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Articles 9901 - 9930 of 15923

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Coming Together To Define Membrane Contact Sites., Luca Scorrano, Maria Antonietta De Matteis, Scott Emr, Francesca Giordano, György Hajnóczky, Benoît Kornmann, Laura L. Lackner, Tim P. Levine, Luca Pellegrini, Karin Reinisch, Rosario Rizzuto, Thomas Simmen, Harald Stenmark, Christian Ungermann, Maya Schuldiner Mar 2019

Coming Together To Define Membrane Contact Sites., Luca Scorrano, Maria Antonietta De Matteis, Scott Emr, Francesca Giordano, György Hajnóczky, Benoît Kornmann, Laura L. Lackner, Tim P. Levine, Luca Pellegrini, Karin Reinisch, Rosario Rizzuto, Thomas Simmen, Harald Stenmark, Christian Ungermann, Maya Schuldiner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Close proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably …

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H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski Mar 2019

H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski

Manuscripts, Articles, Book Chapters and Other Papers

Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro and in vivo. We find that whereas H3K27me3 and H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced in H3.3K27M cells. H3K27me3 is unable to spread from large unmethylated CpG islands, while H3K27me2 can be deposited outside these PRC2 high-affinity sites but to levels corresponding to H3K27me3 deposition in wild-type cells. Our findings indicate that PRC2 recruitment and propagation on …

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Environmental Transmission Of Toxoplasma Gondii: Oocysts In Water, Soil And Food, Karen Shapiro, Lillian Bahia-Oliveira, Brent Dixon, Aurélien Dumètre, Luz A. De Wit, Elizabeth Vanwormer, Isabelle Villena Mar 2019

Environmental Transmission Of Toxoplasma Gondii: Oocysts In Water, Soil And Food, Karen Shapiro, Lillian Bahia-Oliveira, Brent Dixon, Aurélien Dumètre, Luz A. De Wit, Elizabeth Vanwormer, Isabelle Villena

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a zoonotic protozoan parasite that can cause morbidity and mortality in humans, domestic animals, and terrestrial and aquatic wildlife. The environmentally robust oocyst stage of T. gondii is fundamentally critical to the parasite's success, both in terms of its worldwide distribution as well as the extensive range of infected intermediate hosts. Despite the limited definitive host species (domestic and wild felids), infections have been reported on every continent, and in terrestrial as well as aquatic environments. The remarkable resistance of the oocyst wall enables dissemination of T. gondii through watersheds and ecosystems, and long-term persistence in diverse …

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Efficacy Of Leukemia Inhibitory Factor As A Therapeutic For Permanent Large Vessel Stroke Differs Among Aged Male And Female Rats, Stephanie M. Davis, Lisa A. Collier, Sarah J. Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker Mar 2019

Efficacy Of Leukemia Inhibitory Factor As A Therapeutic For Permanent Large Vessel Stroke Differs Among Aged Male And Female Rats, Stephanie M. Davis, Lisa A. Collier, Sarah J. Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker

Neurology Faculty Publications

Preclinical studies using rodent models of stroke have had difficulty in translating their results to human patients. One possible factor behind this inability is the lack of studies utilizing aged rodents of both sexes. Previously, this lab showed that leukemia inhibitory factor (LIF) promoted recovery after stroke through antioxidant enzyme upregulation. This study examined whether LIF promotes neuroprotection in aged rats of both sexes. LIF did not reduce tissue damage in aged animals, but LIF-treated female rats showed partial motor skill recovery. The LIF receptor (LIFR) showed membrane localization in young male and aged rats of both sexes after stroke. …

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Prefrontal Corticotropin-Releasing Factor (Crf) Neurons Act Locally To Modulate Frontostriatal Cognition And Circuit Function., Sofiya Hupalo, Andrea J Martin, Rebecca K Green, David M Devilbiss, Craig W Berridge Mar 2019

Prefrontal Corticotropin-Releasing Factor (Crf) Neurons Act Locally To Modulate Frontostriatal Cognition And Circuit Function., Sofiya Hupalo, Andrea J Martin, Rebecca K Green, David M Devilbiss, Craig W Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated …

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Can Assisted Reproductive Technologies Help Conserve 300 Million Years Of Evolution? A First Attempt At Developing These Technologies For Male Reptiles, Sean M. Perry Mar 2019

Can Assisted Reproductive Technologies Help Conserve 300 Million Years Of Evolution? A First Attempt At Developing These Technologies For Male Reptiles, Sean M. Perry

