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JOURNAL ARTICLE
Jason L Marcus, Benjamin D Westerhaus, Brendan Chernicki, Anthony Giuffrida
Lumbar radiculopathy due to impingement of nerve roots from facet hypertrophy and/or disc herniation can often coincide with vertebrogenic low back pain. This is demonstrated on MRI with foraminal stenosis and Modic changes. We examine the potential of using a combination of basivertebral nerve ablation (BVNA) and lumbar laminotomy as an alternative to traditional spinal fusion in specific patient populations. This unique combination of surgical techniques has not been previously reported in the medical literature...
April 4, 2024: BMJ Case Reports
#2
JOURNAL ARTICLE
Brendan D Manning, Christian C Dibble
Normal cells grow and divide only when instructed to by signaling pathways stimulated by exogenous growth factors. A nearly ubiquitous feature of cancer cells is their capacity to grow independent of such signals, in an uncontrolled, cell-intrinsic manner. This property arises due to the frequent oncogenic activation of core growth factor signaling pathway components, including receptor tyrosine kinases, PI3K-AKT, RAS-RAF, mTORC1, and MYC, leading to the aberrant propagation of pro-growth signals independent of exogenous growth factors...
March 4, 2024: Cold Spring Harbor Perspectives in Medicine
#3
JOURNAL ARTICLE
Romain Pelletier, Thomas Gicquel, Julien Carvelli, Pierre Balaz, Anne-Laure Pelissier-Alicot, Isabelle Morel, Charline Bottinelli, Caroline Solas, Brendan Le Daré, Nicolas Fabresse
N-Benzylphenethylamine derivatives are 5-HT2A receptor agonists with hallucinogenic properties, including NBOMe (N-(2-methoxybenzyl)-2-(3,4,5-trimethoxyphenyl)ethan-1-amine) and NBOH (2-(((2,5-dimethoxyphenethyl)amino)methyl)phenol). We reported here the case of a 23-year-old man who presented a serotoninergic syndrome and a loss of consciousness following the consumption of a powder labelled as 25I-NBOH. Toxicological analyses of biological samples were carried out using a liquid chromatography high-resolution mass spectrometry...
December 20, 2023: International Journal of Legal Medicine
#4
Brendan J Houston, Joseph Nguyen, D Jo Merriner, Anne E O'Connor, Alexandra M Lopes, Liina Nagirnaja, Corinna Friedrich, Sabine Kliesch, Frank Tüttelmann, Kenneth I Aston, Donald F Conrad, Robin M Hobbs, Jessica Em Dunleavy, Moira K O'Bryan
Dynein complexes are large, multi-unit assemblies involved in many biological processes including male fertility via their critical roles in protein transport and axoneme motility. Previously we identified a pathogenic variant in the dynein gene AXDND1 in an infertile man. Subsequently we identified an additional four potentially compound heterozygous variants of unknown significance in AXDND1 in two additional infertile men. We thus tested the role of AXDND1 in mammalian male fertility by generating a knockout mouse model...
November 13, 2023: bioRxiv
#5
JOURNAL ARTICLE
Lena C Quilty, Wanda Tempelaar, Brendan F Andrade, Sean A Kidd, Yona Lunsky, Sheng Chen, Wei Wang, Jimmy K Y Wong, Chloe Lau, Andrew B Sedrak, Rachel Kelly, Harijah Sivakumar, Melanie Jani, Stephanie H Ameis, Kristin Cleverley, Benjamin I Goldstein, Daniel Felsky, Erin W Dickie, George Foussias, Nicole Kozloff, Yuliya S Nikolova, Alexia Polillo, Andreea O Diaconescu, Anne L Wheeler, Darren B Courtney, Lisa D Hawke, Martin Rotenberg, Aristotle N Voineskos
BACKGROUND: Cognition and educational achievement in youth are both linked to psychosis risk. One major aim of the Toronto Adolescent and Youth (TAY) Cohort study is to characterize how cognitive and educational achievement trajectories inform the course of psychosis spectrum symptoms (PSS), functioning, and suicidality. Here, we describe the protocol for the cognitive and educational data, and early baseline data. METHODS: Cognitive assessment design is aligned with youth population cohort studies, including the NIH Toolbox, Rey Auditory Verbal Learning Test, Wechsler Matrix Reasoning Task, and Little Man Task...
