Digital Commons Network^™

Effect Of Bdnf Val66met On Memory Decline And Hippocampal Atrophy In Prodromal Alzheimer's Disease: A Preliminary Study, Yen Y. Lim, Victor L. Villemagne, Simon M. Laws, David Ames, Robert H. Pietrzak, Kathryn A. Ellis, Karra Harrington, Pierrick Bourgeat, Ashley I. Bush, Ralph N. Martins, Colin L. Masters, Christopher C. Rowe, Paul Maruff

Research outputs 2014 to 2021

Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, …

Joint Effect Of Multiple Common Snps Predicts Melanoma Susceptibility, Shenying Fang, Jiali Han, Mingfeng Zhang, Li-E Wang, Qingyi Wei, Christopher I. Amos, Jeffrey E. Lee

Dartmouth Scholarship

Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive …

Inflammatory Cytokine Gene Expression In Mesenteric Adipose Tissue During Acute Experimental Colitis, William Conan Mustain, Marlene E. Starr, Joseph Daniel Valentino, Donald A. Cohen, Daiki Okamura, Chi Wang, B. Mark Evers, Hiroshi Saito

Markey Cancer Center Faculty Publications

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

METHODS: Experimental colitis was induced in 6-month-old C57BL/6 …

Contrast Negation Differentiates Visual Pathways Underlying Dynamic And Invariant Facial Processing, Pamela M. Pallett, Ming Meng

Dartmouth Scholarship

Abstract Bruce and Young (1986) proposed a model for face processing that begins with structural encoding, followed by a split into two processing streams: one for the dynamic aspects of the face (e.g., facial expressions of emotion) and the other for the invariant aspects of the face (e.g., gender, identity). Yet how this is accomplished remains unclear. Here, we took a psychophysical approach using contrast negation to test the Bruce and Young model. Previous research suggests that contrast negation impairs processing of invariant features (e.g., gender) but not dynamic features (e.g., expression). In our first experiment, participants discriminated differences in …

Analgesic Tolerance Of Opioid Agonists In Mutant Mu-Opioid Receptors Expressed In Sensory Neurons Following Intrathecal Plasmid Gene Delivery, Guangwen Li, Fei Ma, Yanping Gu, Li-Yen Mae Huang

Physiology Faculty Publications

Background: Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mutation have not been fully explored due to the complexity in studies of mutant receptors in vivo. To facilitate the determination of the contribution of phosphorylation sites in MOR to opioid-induced analgesic behaviors, we expressed mutant and wild-type human MORs (hMORs) in sensory …

Severe, Fatal Multisystem Manifestations In A Patient With Dolichol Kinase-Congenital Disorder Of Glycosylation., Michelle T Lieu, Bobby G Ng, Jeffrey S. Rush, Tim Wood, Monica J Basehore, Madhuri Hegde, Richard C Chang, Jose E Abdenur, Hudson H Freeze, Raymond Y Wang

Molecular and Cellular Biochemistry Faculty Publications

Congenital disorders of glycosylation are a group of metabolic disorders with an expansive and highly variable clinical presentation caused by abnormal glycosylation of proteins and lipids. Dolichol kinase (DOLK) catalyzes the final step in biosynthesis of dolichol phosphate (Dol-P), which is the oligosaccharide carrier required for protein N-glycosylation. Human DOLK deficiency, also known as DOLK-CDG or CDG-Im, results in a syndrome that has been reported to manifest with dilated cardiomyopathy of variable severity. A male neonate born to non-consanguineous parents of Palestinian origin presented with dysmorphic features, genital abnormalities, talipes equinovarus, and severe, refractory generalized seizures. Additional multi-systemic manifestations developed …

Severe, Fatal Multisystem Manifestations In A Patient With Dolichol Kinase-Congenital Disorder Of Glycosylation., Michelle T Lieu, Bobby G Ng, Jeffrey S Rush, Tim Wood, Monica J Basehore, Madhuri Hegde, Richard C Chang, Jose E Abdenur, Hudson H Freeze, Raymond Y Wang

