• The Formin FMNL1 Contributes to the Macrophage Inflammatory Response by Regulating Podosome-dependent Adhesion and Migration.

      Blystone, Scott; Miller, Matthew (2015)
      Macrophages are indispensible white blood cells (leukocytes) that contribute to both the innate and adaptive immune response. They are crucial for resolving inflammatory events by clearing pathogens and cellular debris, in addition to promoting wound repair. Macrophages are derived from peripherally circulating monocytes, which after stimulation undergo diapedesis from the vasculature into the underlying complex extracellular matrix, where they can become fully differentiated macrophages and migrate to inflammatory loci. Tissues also contain residential populations of macrophages that aid in immediate immune responses and maintain tissue homeostasis. Conversely, unwarranted macrophage activation largely contributes to the onset and progression of inflammatory diseases, such as atherosclerosis and rheumatoid arthritis, in addition to aiding cancer metastasis and facilitating organ transplant rejection. In order for macrophages to effectively resolve inflammatory events or contribute to disease pathology, they must be able to undergo directional migration, which is mediated by integrin-dependent adhesion complexes termed podosomes. Macrophage podosomes are the most prominent structure of the macrophage actin cytoskeleton, containing a pillar-like core of dense filamentous actin that is tethered to the cortical actincytoskeleton via radial actin filaments. Podosomes also contain a variety of proteins that are circumferentially arranged orassociated with the core, and thatare involved in signaling, linking, and scaffolding,as well as modulating the actin cytoskeleton.Historically, our lab has been interested in leukocyte integrin biology and understanding how these receptors mediate adhesion and migration through complex extracellular matrices. Previous studies in our lab demonstrated the novel podosomal association of an actin modulating protein with the ability to processively elongate unbranched linear actin filaments. Subsequent studies determined this protein to be the formin FMNL1, which is predominantly expressed in hematopoietic cells. Consequently, we further revealed that FMNL1 localizes to the apex of the dense actin core, and is required for podosome stability and macrophage adhesion.The work described in this dissertation has greatly expanded on these findings, demonstrating for the first time that primary macrophage migration is dependent on the formin FMNL1. Utilizing in vitro and in vivotechniques with aid of a novel conditional murine FMNL1 KO, we have observed that macrophage podosome formation, migration, and tissue distribution are dependent on FMNL1. Additionally, we have indicated that FMNL1 is required for embryonic development. Remarkably, our findings also suggest that FMNL1-dependent macrophage migration and podosome localization rely on the specific isoform FMNL1γ. Foremost, we have demonstrated that barbed end binding by the FMNL1γ FH2 domain is dispensable for its cellularfunction in macrophages, which has not been previously shown for any other cellular formin function. Thus, these findings, in addition to current formin knowledge, have allowed us develop a working model for FMNL1 function at macrophage podosomes. This work has distinguished FMNL1 as a unique therapeutic target to restrict macrophage migration that contributes to macrophage-mediated diseases. Furthermore, this could translate to treatment of certain cancers, since FMNL1 has been suggested to promote leukemic cell migration.
    • Free & Open Source Software Off The Grid

      Besemer, Benjamin (2011-07-01)
      This thesis project is an autoethnographic look at personally adopting Free & Open Source Software (FOSS) for a period of 8 weeks. During this period I made a switch to entirely FOSS both professionally and personally in hopes of exploring whether FOSS can be effectively used in everyday life. Furthermore, the project looks at what is involved in adopting FOSS and what benefits and/or drawbacks can be expected for individuals looking for alternatives to proprietary software. The daily experiences written about include those from my personal life and that of being a high school teacher performing daily tasks and instruction using only FOSS. A comparative analysis of the data collected is made between my prior experiences with proprietary software and that of FOSS used during this period.
    • Functional alterations and rhythmic disturbances by pan-histone deacetylase inhibition in the heart.

