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Publisher: Elsevier   (Total: 3031 journals)

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Showing 1 - 200 of 3031 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 20, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 16, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 79, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 22, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 27, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 302, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription  
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 195, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 9, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 21, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 5, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 119, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 24, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 21, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 26, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 24, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 8, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 4)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 39, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 38, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 41, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 14)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 18, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 33, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 4)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 7, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 5, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 6, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 20, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 14)
Advances in Pharmacology     Full-text available via subscription   (Followers: 13, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 17, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 56)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 1, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 332, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 7)
Advances in Surgery     Full-text available via subscription   (Followers: 6, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 28, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 14)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 12)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 42, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 303, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 4, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 7, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 389, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 29, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 36, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 48, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 3, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 5)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 7, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 6, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 45, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 45, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 47, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 34, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 25, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 31, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 48, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 173, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 51, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 2)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 22, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 23, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 32, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 13, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 52, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 3)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 38, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 152, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 7, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 10)
Anesthésie & Réanimation     Full-text available via subscription  
Anesthesiology Clinics     Full-text available via subscription   (Followers: 21, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 141, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
Annales de Chirurgie Plastique Esthétique     Full-text available via subscription   (Followers: 2, SJR: 0.354, h-index: 22)
Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

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Journal Cover Advances in Protein Chemistry and Structural Biology
  [SJR: 1.5]   [H-I: 62]   [17 followers]  Follow
    
   Full-text available via subscription Subscription journal  (Not entitled to full-text)
   ISSN (Online) 1876-1623
   Published by Elsevier Homepage  [3031 journals]
  • Chapter Two Roles of SMC Complexes During T Lymphocyte Development and
           Function
    • Authors: J.S. Rawlings
      Pages: 17 - 42
      Abstract: Publication date: 2017
      Source:Advances in Protein Chemistry and Structural Biology, Volume 106
      Author(s): J.S. Rawlings
      T lymphocytes (T cells) comprise a critical component of the immune system charged with diverse functions during an immune response. As a function of maturation in the thymus, T cells become quiescent and remain so until they participate in an immune response in the periphery. Recent work indicates that the control of T cell proliferation is mediated, at least in part, by chromatin architecture. Quiescent T cells possess a condensed chromatin, whereas proliferating T cells have a more open chromatin configuration. The structural maintenance of chromosome (SMC) complexes, which include Cohesin and Condensin, have long been known to play roles in modulating chromatin architecture during cell division; however, they are now known to have additional roles during interphase biology. These roles include the large-scale reorganization of chromatin as well as the regulation of specific gene loci. This review focuses on the roles that SMC complexes play in T cell development and function.

      PubDate: 2017-01-05T17:36:15Z
      DOI: 10.1016/bs.apcsb.2016.08.001
      Issue No: Vol. 106 (2017)
       
  • Stress-Induced NLRP3 Inflammasome in Human Diseases
    • Authors: Elísabet Alcocer-Gómez; Beatriz Castejón-Vega; Mario D. Cordero
      Abstract: Publication date: Available online 27 March 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Elísabet Alcocer-Gómez, Beatriz Castejón-Vega, Mario D. Cordero
      Stress is a complex event that induces disturbances to physiological and psychological homeostasis, and it may have a detrimental impact on certain brain and physiological functions. In the last years, a dual role of the stress effect has been studied in order to elucidate the molecular mechanism by which can induce physiological symptoms after psychological stress exposition and vice versa. In this sense, inflammation has been proposed as an important starring. And in the same line, the inflammasome complex has emerged to give responses because of its role of stress sensor. The implication of the same complex, NLRP3 inflammasome, in different diseases such as cardiovascular, neurodegenerative, psychiatric, and metabolic diseases opens a door to develop new therapeutic perspectives.

      PubDate: 2017-03-28T20:30:18Z
      DOI: 10.1016/bs.apcsb.2017.02.002
       
  • A Computational Approach to Identify the Biophysical and Structural
           Aspects of Methylenetetrahydrofolate Reductase (MTHFR) Mutations (A222V,
           E429A, and R594Q) Leading to Schizophrenia
    • Authors: Himani Tanwar; P. Sneha; D. Thirumal Kumar; R. Siva; Charles Emmanuel Jebaraj Walter; C. George Priya Doss
      Abstract: Publication date: Available online 23 March 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Himani Tanwar, P. Sneha, D. Thirumal Kumar, R. Siva, Charles Emmanuel Jebaraj Walter, C. George Priya Doss
      The association between depression and methylenetetrahydrofolate reductase (MTHFR) has been continually demonstrated in clinical studies, yet there are sparse resources available to build a relationship between the mutations associated with MTHFR and depression. The common mutations found to be associated with schizophrenia and MTHFR are A222V, E429A, and R594Q. Although abundant research on structural and functional effects caused by A222V mutation is available, very less amount of studies have been done on the other two mutants (E429A and R594Q). Hence in this study, a comparative analysis was carried out between the most common A222V mutation, a prevalent E429A mutation, and a less prevalent and less deleterious R594Q mutation. To predict structural rearrangements upon mutation, we proposed a computational pipeline using in silico prediction tools, molecular docking, and molecular dynamics simulation analysis. Since the association of flavin adenine dinucleotide (FAD) is important for the functioning of the protein, binding analysis between protein and the coenzyme was performed. This would enable us to understand the interference level of each mutation over FAD-binding activity. Consequently, we found that two mutations (A222V and E429A) showed lesser binding activity and structural deviations when compared to the native molecule and mutant R594Q. Comparatively, higher structural changes were observed with A222V mutant complex in comparison to other mutant complexes. Computational studies like this could render better insights into the structural changes in the protein and their relationship with the disease condition.

