Digital Commons Network^™

The Specificity Of The Search Template, Mary J. Bravo, Hany Farid

Dartmouth Scholarship

When searching for a target object, observers use an internal representation of the target's appearance as a search template. This study used naturalistic stimuli to examine the specificity of this template. Observers first learned several name-image pairs; they then participated in a search experiment in which the names served as cues and the images served as targets. To test whether the observers searched for the targets using an exact image template, we included targets that were transformations of the studied image and targets that belonged to the same subordinate-level category as the studied image. The same stimuli were also used …

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss

Biology Faculty Publications

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.

RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …

The Sleeping Brain's Influence On Verbal Memory: Boosting Resistance To Interference, Jeffrey M. Ellenbogen, Justin C. Hulbert, Ying Jiang, Robert Stickgold

Dartmouth Scholarship

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater …

Sand Fly Fever: What Have We Learned In One Hundred Years?, David Brett-Major, David M. Claborn

Journal Articles: Epidemiology

Sand fly fever has severely impacted military missions in southern Europe and the Middle East for hundreds of years. After a brief respite following the malaria eradication programs of World War II, it has returned as a significant disease among residents in and travelers to the Mediterranean rim. It is a more severe disease now, with potential vectors in the United States. Sand fly fever is discussed in terms of its viruses, vectors, disease, control, and potential domestic impact.

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Osteoarthritis Associated With Estrogen Deficiency., Jorge A Roman-Blas, Santos Castañeda, Raquel Largo, Gabriel Herrero-Beaumont

Jefferson Institute of Molecular Medicine Papers and Presentations

Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a …

Polyethylenimine-Based Sirna Nanocomplexes Reprogram Tumor-Associated Dendritic Cells Via Tlr5 To Elicit Therapeutic Antitumor Immunity, Juan R. Cubillos-Ruiz, Xavier Engle, Uciane K. Scarlett, Diana Martinez

Dartmouth Scholarship

No abstract provided.

Rhoa/Rho-Kinase Signaling: A Therapeutic Target In Pulmonary Hypertension, Scott A. Barman, Shu Zhu, Richard E. White

PCOM Scholarly Works

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of …

Mrn Complex Function In The Repair Of Chromosomal Rag-Mediated Dna Double-Strand Breaks, Beth A. Helmink, Andrea L. Bredemeyer, Baeck-Seung Lee, Ching-Yu Huang, Girdhar G. Sharma, Laura M. Walker, Jeffrey J. Bednarski, Wan-Ling Lee, Tej K. Pandita, Craig H. Bassing, Barry P. Sleckman

Open Access Publications

The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle. During HR, the MRN complex functions directly in the repair of DNA DSBs and in the initiation of DSB responses through activation of the ataxia telangiectasia-mutated (ATM) serine-threonine kinase. Whether MRN functions in DNA damage responses before DNA replication in G0/G1 phase cells has been less clear. In developing G1-phase lymphocytes, DNA DSBs are generated by the Rag endonuclease and repaired during the assembly of antigen receptor genes by the process of V(D)J recombination. Mice and …

Antibiotic Prophylaxis For Leptospirosis, David Brett-Major, Robert J. Lipnick

Journal Articles: Epidemiology

BACKGROUND: Leptospira infection is a global zoonosis with significant health impact for agricultural workers and those persons whose work or recreation takes them into endemic areas.

OBJECTIVES: This systematic review assessed the current literature for evidence for or against use of antibiotic prophylaxis against Leptospira infection (leptospirosis).

SEARCH STRATEGY: The authors searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and SCI-Expanded as well as relevant professional society meeting abstracts until January 2009.

SELECTION CRITERIA: Prospective, randomised clinical trials studying antibiotic prophylaxis against leptospirosis were selected.

DATA …

Successional Change In Phosphorus Stoichiometry Explains The Inverse Relationship Between Herbivory And Lupin Density On Mount St. Helens, Jennifer L. Apple, Michael Wink, Shannon E. Wills, John G. Bishop

Biology

Background: The average nitrogen-to-phosphorus ratio (N:P) of insect herbivores is less than that of leaves, suggesting that P may mediate plant-insect interactions more often than appreciated. We investigated whether succession-related heterogeneity in N and P stoichiometry influences herbivore performance on N-fixing lupin (Lupinus lepidus) colonizing primary successional volcanic surfaces, where the abundances of several specialist lepidopteran herbivores are inversely related to lupin density and are known to alter lupin colonization dynamics. We examined larval performance in response to leaf nutritional characteristics using gelechiid and pyralid leaf-tiers, and a noctuid leaf-cutter. Methodology/Principal Findings: We conducted four studies. First, growth of larvae …

Eeg During Pedaling: Brain Activity During A Locomotion-Like Task In Humans, Sanket G. Jain

Master's Theses (2009 -)

