Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Humans

  • adult human
  • aged human
  • healthy human
  • infected human
  • many human
  • modern human
  • normal human
  • other human
  • primary human
  • recent human
  • recombinant human
  • virtual human

  • Terms modified by Humans

  • human DC
  • human E cell
  • human EC
  • human NSC
  • human NTD
  • human PBMC
  • human ability
  • human acidic fibroblast growth factor
  • human action
  • human activity
  • human ad brain
  • human adaptation
  • human adenocarcinoma cell line
  • human adipose tissue
  • human adult
  • human affair
  • human ageing
  • human agency
  • human aging
  • human airway
  • human airway epithelial cell
  • human albumin
  • human alcoholic
  • human alteration
  • human amyloid precursor protein
  • human anaplastic thyroid cancer cell
  • human anatomy
  • human androgen receptor gene
  • human anti
  • human antibody
  • human aortic endothelial cell
  • human aortic smooth muscle cell
  • human application
  • human arrival
  • human artery
  • human articular chondrocyte
  • human asthma
  • human astrocyte
  • human astrocytoma
  • human astrocytoma cell
  • human atherosclerosis
  • human atherosclerotic plaque
  • human atrial fibrillation
  • human atrium
  • human autoimmune diseases
  • human b cell
  • human b lymphocyte
  • human basophil
  • human behavior
  • human behaviour
  • human being
  • human bile
  • human biology
  • human biopsy
  • human birth defects
  • human bladder
  • human bladder carcinoma
  • human blood
  • human blood monocyte
  • human blood plasma
  • human blood sample
  • human blood serum
  • human bmp-2
  • human body
  • human body fluid
  • human bone
  • human bone marrow
  • human bone marrow cell
  • human bone marrow mesenchymal stem cell
  • human bone marrow stromal cell
  • human bone morphogenetic
  • human bone morphogenetic protein
  • human brain
  • human brain development
  • human brain microvascular endothelial cell
  • human brain tissue
  • human brain tumor
  • human breast
  • human breast cancer
  • human breast cancer cell
  • human breast cancer cell line
  • human breast cancers
  • human breast carcinoma
  • human breast carcinoma cell
  • human breast carcinoma cell line
  • human breast epithelial cell
  • human bronchial epithelial
  • human bronchial epithelial cell
  • human bronchus
  • human cadaver
  • human cancer
  • human cancer cell
  • human cancer cell line
  • human cancers
  • human capability
  • human capacity
  • human capital
  • human capital accumulation
  • human capital approach
  • human capital characteristic
  • human capital development
  • human capital formation
  • human capital investment
  • human capital model
  • human capital theory
  • human capital variable
  • human carbonic anhydrase ii
  • human carcinogen
  • human carcinogenesi
  • human carcinoma
  • human cardiac fibroblast
  • human case
  • human cd34+ cell
  • human cell
  • human cell line
  • human cell system
  • human cell type
  • human central nervous system
  • human cerebral cortex
  • human cerebrospinal fluid
  • human characteristic
  • human child
  • human choice
  • human chondrocyte
  • human chondrosarcoma cell line
  • human chorionic gonadotrophin
  • human chorionic gonadotropin
  • human chromosome
  • human clinical studies
  • human clinical trial
  • human clinical trials
  • human cognition
  • human cognitive function
  • human colon
  • human colon cancer
  • human colon cancer cell
  • human colon cancer cell line
  • human colon carcinoma
  • human colon carcinoma cell
  • human colon carcinoma cell line
  • human colon tissue
  • human colorectal cancer
  • human colorectal cancer cell
  • human colorectal cancers
  • human colorectal carcinoma
  • human communication
  • human community
  • human condition
  • human connection
  • human consciousness
  • human consumer
  • human consumption
  • human contact
  • human cord blood
  • human cornea
  • human corneal endothelial cell
  • human corneal epithelial cell
  • human coronary artery
  • human corpus cavernosum
  • human cortex
  • human counterpart
  • human cranium
  • human culture
  • human cyp3a4
  • human cytochrome p450
  • human cytochrome p450 enzyme
  • human cytokine
  • human cytomegalovirus
  • human cytomegalovirus infection
  • human data
  • human dc
  • human decidua
  • human dendritic cell
  • human density
  • human dental pulp
  • human dentin
  • human dentine
  • human dermal fibroblast
  • human dermal microvascular endothelial cell
  • human dermis
  • human development
  • human development index
  • human development indicator
  • human development report
  • human diet
  • human dignity
  • human dimension
  • human diploid fibroblast
  • human disease
  • human diseases
  • human disorders
  • human disturbance
  • human diversity
  • human dna
  • human donor
  • human ec
  • human ecology
  • human economy
  • human eeg
  • human effects
  • human element
  • human embryo
  • human embryonic
  • human embryonic development
  • human embryonic kidney
  • human embryonic kidney cell
  • human embryonic stem
  • human embryonic stem cell
  • human emotion
  • human enamel
  • human endometrium
  • human endothelial cell
  • human enteric viruse
  • human environment
  • human enzyme
  • human eosinophil
  • human epidermal cell
  • human epidermal growth factor receptor
  • human epidermal keratinocyte
  • human epidermis
  • human epithelial cell
  • human epo
  • human error
  • human erythrocyte
  • human erythropoietin
  • human esophageal squamous cell carcinoma
  • human estrogen receptor
  • human ether
  • human evolution
  • human evolutionary history
  • human existence
  • human experience
  • human experiment
  • human expert
  • human exploitation
  • human exposure
  • human eye
  • human face
  • human factor viii
  • human faeces
  • human fc
  • human feces
  • human female
  • human femur
  • human fertility
  • human fetal liver
  • human fetal membrane
  • human fetus
  • human fetuse
  • human fibrinogen
  • human fibroblast
  • human fibroblast growth factor
  • human fibrosarcoma cell
  • human food
  • human food chain
  • human foot
  • human foreskin fibroblast
  • human form
  • human freedom
  • human function
  • human fungal pathogen
  • human fviii
  • human gait
  • human gastric
  • human gastric adenocarcinoma
  • human gastric cancer
  • human gastric cancer cell
  • human gastric cancer cell line
  • human gastric carcinoma cell
  • human gastric mucosa
  • human gastrointestinal tract
  • human gene
  • human genetic disease
  • human genetic disorders
  • human genetics
  • human genome
  • human genome project
  • human genome u133 plus
  • human genomic dna
  • human geography
  • human gh
  • human gingiva
  • human gingival epithelial cell
  • human gingival fibroblast
  • human glioblastoma
  • human glioblastoma cell
  • human glioma
  • human glioma cell
  • human glioma cell line
  • human glutamate carboxypeptidase ii
  • human granulocyte
  • human groups
  • human growth
  • human growth hormone
  • human gut
  • human hair
  • human hair follicle
  • human hand
  • human hcc
  • human hcc cell
  • human head and neck squamous cell carcinoma
  • human health
  • human health risk
  • human heart
  • human heat shock protein
  • human hemoglobin
  • human hepatocarcinogenesi
  • human hepatocarcinoma cell line
  • human hepatocellular carcinoma
  • human hepatocellular carcinoma cell
  • human hepatocellular carcinoma cell line
  • human hepatocyte
  • human hepatocyte cell line
  • human hepatoma cell
  • human hepatoma cell line
  • human hepatoma hepg2 cell
  • human hepg2 cell
  • human herpes virus
  • human herpesviru
  • human hippocampus
  • human history
  • human homolog
  • human homologue
  • human host
  • human hosts
  • human identification
  • human identity
  • human ifn
  • human ige
  • human igg
  • human igg1
  • human illness
  • human immune response
  • human immune system
  • human immunodeficiency
  • human immunodeficiency virus
  • human immunodeficiency virus immunodeficiency syndrome
  • human immunodeficiency virus infection
  • human immunodeficiency virus patient
  • human immunodeficiency virus testing
  • human immunodeficiency virus type
  • human immunoglobulin
  • human immunoglobulin g
  • human impact
  • human individual
  • human infant
  • human infection
  • human infections
  • human inflammatory bowel disease
  • human influence
  • human inherited disease
  • human insecurity
  • human insulin
  • human interaction
  • human interest
  • human interference
  • human interferon
  • human interleukin
  • human intervention
  • human intervention studies
  • human intestinal absorption
  • human intestinal epithelial cell
  • human intestinal tract
  • human intestine
  • human investigation
  • human islet
  • human judgment
  • human kallikrein
  • human kc
  • human keratinocyte
  • human keratinocyte cell line
  • human kidney
  • human knee
  • human knowledge
  • human lactoferrin
  • human land use
