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Potential Role Of Orexin And Sleep Modulation In The Pathogenesis Of Alzheimer's Disease, Jee Hoon Roh, Hong Jiang, Mary Beth Finn, Floy R. Stewart, Thomas E. Mahan, John R. Cirrito, Ashish Heda, B. Joy Snider, Mingjie Li, Masashi Yanagisawa, Luis De Lecea, David M. Holtzman Jan 2014

Potential Role Of Orexin And Sleep Modulation In The Pathogenesis Of Alzheimer's Disease, Jee Hoon Roh, Hong Jiang, Mary Beth Finn, Floy R. Stewart, Thomas E. Mahan, John R. Cirrito, Ashish Heda, B. Joy Snider, Mingjie Li, Masashi Yanagisawa, Luis De Lecea, David M. Holtzman

Open Access Publications

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. …


Overfishing And The Replacement Of Demersal Finfish By Shellfish: An Example From The English Channel., Carlotta Molfese, Doug Beare, Jason M. Hall-Spencer Jan 2014

Overfishing And The Replacement Of Demersal Finfish By Shellfish: An Example From The English Channel., Carlotta Molfese, Doug Beare, Jason M. Hall-Spencer

School of Biological and Marine Sciences

The worldwide depletion of major fish stocks through intensive industrial fishing is thought to have profoundly altered the trophic structure of marine ecosystems. Here we assess changes in the trophic structure of the English Channel marine ecosystem using a 90-year time-series (1920-2010) of commercial fishery landings. Our analysis was based on estimates of the mean trophic level (mTL) of annual landings and the Fishing-in-Balance index (FiB). Food webs of the Channel ecosystem have been altered, as shown by a significant decline in the mTL of fishery landings whilst increases in the FiB index suggest increased fishing effort and fishery expansion. …


Comparison Of Intermittent And Continuous Exposures To Inorganic Mercury In The Mussel, Mytilus Edulis: Accumulation And Sub-Lethal Physiological Effects., D Amachree, Aj Moody, Rd Handy Jan 2014

Comparison Of Intermittent And Continuous Exposures To Inorganic Mercury In The Mussel, Mytilus Edulis: Accumulation And Sub-Lethal Physiological Effects., D Amachree, Aj Moody, Rd Handy

School of Biological and Marine Sciences

Aquatic organisms are often subject to intermittent exposure to pollutants in real ecosystems. This study aimed to compare mercury accumulation and the physiological responses of mussels, Mytilus edulis during continuous and intermittent exposure to the metal. Mussels were treated in a semi-static, triplicated design to either a control (no added Hg) or 50 µg l(-1) Hg as HgCl2 in continuous (daily) or intermittent (2 day exposure, 2 days in clean seawater alternately) exposure for 14 days. A time-dependent increase in Hg accumulation was observed in the continuous exposure, while the intermittent treatment showed step-wise changes in Hg concentrations with the …


Combining Motion Analysis And Microfluidics--A Novel Approach For Detecting Whole-Animal Responses To Test Substances., Tabitha S. Rudin-Bitterli, Oliver Tills, John I. Spicer, Phil F. Culverhouse, Eric M. Wielhouwer, Michael K. Richardson, Simon D. Rundle Jan 2014

Combining Motion Analysis And Microfluidics--A Novel Approach For Detecting Whole-Animal Responses To Test Substances., Tabitha S. Rudin-Bitterli, Oliver Tills, John I. Spicer, Phil F. Culverhouse, Eric M. Wielhouwer, Michael K. Richardson, Simon D. Rundle

School of Biological and Marine Sciences

Small, early life stages, such as zebrafish embryos are increasingly used to assess the biological effects of chemical compounds in vivo. However, behavioural screens of such organisms are challenging in terms of both data collection (culture techniques, drug delivery and imaging) and data evaluation (very large data sets), restricting the use of high throughput systems compared to in vitro assays. Here, we combine the use of a microfluidic flow-through culture system, or BioWell plate, with a novel motion analysis technique, (sparse optic flow - SOF) followed by spectral analysis (discrete Fourier transformation - DFT), as a first step towards automating …


Effects Of Dietary Β-(1,3)(1,6)-D-Glucan Supplementation On Growth Performance, Intestinal Morphology And Haemato-Immunological Profile Of Mirror Carp (Cyprinus Carpio L.)., H. Kühlwein, D. L. Merrifield, M. D. Rawling, A. D. Foey, S. J. Davies Jan 2014

