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Role Of Anesthetics And Their Adjuvants In Neurovascular Protection In Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage, Umeshkumar Athiraman, Gregory J Zipfel

Open Access Publications

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or …

Basophils Balance Healing After Myocardial Infarction Via Il-4/Il-13, Florian Sicklinger, Kory J Lavine, Et Al

Open Access Publications

The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7. Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative Ly6Clo macrophages toward increased numbers of inflammatory Ly6Chi monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were …

Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony, Ceazar Nave, Logan Roberts, Patrick Hwu, Jerson D. Estrella, Thanh C. Vo, Thanh H. Nguyen, Tony Thai Bui, Daniel J. Rindner, Nicholas Pervolarakis, Paul J. Shaw, Tanya L. Leise, Todd C. Holmes

Open Access Publications

We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult

Anesthesia For Thoracic Surgery In Infants And Children, Teresa M. Murray-Torres, Peter D. Winch, Aymen N. Naguib, Joseph D. Tobias

Open Access Publications

No abstract provided.

Early Aberrant Angiogenesis Due To Elastic Fiber Fragmentation In Aortic Valve Disease, Robert B Hinton, Amy L Juraszek, Amy M Opoka, Benjamin J Landis, J Michael Smith, Robert P Mecham, Kevin E Bove

Open Access Publications

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.

Models Of Distal Arthrogryposis And Lethal Congenital Contracture Syndrome, Julia Whittle, Aaron Johnson, Matthew B Dobbs, Christina A Gurnett

Open Access Publications

Distal arthrogryposis and lethal congenital contracture syndromes describe a broad group of disorders that share congenital limb contractures in common. While skeletal muscle sarcomeric genes comprise many of the first genes identified for Distal Arthrogyposis, other mechanisms of disease have been demonstrated, including key effects on peripheral nerve function. While Distal Arthrogryposis and Lethal Congenital Contracture Syndromes display superficial similarities in phenotype, the underlying mechanisms for these conditions are diverse but overlapping. In this review, we discuss the important insights gained into these human genetic diseases resulting from in vitro molecular studies and in vivo models in fruit fly, zebrafish, …

Protein Phosphatase 4 Controls Circadian Clock Dynamics By Modulating Clock/Bmal1 Activity, Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C Fiorenza, Irem Kaymak, Anna K Fritzsche, Erik D Herzog, Ralf Stanewsky, Achim Kramer

Open Access Publications

In all organisms with circadian clocks, post-translational modifications of clock proteins control the dynamics of circadian rhythms, with phosphorylation playing a dominant role. All major clock proteins are highly phosphorylated, and many kinases have been described to be responsible. In contrast, it is largely unclear whether and to what extent their counterparts, the phosphatases, play an equally crucial role. To investigate this, we performed a systematic RNAi screen in human cells and identified protein phosphatase 4 (PPP4) with its regulatory subunit PPP4R2 as critical components of the circadian system in both mammals and

Developmental Variation In Testosterone: Cortisol Ratio Alters Cortical- And Amygdala-Based Cognitive Processes, Jimin Lew, Sherri Lee Jones, Christina Caccese, Isobel Orfi, Charlotte Little, Kelly N Botteron, James T Mccracken, Tuong-Vi Nguyen

Open Access Publications

Testosterone (T) and cortisol (C) are the end products of neuroendocrine axes that interact with the process of shaping brain structure and function. Relative levels of T:C (TC ratio) may alter prefrontal-amygdala functional connectivity in adulthood. What remains unclear is whether TC-related effects are rooted to childhood and adolescence. We used a healthy cohort of 4-22-year-olds to test for associations between TC ratios, brain structure (amygdala volume, cortical thickness (CTh), and their coordinated growth), as well as cognitive and behavioral development. We found greater TC ratios to be associated with the growth of specific brain structures: 1) parietal CTh; 2) …

Ser 71 Phosphorylation Inhibits Actin-Binding Of Profilin-1 And Its Apoptosis-Sensitizing Activity, Faliang Wang, Cuige Zhu, Shirong Cai, Aaron Boudreau, Sun-Joong Kim, Mina Bissell, Jieya Shao

Open Access Publications

The essential actin-binding factor profilin-1 (Pfn1) is a non-classical tumor suppressor with the abilities toboth inhibit cellular proliferation and augment chemotherapy-induced apoptosis. Besides actin, Pfn1 interacts with proteins harboring the poly-L-proline (PLP) motifs. Our recent work demonstrated that both nuclear localization and PLP-binding are required for tumor growth inhibition by Pfn1, and this is at least partially due to Pfn1 association with the PLP-containing ENL protein in the Super Elongation Complex (SEC) and the transcriptional inhibition of pro-cancer genes. In this paper, by identifying a phosphorylation event of Pfn1 at Ser

