Article
Neurosciences
Natasha Ranu, Jenni Laitila, Hannah F. Dugdale, Jennifer Mariano, Justin S. Kolb, Carina Wallgren-Pettersson, Nanna Witting, John Vissing, Juan Jesus Vilchez, Chiara Fiorillo, Edmar Zanoteli, Mari Auranen, Manu Jokela, Giorgio Tasca, Kristl G. Claeys, Nicol C. Voermans, Johanna Palmio, Sanna Huovinen, Maurizio Moggio, Thomas Nyegaard Beck, Aikaterini Kontrogianni-Konstantopoulos, Henk Granzier, Julien Ochala
Summary: Nemaline myopathy (NM) is a common genetic muscle disorder associated with mutations in the NEB gene. This study revealed that the myosin stabilizing state, known as super-relaxed state, is impaired in NM patients, leading to increased energy consumption in resting muscle fibers. Proteomics analysis also showed metabolic changes in a nebulin-deficient mouse model. These findings provide insights into the pathophysiology of NM and suggest potential therapeutic targets for NEB-NM.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sami Chu, Joseph M. Muretta, David D. Thomas
Summary: The study aimed to test whether the IHM structure is the structural basis for the SRX state, and the results indicated that the IHM structure is sufficient but not necessary to produce the SRX kinetic state.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
David Rasicci, Prince Tiwari, Skylar M. L. Bodt, Rohini Desetty, Fredrik R. Sadler, Sivaraj Sivaramakrishnan, Roger Craig, Christopher M. Yengo
Summary: The SRX state of cardiac myosin is crucial for heart function, and the E525K DCM mutation may reduce muscle force and power by stabilizing the SRX state. Furthermore, there is a correlation between the SRX biochemical state and the IHM structural state.
Article
Multidisciplinary Sciences
Alison Schroer Vander Roest, Chao Liu, Makenna M. Morck, Kristina Bezold Kooiker, Gwanghyun Jung, Dan Song, Aminah Dawood, Arnav Jhingran, Gaspard Pardon, Sara Ranjbarvaziri, Giovanni Fajardo, Mingming Zhao, Kenneth S. Campbell, Beth L. Pruitt, James A. Spudich, Kathleen M. Ruppel, Daniel Bernstein
Summary: The study found that the P710R mutation results in a shorter step size of the myosin motor, decreased load sensitivity, and destabilization of the super relaxed state, which increases force generation. Through CRISPR editing, cardiac myocytes with the P710R mutation were able to produce more force, leading to hypertrophy and cytoskeletal remodeling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Physiology
Roger Craig, Raul Padron
Summary: Super-relaxation is a muscle state where myosin ATP turnover is significantly slower, serving as a mechanism to switch off energy-consuming myosin motors. The structural basis of this state is usually a motif formed by interactions between myosin heads and the proximal tail.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Elisabetta Brunello, Lorenzo Marcucci, Malcolm Irving, Luca Fusi
Summary: The contraction of skeletal muscle is initiated by an increase in intracellular calcium concentration, causing a change in the structure of actin-containing thin filaments that allows binding of myosin motors from the thick filaments. The release of folded motors is triggered by thick filament stress, suggesting a positive feedback loop. This study reveals the coordination of thin and thick filament activation mechanisms and the coupling of these mechanisms through positive feedback loops, achieving rapid cooperative activation of skeletal muscle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Chen-Ching Yuan, Katarzyna Kazmierczak, Jingsheng Liang, Weikang Ma, Thomas C. Irving, Danuta Szczesna-Cordary
Summary: This study investigates the role of the super-relaxed (SRX) state of myosin in the structure-function relationship of sarcomeres in mouse models of cardiomyopathy. The results suggest that mutation-induced redistribution of myosin energetic states contributes to the development of complex clinical phenotypes associated with human HCM-D166V and DCM-D94A mutations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Cameron Hill, Elisabetta Brunello, Luca Fusi, Jesus Garcia Ovejero, Malcolm Irving
Summary: In this study, the activation of myosin filaments in muscle contraction was found to be mainly influenced by filament stress. A switch-like change in myosin motor conformation at the start of force development was also observed, along with the involvement of filament zonal dynamics in activation.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Biology
Suman Nag, Darshan Trivedi
Summary: The discovery of two functional states of myosin in muscle contraction has shed light on their role in adaptive thermogenesis and increasing cardiac muscle power. This equilibrium state is shown to be affected by various physiological and pathophysiological perturbations.