Molecular and Cellular Biochemistry Faculty Publications

Congenital disorders of glycosylation are a group of metabolic disorders with an expansive and highly variable clinical presentation caused by abnormal glycosylation of proteins and lipids. Dolichol kinase (DOLK) catalyzes the final step in biosynthesis of dolichol phosphate (Dol-P), which is the oligosaccharide carrier required for protein N-glycosylation. Human DOLK deficiency, also known as DOLK-CDG or CDG-Im, results in a syndrome that has been reported to manifest with dilated cardiomyopathy of variable severity. A male neonate born to non-consanguineous parents of Palestinian origin presented with dysmorphic features, genital abnormalities, talipes equinovarus, and severe, refractory generalized seizures. Additional multi-systemic manifestations developed …

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins

Dartmouth Scholarship

Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.

Methods: Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from …

Dopaminergic Modulation Of Memory And Affective Processing In Parkinson Depression, Lee X. Blonder, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Anders H. Andersen, Charles D Smith, Frederick A. Schmitt

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Depression is common in Parkinson's disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson's disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson's disease participated. Ten of these patients were depressed according …

Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd

Department of Cancer Biology Faculty Papers

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability …

Findings From The Peutz-Jeghers Syndrome Registry Of Uruguay, Asadur Tchekmedyian, Christopher I. Amos, Sherri J. Bale, Dakai Zhu, Stefan Arold, Joaquin Berrueta, Natalie Nabon, Thomas Mcgarrity

Dartmouth Scholarship

Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal …

Short Duration Waveforms Recorded Extracellularly From Freely Moving Rats Are Representative Of Axonal Activity, Ashlee A. Robbins, Steven E. Fox, Gregory L. Holmes, Rod C. Scott, Jeremy M. Barry

Dartmouth Scholarship

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation …

Diet And Toenail Arsenic Concentrations In A New Hampshire Population With Arsenic-Containing Water, Kathryn L. Cottingham, Roxanne Karimi, Joann F. Gruber, M Scot Zens, Vicki Sayarath, Carol L. Folt, Tracy Punshon, J. Steven Morris, Margaret R. Karagas

Dartmouth Scholarship

Background: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest.

Methods: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) …

Socially Excluded Individuals Fail To Recruit Medial Prefrontal Cortex For Negative Social Scenes, Katherine E. Powers, Dylan D. Wagner, Catherine J. Norris, Todd F. Heatherton

Dartmouth Scholarship

Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people's responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex …

The Dartmouth Database Of Children’S Faces: Acquisition And Validation Of A New Face Stimulus Set, Kirsten A. Dalrymple, Jesse Gomez, Brad Duchaine

Dartmouth Scholarship

Facial identity and expression play critical roles in our social lives. Faces are therefore frequently used as stimuli in a variety of areas of scientific research. Although several extensive and well-controlled databases of adult faces exist, few databases include children’s faces. Here we present the Dartmouth Database of Children’s Faces, a set of photographs of 40 male and 40 female Caucasian children between 6 and 16 years-of-age. Models posed eight facial expressions and were photographed from five camera angles under two lighting conditions. Models wore black hats and black gowns to minimize extra-facial variables. To validate the images, independent raters …

The Composite Effect For Inverted Faces Is Reliable At Large Sample Sizes And Requires The Basic Face Configuration, Tirta Susilo, Constantin Rezlescu, Bradley Duchaine

Dartmouth Scholarship

Abstract The absence of the face composite effect (FCE) for inverted faces is often considered evidence that holistic processing operates only on upright faces. However, such absence might be explained by power issues: Most studies that have failed to find the inverted FCE tested 24 participants or less. Here we find that the inverted FCE exists reliably when we tested at least 60 participants. The inverted FCE was ∼ 18% the size of the upright FCE, and it was unaffected by testing order: It did not matter whether participants did the upright condition first (Experiment 1, n = 64) or …

Household Wealth And Neurocognitive Development Disparities Among School-Aged Children In Nepal., Shivani A Patel, Laura E Murray-Kolb, Steven C Leclerq, Subarna K Khatry, James M. Tielsch, Joanne Katz, Parul Christian

Global Health Faculty Publications

BACKGROUND: Wealth disparities in child developmental outcomes are well documented in developed countries. We sought to (1) describe the extent of wealth-based neurocognitive development disparities and (2) examine potential mediating factors of disparities among a population-based cohort of children in rural Nepal.

