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Publisher: John Wiley and Sons   (Total: 1577 journals)

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Showing 1 - 200 of 1577 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 61, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 45, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 49, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 145, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 3)
Addiction     Hybrid Journal   (Followers: 33, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 12, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 250, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 35, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 133, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 27, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 31, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 36, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 255, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 16, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 126, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 160)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 210, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 36, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 8, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 44, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 45, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 69, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 141, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 225, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 50, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 28, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 14)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 315, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 13, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 43, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 25, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 13, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 399, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 68, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 15, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 137, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 18, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 35, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 221, SJR: 2.083, h-index: 125)

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Journal Cover Annals of the New York Academy of Sciences
  [SJR: 2.389]   [H-I: 189]   [5 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0077-8923 - ISSN (Online) 1749-6632
   Published by John Wiley and Sons Homepage  [1577 journals]
  • Contemporaneous reproduction of preclinical science: a case study of FSH
           and fat
    • Authors: Clifford J. Rosen; Mone Zaidi
      PubDate: 2017-08-15T12:40:46.869473-05:
      DOI: 10.1111/nyas.13457
       
  • Dreamless: the silent epidemic of REM sleep loss
    • Authors: Rubin Naiman
      Abstract: We are at least as dream deprived as we are sleep deprived. Many of the health concerns attributed to sleep loss result from a silent epidemic of REM sleep deprivation. REM/dream loss is an unrecognized public health hazard that silently wreaks havoc with our lives, contributing to illness, depression, and an erosion of consciousness. This paper compiles data about the causes and extent of REM/dream loss associated with commonly used medications, endemic substance use disorders, rampant sleep disorders, and behavioral and lifestyle factors. It examines the consequences of REM/dream loss and concludes with recommendations for restoring healthy REM/dreaming.
      PubDate: 2017-08-15T12:40:36.779458-05:
      DOI: 10.1111/nyas.13447
       
  • T cell protein tyrosine phosphatase prevents STAT1 induction of claudin-2
           expression in intestinal epithelial cells
    • Authors: Moorthy Krishnan; Declan F. McCole
      Abstract: T cell protein tyrosine phosphatase (TCPTP) dephosphorylates a number of substrates, including JAK–STAT (signal transducer and activator of transcription) signaling proteins, which are activated by interferon (IFN)-γ, a major proinflammatory cytokine involved in conditions such as inflammatory bowel disease. A critical function of the intestinal epithelium is formation of a selective barrier to luminal contents. The structural units of the epithelium that regulate barrier function are the tight junctions (TJs), and the protein composition of the TJ determines the tightness of the barrier. Claudin-2 is a TJ protein that increases permeability to cations and reduces transepithelial electrical resistance (TER). We previously showed that transient knockdown (KD) of TCPTP permits increased expression of claudin-2 by IFN-γ. Here, we demonstrate that the decreased TER in TCPTP-deficient epithelial cells is alleviated by STAT1 KD. Moreover, increased claudin-2 in TCPTP-deficient cells requires enhanced STAT1 activation and STAT1 binding to the CLDN2 promoter. We also show that mutation of this STAT-binding site prevents elevated CLDN2 promoter activity in TCPTP-deficient epithelial cells. In summary, we demonstrate that TCPTP protects the intestinal epithelial barrier by restricting STAT-induced claudin-2 expression. This is a potential mechanism by which loss-of-function mutations in the gene encoding TCPTP may contribute to barrier defects in chronic intestinal inflammatory disease.
      PubDate: 2017-08-14T00:15:41.681748-05:
      DOI: 10.1111/nyas.13439
       
  • Looking beyond the intervertebral disc: the need for behavioral assays in
           models of discogenic pain
    • Authors: Grace E. Mosley; Thomas W. Evashwick-Rogler, Alon Lai, James C. Iatridis
      Abstract: Orthopedic research into chronic discogenic back pain has commonly focused on aging- and degeneration-related changes in intervertebral disc structure, biomechanics, and biology. However, the primary spine-related reason for physician office visits is pain. The ambiguous nature of the human condition of discogenic low back pain motivates the use of animal models to better understand the pathophysiology. Discogenic back pain models must consider both emergent behavioral changes following pain induction and changes in the nervous system that mediate such behavior. Looking beyond the intervertebral disc, we describe the different ways to classify pain in human patients and animal models. We describe several behavioral assays that can be used in rodent models to augment disc degeneration measurements and characterize different types of pain. We review rodent models of discogenic pain that employed behavioral pain assays and highlight a need to better integrate neuroscience and orthopedic science methods to extend current understanding of the complex and multifactorial pathophysiology of discogenic back pain.
      PubDate: 2017-08-10T16:50:32.853484-05:
      DOI: 10.1111/nyas.13429
       
  • Antiobesity effects of resveratrol: which tissues are involved'
    • Authors: Alfredo Fernández-Quintela; Iñaki Milton-Laskibar, Marcela González, Maria P. Portillo
      Abstract: The prevalence of obesity has been increasing in recent decades and is reaching epidemic proportions. The current options for overweight and obesity management are energy restriction and physical activity. However, compliance with these treatments is frequently poor and less successful than expected. Therefore, the scientific community is interested in active biomolecules, which may be useful in body weight management. Among them, resveratrol (3,5,4′-trihydroxy-trans-stilbene) has generated great interest as an antiobesity agent. The focus of this report is the mechanisms of action of resveratrol on several tissues (i.e., white and brown adipose tissues, liver, and skeletal muscle). Resveratrol blunts fat accumulation through decreasing adipogenesis and/or de novo lipogenesis in white adipose tissue. The effects on lipolysis are controversial. Regarding brown adipose tissue, resveratrol increases the capacity for adaptive thermogenesis. As far as liver and skeletal muscle is concerned, resveratrol increases lipid oxidation in both tissues. Therefore, in rodents, there is a general consensus concerning the effect of resveratrol on reducing body fat accumulation. By contrast, in humans, the studies are scarce, and no clear antiobesity action has been revealed so far.
      PubDate: 2017-08-10T14:20:30.251286-05:
      DOI: 10.1111/nyas.13413
       
  • Recent developments in understanding the role of the gut microbiota in
           brain health and disease
    • Authors: Eoin Sherwin; Timothy G. Dinan, John F. Cryan
      Abstract: There is a growing appreciation of the role of the gut microbiota in all aspects of health and disease, including brain health. Indeed, roles for the bacterial commensals in various psychiatric and neurological conditions, such as depression, autism, stroke, Parkinson's disease, and Alzheimer's disease, are emerging. Microbiota dysregulation has been documented in all of these conditions or in animal models thereof. Moreover, depletion or modulation of the gut microbiota can affect the severity of the central pathology or behavioral deficits observed in a variety of brain disorders. However, the mechanisms underlying such effects are only slowly being unraveled. Additionally, recent preclinical and clinical evidence suggest that targeting the microbiota through prebiotic, probiotic, or dietary interventions may be an effective “psychobiotic” strategy for treating symptoms in mood, neurodevelopmental disorders, and neurodegenerative diseases.
      PubDate: 2017-08-02T17:26:36.916386-05:
      DOI: 10.1111/nyas.13416
       
  • Apical cytoskeletons and junctional complexes as a combined system in
           epithelial cell sheets
    • Authors: Tomoki Yano; Hatsuho Kanoh, Atsushi Tamura, Sachiko Tsukita
      Abstract: Epithelial cell sheet formation is central to many aspects of vertebrate development and function. For example, it is a major principle of differentiation in embryogenesis and regeneration, enables the compartmentalization of tissues, and is the basis for the maintenance of homeostasis throughout the body. A key characteristic of biologically functional epithelial cell sheets is a clear difference between the top and bottom sides owing to the apicobasal polarity of the cells in the sheet, as seen in the simple polar epithelia. Epithelial cell sheets are formed by cell–cell adhesion conferred by junctional complexes, in particular via tight junctions (TJs), which thus create a paracellular barrier. This review focuses on the apical side of the sheet, which serves as the front line. The apical membranes and TJs of the various tissues have specific characteristics that enable them to function and adapt to their biological context: each system must be robust, but also dynamic and flexible to maintain homeostasis. Here, we describe various apical cytoskeletal structures that are critical to the integrity of epithelial cell sheets. We also discuss the association of apical cytoskeletal networks with TJs, which thus forms a combined system, tentatively termed the TJ–apical complex.
      PubDate: 2017-08-01T16:26:31.988757-05:
      DOI: 10.1111/nyas.13432
       