Effects Of Dietary Β-(1,3)(1,6)-D-Glucan Supplementation On Growth Performance, Intestinal Morphology And Haemato-Immunological Profile Of Mirror Carp (Cyprinus Carpio L.)., H. Kühlwein, D. L. Merrifield, M. D. Rawling, A. D. Foey, S. J. Davies

School of Biological and Marine Sciences

In recent years, aquaculture research has focused on probiotics, prebiotics, and β-glucans, in order to improve health status and growth performance. Information regarding the effects of β-glucan on growth performance and intestinal immunity of mirror carp (Cyprinus carpio L.) is scarce. An experiment was therefore conducted to investigate the effects of a yeast β-glucan preparation (MacroGard(®) ) on growth performance, intestinal morphology and haemato-immunological indices of mirror carp. Carp (initial weight 11.1 ± 0.0 g) were fed highly purified diets supplemented with 0% (control), 0.1%, 1% or 2% MacroGard(®) for 8 weeks. Fish fed diets containing 1% and 2% MacroGard(®) …


Minimal Effects Of Waterborne Exposure To Single-Walled Carbon Nanotubes On Behaviour And Physiology Of Juvenile Rainbow Trout (Oncorhynchus Mykiss)., D Boyle, Je Fox, Jm Akerman, Ka Sloman, Tb Henry, Rd Handy Jan 2014

Minimal Effects Of Waterborne Exposure To Single-Walled Carbon Nanotubes On Behaviour And Physiology Of Juvenile Rainbow Trout (Oncorhynchus Mykiss)., D Boyle, Je Fox, Jm Akerman, Ka Sloman, Tb Henry, Rd Handy

School of Biological and Marine Sciences

Fish behaviours are often considered to be sensitive endpoints of waterborne contaminants, but little attention has been given to engineered nanomaterials. The present study aimed to determine the locomotor and social behaviours of rainbow trout (Oncorhynchus mykiss) during waterborne exposure to single-walled carbon nanotubes (SWCNTs), and to ascertain the physiological basis for any observed effects. Dispersed stock suspensions of SWCNTs were prepared by stirring in sodium dodecyl sulphate (SDS), an anionic surfactant, on an equal w/w basis. Trout were exposed to control (no SWCNT or SDS), 0.25 mg L(-1) SDS (dispersant control), or 0.25 mg L(-1) of SWCNT for 10 …


The Effects Of A Competitor On The Foraging Behaviour Of The Shore Crab Carcinus Maenas., Lj Chakravarti, Pa Cotton Jan 2014

The Effects Of A Competitor On The Foraging Behaviour Of The Shore Crab Carcinus Maenas., Lj Chakravarti, Pa Cotton

School of Biological and Marine Sciences

Optimal Diet Theory suggests that individuals make foraging decisions that maximise net energy intake. Many studies provide qualitative support for this, but factors such as digestive constraints, learning, predation-risk and competition can influence foraging behaviour and lead to departures from quantitative predictions. We examined the effects of intraspecific competition within a classic model of optimal diet--the common shore crab, Carcinus maenas, feeding on the mussel, Mytilus edulis. Unexpectedly, we found that breaking time (Tb), eating time (Te), and handling time (Th) all decreased significantly in the presence of a conspecific. Reduced handling time in the presence of a competitor resulted …


Going Native? Flower Use By Bumblebees In English Urban Gardens., Mick E. Hanley, Amanda J. Awbi, Miguel Franco Jan 2014

Going Native? Flower Use By Bumblebees In English Urban Gardens., Mick E. Hanley, Amanda J. Awbi, Miguel Franco

School of Biological and Marine Sciences

BACKGROUND AND AIMS: Although urban gardens provide opportunities for pollinators in an otherwise inhospitable environment, most garden plants are not native to the recipient biogeographical region and their value to local pollinators is disputed. This study tested the hypothesis that bumblebees foraging in English urban gardens preferentially visited sympatric Palaearctic-range plants over species originating outside their native range. METHODS: Twenty-seven surveys of flower availability and bumblebee visitation (Bombus spp.) were conducted over a 3-month summer period. Plants were categorized according to whether they were native British, Palaearctic or non-Palaearctic in origin. A phylogeny of the 119 plant species recorded was …


