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Sevoflurane And Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection Against Delayed Cerebral Ischemia, Keshav Jayaraman, Meizi Liu, Gregory J Zipfel, Umeshkumar Athiraman

Open Access Publications

Numerous studies have demonstrated the ability of isoflurane conditioning to provide multifaceted protection against aneurysmal subarachnoid hemorrhage (SAH)-associated delayed cerebral ischemia (DCI); however, preclinical studies have not yet examined whether other commonly used inhalational anesthetics in neurological patients such as sevoflurane or desflurane are also protective against SAH-induced neurovascular deficits. We therefore sought to identify the potential for sevoflurane and desflurane conditioning to protect against DCI in an endovascular perforation mouse model of SAH. Neurological function was assessed daily via neuroscore. Large artery vasospasm and microvessel thrombosis were assessed three days after SAH or sham surgery. Four groups were examined: …

Global Waves Synchronize The Brain's Functional Systems With Fluctuating Arousal, Ryan V Raut, Abraham Z Snyder, Anish Mitra, Dov Yellin, Naotaka Fujii, Rafael Malach, Marcus E Raichle

Open Access Publications

We propose and empirically support a parsimonious account of intrinsic, brain-wide spatiotemporal organization arising from traveling waves linked to arousal. We hypothesize that these waves are the predominant physiological process reflected in spontaneous functional magnetic resonance imaging (fMRI) signal fluctuations. The correlation structure ("functional connectivity") of these fluctuations recapitulates the large-scale functional organization of the brain. However, a unifying physiological account of this structure has so far been lacking. Here, using fMRI in humans, we show that ongoing arousal fluctuations are associated with global waves of activity that slowly propagate in parallel throughout the neocortex, thalamus, striatum, and cerebellum. We …

Autophagy Of Mucin Granules Contributes To Resolution Of Airway Mucous Metaplasia, J.M. Sweeter, K. Kudrna, K. Hunt, P. Thomas, B. F. Dickey, S. L. Brody, J. D. Dickinson

Open Access Publications

No abstract provided.

Taxonomic Changes In The Gut Microbiota Are Associated With Cartilage Damage Independent Of Adiposity, High Fat Diet, And Joint Injury, Kelsey H. Collins, Drew J. Schwartz, Kristin L. Lenz, Charles A. Harris, Farshid Guilak

Open Access Publications

No abstract provided.

Orthogonal Targeting Of Osteoclasts And Myeloma Cells For Radionuclide Stimulated Dynamic Therapy Induces Multidimensional Cell Death Pathways, Alexander Zheleznyak, Matthew Mixdorf, Lynne Marsala, Julie Prior, Xiaoxia Yang, Grace Cui, Baogang Xu, Steven Fletcher, Francesca Fontana, Gregory Lanza, Samuel Achilefu

Open Access Publications

No abstract provided.

Restoration Of The Molecular Clock Is Tumor Suppressive In Neuroblastoma, Myrthala Moreno-Smith, Thomas P. Burris, Et Al.

Open Access Publications

No abstract provided.

Stk39 Promotes Breast Cancer Invasion And Metastasis By Increasing Snai1 Activity Upon Phosphorylation, Zhaoping Qiu, Bo Dong, Weijie Guo, Rychahou Piotr, Greg Longmore, Xiuwei Yang, Zhiyong Yu, Jiong Deng, B. Mark Evers, Yadi Wu

Open Access Publications

No abstract provided.

Focused Crispr‑Cas9 Genetic Screening Reveals Uso1 As A Vulnerability In B‑Cell Acute Lymphoblastic Leukemia, Amit Kumar Jaiswal, Hellen Truong, Tiffany M. Tran, Tasha L. Lin, David Casero, Michael O. Alberti, Dinesh S. Rao

Open Access Publications

No abstract provided.

Psychedelics For Brain Injury: A Mini-Review, Shariq Mansoor Khan, Gregory T Carter, Sunil K Aggarwal, Julie Holland

Open Access Publications

No abstract provided.

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Gordon I. Smith, Samuel Klein, Et Al

Open Access Publications

No abstract provided.

Substrate Reduction Therapy For Krabbe Disease And Metachromatic Leukodystrophy Using A Novel Ceramide Galactosyltransferase Inhibitor, Michael C. Babcock, Christina R. Mikulka, Hemanth R. Nelvagal, Xuntian Jiang, Mark S. Sands, Et Al

Open Access Publications

No abstract provided.