      Veenstra, Richard; Patel, Dakshesh (2016)
      Histone acetyl transferases (HATs) and histone deacetylases (HDACs) maintain a dynamic balance of acetylation and deacetylation of histone and non-histone proteins. HDAC inhibitors are small molecules anti-cancer therapeutics that exhibited dose limiting cardiac toxicities during clinical and preclinical trials. Multiple instances of abnormal T-waves, ST segment depression, QT prolongation, grade 3 sinus bradycardia and non- circumstantial deaths have been observed in patients. The underlying electrophysiological and molecular mechanism of these cardiac side-effects are poorly understood. In our in vivo ECG monitoring using Data Science International® telemetry transmitters, mice injected with panobinostat showed ventricular tachychardic and atrial fibrillation episodes with significant prolongation of ST, QT and QTc intervals. In whole cell patch clamp studies, we observed no significant change in transient and steady state K currents in myocyte ventricular cultures suggesting no role of hERG currents in ventricular arrhythmias. The majority (>90%) of congenital and drug induced QT prolongation is caused by alterations of hERG (IKr, Kv11.1) current. Interestingly, we observed significant reductions of INa and gap junctional conductance along with reductions in protein expression of Nav1.5 & Cx43 in vivo and in vitro. We conclude that pan-HDAC inhibition reduced cardiac INa density and gap junctional coupling with unaltered late INa and K+ currents explaining the cardiac abnormalities exhibited by panHDAC inhibitors. Decreased gap junctional coupling can enhance triggered activity by limiting electrotonic inhibition, combined with reduced INa density which can lead to slow myocardial conduction. Both of them taken together, increases the vulnerability to reentrant arrhythmias.
    • A functional phylogenomic view of the seed plants.

      Lee, Ernest K; Cibrian-Jaramillo, Angelica; Kolokotronis, Sergios-Orestis; Katari, Manpreet S; Stamatakis, Alexandros; Ott, Michael; Chiu, Joanna C; Little, Damon P; Stevenson, Dennis Wm; McCombie, W Richard; et al. (2011-12-15)
      A novel result of the current research is the development and implementation of a unique functional phylogenomic approach that explores the genomic origins of seed plant diversification. We first use 22,833 sets of orthologs from the nuclear genomes of 101 genera across land plants to reconstruct their phylogenetic relationships. One of the more salient results is the resolution of some enigmatic relationships in seed plant phylogeny, such as the placement of Gnetales as sister to the rest of the gymnosperms. In using this novel phylogenomic approach, we were also able to identify overrepresented functional gene ontology categories in genes that provide positive branch support for major nodes prompting new hypotheses for genes associated with the diversification of angiosperms. For example, RNA interference (RNAi) has played a significant role in the divergence of monocots from other angiosperms, which has experimental support in Arabidopsis and rice. This analysis also implied that the second largest subunit of RNA polymerase IV and V (NRPD2) played a prominent role in the divergence of gymnosperms. This hypothesis is supported by the lack of 24nt siRNA in conifers, the maternal control of small RNA in the seeds of flowering plants, and the emergence of double fertilization in angiosperms. Our approach takes advantage of genomic data to define orthologs, reconstruct relationships, and narrow down candidate genes involved in plant evolution within a phylogenomic view of species' diversification.
    • Functional Studies of Tumor Suppressor ECRG2 in the Regulation of Cancer Cell Death and Drug Resistance