  • human language
  • human ldl
  • human leucocyte
  • human leucocyte antigen
  • human leukemia
  • human leukemia cell
  • human leukemic cell
  • human leukocyte
  • human leukocyte antigen
  • human leukocyte elastase
  • human life
  • human life history
  • human lifespan
  • human lip
  • human liver
  • human liver cancer cell
  • human liver cell
  • human liver microsomal preparation
  • human liver microsome
  • human liver protein
  • human liver slice
  • human liver tissue
  • human liver transplantation
  • human longevity
  • human love
  • human low-density lipoprotein
  • human lung
  • human lung adenocarcinoma
  • human lung cancer
  • human lung cancer cell
  • human lung carcinoma
  • human lung carcinoma cell
  • human lung fibroblast
  • human lung mast cell
  • human lupus
  • human lymphoblastoid cell
  • human lymphocyte
  • human lymphoma
  • human lysozyme
  • human macrophage
  • human malaria
  • human malaria parasite plasmodium falciparum
  • human male
  • human malignancy
  • human malignant melanoma
  • human mammary epithelial cell
  • human mandible
  • human mast cell
  • human maxilla
  • human maxillary anterior tooth
  • human medicine
  • human melanocyte
  • human melanoma
  • human melanoma cell
  • human melanoma cell line
  • human memory
  • human meningioma
  • human mesangial cell
  • human mesenchymal stem cell
  • human mesenchymal stromal cell
  • human metabolism
  • human microsome
  • human microvascular endothelial cell
  • human migration
  • human milk
  • human milk oligosaccharide
  • human milk sample
  • human mind
  • human mitochondrial dna
  • human mobility
  • human model
  • human models
  • human modification
  • human molar
  • human molar tooth
  • human monoclonal antibody
  • human monocyte
  • human monocytic cell line
  • human motor cortex
  • human movement
  • human msc
  • human multiple sclerosis
  • human muscle
  • human mutation
  • human myeloma cell
  • human myocardium
  • human myometrium
  • human nail
  • human nasal epithelial cell
  • human nasal mucosa
  • human natural killer
  • human nature
  • human need
  • human neocortex
  • human neonate
  • human neoplasm
  • human neural
  • human neural cell line
  • human neural progenitor cell
  • human neural stem cell
  • human neural tube defects
  • human neuroblastoma
  • human neuroblastoma cell
  • human neuroblastoma cell line
  • human neuroblastoma sh-sy5y cell
  • human neurodegenerative disease
  • human neuron
  • human neutrophil
  • human neutrophil elastase
  • human neutrophil peptide
  • human newborn
  • human nk cell
  • human normal
  • human nutrition
  • human obesity
  • human observer
  • human occupation
  • human oligodendrocyte
  • human oral cavity
  • human oral epithelial cell
  • human oral epithelium
  • human oral keratinocyte
  • human oral mucosa
  • human oral squamous cell carcinoma
  • human organ
  • human organism
  • human origin
  • human origins
  • human ortholog
  • human orthologue
  • human osteoarthritic chondrocyte
  • human osteoarthritis
  • human osteoblast
  • human osteoblast cell
  • human osteoblast-like cell
  • human osteoblastic cell
  • human osteoclast
  • human osteosarcoma
  • human osteosarcoma cell
  • human osteosarcoma cell line
  • human ovarian cancer cell
  • human ovarian carcinoma cell
  • human ovarian surface epithelial cell
  • human pancreas
  • human pancreatic
  • human pancreatic cancer cell
  • human pancreatic cancer cell line
  • human pancreatic carcinoma cell
  • human papilloma virus
  • human papillomavirus
  • human papillomavirus dna
  • human papillomavirus infection
  • human papillomavirus infections
  • human papillomavirus testing
  • human papillomavirus type
  • human papillomavirus vaccine
  • human parasite
  • human parathyroid hormone
  • human participant
  • human pathogen
  • human pathogenic bacteria
  • human pathogenic fungus
  • human pathology
  • human patient
  • human patient simulator
  • human pbmc
  • human pdl cell
  • human perception
  • human performance
  • human performance technology
  • human periodontal disease
  • human periodontal ligament
  • human periodontal ligament cell
  • human periodontal ligament fibroblast
  • human periodontitis
  • human peripheral blood
  • human peripheral blood lymphocyte
  • human peripheral blood monocyte
  • human peripheral blood mononuclear cell
  • human permanent tooth
  • human person
  • human personality
  • human perspective
  • human pharmaceuticals
  • human pharmacokinetic
  • human phenotype
  • human physiology
  • human pigmentation
  • human pituitary adenoma
  • human placenta
  • human placental alkaline phosphatase
  • human plasma
  • human plasma protein
  • human plasma sample
  • human platelet
  • human platelet aggregation
  • human platelet antigen
  • human platelet-rich plasma
  • human polymorphonuclear leucocyte
  • human polymorphonuclear leukocyte
  • human population
  • human population density
  • human population growth
  • human prefrontal cortex
  • human pregnancy
  • human premolar
  • human presence
  • human pressure
  • human primary
  • human prion disease
  • human prion protein
  • human progenitor cell
  • human prospect
  • human prostate
  • human prostate cancer
  • human prostate cancer cell
  • human prostate cancer cell line
  • human prostate cancers
  • human prostate carcinoma
  • human prostate tissue
  • human prostate tumor
  • human protein
  • human proteome
  • human psychology
  • human pulp fibroblast
  • human ra
  • human rcc
  • human recombinant
  • human red blood cell
  • human relation
  • human relationships
  • human renal cell carcinoma
  • human renal epithelial cell
  • human reproduction
  • human resource
  • human resource development
  • human resource issues
  • human resource management
  • human resource management practice
  • human resource practice
  • human resources
  • human resources development
  • human resources management
  • human respiratory syncytial virus
  • human response
  • human responsibility
  • human retina
  • human retinal pigment epithelial cell
  • human rheumatoid arthritis
  • human right
  • human right abuse
  • human right act
  • human right activist
  • human right commission
  • human right concern
  • human right discourse
  • human right education
  • human right instruments
  • human right issues
  • human right law
  • human right norm
  • human right policy
  • human right practice
  • human right protection
  • human right violation
  • human rights law
  • human rpe cell
  • human safety
  • human saliva
  • human salivary gland
  • human sample
  • human saphenou vein
  • human science
  • human security
  • human semen
  • human seminal fluid
  • human seminal plasma
  • human sepsis
  • human sequence
  • human sera
  • human serum
  • human serum albumin
  • human serum protein
  • human serum sample
  • human services
  • human settlement
  • human sewage
  • human sex difference
  • human sexuality
  • human sigmoid colon
  • human situation
  • human skeletal
  • human skeletal muscle
  • human skeletal muscle cell
  • human skeleton
  • human skin
  • human skin cell
  • human skin fibroblast
  • human skull
  • human sle
  • human small intestine
  • human society
  • human soleus muscle
  • human solid tumor
  • human source
  • human species
  • human specimen
  • human sperm
  • human sperm motility
  • human spermatogenesis
  • human spermatozoa
  • human squamous cell carcinoma
  • human stem cell
  • human stomach
  • human strain
  • human stratum corneum
  • human studies
  • human study
  • human subject
  • human substantia nigra
  • human suffering
  • human survival
  • human syndrome
  • human synoviocyte
  • human system
  • human t cell
  • human t lymphocyte
  • human t-lymphotropic virus
  • human tear fluid
  • human telomerase
  • human telomerase reverse transcriptase
  • human telomerase rna
  • human temporal lobe epilepsy
  • human testis
  • human therapeutics
  • human third molar
  • human thought
  • human thrombin
  • human thymus
  • human tissue
  • human tonsil
  • human tooth
  • human tooth enamel
  • human tracheal smooth muscle cell
  • human trafficking
  • human trait
  • human transferrin receptor
  • human transthyretin
  • human trial
  • human trials
  • human tumor
  • human tumor antigen
  • human tumor cell
  • human tumor cell line
  • human tumor xenograft
  • human tumour
  • human tumour cell line
  • human type 1 diabetes
  • human umbilical cord
  • human umbilical cord blood
  • human umbilical vascular endothelial cell
  • human umbilical vein endothelial cell
  • human urine
  • human urine sample
  • human use
  • human user
  • human vaccine
  • human vagina
  • human vaginal
  • human value
  • human variation
  • human vascular endothelial cell
  • human viruse
  • human visceral leishmaniasis
  • human vision
  • human visual system
  • human volunteer
  • human waste
  • human welfare
  • human well-being
  • human white matter
  • human whole blood
  • human y chromosome