November 16, 2023: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
#6
Hui H Zhang, Alex I Lipovsky, Christian C Dibble, Mustafa Sahin, Brendan D Manning
No abstract text is available yet for this article.
September 7, 2023: Molecular Cell
#7
JOURNAL ARTICLE
Brendan F Judy, Jovanna A Tracz, Jordina Rincon-Torroella, A Karim Ahmed, Timothy F Witham
INTRODUCTION: Cervical spondyloptosis is a rare complication of high-energy trauma which often results in significant patient morbidity and mortality. The authors present a case of spondyloptosis of C7 over T1 with minimal radicular symptoms and otherwise complete spinal cord sparing. This case highlights the surgical challenges faced with cervical spondyloptosis and the techniques used when traction fails. CASE PRESENTATION: A 21-year-old man with no significant past medical history presented after a high-speed motor vehicle collision with cervicothoracic pain and mild hand grip weakness in addition to numbness of the fourth and fifth digits bilaterally (American Spinal Injury Association Impairment Scale Grade D)...
September 5, 2023: Spinal Cord Series and Cases
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JOURNAL ARTICLE
Robert Kelly-Bellow, Karen Lee, Richard Kennaway, J Elaine Barclay, Annabel Whibley, Claire Bushell, Jamie Spooner, Man Yu, Paul Brett, Baldeep Kular, Shujing Cheng, Jinfang Chu, Ting Xu, Brendan Lane, James Fitzsimons, Yongbiao Xue, Richard S Smith, Christopher D Whitewoods, Enrico Coen
Growth coordination between cell layers is essential for development of most multicellular organisms. Coordination may be mediated by molecular signaling and/or mechanical connectivity between cells, but how genes modify mechanical interactions between layers is unknown. Here we show that genes driving brassinosteroid synthesis promote growth of internal tissue, at least in part, by reducing mechanical epidermal constraint. We identified a brassinosteroid-deficient dwarf mutant in the aquatic plant Utricularia gibba with twisted internal tissue, likely caused by mechanical constraint from a slow-growing epidermis...
June 23, 2023: Science
#9
JOURNAL ARTICLE
Aaron M Hosios, Meghan E Wilkinson, Molly C McNamara, Krystle C Kalafut, Margaret E Torrence, John M Asara, Brendan D Manning
The mechanistic target of rapamycin complex 1 (mTORC1) senses and relays environmental signals from growth factors and nutrients to metabolic networks and adaptive cellular systems to control the synthesis and breakdown of macromolecules; however, beyond inducing de novo lipid synthesis, the role of mTORC1 in controlling cellular lipid content remains poorly understood. Here we show that inhibition of mTORC1 via small molecule inhibitors or nutrient deprivation leads to the accumulation of intracellular triglycerides in both cultured cells and a mouse tumor model...