Differential Responses Of Emergent Intertidal Coral Reef Fauna To A Large-Scale El-Niño Southern Oscillation Event: Sponge And Coral Resilience., Francisco Kelmo, James J. Bell, Simone Souza Moraes, Rilza Da Costa Tourinho Gomes, Eduardo Mariano-Neto, Martin J. Attrill Jan 2014

Differential Responses Of Emergent Intertidal Coral Reef Fauna To A Large-Scale El-Niño Southern Oscillation Event: Sponge And Coral Resilience., Francisco Kelmo, James J. Bell, Simone Souza Moraes, Rilza Da Costa Tourinho Gomes, Eduardo Mariano-Neto, Martin J. Attrill

School of Biological and Marine Sciences

There is a paucity of information on the impacts of the 1997-8 El Niño event and subsequent climatic episodes on emergent intertidal coral reef assemblages. Given the environmental variability intertidal reefs experience, such reefs may potentially be more resilient to climatic events and provide important insights into the adaptation of reef fauna to future ocean warming. Here we report the results of a 17-year (1995-2011) biodiversity survey of four emergent coral reef ecosystems in Bahia, Brazil, to assess the impact of a major El Niño event on the reef fauna, and determine any subsequent recovery. The densities of two species …


Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton Jan 2014

Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …


Insulin Acutely Improves Mitochondrial Function Of Rat And Human Skeletal Muscle By Increasing Coupling Efficiency Of Oxidative Phosphorylation., Raid B. Nisr, Charles Affourtit Jan 2014

Insulin Acutely Improves Mitochondrial Function Of Rat And Human Skeletal Muscle By Increasing Coupling Efficiency Of Oxidative Phosphorylation., Raid B. Nisr, Charles Affourtit

School of Biomedical Sciences

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the …


Pax Genes: Regulators Of Lineage Specification And Progenitor Cell Maintenance, Judith A. Blake, Mel R. Ziman Jan 2014

Pax Genes: Regulators Of Lineage Specification And Progenitor Cell Maintenance, Judith A. Blake, Mel R. Ziman

Research outputs 2014 to 2021

Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We …


Novel Roles For Actin In Mitochondrial Fission, Anna L. Hatch, Pinar S. Gurel, Henry N. Higgs Jan 2014

Novel Roles For Actin In Mitochondrial Fission, Anna L. Hatch, Pinar S. Gurel, Henry N. Higgs

Dartmouth Scholarship

Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial …


Benthic And Pelagic Pathways Of Methylmercury Bioaccumulation In Estuarine Food Webs Of The Northeast United States, Celia Y. Chen, Mark E. Borsuk, Deenie M. Bugge, Terill Hollweg Jan 2014

Benthic And Pelagic Pathways Of Methylmercury Bioaccumulation In Estuarine Food Webs Of The Northeast United States, Celia Y. Chen, Mark E. Borsuk, Deenie M. Bugge, Terill Hollweg

Dartmouth Scholarship

Methylmercury (MeHg) is a contaminant of global concern that bioaccumulates and bioamagnifies in marine food webs. Lower trophic level fauna are important conduits of MeHg from sediment and water to estuarine and coastal fish harvested for human consumption. However, the sources and pathways of MeHg to these coastal fisheries are poorly known particularly the potential for transfer of MeHg from the sediment to biotic compartments. Across a broad gradient of human land impacts, we analyzed MeHg concentrations in food webs at ten estuarine sites in the Northeast US (from the Hackensack Meadowlands, NJ to the Gulf of Maine). MeHg concentrations …


Obesity Reduces Left Ventricular Strains, Torsion, And Synchrony In Mouse Models: A Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance Study, Sage P. Kramer, David K. Powell, Christopher M. Haggerty, Cassi M. Binkley, Andrea C. Mattingly, Lisa A. Cassis, Frederick H. Epstein, Brandon K. Fornwalt Dec 2013

Obesity Reduces Left Ventricular Strains, Torsion, And Synchrony In Mouse Models: A Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance Study, Sage P. Kramer, David K. Powell, Christopher M. Haggerty, Cassi M. Binkley, Andrea C. Mattingly, Lisa A. Cassis, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

BACKGROUND: Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV).