  • Selected Abstracts

    HLA,B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats

    ARTHRITIS & RHEUMATISM, Issue 9 2009
    Monica L. DeLay
    Objective To determine whether HLA,B27 misfolding and the unfolded protein response (UPR) result in cytokine dysregulation and whether this is associated with Th1 and/or Th17 activation in HLA,B27/human ,2 -microglobulin (Hu,2m),transgenic rats, an animal model of spondylarthritis. Methods Cytokine expression in lipopolysaccharide (LPS),stimulated macrophages was analyzed in the presence and absence of a UPR induced by chemical agents or by HLA,B27 up-regulation. Cytokine expression in colon tissue and in cells purified from the lamina propria was determined by real-time reverse transcription,polymerase chain reaction analysis, and differences in Th1 and Th17 CD4+ T cell populations were quantified after intracellular cytokine staining. Results Interleukin-23 (IL-23) was found to be synergistically up-regulated by LPS in macrophages undergoing a UPR induced by pharmacologic agents or by HLA,B27 misfolding. IL-23 was also increased in the colon tissue from B27/Hu,2m-transgenic rats concurrently with the development of intestinal inflammation, and IL-17, a downstream target of IL-23, exhibited robust up-regulation in a similar temporal pattern. IL-23 and IL-17 transcripts were localized to CD11+ antigen-presenting cells and CD4+ T cells, respectively, from the colonic lamina propria. Colitis was associated with a 6-fold expansion of CD4+ IL-17,expressing T cells. Conclusion The IL-23/IL-17 axis is strongly activated in the colon of B27/Hu,2m-transgenic rats with spondylarthritis-like disease. HLA,B27 misfolding and UPR activation in macrophages can result in enhanced induction of the pro-Th17 cytokine IL-23. These results suggest a possible link between HLA,B27 misfolding and immune dysregulation in this animal model, with implications for human disease. [source]

    Spondylarthritis in HLA,B27/human ,2 -microglobulin,transgenic rats is not prevented by lack of CD8

    ARTHRITIS & RHEUMATISM, Issue 7 2009
    Joel D. Taurog
    Objective HLA,B27 predisposes to spondylarthritis by an unknown mechanism. A logical candidate mechanism is through recognition of B27 by CD8+ T cells. The purpose of this study was to examine the effects of a lack of CD8 on the spondylarthritis that develops in B27/human ,2 -microglobulin (Hu,2m),transgenic rats. Methods A missense mutation in the CD8a gene that causes a loss of CD8, expression was identified in offspring of a male Sprague-Dawley rat that had been treated with the mutagen N -ethyl- N -nitrosourea. The mutation was crossed into B27/Hu,2m-transgenic lines on the Lewis background. CD8a,/, and CD8a+/, progeny were compared on a mixed SD-LEW background as well as after at least 10 backcrosses to LEW rats. CD8 function was assessed by generating cytolytic T lymphocytes (CTLs) against allogeneic DA strain antigens. Results Homozygous mutant rats showed normal CD8a and CD8b messenger RNA levels but no detectable expression of either protein and an almost complete abrogation of the allogeneic CTL response. Two disease phenotypes previously observed in different B27/Hu,2m-transgenic lines also occurred in the respective CD8a,/, -transgenic rat lines. There was no significant difference in disease prevalence or severity between CD8a,/, rats and CD8a+/, rats. Conclusion All of the previously described disease manifestations in HLA,B27/Hu,2m-transgenic rats arise in the absence of any functional CD8+ T cells. It thus seems unlikely that classic T cell recognition of HLA,B27 is of primary importance in this animal model. The possibility of a secondary role of a CD8-dependent mechanism cannot be entirely excluded. [source]

    HLA,B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: Implications for the pathogenesis of spondylarthritis-like disease