December 19, 2022: Nature metabolism
#10
JOURNAL ARTICLE
Sandra Díaz, Jens Kattge, Johannes H C Cornelissen, Ian J Wright, Sandra Lavorel, Stéphane Dray, Björn Reu, Michael Kleyer, Christian Wirth, I Colin Prentice, Eric Garnier, Gerhard Bönisch, Mark Westoby, Hendrik Poorter, Peter B Reich, Angela T Moles, John Dickie, Amy E Zanne, Jérôme Chave, S Joseph Wright, Serge N Sheremetiev, Hervé Jactel, Christopher Baraloto, Bruno E L Cerabolini, Simon Pierce, Bill Shipley, Fernando Casanoves, Julia S Joswig, Angela Günther, Valeria Falczuk, Nadja Rüger, Miguel D Mahecha, Lucas D Gorné, Bernard Amiaud, Owen K Atkin, Michael Bahn, Dennis Baldocchi, Michael Beckmann, Benjamin Blonder, William Bond, Ben Bond-Lamberty, Kerry Brown, Sabina Burrascano, Chaeho Byun, Giandiego Campetella, Jeannine Cavender-Bares, F Stuart Chapin, Brendan Choat, David Anthony Coomes, William K Cornwell, Joseph Craine, Dylan Craven, Matteo Dainese, Alessandro Carioca de Araujo, Franciska T de Vries, Tomas Ferreira Domingues, Brian J Enquist, Jaime Fagúndez, Jingyun Fang, Fernando Fernández-Méndez, Maria T Fernandez-Piedade, Henry Ford, Estelle Forey, Gregoire T Freschet, Sophie Gachet, Rachael Gallagher, Walton Green, Greg R Guerin, Alvaro G Gutiérrez, Sandy P Harrison, Wesley Neil Hattingh, Tianhua He, Thomas Hickler, Steven I Higgins, Pedro Higuchi, Jugo Ilic, Robert B Jackson, Adel Jalili, Steven Jansen, Fumito Koike, Christian König, Nathan Kraft, Koen Kramer, Holger Kreft, Ingolf Kühn, Hiroko Kurokawa, Eric G Lamb, Daniel C Laughlin, Michelle Leishman, Simon Lewis, Frédérique Louault, Ana C M Malhado, Peter Manning, Patrick Meir, Maurizio Mencuccini, Julie Messier, Regis Miller, Vanessa Minden, Jane Molofsky, Rebecca Montgomery, Gabriel Montserrat-Martí, Marco Moretti, Sandra Müller, Ülo Niinemets, Romà Ogaya, Kinga Öllerer, Vladimir Onipchenko, Yusuke Onoda, Wim A Ozinga, Juli G Pausas, Begoña Peco, Josep Penuelas, Valério D Pillar, Clara Pladevall, Christine Römermann, Lawren Sack, Norma Salinas, Brody Sandel, Jordi Sardans, Brandon Schamp, Michael Scherer-Lorenzen, Ernst-Detlef Schulze, Fritz Schweingruber, Satomi Shiodera, Ênio Sosinski, Nadejda Soudzilovskaia, Marko J Spasojevic, Emily Swaine, Nathan Swenson, Susanne Tautenhahn, Ken Thompson, Alexia Totte, Rocío Urrutia-Jalabert, Fernando Valladares, Peter van Bodegom, François Vasseur, Kris Verheyen, Denis Vile, Cyrille Violle, Betsy von Holle, Patrick Weigelt, Evan Weiher, Michael C Wiemann, Mathew Williams, Justin Wright, Gerhard Zotz
Here we provide the 'Global Spectrum of Plant Form and Function Dataset', containing species mean values for six vascular plant traits. Together, these traits -plant height, stem specific density, leaf area, leaf mass per area, leaf nitrogen content per dry mass, and diaspore (seed or spore) mass - define the primary axes of variation in plant form and function. The dataset is based on ca. 1 million trait records received via the TRY database (representing ca. 2,500 original publications) and additional unpublished data...
December 7, 2022: Scientific Data
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JOURNAL ARTICLE
Jordan Jafarnia, Austin E Wininger, Brendan M Holderread, Joshua D Harris, Anthony Echo
CASE: Large acetabular paralabral cysts can cause compression of the surrounding neurovascular structures leading to sensory and motor deficits. We present a 68-year-old man with obturator nerve denervation from a paralabral cyst secondary to a labral tear associated with femoroacetabular impingement syndrome. Resolution of symptoms and return to full activities were achieved at 3 months and maintained beyond 1 year through open cyst excision, obturator neurolysis, arthroscopic femoral osteoplasty, and labral repair in the same surgical setting...
