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2020

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Impact Of Trem2r47h Variant On Tau Pathology-Induced Gliosis And Neurodegeneration, Maud Gratuze, Cheryl Eg Leyns, Andrew D Sauerbeck, Marie-Kim St-Pierre, Monica Xiong, Nayeon Kim, Javier Remolina Serrano, Marie-Ève Tremblay, Terrance T Kummer, Marco Colonna, Jason D Ulrich, David M Holtzman Jan 2020

Impact Of Trem2r47h Variant On Tau Pathology-Induced Gliosis And Neurodegeneration, Maud Gratuze, Cheryl Eg Leyns, Andrew D Sauerbeck, Marie-Kim St-Pierre, Monica Xiong, Nayeon Kim, Javier Remolina Serrano, Marie-Ève Tremblay, Terrance T Kummer, Marco Colonna, Jason D Ulrich, David M Holtzman

Open Access Publications

Alzheimer's disease (AD) is characterized by plaques containing amyloid-β (Aβ) and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglia-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2- to 4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicity. However, neocortical Aβ pathology occurs many years before neocortical tau pathology in AD. Thus, it will be important to understand the role of TREM2 in …

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Pain Relief After Surgical Decompression Of The Distal Brachial Plexus, Richard Morgan, Iain Elliot, Vibhu Banala, Christopher Dy, Briana Harris, Elizabeth Anne Ouellette Jan 2020

Pain Relief After Surgical Decompression Of The Distal Brachial Plexus, Richard Morgan, Iain Elliot, Vibhu Banala, Christopher Dy, Briana Harris, Elizabeth Anne Ouellette

Open Access Publications

No abstract provided.

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Assaying Three-Dimensional Cellular Architecture Using X-Ray Tomographic And Correlated Imaging Approaches, Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick Jan 2020

Assaying Three-Dimensional Cellular Architecture Using X-Ray Tomographic And Correlated Imaging Approaches, Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick

Open Access Publications

No abstract provided.

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Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao Jan 2020

Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao

Open Access Publications

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have …

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Cd46 And Oncologic Interactions: Friendly Fire Against Cancer, Michelle Elvington, M Kathryn Liszewski, John P Atkinson Jan 2020

Cd46 And Oncologic Interactions: Friendly Fire Against Cancer, Michelle Elvington, M Kathryn Liszewski, John P Atkinson

Open Access Publications

One of the most challenging aspects of cancer therapeutics is target selection. Recently, CD46 (membrane cofactor protein; MCP) has emerged as a key player in both malignant transformation as well as in cancer treatments. Normally a regulator of complement activation, CD46 is co-expressed as four predominant isoforms on almost all cell types. CD46 is highly overexpressed on a variety of human tumor cells. Clinical and experimental data support an association between increased CD46 expression and malignant transformation and metastasizing potential. Further, CD46 is a newly discovered driver of metabolic processes and plays a role in the intracellular complement system (complosome). …

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Chemical Mutagenesis Of A Gpcr Ligand: Detoxifying “Inflammo-Attraction” To Direct Therapeutic Stem Cell Migration, Jean-Pyo Lee, Edward B. Han, Et Al. Jan 2020

Chemical Mutagenesis Of A Gpcr Ligand: Detoxifying “Inflammo-Attraction” To Direct Therapeutic Stem Cell Migration, Jean-Pyo Lee, Edward B. Han, Et Al.

Open Access Publications

No abstract provided.

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Tumor Microenvironment As A Regulator Of Radiation Therapy: New Insights Into Stromal-Mediated Radioresistance, Varintra E Krisnawan, Jennifer A Stanley, Julie K Schwarz, David G Denardo Jan 2020

Tumor Microenvironment As A Regulator Of Radiation Therapy: New Insights Into Stromal-Mediated Radioresistance, Varintra E Krisnawan, Jennifer A Stanley, Julie K Schwarz, David G Denardo

Open Access Publications

No abstract provided.