    ARTHRITIS & RHEUMATISM, Issue 1 2007
    Matthew J. Turner
    Objective HLA,B27 is implicated in the pathogenesis of spondylarthritis (SpA), yet the molecular mechanisms are incompletely defined. HLA,B27 misfolding has been associated with endoplasmic reticulum stress and activation of the unfolded protein response (UPR) in macrophages from HLA,B27/human ,2 -microglobulin,transgenic (B27-transgenic) rats. This study was performed to assess the mechanisms that drive activation of the HLA,B27,induced UPR and to determine whether splenocytes respond in a similar manner. Methods Splenocytes were isolated and bone marrow macrophages were derived from B27-transgenic and wild-type rats. Cells were treated for up to 24 hours with cytokines that induce class I major histocompatibility complex expression. HLA,B27 expression and misfolding were assessed by real-time reverse transcription,polymerase chain reaction, flow cytometry, and immunoblotting. Activation of the UPR was measured by quantifying UPR target gene expression and X-box binding protein 1 messenger RNA (mRNA) splicing. Results HLA,B27 mRNA up-regulation was accompanied by a dramatic increase in the accumulation of misfolded heavy chains and preceded robust activation of the UPR in macrophages. When macrophages were treated with various cytokines, the magnitude of the UPR correlated strongly with the degree of HLA,B27 up-regulation. In contrast, B27-transgenic splenocytes exhibited only low-level differences in the expression of UPR target genes after exposure to interferon-, or concanavalin A, which resulted in minimal HLA,B27 up-regulation. Conclusion These results suggest that HLA,B27,associated activation of the UPR in macrophages is attributable to the accumulation of misfolded heavy chains, and that certain cell types may be more susceptible to the effects of HLA,B27 misfolding. Strategies that eliminate HLA,B27 up-regulation and/or the accumulation of misfolded heavy chains may be useful in evaluating the role of these events in the pathogenesis of SpA. [source]

    Endoplasmic reticulum stress and the unfolded protein response are linked to synergistic IFN-, induction via X-box binding protein 1

    Judith A. Smith Dr.
    Abstract Type,I IFN are strongly induced upon engagement of certain pattern recognition receptors by microbial products, and play key roles in regulating innate and adaptive immunity. It has become apparent that the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR), in addition to restoring ER homeostasis, also influences the expression of certain inflammatory cytokines. However, the extent to which UPR signaling regulates type,I IFN remains unclear. Here we show that cells undergoing a UPR respond to TLR4 and TLR3 ligands, and intracellular dsRNA, with log-fold greater IFN-, induction. This synergy is not dependent on autocrine type,I IFN signaling, but unexpectedly requires the UPR transcription factor X-box binding protein,1 (XBP-1). Synergistic IFN-, induction also occurs in HLA-B27/human ,2m-transgenic rat macrophages exhibiting a UPR as a consequence of HLA-B27 up-regulation, where it correlates with activation of XBP-1 splicing. Together these findings indicate that the cellular response to endogenous ,danger' that disrupts ER homeostasis is coupled to IFN-, induction by XBP-1, which has implications for the immune response and the pathogenesis of diseases involving the UPR. [source]


    EVOLUTION, Issue 3 2005
    Maciej F. Boni
    Abstract Antibiotic treatment by humans generates strong viability selection for antibiotic-resistant bacterial strains. The frequency of host antibiotic use often determines the strength of this selection, and changing patterns of antibiotic use can generate many types of behaviors in the population dynamics of resistant and sensitive bacterial populations. In this paper, we present a simple model of hosts dimorphic for their tendency to use/avoid antibiotics and bacterial pathogens dimorphic in their resistance/sensitivity to antibiotic treatment. When a constant fraction of hosts uses antibiotics, the two bacterial strain populations can coexist unless host use-frequency is above a critical value; this critical value is derived as the ratio of the fitness cost of resistance to the fitness cost of undergoing treatment. When strain frequencies can affect host behavior, the dynamics may be analyzed in the light of niche construction. We consider three models underlying changing host behavior: conformism, the avoidance of long infections, and adherence to the advice of public health officials. In the latter two, we find that the pathogen can have quite a strong effect on host behavior. In particular, if antibiotic use is discouraged when resistance levels are high, we observe a classic niche-construction phenomenon of maintaining strain polymorphism even in parameter regions where it would not be expected. [source]


    ABSTRACT. Carl Ortwin Sauer (1889,1975) is widely regarded as one of the most influential geographers of the twentieth century, admired particularly for his studies in cultural and historical geography. His contribution to the study of prehistory is less widely acknowledged, but, between 1944 and 1962, he published a series of speculative yet scholarly papers that contain many prescient insights into humanity's remote past and the relationships of our ancestors to the environments they occupied,and modified. In this essay, based on the Carl O. Sauer Memorial Lecture given at the University of California, Berkeley, in October 2001, I reflect on Sauer's contribution to the science of prehistory by examining, in the light of recent advances in knowledge, two major themes of Sauer's work: the early dispersal of Homo sapiens in the Old World, and the origins and prehistoric spread of agriculture. [source]


    BIOETHICS, Issue 5 2006
    ABSTRACT Accepting the claim that the living have some moral duties with regard to dead bodies, this paper explores those duties and how they bear on the popular travelling exhibition Bodyworlds. I argue that the concept of informed consent presupposes substantial duties to the dead, namely duties that reckon with the meaning of the act in question. An attitude of respect and not regarding human remains as mere raw material are non-alienable substantial duties. I found the ethos of Bodyworlds premature but full of promises such as public attitudes to organ donations. At the practical level I conclude that Bodyworlds should use only willed donations or unclaimed bodies for which dignified funerals are not available. In the case of live donations, Bodyworlds has a duty to participate in the medical care of needy donors. However, secrecy with regard to the sources of cadavers seems to be the most troublesome aspect of Bodyworlds. [source]


    ADDICTION, Issue 4 2009
    No abstract is available for this article. [source]


