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The real-time identification of protein biomarkers is crucial for the development of point-of-care and portable devices. Here, we use a PlyAB biological nanopore to detect haemoglobin (Hb) variants. Adult haemoglobin (HbA) and sickle cell anaemia haemoglobin (HbS), which differ by just one amino acid, were distinguished in a mixture with more than 97 % accuracy based on individual blockades. Foetal Hb, which shows a larger sequence variation, was distinguished with near 100 % accuracy. Continuum and Brownian dynamics simulations revealed that Hb occupies two energy minima, one near the inner constriction and one at the trans entry of the nanopore. Thermal fluctuations, the charge of the protein, and the external bias influence the dynamics of Hb within the nanopore, which in turn generates the unique ionic current signal in the Hb variants. Finally, Hb was counted from blood samples, demonstrating that direct discrimination and quantification of Hb from blood using nanopores, is feasible.
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http://dx.doi.org/10.1002/anie.202206227 | DOI Listing |
Genetics
September 2025
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Protein translation regulation is critical for cellular responses and development, yet how elongation stage disruptions shape these processes remains incompletely understood. Here, we identify a single amino acid substitution (P55Q) in the ribosomal protein RPL-36A of Caenorhabditis elegans that confers complete resistance to the elongation inhibitor cycloheximide (CHX). Heterozygous animals carrying both wild-type RPL-36A and RPL-36A(P55Q) develop normally but show intermediate CHX resistance, indicating a partial dominant effect.
View Article and Find Full Text PDFSci Transl Med
September 2025
Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.
View Article and Find Full Text PDFSci Transl Med
September 2025
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V1-138, the macaque homolog of human V1-69, a V gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs).
View Article and Find Full Text PDFPLoS One
September 2025
Department of Computer Science, Emory University, Atlanta, Georgia, United States of America.
Background: Erythema, an early visual indicator of tissue damage preceding pressure injuries (PrIs), presents as redness in light skin tones but is harder to detect in dark skin tones. While thermography shows promise for early PrI detection, validation across different skin tones remains limited. Furthermore, most protocols and models have been developed under highly controlled conditions.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Division of Medical Sciences, NOSM University, Ontario, Canada.
Cancer induced skeletal muscle wasting (cachexia) is responsible for over 20% of cancer related deaths, yet much about the pathophysiology of the condition remains unknown. Importantly, cancer cachexia does not seem wholly responsive to traditional anabolic stimuli such as nutritional interventions. It is possible that tumours directly or indirectly target skeletal muscle for their dynamic and abundant pool of amino acids that can be reliably used by tumours to supplement energy production and biomass synthesis.
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