Article
Cell Biology
Alexander Sonne, Lorenzo Peverelli, Aurelio Hernandez-Lain, Cristina Dominguez-Gonzalez, Jesper L. Andersen, Margherita Milone, Alan H. Beggs, Julien Ochala
Summary: In this study, we investigated the effects of MYH2 truncating mutations on the presence and post-translational modifications of myosin heavy chains, as well as the functionality of myosin molecules. We found that these mutations resulted in the presence of type IIa myosin heavy chains with an additional acetylated lysine in patients, accompanied by increased ATP demand, faster actomyosin kinetics, and reduced muscle fiber force.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Atsuki Fukutani, Shiho Kunimatsu, Tadao Isaka
Summary: This study examined the influence of caffeine on cross-bridge dynamics and found that the effect of caffeine on cross-bridge dynamics is negligible. The ergogenic effect of caffeine is primarily achieved through facilitating Ca2+ release.
SCIENTIFIC REPORTS
(2022)
Article
Nutrition & Dietetics
Ian C. Smith, Curtis Ostertag, Jennifer J. O'Reilly, Jaqueline L. Rios, Teja Klancic, Graham Z. MacDonald, Kelsey H. Collins, Raylene A. Reimer, Walter Herzog
Summary: This study investigated the impact of diet-induced obesity on contractile function of skeletal muscle fibers in male Sprague-Dawley rats. The results showed that a high-fat, high-sucrose diet led to impaired force output in fibers expressing MHC I or MHC IIa in some cohorts of rats, while other measures of contractile function were not significantly affected by the diet.
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2021)
Article
Multidisciplinary Sciences
Andre Tomalka, Maximilian Heim, Annika Klotz, Christian Rode, Tobias Siebert
Summary: This study investigates the functioning of mammalian skeletal muscle at short lengths and finds that sarcomeres can maintain regular thick filament arrangement and generate force even at extremely short lengths. Furthermore, the sarcomeres exhibit a bimodal length distribution and fibers remain shortened after deactivation, showing increased forces during passive re-elongation. These findings contradict the assumption of thick filament compression and support the model of thick filament sliding.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Nutrition & Dietetics
Carlijn A. Wagenaar, Louise H. Dekker, Gerjan J. Navis
Summary: The study assessed the prevalence and determinants of sarcopenic obesity (SO) and sarcopenia in overweight (SOW) in a general population, finding higher prevalence of SOW and SO in females across all age groups, with age being a significant determinant of both conditions. Subjects over 70 years old accounted for 82.5% and 80.4% of SO and SOW patients, respectively.
CLINICAL NUTRITION
(2021)
Review
Biochemistry & Molecular Biology
Gabryela Kuhnen, Tiago Guedes Russomanno, Marta Murgia, Nicolas J. Pillon, Martin Schoenfelder, Henning Wackerhage
Summary: Adult skeletal muscle fibres can be classified into different types based on the expression of specific genes. The proportions of these muscle fibre types can be altered through gene gain or loss-of-function. In particular, transcriptional regulators play a significant role in regulating the expression of muscle fibre-specific genes. After exercise, the expression of certain genes increases or decreases, suggesting their involvement in muscle fibre adaptation. DNA sequence variants of muscle fibre genes may contribute to the variation in muscle fibre type proportions in the human population.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Immunology
Ricardo Sanchez-Rodriguez, Fabio Munari, Roberta Angioni, Francisca Venegas, Andrielly Agnellini, Maria Paulette Castro-Gil, Alessandra Castegna, Roberto Luisetto, Antonella Viola, Marcella Canton
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
R. S. J. Sparks, W. P. Aspinall, E. Brooks-Pollock, R. M. Cooke, L. Danon, J. Barclay, J. H. Scarrow, J. Cox
Summary: After primary schools in the UK partially reopened with social distancing measures in place, a structured expert elicitation study found that the mean number of daily contacts significantly decreased for students and staff, indicating successful reduction in infection risk through new risk mitigation strategies.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Article
Public, Environmental & Occupational Health
Roger M. Cooke, Harry Joe, Bo Chang
Summary: Regular vines copulas and saturated continuous nonparametric Bayes nets (CNPBN) are methods used for constructing high dimensional joint densities. Vine regression can address complex issues such as model fitting, transformations, heteroscedasticity, etc. By applying vine regression, the impact of breastfeeding on IQ can be calculated, taking into account various factors such as IQ levels and duration of breastfeeding.
Article
Biochemistry & Molecular Biology
Alessio Menga, Maria Favia, Iolanda Spera, Maria C. Vegliante, Rosanna Gissi, Anna De Grassi, Luna Laera, Annalisa Campanella, Andrea Gerbino, Giovanna Carra, Marcella Canton, Vera Loizzi, Ciro L. Pierri, Gennaro Cormio, Massimiliano Mazzone, Alessandra Castegna
Summary: Glutaminolysis plays a crucial role in modulating the interaction between ovarian cancer cells and macrophages, with ovarian cancer cells becoming addicted to extracellular glutamine when silenced for glutamine synthetase. The study uncovers the unprecedented role of glutamine metabolism in modulating macrophage polarization in highly invasive ovarian cancer.