  • Muscle–bone interactions: movement in the field of mechano–humoral
           coupling of muscle and bone
    • Authors: Christopher P. Cardozo; Zachary A. Graham
      Abstract: Cyclical, mechanical loading of bone by skeletal muscle is widely recognized as a critical determinant of bone structure and mass. A growing body of evidence indicates that substances released from skeletal muscle into the bloodstream also regulate bone mass and metabolism. In this commentary, we discuss the status of research in the area of humoral regulation of bone mass by the skeletal muscle secretome, with an emphasis on the roles of myostatin, irisin, interleukin-6, and exosomes. The interplay between muscle, bone, and other modulators of bone mass, including circadian rhythm and sympathetic tone, is also discussed.
      PubDate: 2017-08-01T16:26:17.444075-05:
      DOI: 10.1111/nyas.13411
       
  • Preparation-related structural diversity and medical potential in the
           treatment of diabetes mellitus with ginseng pectins
    • Authors: Qilei Chen; Lin Zhu, Yina Tang, Zhongzhen Zhao, Tao Yi, Hubiao Chen
      Abstract: Pectins isolated from Panax ginseng C.A. Meyer are potential therapeutic agents for the treatment of diabetes mellitus, a global health challenge. Soil-to-bench procedures of ginseng pectin preparation significantly affect the polysaccharide structures. Various forms of ginseng pectins rich in homogalacturonan, rhamnogalacturonan-I, rhamnogalacturonan-II, and arabinogalactan have demonstrated independent or collaborative effects on hyperglycemia, oxidative stress, immunological dysfunction, and neoplasms. Monosaccharide compositions, peptide contents, degrees of esterification and methylation, and inter- and intramolecular linkages all influence pectin bioactivity. Understanding the preparation–structure and structure–function relationships of ginseng pectins can lead to safer and more pertinent treatment of diabetes with efficacy-oriented modifications of the pectins. To reach this goal, standardization of preparation procedures, understanding of intricate structures, and exploration of complex interactions with receptors are crucial steps to take full advantage of the medical potential of ginseng pectins.
      PubDate: 2017-08-01T16:26:13.657916-05:
      DOI: 10.1111/nyas.13424
       
  • Deciphering adipose tissue heterogeneity
    • Authors: Matthew D. Lynes; Yu-Hua Tseng
      Abstract: Obesity is an excess accumulation of adipose tissue mass, and, together with its sequelae, in particular type II diabetes and metabolic syndrome, obesity presents a major health crisis. Although obesity is simply caused by increased adipose mass, the heterogeneity of adipose tissue in humans means that the response to increased energy balance is highly complex. Individual subjects with similar phenotypes may respond very differently to the same treatments; therefore, obesity may benefit from a personalized precision medicine approach. The variability in the development of obesity is indeed driven by differences in sex, genetics, and environment, but also by the various types of adipose tissue as well as the different cell types that compose it. By describing the distinct cell populations that reside in different fat depots, we can interpret the complex effect of these various players in the maintenance of whole-body energy homeostasis. To further understand adipose tissue, adipogenic differentiation and the transcriptional program of lipid accumulation must be investigated. As the cell- and depot-specific functions are described, they can be placed in the context of energy excess to understand how the heterogeneity of adipose tissue shapes individual metabolic status and condition.
      PubDate: 2017-08-01T16:26:02.143338-05:
      DOI: 10.1111/nyas.13398
       
  • Mechanisms of action of nonpeptide hormones on resveratrol-induced
           antiproliferation of cancer cells
    • Authors: Hung-Yun Lin; Meng-Ti Hsieh, Guei-Yun Cheng, Hsuan-Yu Lai, Yu-Tang Chin, Ya-Jung Shih, André Wendindondé Nana, Shin-Ying Lin, Yu-Chen S.H. Yang, Heng-Yuan Tang, I-Jen Chiang, Kuan Wang
      Abstract: Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin αvβ3 for nonpeptide hormones. Interaction between hormones and integrin αvβ3 can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2–dependent antiproliferation via integrin αvβ3. Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53–COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2–/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin αvβ3 blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments. 
      PubDate: 2017-07-31T11:55:47.821579-05:
      DOI: 10.1111/nyas.13423
       
  • What is “the unconscious,” and where is it located in the brain' A
           neuropsychoanalytic perspective
    • Authors: Mark Solms
      Abstract: This is a brief overview of my “neuropsychoanalytic” perspective on the unconscious. It should make clear how much psychoanalysis has to gain from incorporating the findings of neuroscientific disciplines studying the same part of nature—the workings of the human mind. I hope it makes equally clear what useful new perspectives can be cast on current issues in cognitive neuroscience, if they, in turn, incorporate the findings of psychoanalysis.
      PubDate: 2017-07-31T11:55:36.345134-05:
      DOI: 10.1111/nyas.13437
       
  • Biphasic influence of Staphylococcus aureus on human epidermal tight
           junctions
    • Authors: Katja Bäsler; Marie-Florence Galliano, Sophia Bergmann, Holger Rohde, Ewa Wladykowski, Sabine Vidal-y-Sy, Beatrice Guiraud, Pia Houdek, Germar Schüring, Thomas Volksdorf, Antony Caruana, Sandrine Bessou-Touya, Stefan W. Schneider, Hélène Duplan, Johanna M. Brandner
      Abstract: Bacterial infections (e.g., with Staphylococcus aureus) are serious problems in skin with a compromised barrier, such as in patients with atopic dermatitis. Previously, it was shown that tight junction (TJ) proteins are influenced by staphylococcal infection, and TJ function is impaired after infection of the keratinocyte cell line HaCaT. However, functional studies in cells or models more similar to human skin are missing. Therefore, we investigated bacterial colonialization and infection with live S. aureus in primary human keratinocytes and reconstructed human epidermis (RHE). We show that short-term inoculation results in increased TJ barrier function—which could not be seen in HaCaT cells—hinting at an early protective effect. This is accompanied by occludin phosphorylation and sustained localization of occludin and claudin-4 at cell membranes. Long-term incubation resulted in decreased presence of claudin-1 and claudin-4 at cell membranes and decreased TJ barrier function. The agr regulon of S. aureus plays a role in the increasing but not in the decreasing effect. Proinflammatory cytokines, which are produced as a result of S. aureus inoculation, influence both phases. In summary, we show here that S. aureus can have short-term promoting effects on the TJ barrier, while in the long term it results in disturbance of TJs.
      PubDate: 2017-07-28T08:01:34.052179-05:
      DOI: 10.1111/nyas.13418
       