      PubDate: 2017-03-28T20:30:18Z
      DOI: 10.1016/bs.apcsb.2017.01.007
       
  • Neuroinflammation in Alzheimer's Disease: The Preventive and Therapeutic
           Potential of Polyphenolic Nutraceuticals
    • Authors: Yousef Sawikr; Nagendra Sastry Yarla; Ilaria Peluso; Mohammad Amjad Kamal; Gjumrakch Aliev; Anupam Bishayee
      Abstract: Publication date: Available online 22 March 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Yousef Sawikr, Nagendra Sastry Yarla, Ilaria Peluso, Mohammad Amjad Kamal, Gjumrakch Aliev, Anupam Bishayee
      Brain inflammation, characterized by increased microglia and astrocyte activation, increases during aging and is a key feature of neurodegenerative diseases, such as Alzheimer's disease (AD). In AD, neuronal death and synaptic impairment, induced by amyloid-β (Aβ) peptide, are at least in part mediated by microglia and astrocyte activation. Glial activation results in the sustained production of proinflammatory cytokines and reactive oxygen species, giving rise to a chronic inflammatory process. Astrocytes are the most abundant glial cells in the central nervous system and are involved in the neuroinflammation. Astrocytes can be activated by numerous factors, including free saturated fatty acids, pathogens, lipopolysaccharide, and oxidative stress. Activation of astrocytes produces inflammatory cytokines and the enzyme cyclooxygenase-2, enhancing the production of Aβ. Furthermore, the role of the receptor for advanced glycation end products/nuclear factor-κB (NF-κB) axis in neuroinflammation is in line with the nonenzymatic glycosylation theory of aging, suggesting a central role of the advanced glycation end products in the age-related cognitive and a possible role of nutraceuticals in the prevention of neuroinflammation and AD. However, modulation of P-glycoprotein, rather than antioxidant and anti-inflammatory effects, could be the major mechanism of polyphenolic compounds, including flavonoids. Curcumin, resvertrol, piperine, and other polyphenols have been explored as novel therapeutic and preventive agents for AD. The aim of this review is to critically analyze and discuss the mechanisms involved in neuroinflammation and the possible role of nutraceuticals in the prevention and therapy of AD by targeting neuroinflammation.

      PubDate: 2017-03-28T20:30:18Z
      DOI: 10.1016/bs.apcsb.2017.02.001
       
  • Analyzing the Effect of V66M Mutation in BDNF in Causing Mood Disorders: A
           Computational Approach
    • Authors: Sneha Thirumal; Kumar Sugandhi Saini Kreeti Kajal Magesh Siva George
      Abstract: Publication date: Available online 9 March 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): P. Sneha, D. Thirumal Kumar, Sugandhi Saini, Kreeti Kajal, R. Magesh, R. Siva, C. George Priya Doss
      Mental disorders or mood disorders are prevalent globally irrespective of region, race, and ethnic groups. Of the types of mood disorders, major depressive disorder (MDD) and bipolar disorder (BPD) are the most prevalent forms of psychiatric condition. A number of preclinical studies emphasize the essential role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders. Additionally, BDNF is the most common growth factor in the central nervous system along with their essential role during the neural development and the synaptic elasticity. A malfunctioning of this protein is associated with many types of mood disorders. The variant methionine replaces valine at 66th position is strongly related to BPD, and an individual with a homozygous condition of this allele is at a greater risk of developing MDD. There are very sparse reports suggesting the structural changes of the protein occurring upon the mutation. Consequently, in this study, we applied a computational pipeline to understand the effects caused by the mutation on the protein's structure and function. With the use of in silico tools and computational macroscopic methods, we identified a decrease in the alpha-helix nature, and an overall increase in the random coils that could have probably resulted in deformation of the protein.

      PubDate: 2017-03-09T16:01:25Z
       
  • Oxidative Stress: Love and Hate History in Central Nervous System
    • Authors: Genaro Gabriel Ortiz; Fermín P. Pacheco Moisés; Mario Mireles-Ramírez; Luis J. Flores-Alvarado; Héctor González-Usigli; Víctor J. Sánchez-González; Angélica L. Sánchez-López; Lorenzo Sánchez-Romero; Eduardo I. Díaz-Barba; J. Francisco Santoscoy-Gutiérrez; Paloma Rivero-Moragrega
      Abstract: Publication date: Available online 7 March 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Genaro Gabriel Ortiz, Fermín P. Pacheco Moisés, Mario Mireles-Ramírez, Luis J. Flores-Alvarado, Héctor González-Usigli, Víctor J. Sánchez-González, Angélica L. Sánchez-López, Lorenzo Sánchez-Romero, Eduardo I. Díaz-Barba, J. Francisco Santoscoy-Gutiérrez, Paloma Rivero-Moragrega
      Molecular oxygen is essential for aerobic organisms in order to synthesize large amounts of energy during the process of oxidative phosphorylation and it is harnessed in the form of adenosine triphosphate, the chemical energy of the cell. Oxygen is toxic for anaerobic organisms but it is also less obvious that oxygen is poisonous to aerobic organisms at higher concentrations of oxygen. For instance, oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at increased partial pressures. Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen that are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis. However, in pathological conditions ROS levels can increase dramatically. This may result in significant damage to cell structures. Living organisms have been adapted to the ROS in two ways: they can mitigate the unwanted effects through removal by the antioxidant systems and can advantageously use them as messengers in cell signaling and regulation of body functions. Some other physiological functions of ROS include the regulation of vascular tone, detection, and adaptation to hypoxia. In this review, we describe the mechanisms of oxidative damage and its relationship with the most highly studied neurodegenerative diseases.

      PubDate: 2017-03-09T16:01:25Z
      DOI: 10.1016/bs.apcsb.2017.01.003
       
  • Inflammation in Epileptic Encephalopathies
    • Authors: Oleksii Shandra; Solomon L. Moshé; Aristea S. Galanopoulou
      Abstract: Publication date: Available online 28 February 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Oleksii Shandra, Solomon L. Moshé, Aristea S. Galanopoulou
      West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural–metabolic pathologies (~60%), genetic (12%–15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox–Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation?