METHODS: We investigated household wealth-based differences in intellectual, executive and motor function of n = 1692 children aged between 7 and 9 years in Nepal. Using linear mixed models, wealth-based differences were estimated before and after controlling for child and household demographic characteristics. We further examined wealth-based differences adjusted for three sets of mediators: child nutritional status, home …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Randomized Clinical Trial Examining Duration Of Voucher-Based Reinforcement Therapy For Cocaine Abstinence., Kimberly C Kirby, Carolyn M Carpenedo, Karen L Dugosh, Beth J Rosenwasser, Lois A Benishek, Alicia Janik, Rachel Keashen, Elena Bresani, Kenneth Silverman

College of Science & Mathematics Departmental Research

BACKGROUND: This is the first study to systematically manipulate duration of voucher-based reinforcement therapy (VBRT) to see if extending the duration increases abstinence during and following VBRT.

METHODS: We randomized cocaine-dependent methadone-maintained adults to Standard (12 weeks; n=62) or Extended (36 weeks; n=68) VBRT and provided escalating voucher amounts contingent upon urinalysis verification of cocaine abstinence. Urinalysis was scheduled at least every 2 weeks during the 48-week study and more frequently during VBRT (3/week) and 12 weeks of Aftercare (2/week).

RESULTS: Extended VBRT produced longer durations of continuous cocaine abstinence during weeks 1-24 (5.7 vs 2.7 weeks; p=0.003) and proportionally …

Increased Abundance Of Frost Mrna During Recovery From Cold Stress Is Not Essential For Cold Tolerance In Adult Drosophila Melanogaster., H Udaka, A Percival-Smith, B J Sinclair

Biology Publications

Frost (Fst) is a candidate gene associated with the response to cold in Drosophila melanogaster because Fst mRNA accumulation increases during recovery from low temperature exposure. We investigated the contribution of Fst expression to chill-coma recovery time, acute cold tolerance and rapid cold hardening (RCH) in adult D. melanogaster by knocking down Fst mRNA expression using GAL4/UAS-mediated RNA interference. In this experiment, four UAS-Fst and one tubulin-GAL4 lines were used. We predicted that if Fst is essential for cold tolerance phenotypes, flies with low Fst mRNA levels should be less cold tolerant than flies with normal levels of cold-induced Fst …

Diabetes And Prostate Cancer Screening In Black And White Men, Maureen Sanderson, Jay H. Fowke, Loren Lipworth, Xijing Han, Flora Ukoli, Ann L. Coker, William J. Blot, Margaret K. Hargreaves

CRVAW Faculty Journal Articles

PURPOSE: Prior studies conducted primarily among white men find a reduced risk of prostate cancer associated with time since developing diabetes. While biologic explanations are plausible, the association may in part arise from more frequent prostate cancer screening among those with a diabetes diagnosis. The purpose of the present study was to investigate the association between diabetes and prostate cancer screening.

METHODS: We examined differences in prostate cancer screening (prostate-specific antigen and/or digital rectal examination) testing practices after a diabetes diagnosis among lower-income persons living in the southeastern United States and enrolled in the Southern Community Cohort Study between 2002 …

A Population-Based Case–Control Study Of Urinary Arsenic Species And Squamous Cell Carcinoma In New Hampshire, Usa, Diane Gilbert-Diamond, Zhigang Li, Ann E. Perry, Steven K. Spencer, A Jay Gandolfi, Margaret R. Karagas

Dartmouth Scholarship

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States.

Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population.

Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and …

Outdated Dermatologic Drug Samples And Obligations To The Patient., Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

CASE SCENARIO

A 37-year-old man with a slightly raised, red, scaly patch on his left arm is seen in the clinic of an academic teaching hospital by a young dermatologist. Following examination and biopsy, he is found to have squamous cell carcinoma in situ. The patient was recently laid off from work and had lost access to his health insurance. He is struggling to make ends meet for his family, so it would be difficult for him to cover any extraneous health-related expenses. Upon relaying this information to the dermatologist, the patient is provided with a full course of 5-fluorouracil …

Thioredoxin Reductase Was Nitrated In The Aging Heart After Myocardial Ischemia/Reperfusion., Ke Wang, Jie Zhang, Xiaoliang Wang, Xin Liu, Lin Zuo, Kehua Bai, Jianyu Shang, Lu Ma, Teng Liu, Li Wang, Wen Wang, Xin-Liang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young …

The Flexible Fairness: Equality, Earned Entitlement, And Self-Interest, Chunliang Feng, Yi Luo, Ruolei Gu, Lucas S. Broster, Xueyi Shen, Tengxiang Tian, Yue-Jia Luo, Frank Krueger

Behavioral Science Faculty Publications

The current study explored whether earned entitlement modulated the perception of fairness in three experiments. A preliminary resource earning task was added before players decided how to allocate the resource they jointly earned. Participants' decision in allocation, their responses to equal or unequal offers, whether advantageous or disadvantageous, and subjective ratings of fairness were all assessed in the current study. Behavioral results revealed that participants proposed more generous offers and showed enhanced tolerance to disadvantageous unequal offers from others when they performed worse than their presumed "partners," while the reverse was true in the better-performance condition. The subjective ratings also …

Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester

Dartmouth Scholarship

Background:

Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from …

The Effect Of Malnutrition On Patients Undergoing Elective Joint Arthroplasty., Ronald Huang, Md, Max Greenky, Bs, Glenn J. Kerr, Md, Mathew S. Austin, Md, Javad Parvizi, Md, Frcs

Rothman Institute Papers

Malnutrition has been linked to serious complications in patients undergoing elective total joint arthroplasty (TJA). This study prospectively evaluated 2,161 patients undergoing elective TJA for malnutrition as defined by either an abnormal serum albumin or transferrin. The overall incidence of malnutrition was 8.5% (184 of 2,161) and the rate of overall complications in the malnourished group was 12% as compared to 2.9% in patients with normal parameters (P55years-old undergoing TJA and is associated with a significant increase in post-operative complications.

Equivalence Of Students' Scores On Timed And Untimed Anatomy Practical Examinations., Guiyan Zhang, Bruce Fenderson, Richard R Schmidt, J J. Veloski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Untimed examinations are popular with students because there is a perception that first impressions may be incorrect, and that difficult questions require more time for reflection. In this report, we tested the hypothesis that timed anatomy practical examinations are inherently more difficult than untimed examinations. Students in the Doctor of Physical Therapy program at Thomas Jefferson University were assessed on their understanding of anatomic relationships using multiple-choice questions. For the class of 2012 (n = 46), students were allowed to circulate freely among 40 testing stations during the 40-minute testing session. For the class of 2013 (n = 46), students …

Self-Regulatory Depletion Increases Emotional Reactivity In The Amygdala, Dylan D. Wagner, Todd F. Heatherton

Dartmouth Scholarship

The ability to self-regulate can become impaired when people are required to engage in successive acts of effortful self-control, even when self-control occurs in different domains. Here, we used functional neuroimaging to test whether engaging in effortful inhibition in the cognitive domain would lead to putative dysfunction in the emotional domain. Forty-eight participants viewed images of emotional scenes during functional magnetic resonance imaging in two sessions that were separated by a challenging attention control task that required effortful inhibition (depletion group) or not (control group). Compared to the control group, depleted participants showed increased activity in the left amygdala to …

Tricellulin Deficiency Affects Tight Junction Architecture And Cochlear Hair Cells, Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin

Physiology Faculty Publications

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while …