Neurodegenerative disorders are among the most common diseases in modern society. However, the molecular bases of diseases such as multiple sclerosis or Charcot-Marie-Tooth disease remain far from being fully understood. Research in this field is limited by the complex nature of native myelin and by difficulties in obtaining good in vitro model systems of myelin. Here, we introduce an easy-to-use model system of the myelin sheath that can be used to study myelin proteins in a native-like yet well-controlled environment. To this end, we present myelin-mimicking nanodiscs prepared through one of the amphiphilic copolymers styrene/maleic acid (SMA), diisobutylene/maleic acid (DIBMA), and styrene/maleimide sulfobetaine (SMA-SB). These nanodiscs were tested for their lipid composition using chromatographic (HPLC) and mass spectrometric (MS) methods and, utilizing spin probes within the nanodisc, their comparability with liposomes was studied. In addition, their binding behavior with bovine myelin basic protein (MBP) was scrutinized to ensure that the nanodiscs represent a suitable model system of myelin. Our results suggest that both SMA and SMA-SB are able to solubilize the myelin-like (cytoplasmic) liposomes without preferences for specific lipid headgroups or fatty acyl chains. In nanodiscs of both SMA and SMA-SB (called SMA(-SB)-lipid particles, short SMALPs or SMA-SBLPs, respectively), the polymers restrict the lipids' motion in the hydrophobic center of the bilayer. The headgroups of the lipids, however, are sterically less hindered in nanodiscs when compared with liposomes. Myelin-like SMALPs are able to bind bovine MBP, which can stack the lipid bilayers like in native myelin, showing the usability of these simple, well-controlled systems in further studies of protein-lipid interactions of native myelin.
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http://dx.doi.org/10.1021/acs.biomac.1c00714 | DOI Listing |
Elife
December 2024
Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Defining the cellular factors that drive growth rate and proteome composition is essential for understanding and manipulating cellular systems. In bacteria, ribosome concentration is known to be a constraining factor of cell growth rate, while gene concentration is usually assumed not to be limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, and modeling, we show that genome dilution in cells arrested for DNA replication limits total RNA polymerase activity within physiological cell sizes across tested nutrient conditions.
View Article and Find Full Text PDFJAMA Surg
December 2024
Department of Surgery, Stanford University School of Medicine, Stanford, California.
Importance: Surgical quality improvement efforts have largely focused on 30-day outcomes, such as readmissions and complications. Surgery may have a sustained impact on the health and quality of life of patients considered frail, yet data are lacking on the long-term health care utilization of patients with frailty following surgery.
Objective: To examine the independent association of preoperative frailty on long-term health care utilization (up to 24 months) following surgery.
JAMA Netw Open
December 2024
Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Importance: Access to appropriate postpartum care is essential for improving maternal health outcomes and promoting maternal health equity.
Objective: To analyze the impact of the Nurse-Family Partnership (NFP) home visiting program on use of routine and emergency postpartum care.
Design, Setting, And Participants: This study was a secondary analysis of a randomized clinical trial that enrolled eligible participants between 2016 and 2020 to receive NFP or usual care from a South Carolina Medicaid program.
Sports Med Open
December 2024
Alliance for Research in Exercise, Nutrition and Activity (ARENA), Allied Health and Human Performance, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia.
Background: Handgrip strength (HGS) is an excellent marker of general strength capacity and health among adults. We aimed to calculate temporal trends in HGS for adults from Shanghai between 2000 and 2020.
Methods: Adults aged 20-59 years from Shanghai, China, were included.
Arch Toxicol
December 2024
Faculty of Medicine, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Leipzig, Germany.
The Hedgehog (Hh) signaling pathway is essential for maintaining homeostasis during embryogenesis and in adult tissues. In the liver, dysregulation of this pathway often leads to liver cancer development. Recent studies also suggest that disturbances in the Hh pathway can affect liver metabolism in healthy livers through interactions with other signaling pathways, such as the Wnt/β-catenin pathway.
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