurodevelopmental disorder characterized by three core symptom domains: ritualistic-repetitive behaviors, impaired social interaction, and impaired communication and language. Karyotypically detectable chromosomal abnormalities account for ~5-7% of autism cases. With the exception of these patients, autism has traditionally been considered a complex genetic disorder with roughly 10-15 genes interacting, each contributing a small individual effect but having a large effect when combined. However, the identification of various dominant acting mutations in a small number of autism families is beginning to challenge that assumption. Recently, the advent of oligonucleotide micro-array technology has enabled identification of genomic variation termed copy number variants (CNVs) that was previously undetectable. These microdeletions and duplications are known to cause a number of single gene disorders, including Sotos syndrome, Prader-Willi/Angelman syndrome, Williams-Beuren syndrome, and Bardet-Biedl syndrome. Through careful identification of patients likely to harbor pathogenic CNVs we have discovered novel chromosomal abnormalities that include promising candidate genes for autsim such as syntaxin binding protein 5 and leucine rich neuronal repeat 1.
Matthew Schmidt
Medicinal and Natural Products Chemistry Total Synthesis of Ring-Opened Analogs of Salvinorin A, A Novel Hallucinogen from Salvia divinorum
Salvia divinorum, a type of sage endemic to the mountainous regions of Oaxaca, Mexico, has played an important role in native spiritual rituals for hundreds of years due to the intense hallucinations it is capable of producing. Salvinorin A, the major psychoactive component, is the most potent naturally-occurring hallucinogen, yet it binds selectively at kappa opioid receptors and not to any receptors traditionally associated with hallucinogenic activity (acetylcholine, NMDA, serotonin). Structurally, however, it does not resemble any known opioids or hallucinogens/dissociatives. Additionally, salvinorin A lacks a basic nitrogen previously thought to be essential for opioid activity. Collectively, these characteristics indicate that salvinorin A interacts with the receptor in a unique fashion. Ring-opened analogues of salvinorin A are being prepared to understand the importance of the molecule s overall confirmation and stereochemical configuration on affinity and activity. Progress in the synthesis of these compounds will be discussed.
Kanchna Ramchandran
Neurology The risky business of growing old: (aging effects on risk engagement)
Older adults face frequent and notable challenges regarding financial allocations and health related decisions, so much so that such decision-making may dominate their life space. In this study, we administered the Domain Specific Risk Taking Scale to a healthy sample of community-dwelling older adults. This scale evaluates how we perceive and take risks in various domains of our life, such as finance, health/safety, recreation, ethical, and social decisions. For the analysis, risk perception and risk taking were regressed on age. Significant interactions by age revealed that (1) as perceptions of risk decrease, risk taking behavior increases in the domains of health and safety, and finance; and (2) risk perceptions in these domains decrease with age, resulting in increased risk taking behavior. Contrary to standard intuition that the elderly are more conservative, our results suggested that older people (>71 years of age) perceive lesser health and financial risk and are more likely to take greater risk (p < .05) in these areas of their lives compared to the younger-old (<71 years of age).Possible explanations point to decision-making deficits, reduced temporal construal and frequency/familiarity bias. These findings point to the increased vulnerability of aging populations in the domains of financial and medical decision making.
Olayinka Oladimeji
Pharmaceutical Socioeconomics Risk Factors for Adverse Drug events among Medicare Enrollees before and after Medicare Part D
An adverse drug event (ADE) is an injury resulting from medical interventions related to the use of a drug. Medicare Part D began in 2006 and may have an impact on the problems of inappropriate medication therapy and ADEs. Objectives: Re-examine risk factors for self-reported ADEs in 2007 after the implementation of the program and determine if there were changes in reports of ADEs before and after the program. Design: Longitudinal Participants: Had to be 65 or older, US residents and enrolled in Medicare. Data used in the analysis included socio-demographic data, number of medications, symptoms experienced, concern and necessity beliefs about medicines, number of pharmacies, self-reported ADE and self rated health. Higher concern beliefs about medicines were significantly related to self-reporting an ADE. Patients who reported more symptoms were more likely to report an ADE. Older age was statistically associated with a higher risk for having an ADE.
Yin Wan
Clinical & Administrative Pharmacy cost-analysis of adverse drug reaction in two internal medicine units at a tertiary university hospital
Objectives: the study is to 1) identify the occurrence rate and characteristics of adverse drug reactions(ADRs); 2) assess the excess length of stay and minimum direct costs causing by suspected ADRs. Methods: All patients at two internal medicine units in a Chinese tertiary hospital were evaluated under an intensified spontaneous surveillance system. Kaplan-Meier method was used to estimate the time of occurring ADR. A regression model was used to estimate the excess direct costs with other influential factors controlled. Results: 16% of all patients admitted had ADRs. 10 serious ADRs were mostly involved in White cell and RES system and Urinary system. Cost of per ADR evaluated by doctors was £¤5055.5, lower than the result of £¤5659.2 estimated by model. Conclusions: Because of the predominantly predicable economic burden of ADR on health system, some effective measures are needed to reduce the rate of occurrence of ADR.