This study characterized the brain electrical activity during pedaling, a locomotor-like task, in humans. We postulated that phasic brain activity would be associated with active pedaling, consistent with a cortical role in locomotor tasks. 64 channels of electroencephalogram (EEG) and 10 channels of electromyogram (EMG) data were recorded from 10 neurologically-intact volunteers while they performed active and passive (no effort) pedaling on a custom-designed stationary bicycle. Ensemble average waveforms, two dimensional topographic maps and amplitude of the beta (13-35 Hz) frequency band were analyzed and compared between active and passive trials. The absolute amplitude (peak positive-peak negative) of the EEG …

Staphylococcus Aureus Activates Type I Ifn Signaling In Mice And Humans Through The Xr Repeated Sequences Of Protein A, Francis J. Martin, Marisa I. Gomez, Dawn M. Wetzel, Guido Memmi

Dartmouth Scholarship

No abstract provided.

The Efficacy Of Surgical Decompression Before 24 Hours Versus 24 To 72 Hours In Patients With Spinal Cord Injury From T1 To L1--With Specific Consideration On Ethics: A Randomized Controlled Trial., Vafa Rahimi-Movaghar, Soheil Saadat, Alexander R Vaccaro, Seyed Mohammad Ghodsi, Mohammad Samadian, Arya Sheykhmozaffari, Seyed Mohammad Safdari, Bahram Keshmirian

Department of Neurosurgery Faculty Papers

BACKGROUND: There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24-72 hours) surgical decompression in terms of neurological …

Increased Susceptibility Of Spinal Muscular Atrophy Fibroblasts To Camptothecin Is P53-Independent., Chia-Yen Wu, Ilsa Gómez-Curet, Vicky L Funanage, Mena Scavina, Wenlan Wang

Department of Pediatrics Faculty Papers

BACKGROUND: Deletion or mutation(s) of the survival motor neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA). The SMN protein is known to play a role in RNA metabolism, neurite outgrowth, and cell survival. Yet, it remains unclear how SMN deficiency causes selective motor neuron death and muscle atrophy seen in SMA. Previously, we have shown that skin fibroblasts from SMA patients are more sensitive to the DNA topoisomerase I inhibitor camptothecin, supporting a role for SMN in cell survival. Here, we examine the potential mechanism of camptothecin sensitivity in SMA fibroblasts.

RESULTS: Camptothecin treatment reduced the DNA relaxation activity …

Regulation Of The Fibrosis And Angiogenesis Promoter Sparc/Osteonectin In Human Adipose Tissue By Weight Change, Leptin, Insulin, And Glucose., Katrina Kos, Steve Wong, Bee Tan, Anders Gummesson, Margareta Jernas, Niclas Franck, David Kerrigan, Fredrik H. Nystrom, Lena M.S. Carlsson, Harpal S. Randeva, Jonathan H. Pinkney, John P.H. Wilding

Peninsula Medical School

OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ …

Noninvasive Measurement Of Aminolevulinic Acid-Induced Protoporphyrin Ix Fluorescence Allowing Detection Of Murine Glioma In Vivo, Summer L. Gibbs-Strauss, Julia A. O'Hara, P Jack Hoopes, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence is studied as a contrast agent for noninvasive detection of murine glioma, using the fluorescence-to-transmission ratio measured through the cranium. Signals measured prior to administration of ALA are very similar between control animals, 9L-GFP, and U251 tumor-bearing animals. However, 2 h after ALA administration, the PpIX signal from both tumor-bearing groups is significantly higher than the control group (9L-GFP group p-value=0.016, and U251 group p-value=0.004, relative to the control group). The variance in signal from the 9L-GFP group is much larger than either the control group or the U251 group, which is consistent …

Intergenerational Wealth Transmission And The Dynamics Of Inequality In Small-Scale Societies, Monique Borgerhoff Mulder, Samuel Bowles, Tom Hertz, Adrian Bell, Jan Beise, Greg Clark, Ila Fazzio, Michael Gurven, Kim Hill, Paul L. Hooper, William Irons, Hillard Kaplan, Donna Leonetti, Bobbi Low, Frank Marlowe, Richard Mcelreath, Suresh Naidu, David Nolan, Patrizio Piraino, Robert Quinlan, Eric Schniter, Rebecca Sear, Mary Shenk, Eric Alden Smith, Christopher Von Reuden, Polly Wiessner

Psychology Faculty Articles and Research

Small-scale human societies range from foraging bands with a strong egalitarian ethos to more economically stratified agrarian and pastoral societies. We explain this variation in inequality using a dynamic model in which a population’s long-run steady-state level of inequality depends on the extent to which its most important forms of wealth are transmitted within families across generations. We estimate the degree of intergenerational transmission of three different types of wealth (material, embodied, and relational), as well as the extent of wealth inequality in 21 historical and contemporary populations. We show that intergenerational transmission of wealth and wealth inequality are substantial …