  • Blood–spinal cord barrier breakdown and pericyte deficiency in
           peripheral neuropathy
    • Authors: Reine-Solange Sauer; Juliane Kirchner, Shaobing Yang, Liu Hu, Mathias Leinders, Claudia Sommer, Alexander Brack, Heike L. Rittner
      Abstract: The blood–spinal cord barrier (BSCB) prevents leakage of molecules, such as pronociceptive mediators, into the spinal cord, but its role in the pathophysiology of neuropathic pain is not completely understood. Rats with chronic constriction injury (CCI) develop mechanical allodynia, thermal hypersensitivity, and reduced motor performance (Rota-Rod test) compared with sham-injured mice—similar to mice with spared nerve injury (SNI). The BSCB becomes permeable for small and large tracers 1 day after nerve ligation. Messenger RNA (mRNA) expression of tight junction proteins (TJPs) occludin, claudin-1, claudin-5, claudin-19, tricellulin, and ZO-1 significantly declines 7–14 days after CCI or SNI. ZO-1 and occludin are reduced in the cell membrane. In capillaries isolated from the spinal cord, immunoreactivity of claudin-5 and ZO-1 is fainter. In parallel, the number of platelet-derived growth factor receptor β (PDGF-β)+ and CD13+ pericytes in the spinal cord drops. Reduced levels of cytosolic transcription factors like β-catenin, but not SMAD4 and SLUG, could account for reduced TJP mRNA. In summary, neuropathy-induced allodynia/hypersensitivity is accompanied by a loss of pericytes in the spinal cord and a leaky BSCB. A better understanding of these pathways and mechanisms in neuropathic pain might foster the design of novel treatments to maintain spinal cord homeostasis.
      PubDate: 2017-07-28T08:00:51.228872-05:
      DOI: 10.1111/nyas.13436
       
  • A comprehensive review of agrimoniin
    • Authors: Daniel M. Grochowski; Krystyna Skalicka-Woźniak, Ilkay Erdogan Orhan, Jianbo Xiao, Marcello Locatelli, Jakub P. Piwowarski, Sebastian Granica, Michał Tomczyk
      Abstract: Plant tannins are a unique class of polyphenols with relatively high molecular weights. Within the ellagitannins group, agrimoniin––dimeric ellagitannin––is one of the most representative compounds found in many plant materials belonging to the Rosaceae family. Agrimoniin was first isolated in 1982 from roots of Agrimonia pilosa Ledeb. (Rosaceae), a plant traditionally used in Japan and China as an antidiarrheal, hemostatic, and antiparasitic agent. Agrimoniin is a constituent of medicinal plants, which are often applied orally in the form of infusions, decoctions, or tinctures. It is also present in commonly consumed food products, such as strawberries and raspberries. It is metabolized by human gut microbiota into a series of low-molecular-weight urolithins with proven anti-inflammatory and anticancer in vivo and in vitro bioactivities. The compound has received widespread interest owing to some interesting biological effects and therapeutic activities, which we elaborate in the present review. Additionally, we present an overview of the techniques used for the analysis, isolation, and separation of agrimoniin from the practical perspective.
      PubDate: 2017-07-21T04:20:28.414577-05:
      DOI: 10.1111/nyas.13421
       
  • International summit on the nutrition of adolescent girls and young women:
           consensus statement
    • Authors: Nancy Krebs; Susan Bagby, Zulfiqar A. Bhutta, Kathryn Dewey, Caroline Fall, Fred Gregory, William Hay, Lisa Rhuman, Christine Wallace Caldwell, Kent L. Thornburg
      Abstract: An international summit focusing on the difficult challenge of providing adequate nutrition for adolescent girls and young women in low- and middle-income countries was held in Portland, Oregon in 2015. Sixty-seven delegates from 17 countries agreed on a series of recommendations that would make progress toward improving the nutritional status of girls and young women in countries where their access to nutrition is compromised. Delegate recommendations include: (1) elevate the urgency of nutrition for girls and young women to a high international priority, (2) raise the social status of girls and young women in all regions of the world, (3) identify major knowledge gaps in the biology of adolescence that could be filled by robust research efforts, (4) and improve access to nutrient-rich foods for girls and young women. Attention to these recommendations would improve the health of young women in all nations of the world.
      PubDate: 2017-07-19T09:00:01.210199-05:
      DOI: 10.1111/nyas.13417
       
  • Characterizing a mouse model for evaluation of countermeasures against
           hydrogen sulfide–induced neurotoxicity and neurological sequelae
    • Authors: Poojya Anantharam; Elizabeth M. Whitley, Belinda Mahama, Dong-Suk Kim, Paula M. Imerman, Dahai Shao, Monica R. Langley, Arthi Kanthasamy, Wilson K. Rumbeiha
      Abstract: Hydrogen sulfide (H2S) is a highly neurotoxic gas. It is the second most common cause of gas-induced deaths. Beyond mortality, surviving victims of acute exposure may suffer long-term neurological sequelae. There is a need to develop countermeasures against H2S poisoning. However, no translational animal model of H2S-induced neurological sequelae exists. Here, we describe a novel mouse model of H2S-induced neurotoxicity for translational research. In paradigm I, C57/BL6 mice were exposed to 765 ppm H2S for 40 min on day 1, followed by 15-min daily exposures for periods ranging from 1 to 6 days. In paradigm II, mice were exposed once to 1000 ppm H2S for 60 minutes. Mice were assessed for behavioral, neurochemical, biochemical, and histopathological changes. H2S intoxication caused seizures, dyspnea, respiratory depression, knockdowns, and death. H2S-exposed mice showed significant impairment in locomotor and coordinated motor movement activity compared with controls. Histopathology revealed neurodegenerative lesions in the collicular, thalamic, and cortical brain regions. H2S significantly increased dopamine and serotonin concentration in several brain regions and caused time-dependent decreases in GABA and glutamate concentrations. Furthermore, H2S significantly suppressed cytochrome c oxidase activity and caused significant loss in body weight. Overall, male mice were more sensitive than females. This novel translational mouse model of H2S-induced neurotoxicity is reliable, reproducible, and recapitulates acute H2S poisoning in humans.
      PubDate: 2017-07-18T11:56:17.351533-05:
      DOI: 10.1111/nyas.13419
       
  • Winter storm intensity, hazards, and property losses in the New York
           tristate area
    • Authors: Cari E. Shimkus; Mingfang Ting, James F. Booth, Susana B. Adamo, Malgosia Madajewicz, Yochanan Kushnir, Harald E. Rieder
      Abstract: Winter storms pose numerous hazards to the Northeast United States, including rain, snow, strong wind, and flooding. These hazards can cause millions of dollars in damages from one storm alone. This study investigates meteorological intensity and impacts of winter storms from 2001 to 2014 on coastal counties in Connecticut, New Jersey, and New York and underscores the consequences of winter storms. The study selected 70 winter storms on the basis of station observations of surface wind strength, heavy precipitation, high storm tide, and snow extremes. Storm rankings differed between measures, suggesting that intensity is not easily defined with a single metric. Several storms fell into two or more categories (multiple-category storms). Following storm selection, property damages were examined to determine which types lead to high losses. The analysis of hazards (or events) and associated damages using the Storm Events Database of the National Centers for Environmental Information indicates that multiple-category storms were responsible for a greater portion of the damage. Flooding was responsible for the highest losses, but no discernible connection exists between the number of storms that afflict a county and the damage it faces. These results imply that losses may rely more on the incidence of specific hazards, infrastructure types, and property values, which vary throughout the region.
      PubDate: 2017-07-17T13:46:09.054261-05:
      DOI: 10.1111/nyas.13396
       
  • How to select a nanosimilar
    • Authors: Alain Astier; Amy Barton Pai, Marco Bissig, Daan J.A. Crommelin, Beat Flühmann, Jean-Daniel Hecq, Josefien Knoeff, Hans-Peter Lipp, Alberto Morell-Baladrón, Stefan Mühlebach
      Abstract: Nanomedicines in the class of nonbiological complex drugs (NBCDs) are becoming increasingly available. Up to 23 nanomedicines have been approved, and approximately 50 are in clinical development. Meanwhile, the first nanosimilars have entered the market through the generic approval pathway, but clinical differences have been observed. Many healthcare professionals may be unaware of this issue and must be informed of these clinically relevant variances. This article provides a tool for rational decision making for the inclusion of nanomedicines into the hospital formulary, including defined criteria for evaluation of substitutability or interchangeability. The tool was generated by conducting a roundtable with an international panel of experts and follows the same thought process that was developed and published earlier for the selection of biologicals/biosimilars. In addition to the existing criteria for biosimilars, a set of seven criteria was identified that specifically apply to nanosimilars. These include (1) particle size and size distribution, (2) particle surface characteristics, (3) fraction of uncaptured bioactive moiety, (4) stability on storage, (5) bioactive moiety uptake and (6) distribution, and (7) stability for ready-to-use preparation. Pharmacists should utilize their pharmaceutical expertise to use the appropriate criteria to evaluate the comparability of the drug to decide on interchangeability or substitutability.
      PubDate: 2017-07-17T13:45:32.683436-05:
      DOI: 10.1111/nyas.13382
       