Using Monozygotic Twins To Dissect Common Genes In Posttraumatic Stress Disorder And Migraine, Charlotte K Bainomugisa, Heidi G Sutherland, Richard Parker, Allan F Mcrae, Larisa M Haupt, Lyn R Griffiths, Andrew Heath, Elliot C Nelson, Margaret J Wright, Ian B Hickie, Nicholas G Martin, Dale R Nyholt, Divya Mehta

Open Access Publications

Epigenetic mechanisms have been associated with genes involved in Posttraumatic stress disorder (PTSD). PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved. The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC …

Loureirin B Exerts Its Immunosuppressive Effects By Inhibiting Stim1/Orai1 And K V 1.3 Channels, Shujuan Shi, Qianru Zhao, Caihua Ke, Siru Long, Feng Zhang, Xu Zhang, Yi Li, Xinqiao Liu, Hongzhen Hu, Shijin Yin

Open Access Publications

Loureirin B (LrB) is a constituent extracted from traditional Chinese medicine Resina Draconis. It has broad biological functions and an impressive immunosuppressive effect that has been supported by numerous studies. However, the molecular mechanisms underlying Loureirin B-induced immune suppression are not fully understood. We previously reported that Loureirin B inhibited K

Disentangling The Complexity Of The Rumen Microbial Diversity Through Fractionation Using A Sucrose Density Gradient, Ruth Hernández, Hugo Jimenez, Cesar Vargas-Garcia, Alejandro Caro-Quintero, Alejandro Reyes

Open Access Publications

The ruminal microbial community is an important element in health, nutrition, livestock productivity, and climate impact. Despite the historic and current efforts to characterize this microbial diversity, many of its members remain unidentified, making it challenging to associate microbial groups with functions. Here we present a low-cost methodology for rumen sample treatment that separates the microbial community based on cell size, allowing for the identification of subtle compositional changes. In brief, the sample is centrifuged through a series of sucrose density gradients, and cells migrate to their corresponding density fraction. From each fraction, DNA is extracted and

Structure-Guided Microbial Targeting Of Antistaphylococcal Prodrugs, Justin J. Miller, Ishaan T. Shah, Jayda Hatten, Yasaman Barekatain, Elizabeth A. Mueller, Ahmed M. Moustafa, Rachel L. Edwards, Cynthia S. Dowd, Paul J. Planet, Florian L. Muller, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in

Glembatumumab Vedotin For Patients With Metastatic, Gpnmb Overexpressing, Triple-Negative Breast Cancer (“Metric”): A Randomized Multicenter Study, Linda T. Vahdat, Cynthia Ma, Et Al.

Open Access Publications

No abstract provided.

Visceral Obesity And Insulin Resistance Associate With Cd36 Deletion In Lymphatic Endothelial Cells, Vincenza Cifarelli, Sila Appak-Baskoy, Vivek S. Peche, Andrew Kluzak, Trevor Shew, Ramkumar Narendran, Kathryn M. Pietka, Marina Cella, Curtis W. Walls, Rafael Czepielewski, Stoyan Ivanov, Gwendalyn J. Randolph, Hellmut G. Augustin, Nada A. Abumrad

Open Access Publications

No abstract provided.

Altered Mapping Of Sound Frequency To Cochlear Place In Ears With Endolymphatic Hydrops Provide Insight Into The Pitch Anomaly Of Diplacusis, J.J. Guinan Jr., S.M. Lefler, C.A. Buchman, S.S. Goodman, J.T. Lichtenhan

Open Access Publications

No abstract provided.

Selective Sweep For An Enhancer Involucrin Allele Identifies Skin Barrier Adaptation Out Of Africa, Mary Elizabeth Mathyer, Erin A. Brettmann, Alina D. Schmidt, Zane A. Goodwin, Inez Y. Oh, Ashley M. Quiggle, Eric Tycksen, Natasha Ramakrishnan, Scot J. Matkovich, Emma Guttman-Yassky, John R. Edwards, Cristina De Guzman Strong

Open Access Publications

No abstract provided.

Dopamine D1 + D3 Receptor Density May Correlate With Parkinson Disease Clinical Features, Pengfei Yang, William C Knight, Huifangjie Li, Yingqiu Guo, Joel S Perlmutter, Tammie L S Benzinger, John C Morris, Jinbin Xu

Open Access Publications

OBJECTIVE: Dopamine D2-like receptors - mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) - are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations.

METHODS: We analyzed the densities of D1R, D2R, and D3R …

A Decade In Review After Idiopathic Scoliosis Was First Called A Complex Trait-A Tribute To The Late Dr. Yves Cotrel For His Support In Studies Of Etiology Of Scoliosis, Nelson L S Tang, Matthew B Dobbs, Christina A Gurnett, Yong Qiu, T P Lam, Jack C Y Cheng, Nancy Hadley-Miller

Open Access Publications

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model …

Consequences Of Sur2[A478v] Mutation In Skeletal Muscle Of Murine Model Of Cantu Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Giuseppe Passantino, Antonietta Mele, Giulia Maria Camerino, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the

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.