      PubDate: 2017-03-03T12:44:54Z
      DOI: 10.1016/bs.apcsb.2017.01.005
       
  • Molecular Targets of Ascochlorin and Its Derivatives for Cancer Therapy
    • Authors: Jason Chua Min-Wen; Benjamin Chua Yan-Jiang; Srishti Mishra; Xiaoyun Dai; Junji Magae; Ng Shyh-Chang; Alan Prem Kumar; Gautam Sethi
      Abstract: Publication date: Available online 15 February 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Jason Chua Min-Wen, Benjamin Chua Yan-Jiang, Srishti Mishra, Xiaoyun Dai, Junji Magae, Ng Shyh-Chang, Alan Prem Kumar, Gautam Sethi
      Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease. Ascochlorin (ASC), an isoprenoid antibiotic isolated initially from the fermented broth of Ascochyta viciae, and its synthetic derivatives have recently demonstrated substantial antineoplastic effects in a variety of tumor cell lines and mouse models. The major focus of this review article is to briefly analyze the chemopreventive as well as therapeutic properties of ASC and its derivatives and to identify the multiple molecular targets modulated by this novel class of anticancer agent.

      PubDate: 2017-02-17T07:31:15Z
      DOI: 10.1016/bs.apcsb.2017.01.001
       
  • Stress-Adaptive Response in Ovarian Cancer Drug Resistance: Role of TRAP1
           in Oxidative Metabolism-Driven Inflammation
    • Authors: Maria Rosaria Amoroso; Danilo Swann Matassa; Ilenia Agliarulo; Rosario Avolio; Francesca Maddalena; Valentina Condelli; Matteo Landriscina; Franca Esposito
      Abstract: Publication date: Available online 12 February 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Maria Rosaria Amoroso, Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Francesca Maddalena, Valentina Condelli, Matteo Landriscina, Franca Esposito
      Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts. In recent years, oxidative phosphorylation has been linked to a remodeling of inflammatory response due to autocrine or paracrine secretion of interleukines that, in turn, induces a regulation of gene expression involving, among others, molecules responsible for the onset of drug resistance. This process is especially relevant in ovarian cancer, characterized by low survival, high frequency of disease relapse and chemoresistance. Recently, the molecular chaperone TRAP1 (tumor necrosis factor-associated protein 1) has been identified as a key junction molecule in these processes in ovarian cancer: in fact, TRAP1 mediates a metabolic switch toward oxidative phosphorylation that, in turn, triggers cytokines secretion, with consequent gene expression remodeling, finally leading to cisplatin resistance and epithelial-to-mesenchymal transition in ovarian cancer models. This review summarizes how metabolism, chemoresistance, inflammation, and epithelial-to-mesenchymal transition are strictly interconnected, and how TRAP1 stays at the crossroads of these processes, thus shedding new lights on molecular networks at the basis of ovarian cancer.

      PubDate: 2017-02-17T07:31:15Z
      DOI: 10.1016/bs.apcsb.2017.01.004
       
  • Cardiokines as Modulators of Stress-Induced Cardiac Disorders
    • Authors: Anna Planavila; Joaquim Fernández-Solà; Francesc Villarroya
      Abstract: Publication date: Available online 10 February 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Anna Planavila, Joaquim Fernández-Solà, Francesc Villarroya
      Almost 30 years ago, the protein, atrial natriuretic peptide, was identified as a heart-secreted hormone that provides a peripheral signal from the myocardium that communicates to the rest of the organism to modify blood pressure and volume under conditions of heart failure. Since then, additional peripheral factors secreted by the heart, termed cardiokines, have been identified and shown to coordinate this interorgan cross talk. In addition to this interorgan communication, cardiokines also act in an autocrine/paracrine manner to play a role in intercellular communication within the myocardium. This review focuses on the roles of newly emerging cardiokines that are mainly increased in stress-induced cardiac diseases. The potential of these cardiokines as clinical biomarkers for diagnosis and prognosis of cardiac disorders is also discussed.

      PubDate: 2017-02-11T02:26:12Z
      DOI: 10.1016/bs.apcsb.2017.01.002
       
  • Targeting IKK and NF-κB for Therapy
    • Authors: J.K. Durand; A.S. Baldwin
      Abstract: Publication date: Available online 11 January 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): J.K. Durand, A.S. Baldwin
      In addition to regulating immune responses, the NF-κB family of transcription factors also promotes cellular proliferation and survival. NF-κB and its activating kinase, IKK, have become appealing therapeutic targets because of their critical roles in the progression of many diseases including chronic inflammation and cancer. Here, we discuss the conditions that lead to pathway activation, the effects of constitutive activation, and some of the strategies used to inhibit NF-κB signaling.

      PubDate: 2017-01-13T18:51:36Z
      DOI: 10.1016/bs.apcsb.2016.11.006
       
  • Elucidating the Mutational Landscape in Hepatocyte Nuclear Factor 1β
           (HNF1B) by Computational Approach
    • Authors: Sneha C.G.P.; Doss
      Abstract: Publication date: Available online 3 January 2017
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): P. Sneha, C.G.P. Doss
      Transcription factors are the major gene-regulatory proteins that recognize specific nucleotide sequences and bind to them. Missense mutations in transcription factors play a significant role in misregulation of gene expression contributing to various diseases and disorders. Understanding their structural and functional impact of the disease-causing mutations becomes prime importance in treating a disease. Commonly associated defect with the mutations of hepatocyte nuclear factor 1 beta (HNF1B) protein, a transcription factor results in maturity-onset diabetes of the young-5 (MODY-5) leading to loss of function. In the study presented, we applied a series of computational strategies to analyze the effect of mutations on protein structure or function in protein–DNA complex. The mutations from publicly available databases were retrieved and subjected to an array of in silico prediction methods. Key implementation of the present study consists of a pipeline drawn using well established in silico prediction methods of different algorithms to explain the biochemical changes impaired upon mutations in the binding sites of protein–DNA complex using HNF1B. Prediction scores obtained from the in silico tools suggested H153N and A241T as the major nsSNPs involved in destabilizing the protein. Further, high-end microscopic computational study, such as molecular dynamics simulations was utilized to relate the structural and functional effects upon mutations. Although, both the mutations exhibited similar structural differences, we observed A241T with higher destabilizing effect on the protein. The presented work is a step toward understanding the genotype–phenotype relationships in transcription factor genes using fast and accurate computational approach.