METHODS: Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on …


Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak Dec 2013

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …


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 Dec 2013

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 Enhanced-Magnetic Resonance Imaging As A Surrogate To Map Verteporfin Delivery In Photodynamic Therapy, Kimberley S. Samkoe, Amber Bryant, Jason R. Gunn, Stephen P. Pereira, Tayyaba Hasan, Brian W. Pogue Dec 2013

Contrast Enhanced-Magnetic Resonance Imaging As A Surrogate To Map Verteporfin Delivery In Photodynamic Therapy, Kimberley S. Samkoe, Amber Bryant, Jason R. Gunn, Stephen P. Pereira, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The use of in vivo contrast-enhanced magnetic resonance (MR) imaging as a surrogate for photosensitizer (verteporfin) dosimetry in photodynamic therapy of pancreas cancer is demonstrated by correlating MR contrast uptake to ex vivo fluorescence images on excised tissue. An orthotopic pancreatic xenograft mouse model was used for the study. A strong correlation ([i]r=0.57 ) was found for bulk intensity measurements of T1-weighted gadolinium enhancement and verteporfin fluorescence in the tumor region of interest. The use of contrast-enhanced MR imaging shows promise as a method for treatment planning and photosensitizer dosimetry in human photodynamic therapy (PDT) of pancreas …


Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman Dec 2013

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.


Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott Dec 2013

Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott

Dartmouth Scholarship

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group …


Adiponectin Inhibits Oxidative/Nitrative Stress During Myocardial Ischemia And Reperfusion Via Pka Signaling., Yanqing Zhang, Xiao-Liang Wang, Jianli Zhao, Ya-Jing Wang, Wayne Bond Lau, Yue-Xing Yuan, Er-He Gao, Walter J. Koch, Xin-Liang Ma Dec 2013

Adiponectin Inhibits Oxidative/Nitrative Stress During Myocardial Ischemia And Reperfusion Via Pka Signaling., Yanqing Zhang, Xiao-Liang Wang, Jianli Zhao, Ya-Jing Wang, Wayne Bond Lau, Yue-Xing Yuan, Er-He Gao, Walter J. Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

The cardioprotective effects of adiponectin (APN) against myocardial ischemia/reperfusion (MI/R) injury are well known. However, comprehension of the mechanisms mediating intracellular APN signaling remains incomplete. We recently demonstrate the antioxidant/antinitrative effects of APN are not dependent on AMPK. Protein kinase A (PKA) has been previously shown to be activated by APN, with uncertain relevance to APN cardiac protection. The current study determined whether the antioxidative/antinitrative effect of APN is mediated by PKA. Administration of APN (2 μg/g) 10 min before reperfusion significantly enhanced cardiac PKA activity, reduced oxidative stress, and decreased infarct size. Knockdown of cardiac PKA expression (PKA-KD) by …


Defects In Synapse Structure And Function Precede Motor Neuron Degeneration In Drosophila Models Of Fus-Related Als., Mohammad Shahidullah, Sylvain J Le Marchand, Hong Fei, Jiaming Zhang, Udai Bhan Pandey, Matthew B. Dalva, Piera Pasinelli, Irwin B. Levitan Dec 2013

Defects In Synapse Structure And Function Precede Motor Neuron Degeneration In Drosophila Models Of Fus-Related Als., Mohammad Shahidullah, Sylvain J Le Marchand, Hong Fei, Jiaming Zhang, Udai Bhan Pandey, Matthew B. Dalva, Piera Pasinelli, Irwin B. Levitan

Department of Neuroscience Faculty Papers

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads invariably to fatal paralysis associated with motor neuron degeneration and muscular atrophy. One gene associated with ALS encodes the DNA/RNA-binding protein Fused in Sarcoma (FUS). There now exist two Drosophila models of ALS. In one, human FUS with ALS-causing mutations is expressed in fly motor neurons; in the other, the gene cabeza (caz), the fly homolog of FUS, is ablated. These FUS-ALS flies exhibit larval locomotor defects indicative of neuromuscular dysfunction and early death. The locus and site of initiation of this neuromuscular dysfunction remain unclear. We show here …


Use Of Irf-3 And/Or Irf-7 Knockout Mice To Study Viral Pathogenesis: Lessons From A Murine Retrovirus-Induced Aids Model, Megan A. O'Connor, William R. Green Dec 2013

Use Of Irf-3 And/Or Irf-7 Knockout Mice To Study Viral Pathogenesis: Lessons From A Murine Retrovirus-Induced Aids Model, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Interferon regulatory factor (IRF) regulation of the type I interferon response has not been extensively explored in murine retroviral infections. IRF-3(-/-) and select IRF-3/7(-/-) mice were resistant to LP-BM5-induced pathogenesis. However, further analyses strongly suggested that resistance could be attributed to strain 129-specific contamination of the known retrovirus resistance gene Fv1. Therefore, caution should be taken when interpreting phenotypes observed in these knockout mice, as strain 129-derived genetic polymorphisms may explain observed differences.