LSU Doctoral Dissertations

Biodiversity loss is the most critical environmental problem threatening ecosystem, animal, and human health today. Increases in extinction rates have been observed over the past 50 years, with reptile losses occurring twelve times faster than traditional extinction rates. This demonstrated biodiversity loss is secondary to climate change, habitat destruction, infectious disease, invasive species, poaching, and unsustainable trade. Approximately 20% of all reptiles are threatened with extinction and population declines are approaching rates similar to the current amphibian extinction crisis. Preventing the extinction of reptiles will require humans to acknowledge these losses and develop plans to preserve these evolutionary sentinel species. …

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A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang Mar 2019

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

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New Insights On Age-Related Hearing Loss, Judy R. Dubno Mar 2019

New Insights On Age-Related Hearing Loss, Judy R. Dubno

Journal of the South Carolina Academy of Science

No abstract provided.

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An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey Mar 2019

An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey

UNO Student Research and Creative Activity Fair

Stimulants are a class of drugs that have a variety of effects on the brain, including changes in receptor activity in the brain areas responsible for- memory, attention, emotion, motor control, and the reward pathway. Stimulants may be generally classified by their availability. For example, prescription stimulants, which include drugs such as methylphenidate (Concerta™, Ritalin™) and mixed amphetamine salts (Adderall™), must be prescribed by medical professionals. Another regulated stimulant, albeit one available without a prescription, is nicotine; a highly addictive chemical that is age-restricted by the U.S. federal government. Nicotine is found in tobacco products, and in tobacco-free alternatives including …

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Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Sean T. Bresnahan, Matthew M. Froid Mar 2019

Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Sean T. Bresnahan, Matthew M. Froid

UNO Student Research and Creative Activity Fair

Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over …

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Unique Regulation Of Enterocyte Brush Border Membrane Na-Glutamine And Na-Alanine Co-Transport By Peroxynitrite During Chronic Intestinal Inflammation, Subha Arthur, Palanikumar Manoharan, Shanmuga Sundaram, M. M. Rahman, Balasubramanian Palaniappan, Uma Sundaram Mar 2019

Unique Regulation Of Enterocyte Brush Border Membrane Na-Glutamine And Na-Alanine Co-Transport By Peroxynitrite During Chronic Intestinal Inflammation, Subha Arthur, Palanikumar Manoharan, Shanmuga Sundaram, M. M. Rahman, Balasubramanian Palaniappan, Uma Sundaram

Clinical & Translational Sciences

Na-amino acid co-transporters (NaAAcT) are uniquely affected in rabbit intestinal villus cell brush border membrane (BBM) during chronic intestinal inflammation. Specifically, Na-alanine co-transport (ASCT1) is inhibited secondary to a reduction in the affinity of the co-transporter for alanine, whereas Na-glutamine co-transport (B0AT1) is inhibited secondary to a reduction in BBM co-transporter numbers. During chronic intestinal inflammation, there is abundant production of the potent oxidant peroxynitrite (OONO). However, whether OONO mediates the unique alteration in NaAAcT in intestinal epithelial cells during chronic intestinal inflammation is unknown. In this study, ASCT1 and B0AT1 were inhibited by OONO in vitro. The mechanism of …

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The Gradient Of The Reinforcement Landscape Influences Sensorimotor Learning, Joshua G.A. Cashaback, Christopher K. Lao, Dimitrios J. Palidis, Susan K. Coltman, Heather R. Mcgregor, Paul L. Gribble Mar 2019

The Gradient Of The Reinforcement Landscape Influences Sensorimotor Learning, Joshua G.A. Cashaback, Christopher K. Lao, Dimitrios J. Palidis, Susan K. Coltman, Heather R. Mcgregor, Paul L. Gribble

Brain and Mind Institute Researchers' Publications

© 2019 Cashaback et al. Consideration of previous successes and failures is essential to mastering a motor skill. Much of what we know about how humans and animals learn from such reinforcement feedback comes from experiments that involve sampling from a small number of discrete actions. Yet, it is less understood how we learn through reinforcement feedback when sampling from a continuous set of possible actions. Navigating a continuous set of possible actions likely requires using gradient information to maximize success. Here we addressed how humans adapt the aim of their hand when experiencing reinforcement feedback that was associated with …