Pge2-Jnk Signaling Axis Non-Canonically Promotes Gli Activation By Protecting Gli2 From Ubiquitin-Proteasomal Degradation, Jun Yang, Weijun Liu, Et Al.

Open Access Publications

No abstract provided.

Lower Extremity Nerve Transfers In Acute Flaccid Myelitis Patients: A Case Series, Amy M. Moore, Carrie Roth Bettlach, Thomas T. Tung, Julie M. West, Stephanie A. Russo

Open Access Publications

No abstract provided.

Irradiation-Modulated Murine Brain Microenvironment Enhances Gl261-Tumor Growth And Inhibits Anti-Pd-L1 Immunotherapy, Joel R Garbow, Tanner M Johanns, Xia Ge, John A Engelbach, Liya Yuan, Sonika Dahiya, Christina I Tsien, Feng Gao, Keith M Rich, Joseph J H Ackerman

Open Access Publications

Purpose: Clinical evidence suggests radiation induces changes in the brain microenvironment that affect subsequent response to treatment. This study investigates the effect of previous radiation, delivered six weeks prior to orthotopic tumor implantation, on subsequent tumor growth and therapeutic response to anti-PD-L1 therapy in an intracranial mouse model, termed the Radiation Induced Immunosuppressive Microenvironment (RI

Method and Materials: C57Bl/6 mice received focal (hemispheric) single-fraction, 30-Gy radiation using the Leksell GammaKnife

Results: Tumors in previously irradiated brain display aggressive, invasive growth, characterized by viable tumor and large regions of hemorrhage and necrosis. Mice challenged intracranially with GL261 six weeks after prior …

Structure And Function Of Pancreatic Lipase-Related Protein 2 And Its Relationship With Pathological States, Guoying Zhu, Qing Fang, Fengshang Zhu, Dongping Huang, Changqing Yang

Open Access Publications

Pancreatic lipase is critical for the digestion and absorption of dietary fats. The most abundant lipolytic enzymes secreted by the pancreas are pancreatic triglyceride lipase (PTL or PNLIP) and its family members, pancreatic lipase-related protein 1 (PNLIPRP1or PLRP1) and pancreatic lipase-related protein 2 (PNLIPRP2 or PLRP2). Unlike the family's other members, PNLIPRP2 plays an elemental role in lipid digestion, especially for newborns. Therefore, if genetic factors cause gene mutation, or other factors lead to non-expression, it may have an effect on fat digestion and absorption, on the susceptibility to pancreas and intestinal pathogens. In this review, we will summarize what …

Reducing Auditory Nerve Excitability By Acute Antagonism Of Ca2+-Permeable Ampa Receptors, Amit Walia, Choongheon Lee, Jared Hartsock, Shawn S Goodman, Roland Dolle, Alec N Salt, Jeffery T Lichtenhan, Mark A Rutherford

Open Access Publications

Hearing depends on glutamatergic synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are tetramers, where inclusion of the GluA2 subunit reduces overall channel conductance and Ca

Markers Of Early Changes In Cognition Across Cohorts Of Adults With Down Syndrome At Risk Of Alzheimer's Disease, Andrew J Aschenbrenner, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.

Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria.

Results: There were common cognitive domains across site composites, which were sensitive to …

Distinct Microrna Profiles In The Perilymph And Serum Of Patients With Menière's Disease, Matthew Shew, Helena Wichova, Madeleine St Peter, Athanasia Warnecke, Hinrich Staecker

Open Access Publications

No abstract provided.

Maturation Of Heterogeneity In Afferent Synapse Ultrastructure In The Mouse Cochlea, Shelby A Payne, Matthew S Joens, Heather Chung, Natalie Skigen, Adam Frank, Sonali Gattani, Kya Vaughn, Allison Schwed, Matt Nester, Atri Bhattacharyya, Guhan Iyer, Bethany Davis, Jason Carlquist, Honey Patel, James A J Fitzpatrick, Mark A Rutherford

Open Access Publications

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured …

Inhibition Of Discoidin Domain Receptors By Imatinib Prevented Pancreatic Fibrosis Demonstrated In Experimental Chronic Pancreatitis Model, Sapana Bansod, Mohd Aslam Saifi, Chandraiah Godugu

Open Access Publications

No abstract provided.

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Yin Cao, Et Al

Open Access Publications

No abstract provided.

