DOCSLIB.ORG

The Fall and Rise of Pharmacology – (Re-)Defining the Discipline?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Fall and Rise of Pharmacology – (Re-)Defining the Discipline? Biochemical Pharmacology 87 (2014) 4–24 Contents lists available at ScienceDirect Biochemical Pharmacology jo urnal homepage: www.elsevier.com/locate/biochempharm Review – Part of the Special Issue – Pharmacology in 21st Century Biomedical Research The fall and rise of pharmacology – (Re-)defining the discipline? a b c, Raymond J. Winquist , Kevin Mullane , Michael Williams * a Department of Pharmacology, Vertex Pharmaceuticals Inc., Cambridge, MA, United States b Profectus Pharma Consulting Inc., San Jose, CA, United States c Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States A R T I C L E I N F O A B S T R A C T Article history: Pharmacology is an integrative discipline that originated from activities, now nearly 7000 years old, to Received 7 September 2013 identify therapeutics from natural product sources. Research in the 19th Century that focused on the Law Accepted 9 September 2013 of Mass Action (LMA) demonstrated that compound effects were dose-/concentration-dependent Available online 23 September 2013 eventually leading to the receptor concept, now a century old, that remains the key to understanding disease causality and drug action. As pharmacology evolved in the 20th Century through successive Keywords: biochemical, molecular and genomic eras, the precision in understanding receptor function at the Pharmacology molecular level increased and while providing important insights, led to an overtly reductionistic Receptors emphasis. This resulted in the generation of data lacking physiological context that ignored the LMA and Drug discovery was not integrated at the tissue/whole organism level. As reductionism became a primary focus in Systems biology biomedical research, it led to the fall of pharmacology. However, concerns regarding the disconnect between basic research efforts and the approval of new drugs to treat 21st Century disease tsunamis, e.g., neurodegeneration, metabolic syndrome, etc. has led to the reemergence of pharmacology, its rise, often in the semantic guise of systems biology. Against a background of limited training in pharmacology, this has resulted in issues in experimental replication with a bioinformatics emphasis that often has a limited relationship to reality. The integration of newer technologies within a pharmacological context where research is driven by testable hypotheses rather than technology, together with renewed efforts in teaching pharmacology, is anticipated to improve the focus and relevance of biomedical research and lead to novel therapeutics that will contain health care costs. ß 2013 Elsevier Inc. All rights reserved. Contents 1. Introduction . 5 2. Pharmacology – its fall and rise . 5 2.1. In the beginning. 6 2.2. Pharmacology as a distinct discipline . 6 2.3. The receptor concept . 6 2.3.1. Receptors as drug targets . 6 2.4. Evolution of the receptor concept . 7 2.4.1. Occupancy theory . 8 2.4.2. The ternary complex model (TCM) . 8 2.4.3. Constitutive receptor activity . 8 2.4.4. Regulation of receptor function . 8 2.4.5. Receptor complexes and allosteric modulation . 10 3. The biochemical era in pharmacology . 10 3.1. Receptor isolation . 10 3.2. Receptor subtypes. 11 3.3. Receptor binding assays . 11 3.3.1. Neurotransmitter binding assays . 12 3.3.2. Autoradiographical techniques . 12 * Corresponding author. E-mail address: [email protected] (M. Williams). 0006-2952/$ – see front matter ß 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.bcp.2013.09.011 R.J. Winquist et al. / Biochemical Pharmacology 87 (2014) 4–24 5 3.3.3. Drug mechanism(s) of action; drug receptors . 12 3.3.4. Compound screening . 13 3.4. Biochemical pharmacology – the first circle of reductionism. 13 4. The molecular phase of pharmacology . 13 4.1. Cloning . 13 4.2. Orphan receptors . 14 4.3. Mutagenesis . 14 4.4. Receptor crystallization . 14 4.5. Molecular pharmacology – cloning and expression – the second circle of reductionism . 14 4.5.1. Patenting novel drug targets and their use . 15 4.5.2. Reductionism in signaling pathways . 15 5. Genomic pharmacology . 15 5.1. Pharmacology post the human genome map . 16 5.2. Genomic pharmacology – genome-based targets – the third circle of reductionism . 17 6. The return to holistic, hierarchical pharmacology – reductionism redux . 17 7. Applied pharmacology and drug hunters . 18 7.1. The drug hunter – anachronism or enabler?. 18 8. Future considerations . 18 8.1. Imponderables, complication, unknowns and necessary context – it all depends. 18 8.2. Emerging trends . ..