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Transcranial Doppler Assessment Of Patients With Cerebral Small Vessel Disease, Alaa Ebrahim Ata Ata Shaaban, Mahmoud H. Ebrahim, Mohamed M. T. Elbaghdady, Salma H. M. Khalil Mar 2019

Transcranial Doppler Assessment Of Patients With Cerebral Small Vessel Disease, Alaa Ebrahim Ata Ata Shaaban, Mahmoud H. Ebrahim, Mohamed M. T. Elbaghdady, Salma H. M. Khalil

Journal of Medicine in Scientific Research

Background Cerebral small vessel disease (SVD) refers to any pathology in all vascular structures (small arteries, arterioles, capillaries, venules, and small veins). Transcranial Doppler is a bedside, inexpensive, noninvasive technique that can assess intracerebral circulation in real time and can be used for continuous monitoring. Aim of the work Our study tried to detect the pathogenesis of cerebral SVD, especially the implication of the cerebral large artery disease. Moreover, it assessed the ability of transcranial Doppler in evaluating the severity of cerebral SVD and people who are at risk. Patients with cardioembolic risk were excluded. Patients and methods A cross-sectional …

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Design And Actuation Of A Fabric-Based Worm-Like Robot, Akhil Kandhari, Anna Mehringer, Hillel J. Chiel, Roger D. Quinn, Kathryn A. Daltorio Mar 2019

Design And Actuation Of A Fabric-Based Worm-Like Robot, Akhil Kandhari, Anna Mehringer, Hillel J. Chiel, Roger D. Quinn, Kathryn A. Daltorio

Faculty Scholarship

Soft-bodied animals, such as earthworms, are capable of contorting their body to squeeze through narrow spaces, create or enlarge burrows, and move on uneven ground. In many applications such as search and rescue, inspection of pipes and medical procedures, it may be useful to have a hollow-bodied robot with skin separating inside and outside. Textiles can be key to such skins. Inspired by earthworms, we developed two new robots: FabricWorm and MiniFabricWorm. We explored the application of fabric in soft robotics and how textile can be integrated along with other structural elements, such as three-dimensional (3D) printed parts, linear springs, …

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The Use Of Microplates For Fixation Of Mandibular Fractures: A Systematic Review, Magdy M. Zaky, Mohamed F. Shehab, Nabila A. Fayed, Usama S. Hellal Mar 2019

The Use Of Microplates For Fixation Of Mandibular Fractures: A Systematic Review, Magdy M. Zaky, Mohamed F. Shehab, Nabila A. Fayed, Usama S. Hellal

Journal of Medicine in Scientific Research

Background Microplates have thin diameter making them less palpable, more malleable, easily applied, and adaptable to fracture site. In the past, microplates were used in midface fractures only, but we can obtain their benefits in mandibular fractures as well. Objective The aim of this systematic review was to verify the efficiency of microplates either alone or in combination with miniplates for fixation of mandibular fractures in comparison with miniplates. Materials and methods A systematic review was conducted using electronic databases for collecting articles that met the inclusion and exclusion criteria. Data were extracted from each article, and the quality of …

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Role Of Sclerostin, Fibroblast Growth Factor-23, And Klotho In Hemodialysis Patients, Ahmed Hassan, Azza A. I. Elmenyawi Mar 2019

Role Of Sclerostin, Fibroblast Growth Factor-23, And Klotho In Hemodialysis Patients, Ahmed Hassan, Azza A. I. Elmenyawi

Journal of Medicine in Scientific Research

Introduction Chronic kidney disease–mineral bone disorder leads to decreasing bone health. Sclerostin is produced by osteocytes similar to fibroblast growth factor-23 (FGF-23) and might upregulate the FGF-23 production by the osteocyte. FGF-23 may act as a mineralization inhibitor. Klotho serves as an obligate coreceptor for the FGF-23 and represents a marker of chronic kidney disease–mineral bone disorder. Aim We examined the association between serum sclerostin, FGF-23, Klotho, parathyroid hormone, high-sensitivity C-reactive protein (hsCRP), and phosphorus levels in hemodialysis (HD) patients. Patients and methods A total of 63 HD patients in the National Institute of Urology and Nephrology and 20 controls …

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Effect Of Different Doses Of Low-Intensity Laser Therapy On Total Active Range Of Motion After Hand Flexor Tendon Repair, Amir A. Saidi, Amir N. Wadee, Eid R. Abd El Azim, Feify A. Badawy, Osama F. Al Balah, Wadida H. Elsayed Mar 2019