  • Assessing musical ability quickly and objectively: development and
           validation of the Short-PROMS and the Mini-PROMS
    • Authors: Marcel Zentner; Hannah Strauss
      Abstract: The study of musical ability has gained considerable traction across disciplines in recent years. In comparison, less effort has been invested in the development of sound measures of musical ability. To redress this gap, we conducted four studies to empirically validate two brief measures derived from the Profile of Music Perception Skills (PROMS)—an exceptionally inclusive battery of musical abilities that takes about 1 h to complete. In the Short-PROMS, test duration was reduced to less than half an hour by substantially reducing the number of trials per subtest. In the Mini-PROMS, the number of subtests was reduced to four, resulting in a battery that takes 15 min to complete. Both measures exhibited good internal consistency and retest reliability. Support for convergent, discriminant, and criterion validity was found across the studies. Additional strengths of the new instruments include their suitability for online administration and a feature called Modular PROMS, which offers researchers the possibility to request customized batteries that may include any combination of the subtests. The role of refining objective assessment instruments in research on music and the mind is discussed.
      PubDate: 2017-07-13T16:50:26.085345-05:
      DOI: 10.1111/nyas.13410
       
  • Mesenchymal stem cells and their immunosuppressive role in transplantation
           tolerance
    • Authors: Pamina Contreras-Kallens; Claudia Terraza, Karina Oyarce, Tania Gajardo, Mauricio Campos-Mora, María Teresa Barroilhet, Carla Álvarez, Ricardo Fuentes, Fernando Figueroa, Maroun Khoury, Karina Pino-Lagos
      Abstract: Since they were first described, mesenchymal stem cells (MSCs) have been shown to have important effector mechanisms and the potential for use in cell therapy. A great deal of research has been focused on unveiling how MSCs contribute to anti-inflammatory responses, including describing several cell populations involved and identifying soluble and other effector molecules. In this review, we discuss some of the contemporary evidence for use of MSCs in the field of immune tolerance, with a special emphasis on transplantation. Although considerable effort has been devoted to understanding the biological function of MSCs, additional resources are required to clarify the mechanisms of their induction of immune tolerance, which will undoubtedly lead to improved clinical outcomes for MSC-based therapies.
      PubDate: 2017-07-12T12:55:29.241734-05:
      DOI: 10.1111/nyas.13364
       
  • Resveratrol derivatives as a pharmacological tool
    • Authors: Lucia Biasutto; Andrea Mattarei, Michele Azzolini, Martina Spina, Nicola Sassi, Matteo Romio, Cristina Paradisi, Mario Zoratti
      Abstract: Prodrugs of resveratrol are under development. Among the long-term goals, still largely elusive, are (1) modulating physical properties (e.g., water-soluble derivatives bearing polyethylene glycol chains), (2) changing distribution in the body (e.g., galactosyl derivatives restricted to the intestinal lumen), (3) increasing absorption from the gastrointestinal tract (e.g., derivatives imitating the natural substrates of endogenous transporters), and (4) hindering phase II metabolism (e.g., temporarily blocking the hydroxyls), all contributing to (5) increasing bioavailability. The chemical bonds that have been tested for functionalization include carboxyester, acetal, and carbamate groups. A second approach, which can be combined with the first, seeks to reinforce or modify the biochemical activities of resveratrol by concentrating the compound at specific subcellular sites. An example is provided by mitochondria-targeted derivatives. These proved to be pro-oxidant and cytotoxic in vitro, selectively killing fast-growing and tumor cells when supplied in the low micromolar range. This suggests the possibility of anticancer applications.
      PubDate: 2017-07-04T14:00:26.356237-05:
      DOI: 10.1111/nyas.13401
       
  • Effects of resveratrol on eNOS in the endothelium and the perivascular
           adipose tissue
    • Authors: Ning Xia; Ulrich Förstermann, Huige Li
      Abstract: Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). Experiments using gene-disrupted mice have demonstrated that eNOS has antihypertensive, antithrombotic, and antiatherosclerotic effects. Recent studies show that eNOS is expressed not only in the endothelium but also in the perivascular adipose tissue (PVAT). Resveratrol prevents eNOS uncoupling and upregulates eNOS expression and activity. These effects of resveratrol are well established for the eNOS enzyme in the endothelium. Interestingly, resveratrol also improves PVAT function. However, a causal role for eNOS in the effects of resveratrol on PVAT function has not yet been verified and needs to be studied in the future.
      PubDate: 2017-07-03T16:45:35.631327-05:
      DOI: 10.1111/nyas.13397
       
  • Resveratrol and polydatin as modulators of Ca2+ mobilization in the
           cardiovascular system
    • Authors: Wenjuan Liu; Peiya Chen, Jianxin Deng, Jingzhang Lv, Jie Liu
      Abstract: In the cardiovascular system, Ca2+ controls cardiac excitation–contraction coupling and vascular contraction and dilation. Disturbances in intracellular Ca2+ homeostasis induce malfunctions of the cardiovascular system, including cardiac pump dysfunction, arrhythmia, remodeling, and apoptosis, as well as hypertension and impairment of vascular reactivity. Therefore, developing drugs and strategies manipulating Ca2+ handling are highly valued in the treatment of cardiovascular disease. Resveratrol (Res) and polydatin (PD), a Res glucoside, have been well established to have beneficial effects on improving cardiovascular function. Studies from our laboratory and others have demonstrated that they exhibit inotropic effects on normal heart and therapeutic effects on hypertension, cardiac ischemia/reperfusion injury, hypertrophy, and heart failure by manipulating Ca2+ mobilization. The actions of Res and PD on Ca2+ signals delicately manipulated by multiple Ca2+-handling proteins are pleiotropic and somewhat controversial, depending on cellular species and intracellular oxidative status. Here, we focus on the effects of Res and PD on controlling Ca2+ homeostasis in the heart and vasculature under normal and diseased conditions and highlight the key direct and indirect molecules mediating these effects.
      PubDate: 2017-06-30T04:50:24.038549-05:
      DOI: 10.1111/nyas.13386
       
  • Oxidative stress and chronic inflammation in osteoarthritis: can NRF2
           counteract these partners in crime'
    • Authors: Andrey S. Marchev; Petya A. Dimitrova, Andrew J. Burns, Rumen V. Kostov, Albena T. Dinkova-Kostova, Milen I. Georgiev
      Abstract: Osteoarthritis (OA) is an age-related joint degenerative disease associated with pain, joint deformity, and disability. The disease starts with cartilage damage but then progressively involves subchondral bone, causing an imbalance between osteoclast-driven bone resorption and osteoblast-driven remodeling. Here, we summarize the data for the role of oxidative stress and inflammation in OA pathology and discuss how these two processes are integrated during OA progression, as well as their contribution to abnormalities in cartilage/bone metabolism and integrity. At the cellular level, oxidative stress and inflammation are counteracted by transcription factor nuclear factor erythroid p45–related factor 2 (NRF2), and we describe the regulation of NRF2, highlighting its role in OA pathology. We also discuss the beneficial effect of some phytonutrients, including the therapeutic potential of NRF2 activation, in OA.
      PubDate: 2017-06-29T14:26:31.386227-05:
      DOI: 10.1111/nyas.13407
       