Load more

Recommended publications
  • Functional Selectivity and Classical Concepts of Quantitative Pharmacology
    JPET Fast Forward. Published on June 27, 2006 as DOI: 10.1124/jpet.106.104463 JPET ThisFast article Forward. has not been Published copyedited andon formatted.June 27, The 2006 final versionas DOI:10.1124/jpet.106.104463 may differ from this version. JPET #104463 PiP Title Page Functional selectivity and classical concepts of quantitative pharmacology Jonathan D. Urban, William P. Clarke, Mark von Zastrow, David E. Nichols, Brian Kobilka, Harel Weinstein, Jonathan A. Javitch, Bryan L. Roth, Arthur Christopoulos Patrick M. Sexton, Keith J. Miller, Michael Spedding, Richard B. Mailman Downloaded from Curriculum in Toxicology (JDU, RBM) and Departments of Pharmacology, Psychiatry Medicinal Chemistry (BLR, RBM), and Neurology (RBM), University of North Carolina, Chapel Hill, NC Department of Pharmacology, University of Texas Health Science Center, San Antonio, jpet.aspetjournals.org TX (WPC) Departments of Psychiatry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA (MvZ) at ASPET Journals on September 25, 2021 Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN (DEN) Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA Department of Physiology and Biophysics, and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY (HW) Center for Molecular Recognition, and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY (JJ) Department of Pharmacology, Monash University, Clayton, Victoria, Australia (AC, PMS) Obesity Department, Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ (KJM) Institute de Recherches Servier, Suresnes 92150, France MS) 1 Copyright 2006 by the American Society for Pharmacology and Experimental Therapeutics.
    [Show full text]
  • Residence Time, Chemical and Isotopic Analysis of Nitrate in The
    Residence Time, Chemical and Isotopic Analysis of Nitrate in the Groundwater and Surface Water of a Small Agricultural Watershed in the Coastal Plain, Bucks Branch, Sussex County, Delaware John Clune ([email protected]) Judy Denver ([email protected]) Introduction Introduction Problem/Need Resource managers need a practical perspective on travel time of groundwater to streams, detailed understanding of the sources of nitrogen for targeting management efforts and to better quantify water-quality improvements Introduction High TN Bucks Branch has some of the highest measured concentrations of total nitrogen in any stream in the State (Delaware Department of Natural Resources and Environmental Control, 2010) and most of the nitrogen is in the form of nitrate. Introduction Sources The vast majority of nitrogen inputs in this part of Sussex County, Delaware are from manure and fertilizer Purpose/Objectives The purpose of this study was to present (1) estimated residence times of groundwater and (2) and provide a chemical and isotopic analysis of nitrate in the groundwater and surface water of the Bucks Branch watershed Purpose/Objectives The purpose of this study was to present Concentrations of sulfur (1) estimated residence times hexafluoride (SF6), dissolved gases and silica of groundwater and (2) and provide a in groundwater and chemical and isotopic analysis of nitrate surface water to in the groundwater and surface water of determine the apparent the Bucks Branch watershed age of groundwater in the aquifer and to estimate the average residence
    [Show full text]
  • Estimation of Groundwater Mean Residence Time in Unconfined Karst Aquifers Using Recession Curves