Letter
Public, Environmental & Occupational Health
Ian Lawson, Roger Cooke
OCCUPATIONAL MEDICINE-OXFORD
(2021)
Review
Public, Environmental & Occupational Health
Roger Cooke, Ian Lawson, Susanna Gillibrand, Andrew Cooke
Summary: It is recommended to formally exclude CTS before attributing symptoms to HAVS in vibration-exposed individuals who report concurrent RP and separate sensory symptoms suggestive of, or compatible with CTS.
OCCUPATIONAL MEDICINE-OXFORD
(2022)
Review
Immunology
Marcella Canton, Ricardo Sanchez-Rodriguez, Iolanda Spera, Francisca C. Venegas, Maria Favia, Antonella Viola, Alessandra Castegna
Summary: Reactive oxygen species (ROS) are essential for macrophages to eliminate microorganisms, but also play roles in signal transduction, differentiation, and gene expression; different outcomes may result from ROS formation in specific subcellular sites; identifying the intracellular sources of ROS and their impact on cellular processes is crucial for developing therapies targeting oxidative signaling networks.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Iolanda Spera, Ricardo Sanchez-Rodriguez, Maria Favia, Alessio Menga, Francisca C. Venegas, Roberta Angioni, Fabio Munari, Martina Lanza, Annalisa Campanella, Ciro L. Pierri, Marcella Canton, Alessandra Castegna
Summary: The study validated an in-house generated immortalized macrophage cell line from BMDMs by comparing its functional and metabolic characteristics to primary macrophages, showing similar features. This immortalized cell line can be used as a suitable model for evaluating how perturbations can influence the phenotypical and functional features of murine macrophages in vitro.
Article
Engineering, Environmental
Kyle J. Colonna, Petros Koutrakis, Patrick L. Kinney, Roger M. Cooke, John S. Evans
Summary: Long-term exposure to ambient fine particles (PM2.5) is associated with mortality, although the extrapolation of results to understudied locations may involve uncertainty. Causation is supported, and the composition of PM2.5 and population characteristics can alter the effect.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Editorial Material
Public, Environmental & Occupational Health
Roger Anthony Cooke, Ian James Lawson
OCCUPATIONAL MEDICINE-OXFORD
(2022)
Article
Multidisciplinary Sciences
Kevin Rennert, Frank Errickson, Brian C. Prest, Lisa Rennels, Richard G. Newell, William Pizer, Cora Kingdon, Jordan Wingenroth, Roger Cooke, Bryan Parthum, David Smith, Kevin Cromar, Delavane Diaz, Frances C. Moore, Ulrich K. Muller, Richard J. Plevin, Adrian E. Raftery, Hana Sevcikova, Hannah Sheets, James H. Stock, Tammy Tan, Mark Watson, Tony E. Wong, David Anthoff
Summary: This study shows that improved probabilistic socioeconomic projections, climate models, damage functions, and discounting methods can significantly increase the estimates of the social cost of carbon dioxide (SC-CO2). The study's estimates are higher than the current values used in policy evaluation, thereby increasing the expected benefits of greenhouse gas mitigation.
Article
Environmental Sciences
J. L. Bamber, M. Oppenheimer, R. E. Kopp, W. P. Aspinall, Roger M. Cooke
Summary: The ice sheets on Antarctica and Greenland have significant uncertainties and potential contributions to future sea level rise. The dominant sources of uncertainty in 21st-century projections are surface melting in Greenland and ice dynamics in West Antarctica. In the 22nd century, the dominant drivers of uncertainty shift to ice dynamics in East Antarctica. These findings highlight the key processes and factors that need to be addressed to reduce uncertainties in ice sheet projections.
Article
Multidisciplinary Sciences
Kyle J. Colonna, Gabriela F. Nane, Ernani F. Choma, Roger M. Cooke, John S. Evans
Summary: This study evaluates the predictive and probabilistic performance of COVID-19 forecasting models in 2021. Results show that predictive performance and probabilistic performance are not necessarily correlated, and most models perform worse than a baseline model. The CDC and CM ensembles both perform well, but the CM ensemble is more statistically accurate.
ROYAL SOCIETY OPEN SCIENCE
(2022)
Meeting Abstract
Biophysics
Clyde F. Wilson, Nariman I. Naber, Roger Cooke
BIOPHYSICAL JOURNAL
(2022)
Article
Economics
Kevin Rennert, Brian C. Prest, William A. Pizer, Richard G. Newell, David Anthoff, Cora Kingdon, Lisa Rennels, Roger Cooke, Adrian E. Raftery, Hana Sevcikova, Frank Errickson
Summary: The social cost of carbon is a crucial metric for climate policy, requiring consideration of uncertainty and transparency of assumptions. Challenges in estimation push the boundaries of analytical techniques, necessitating augmented approaches to assess uncertainty and discounting.
BROOKINGS PAPERS ON ECONOMIC ACTIVITY
(2021)