      Huang, Ying; Lucchesi, Chris (2015)
      Esophageal Cancer Related Gene 2 (ECRG2) is a newer tumor suppressor whose mRNAhas previously been shown to be decreased in multiple human malignanceswhencompared to normal/adjacent tissues.Of importance, ECRG2 has previously been revealedto possess tumor suppressive attributes,including the ability to induce cell death in cancer cells. However, how ECRG2 is able to activate the apoptotic machinery has yet to be elucidated. In the present study,we highlight multiple angles that ECRG2 leverages in order to sensitize cancer cells to apoptosis. Moreover, we report for the first time,that ECRG2 protein expression in lung cancer patientsamples is lost/decreased in upwards of 90% ofthecancer tissues evaluatedcompared to normal tissue. Additionally, a single somatic point mutant found in patient tumor samples, V30E, was shown to lose tumor suppressive abilities and acquired resistance against multiple anticancer drugs. Our results demonstrate that ECRG2is upregulated in response to DNA damage, andis capable of inducing the activation of both caspase cascades (intrinsic and extrinsic) leadingto cancer cell death. We further illustratedthat ECRG2-mediated cell deathwasattributed to a reduction in the levels of apoptosis inhibitor, X chromosome-linked inhibitor of apoptosis protein (XIAP). ECRG2 was revealedto regulate XIAP protein levels via RNA-binding protein,human antigen R(HuR).We further highlight that ECRG2 causes increased HuR ubiquitination,subsequently leading to its degradation. Thus, we demonstrate that ECRG2 sensitizescancer cells to apoptosis through the downregulation of HuR, and consequent downregulation of XIAP. Next, we have identified ECRG2 as a potent positive regulator of death receptor 5 (DR5) gene expression.ECRG2-mediated upregulation of DR5 was shown to be facilitated through the upregulation of tumor suppressor p53 and transcription factors ATF3 and NFⱪB. Together, in a cooperative fashion, increased levelsof p53, ATF3 and NFⱪB stimulateDR5 gene expression. Contrastingly, silencing of ECRG2 not only decreased the levels of NFⱪB and DR5, but also resulted in decreased cancer cell sensitivity to genotoxic stressandTRAIL treatment. Collectively,our work establishes that ECRG2 is capable of inducing apoptosis in cancer cells by increasing the expression of pro-apoptotic proteins, while also negatively influencing anti-apoptotic proteins.Further, the loss of ECRG2’stumor suppressive abilities, as wehaveshownby the loss of ECRG2in lung patient tumor samples,and through the somatic point mutantV30E, illuminates possible mechanismsin which cancer cells can acquiremultiple drug resistance.
    • Further evidence of an association between maternal smoking during pregnancy and attention deficit hyperactivity disorder: Findings from a high-risk sample of siblings

      Milberger, Sharon; Biederman, Joseph; Faraone, Stephen V.; Jones, Janice (Informa UK Limited, 1998-09)
      The authors investigated the relationship between attentiondeficit/byperactivity disorder (ADHD) and cigarette smoking in siblings of ADHD and non-ADHD probands. They conducted a 4-year follow-up of siblings from ADHD and control-group families. In the siblings of ADHD probands, ADHD was associated with higher rates and earlier onset of cigarette smoking. There was also a significant positive association between cigarette smoking and conduct disorder, major depression, and drug abuse in the siblings, even after adjusting for confounding variables. Moreover, smoking was found to be familial among ADHD families but not control-group families. Our findings indicate that ADHD is a risk factor for early initiation of cigarette smoking in the high-risk siblings of ADHD probands
    • Further Evidence of Association Between Behavioral Inhibition and Social Anxiety in Children

      Biederman, Joseph; Hirshfeld-Becker, Dina R.; Rosenbaum, Jerrold F.; Hérot, Christine; Friedman, Deborah; Snidman, Nancy; Kagan, Jerome; Faraone, Stephen V. (American Psychiatric Association Publishing, 2001-10)
      Objective: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. Method: Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2–6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children ≥5 years was compared between children with behavioral inhibition (N=64) and without (N=152). Results: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). Conclusions: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders.
    • Further investigation of a chromosome 15 locus in schizophrenia: Analysis of affected sibpairs from the NIMH genetics initiative

      Leonard, Sherry; Gault, Judith; Moore, Theodore; Hopkins, Jan; Robinson, Misi; Olincy, Ann; Adler, Lawrence E.; Cloninger, C. Robert; Kaufmann, Charles A.; Tsuang, Ming T.; et al. (Wiley, 1998-07-10)
      Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the α7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:308–312, 1998. © 1998 Wiley-Liss, Inc.
    • The Future Impact of Immersive Virtual Reality Simulations on the Suburban Training Experience of Firefighters in Westchester, NY

      Tatton III, Edward J (2014-12-01)
      This paper describes a prototype of a firefighter training platform utilizing an immersive virtual reality environment. Advances in technology, with the adoption of virtual reality (VR) systems for training purposes, may provide learners with educational environments with life-like simulation interfaces. A prototype was created to simulate interactions a firefighter might experience in a fully immersive environment. The prototype was used to educate firefighters on the cocncept and survey them for feedback on the proposed learning environment. To achieve a fully immersive virtual reality, visual, tactile, auditory, olfactory and gustatory feedback was used. It was found that a fully immersive virtual reality environment would meet the needs of a successful multimedia design as regards cognition and motivation.
    • Game Streaming in the Wake of a Pandemic: Topic: Live Streaming and Branding

