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Sample records for early development innate

  1. Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring.

    PubMed

    Sharkey, Don; Gardner, David S; Symonds, Michael E; Budge, Helen

    2009-11-01

    Obesity is an independent risk factor for developing chronic kidney disease. Toll-like receptor 4 (TLR4), interleukin (IL)-18, and uncoupling protein 2 (UCP2) are important components of the innate immune system mediating inflammatory renal damage. Early to midgestation maternal nutrient restriction appears to protect the kidney from the deleterious effects of early onset obesity, although the mechanisms remain unclear. We examined the combined effects of gestational maternal nutrient restriction during early fetal kidney development and early onset obesity on the renal innate immune response in offspring. Pregnant sheep were randomly assigned to a normal (control, 100%) or nutrient-restricted (NR, 50%) diet from days 30 to 80 gestation and 100% thereafter. Offspring were killed humanely at 7 days or, following rearing in an obesogenic environment, at 1 yr of age, and renal tissues were collected. IL-18 and TLR4 expression were strongly correlated irrespective of intervention. Seven-day NR offspring had significantly lower relative renal mass and IL-18 mRNA expression. At 1 yr of age, obesity resulted in increased mRNA abundance of TLR4, IL-18, and UCP2, coupled with tubular atrophy and greater immunohistological staining of glomerular IL-6 and medullary tumor necrosis factor (TNF)-alpha. NR obese offspring had a marked reduction of TLR4 abundance and renal IL-6 staining. In conclusion, maternal nutrient restriction during early fetal kidney development attenuates the effects of early onset obesity-related nephropathy, in part, through the downregulation of the innate inflammatory response. A better understanding of maternal nutrition and the in utero nutritional environment may offer therapeutic strategies aimed at reducing the burden of later kidney disease.

  2. The involvement of cysteine-rich intestinal protein in early development and innate immunity of Asiatic hard clam, Meretrix meretrix.

    PubMed

    Chen, Hongjian; Yang, Xue; Tang, Ting; Li, Juan; Liu, Baozhong; Liu, Fengsong; Xie, Song

    2014-10-01

    Cysteine-rich intestinal protein (CRIP), a Zn(2+)-binding protein, contains a single copy of the highly conserved double-zinc-finger structure known as the LIM (lin-11-isl-1-mec-3) motif. In this paper, a cDNA encoding MmCRIP was isolated from the Asiatic hard clam Meretrix meretrix. The full-length cDNA of MmCRIP consists of a 237-bp open reading frame that encodes a polypeptide of 78 amino acids with a predicted molecular weight (MW) of 8635.8 Da and theoretical isoelectric point (pI) of 9.01. Bioinformatics analysis showed that it belonged to a new member of the CRIP subfamily. Relationship analysis revealed that MmCRIP has high-levels of sequence similarity to many CRIPs reported in other animals, particularly in invertebrates. Real-time PCR analysis showed that the highest level of MmCRIP expression was in hemocyte tissue and at pediveligers stage. To investigate immune function, mature clams were challenged with Aeromonas hydrophila. During A. hydrophila infection, up-regulation of MmCRIP transcript in clam's hemocyte, gill and hepatopancreas was detected. DsRNAi (double-strand RNA interference) approach was employed to study the function of MmCRIP and the data showed that inactivation of the MmCRIP gene blocked larvae development and caused mass mortalities. The probable roles of MmCRIP in clam early development and innate immunity are presented for the first time.

  3. Immune system development during early childhood in tropical Latin America: evidence for the age-dependent down regulation of the innate immune response.

    PubMed

    Teran, Rommy; Mitre, Edward; Vaca, Maritza; Erazo, Silvia; Oviedo, Gisela; Hübner, Marc P; Chico, Martha E; Mattapallil, Joseph J; Bickle, Quentin; Rodrigues, Laura C; Cooper, Philip J

    2011-03-01

    The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5 years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6-9 months, 22-26 months, and 48-60 months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4(+) and CD8(+) T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3(+) T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology.

  4. Immune system development during early childhood in tropical Latin America: Evidence for the age-dependent down regulation of the innate immune response

    PubMed Central

    Teran, Rommy; Mitre, Edward; Vaca, Maritza; Erazo, Silvia; Oviedo, Gisela; Hübner, Marc P.; Chico, Martha E.; Mattapallil, Joseph J.; Bickle, Quentin; Rodrigues, Laura C.; Cooper, Philip J.

    2011-01-01

    The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5 years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6–9 months, 22–26 months, and 48–60 months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4+ and CD8+ T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3+ T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology. PMID:21247809

  5. The Development of Adult Innate Lymphoid Cells

    PubMed Central

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  6. [Perinatal innate immune activation and neuropsychological development].

    PubMed

    Nagai, Taku

    2013-08-01

    Development of animal models is a crucial issue in biological psychiatry for the search of novel drug targets as well as the screening of candidate compounds. Epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development of schizophrenia. Recently, we have developed a novel mouse model of viral infection during the perinatal stage by injecting polyriboinosinic-polyribocytidilic acid (polyI:C) into neonatal mice. Neonatal treatment of mice with polyI:C, an inducer of innate immune responses via toll-like receptor 3, caused a significant increase in interferon-induced transmembrane protein 3 (IFITM3) levels in the astrocytes of the hippocampus, which resulted in long-lasting brain dysfunction, including cognitive and emotional impairments as well as a deficit in depolarization-evoked glutamate release in the hippocampus in adulthood. Neonatal polyI:C-induced neuronal impairments have not been observed in IFITM3-KO mice. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of neurodevelopment has non-cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes.

  7. Postnatal Innate Immune Development: From Birth to Adulthood

    PubMed Central

    Georgountzou, Anastasia; Papadopoulos, Nikolaos G.

    2017-01-01

    It is well established that adaptive immune responses are deficient in early life, contributing to increased mortality and morbidity. The developmental trajectories of different components of innate immunity are only recently being explored. Individual molecules, cells, or pathways of innate recognition and signaling, within different compartments/anatomical sites, demonstrate variable maturation patterns. Despite some discrepancies among published data, valuable information is emerging, showing that the developmental pattern of cytokine responses during early life is age and toll-like receptor specific, and may be modified by genetic and environmental factors. Interestingly, specific environmental exposures have been linked both to innate function modifications and the occurrence of chronic inflammatory disorders, such as respiratory allergies. As these conditions are on the rise, our knowledge on innate immune development and its modulating factors needs to be expanded. Improved understanding of the sequence of events associated with disease onset and persistence will lead toward meaningful interventions. This review describes the state-of-the-art on normal postnatal innate immune ontogeny and highlights research areas that are currently explored or should be further addressed. PMID:28848557

  8. B cells enhance early innate immune responses during bacterial sepsis

    PubMed Central

    Kelly-Scumpia, Kindra M.; Scumpia, Philip O.; Weinstein, Jason S.; Delano, Matthew J.; Cuenca, Alex G.; Nacionales, Dina C.; Wynn, James L.; Lee, Pui Y.; Kumagai, Yutaro; Efron, Philip A.; Akira, Shizuo; Wasserfall, Clive; Atkinson, Mark A.

    2011-01-01

    Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1−/− mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell–deficient or anti-CD20 B cell–depleted mice, but not α/β T cell–deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell–deficient mice with serum from wild-type (WT) mice and repletion of Rag1−/− mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1−/− mice with WT, but not IFNAR−/−, B cells improves IFN-I–dependent and –independent early cytokine responses. Repleting B cell–deficient mice with the IFN-I–dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I–activated B cells in protective early innate immune responses during bacterial sepsis. PMID:21746813

  9. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  10. Innate immune response development in nestling tree swallows

    USGS Publications Warehouse

    Stambaugh, T.; Houdek, B.J.; Lombardo, M.P.; Thorpe, P.A.; Caldwell, Hahn D.

    2011-01-01

    We tracked the development of innate immunity in nestling Tree Swallows (Tachycineta bicolor) and compared it to that of adults using blood drawn from nestlings during days 6, 12, and 18 of the ???20-day nestling period and from adults. Innate immunity was characterized using an in vitro assay of the ability of whole blood to kill Escherichia coli. The ability of whole blood to kill E. coli increased as nestlings matured. Neither this component of innate immunity nor right wing chord length on day18 were as developed as in adults indicating that development of the innate immune system and growth both continued after fledging. Narrow sense heritability analyses suggest that females with strong immune responses produced nestlings with strong immune responses. These data suggest nestling Tree Swallows allocated sufficient energy to support rapid growth to enable fledging by day 18, but that further development of innate immunity occurred post-fledging. ?? 2011 by the Wilson Ornithological Society.

  11. Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells

    PubMed Central

    Zhong, Chao; Zhu, Jinfang

    2015-01-01

    Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the “innate” feature of conventional natural killer (cNK) cells and the “helper” feature of CD4+ T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs. PMID:26379372

  12. Innate immune gene expression differentiates the early avian intestinal response between Salmonella and Campylobacter.

    PubMed

    Shaughnessy, Ronan G; Meade, Kieran G; Cahalane, Sarah; Allan, Brenda; Reiman, Carla; Callanan, John J; O'Farrelly, Cliona

    2009-12-15

    Salmonella enterica serovar Typhimurium and Campylobacter jejuni are major human pathogens, yet colonise chickens without causing pathology. The aim of this study was to compare intestinal innate immune responses to both bacterial species, in a 4-week-old broiler chicken model. Challenged and control birds were sacrificed and tissue samples taken for histopathology and RNA extraction. No significant clinical or pathological changes were observed in response to infection with either bacterial species. Expression of selected genes involved in pathogen detection and the innate immune response were profiled in caecal tissues by quantitative real-time PCR. TLR4 and TLR21 gene expression was transiently increased in response to both bacterial species (P<0.05). Significant increases in TLR5 and TLR15 gene expression were detected in response to S. Typhimurium but not to C. jejuni. Transient increases of proinflammatory cytokine (IL6 and IFNG) and chemokine (IL8 and K60) genes increased as early as 6h in response to S. Typhimurium. Minimal cytokine gene expression was detected in response to C. jejuni after 20h. IL8 gene expression however, was significantly increased by 24-fold (P<0.01). The differential expression profiles of innate immune genes in both infection models shed light on the tailored responses of the host immune system to specific microbes. It is further evidence that innate regulation of these responses is an important prerequisite to preventing development of disease.

  13. Immune adjuvants in early life: targeting the innate immune system to overcome impaired adaptive response.

    PubMed

    de Brito, Cyro Alves; Goldoni, Adriana Letícia; Sato, Maria Notomi

    2009-09-01

    The neonatal phase is a transitory period characterized by an absence of memory cells, favoring a slow adaptive response prone to tolerance effects and the development of Th2-type responses. However, when appropriately stimulated, neonates may achieve an immune response comparable with adult counterparts. One strategy to stimulate the immunological response of neonates or children in early infancy has been to explore natural or synthetic ligands of cell receptors to stimulate innate immunity. The use of adjuvants for activating different cell receptors may be the key to enhancing neonatal adaptive immunity. This review highlights recent advances in the emerging field of molecular adjuvants of innate immune response and their implications for the development of immunotherapies, with particular focus on the neonatal period.

  14. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

    PubMed

    Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

    2015-11-01

    Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole

  15. Beyond empiricism: informing vaccine development through innate immunity research.

    PubMed

    Levitz, Stuart M; Golenbock, Douglas T

    2012-03-16

    Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection.

  16. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    PubMed Central

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  17. Transcription factor networks directing the development, function, and evolution of innate lymphoid effectors.

    PubMed

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity.

  18. Role of Innate Host Defenses in Susceptibility to Early Onset Neonatal Sepsis

    PubMed Central

    Wynn, James L.; Levy, Ofer

    2010-01-01

    Neonatal sepsis continues to take a devastating toll globally. Although adequate to protect against invasive infection in most newborns, the distinct function of neonatal innate host defense coupled with impairments in adaptive immune responses, increases the likelihood of acquiring infection early in life with subsequent rapid dissemination and death. Unique differences exist between neonates and older populations with respect to the capacity, quantity, and quality of innate host responses to pathogens. Recent characterization of the age-dependent maturation of neonatal innate immune function has identified novel translational approaches that may lead to improved diagnostic, prophylactic and therapeutic modalities. PMID:20569810

  19. Innate immunity in the lung regulates the development of asthma.

    PubMed

    DeKruyff, Rosemarie H; Yu, Sanhong; Kim, Hye Young; Umetsu, Dale T

    2014-07-01

    The lung, while functioning as a gas exchange organ, encounters a large array of environmental factors, including particulate matter, toxins, reactive oxygen species, chemicals, allergens, and infectious microbes. To rapidly respond to and counteract these elements, a number of innate immune mechanisms have evolved that can lead to lung inflammation and asthma, which is the focus of this review. These innate mechanisms include a role for two incompletely understood cell types, invariant natural killer T (iNKT) cells and innate lymphoid cells (ILCs), which together produce a wide range of cytokines, including interleukin-4 (IL-4), IL-5, IL-13, interferon-γ, IL-17, and IL-22, independently of adaptive immunity and conventional antigens. The specific roles of iNKT cells and ILCs in immunity are still being defined, but both cell types appear to play important roles in the lungs, particularly in asthma. As we gain a better understanding of these innate cell types, we will acquire great insight into the mechanisms by which allergic and non-allergic asthma phenotypes develop.

  20. Effects of early developmental conditions on innate immunity are only evident under favourable adult conditions in zebra finches

    NASA Astrophysics Data System (ADS)

    de Coster, Greet; Verhulst, Simon; Koetsier, Egbert; de Neve, Liesbeth; Briga, Michael; Lens, Luc

    2011-12-01

    Long-term effects of unfavourable conditions during development can be expected to depend on the quality of the environment experienced by the same individuals during adulthood. Yet, in the majority of studies, long-term effects of early developmental conditions have been assessed under favourable adult conditions only. The immune system might be particularly vulnerable to early environmental conditions as its development, maintenance and use are thought to be energetically costly. Here, we studied the interactive effects of favourable and unfavourable conditions during nestling and adult stages on innate immunity (lysis and agglutination scores) of captive male and female zebra finches ( Taeniopygia guttata). Nestling environmental conditions were manipulated by a brood size experiment, while a foraging cost treatment was imposed on the same individuals during adulthood. This combined treatment showed that innate immunity of adult zebra finches is affected by their early developmental conditions and varies between both sexes. Lysis scores, but not agglutination scores, were higher in individuals raised in small broods and in males. However, these effects were only present in birds that experienced low foraging costs. This study shows that the quality of the adult environment may shape the long-term consequences of early developmental conditions on innate immunity, as long-term effects of nestling environment were only evident under favourable adult conditions.

  1. Toll-like receptor 7 mediates early innate immune responses to malaria.

    PubMed

    Baccarella, Alyssa; Fontana, Mary F; Chen, Eunice C; Kim, Charles C

    2013-12-01

    Innate immune recognition of malaria parasites is the critical first step in the development of the host response. At present, Toll-like receptor 9 (TLR9) is thought to play a central role in sensing malaria infection. However, we and others have observed that Tlr9(-/-) mice, in contrast to mice deficient in the downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies in immune function during early infection with the malaria parasite Plasmodium chabaudi, implying that another MYD88-dependent receptor also contributes to the antimalarial response. Here we use candidate-based screening to identify TLR7 as a key sensor of early P. chabaudi infection. We show that TLR7 mediates a rapid systemic response to infection through induction of cytokines such as type I interferons (IFN-I), interleukin 12, and gamma interferon. TLR7 is also required for induction of IFN-I by other species and strains of Plasmodium, including an etiological agent of human disease, P. falciparum, suggesting that malaria parasites harbor a common pathogen-associated molecular pattern (PAMP) recognized by TLR7. In contrast to the nonredundant requirement for TLR7 in early immune activation, sensing through both TLR7 and TLR9 was required for proinflammatory cytokine production and immune cell activation during the peak of parasitemia. Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses.

  2. Modeling Innate Immune Response to Early Mycobacterium Infection

    PubMed Central

    Carvalho, Rafael V.; Kleijn, Jetty; Meijer, Annemarie H.

    2012-01-01

    In the study of complex patterns in biology, mathematical and computational models are emerging as important tools. In addition to experimental approaches, these modeling tools have recently been applied to address open questions regarding host-pathogen interaction dynamics, including the immune response to mycobacterial infection and tuberculous granuloma formation. We present an approach in which a computational model represents the interaction of the Mycobacterium infection with the innate immune system in zebrafish at a high level of abstraction. We use the Petri Net formalism to model the interaction between the key host elements involved in granuloma formation and infection dissemination. We define a qualitative model for the understanding and description of causal relations in this dynamic process. Complex processes involving cell-cell or cell-bacteria communication can be modeled at smaller scales and incorporated hierarchically into this main model; these are to be included in later elaborations. With the infection mechanism being defined on a higher level, lower-level processes influencing the host-pathogen interaction can be identified, modeled, and tested both quantitatively and qualitatively. This systems biology framework incorporates modeling to generate and test hypotheses, to perform virtual experiments, and to make experimentally verifiable predictions. Thereby it supports the unraveling of the mechanisms of tuberculosis infection. PMID:23365620

  3. Role of innate immunity in the development of hepatocellular carcinoma

    PubMed Central

    Aravalli, Rajagopal N

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. It is caused by a variety of risk factors, most common ones being infection with hepatitis viruses, alcohol, and obesity. HCC often develops in the background of underlying cirrhosis, and even though a number of interventional treatment methods are currently in use, recurrence is fairly common among patients who have had a resection. Therefore, whole liver transplantation remains the most practical treatment option for HCC. Due to the growing incidence of HCC, intense research efforts are being made to understand cellular and molecular mechanisms of the disease so that novel therapeutic strategies can be developed to combat liver cancer. In recent years, it has become clear that innate immunity plays a critical role in the development of a number of liver diseases, including HCC. In particular, the activation of Toll-like receptor signaling results in the generation of immune responses that often results in the production of pro-inflammatory cytokines and chemokines, and could cause acute inflammation in the liver. In this review, the current knowledge on the role of innate immune responses in the development and progression of HCC is examined, and emerging therapeutic strategies based on molecular mechanisms of HCC are discussed. PMID:24282342

  4. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens

    PubMed Central

    Geiger, Theresa L.; Abt, Michael C.; Gasteiger, Georg; Firth, Matthew A.; O’Connor, Margaret H.; Geary, Clair D.; O’Sullivan, Timothy E.; van den Brink, Marcel R.; Pamer, Eric G.; Hanash, Alan M.

    2014-01-01

    The bZIP transcription factor Nfil3 (also known as E4BP4) is required for the development of natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s). We find that Nfil3 plays a critical role in the development of other mucosal tissue-associated innate lymphocytes. Type 3 ILCs (ILC3s), including lymphoid tissue inducer (LTi)–like cells, are severely diminished in both numbers and function in Nfil3-deficient mice. Using mixed bone marrow chimeric mice, we demonstrate that Nfil3 is critical for normal development of gut-associated ILC3s in a cell-intrinsic manner. Furthermore, Nfil3 deficiency severely compromises intestinal innate immune defense against acute bacterial infection with Citrobacter rodentium and Clostridium difficile. Nfil3 deficiency resulted in a loss of the recently identified ILC precursor, yet conditional ablation of Nfil3 in the NKp46+ ILC3 subset did not perturb ILC3 numbers, suggesting that Nfil3 is required early during ILC3 development but not for lineage maintenance. Lastly, a marked defect in type 2 ILCs (ILC2s) was also observed in the lungs and visceral adipose tissue of Nfil3-deficient mice, revealing a general requirement for Nfil3 in the development of all ILC lineages. PMID:25113970

  5. Early life programming of innate fear and fear learning in adult female rats.

    PubMed

    Stevenson, Carl W; Meredith, John P; Spicer, Clare H; Mason, Rob; Marsden, Charles A

    2009-03-02

    The early rearing environment can impact on emotional reactivity and learning later in life. In this study the effects of neonatal maternal separation (MS) on innate fear and fear learning were assessed in the adult female rat. Pups were subjected to MS (360 min), brief handling (H; 15 min), or animal facility rearing (AFR) on post-natal days 2-14. In the first experiment, innate fear was tested in the open field. No differences between the early rearing groups were observed in unconditioned fear. In the second experiment, separate cohorts were used in a 3-day fear learning paradigm which tested the acquisition (Day 1), expression and extinction (both Day 2) of conditioning to an auditory cue; extinction recall was determined as well (Day 3). Contextual fear conditioning was also assessed prior to cue presentations on Days 2 and 3. Whereas MS attenuated the acquisition and expression of fear conditioning to the cue, H potentiated extinction learning. Cue-induced fear was reduced on Day 3, compared to Day 2, indicating that the recall of extinction learning was evident; however, no early rearing group differences in extinction recall were observed. Similarly, while contextual fear was decreased on Day 3, compared to Day 2, there were no differences between the early rearing groups on either day tested. The present findings of altered cue-conditioned fear learning, in the absence of innate fear changes, lend further support for the important role of the early rearing environment in mediating cognition in adulthood.

  6. Innate immune memory: implications for development of pediatric immunomodulatory agents and adjuvanted vaccines.

    PubMed

    Levy, Ofer; Netea, Mihai G

    2014-01-01

    Unique features of immunity early in life include a distinct immune system particularly reliant on innate immunity, with weak T helper (Th)1-polarizing immune responses, and impaired responses to certain vaccines leading to a heightened susceptibility to infection. To these important aspects, we now add an increasingly appreciated concept that the innate immune system displays epigenetic memory of an earlier infection or vaccination, a phenomenon that has been named "trained immunity." Exposure of neonatal leukocytes in vitro or neonatal animals or humans in vivo to specific innate immune stimuli results in an altered innate immune set point. Given the particular importance of innate immunity early in life, trained immunity to early life infection and/or immunization may play an important role in modulating both acute and chronic diseases.

  7. The effects of early weaning on innate immune responses of Holstein calves

    USDA-ARS?s Scientific Manuscript database

    The objectives of this study were to compare innate immune responses of calves weaned early (EW; n = 23; weaned at 23.7 ± 2.3 d of age) to conventionally-weaned calves (CW; n = 22; weaned at 44.7 ± 2.3 d of age). All calves were fed 3.8 L of colostrum within 12 h of birth and were subsequently fed m...

  8. Bcl-2 Inhibits the Innate Immune Response during Early Pathogenesis of Murine Congenital Muscular Dystrophy

    PubMed Central

    Jeudy, Sheila; Wardrop, Katherine E.; Alessi, Amy; Dominov, Janice A.

    2011-01-01

    Laminin α2 (LAMA2)-deficient congenital muscular dystrophy is a severe, early-onset disease caused by abnormal levels of laminin 211 in the basal lamina leading to muscle weakness, transient inflammation, muscle degeneration and impaired mobility. In a Lama2-deficient mouse model for this disease, animal survival is improved by muscle-specific expression of the apoptosis inhibitor Bcl-2, conferred by a MyoD-hBcl-2 transgene. Here we investigated early disease stages in this model to determine initial pathological events and effects of Bcl-2 on their progression. Using quantitative immunohistological and mRNA analyses we show that inflammation occurs very early in Lama2-deficient muscle, some aspects of which are reduced or delayed by the MyoD-hBcl-2 transgene. mRNAs for innate immune response regulators, including multiple Toll-like receptors (TLRs) and the inflammasome component NLRP3, are elevated in diseased muscle compared with age-matched controls expressing Lama2. MyoD-hBcl-2 inhibits induction of TLR4, TLR6, TLR7, TLR8 and TLR9 in Lama2-deficient muscle compared with non-transgenic controls, and leads to reduced infiltration of eosinophils, which are key death effector cells. This congenital disease model provides a new paradigm for investigating cell death mechanisms during early stages of pathogenesis, demonstrating that interactions exist between Bcl-2, a multifunctional regulator of cell survival, and the innate immune response. PMID:21850221

  9. SAP is required for the development of innate phenotype in H2-M3-restricted CD8+ T cells1

    PubMed Central

    Bediako, Yaw; Bian, Yao; Zhang, Hong; Cho, Hoonsik; Stein, Paul L.; Wang, Chyung-Ru

    2012-01-01

    H2-M3-restricted T cells have a pre-activated surface phenotype, rapidly expand and produce cytokines upon stimulation and as such, are classified as innate T cells. Unlike most innate T cells, M3-restricted T cells also express CD8αβ co-receptors and a diverse TCR repertoire: hallmarks of conventional MHC Ia-restricted CD8+ T cells. Although iNKT cells are also innate lymphocytes, they are selected exclusively on hematopoietic cells (HC), while M3-restricted T cells can be selected on either hematopoietic or thymic epithelial cells (TEC). Moreover, their phenotypes differ depending on what cells mediate their selection. Though there is a clear correlation between selection on HC and development of innate phenotype, the underlying mechanism remains unclear. SAP is required for the development of iNKT cells and mediates signals from SLAM receptors that are exclusively expressed on HC. Based on their dual selection pathway, M3-restricted T cells present a unique model for studying the development of innate T cell phenotype. Using both polyclonal and transgenic mouse models we demonstrate that while M3-restricted T cells are capable of developing in the absence of SAP, SAP is required for HC-mediated selection, development of pre-activated phenotype and heightened effector functions of M3-restricted T cells. These findings are significant because they directly demonstrate the need for SAP in HC-mediated acquisition of innate T cell phenotype and suggest that due to their SAP-dependent HC-mediated selection, M3-restricted T cells develop a pre-activated phenotype and an intrinsic ability to proliferate faster upon stimulation, allowing for an important role in the early response to infection. PMID:23041566

  10. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.

    PubMed

    Seehus, Corey R; Aliahmad, Parinaz; de la Torre, Brian; Iliev, Iliyan D; Spurka, Lindsay; Funari, Vincent A; Kaye, Jonathan

    2015-06-01

    Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.

  11. Gata3 drives development of RORγt+ group 3 innate lymphoid cells

    PubMed Central

    Serafini, Nicolas; Klein Wolterink, Roel G.J.; Satoh-Takayama, Naoko; Xu, Wei; Vosshenrich, Christian A.J.; Hendriks, Rudi W.

    2014-01-01

    Group 3 innate lymphoid cells (ILC3) include IL-22–producing NKp46+ cells and IL-17A/IL-22–producing CD4+ lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal RORγt+ ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut RORγt+ ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets. PMID:24419270

  12. A neonatal model of intravenous Staphylococcus epidermidis infection in mice <24 h old enables characterization of early innate immune responses.

    PubMed

    Kronforst, Kenny D; Mancuso, Christy J; Pettengill, Matthew; Ninkovic, Jana; Power Coombs, Melanie R; Stevens, Chad; Otto, Michael; Mallard, Carina; Wang, Xiaoyang; Goldmann, Donald; Levy, Ofer

    2012-01-01

    Staphylococcus epidermidis (SE) causes late onset sepsis and significant morbidity in catheterized preterm newborns. Animal models of SE infection are useful in characterizing disease mechanisms and are an important approach to developing improved diagnostics and therapeutics. Current murine models of neonatal bacterial infection employ intraperitoneal or subcutaneous routes at several days of age, and may, therefore, not accurately reflect distinct features of innate immune responses to bacteremia. In this study we developed, validated, and characterized a murine model of intravenous (IV) infection in neonatal mice <24 hours (h) old to describe the early innate immune response to SE. C57BL/6 mice <24 h old were injected IV with 10(6), 10(7), 10(8) colony-forming units (CFU) of SE 1457, a clinical isolate from a central catheter infection. A prospective injection scoring system was developed and validated, with only high quality injections analyzed. Newborn mice were euthanized between 2 and 48 h post-injection and spleen, liver, and blood collected to assess bacterial viability, gene expression, and cytokine production. High quality IV injections demonstrated inoculum-dependent infection of spleen, liver and blood. Within 2 h of injection, SE induced selective transcription of TLR2 and MyD88 in the liver, and increased systemic production of plasma IL-6 and TNF-α. Despite clearance of bacteremia and solid organ infection within 48 h, inoculum-dependent impairment in weight gain was noted. We conclude that a model of IV SE infection in neonatal mice <24 h old is feasible, demonstrating inoculum-dependent infection of solid organs and a pattern of bacteremia, rapid and selective innate immune activation, and impairment of weight gain typical of infected human neonates. This novel model can now be used to characterize immune ontogeny, evaluate infection biomarkers, and assess preventative and therapeutic modalities.

  13. Development of human natural killer cells and other innate lymphoid cells.

    PubMed

    Montaldo, Elisa; Vacca, Paola; Moretta, Lorenzo; Mingari, Maria Cristina

    2014-04-01

    Innate lymphoid cells (ILC) have recently gained much attention in immunology. They represent a novel developmentally related family. Three distinct subsets have been identified on the basis of phenotypic and functional criteria and termed ILC1, ILC2, and ILC3. The available data suggest that ILC play an important role in innate defenses against different pathogens, in lymphoid organogenesis, and in tissue remodeling. All these aspects are relevant in hematopoietic stem cell transplantation (HSCT), particularly in the haplo-HSCT setting, in which donor NK cells are known to play a major therapeutic role, while the involvement of other ILC is still undefined. In this context, it has been postulated that all ILC share a common precursor expressing the ID2 transcription factor. While the differentiation of human NK cells (belonging to ILC1) is now well characterized both in vitro and in vivo, limited information is available on the development of human ILC2 and ILC3 and of their relationships with NK cells. In this review, we will summarize the present knowledge on the developmental relationship among different ILC, with particular focus on early stages of NK cell differentiation, and their features shared with ILC2 and ILC3.

  14. Development, differentiation and diversity of innate lymphoid cells

    PubMed Central

    Diefenbach, Andreas; Colonna, Marco; Koyasu, Shigeo

    2014-01-01

    Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILC). ILC are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILC has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILC can be grouped into two separate lineages, cytotoxic ILC represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILC (i.e., ILC1, ILC2, ILC3). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and T cell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces. PMID:25238093

  15. Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA.

    PubMed

    Chang, David C; Hoang, Long T; Mohamed Naim, Ahmad Nazri; Dong, Hongping; Schreiber, Mark J; Hibberd, Martin L; Tan, Min Jie Alvin; Shi, Pei-Yong

    2016-12-01

    Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection. This early attenuation is not dependent on a functional type I interferon response and coincides with early activation of the innate immune response. Taken together, our data suggest that 2'-O-methylation of DENV genomic RNA is important for evasion of the host immune response during the very early stages of infection as the virus seeks to establish infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The Role of TOX in the Development of Innate Lymphoid Cells.

    PubMed

    Seehus, Corey R; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  17. Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis

    PubMed Central

    Butchi, Niranjan; Kapil, Parul; Puntambekar, Shweta; Stohlman, Stephen A.; Hinton, David R.

    2015-01-01

    ABSTRACT Myd88 signaling is critical to the control of numerous central nervous system (CNS) infections by promoting both innate and adaptive immune responses. Nevertheless, the extent to which Myd88 regulates type I interferon (IFN) versus proinflammatory factors and T cell function, as well as the anatomical site of action, varies extensively with the pathogen. CNS infection by neurotropic coronavirus with replication confined to the brain and spinal cord induces protective IFN-α/β via Myd88-independent activation of melanoma differentiation-associated gene 5 (MDA5). However, a contribution of Myd88-dependent signals to CNS pathogenesis has not been assessed. Infected Myd88−/− mice failed to control virus, exhibited enhanced clinical disease coincident with increased demyelination, and succumbed to infection within 3 weeks. The induction of IFN-α/β, as well as of proinflammatory cytokines and chemokines, was impaired early during infection. However, defects in both IFN-α/β and select proinflammatory factors were rapidly overcome prior to T cell recruitment. Myd88 deficiency also specifically blunted myeloid and CD4 T cell recruitment into the CNS without affecting CD8 T cells. Moreover, CD4 T cells but not CD8 T cells were impaired in IFN-γ production. Ineffective virus control indeed correlated most prominently with reduced antiviral IFN-γ in the CNS of Myd88−/− mice. The results demonstrate a crucial role for Myd88 both in early induction of innate immune responses during coronavirus-induced encephalomyelitis and in specifically promoting protective CD4 T cell activation. In the absence of these responses, functional CD8 T cells are insufficient to control viral spread within the CNS, resulting in severe demyelination. IMPORTANCE During central nervous system (CNS) infections, signaling through the adaptor protein Myd88 promotes both innate and adaptive immune responses. The extent to which Myd88 regulates antiviral type I IFN, proinflammatory

  18. The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response.

    PubMed

    Gilli, Francesca; Li, Libin; Pachner, Andrew R

    2016-02-01

    Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD. Also, we measured 32 cytokines/chemokines by multiplex Luminex analysis in CSF specimens from early and late TMEV-IDD as well as sham-treated mice. Results indicate that, in the later stage of TMEV-IDD, activation of the innate immune response is most prominent: TLRs, type I IFN response genes, and innate immunity-associated cytokines were highly expressed in late TMEV-IDD compared to sham (p ≤ 0.0001) and early TMEV-IDD (p < 0.05). Conversely, several molecular mediators of adaptive immune response were highly expressed in early TMEV-IDD (all p ≤ 0.001). Protein detection in the CSF was broadly concordant with mRNA abundance of the corresponding gene measured by real-time RT-PCR in the spinal cord, since several cytokines/chemokines were increased in the CSF of TMEV-IDD mice. Results show a clear shift from adaptive to innate immunity from early to late TMEV-IDD, indicating that adaptive and innate immune pathways are likely involved in the development and progression of the disease to different extents. CSF provides an optimal source of biomarkers of CNS neuroinflammation.

  19. The effects of early weaning on innate immune responses of Holstein calves.

    PubMed

    Hulbert, L E; Cobb, C J; Carroll, J A; Ballou, M A

    2011-05-01

    The objectives of this study were to compare innate immune responses of calves weaned early (EW; n=23; weaned at 23.7 ± 2.3 d of age) with those of conventionally weaned calves (CW; n=22; weaned at 44.7 ± 2.3 d of age). All calves were fed 3.8L of colostrum within 12h of birth and were subsequently fed milk replacer twice daily. The weaning process began by withdrawal of the afternoon milk-replacer feeding. Milk was fully withdrawn, and the calf was considered completely weaned when it consumed 900 g of calf starter as-fed for 2 consecutive days. Blood samples were collected from all calves at 24, 27, 31, 45, 48, 52, and 66 ± 2.3 d of age. Early weaned calves took a variable amount of time to completely wean from milk replacer; therefore, data were also analyzed by comparing calves grouped by latency to completely weaned (fast=1 to 5 d; intermediate=6 to 8 d; slow=15 to 17 d). Slow-EW calves weighed less than either the fast- or intermediate-EW calves before initiating weaning. At 27 d of age, circulating neutrophils were greater among EW calves than CW calves. Moreover, fast-EW calves had lower neutrophil:mononuclear cell ratios at 45 d of age than other EW calves. Slow-EW calves had lower TNF-α concentrations from whole blood stimulated with endotoxin at 27 and 31 d of age compared with fast- and intermediate-EW calves. All EW calves had decreased neutrophil L-selectin at d 27 and increased neutrophil L-selectin at 31 d of age. At 31 d of age, neutrophil β(2)-integrin was the greatest among the fast-EW calves. All EW calves had decreased neutrophil oxidative burst at 27 and 31 d of age. Three days after CW calves were weaned they had higher neutrophils, hematocrit percentages, and circulating cortisol than EW calves. In addition, 3 d after CW calves were weaned they had decreased neutrophil oxidative burst responses to Escherichia coli. Weaning, irrespective of age, suppressed many innate immune responses. In addition, early weaning transiently suppressed L

  20. G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program

    PubMed Central

    Chenery, Alistair L.; Burrows, Kyle; Gold, Matthew J.; Cait, Alissa; Rossi, Fabio M.

    2016-01-01

    Innate lymphoid cells (ILCs) are emerging as important regulators of homeostatic and disease-associated immune processes. Despite recent advances in defining the molecular pathways that control development and function of ILCs, the epigenetic mechanisms that regulate ILC biology are unknown. Here, we identify a role for the lysine methyltransferase G9a in regulating ILC2 development and function. Mice with a hematopoietic cell–specific deletion of G9a (Vav.G9a−/− mice) have a severe reduction in ILC2s in peripheral sites, associated with impaired development of immature ILC2s in the bone marrow. Accordingly, Vav.G9a−/− mice are resistant to the development of allergic lung inflammation. G9a-dependent dimethylation of histone 3 lysine 9 (H3K9me2) is a repressive histone mark that is associated with gene silencing. Genome-wide expression analysis demonstrated that the absence of G9a led to increased expression of ILC3-associated genes in developing ILC2 populations. Further, we found high levels of G9a-dependent H3K9me2 at ILC3-specific genetic loci, demonstrating that G9a-mediated repression of ILC3-associated genes is critical for the optimal development of ILC2s. Together, these results provide the first identification of an epigenetic regulatory mechanism in ILC development and function. PMID:27298444

  1. Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells.

    PubMed

    Scoville, Steven D; Freud, Aharon G; Caligiuri, Michael A

    2017-01-01

    Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development.

  2. Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

    PubMed Central

    Scoville, Steven D.; Freud, Aharon G.; Caligiuri, Michael A.

    2017-01-01

    Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development. PMID:28396671

  3. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    PubMed

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. SAP-Dependent and -Independent Regulation of Innate T Cell Development Involving SLAMF Receptors.

    PubMed

    De Calisto, Jaime; Wang, Ninghai; Wang, Guoxing; Yigit, Burcu; Engel, Pablo; Terhorst, Cox

    2014-01-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF) of receptors, whose expression is essential for T, NK, and B-cell responses. Additionally, the expression of SAP in double-positive thymocytes is mandatory for natural killer T (NKT) cells and, in mouse, for innate CD8(+) T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1 + 6](-/-) and Slamf[1 + 5 + 6](-/-) B6 mice have ~70% reduction of NKT cells compared to wild-type B6 mice. Unexpectedly, the proportion of innate CD8(+) T cells slightly increased in the Slamf[1 + 5 + 6](-/-) , but not in the Slamf[1 + 6](-/-) strain, suggesting that Slamf5 may function as a negative regulator of innate CD8(+) T cell development. Accordingly, Slamf5(-/-) B6 mice showed an exclusive expansion of innate CD8(+) T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7(-/-) strain showed an expansion of both splenic innate CD8(+) T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3(-/-) BALB/c mice, the proportions of thymic promyelocytic leukemia zinc finger (PLZF(hi)) NKT cells and innate CD8(+) T cells significantly increased in the SAP-independent Slamf8(-/-) BALB/c strain. In summary, these results show that NKT and innate CD8(+) T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8(+) T cells.

  5. A Role for Innate Immunity in the Development of Hypertension

    PubMed Central

    Gomolak, Jessica R.; Didion, Sean P.

