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Articles 5761 - 5790 of 7166

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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 …

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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. …

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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 …

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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 …

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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.

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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 Nov 2013

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 …

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Implication Of Lateral Genetic Transfer In The Emergence Of Aeromonas Hydrophila Isolates Of Epidemic Outbreaks In Channel Catfish., Mohammad J. Hossain, Geoffrey C. Waldbieser, Dawei Sun, Nancy K. Capps, William B. Hemstreet, Kristen Carlisle, Matt J. Griffin, Lester Khoo, Andrew E. Goodwin, Tad S. Sonstegard, Steven Schroeder, Karl Hayden, Joseph C. Newton, Jeffery S. Terhune, Mark R. Liles Nov 2013

Implication Of Lateral Genetic Transfer In The Emergence Of Aeromonas Hydrophila Isolates Of Epidemic Outbreaks In Channel Catfish., Mohammad J. Hossain, Geoffrey C. Waldbieser, Dawei Sun, Nancy K. Capps, William B. Hemstreet, Kristen Carlisle, Matt J. Griffin, Lester Khoo, Andrew E. Goodwin, Tad S. Sonstegard, Steven Schroeder, Karl Hayden, Joseph C. Newton, Jeffery S. Terhune, Mark R. Liles

CVM Publications

To investigate the molecular basis of the emergence of Aeromonas hydrophila responsible for an epidemic outbreak of motile aeromonad septicemia of catfish in the Southeastern United States, we sequenced 11 A. hydrophila isolates that includes five reference and six recent epidemic isolates. Comparative genomics revealed that recent epidemic A. hydrophila isolates are highly clonal, whereas reference isolates are greatly diverse. We identified 55 epidemic-associated genetic regions with 313 predicted genes that are present in epidemic isolates but absent from reference isolates and 35% of these regions are located within genomic islands, suggesting their acquisition through lateral gene transfer. The epidemic-associated …

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Molecular Cloning And Characterization Of A P-Glycoprotein From The Diamondback Moth, Plutella Xylostella (Lepidoptera: Plutellidae), Lixia Tian, Jiaqiang Yang, Wenjie Hou, Baoyun Xu, Wen Xie, Shaoli Wang, Youjun Zhang, Xuguo Zhou, Qingjun Wu Nov 2013

Molecular Cloning And Characterization Of A P-Glycoprotein From The Diamondback Moth, Plutella Xylostella (Lepidoptera: Plutellidae), Lixia Tian, Jiaqiang Yang, Wenjie Hou, Baoyun Xu, Wen Xie, Shaoli Wang, Youjun Zhang, Xuguo Zhou, Qingjun Wu

Entomology Faculty Publications

Macrocyclic lactones such as abamectin and ivermectin constitute an important class of broad-spectrum insecticides. Widespread resistance to synthetic insecticides, including abamectin and ivermectin, poses a serious threat to the management of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), a major pest of cruciferous plants worldwide. P-glycoprotein (Pgp), a member of the ABC transporter superfamily, plays a crucial role in the removal of amphiphilic xenobiotics, suggesting a mechanism for drug resistance in target organisms. In this study, PxPgp1, a putative Pgp gene from P. xylostella, was cloned and characterized. The open reading frame (ORF) of PxPgp1 consists of 3774 …

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Novel Pancreatic Cancer Cell Lines Derived From Genetically Engineered Mouse Models Of Spontaneous Pancreatic Adenocarcinoma: Applications In Diagnosis And Therapy., María P. Torres, Satyanarayana Rachagani, Joshua J. Souchek, Kavita Mallya, Sonny L. Johansson, Surinder K. Batra Nov 2013

Novel Pancreatic Cancer Cell Lines Derived From Genetically Engineered Mouse Models Of Spontaneous Pancreatic Adenocarcinoma: Applications In Diagnosis And Therapy., María P. Torres, Satyanarayana Rachagani, Joshua J. Souchek, Kavita Mallya, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) remains one of the most lethal human malignancies with poor prognosis. Despite all advances in preclinical research, there have not been significant translation of novel therapies into the clinics. The development of genetically engineered mouse (GEM) models that produce spontaneous pancreatic adenocarcinoma (PDAC) have increased our understanding of the pathogenesis of the disease. Although these PDAC mouse models are ideal for studying potential therapies and specific genetic mutations, there is a need for developing syngeneic cell lines from these models. In this study, we describe the successful establishment and characterization of three cell lines derived from two …