Alok Shah
Internal Medicine Loss of Bardet Biedl Syndrome Proteins Alters the Morphology and Function of Motile Cilia in Airway Epithelia
Mutations in a group of genes contributing to ciliary function cause Bardet-Biedl syndrome (BBS). Studies of BBS have focused on primary, sensory cilia. We asked whether loss of BBS proteins would also affect respiratory motile cilia. We found BBS genes were expressed in human airway epithelia, and BBS2 and BBS4 localized to cellular structures associated with motile cilia. Although BBS proteins were not required for ciliogenesis, their loss caused structural defects in cilia. The most common abnormality was bulges filled with vesicles. The structural abnormalities were accompanied by functional defects; ciliary beat frequency was reduced in Bbs-/- mice. Previous reports suggested BBS might increase the incidence of asthma. However, compared to wild-type controls, neither airway hyperresponsiveness nor inflammation increased in Bbs2-/- or Bbs4-/- mice. Instead, animals were partially protected from airway hyperresponsiveness. These results emphasize the role of BBS proteins in both the structure and function of motile cilia.
Andrea Laake
Medical Engineering Torque-velocity characteristics of the elbow and knee
Muscle strength has long been studied at various levels of detail, from muscle fiber to multiple muscle synergists. While it may seem reasonable to apply muscle fiber relationships to muscles acting together at a joint, due to the complexity of synergistic muscles, these relationships may not fully translate. The purpose of this study was to investigate the degree to which Hill s force-velocity relationship holds at the joint level, considering angle-specific torque at two different joints. Strength testing was performed on the knee and elbow joints of 52 subjects using an isokinetic dynamometer. While torque produced at the joint level generally followed the single muscle force-velocity relationship, the Hill equation couldn t be applied to the joint level uniformly across all angles, joint movement directions and between men and women. The Hill model does not accurately account for all gender, motion, and angle factors that are important at the joint level.
Man Su Kim
Pharmacology Mitochondria regulate activation of the transcription factor NFAT in DRG neurons
NFAT is a Ca2+/calcineurin-dependent transcription factor. Recent data demonstrate that NFAT plays important roles in nervous system. Here, I examined the mechanisms of NFAT activation by electrical stimulation. By simultaneously monitoring [Ca2+]i and nuclear import/export of GFP-NFAT4, I found that trains of action potentials, depolarization and capsaicin induced a rapid translocation of NFAT to the nucleus generating the characteristic long-lasting [Ca2+]i plateau phase. Blockade of mitochondrial Ca2+ uptake eliminated the [Ca2+]i plateau and reduced nuclear translocation of NFAT by 40-60%. The inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 produced similar effects. Importantly, disruption of mitochondrial Ca2+ cycling significantly reduced NFAT-dependent transcription activity. Therefore, I propose that by rapidly accumulating and then slowly releasing Ca2+, mitochondria produce a sustained elevation of [Ca2+]i that is required to maximally activate NFAT, suggesting mitochondrial Ca2+ cycling may represent a novel mechanism to potentiate excitation-transcription coupling in neurons.
Song Yi
Biological Sciences Identification and Characterization of Signaling Circuitry for Novel White Pheromone Response in the Human Pathogen Candida albicans
Candida albicans is the most prevalent human fungal pathogen. It is an opportunistic fungus existing in healthy human hosts as a commensal organism, but capable of causing more serious invasive and disseminated diseases in patients with compromised immune systems. C. albicans is heterozygous (a/á) for the mating type locus and must undergo homozygosis to a/a or á/á to mate. But to truly become mating competent, C. albicans must switch from white to opaque phase. Opaque cells release pheromones that induce opaque mating responses. Recently, it was discovered that the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a surface and generate a thicker biofilm, which has been shown to facilitate mating between minority opaque cells. Through mutant analysis, it is demonstrated that the pathways regulating the white and opaque pheromone responses share the same upstream components, including receptors, heterotrimeric G-protein and mitogen-activated protein (MAP) kinase cascade, but use different downstream transcription factors to regulate the expression of genes specific to the alternative responses. This configuration, while common in higher, multicellular systems, is not common in fungi. The induction of the formation of a biofilm, a primitive tissue, and the unique configuration of the regulatory pathways, are consistent with the hypothesis that the sexual system in C. albicans may represent an evolutionary antecedent to multicellularity in higher eukaryotes, besides representing a pathogenic strategy for virulence.