  • Campylobacter fetus impairs barrier function in HT-29/B6 cells through
           focal tight junction alterations and leaks
    • Authors: Roland Bücker; Susanne M. Krug, Anja Fromm, Hans Linde Nielsen, Michael Fromm, Henrik Nielsen, Jörg-Dieter Schulzke
      Abstract: Infections by Campylobacter species are the most common foodborne zoonotic disease worldwide. Campylobacter jejuni and C. coli are isolated most frequently from human stool samples, but severe infections by C. fetus (Cf), which can cause gastroenteritis, septicemia, and abortion, are also found. This study aims at the characterization of pathological changes in Cf infection using an intestinal epithelial cell model. The Cf-induced epithelial barrier defects appeared earlier than those of avian Campylobacter species like C. jejuni/C. coli. Two-path impedance spectroscopy (2PI) distinguished transcellular and paracellular resistance contributions to the overall epithelial barrier impairment. Both transcellular and paracellular resistance of Cf-infected HT-29/B6 monolayers were reduced. The latter was attributed to activation of active anion secretion. Western blot analysis showed no decrease in tight junction (TJ) protein expression (claudin-1, -2, -3, and -4) but showed redistribution of claudin-1 off the TJ domain. In addition, Cf induced epithelial cell death, cell detachment, and lesions (focal leaks), as the result of which macromolecule flux (10-kDa dextran) was increased in Cf-invaded cell monolayers. In conclusion, barrier dysfunction from Cf infection was due to TJ protein redistribution, cell death induction, and leak formation, resulting in bacterial translocation, ion leak flux, and antigen uptake (leaky gut).
      PubDate: 2017-06-29T14:26:20.782469-05:
      DOI: 10.1111/nyas.13406
       
  • Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and
           therapeutic strategy in prostate cancer
    • Authors: Avinash Kumar; Agnes M. Rimando, Anait S. Levenson
      Abstract: Growing evidence indicates that deregulation of the epigenetic machinery comprising the microRNA (miRNA) network is a critical factor in the progression of various diseases, including cancer. Concurrently, dietary phytochemicals are being intensively studied for their miRNA-mediated health-beneficial properties, such as anti-inflammatory, cardioprotective, antioxidative, and anticancer properties. Available experimental data have suggested that dietary polyphenols may be effective miRNA-modulating chemopreventive and therapeutic agents. Moreover, noninvasive detection of changes in miRNA expression in liquid biopsies opens enormous possibilities for their clinical utilization as novel prognostic and predictive biomarkers. In our published studies, we identified resveratrol-regulated miRNA profiles in prostate cancer. Resveratrol downregulated the phosphatase and tensin homolog (PTEN)–targeting members of the oncogenic miR-17 family of miRNAs, which are overexpressed in prostate cancer. We have functionally validated the miRNA-mediated ability of resveratrol and its potent analog pterostilbene to rescue the tumor suppressor activity of PTEN in vitro and in vivo. Taken together, our findings implicate the use of resveratrol and its analogs as an attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer and the use of circulating miRNAs as potential predictive biomarkers for clinical development.
      PubDate: 2017-06-29T14:25:55.369816-05:
      DOI: 10.1111/nyas.13372
       
  • Therapeutic potential of Rhizoma Alismatis: a review on ethnomedicinal
           application, phytochemistry, pharmacology, and toxicology
    • Authors: Le-Le Zhang; Wen Xu, Yu-Lian Xu, Xiuping Chen, Mingqing Huang, Jin-Jian Lu
      Abstract: Rhizoma Alismatis (RA), the dried rhizome of Alisma orientale (Sam.) Juzep, is a common traditional herbal medicine named Ze Xie in Chinese. RA is an important herbal component of a number of well-known Chinese medicinal preparations. It has been used to treat various ailments, such as dysuria, edema, nephropathy, hyperlipidemia, and diabetes. A wide range of chemical compounds, mainly triterpenoids, sesquiterpenoids, and diterpenoids, have been isolated from RA; among which the protostane-type triterpenoids, termed alisols, have attracted the most attention owing to their unique chemical structures and various biological activities. The extract and active compounds of RA possess a wide spectrum of pharmacological effects (e.g., diuretic, antimetabolic disorder, hepatoprotective, immunomodulatory, antiosteoporotic, anti-inflammatory, antitumor, antibacterial, and antiviral activities). Previous toxicological evaluations indicated that the RA extracts are relatively safe and have no serious side effects within certain dose ranges. This paper reviews the up-to-date information on the ethnomedicinal application, phytochemistry, pharmacology, and toxicology of RA. This information will be useful for a better understanding of the therapeutic potential of RA.
      PubDate: 2017-06-29T14:25:44.134052-05:
      DOI: 10.1111/nyas.13381
       
  • Childhood cancer chemotherapy–induced bone damage: pathobiology and
           protective effects of resveratrol and other nutraceuticals
    • Authors: Yu-Wen Su; Ke-Ming Chen, Mohammadhossein Hassanshahi, Qian Tang, Peter R. Howe, Cory J. Xian
      Abstract: Intensive cancer chemotherapy causes significant bone loss, for which the mechanisms remain unclear and effective treatments are lacking. This is a significant issue particularly for childhood cancers, as the most common ones have a>75% cure rate following chemotherapy; there is an increasing population of survivors who live with chronic bone defects. Studies suggest that these defects are the result of reduced bone from increased marrow fat formation and increased bone resorption following chemotherapy. These changes probably result from altered expression/activation of regulatory molecules or pathways regulating skeletal cell formation and activity. Treatment with methotrexate, an antimetabolite commonly used in childhood oncology, has been shown to increase levels of proinflammatory/pro-osteoclastogenic cytokines (e.g., enhanced NF-κB activation), leading to increased osteoclast formation and bone resorption, as well as to attenuate Wnt signaling, leading to both decreased bone and increased marrow fat formation. In recent years, understanding the mechanisms of action and potential health benefits of selected nutraceuticals, including resveratrol, genistein, icariin, and inflammatory fatty acids, has led to preclinical studies that, in some cases, indicate efficacy in reducing chemotherapy-induced bone defects. We summarize the supporting evidence.
      PubDate: 2017-06-29T14:25:26.157044-05:
      DOI: 10.1111/nyas.13380
       
  • Crystal structure of the tricellulin C-terminal coiled-coil domain reveals
           a unique mode of dimerization
    • Authors: Anja Schuetz; Veselina Radusheva, Susanne M. Krug, Udo Heinemann
      Abstract: Tricellulin is a tight junction protein localized to tricellular contacts in many epithelial tissues, where it is required for full barrier control. Here, we present crystal structures of the tricellulin C-terminal coiled-coil domain, revealing a potential dimeric arrangement. By combining structural, biochemical, functional, and mutation analyses, we gain insight into the mode of tricellulin oligomerization and suggest a model where dimerization of its cytoplasmic C-terminus may play an auxiliary role in stabilizing homophilic and potentially also heterophilic cis-interactions within tight junctions.
      PubDate: 2017-06-29T10:30:51.113407-05:
      DOI: 10.1111/nyas.13408
       
  • Understanding adaptogenic activity: specificity of the pharmacological
           action of adaptogens and other phytochemicals
    • Authors: Alexander Panossian
      Abstract: Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of “adaptability” and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical. Molecular targets, signaling pathways, and networks common to adaptogens have been identified. They are associated with stress hormones and key mediators of the regulation of homeostasis. In this context, the mechanisms of action of adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Consequently, adaptogens exhibit polyvalent beneficial effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases. Current and potential uses of adaptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. Their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication.
      PubDate: 2017-06-22T14:56:07.56352-05:0
      DOI: 10.1111/nyas.13399
       