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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 Nov 2013

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 …

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Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman Nov 2013

Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …

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Drawing Lines At The Sand: Evidence For Functional Vs. Visual Reef Boundaries In Temperate Marine Protected Areas., E. V. Sheehan, S. L. Cousens, S. J. Nancollas, C. Stauss, J. Royle, M. J. Attrill Nov 2013

Drawing Lines At The Sand: Evidence For Functional Vs. Visual Reef Boundaries In Temperate Marine Protected Areas., E. V. Sheehan, S. L. Cousens, S. J. Nancollas, C. Stauss, J. Royle, M. J. Attrill

School of Biological and Marine Sciences

Marine Protected Areas (MPAs) can either protect all seabed habitats within them or discrete features. If discrete features within the MPA are to be protected humans have to know where the boundaries are. In Lyme Bay, SW England a MPA excluded towed demersal fishing gear from 206 km(2) to protect rocky reef habitats and the associated species. The site comprised a mosaic of sedimentary and reef habitats and so 'non reef' habitat also benefited from the MPA. Following 3 years protection, video data showed that sessile Reef Associated Species (RAS) had colonised sedimentary habitat indicating that 'reef' was present. This …

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Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey Nov 2013

Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Successful memory involves not only remembering information over time, but also keeping memories distinct and less confusable. The computational process for making representations for similar input patterns more distinct from each other has been referred to as "pattern separation." In this work, we developed a set of behavioral conditions that allowed us to manipulate the load for pattern separation at different stages of memory. Thus, we provide experimental evidence that a brain-derived neurotrophic factor (BDNF)-dependent pattern separation process occurs during the encoding/storage/consolidation, but not the retrieval stage of memory processing. We also found that a spontaneous increase in BDNF in …

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Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist Nov 2013

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

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Adam17-Mediated Processing Of Tnf-Α Expressed By Antiviral Effector Cd8+ T Cells Is Required For Severe T-Cell-Mediated Lung Injury, Matthew P. Deberge, Kenneth H. Ely, Guang-Shing Cheng, Richard I. Enelow Nov 2013

Adam17-Mediated Processing Of Tnf-Α Expressed By Antiviral Effector Cd8+ T Cells Is Required For Severe T-Cell-Mediated Lung Injury, Matthew P. Deberge, Kenneth H. Ely, Guang-Shing Cheng, Richard I. Enelow

Dartmouth Scholarship

Influenza infection in humans evokes a potent CD8+ T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8+ T-cell expression of TNF-a is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-a is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-a processing in CD8+ T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-a by …

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The Need To Include Animal Protection In Public Health Policies, Aysha Akhtar Nov 2013

The Need To Include Animal Protection In Public Health Policies, Aysha Akhtar

Animal Welfare Collection

Many critical public health issues require non-traditional approaches. Although many novel strategies are used, one approach not widely applied involves improving the treatment of animals. Emerging infectious diseases are pressing public health challenges that could benefit from improving the treatment of animals. Other human health issues, that overlap with animal treatment issues, and that warrant further exploration, are medical research and domestic violence. The diverse nature of these health issues and their connection with animal treatment suggest that there may be other similar intersections. Public health would benefit by including the treatment of animals as a topic of study and …

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Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla Nov 2013

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

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Epigenetic Dominance Of Prion Conformers, Eri Saijo, Hae-Eun Kang, Jifeng Bian, Kristi G. Bowling, Shawn Browning, Sehun Kim, Nora Hunter, Glenn C. Telling Oct 2013

Epigenetic Dominance Of Prion Conformers, Eri Saijo, Hae-Eun Kang, Jifeng Bian, Kristi G. Bowling, Shawn Browning, Sehun Kim, Nora Hunter, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP) primary structures interact with distinct prion conformations to influence pathogenesis, …

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Dmsp Biosynthesis By An Animal And Its Role In Coral Thermal Stress Response, Jean Baptiste Raina, Dianne M. Tapiolas, Sylvain Forêt, Adrian Lutz, David Abrego, Janja Ceh, Francois O. Seneca, Peta L. Clode, David G. Bourne, Bette L. Willis, Cherie A. Motti Oct 2013