    Article first published online: 24 SEP 200
    Carmichael, W. W. Department of Biological Sciences, Wright State University, Dayton, Ohio 45435 USA Cyanobacteria toxins (cyanotoxins) include cytotoxins and biotoxins with cytotoxins including about 60 compounds ranging from phytoalexins to animicrobials to enzyme inhibitors to compounds that can reverse multidrug resistance. Producer organisms include marine/brackish water Cystoseira, Hormothamnin, Lyngbya, Nodularia and Synechocystis, and the freshwater/terrestrial genera Anabaena, Dichotrix, Fischerella, Hapalosiphon, Lyngbya, Microcystis, Nostoc, Oscillatoria, Planktothrix, Phormidium, Schizothrix, Scytonema, Spirulina, Stigonema and Symploca. Since many of these compounds have been identified, not during ecological studies, but during drug discovery investigations, their ecological role is only speculative. Biotoxins are responsible for acute lethal, acute, chronic and sub-chronic poisonings of wild/domestic animals and humans. They include the neurotoxins; anatoxin-a, anatoxin-a(s) and saxitoxins plus the hepatotoxins; microcystins, nodularins and cylindrospermopsin. These compounds are included when referencing harmful algal blooms (HAB's) such as the more predominate marine PSP (paralytic shellfish poisoning), DSP (diarrhetic shellfish poisoning), NSP (neurotoxic shellfish poisoning), ASP (amnesic shellfish poisoning) and EAS (estuary associated syndrome). The CTP (cyanobacteria toxin poisoning) organisms occur in freshwater lakes, ponds, rivers and reservoirs throughout the world. Organisms responsible for CTP's are Anabaena, Aphanizomenon, Cylindrosperm- opsis, Microcystis, Nodularia, Nostoc Oscillatoria (Planktothrix), Trichodesmium and certain picoplanktic genera. Concern for animal and human health impairments arises from animal poisonings, associated with cyanobacteria waterblooms, beginning with the later part of the 1800's. It was not until the 1950's that we began to understand that cyanobacteria could indeed produce highly toxic compounds. A recent 1998 compilation of all available information on toxic cyanobacteria was published by the World Health Organization. This increasing focus on the role of cyanobacteria metabolites in chemical ecology, drug discovery and toxinology has placed new importance on using correct taxonomy for communication of responsible organisms. [source]


    Georgios E. Pavlikakis
    ABSTRACT: The Ecosystem Management (EM) process belongs to the category of Multi-Criteria Decision Making (MCDM) problems. It requires appropriate decision support systems (DSS) where "all interested people" would be involved in the decision making process. Environmental values critical to EM, such as the biological diversity, health, productivity and sustainability, have to be studied, and play an important role in modeling the ecosystem functions; human values and preferences also influence decision making. Public participation in decision and policy making is one of the elements that differentiate EM from the traditional methods of management. Here, a methodology is presented on how to quantify human preferences in EM decision making. The case study of the National Park of River Nestos Delta and Lakes Vistonida and Ismarida in Greece, presented as an application of this methodology, shows that the direct involvement of the public, the quantification of its preferences and the decision maker's attitude provide a strong tool to the EM decision making process. Public preferences have been given certain weights and three MCDM methods, namely, the Expected Utility Method, Compromise Programming and the Analytic Hierarchy Process, have been used to select alternative management solutions that lead to the best configuration of the ecosystem and are also socially acceptable. [source]


    NEPHROLOGY, Issue 1 2002
    Robyn Langham


    Article first published online: 11 JAN 200
    No abstract is available for this article. [source]

    Special issue "Physiological Human"

    James Kwangjune Hahn
    No abstract is available for this article. [source]

    98% Human: 91% Extinct

    Thomas R. Gillespie
    No abstract is available for this article. [source]

    Europe as a "Special Area for Human Hope"

    Alessandro Ferrara
    First page of article [source]

    Being Human: Race, Culture, and Religion , By Dwight N. Hopkins

    Maureen Dallison Kemeza
    First page of article [source]

    A Randomized, Bilateral, Prospective Comparison of Calcium Hydroxylapatite Microspheres versus Human-Based Collagen for the Correction of Nasolabial Folds

    BACKGROUND Current soft tissue fillers are a compromise between ease of use, duration of correction, reactivity, and cost. A product utilizing calcium hydroxylapatite (CaHA) is currently being used as a soft tissue filler. OBJECTIVE The objective was to compare the efficacy and safety of CaHA microspheres versus human-based collagen for the correction of nasolabial folds. MATERIALS AND METHODS Four centers enrolled 117 subjects with moderate to deep nasolabial folds. Subjects received CaHA on one side of the face and human collagen on the other. Up to two touch-ups were allowed. A blinded panel of experts evaluated subject photographs from initial and follow-up visits. RESULTS Seventy-nine percent of subjects had superior improvement on the CaHA side through 6 months (p<.0001). For optimal correction, significantly less volume and fewer injections were needed for CaHA than for collagen (p<.0001). Adverse event rates were comparable, with some increase in bruising and edema for CaHA-treated sides. Adverse event duration was similar for both groups and generally resolved within 14 to 21 days. CONCLUSION This CaHA-based product gives significantly longer-lasting correction of nasolabial folds compared to human collagen. Less total material and fewer injections are required. The adverse event profile of the product is similar to the collagen-based product. [source]

    Use of a Living Dermal Equivalent for a Refractory Abdominal Defect after Pediatric Multivisceral Transplantation

    Carlos A. Charles MD
    Background. Primary closure is not always possible after pediatric multivisceral transplantation. Reepithelialization may require extended periods of postoperative time, which can be associated with significant morbidity Objective. The objective was to accelerate secondary wound closure thereby minimizing infection or further complications in a pediatric multivisceral transplant patient. Methods. Five applications of human fibroblast-derived dermis (Dermagraft, Smith and Nephew) were applied to the postsurgical defect of a pediatric multivisceral transplant patient over the course of 8 months. Routine wound care and observation was performed between human fibroblast-derived dermis applications. Results. Human fibroblast-derived dermis stimulated healing and accelerated reepithelialization. Signs of clinical rejection or infection were not observed. Conclusion. Reepithelialization can be aided in the postoperative period in pediatric multivisceral transplant patients with human fibroblast-derived dermis, thereby helping to deter complications associated with secondary wound closure. We have illustrated the successful use of a human fibroblast-derived dermis as an adjunct for wound healing in a complicated surgical defect. [source]

    Human and pig SRY 5, flanking sequences can direct reporter transgene expression to the genital ridge and to migrating neural crest cells

    Alexandre Boyer
    Abstract Mechanisms for sex determination vary greatly between animal groups, and include chromosome dosage and haploid,diploid mechanisms as seen in insects, temperature and environmental cues as seen in fish and reptiles, and gene-based mechanisms as seen in birds and mammals. In eutherian mammals, sex determination is genetic, and SRY is the Y chromosome located gene representing the dominant testes determining factor. How SRY took over this function from ancestral mechanisms is not known, nor is it known what those ancestral mechanisms were. What is known is that SRY is haploid and thus poorly protected from mutations, and consequently is poorly conserved between mammalian species. To functionally compare SRY promoter sequences, we have generated transgenic mice with fluorescent reporter genes under the control of various lengths of human and pig SRY 5, flanking sequences. Human SRY 5, flanking sequences (5 Kb) supported reporter transgene expression within the genital ridge of male embryos at the time of sex determination and also supported expression within migrating truncal neural crest cells of both male and female embryos. The 4.6 Kb of pig SRY 5, flanking sequences supported reporter transgene expression within the male genital ridge but not within the neural crest; however, 2.6 Kb and 1.6 Kb of pig SRY 5, flanking sequences retained male genital ridge expression and now supported extensive expression within cells of the neural crest in embryos of both sexes. When 2 Kb of mouse SRY 5, flanking sequences (,3 to ,1 Kb) were placed in front of the 1.6 Kb of pig SRY 5, flanking sequences and this transgene was introduced into mice, reporter transgene expression within the male genital ridge was retained but neural crest expression was lost. These observations suggest that SRY 5, flanking sequences from at least two mammalian species contain elements that can support transgene expression within cells of the migrating neural crest and that additional SRY 5, flanking sequences can extinguish this expression. Developmental Dynamics 235:623,632, 2006. © 2006 Wiley-Liss, Inc. [source]