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Pd-L1 Blockade In Combination With Inhibition Of Mapk Oncogenic Signaling In Patients With Advanced Melanoma, Antoni Ribas, Alain Algazi, Paolo A. Ascierto, Marcus O. Butler, Sunandana Chandra, Michael Gordon, Leonel Hernandez-Aya, Donald Lawrence, Jose Lutzky, Wilson H. Miller Jr., Katie M. Campbell, Bruno Delafont, Shannon Marshall, Nancy Mueller, Caroline Robert Jan 2020

Pd-L1 Blockade In Combination With Inhibition Of Mapk Oncogenic Signaling In Patients With Advanced Melanoma, Antoni Ribas, Alain Algazi, Paolo A. Ascierto, Marcus O. Butler, Sunandana Chandra, Michael Gordon, Leonel Hernandez-Aya, Donald Lawrence, Jose Lutzky, Wilson H. Miller Jr., Katie M. Campbell, Bruno Delafont, Shannon Marshall, Nancy Mueller, Caroline Robert

Open Access Publications

No abstract provided.

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Histone H3.3 Beyond Cancer: Germline Mutations In Histone 3 Family 3a And 3b Cause A Previously Unidentified Neurodegenerative Disorder In 46 Patients, Laura Bryant, Marcia C Willing, Linda Manwaring, Et Al Jan 2020

Histone H3.3 Beyond Cancer: Germline Mutations In Histone 3 Family 3a And 3b Cause A Previously Unidentified Neurodegenerative Disorder In 46 Patients, Laura Bryant, Marcia C Willing, Linda Manwaring, Et Al

Open Access Publications

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (

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A Matricellular Protein Fibulin-4 Is Essential For The Activation Of Lysyl Oxidase, Kazuo Noda, Kaori Kitagawa, Takao Miki, Masahito Horiguchi, Tomoya O Akama, Takako Taniguchi, Hisaaki Taniguchi, Kazuaki Takahashi, Yasumitsu Ogra, Robert P Mecham, Masahiko Terajima, Mitsuo Yamauchi, Tomoyuki Nakamura Jan 2020

A Matricellular Protein Fibulin-4 Is Essential For The Activation Of Lysyl Oxidase, Kazuo Noda, Kaori Kitagawa, Takao Miki, Masahito Horiguchi, Tomoya O Akama, Takako Taniguchi, Hisaaki Taniguchi, Kazuaki Takahashi, Yasumitsu Ogra, Robert P Mecham, Masahiko Terajima, Mitsuo Yamauchi, Tomoyuki Nakamura

Open Access Publications

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (

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Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz Jan 2020

Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz

Open Access Publications

No abstract provided.

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Pathophysiological Consequences Of Katp Channel Overactivity And Pharmacological Response To Glibenclamide In Skeletal Muscle Of A Murine Model Of Cantù Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Antonietta Mele, Giulia Maria Camerino, Francesco Alfredo Zito, Girolamo Ranieri, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico Jan 2020

Pathophysiological Consequences Of Katp Channel Overactivity And Pharmacological Response To Glibenclamide In Skeletal Muscle Of A Murine Model Of Cantù Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Antonietta Mele, Giulia Maria Camerino, Francesco Alfredo Zito, Girolamo Ranieri, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

Cantù syndrome (CS) arises from mutations in

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Deep Brain Stimulation Of The Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review, Yvan M Vachez, Meaghan C Creed Jan 2020

Deep Brain Stimulation Of The Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review, Yvan M Vachez, Meaghan C Creed

Open Access Publications

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease (PD). Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBS

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A 2020 View Of Tension-Based Cortical Morphogenesis, David C. Van Essen Jan 2020

A 2020 View Of Tension-Based Cortical Morphogenesis, David C. Van Essen

Open Access Publications

No abstract provided.

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From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al. Jan 2020

From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al.

Open Access Publications

No abstract provided.