Dmsp Biosynthesis By An Animal And Its Role In Coral Thermal Stress Response, Jean Baptiste Raina, Dianne M. Tapiolas, Sylvain Forêt, Adrian Lutz, David Abrego, Janja Ceh, Francois O. Seneca, Peta L. Clode, David G. Bourne, Bette L. Willis, Cherie A. Motti

All Works

Globally, reef-building corals are the most prolific producers of dimethylsulphoniopropionate (DMSP), a central molecule in the marine sulphur cycle and precursor of the climate-active gas dimethylsulphide. At present, DMSP production by corals is attributed entirely to their algal endosymbiont, Symbiodinium. Combining chemical, genomic and molecular approaches, we show that coral juveniles produce DMSP in the absence of algal symbionts. DMSP levels increased up to 54% over time in newly settled coral juveniles lacking algal endosymbionts, and further increases, up to 76%, were recorded when juveniles were subjected to thermal stress. We uncovered coral orthologues of two algal genes recently identified …

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An Expanded View Of The Eukaryotic Cytoskeleton, James B. Moseley Oct 2013

An Expanded View Of The Eukaryotic Cytoskeleton, James B. Moseley

Dartmouth Scholarship

A rich and ongoing history of cell biology research has defined the major polymer systems of the eukaryotic cytoskeleton. Recent studies have identified additional proteins that form filamentous structures in cells and can self-assemble into linear polymers when purified. This suggests that the eukaryotic cytoskeleton is an even more complex system than previously considered. In this essay, I examine the case for an expanded definition of the eukaryotic cytoskeleton and present a series of challenges for future work in this area.

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Identification And Developmental Profiling Of Micrornas In Diamondback Moth, Plutellaxylostella (L.), Pei Liang, Bing Feng, Xuguo Zhou, Xiwu Gao Oct 2013

Identification And Developmental Profiling Of Micrornas In Diamondback Moth, Plutellaxylostella (L.), Pei Liang, Bing Feng, Xuguo Zhou, Xiwu Gao

Entomology Faculty Publications

MicroRNAs (miRNAs) are a group of small RNAs involved in various biological processes through negative regulation of mRNAs at the post-transcriptional level. Although miRNA profiles have been documented in over two dozen insect species, few are agricultural pests. In this study, both conserved and novel miRNAs in the diamondback moth, Plutella xylostella L., a devastating insect pest of cruciferous crops worldwide, were documented. High-throughput sequencing of a small RNA library constructed from a mixed life stages of P. xylostella, including eggs, 1st to 4th (last) instar larvae, pupae and adults, identified 384 miRNAs, of which 174 were P. xylostella specific. …

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Catp-6, A C. Elegans Ortholog Of Atp13a2 Park9, Positively Regulates Gem-1, An Slc16a Transporter, Eric J. Lambie, Pamela J. Tieu, Nadja Lebedeva, Diane L. Church, Barbara Conradt Oct 2013

Catp-6, A C. Elegans Ortholog Of Atp13a2 Park9, Positively Regulates Gem-1, An Slc16a Transporter, Eric J. Lambie, Pamela J. Tieu, Nadja Lebedeva, Diane L. Church, Barbara Conradt

Dartmouth Scholarship

In previous work, we found that gain-of-function mutations that hyperactivate GEM-1 (an SLC16A transporter protein) can bypass the requirement for GON-2 (a TRPM channel protein) during the initiation of gonadogenesis in C. elegans . Consequently, we proposed that GEM-1 might function as part of a Mg 2 + uptake pathway that functions in parallel to GON- 2. In this study, we report that CATP-6, a C. elegans ortholog of the P5B ATPase, ATP13A2 (PARK9), is necessary for gem-1 gain-of-function mutations to suppress the effects of gon-2 inactivation. One possible explanation for this observation is that GEM-1 serves to activate CATP-6, …

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Emerging Trends For Radioimmunotherapy In Solid Tumors., Maneesh Jain, Suprit Gupta, Sukhwinder Kaur, Moorthy P. Ponnusamy, Surinder K. Batra Oct 2013

Emerging Trends For Radioimmunotherapy In Solid Tumors., Maneesh Jain, Suprit Gupta, Sukhwinder Kaur, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of …

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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 Oct 2013