Evidence For Menstrual Cycle Shifts In Women’S Preferences For Masculinity: A Response To Harris (In Press) “Menstrual Cycle And Facial Preferences Reconsidered", Lisa Debruine, Benedict C. Jones, David Frederick, Martie Haselton, Ian S. Penton-Voak, David I. Perrett

Psychology Faculty Articles and Research

Over the last decade, a growing literature has shown that women in the fertile phase of the menstrual cycle demonstrate stronger preferences for men with masculine traits than they do when in the non-fertile phases of the cycle (see Gangestad and Thornhill, 2008 and Jones et al., 2008 for recent reviews). In a recent article, Harris (in press; Sex Roles) failed to replicate this increase in women's preferences for masculine faces when women are near ovulation. Harris represented her study as one of only three studies on the topic, and as the largest of the existing studies. There are, however, …

Molluscan Memory Of Injury: Evolutionary Insights Into Chronic Pain And Neurological Disorders, Edgar T Walters, Leonid L Moroz

Faculty, Staff and Student Publications

Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan …

Is Paromomycin An Effective And Safe Treatment Against Cutaneous Leishmaniasis? A Meta-Analysis Of 14 Randomized Controlled Trials, Dae Hyun Kim, Hye Jin Chung, Joachim Bleys, Reza F Ghohestani

Faculty, Staff and Student Publications

BACKGROUND: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting.

METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled …

Key Role Of T Cell Defects In Age-Related Vulnerability To West Nile Virus, James D. Brien, Jennifer L. Uhrlaub, Alec Hirsch, Clayton A. Wiley, Janko Nikolich-Zugich

Open Access Publications

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40-50x more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

What Determines Auditory Similarity? The Effect Of Stimulus Group And Methodology., Kirsteen M. Aldrich, Elizabeth J. Hellier, Judy Edworthy

School of Psychology

Two experiments on the internal representation of auditory stimuli compared the pairwise and grouping methodologies as means of deriving similarity judgements. A total of 45 undergraduate students participated in each experiment, judging the similarity of short auditory stimuli, using one of the methodologies. The experiments support and extend Bonebright's (1996) findings, using a further 60 stimuli. Results from both methodologies highlight the importance of category information and acoustic features, such as root mean square (RMS) power and pitch, in similarity judgements. Results showed that the grouping task is a viable alternative to the pairwise task with N > 20 sounds whilst …

The Root Of Dental Anatomy: A Case For Naming Eustachius The "Father Of Dental Anatomy"., Gregory W. Bennett

Journal Articles: College of Dentistry

When one considers the names of those whose affect on dentistry reached far beyond their lifetimes, one may think of Fauchard, Wells, Morton and Black. One name that deserves to be called among the pantheon of the greats is Bartholomaeus Eustachius. Eustachius was not the first to study the anatomy of the teeth and jaws, having been preceded by Da Vinci; however, he was the first to publish a treatise devoted entirely to this subject, Libellus de Dentibus, in 1563. As Sir William Osler, the father of modern medicine, stated: "In Science, the credit goes to the man who convinces …

Micrornas: Key Modulators Of Posttranscriptional Gene Expression., Steven P. O'Hara, Justin L. Mott, Patrick L. Splinter, Gregory J. Gores, Nicholas F. Larusso

Journal Articles: Biochemistry & Molecular Biology

No abstract provided.

Elevated Expression Of L-Selectin Ligand In Lymph Node-Derived Human Prostate Cancer Cells Correlates With Increased Tumorigenicity., Prakash Radhakrishnan, Ming-Fong Lin, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Human prostate cancer LNCaP cells including C-33 and C-81 cells were originally derived from the lymph nodes of a patient with metastatic prostate cancer. These two cells were employed for characterization of L-selectin ligand and in vitro tumorigenicity, because they mimic the clinical conditions of early and late-stage human prostate cancer. C-81 cells exhibit higher in vitro migratory and invasive properties as compared with C-33 cells. We find that the L-selectin ligand and mucin glycan-associated MECA-79 epitope were elevated in C-81 cells. An increase of these glycotopes positively correlates with elevated tumorigenicity and expression of key glycosyl- and sulfotransferase genes. …

Effector Memory T Cell Responses Are Associated With Protection Of Rhesus Monkeys From Mucosal Simian Immunodeficiency Virus Challenge., Scott G. Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Michael K. Axthelm, Kelli Oswald, Charles M. Trubey, Michael Piatak, Jeffrey D. Lifson, Jay A. Nelson, Michael A. Jarvis, Louis J. Picker

School of Biomedical Sciences

The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion and differentiation. We hypothesized that vaccines designed to maintain differentiated effector memory T cell (TEM cell) responses at viral entry sites might improve efficacy by impairing viral replication at its earliest stage, and we have therefore developed SIV protein-encoding vectors based on rhesus cytomegalovirus (RhCMV), the prototypical inducer of life-long TEM cell responses. RhCMV vectors expressing SIV Gag, …