    Philip Melanchthon on Human and Divine Freedom

    DIALOG, Issue 4 2000
    Timothy J. Wengert
    First page of article [source]

    Sulfonated molecules that bind a partially structured species of ,2 -microglobulin also influence refolding and fibrillogenesis

    ELECTROPHORESIS, Issue 7 2008
    Chiara Carazzone
    Abstract Human ,2 -microglobulin (,2 -m) is a small amyloidogenic protein responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of ,2 -m through the binding to a small molecule, to possibly inhibit protein misfolding and amyloid fibril formation. The search of a strong ligand of this protein is extremely challenging: by using CE in affinity and refolding experiments we study the effect that previously selected sulfonated molecules have on the equilibrium between the native form and an ensemble of conformers populating the slow phase of ,2 -m folding. These data are correlated with the effect that the same molecules exert on in vitro fibrillogenesis experiments. [source]

    Epilepsy-induced Changes in Signaling Systems of Human and Rat Postsynaptic Densities

    EPILEPSIA, Issue 2 2003
    Ursula Wyneken
    Summary: ,Purpose: To study seizure-induced changes in signaling proteins present in postsynaptic densities (PSDs) isolated from human epileptic neocortex and from rat cortex in which seizures were induced by injection of kainic acid. Methods: We performed Western blot analysis of signaling proteins in PSDs isolated from cortical tissue. Results: Seizures induce a strong upregulation of TrkB, the receptor for brain-derived neurotrophic factor (BDNF), whereas components of the N -methyl- d -aspartate (NMDA)-receptor complex are downregulated in both human and rat PSDs. Conclusions: These data show that long-term changes in PSD composition occur as a consequence of epileptic seizure activity. [source]

    Improving the Evaluation of Rural Development Policy Pour une meilleure évaluation de la politique de développement rural Die Evaluation der Politik zur Entwicklung des ländlichen Raums verbessern

    EUROCHOICES, Issue 1 2010
    David Blandford
    Summary Improving the Evaluation of Rural Development Policy A previous EuroChoices (Vol. 7, No. 1) compared and contrasted approaches to rural development policy in the EU and US. This Special Issue focuses on the evaluation of these policies, drawing on a workshop held in June 2009 at OECD Conference Center in Paris. Evaluation is an activity that runs parallel with policymaking and is capable of contributing to effectiveness and efficiency at all stages. Evaluators, wherever they work and whatever aspect of rural development is their focus, face some common technical problems. These include multiple (and often ill-defined) policy objectives, the choice of appropriate indicators (especially the need to distinguish between outputs and outcomes), how to establish baseline values, where to draw boundaries in terms of impact and time, and the identification of additionality and causality. Ensuring that lessons learned from evaluation are actually applied is problematic. Experiences covered in this Issue include the use of macro and case-study approaches, and various schemes (investment in human and social capital, and agri-environment and forestry). There is an inherent tension between using a common approach across countries and regions in the interests of comparability and the flexibility needed to capture all the relevant factors in the diverse situations in which rural development actions take place. Un précédent numéro de EuroChoices (Vol. 7, No. 1) comparait et mettait en regard les approches de l'Union européenne et des États-Unis en terme de politique de développement rural. Ce numéro spécial est consacréà l'évaluation de la politique et tire parti d'un atelier qui s'est tenu en juin 2009 au Centre de Conférences de l'OCDE à Paris. L'évaluation va de pair avec l'élaboration des politiques et peut contribuer à améliorer l'efficacité et l'efficience à tous les stades. Quels que soient leur affiliation et l'aspect du développement rural sur lequel ils se concentrent, les évaluateurs sont confrontés à certains problèmes techniques communs. Il s'agit des objectifs multiples (et souvent mal définis) de la politique, du choix d'indicateurs pertinents (en particulier la nécessité de faire la différence entre produit et résultat), de la manière d'établir des valeurs de référence, de la fixation de limites en terme d'incidence et de durée, et de l'identification des effets additifs et de la causalité. Il est difficile de s'assurer que les leçons tirées des évaluations sont effectivement retenues. Les expériences rapportées dans ce numéro comprennent des approches macroéconomiques ou fondées sur des études de cas, et couvrent différents programmes (investissements dans le capital social et humain, mesures agroenvironnementales, mesures forestières). Il existe une tension évidente entre l'utilisation d'une approche commune entre chaque pays et région, qui vise la comparabilité, et la flexibilité qui permet de prendre en compte l'ensemble des différents facteurs des situations variées dans lesquelles les mesures de développement rural sont appliquées. In einer vorherigen Ausgabe von EuroChoices (7:1) wurden Herangehensweisen an die Politik zur Entwicklung des ländlichen Raums in der EU und in den USA verglichen und diskutiert. Diese Sonderausgabe beschäftigt sich auf der Grundlage eines Workshops, der im Juni 2009 am OECD-Hauptsitz in Paris abgehalten wurde, mit Politikevaluation. Die Evaluation erfolgt parallel zur Politikgestaltung und kann in jeder Phase zur Steigerung von Wirksamkeit und Effizienz beitragen. Evaluatoren stehen einigen allgemeinen technischen Problemen gegenüber , ganz gleich, wo sie arbeiten und welchen Aspekten ländlicher Entwicklung sie sich widmen. Dazu zählen multiple (und oftmals unzureichend definierte) politische Ziele; die Auswahl von geeigneten Indikatoren (hier muss insbesondere zwischen Endprodukten und Ergebnissen unterschieden werden); die Frage, wie Ausgangswerte festzulegen und wo Grenzen im Hinblick auf Auswirkungen und den zeitlichen Rahmen zu setzen sind; sowie die Identifizierung von Additionalität und Kausalität. Es ist schwierig sicherzustellen, dass die Erkenntnisse aus der Evaluation auch umgesetzt werden. Die in dieser Ausgabe aufgegriffenen Erfahrungen berücksichtigen u.a. Makro- und Fallstudienansätze sowie verschiedene Maßnahmen (Investitionen in Human-/Sozialkapital sowie Agrarumwelt und Forstwirtschaft). Es besteht eine grundsätzliche Spannung zwischen einer im Interesse der Vergleichbarkeit einheitlichen länder- und regionenübergreifenden Herangehensweise und einer Flexibilität bei der Erfassung aller relevanten Faktoren in den verschiedenen Situationen, in denen ländliche Entwicklung stattfindet. [source]

    Directions in Rural Development Policy , Lessons from Both Sides of the Atlantic Richtlinien für die ländliche Entwicklungspolitik , Beispiele von diesseits und jenseits des Atlantiks Les orientations de la politique de développement rural , Enseignements en provenance des deux côtés de l'Atlantique