      PubDate: 2017-01-05T17:36:15Z
       
  • The Functional Stability of FOXP3 and RORγt in Treg and Th17 and
           Their Therapeutic Applications
    • Authors: Ren
      Abstract: Publication date: Available online 15 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): J. Ren, B. Li
      The balance of CD4+CD25+FOXP3+ regulatory T cells (Tregs) and effector T cells plays a key role in maintaining immune homeostasis, while the imbalance of them is related to many inflammatory diseases in both human and mice. Here we discuss about the plasticity of Tregs and Th17 cells, and the related human diseases resulted from the imbalance of them. Further, we will focus on the mechanisms regulating the plasticity between Tregs and Th17 cells and the potential therapeutic strategies by targeting regulators of the expression and activity of FOXP3 and RORγt or regulators of Treg/Th17 balance in autoimmune diseases, allergy, infection, and cancer.

      PubDate: 2016-12-20T14:47:01Z
       
  • Transcription Factors in Breast Cancer—Lessons From Recent Genomic
           Analyses and Therapeutic Implications
    • Authors: E. Zacksenhaus; J.C. Liu; Z. Jiang; Y. Yao; L. Xia; M. Shrestha; Y. Ben-David
      Abstract: Publication date: Available online 12 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): E. Zacksenhaus, J.C. Liu, Z. Jiang, Y. Yao, L. Xia, M. Shrestha, Y. Ben-David
      Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways. A notable observation is that DB-TFs that mediate major oncogenic signaling (e.g., WNT, receptor tyrosine kinase (RTK), NOTCH, and HIPPO), which switch from default repression (signal OFF) to transcriptional activation (signal ON), are not altered in breast cancer. Instead, corepressors (e.g., pRb for E2F1 downstream of various proliferation signals) or upstream factors (e.g., APC and AXIN for TCF, downstream of canonical WNT signaling) are lost, or coactivators (e.g., NOTCH1/2 for CSL/RBPJk) are induced. In contrast, constitutive (MYC, TBX3) and signal-induced (TP53, FOXA1) DB-TFs that do not mediate default repression are directly altered in breast cancer. Some of these TFs have been implicated in the establishment of super-enhancers and positive transcriptional elongation. In addition, oncogenic transcription is induced by mutations affecting regulatory elements or chromatin conformation that create new TF-binding sites in promoters and enhancers of oncogenic genes to promote tumorigenesis. Here we review these diverse oncogenic alterations in TFs in BC and discuss implications for therapy.

      PubDate: 2016-12-12T13:51:49Z
      DOI: 10.1016/bs.apcsb.2016.10.003
       
  • NF-κB as a Therapeutic Target in Inflammatory-Associated Bone
           Diseases
    • Authors: T.-h. Lin; J. Pajarinen; L. Lu; A. Nabeshima; L.A. Cordova; Z. Yao; S.B. Goodman
      Abstract: Publication date: Available online 9 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): T.-h. Lin, J. Pajarinen, L. Lu, A. Nabeshima, L.A. Cordova, Z. Yao, S.B. Goodman
      Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system.

      PubDate: 2016-12-12T13:51:49Z
      DOI: 10.1016/bs.apcsb.2016.11.002
       
  • The Complex Role of the ZNF224 Transcription Factor in Cancer
    • Authors: E. Cesaro; G. Sodaro; G. Montano; M. Grosso; A. Lupo; P. Costanzo
      Abstract: Publication date: Available online 5 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): E. Cesaro, G. Sodaro, G. Montano, M. Grosso, A. Lupo, P. Costanzo
      ZNF224 is a member of the Kruppel-associated box zinc finger proteins (KRAB-ZFPs) family. It was originally identified as a transcriptional repressor involved in gene-specific silencing through the recruitment of the corepressor KAP1, chromatin-modifying activities, and the arginine methyltransferase PRMT5 on the promoter of its target genes. Recent findings indicate that ZNF224 can behave both as a tumor suppressor or an oncogene in different human cancers. The transcriptional regulatory properties of ZNF224 in these systems appear to be complex and influenced by specific sets of interactors. ZNF224 can also act as a transcription cofactor for other DNA-binding proteins. A role for ZNF224 in transcriptional activation has also emerged. Here, we review the state of the literature supporting both roles of ZNF224 in cancer. We also examine the functional activity of ZNF224 as a transcription factor and the influence of protein partners on its dual behavior. Increasing information on the mechanism through which ZNF224 can operate could lead to the identification of agents capable of modulating ZNF224 function, thus potentially paving the way to new therapeutic strategies for treatment of cancer.

      PubDate: 2016-12-12T13:51:49Z
      DOI: 10.1016/bs.apcsb.2016.11.003
       
  • Transcription Factors as a Target for Vaccination Against Ticks and Mites
    • Authors: O.A.E. Sparagano
      Abstract: Publication date: Available online 5 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): O.A.E. Sparagano
      Ticks and mites are well-known ectoparasites as potential vectors for numerous bacteria, viruses, and parasites. Many being blood feeders add to physiological deterioration, morbidity, and mortality of their vertebrate hosts. To control them, transcription factors have been identified and studied in their role to sustain such arthropod pests. This paper summarizes some of the work done on those factors involved during blood feeding, reproduction, or when interacting with their pathogens and symbiont populations. Any transcription factor supporting the equilibrium developed by the ticks/mites could become a potential target for new control methods to prevent some of their key physiological functions.