Effect Of Different Doses Of Low-Intensity Laser Therapy On Total Active Range Of Motion After Hand Flexor Tendon Repair, Amir A. Saidi, Amir N. Wadee, Eid R. Abd El Azim, Feify A. Badawy, Osama F. Al Balah, Wadida H. Elsayed

Journal of Medicine in Scientific Research

Objective To investigate the difference between the effects of different doses of low-level laser therapy (4 or 1 J/cm2) on the return of hand active range of motion (ROM) after flexor tendon repair. Participants and methods A small trial was conducted on 33 patients with 45 injured fingers of both sexes who underwent primary repair after complete cut of hand flexor tendon. Their age ranged from 20 to 40 years old. They were recruited from the plastic surgery department. The treatment began the first day postoperatively after permission by surgeons using Duran protocol and splinting. Transcutaneous electrical nerve …

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Relationship Between Dietary Intake And Obesity Among A Group Of Primary School-Aged Children In Cairo Governorate, Ahmed S. Marei, Hany H. El-Gazzar, Khaled Elkelany, Mohamed F. Al Soda, Saher A. Khairy, Salwa M. Saleh, Mahmood D. Al-Mendalawi Mar 2019

Relationship Between Dietary Intake And Obesity Among A Group Of Primary School-Aged Children In Cairo Governorate, Ahmed S. Marei, Hany H. El-Gazzar, Khaled Elkelany, Mohamed F. Al Soda, Saher A. Khairy, Salwa M. Saleh, Mahmood D. Al-Mendalawi

Journal of Medicine in Scientific Research

No abstract provided.

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Ripk1 Can Mediate Apoptosis In Addition To Necroptosis During Embryonic Development., Xuhua Zhang, John P. Dowling, Jianke Zhang Mar 2019

Ripk1 Can Mediate Apoptosis In Addition To Necroptosis During Embryonic Development., Xuhua Zhang, John P. Dowling, Jianke Zhang

Department of Microbiology and Immunology Faculty Papers

RIPK1 has emerged as a key effector in programmed necrosis or necroptosis. This function of RIPK1 is mediated by its protein serine/threonine kinase activity and through the downstream kinase RIPK3. Deletion of RIPK1 prevents embryonic lethality in mice lacking FADD, a signaling adaptor protein required for activation of Caspase 8 in extrinsic apoptotic pathways. This indicates that FADD-mediated apoptosis inhibits RIPK1-dependent necroptosis to ensure successful embryogenesis. However, the molecular mechanism for this critical regulation remains unclear. In the current study, a novel mouse model has been generated, by disrupting a potential caspase cleavage site at aspartic residue (D)324 in RIPK1. …

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Use Of 3d Imaging For Providing Insights Into High-Order Structure Of Mitotic Chromosomes, Mohammad Yusuf, Kohei Kaneyoshi, Kiichi Fukui, Ian Robinson Mar 2019

Use Of 3d Imaging For Providing Insights Into High-Order Structure Of Mitotic Chromosomes, Mohammad Yusuf, Kohei Kaneyoshi, Kiichi Fukui, Ian Robinson

Centre for Regenerative Medicine & Stem Cell Research

The high-order structure of metaphase chromosomes remains still under investigation, especially the 30-nm structure that is still controversial. Advanced 3D imaging has provided useful information for our understanding of this detailed structure. It is evident that new technologies together with improved sample preparations and image analyses should be adequately combined. This mini review highlights 3D imaging used for chromosome analysis so far with future imaging directions also highlighted.

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Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard Feb 2019

Osteoblasts Are "Educated" By Crosstalk With Metastatic Breast Cancer Cells In The Bone Tumor Microenvironment., Alexus D. Kolb, Alison B. Shupp, Dimpi Mukhopadhyay, Frank C. Marini, Karen M. Bussard

Department of Cancer Biology Faculty Papers

INTRODUCTION: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are …

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Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath Feb 2019

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …

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Ephrin-B3 Controls Excitatory Synapse Density Through Cell-Cell Competition For Ephbs., Nathan T. Henderson, Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, Matthew B. Dalva Feb 2019

Ephrin-B3 Controls Excitatory Synapse Density Through Cell-Cell Competition For Ephbs., Nathan T. Henderson, Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control …

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Understanding Perirhinal Contributions To Perception And Memory: Evidence Through The Lens Of Selective Perirhinal Damage, Marika C. Inhoff, Andrew C. Heusser, Arielle Tambini, Chris B. Martin, Edward B. O'Neil, Stefan Köhler, Michael R. Meager, Karen Blackmon, Blanca Vazquez, Orrin Devinsky, Lila Davachi Feb 2019