    2014-01-01

    Clinically, Angiotensin II (Ang II) has been implicated in some forms of hypertension and linked to vascular injury. Experimentally, chronic Ang II infusion leads to an increase in blood pressure, resulting in impaired endothelial function and vascular hypertrophy. Ang II also upregulates the activity and expression of a number of inflammatory molecules, including nuclear factor kappa B (NFκB) and pro-inflammatory cytokines, such as interleukin-6 (IL-6). More recently, it has been reported that Ang II is associated with upregulation of toll-like receptor TLR expression, specifically TLR4. Classical TLR4 signaling is mediated in large part by the effector protein myeloid differentiation factor 88 (MyD88), with resultant activation of NFκB, a transcription factor that promotes expression of a number of inflammatory gene products, including IL-6. A role for IL-6 has been previously implicated in the vascular dysfunction associated with Ang II-dependent hypertension. It is not known whether the MyD88 signaling pathway represents a cellular mechanism by which Ang II promotes endothelial dysfunction via NFκB activation and increases in IL-6. Taken together, we propose to mechanistically elucidate the role of innate immune signaling in Ang II-dependent hypertension. We hypothesize MyD88-deficiency will prevent the activation and transcription of NFκB-related gene products, including IL-6, thereby limiting Ang II-dependent hypertension and vascular complications. PMID:25441337

  6. Early Program Development

    NASA Image and Video Library

    2004-04-15

    During the Space Shuttle development phase, Marshall plarners concluded a Heavy Lift Launch Vehicle (HLLV) would be needed for successful Space Industrialization. Shown here in this 1976's artist's conception is an early version of the HLLV during launch.

  7. Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.

    PubMed

    Clay, Candice C; Maniar-Hew, Kinjal; Gerriets, Joan E; Wang, Theodore T; Postlethwait, Edward M; Evans, Michael J; Fontaine, Justin H; Miller, Lisa A

    2014-01-01

    Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s) behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripheral blood cytokine response to lipopolysaccharide (LPS) that persists with maturity. As the lung is closely interfaced with the external environment, we hypothesized that the conducting airway epithelium of neonates may also be a target of immunomodulation by ozone. To test this hypothesis, we evaluated primary airway epithelial cell cultures derived from juvenile rhesus macaque monkeys with a prior history of episodic postnatal ozone exposure. Innate immune function was measured by expression of the proinflammatory cytokines IL-6 and IL-8 in primary cultures established following in vivo LPS challenge or, in response to in vitro LPS treatment. Postnatal ozone exposure resulted in significantly attenuated IL-6 mRNA and protein expression in primary cultures from juvenile animals; IL-8 mRNA was also significantly reduced. The effect of antecedent ozone exposure was modulated by in vivo LPS challenge, as primary cultures exhibited enhanced cytokine expression upon secondary in vitro LPS treatment. Assessment of potential IL-6-targeting microRNAs miR-149, miR-202, and miR-410 showed differential expression in primary cultures based upon animal exposure history. Functional assays revealed that miR-149 is capable of binding to the IL-6 3' UTR and decreasing IL-6 protein synthesis in airway epithelial cell lines. Cumulatively, our findings suggest that episodic ozone during early life contributes to the molecular programming of airway epithelium, such that memory from prior exposures is retained in the form of a dysregulated IL-6 and IL-8 response to LPS; differentially expressed microRNAs such as miR-149 may play a role in the persistent modulation of the epithelial innate

  8. Early Life Ozone Exposure Results in Dysregulated Innate Immune Function and Altered microRNA Expression in Airway Epithelium

    PubMed Central

    Gerriets, Joan E.; Wang, Theodore T.; Postlethwait, Edward M.; Evans, Michael J.; Fontaine, Justin H.; Miller, Lisa A.

    2014-01-01

    Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s) behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripheral blood cytokine response to lipopolysaccharide (LPS) that persists with maturity. As the lung is closely interfaced with the external environment, we hypothesized that the conducting airway epithelium of neonates may also be a target of immunomodulation by ozone. To test this hypothesis, we evaluated primary airway epithelial cell cultures derived from juvenile rhesus macaque monkeys with a prior history of episodic postnatal ozone exposure. Innate immune function was measured by expression of the proinflammatory cytokines IL-6 and IL-8 in primary cultures established following in vivo LPS challenge or, in response to in vitro LPS treatment. Postnatal ozone exposure resulted in significantly attenuated IL-6 mRNA and protein expression in primary cultures from juvenile animals; IL-8 mRNA was also significantly reduced. The effect of antecedent ozone exposure was modulated by in vivo LPS challenge, as primary cultures exhibited enhanced cytokine expression upon secondary in vitro LPS treatment. Assessment of potential IL-6-targeting microRNAs miR-149, miR-202, and miR-410 showed differential expression in primary cultures based upon animal exposure history. Functional assays revealed that miR-149 is capable of binding to the IL-6 3′ UTR and decreasing IL-6 protein synthesis in airway epithelial cell lines. Cumulatively, our findings suggest that episodic ozone during early life contributes to the molecular programming of airway epithelium, such that memory from prior exposures is retained in the form of a dysregulated IL-6 and IL-8 response to LPS; differentially expressed microRNAs such as miR-149 may play a role in the persistent modulation of the epithelial innate

  9. Pathogen Entrapment by Transglutaminase—A Conserved Early Innate Immune Mechanism

    PubMed Central

    Dobes, Pavel; Klupp, Martina; Loseva, Olga; Mörgelin, Matthias; Iklé, Jennifer; Cripps, Richard M.; Herwald, Heiko; Theopold, Ulrich

    2010-01-01

    Clotting systems are required in almost all animals to prevent loss of body fluids after injury. Here, we show that despite the risks associated with its systemic activation, clotting is a hitherto little appreciated branch of the immune system. We compared clotting of human blood and insect hemolymph to study the best-conserved component of clotting systems, namely the Drosophila enzyme transglutaminase and its vertebrate homologue Factor XIIIa. Using labelled artificial substrates we observe that transglutaminase activity from both Drosophila hemolymph and human blood accumulates on microbial surfaces, leading to their sequestration into the clot. Using both a human and a natural insect pathogen we provide functional proof for an immune function for transglutaminase (TG). Drosophila larvae with reduced TG levels show increased mortality after septic injury. The same larvae are also more susceptible to a natural infection involving entomopathogenic nematodes and their symbiotic bacteria while neither phagocytosis, phenoloxidase or—as previously shown—the Toll or imd pathway contribute to immunity. These results firmly establish the hemolymph/blood clot as an important effector of early innate immunity, which helps to prevent septic infections. These findings will help to guide further strategies to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions. PMID:20169185

  10. A stress-induced early innate response causes multidrug tolerance in melanoma.

    PubMed

    Ravindran Menon, D; Das, S; Krepler, C; Vultur, A; Rinner, B; Schauer, S; Kashofer, K; Wagner, K; Zhang, G; Bonyadi Rad, E; Haass, N K; Soyer, H P; Gabrielli, B; Somasundaram, R; Hoefler, G; Herlyn, M; Schaider, H

    2015-08-20

    Acquired drug resistance constitutes a major challenge for effective cancer therapies with melanoma being no exception. The dynamics leading to permanent resistance are poorly understood but are important to design better treatments. Here we show that drug exposure, hypoxia or nutrient starvation leads to an early innate cell response in melanoma cells resulting in multidrug resistance, termed induced drug-tolerant cells (IDTCs). Transition into the IDTC state seems to be an inherent stress reaction for survival toward unfavorable environmental conditions or drug exposure. The response comprises chromatin remodeling, activation of signaling cascades and markers implicated in cancer stemness with higher angiogenic potential and tumorigenicity. These changes are characterized by a common increase in CD271 expression concomitantly with loss of differentiation markers such as melan-A and tyrosinase, enhanced aldehyde dehydrogenase (ALDH) activity and upregulation of histone demethylases. Accordingly, IDTCs show a loss of H3K4me3, H3K27me3 and gain of H3K9me3 suggesting activation and repression of differential genes. Drug holidays at the IDTC state allow for reversion into parental cells re-sensitizing them to the drug they were primarily exposed to. However, upon continuous drug exposure IDTCs eventually transform into permanent and irreversible drug-resistant cells. Knockdown of CD271 or KDM5B decreases transition into the IDTC state substantially but does not prevent it. Targeting IDTCs would be crucial for sustainable disease management and prevention of acquired drug resistance.

  11. A stress-induced early innate response causes multidrug tolerance in melanoma

    PubMed Central

    Menon, D Ravindran; Das, S; Krepler, C; Vultur, A; Rinner, B; Schauer, S; Kashofer, K; Wagner, K; Zhang, G; Rad, E Bonyadi; Haass, NK; Soyer, HP; Gabrielli, B; Somasundaram, R; Hoefler, G; Herlyn, M; Schaider, H

    2015-01-01

    Acquired drug resistance constitutes a major challenge for effective cancer therapies with melanoma being no exception. The dynamics leading to permanent resistance are poorly understood but are important to design better treatments. Here we show that drug exposure, hypoxia or nutrient starvation leads to an early innate cell response in melanoma cells resulting in multidrug resistance, termed induced drug-tolerant cells (IDTCs). Transition into the IDTC state seems to be an inherent stress reaction for survival toward unfavorable environmental conditions or drug exposure. The response comprises chromatin remodeling, activation of signaling cascades and markers implicated in cancer stemness with higher angiogenic potential and tumorigenicity. These changes are characterized by a common increase in CD271 expression concomitantly with loss of differentiation markers such as melan-A and tyrosinase, enhanced aldehyde dehydrogenase (ALDH) activity and upregulation of histone demethylases. Accordingly, IDTCs show a loss of H3K4me3, H3K27me3 and gain of H3K9me3 suggesting activation and repression of differential genes. Drug holidays at the IDTC state allow for reversion into parental cells re-sensitizing them to the drug they were primarily exposed to. However, upon continuous drug exposure IDTCs eventually transform into permanent and irreversible drug-resistant cells. Knockdown of CD271 or KDM5B decreases transition into the IDTC state substantially but does not prevent it. Targeting IDTCs would be crucial for sustainable disease management and prevention of acquired drug resistance. PMID:25417704

  12. The draft genome of the large yellow croaker reveals well-developed innate immunity

    PubMed Central

    Wu, Changwen; Zhang, Di; Kan, Mengyuan; Lv, Zhengmin; Zhu, Aiyi; Su, Yongquan; Zhou, Daizhan; Zhang, Jianshe; Zhang, Zhou; Xu, Meiying; Jiang, Lihua; Guo, Baoying; Wang, Ting; Chi, Changfeng; Mao, Yong; Zhou, Jiajian; Yu, Xinxiu; Wang, Hailing; Weng, Xiaoling; Jin, Jason Gang; Ye, Junyi; He, Lin; Liu, Yun

    2014-01-01

    The large yellow croaker, Larimichthys crocea, is one of the most economically important marine fish species endemic to China. Its wild stocks have severely suffered from overfishing, and the aquacultured species are vulnerable to various marine pathogens. Here we report the creation of a draft genome of a wild large yellow croaker using a whole-genome sequencing strategy. We estimate the genome size to be 728 Mb with 19,362 protein-coding genes. Phylogenetic analysis shows that the stickleback is most closely related to the large yellow croaker. Rapidly evolving genes under positive selection are significantly enriched in pathways related to innate immunity. We also confirm the existence of several genes and identify the expansion of gene families that are important for innate immunity. Our results may reflect a well-developed innate immune system in the large yellow croaker, which could aid in the development of wild resource preservation and mariculture strategies. PMID:25407894

  13. The draft genome of the large yellow croaker reveals well-developed innate immunity.

    PubMed

    Wu, Changwen; Zhang, Di; Kan, Mengyuan; Lv, Zhengmin; Zhu, Aiyi; Su, Yongquan; Zhou, Daizhan; Zhang, Jianshe; Zhang, Zhou; Xu, Meiying; Jiang, Lihua; Guo, Baoying; Wang, Ting; Chi, Changfeng; Mao, Yong; Zhou, Jiajian; Yu, Xinxiu; Wang, Hailing; Weng, Xiaoling; Jin, Jason Gang; Ye, Junyi; He, Lin; Liu, Yun

    2014-11-19

    The large yellow croaker, Larimichthys crocea, is one of the most economically important marine fish species endemic to China. Its wild stocks have severely suffered from overfishing, and the aquacultured species are vulnerable to various marine pathogens. Here we report the creation of a draft genome of a wild large yellow croaker using a whole-genome sequencing strategy. We estimate the genome size to be 728 Mb with 19,362 protein-coding genes. Phylogenetic analysis shows that the stickleback is most closely related to the large yellow croaker. Rapidly evolving genes under positive selection are significantly enriched in pathways related to innate immunity. We also confirm the existence of several genes and identify the expansion of gene families that are important for innate immunity. Our results may reflect a well-developed innate immune system in the large yellow croaker, which could aid in the development of wild resource preservation and mariculture strategies.

  14. Breastmilk-Saliva Interactions Boost Innate Immunity by Regulating the Oral Microbiome in Early Infancy

    PubMed Central

    Al-Shehri, Saad S.; Knox, Christine L.; Liley, Helen G.; Cowley, David M.; Wright, John R.; Henman, Michael G.; Hewavitharana, Amitha K.; Charles, Bruce G.; Shaw, Paul N.; Sweeney, Emma L.; Duley, John A.

    2015-01-01

    Introduction Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined. Results Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 μM). Fresh breastmilk contained 27.3±12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2–449) compared to adults (620 U/L, 48–1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns. Discussion and Conclusion During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral–and hence gut–microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity. PMID:26325665

  15. Early Developments, 1998.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    1998-01-01

    This document consists of the two 1998 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. In the Spring 1998 issue, articles highlight the Center's diverse cross-cultural projects and global research, training and…

  16. Early Developments, 2002.

    ERIC Educational Resources Information Center

    Winton, Pam, Ed.; Buysse, Virginia, Ed.

    2002-01-01

    This document consists of the three 2002 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center (FPG) at the University of North Carolina at Chapel Hill. Articles in the Winter 2002 issue highlight some current work at FPG on factors that enhance or inhibit social and…

  17. Early Developments, 2000.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    2000-01-01

    This document consists of the three 2000 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. Articles in the spring 2000 issue focus on a follow-up study of the Abecedarian Project, children of depressed mothers,…

  18. The Roles of Innate Lymphoid Cells in the Development of Asthma

    PubMed Central

    Woo, Yeonduk; Jeong, Dongjin; Chung, Doo Hyun

    2014-01-01

    Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma. PMID:25177249

  19. Early Program Development

    NASA Image and Video Library

    1971-01-01

    This 1971 artist's concept shows a Nuclear Shuttle and an early Space Shuttle docked with an Orbital Propellant Depot. As envisioned by Marshall Space Flight Center Program Development persornel, an orbital modular propellant storage depot, supplied periodically by the Space Shuttle or Earth-to-orbit fuel tankers, would be critical in making available large amounts of fuel to various orbital vehicles and spacecraft.

  20. Early Program Development

    NASA Image and Video Library

    1970-01-01

    This artist's concept from 1970 shows a Nuclear Shuttle docked to an Orbital Propellant Depot and an early Space Shuttle. As envisioned by Marshall Space Flight Center Program Development plarners, the Nuclear Shuttle, in either manned or unmanned mode, would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additonal missions.

  1. Wired for behaviors: from development to function of innate limbic system circuitry

    PubMed Central

    Sokolowski, Katie; Corbin, Joshua G.

    2012-01-01

    The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional, or motivational salience, which includes innate behaviors such as mating, aggression, and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents), and is then processed in the brain by a set of delineated structures that primarily includes the amygdala and hypothalamus. While the basic neuroanatomy of these connections is well-established, much remains unknown about how information is processed within innate circuits and how genetic hierarchies regulate development and function of these circuits. Utilizing innovative technologies including channel rhodopsin-based circuit manipulation and genetic manipulation in rodents, recent studies have begun to answer these central questions. In this article we review the current understanding of how limbic circuits regulate sexually dimorphic behaviors and how these circuits are established and shaped during pre- and post-natal development. We also discuss how understanding developmental processes of innate circuit formation may inform behavioral alterations observed in neurodevelopmental disorders, such as autism spectrum disorders, which are characterized by limbic system dysfunction. PMID:22557946

  2. Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections.

    PubMed

    Biron, C A

    1998-10-01

    Innate cytokine responses are important mediators of early defense against infections. Certain of their effects can be delivered directly to activate protective mechanisms in infected cells. Others activate innate immune cells, including natural killer (NK) cells and macrophages, to mediate defense. Still others shape adaptive immune responses. The compositions and magnitudes of innate cytokine responses are modulated, by the nature of the infectious agent, to facilitate accessing of the anti-microbial defense functions most beneficial in defense against the particular infection. In the context of viral infections, interferons alpha and beta (IFN-alpha/beta) are induced to high levels, and help to mediate and regulate immune responses most effective against this class of agents. The cytokines induce anti-viral mechanisms in infected cells, negatively regulate interleukin 12 expression, and activate NK cell-mediated lysis. Protective development of adaptive immunity to viral infections includes prominent CD8 T cell expansion and activation, and IFN-alpha/beta can mediate functions with the potential to promote these T cell responses. Together, the characteristics define regulation of unique or unique prominent defense mechanisms in place to fight off viral infections.

  3. Nfil3 is required for the development of all innate lymphoid cell subsets

    PubMed Central

    Seillet, Cyril; Rankin, Lucille C.; Groom, Joanna R.; Mielke, Lisa A.; Tellier, Julie; Chopin, Michael; Huntington, Nicholas D.

    2014-01-01

    Innate lymphoid cell (ILC) populations protect against infection and are essential for lymphoid tissue formation and tissue remodeling after damage. Nfil3 is implicated in the function of adaptive immune lineages and NK cell development, but it is not yet known if Nfil3 regulates other innate lymphoid lineages. Here, we identify that Nfil3 is essential for the development of Peyer’s patches and ILC2 and ILC3 subsets. Loss of Nfil3 selectively reduced Peyer’s patch formation and was accompanied by impaired recruitment and distribution of lymphocytes within the patches. ILC subsets exhibited high Nfil3 expression and genetic deletion of Nfil3 severely compromised the development of all subsets. Subsequently, Nfil3−/− mice were highly susceptible to disease when challenged with inflammatory or infectious agents. Thus, we demonstrate that Nfil3 is a key regulator of the development of ILC subsets essential for immune protection in the lung and gut. PMID:25092873

  4. Early innate immune response of immune proteins in juvenile channel catfish Ictalurus punctatus

    USDA-ARS?s Scientific Manuscript database

    Channel catfish (Ictalurus punctatus) are raised for aquaculture in the Southeast U.S. and are susceptible to bacterial and viral infections acquired from their pond environment. Innate immune proteins mannose-binding lectin (MBL) and lysozyme were studied during two consecutive years in channel cat...

  5. Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.

    PubMed

    Lavin, Yonit; Kobayashi, Soma; Leader, Andrew; Amir, El-Ad David; Elefant, Naama; Bigenwald, Camille; Remark, Romain; Sweeney, Robert; Becker, Christian D; Levine, Jacob H; Meinhof, Klaus; Chow, Andrew; Kim-Shulze, Seunghee; Wolf, Andrea; Medaglia, Chiara; Li, Hanjie; Rytlewski, Julie A; Emerson, Ryan O; Solovyov, Alexander; Greenbaum, Benjamin D; Sanders, Catherine; Vignali, Marissa; Beasley, Mary Beth; Flores, Raja; Gnjatic, Sacha; Pe'er, Dana; Rahman, Adeeb; Amit, Ido; Merad, Miriam

    2017-05-04

    To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Human innate lymphoid cells.

    PubMed

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  8. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection.

  9. Early Interactive Emotional Development

    PubMed Central

    Messinger, Daniel S.; Mahoor, Mohammad H.; Cadavid, Steven; Chow, Sy-Miin; Cohn, Jeffrey F.

    2010-01-01

    Early infant emotional development concerns the interactive emergence of emotional states that motivate approach and withdrawal. These are indexed by different patterns of infant facial expressions, vocalization, and gazing that emerge within parent-infant interactions in the first 10 months of life. Specifically, the interface of a limited number of interactive parameters creates complex real-time patterns which change over developmental time. These phenomena are described below using techniques from our laboratory such as statistical simulations, continuous ratings, and computer vision modeling. PMID:21804955

  10. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances

    PubMed Central

    Haapakoski, Rita; Ebmeier, Klaus P.; Alenius, Harri; Kivimäki, Mika

    2016-01-01

    The inflammation theory of depression, proposed over 20 years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced ‘omics’ technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account. PMID:26631274

  11. The Timing of IFNβ Production Affects Early Innate Responses to Listeria monocytogenes and Determines the Overall Outcome of Lethal Infection

    PubMed Central

    Pontiroli, Francesca; Dussurget, Olivier; Zanoni, Ivan; Urbano, Matteo; Beretta, Ottavio; Granucci, Francesca; Ricciardi-Castagnoli, Paola; Cossart, Pascale; Foti, Maria

    2012-01-01

    Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a crucial role in the first phase of host defense against infections and tumors. Listeria monocytogenes (Lm) is an intracellular pathogen that colonizes the cytosol of eukaryotic cells. Recent findings have shown Lm specifically in splenic CD8a+ DCs shortly after intravenous infection. We examined gene expression profiles of mouse DCs exposed to Lm to elucidate the molecular mechanisms underlying DCs interaction with Lm. Using a functional genomics approach, we found that Lm infection induced a cluster of late response genes including type I IFNs and interferon responsive genes (IRGs) in DCs. Type I INFs were produced at the maximal level only at 24 h post infection indicating that the regulation of IFNs in the context of Lm infection is delayed compared to the rapid response observed with viral pathogens. We showed that during Lm infection, IFNγ production and cytotoxic activity were severely impaired in NK cells compared to E. coli infection. These defects were restored by providing an exogenous source of IFNβ during the initial phase of bacterial challenge. Moreover, when treated with IFNβ during early infection, NK cells were able to reduce bacterial titer in the spleen and significantly improve survival of infected mice. These findings show that the timing of IFNβ production is fundamental to the efficient control of the bacterium during the early innate phase of Lm infection. PMID:22912878

  12. Innate Lymphoid Cells Are the Predominant Source of IL-17A during the Early Pathogenesis of Acute Respiratory Distress Syndrome.

    PubMed

    Muir, Roshell; Osbourn, Megan; Dubois, Alice V; Doran, Emma; Small, Donna M; Monahan, Avril; O'Kane, Cecilia M; McAllister, Katherine; Fitzgerald, Denise C; Kissenpfennig, Adrien; McAuley, Daniel F; Ingram, Rebecca J

    2016-02-15

    IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Although IL-17A is the archetypal cytokine of T-helper 17 cells, it is produced by a number of lymphocytes, the source during ARDS being unknown. To identify the cellular source and the role of IL-17A in the early phase of lung injury. Lung injury was induced in wild-type (C57BL/6) and IL-17 knockout (KO) mice with aerosolized LPS (100 μg) or Pseudomonas aeruginosa infection. Detailed phenotyping of the cells expressing RORγt, the transcriptional regulator of IL-17 production, in the mouse lung at 24 hours was performed by flow cytometry. A 100-fold reduction in neutrophil infiltration was observed in the lungs of the IL-17A KO compared with wild-type mice. The majority of RORγt(+) cells in the mouse lung were the recently identified group 3 innate lymphoid cells (ILC3s). Detailed characterization revealed these pulmonary ILC3s (pILC3s) to be discrete from those described in the gut. The critical role of these cells was verified by inducing injury in recombinase-activating gene 2 KO mice, which lack T cells but retain innate lymphoid cells. No amelioration of pathology was observed in the recombinase-activating gene 2 KO mice. IL-17 is rapidly produced during lung injury and significantly contributes to early immunopathogenesis. This is orchestrated largely by a distinct population of pILC3s. Modulation of the activity of pILC3s may potentiate early control of the inflammatory dysregulation seen in ARDS, opening up new therapeutic targets.

  13. Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus.

    PubMed

    Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Antoniazzi, Alfredo Q; Morarie, Susan E; Hansen, Thomas R

    2012-08-01

    Transplacental viral infections are dependent upon complex interactions between feto-placental and maternal immune responses and the stage of fetal development at which the infection occurs. Bovine viral diarrhea virus (BVDV) has the ability to cross the placenta and infect the fetus. Infection early in gestation with non-cytopathic (ncp) BVDV leads to persistent infection. Establishment of fetal persistent infection results in life-long viremia, virus-specific immunotolerance, and may have detrimental developmental consequences. We have previously shown that heifers infected experimentally with ncp BVDV type 2 on d. 75 of gestation had transient robust up-regulation of the type I interferon (IFN) stimulated genes (ISGs) 3-15 days after viral inoculation. Blood from persistently infected (PI) fetuses, collected 115 days post maternal infection, demonstrated moderate chronic up-regulation of ISGs. This infection model was used to delineate timing of the development of innate immune responses in the fetus and placenta during establishment of persistent infection. It was hypothesized that: (i) chronic stimulation of innate immune responses occurs following infection of the fetus and (ii) placental production of the type I IFN contributes to up-regulation of ISGs in PI fetuses. PI fetuses, generated by intranasal inoculation of pregnant heifers with ncp BVDV, and control fetuses from uninfected heifers, were collected via Cesarean sections on d. 82, 89, 97, 192, and 245 of gestation. Fetal viremia was confirmed starting on d. 89. Significant up-regulation of mRNA encoding cytosolic dsRNA sensors -RIG-I and MDA5 - was detected on d. 82-192. Detection of viral dsRNA by cytosolic sensors leads to the stimulation of ISGs, which was reflected in significant up-regulation of ISG15 mRNA in fetal blood on d. 89, 97, and 192. No difference in IFN-α and IFN-β mRNA concentration was found in fetal blood or caruncular tissue, while a significant increase in both IFN-α and IFN

  14. Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis.

    PubMed

    Ngo, Lisa Y; Kasahara, Shinji; Kumasaka, Debra K; Knoblaugh, Sue E; Jhingran, Anupam; Hohl, Tobias M

    2014-01-01

    Candida albicans is a commensal fungus that can cause systemic disease in patients with breaches in mucosal integrity, indwelling catheters, and defects in phagocyte function. Although circulating human and murine monocytes bind C. albicans and promote inflammation, it remains unclear whether C-C chemokine receptor 2 (CCR2)- and Ly6C-expressing inflammatory monocytes exert a protective or a deleterious function during systemic infection. During murine systemic candidiasis, interruption of CCR2-dependent inflammatory monocyte trafficking into infected kidneys impaired fungal clearance and decreased murine survival. Depletion of CCR2-expressing cells led to uncontrolled fungal growth in the kidneys and brain and demonstrated an essential antifungal role for inflammatory monocytes and their tissue-resident derivatives in the first 48 hours postinfection. Adoptive transfer of purified inflammatory monocytes in depleted hosts reversed the defect in fungal clearance to a substantial extent, indicating a compartmentally and temporally restricted protective function that can be transferred to enhance systemic innate antifungal immunity.

  15. Super-resolution microscopy reveals protein spatial reorganization in early innate immune responses.

    SciTech Connect

    Carson, Bryan D.; Aaron, Jesse S.; Timlin, Jerilyn Ann

    2010-10-01

    Over the past decade optical approaches were introduced that effectively break the diffraction barrier. Of particular note were introductions of Stimulated Emission/Depletion (STED) microscopy, Photo-Activated Localization Microscopy (PALM), and the closely related Stochastic Optical Reconstruction Microscopy (STORM). STORM represents an attractive method for researchers, as it does not require highly specialized optical setups, can be implemented using commercially available dyes, and is more easily amenable to multicolor imaging. We implemented a simultaneous dual-color, direct-STORM imaging system through the use of an objective-based TIRF microscope and filter-based image splitter. This system allows for excitation and detection of two fluorophors simultaneously, via projection of each fluorophor's signal onto separate regions of a detector. We imaged the sub-resolution organization of the TLR4 receptor, a key mediator of innate immune response, after challenge with lipopolysaccharide (LPS), a bacteria-specific antigen. While distinct forms of LPS have evolved among various bacteria, only some LPS variations (such as that derived from E. coli) typically result in significant cellular immune response. Others (such as from the plague bacteria Y. pestis) do not, despite affinity to TLR4. We will show that challenge with LPS antigens produces a statistically significant increase in TLR4 receptor clusters on the cell membrane, presumably due to recruitment of receptors to lipid rafts. These changes, however, are only detectable below the diffraction limit and are not evident using conventional imaging methods. Furthermore, we will compare the spatiotemporal behavior of TLR4 receptors in response to different LPS chemotypes in order to elucidate possible routes by which pathogens such as Y. pestis are able to circumvent the innate immune system. Finally, we will exploit the dual-color STORM capabilities to simultaneously image LPS and TLR4 receptors in the cellular

  16. Innate immunity and intestinal microbiota in the development of Type 1 diabetes.

    PubMed

    Wen, Li; Ley, Ruth E; Volchkov, Pavel Yu; Stranges, Peter B; Avanesyan, Lia; Stonebraker, Austin C; Hu, Changyun; Wong, F Susan; Szot, Gregory L; Bluestone, Jeffrey A; Gordon, Jeffrey I; Chervonsky, Alexander V

    2008-10-23

    Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T-cell-mediated destruction of insulin-producing beta-cells. Its incidence has increased during the past several decades in developed countries, suggesting that changes in the environment (including the human microbial environment) may influence disease pathogenesis. The incidence of spontaneous T1D in non-obese diabetic (NOD) mice can be affected by the microbial environment in the animal housing facility or by exposure to microbial stimuli, such as injection with mycobacteria or various microbial products. Here we show that specific pathogen-free NOD mice lacking MyD88 protein (an adaptor for multiple innate immune receptors that recognize microbial stimuli) do not develop T1D. The effect is dependent on commensal microbes because germ-free MyD88-negative NOD mice develop robust diabetes, whereas colonization of these germ-free MyD88-negative NOD mice with a defined microbial consortium (representing bacterial phyla normally present in human gut) attenuates T1D. We also find that MyD88 deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of specific pathogen-free MyD88-negative NOD donors attenuates T1D in germ-free NOD recipients. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition.

  17. Role of MicroRNAs in the development and function of innate immune cells.

    PubMed

    Kumar Kingsley, S Manoj; Vishnu Bhat, B

    2017-05-04

    MicroRNAs act as crucial post-transcriptional regulators of various biological processes. Their role in regulating the differentiation and development of the various immune cells of the body is of paramount importance. The development of immune cells from the hematopoietic progenitors involves the complex interplay of transcription factors, cell signaling proteins and growth factors. MicroRNAs govern and sometimes work in a common axis alongside these factors to regulate the differentiation of immune cells. MicroRNAs are also involved in regulating the functions of innate immune cells such as phagocytosis, antigen presentation, endotoxin tolerance and natural killer cell cytotoxicity. Several microRNAs have shown to be activated during the inflammatory response and they limit the excessive immune response. The dysregulation of several microRNAs have shown to cause uncontrolled production of inflammatory cytokines resulting in various diseases. Overall, microRNAs are found to be crucial regulators of the development and function of innate immune cells and maintenance of immune homeostasis.

  18. Development and function of human innate immune cells in a humanized mouse model

    PubMed Central

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V.; Teichmann, Lino L.; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A. Karolina; Manz, Markus G.; Flavell, Richard A.

    2014-01-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models are unable to support development of human innate immune cells, including myeloid cells and NK cells. Here we describe a mouse strain, called MI(S)TRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked in to their respective mouse loci. The human cytokines support the development and function of monocytes/macrophages and natural killer cells derived from human fetal liver or adult CD34+ progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MI(S)TRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology. PMID:24633240

  19. The Innate Lymphoid Cell Precursor.

    PubMed

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  20. Kidney and innate immunity.

    PubMed

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed.

  1. Early Adolescent Ego Development.

    ERIC Educational Resources Information Center

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  2. Early Program Development

    NASA Image and Video Library

    1969-01-01

    As part of the Space Task Group's recommendations for more commonality and integration in America's space program, Marshall Space Flight Center engineers proposed an orbiting propellant storage facility to augment Space Shuttle missions. In this artist's concept from 1969 an early version of the Space Shuttle is shown refueling at the facility.

  3. Early Adolescent Ego Development.

    ERIC Educational Resources Information Center

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  4. Human Immunodeficiency Virus-1 Inhibition of Immunoamphisomes in Dendritic Cells Impairs Early Innate and Adaptive Immune Responses

    PubMed Central

    Blanchet, Fabien P.; Moris, Arnaud; Nikolic, Damjan S.; Lehmann, Martin; Cardinaud, Sylvain; Stalder, Romaine; Garcia, Eduardo; Dinkins, Christina; Leuba, Florence; Wu, Li; Schwartz, Olivier; Deretic, Vojo; Piguet, Vincent

    2010-01-01

    SUMMARY Dendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter. However, immune response in the early events of HIV-1 transmission appears limited, suggesting that HIV-1 evade early immune control by DCs. We report that HIV-1 induces a rapid shutdown of autophagy and immunoamphisomes in DCs. HIV-1 envelope activated the mammalian target of rapamycin pathway in DCs, leading to autophagy exhaustion. HIV-1-induced inhibition of autophagy in DC increased cell-associated HIV-1 and transfer of HIV-1 infection to CD4+ T cells. HIV-1-mediated downregulation of autophagy in DCs impaired innate and adaptive immune responses. Immunoamphisomes in DCs engulf incoming pathogens and appear to amplify pathogen degradation as well as Toll-like receptor responses and antigen presentation. The findings that HIV-1 downregulates autophagy and impedes immune functions of DCs represent a pathogenesis mechanism that can be pharmacologically countered with therapeutic and prophylactic implications. PMID:20451412

  5. Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV.

    PubMed

    Rechtien, Anne; Richert, Laura; Lorenzo, Hadrien; Martrus, Gloria; Hejblum, Boris; Dahlke, Christine; Kasonta, Rahel; Zinser, Madeleine; Stubbe, Hans; Matschl, Urte; Lohse, Ansgar; Krähling, Verena; Eickmann, Markus; Becker, Stephan; Thiébaut, Rodolphe; Altfeld, Marcus; Addo, Marylyn M

    2017-08-29

    Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Early local and systemic innate immune responses in the teleost gilthead seabream after intraperitoneal injection of whole yeast cells.

    PubMed

    Cuesta, Alberto; Rodríguez, Alejandro; Salinas, Irene; Meseguer, José; Esteban, M Angeles

    2007-03-01

    The early cellular innate immune responses of the teleost gilthead seabream (Sparus aurata L.) against whole yeast cells were studied. Fish received a single intraperitoneal (i.p.) injection of Saccharomyces cerevisiae and leukocyte mobilization, degranulation, peroxidase content, respiratory burst, phagocytic and cytotoxic activities were assayed in both head-kidney leukocytes (HKLs) and peritoneal exudate leukocytes (PELs). The total number of PELs significantly increased from 4 h post-injection until the end of the experiment (3 days). Interestingly, flow cytometric analysis revealed variations in the proportion of cell-types in the PE. Thus, PE acidophilic granulocytes increased to a significant extent 4 h post-injection and were restored thereafter. Moreover, PE monocyte-macrophages started to increase from 24 h, the enhancement being statistically significant after 48 and 72 h. Degranulation was greater in PELs throughout the assay. The peroxidase content of the leukocytes was affected differently in HKLs and PELs. The respiratory burst activity was not affected in HKLs but significantly increased in PELs from 4 to 48 h post-injection with yeast cells. On the other hand, HKL phagocytosis had decreased 72 h post-injection with yeast cells while it increased after 4 and 24 h post-injection in the PELs. Conversely, the cytotoxic activity was significantly enhanced in HKLs from 24 to 72 h post-injection but slightly decreased in PELs. Finally, our data demonstrate that seabream injected with the yeast Saccharomyces cerevisiae show leukocyte mobilization and cellular innate immune response activation at the site of invasion and also in the head-kidney. The implications of the leukocyte-types and the immune responses observed, as well as analogies with other particulated antigens, will be discussed as possible models for investigating the effect of potential pathogens.

  7. Early Program Development

    NASA Image and Video Library

    1969-01-01

    This 1969 artist's concept illustrates the use of three major elements of NASA's Integrated program, as proposed by President Nixon's Space Task Group. In Phases I and II, a Space Tug with a manipulator-equipped crew module removes a cargo module from an early Space Shuttle Orbiter and docks with it. In Phases III and IV, the Space Tug with attached cargo module flys toward a Nuclear Shuttle. As a result of the Space Task Group's recommendations for more commonality and integration in the American space program, Marshall Space Flight Center engineers studied many of the spacecraft depicted here.

  8. Early experience and brain development.

    PubMed

    Bick, Johanna; Nelson, Charles A

    2017-01-01

    Healthy brain development takes place within the context of individual experience. Here, we describe how certain early experiences are necessary for typical brain development. We present evidence from multiple studies showing that severe early life neglect leads to alterations in brain development, which compromises emotional, behavioral, and cognitive functioning. We also show how early intervention can reverse some of the deleterious effects of neglect on brain development. We conclude by emphasizing that early interventions that start at the earliest possible point in human development are most likely to support maximal recovery from early adverse experiences. WIREs Cogn Sci 2017, 8:e1387. doi: 10.1002/wcs.1387 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  9. CRITICAL READING DEVELOPS EARLY.

    ERIC Educational Resources Information Center

    LEE, DORRIS; AND OTHERS

    THIS ISSUE OF THE READING AIDS SERIES PRESENTS A DISCUSSION OF THE POTENTIAL FOR CRITICAL READING AMONG YOUNG CHILDREN AND HOW IT CAN BE DEVELOPED. IT OFFERS SUGGESTIONS FOR THE MAXIMUM DEVELOPMENT OF THINKING SKILLS AND ATTITUDES OF INQUIRY AND EVALUATION. SOME OF THE TOPICS DISCUSSED ARE -- (1) THE DEVELOPMENT OF PERCEPTS, CONCEPTS, AND COMMON…

  10. Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus

    PubMed Central

    Baskin, Carole R.; Bielefeldt-Ohmann, Helle; Tumpey, Terrence M.; Sabourin, Patrick J.; Long, James P.; García-Sastre, Adolfo; Tolnay, Airn-E.; Albrecht, Randy; Pyles, John A.; Olson, Pam H.; Aicher, Lauri D.; Rosenzweig, Elizabeth R.; Murali-Krishna, Kaja; Clark, Edward A.; Kotur, Mark S.; Fornek, Jamie L.; Proll, Sean; Palermo, Robert E.; Sabourin, Carol L.; Katze, Michael G.