    A. Kavousi and E. Raeisi – Estimation of groundwater mean residence time in unconfined karst aquifers using recession curves. Journal of Cave and Karst Studies, v. 77, no. 2, p. 108–119. DOI: 10.4311/2014ES0106 ESTIMATION OF GROUNDWATER MEAN RESIDENCE TIME IN UNCONFINED KARST AQUIFERS USING RECESSION CURVES ALIREZA KAVOUSI AND EZZAT RAEISI Dept. of Earth Sciences, College of Sciences, Shiraz University, 71454 Shiraz, Iran, [email protected], [email protected] Abstract: A new parsimonious method is proposed to estimate the mean residence time of groundwater emerging at any specific time during recession periods from karst springs. The method is applicable to unconfined karstic aquifers with no-flow boundaries. The only required data are numerous consecutive spring hydrographs involving a wide range of discharge from high to low flow and the relevant precipitation hyetographs. First, a master recession curve is constructed using the matching-strip method. Then, discharge components corresponding to the individual hydrographs at any desired time are estimated by extrapolation of recession curves based on the master curve. Residence times are also taken from the time elapsed since the events’ centroids. Finally, the mean residence time is calculated by a discharge-weighted average. The proposed method was evaluated for the Sheshpeer Spring in Iran. There are 259 sinkholes in the catchment area of the Sheshpeer unconfined aquifer, and all the boundaries are physically no-flow. The mean residence time calculated by the proposed method was about one year longer than that of uranine dye tracer. The tracer mean time is representative of flowing water between the injection and emergence points, but the mean time by the proposed method is representative of all active circulating water throughout the entire aquifer.
    [Show full text]
  • Stocks, Flows, and Residence Times Box Models
    Box Models: Stocks, Flows, and Residence Times IPOL 8512 Reservoirs • Natural systems can be characterized by the transport or transformation of matter (e.g. water, gases, nutrients, toxics), energy, and organisms in and out of a reservoir. • Reservoirs can be physical (e.g. a human body, the atmosphere, ocean mixed layer), chemical (different chemical species), or biological (e.g. populations, live biomass, dead organic matter) • Transport/transformation can involve bulk movement of matter, diffusion, convection, conduction, radiation, chemical or nuclear reactions, phase changes, births and deaths, etc. Box Models • We make a simple model of a system by representing the reservoirs with a “box” and the transport/transformation with arrows. • We usually assume the box is well-mixed, and we usually are not concerned with internal details. Stock, S Inflow, Fin Outflow, Fout • Stock = the amount of stuff (matter, energy, electric charge, chemical species, organisms, pollutants, etc.) in the reservoir • Flows = the amount of stuff flowing into and out of the reservoir as a function of time Why Use Box Models? To understand or predict: • Concentrations of pollutants in various environmental reservoirs as a function of time: e.g. water pollution, outdoor/ indoor air pollution • Concentrations of toxic substance in organs after inhalation or ingestion; setting standards for toxic exposure or intake • Population dynamics, predator-prey and food- chain models, fisheries, wildlife management • Biogeochemical cycles and climate dynamics (nutrients, energy, air, trace gases, water) How Box Models Work Basic rule of box models: change in stock over time = inflow – outflow S/t = Fin –Fout Situation 1: Equilibrium Fin = Fout S/t = 0 Situation 2: Non-equilibrium Fin > Fout S/t > 0 F < F S/ t < 0 in out 5 Equilibrium: The Balance • In many problems in environmental science, it is reasonable to start with the assumption that a particular stock is in equilibrium, meaning that the stock does not change over time.