    EUROCHOICES, Issue 1 2008
    David Blandford
    Directions in Rural Development Policy , Lessons from Both Sides of the Atlantic A workshop comparing rural development policies in Europe and the US found differences in the social values that shape them. These include different attachments to place, concerns with lagging regions, and interests in the assessment of public interventions. There is also a difference in coverage. In the EU environmental and landscape issues form part of the CAP's Rural Development Pillar, using agriculture as an instrument, whereas in the US these are handled by other policies, some of which can claim deeper historical roots. In the context of rural development policy, the EU attaches intrinsic value to the environment, while in the US the focus is more on economic spin-offs from environmental quality. There are also differences in governance; a complete US view requires taking in Federal, State and local initiatives whereas in the EU a more organised framework is apparent. Nevertheless, when policy is viewed from a bottom-up perspective many common features are found. Improving human and social capital and infrastructure are key factors to stimulating economic development on both sides of the Atlantic, though only some of these drivers form part of the CAP's Pillar II. While in the EU the role of rural development is set to expand, this is far less certain in the US where the emphasis on agricultural support is likely to continue to dominate the political agenda. Les orientations de la politique de développement rural , Enseignements en provenance des deux côtés de l'Atlantique Un atelier comparant les politiques de développement rural en Europe et aux États-Unis a mis en évidence des différences entre les valeurs sociales sur lesquelles sont fondées ces politiques. Ces différences concernent entre autre l'attachement à des lieux particuliers, l'inquiétude pour les régions en retard de croissance, et l'intérêt pour une évaluation des pouvoirs publics. Les différences portent aussi sur l'étendue de la question. Dans l'Union européenne, les questions portant sur le paysage et l'environnement sont abordées dans le cadre du pilier de la PAC sur le développement rural, qui porte sur l'agriculture comme instrument du développement rural, alors qu'aux États-Unis, ces questions sont traitées par d'autres politiques dont certaines remontent à loin. Dans le contexte de la politique de développement rural, l'Union européenne attache une valeur intrinsèque à l'environnement tandis qu'aux États-Unis, l'accent est mis plutôt sur les retombées économiques d'un environnement de qualité. Les différences portent également sur la gouvernance : pour avoir une vue d'ensemble sur les États-Unis, il faut considérer les actions aux niveaux fédéral, des États et du local alors que dans l'Union européenne, un cadre plus organisé est apparent. Cependant, dans le cas de politiques partant de la base (bottom-up), de nombreux points communs existent. L'amélioration du capital social et humain, et celle des infrastructures sont des éléments clés pour stimuler le développement économique des deux côtés de l'Atlantique, même si seuls quelques uns de ces facteurs sont compris dans le deuxième pilier de la PAC. Alors que le rôle du développement rural devrait s'étendre dans l'Union européenne, c'est beaucoup moins certain aux États-Unis où l'accent sur le soutien à l'agriculture continuera probablement à dominer l'ordre du jour de la politique. Richtlinien für die ländliche Entwicklungspolitik , Beispiele von diesseits und jenseits des Atlantiks Im Rahmen eines Workshops wurden europäische und US-amerikanische Politikmaßnahmen zur Entwicklung des ländlichen Raums miteinander verglichen. Die Ergebnisse zeigen, dass sich die gesellschaftlichen Werte für die Ausgestaltung der Politikmaßnahmen im Hinblick auf Ortsverbundenheit, die Belange der rückständigen Regionen und das Interesse bei der Bewertung öffentlicher Interventionen unterscheiden. Die jeweiligen Geltungsbereiche unterscheiden sich ebenfalls. In der EU bilden Fragestellungen in Bezug auf Umwelt und landschaftliche Gestaltung einen Teil der zweiten Säule der GAP (Entwicklung des ländlichen Raums), und die Landwirtschaft ist dabei ein Mittel zum Zweck. In den USA hingegen werden diese Fragestellungen durch andere Politikmaßnahmen abgedeckt, von denen einige über längere historische Wurzeln verfügen. Im Rahmen der Politik zur Entwicklung des ländlichen Raums misst die EU der Umwelt intrinsischen Wert bei, während sich die USA mehr auf aus der Umweltqualität resultierende wirtschaftliche Nebeneffekte konzentriert. Im Hinblick auf die Governance sind ebenfalls Unterschiede vorhanden: Während es im Falle der USA erforderlich ist, in einer Gesamtbetrachtung die Initiativen auf staatlicher, bundesstaatlicher und kommunaler Ebene zu berücksichtigen, lassen die Rahmenbedingungen in Europa ein höheres Maß an Organisation erkennen. Wird die Politik jedoch aus einer Bottom-up-Perspektive heraus betrachtet, können zahlreiche Gemeinsamkeiten gefunden werden. Bei der Verbesserung des Human- und Sozialkapitals und der Infrastruktur handelt es sich um Schlüsselfaktoren für die Ankurbelung der wirtschaftlichen Entwicklung diesseits und jenseits des Atlantiks, wenngleich nur einige dieser Triebfedern die zweite Säule der GAP ausmachen. Während die Entwicklung des ländlichen Raums in der EU eine immer größere Rolle spielen wird, ist dies in den USA längst nicht sicher; dort wird der Schwerpunkt auf die Agrarstützung wahrscheinlich weiterhin die politische Agenda dominieren. [source]

    REVIEW: Human and laboratory rodent low response to alcohol: is better consilience possible?

    ADDICTION BIOLOGY, Issue 2 2010
    John C. Crabbe
    ABSTRACT If people are brought into the laboratory and given alcohol, there are pronounced differences among individuals in many responses to the drug. Some participants in alcohol challenge protocols show a cluster of ,low level of responses to alcohol' determined by observing post-drinking-related changes in subjective, motor and physiological effects at a given dose level. Those individuals characterized as having low level of response (LR) to alcohol have been shown to be at increased risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship between low LR and AD appears to be in part genetic. LR to alcohol is an area where achieving greater consilience between the human and the rodent phenotypes would seem to be highly likely. However, despite extensive data from both human and rodent studies, few attempts have been made to evaluate the human and animal data systematically in order to understand which aspects of LR appear to be most directly comparable across species and thus the most promising for further study. We review four general aspects of LR that could be compared between humans and laboratory animals: (1) behavioral measures of subjective intoxication; (2) body sway; (3) endocrine responses; and (4) stimulant, autonomic and electrophysiological responses. None of these aspects of LR provide completely face-valid direct comparisons across species. Nevertheless, one of the most replicated findings in humans is the low subjective response, but, as it may reflect either aversively valenced and/or positively valenced responses to alcohol as usually assessed, it is unclear which rodent responses are analogous. Stimulated heart rate appears to be consistent in animal and human studies, although at-risk subjects appear to be more rather than less sensitive to alcohol using this measure. The hormone and electrophysiological data offer strong possibilities of understanding the neurobiological mechanisms, but the rodent data in particular are rather sparse and unsystematic. Therefore, we suggest that more effort is still needed to collect data using refined measures designed to be more directly comparable in humans and animals. Additionally, the genetically mediated mechanisms underlying this endophenotype need to be characterized further across species. [source]