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 Dec 2013

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 …


Neuronal Clearance Of Amyloid-Β By Endocytic Receptor Lrp1, Takahisa Kanekiyo, John R. Cirrito, Chia-Chen Liu, Mitsuru Shinohara, Jie Li, Dorothy R. Schuler, Motoko Shinohara, David M. Holtzman, Guojun Bu Dec 2013

Neuronal Clearance Of Amyloid-Β By Endocytic Receptor Lrp1, Takahisa Kanekiyo, John R. Cirrito, Chia-Chen Liu, Mitsuru Shinohara, Jie Li, Dorothy R. Schuler, Motoko Shinohara, David M. Holtzman, Guojun Bu

Open Access Publications

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population. Accumulation, aggregation, and deposition of amyloid-β (Aβ) peptides generated through proteolytic cleavage of amyloid precursor protein (APP) are likely initiating events in the pathogenesis of AD. While Aβ production is accelerated in familial AD, increasing evidence indicates that impaired clearance of Aβ is responsible for late-onset AD. Because Aβ is mainly generated in neurons, these cells are predicted to have the highest risk of encountering Aβ among all cell types in the brain. However, it is still unclear whether they are also involved in Aβ clearance. …


In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller Dec 2013

In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller

Dartmouth Scholarship

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to devel


The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea Dec 2013

The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …


Children's Ideas About The Moral Standing And Social Welfare Of Non-Human Species, Gail F. Melson Dec 2013

Children's Ideas About The Moral Standing And Social Welfare Of Non-Human Species, Gail F. Melson

The Journal of Sociology & Social Welfare

Moral and social welfare issues related to humane treatment of animals confront children and continue to be important societal issues through adulthood. Despite this, children's moral reasoning about animals has been largely ignored. This paper addresses six questions concerning how children reason morally about non-human animals: (1) How do children think about the moral claims of animals? Is there a developmental progression in such reasoning? (2) How does moral reasoning about animals differ from moral reasoning about other life forms-plants and ecological systems? (3) What is the relation, if any, between children's moral reasoning about non-human animals and their moral …


Staff Views On The Involvement Of Animals In Care Home Life: An Exploratory Study, Jane Fossey, Vanessa Lawrence Dec 2013

Staff Views On The Involvement Of Animals In Care Home Life: An Exploratory Study, Jane Fossey, Vanessa Lawrence

The Journal of Sociology & Social Welfare

This qualitative study examined the views of one hundred and eight care staff working in fifteen care homes in the United Kingdom about the involvement Of animals in the care practices of the home. The perceived benefits and difficulties ofdelivering person-centered and psychosocial care, including the involvement of animals were explored. The findings describe the main themes related to animal involvement elicited from staff. These include the benefits to residents' well-being and the varying challenges that visiting and residential animals pose. The implicationsfor practice are discussed and the need for clearer information for care home teams is identified.


Occupational Injuries On Thoroughbred Horse Farms: A Description Of Latino And Non-Latino Workers' Experiences, Jennifer E. Swanberg, Jessica M. Clouser, Susan C. Westneat, Mary W. Marsh, Deborah B. Reed Nov 2013

Occupational Injuries On Thoroughbred Horse Farms: A Description Of Latino And Non-Latino Workers' Experiences, Jennifer E. Swanberg, Jessica M. Clouser, Susan C. Westneat, Mary W. Marsh, Deborah B. Reed

Health, Behavior & Society Faculty Publications

Animal production is a dangerous industry and increasingly reliant on a Latino workforce. Within animal production, little is known about the risks or the occupational hazards of working on farms involved in various aspects of thoroughbred horse breeding. Extant research suggests that horse workers are at risk of musculoskeletal and respiratory symptoms, kicks, and other injuries. However, limited known research has examined the experiences of the industry's workers, including immigrant workers, despite their prominence and increased vulnerability. Using data collected from thoroughbred farm representatives via a phone-administered survey, a 2-hour face-to-face semi-structured interview, and farm injury logs, this article identifies …