    [Show full text]
  • Pharmacogenetic Testing: a Tool for Personalized Drug Therapy Optimization
    pharmaceutics Review Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization Kristina A. Malsagova 1,* , Tatyana V. Butkova 1 , Arthur T. Kopylov 1 , Alexander A. Izotov 1, Natalia V. Potoldykova 2, Dmitry V. Enikeev 2, Vagarshak Grigoryan 2, Alexander Tarasov 3, Alexander A. Stepanov 1 and Anna L. Kaysheva 1 1 Biobanking Group, Branch of Institute of Biomedical Chemistry “Scientific and Education Center”, 109028 Moscow, Russia; [email protected] (T.V.B.); [email protected] (A.T.K.); [email protected] (A.A.I.); [email protected] (A.A.S.); [email protected] (A.L.K.) 2 Institute of Urology and Reproductive Health, Sechenov University, 119992 Moscow, Russia; [email protected] (N.V.P.); [email protected] (D.V.E.); [email protected] (V.G.) 3 Institute of Linguistics and Intercultural Communication, Sechenov University, 119992 Moscow, Russia; [email protected] * Correspondence: [email protected]; Tel.: +7-499-764-9878 Received: 2 November 2020; Accepted: 17 December 2020; Published: 19 December 2020 Abstract: Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician’s ability to understand the obtained results in a standardized way for each particular patient.
    [Show full text]
  • Reigniting Pharmaceutical Innovation Through Holistic Drug Targeting
    Drug Discovery Reigniting pharmaceutical innovation through holistic drug targeting Modern drug discovery approaches take too long, are too expensive, have too many clinical failures and uncertain outcomes. There are many reasons for this unsustainable business model, but primarily, the approaches are not comprehensively holistic. Secondly, none of the pharmaceutical companies openly share the reasons for the failure of their clinical candidates in real time to effectively navigate the ‘industry’ from committing the same mistakes. It is time for the pharmaceutical industry to embrace, metaphorically speaking, a community-driven ‘Wikipedia’ or ‘Waze’-type shared-knowledge, openly- accessible innovation model to harvest data and create a crowd-sourced path towards a safer and faster road to the discovery and development of life-saving medicines. This may be a bitter pill for Pharma to swallow, but one that ought to be given serious consideration. The time is now for a paradigm shift towards multi-target-network polypharmacology drugs exalting symphonic or concert performance with occasional soloists to reignite pharmaceutical innovation. rom the turn of the 20th century, pharma- and ultra-high throughput workflows enabled By Dr Anuradha Roy, cognosy and ethnopharmacology combined screening of millions of compounds to identify hit Professor Bhushan F with anecdotal clinical evidence accumulat- can didates for lead development. Despite billions Patwardhan and ed over centuries of hands-on knowledge from pri- of dollars spent on R&D, only a fraction of the Dr Rathnam mordial disease management practices, albeit with molecules identified from the screening operations Chaguturu uncertain outcomes, formed the basis for the devel- find their way into clinical trials.
    [Show full text]
  • Development of a FLIPR Assay for the Simultaneous Identification of Mrgd
    Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2010, Article ID 326020, 8 pages doi:10.1155/2010/326020 Research Article Development of a FLIPR Assay for the Simultaneous Identification of MrgD Agonists and Antagonists from a Single Screen Seena K. Ajit,1, 2 Mark H. Pausch,2 Jeffrey D. Kennedy,2 and Edward J. Kaftan2 1 Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, MS number 488, Philadelphia, PA 19102, USA 2 Neuroscience Discovery, Pfizer Global Research and Development, CN 8000, Princeton, NJ 08543, USA Correspondence should be addressed to Seena K. Ajit, [email protected] Received 1 April 2010; Revised 8 July 2010; Accepted 6 August 2010 Academic Editor: John V. Moran Copyright © 2010 Seena K. Ajit et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MrgD, a member of the Mas-related gene family, is expressed exclusively in small diameter IB4+ neurons in the dorsal root ganglion. This unique expression pattern, the presence of a single copy of MrgD in rodents and humans, and the identification of a putative ligand, beta-alanine, make it an experimentally attractive therapeutic target for pain with limited likelihood of side effects. We have devised a high throughput calcium mobilization assay that enables identification of both agonists and antagonists from a single screen for MrgD. Screening of the Library of Pharmacologically Active Compounds (LOPAC) validated this assay approach, and we identified both agonists and antagonists active at micromolar concentrations in MrgD expressing but not in parental CHO-DUKX cell line.