    Human resting CD16,, CD16+ and IL-2-, IL-12-, IL-15- or IFN-,-activated natural killer cells differentially respond to sphingosylphosphorylcholine, lysophosphatidylcholine and platelet-activating factor

    Yixin Jin
    Abstract The phosphorylcholine-containing lipid lysophosphatidylcholine (LPC) is abundant in the bloodstream, whereas sphingosylphosphorylcholine (SPC) and platelet-activating factor (PAF) highly accumulate at inflamed sites. Utilizing RT-PCR, flow cytometry and immunoblot analyses, we show for the first time that ovarian cancer G,protein-coupled receptor,1, the receptor for SPC, is expressed in IL-2-, IL-12- and IL-15-activated but not in resting CD16,, resting CD16+ or IFN-,-activated NK,cells. Similarly, G2 accumulation and PAF receptor are variably expressed in these subsets of NK,cells. SPC, LPC and PAF differentially induce the chemotaxis of resting and activated NK,cells. In the chemotaxis assay, it is observed that resting CD16,CD56bright and CD16+CD56dim cells predominantly respond to LPC, whereas activated NK,cells, regardless of the sort of stimulus, robustly respond to PAF. SPC is also a potent chemoattractant for IL-2-, IL-12- and IL-15- but not for IFN-,-activated NK,cells. Further analysis shows that, depending on the cytokine pattern of NK,cell activation, phosphorylcholine-containing lipids differentially affect IFN-, secretion by these cells. Our results provide one possible explanation for the tissue compartmentation of NK,cells and their ability to secrete IFN-,. Furthermore, these results may provide novel information regarding NK,cell regulation during inflammation. [source]

    HHV-6 infection in multiple sclerosis.

    A clinical, laboratory analysis
    Background and purpose:, To elucidate the role of human herpesvirus-6 (HHV-6) in the development of multiple sclerosis (MS). Patients and methods:, Nine patients with MS and with acute or chronic HHV-6 infection were evaluated. Results:, Intrathecal antibody production to HHV-6 and oligoclonal IgG bands in the cerebrospinal fluid (CSF) was observed in two patients with a clinically definite MS and chronic HHV-6 infection (based on the presence of HHV-6 specific antibodies in the CSF). A temporal association between the symptoms of clinically possible MS and acute primary HHV-6A infection (based on avidity of HHV-6 specific antibodies) was observed in two patients. Conclusions:, Human herpesvirus-6 infection may be an associated agent in some MS cases. Viral studies are needed to identify a possible viral etiology and give specific therapy. [source]

    Neuronal substrates of gaze following in monkeys

    Simone Kamphuis
    Abstract Human and non-human primates follow the gaze of their respective conspecific to identify objects of common interest. Whereas humans rely on eye-gaze for such purposes, monkeys preferentially use head-gaze information. Functional magnetic resonance imaging (fMRI) studies have delineated an area in the human superior temporal sulcus (STS), which is specifically activated when subjects actively follow the eye-gaze of others. Similarly, using fMRI, we have identified an analogous region in the monkey's middle STS responding to gaze following. Hence, although humans and monkeys might rely on different directional cues guiding their attention, they seem to deploy a similar and possibly homologous cortical area to follow the gaze of a conspecific. Our results support the idea that the eyes developed a new social function in human evolution, most likely to support cooperative mutual social interactions building on a phylogenetically old STS module for the processing of head cues. [source]

    Glycation of low-density lipoprotein results in the time-dependent accumulation of cholesteryl esters and apolipoprotein B-100 protein in primary human monocyte-derived macrophages

    FEBS JOURNAL, Issue 6 2007
    Bronwyn E. Brown
    Nonenzymatic covalent binding (glycation) of reactive aldehydes (from glucose or metabolic processes) to low-density lipoproteins has been previously shown to result in lipid accumulation in a murine macrophage cell line. The formation of such lipid-laden cells is a hallmark of atherosclerosis. In this study, we characterize lipid accumulation in primary human monocyte-derived macrophages, which are cells of immediate relevance to human atherosclerosis, on exposure to low-density lipoprotein glycated using methylglyoxal or glycolaldehyde. The time course of cellular uptake of low-density lipoprotein-derived lipids and protein has been characterized, together with the subsequent turnover of the modified apolipoprotein B-100 (apoB) protein. Cholesterol and cholesteryl ester accumulation occurs within 24 h of exposure to glycated low-density lipoprotein, and increases in a time-dependent manner. Higher cellular cholesteryl ester levels were detected with glycolaldehyde-modified low-density lipoprotein than with methylglyoxal-modified low-density lipoprotein. Uptake was significantly decreased by fucoidin (an inhibitor of scavenger receptor SR-A) and a mAb to CD36. Human monocyte-derived macrophages endocytosed and degraded significantly more 125I-labeled apoB from glycolaldehyde-modified than from methylglyoxal-modified, or control, low-density lipoprotein. Differences in the endocytic and degradation rates resulted in net intracellular accumulation of modified apoB from glycolaldehyde-modified low-density lipoprotein. Accumulation of lipid therefore parallels increased endocytosis and, to a lesser extent, degradation of apoB in human macrophages exposed to glycolaldehyde-modified low-density lipoprotein. This accumulation of cholesteryl esters and modified protein from glycated low-density lipoprotein may contribute to cellular dysfunction and the increased atherosclerosis observed in people with diabetes, and other pathologies linked to exposure to reactive carbonyls. [source]

    Human and Drosophila UDP-galactose transporters transport UDP- N -acetylgalactosamine in addition to UDP-galactose

    FEBS JOURNAL, Issue 1 2002
    Hiroaki Segawa
    A putative Drosophila nucleotide sugar transporter was characterized and shown to be the Drosophila homologue of the human UDP-Gal transporter (hUGT). When the Drosophila melanogaster UDP-Gal transporter (DmUGT) was expressed in mammalian cells, the transporter protein was localized in the Golgi membranes and complemented the UDP-Gal transport deficiency of Lec8 cells but not the CMP-Sia transport deficiency of Lec2 cells. DmUGT and hUGT were expressed in Saccharomyces cerevisiae cells in functionally active forms. Using microsomal vesicles isolated from Saccharomyces cerevisiae expressing these transporters, we unexpectedly found that both hUGT and DmUGT could transport UDP-GalNAc as well as UDP-Gal. When amino-acid residues that are conserved among human, murine, fission yeast and Drosophila UGTs, but are distinct from corresponding ones conserved among CMP-Sia transporters (CSTs), were substituted by those found in CST, the mutant transporters were still active in transporting UDP-Gal. One of these mutants in which Asn47 was substituted by Ala showed aberrant intracellular distribution with concomitant destabilization of the protein product. However, this mutation was suppressed by an Ile51 to Thr second-site mutation. Both residues were localized within the first transmembrane helix, suggesting that the structure of the helix contributes to the stabilization and substrate recognition of the UGT molecule. [source]