      PubDate: 2016-12-12T13:51:49Z
      DOI: 10.1016/bs.apcsb.2016.11.004
       
  • HMGB1 Protein: A Therapeutic Target Inside and Outside the Cell
    • Authors: I. Ugrinova; E. Pasheva
      Abstract: Publication date: Available online 2 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): I. Ugrinova, E. Pasheva
      High-mobility group box 1 protein (HMGB1) is a nonhistone chromosomal protein discovered more than 30 years ago. It is an abundant nuclear protein that has a dual function—in the nucleus, it binds DNA and participates in practically all DNA-dependent processes serving as an architectural factor. Outside the cell, HMGB1 plays a different role—it acts as an alarmine that activates a large number of HMGB1-“competent” cells and mediates a broad range of physiological and pathological responses. This universality makes it an attractive target for innovative therapeutic strategies in the treatment of various diseases. Here we present an overview of the major nuclear and extracellular properties of HMGB1 and describe its interaction with different molecular partners as specific receptors or inhibitors, which are important for its role as a target in multiple diseases. We highlight its pivotal role as a target for cancer treatment at two aspects: first in terms of its substantial impact on the repair capacity of cancer cells, thus affecting the effectiveness of chemotherapy with the antitumor drug cis-platinum and, second, the possibility to be targeted by microRNAs influencing different pathways of human diseases, thus making it a promising candidate for a new strategy for therapeutic interventions against various pathological conditions but mainly cancer.

      PubDate: 2016-12-05T13:01:11Z
      DOI: 10.1016/bs.apcsb.2016.10.001
       
  • Targeting Chromatin Remodeling in Inflammation and Fibrosis
    • Authors: J. Yang; B. Tian; A.R. Brasier
      Abstract: Publication date: Available online 1 December 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): J. Yang, B. Tian, A.R. Brasier
      Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader. The RelA·BRD4·P-TEFb complex produces acute inflammation by regulating transcriptional elongation, which produces a rapid genomic response by inactive genes maintained in an open chromatin configuration engaged with hypophosphorylated RNA polymerase II. We describe recent studies that have linked prolonged activation of the RelA–BRD4 pathway with the epithelial–mesenchymal transition (EMT) by inducing a core of EMT corepressors, stimulating secretion of growth factors promoting airway fibrosis. The mesenchymal state produces rewiring of the kinome and reprogramming of innate responses toward inflammation. In addition, the core regulator Zinc finger E-box homeodomain 1 (ZEB1) silences the expression of the interferon response factor 1 (IRF1), required for type III IFN expression. This epigenetic silencing is mediated by the Enhancer of Zeste 2 (EZH2) histone methyltransferase. Because of their potential applications in cancer and inflammation, small-molecule inhibitors of NFκB/RelA, CDK9, BRD4, and EZH2 have been the targets of medicinal chemistry efforts. We suggest that disruption of the RelA·BRD4·P-TEFb pathway and EZH2 methyltransferase has important implications for reversing fibrosis and restoring normal mucosal immunity in chronic inflammatory diseases.

      PubDate: 2016-12-05T13:01:11Z
      DOI: 10.1016/bs.apcsb.2016.11.001
       
  • Chromatin Remodeling in Monocyte and Macrophage Activation
    • Authors: J.L. Schultze
      Abstract: Publication date: Available online 18 October 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): J.L. Schultze
      Increasing evidence collected during the last years supports the idea that monocyte and macrophage activation is not only associated with transcriptional changes but also changes in the chromatin landscape. Moreover, the introduction of a multidimensional model of macrophage activation allows a more precise description of monocytes and macrophages under homeostatic and pathophysiological conditions. Monocytes and macrophages are masters of integrating microenvironmental signals, thereby reshaping their chromatin landscape and as a consequence their transcriptional and functional programs. Albeit these cells share a large number of epigenetic landmarks, their chromatin is significantly shaped by environmental signals. The chromatin landscape of any given tissue macrophage is a rather specific fingerprint of these cells, which is directly linked to tissue-specific functions of these cells. Moreover, chromatin remodeling in response to stress signals also seems to be an important mechanism of these cells to increase their readiness for future stressors. Understanding this sophisticated epigenetic regulatory network in monocytes and macrophages will open up new avenues toward tissue- and disease-specific therapeutic strategies in many of the chronic inflammatory diseases our societies are currently facing.

      PubDate: 2016-10-24T19:23:18Z
      DOI: 10.1016/bs.apcsb.2016.09.001
       
  • Epigenetic Changes in Chronic Inflammatory Diseases
    • Authors: O. Fogel; C. Richard-Miceli; J. Tost
      Abstract: Publication date: Available online 18 October 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): O. Fogel, C. Richard-Miceli, J. Tost
      The number of people diagnosed with chronic inflammatory diseases has increased noteworthy in the last 40 years. Spondyloarthritis (SpA), inflammatory bowel diseases (IBD), and psoriasis are the most frequent chronic inflammatory diseases, resulting from a combination of genetic predisposition and environmental factors. Epigenetic modifications include DNA methylation, histone modifications, and small and long noncoding RNAs. They are influenced by environmental exposure, life-style, and aging and have recently been shown to be altered in many complex diseases including inflammatory diseases. While epigenetic modifications have been well characterized in other diseases such as cancer and autoimmune diseases, knowledge on changes in inflammatory diseases is lagging behind with some disease-specific differences. While the DNA methylation profile of different cell types in patients with IBD has been relatively well described, less is known on changes implicated in psoriasis, and no systematic genome-wide studies have so far been performed in SpA. In this chapter, we review in detail the reported changes in patterns of DNA methylation and posttranslational histone modifications in chronic inflammatory diseases highlighting potential connections between disease-associated pathophysiological changes such as the dysbiosis of the microbiome or genetic variations associated with disease susceptibility and the epigenome. We also discuss important parameters of meaningful epigenetic studies such as the use of well defined, disease-relevant cell populations, and elude on the potential future of engineering of the epigenome in inflammatory diseases.