    [Show full text]
  • Innovative Approaches in Drug Discovery
    See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/313600306 Reverse pharmacology and system approach for drug discovery and development Article · January 2008 CITATIONS READS 9 428 4 authors: Bhushan K Patwardhan Ashok D B Vaidya Savitribai Phule Pune University Saurashtra University 229 PUBLICATIONS 5,729 CITATIONS 237 PUBLICATIONS 2,356 CITATIONS SEE PROFILE SEE PROFILE Mukund S Chorghade Swati P Joshi THINQ Pharma and Empiriko CSIR - National Chemical Laboratory, Pune 117 PUBLICATIONS 1,428 CITATIONS 59 PUBLICATIONS 541 CITATIONS SEE PROFILE SEE PROFILE Some of the authors of this publication are also working on these related projects: graduate studies View project Standardization of an Ayurveda-inspired antidiabetic and experimental studie with state-of--the artinvitro and in vivo models, View project All content following this page was uploaded by Mukund S Chorghade on 24 May 2017. The user has requested enhancement of the downloaded file. Chapter 4 Reverse Pharmacology Ashwinikumar A. Raut1, Mukund S. Chorghade2 and Ashok D.B. Vaidya1 1Kasturba Health Society-Medical Research Centre, Mumbai, Maharashtra, India, 2THINQ, Boston, MA, United States INTRODUCTION AND BACKGROUND I never found it [drug discovery] easy. People say I was lucky twice but I resent that. We stuck with [cimetidine] for 4 years with no progress until we eventually succeeded. It was not luck, it was bloody hard work. — Sir James Black, Nobel Laureate (Jack, 2009). Introduction The aforementioned quote from Sir James Black, the discoverer of β-adrenergic and H2- blockers, expresses the exasperation so often felt by many scientists who have dedicated their lives to new drug discoveries.
    [Show full text]
  • A Brief View of Molecular Modeling Approaches to P2 Receptors Anael V.P
    Chapter A Brief View of Molecular Modeling Approaches to P2 Receptors Anael V.P. Alberto, Lucianna H.S. Santos, Rafael Ferreira, Dinarte N.M. Ferreira and Luiz A. Alves Abstract Purinergic receptors are a class of receptors distributed into two groups, P1 and P2. P1 receptors are activated by nucleosides, like adenosine, while nucleotides active P2 receptors. In turn, P2 receptors comprise two families, metabotropic P2Y and ionotropic P2X. P2Y receptors consist in eight members, namely, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, described in mammals, while P2X includes seven members, numbered P2X1 to P2X7. These receptors have been described as expressed in practically all cells studied to date. In this context, P2 receptors are suggested as participating in certain diseases. The general approach applied in the discovery of new drugs is expensive and lengthy. Alternatively, in the last 20 years, molecular modeling has emerged as an exciting tool for the design of new drugs, in less time and at low costs. These tools allow for in silico testing of thousands of molecules against a target protein, as well as toxicity, absorption, distribution, metabolism, and constant affinity predictions of a given interaction. Thus, molecular modeling algorithms emerge as an increasingly important tool for the design of drugs targeting purinergic receptors as therapeutic targets of many diseases, including cancer, pain, inflammation, cardiovascular, and endocrine conditions. Keywords: molecular modeling, molecular dynamics, virtual screening, homology modeling, drug discovery, P2X receptors, P2Y receptors 1. Introduction Purinergic receptors are a class of transmembrane proteins activated by extracellular nucleotides and nucleosides. They consist in the P1 receptor (mainly activated by adenosine) and P2 receptors distributed into two families, P2Y (G protein-coupled receptors) and P2X (ionotropic receptor).