    2009-01-01

    The mechanisms responsible for the virulence of the highly pathogenic avian influenza (HPAI) and of the 1918 pandemic influenza virus in humans remain poorly understood. To identify crucial components of the early host response during these infections by using both conventional and functional genomics tools, we studied 34 cynomolgus macaques (Macaca fascicularis) to compare a 2004 human H5N1 Vietnam isolate with 2 reassortant viruses possessing the 1918 hemagglutinin (HA) and neuraminidase (NA) surface proteins, known conveyors of virulence. One of the reassortants also contained the 1918 nonstructural (NS1) protein, an inhibitor of the host interferon response. Among these viruses, HPAI H5N1 was the most virulent. Within 24 h, the H5N1 virus produced severe bronchiolar and alveolar lesions. Notably, the H5N1 virus targeted type II pneumocytes throughout the 7-day infection, and induced the most dramatic and sustained expression of type I interferons and inflammatory and innate immune genes, as measured by genomic and protein assays. The H5N1 infection also resulted in prolonged margination of circulating T lymphocytes and notable apoptosis of activated dendritic cells in the lungs and draining lymph nodes early during infection. While both 1918 reassortant viruses also were highly pathogenic, the H5N1 virus was exceptional for the extent of tissue damage, cytokinemia, and interference with immune regulatory mechanisms, which may help explain the extreme virulence of HPAI viruses in humans. PMID:19218453

  11. Early Program Development

    NASA Image and Video Library

    1970-01-01

    In 1970, NASA initiated Phase A contracts to study alternate Space Shuttle designs in addition to the two-stage fully-reusable Space Shuttle system already under development. A number of alternate systems were developed to ensure the development of the optimum earth-to-orbit system, including the Stage-and-a-half Chemical Interorbital Shuttle, shown here. The concept would utilize a reusable marned spacecraft with an onboard propulsion system attached to an expendable fuel tank to provide supplementary propellants.

  12. The genome of the miiuy croaker reveals well-developed innate immune and sensory systems

    PubMed Central

    Xu, Tianjun; Xu, Guoliang; Che, Rongbo; Wang, Rixin; Wang, Yanjin; Li, Jinrui; Wang, Shanchen; Shu, Chang; Sun, Yuena; Liu, Tianxing; Liu, Jiang; Wang, Aishuai; Han, Jingjing; Chu, Qing; Yang, Qiong

    2016-01-01

    The miiuy croaker, Miichthys miiuy, is a representative Sciaenidae known for its exceptionally large otoliths. This species mainly inhabits turbid aquatic environments with mud to sandy mud bottoms. However, the characteristics of the immune system of this organism and its specific aquatic environment adaptations are poorly understood. Thus, we present a high-quality draft genome of miiuy croaker. The expansions of several gene families which are critical for the fish innate immune system were identified. Compared with the genomes of other fishes, some changes have occurred in the miiuy croaker sensory system including modification of vision and expansion of taste and olfaction receptors. These changes allow miiuy croaker to adapt to the environment during the long-term natural selection. The genome of miiuy croaker may elucidate its relatively well-developed immune defense and provide an adaptation model of the species thriving in turbid deep aquatic environments. PMID:26902509

  13. The genome of the miiuy croaker reveals well-developed innate immune and sensory systems.

    PubMed

    Xu, Tianjun; Xu, Guoliang; Che, Rongbo; Wang, Rixin; Wang, Yanjin; Li, Jinrui; Wang, Shanchen; Shu, Chang; Sun, Yuena; Liu, Tianxing; Liu, Jiang; Wang, Aishuai; Han, Jingjing; Chu, Qing; Yang, Qiong

    2016-02-23

    The miiuy croaker, Miichthys miiuy, is a representative Sciaenidae known for its exceptionally large otoliths. This species mainly inhabits turbid aquatic environments with mud to sandy mud bottoms. However, the characteristics of the immune system of this organism and its specific aquatic environment adaptations are poorly understood. Thus, we present a high-quality draft genome of miiuy croaker. The expansions of several gene families which are critical for the fish innate immune system were identified. Compared with the genomes of other fishes, some changes have occurred in the miiuy croaker sensory system including modification of vision and expansion of taste and olfaction receptors. These changes allow miiuy croaker to adapt to the environment during the long-term natural selection. The genome of miiuy croaker may elucidate its relatively well-developed immune defense and provide an adaptation model of the species thriving in turbid deep aquatic environments.

  14. Family Influences on Early Development.

    ERIC Educational Resources Information Center

    Silber, Sharon

    1989-01-01

    The article reviews the literature concerning family influences on early childhood development. Implications of this literature for intervention planning with high risk children and families are suggested. Topics covered include the early parent-child relationship, disciplinary strategies, stimulation, parental instruction and expectations, the…

  15. Early Program Development

    NASA Image and Video Library

    1963-01-01

    This artist's concept from 1963 shows a proposed NERVA (Nuclear Engine for Rocket Vehicle Application) incorporating the NRX-A1, the first NERVA-type cold flow reactor. The NERVA engine, based on Kiwi nuclear reactor technology, was intended to power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which Marshall Space Flight Center had development responsibility.

  16. Early Program Development

    NASA Image and Video Library

    1971-01-01

    This 1971 artist's concept shows the Nuclear Shuttle in both its lunar logistics configuraton and geosynchronous station configuration. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to lunar orbits or other destinations then return to Earth orbit for refueling and additional missions.

  17. Early Program Development

    NASA Image and Video Library

    1970-01-01

    This 1970 artist's concept shows a Nuclear Shuttle in flight. As envisioned by Marshall Space Flight Center Program Development engineers, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additional missions.

  18. Early Program Development

    NASA Image and Video Library

    1970-01-01

    This artist's concept from 1970 shows a Nuclear Shuttle taking on fuel from an orbiting Liquid Hydrogen Depot. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additional missions.

  19. Early Program Development

    NASA Image and Video Library

    1971-01-01

    This 1971 artist's concept illustrates a proposed Orbital Liquid Hydrogen Depot. As envisioned by Marshall Space Flight Center Program Development persornel, an orbital modular propellant storage depot, supplied periodically by the Space Shuttle or Earth-to-orbit fuel tankers, would be critical in making available large amounts of fuel to various orbital vehicles and spacecraft.

  20. Early Program Development

    NASA Image and Video Library

    1971-01-01

    In this 1971 artist's concept, the Nuclear Shuttle is shown in various space-based applications. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to geosychronous Earth orbits or lunar orbits then return to low Earth orbit for refueling. A cluster of Nuclear Shuttle units could form the basis for planetary missions.

  1. Effect of hen age and maternal vitamin D source on performance, hatchability, bone mineral density, and progeny in vitro early innate immune function.

    PubMed

    Saunders-Blades, J L; Korver, D R

    2015-06-01

    The metabolite 25-hydroxy vitamin D3 (25-OHD) can complement or replace vitamin D3 in poultry rations, and may influence broiler production and immune function traits. The effect of broiler breeder dietary 25-OHD on egg production, hatchability, and chick early innate immune function was studied. We hypothesized that maternal dietary 25-OHD would support normal broiler breeder production and a more mature innate immune system of young chicks. Twenty-three-week-old Ross 308 hens (n=98) were placed in 4 floor pens and fed either 2,760 IU vitamin D3 (D) or 69 μg 25-OHD/kg feed. Hen weights were managed according to the primary breeder management guide. At 29 to 31 wk (Early), 46 to 48 wk (Mid), and 61 to 63 wk (Late), hens were artificially inseminated and fertile eggs incubated and hatched. Chicks were placed in cages based on maternal treatment and grown to 7 d age. Innate immune function and plasma 25-OHD were assessed at 1 and 4 d post-hatch on 15 chicks/treatment. Egg production, hen BW, and chick hatch weight were not affected by diet (P>0.05). Total in vitro Escherichia coli (E. coli) killing by 25-OHD chicks was greater than the D chicks at 4 d for the Early and Mid hatches, and 1 and 4 d for the Late hatch. This can be partly explained by the 25-OHD chicks from the Late hatch also having a greater E. coli phagocytic capability. No consistent pattern of oxidative burst response was observed. Chicks from the Mid hatch had greater percent phagocytosis, phagocytic capability, and E. coli killing than chicks from Early and Late hatches. Overall, maternal 25-OHD increased hatchability and in vitro chick innate immunity towards E. coli. Regardless of treatment, chicks from Late and Early hens had weaker early innate immune responses than chicks from Mid hens. The hen age effect tended to be the greatest factor influencing early chick innate immunity, but maternal 25-OHD also increased several measures relative to D.

  2. Early Program Development

    NASA Image and Video Library

    2004-04-15

    This artist's concept illustrates the NERVA (Nuclear Engine for Rocket Vehicle Application) engine's hot bleed cycle in which a small amount of hydrogen gas is diverted from the thrust nozzle, thus eliminating the need for a separate system to drive the turbine. The NERVA engine, based on KIWI nuclear reactor technology, would power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which the Marshall Space Flight Center had development responsibility.

  3. Early Program Development

    NASA Image and Video Library

    1970-01-01

    In this 1970 artist's concept, the Nuclear Shuttle is shown in its lunar and geosynchronous orbit configuration and in its planetary mission configuration. As envisioned by Marshall Space Flight Center Program Development plarners, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling. A cluster of Nuclear Shuttle units could form the basis for planetary missions.

  4. Early Program Development

    NASA Image and Video Library

    1996-06-20

    Engineers at one of MSFC's vacuum chambers begin testing a microthruster model. The purpose of these tests are to collect sufficient data that will enabe NASA to develop microthrusters that will move the Space Shuttle, a future space station, or any other space related vehicle with the least amount of expended energy. When something is sent into outer space, the forces that try to pull it back to Earth (gravity) are very small so that it only requires a very small force to move very large objects. In space, a force equal to a paperclip can move an object as large as a car. Microthrusters are used to produce these small forces.

  5. Biomechanics of Early Cardiac Development

    PubMed Central

    Goenezen, Sevan; Rennie, Monique Y.

    2012-01-01

    Biomechanics affect early cardiac development, from looping to the development of chambers and valves. Hemodynamic forces are essential for proper cardiac development, and their disruption leads to congenital heart defects. A wealth of information already exists on early cardiac adaptations to hemodynamic loading, and new technologies, including high resolution imaging modalities and computational modeling, are enabling a more thorough understanding of relationships between hemodynamics and cardiac development. Imaging and modeling approaches, used in combination with biological data on cell behavior and adaptation, are paving the road for new discoveries on links between biomechanics and biology and their effect on cardiac development and fetal programming. PMID:22760547

  6. Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system

    PubMed Central

    Erlebacher, Adrian; Zhang, Dorothy; Parlow, Albert F.; Glimcher, Laurie H.

    2004-01-01

    We describe a murine model of early pregnancy failure induced by systemic activation of the CD40 immune costimulatory pathway. Although fetal loss involved an NK cell intermediate, it was not due to lymphocyte-mediated destruction of the fetus and placenta. Rather, pregnancy failure resulted from impaired progesterone synthesis by the corpus luteum of the ovary, an endocrine defect in turn associated with ovarian resistance to the gonadotropic effects of prolactin. Pregnancy failure also required the proinflammatory cytokine TNF-α and correlated with the luteal induction of the prolactin receptor signaling inhibitors suppressor of cytokine signaling 1 (Socs1) and Socs3. Such links between immune activation and reproductive endocrine dysfunction may be relevant to pregnancy loss and other clinical disorders of reproduction. PMID:15232610

  7. Bcl11b is essential for group 2 innate lymphoid cell development

    PubMed Central

    Oliphant, Christopher J.; Englezakis, Alexandros; Yu, Yong; Clare, Simon; Rodewald, Hans-Reimer; Belz, Gabrielle; Liu, Pentao; Fallon, Padraic G.

    2015-01-01

    Group 2 innate lymphoid cells (ILC2s) are often found associated with mucosal surfaces where they contribute to protective immunity, inappropriate allergic responses, and tissue repair. Although we know they develop from a common lymphoid progenitor in the bone marrow (BM), the specific lineage path and transcriptional regulators that are involved are only starting to emerge. After ILC2 gene expression analysis we investigated the role of Bcl11b, a factor previously linked to T cell commitment, in ILC2 development. Using combined Bcl11b-tom and Id2-gfp reporter mice, we show that Bcl11b is expressed in ILC2 precursors in the BM and maintained in mature ILC2s. In vivo deletion of Bcl11b, by conditional tamoxifen-induced depletion or by Bcl11b−/− fetal liver chimera reconstitution, demonstrates that ILC2s are wholly dependent on Bcl11b for their development. Notably, in the absence of Bcl11b there is a concomitant expansion of the RORγt+ ILC3 population, suggesting that Bcl11b may negatively regulate this lineage. Using Nippostrongylus brasiliensis infection, we reveal that the absence of Bcl11b leads to impaired worm expulsion, caused by a deficit in ILC2s, whereas Citrobacter rodentium infection is cleared efficiently. These data clearly establish Bcl11b as a new factor in the differentiation of ILC2s. PMID:25964370

  8. Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity.

    PubMed

    Buschor, Stefanie; Cuenca, Miguelangel; Uster, Stephanie S; Schären, Olivier P; Balmer, Maria L; Terrazos, Miguel A; Schürch, Christian M; Hapfelmeier, Siegfried

    2017-06-01

    Citrobacter rodentium infection is a mouse model for the important human diarrheal infection caused by enteropathogenic E. coli (EPEC). The pathogenesis of both species is very similar and depends on their unique ability to form intimately epithelium-adherent microcolonies, also known as "attachment/effacement" (A/E) lesions. These microcolonies must be dynamic and able to self-renew by continuous re-infection of the rapidly regenerating epithelium. It is unknown whether sustained epithelial A/E lesion pathogenesis is achieved through re-infection by planktonic bacteria from the luminal compartment or local spread of sessile bacteria without a planktonic phase. Focusing on the earliest events as C. rodentium becomes established, we show here that all colonic epithelial A/E microcolonies are clonal bacterial populations, and thus depend on local clonal growth to persist. In wild-type mice, microcolonies are established exclusively within the first 18 hours of infection. These early events shape the ongoing intestinal geography and severity of infection despite the continuous presence of phenotypically virulent luminal bacteria. Mechanistically, induced resistance to A/E lesion de-novo formation is mediated by TLR-MyD88/Trif-dependent signaling and is induced specifically by virulent C. rodentium in a virulence gene-dependent manner. Our data demonstrate that the establishment phase of C. rodentium pathogenesis in vivo is restricted to a very short window of opportunity that determines both disease geography and severity.

  9. Epigenetics of Early Child Development

    PubMed Central

    Murgatroyd, Chris; Spengler, Dietmar

    2011-01-01

    Comprehensive clinical studies show that adverse conditions in early life can severely impact the developing brain and increase vulnerability to mood disorders later in life. During early postnatal life the brain exhibits high plasticity which allows environmental signals to alter the trajectories of rapidly developing circuits. Adversity in early life is able to shape the experience-dependent maturation of stress-regulating pathways underlying emotional functions and endocrine responses to stress, such as the hypothalamo–pituitary–adrenal (HPA) system, leading to long-lasting altered stress responsivity during adulthood. To date, the study of gene–environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene–environment interactions can predispose individuals toward psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene–environment dialog in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give rise to lasting epigenetic marks conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions. PMID:21647402

  10. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    PubMed

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. The ontogeny of immunity: development of innate immune strength in the honey bee (Apis mellifera).

    PubMed

    Wilson-Rich, Noah; Dres, Stephanie T; Starks, Philip T

    2008-01-01

    Honey bees (Apis mellifera) are of vital economic and ecological importance. These eusocial animals display temporal polyethism, which is an age-driven division of labor. Younger adult bees remain in the hive and tend to developing brood, while older adult bees forage for pollen and nectar to feed the colony. As honey bees mature, the types of pathogens they experience also change. As such, pathogen pressure may affect bees differently throughout their lifespan. We provide the first direct tests of honey bee innate immune strength across developmental stages. We investigated immune strength across four developmental stages: larvae, pupae, nurses (1-day-old adults), and foragers (22-30 days old adults). The immune strength of honey bees was quantified using standard immunocompetence assays: total hemocyte count, encapsulation response, fat body quantification, and phenoloxidase activity. Larvae and pupae had the highest total hemocyte counts, while there was no difference in encapsulation response between developmental stages. Nurses had more fat body mass than foragers, while phenoloxidase activity increased directly with honey bee development. Immune strength was most vigorous in older, foraging bees and weakest in young bees. Importantly, we found that adult honey bees do not abandon cellular immunocompetence as has recently been proposed. Induced shifts in behavioral roles may increase a colony's susceptibility to disease if nurses begin foraging activity prematurely.

  12. Is Early Pragmatic Development Measurable?

    ERIC Educational Resources Information Center

    Dale, Philip S.

    1980-01-01

    Measures of pragmatic development for children in the second year of life were developed based on a 30-minute language sample drawn from 20 children. Results support the view that the range of pragmatic functions grows steadily during the one-word and early two-word stage and that it is measurable. (Author/AM)

  13. Early clearance of Chikungunya virus in children is associated with a strong innate immune response.

    PubMed

    Simarmata, Diane; Ng, David Chun Ern; Kam, Yiu-Wing; Lee, Bernett; Sum, Magdline Sia Henry; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Cardosa, Jane; Perera, David; Ooi, Mong H; Ng, Lisa F P

    2016-05-16

    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.

  14. Early clearance of Chikungunya virus in children is associated with a strong innate immune response

    PubMed Central

    Simarmata, Diane; Ng, David Chun Ern; Kam, Yiu-Wing; Lee, Bernett; Sum, Magdline Sia Henry; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Cardosa, Jane; Perera, David; Ooi, Mong H.; Ng, Lisa F. P.

    2016-01-01

    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children. PMID:27180811

  15. The role of the innate immune response regulatory gene ABCF1 in mammalian embryogenesis and development.

    PubMed

    Wilcox, Sara M; Arora, Hitesh; Munro, Lonna; Xin, Jian; Fenninger, Franz; Johnson, Laura A; Pfeifer, Cheryl G; Choi, Kyung Bok; Hou, Juan; Hoodless, Pamela A; Jefferies, Wilfred A

    2017-01-01

    ABCF1 is an ABC transporter family protein that has been shown to regulate innate immune response and is a risk gene for autoimmune pancreatitis and arthritis. Unlike other members of ABC transporter family, ABCF1 lacks trans-membrane domains and is thought to function in translation initiation through an interaction with eukaryotic translation initiation factor 2 (eIF2). To study ABCF1 expression and function in development and disease, we used a single gene trap insertion in the Abcf1 gene in murine embryonic stem cells (ES cells) that allowed lineage tracing of the endogenous Abcf1 promoter by following the expression of a β-galactosidase reporter gene. From the ES cells, heterozygous mice (Abcf1+/-) were produced. No live born Abcf1-/- progeny were ever generated, and the lethality was not mouse strain-specific. Thus, we have determined that Abcf1 is an essential gene in development. Abcf1-/- mice were found to be embryonic lethal at 3.5 days post coitum (dpc), while Abcf1+/- mice appeared developmentally normal. Abcf1+/- mice were fertile and showed no significant differences in their anatomy when compared with their wild type littermates. The Abcf1 promoter was found to be active in all organs in adult mice, but varies in levels of expression in specific cell types within tissues. Furthermore, we observed high promoter activity in the blastocysts and embryos. Overall, Abcf1 expression in embryos is required for development and its expression in adults was highly correlated with actively proliferating and differentiating cell types.

  16. Toll-like receptors in antiviral innate immunity

    PubMed Central

    Lester, Sandra N.; Li, Kui

    2014-01-01

    Toll-like receptors (TLRs) are fundamental sensor molecules of the host innate immune system, which detect conserved molecular signatures of a wide range of microbial pathogens and initiate innate immune responses via distinct signaling pathways. Various TLRs are implicated in the early interplay of host cells with invading viruses, which regulates viral replication and/or host responses, ultimately impacting on viral pathogenesis. To survive the host innate defense mechanisms, many viruses have developed strategies to evade or counteract signaling through the TLR pathways, creating an advantageous environment for their propagation. Here we review the current knowledge of the roles TLRs play in antiviral innate immune responses, discuss examples of TLR-mediated viral recognition, and describe strategies used by viruses to antagonize the host antiviral innate immune responses. PMID:24316048

  17. Statistical Modeling Using Early Markers of Innate Immunity to Explain Variation in Humoral Responses to Influenza Vaccine in Older Adults

    PubMed Central

    Kennedy, Richard B.; Tosh, Pritish K.; Goergen, Krista M.; Grill, Diane E.; Oberg, Ann L.; Poland, Gregory A.

    2015-01-01

    Greater understanding of the factors associated with a protective response to influenza vaccine in older adults could have tremendous public health benefits. We studied 158 participants age 50–74 years vaccinated with 2010–2011 inactivated influenza vaccine and performed innate immunity and humoral immunity assays directed against influenza A/California/2009 (H1N1) as measured through hemagglutination inhibition (HAI), microneutralization, and B cell ELISPOT at days 0, 3, and 28 postvaccination. We report the results of statistical modeling using Day 3 cytokines, chemokines, and innate cell populations to model Day 0 to Day 28 HAI seroconversion, viral neutralization seroconversion, and B cell ELISPOT results. PMID:26087295

  18. Choreography of early thalamocortical development.

    PubMed

    Molnár, Zoltán; Higashi, Shuji; López-Bendito, Guillermina

    2003-06-01

    Thalamic axons, which carry most of the information from the sensory environment, are amongst the first projections to reach the cerebral cortex during embryonic development. It has been proposed that the scaffold of early generated cells in the ventral thalamus, internal capsule and preplate play a pivotal role in their deployment through sharp gene expression boundaries. These ideas were recently evaluated in various strains of mutant mice. In Tbr1, Gbx2, Pax6 KO both thalamic and corticofugal projections fail to traverse the striatocortical junction. In both Emx2 and Pax6 KO brains, the misrouted thalamic afferents are accompanied by displacements of the pioneering projections from the internal capsule. Regardless of their altered route, thalamic afferents in the reeler and L1 KO mice seem to be able to redistribute themselves on the cortical sheet and establish normal periphery-related representation in the somatosensory cortex. Early neural activity delivered through the thalamic projections is thought to be involved in the realignment process of thalamic axons at the time of their accumulation in the subplate layer. However, axonal growth and the early topographic arrangement of thalamocortical fiber pathways appear normal in the Snap25 KO, where action potential mediated synaptic vesicle release is disrupted. We therefore suggest that intercellular communication mediated by constitutive secretion of transmitters or growth factors might play a dominant role during early thalamocortical development.

  19. Early prosocial development across cultures.

    PubMed

    Callaghan, Tara; Corbit, John

    2017-08-17

    Human prosociality is ubiquitous, even though it may be manifested differently across cultures. Low cost helping and sharing emerge early in development, and at similar levels, across cultures having vastly different sociocultural niches. Developmental trajectories for costly sharing diverge across cultures around middle childhood, in line with differences in the sociocultural niches that children experience. Cultural developmental research has focussed primarily on the emergence and development of prosocial behaviour, and would benefit from an examination of the interplay between psychological (cognitive, motivational) and sociocultural (norms, developmental niche) foundations over ontogeny. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Arguing about innateness.

    PubMed

    Valian, Virginia

    2014-07-01

    This paper lays out the components of a language acquisition model, the interconnections among the components, and the differing stances of nativism and empiricism about syntax. After demonstrating that parsimony cannot decide between the two stances, the paper analyzes nine examples of evidence that have been used to argue for or against nativism, concluding that most pieces of evidence are either irrelevant or suggest that language is special but need not invoke innate ideas. Two pieces of evidence - the development of home sign languages and the acquisition of Determiners - do show not just that language is special but that the child has innate syntactic content. The existential claim that nativism makes - there is at least one innate syntactic idea - is an easier claim to verify than the universal claim that empiricism makes - there are no innate syntactic ideas.

  1. Curating the innate immunity interactome

    PubMed Central

    2010-01-01

    Background The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity. Results Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity. Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response. Conclusions In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity. PMID:20727158

  2. Innate Immune Memory: Activation of Macrophage Killing Ability by Developmental Duties.

    PubMed

    Schneider, David; Tate, Ann Thomas

    2016-06-20

    Innate immune systems in many taxa exhibit hallmarks of memory in response to previous microbial exposure. A new study demonstrates that innate immune memory in Drosophila embryonic macrophages can also be induced by the successful engulfment of apoptotic cells, highlighting the importance of early exposure events for developing responsive immune systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Innate immunity dictates cytokine polarization relevant to the development of pulmonary fibrosis

    PubMed Central

    Strieter, Robert M.; Keane, Michael P.

    2004-01-01

    New data support the importance of the innate immune response in the resolution or progression of pulmonary fibrosis. The presence of CXC chemokine receptor 3–expressing cells, specifically pulmonary NK cells, is necessary to produce IFN-γ. This is critical in the polarization of the immune response to injury toward a favorable Th1 response and resolution. In contrast, a Th2 response is associated with progressive fibrosis. PMID:15254582

  4. Innate Immunity to Adenovirus

    PubMed Central

    Hendrickx, Rodinde; Stichling, Nicole; Koelen, Jorien; Kuryk, Lukasz; Lipiec, Agnieszka

    2014-01-01

    Abstract Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate–adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features. PMID:24512150

  5. Innate immunity to adenovirus.

    PubMed

    Hendrickx, Rodinde; Stichling, Nicole; Koelen, Jorien; Kuryk, Lukasz; Lipiec, Agnieszka; Greber, Urs F

    2014-04-01

    Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate-adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features.

  6. Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands

    PubMed Central

    2014-01-01

    The commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogen Klebsiella pneumoniae. After microbiota depletion, early clearance of K. pneumoniae was impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTriDAP and NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll-like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species-mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues. PMID:25135683

  7. Early steps in neural development.

    PubMed

    Callebaut, Marc; Van Nueten, Emmy; Van Passel, Hanalie; Harrisson, Fernand; Bortier, Hilde

    2006-07-01

    We studied early neurulation events in vitro by transplanting quail Hensen's node, central prenodal regions (before the nodus as such develops), or upper layer parts of it on the not yet definitively committed upper layer of chicken anti-sickle regions (of unincubated blastoderms), eventually associated with central blastoderm fragments. We could demonstrate by this quail-chicken chimera technique that after the appearance of a pronounced thickening of the chicken upper layer by the early inductive effect of neighboring endophyll, a floor plate forms by insertion of Hensen's node-derived quail cells into the median part of the groove. This favors, at an early stage, the floor plate "allocation" model that postulates a common origin for notochord and median floor plate cells from the vertebrate's secondary major organizer (Hensen's node in this case). A comparison is made with results obtained after transplantation of similar Hensen's nodes in isolated chicken endophyll walls or with previously obtained results after the use of the grafting procedure in the endophyll walls of whole chicken blastoderms.

  8. [Early childhood growth and development].

    PubMed

    Arce, Melitón

    2015-01-01

    This article describes and discusses issues related to the process of childhood growth and development, with emphasis on the early years, a period in which this process reaches critical speed on major structures and functions of the human economy. We reaffirm that this can contribute to the social availability of a generation of increasingly better adults, which in turn will be able to contribute to building a better world and within it a society that enjoys greater prosperity. In the first chapter, we discuss the general considerations on the favorable evolution of human society based on quality of future adults, meaning the accomplishments that today’s children will gain. A second chapter mentions the basics of growth and development in the different fields and the various phenomena that occur in it. In the third we refer to lost opportunities and negative factors that can affect delaying the process and thereby result in not obtaining the expected accomplishments. In the fourth, conclusions and recommendations are presented confirming the initial conception that good early child care serves to build a better society and some recommendations are formulated to make it a good practice.

  9. Establishing Pluripotency in Early Development

    PubMed Central

    Paranjpe, Sarita S.; Veenstra, Gert Jan C.

    2015-01-01

    The earliest steps of embryonic development involve important changes in chromatin and transcription factor networks, which are orchestrated to establish pluripotent cells that will form the embryo. DNA methylation, histone modifications, the pluripotency regulatory network of transcription factors, maternal factors and newly translated proteins all contribute to these transitions in dynamic ways. Moreover, these dynamics are linked to the onset of zygotic transcription. We will review recent progress in our understanding of chromatin state and regulation of gene expression in the context of embryonic development in vertebrates, in particular mouse, Xenopus and zebrafish. We include work on mouse embryonic stem cells and highlight work that illustrates how early embryonic dynamics establish gene regulatory networks and the state of pluripotency. PMID:25857441

  10. Diversity, function, and transcriptional regulation of gut innate lymphocytes

    PubMed Central

    Rankin, Lucille; Groom, Joanna; Mielke, Lisa A.; Seillet, Cyril; Belz, Gabrielle T.

    2013-01-01

    The innate immune system plays a critical early role in host defense against viruses, bacteria, and tumor cells. Until recently, natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were the primary members of the innate lymphocyte family: NK cells form the front-line interface between the external environment and the adaptive immune system, while LTi cells are essential for secondary lymphoid tissue formation. More recently, it has become apparent that the composition of this family is much more diverse than previously appreciated and newly recognized populations play distinct and essential functions in tissue protection. Despite the importance of these cells, the developmental relationships between different innate lymphocyte populations remain unclear. Here we review recent advances in our understanding of the development of different innate immune cell subsets, the transcriptional programs that might be involved in driving fate decisions during development, and their relationship to NK cells. PMID:23508190

  11. Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.

    PubMed

    Wolferstätter, Michael; Schweneker, Marc; Späth, Michaela; Lukassen, Susanne; Klingenberg, Marieken; Brinkmann, Kay; Wielert, Ursula; Lauterbach, Henning; Hochrein, Hubertus; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

    2014-12-01

    Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral

  12. Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

    PubMed Central

    Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

    2015-01-01

    Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

  13. Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).

    PubMed

    Minang, Jacob T; Inglefield, Jon R; Harris, Andrea M; Lathey, Janet L; Alleva, David G; Sweeney, Diane L; Hopkins, Robert J; Lacy, Michael J; Bernton, Edward W

    2014-11-28

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24-48 h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity. Copyright © 2014 The Authors

  14. Enhanced Early Innate and T Cell-mediated Responses in Subjects Immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909)

    PubMed Central

    Minang, Jacob T.; Inglefield, Jon R.; Harris, Andrea M.; Lathey, Janet L.; Alleva, David G.; Sweeney, Diane L.; Hopkins, Robert J; Lacy, Michael J.; Bernton, Edward W.

    2014-01-01

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a Phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax® (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24 to 48 hours after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALC), correlated with transiently increased IP-10. Cellular recall responses to anthrax Protective Antigen (PA) or PA peptides were assessed by IFN-gamma ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25 mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 hours (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity. PMID:24530403

  15. Early influences on the development of food preferences.

    PubMed

    Ventura, Alison K; Worobey, John

    2013-05-06

    The ability to perceive flavors begins in utero with the development and early functioning of the gustatory and olfactory systems. Because both amniotic fluid and breast milk contain molecules derived from the mother's diet, learning about flavors in foods begins in the womb and during early infancy. This early experience serves as the foundation for the continuing development of food preferences across the lifespan, and is shaped by the interplay of biological, social, and environmental factors. Shortly after birth, young infants show characteristic taste preferences: sweet and umami elicit positive responses; bitter and sour elicit negative responses. These taste preferences may reflect a biological drive towards foods that are calorie- and protein-dense and an aversion to foods that are poisonous or toxic. Early likes and dislikes are influenced by these innate preferences, but are also modifiable. Repeated exposure to novel or disliked foods that occurs in a positive, supportive environment may promote the acceptance of and eventually a preference for those foods. Alternatively, children who are pressured to eat certain foods may show decreased preference for those foods later on. With increasing age, the influence of a number of factors, such as peers and food availability, continue to mold food preferences and eating behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Innate microbial sensors and their relevance to allergy.

    PubMed

    Liu, Andrew H

    2008-11-01

    The innate immune system oversees the gateway to immunity with its microbial sensors. Innate microbial sensors are germ line-encoded receptors with genetically predetermined specificities for microbes. The readiness and effectiveness of the innate immune system to provide immediate and appropriate responses at the host-environment interface is dependent on its sensitive and comprehensive microbial detection systems. The purpose of this review is to provide an overview of innate microbial sensors, our growing understanding of their diverse repertoire, and their elegant structural and functional approaches to microbial recognition. Their relevance to allergic disease is also discussed: the potential recognition and uptake of allergens by some of these receptors, inhibited expression of other microbial sensors by allergic immune responses and inflammation, and their upregulation by microbial exposures in early life that may help to protect against the development of allergic immune responses and disease.

  17. Taiwanese Early Childhood Educators' Professional Development

    ERIC Educational Resources Information Center

    Hsu, Ching-Yun

    2008-01-01

    This study was designed based on a qualitative paradigm to explore the professional development of Taiwanese early childhood educators. The method of phenomenology was employed. The main research question addressed was "How do early childhood educators construe their professional development experience?" Seven Taiwanese early childhood…

  18. Innate Memory T cells

    PubMed Central

    Jameson, Stephen C.; Lee, You Jeong; Hogquist, Kristin A.

    2015-01-01

    Memory T cells are usually considered to be a feature of a successful immune response against a foreign antigen, and such cells can mediate potent immunity. However, in mice, alternative pathways have been described, through which naïve T cells can acquire the characteristics and functions of memory T cells without encountering specific foreign antigen or the typical signals required for conventional T cell differentiation. Such cells reflect a response to the internal rather the external environment, and hence such cells are called innate memory T cells. In this review, we describe how innate memory subsets were identified, the signals that induce their generation and their functional properties and potential role in the normal immune response. The existence of innate memory T cells in mice raises questions about whether parallel populations exist in humans, and we discuss the evidence for such populations during human T cell development and differentiation. PMID:25727290

  19. Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

    PubMed

    Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

    2015-04-01

    Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing.

  20. Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development

    NASA Astrophysics Data System (ADS)

    Leeansyah, Edwin; Loh, Liyen; Nixon, Douglas F.; Sandberg, Johan K.

    2014-01-01

    Innate-like, evolutionarily conserved MR1-restricted mucosa-associated invariant T (MAIT) cells represent a large antimicrobial T-cell subset in humans. Here, we investigate the development of these cells in second trimester human fetal tissues. MAIT cells are rare and immature in the fetal thymus, spleen and mesenteric lymph nodes. In contrast, mature IL-18Rα+ CD8αα MAIT cells are enriched in the fetal small intestine, liver and lung. Independently of localization, MAIT cells express CD127 and Ki67 in vivo and readily proliferate in response to Escherichia coli in vitro. Maturation is accompanied by the gradual post-thymic acquisition of the PLZF transcription factor and the ability to produce IFNγ and IL-22 in response to bacteria in mucosa. Thus, MAIT cells acquire innate-like antimicrobial responsiveness in mucosa before exposure to environmental microbes and the commensal microflora. Establishment of this arm of immunity before birth may help protect the newborn from a range of pathogenic microbes.

  1. Early Childhood Development Policy Advances in Uganda

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2012-01-01

    Knowledge of the history and development of early childhood development in Uganda is paramount if we are to know how far we have come and where we are going. This article explores the introduction of early childhood development in Ugandan policy and government interventions from 1960 to 2011. Data was obtained from a review of available early…

  2. Early Childhood Development Policy Advances in Uganda

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2012-01-01

    Knowledge of the history and development of early childhood development in Uganda is paramount if we are to know how far we have come and where we are going. This article explores the introduction of early childhood development in Ugandan policy and government interventions from 1960 to 2011. Data was obtained from a review of available early…

  3. Cutting edge: Ly9 (CD229), a SLAM family receptor, negatively regulates the development of thymic innate memory-like CD8+ T and invariant NKT cells.

    PubMed

    Sintes, Jordi; Cuenca, Marta; Romero, Xavier; Bastos, Ricardo; Terhorst, Cox; Angulo, Ana; Engel, Pablo

    2013-01-01

    Signaling lymphocytic activation molecule family receptors and the specific adapter signaling lymphocytic activation molecule-associated protein modulate the development of innate-like lymphocytes. In this study, we show that the thymus of Ly9-deficient mice contains an expanded population of CD8 single-positive cells with the characteristic phenotype of innate memory-like CD8(+) T cells. Moreover, the proportion of these innate CD8(+) T cells increased dramatically postinfection with mouse CMV. Gene expression profiling of Ly9-deficient mice thymi showed a significant upregulation of IL-4 and promyelocytic leukemia zinc finger. Analyses of Ly9(-/-)IL4ra(-/-) double-deficient mice revealed that IL-4 was needed to generate the thymic innate CD8(+) T cell subset. Furthermore, increased numbers of invariant NKT cells were detected in Ly9-deficient thymi. In wild-type mice, IL-4 levels induced by α-galactosylceramide injection could be inhibited by a mAb against Ly9. Thus, Ly9 plays a unique role as an inhibitory cell surface receptor regulating the size of the thymic innate CD8(+) T cell pool and the development of invariant NKT cells.

  4. Ly9 (CD229), a SLAM family receptor, negatively regulates the development of thymic innate memory-like CD8+ T and iNKT cells

    PubMed Central

    Sintes, Jordi; Cuenca, Marta; Romero, Xavier; Bastos, Ricardo; Terhorst, Cox; Angulo, Ana; Engel, Pablo

    2012-01-01

    Signaling lymphocytic activation molecule family (SLAMF) receptors and the specific adapter SLAM-associated protein (SAP) modulate the development of innate-like lymphocytes. Here, we show that the thymus of Ly9-deficient mice contains an expanded population of CD8 single-positive cells with the characteristic phenotype of innate memory-like CD8+ T-cells. Moreover, the proportion of these innate CD8+ T-cells increased dramatically after infection with mouse cytomegalovirus. Gene expression profiling of Ly9-deficient mice thymi showed a significant up-regulation of IL-4 and PLZF. Analyses of Ly9−/−IL4ra−/− double-deficient mice revealed that IL-4 was needed to generate the thymic innate CD8+ T-cell subset. Furthermore, increased numbers of iNKT cells were detected in Ly9-deficient thymi. In wild-type mice IL-4 levels induced by αGalCer injection could be inhibited by a monoclonal antibody against Ly9. Thus, Ly9 plays a unique role as an inhibitory cell-surface receptor regulating the size of the thymic innate CD8+ T-cell pool and the development of iNKT cells. PMID:23225888

  5. Innate cellular immunity and xenotransplantation

    PubMed Central

    Wang, Hui; Yang, Yong-Guang

    2012-01-01

    Purpose of review This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity. Recent findings Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia. Summary Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation. PMID:22262106

  6. Habitat odor can alleviate innate stress responses in mice.

    PubMed

    Matsukawa, Mutsumi; Imada, Masato; Aizawa, Shin; Sato, Takaaki

    2016-01-15

    Predatory odors, which can induce innate fear and stress responses in prey species, are frequently used in the development of animal models for several psychiatric diseases including post-traumatic stress disorder (PTSD) following a life-threatening event. We have previously shown that odors can be divided into at least three types; odors that act as (1) innate stressors, (2) as innate relaxants, or (3) have no innate effects on stress responses. Here, we attempted to verify whether an artificial odor, which had no innate effect on predatory odor-induced stress, could alleviate stress if experienced in early life as a habitat odor. In the current study, we demonstrated that the innate responses were changed to counteract stress following a postnatal experience. Moreover, we suggest that inhibitory circuits involved in stress-related neuronal networks and the concentrations of norepinephrine in the hippocampus may be crucial in alleviating stress induced by the predatory odor. Overall, these findings may be important for understanding the mechanisms involved in differential odor responses and also for the development of pharmacotherapeutic interventions that can alleviate stress in illnesses like PTSD.