David Anderson
Medicinal and Natural Products Chemistry Mitochondria regulate activation of the transcription factor NFAT in DRG neurons
Parkinson s disease is a progressive neurodegenerative disorder that affects over a million patients in the U.S. The disease pathology is known to involve dopaminergic neuronal death. While the neurotransmitter dopamine (DA) itself is neurotoxic, neuronal death may be due to the inherent toxicity of certain dopaminergic metabolites such as 3,4-dihydroxyphenylacetaldehyde (DOPAL). This aldehyde is several orders of magnitude more toxic than the parent amine. The ability of DA to auto-oxidize to an ortho-quinone is believed to contribute to its cytotoxicity due to resultant protein reactivity and oxidative stress through redox cycling, reactive oxygen species production, and thiol depletion. However, little is known about the ability of DOPAL to similarly undergo auto-oxidation to a reactive quinone. If confirmed, the formation of DOPAL-quinone species would help explain the high toxicity of this aldehyde metabolite. NaIO4 and Tyrosinase, which are known to induce DA-quinone formation, were investigated for their ability to oxidize DOPAL. Colorimetric and spectrophotometric evidence suggests that these methods induce oxidative rearrangement of DOPAL. Such species were found to be reactive toward glutathione and N-acetyl cysteine, which are good indicators of protein reactivity. Following oxidation of DOPAL to the suspected quinone species, it was then trapped with N-acetyl cysteine, analyzed by HPLC, and purified by solid phase extraction for NMR analysis. Such spectrometric and chromatographic methods were utilized for analyzing and characterizing the rearranged and adduct-formation products of oxidized DOPAL in order to eventually determine their biological and cellular relevance, and establish any potential involvement in Parkinson s disease.
Shawn Lesh
Biostatistics The Effect of Advanced Bionic s HiRes 120 CI on Listening to Music
This study tested the effect HiRes 120 Cochlear Implants (CI) have on music pleasantness and musical distinction measures over a three month period. Fifty subjects using an Advanced Bionics HiRes implant completed a baseline survey including measures of music training, music pleasantness, sound processing, and ability to comprehend and differentiate forms of music. Subjects were subsequently fitted with the Advanced Bionic s HiRes 120 CI and readministered the questionnaire one and three months after use. Data were analyzed using repeated measures ANCOVA, with musical training as a covariate, to evaluate the effectiveness of the new device. The HiRes 120 wearers reported significantly improved listening pleasantness and sound processing measures from baseline to 1 month and baseline to 3 months (all p<.03) with no change in these measures from 1 to 3 months. The study found no significant improvement in musical and lyrical distinction over the three month period.
Annalisa Jordan
Chemistry Phomactin Analogues from a Hawaiian Fungicolous Fungus
Mycoparasitic and fungicolous fungi have proven to be rich sources of biologically active secondary metabolites. In the course of our ongoing studies of such fungi, an unidentified grayish-black isolate of Mycelia sterilia (MYC-1969) was obtained from the surface of a white mycelial growth found on a dead hardwood branch collected in a Hawaiian coastal forest. The ethyl acetate extract of solid-substrate fermentation cultures of this isolate showed antifungal activity against Aspergillus flavus, and antiinsectan effects against the fall army worm Spodoptera frugiperda. Subjecting this extract to column chromatography, VLC, and HPLC afforded three new phomactin analogs. Details of the isolation, structure determination, and biological activity of these analogs will be presented.
Scott D. Maddux
Anthropology Allometric Scaling of Infraorbital Surface Topography in Homo
Infraorbital morphology is often included in phylogenetic and functional analyses of Homo. The inclusion of distinct infraorbital configurations, such as the canine fossa in Homo sapiens, or the inflated maxilla in Neandertals, is generally based on either descriptive or qualitative assessments of this morphology, or simple linear chord and subtense measurements. However, the complex curvilinear surface of the infraorbital region has proven difficult to quantify through these traditional methods. In this study, I assess infraorbital shape, and its allometric scaling, in fossil Homo (n = 15) and recent humans (n = 56) with a geometric morphometric method well-suited for quantifying complex surface topographies. The results indicate important aspects of infraorbital shape are significantly correlated with overall infraorbital size across Homo.