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Roles Of The Vagina And The Vaginal Microbiota In Urinary Tract Infection: Evidence From Clinical Correlations And Experimental Models, Amanda L Lewis, Nicole M Gilbert Jan 2020

Roles Of The Vagina And The Vaginal Microbiota In Urinary Tract Infection: Evidence From Clinical Correlations And Experimental Models, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Mounting evidence indicates that the vagina can harbor uropathogenic bacteria. Here, we consider three roles played by the vagina and its bacterial inhabitants in urinary tract infection (UTI) and urinary health. First, the vagina can serve as a reservoir for

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Pancreatic Triglyceride Lipase Mediates Lipotoxic Systemic Inflammation, Cristiane De Oliveira, Mark E Lowe, Et Al Jan 2020

Pancreatic Triglyceride Lipase Mediates Lipotoxic Systemic Inflammation, Cristiane De Oliveira, Mark E Lowe, Et Al

Open Access Publications

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence …

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Metabolic Dysfunction In Hutchinson-Gilford Progeria Syndrome, Ray Kreienkamp, Susana Gonzalo Jan 2020

Metabolic Dysfunction In Hutchinson-Gilford Progeria Syndrome, Ray Kreienkamp, Susana Gonzalo

Open Access Publications

Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction. Although HGPS does not totally recapitulate normal aging, it does harbor many similarities to the normal aging process, with patients also developing cardiovascular disease, alopecia, bone and joint abnormalities, and adipose changes. It is unsurprising, then, that as physicians and scientists have searched for treatments for HGPS, they have targeted many pathways known to be involved in normal aging, including inflammation, DNA damage, epigenetic changes, and stem cell exhaustion. Although less studied at a mechanistic level, severe metabolic problems are …

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Dopamine Buffering Capacity Imaging: A Pharmacodynamic Fmri Method For Staging Parkinson Disease, Kevin J Black, Haley K Acevedo, Jonathan M Koller Jan 2020

Dopamine Buffering Capacity Imaging: A Pharmacodynamic Fmri Method For Staging Parkinson Disease, Kevin J Black, Haley K Acevedo, Jonathan M Koller

Open Access Publications

We propose a novel pharmacological fMRI (phMRI) method for objectively quantifying disease severity in Parkinson disease (PD). It is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled based on clinical effects, but clinical measurements are influenced by confounding factors. The new method proposes to measure the effect objectively based on the timing of the known response of several brain regions to exogenous levodopa. Such responses are robust …

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Positive Allosteric Modulation Of Cd11b As A Novel Therapeutic Strategy Against Lung Cancer, Terese Geraghty, Anugraha Rajagopalan, Rabail Aslam, Alexander Pohlman, Ishwarya Venkatesh, Andrew Zloza, David Cimbaluk, David G Denardo, Vineet Gupta Jan 2020

Positive Allosteric Modulation Of Cd11b As A Novel Therapeutic Strategy Against Lung Cancer, Terese Geraghty, Anugraha Rajagopalan, Rabail Aslam, Alexander Pohlman, Ishwarya Venkatesh, Andrew Zloza, David Cimbaluk, David G Denardo, Vineet Gupta

Open Access Publications

Lung cancer is one of the leading causes of cancer-related deaths in the United States. A major hurdle for improved therapies is immune suppression mediated by the tumor and its microenvironment. The lung tumor microenvironment (TME) contains large numbers of tumor-associated macrophages (TAMs), which suppress the adaptive immune response, increase neo-vascularization of the tumor, and provide pro-tumor factors to promote tumor growth. CD11b is highly expressed on myeloid cells, including TAMs, where it forms a heterodimeric integrin receptor with CD18 (known as CD11b/CD18, Mac-1, CR3, and αMβ2), and plays an important role in recruitment and biological functions of these cells, …

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Matriptase Cleaves Epcam And Trop2 In Keratinocytes, Destabilizing Both Proteins And Associated Claudins, Chuan-Jin Wu, Michael Lu, Xu Feng, Gaku Nakato, Mark C Udey Jan 2020

Matriptase Cleaves Epcam And Trop2 In Keratinocytes, Destabilizing Both Proteins And Associated Claudins, Chuan-Jin Wu, Michael Lu, Xu Feng, Gaku Nakato, Mark C Udey