      Jofre, Ana; Martucci, Nicholas; Jofre, Ana; First Reader; Lizardi, Ryan; Second Reader (SUNY Polytechnic Institute, 2020-12)
      The purpose of this study is to determine what the key motivational factors for creating a live stream gaming channel in the wake of a global pandemic are. This is executed by generating a series of podcast interviews from live streamers, generating branding for the launch of a live stream gaming channel and launching the channel. With the world in a current state of emergency, the live streaming industry under Twitch.tv has boomed, giving streamers and viewers alike an opportunity to interact, communicate, and form communities like never before in the shadow of these pressing times. In light of this, we seek an escape from the harsh reality that is quarantine and find comfort in engaging with others all the while having fun indoors.
    • GAMES THAT CAN SAVE LIVES Designing the next generation NYCAMH safety game

      VanDusen, Michael (2012-06-01)
      Abstract not present in the Thesis
    • Gamification & 21st Century Digital Learning

      Galimore, Zipporah; Yucel, Ibrahim; Thesis Advisor; Stam, Kathryn; Second Reader (2018-05)
      Gamification application to instructional methodologies could enhance learning when appropriately implemented. Current research suggests several instructional design principles support principles of gamification. Experts in both gamification and instructional design emphasize certain learning theories and instructional strategies that need to be taken into consideration when integrating gamification in the learning process. Examples provided where effective gamification implemented closely aligns with what current research shows regarding successful multimedia learning and instruction. A virtual learning museum with a butterfly exhibit prototype with examples provided in this paper has been created to give an idea of how gamification and learning design principles should be used simultaneously to enhance cognitive development. Sections of the exhibit are labeled with both gamification and instructional design principals.
    • Gamification of Mobile Fitness Applications for Newly Diagnosed Multiple Sclerosis Patients

      Coupe, Brian (2016-01)
      We can think of our life with mobile technology as a constant classroom and learning environment. Mobile Fitness is a prototype application which will be used by newly diagnosed Multiple Sclerosis patients. The application uses the theory of fun and engagement to keep the user interested and motivated to complete daily workouts. Mobile Fitness uses these game based learning characteristics and human centered design to better suit the user. Recreational therapy also integrates well with gamification because both can be considered with the same end goals in mind. Successful completion of tasks with a reward.
    • Gap Junctional Coupling between Retinal Amacrine and Ganglion Cells Underlies Coherent Spike Activity Integral to Global Object Perception

      Roy, Kaushambi (2017-08)
      Coherent spike activity between neighboring cells is a ubiquitous phenomenon exhibited by ensembles of neurons throughout the central nervous system, including the retina. In addition to the robust coherent activity between neighboring retinal ganglion cells (RGCs), there is evidence that widely separated RGCs can also show correlated spiking. These long range correlations can be evoked by large, contiguous light stimuli, but not to smaller, discontinuous objects. It has thus been posited that long range spike correlations between distant RGCs encode information critical to global object perception. Since the wide separation of the RGCs precludes common excitatory drive from bipolar cells, the mechanism underlying long range concerted activity has remained elusive. Most RGCs show gap junctional coupling to polyaxonal amacrine cells (PACs), which maintain extensive axonal arbors that can extend >1mm across the retina. The electrical coupling between RGCs and PACs thereby form a plausible circuit that can underlie long range correlated activity in the retina. In the current study we tested this hypothesis by targeting and recording from pairs of widely separated ON α-RGCs in the mouse retina, which are coupled indirectly through intermediary PACs. Pharmacological blockade of gap junctions or genetic ablation of connexin36 (Cx36) subunits eliminated the long range correlated spiking between the α-RGCs. These data indicated that electrical coupling between RGCs and PACs was responsible for the long range spike activity. In contrast, I found that direct, serial RGC-RGC coupling was incapable of supporting long range spike correlations. Finally, behavioral experiments were performed to test whether blockade of retinal gap junctions or ablation of Cx36 attenuates the ability of mice to discriminate large, global objects from small, disjointed stimuli. I found that Cx36 knockout mice indeed have significantly reduced ability to discriminate global objects from smaller discontinuous stimuli as compared to wild type littermates. This reduced perception of global objects was not due to a general reduction in spatial acuity that measured in knockout animals was similar to that for wild type mice. Taken together, our results indicate that long range concerted firing between RGCs, derived from electrical coupling with amacrine cells, encodes information critical to global object perception.
    • Generating Facial Character: A Systematic Method Accumulating Expressive Histories