      PubDate: 2016-10-24T19:23:18Z
      DOI: 10.1016/bs.apcsb.2016.09.003
       
  • The Role of Epigenetic Regulation in Transcriptional Memory in the Immune
           System
    • Authors: A.M. Woodworth; A.F. Holloway
      Abstract: Publication date: Available online 8 October 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): A.M. Woodworth, A.F. Holloway
      The immune system is exquisitely poised to identify, respond to, and eradicate pathogens from the body, as well as to produce a more rapid and augmented response to a subsequent encounter with the pathogen. These cellular responses rely on the highly coordinated and rapid activation of gene expression programs as well as the ability of the cell to retain a memory of the initial gene response. It is clear that chromatin structure and epigenetic mechanisms play a crucial role in determining these gene responses, and in fact the immune system has proved an instructive model for investigating the multifaceted mechanisms through which the chromatin landscape contributes to gene expression programs. These mechanisms include modifications to the DNA and histone proteins, the positioning, composition, and remodeling of nucleosomes, as well as the formation of higher-order chromatin structures. Moreover, it is now apparent that epigenetic mechanisms also provide an instrument by which cells can retain memory of the initial transcriptional response, “priming” the genome so that it can respond more quickly to subsequent exposure to the signal. Here, we use the immune system as a model to demonstrate the complex interplay between transcription factors and the chromatin landscape required to orchestrate precise gene responses to external stimuli and further to demonstrate how these interactions can establish memory of past transcriptional events. We focus on what we have learnt from the immune system and how this can inform our understanding of other cellular systems.

      PubDate: 2016-10-12T00:57:14Z
      DOI: 10.1016/bs.apcsb.2016.09.002
       
  • Chromatin Remodeling and Plant Immunity
    • Authors: W. Chen; Q. Zhu; Y. Liu; Q. Zhang
      Abstract: Publication date: Available online 28 September 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): W. Chen, Q. Zhu, Y. Liu, Q. Zhang
      Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance'

      PubDate: 2016-10-04T21:19:48Z
      DOI: 10.1016/bs.apcsb.2016.08.006
       
  • Mechanisms of Chromatin Remodeling and Repurposing During Extracellular
           Translocation
    • Authors: D.S. Pisetsky
      Abstract: Publication date: Available online 23 September 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): D.S. Pisetsky
      Chromatin is a highly conserved molecular structure that provides genetic information to regulate cell function. Comprised of DNA, histones and interacting proteins, chromatin is inherently dynamic and subject to remodeling. While usually conceptualized as an intranuclear event, remodeling can also involve extracellular movement. Indeed, chromatin can translocate entirely from the inside to the outside of the cell during cell death processes that include apoptosis, necrosis, and NETosis. During these processes, DNA and proteins can undergo other changes impacting on their activity. Thus, during apoptosis, DNA can be cleaved, histones can be posttranslationally modified and a nuclear protein called HMGB1 (high mobility group box 1) can undergo redox changes. Outside the cell, chromatin components can display powerful immunological activities. These activities result from the ability of DNA and RNA, once taken up by immune cells, to activate internal nucleic acid sensors; the likely function of these sensors is to recognize nucleic acids from intracellular infection. Depending on redox state, the prototype alarmin HMGB1 can interact with a variety of immune receptors including Toll-like receptors. As such, extracellular chromatin can stimulate inflammation and drive the pathogenesis of immune-mediated diseases; in experimental models in animals, agents that bind chromatin components can block disease. Thus, extracellular chromatin can have far-reaching biological effects involving a form of molecular repurposing.

      PubDate: 2016-09-27T18:54:15Z
      DOI: 10.1016/bs.apcsb.2016.08.003
       
  • Histone Acetylation and the Regulation of Major Histocompatibility Class
           II Gene Expression
    • Authors: K. Suzuki; Y. Luo
      Abstract: Publication date: Available online 23 September 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): K. Suzuki, Y. Luo
      Major histocompatibility complex (MHC) class II molecules are essential for processing and presenting exogenous pathogen antigens to activate CD4+ T cells. Given their central role in adaptive immune responses, MHC class II genes are tightly regulated in a tissue- and activation-specific manner. The regulation of MHC class II gene expression involves various transcription factors that interact with conserved proximal cis-acting regulatory promoter elements, as well as MHC class II transactivator that interacts with a variety of chromatin remodeling machineries. Recent studies also identified distal regulatory elements within MHC class II gene locus that provide enormous insight into the long-range coordination of MHC class II gene expression. Novel therapeutic modalities that can modify MHC class II genes at the epigenetic level are emerging and are currently in preclinical and clinical trials. This review will focus on the role of chromatin remodeling, particularly remodeling that involves histone acetylation, in the constitutive and inducible regulation of MHC class II gene expression.

      PubDate: 2016-09-27T18:54:15Z
      DOI: 10.1016/bs.apcsb.2016.08.002
       
  • A New Molecular Mechanism Underlying the Antitumor Effect of DNA
           Methylation Inhibitors via an Antiviral Immune Response
    • Authors: Y. Saito; T. Nakaoka; H. Saito
      Abstract: Publication date: Available online 23 September 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): Y. Saito, T. Nakaoka, H. Saito
      Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27. Chromatin-modifying drugs such as DNA methylation inhibitors and histone deacetylase inhibitors have clinical promise for cancer therapy. However, details of the mechanisms responsible for the antitumor effects of these drugs have been unclear. Recently, a new molecular mechanism for the antitumor effect of DNA methylation inhibitors has been proposed: induction of interferon-responsive genes via double-stranded RNAs derived from ERVs. We have also confirmed the same effect of DNA demethylation using a 3D culture system for stem cells known as organoid culture. Our findings indicated that DNA demethylation suppresses the proliferation of cancer-initiating cells by inducing an antiviral response, including activation of interferon-responsive genes. Treatment with DNA methylation inhibitors to activate a growth-inhibiting immune response may be an effective therapeutic approach for malignant disorders.