Open Access Publications

The homologs EpCAM and TROP2, which both interact with claudin-1 and claudin-7, are frequently coexpressed in epithelia including skin. Intestine uniquely expresses high levels of EpCAM but not TROP2. We previously identified EpCAM as a substrate of the membrane-anchored protease matriptase and linked HAI-2, matriptase, EpCAM and claudin-7 in a pathway that is pivotal for intestinal epithelial cells (IEC) homeostasis. Herein, we reveal that TROP2 is also a matriptase substrate. Matriptase cleaved TROP2 when purified recombinant proteins were mixed in vitro. TROP2, like EpCAM, was also cleaved after co-transfection of matriptase in 293T cells. Neither EpCAM nor TROP2 cleavage was …

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Structural Mechanism For Gating Of A Eukaryotic Mechanosensitive Channel Of Small Conductance, Zengqin Deng, Grigory Maksaev, Angela M. Schlegel, Jingying Zhang, Michael Rau, James A. J. Fitzpatrick, Elizabeth S. Haswell, Peng Yuan Jan 2020

Structural Mechanism For Gating Of A Eukaryotic Mechanosensitive Channel Of Small Conductance, Zengqin Deng, Grigory Maksaev, Angela M. Schlegel, Jingying Zhang, Michael Rau, James A. J. Fitzpatrick, Elizabeth S. Haswell, Peng Yuan

Open Access Publications

No abstract provided.

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The Gut Microbiome Defines Social Group Membership In Honey Bee Colonies, Cassondra L Vernier, Iris M Chin, Boahemaa Adu-Oppong, Joshua J Krupp, Joel Levine, Gautam Dantas, Yehuda Ben-Shahar Jan 2020

The Gut Microbiome Defines Social Group Membership In Honey Bee Colonies, Cassondra L Vernier, Iris M Chin, Boahemaa Adu-Oppong, Joshua J Krupp, Joel Levine, Gautam Dantas, Yehuda Ben-Shahar

Open Access Publications

In the honey bee, genetically related colony members innately develop colony-specific cuticular hydrocarbon profiles, which serve as pheromonal nestmate recognition cues. Yet, despite high intracolony relatedness, the innate development of colony-specific chemical signatures by individual colony members is largely determined by the colony environment, rather than solely relying on genetic variants shared by nestmates. Therefore, it is puzzling how a nongenic factor could drive the innate development of a quantitative trait that is shared by members of the same colony. Here, we provide one solution to this conundrum by showing that nestmate recognition cues in honey bees are defined, at …

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Canonical Signaling By Tgf Family Members In Mesenchymal Stromal Cells Is Dispensable For Hematopoietic Niche Maintenance Under Basal And Stress Conditions, Joseph Ryan Krambs, Grazia Abou Ezzi, Juo-Chin Yao, Daniel C. Link Jan 2020

Canonical Signaling By Tgf Family Members In Mesenchymal Stromal Cells Is Dispensable For Hematopoietic Niche Maintenance Under Basal And Stress Conditions, Joseph Ryan Krambs, Grazia Abou Ezzi, Juo-Chin Yao, Daniel C. Link

Open Access Publications

Mesenchymal stromal cells are an important component of the bone marrow hematopoietic niche. Prior studies showed that signaling from members of the transforming growth factor (TGF) superfamily in mesenchymal stromal cells is required for normal niche development. Here, we assessed the impact of TGF family signaling on niche maintenance and stress responses by deleting Smad4 in mesenchymal stromal cells at birth, thereby abrogating canonical TGF signaling. No alteration in the number or spatial organization of CXCL12-abundant reticular (CAR) cells, osteoblasts, or adipocytes was observed in Osx-Cre, Smad4fl/fl mice, and expression of key niche factors was normal. Basal hematopoiesis and stress …

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Diet-Induced Metabolic Dysregulation In Female Mice Causes Osteopenia In Adult Offspring, Yu Shi, Jessica L. Saben, Guangxu He, Kelle H. Moley, Fanxin Long Jan 2020