    [Show full text]
  • Application of Multi-Target Phytotherapeutic Concept in Malaria
    Tarkang et al. Biomarker Research (2016) 4:25 https://doi.org/10.1186/s40364-016-0077-0 REVIEW Open Access Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification Protus Arrey Tarkang1,2*, Regina Appiah-Opong2, Michael F. Ofori3, Lawrence S. Ayong4 and Alexander K. Nyarko2,5 Abstract There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly- pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers.
    [Show full text]
  • Wastewater Residence Time in Sewers
    October 1969 Report No. EVE 19-69-7 THE EFFECT AND REGULATION OF WASTEWATER RESIDENCE TIME IN SEWERS David R. O'Toole and Donald Dean Adrian, Project Investigator Partially Funded by Office of Water Resources Research Grant WR-BO 11-MASS and Federal Water Pollution Control Administration Training Grant 5T1-WP-77-04 ENVIRONMENTAL ENGINEERING DEPARTMENT OF CIVIL ENGINEERING UNIVERSITY OF MASSACHUSETTS AMHERST, MASSACHUSETTS TKE EFFECT AND REGULATION OF WASTEWATER RESIDENCE TIME IN SEWERS by ! David R. O'Toole and Donald Dean Adrian, Project Investigator October 1969 THE AUTHORS w David Richard O'Toole received his B.S. degree in 0 Civil Engineering from the University of Massachusetts in June 1968, After a summer working for a consulting engineering firm he enroiled as a graduate student in the Environmental Engineering Program, Department of Civil Engineering, University of Massachusetts. Upon receipt of his Master's degree in September 1969, he was "commissioned by the U. S. Public Health Service to work as an Assistant Sanitary Engineer with the Indian Health Service in Portland, Oregon. Donald Dean Adrian received his B.A. degree in Liberal Arts and his B.S. degree in Civil Engineering from the University of Notre Dame in 1957 and 1958, respectively. He enrolled in the graduate program in Sanitary Engineering at the University of California at Berkeley and was awarded the M.S. degree in 1959. The Ph.D. was obtained from Stanford University in Civil Engineering in 1964. Experience has been obtained with the California Health Department, Vanderbilt University and the University of Massachusetts. He is presently an Associate Professor of Civil Engineering.
    [Show full text]
  • 14C Mean Residence Time and Its Relationship with Thermal Stability
    Geoderma 308 (2017) 1–8 Contents lists available at ScienceDirect Geoderma journal homepage: www.elsevier.com/locate/geoderma 14C mean residence time and its relationship with thermal stability and MARK molecular composition of soil organic matter: A case study of deciduous and coniferous forest types ⁎ Tsutomu Ohnoa, , Katherine A. Heckmanb, Alain F. Plantec, Ivan J. Fernandezd, Thomas B. Parre a School of Food and Agriculture, University of Maine, Orono, ME 04469, USA b USDA Forest Service, Northern Research Station, Houghton, MI 49931, USA c Department of Earth and Environmental Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA d School of Forest Resources, University of Maine, Orono, ME 04469, USA e Department of Biology, University of Oklahoma, Norman, OK 73019, USA ARTICLE INFO ABSTRACT Keywords: Soil organic matter (SOM) plays a critical role in the global terrestrial carbon cycle, and a better understanding Soil organic carbon of soil processes involved in SOM stability is essential to determine how projected climate-driven changes in soil Carbon sequestration processes will influence carbon dynamics. We used 14C signature, analytical thermal analysis, and ultrahigh Soil minerals resolution mass spectrometry to determine the influence of deciduous and coniferous forest vegetation type and Radiocarbon dating soil depth on the stability of soil C. The 14C mean residence time (MRT) of the illuvial B horizon soils averaged Thermal analysis 1350 years for the deciduous soils and 795 years for the coniferous soils. The difference of MRT between mineral Ultrahigh resolution mass spectrometry soils by forest type may be due to the saturation of extractable Fe and Al minerals binding sites by SOM in the coniferous soils, allowing greater transport of modern SOM from the O horizon down the soil profile, as com- pared with the non-saturated minerals in the deciduous soil profile.
    [Show full text]