As we commemorate 40 years of the International Conference of Primary Health Care celebrated in Alma-Ata (Kazakhstan, ex-USSR) in 1978, the currency of its fundamental principles holds strong, and it is important to remember them as a referent for the near future, and to project them to every individual's health, to be built by all.
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Symmetry breaking and mismatch in the torsional mechanism of ATP synthesis by FF-ATP synthase: mathematical number theory proof and its chemical and biological implications.
Theory Biosci
December 2024
Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
Can mathematical proofs be employed for the solution of fundamental molecular-level problems in biology? Recently, I mathematically tackled complex mechanistic problems arising during the synthesis of the universal biological currency, adenosine triphosphate (ATP) by the FF-ATP synthase, nature's smallest rotary molecular motor, using graph-theoretical and combinatorial approaches for the membrane-bound F and water-soluble F domains of this fascinating molecule (see Nath in Theory Biosci 141:249‒260, 2022 and Theory Biosci 143:217‒227, 2024). In the third part of this trilogy, I investigate another critical aspect of the molecular mechanism-that of coupling between the F and F domains of the ATP synthase mediated by the central γ-subunit of nanometer diameter. According to Nath's torsional mechanism of energy transduction and ATP synthesis the γ-subunit twists during ATP synthesis and the release of stored torsional energy in the central γ-stalk causes conformational changes in the catalytic sites that lead to ATP synthesis, with 1 ATP molecule synthesized per discrete 120° rotation.
View Article and Find Full Text PDFIn the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate.
Int J Mol Sci
November 2024
Department of Biological Sciences, Faculty of Science, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
Water exists in the beginning and hydrates all matter. Life emerged in water, requiring three essential components in compartmentalized spaces: (1) universal energy sources driving biochemical reactions and processes, (2) molecules that store, encode, and transmit information, and (3) functional players carrying out biological activities and structural organization. Phosphorus has been selected to create adenosine triphosphate (ATP) as the universal energy currency, nucleic acids for genetic information storage and transmission, and phospholipids for cellular compartmentalization.
View Article and Find Full Text PDFWoman or surgeon - Not both: Perceptions of support, enablers and barriers in general surgery.
Surg Open Sci
December 2024
The Leeds Institute of Medical Education, School of Medicine, University of Leeds, United Kingdom of Great Britain and Northern Ireland.
Introduction: The General Surgery (GS) educational community of practice faces crisis. Recruitment is challenged by cultural norms of postponing post-foundation training; and retention with perceptions of elitism, discrimination and inflexibility (UK Shape of Training Steering Group, 2017; Kennedy, 2021) [1,45]. Surgical pedagogy has been examined through skill acquisition but what of the hidden curriculum (Brown et al.
View Article and Find Full Text PDFProteins occurring in significantly high concentrations in cellular environments (over 100 mg/ml) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here, we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein aggregates. We show that ATP prevents both condensation of aggregation-prone intrinsically disordered protein Aβ40 and promotes dissolution of preformed aggregates.
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Langmuir
October 2024
Center for Interdisciplinary Sciences, Tata Institute of Fundamental Research, Hyderabad 500046, India.
Adenosine triphosphate (ATP), ubiquitous in all living organisms, is conventionally recognized as a fundamental energy currency essential for a myriad of cellular processes. While its traditional role in energy metabolism requires only micromolar concentrations, the cellular content of ATP has been found to be significantly higher at the millimolar level. Recent studies have attempted to correlate this higher concentration of ATP with its nonenergetic role in maintaining protein homeostasis, leaving the investigation of ATP's nontrivial activities in biology an open question.
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