Diet-Induced Metabolic Dysregulation In Female Mice Causes Osteopenia In Adult Offspring, Yu Shi, Jessica L. Saben, Guangxu He, Kelle H. Moley, Fanxin Long

Open Access Publications

Bone mass and quality in humans are controlled by numerous genetic and environmental factors that are not fully understood. Increasing evidence has indicated that maternal metabolic dysregulation impairs multiple physiological processes in the adult offspring, but a similar effect on bone health is yet to be established. Here, we have analyzed the bones of first-generation offspring from murine dams that present metabolic syndrome due to a high-fat and high-sugar (HF/HS) diet. Micro-CT analyses show that the long bones of HF/HS offspring possess lower cortical bone mass and weaker mechanical strength than normal, even though the trabecular bone is not affected. …

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Rev-Erb Agonism Improves Liver Pathology In A Mouse Model Of Nash, Kristine Griffett, Gonzalo Bedia-Diaz, Bahaa Elgendy, Thomas P. Burris Jan 2020

Rev-Erb Agonism Improves Liver Pathology In A Mouse Model Of Nash, Kristine Griffett, Gonzalo Bedia-Diaz, Bahaa Elgendy, Thomas P. Burris

Open Access Publications

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using …

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Human Ipsc-Derived Neuronal Cells From Ctbp1-Mutated Patients Reveal Altered Expression Of Neurodevelopmental Gene Networks, S Vijayalingam, Eric Tycksen, Christina A Gurnett, Et Al Jan 2020

Human Ipsc-Derived Neuronal Cells From Ctbp1-Mutated Patients Reveal Altered Expression Of Neurodevelopmental Gene Networks, S Vijayalingam, Eric Tycksen, Christina A Gurnett, Et Al

Open Access Publications

A recurrent

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Fenofibrate Prevents Iron Induced Activation Of Canonical Wnt/Β-Catenin And Oxidative Stress Signaling In The Retina, Ashok Mandala, Austin Armstrong, Becky Girresch, Jiyao Zhu, Aruna Chilakala, Sanmathi Chavalmane, Kapil Chaudhary, Pratim Biswas, Judith Ogilvie, Jaya P. Gnana-Prakasam Jan 2020

Fenofibrate Prevents Iron Induced Activation Of Canonical Wnt/Β-Catenin And Oxidative Stress Signaling In The Retina, Ashok Mandala, Austin Armstrong, Becky Girresch, Jiyao Zhu, Aruna Chilakala, Sanmathi Chavalmane, Kapil Chaudhary, Pratim Biswas, Judith Ogilvie, Jaya P. Gnana-Prakasam

Open Access Publications

No abstract provided.

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Hla‑A Alleles Including Hla‑A29 Affect The Composition Of The Gut Microbiome: A Potential Clue To The Pathogenesis Of Birdshot Retinochoroidopathy, Peter R. Sternes, Tammy M. Martin, Michael Paley, Sarah Diamond, Mark J. Asquith, Matthew A. Brown, James T. Rosenbaum Jan 2020

Hla‑A Alleles Including Hla‑A29 Affect The Composition Of The Gut Microbiome: A Potential Clue To The Pathogenesis Of Birdshot Retinochoroidopathy, Peter R. Sternes, Tammy M. Martin, Michael Paley, Sarah Diamond, Mark J. Asquith, Matthew A. Brown, James T. Rosenbaum

Open Access Publications

No abstract provided.

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A Harmonized Meta-Knowledgebase Of Clinical Interpretations Of Somatic Genomic Variants In Cancer, Alex H. Wagner, Kilannin Krysiak, Malachi Griffith, Obi L. Griffith, Et Al. Jan 2020

A Harmonized Meta-Knowledgebase Of Clinical Interpretations Of Somatic Genomic Variants In Cancer, Alex H. Wagner, Kilannin Krysiak, Malachi Griffith, Obi L. Griffith, Et Al.

Open Access Publications

No abstract provided.

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