October 1, 2022: JBJS Case Connector
#12
JOURNAL ARTICLE
Molly C McNamara, Aaron M Hosios, Margaret E Torrence, Ting Zhao, Cameron Fraser, Meghan Wilkinson, David J Kwiatkowski, Elizabeth P Henske, Chin-Lee Wu, Kristopher A Sarosiek, Alexander J Valvezan, Brendan D Manning
mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC complex, a negative regulator of mTORC1. Clinically approved mTORC1 inhibitors, such as rapamycin, elicit a cytostatic effect that fails to eliminate tumors and is rapidly reversible. We sought to determine the effects of mTORC1 on the core regulators of intrinsic apoptosis. In TSC2-deficient cells and tumors, we find that mTORC1 inhibitors shift cellular dependence from MCL-1 to BCL-2 and BCL-XL for survival, thereby altering susceptibility to BH3 mimetics that target specific pro-survival BCL-2 proteins...
November 18, 2022: IScience
#13
JOURNAL ARTICLE
Christopher J Yuskaitis, Jinita B Modasia, Sandra Schrötter, Leigh-Ana Rossitto, Karenna J Groff, Christopher Morici, Divakar S Mithal, Ram P Chakrabarty, Navdeep S Chandel, Brendan D Manning, Mustafa Sahin
Caloric restriction and acute fasting are known to reduce seizures but through unclear mechanisms. mTOR signaling has been suggested as a potential mechanism for seizure protection from fasting. We demonstrate that brain mTORC1 signaling is reduced after acute fasting of mice and that neuronal mTORC1 integrates GATOR1 complex-mediated amino acid and tuberous sclerosis complex (TSC)-mediated growth factor signaling. Neuronal mTORC1 is most sensitive to withdrawal of leucine, arginine, and glutamine, which are dependent on DEPDC5, a component of the GATOR1 complex...
August 30, 2022: Cell Reports
#14
JOURNAL ARTICLE
Sandra Schrötter, Christopher J Yuskaitis, Michael R MacArthur, Sarah J Mitchell, Aaron M Hosios, Maria Osipovich, Margaret E Torrence, James R Mitchell, Gerta Hoxhaj, Mustafa Sahin, Brendan D Manning
The tuberous sclerosis complex (TSC) 1 and 2 proteins associate with TBC1D7 to form the TSC complex, which is an essential suppressor of mTOR complex 1 (mTORC1), a ubiquitous driver of cell and tissue growth. Loss-of-function mutations in TSC1 or TSC2, but not TBC1D7, give rise to TSC, a pleiotropic disorder with aberrant activation of mTORC1 in various tissues. Here, we characterize mice with genetic deletion of Tbc1d7, which are viable with normal growth and development. Consistent with partial loss of function of the TSC complex, Tbc1d7 knockout (KO) mice display variable increases in tissue mTORC1 signaling with increased muscle fiber size but with strength and motor defects...
May 17, 2022: Cell Reports
#15
JOURNAL ARTICLE
Mona Hoseini Soflaee, Rushendhiran Kesavan, Umakant Sahu, Alpaslan Tasdogan, Elodie Villa, Zied Djabari, Feng Cai, Diem H Tran, Hieu S Vu, Eunus S Ali, Halie Rion, Brendan P O'Hara, Sherwin Kelekar, James Hughes Hallett, Misty Martin, Thomas P Mathews, Peng Gao, John M Asara, Brendan D Manning, Issam Ben-Sahra, Gerta Hoxhaj
Purine nucleotides are necessary for various biological processes related to cell proliferation. Despite their importance in DNA and RNA synthesis, cellular signaling, and energy-dependent reactions, the impact of changes in cellular purine levels on cell physiology remains poorly understood. Here, we find that purine depletion stimulates cell migration, despite effective reduction in cell proliferation. Blocking purine synthesis triggers a shunt of glycolytic carbon into the serine synthesis pathway, which is required for the induction of cell migration upon purine depletion...