  7. Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status

    PubMed Central

    Willing, Benjamin P.; Croxen, Matthew A.; Dufour, Nicolas; Dion, Sara; Wachtel, Sarah; Denamur, Erick; Finlay, B. Brett

    2016-01-01

    Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity. PMID:27096607

  8. Progressive Changes in CXCR4 Expression That Define Thymocyte Positive Selection Are Dispensable For Both Innate and Conventional αβT-cell Development.

    PubMed

    Lucas, Beth; White, Andrea J; Parnell, Sonia M; Henley, Peter M; Jenkinson, William E; Anderson, Graham

    2017-07-11

    The ordered migration of immature thymocytes through thymic microenvironments generates both adaptive MHC restricted αβT-cells and innate CD1d-restricted iNKT-cells. While several chemokine receptors and ligands control multiple stages of this process, their involvement during early thymocyte development often precludes direct analysis of potential roles during later developmental stages. For example, because of early lethality of CXCR4(-/-) mice, and stage-specific requirements for CXCR4 in thymus colonisation and pre-TCR mediated selection, its role in thymic positive selection is unclear. Here we have examined CXCR4-CXCL12 interactions during the maturation of CD4(+)CD8(+) thymocytes, including downstream stages of iNKT and αβT-cell development. We show CXCL12 expression is a common feature of cortical thymic epithelial cells, indicating widespread availability throughout the cortex. Moreover, CXCR4 expression by CD4(+)CD8(+) pre-selection thymocytes is progressively downregulated following both MHC and CD1d-restricted thymic selection events. However, using CD4(Cre)-mediated deletion to bypass its involvement in CD4(-)CD8(-) thymocyte development, we show CXCR4 is dispensable for the maintenance and intrathymic positioning of CD4(+)CD8(+) thymocytes, and their ability to generate mature αβT-cells and CD1d-restricted iNKT-cells. Collectively, our data define dynamic changes in CXCR4 expression as a marker for intrathymic selection events, and show its role in T-cell development is restricted to pre-CD4(+)CD8(+) stages.

  9. ID'ing innate and innate-like lymphoid cells.

    PubMed

    Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L

    2014-09-01

    The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. ID’ing Innate and Innate-like Lymphoid Cells

    PubMed Central

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  11. The Development of STAR Early Literacy. Report.

    ERIC Educational Resources Information Center

    School Renaissance Inst., Inc., Madison, WI.

    This report describes the development and testing of a computerized early literacy diagnostic assessment for students in prekindergarten to grade 3 that can measure skills across a variety of preliteracy and reading domains. The STAR Early Literacy assessment was developed by a team of more than 50 people, including literacy experts,…

  12. Critical Issues in Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Zaslow, Martha, Ed.; Martinez-Beck, Ivelisse, Ed.

    2005-01-01

    Effective teaching leads to positive student outcomes, and professional development for early childhood teachers is key to improving both. But what exactly is meant by "professional development"? What effect does it have on school readiness? Which models and approaches really work? This is the book the early childhood field needs to take the…

  13. Critical Issues in Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Zaslow, Martha, Ed.; Martinez-Beck, Ivelisse, Ed.

    2005-01-01

    Effective teaching leads to positive student outcomes, and professional development for early childhood teachers is key to improving both. But what exactly is meant by "professional development"? What effect does it have on school readiness? Which models and approaches really work? This is the book the early childhood field needs to take the…

  14. Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

    USGS Publications Warehouse

    Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

    2013-01-01

    The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

  15. IFN-γ, produced by NK cells that infiltrate liver allografts early after transplantation, links the innate and adaptive immune responses1

    PubMed Central

    Obara, Hideaki; Nagasaki, Kazuhito; Hsieh, Christine L.; Ogura, Yasuhiro; Esquivel, Carlos O.; Martinez, Olivia M.; Krams, Sheri M.

    2005-01-01

    The role of NK cells following solid organ transplantation remains unclear. We examined NK cells in acute allograft rejection using a high responder model (DA → Lewis) of rat orthotopic liver transplantation. Recipient-derived NK cells infiltrated liver allografts early after transplantation. Since chemokines are important in the trafficking of cells to areas of inflammation, we determined the intragraft expression of chemokines known to attract NK cells. CCL3 was significantly increased in allografts at 6 h post-transplant as compared to syngeneic grafts whereas CCL2 and CXCL10 were elevated in both syngeneic and allogeneic grafts. CXCL10 and CX3CL1 were significantly upregulated in allografts by day three post-transplant as compared to syngeneic grafts suggesting a role for these chemokines in the recruitment of effector cells to allografts. Graft-infiltrating NK cells were shown to be a major source of IFNγ and IFNγ levels in the serum were markedly increased, specifically in allograft recipients, by day three post-transplant. Accordingly, in the absence of NK cells the levels of IFNγ were significantly decreased. Furthermore, graft survival was significantly prolonged. These data suggest that IFNγ-producing NK cells are an important link between the innate and adaptive immune responses early after transplantation. PMID:16095488

  16. Development of immunity in early life.

    PubMed

    Goenka, Anu; Kollmann, Tobias R

    2015-06-01

    The immune system in early life goes through rapid and radical changes. Early life is also the period with the highest risk of infections. The foetal immune system is programmed to coexist with foreign antigenic influences in utero, and postnatally to rapidly develop a functional system capable of distinguishing helpful microbes from harmful pathogens. Both host genetics and environmental influences shape this dramatic transition and direct the trajectory of the developing immune system into early childhood and beyond. Given the malleability of the immune system in early life, interventions aimed at modulating this trajectory thus have the potential to translate into considerable reductions in infectious disease burden with immediate as well as long-lasting benefit. However, an improved understanding of the underlying molecular drivers of early life immunity is prerequisite to optimise such interventions and transform the window of early life vulnerability into one of opportunity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  17. IFN-γ Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells.

    PubMed

    Han, Mingyuan; Hong, Jun Young; Jaipalli, Suraj; Rajput, Charu; Lei, Jing; Hinde, Joanna L; Chen, Qiang; Hershenson, Natalie M; Bentley, J Kelley; Hershenson, Marc B

    2017-02-01

    Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of 6-day-old mice induces mucous metaplasia and airways hyperresponsiveness, which is dependent on IL-13, IL-25, and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-γ expression, in contrast to mature 8-week-old mice with a robust IFN-γ response, consistent with the notion that deficient IFN-γ production in immature mice permits RV-induced type 2 immune responses. We therefore examined the effects of intranasal IFN-γ administration on RV-induced ILC2 expansion and IL-13 expression in 6-day-old BALB/c and IL-13 reporter mice. Airway responses were assessed by histology, immunofluorescence microscopy, quantitative polymerase chain reaction, ELISA, and flow cytometry. Lung ILC2s were also treated with IFN-γ ex vivo. We found that, compared with untreated RV-infected immature mice, IFN-γ treatment attenuated RV-induced IL-13 and Muc5ac mRNA expression and mucous metaplasia. IFN-γ also reduced ILC2 expansion and the percentage of IL-13-secreting ILC2s. IFN-γ had no effect on the mRNA or protein expression of IL-25, IL-33, or thymic stromal lymphoprotein. Finally, IFN-γ treatment of sorted ILC2s reduced IL-5, IL-13, IL-17RB, ST2, and GATA-3 mRNA expression. We conclude that, in immature mice, IFN-γ inhibits ILC2 expansion and IL-13 expression in vivo and ex vivo, thereby attenuating RV-induced mucous metaplasia. These findings demonstrate the antagonistic function of IFN-γ on ILC2 expansion and gene expression, the absence of which may contribute to the development of an asthma-like phenotype after early-life RV infection.

  18. Online Early Childhood Professional Development: Selected Experiences

    ERIC Educational Resources Information Center

    Olsen, Heather

    2010-01-01

    Early childhood professional development opportunities are expanding rapidly throughout the country. With nearly 12 million children under the age of 5 in some kind of early childhood setting, there is an effort to increase the quality of care and education. In fact, 97% of states require child care professionals to commit to ongoing professional…

  19. Innate immunity.

    PubMed

    Revillard, Jean-Pierre

    2002-01-01

    For more than half a century immunological research has been almost exclusively orientated towards the acquired immune response and the mechanisms of immune tolerance. Major discoveries have enabled us to better understand the functioning of the specific immune system: the structure of antibody molecules, the genetic mechanisms leading to the molecular diversity of B (BCR) and T (TCR) lymphocyte antigen receptors, the biological function of major histocompatibility complex (MHC) molecules in the presentation of peptides to alpha/beta receptor bearing T lymphocytes, the processes of positive and negative selection of lymphocytes during the course of their differentiation. The major role of specific or acquired immunity has been shown by the rapidly lethal character of severe combined immune deficiency diseases and various alterations in the mechanisms of tolerance have been proposed to explain the chronic inflammatory illnesses which are considered to be auto-immune. Natural or innate immunity has been known since the first description of an inflammatory reaction attributed to Cornelius Celsus. It entered into the scientific era at the end of the 19th century with the discovery of phagocytes by Metchnikoff and of the properties of the complement system by Bordet [1] but due to the vastness of the field and its lack of clear definition, it failed to excite the interest of researchers. The discovery of cytokines and progress in knowledge of the mechanisms of the inflammatory reaction have certainly helped to banish preconceived ideas about natural immunity, which was wrongly labelled as non-specific. This has led to the proposition of a wider role for immune functions beyond the level of the cell or the organism [2] and to a better understanding of the importance of the immediate defence mechanisms and their role in the later orientation of the acquired response.

  20. Trisomy and early brain development

    PubMed Central

    Haydar, Tarik F.; Reeves, Roger H.

    2011-01-01

    Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS). The finished human genome sequence provides a thorough catalog of the genetic elements whose altered dosage perturbs development and function in DS. However, understanding how small alterations in the steady state transcript levels for <2% of human genes can disrupt development and function of essentially every cell presents a more complicated problem. Mouse models that recapitulate specific aspects of DS have been used to identify changes in brain morphogenesis and function. Here we provide a few examples of how trisomy for specific genes affects the development of the cortex and cerebellum to illustrate how gene dosage effects might contribute to divergence between the trisomic and euploid brains. PMID:22169531

  1. Variability in early communicative development.

    PubMed

    Fenson, L; Dale, P S; Reznick, J S; Bates, E; Thal, D J; Pethick, S J

    1994-01-01

    Data from parent reports on 1,803 children--derived from a normative study of the MacArthur Communicative Development Inventories (CDIs)--are used to describe the typical course and the extent of variability in major features of communicative development between 8 and 30 months of age. The two instruments, one designed for 8-16-month-old infants, the other for 16-30-month-old toddlers, are both reliable and valid, confirming the value of parent reports that are based on contemporary behavior and a recognition format. Growth trends are described for children scoring at the 10th-, 25th-, 50th-, 75th-, and 90th-percentile levels on receptive and expressive vocabulary, actions and gestures, and a number of aspects of morphology and syntax. Extensive variability exists in the rate of lexical, gestural, and grammatical development. The wide variability across children in the time of onset and course of acquisition of these skills challenges the meaningfulness of the concept of the modal child. At the same time, moderate to high intercorrelations are found among the different skills both concurrently and predictively (across a 6-month period). Sex differences consistently favor females; however, these are very small, typically accounting for 1%-2% of the variance. The effects of SES and birth order are even smaller within this age range. The inventories offer objective criteria for defining typicality and exceptionality, and their cost effectiveness facilitates the aggregation of large data sets needed to address many issues of contemporary theoretical interest. The present data also offer unusually detailed information on the course of development of individual lexical, gestural, and grammatical items and features. Adaptations of the CDIs to other languages have opened new possibilities for cross-linguistic explorations of sequence, rate, and variability of communicative development.

  2. Moral Development Interventions in Early Adolescence.

    ERIC Educational Resources Information Center

    Enright, Robert D; And Others

    1983-01-01

    Strategies for promoting moral development in early adolescence reviewed include the "plus-one" model, Deliberate Psychological Education, didactic courses in social studies, and a high school Just Community on moral reasoning. (CJ)

  3. Early Developments in Joint Action

    PubMed Central

    Brownell, Celia A.

    2012-01-01

    Joint action, critical to human social interaction and communication, has garnered increasing scholarly attention in many areas of inquiry, yet its development remains little explored. This paper reviews research on the growth of joint action over the first 2 years of life to show how children become progressively more able to engage deliberately, autonomously, and flexibly in joint action with adults and peers. It is suggested that a key mechanism underlying the dramatic changes in joint action over the second year of life is the ability to reflect consciously on oneself and one’s behavior and volition and correspondingly, on the behavior, goals, and intentions of others. PMID:23087769

  4. Subversion of early innate antiviral responses during antibody-dependent enhancement of Dengue virus infection induces severe disease in immunocompetent mice.

    PubMed

    Costa, Vivian V; Fagundes, Caio T; Valadão, Deborah F; Ávila, Thiago V; Cisalpino, Daniel; Rocha, Rebeca F; Ribeiro, Lucas S; Ascenção, Fernando R; Kangussu, Lucas M; Celso, M Q; Astigarraga, Ruiz G; Gouveia, Frederico L; Silva, Tarcília A; Bonaventura, Daniela; Sampaio, Divaldo de Almeida; Leite, Ana Cristina L; Teixeira, Mauro M; Souza, Danielle G

    2014-08-01

    Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1-4). Epidemiologic and observational studies demonstrate that the majority of severe dengue cases, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), occurs predominantly in either individuals with cross-reactive immunity following a secondary heterologous infection or in infants with primary DENV infections born from dengue-immune mothers, suggesting that B-cell-mediated and antibody responses impact on disease evolution. We demonstrate here that B cells play a pivotal role in host responses against primary DENV infection in mice. After infection, μMT(-/-) mice showed increased viral loads followed by severe disease manifestation characterized by intense thrombocytopenia, hemoconcentration, cytokine production and massive liver damage that culminated in death. In addition, we show that poly and monoclonal anti-DENV-specific antibodies can sufficiently increase viral replication through a suppression of early innate antiviral responses and enhance disease manifestation, so that a mostly non-lethal illness becomes a fatal disease resembling human DHF/DSS. Finally, treatment with intravenous immunoglobulin containing anti-DENV antibodies confirmed the potential enhancing capacity of subneutralizing antibodies to mediate virus infection and replication and induce severe disease manifestation of DENV-infected mice. Thus, our results show that humoral responses unleashed during DENV infections can exert protective or pathological outcomes and provide insight into the pathogenesis of this important human pathogen.

  5. Early development of visual recognition.

    PubMed

    Plebe, Alessio; Domenella, Rosaria Grazia

    2006-01-01

    The most important ability of the human vision is object recognition, yet it is exactly the less understood aspect of the vision system. Computational models have been helpful in progressing towards an explanation of this obscure cognitive ability, and today it is possible to conceive more refined models, thanks to the new availability of neuroscientific data about the human visual cortex. This work proposes a model of the development of the object recognition capability, under a different perspective with respect to the most common approaches, with a precise theoretical epistemology. It is assumed that the main processing functions involved in recognition are not genetically determined and hardwired in the neural circuits, but are the result of interactions between epigenetic influences and the basic neural plasticity mechanisms. The model is organized in modules related with the main visual biological areas, and is implemented mainly using the LISSOM architecture, a recent self-organizing algorithm closely reflecting the essential behavior of cortical circuits.

  6. Regulation of Innate Immune Responses is Required for S. mansoni Development

    DTIC Science & Technology

    2013-01-07

    71 Figure 8. Chronic stimulation of TLR2 with bacterial Pam3CSK4 facilitates S. mansoni development in RAG-/- mice and results in regulation of pro...prepatent infection…… ……………………………………………..…..138 Figure 18. Chronic stimulation of TLR4 with bacterial LPS facilitates S. mansoni Development in γc...shift in regards to schistosome vaccines, from the idea of achieving sterile immunity as is generally the goal of bacterial and viral vaccine

  7. Innate immune memory in plants.

    PubMed

    Reimer-Michalski, Eva-Maria; Conrath, Uwe

    2016-08-01

    The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Early development of cephalochordates (amphioxus).

    PubMed

    Holland, Linda Z; Onai, Takayuki

    2012-01-01

    The Phylum Chordata includes three groups--Vertebrata, Tunicata, and Cephalochordata. In cephalochordates, commonly called amphioxus or lancelets, which are basal in the Chordata, the eggs are small and relatively non-yolky. As in vertebrates, cleavage is indeterminate with cell fates determined gradually as development proceeds. The oocytes are attached to the ovarian follicle at the animal pole, where the oocyte nucleus is located. The cytoplasm at the opposite side of the egg, the vegetal pole, contains the future germ plasm or pole plasm, which includes determinants of the germline. After fertilization, additional asymmetries are established by movements of the egg and sperm nuclei, resulting in a concentration of mitochondria at one side of the animal hemisphere. This may be related to establishment of the dorsal/ventral axis. Patterning along the embryonic axes is mediated by secreted signaling proteins. Dorsal identity is specified by Nodal/Vg1 signaling, while during the gastrula stage, opposition between Nodal/Vg1 and BMP signaling establishes dorsal/anterior (i.e., head) and ventral/posterior (i.e., trunk/tail) identities, respectively. Wnt/β-catenin signaling specifies posterior identity while retinoic acid signaling specifies positions along the anterior/posterior axis. These signals are further modulated by a number of secreted antagonists. This fundamental patterning mechanism is conserved, with some modifications, in vertebrates.

  9. An Immediate Innate Immune Response Occurred In the Early Stage of E.granulosus Eggs Infection in Sheep: Evidence from Microarray Analysis

    PubMed Central

    Tang, Jishun; Hou, Hongyan; Chen, Sheng; Jia, Bin; Ban, Qian

    2015-01-01

    Background Cystic Echinococcosis(CE), caused by infection with the larval stage of the cestode Echinococcus granulosus (E. granulosus), is a chronic parasitic zoonosis, with highly susceptible infection in sheep. However, the comprehensive molecular mechanisms that underlie the process of E. granulosus infection in the early stage remain largely unknown. The objective of this present study was to gain a cluster of genes expression profiles in the intestine tissue of sheep infected with CE. Methods Nine healthy sheep were divided into infection group and healthy controls, with six infected perorally 5000 E. granulosus eggs suspended in 1000μl physiological saline and three controls perorally injected 1000μl physiological saline. All animals were sacrificed at 4 hours post-infection, respectively. The intestine tissue was removed and the RNA was extracted. In the infection group, the biology replicates were designed to make sure the accuracy of the data. The ovine microarrays were used to analyze changes of gene expression in the intestine tissue between CE infected sheep and healthy controls. Real-time PCR was used to assess reliability of the microarray data. Results By biology repeats, a total of 195 differentially expressed genes were identified between infected group and controls at 4 hours post-infection, with 105 genes related to immune responses, while 90 genes associated with functions including energy metabolism, fat soluble transport, etc. Among the 105 immunity genes, 72 genes showed up-regulated expression levels while 33 showed down-regulation levels. Function analysis showed that most of up-regulated genes were related to innate immune responses, such as mast cell, NK cell, cytokines, chemokines and complement. In addition, Real-time PCR analysis of a random selection of nine genes confirmed the reliability of the microarray data. Conclusion To our knowledge, this is the first report describing gene expression profiles in the intestine tissue of CE

  10. An Immediate Innate Immune Response Occurred In the Early Stage of E. granulosus Eggs Infection in Sheep: Evidence from Microarray Analysis.

    PubMed

    Hui, Wenqiao; Jiang, Song; Tang, Jishun; Hou, Hongyan; Chen, Sheng; Jia, Bin; Ban, Qian

    2015-01-01

    Cystic Echinococcosis(CE), caused by infection with the larval stage of the cestode Echinococcus granulosus (E. granulosus), is a chronic parasitic zoonosis, with highly susceptible infection in sheep. However, the comprehensive molecular mechanisms that underlie the process of E. granulosus infection in the early stage remain largely unknown. The objective of this present study was to gain a cluster of genes expression profiles in the intestine tissue of sheep infected with CE. Nine healthy sheep were divided into infection group and healthy controls, with six infected perorally 5000 E. granulosus eggs suspended in 1000 μl physiological saline and three controls perorally injected 1000 μl physiological saline. All animals were sacrificed at 4 hours post-infection, respectively. The intestine tissue was removed and the RNA was extracted. In the infection group, the biology replicates were designed to make sure the accuracy of the data. The ovine microarrays were used to analyze changes of gene expression in the intestine tissue between CE infected sheep and healthy controls. Real-time PCR was used to assess reliability of the microarray data. By biology repeats, a total of 195 differentially expressed genes were identified between infected group and controls at 4 hours post-infection, with 105 genes related to immune responses, while 90 genes associated with functions including energy metabolism, fat soluble transport, etc. Among the 105 immunity genes, 72 genes showed up-regulated expression levels while 33 showed down-regulation levels. Function analysis showed that most of up-regulated genes were related to innate immune responses, such as mast cell, NK cell, cytokines, chemokines and complement. In addition, Real-time PCR analysis of a random selection of nine genes confirmed the reliability of the microarray data. To our knowledge, this is the first report describing gene expression profiles in the intestine tissue of CE infection sheep. These results

  11. Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

    PubMed Central

    Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

    2015-01-01

    A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

  12. Early Years Educators at Play: A Research-Based Early Childhood Professional Development Program

    ERIC Educational Resources Information Center

    Kilinc, Sultan; Kelley, Michael F.; Millinger, Jenny; Adams, Korbi

    2016-01-01

    Every culture has developed some version of performance art. Children especially appreciate performance; their innate openness, forgiveness, and self-love make them delightful performers and audience members. Every time they engage with performance art, children are learning about storytelling, history, sociability, artistry, and physicality.…

  13. Early Years Educators at Play: A Research-Based Early Childhood Professional Development Program

    ERIC Educational Resources Information Center

    Kilinc, Sultan; Kelley, Michael F.; Millinger, Jenny; Adams, Korbi

    2016-01-01

    Every culture has developed some version of performance art. Children especially appreciate performance; their innate openness, forgiveness, and self-love make them delightful performers and audience members. Every time they engage with performance art, children are learning about storytelling, history, sociability, artistry, and physicality.…

  14. MicroRNA-29b mediates altered innate immune development in acute leukemia

    PubMed Central

    Mundy-Bosse, Bethany L.; Scoville, Steven D.; Chen, Li; McConnell, Kathleen; Mao, Hsiaoyin C.; Ahmed, Elshafa H.; Zorko, Nicholas; Harvey, Sophia; Cole, Jordan; Zhang, Xiaoli; Costinean, Stefan; Croce, Carlo M.; Larkin, Karilyn; Byrd, John C.; Vasu, Sumithira; Blum, William; Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A.

    2016-01-01

    Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell–depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients. This absence was not due to elimination by cell death or selective reduction in proliferation, but rather to the result of a block in NK cell differentiation. Indeed, NK cells from leukemic mice and humans with AML showed lower levels of TBET and EOMES, transcription factors that are critical for terminal NK cell differentiation. Further, the microRNA miR-29b, a regulator of T-bet and EOMES, was elevated in leukemic NK cells. Finally, deletion of miR-29b in NK cells reversed the depletion of this NK cell subset in leukemic mice. These results indicate that leukemic evasion of NK cell surveillance occurs through miR-mediated dysregulation of lymphocyte development, representing an additional mechanism of immune escape in cancer. PMID:27775550

  15. MicroRNA-29b mediates altered innate immune development in acute leukemia.

    PubMed

    Mundy-Bosse, Bethany L; Scoville, Steven D; Chen, Li; McConnell, Kathleen; Mao, Hsiaoyin C; Ahmed, Elshafa H; Zorko, Nicholas; Harvey, Sophia; Cole, Jordan; Zhang, Xiaoli; Costinean, Stefan; Croce, Carlo M; Larkin, Karilyn; Byrd, John C; Vasu, Sumithira; Blum, William; Yu, Jianhua; Freud, Aharon G; Caligiuri, Michael A

    2016-12-01

    Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients. This absence was not due to elimination by cell death or selective reduction in proliferation, but rather to the result of a block in NK cell differentiation. Indeed, NK cells from leukemic mice and humans with AML showed lower levels of TBET and EOMES, transcription factors that are critical for terminal NK cell differentiation. Further, the microRNA miR-29b, a regulator of T-bet and EOMES, was elevated in leukemic NK cells. Finally, deletion of miR-29b in NK cells reversed the depletion of this NK cell subset in leukemic mice. These results indicate that leukemic evasion of NK cell surveillance occurs through miR-mediated dysregulation of lymphocyte development, representing an additional mechanism of immune escape in cancer.

  16. Teacher Knowledge Development in Early Field Experiences

    ERIC Educational Resources Information Center

    Ingersoll, Casey; Jenkins, Jayne M.; Lux, Karen

    2014-01-01

    Investigation of physical education preservice teacher knowledge development has been primarily limited to study of a single semester of early field experience (EFE), with findings from these investigations driving EFE design. The purpose of this research was to investigate what types of knowledge develop and how knowledge evolves and interacts to…

  17. Early Brain Development Research Review and Update

    ERIC Educational Resources Information Center

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  18. Early Brain Development Research Review and Update

    ERIC Educational Resources Information Center

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  19. Current Issues in Research on Early Development.

    ERIC Educational Resources Information Center

    Siegel, Alberta E.

    Research on early development is moving apace. Developmental psychology is again giving serious attention to ages and stages. This attention is due, in great part, to the formulations about cognitive development by Piaget. Earlier in the century, the experimental approach to child study came to reflect psychology's generally heavy commitment to…

  20. Teacher Knowledge Development in Early Field Experiences

    ERIC Educational Resources Information Center

    Ingersoll, Casey; Jenkins, Jayne M.; Lux, Karen

    2014-01-01

    Investigation of physical education preservice teacher knowledge development has been primarily limited to study of a single semester of early field experience (EFE), with findings from these investigations driving EFE design. The purpose of this research was to investigate what types of knowledge develop and how knowledge evolves and interacts to…

  1. Transcriptome Encyclopedia of Early Human Development.

    PubMed

    Sahakyan, Anna; Plath, Kathrin

    2016-05-05

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development.

  2. Developing Early to Mid Career Teachers

    ERIC Educational Resources Information Center

    Berl, Patricia Scallan

    2005-01-01

    The consequences of poorly planned or random professional development for teachers in the early to mid career cycle are serious. Without input from knowledgeable mentors or supervisors, these teachers can flail about professionally. Without the benefit of individualized staff development plans, they may perpetuate ineffective teaching practices or…

  3. The innate immunity receptor TIR8/SIGIRR is expressed in the early developmental stages of chicken embryos.

    PubMed

    Turin, L; Manarolla, G; Rampin, T; Riva, F

    2014-01-01

    The orphan receptor TIR8, also known as SIGIRR (Single Immunoglobulin IL-1R-Related molecule), belongs to the IL-1R/TLR (TIR) superfamily and plays an important role in the inflammatory responses. The signaling pathways of the receptors belonging to the TIR family are tightly regulated by both extracellular and intracellular mechanisms. TIR8 does not activate the transcription factors NFkB (nuclear factor kB) and IRF3 (interferon regulatory factor 3), although it negatively modulates the inflammatory responses. It acts as an antagonist for the IL-1 receptor family and triggers a negative pathway of the Toll-like/IL-1 receptor system, crucial for dampening inflammation stimuli in the gastrointestinal (GI) tract and in other organs (e.g. lung and kidney). The recent findings of TLRs expression in ovary and embryos of different species (mammals and chickens) are very important for an understanding of reproductive physiology and transovarian pathogen transmission. TIR8 was well characterized in mouse, humans and in other mammalian species, but it is still poorly characterized in the chicken. When TIR8 expression was measured in selected organs of chicken embryos of both broiler and layer types at different time points a unique pattern of expression was observed. Interestingly, TIR8 was detected during the first stages of chicken development (day 1 of incubation), and reached a remarkable level of expression by day 10. We observed this receptor to be ubiquitously expressed in the kidney, GI tract, Bursa of Fabricius, with the highest expression levels in liver and kidney. This pattern was comparable to those observed in post-hatching chickens and in mammals examined to date. No expression differences were observed between the two different chicken breeds (layer- and broiler-type) in the first incubation period (8 days). Whereas in some organs starting from day 10, higher TIR8 expression was observed in broiler-type compared to layer-type. These are the first findings

  4. RFamide Peptides in Early Vertebrate Development

    PubMed Central

    Sandvik, Guro Katrine; Hodne, Kjetil; Haug, Trude Marie; Okubo, Kataaki; Weltzien, Finn-Arne

    2014-01-01

    RFamides (RFa) are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here, we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play. PMID:25538682

  5. Early Childhood Development and E-Learning in Africa: The Early Childhood Development Virtual University Programme

    ERIC Educational Resources Information Center

    Pence, Alan

    2007-01-01

    This article explores the development and evaluation of the graduate-level Early Childhood Development Virtual University (ECDVU) programme in Sub-Saharan Africa from 2001 through to 2004. It outlines the history of the ECDVU and the establishing of a Sub-Saharan programme for future leaders in the early childhood field guided by the key principle…

  6. Early Childhood Development and E-Learning in Africa: The Early Childhood Development Virtual University Programme

    ERIC Educational Resources Information Center

    Pence, Alan

    2007-01-01

    This article explores the development and evaluation of the graduate-level Early Childhood Development Virtual University (ECDVU) programme in Sub-Saharan Africa from 2001 through to 2004. It outlines the history of the ECDVU and the establishing of a Sub-Saharan programme for future leaders in the early childhood field guided by the key principle…

  7. Bioecological Theory, Early Child Development and the Validation of the Population-Level Early Development Instrument

    ERIC Educational Resources Information Center

    Guhn, Martin; Goelman, Hillel

    2011-01-01

    The Early Development Instrument (EDI; Janus and Offord in "Canadian Journal of Behavioural Science" 39:1-22, 2007) project is a Canadian population-level, longitudinal research project, in which teacher ratings of Kindergarten children's early development and wellbeing are linked to health and academic achievement variables at the…

  8. Early executive function predicts reasoning development.

    PubMed

    Richland, Lindsey E; Burchinal, Margaret R

    2013-01-01

    Analogical reasoning is a core cognitive skill that distinguishes humans from all other species and contributes to general fluid intelligence, creativity, and adaptive learning capacities. Yet its origins are not well understood. In the study reported here, we analyzed large-scale longitudinal data from the Study of Early Child Care and Youth Development to test predictors of growth in analogical-reasoning skill from third grade to adolescence. Our results suggest an integrative resolution to the theoretical debate regarding contributory factors arising from smaller-scale, cross-sectional experiments on analogy development. Children with greater executive-function skills (both composite and inhibitory control) and vocabulary knowledge in early elementary school displayed higher scores on a verbal analogies task at age 15 years, even after adjusting for key covariates. We posit that knowledge is a prerequisite to analogy performance, but strong executive-functioning resources during early childhood are related to long-term gains in fundamental reasoning skills.

  9. Early detection of tumor cells by innate immune cells leads to T(reg) recruitment through CCL22 production by tumor cells.

    PubMed

    Faget, Julien; Biota, Cathy; Bachelot, Thomas; Gobert, Michael; Treilleux, Isabelle; Goutagny, Nadège; Durand, Isabelle; Léon-Goddard, Sophie; Blay, Jean Yves; Caux, Christophe; Ménétrier-Caux, Christine

    2011-10-01

    In breast carcinomas, patient survival seems to be negatively affected by the recruitment of regulatory T cells (T(reg)) within lymphoid aggregates by CCL22. However, the mechanisms underpinning this process, which may be of broader significance in solid tumors, have yet to be described. In this study, we determined how CCL22 production is controlled in tumor cells. In human breast carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly increased in response to inflammatory signals [TNF-α, IFN-γ, and interleukin (IL)-1β], contrasting with CCL17. Primary breast tumors and CD45(+) infiltrating immune cells appeared to cooperate in driving CCL22 secretion, as shown clearly in cocultures of breast tumor cell lines and peripheral blood mononuclear cells (PBMC) or their supernatants. We determined that monocyte-derived IL-1β and TNF-α are key players as monocyte depletion or neutralization of these cytokines attenuated secretion of CCL22. However, when purified monocytes were used, exogenous human IFN-γ was also required to generate this response suggesting a role for IFN-γ-producing cells within PBMCs. In this setting, we found that human IFN-γ could be replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of T(reg). As one validation of this conclusion in primary breast tumors, we showed that NK cells and macrophages tend to colocalize within tumors. In summary, our findings suggest that at early times during tumorigenesis, the detection of tumor cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22 secretion that recruits T(reg) to evade this early antitumor immune response.

  10. Early Phonological Development: Creating an Assessment Test

    ERIC Educational Resources Information Center

    Stoel-Gammon, Carol; Williams, A. Lynn

    2013-01-01

    This paper describes a new protocol for assessing the phonological systems of two-year-olds with typical development and older children with delays in vocabulary acquisition. The test (Profiles of Early Expressive Phonological Skills ("PEEPS"), Williams & Stoel-Gammon, in preparation) differs from currently available assessments in…

  11. Early Intervention, Maternal Development and Children's Play.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    The purposes of this longitudinal study of early intervention with 83 black mother-child dyads were (a) to test the thesis that sociocultural transmission influences childhood development in educationally significant ways, and (b) to describe the process through which such transmission can occur. Two social intervention programs were contrasted;…

  12. Early Childhood Development in Texas. Special Report.

    ERIC Educational Resources Information Center

    Watson, Jeanette; Lanham, Fritz

    Programs and activities for young children in Texas are reported, based on data collected from the state agencies who administer these programs. Two sections are presented, the first dealing with early childhood development in the state, and the second with a survey of state agency programs. A history of federal and state involvement is followed…

  13. The Early Years: Development, Learning and Teaching.

    ERIC Educational Resources Information Center

    Boulton-Lewis, Gillian, Ed.; Catherwood, Di, Ed.

    Designed for teachers, students, caregivers, and health professionals who work with children from birth to age 8, this book provides a review of recent research and theories of development and learning in the early childhood years, with an emphasis on implications for effective teaching. Where appropriate, the book takes an Australian perspective,…

  14. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

    Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

    Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

  15. Rural Outreach and Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Warren, Claudia; Hamlin, Kay

    2005-01-01

    In an attempt to meet the growing professional development needs of early childhood practitioners in North Carolina, Winston-Salem State University (WSSU) is reaching out to the rural areas of North Carolina by offering programs that will certify North Carolina teachers in birth through kindergarten education (BKE). In this article, the author…

  16. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

    Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

    Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

  17. Early Phonological Development: Creating an Assessment Test

    ERIC Educational Resources Information Center

    Stoel-Gammon, Carol; Williams, A. Lynn

    2013-01-01

    This paper describes a new protocol for assessing the phonological systems of two-year-olds with typical development and older children with delays in vocabulary acquisition. The test (Profiles of Early Expressive Phonological Skills ("PEEPS"), Williams & Stoel-Gammon, in preparation) differs from currently available assessments in…

  18. Rural Outreach and Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Warren, Claudia; Hamlin, Kay

    2005-01-01

    In an attempt to meet the growing professional development needs of early childhood practitioners in North Carolina, Winston-Salem State University (WSSU) is reaching out to the rural areas of North Carolina by offering programs that will certify North Carolina teachers in birth through kindergarten education (BKE). In this article, the author…

  19. Early Childhood Development: Trends and Likely Scenarios.

    ERIC Educational Resources Information Center

    van Oudenhoven, Nico; Wazir, Rekha

    The following trends have been in motion in the field of early childhood development (ECD) for some time: (1) the concept of ECD is increasingly taking on additional connotations; (2) in Europe children are becoming a minority group and other age groups, such as the elderly, see them as competitors for the same limited resources; (3) the downward…

  20. Stress, Early Brain Development, and Behavior.

    ERIC Educational Resources Information Center

    Gunnar, Megan R.; Barr, Ronald G.

    1998-01-01

    Reviews research on the effect of stress hormones, particularly glucocorticoids, on the brain and early development. It describes the psychological and social processes that reduce stress hormone responses to threatening and painful procedures. Research on the cognitive and emotional effects of synthetic glucocorticoids is also discussed.…

  1. The Innate Immune Responses of Colonic Epithelial Cells to Trichuris muris Are Similar in Mouse Strains That Develop a Type 1 or Type 2 Adaptive Immune Response

    PubMed Central

    deSchoolmeester, Matthew L.; Manku, Harinder; Else, Kathryn J.

    2006-01-01

    Trichuris muris resides in intimate contact with its host, burrowing within cecal epithelial cells. However, whether the enterocyte itself responds innately to T. muris is unknown. This study investigated for the first time whether colonic intestinal epithelial cells (IEC) produce cytokines or chemokines following T. muris infection and whether divergence of the innate response could explain differentially polarized adaptive immune responses in resistant and susceptible mice. Increased expression of mRNA for the proinflammatory cytokines gamma interferon (IFN-γ) and tumor necrosis factor and the chemokine CCL2 (MCP-1) were seen after infection of susceptible and resistant strains, with the only difference in expression being a delayed increase in CCL2 in BALB/c IEC. These increases were ablated in MyD88−/− mice, and NF-κB p65 was phosphorylated in response to T. muris excretory/secretory products in the epithelial cell line CMT-93, suggesting involvement of the MyD88-NF-κB signaling pathway in IEC cytokine expression. These data reveal that IEC respond innately to T. muris. However, the minor differences identified between resistant and susceptible mice are unlikely to underlie the subsequent development of a susceptible type 1 (IFN-γ-dominated) or resistant type 2 (interleukin-4 [IL-4]/IL-13-dominated) adaptive immune response. PMID:17057095

  2. The innate immune responses of colonic epithelial cells to Trichuris muris are similar in mouse strains that develop a type 1 or type 2 adaptive immune response.