      PubDate: 2016-09-27T18:54:15Z
      DOI: 10.1016/bs.apcsb.2016.08.005
       
  • Regulation of Cellular Immune Responses in Sepsis by Histone Modifications
    • Authors: W.F. Carson; S.L. Kunkel
      Abstract: Publication date: Available online 21 September 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): W.F. Carson, S.L. Kunkel
      Severe sepsis, septic shock, and related inflammatory syndromes are driven by the aberrant expression of proinflammatory mediators by immune cells. During the acute phase of sepsis, overexpression of chemokines and cytokines drives physiological stress leading to organ failure and mortality. Following recovery from sepsis, the immune system exhibits profound immunosuppression, evidenced by an inability to produce the same proinflammatory mediators that are required for normal responses to infectious microorganisms. Gene expression in inflammatory responses is influenced by the transcriptional accessibility of the chromatin, with histone posttranslational modifications determining whether inflammatory gene loci are set to transcriptionally active, repressed, or poised states. Experimental evidence indicates that histone modifications play a central role in governing the cytokine storm of severe sepsis, and that aberrant chromatin modifications induced during the acute phase of sepsis may mediate chronic immunosuppression in sepsis survivors. This review will focus on the role of histone modifications in governing immune responses in severe sepsis, with an emphasis on specific leukocyte subsets and the histone modifications observed in these cells during chronic stages of sepsis. Additionally, the expression and function of chromatin-modifying enzymes (CMEs) will be discussed in the context of severe sepsis, as potential mediators of epigenetic regulation of gene expression in sepsis responses. In summary, this review will argue for the use of chromatin modifications and CME expression in leukocytes as potential biomarkers of immunosuppression in patients with severe sepsis.

      PubDate: 2016-09-23T11:14:39Z
      DOI: 10.1016/bs.apcsb.2016.08.004
       
  • Cytochromes P450: History, Classes, Catalytic Mechanism, and Industrial
           Application
    • Authors: D.J. Cook; J.D. Finnigan Cook G.W. Black S.J. Charnock
      Abstract: Publication date: Available online 9 August 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): D.J. Cook, J.D. Finnigan, K. Cook, G.W. Black, S.J. Charnock
      Cytochromes P450, a family of heme-containing monooxygenases that catalyze a diverse range of oxidative reactions, are so-called due to their maximum absorbance at 450nm, ie, “Pigment–450nm,” when bound to carbon monoxide. They have appeal both academically and commercially due to their high degree of regio- and stereoselectivity, for example, in the area of active pharmaceutical ingredient synthesis. Despite this potential, they often exhibit poor stability, low turnover numbers and typically require electron transport protein(s) for catalysis. P450 systems exist in a variety of functional domain architectures, organized into 10 classes. P450s are also divided into families, each of which is based solely on amino acid sequence homology. Their catalytic mechanism employs a very complex, multistep catalytic cycle involving a range of transient intermediates. Mutagenesis is a powerful tool for the development of improved biocatalysts and has been used extensively with the archetypal Class VIII P450, BM3, from Bacillus megaterium, but with the increasing scale of genomic sequencing, a huge resource is now available for the discovery of novel P450s.

      PubDate: 2016-08-19T17:02:15Z
       
  • Structural Plasticity in Globins: Role of Protein Dynamics in Defining
           Ligand Migration Pathways
    • Authors: Estarellas Capece; Seira Bidon-Chanal D.A. Estrin F.J. Luque
      Abstract: Publication date: Available online 29 July 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): C. Estarellas, L. Capece, C. Seira, A. Bidon-Chanal, D.A. Estrin, F.J. Luque
      Globins are a family of proteins characterized by the presence of the heme prosthetic group and involved in variety of biological functions in the cell. Due to their biological relevance and widespread distribution in all kingdoms of life, intense research efforts have been devoted to disclosing the relationships between structural features, protein dynamics, and function. Particular attention has been paid to the impact of differences in amino acid sequence on the topological features of docking sites and cavities and to the influence of conformational flexibility in facilitating the migration of small ligands through these cavities. Often, tunnels are carved in the interior of globins, and ligand exchange is regulated by gating residues. Understanding the subtle intricacies that relate the differences in sequence with the structural and dynamical features of globins with the ultimate aim of rationalizing the thermodynamics and kinetics of ligand binding continues to be a major challenge in the field. Due to the evolution of computational techniques, significant advances into our understanding of these questions have been made. In this review we focus our attention on the analysis of the ligand migration pathways as well as the function of the structural cavities and tunnels in a series of representative globins, emphasizing the synergy between experimental and theoretical approaches to gain a comprehensive knowledge into the molecular mechanisms of this diverse family of proteins.