Jennifer Rees
Medicinal and Natural Products Chemistry Protein Modification by Dopamine Aldehyde, a Potential Neurotoxin of Parkinson's Disease
Parkinson s disease is a neurodegenerative disorder characterized by cell death of dopaminergic neurons. Current studies have indicated that cell death may originate from increased oxidative stress leading to augmented levels of an endogenous neurotoxin. This neurotoxin could inhibit the metabolism of dopamine causing detrimental effects to neurons. During metabolism, dopamine (DA) is first converted to 3,4-dihydroxyphenylacetaldehyde (DOPAL) by monoamine oxidase and then oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase (ALDH). Previous work has established that upon addition of 4-hydroxy-2-nonenal (4HNE), a product of increased oxidative stress, to rat striatal synaptosomes- ALDH is inhibited causing a decrease in DOPAC levels and a corresponding increase in DOPAL concentrations. Based on this information, it is hypothesized that DOPAL, generated at aberrant levels due to impairment of DA metabolism, will cause protein modification. The data establish the ability of DOPAL to modify proteins thus indicating its potential role in the pathogenesis of neurodegenerative diseases.
Unni Jensen
Neuroscience Investigating The Role of The Hippocampus In Episodic Event Construction In Different Time Frames
Hippocampal amnesics have been found to be impaired in the elaboration of newly imagined events (Hassabis, 2007). However, whether amnesics can construct (Schacter, 2007) episodic events in different time frames has not been characterized. Patients with hippocampal amnesia and healthy comparison participants were given neutral cue-words and then instructed to construct episodic (a specific time and place) events in two different time frames, past and future, and to elaborate on these events by describing 1) an overview of an event and 2) a specific contextual event scene. Amnesics were impaired in constructing episodic events in both time frames as compared to the comparison group. Specifically, the amnesic patients were unable to construct all the required episodic events, and their mental representations were impoverished. These findings converge with fMRI data (Addis, 2007), and support the idea that the construction of episodic events in different time frames is linked to the hippocampus.
James Jacobus
Human Toxicology The End Draws Near: Telemore Shortening Induced by a Quinone Metabolite of PCB3
Telomeres, which protect the ends of the chromosomes from damage, play an important role in carcinogenesis and senescence. They are damaged by oxidative stress. Our working hypothesis is that PCB3-quinone metabolites are carcinogenic by producing oxidative stress-related damage to the telomeres. Human keratinocytes (HaCaT cells) and primary fibroblasts were treated continuously for 12 weeks with 2-(4 -chlorophenyl)-1,4-benzoquinone (PCB3pQ). Telomere length was determined using the quantitative polymerase chain reaction (qPCR) method. Telomeric DNA levels decreased approximately 40% in HaCaT cells treated with PCB3pQ at 5 µM compared to solvent control-treated cells. The telomere signal of primary fibroblasts also shows a decreasing trend with PCB3pQ treatment, but this effect was not statistically significant and confounded by differences in cell doublings during the 12 week period. These preliminary results urge further mechanistic studies concerning the effects of PCB congeners and metabolites on telomeres. (Supported by NIEHS P42 ES013661 and an Iowa CHEEC Seed Grant.)
Ian Lai
Human Toxicology The Low Dose Effects of PCB126 on Rat Liver Metabolism in Rats given a Controlled Dietary Level of Selenium
PCB126 (3,3 ,4,4 ,5-pentachlorobiphenyl) is able to mimic dioxin and bind to Ah receptors and elicit numerous toxic effects including oxidative stress. We hypothesized that even at a low dose exposure this PCB congener will lower selenium levels in the rat liver. Male Sprague-Dawley rats were given a modified AIN-93 purified diet with a controlled selenium level, and receiving a single intraperitoneal injection of the corn oil (control) or PCB126 (1mol/kg body weight). We observed that PCB126-treated rats had a significant decrease in hepatic selenium and glutathione levels, correlating with a decrease in hepatic glutathione peroxidase (GPx) activity. This controlled dietary study shows that even a single low dose exposure to PCB126 may significantly perturb metal homeostasis and antioxidant and enzyme levels in the liver with yet unknown consequences.
Melanie House
Physical Therapy and Rehabilitation Science Wheelchair Seating Interventions Resolve Spinal Deformities and Pressure Ulcers: A Case Series
People with spinal cord injury are described in the research literature as having a characteristic posture of posteriorly tilted pelvis and kyphotic spine posture. In persons with complete motor and sensory paraplegia, pressure sores are the number one reason for re-hospitalization, at five years post-injury. Wheelchair seating prescription is critical to managing posture and pressure distribution over the seated area, however there is a paucity of information available as to how to identify and treat persons in need of prescriptive wheelchair configuration changes. This case series highlights specific guidelines which demonstrate that routine clinic-based wheelchair seating interventions can correct characteristic posture (flexible postural deformities) and facilitate healing of pressure ulcers thus decreasing morbidity and mortality in persons with complete SCI.
Contact Division Head
Matt McNeill
Biological & Health Sciences
Neuroscience matthew-mcneill@uiowa.edu