  • Modulation of tumor microenvironment by chemopreventive natural products
    • Authors: Sin-Aye Park; Young-Joon Surh
      Abstract: The tumor microenvironment provides a niche in which cancer cells and their surrounding stromal cells reside and in which their interactions occur. The cross talk between cancer and stromal cells in the tumor microenvironment promotes many biological processes to support cancer cell growth, invasion, angiogenesis, and metastasis. Recently, not only cancer cells but also multiple types of surrounding stromal cells, including endothelial cells, immune cells, and fibroblasts in the tumor microenvironment, have been recognized to be attractive targets for reducing resistance to anticancer therapy and tumor recurrence. Many natural products present in fruits, vegetables, herbs, spices, and some marine organisms have been reported to inhibit, delay, or reverse multistage carcinogenesis and to inhibit the proliferation of cancerous cells and the self-renewal capacity of preexisting cancer stem-like cells. Some of these naturally occurring chemopreventive and anticarcinogenic substances can modulate the signal transduction involved in maintaining the activities/functions of stromal cells and their interactions with cancer cells within the tumor microenvironment.
      PubDate: 2017-06-22T14:55:52.785989-05:
      DOI: 10.1111/nyas.13395
       
  • The deeper self: an expanded view of consciousness
    • Authors: Steve Paulson; Siri Hustvedt, Mark Solms, Sonu Shamdasani
      Abstract: As science continues to explore the mysteries of the unconscious, two critical questions remain. First, can unconscious impulses, desires, and feelings be willfully raised to the level of the conscious self', and, if so, would the unveiling of unconscious mechanisms lead to genuine self-knowledge or empowerment' Second, can we methodically tap into the unconscious to gear ourselves along more creative lines' If the unconscious is a source of intuitive and creative inspiration, how might a more expansive understanding of consciousness help us to flourish' How can we harness the intuitive parts of ourselves to think “outside the box,” transcending the limitations of preconceived categories' And along those same lines, how would an expanded view of the unconscious frame our spiritual experiences or offer spiritual nourishment' Writer Siri Hustvedt, historian of psychology Sonu Shamdasani, and neuropsychologist Mark Solms will tackle everything from noetic experiences and the role of intuition to the phenomenon of peak experience and Jung's “collective unconscious.”
      PubDate: 2017-06-22T14:55:45.305497-05:
      DOI: 10.1111/nyas.13403
       
  • The impact of Andean Patagonian mycoflora in the search for new lead
           molecules
    • Authors: Pedro M. Aqueveque; Carlos L. Cespedes, Isao Kubo, David S. Seigler, Olov Sterner
      Abstract: Secondary metabolites from fungi have become a major source of chemical innovation in programs searching for lead molecules with bioactivities, especially over the last 50 years. In this review, we discuss the fundamental considerations in the discovery of molecules for agricultural and medicinal uses. This group of organisms possesses a strong potential for scientific and industrial communities. Recently, the incorporation of new technologies for the artificial cultivation of fungi and the use of better equipment to isolate and identify active metabolites has allowed the discovery of leading molecules for the design of new and safer drugs and pesticides. The geographical region including the Patagonian Andes mountains harbors a wide diversity of fungi, many of them still unknown and so far associated with Chilean–Argentinian Andean endemic forests. There have been very few chemical studies of the fungi located in this region. However, those few studies have allowed the discovery of new molecules. We argue that the richness of fungal biodiversity in this region offers an interesting source for the discovery of bioactive molecules for the basic and applied sciences.
      PubDate: 2017-06-22T14:55:41.187215-05:
      DOI: 10.1111/nyas.13402
       
  • Dreams and creative problem-solving
    • Authors: Deirdre Barrett
      Abstract: Dreams have produced art, music, novels, films, mathematical proofs, designs for architecture, telescopes, and computers. Dreaming is essentially our brain thinking in another neurophysiologic state—and therefore it is likely to solve some problems on which our waking minds have become stuck. This neurophysiologic state is characterized by high activity in brain areas associated with imagery, so problems requiring vivid visualization are also more likely to get help from dreaming. This article reviews great historical dreams and modern laboratory research to suggest how dreams can aid creativity and problem-solving.
      PubDate: 2017-06-22T14:55:33.099165-05:
      DOI: 10.1111/nyas.13412
       
  • Linking the degree of virilization in females with congenital adrenal
           hyperplasia to genotype
    • Authors: Semyon Gurgov; Kerlly J. Bernabé, John Stites, Christopher M. Cunniff, Karen Lin-Su, Diane Felsen, Maria I. New, Dix P. Poppas
      Abstract: Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations. One hundred fifty-eight patients were sorted into groups by expected enzyme activity (percent of normal activity) of the less severely affected allele: (A) null, 0%; (B) I2G, 1%; (C) I172N, 2%; and (D) V281L,>2%. We observed an inverse relationship between virilization and residual enzyme activity (P < 0.001). Subjects in group A or B had a significantly higher likelihood (unadjusted odds ratio: 16; P < 0.001) of developing severe virilization compared with those in group C. Surprisingly, 24% of group D patients, whose mutation is usually associated with nonclassical (NC) CAH, had severe virilization. Among subjects with the NC P30L mutation, 66% expressed unexpected virilization. Virilization, usually leading to extensive reconstructive surgery, is highly likely in patients with null or I2G mutations; however, NC mutations (P30L/V281L) may also lead to unexpected virilization. These findings have implications for prenatal counseling and highlight the need for additional investigations into other factors that influence virilization in CAH.
      PubDate: 2017-06-22T14:55:23.880375-05:
      DOI: 10.1111/nyas.13370
       
  • Tight junction strand formation by claudin-10 isoforms and
           claudin-10a/-10b chimeras
    • Authors: Susanne Milatz; Jörg Piontek, Caroline Hempel, Luca Meoli, Christoph Grohe, Anja Fromm, In-Fah M. Lee, Rukeia El-Athman, Dorothee Günzel
      Abstract: Claudins are integral components of tight junctions (TJs) in epithelia and endothelia. When expressed in cell lines devoid of TJs, claudins are able to form TJ-like strands at contacts between adjacent cells. According to a current model of TJ strand formation, claudin protomers assemble in an antiparallel double row within the plasma membrane of each cell (cis-interaction) while binding to corresponding double rows from the neighboring cells (trans-interaction). Cis-interaction was proposed to involve two interfaces of the protomers’ first extracellular segment (extracellular loop (ECL)1). In the current study, three naturally occurring claudin-10 isoforms and two claudin-10 chimeras were used to investigate strand formation. All constructs were able to interact in cis (Förster/fluorescence resonance energy transfer (FRET)), to integrate into TJs of MDCK-C7 cells (confocal laser scanning microscopy), and to form TJ-like strands in HEK293 cells (freeze-fracture electron microscopy). Strand formation occurred despite the fact that isoform claudin-10a_i1 lacks both structural ECL1 elements reported to be crucial for cis-interaction. Furthermore, results from FRET experiments on claudin-10 chimeras indicated that identity of the first transmembrane region rather than ECL1 is decisive for claudin-10 cis-interaction. Therefore, in addition to the interaction interfaces suggested in the current model for TJ strand assembly, alternative interfaces must exist.
      PubDate: 2017-06-20T16:56:09.763419-05:
      DOI: 10.1111/nyas.13393
       