    PubMed

    deSchoolmeester, Matthew L; Manku, Harinder; Else, Kathryn J

    2006-11-01

    Trichuris muris resides in intimate contact with its host, burrowing within cecal epithelial cells. However, whether the enterocyte itself responds innately to T. muris is unknown. This study investigated for the first time whether colonic intestinal epithelial cells (IEC) produce cytokines or chemokines following T. muris infection and whether divergence of the innate response could explain differentially polarized adaptive immune responses in resistant and susceptible mice. Increased expression of mRNA for the proinflammatory cytokines gamma interferon (IFN-gamma) and tumor necrosis factor and the chemokine CCL2 (MCP-1) were seen after infection of susceptible and resistant strains, with the only difference in expression being a delayed increase in CCL2 in BALB/c IEC. These increases were ablated in MyD88-/- mice, and NF-kappaB p65 was phosphorylated in response to T. muris excretory/secretory products in the epithelial cell line CMT-93, suggesting involvement of the MyD88-NF-kappaB signaling pathway in IEC cytokine expression. These data reveal that IEC respond innately to T. muris. However, the minor differences identified between resistant and susceptible mice are unlikely to underlie the subsequent development of a susceptible type 1 (IFN-gamma-dominated) or resistant type 2 (interleukin-4 [IL-4]/IL-13-dominated) adaptive immune response.

  3. Nurturing care: promoting early childhood development.

    PubMed

    Britto, Pia R; Lye, Stephen J; Proulx, Kerrie; Yousafzai, Aisha K; Matthews, Stephen G; Vaivada, Tyler; Perez-Escamilla, Rafael; Rao, Nirmala; Ip, Patrick; Fernald, Lia C H; MacMillan, Harriet; Hanson, Mark; Wachs, Theodore D; Yao, Haogen; Yoshikawa, Hirokazu; Cerezo, Adrian; Leckman, James F; Bhutta, Zulfiqar A

    2017-01-07

    The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Early development and neurogenesis of Temnopleurus reevesii.

    PubMed

    Yaguchi, Shunsuke; Yamazaki, Atsuko; Wada, Wakana; Tsuchiya, Yasutaka; Sato, Toshihiko; Shinagawa, Hideo; Yamada, Yutaro; Yaguchi, Junko

    2015-04-01

    Sea urchins are model non-chordate deuterostomes, and studying the nervous system of their embryos can aid in the understanding of the universal mechanisms of neurogenesis. However, despite the long history of sea urchin embryology research, the molecular mechanisms of their neurogenesis have not been well investigated, in part because neurons appear relatively late during embryogenesis. In this study, we used the species Temnopleurus reevesii as a new sea urchin model and investigated the detail of its development and neurogenesis during early embryogenesis. We found that the embryos of T. reevesii were tolerant of high temperatures and could be cultured successfully at 15-30°C during early embryogenesis. At 30°C, the embryos developed rapidly enough that the neurons appeared at just after 24 h. This is faster than the development of other model urchins, such as Hemicentrotus pulcherrimus or Strongylocentrotus purpuratus. In addition, the body of the embryo was highly transparent, allowing the details of the neural network to be easily captured by ordinary epifluorescent and confocal microscopy without any additional treatments. Because of its rapid development and high transparency during embryogenesis, T. reevesii may be a suitable sea urchin model for studying neurogenesis. Moreover, the males and females are easily distinguishable, and the style of early cleavages is intriguingly unusual, suggesting that this sea urchin might be a good candidate for addressing not only neurology but also cell and developmental biology.

  5. [Innate immunity primary immunodeficiencies and infections].

    PubMed

    Duchamp, M; Miot, C; Bustamante, J C; Picard, C

    2016-07-01

    The diagnosis of primary immunodeficiency diseases (PIDs) is important for the early and adaptive care of patients and their families. Among the various known PIDs, a number of them concern the innate immune system, which involve a set of cells and mechanisms involved in the host defense by a nonspecific and fast response. The majority of patients with innate immunity defects have a predisposition to one isolated type of infection (bacterial, viral, or fungal), dependent on the genetic defect involved. This article describes the different PIDs involving innate immunity and the immunological investigations allowing for their diagnosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Early Adverse Experiences and the Developing Brain

    PubMed Central

    Bick, Johanna; Nelson, Charles A

    2016-01-01

    Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of adversity, one in which children are exposed to childhood maltreatment in family environments, and another in which children are exposed to extreme psychosocial deprivation in contexts of institutional rearing. We discuss ways in which each of these experiences represent violations of species-expected caregiving conditions, thereby imposing challenges to the developing brain. We also review emerging data pointing to the effectiveness of early intervention in remediating neurodevelopmental consequences associated with maltreatment or institutional rearing. We conclude by discussing implications of this work for public health efforts and highlight important directions for the field. PMID:26334107

  7. Early development and regression in Rett syndrome.

    PubMed

    Lee, J Y L; Leonard, H; Piek, J P; Downs, J

    2013-12-01

    This study utilized developmental profiling to examine symptoms in 14 girls with genetically confirmed Rett syndrome and whose families were participating in the Australian Rett syndrome or InterRett database. Regression was mostly characterized by loss of hand and/or communication skills (13/14) except one girl demonstrated slowing of skill development. Social withdrawal and inconsolable crying often developed simultaneously (9/14), with social withdrawal for shorter duration than inconsolable crying. Previously acquired gross motor skills declined in just over half of the sample (8/14), mostly observed as a loss of balance. Early abnormalities such as vomiting and strabismus were also seen. Our findings provide additional insight into the early clinical profile of Rett syndrome.

  8. QCD development in the early universe

    NASA Astrophysics Data System (ADS)

    Gromov, N. A.

    2017-03-01

    The high-energy limit of Quantum Chromodynamics is generated by the contraction of its gauge groups. Contraction parameters are taken identical with those of the Electroweak Model and tend to zero when energy increases. At the infinite energy limit all quarks lose masses and have only one color degree of freedom. The limit model represents the development of Quantum Chromodynamics in the early Universe from the Big Bang up to the end of several milliseconds.

  9. Innate Immune Activation in Obesity

    PubMed Central

    Lumeng, Carey N.

    2014-01-01

    The innate immune system is a prewired set of cellular and humoral components that has developed to sense perturbations in normal physiology and trigger responses to restore the system back to baseline. It is now understood that many of these components can also sense the physiologic changes that occur with obesity and be activated. While the exact reasons for this chronic immune response to obesity are unclear, there is strong evidence to suggest that innate inflammatory systems link obesity and disease. Based on this, anti-inflammatory therapies for diseases like type 2 diabetes and metabolic syndrome may form the core of future treatment plans. This review will highlight the components involved in the innate immune response and discuss the evidence that they contribute to the pathogenesis of obesity-associated diseases. PMID:23068074

  10. Developmental programming of natural killer and innate lymphoid cells.

    PubMed

    Vosshenrich, Christian A J; Di Santo, James P

    2013-04-01

    In recent years we have witnessed a blooming interest in innate lymphoid cell (ILC) biology thanks to the discovery of novel lineages of ILC that are phenotypically and functionally distinct from NK cells. While the importance of these novel ILC subsets as essential functional components of the early immune responses are now clearly established, many questions remain as to how early ILC developmental fates are determined and how specific effector functions associated with individual ILC subsets are achieved. As the founding member of the ILC family, properties of NK cells have defining attributes that characterize this group of innate effectors. Analysing their developmental rules may provide clues to principles that guide ILC development in general.

  11. Chapter 2: Innate Immunity

    PubMed Central

    Turvey, Stuart E.; Broide, David H.

    2009-01-01

    Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

  12. Innate Immunity and the Role of Defensins in Otitis Media

    PubMed Central

    Underwood, Mark; Bakaletz, Lauren

    2011-01-01

    Otitis media is the most common pediatric disease in developed countries and a significant cause of morbidity and hearing loss in developing countries. The innate immune system is essential to protecting the middle ear from infection. Defensins, broad-spectrum cationic antimicrobial peptides, have been implicated in prevention of and the early response to acute otitis media; however, the mechanisms by which defensins and other antimicrobial molecules mediate this protection have not been completely elucidated. In both animal otitis media models and human middle ear epithelial cell culture models, β-defensins are highly induced and effectively kill the common pathogens associated with otitis media. We review the importance of innate immunity in protecting the middle ear and recent advances in understanding the roles of defensins and other antimicrobial molecules in the prevention and treatment of otitis media. The extremely high prevalence of otitis media, in spite of sophisticated innate and adaptive immune systems, is a vexing problem for clinicians and scientists. We therefore also review mechanisms by which bacteria evade innate immune defenses. PMID:21901304

  13. The innate and adaptive immune response to avian influenza virus

    USDA-ARS?s Scientific Manuscript database

    Protective immunity against viruses is mediated by the early innate immune responses and later on by the adaptive immune responses. The early innate immunity is designed to contain and limit virus replication in the host, primarily through cytokine and interferon production. Most all cells are cap...

  14. Early and Middle Adolescents’ Autonomy Development

    PubMed Central

    Murphy, Debra A.; Greenwell, Lisa; Resell, Judith; Brecht, Mary-Lynn; Schuster, Mark A.

    2008-01-01

    Progression toward autonomy is considered of central importance during the adolescent period. For young adolescents with an HIV-infected parent, there may be additional challenges. This study investigated current autonomy among early and middle adolescents affected by maternal HIV (N = 108), as well as examined longitudinally the children’s responsibility taking when they were younger (age 6 - 11; N = 81) in response to their mother’s illness and their current autonomy as early/middle adolescents. In analyses of self-care and family autonomy, children with greater attachment to their mothers had higher autonomy, and there was a trend for children who drink or use drugs alone to have lower autonomy. In analyses of management autonomy, attachment to peers was associated with higher autonomy. Trajectory group findings indicate that those children who had taken on more responsibility for instrumental caretaking roles directly because of their mother’s illness showed better autonomy development as early and middle age adolescents. Therefore, “parentification” of young children with a mother with HIV may not negatively affect later autonomy development. PMID:18540228

  15. Early Childhood Development in Saskatoon, Saskatchewan. Understanding the Early Years

    ERIC Educational Resources Information Center

    Willms, J. Douglas

    2002-01-01

    Understanding the Early Years (UEY) is a national research initiative. It provides communities with information to enable them to make informed decisions about the best policies and most appropriate programs for families with young children. It seeks to provide information about the influence of community factors on children's early development…

  16. Photobiomodulation of early mouse embryo development

    NASA Astrophysics Data System (ADS)

    Sviridova-Chailakhyan, T. A.; Fakhranurova, L. I.; Simonova, N. B.; Khramov, R. N.; Manokhin, A. A.; Paskevich, S. I.; Chailakhyan, L. M.

    2008-04-01

    The effect of artificial sunlight (AS) from a xenon source and of converted AS with an additional orange-red luminescent (λ MAX=626 nm) component (AS+L) on the development of mouse zygotes was investigated. A plastic screen with a photoluminophore layer was used for production of this orange-red luminescent (L) component. A single short-term (15 min) exposure produced a long-term stable positive effect on early embryo development of mice, which persisted during several days. After exposure to AS+L, a stimulating influence on preimplantation development was observed, in comparison with the control group without AS exposure. The positive effects were as follows: increase in percent of embryos (P <= 0.05) developed to the blastocyst stage (96.2 %) with hatching from the zona pellucida (80.8 %) within 82-96 hours in vitro compared to the control (67.1 % and 28.8 %, respectively).

  17. Cognitive theories of early gender development.

    PubMed

    Martin, Carol Lynn; Ruble, Diane N; Szkrybalo, Joel

    2002-11-01

    The contribution of cognitive perspectives (cognitive-developmental theory and gender schema theory) to a contemporary understanding of gender development is evaluated. Recent critiques of cognitive approaches are discussed and empirical evidence is presented to counter these critiques. Because of the centrality of early gender development to the cognitive perspective, the latest research is reviewed on how infants and toddlers discriminate the sexes and learn the attributes correlated with sex. The essence of cognitive approaches--emphasis on motivational consequences of gender concepts; the active, self-initiated view of development; and focus on developmental patterns-is highlighted and contrasted with social-cognitive views. The value of cognitive theories to the field is illustrated, and recommendations are made concerning how to construct comprehensive, integrative perspectives of gender development.

  18. Innate Immunity in Disease

    PubMed Central

    Elliott, David E.; Siddique, Sana S.; Weinstock, Joel V.

    2014-01-01

    Cells can innately recognize generic products of viruses, bacteria, fungi, or injured tissue by engagement of pattern recognition receptors. Innate immune cells rapidly respond to this engagement in order to control commensals, thwart pathogens and/or prompt repair. Insufficient or excessive activation of the innate immune response results in disease. This review focuses on pattern recognition receptors and cells of the innate immune system important for intestinal function. Our improving knowledge pertaining to this important aspect of our immune response is opening potential important new therapeutic opportunities for the treatment of disease. PMID:24632348

  19. ROCK inhibition prevents early mouse embryo development.

    PubMed

    Duan, Xing; Chen, Kun-Lin; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    ROCK is a Rho-GTPase effector that is important for actin assembly and is involved in various cellular functions, including cell contraction, migration, motility, and tumor cell invasion. In this study, we investigated ROCK expression and function during early mouse embryo development. Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in first cleavage failure, and most embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell stage, embryos failed to undergo compaction and could not develop into blastocysts. In addition, fluorescence staining intensity analysis indicated that actin expression at blastomere membranes was significantly reduced. After ROCK inhibition, two or more nuclei were observed in a cell, which indicated possible cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased at blastomere membranes. Thus, our results showed conserved roles for ROCK in this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might regulate cleavage and blastocyst formation during early mouse embryo development.

  20. Lipidome signatures in early bovine embryo development.

    PubMed

    Sudano, Mateus J; Rascado, Tatiana D S; Tata, Alessandra; Belaz, Katia R A; Santos, Vanessa G; Valente, Roniele S; Mesquita, Fernando S; Ferreira, Christina R; Araújo, João P; Eberlin, Marcos N; Landim-Alvarenga, Fernanda D C

    2016-07-15

    Mammalian preimplantation embryonic development is a complex, conserved, and well-orchestrated process involving dynamic molecular and structural changes. Understanding membrane lipid profile fluctuation during this crucial period is fundamental to address mechanisms governing embryogenesis. Therefore, the aim of the present work was to perform a comprehensive assessment of stage-specific lipid profiles during early bovine embryonic development and associate with the mRNA abundance of lipid metabolism-related genes (ACSL3, ELOVL5, and ELOVL6) and with the amount of cytoplasmic lipid droplets. Immature oocytes were recovered from slaughterhouse-derived ovaries, two-cell embryos, and eight- to 16-cell embryos, morula, and blastocysts that were in vitro produced under different environmental conditions. Lipid droplets content and mRNA transcript levels for ACSL3, ELOVL5, and ELOVL6, monitored by lipid staining and quantitative polymerase chain reaction, respectively, increased at morula followed by a decrease at blastocyst stage. Relative mRNA abundance changes of ACSL3 were closely related to cytoplasmic lipid droplet accumulation. Characteristic dynamic changes of phospholipid profiles were observed during early embryo development and related to unsaturation level, acyl chain length, and class composition. ELOVL5 and ELOVL6 mRNA levels were suggestive of overexpression of membrane phospholipids containing elongated fatty acids with 16, 18, and 20 carbons. In addition, putative biomarkers of key events of embryogenesis, embryo lipid accumulation, and elongation were identified. This study provides a comprehensive description of stage-specific lipidome signatures and proposes a mechanism to explain its potential relationship with the fluctuation of both cytoplasmic lipid droplets content and mRNA levels of lipid metabolism-related genes during early bovine embryo development.

  1. Early Childhood Development: Laying the Foundations of Learning.

    ERIC Educational Resources Information Center

    Faccini, Benedict; Combes, Bernard

    Early childhood development is increasingly viewed as an affirmation of children's rights. This report describes the concept of early childhood development and presents several viewpoints regarding early childhood care and development, parenting, and approaches to early education. The report also presents 10 case studies of programs to enhance the…

  2. The developing hypopharyngeal microbiota in early life.

    PubMed

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes

    2016-12-30

    The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

  3. Reading development subtypes and their early characteristics.

    PubMed

    Torppa, Minna; Tolvanen, Asko; Poikkeus, Anna-Maija; Eklund, Kenneth; Lerkkanen, Marja-Kristiina; Leskinen, Esko; Lyytinen, Heikki

    2007-06-01

    The present findings are drawn from the Jyväskylä Longitudinal Study of Dyslexia (JLD), in which approximately 100 children with familial risk of dyslexia and 100 control children have been followed from birth. In this paper we report data on the reading development of the JLD children and their classmates, a total of 1,750 children from four measurement points during the first two school years. In the total sample, we examined whether heterogeneous developmental paths can be identified based on profiles of word recognition and reading comprehension. Secondly, we studied what kind of early language and literacy skill profiles and reading experiences characterize the children with differing reading development in the follow-up sample. The mixture modeling procedure resulted in five subtypes: (1) poor readers, (2) slow decoders, (3) poor comprehenders, (4) average readers, and (5) good readers. The children with familial risk for dyslexia performed on average at a lower level in all reading tasks than both their classmates and the controls, and they were overrepresented in slow decoders subtype. Differences between the subtypes were found in the early language and literacy skill development, as well as in the reading experiences of the reading subtypes.

  4. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

    Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

  5. Kepler Mission Development Challenges and Early Results

    NASA Technical Reports Server (NTRS)

    Fanson, J.

    2011-01-01

    Kepler is NASA`s first mission capable of detecting Earth-size planets orbiting in the habitable zone of stars other than the sun. Kepler comprises a space telescope designed to continuously monitor the brightnesses of more than 100,000 target stars, and a ground segment to analyze the measured stellar light curves and detect the signatures of orbiting planets. In order to detect Earth-size planets orbiting Sun-like stars Kepler was designed to provide unprecedented photometric sensitivity and stability. This paper addresses some of the technical challenges encountered during the development of the Kepler mission and the measures taken to overcome them. Early scientific results are summarized.

  6. Kepler Mission Development Challenges and Early Results

    NASA Technical Reports Server (NTRS)

    Fanson, J.; Duren, R.; Frerking, M.

    2011-01-01

    Kepler is NASA s first mission capable of detecting Earth-size planets orbiting in the habitable zone of stars other than the Sun. Kepler comprises a space telescope designed to continuously monitor the brightnesses of more than 100,000 target stars, and a ground segment to analyze the measured stellar light curves and detect the signatures of orbiting planets. In order to detect Earth-size planets orbiting Sun-like stars Kepler was designed to provide unprecedented photometric sensitivity and stability. This paper addresses some of the technical challenges encountered during the development of the Kepler mission and the measures taken to overcome them. Early scientific results are summarized.

  7. The Innate Immune System in Acute and Chronic Wounds

    PubMed Central

    MacLeod, Amanda S.; Mansbridge, Jonathan N.

    2016-01-01

    Significance: This review article provides an overview of the critical roles of the innate immune system to wound healing. It explores aspects of dysregulation of individual innate immune elements known to compromise wound repair and promote nonhealing wounds. Understanding the key mechanisms whereby wound healing fails will provide seed concepts for the development of new therapeutic approaches. Recent Advances: Our understanding of the complex interactions of the innate immune system in wound healing has significantly improved, particularly in our understanding of the role of antimicrobials and peptides and the nature of the switch from inflammatory to reparative processes. This takes place against an emerging understanding of the relationship between human cells and commensal bacteria in the skin. Critical Issues: It is well established and accepted that early local inflammatory mediators in the wound bed function as an immunological vehicle to facilitate immune cell infiltration and microbial clearance upon injury to the skin barrier. Both impaired and excessive innate immune responses can promote nonhealing wounds. It appears that the switch from the inflammatory to the proliferative phase is tightly regulated and mediated, at least in part, by a change in macrophages. Defining the factors that initiate the switch in such macrophage phenotypes and functions is the subject of multiple investigations. Future Directions: The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing. PMID:26862464

  8. Trade-offs between acquired and innate immune defenses in humans

    PubMed Central

    McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  9. Crosstalk between innate and adaptive immunity in hepatitis B virus infection.

    PubMed

    Wang, Li; Wang, Kai; Zou, Zhi-Qiang

    2015-12-28

    Hepatitis B virus (HBV) infection is a major public health problem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is responsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.

  10. Crosstalk between innate and adaptive immunity in hepatitis B virus infection

    PubMed Central

    Wang, Li; Wang, Kai; Zou, Zhi-Qiang

    2015-01-01

    Hepatitis B virus (HBV) infection is a major public health problem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is responsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection. PMID:26730277

  11. A comparative analysis of frog early development

    PubMed Central

    del Pino, Eugenia M.; Venegas-Ferrín, Michael; Romero-Carvajal, Andrés; Montenegro-Larrea, Paola; Sáenz-Ponce, Natalia; Moya, Iván M.; Alarcón, Ingrid; Sudou, Norihiro; Yamamoto, Shinji; Taira, Masanori

    2007-01-01

    The current understanding of Xenopus laevis development provides a comparative background for the analysis of frog developmental modes. Our analysis of development in various frogs reveals that the mode of gastrulation is associated with developmental rate and is unrelated to egg size. In the gastrula of the rapidly developing embryos of the foam-nesting frogs Engystomops coloradorum and Engystomops randi, archenteron and notochord elongation overlapped with involution at the blastopore lip, as in X. laevis embryos. In embryos of dendrobatid frogs and in the frog without tadpoles Eleutherodactylus coqui, which develop somewhat more slowly than X. laevis, involution and archenteron elongation concomitantly occurred during gastrulation; whereas elongation of the notochord and, therefore, dorsal convergence and extension, occurred in the postgastrula. In contrast, in the slow developing embryos of the marsupial frog Gastrotheca riobambae, only involution occurred during gastrulation. The processes of archenteron and notochord elongation and convergence and extension were postgastrulation events. We produced an Ab against the homeodomain protein Lim1 from X. laevis as a tool for the comparative analysis of development. By the expression of Lim1, we were able to identify the dorsal side of the G. riobambae early gastrula, which otherwise was difficult to detect. Moreover, the Lim1 expression in the dorsal lip of the blastopore and notochord differed among the studied frogs, indicating variation in the timing of developmental events. The variation encountered gives evidence of the modular character of frog gastrulation. PMID:17606898

  12. Astronewt: early development of newt in space

    NASA Astrophysics Data System (ADS)

    Mogami, Y.; Imamizo, M.; Yamashita, M.; Izumi-Kurotani, A.; Wiederhold, M. L.; Koike, H.; Asashima, M.

    AstroNewt experiment explores the effects of earth gravity on the early development of Japanese red-bellied newt, Cynops pyrrhogaster. Since female newts keep spermatophore in cloaca, fertilized eggs could be obtained without mating. Fertilization of newt's egg occurs just prior to spawning, so that gonadotrophic cues applied to females in orbit leads to laying eggs fertilized just in space. A property of newt being kept in hibernation at low temperature may be of great help for the space experiment carried out with much limited resources. A general outline of the AstroNewt project is shown here in addition to some technical advances for the development of the project. Experimental schemes of two space experiments (IML-2 in summer 1994 and unmanned SFU at the beginning of 1995) are also shown.

  13. Vegfa Impacts Early Myocardium Development in Zebrafish

    PubMed Central

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P.; Li, Fen

    2017-01-01

    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk. PMID:28230770

  14. Early development of the vertebral column.

    PubMed

    Scaal, Martin

    2016-01-01

    The segmental organization of the vertebrate body is most obviously visible in the vertebral column, which consists of a series of vertebral bones and interconnecting joints and ligaments. During embryogenesis, the vertebral column derives from the somites, which are the primary segments of the embryonic paraxial mesoderm. Anatomical, cellular and molecular aspects of vertebral column development have been of interest to developmental biologists for more than 150 years. This review briefly summarizes the present knowledge on early steps of vertebral column development in amniotes, starting from sclerotome formation and leading to the establishment of the anatomical bauplan of the spine composed of vertebral bodies, vertebral arches, intervertebral discs and ribs, and their specific axial identities along the body axis.

  15. The Crosstalk between Hypoxia and Innate Immunity in the Development of Obesity-Related Nonalcoholic Fatty Liver Disease.

    PubMed

    Arias-Loste, María Teresa; Fábrega, Emilio; López-Hoyos, Marcos; Crespo, Javier

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become a major health issue in western countries in parallel with the dramatic increase in the prevalence of obesity and all obesity related conditions, including respiratory diseases as obstructive sleep apnea-hypopnea syndrome (OSAHS). Interestingly, the severity of the liver damage in obesity-related NAFLD has been associated with the concomitant presence of OSAHS. In the presence of obesity, the proinflammatory state in these patients together with intermittent episodes of hypoxia, characteristic of OSAHS pathogenesis, may lead to an enhanced inflammatory response mediated by a positive feedback loop mechanism that implicates HIF-1 and NFκB. Thus, the severity of liver involvement in obese NAFLD patients with a concomitant diagnosis of OSAHS could be explained. In this review, we focus on the molecular mechanisms underlying the hepatic response to chronic intermittent hypoxia and its interaction with innate immunity in obesity-related NAFLD.

  16. Development of Life on Early Mars

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2009-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  17. Cell fate regulation in early mammalian development

    NASA Astrophysics Data System (ADS)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  18. How Early Hormones Shape Gender Development

    PubMed Central

    Berenbaum, Sheri A.; Beltz, Adriene M.

    2015-01-01

    Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women’s underrepresentation in science and math, and clinical care of individuals with variations in gender expression. PMID:26688827

  19. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Education and early childhood development. 1304.21... GRANTEE AND DELEGATE AGENCIES Early Childhood Development and Health Services § 1304.21 Education and early childhood development. (a) Child development and education approach for all children. (1) In order...

  20. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    ERIC Educational Resources Information Center

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  1. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    ERIC Educational Resources Information Center

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  2. Attachment and Early Language Development: Implications for Early Intervention

    ERIC Educational Resources Information Center

    Day, Crystal

    2007-01-01

    It has been proposed that early language is acquired in the context of interpersonal interactions, with parent-child interactions serving as an important foundation (Nicely, Tamis-LeMonda, & Bornstein, 1999; Sachs, 2005; Tamis-LeMonda, Cristofaro, Rodriguez, & Bornstein, 2006). The purpose of this article is to review the literature on maternal…

  3. Early development of grateloupia turuturu (Halymeniaceae, Rhodophyta)

    NASA Astrophysics Data System (ADS)

    Wang, Gaoge; Jiang, Chunmei; Wang, Shasha; Wei, Xiaojiao; Zhao, Fengjuan

    2012-03-01

    Grateloupia turuturu is a commercial red alga with potential value in nutraceuticals and pharmaceuticals. To supplement information on its life history and verify whether carpospores can be used for seedling culture, early development of G. turuturu was investigated under culture conditions (27°C, 10-13 μol/(m2·s) in irradiance, photoperiod 10:14 h L:D). Three physiological stages were recognized by continuous microscopic observation: division stage, discoid crust stage, and juvenile seedling stage. At the beginning of the division stage, the carpospores developed germ tubes into which the carpospore protoplasm was evacuated, and then the carpospore protoplasm in the germ tubes began to divide continuously until discoid crusts formed. Finally, upright thalli appeared on the discoid crusts and developed into juvenile seedlings. It took about 60 days for carpospores to develop into juvenile seedlings. The growth parameters, including germination rate for carpospores and discoid crust diameter, were recorded. These results contribute more information on the life cycle, and at the same time are of great significance in the scaling-up of artificial seedling cultures of G. turuturu.

  4. Purpose and Character Development in Early Adolescence.

    PubMed

    Malin, Heather; Liauw, Indrawati; Damon, William

    2017-02-08

    Character development in adolescence is of growing interest among psychology researchers and educators, yet there is little consensus about how character should be defined and studied among developmental scientists. In particular, there is no fully developed framework for investigating the developmental relationships among different character strengths. This study examines the developmental relations between purpose and three other key character strengths that emerge during early adolescence: gratitude, compassion, and grit. We analyzed survey (n = 1005, 50.1% female, 24.1% Caucasian, 43.6% African American, 18.9% Hispanic, 11.9% Asian American) and interview (n = 98) data from a longitudinal study of character development among middle school students from the United States. Data were collected over the course of 2 years, with surveys conducted four times at 6-month intervals and interviews conducted twice at 12-month intervals. Data analyses showed small but significant correlations between purpose and each of the other three character strengths under investigation. Interview data revealed patterns in ways that adolescents acted on their purposeful aspirations; and interview analyses identified qualitative differences in expressions of gratitude and compassion between adolescents who were fully purposeful and those who were not. The findings suggest that character development can be better understood by investigating the multidirectional developmental relationships among different character strengths.

  5. Communication and community development: early child development programs.

    PubMed

    Wood, F; Reinhold, A J

    1993-01-01

    Community-based groups are organized around particular aspects of early childhood development (ECD), such as literacy, parent education, and early childhood activities. In the Colombian national program, community households call upon women to devote a portion of their home to organized child care for minimal material reward. The Indian Child Development Service subsidizes the payment of organizers; and Kenyan parents construct basic preschool facilities, provide school lunches, and subsidize a teacher. In such cases the government plays a subordinate role, while the burden of program maintenance is carried by the community. These programs share the characteristics that children and adults learn side by side; adult learning ranges from women's literacy, to health, organizational issues, or small-scale economic development; a strong cultural component emphasizes mother tongue language learning, indigenous child-rearing practices, and local working models; physical structures are in homes; capacity-building for the adults is central which will be transferred to other spheres of community life. In the remote coastal villages of Colombia, an organization called Promesa works with mothers on designing their preschool children's educational activities. Promesa began to confront other priority needs in the villages, especially in environmental health and malaria control. A 1990 assessment related that participants' pride, self-confidence, and ability to solve problems regarding the healthy development of their children increased; groups learned to make use of the physical, human, and institutional resources from their environments; and participants' children remained in school and performed better. Conclusions from a decade of loose experimentation suggest that through communication community women can be organized to provide basic early education and early childhood activities can help rural children over the cultural barrier of school.

  6. Early development and embryology of the platypus.

    PubMed Central

    Hughes, R L; Hall, L S

    1998-01-01

    Information on the pre-hatching development of the platypus, Ornithorhynchus anatinus, is reliant on a small number of specimens, whose precise age is unknown. Material collected for J. P. Hill and now housed in the Hubrecht International Embryological Laboratory, Utrecht, contributes a major source of specimens. This paper presents new observations on developmental stages from the Hill collection, which allow for a more complete description of pre-hatching development. A feature of the pre-embryonic development of the platypus is the incomplete meroblastic cleavage. A column of fine yolk spheres extends from beneath the embryonic blastodisc towards the centre of a yolky vitellus, as seen in birds. The major expansion of extra-embryonic membranes occurs after the formation of the primitive streak. The primitive streak develops within an embryonal area as part of the superficial wall of the yolk-sac, a feature also shared with marsupials, birds and reptiles. The full-term, subspheroidal, intrauterine egg of the platypus has a major axis of about 17 mm and contains a flat, 19-20 somite, neurula-stage embryo which has prominent trigeminal ganglion primordia. The embryo at this stage is in a period of rapid modelling of the major early organ primordia of the nervous system, cardiovascular system, excretory system, and somite-derived components of the body wall. Soon after laying, five primary brain vesicles are present, the trigeminal ganglia CN5 as well as CN7, CN8, CN9, CN10, CN11 and CN12 are well developed. The alimentary system has an expanded stomach, pancreatic primordia and a gall bladder. Mesonephric tubules are associated with patent mesonephric ducts, which empty laterally into the cloaca. Extra-embryonic membranes at this stage show an extensive chorioamniotic connection that extends through the greater part of the caudal half of fused amniotic folds. The vascularized yolk-sac consists of a superficial yolk-sac omphalopleura and a deep yolk

  7. Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

    PubMed

    Weisblum, Yiska; Oiknine-Djian, Esther; Vorontsov, Olesya M; Haimov-Kochman, Ronit; Zakay-Rones, Zichria; Meir, Karen; Shveiky, David; Elgavish, Sharona; Nevo, Yuval; Roseman, Moshe; Bronstein, Michal; Stockheim, David; From, Ido; Eisenberg, Iris; Lewkowicz, Aya A; Yagel, Simcha; Panet, Amos; Wolf, Dana G

    2017-02-15

    Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn

  8. The Early Development of Kinetic Theory.

    ERIC Educational Resources Information Center

    Whitaker, Robert D.

    1979-01-01

    A review of the work of Bernoulli and other early contributors to kinetic theory. One significant point is that the most outstanding work in this early period was done by a little-known Scotsman, John J. Waterston. (BB)

  9. The Early Development of Kinetic Theory.

    ERIC Educational Resources Information Center

    Whitaker, Robert D.

    1979-01-01

    A review of the work of Bernoulli and other early contributors to kinetic theory. One significant point is that the most outstanding work in this early period was done by a little-known Scotsman, John J. Waterston. (BB)

  10. Early development of sigma-receptor ligands.

    PubMed

    Narayanan, Sanju; Bhat, Rohit; Mesangeau, Christophe; Poupaert, Jacques H; McCurdy, Christopher R

    2011-01-01

    Sigma receptors (σ-1 and σ-2) are non-opioid proteins implicated in the pathophysiology of various neurological disorders and cancer. The σ-1 subtype is a chaperon protein widely distributed in the CNS and peripheral tissues. These receptors are involved in the modulation of K(+)- and Ca(2+)-dependent signaling cascades at the endoplasmic reticulum and modulation of neurotransmitter release. σ-1 receptors are emerging targets for the treatment of neurophychiatric diseases (schizophrenia and depression) and cocaine addiction. σ-2 receptors are lipid raft proteins. They are highly expressed on many tumor cells and hence considered potential targets for anticancer drugs. σ receptors bind to a diverse class of pharmacological compounds like cocaine, methamphetamine, benzomorphans like (±)-pentazocine, (±)-SKF-10,047 and endogenous neurosteroids and sphingolipids. In this review we focus on the early development of σ receptor-specific ligands and radiolabeling agents.

  11. Elfin is expressed during early heart development.

    PubMed

    Kotaka, M; Lau, Y M; Cheung, K K; Lee, S M; Li, H Y; Chan, W Y; Fung, K P; Lee, C Y; Waye, M M; Tsui, S K

    Elfin (previously named CLIM1) is a protein that possesses an N-terminal PDZ domain and a C-terminal LIM domain. It belongs to the family of Enigma proteins. Enigma proteins are a family of cytoplasmic proteins that contain an N-terminal PDZ domain and a series of C-terminal LIM domains. By virtue of these two protein interacting domains, Enigma proteins are capable of protein-protein interactions. It has been proposed that Enigma proteins may act as adapters between kinases and the cytoskeleton. We have previously shown that Elfin is most abundantly expressed in the heart and it colocalizes with alpha-actinin 2 at the Z-disks of the myocardium. In this report, Elfin was shown to localize at the actin stress fibers of myoblasts, as revealed by green fluorescent protein (GFP) tagging. In situ hybridization and immunostaining showed that Elfin expression begins at an early stage in mouse development and is present throughout the developing heart. Taken together, our experimental results suggest that Elfin may play an important role in myofibrillogenesis and heart development.

  12. Innate Immune Signaling Induces Interleukin-7 Production from Salivary Gland Cells and Accelerates the Development of Primary Sjӧgren’s Syndrome in a Mouse Model

    PubMed Central

    Jin, Jun-O; Shinohara, Yoshinori; Yu, Qing

    2013-01-01

    Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren’s syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues. PMID:24147035

  13. Beyond NK Cells: The Expanding Universe of Innate Lymphoid Cells

    PubMed Central

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development. PMID:24982658

  14. Beyond NK cells: the expanding universe of innate lymphoid cells.

    PubMed

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  15. Gammadelta (γδ) T lymphocytes do not impact the development of early atherosclerosis.

    PubMed

    Cheng, Hsin-Yuan; Wu, Runpei; Hedrick, Catherine C

    2014-06-01

    Gammadelta (γδ) T cells are a subset of pro-inflammatory innate-like T lymphocytes that serve as a bridge between innate and adaptive immunity. γδ T cells are highly enriched in cholesterol compared to αβ T cells. In this study, we aimed to identify the role of γδ T cells in atherosclerosis, a cholesterol and inflammation-driven disease. We found that the percentages of γδ T cells are increased in ApoE(-/-) mice fed a Western diet. We generated TCRδ(-/-)ApoE(-/-) mice and fed them either rodent chow or a Western diet for ten weeks for the assessment of atherosclerosis. The atherosclerotic lesion size in diet-fed TCRδ(-/-)ApoE(-/-) mice was similar to that of diet-fed ApoE(-/-) mice. There were no differences in cytokine production or numbers of αβ T cells in aorta of TCRδ(-/-)ApoE(-/-) mice. Plasma lipoprotein profiles were unchanged by the absence of γδ T cells. Our data suggest that γδ T cells do not contribute to early atherosclerotic plaque development. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Calcium at fertilization and in early development

    PubMed Central

    Whitaker, Michael

    2012-01-01

    Fertilization calcium waves are introduced and the evidence from which we can infer general mechanisms of these waves is presented. The two main classes of hypothesis put forward to explain the generation of the fertilization calcium wave are set out and it is concluded that initiation of the fertilization calcium wave can be most generally explained in inverterbrates by a mechanism in which an activating substance enters the egg from the sperm on sperm-egg fusion, activating the egg by stimulating phospholipase C activation through a src family kinase pathway and in mammals by the diffusion of a sperm-specific phospholipase C from sperm to egg on sperm-egg fusion. The fertilization calcium wave is then set into the context of cell cycle control and the mechanism of repetitive calcium spiking in mammalian eggs is investigated. Evidence that calcium signals control cell division in early embryos is reviewed, and it is concluded that calcium signals are essential at all three stages of cell division in early embryos. Evidence that phosphoinositide signalling pathways control the resumption of meiosis during oocyte maturation is considered. It is concluded on balance that the evidence points to a need for phosphoinositide/calcium signalling during resumption of meiosis. Changes to the calcium signalling machinery occur during meiosis to enable the production of a calcium wave in the mature oocyte when it is fertilized; evidence that the shape and structure of the endoplasmic reticulum alters dynamically during maturation and after fertilization is reviewed and the link between ER dynamics and the cytoskeleton is discussed. There is evidence that calcium signalling plays a key part in the development of patterning in early embryos. Morphogenesis in ascidian, frog and zebrafish embryos is briefly described to provide the developmental context in which calcium signals act. Intracellular calcium waves that may play a role in axis formation in ascidian are discussed

  17. Adaptive immune cells temper initial innate responses.

    PubMed

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2007-10-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

  18. Adaptive immune cells temper initial innate responses

    PubMed Central

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2008-01-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25−Foxp3− or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. PMID:17891146

  19. Approaching archetypes: reconsidering innateness.

    PubMed

    Goodwyn, Erik

    2010-09-01

    The question of innateness has hounded Jungian psychology since Jung originally postulated the archetype as an a priori structure within the psyche. During his life and after his death he was continually accused of Lamarckianism and criticized for his theory that the archetypes existed as prior structures. More recently, with the advent of genetic research and the human genome project, the idea that psychological structures can be innate has come under even harsher criticism even within Jungian thought. There appears to be a growing consensus that Jung's idea of innate psychological structures was misguided, and that perhaps the archetype-as-such should be abandoned for more developmental and 'emergent' theories of the psyche. The purpose of this essay is to question this conclusion, and introduce some literature on psychological innateness that appears relevant to this discussion.