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 …

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Cross-Tolerance And Cross-Talk In The Cold: Relating Low Temperatures To Desiccation And Immune Stress In Insects., Brent J Sinclair, Laura V Ferguson, Golnaz Salehipour-Shirazi, Heath A Macmillan Oct 2013

Cross-Tolerance And Cross-Talk In The Cold: Relating Low Temperatures To Desiccation And Immune Stress In Insects., Brent J Sinclair, Laura V Ferguson, Golnaz Salehipour-Shirazi, Heath A Macmillan

Biology Publications

Multiple stressors, both abiotic and biotic, often are experienced simultaneously by organisms in nature. Responses to these stressors may share signaling pathways ("cross-talk") or protective mechanisms ("cross-tolerance"). Temperate and polar insects that must survive the winter experience low temperatures accompanied by additional abiotic stressors, such as low availability of water. Cold and desiccation have many similar effects at a cellular level, and we present evidence that the cellular mechanisms that protect against cold stress also protect against desiccation, and that the responses to cold and dehydration likely evolved as cross-tolerance. By contrast, there are several lines of evidence suggesting that …

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Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati Oct 2013

Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels …

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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 Oct 2013

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 …

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Continuous Cyclic Mechanical Tension Increases Ank Expression In Endplate Chondrocytes Through The Tgf-Β1 And P38 Pathway, H Xu, X Zhang, H Wang, Y Zhang, Y Shi, X Zhang Sep 2013

Continuous Cyclic Mechanical Tension Increases Ank Expression In Endplate Chondrocytes Through The Tgf-Β1 And P38 Pathway, H Xu, X Zhang, H Wang, Y Zhang, Y Shi, X Zhang

Open Access Publications

The normal ANK protein has a strong influence on anti-calcification. It is known that TGF-β1 is also able to induce extracellular inorganic pyrophosphate (ePPi) elaboration via the TGF-β1-induced ank gene expression and the mitogen-activated protein kinase (MAPK) signaling acts as a downstream effector of TGF-β1. We hypothesized that the expression of the ank gene is regulated by mechanics through TGF-β1-p38 pathway. In this study, we investigated the mechanism of short-time mechanical tension-induced ank gene expression. We found that the continuous cyclic mechanical tension (CCMT) increased the ank gene expression in the endplate chondrocytes, and there was an increase in the …

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Ultrasonic Incisions Produce Less Inflammatory Mediator Response During Early Healing Than Electrosurgical Incisions., Bindu Nanduri, Ken Pendarvis, Leslie A. Shack, Ranjit Kumar, Jeffrey W. Clymer, Donna L. Korvick, Shane C. Burgess Sep 2013

Ultrasonic Incisions Produce Less Inflammatory Mediator Response During Early Healing Than Electrosurgical Incisions., Bindu Nanduri, Ken Pendarvis, Leslie A. Shack, Ranjit Kumar, Jeffrey W. Clymer, Donna L. Korvick, Shane C. Burgess

CVM Publications

As the use of laparoscopic surgery has become more widespread in recent years, the need has increased for minimally-invasive surgical devices that effectively cut and coagulate tissue with reduced tissue trauma. Although electrosurgery (ES) has been used for many generations, newly-developed ultrasonic devices (HARMONIC? Blade, HB) have been shown at a macroscopic level to offer better coagulation with less thermally-induced tissue damage. We sought to understand the differences between ES and HB at a microscopic level by comparing mRNA transcript and protein responses at the 3-day timepoint to incisions made by the devices in subcutaneous fat tissue in a porcine …

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Four Decades Of Andean Timberline Migration And Implications For Biodiversity Loss With Climate Change, David A. Lutz, Rebecca L. Powell, Miles R. Silman Sep 2013

Four Decades Of Andean Timberline Migration And Implications For Biodiversity Loss With Climate Change, David A. Lutz, Rebecca L. Powell, Miles R. Silman

Dartmouth Scholarship

Rapid 21st-century climate change may lead to large population decreases and extinction in tropical montane cloud forest species in the Andes. While prior research has focused on species migrations per se, ecotones may respond to different environmental factors than species. Even if species can migrate in response to climate change, if ecotones do not they can function as hard barriers to species migrations, making ecotone migrations central to understanding species persistence under scenarios of climate change. We examined a 42-year span of aerial photographs and high resolution satellite imagery to calculate migration rates of timberline–the grassland-forest ecotone–inside and outside of …

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