      PubDate: 2016-07-30T09:34:11Z
       
  • Molecular Modeling and Chemoinformatics to Advance the Development of
           Modulators of Epigenetic Targets: A Focus on DNA Methyltransferases
    • Authors: F.D. Gortari; J.L. Medina-Franco
      Abstract: Publication date: Available online 14 June 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): F.D. Prieto-Martínez, A. Peña-Castillo, O. Méndez-Lucio, E. Fernández-de Gortari, J.L. Medina-Franco
      In light of the emerging field of Epi-informatics, ie, computational methods applied to epigenetic research, molecular docking, and dynamics, pharmacophore and activity landscape modeling and QSAR play a key role in the development of modulators of DNA methyltransferases (DNMTs), one of the major epigenetic target families. The increased chemical information available for modulators of DNMTs has opened up the avenue to explore the epigenetic relevant chemical space (ERCS). Herein, we discuss recent progress on the identification and development of inhibitors of DNMTs as potential epi-drugs and epi-probes that have been driven by molecular modeling and chemoinformatics methods. We also survey advances on the elucidation of their structure–activity relationships and exploration of ERCS. Finally, it is illustrated how computational approaches can be applied to identify modulators of DNMTs in food chemicals.

      PubDate: 2016-06-16T18:00:09Z
       
  • Recent Advances in Computational Models for the Study of
           Protein–Peptide Interactions
    • Authors: D. Kilburg; E. Gallicchio
      Pages: 27 - 57
      Abstract: Publication date: Available online 3 August 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): D. Kilburg, E. Gallicchio
      We review computational models and software tools in current use for the study of protein–peptide interactions. Peptides and peptide derivatives are growing in interest as therapeutic agents to target protein–protein interactions. Protein–protein interactions are pervasive in biological systems and are responsible for the regulation of critical functions within the cell. Mutations or dysregulation of expression can alter the network of interactions among proteins and cause diseases such as cancer. Protein–protein binding interfaces, which are often large, shallow, and relatively feature-less, are difficult to target with small-molecule inhibitors. Peptide derivatives based on the binding motifs present in the target protein complex are increasingly drawing interest as superior alternatives to conventional small-molecule inhibitors. However, the design of peptide-based inhibitors also presents novel challenges. Peptides are more complex and more flexible than standard medicinal compounds. They also tend to form more extended and more complex interactions with their protein targets. Computational modeling is increasingly being employed to supplement synthetic and biochemical work to offer guidance and energetic and structural insights. In this review, we discuss recent in silico structure-based and physics-based approaches currently employed to model protein–peptide interactions with a few examples of their applications.

      PubDate: 2016-08-04T10:58:54Z
      DOI: 10.1016/bs.apcsb.2016.06.002
       
  • Dynamic Reorganization and Enzymatic Remodeling of Type IV Collagen at
           Cell–Biomaterial Interface
    • Authors: N.M. Coelho; V. Llopis-Hernández; M. Salmerón-Sánchez; G. Altankov
      Pages: 81 - 104
      Abstract: Publication date: Available online 14 July 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): N.M. Coelho, V. Llopis-Hernández, M. Salmerón-Sánchez, G. Altankov
      Vascular basement membrane remodeling involves assembly and degradation of its main constituents, type IV collagen (Col IV) and laminin, which is critical during development, angiogenesis, and tissue repair. Remodeling can also occur at cell–biomaterials interface altering significantly the biocompatibility of implants. Here we describe the fate of adsorbed Col IV in contact with endothelial cells adhering on positively charged NH2 or hydrophobic CH3 substrata, both based on self-assembly monolayers (SAMs) and studied alone or mixed in different proportions. AFM studies revealed distinct pattern of adsorbed Col IV, varying from single molecular deposition on pure NH2 to network-like assembly on mixed SAMs, turning to big globular aggregates on bare CH3. Human umbilical endothelial cells (HUVECs) interact better with Col IV adsorbed as single molecules on NH2 surface and readily rearrange it in fibril-like pattern that coincide with secreted fibronectin fibrils. The cells show flattened morphology and well-developed focal adhesion complexes that are rich on phosphorylated FAK while expressing markedly low pericellular proteolytic activity. Conversely, on hydrophobic CH3 substrata HUVECs showed abrogated spreading and FAK phosphorylation, combined with less reorganization of the aggregated Col IV and significantly increased proteolytic activity. The later involves both MMP-2 and MMP-9, as measured by zymography and FITC-Col IV release. The mixed SAMs support intermediate remodeling activity. Taken together these results show that chemical functionalization combined with Col IV preadsorption provides a tool for guiding the endothelial cells behavior and pericellular proteolytic activity, events that strongly affect the fate of cardiovascular implants.

      PubDate: 2016-07-25T06:33:13Z
      DOI: 10.1016/bs.apcsb.2016.06.001
       
  • Understanding the Multifaceted Role of Human Down Syndrome Kinase DYRK1A
    • Authors: L.J. Kay; T.K. Smulders-Srinivasan; M. Soundararajan
      Pages: 127 - 171
      Abstract: Publication date: Available online 9 August 2016
      Source:Advances in Protein Chemistry and Structural Biology
      Author(s): L.J. Kay, T.K. Smulders-Srinivasan, M. Soundararajan
      The dual-specificity tyrosine (Y) phosphorylation-regulated kinase DYRK1A, also known as Down syndrome (DS) kinase, is a dosage-dependent signaling kinase that was originally shown to be highly expressed in DS patients as a consequence of trisomy 21. Although this was evident some time ago, it is only in recent investigations that the molecular roles of DYRK1A in a wide range of cellular processes are becoming increasingly apparent. Since initial knowledge on DYRK1A became evident through minibrain mnb, the Drosophila homolog of DYRK1A, this review will first summarize the scientific reports on minibrain and further expand on the well-established neuronal functions of mammalian and human DYRK1A. Recent investigations across the current decade have provided rather interesting and compelling evidence in establishing nonneuronal functions for DYRK1A, including its role in infection, immunity, cardiomyocyte biology, cancer, and cell cycle control. The latter part of this review will therefore focus in detail on the emerging nonneuronal functions of DYRK1A and summarize the regulatory role of DYRK1A in controlling Tau and α-synuclein. Finally, the emerging role of DYRK1A in Parkinson's disease will be outlined.

      PubDate: 2016-08-19T17:02:15Z
      DOI: 10.1016/bs.apcsb.2016.07.001
       
 
 
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