  20. Alzheimer's disease: Innate immunity gone awry?

    PubMed

    VanItallie, Theodore B

    2017-01-11

    Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline. In contrast, cognitive deficits in AD correlate well with synapse loss. Oligomeric forms of amyloid-beta (oAβs) can be synaptotoxic and evidence of their deposition inside synaptic terminals of cognition-associated neurons explains early memory loss in AD better than formation of extracellular Aβ plaques. Among innate immune cells that reside in the brain, microglia sense danger signals represented by proteins like oAβ and become activated by neuronal damage such as that caused by bacterial endotoxins. The resulting reactive microgliosis has been implicated in generating the chronic form of microglial activation believed to promote AD's development. Genome-wide association studies (GWASs) have yielded data from patients with sporadic AD indicating that its causes include genetic variation in the innate immune system. Recent preclinical studies have reported that β-hydroxybutyrate (βOHB) may protect the brain from the adverse effects of both the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and the deacetylation of histone. Consequently, there is an urgent need for clinical investigations designed to test whether an orally administered βOHB preparation, such as a ketone ester, can have a similar beneficial effect in human subjects.

  1. Roles of Toll-like receptors in innate immune responses.

    PubMed

    Takeda, K; Akira, S

    2001-09-01

    Innate immunity recognizes invading micro-organisms and triggers a host defence response. However, the molecular mechanism for innate immune recognition was unclear. Recently, a family of Toll-like receptors (TLRs) was identified, and crucial roles for these receptors in the recognition of microbial components have been elucidated. The TLR family consists of 10 members and will be expanding. Each TLR distinguishes between specific patterns of microbial components to provoke innate immune responses. The activation of innate immunity then leads to the development of antigen-specific adaptive immunity. Thus, TLRs control both innate and adaptive immune responses.

  2. Innate immunity interactome dynamics.

    PubMed

    Elzawahry, Asmaa; Patil, Ashwini; Kumagai, Yutaro; Suzuki, Yutaka; Nakai, Kenta

    2014-01-06

    Innate immune response involves protein-protein interactions, deoxyribonucleic acid (DNA)-protein interactions and signaling cascades. So far, thousands of protein-protein interactions have been curated as a static interaction map. However, protein-protein interactions involved in innate immune response are dynamic. We recorded the dynamics in the interactome during innate immune response by combining gene expression data of lipopolysaccharide (LPS)-stimulated dendritic cells with protein-protein interactions data. We identified the differences in interactome during innate immune response by constructing differential networks and identifying protein modules, which were up-/down-regulated at each stage during the innate immune response. For each protein complex, we identified enriched biological processes and pathways. In addition, we identified core interactions that are conserved throughout the innate immune response and their enriched gene ontology terms and pathways. We defined two novel measures to assess the differences between network maps at different time points. We found that the protein interaction network at 1 hour after LPS stimulation has the highest interactions protein ratio, which indicates a role for proteins with large number of interactions in innate immune response. A pairwise differential matrix allows for the global visualization of the differences between different networks. We investigated the toll-like receptor subnetwork and found that S100A8 is down-regulated in dendritic cells after LPS stimulation. Identified protein complexes have a crucial role not only in innate immunity, but also in circadian rhythms, pathways involved in cancer, and p53 pathways. The study confirmed previous work that reported a strong correlation between cancer and immunity.

  3. Early Years Practitioners' Views on Early Personal, Social and Emotional Development

    ERIC Educational Resources Information Center

    Aubrey, Carol; Ward, Karen

    2013-01-01

    Current policy guidance stresses the need for early identification of obstacles to learning and appropriate intervention. New standards for learning (Early Years Foundation Stage) place personal, social and emotional development (PSED) as central to learning and development. This paper reports a survey and follow-up interviews with early years…

  4. Early development and embryology of the platypus.

    PubMed

    Hughes, R L; Hall, L S

    1998-07-29

    Information on the pre-hatching development of the platypus, Ornithorhynchus anatinus, is reliant on a small number of specimens, whose precise age is unknown. Material collected for J. P. Hill and now housed in the Hubrecht International Embryological Laboratory, Utrecht, contributes a major source of specimens. This paper presents new observations on developmental stages from the Hill collection, which allow for a more complete description of pre-hatching development. A feature of the pre-embryonic development of the platypus is the incomplete meroblastic cleavage. A column of fine yolk spheres extends from beneath the embryonic blastodisc towards the centre of a yolky vitellus, as seen in birds. The major expansion of extra-embryonic membranes occurs after the formation of the primitive streak. The primitive streak develops within an embryonal area as part of the superficial wall of the yolk-sac, a feature also shared with marsupials, birds and reptiles. The full-term, subspheroidal, intrauterine egg of the platypus has a major axis of about 17 mm and contains a flat, 19-20 somite, neurula-stage embryo which has prominent trigeminal ganglion primordia. The embryo at this stage is in a period of rapid modelling of the major early organ primordia of the nervous system, cardiovascular system, excretory system, and somite-derived components of the body wall. Soon after laying, five primary brain vesicles are present, the trigeminal ganglia CN5 as well as CN7, CN8, CN9, CN10, CN11 and CN12 are well developed. The alimentary system has an expanded stomach, pancreatic primordia and a gall bladder. Mesonephric tubules are associated with patent mesonephric ducts, which empty laterally into the cloaca. Extra-embryonic membranes at this stage show an extensive chorioamniotic connection that extends through the greater part of the caudal half of fused amniotic folds. The vascularized yolk-sac consists of a superficial yolk-sac omphalopleura and a deep yolk

  5. State Developments in Child Care and Early Education, 1999.

    ERIC Educational Resources Information Center

    Blank, Helen; Poersch, Nicole Oxendine

    This report provides highlights and updates regarding state actions on child care and early education issues during 1999. It is intended to serve as a supplement to "State Child Care and Early Education Development: Highlights and Updates for 1998" and "State Developments in Child Care and Early Education 1997." The information…

  6. From Neurons to Neighborhoods: The Science of Early Childhood Development.

    ERIC Educational Resources Information Center

    Shonkoff, Jack P., Ed.; Phillips, Deborah A., Ed.

    The Committee on Integrating the Science of Early Childhood Development reviewed an extensive, multi-disciplinary, and complex body of research covering the period from before birth to entry into Kindergarten to generate an integrated science of early childhood development and the role of early experiences. The result of the committee's review,…

  7. Early Parental Depression and Child Language Development

    ERIC Educational Resources Information Center

    Paulson, James F.; Keefe, Heather A.; Leiferman, Jenn A.

    2009-01-01

    Objective: To examine the effects of early maternal and paternal depression on child expressive language at age 24 months and the role that parent-to-child reading may play in this pathway. Participants and methods: The 9-month and 24-month waves from a national prospective study of children and their families, the Early Childhood Longitudinal…

  8. Early Childhood Development: Upgrading the Downgrader

    ERIC Educational Resources Information Center

    Parnell, Dale

    1973-01-01

    Argues that, properly implemented, early childhood education in basic skills will drastically cut the waste of millions of students sitting in classes and learning little or nothing because they have not mastered the prerequisites. The next step in education, according to the author, must be preschool and home-based early childhood education…

  9. Oral innate immunity in HIV infection in HAART era.

    PubMed

    Nittayananta, Wipawee; Tao, Renchuan; Jiang, Lanlan; Peng, Yuanyuan; Huang, Yuxiao

    2016-01-01

    Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces not only provide a physical barrier but also produce different antimicrobial peptides, including human β-defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co-infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection, contributed to a global reduction of HIV-associated oral lesions. However, prolonged use of HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: (i) What are the roles of oral innate immunity in health and disease?, (ii) What are the effects of HIV infection on oral innate immunity?, (iii) What are the roles of oral innate immunity against other co-infections?, (iv) What are the effects of HAART on oral innate immunity?, and (v) Is oral innate immunity enhanced by HAART?

  10. Parental Obesity and Early Childhood Development.

    PubMed

    Yeung, Edwina H; Sundaram, Rajeshwari; Ghassabian, Akhgar; Xie, Yunlong; Buck Louis, Germaine

    2017-02-01

    Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development. Copyright © 2017 by the American Academy of Pediatrics.

  11. Mast cells in innate immunity.

    PubMed

    Marshall, Jean S; Jawdat, Dunia M

    2004-07-01

    Mast cells have been most extensively studied in their traditional role as an early effector cell of allergic disease. However, in the majority of individuals, it might be the role of this cell as a sentinel in host defense that is most important. Mast cells have been repeatedly demonstrated to play a critical role in defense against bacterial infections, and evidence for their involvement in early responses to viral and fungal pathogens is growing. Mast cells are activated during innate immune responses by multiple mechanisms, including well-established responses to complement components. In addition, novel mechanisms have emerged as a result of the explosion of knowledge in our understanding of pattern-recognition receptors. The mast cell shares many features with other innate immune effector cells, such as neutrophils and macrophages. However, a unique role for mast cells is defined not only by their extensive mediator profile but also by their ability to interact with the vasculature, to expedite selective cell recruitment, and to set the stage for an appropriate acquired response. Copyright 2004 American Academy of Allergy, Asthma and Immunology

  12. The interaction between maternal stress and the ontogeny of the innate immune system during teleost embryogenesis: implications for aquaculture practice.

    PubMed

    Li, M; Leatherland, J F

    2012-11-01

    The barrier defences and acellular innate immune proteins play critical roles during the early-stage fish embryos prior to the development of functional organ systems. The innate immune proteins in the yolk of embryos are of maternal origin. Maternal stress affects the maternal-to-embryo transfer of these proteins and, therefore, environmental stressors may change the course of embryo development, including embryonic immunocompetency, via their deleterious effect on maternal physiology. This review focuses on the associations that exist between maternal stress, maternal endocrine disturbance and the responses of the acellular innate immune proteins of early-stage fish embryos. Early-stage teleostean embryos are dependent upon the adult female for the formation of the zona pellucida as an essential barrier defence, for their supply of nutrients, and for the innate immunity proteins and antibodies that are transferred from the maternal circulation to the oocytes; maternally derived hormones are also transferred, some of which (such as cortisol) are known to exert a suppressive action on some aspects of the immune defences. This review summarizes what is known about the effects of oocyte cortisol content on the immune system components in early embryos. The review also examines recent evidence that embryonic cells during early cleavage have the capacity to respond to increased maternal cortisol transfer; this emphasizes the importance of maternal and early immune competence on the later life of fishes, both in the wild and in intensive culture.

  13. Innate immunity modulation in virus entry.

    PubMed

    Faure, Mathias; Rabourdin-Combe, Chantal

    2011-07-01

    Entry into a cell submits viruses to detection by pattern recognition receptors (PRRs) leading to an early innate anti-viral response. Several viruses evolved strategies to avoid or subvert PRR recognition at the step of virus entry to promote infection. Whereas viruses mostly escape from soluble PRR detection, endocytic/phagocytic PRRs, such as the mannose receptor or DC-SIGN, are commonly used for virus entry. Moreover, virion-incorporated proteins may also offer viruses a way to dampen anti-viral innate immunity upon virus entry, and entering viruses might usurp autophagy to improve their own infectivity. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Systems biology of innate immunity

    PubMed Central

    Zak, Daniel E.; Aderem, Alan

    2009-01-01

    Summary Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and tools then open new frontiers that revolutionize biology. Innate immunity is well suited for systems analysis, because the relevant cells can be isolated in various functional states and their interactions can be reconstituted in a biologically meaningful manner. Application of the tools of systems biology to the innate immune system will enable comprehensive analysis of the complex interactions that maintain the difficult balance between host defense and inflammatory disease. In this review, we discuss innate immunity in the context of the systems biology concepts, emergence, robustness, and modularity, and we describe emerging technologies we are applying in our systems-level analyses. These technologies include genomics, proteomics, computational analysis, forward genetics screens, and analyses that link human genetic polymorphisms to disease resistance. PMID:19120490

  15. Innate lymphoid cells, precursors and plasticity.

    PubMed

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2016-11-01

    Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. First Principles for Early Grades Reading Programs in Developing Countries

    ERIC Educational Resources Information Center

    Roskos, Kathy; Strickland, Dorothy; Haase, Janeen; Malik, Sakil

    2009-01-01

    The United States Agency for International Development (USAID)-funded Early Grade Reading Assessment (EGRA) program is an oral assessment designed to measure the most basic foundation skills for literacy acquisition in the early grades. EGRA's purpose is to document student performance on early grade reading skills in order to inform ministries…

  17. Acute dengue virus 2 infection in Gabonese patients is associated with an early innate immune response, including strong interferon alpha production.

    PubMed

    Becquart, Pierre; Wauquier, Nadia; Nkoghe, Dieudonné; Ndjoyi-Mbiguino, Angélique; Padilla, Cindy; Souris, Marc; Leroy, Eric M

    2010-12-17

    Dengue is now a leading cause of morbidity and mortality throughout the tropics. We conducted the first ex vivo study of dengue fever (DF) in African patients infected during the first Gabonese dengue virus 2 (DENV-2) outbreak in 2007, in order to investigate cytokine production, including the antiviral cytokine IFN-α, reported to be a potent inhibitor of DENV replication in vitro. Levels of 50 cytokines, chemokines and growth factors were measured in plasma from 36 patients with DENV-2 infection, and in uninfected controls, using Luminex multiplex technology. The results were interpreted according to the day of sampling after symptom onset. PBMC from six patients were also studied for T lymphocyte cell surface marker expression by flow cytometry. Acute DENV-2 infection elicited high levels of several pro-inflammatory cytokines (IL-6 and IL-17), chemokines (MIF, RANTES, IP-10 and MCP-1) and growth factors (G-CSF, GM-CSF and VEGF-A). We also observed high levels of IFN-α for the first time in adult DF patients, and CD4+ and CD8+ T cell activation at symptom onset. Acute DENV-2 infection in African patients elicits a strong innate response involving IFN-α production, as well as an adaptive immune response.

  18. Acute dengue virus 2 infection in Gabonese patients is associated with an early innate immune response, including strong interferon alpha production

    PubMed Central

    2010-01-01

    Background Dengue is now a leading cause of morbidity and mortality throughout the tropics. We conducted the first ex vivo study of dengue fever (DF) in African patients infected during the first Gabonese dengue virus 2 (DENV-2) outbreak in 2007, in order to investigate cytokine production, including the antiviral cytokine IFN-α, reported to be a potent inhibitor of DENV replication in vitro. Methods Levels of 50 cytokines, chemokines and growth factors were measured in plasma from 36 patients with DENV-2 infection, and in uninfected controls, using Luminex multiplex technology. The results were interpreted according to the day of sampling after symptom onset. PBMC from six patients were also studied for T lymphocyte cell surface marker expression by flow cytometry. Results Acute DENV-2 infection elicited high levels of several pro-inflammatory cytokines (IL-6 and IL-17), chemokines (MIF, RANTES, IP-10 and MCP-1) and growth factors (G-CSF, GM-CSF and VEGF-A). We also observed high levels of IFN-α for the first time in adult DF patients, and CD4+ and CD8+ T cell activation at symptom onset. Conclusion Acute DENV-2 infection in African patients elicits a strong innate response involving IFN-α production, as well as an adaptive immune response. PMID:21167041

  19. The Development of Self-Regulation across Early Childhood

    ERIC Educational Resources Information Center

    Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

    2016-01-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and…

  20. Early Development and the Brain: Teaching Resources for Educators

    ERIC Educational Resources Information Center

    Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.

    2008-01-01

    This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…

  1. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    ERIC Educational Resources Information Center

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  2. The Development of Self-Regulation across Early Childhood

    ERIC Educational Resources Information Center

    Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

    2016-01-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and…

  3. Parents' Role in the Early Head Start Children's Language Development

    ERIC Educational Resources Information Center

    Griswold, Cecelia Smalls

    2014-01-01

    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  4. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    ERIC Educational Resources Information Center

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  5. Early Development and the Brain: Teaching Resources for Educators

    ERIC Educational Resources Information Center

    Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.

    2008-01-01

    This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…

  6. Parents' Role in the Early Head Start Children's Language Development

    ERIC Educational Resources Information Center

    Griswold, Cecelia Smalls

    2014-01-01

    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  7. Innate immune system cells in atherosclerosis.

    PubMed

    Chávez-Sánchez, Luis; Espinosa-Luna, Jose E; Chávez-Rueda, Karina; Legorreta-Haquet, María V; Montoya-Díaz, Eduardo; Blanco-Favela, Francisco

    2014-01-01

    Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by innate and adaptive immune system involvement. A key component of atherosclerotic plaque inflammation is the persistence of different innate immune cell types including mast cells, neutrophils, natural killer cells, monocytes, macrophages and dendritic cells. Several endogenous signals such as oxidized low-density lipoproteins, and exogenous signals such as lipopolysaccharides, trigger the activation of these cells. In particular, these signals orchestrate the early and late inflammatory responses through the secretion of pro-inflammatory cytokines and contribute to plaque evolution through the formation of foam cells, among other events. In this review we discuss how innate immune system cells affect atherosclerosis pathogenesis.

  8. Development of an Early Intervention Program

    ERIC Educational Resources Information Center

    Gil, Isidoro Candel

    2005-01-01

    The following paper presents the main evaluation instruments used in early intervention, and reflects upon their use, taking into account that they were created with and for the normal population. Likewise, developmental characteristics of some child groups are described, more notably the x fragile syndrome, Williams syndrome and Prader Willi…

  9. Early Developments in Argumentation in Physics.

    ERIC Educational Resources Information Center

    Bazerman, Charles

    An evaluation of four seventeenth and eighteenth century essays on optics revealed early trends in the evolution of scientific articles. The later articles showed a growing tendency to (1) separate practice from pure knowledge, (2) organize information around problems of knowledge and theory rather than around chronological events, (3) emphasize…

  10. Early Adolescence: A Critical Development Transition?

    ERIC Educational Resources Information Center

    Petersen, Anne C.

    A longitudinal study of early adolescents examined gender differences in attitude and behavior, as well as the effects of pubertal change, parental expectations, and parental support. It was hypothesized that sex differences would emerge during preadolescence and that males' and females' rates of change would be significantly different. Subjects…

  11. A prime time for trained immunity: innate immune memory in newborns and infants.

    PubMed

    Levy, Ofer; Wynn, James L

    2014-01-01

    The newborn and infant periods of early life are associated with heightened vulnerability to infection. Limited antigen exposure and distinct adaptive immune function compared to the adult places a greater burden on innate immunity for host defense to microbial challenge during this time. Trained immunity describes the phenomenon of augmented innate immune function following a stimulus that is not specific to the original stimulus. We review the concept of trained immunity in the context of the newborn's unique innate immune system function, the preclinical and clinical evidence that supports the tenet of innate immune memory in early life, and potential consequences of altered innate immune host responses. © 2013 S. Karger AG, Basel.

  12. [The role of the innate immune system in atopic dermatitis].

    PubMed

    Volz, T; Kaesler, S; Skabytska, Y; Biedermann, T

    2015-02-01

    The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

  13. Dual Language Exposure and Early Bilingual Development

    ERIC Educational Resources Information Center

    Hoff, Erifka; Core, Cynthia; Place, Silvia; Rumiche, Rosario; Senor, Melissa; Parra, Marisol

    2012-01-01

    The extant literature includes conflicting assertions regarding the influence of bilingualism on the rate of language development. The present study compared the language development of equivalently high-SES samples of bilingually and monolingually developing children from 1 ; 10 to 2 ; 6. The monolingually developing children were significantly…

  14. The Chlamydia trachomatis Type III Secretion Chaperone Slc1 Engages Multiple Early Effectors, Including TepP, a Tyrosine-phosphorylated Protein Required for the Recruitment of CrkI-II to Nascent Inclusions and Innate Immune Signaling

    PubMed Central

    Chen, Yi-Shan; Bastidas, Robert J.; Saka, Hector A.; Carpenter, Victoria K.; Richards, Kristian L.; Plano, Gregory V.; Valdivia, Raphael H.

    2014-01-01

    Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole. Aside from the phosphoprotein TARP, a Chlamydia effector that promotes actin re-arrangements, very few factors mediating bacterial entry and early inclusion establishment have been characterized. Like many T3S effectors, TARP requires a chaperone (Slc1) for efficient translocation into host cells. In this study, we defined proteins that associate with Slc1 in invasive C. trachomatis elementary bodies (EB) by immunoprecipitation coupled with mass spectrometry. We identified Ct875, a new Slc1 client protein and T3S effector, which we renamed TepP (Translocated early phosphoprotein). We provide evidence that T3S effectors form large molecular weight complexes with Scl1 in vitro and that Slc1 enhances their T3S-dependent secretion in a heterologous Yersinia T3S system. We demonstrate that TepP is translocated early during bacterial entry into epithelial cells and is phosphorylated at tyrosine residues by host kinases. However, TepP phosphorylation occurs later than TARP, which together with the finding that Slc1 preferentially engages TARP in EBs leads us to postulate that these effectors are translocated into the host cell at different stages during C. trachomatis invasion. TepP co-immunoprecipitated with the scaffolding proteins CrkI-II during infection and Crk was recruited to EBs at entry sites where it remained associated with nascent inclusions. Importantly, C. trachomatis mutants lacking TepP failed to recruit CrkI-II to inclusions, providing genetic confirmation of a direct role for this effector in the recruitment of a host factor. Finally, endocervical epithelial cells infected with a tepP mutant showed altered expression of a subset of genes associated with innate immune responses. We propose a model wherein TepP acts downstream of TARP

  15. The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling.

    PubMed

    Chen, Yi-Shan; Bastidas, Robert J; Saka, Hector A; Carpenter, Victoria K; Richards, Kristian L; Plano, Gregory V; Valdivia, Raphael H

    2014-02-01

    Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole. Aside from the phosphoprotein TARP, a Chlamydia effector that promotes actin re-arrangements, very few factors mediating bacterial entry and early inclusion establishment have been characterized. Like many T3S effectors, TARP requires a chaperone (Slc1) for efficient translocation into host cells. In this study, we defined proteins that associate with Slc1 in invasive C. trachomatis elementary bodies (EB) by immunoprecipitation coupled with mass spectrometry. We identified Ct875, a new Slc1 client protein and T3S effector, which we renamed TepP (Translocated early phosphoprotein). We provide evidence that T3S effectors form large molecular weight complexes with Scl1 in vitro and that Slc1 enhances their T3S-dependent secretion in a heterologous Yersinia T3S system. We demonstrate that TepP is translocated early during bacterial entry into epithelial cells and is phosphorylated at tyrosine residues by host kinases. However, TepP phosphorylation occurs later than TARP, which together with the finding that Slc1 preferentially engages TARP in EBs leads us to postulate that these effectors are translocated into the host cell at different stages during C. trachomatis invasion. TepP co-immunoprecipitated with the scaffolding proteins CrkI-II during infection and Crk was recruited to EBs at entry sites where it remained associated with nascent inclusions. Importantly, C. trachomatis mutants lacking TepP failed to recruit CrkI-II to inclusions, providing genetic confirmation of a direct role for this effector in the recruitment of a host factor. Finally, endocervical epithelial cells infected with a tepP mutant showed altered expression of a subset of genes associated with innate immune responses. We propose a model wherein TepP acts downstream of TARP

  16. Investments for Future: Early Childhood Development and Education

    ERIC Educational Resources Information Center

    Kartal, Hulya

    2007-01-01

    Investments relevant to the first years of life are directly connected to the future of societies. It can be argued that investments for early childhood development and education are one of the best ways of decreasing social inequality caused by adverse environments which hinder development in early ages and tackling poverty by reducing the rate…

  17. Supporting Early Childhood Educators through Professional Development Partnerships

    ERIC Educational Resources Information Center

    Mraz, Maryann

    2011-01-01

    This article summarizes the findings of a study that examined instruction in early childhood classrooms where teachers participated in high-quality, sustained, and intensive professional development through an Early Childhood Educator Professional Development partnership on literacy practices essential to school success. Comparisons made between…

  18. Study of Early Child Care and Youth Development (SECCYD)

    MedlinePlus

    ... Supported Research Networks & Programs NICHD Study of Early Child Care and Youth Development (SECCYD) Sunsetted/For Reference Only Skip sharing on ... is not being updated . The Study of Early Child Care and Youth Development (SECCYD), now complete, began as the Study of ...

  19. Promoting Professional Development for Physical Therapists in Early Intervention

    ERIC Educational Resources Information Center

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla

    2015-01-01

    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  20. Rethinking the Brain: New Insights into Early Development.

    ERIC Educational Resources Information Center

    Shore, Rima

    Recent research on early brain development holds several implications for parents, teachers, health professionals, and policymakers. This report, based on the proceedings from a 1996 national conference on the importance of early brain development for the nation's future well-being, highlights major findings, summarizes their implications for…

  1. Assessing Home Environment for Early Child Development in Pakistan

    ERIC Educational Resources Information Center

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  2. Investments for Future: Early Childhood Development and Education

    ERIC Educational Resources Information Center

    Kartal, Hulya

    2007-01-01

    Investments relevant to the first years of life are directly connected to the future of societies. It can be argued that investments for early childhood development and education are one of the best ways of decreasing social inequality caused by adverse environments which hinder development in early ages and tackling poverty by reducing the rate…

  3. Early Communication Development and Intervention for Children with Autism

    ERIC Educational Resources Information Center

    Landa, Rebecca

    2007-01-01

    Autism is a neurodevelopmental disorder defined by impairments in social and communication development, accompanied by stereotyped patterns of behavior and interest. The focus of this paper is on the early development of communication in autism, and early intervention for impairments in communication associated with this disorder. An overview of…

  4. Assessing Home Environment for Early Child Development in Pakistan

    ERIC Educational Resources Information Center

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  5. Promoting Professional Development for Physical Therapists in Early Intervention

    ERIC Educational Resources Information Center

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla

    2015-01-01

    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  6. Innate Immunity and Breast Milk

    PubMed Central

    Cacho, Nicole Theresa; Lawrence, Robert M.

    2017-01-01

    Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing

  7. Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells requires stronger T-cell receptor signals than conventional CD4 T cells.

    PubMed

    Qiao, Yu; Zhu, Lingqiao; Sofi, Hanief; Lapinski, Philip E; Horai, Reiko; Mueller, Kristen; Stritesky, Gretta L; He, Xi; Teh, Hung-Sia; Wiest, David L; Kappes, Dietmar J; King, Philip D; Hogquist, Kristin A; Schwartzberg, Pamela L; Sant'Angelo, Derek B; Chang, Cheong-Hee

    2012-10-02

    MHC class II-expressing thymocytes and thymic epithelial cells can mediate CD4 T-cell selection resulting in functionally distinct thymocyte-selected CD4 (T-CD4) and epithelial-selected CD4 (E-CD4) T cells, respectively. However, little is known about how T-cell receptor (TCR) signaling influences the development of these two CD4 T-cell subsets. To study TCR signaling for T-CD4 T-cell development, we used a GFP reporter system of Nur77 in which GFP intensity directly correlates with TCR signaling strength. T-CD4 T cells expressed higher levels of GFP than E-CD4 T cells, suggesting that T-CD4 T cells received stronger TCR signaling than E-CD4 T cells during selection. Elimination of Ras GTPase-activating protein enhanced E-CD4 but decreased T-CD4 T-cell selection efficiency, suggesting a shift to negative selection. Conversely, the absence of IL-2-inducible T-cell kinase that causes poor E-CD4 T-cell selection due to insufficient TCR signaling improved T-CD4 T-cell generation, consistent with rescue from negative selection. Strong TCR signaling during T-CD4 T-cell development correlates with the expression of the transcription factor promyelocytic leukemia zinc finger protein. However, although modulation of the signaling strength affected the efficiency of T-CD4 T-cell development during positive and negative selection, the signaling strength is not as important for the effector function of T-CD4 T cells. These findings indicate that innate T-CD4 T cells, together with invariant natural killer T cells and γδ T cells, receive strong TCR signals during their development and that signaling requirements for the development and the effector functions are distinct.

  8. Early evolutionary trends in ammonoid embryonic development.

    PubMed

    De Baets, Kenneth; Klug, Christian; Korn, Dieter; Landman, Neil H

    2012-06-01

    During the Devonian Nekton Revolution, ammonoids show a progressive coiling of their shell just like many other pelagic mollusk groups. These now extinct, externally shelled cephalopods derived from bactritoid cephalopods with a straight shell in the Early Devonian. During the Devonian, evolutionary trends toward tighter coiling and a size reduction occurred in ammonoid embryonic shells. In at least three lineages, descendants with a closed umbilicus evolved convergently from forms with an opening in the first whorl (umbilical window). Other lineages having representatives with open umbilici became extinct around important Devonian events whereas only those with more tightly coiled embryonic shells survived. This change was accompanied by an evolutionary trend in shape of the initial chamber, but no clear trend in its size. The fact that several ammonoid lineages independently reduced and closed the umbilical window more or less synchronously indicates that common driving factors were involved. A trend in size decrease of the embryos as well as the concurrent increase in adult size in some lineages likely reflects a fundamental change in reproductive strategies toward a higher fecundity early in the evolutionary history of ammonoids. This might have played an important role in their subsequent success as well as in their demise. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  9. History and early development of INCAP.

    PubMed

    Scrimshaw, Nevin S

    2010-02-01

    Nevin Scrimshaw was the founding Director of the Institute of Nutrition of Central America and Panama (INCAP), serving as Director from 1949 to 1961. In this article, he reviews the history of the founding of INCAP, including the role of the Rockefeller and Kellogg Foundations, the Central American governments, and the Pan American Health Organization. The objectives pursued by INCAP in its early years were to assess the nutrition and related health problems of Central America, to carry out research to find practical solutions to these problems, and to provide technical assistance to its member countries to implement solutions. INCAP pursued a strategy of selecting promising Central Americans for advanced education and training in the US who assumed positions of leadership on their return. After this early phase, talented non-Central Americans of diverse origins were brought to INCAP, as well as additional researchers from the region. Growth of INCAP, as reflected in its annual budget and in the physical plant, was rapid and this was accompanied by high scientific productivity. Several field studies were launched that contributed impetus and design elements for the Oriente Longitudinal Study, which is the focus of this supplement.

  10. Cognition and Affect in Early Literacy Development.

    ERIC Educational Resources Information Center

    McNamee, Gillian D.; And Others

    1985-01-01

    Using Vygotsky's theory of development, explores the significance of storytelling and dramatization activities on the intellectual and emotional development of preschool children. Results indicate that dramatizing of children's stories enhances the storytelling of preschool children and, thus, influences their literacy development. (DST)

  11. Ion Channels in Innate and Adaptive Immunity

    PubMed Central

    Feske, Stefan; Wulff, Heike; Skolnik, Edward Y.

    2016-01-01

    Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, and zinc have important roles as second messengers to regulate intracellular signaling pathways. By contrast, monovalent cations such as sodium and potassium mainly regulate the membrane potential, which indirectly controls the influx of calcium and immune cell signaling. Studies investigating human patients with mutations in ion channels and transporters, analysis of gene-targeted mice, or pharmacological experiments with ion channel inhibitors have revealed important roles of ionic signals in lymphocyte development and in innate and adaptive immune responses. We here review the mechanisms underlying the function of ion channels and transporters in lymphocytes and innate immune cells and discuss their roles in lymphocyte development, adaptive and innate immune responses, and autoimmunity, as well as recent efforts to develop pharmacological inhibitors of ion channels for immunomodulatory therapy. PMID:25861976

  12. Dual language exposure and early bilingual development*

    PubMed Central

    HOFF, ERIKA; CORE, CYNTHIA; PLACE, SILVIA; RUMICHE, ROSARIO; SEÑOR, MELISSA; PARRA, MARISOL

    2015-01-01

    The extant literature includes conflicting assertions regarding the influence of bilingualism on the rate of language development. The present study compared the language development of equivalently high-SES samples of bilingually and monolingually developing children from 1;10 to 2;6. The monolingually developing children were significantly more advanced than the bilingually developing children on measures of both vocabulary and grammar in single language comparisons, but they were comparable on a measure of total vocabulary. Within the bilingually developing sample, all measures of vocabulary and grammar were related to the relative amount of input in that language. Implications for theories of language acquisition and for understanding bilingual development are discussed. PMID:21418730

  13. Crystallization of Spätzle, a cystine-knot protein involved in embryonic development and innate immunity in Drosophila melanogaster

    SciTech Connect

    Hoffmann, Anita; Neumann, Piotr; Schierhorn, Angelika; Stubbs, Milton T.

    2008-08-01

    Crystallization of the cystine-knot protein Spätzle occurred following serendipitous limited degradation of the pro-Spätzle propeptide during the crystallization experiment. The Spätzle protein is involved in both the definition of the dorsal–ventral axis during embryonic development and in the adult innate immune response. The disulfide-linked dimeric cystine-knot protein has been expressed as a proprotein in inclusion bodies in Escherichia coli and refolded in vitro by rapid dilution. Initial orthorhombic crystals that diffracted to 7 Å resolution were obtained after three months by the sitting-drop vapour-diffusion method. Optimization of the crystallization conditions resulted in orthorhombic crystals (space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 53.0, b = 59.2, c = 62.5 Å) that diffracted to 2.8 Å resolution in-house. The small volume of the asymmetric unit indicated that it was not possible for the crystals to contain the complete pro-Spätzle dimer. Mass spectrometry, N-terminal sequencing and Western-blot analysis revealed that the crystals contained the C-terminal disulfide-linked cystine-knot dimer. Comparison of various crystallization experiments indicated that degradation of the N-terminal prodomain was dependent on the buffer conditions.

  14. The Innate Sense of the Body Develops to Become a Public Affair by 2-3 Years

    ERIC Educational Resources Information Center

    Rochat, Philippe

    2010-01-01

    Infants from birth do express a sense of their own body as a differentiated entity among other entities in the world, an entity that is situated, physically bounded, organized, and agent in the environment. Quickly however, this implicit sense of self develops to become explicit, conceptual, and more importantly, public and social. This…

  15. The Innate Sense of the Body Develops to Become a Public Affair by 2-3 Years

    ERIC Educational Resources Information Center

    Rochat, Philippe

    2010-01-01

    Infants from birth do express a sense of their own body as a differentiated entity among other entities in the world, an entity that is situated, physically bounded, organized, and agent in the environment. Quickly however, this implicit sense of self develops to become explicit, conceptual, and more importantly, public and social. This…

  16. Early environmental influences on vascular development.

    PubMed

    Gardiner, Helena M

    2007-12-01

    The "fetal origins hypothesis" proposes that a fetus' adaptation to its intrauterine environment and postnatal stressors may have life-long consequences and that the fetal response to an environmental challenge may result in programming of different organ systems, depending on the timing of the insult. Growth restriction in the last trimester of pregnancy has been associated with later cardiovascular disease, not only through disturbances of normal cardiovascular and neuro-hormonal control mechanisms, but also because the "catch-up growth" observed in growth restricted infants disturbs the "thrifty phenotype" that permits an individual to live within its predicted environment. Problems in testing the fetal programming hypothesis include the measurement of an individual's failure to achieve their growth potential and the absence of an effective early measurement of later cardiovascular risk. However, individuals studied during fetal life are now reaching adulthood and will provide us with new insights into vascular programming.

  17. Parents Resourcing Children's Early Development and Learning

    ERIC Educational Resources Information Center

    Nichols, Sue; Nixon, Helen; Pudney, Valerie; Jurvansuu, Sari

    2009-01-01

    Parents deal with a complex web of choices when seeking and using knowledge and resources related to their young children's literacy development. Information concerning children's learning and development comes in many forms and is produced by an increasingly diverse range of players including governments, non-government organizations and…

  18. The Early Development of Pharmacology in America.

    ERIC Educational Resources Information Center

    Parascandola, John

    Presented is a review of the development of the science of pharmacology, the study of the interaction of chemical agents with living matter. The origins of the field are traced from 17th century Europe to the present, with major emphasis upon the scientists and developments made in the field in the United States. (SL)

  19. Corruption of innate immunity by bacterial proteases.

    PubMed

    Potempa, Jan; Pike, Robert N

    2009-01-01

    The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from non-specific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host's innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections.

  20. Corruption of Innate Immunity by Bacterial Proteases

    PubMed Central

    Potempa, Jan; Pike, Robert N.

    2009-01-01

    The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from non-specific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host’s innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections. PMID:19756242

  1. Innateness and the instinct to learn.

    PubMed

    Marler, Peter

    2004-06-01

    Concepts of innateness were at the heart of Darwin's approach to behavior and central to the ethological theorizing of Lorenz and, at least to start with, of Tinbergen. Then Tinbergen did an about face, and for some twenty years the term 'innate' became highly suspect. He attributed the change to Lehrman's famous 1953 critique in which he asserted that classifying behaviors as innate tells us nothing about how they develop. Although Lehrman made many valid points, I will argue that this exchange also led to profound misunderstandings that were ultimately damaging to progress in research on the development of behavior. The concept of 'instincts to learn', receiving renewed support from current theorizing among geneticists about phenotypic plasticity, provides a potential resolution of some of the controversies that Lehrman created. Bioacoustical studies, particularly on song learning in birds, serve both to confirm some of Lehrman's anxieties about the term 'innate', but also to make a case that he threw out the genetic baby with the bathwater. The breathtaking progress in molecular and developmental genetics has prepared the way for a fuller understanding of the complexities underlying even the simplest notions of innate behavior, necessary before we can begin to comprehend the ontogeny of behavior.

  2. Innate inflammation in Type 1 diabetes

    PubMed Central

    Cabrera, Susanne M.; Henschel, Angela M.; Hessner, Martin J.