  • Trictide, a tricellulin-derived peptide to overcome cellular barriers
    • Authors: Jimmi Cording; Basak Arslan, Christian Staat, Sophie Dithmer, Susanne M. Krug, Anneliese Krüger, Philipp Berndt, Ramona Günther, Lars Winkler, Ingolf E. Blasig, Reiner F. Haseloff
      Abstract: The majority of tight junction (TJ) proteins restrict the paracellular permeation of solutes via their extracellular loops (ECLs). Tricellulin tightens tricellular TJs (tTJs) and regulates bicellular TJ (bTJ) proteins. We demonstrate that the addition of recombinantly produced extracellular loop 2 (ECL2) of tricellulin opens cellular barriers. The peptidomimetic trictide, a synthetic peptide derived from tricellulin ECL2, increases the passage of ions, as well as of small and larger molecules up to 10 kDa, between 16 and 30 h after application to human epithelial colorectal adenocarcinoma cell line 2. Tricellulin and lipolysis-stimulated lipoprotein receptor relocate from tTJs toward bTJs, while the TJ proteins claudin-1 and occludin redistribute from bTJs to the cytosol. Analyzing the opening of the tricellular sealing tube by the peptidomimetic using super-resolution stimulated-emission depletion microscopy revealed a tricellulin-free area at the tricellular region. Cis-interactions (as measured by fluorescence resonance energy transfer) of tricellulin–tricellulin (tTJs), tricellulin–claudin-1, tricellulin–marvelD3, and occludin–occludin (bTJs) were strongly affected by trictide treatment. Circular dichroism spectroscopy and molecular modeling suggest that trictide adopts a β-sheet structure, resulting in a peculiar interaction surface for its binding to tricellulin. In conclusion, trictide is a novel and promising tool for overcoming cellular barriers at bTJs and tTJs with the potential to transiently improve drug delivery.
      PubDate: 2017-06-20T16:55:43.903908-05:
      DOI: 10.1111/nyas.13392
       
  • Delving within: the new science of the unconscious
    • Authors: Steve Paulson; Heather A. Berlin, Efrat Ginot, George Makari
      Abstract: What exactly is the relationship between conscious awareness and the unconscious mind' How, for example, does the brain classify and sort its different functions into conscious or unconscious processes' How has the history of human conceptualizations about the unconscious influenced current theories' Steve Paulson, executive producer of To the Best of Our Knowledge, moderated a discussion among neuroscientist Heather Berlin, psychologist Efrat Ginot, and psychiatrist George Makari to shed light on the history of the mind and the latest insights into the still emerging science of the unconscious.
      PubDate: 2017-06-20T15:20:21.868869-05:
      DOI: 10.1111/nyas.13390
       
  • Heterogeneity of tight junctions in the thick ascending limb
    • Authors: Markus Bleich; Vera C. Wulfmeyer, Nina Himmerkus, Susanne Milatz
      Abstract: Renal tubular transport mechanisms are optimized to be energy efficient and tailored to local gradients and transport rates. The combined transcellular action of ion channels, transporters, and pumps, together with the paracellular pathway, enables kidney function. Monogenetic diseases and mouse models indicate that both trans- and paracellular proteins can become disease-causing candidates and may be targets for future therapeutic approaches. Recent advances in tight junction research have provided new insights into their structure, function, and regulation. The thick ascending limb (TAL) is a nephron segment with specific requirements for the paracellular pathway. It has to fuel the generation of the corticomedullary concentration gradient, to be watertight, and to provide a highly selective permeability for Na+ and divalent cations. Tight junction composition and function in the TAL is organized along the corticomedullary axis. Even on the level of a seemingly homogeneous tubular epithelium like the TAL, there is a separation of tight junction protein expression in the strands between the respective tricellular nexus of the junctional network. Here, we highlight some new insights from our recent work and that of others in this context. In addition, we provide some perspectives for the further study of paracellular transport mechanisms.
      PubDate: 2017-06-19T10:55:50.514954-05:
      DOI: 10.1111/nyas.13400
       
  • Modulation of epithelial cell polarity by bacterial pathogens
    • Authors: Rocio Tapia; Sarah E. Kralicek, Gail A. Hecht
      Abstract: Epithelial cells constitute a physical barrier that aids in protecting the host from microbial pathogens. Polarized epithelial cells contain distinct apical and basolateral membrane domains separated by intercellular junctions, including tight junctions (TJs), which contribute to the maintenance of apical–basal polarity. Polarity complexes also contribute to the establishment of TJ formation. Several pathogens perturb epithelial TJ barrier function and structure in addition to causing a loss of apical–basal polarity. Here, we review the impact of pathogenic bacteria on the disruption of cell–cell junctions and epithelial polarity.
      PubDate: 2017-06-19T10:55:34.746169-05:
      DOI: 10.1111/nyas.13388
       
  • The future of dream science
    • Authors: Kelly Bulkeley
      Abstract: This article describes the future prospects of scientific dream research. Three frontiers of investigation hold special promise: neuroscientific studies of the brain–mind system's activities during sleep (such as during lucid dreaming); systematic analyses of large collections of dream reports from diverse populations of people; and psychotherapeutic explorations of the multiple dimensions of personal and collective meaning woven into the dream experiences of each individual. Several helpful books on the science of sleep and dreaming are mentioned for further study.
      PubDate: 2017-06-19T10:55:22.158986-05:
      DOI: 10.1111/nyas.13415
       
  • Dreaming: a gateway to the unconscious'
    • Authors: Steve Paulson; Deirdre Barrett, Kelly Bulkeley, Rubin Naiman
      Abstract: Where do our dreams originate from, and what do they tell us' Is there a universal set of symbols that are common to all dreams, regardless of a person's ethnicity or culture' What does dreaming reveal about the unconscious' Why do some dreams remain etched in our memories, whereas others are almost instantly forgotten' Some scientists have adopted the position that dreams are little more than noise in the brain, without any substantive purpose or function. Yet, such a stance seemingly runs counter to the experience of many people who reflect upon and even analyze their dreams, often in search of clues to their daily lives or insights into their deeper selves. Similarly, in virtually all wisdom traditions, dreams are invoked as an important source of revelation or prophecy. Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included psychologist Deirdre Barrett, dream researcher Kelly Bulkeley, and psychologist and sleep/dream medicine specialist Rubin Naiman; they examined dreams from a variety of perspectives to answer these questions.
      PubDate: 2017-06-15T16:25:22.870131-05:
      DOI: 10.1111/nyas.13389
       
  • The enacted unconscious: a neuropsychological model of unconscious
           processes
    • Authors: Efrat Ginot
      Abstract: Integrating neuropsychology with psychoanalytic thinking and experience, this paper offers a new view of the unconscious that veers away from more traditional conceptualizations. Rather, it emphasizes the ever-present influence of ongoing unconscious processes on much of our behaviors and mental states. Importantly, this new understanding is based on the functional unity of the brain/mind.
      PubDate: 2017-06-15T16:25:20.493298-05:
      DOI: 10.1111/nyas.13404
       
  • Cell-specific diversity in the expression and organization of cytoplasmic
           plaque proteins of apical junctions
    • Authors: Ekaterina Vasileva; Sophie Sluysmans, Marie-Luce Bochaton-Piallat, Sandra Citi
      Abstract: Tight and adherens junctions play critical roles in the barrier, adhesion, and signaling functions of epithelial and endothelial cells. How the molecular organization of these junctions is tuned to the widely diverse physiological requirements of each tissue type is not well understood. Here, we address this question by examining the expression, localization, and interactions of major cytoplasmic plaque proteins of tight and adherens junctions in different cultured epithelial and endothelial cell lines. Immunoblotting and immunofluorescence analyses show that the expression profiles of cingulin, paracingulin, ZO-1, ZO-2, ZO-3, PLEKHA7, afadin, PDZD11, p120-catenin, and α-catenin, as well as the transmembrane junctional proteins occludin, E-cadherin, and VE-cadherin, are significantly diverse when comparing kidney cells (MDCK, mCCD), keratinocytes (HaCaT), lung carcinoma (A427, A549), and endothelium-derived cells (bEnd.3, meEC, H5V). Proximity ligation and co-immunoprecipitation assays show that PLEKHA7 and PDZD11 are significantly more associated with the tight junction proteins cingulin and ZO-1 in aortic endothelium–derived (meEC) cells but not kidney collecting duct epithelial (mCCD) cells. These results provide evidence that the cytoplasmic plaques of tight and adherens junctions are diverse in their composition and molecular architecture and establish a conceptual framework by which we can rationally address the mechanisms of tissue-dependent junction physiology and signaling by cytoplasmic junctional proteins.
      PubDate: 2017-06-15T15:00:29.430861-05:
      DOI: 10.1111/nyas.13391
       