Dysregulation Of Mannose-6-Phosphate-Dependent Cholesterol Homeostasis In Acinar Cells Mediates Pancreatitis, Olga A Mareninova, Yan Xie, Nicholas O Davidson, Et Al

Open Access Publications

Disordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake. We found similar dysregulation of acinar cell cholesterol, and a decrease in GNPTAB levels, in both WT experimental pancreatitis and human disease. The …

Listeria Exploits Ifitm3 To Suppress Antibacterial Activity In Phagocytes, Joel M. J. Tan, Michael S. Diamond, Et Al

Open Access Publications

No abstract provided.

Multi-Omics Integration Analysis Identifies Novel Genes For Alcoholism With Potential Overlap With Neurodegenerative Diseases, Manav Kapoor, Michael J. Chao, Emma C. Johnson, Gloriia Novikova, Dongbing Lai, Jacquelyn L. Meyers, Jessica Schulman, John I. Nurnberger Jr., Bernice Porjesz, Yunlong Liu, The Collaborative Study On Genetics Of Alcoholism (Coga), Tatiana Foroud, Howard J. Edenberg, Edoardo Marcora, Arpana Agrawal, Alison Goate

Open Access Publications

No abstract provided.

A Ligand-Insensitive Unc5b Splicing Isoform Regulates Angiogenesis By Promoting Apoptosis, David Pradella, William Vermi, Et Al

Open Access Publications

No abstract provided.

Regulation Of Beta-Amyloid Production In Neurons By Astrocyte-Derived Cholesterol, Hao Wang, Joshua A. Kulas, Chao Wang, David M. Holtzman, Heather A. Ferris, Scott B. Hansen

Open Access Publications

No abstract provided.

Critical Roles Of Calpastatin In Ischemia/Reperfusion Injury In Aged Livers, Joseph Flores-Toro, Sung-Kook Chun, Jun-Kyu Shin, Joan Campbell, Melissa Lichtenberger, William Chapman, Ivan Zendejas, Kevin Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim

Open Access Publications

Ischemia/reperfusion (I/R) injury unavoidably occurs during hepatic resection and transplantation. Aged livers poorly tolerate I/R during surgical treatment. Although livers have a powerful endogenous inhibitor of calpains, calpastatin (CAST), I/R activates calpains, leading to impaired autophagy, mitochondrial dysfunction, and hepatocyte death. It is unknown how I/R in aged livers affects CAST. Human and mouse liver biopsies at different ages were collected during in vivo I/R. Hepatocytes were isolated from 3-month- (young) and 26-month-old (aged) mice, and challenged with short in vitro simulated I/R. Cell death, protein expression, autophagy, and mitochondrial permeability transition (MPT) between the two age groups were compared. …

Parallel Hippocampal-Parietal Circuits For Self- And Goal-Oriented Processing, Annie Zheng, David F. Montez, Scott Marek, Adrian W. Gilmore, Dillan J. Newbold, Timothy O. Laumann, Benjamin P. Kay, Nicole A. Seider, Andrew N. Van, Jacqueline M. Hampton, Dimitrios Alexopoulos, Bradley L. Schlaggar, Chad M. Sylvester, Deanna J. Greene, Joshua S. Shimony, Steven M. Nelson, Gagan S. Wig, Caterina Gratton, Kathleen B. Mcdermott, Marcus E. Raichle, Evan M. Gordon, Nico U. F. Dosenbach

Open Access Publications

No abstract provided.

Ngn3-Positive Cells Arise From Pancreatic Duct Cells, Chiemi Kimura-Nakajima, Kousuke Sakaguchi, Yoshiko Hatano, Masahito Matsumoto, Yasushi Okazaki, Keisuke Tanaka, Takumi Yamane, Yuichi Oishi, Kenji Kamimoto, Ken Iwatsuki

Open Access Publications

The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to be maintained by the self-duplication of differentiated cells, and pancreatic endocrine neogenesis can only be observed when the tissue is severely damaged. Experimentally, this can be performed using a method named partial duct ligation (PDL). As the success rate of PDL surgery is low because of difficulties in identifying the pancreatic duct, we previously proposed a method for fluorescently labeling the duct in live animals. Using this method, we performed PDL on neurogenin3 (Ngn3)-GFP transgenic mice …

Tyk2 In Cancer Metastases: Genomic And Proteomic Discovery, Dana C Borcherding, Kevin He, Neha V Amin, Angela C Hirbe

Open Access Publications

Advances in genomic analysis and proteomic tools have rapidly expanded identification of biomarkers and molecular targets important to cancer development and metastasis. On an individual basis, personalized medicine approaches allow better characterization of tumors and patient prognosis, leading to more targeted treatments by detection of specific gene mutations, overexpression, or activity. Genomic and proteomic screens by our lab and others have revealed tyrosine kinase 2 (