    2015-01-01

    Type 1 diabetes mellitus (T1D) is an autoimmune disease often diagnosed in childhood that results in pancreatic β-cell destruction and life-long insulin dependence. T1D susceptibility involves a complex interplay of genetic and environmental factors and has historically been attributed to adaptive immunity, though there is now increasing evidence for a role of innate inflammation. Here, we review studies that define a heightened age-dependent innate inflammatory state in T1D families that is paralleled with high fidelity by the T1D-susceptible BioBreeding rat. Innate inflammation may be driven by changes in interactions between the host and environment, such as through an altered microbiome, intestinal hyper-permeability, or viral exposures. Special focus is placed on the temporal measurement of plasma induced transcriptional signatures of recent onset T1D patients and their siblings as well as in the Biobreeding rat as it defines the natural history of innate inflammation. These sensitive and comprehensive analyses have also revealed that those who successfully managed T1D risk develop an age-dependent immunoregulatory state, providing a possible mechanism for the juvenile nature of T1D. Therapeutic targeting of innate inflammation has been proven effective in preventing and delaying T1D in rat models. Clinical trials of agents that suppress innate inflammation have had more modest success, but efficacy is improved by the addition of combinatorial approaches that target other aspects of T1D pathogenesis. An understanding of innate inflammation and mechanisms by which this susceptibility is both potentiated and mitigated offers important insight into T1D progression and avenues for therapeutic intervention. PMID:25980926

  3. Innate immunity in rice

    PubMed Central

    Chen, Xuewei; Ronald, Pamela C.

    2011-01-01

    Advances in studies of rice innate immunity have led to the identification and characterization of host sensors encoding receptor kinases that perceive conserved microbial signatures. The non-RD domain, a newly recognized hallmark of these receptor kinases is highly expanded in rice (Oryza sativa) compared with Arabidopsis (Arabidopsis thaliana). Researchers have also identified a diverse array of microbial effectors from bacterial and fungal pathogens that triggers immune responses upon perception. These include both, effectors that indirectly target host Nucleotide binding site/Leucine rice repeat (NBS-LRR) proteins and transcription activator-like (TAL) effectors that directly bind promoters of host genes. Here we review the recognition and signaling events that govern rice innate immunity. PMID:21602092

  4. Innate immunity in lophotrochozoans: the annelids.

    PubMed

    Salzet, Michel; Tasiemski, Aurélie; Cooper, Edwin

    2006-01-01

    Innate immunity plays a major role as a first defense against microbes. Effectors of the innate response include pattern recognition receptors (PRR), phagocytic cells, proteolytic cascades and peptides/proteins with antimicrobial properties. Each element of these events has been well studied in vertebrates and in some invertebrates such as annelids. From these different researches, it appears that mammalian innate immunity could be considered as a mosaic of invertebrate immune responses. Annelids belonging to the lophotrochozoans' group are primitive coelomates that possess specially developed cellular immunity against pathogens including phagocytosis, encapsulation and spontaneous cytotoxicity of coelomocytes against allogenic or xenogenic cells. They have also developed an important humoral immunity that is based on antimicrobial, hemolytic and clotting properties of their body fluid. In the present review, we will emphasize the different immunodefense strategies that adaptation has taken during the course of evolution of two classes of annelids i.e. oligochaetes and achaetes.

  5. Understanding Early Sexual Development (For Parents)

    MedlinePlus

    ... this age start to understand the difference between boys and girls, and can identify themselves as one or the ... have developed a strong sense of being a boy or girl, and continue to explore their bodies even more ...

  6. Early development of fern gametophytes in microgravity

    NASA Technical Reports Server (NTRS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    2003-01-01

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from 1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in micro-g compared to those developing on earth. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  7. Early development of fern gametophytes in microgravity

    NASA Technical Reports Server (NTRS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    2003-01-01

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from 1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in micro-g compared to those developing on earth. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  8. Early development of fern gametophytes in microgravity

    NASA Astrophysics Data System (ADS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of /micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from /1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in /micro-g compared to those developing on earth.

  9. Pascal's Wager: from science to policy on early childhood development.

    PubMed

    Denburg, Avram E; Daneman, Denis

    2010-01-01

    Evidence suggests that our brains are shaped profoundly by experiences in early life, with long-lasting implications for development. This science has yet to make the leap to policy on early childhood development in Canada--a shortcoming that has left this country well behind other developed nations. The Pascal Report, released in June 2009, marks an historic opportunity to enact comprehensive early childhood education and care policy in Ontario. Properly implemented, it could serve as a model for such policy across the country. Its successful adoption will require sustained advocacy and ongoing research by the Canadian medical community.

  10. Chaos, Poverty, and Parenting: Predictors of Early Language Development

    ERIC Educational Resources Information Center

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael; Mills-Koonce, Roger

    2012-01-01

    Studies have shown that distal family risk factors like poverty and maternal education are strongly related to children's early language development. Yet, few studies have examined these risk factors in combination with more proximal day-to-day experiences of children that might be critical to understanding variation in early language. Young…

  11. Development of the Visual System and Implications for Early Intervention.

    ERIC Educational Resources Information Center

    Glass, Penny

    2002-01-01

    This article summarizes the early development of the visual system within the context of the other sensory systems and preterm birth and relates this information to early intervention. Retinopathy of prematurely, ocular defects, cortical visual impairment and potential impact of the neonatal intensive care unit environment are discussed. (Contains…

  12. Teacher Training for Early Childhood Development and Education in Kenya

    ERIC Educational Resources Information Center

    Mbugua, Tata

    2009-01-01

    The training of early childhood development and education (ECDE) teachers in Kenya remains a priority in recognition of the vital role well-trained professionals play in the quality of early childhood experiences for children ages 0+ to 5+. This article provides a detailed overview of the current structure and training of ECDE professionals,…

  13. Childhood Immunization: A Key Component of Early Childhood Development

    ERIC Educational Resources Information Center

    Messonnier, Nancy

    2017-01-01

    Physical health is a key component of early childhood development and school readiness. By keeping children healthy and decreasing the chances of disease outbreaks, immunizations help early childhood programs create a safe environment for children. While overall vaccination rates are high nationally for most vaccines routinely recommended for…

  14. Teacher Training for Early Childhood Development and Education in Kenya

    ERIC Educational Resources Information Center

    Mbugua, Tata

    2009-01-01

    The training of early childhood development and education (ECDE) teachers in Kenya remains a priority in recognition of the vital role well-trained professionals play in the quality of early childhood experiences for children ages 0+ to 5+. This article provides a detailed overview of the current structure and training of ECDE professionals,…

  15. Family Strategies to Support and Develop Resilience in Early Childhood

    ERIC Educational Resources Information Center

    Taket, A. R.; Nolan, A.; Stagnitti, K.

    2014-01-01

    Early childhood is an important time for the development of resilience. A recently completed study has followed three cohorts of resilient children and young people living in disadvantaged areas in Victoria, Australia, through different transitions in their educational careers. This paper focuses on the early childhood cohort, where we have…

  16. The Role of Storytelling in Early Literacy Development.

    ERIC Educational Resources Information Center

    Phillips, Louise

    Many storytellers, educators, and researchers advocate that storytelling can contribute significantly to early literacy development. Early childhood education needs to embrace literacy programs that actively employ storytelling to bridge students' established oracy skills and their newfound literacy skills. By doing this, children will encounter a…

  17. Family Strategies to Support and Develop Resilience in Early Childhood

    ERIC Educational Resources Information Center

    Taket, A. R.; Nolan, A.; Stagnitti, K.

    2014-01-01

    Early childhood is an important time for the development of resilience. A recently completed study has followed three cohorts of resilient children and young people living in disadvantaged areas in Victoria, Australia, through different transitions in their educational careers. This paper focuses on the early childhood cohort, where we have…

  18. Early Development of Self-Injurious Behavior: An Empirical Study.

    ERIC Educational Resources Information Center

    Hall, Scott; Oliver, Chris; Murphy, Glynis

    2001-01-01

    The early development of self-injurious behavior (SIB) in 16 young children with developmental disabilities was tracked over an 18-month period. Naturalistic observations in each child's classroom found a significant association between early SIB and low levels of social contact, which may be considered as a risk marker for SIB exacerbation.…

  19. Early Speech Motor Development: Cognitive and Linguistic Considerations

    ERIC Educational Resources Information Center

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2009-01-01

    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  20. Supporting Communication Development in the Early Years: A Practitioner's Perspective

    ERIC Educational Resources Information Center

    Bain, Julie; James, Deborah; Harrison, Mary

    2015-01-01

    This research study set out to explore the education practitioner's role in promoting communication development in early years classrooms. The study was undertaken in the combined nursery and reception early years unit of a small primary school using an ethnographic approach. Qualitative data was collected through 18 three-hour visits to the…

  1. Chaos, Poverty, and Parenting: Predictors of Early Language Development

    ERIC Educational Resources Information Center

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael; Mills-Koonce, Roger

    2012-01-01

    Studies have shown that distal family risk factors like poverty and maternal education are strongly related to children's early language development. Yet, few studies have examined these risk factors in combination with more proximal day-to-day experiences of children that might be critical to understanding variation in early language. Young…

  2. Promoting Early Literacy through the Professional Development of Preschool Teachers

    ERIC Educational Resources Information Center

    Lane, Cristianne; Prokop, Mary Jo Surges; Johnson, Evelyn; Podhajski, Blanche; Nathan, Jane

    2014-01-01

    The purpose of this study was to examine the effect of a professional learning program on the emergent literacy skills of preschool children. Building Blocks for Literacy® is a program consisting of training supported by mentoring designed to teach early childcare providers how to promote the development of early literacy skills. A previous…

  3. Development of the Visual System and Implications for Early Intervention.

    ERIC Educational Resources Information Center

    Glass, Penny

    2002-01-01

    This article summarizes the early development of the visual system within the context of the other sensory systems and preterm birth and relates this information to early intervention. Retinopathy of prematurely, ocular defects, cortical visual impairment and potential impact of the neonatal intensive care unit environment are discussed. (Contains…

  4. Online Professional Development: Choices for Early Childhood Educators

    ERIC Educational Resources Information Center

    Olsen, Heather; Donaldson, Ana J.; Hudson, Susan D.

    2010-01-01

    Early childhood educators are responsible for providing young children with the best possible early care and education. Research on child care workers' education has shown that professional preparation makes a significant impact on children's cognitive and emotional development (National Association for the Education of Young Children [NAEYC],…

  5. Early Speech Motor Development: Cognitive and Linguistic Considerations

    ERIC Educational Resources Information Center

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2009-01-01

    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  6. Early psychosis workforce development: Core competencies for mental health professionals working in the early psychosis field.

    PubMed

    Osman, Helen; Jorm, Anthony F; Killackey, Eoin; Francey, Shona; Mulcahy, Dianne

    2017-08-09

    The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform. © 2017 John Wiley & Sons Australia, Ltd.

  7. Structure of the Toll-Spätzle complex, a molecular hub in Drosophila development and innate immunity

    PubMed Central

    Parthier, Christoph; Stelter, Marco; Ursel, Christian; Fandrich, Uwe; Lilie, Hauke; Breithaupt, Constanze; Stubbs, Milton T.

    2014-01-01

    Drosophila Toll receptors are involved in embryonic development and the immune response of adult flies. In both processes, the only known Toll receptor ligand is the human nerve growth factor-like cystine knot protein Spätzle. Here we present the crystal structure of a 1:1 (nonsignaling) complex of the full-length Toll receptor ectodomain (ECD) with the Spätzle cystine knot domain dimer. The ECD is divided into two leucine-rich repeat (LRR) domains, each of which is capped by cysteine-rich domains. Spätzle binds to the concave surface of the membrane-distal LRR domain, in contrast to the flanking ligand interactions observed for mammalian Toll-like receptors, with asymmetric contributions from each Spätzle protomer. The structure allows rationalization of existing genetic and biochemical data and provides a framework for targeting the immune systems of insects of economic importance, as well as a variety of invertebrate disease vectors. PMID:24733933

  8. Transitions in oral and intestinal microflora composition and innate immune receptor-dependent stimulation during mouse development.

    PubMed

    Hasegawa, Mizuho; Osaka, Toshifumi; Tawaratsumida, Kazuki; Yamazaki, Takashi; Tada, Hiroyuki; Chen, Grace Y; Tsuneda, Satoshi; Núñez, Gabriel; Inohara, Naohiro

    2010-02-01

    Commensal bacteria possess immunostimulatory activities that can modulate host responses to affect development and homeostasis in the intestine. However, how different populations of resident bacteria stimulate the immune system remains largely unknown. We characterized here the ability of intestinal and oral microflora to stimulate individual pattern recognition receptors (PRRs) in bone marrow-derived macrophages and mesothelial cells. The intestinal but not oral microflora elicited age- and cell type-specific immunostimulation. The immunostimulatory activity of the intestinal microflora varied among individual mice but was largely mediated via Toll-like receptor 4 (TLR4) during breast-feeding, whereas it became TLR4 independent after weaning. This transition was associated with a change from a microflora rich in TLR4-stimulatory proteobacteria to one dominated by Bacteroidales and/or Clostridiales that poorly stimulate TLR4. The major stimulatory activity of the intestinal microflora was still intact in NOD1-, NOD2-, TLR2-, TLR4-, TLR5-, TLR9-, TLR11-, ASC-, or RICK-deficient cells but still relied on the adaptor MyD88. These studies demonstrate a transition in the intestinal microflora accompanied by a dynamic change of its ability to stimulate different PRRs which control intestinal homeostasis.

  9. In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice.

    PubMed

    Copin, Richard; Vitry, Marie-Alice; Hanot Mambres, Delphine; Machelart, Arnaud; De Trez, Carl; Vanderwinden, Jean-Marie; Magez, Stefan; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean-Jacques; Muraille, Eric

    2012-01-01

    Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b⁺ F4/80⁺ MHC-II⁺ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS⁺ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis.

  10. Reading Development Subtypes and Their Early Characteristics

    ERIC Educational Resources Information Center

    Torppa, Minna; Tolvanen, Asko; Poikkeus, Anna-Maija; Eklund, Kenneth; Lerkkanen, Marja-Kristiina; Leskinen, Esko; Lyytinen, Heikki

    2007-01-01

    The present findings are drawn from the Jyvaskyla Longitudinal Study of Dyslexia (JLD), in which approximately 100 children with familial risk of dyslexia and 100 control children have been followed from birth. In this paper we report data on the reading development of the JLD children and their classmates, a total of 1,750 children from four…

  11. The Early Development of Programmable Machinery.

    ERIC Educational Resources Information Center

    Collins, Martin D.

    1985-01-01

    Programmable equipment innovations, precursors of today's technology, are examined, including the development of the binary code and feedback control systems, such as temperature sensing devices, interchangeable parts, punched cards carrying instructions, continuous flow oil refining process, assembly lines for mass production, and the…

  12. Early Imagining and the Development of Empathy.

    ERIC Educational Resources Information Center

    Sutherland, Margaret B.

    1985-01-01

    Considers possible links between development of empathy and some children's spontaneous creation of imaginary companions or situations, citing examples of Agatha Christie's "Autobiography." Questions if such activities show ability to "decenter emotionally." Suggests need for better methods of assessing emotional decentering…

  13. The Early Development of Programmable Machinery.

    ERIC Educational Resources Information Center

    Collins, Martin D.

    1985-01-01

    Programmable equipment innovations, precursors of today's technology, are examined, including the development of the binary code and feedback control systems, such as temperature sensing devices, interchangeable parts, punched cards carrying instructions, continuous flow oil refining process, assembly lines for mass production, and the…

  14. Developing an Engineering Identity in Early Childhood

    ERIC Educational Resources Information Center

    Pantoya, Michelle L.; Aguirre-Munoz, Zenaida; Hunt, Emily M.

    2015-01-01

    This project describes a strategy to introduce young children to engineering in a way that develops their engineering identity. The targeted age group is 3-7 year old students because they rarely experience purposeful engineering instruction. The curriculum was designed around an engineering storybook and included interactive academic discussions…

  15. On Class Differences and Early Development.

    ERIC Educational Resources Information Center

    Kagan, Jerome

    There are seven major sets of differences between young children of different economic backgrounds. The middle class child, compared to the lower class child, generally exhibits: (1) better language comprehension and expression, (2) richer schema development, involving mental preparation for the unusual, (3) stronger attachment to the mother,…

  16. Conceptual Development and Early Multiword Speech.

    ERIC Educational Resources Information Center

    Shore, Cecilia

    The purposes of this study were to investigate (1) the level of development of four target vocal and gestural symbols (Doggie, Cup, Car, and Fiffin, a novel concept), and (2) the relationship of symbolic maturity to the use of symbols in combinations. Thirty infants (15 boys and 15 girls), between 82 and 91 weeks of age, were observed for…

  17. Maternal DNA Methylation Regulates Early Trophoblast Development

    PubMed Central

    Branco, Miguel R.; King, Michelle; Perez-Garcia, Vicente; Bogutz, Aaron B.; Caley, Matthew; Fineberg, Elena; Lefebvre, Louis; Cook, Simon J.; Dean, Wendy; Hemberger, Myriam; Reik, Wolf

    2016-01-01

    Summary Critical roles for DNA methylation in embryonic development are well established, but less is known about its roles during trophoblast development, the extraembryonic lineage that gives rise to the placenta. We dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b mutants. We find that oocyte-derived methylation plays a major role in regulating trophoblast development but that imprinting of the key placental regulator Ascl2 is only partially responsible for these effects. We have identified several methylation-regulated genes associated with trophoblast differentiation that are involved in cell adhesion and migration, potentially affecting trophoblast invasion. Specifically, trophoblast-specific DNA methylation is linked to the silencing of Scml2, a Polycomb Repressive Complex 1 protein that drives loss of cell adhesion in methylation-deficient trophoblast. Our results reveal that maternal DNA methylation controls multiple differentiation-related and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. PMID:26812015

  18. Parental alcoholism and early child development.

    PubMed

    Nordberg, L; Rydelius, P A; Zetterström, R

    1994-11-01

    In a cohort of 532 pregnant women from the general population, it was found by compilation of the results from interviews, police records, hospital records and social welfare records that 23 mothers and 51 fathers in 64 families (12%) were suffering from alcoholism/heavy drinking. In these 64 families, the mother was an addict in only 13 families, both parents were addicts in 10 families, and in the remaining 41 families only the father was an addict. Pregnancy, delivery, the newborn child and the child's development until their fourth year of life have been described using a multidisciplinary approach and a longitudinal prospective design. An hypothesis on mental and physical development, and the occurrence of psychopathological symptoms in the children was tested. None of the children of the 13 alcoholic mothers was born with foetal alcohol syndrome, but foetal hazard was indicated by lower birth weight and a higher rate of perinatal deaths. Children of alcoholic parents had retarded mental development and showed more behavioural problems until 4 years of age than controls, but the differences related to physical development during the first year of life had then disappeared. Boys were found to be more vulnerable than girls. The consequences of behaviour seemed to be more pronounced when both parents were alcoholics. No obvious deviation was found when only the father was addicted. Regarding mental development, it appears that factors related to parental alcoholism, including genetic and social factors, and the sex of the child, are of greater importance than the neonatal score on reduced optimality.

  19. Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

    PubMed

    Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

    2017-04-01

    Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building.

  20. Early bilingualism, language attainment, and brain development.

    PubMed

    Berken, Jonathan A; Gracco, Vincent L; Klein, Denise

    2016-09-01

    The brain demonstrates a remarkable capacity to undergo structural and functional change in response to experience throughout the lifespan. Evidence suggests that, in many domains of skill acquisition, the manifestation of this neuroplasticity depends on the age at which learning begins. The fact that most skills are acquired late in childhood or in adulthood has proven to be a limitation in studies aimed at determining the relationship between age of acquisition and brain plasticity. Bilingualism, however, provides an optimal model for discerning differences in how the brain wires when a skill is acquired from birth, when the brain circuitry for language is being constructed, versus later in life, when the pathways subserving the first language are already well developed. This review examines some of the existing knowledge about optimal periods in language development, with particular attention to the attainment of native-like phonology. It focuses on the differences in brain structure and function between simultaneous and sequential bilinguals and the compensatory mechanisms employed when bilingualism is achieved later in life, based on evidence from studies using a variety of neuroimaging modalities, including positron emission tomography (PET), task-based and resting-state functional magnetic resonance imaging (fMRI), and structural MRI. The discussion concludes with the presentation of recent neuroimaging studies that explore the concept of nested optimal periods in language development and the different neural paths to language proficiency taken by simultaneous and sequential bilinguals, with extrapolation to general notions of the relationship between age of acquisition and ultimate skill performance.

  1. Challenges in early clinical development of adjuvanted vaccines.

    PubMed

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.

  2. Early development of the gut microbiome and immune-mediated childhood disorders.

    PubMed

    Li, Min; Wang, Mei; Donovan, Sharon M

    2014-01-01

    The human gastrointestinal tract inhabits a complex microbial ecosystem that plays a vital role in host health through its contributions to nutrient synthesis and digestion, protection from pathogens, and promoting maturation of host innate and adapt immune systems. The development of gut microbiota primarily occurs during infancy and is influenced by multiple factors, including prenatal exposure; gestational age; mode of delivery; feeding type; pre-, pro-, and antibiotic use; and host genetics. In genetically susceptible individuals, changes in the gut microbiota induced by environmental factors may contribute to the development of immune-related disorders in childhood, including atopic diseases, inflammatory bowel disease, irritable bowel syndrome, and necrotizing enterocolitis. Pre- and probiotics may be useful in the prevention and treatment of some immune-related diseases by modulating gut microbiota and regulating host mucosal immune function. The review will discuss recent findings on the environmental factors that influence development of gut microbiota during infancy and its potential impact on some immune-related diseases in childhood. The use of pre- and probiotics for prevention and intervention of several important diseases in early life will also be reviewed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Early Development of Children with Sex Chromosome Aberrations.

    ERIC Educational Resources Information Center

    Haka-Ilse, Katerina; And Others

    1978-01-01

    Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. A prospective study was made of the early development of 42 children with sex chromosome aberrations. (Author)

  4. Vaccine adjuvants: putting innate immunity to work.

    PubMed

    Coffman, Robert L; Sher, Alan; Seder, Robert A

    2010-10-29

    Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens.

  5. Vaccine Adjuvants: Putting Innate Immunity to Work

    PubMed Central

    Coffman, Robert L.; Sher, Alan; Seder, Robert A.

    2012-01-01

    Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. PMID:21029960

  6. Innate cellular responses to rotavirus infection.

    PubMed

    Holloway, Gavan; Coulson, Barbara S

    2013-06-01

    Rotavirus is a leading cause of severe dehydrating diarrhoea in infants and young children. Following rotavirus infection in the intestine an innate immune response is rapidly triggered. This response leads to the induction of type I and type III interferons (IFNs) and other cytokines, resulting in a reduction in viral replication. Here we review the current literature describing the detection of rotavirus infection by pattern recognition receptors within host cells, the subsequent molecular mechanisms leading to IFN and cytokine production, and the processes leading to reduced rotavirus replication and the development of protective immunity. Rotavirus countermeasures against innate responses, and their roles in modulating rotavirus replication in mice, also are discussed. By linking these different aspects of innate immunity, we provide a comprehensive overview of the host's first line of defence against rotavirus infection. Understanding these processes is expected to be of benefit in improving strategies to combat rotavirus disease.

  7. Lineage determinants in early endocrine development

    PubMed Central

    Rieck, Sebastian; Bankaitis, Eric D.; Wright, Christopher V.E.

    2013-01-01

    Pancreatic endocrine cells are produced from a dynamic epithelium in a process that, as in any developing organ, is driven by interacting programs of spatiotemporally regulated intercellular signals and autonomous gene regulatory networks. These algorithms work to push progenitors and their transitional intermediates through a series of railroad-station-like switching decisions to regulate flux along specific differentiation tracks. Extensive research on pancreas organogenesis over the last 20 years, greatly spurred by the potential to restore functional β-cell mass in diabetic patients by transplantation therapy, is advancing our knowledge of how endocrine lineage bias is established and allocation is promoted. The field is working towards the goal of generating a detailed blueprint of how heterogeneous cell populations interact and respond to each other, and other influences such as the extracellular matrix, to move into progressively refined and mature cell states. Here, we highlight how signaling codes and transcriptional networks might determine endocrine lineage within a complex and dynamic architecture, based largely on studies in the mouse. The process begins with the designation of multipotent progenitor cells (MPC) to pancreatic buds that subsequently move through a newly proposed period involving epithelial plexus formation-remodeling, and ends with formation of clustered endocrine islets connected to the vascular and peripheral nervous systems. Developing this knowledge base, and increasing the emphasis on direct comparisons between mouse and human, will yield a more complete and focused picture of pancreas development, and thereby inform β-cell-directed differentiation from human embryonic stem or induced pluripotent stem cells (hESC, iPSC). Additionally, a deeper understanding may provide surprising therapeutic angles by defining conditions that allow the controllable reprogramming of endodermal or pancreatic cell populations. PMID:22728667

  8. Early Events in Maize Seed Development 1

    PubMed Central

    Fong, Franklin; Smith, James D.; Koehler, Don E.

    1983-01-01

    Preharvest sprouting or vivipary is induced in developing maize (Zea mays, inbred Tx 5855 and Va 35) seeds by fluridone, a pyridinone inhibitor of carotenoid biosynthesis. Fluridone has a maximal effect on vivipary at 11 days after pollination (DAP) and little effect at 13 DAP in the inbred maize line Tx 5855. Abscisic acid partially reversed the chemically induced vivipary. Though the precise mechanism of fluridone-induced vivipary is unknown, these results indicate that there are important developmental changes occurring at 11 DAP which reversibly commit the immature embryo to vivipary or dormancy. Images Fig. 1 PMID:16663339

  9. Innatism, Concept Formation, Concept Mastery and Formal Education

    ERIC Educational Resources Information Center

    Winch, Christopher

    2015-01-01

    This article will consider the claim that the possession of concepts is innate rather than learned. Innatism about concept learning is explained through consideration of the work of Fodor and Chomsky. First, an account of concept formation is developed. Second the argument against the claim that concepts are learned through the construction of a…

  10. Innatism, Concept Formation, Concept Mastery and Formal Education

    ERIC Educational Resources Information Center

    Winch, Christopher

    2015-01-01

    This article will consider the claim that the possession of concepts is innate rather than learned. Innatism about concept learning is explained through consideration of the work of Fodor and Chomsky. First, an account of concept formation is developed. Second the argument against the claim that concepts are learned through the construction of a…

  11. Resource Prospector (RP) - Early Prototyping and Development

    NASA Technical Reports Server (NTRS)

    Andrews, D.; Colaprete, A.; Quinn, J.; Bluethmann, B.; Trimble, J.

    2015-01-01

    The Resource Prospector (RP) is an In-Situ Resource Utilization (ISRU) technology demonstration mission under study by the NASA Human Exploration and Operations Mission Directorate's (HEOMD) Advanced Exploration Systems (AES) Division. The mission, currently planned to launch in 2020, will demonstrate extraction of oxygen from lunar regolith to validate ISRU capability. The mission will address key Strategic Knowledge Gaps (SKGs) for robotic and human exploration to the Moon, Near Earth Asteroids (NEAs), and ultimately Mars, as well as meet the strategic goals of the Global Exploration Roadmap (GER), offered by the International Space Exploration Coordination Group (ISECG). In this roadmap, the use of local resources is specifically addressed relating to human exploration. RP will provide knowledge to inform the selection of future mission destinations, support the development of exploration systems, and reduce the risk associated with human exploration. Expanding human presence beyond low-Earth orbit to asteroids and Mars will require the maximum possible use of local materials, so-called in-situ resources. The moon presents a unique destination to conduct robotic investigations that advance ISRU capabilities, as well as providing significant exploration and science value. Lunar regolith contains useful resources such as oxygen, water, silicon, and light metals, like aluminum and titanium. Oxygen can be separated from the regolith for life support (breathable air), or used to create rocket propellant (oxidizer). Regolith can be used to protect against radiation exposure, be processed into solar cells, or used to manufacture construction materials such as bricks and glass. RP will characterize the constituents and distribution of water and other volatiles at the poles of the Moon, enabling innovative uses of local resources, in addition to validating ISRU capabilities. This capability, as well as a deeper understanding of regolith, will be valuable in the

  12. National Outcome Measures for Early Childhood Development: Development of an Indicator-Based Reporting Framework

    ERIC Educational Resources Information Center

    Australian Institute of Health and Welfare, 2011

    2011-01-01

    The Council of Australian Governments released the National Early Childhood Development Strategy, Investing in the Early Years in July 2009 (COAG 2009). One of the key reform priorities in the strategy is to build better information and a solid evidence base, and establishing national outcome measures for early childhood development has been…

  13. National Outcome Measures for Early Childhood Development: Development of an Indicator-Based Reporting Framework

    ERIC Educational Resources Information Center

    Australian Institute of Health and Welfare, 2011

    2011-01-01

    The Council of Australian Governments released the National Early Childhood Development Strategy, Investing in the Early Years in July 2009 (COAG 2009). One of the key reform priorities in the strategy is to build better information and a solid evidence base, and establishing national outcome measures for early childhood development has been…

  14. Adaptation in the innate immune system and heterologous innate immunity.

    PubMed

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  15. Innate immunity in the Aegean: ancient pathways for today's survival.

    PubMed

    Vasta, G R; Lambris, J D

    2002-04-01

    A workshop on innate immunity that took place this past autumn in Fira, Santorini, as part of the Aegean Conferences, provided tantalizing evidence about the early origin and evolutionary conservation of humoral and cellular components of innate immunity from sponges, flies and sea squirts to man, uncovered mechanistic aspects of its fundamental role in defense against disease, as well as the serious consequences of misdirected responses, and revealed the untapped potential of novel therapeutic approaches.

  16. Early development of Negro and White babies

    PubMed Central

    Pollak, Margaret; Mitchell, Susan

    1974-01-01

    Seventy-five babies, 25 English, 25 West Indian, and 25 Cypriot, all born in London, were examined at 1, 3, and 9 months of age on Gesell and Sheridan scales. The age of walking alone was measured. All the babies were term normal deliveries, weighing 2500 g or more. They were examined under identical conditions. A statistically significant acceleration in gross motor function was found in the West Indian infants at 1 month, compared with the English and Cypriot infants. The acceleration related to extension. At 3 months all three groups were at the same developmental level, and at 9 months both the English and Cypriot babies were ahead of the West Indian infants in adaptive, language, and personal-social development. No significant difference in mean age of walking between the three groups was found. PMID:4818091

  17. Early intestinal growth and development in poultry.

    PubMed

    Lilburn, M S; Loeffler, S

    2015-07-01

    While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology. © 2015 Poultry Science Association Inc.

  18. Continuing Professional Development in Early Childhood Education in New Zealand

    ERIC Educational Resources Information Center

    Cherrington, Sue; Thornton, Kate

    2013-01-01

    This article explores the influences on and nature of continuing professional development in the New Zealand early childhood education sector. In addition to discussing the nature of professional development and providing an explanation of the policy context that informs the delivery of professional development, the paper draws on evaluations of…

  19. Yersinia pestis requires the 2-component regulatory system OmpR-EnvZ to resist innate immunity during the early and late stages of plague.

    PubMed

    Reboul, Angéline; Lemaître, Nadine; Titecat, Marie; Merchez, Maud; Deloison, Gaspard; Ricard, Isabelle; Pradel, Elizabeth; Marceau, Michaël; Sebbane, Florent

    2014-11-01

    Plague is transmitted by fleas or contaminated aerosols. To successfully produce disease, the causal agent (Yersinia pestis) must rapidly sense and respond to rapid variations in its environment. Here, we investigated the role of 2-component regulatory systems (2CSs) in plague because the latter are known to be key players in bacterial adaptation to environmental change. Along with the previously studied PhoP-PhoQ system, OmpR-EnvZ was the only one of Y. pestis' 23 other 2CSs required for production of bubonic, septicemic, and pneumonic plague. In vitro, OmpR-EnvZ was needed to counter serum complement and leukocytes but was not required for the secretion of antiphagocyte exotoxins. In vivo, Y. pestis lacking OmpR-EnvZ did not induce an early immune response in the skin and was fully virulent in neutropenic mice. We conclude that, throughout the course of Y. pestis infection, OmpR-EnvZ is required to counter toxic effectors secreted by polymorphonuclear leukocytes in the tissues. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Oral innate immunity in HIV infection in HAART era

    PubMed Central

    Nittayananta, Wipawee; Tao, Renchuan; Jiang, Lanlan; Peng, Yuanyuan; Huang, Yuxiao

    2015-01-01

    Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces provide not only a physical barrier but also produce different antimicrobial peptides, including human β-defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co-infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection contributed to a global reduction of HIV-associated oral lesions. However, prolonged treatment by HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: 1) What are the roles of oral innate immunity in health and disease?, 2) What are the effects of HIV infection on oral innate immunity?, 3) What are the roles of oral innate immunity against other co-infections?, 4) What are the effects of HAART on oral innate immunity?, and 5) Is oral innate immunity enhanced by HAART? PMID:25639844

  1. Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways.

    PubMed

    Rajsbaum, Ricardo; García-Sastre, Adolfo

    2013-08-01

    Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections by counteracting host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin (Ub) system. Virus-mediated inhibition of antiviral factors by Ub-dependent degradation is emerging as a crucial mechanism for evading the antiviral response. In addition, recent studies have uncovered new mechanisms by which virus-encoded proteins inhibit Ub and Ub-like (Ubl) modification of host proteins involved in innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses.

  2. Early development of an enterprise health data warehouse.

    PubMed

    Househ, Mowafa Said; Al-Tuwaijri, Majid

    2011-01-01

    The purpose of this study is to describe early development challenges of an enterprise data warehouse within a Saudi Arabian academic healthcare facility. An action case research method was selected for this paper. The study took place between December 2009 and February 2010. Data collection included interviews, meeting observations, and meeting minutes. Early development challenges centered on the development of clear contracts with vendors; development of a clear project plan; a need to fast-track bureaucracy; and educate clinicians and staff about the project; and lack of data standardization.

  3. Adaptive Control of Innate Immunity

    PubMed Central

    Shanker, Anil

    2010-01-01

    1. Summary The mechanisms by which the immune system responds to an infection or disease depend on a complex interplay between the elements of innate and adaptive immunity. While most of the focus so far has been on the innate instruction of the adaptive immune responses, considerable evidence now suggests an equally important adaptive control of the innate immunity. Several studies yield new insights into how the adaptive immunity by initiating an antigen–specific response can compensate, suppress and activate innate responses at the site of tissue antigen. Here we discuss recent advances in our understanding of the adaptive control of immune effector functions in various pathological and physiological conditions. PMID:20394777

  4. Innate immune memory in mammals.

    PubMed

    Hamon, Melanie A; Quintin, Jessica

    2016-08-01

    Innate and adaptive immunity have evolved as sophisticated mechanisms of host defence against invading pathogens. Classically the properties attributed to innate immunity are its rapid pleiotropic response, and to adaptive immunity its specificity and ability to retain a long-term memory of past infections. It is now clear that innate immunity also contributes to raising a memory response upon pathogenic assault. In this review we will discuss the interaction between bacterial, viral, fungal and parasitic molecular patterns and innate immune cells in which a memory response is imposed, or has the potential to be imposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. The Early Motor Questionnaire (EMQ): A Parental Report Measure of Early Motor Development

    PubMed Central

    Libertus, Klaus; Landa, Rebecca J.

    2013-01-01

    Children's early motor skills are critical for development across language, social, and cognitive domains, and warrant close examination. However, examiner-administered motor assessments are time consuming and expensive. Parent-report questionnaires offer an efficient alternative, but validity of parent report is unclear and only few motor questionnaires exist. In this report, we use cross-sectional and longitudinal data to investigate the validity of parent report in comparison to two examiner-administered measures (Mullen Scales of Early Learning, MSEL; Peabody Developmental Motor Scales, PDMS-2), and introduce a new parent-report measure called the Early Motor Questionnaire (EMQ). Results indicate strong correlations between parent report on the EMQ and a child's age, robust concurrent and predictive validity of parent report with both the MSEL and PDMS-2, and good test-re-test reliability of parent report on the EMQ. Together, our findings support the conclusion that parents provide dependable accounts of early motor and cognitive development. PMID:24140841

  6. The Hong Kong Early Child Development Scale: A Validation Study.

    PubMed

    Rao, Nirmala; Sun, Jin; Ng, Sharon Sui Ngan; Ma, Kitty; Becher, Yvonne; Lee, Diana; Lau, Carrie; Zhang, Li; Chow, Chun Bong; Ip, Patrick

    2013-03-01

    This paper reports on the development and validation of the Hong Kong Early Child Development Scale (HKECDS), a holistic measure of child development designed specifically for preschool children in Hong Kong. Scale development was an iterative process and the first version of the scale contained 190 items whereas the final version includes only 95. Children ranging in age from three to six years were administered trial versions of the HKECDS in Studies 1 (n = 60) and 2 (n = 240). Item analyses indicated that it is a developmental scale and that it has an appropriate level of difficulty for preschool children. It also discriminates between three- to six-year-olds from different social backgrounds in Hong Kong. The final version of the HKECDS includes items from the following eight subscales: Personal, Social and Self-Care (7 items), Language Development (13 items), Pre-academic Learning (27 items), Cognitive Development (10 items), Gross Motor (12 items), Fine Motor (9 items), Physical Fitness, Health and Safety (7 items), and Self and Society (10 items). The HKECDS is the first early child development scale which considers both the holistic development of preschool children and incorporates current expectations of early child development in Hong Kong. In this era of evidence-based decision making, it can be used to evaluate both the efficacy of targeted interventions and broader child-related public policies on early child development in Hong Kong.

  7. Innate immune receptors in solid organ transplantation.

    PubMed

    Georgel, Philippe

    2016-11-01

    The discovery of Pattern Recognition Receptors (PRRs) followed by that of their role in the early detection of pathogens and the ignition of the innate immune response has been a formidable progress for immunological research in the past 15years. This has massively fueled investigations aiming at developing better strategies to fight off infectious diseases and/or to prevent their occurrence. However, infected individuals are for most part outliers in a given population and therefore, the primary function of these receptors should be considered in pathogen-free conditions. Our current understanding indicates that an important physiological function of PRRs resides in their capacity to maintain epithelial homeostasis in response to colonizing commensals. In addition, endogenous host-derived ligands, expressed under stressed, albeit sterile, conditions (called DAMPs for Danger-Associated Molecular Patterns) are also able to trigger PRR signaling. Solid organ transplantation represents a unique situation where both contributions of PRRs signaling can be studied. Indeed, dysbiosis (either caused by antibiotherapy preceding organ transplantation or simply due to the microbiota differences between the transplanted organ and the recipient host) is a characteristic feature of this situation, which is also marked by a massive synthesis and liberation of DAMPs as a result of hypoxia/reperfusion injury. Therefore, in the transplanted organ, at least two compartments (epithelial and that composed of immune cells) participate in graft rejection/acceptance depending on the activation status of expressed PRRs.