      Jofre, Ana (MIT Press, 2022-04)
      The author presents a method to simulate facial character development by accumulating an expressive history onto a face. The model analytically combines facial features from Paul Ekman’s seven universal facial expressions using a simple Markov chain algorithm. The output is a series of 3D digital faces created in Blender with Python. The results show that systematically imprinting features from emotional expressions onto a neutral face transforms it into one with distinct character. This method could be applied to creative works that depend on character creation, ranging from figurative sculpture to game design, and allows the creator to incorporate chance into the creative process. The author demonstrates the method’s application to sculpture with ceramic casts of generated faces.
    • ?Generic Datasets, Beamforming Vectors Prediction of 5G Celleular Networks

      Kholidy, Hisham A.; Singh, Manjit; Kholidy, Hisham A.; Advisor (SUNY Polytechnic Institute, 2020)
      The early stages of 5G evolution revolves around delivering higher data speeds, latency improvements and the functional redesign of mobile networks to enable greater agility, efficiency and openness. The millimeter-wave (mmWave) massive multiple-input-multiple-output (massive MIMO) system is one of the dominant technology that consistently features in the list of the 5G enablers and opens up new frontiers of services and applications for next-generation 5G cellular networks. The mmWave massive MIMO technology shows potentials to significantly raise user throughput, enhances spectral and energy efficiencies and increases the capacity of mobile networks using the joint capabilities of the huge available bandwidth in the mmWave frequency bands and high multiplexing gains achievable with massive antenna arrays. In this report, we present the preliminary outcomes of research on mmWave massive MIMO (as research on this subject is still in the exploratory phase) and study two papers related to the Millimeter Wave (mmwave) and massive MIMO for next-gen 5G wireless systems. We focus on how a generic dataset uses accurate real-world measurements using ray tracing data and how machine learning/Deep learning can find correlations for better beam prediction vectors through this ray tracing data. We also study a generated deep learning model to be trained using TensorFlow and Google Collaboratory.
    • GENESIS AND MAINTENANCE OF LONG-TERM IgM+ T-BET+ B CELLS

      Papillion, Amber (2017)
      IgM memory cells are recognized as an important component of B cell memory, based on several studies both in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c/T-bet-positive IgM memory cells and an IgM T-bet-positive bone marrow antibody-secreting cell population (ASCs). The origin of these populations was unknown, although an early T-independent spleen CD11c-and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship. The majority of IgM memory cells detected after day 30 post-infection had undergone somatic hypermutation, indicating that they expressed activation-induced cytidine deaminase (AID). Therefore, to identify early AID-expressing precursor cells, we infected an AID-regulated tamoxifen-inducible Cre-recombinase-EYFP reporter strain. Tamoxifen administration led to labeling of both the IgM memory cells and bone marrow ASCs on day 30 and later post-infection. High frequencies of labeled cells were identified on day 30 post-infection,following tamoxifen administration on day 10 post-infection. Both IgM memory cells and IgM bone marrow ASCs were labeled when tamoxifen was administered as early as day 4 post-infection. We also identified mechanisms involved in maintenance of the IgM bone marrow ASCs and IgM+ memory cells, namely proliferation and FcγRIIb respectively. BrdU studies revealed that the bone marrow IgM ASCs were maintained by proliferation, unlike the IgM memory cells. RNAseq analysis revealed a 2-fold higher expression of inhibitory Fc receptor, FcγRIIb. Because FcγRIIb inhibits B cell activation, we hypothesized that FcγRIIb negatively regulates IgM+ memory B cells by binding immune complexes present during low-level chronic infection. E. murisinfection of FcγRIIb-deficientmice revealed a 3-fold expansion of the IgM+ memory 30 days post-infection. We further demonstrated that the expansion of the IgM+ memory cells was not due to increased proliferation, but a decrease of apoptosis, due to a lack of Fas expression in FcγRIIb-deficient mice. This result was mimicked in AID-deficient mice, which lack the ability to class switch to IgG and make immune complexes, revealing a role for immune complexes in regulating IgM+ memory. Altogether, these studies demonstrate a novel germinal center-independent pathway for the generation of two distinct long-term IgM-positive B cell populations.
    • A Genetic Algorithm for Locating Acceptable Structure Models of Systems (Reconstructability Analysis)