Understanding Perirhinal Contributions To Perception And Memory: Evidence Through The Lens Of Selective Perirhinal Damage, Marika C. Inhoff, Andrew C. Heusser, Arielle Tambini, Chris B. Martin, Edward B. O'Neil, Stefan Köhler, Michael R. Meager, Karen Blackmon, Blanca Vazquez, Orrin Devinsky, Lila Davachi

Brain and Mind Institute Researchers' Publications

© 2019 Elsevier Ltd Although a memory systems view of the medial temporal lobe (MTL) has been widely influential in understanding how memory processes are implemented, a large body of work across humans and animals has converged on the idea that the MTL can support various other decisions, beyond those involving memory. Specifically, recent work suggests that perception of and memory for visual representations may interact in order to support ongoing cognition. However, given considerations involving lesion profiles in neuropsychological investigations and the correlational nature of fMRI, the precise nature of representations supported by the MTL are not well understood …

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Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio Feb 2019

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under …

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Treatment Combinations For Alzheimer’S Disease: Current And Future Pharmacotherapy Options, Jeffrey L. Cummings, Gary Tong, Clive Ballard Feb 2019

Treatment Combinations For Alzheimer’S Disease: Current And Future Pharmacotherapy Options, Jeffrey L. Cummings, Gary Tong, Clive Ballard

Integrated Health Sciences Faculty Research

Although Alzheimer’s disease (AD) is the world’s leading cause of dementia and the population of patients with AD continues to grow, no new therapies have been approved in more than a decade. Many clinical trials of single-agent therapies have failed to affect disease progression or symptoms compared with placebo. The complex pathophysiology of AD may necessitate combination treatments rather than monotherapy. The goal of this narrative literature review is to describe types of combination therapy, review the current clinical evidence for combination therapy regimens (both symptomatic and disease-modifying) in the treatment of AD, describe innovative clinical trial study designs that …

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Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang Feb 2019

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …

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Is Retinal Metabolic Dysfunction At The Center Of The Pathogenesis Of Age-Related Macular Degeneration?, Thierry Léveillard, Nancy J. Philp, Florian Sennlaub Feb 2019

Is Retinal Metabolic Dysfunction At The Center Of The Pathogenesis Of Age-Related Macular Degeneration?, Thierry Léveillard, Nancy J. Philp, Florian Sennlaub

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The retinal pigment epithelium (RPE) forms the outer blood⁻retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized …

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Tradd Regulates Perinatal Development And Adulthood Survival In Mice Lacking Ripk1 And Ripk3., John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang Feb 2019

Tradd Regulates Perinatal Development And Adulthood Survival In Mice Lacking Ripk1 And Ripk3., John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang

Department of Microbiology and Immunology Faculty Papers

TRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd −/− embryos from necroptosis, and ablation of TRADD rescues Ripk1 −/− mice from perinatal lethality when RIPK3-mediated necroptosis is disabled. The resulting Ripk1 −/− Ripk3 −/− Tradd −/− mice survive until early adulthood, but die thereafter. A …

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Ambroxol As A Novel Disease-Modifying Treatment For Parkinson's Disease Dementia: Protocol For A Single-Centre, Randomized, Double-Blind, Placebo-Controlled Trial, C. R.A. Silveira, J. Mackinley, K. Coleman, Z. Li, E. Finger, R. Bartha, S. A. Morrow, J. Wells, M. Borrie, R. G. Tirona, C. A. Rupar, G. Zou, R. A. Hegele, D. Mahuran, Penny A. Macdonald, M. E. Jenkins, M. Jog, S. H. Pasternak Feb 2019

Ambroxol As A Novel Disease-Modifying Treatment For Parkinson's Disease Dementia: Protocol For A Single-Centre, Randomized, Double-Blind, Placebo-Controlled Trial, C. R.A. Silveira, J. Mackinley, K. Coleman, Z. Li, E. Finger, R. Bartha, S. A. Morrow, J. Wells, M. Borrie, R. G. Tirona, C. A. Rupar, G. Zou, R. A. Hegele, D. Mahuran, Penny A. Macdonald, M. E. Jenkins, M. Jog, S. H. Pasternak

Medical Biophysics Publications

© 2019 The Author(s). Background: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for β-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The …

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