  • Lactoferrin protects against intestinal inflammation and bacteria-induced
           barrier dysfunction in vitro
    • Authors: Nina A. Hering; Julia Luettig, Susanne M. Krug, Stephanie Wiegand, Gabriele Gross, Eric A. Tol, Jörg D. Schulzke, Rita Rosenthal
      Abstract: The iron-binding glycoprotein lactoferrin (LF) is naturally present in human breast milk. Several studies suggest that LF contributes to infant health and development owing to a variety of protective effects, including antimicrobial and anti-inflammatory features. Therefore, we aimed to elucidate its protective properties on intestinal epithelial barrier dysfunction induced by infection or inflammation using the human epithelial cell culture models HT-29/B6 and T84. During barrier perturbation induced by the proinflammatory cytokine tumor necrosis factor α (TNF-α), bovine LF restored tight junction (TJ) morphometry and inhibited TNF-α–induced epithelial apoptosis. This resulted in an attenuation of the TNF-α–induced decrease in transepithelial resistance (TER) and increases in permeability of fluorescein and FITC–dextran (4 kDa) and was as effective as the apoptosis inhibitor Q-VD-Oph. The enteropathogenic bacterium Yersinia enterocolitica is a frequent cause of diarrhea in early childhood. This involves focal changes in TJ protein expression and localization. LF diminished the Y. enterocolitica–induced drop in TER in the present in vitro model, which was paralleled by an inhibition of the Yersinia-induced reduction of claudin-8 expression via c-Jun kinase signaling. In conclusion, LF exerts protective effects against inflammation- or infection-induced barrier dysfunction in human intestinal cell lines, supporting its relevance for healthy infant development.
      PubDate: 2017-06-14T15:00:45.088103-05:
      DOI: 10.1111/nyas.13405
       
  • Architecture of the paracellular channels formed by claudins of the
           blood–brain barrier tight junctions
    • Authors: Flaviyan Jerome Irudayanathan; Nan Wang, Xiaoyi Wang, Shikha Nangia
      Abstract: Tight junctions (TJs) are key players in determining tissue-specific paracellular permeability across epithelial and endothelial membranes. Claudin proteins, the primary determinants of TJs structure and functionality, assemble in paracellular spaces to form channels and pores that are charge and size selective. Here, using molecular dynamics (MD) simulations, we elucidate the molecular assembly of claudin-3 and claudin-5 proteins of blood–brain barrier TJs. Despite having a high degree of sequence and structural similarity, these two claudins form different types of cis-interactions. Molecular docking of the observed cis-interfaces into trans-forms revealed two putative pore models that were also observed in the self-assembly simulations. The observed pore structures (pore I and II) have pore-lining residues that have been previously reported in the literature. The pore I model is consistent with a previously reported claudin-15 model. The pore II model, also consistent with biochemical results, has not been reported previously. Further analysis using in silico site-directed mutations provide convincing support for the validity of the pore II model. Using steered MD and umbrella sampling, we computed the transport properties of water and α-d-glucose through pore II. The study offers new insight into the selectivity of blood–brain barrier TJs.
      PubDate: 2017-06-14T14:55:32.501696-05:
      DOI: 10.1111/nyas.13378
       
  • Genomics of antibiotic-resistance prediction in Pseudomonas aeruginosa
    • Authors: Julie Jeukens; Luca Freschi, Irena Kukavica-Ibrulj, Jean-Guillaume Emond-Rheault, Nicholas P. Tucker, Roger C. Levesque
      Abstract: Antibiotic resistance is a worldwide health issue spreading quickly among human and animal pathogens, as well as environmental bacteria. Misuse of antibiotics has an impact on the selection of resistant bacteria, thus contributing to an increase in the occurrence of resistant genotypes that emerge via spontaneous mutation or are acquired by horizontal gene transfer. There is a specific and urgent need not only to detect antimicrobial resistance but also to predict antibiotic resistance in silico. We now have the capability to sequence hundreds of bacterial genomes per week, including assembly and annotation. Novel and forthcoming bioinformatics tools can predict the resistome and the mobilome with a level of sophistication not previously possible. Coupled with bacterial strain collections and databases containing strain metadata, prediction of antibiotic resistance and the potential for virulence are moving rapidly toward a novel approach in molecular epidemiology. Here, we present a model system in antibiotic-resistance prediction, along with its promises and limitations. As it is commonly multidrug resistant, Pseudomonas aeruginosa causes infections that are often difficult to eradicate. We review novel approaches for genotype prediction of antibiotic resistance. We discuss the generation of microbial sequence data for real-time patient management and the prediction of antimicrobial resistance.
      PubDate: 2017-06-02T08:00:46.444097-05:
      DOI: 10.1111/nyas.13358
       
  • Equivalence of complex drug products: advances in and challenges for
           current regulatory frameworks
    • Authors: Leonie Hussaarts; Stefan Mühlebach, Vinod P. Shah, Scott McNeil, Gerrit Borchard, Beat Flühmann, Vera Weinstein, Sesha Neervannan, Elwyn Griffiths, Wenlei Jiang, Elena Wolff-Holz, Daan J.A. Crommelin, Jon S.B. Vlieger
      Abstract: Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron–carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified.
      PubDate: 2017-04-26T12:10:34.962138-05:
      DOI: 10.1111/nyas.13347
       
  • Irisin and musculoskeletal health
    • Authors: Graziana Colaianni; Saverio Cinti, Silvia Colucci, Maria Grano
      Abstract: Irisin is a hormone-like myokine produced in abundance by skeletal muscle in response to exercise, both in mice and humans. Once released into the circulation, irisin acts on white adipocytes to induce the browning response and subsequently activates nonshivering thermogenesis. We have examined the premise that irisin produced during exercise may subserve further functions in the musculoskeletal system. We review evidence for its possible skeletal effects, including the central role that irisin plays in the control of bone mass, with positive effects on cortical mineral density and geometry in mice. We also review the autocrine effects of irisin in skeletal muscle, in which it upregulates the expression of its precursor (FNDC5). Since loss of bone and muscle mass occurs with aging, immobility, and several metabolic diseases, future studies exploring the efficacy of irisin in restoring bone and reversing muscle wasting could be important to establishing irisin as a molecule that combines beneficial effects for treating osteoporosis and muscular atrophy. If the results from mice were confirmed in human studies, an irisin-based therapy could be developed for physically disabled or bedridden patients.
      PubDate: 2017-04-24T12:56:03.388678-05:
      DOI: 10.1111/nyas.13345
       
  • Issue Information
    • Pages: 1 - 2
      PubDate: 2017-08-08T11:37:51.770951-05:
      DOI: 10.1111/nyas.13244
       
  • Not all about sex: neural and biobehavioral functions of human dance
    • Authors: Julia F. Christensen; Camilo José Cela-Conde, Antoni Gomila
      Pages: 8 - 32
      Abstract: This paper provides an integrative review of neuroscientific and biobehavioral evidence about the effects of dance on the individual across cultural differences. Dance moves us, and many derive aesthetic pleasure from it. However, in addition—and beyond aesthetics—we propose that dance has noteworthy, deeper neurobiological effects. We first summarize evidence that illustrates the centrality of dance to human life indirectly from archaeology, comparative psychology, developmental psychology, and cross-cultural psychology. Second, we review empirical evidence for six neural and biobehavioral functions of dance: (1) attentional focus/flow, (2) basic emotional experiences, (3) imagery, (4) communication, (5) self-intimation, and (6) social cohesion. We discuss the reviewed evidence in relation to current debates in the field of empirical enquiry into the functions of human dance, questioning the positions that dance is (1) just for pleasure, (2) all about sex, (3) just for mood management and well-being, and (4) for experts only.Being a young field, evidence is still piecemeal and inconclusive. This review aims to take a step toward a systematization of an emerging avenue of research: a neuro- and biobehavioral science of dance.
      PubDate: 2017-08-08T11:37:52.083059-05:
      DOI: 10.1111/nyas.13420
       
 
 
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