      Heath, Joshua; Cavallo, Roger; Advisor; Reale, Michael; Reviewer; Sengupta, Saumendra; Reviewer (2018-05)
      The emergence of the field of General Systems Theory (GST) can be best attributed to the belief that all systems, irrespective of context, share simple, organizational principles capable of being mathematically modeled with any of many forms of abstraction. Structure  modeling is a well‐developed aspect of GST specializing in analyzing the structure of a system ‐ that is, the interactions between the attributes of a system. These interactions, while intuitive in smaller systems, become increasingly difficult to comprehend as the number of measurable attributes of a system increases. To combat this, one may approach an overall system by analyzing its various subsystems and, potentially, reconstruct properties of that system using  knowledge gained from considering a collection of these subsystems (a structure model). In situations where the overall system cannot be fully reconstructed based on a given structure model, the benefits and detriments associated with using such a model should both be considered. For example, while a model may be simpler to understand, or require less storage space in memory than the system as a whole, all information regarding that system may not be inferable from that model. As systems grow in size, determining the acceptability of every meaningful structure model of a system in order tofind the most acceptable becomes exceedingly resource-intensive. In this thesis, a measure of the memory requirements associated with storing a system or a set of subsystems (a structure model) is defined and is used in defining an objective measure of the acceptability of a structure as a representation of an overall system. A Genetic Algorithm for Locating Acceptable Structures (GALAS) is then outlined, with this acceptability criterion serving as an optimizable fitness function. The goal of this heuristic is to search the set of all meaningful structure models, without the need for exhaustively generating each, and produce those that are the most acceptable, based on predefined acceptability criteria. 
    • Genetic variation at hair length candidate genes in elephants and the extinct woolly mammoth

      Roca, Alfred L; Ishida, Yasuko; Nikolaidis, Nikolas; Kolokotronis, Sergios-Orestis; Fratpietro, Stephen; Stewardson, Kristin; Hensley, Shannon; Tisdale, Michele; Boeskorov, Gennady; Greenwood, Alex D (Springer Science and Business Media LLC, 2009)
      Background: Like humans, the living elephants are unusual among mammals in being sparsely covered with hair. Relative to extant elephants, the extinct woolly mammoth, Mammuthus primigenius, had a dense hair cover and extremely long hair, which likely were adaptations to its subarctic habitat. The fibroblast growth factor 5 (FGF5) gene affects hair length in a diverse set of mammalian species. Mutations in FGF5 lead to recessive long hair phenotypes in mice, dogs, and cats; and the gene has been implicated in hair length variation in rabbits. Thus, FGF5 represents a leading candidate gene for the phenotypic differences in hair length notable between extant elephants and the woolly mammoth. We therefore sequenced the three exons (except for the 3' UTR) and a portion of the promoter of FGF5 from the living elephantid species (Asian, African savanna and African forest elephants) and, using protocols for ancient DNA, from a woolly mammoth. Results: Between the extant elephants and the mammoth, two single base substitutions were observed in FGF5, neither of which alters the amino acid sequence. Modeling of the protein structure suggests that the elephantid proteins fold similarly to the human FGF5 protein. Bioinformatics analyses and DNA sequencing of another locus that has been implicated in hair cover in humans, type I hair keratin pseudogene (KRTHAP1), also yielded negative results. Interestingly, KRTHAP1 is a pseudogene in elephantids as in humans (although fully functional in non-human primates). Conclusion: The data suggest that the coding sequence of the FGF5 gene is not the critical determinant of hair length differences among elephantids. The results are discussed in the context of hairlessness among mammals and in terms of the potential impact of large body size, subarctic conditions, and an aquatic ancestor on hair cover in the Proboscidea.