May 16, 2022: Nature Communications
#16
Andrew R Tee, Brendan D Manning, Philippe P Roux, Lewis C Cantley, John Blenis
No abstract text is available yet for this article.
February 7, 2022: Current Biology: CB
#17
JOURNAL ARTICLE
Matthew Maksimoski, Andrew J Bauer, Ken Kazahaya, Scott C Manning, Sanjay R Parikh, Jeffrey P Simons, Jill D'Souza, John Maddalozzo, Matthew R Purkey, Karen Rychlik, Brian Ho, Michael J Rutter, Wen Jiang, Jeremy D Prager, Gillian Diercks, Evan J Propst, R Christopher Miyamoto, Brendan C Stack, Gregory W Randolph, Jeffrey C Rastatter
OBJECTIVE: Traditionally, data regarding thyroidectomy were extracted from billing databases, but information may be missed. In this study, a multi-institutional pediatric thyroidectomy database was used to evaluate recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. STUDY DESIGN: Retrospective multi-institutional cohort study. SETTING: Tertiary care pediatric hospital systems throughout North America. METHODS: Data were individually collected for thyroidectomies, then entered into a centralized database and analyzed using univariate and multivariable regression models...
November 2022: Otolaryngology—Head and Neck Surgery
#18
JOURNAL ARTICLE
Brendan J Houston, Anne E O'Connor, Degang Wang, Georgia Goodchild, D Jo Merriner, Haitong Luan, Don F Conrad, Liina Nagirnaja, Kenneth I Aston, Sabine Kliesch, Margot J Wyrwoll, Corinna Friedrich, Frank Tüttelmann, Craig Harrison, Moira K O'Bryan, Kelly Walton
Testicular-derived inhibin B (α/β B dimers) acts in an endocrine manner to suppress pituitary production of follicle-stimulating hormone (FSH), by blocking the actions of activins (β A/B/β A/B dimers). Previously, we identified a homozygous genetic variant (c.1079T>C:p.Met360Thr) arising from uniparental disomy of chromosome 2 in the INHBB gene (β B-subunit of inhibin B and activin B) in a man suffering from infertility (azoospermia). In this study, we aimed to test the causality of the p.Met360Thr variant in INHBB and testis function...
March 1, 2022: Endocrinology
#19
JOURNAL ARTICLE
Man Melody Luo, Peijuan Penny Zhu, Ivo Nnane, Yuan Xiong, Giampaolo Merlini, Raymond L Comenzo, Efstathios Kastritis, Ashutosh D Wechalekar, Brendan M Weiss, NamPhuong Tran, Xiang Qin, Jessica Vermeulen, Amarnath Sharma, Yu-Nien Sun, Honghui Zhou
The purpose of this study is to characterize the population pharmacokinetics (popPK) of subcutaneous (SC) daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone and explore the relationship between daratumumab systemic exposure and selected efficacy and safety end points in patients with newly diagnosed systemic amyloid light-chain amyloidosis. The popPK analysis included pharmacokinetic and immunogenicity data from patients receiving daratumumab SC in combination with bortezomib, cyclophosphamide, and dexamethasone in the ANDROMEDA study (AMY3001; safety run-in, n = 28; randomized phase, n = 183)...
May 2022: Journal of Clinical Pharmacology
#20
COMMENT
Aaron M Hosios, Brendan D Manning
The Warburg effect, the propensity of some cells to metabolize glucose to lactate in the presence of oxygen (also known as aerobic glycolysis), has long been observed in cancer and other contexts of cell proliferation, but only in the past two decades have significant gains been made in understanding how and why this metabolic transformation occurs. In 2004, Cancer Research published a study by Elstrom and colleagues that provided one of the first connections between a specific oncogene and aerobic glycolysis...
October 1, 2021: Cancer Research
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