  8. Early life origins of psychological development and mental health.

    PubMed

    Räikkönen, Katri; Pesonen, Anu-Katriina

    2009-12-01

    According to the Developmental Origins of Health and Disease (DOHaD)-hypothesis, conditions early in life may have life-long consequences. In a series of epidemiological birth cohort and clinical studies and natural experiments, we have had the chance to test the extent to which this hypothesis is useful in understanding individual differences in psychological development and mental health. Our findings have provided evidence that individual differences in cognitive, social and emotional development and in mental health may lie in early life circumstances, and add significantly to the literature by pointing out which periods of early growth are the most critical. These findings are also important in translating pre-clinical evidence to humans. What remains less clear, however, is what the mechanisms of programming are. Thus, further research is needed to elucidate these mechanisms before information on the early life origins of health and disease can be used in designing prevention and intervention programs.

  9. Promoting equity through integrated early child development and nutrition interventions.

    PubMed

    Black, Maureen M; Dewey, Kathryn G

    2014-01-01

    Sustainable development, a foundation of the post-2015 global agenda, depends on healthy and productive citizens. The origins of adult health begin early in life, stemming from genetic-environmental interactions that include adequate nutrition and opportunities for responsive learning. Inequities associated with inadequate nutrition and early learning opportunities can undermine children's health and development, thereby compromising their productivity and societal contributions. Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children and the environment, mediated through caregiver interactions. Although single interventions targeting early child development or nutrition can be effective, there is limited evidence on the development, implementation, evaluation, and scaling up of integrated interventions. This manuscript introduces a special edition of papers on six topics central to integrated child development/nutrition interventions: (1) review of integrated interventions; (2) methods and topics in designing integrated interventions; (3) economic considerations related to integrated interventions; (4) capacity-building considerations; (5) examples of integrated interventions; and (6) policy implications of integrated interventions. Ensuring the health and development of infants and young children through integrated child development/nutrition interventions promotes equity, a critical component of sustainable development.

  10. Seeing, Making, Doing: Creative Development in Early Years Settings. Early Education Support Series.

    ERIC Educational Resources Information Center

    Orley, Ray

    Part of a series for early years teachers in Scotland, this guide focuses on ways to provide creative opportunities that support and enhance child development. The guide discusses how to respect children's creativity while observing and developing their skills and suggests practical and creative alternatives to the mass production of identical…

  11. Early Brain and Child Development: Connections to Early Education and Child Care

    ERIC Educational Resources Information Center

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  12. Getting an Early Start on Early Child Development. Education Notes. 30194

    ERIC Educational Resources Information Center

    Young, Mary Eming; Dunkelberg, Erika

    2004-01-01

    The children born this year--2004--will be eleven years old in 2015--the age of primary school completion in most countries. This is the MDG (Millennium Development Goal) generation--for whom the international community has pledged that by 2015, all children will be able to complete primary schooling. Ensuring good early child development is the…

  13. Early Brain and Child Development: Connections to Early Education and Child Care

    ERIC Educational Resources Information Center

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  14. Integrated and Early Childhood Education: Preparation for Social Development. Theme A: Relevant Provision for Early Childhood.

    ERIC Educational Resources Information Center

    Axton, J. H. M.

    Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…

  15. Getting an Early Start on Early Child Development. Education Notes. 30194

    ERIC Educational Resources Information Center

    Young, Mary Eming; Dunkelberg, Erika

    2004-01-01

    The children born this year--2004--will be eleven years old in 2015--the age of primary school completion in most countries. This is the MDG (Millennium Development Goal) generation--for whom the international community has pledged that by 2015, all children will be able to complete primary schooling. Ensuring good early child development is the…

  16. Development of pattern vision following early and extended blindness

    PubMed Central

    Kalia, Amy; Lesmes, Luis Andres; Dorr, Michael; Gandhi, Tapan; Chatterjee, Garga; Ganesh, Suma; Bex, Peter J.; Sinha, Pawan

    2014-01-01

    Visual plasticity peaks during early critical periods of normal visual development. Studies in animals and humans provide converging evidence that gains in visual function are minimal and deficits are most severe when visual deprivation persists beyond the critical period. Here we demonstrate visual development in a unique sample of patients who experienced extended early-onset blindness (beginning before 1 y of age and lasting 8–17 y) before removal of bilateral cataracts. These patients show surprising improvements in contrast sensitivity, an assay of basic spatial vision. We find that contrast sensitivity development is independent of the age of sight onset and that individual rates of improvement can exceed those exhibited by normally developing infants. These results reveal that the visual system can retain considerable plasticity, even after early blindness that extends beyond critical periods. PMID:24449865

  17. The effectiveness of early childhood development programs. A systematic review.

    PubMed

    Anderson, Laurie M; Shinn, Carolynne; Fullilove, Mindy T; Scrimshaw, Susan C; Fielding, Jonathan E; Normand, Jacques; Carande-Kulis, Vilma G

    2003-04-01

    Early childhood development is influenced by characteristics of the child, the family, and the broader social environment. Physical health, cognition, language, and social and emotional development underpin school readiness. Publicly funded, center-based, comprehensive early childhood development programs are a community resource that promotes the well-being of young children. Programs such as Head Start are designed to close the gap in readiness to learn between poor children and their more economically advantaged peers. Systematic reviews of the scientific literature demonstrate effectiveness of these programs in preventing developmental delay, as assessed by reductions in retention in grade and placement in special education.

  18. Professional Development Needs and Interests of Early Childhood Education Trainers

    ERIC Educational Resources Information Center

    Byington, Teresa A.; Tannock, Michelle T.

    2011-01-01

    An online survey of early childhood education (ECE) trainers was conducted to assess their professional development needs and determine any differences between new and experienced trainers. Trainers identified teaching techniques and resources commonly used. The survey information is guiding the development of ECE trainer criteria in a…

  19. Understanding Emotional Development: Helping Early Childhood Providers Better Support Families

    ERIC Educational Resources Information Center

    Edwards, Nicole Megan

    2012-01-01

    This article is intended to provide early childhood providers with a concise overview of emerging emotional development in young children (birth-5), the important role of primary caregivers, and the link between parenting, emotional development, and behavior. Specific suggestions that have been shared with urban Head Start mothers are offered,…

  20. Culture and Early Language Development: Implications for Assessment and Intervention

    ERIC Educational Resources Information Center

    Parada, Patricia M.

    2013-01-01

    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  1. Symbolic Play and Early Language Development in Normal Children.

    ERIC Educational Resources Information Center

    Ogura, Tamiko

    Examined in a longitudinal study of children were correspondences and correlations between early language development on the one hand, and the manipulation of objects and play development on the other. There were developmental correspondences between the onset of five language landmarks (the emergence of first word, referential word, demonstrative…

  2. Culture and Early Language Development: Implications for Assessment and Intervention

    ERIC Educational Resources Information Center

    Parada, Patricia M.

    2013-01-01

    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  3. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    ERIC Educational Resources Information Center

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  4. Helping Families Connect Early Literacy with Social-Emotional Development

    ERIC Educational Resources Information Center

    Santos, Rosa Milagros; Fettig, Angel; Shaffer, LaShorage

    2012-01-01

    Early childhood educators know that home is a child's first learning environment. From birth, children are comforted by hearing and listening to their caregivers' voices. The language used by families supports young children's development of oral language skills. Exposure to print materials in the home also supports literacy development. Literacy…

  5. Early Learning and Development: Cultural-Historical Concepts in Play

    ERIC Educational Resources Information Center

    Fleer, Marilyn

    2010-01-01

    "Early Learning and Development" provides a unique synthesis of cultural-historical theory from Vygotsky, Elkonin and Leontiev in the 20th century to the ground-breaking research of scholars such as Siraj-Blatchford, Kratsova and Hedegaard today. It demonstrates how development and learning are culturally embedded and institutionally defined, and…

  6. Professional development session for early career scientists at SITC 2012

    PubMed Central

    2013-01-01

    The Society for Immunotherapy of Cancer (SITC) 2012 Professional Development Session was held as part of the SITC 27th Annual Meeting, Washington, DC, on October 24, 2012. The session was designed as a new opportunity for early career investigators to learn about relevant career development topics in a didactic setting. PMID:25742323

  7. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    ERIC Educational Resources Information Center

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  8. Child Development, Early Childhood Education and Family Life: A Bibliography.

    ERIC Educational Resources Information Center

    Reardon, Beverly, Comp.

    This bibliographical listing of approximately 2500 books on child development, early childhood education and family life was compiled as a resource for parents and students. Books are listed alphabetically by author and are grouped according to the following categories: child development; observation of children; adolescence; language…

  9. Child Development, Early Childhood Education and Family Life: A Bibliography.

    ERIC Educational Resources Information Center

    Reardon, Beverly, Comp.

    This bibliographical listing of approximately 2500 books on child development, early childhood education and family life was compiled as a resource for parents and students. Books are listed alphabetically by author and are grouped according to the following categories: child development; observation of children; adolescence; language…

  10. Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

    PubMed Central

    Lisciandro, Joanne G.; Prescott, Susan L.; Nadal-Sims, Marie G.; Devitt, Catherine J.; Pomat, William; Siba, Peter M.; Tulic, Meri C.; Holt, Patrick G.; Strickland, Deborah; van den Biggelaar, Anita H. J.

    2012-01-01

    Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure. PMID:22649499

  11. Development of Early Measures of Comprehension: Innovation in Individual Growth and Development Indicators

    ERIC Educational Resources Information Center

    Wackerle-Hollman, Alisha K.; Rodriguez, Megan I.; Bradfield, Tracy A.; Rodriguez, Michael C.; McConnell, Scott R.

    2015-01-01

    Early comprehension is an important, but not well-understood, contribution to early literacy and language development. Specifically, research regarding the nature of skills representative of early comprehension, including how they contribute to later reading success, is needed to support best practices to adequately prepare students. This article…

  12. Development of Early Measures of Comprehension: Innovation in Individual Growth and Development Indicators

    ERIC Educational Resources Information Center

    Wackerle-Hollman, Alisha K.; Rodriguez, Megan I.; Bradfield, Tracy A.; Rodriguez, Michael C.; McConnell, Scott R.

    2015-01-01

    Early comprehension is an important, but not well-understood, contribution to early literacy and language development. Specifically, research regarding the nature of skills representative of early comprehension, including how they contribute to later reading success, is needed to support best practices to adequately prepare students. This article…

  13. Developing Early Literacy: Report of the National Early Literacy Panel. A Scientific Synthesis of Early Literacy Development and Implications for Intervention

    ERIC Educational Resources Information Center

    National Institute for Literacy, 2008

    2008-01-01

    The National Early Literacy Panel (NELP) was appointed in 2002 and carried out its work under the auspices of the National Center for Family Literacy (NCFL). NELP's primary goal was to identify interventions, parenting activities, and instructional practices that promote the development of children's early literacy skills. The National Institute…

  14. Analysis of the Impact of Isoquinoline Alkaloids, Derived from Macleaya cordata Extract, on the Development and Innate Immune Response in Swine and Poultry

    PubMed Central

    Martínez, Yordan; Rodríguez, Román; Más, Dairon; Peng, Hanhui; Valdivié Navarro, Manuel

    2016-01-01

    Medicinal extract has been chronicled extensively in traditional Chinese medicine. Isoquinoline alkaloids, extract of Macleaya cordata (Willd.) R. Br., have been used as feed additive in both swine and poultry. Dietary supplementation with isoquinoline alkaloids increases feed intake and weight gain. In addition, recent researches have demonstrated that isoquinoline alkaloids can regulate metabolic processes, innate immune system, and digestive functioning in animals. This review summarizes the latest scientific researches on isoquinoline alkaloids which are extracted from Macleaya cordata (Willd.) R. Br. This review specifically focuses on its role as a feed supplement and its associated impact on growth performance and innate immune system, as well as its capacity to act as a substitute for oral antibiotics. PMID:28042566

  15. Analysis of the Impact of Isoquinoline Alkaloids, Derived from Macleaya cordata Extract, on the Development and Innate Immune Response in Swine and Poultry.

    PubMed

    Ni, Hengjia; Martínez, Yordan; Guan, Guiping; Rodríguez, Román; Más, Dairon; Peng, Hanhui; Valdivié Navarro, Manuel; Liu, Gang

    2016-01-01

    Medicinal extract has been chronicled extensively in traditional Chinese medicine. Isoquinoline alkaloids, extract of Macleaya cordata (Willd.) R. Br., have been used as feed additive in both swine and poultry. Dietary supplementation with isoquinoline alkaloids increases feed intake and weight gain. In addition, recent researches have demonstrated that isoquinoline alkaloids can regulate metabolic processes, innate immune system, and digestive functioning in animals. This review summarizes the latest scientific researches on isoquinoline alkaloids which are extracted from Macleaya cordata (Willd.) R. Br. This review specifically focuses on its role as a feed supplement and its associated impact on growth performance and innate immune system, as well as its capacity to act as a substitute for oral antibiotics.

  16. Shades of grey--the blurring view of innate and adaptive immunity.

    PubMed

    Lanier, Lewis L

    2013-02-01

    This special issue of Nature Reviews Immunology focuses on the types of lymphocyte that blur the traditional boundaries between the innate and adaptive immune systems. The development and functional properties of 'innate-like' B and T cells and natural killer (NK) cells are reviewed and the emerging understanding of newly discovered innate lymphoid cells (ILCs) is considered.

  17. Innate cell communication kick-starts pathogen-specific immunity

    PubMed Central

    Rivera, Amariliz; Siracusa, Mark C.; Yap, George S.; Gause, William C.

    2016-01-01

    Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of ‘trained’ innate cells that facilitate the rapid elimination of homologous or heterologous infections. PMID:27002843

  18. What rheumatologists need to know about innate lymphocytes.

    PubMed

    Exley, Mark A; Tsokos, George C; Mills, Kingston H G; Elewaut, Dirk; Mulhearn, Ben

    2016-11-01

    Many rheumatic diseases are characterized by having an autoimmune background. Determining the mechanisms underlying autoimmunity is, therefore, important to further understand these diseases and to inform future lines of research aimed at developing new treatments and cures. As fast responders, innate lymphocytes have protective or pathogenic roles in the initiation as well as the maintenance of immune responses in general, and they contribute to tissue homeostasis, among other functions. Innate lymphocytes also seem to be involved in autoimmunity in particular. Since 2010, accumulating evidence clearly shows that different populations of innate lymphocytes have roles in responding to antigen-specific autoantibody and autoreactive T cells, thereby amplifying or attenuating disease processes. Cytotoxicity is a cardinal feature of many innate lymphocytes and can contribute to inflammatory tissue damage. Finally, innate lymphocytes can respond to biologic therapies for autoimmune diseases. Consequently, like TNF and other effector molecules, certain innate lymphocyte subsets might be appropriate therapeutic targets to ameliorate various autoimmune diseases. In this Review, we summarize the main characteristics and functions of innate lymphocyte subsets, and describe their roles in autoimmune disease. We also discuss how biologic therapies influence innate lymphocyte function and consider the potential for these cell subsets to act as future therapeutic targets.

  19. The development of self-regulation across early childhood.

    PubMed

    Montroy, Janelle J; Bowles, Ryan P; Skibbe, Lori E; McClelland, Megan M; Morrison, Frederick J

    2016-11-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and 7 years, with a direct focus on possible heterogeneity in the developmental trajectories, and a set of potential indicators that distinguish unique behavioral self-regulation trajectories. Across 3 diverse samples, 1,386 children were assessed on behavioral self-regulation from preschool through first grade. Results indicated that majority of children develop self-regulation rapidly during early childhood, and that children follow 3 distinct developmental patterns of growth. These 3 trajectories were distinguishable based on timing of rapid gains, as well as child gender, early language skills, and maternal education levels. Findings highlight early developmental differences in how self-regulation unfolds, with implications for offering individualized support across children. (PsycINFO Database Record

  20. Early determinants of development: a lipid perspective1234

    PubMed Central

    Carlson, Susan E

    2009-01-01

    This article results from an International Life Sciences Institute workshop on early nutritional determinants of health and development. The presentation on lipids focused mainly on the longer-chain products of the essential fatty acids, particularly docosahexaenoic acid (22:6n–3), and cognitive development as among the most studied lipids and outcomes, respectively, in early human nutrition. Because there have been several recent reviews on this topic, the present review takes a broader perspective with respect to both early development and lipids: an expanded research agenda is plausible on the basis of observations from some human studies and from animal studies. Other lipids known to be provided in variable amounts to infants through human milk are cholesterol and gangliosides. Short sections address the current state of knowledge and some questions that could be pursued. PMID:19321568

  1. Fertilization and early embryonic development in the porcine fallopian tube.

    PubMed

    Brüssow, K-P; Rátky, J; Rodriguez-Martinez, H

    2008-07-01

    Fertilization and early embryo development relies on a complex interplay between the Fallopian tube and the gametes before and after fertilization. Thereby the oviduct, as a dynamic reproductive organ, enables reception, transport and maturation of male and female gametes, their fusion, and supports early embryo development. This paper reviews current knowledge regarding physiological processes behind the transport of boar spermatozoa, their storage in and release from the functional sperm reservoir (SR), and of the interactions that newly ovulated oocytes play within the tube during their transport to the site of fertilization. Experimental evidence of an ovarian control on sperm release from the SR is highlighted. Furthermore, the impact of oviductal secretion on sperm capacitation, oocyte maturation, fertilization and early embryo development is stressed.

  2. Sleep and innate immunity.

    PubMed

    Zielinski, Mark R; Krueger, James M

    2011-01-01

    Many pro-inflammatory molecules, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are somnogenic, while many anti-inflammatory molecules inhibit sleep. Sleep loss increases the production/release of these sleep regulatory pro-inflammatory molecules. Further, sleep changes occurring during various pathologies are mediated by these inflammatory substances in response to pathogen recognition and subsequent inflammatory cellular pathways. This review summarizes information and concepts regarding inflammatory mechanisms of the innate immune system that mediate sleep. Further, we discuss sleep-immune interactions in regards to sleep in general, pathologies, and sleep as a local phenomenon including the central role that extracellular ATP plays in the initiation of sleep.

  3. Early cardiac development: a view from stem cells to embryos

    PubMed Central

    Van Vliet, Patrick; Wu, Sean M.; Zaffran, Stéphane; Pucéat, Michel

    2012-01-01

    From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the endocardium, myocardium, and epicardium. More recently, mouse and human embryonic stem cells (ESCs) have demonstrated faithful recapitulation of early cardiogenesis and have contributed significantly to this research over the past few decades. Derived almost 15 years ago, human ESCs have provided a unique developmental model for understanding the genetic and epigenetic regulation of early human cardiogenesis. Here, we review the biological concepts underlying cell fate decisions during early cardiogenesis in model organisms and ESCs. We draw upon both pioneering and recent studies and highlight the continued role for in vitro stem cells in cardiac developmental biology. PMID:22893679

  4. Innate Visual Learning through Spontaneous Activity Patterns

    PubMed Central

    Albert, Mark V.; Schnabel, Adam; Field, David J.

    2008-01-01

    Patterns of spontaneous activity in the developing retina, LGN, and cortex are necessary for the proper development of visual cortex. With these patterns intact, the primary visual cortices of many newborn animals develop properties similar to those of the adult cortex but without the training benefit of visual experience. Previous models have demonstrated how V1 responses can be initialized through mechanisms specific to development and prior to visual experience, such as using axonal guidance cues or relying on simple, pairwise correlations on spontaneous activity with additional developmental constraints. We argue that these spontaneous patterns may be better understood as part of an “innate learning” strategy, which learns similarly on activity both before and during visual experience. With an abstraction of spontaneous activity models, we show how the visual system may be able to bootstrap an efficient code for its natural environment prior to external visual experience, and we continue the same refinement strategy upon natural experience. The patterns are generated through simple, local interactions and contain the same relevant statistical properties of retinal waves and hypothesized waves in the LGN and V1. An efficient encoding of these patterns resembles a sparse coding of natural images by producing neurons with localized, oriented, bandpass structure—the same code found in early visual cortical cells. We address the relevance of higher-order statistical properties of spontaneous activity, how this relates to a system that may adapt similarly on activity prior to and during natural experience, and how these concepts ultimately relate to an efficient coding of our natural world. PMID:18670593

  5. Essential role for Max in early embryonic growth and development

    PubMed Central

    Shen-Li, Hong; O'Hagan, Rónán C.; Hou, Harry; Horner, James W.; Lee, Han-Woong; DePinho, Ronald A.

    2000-01-01

    Loss of Max function in the mouse resulted in generalized developmental arrest of both embryonic and extraembryonic tissues at early postimplantation (∼E5.5–6.5), coincident with loss or dilution of maternal Max stores in the expanding embryo in vivo and in blastocyst outgrowths in vitro. Developmentally arrested embryos were reduced in size and exhibited widespread cytological degeneration and feeble BrdU incorporation. Max and, by extension, the Myc superfamily, serve essential roles in early mammalian development and a maternal reservoir of Max exists in sufficient amount to sustain Myc superfamily function through preimplantation stages of development. PMID:10640271

  6. Early feeding practices and development of food allergies.

    PubMed

    Lack, Gideon; Penagos, Martin

    2011-01-01

    Despite increasing efforts to prevent food allergies in children, IgE-mediated food allergies continue to rise in westernized countries. Previous preventive strategies such as prolonged exclusive breastfeeding and delayed weaning onto solid foods have more recently been called into question. The present review discusses possible risk factors and theories for the development of food allergy. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure of food allergen induces tolerance. Novel interventional strategies to prevent the development of food allergies are also discussed.

  7. Early childhood growth and development in rural Guatemala.

    PubMed

    Kuklina, Elena V; Ramakrishnan, Usha; Stein, Aryeh D; Barnhart, Huiman H; Martorell, Reynaldo

    2006-07-01

    Small size at birth and in early childhood has been associated with impaired neurodevelopment in studies from developing countries, but few have examined associations with growth. The objective of this study was to assess the relationship between growth and neurodevelopment during early childhood (birth-36 months). Multivariate regression models were used to analyze the data collected in the course of a study of pregnancy outcomes and early childhood growth and development carried out in rural Guatemala in 1991-1999. Motor and mental development scores were based on the Psychomotor and Mental Development Indices, respectively, derived from the administration of an adapted version of the Bayley Scales of Infant Development (Second Edition, 1993) at 6, 24 and 36 months. Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and head circumference-for-age (HCZ) were used as indicators of attained size; changes in these Z-scores over time represent growth. Birth size was significantly associated with child development at 6 and 24 months. Gains in length and weight during the first 24 months were positively associated with child development, whereas growth from 24 to 36 months age was not associated with child development at 36 months. Motor development was more strongly and consistently related to child growth than was mental development. Head circumference gain after 6 months was not a significant predictor of child development at 24 and 36 months. Small size at birth and poor physical growth during the first 24 months are related to neurodevelopmental delays. More evidence from developing countries will help explain the underlying mechanisms and identify appropriate interventions to prevent neurodevelopmental delay in early childhood.

  8. Biophoton emission in synchronously developing population of early Drosophila embryos

    NASA Astrophysics Data System (ADS)

    Zhou, Yu-Ming; Ho, Mae-Wan; Bolton, John P.; Milani, Marziale; Costato, Michele; Musumeci, Francesco

    1996-11-01

    Ultraweak biophoton emission has been recorded in synchronously developing populations of early Drosophila embryos. On being stimulated briefly with white light within the first 40 minutes of development, a new kind of luminescence is observed in the form of superdelayed, intense flashes. We assume that the initial light stimulation sets up some kind of coherent interaction inside the system and develop a phenomenological number-phase-angle model to give a general interpretation of the superdelayed radiation patterns.

  9. Temperament, Executive Control, and ADHD across Early Development

    PubMed Central

    Rabinovitz, Beth B.; O’Neill, Sarah; Rajendran, Khushmand; Halperin, Jeffrey M.

    2015-01-01

    Research examining factors linking early temperament and later ADHD is limited by cross-sectional approaches and having the same informant rate both temperament and psychopathology. We used multi-informant/multi-method longitudinal data to test the hypothesis that negative emotionality during preschool is positively associated with ADHD symptom severity in middle childhood, but developing executive control mediates this relation. Children (N=161) with and without ADHD were evaluated three times: Parent and teacher temperament ratings and NEPSY Visual Attention at ages 3–4 years; WISC-IV Working Memory Index and NEPSY Response Set at age 6 years; and ADHD symptoms using the Kiddie-SADS at age 7 years. Parent and teacher ratings of preschoolers’ temperament were combined to form an Anger/Frustration composite. Similarly, an Executive Functioning composite was derived from age 6 measures. Bootstrapping was used to determine whether age 6 Executive Functioning mediated the relation between early Anger/Frustration and later ADHD symptom severity, while controlling for early executive functioning. Preschoolers’ Anger/Frustration was significantly associated with later ADHD symptoms, with this relation partially mediated by age 6 Executive Functioning. Developing executive control mediates the relation between early Anger/Frustration and later ADHD symptom severity, suggesting that Anger/Frustration influences ADHD symptom severity through its impact on developing executive control. Early interventions targeting the harmful influences of negative emotionality or enhancing executive functioning may diminish later ADHD severity. PMID:26854505

  10. Chemokines in Innate and Adaptive Granuloma Formation

    PubMed Central

    Chensue, Stephen W.

    2012-01-01

    Granulomas are cellular inflammations that vary widely in histologic appearance depending upon the inciting agent and immunologic status of the responding host. Despite their heterogeneity, granulomas are at their core an ancient innate sequestration response characterized by the accumulation of mononuclear phagocytes. In fact, this innate cellular response was first observed by Metchnikov in simple invertebrates. Among higher vertebrates, environmental pressures have resulted in the evolution of more sophisticated adaptive immune responses which can be superimposed upon and modify the character of granulomatous inflammation. Compared to immune responses that rapidly neutralize and eliminate infectious agents, the granuloma represents a less desirable “fall back” response which still has value to the host but can be co-opted by certain infectious agents and contribute to bystander organ damage. Understanding granulomas requires an analysis of the complex interplay of innate and adaptive molecular signals that govern the focal accumulation and activity of their cellular components. Among these signals, small molecular weight chemoattractant proteins known as chemokines are potentially important contributors as they participate in both directing leukocyte migration and function. This tract will discuss the contribution of chemokines to the development of innate and adaptive granuloma formation, as well as describe their relationship to more recently evolved cytokines generated during adaptive immune responses. PMID:23444049

  11. Does preterm period sleep development predict early childhood growth trajectories?

    PubMed

    Winkler, M R; Park, J; Pan, W; Brandon, D H; Scher, M; Holditch-Davis, D

    2017-09-01

    The current study examined the relationship between sleep state development across the preterm and early post-term periods and subsequent growth trajectories from 1 to 27 months corrected age. Retrospective analysis of data collected prospectively from 111 preterm infants (⩽34 weeks gestation) who participated in a multi-site longitudinal study. Separate longitudinal parallel process models were calculated for each sleep state (active and quiet sleep) and growth (weight, length and body mass index (BMI) Z-scores) variable to estimate the associations between their developmental trajectories. Significant associations were identified between the trajectories of quiet sleep and weight, active sleep and weight, quiet sleep and BMI, and active sleep and BMI. No statistically meaningful associations were identified between the trajectories of early childhood length and the preterm sleep states. Faster preterm period sleep development appears to predict more favorable early childhood growth trajectories, particularly for weight, indicating preterm sleep may be an important biomarker for subsequent growth outcomes.

  12. Early childhood obesity is associated with compromised cerebellar development.

    PubMed

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

  13. Early Childhood Obesity is Associated with Compromised Cerebellar Development

    PubMed Central

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS — a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric MRI images. Individuals with PWS (n=16) and EMO (n=12) had smaller cerebellar volumes than a control group of 15 siblings (p=0.02 control vs. EMO; p=0.0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 ± 25; EMO 81 ± 19; and Controls 112 ± 13 (p<0.0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development. PMID:19437203

  14. Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching

    ERIC Educational Resources Information Center

    Amendum, Steven J.

    2014-01-01

    The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

  15. Social Contexts of Early Development in Education. Advances in Early Education and Day Care.

    ERIC Educational Resources Information Center

    Reifel, Stuart, Ed.

    This volume reflects some of the disciplinary and interdisciplinary diversity found in the study of programs for young children, and its chapters cover a number of matters central to early childhood development and practice, including preparation for practice. The book has 11 chapters divided into 4 parts that cover family and community, adults…

  16. The Australian Early Development Index: Reshaping Family-Child Relationships in Early Childhood Education

    ERIC Educational Resources Information Center

    Peers, Chris

    2011-01-01

    This article addresses the cultural significance of the Australian Early Development Index (AEDI) and discusses changes that the discourse of this instrument makes to the way in which the child is conceptualised. It analyses the technological function of the AEDI to examine how it makes the child a universal resource for human capital. The article…

  17. The Australian Early Development Index: Reshaping Family-Child Relationships in Early Childhood Education

    ERIC Educational Resources Information Center

    Peers, Chris

    2011-01-01

    This article addresses the cultural significance of the Australian Early Development Index (AEDI) and discusses changes that the discourse of this instrument makes to the way in which the child is conceptualised. It analyses the technological function of the AEDI to examine how it makes the child a universal resource for human capital. The article…

  18. Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching

    ERIC Educational Resources Information Center

    Amendum, Steven J.

    2014-01-01

    The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

  19. Early Learning Foundations. Indiana's Early Learning Development Framework Aligned to the Indiana Academic Standards, 2014

    ERIC Educational Resources Information Center

    Indiana Department of Education, 2015

    2015-01-01

    The "Foundations" (English/language arts, mathematics, social emotional skills, approaches to play and learning, science, social studies, creative arts, and physical health and growth) are Indiana's early learning development framework and are aligned to the 2014 Indiana Academic Standards. This framework provides core elements that…

  20. GATA-3 function in innate and adaptive immunity.

    PubMed

    Tindemans, Irma; Serafini, Nicolas; Di Santo, James P; Hendriks, Rudi W

    2014-08-21

    The zinc-finger transcription factor GATA-3 has received much attention as a master regulator of T helper 2 (Th2) cell differentiation, during which it controls interleukin-4 (IL-4), IL-5, and IL-13 expression. More recently, GATA-3 was shown to contribute to type 2 immunity through regulation of group 2 innate lymphoid cell (ILC2) development and function. Furthermore, during thymopoiesis, GATA-3 represses B cell potential in early T cell precursors, activates TCR signaling in pre-T cells, and promotes the CD4(+) T cell lineage after positive selection. GATA-3 also functions outside the thymus in hematopoietic stem cells, regulatory T cells, CD8(+) T cells, thymic natural killer cells, and ILC precursors. Here we discuss the varied functions of GATA-3 in innate and adaptive immune cells, with emphasis on its activity in T cells and ILCs, and examine the mechanistic basis for the dose-dependent, developmental-stage- and cell-lineage-specific activity of this transcription factor.

  1. Etiology of myasthenia gravis: innate immunity signature in pathological thymus.

    PubMed

    Cavalcante, Paola; Cufi, Perrine; Mantegazza, Renato; Berrih-Aknin, Sonia; Bernasconi, Pia; Le Panse, Rozen

    2013-07-01

    Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction (NMJ), whose clinical hallmark is muscle weakness and early fatigability. The main target of autoimmunity in MG is the acetylcholine receptor (AChR) located in the NMJ. It is now widely accepted that the thymus is probably the prime site of autoimmunity development and maintenance in AChR-positive MG patients; however, the exact mechanisms triggering and perpetuating the intra-thymic autoimmune response to AChR are still unknown. As with many autoimmune diseases, MG has a multifactorial etiology, resulting from complex interactions between genetic and environmental factors, as fully described in this review. Among environmental factors, viral infections could play a central role in autoimmunity, mainly through the induction of dysregulated Toll-like receptor (TLR)-mediated innate immune responses, which can lead to inflammation and adaptive autoimmune response. Growing evidence of chronic inflammation, TLR activation, and persistent viral infections in the thymus of MG patients, strongly supports the hypothesis that, in the context of a genetic susceptible background, the intrathymic innate immune responses to pathogen infections might contribute to MG etiology.

  2. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  3. Rethinking Early Learning and Development Standards in the Ugandan Context

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2013-01-01

    Concerns that the African child is being tailored to be a "global child," alongside other homogenizing and dominating projections, such as early learning and development standards (ELDS), have increased. African communities need to be assured that global standards and global indicators will not further homogenize nations and thereby risk…

  4. More Alike than Different: Early Childhood Professional Development in Guatemala

    ERIC Educational Resources Information Center

    Hardin, Belinda J.; Vardell, Rosemarie; de Castaneda, Albertina

    2008-01-01

    This article describes an early childhood professional development project that took place in the summer of 2005 in Guatemala City. Located in Central America, Guatemala has a population of approximately 12.3 million people, including more than two million children under the age of 5 (UNESCO Institute for Statistics, 2007; UNICEF, 2004). Events…

  5. Career Planning and Development for Early-Career Scientists

    EPA Science Inventory

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  6. Early Childhood Education for Sustainability: Recommendations for Development

    ERIC Educational Resources Information Center

    Daries, Julie; Engdahl, Ingrid; Otieno, Lorraine; Pramling-Samuelson, Ingrid; Siraj-Blatchford, John; Vallabh, Priya

    2009-01-01

    The following recommendations for "Education for Sustainable Development (ESD)" in Early Childhood Education were the product of an extended international collaboration that was supported by a number of bodies including the Centre for Environment and Sustainability in Gothenburg, the Swedish Ministry of Education and Research, the…

  7. HIV Infection: Transmission, Effects on Early Development, and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1997-01-01

    Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

  8. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  9. Regionalism and Development in Early Nineteenth Century Spanish America.

    ERIC Educational Resources Information Center

    Friedman, Douglas

    An understanding of regionalism in early 19th century Spanish America is crucial to any understanding of this region's economic development. Regionalism became the barrier to the kind of integrated national economy that some writers claim could have been implemented had it not been for the imposition of dependency by external forces. This…

  10. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  11. Early Journals and Their Influences on the Development of Gerontology

    ERIC Educational Resources Information Center

    Mercer, Lorraine; Carter, Lorraine

    2012-01-01

    This examination of early gerontology journals identifies the multidisciplinary backgrounds of contributors, methods of investigation, nascent theory development, and formative themes and controversies. Through use of content, thematic, and critical analyses of second year issues of "The Gerontologist," "Educational Gerontology," "Research on…

  12. Teacher Efficacy in an Early Childhood Professional Development School

    ERIC Educational Resources Information Center

    Epstein, Ann; Willhite, Gary L.

    2015-01-01

    Teacher efficacy is the belief teachers have in their ability to impact student learning. Efficacy includes teacher confidence in instructional, management and collaboration skills. The following study addresses teacher efficacy in an Early Childhood Professional Development School (PDS). The PDS experience provides an opportunity for mentor…

  13. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  14. Early Intervention and Its Effects on Maternal and Child Development.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    1983-01-01

    The longitudinal study reported used an intervention strategy to test the thesis that sociocultural background, mediated by maternal attitudes and behaviors, influences Black children's early development in educationally significant ways. Two models of parent education were contrasted: the Levenstein toy demonstration program and the…

  15. Early Childhood Development Program, 1986-87. Interim Evaluation Report.

    ERIC Educational Resources Information Center

    Rachal, Janella

    This interim evaluation of Louisiana's 1986-87 Early Childhood Development Program focuses primarily on ongoing second and third year projects, but also provides some descriptive information about the general characteristics and implementation strategies of first year projects. The purpose of the evaluation was to provide information to decision…

  16. Developing Early Undergraduate Research at a Two-Year College

    ERIC Educational Resources Information Center

    Sibbernsen, Kendra

    2013-01-01

    Two-year college (TYC) physics teachers are not often required to provide student research experiences as a part of their contracted duties. However, some TYC physics faculty members are interested in developing research opportunities for their freshman- and sophomore-level students, often called "early undergraduate research" (EUR).…

  17. State Guide to Developing Successful Early Childhood Data Systems

    ERIC Educational Resources Information Center

    ICF International (NJ1), 2012

    2012-01-01

    Early education leaders--inside and outside of government--are looking for new ways to improve quality, accountability, and efficiency across many different programs serving young children and their families, and they see investment in data systems as a pivotal part of that effort. However, it can be challenging to develop and implement effective…

  18. Investigating the Validity of the Australian Early Development Index

    ERIC Educational Resources Information Center

    Brinkman, Sally A.; Silburn, Sven; Lawrence, David; Goldfeld, Sharon; Sayers, Mary; Oberklaid, Frank

    2007-01-01

    This article aims to contribute to the ongoing evaluation of the Australian Early Development Index (AEDI) by investigating its construct and concurrent validity with a subsample of 642 children aged 4 to 5 years drawn from the Longitudinal Study of Australian Children (LSAC). Construct validity was examined by considering the theoretical…

  19. Career Planning and Development for Early-Career Scientists

    EPA Science Inventory

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  20. The Use of Electrophysiology in the Study of Early Development

    ERIC Educational Resources Information Center

    Szucs, Denes

    2005-01-01

    Electrophysiology is a timely and important tool in the study of early cognitive development. This commentary polishes the definition of event-related potential (ERP) components; often interpreted as expressions of mental processes. Further, attention is drawn to time-frequency analysis of the electroencephalogram (EEG) which conveys much more…

  1. Identification of the Social Development in Early Childhood in Pakistan

    ERIC Educational Resources Information Center

    Malik, Asif; Sarwar, Muhammad; Khan, Naeemullah

    2010-01-01

    This study was conducted to identify the social development in early childhood years. It was delimited to eight private schools of Lahore City from the area of Faisal Town and Shadman. Forty students (male and female) were randomly selected as the sample. Five students from Nursery, Prep and grade one were selected from each school. A checklist…

  2. Landing Profile Development During the Early Shuttle Program

    NASA Technical Reports Server (NTRS)

    Bobko, Karol Joseph

    2012-01-01

    I was asked to speak about my experiences as an astronaut during the early Shuttle program. There were many challenging and exciting things that I participated in during the Shuttle program but the item I believe is most appropriate for this audience is the development of the landing trajectory for both manual and automatic landings of the Space Shuttle.

  3. Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

    ERIC Educational Resources Information Center

    Hawley, Theresa

    Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

  4. More Alike than Different: Early Childhood Professional Development in Guatemala

    ERIC Educational Resources Information Center

    Hardin, Belinda J.; Vardell, Rosemarie; de Castaneda, Albertina

    2008-01-01

    This article describes an early childhood professional development project that took place in the summer of 2005 in Guatemala City. Located in Central America, Guatemala has a population of approximately 12.3 million people, including more than two million children under the age of 5 (UNESCO Institute for Statistics, 2007; UNICEF, 2004). Events…

  5. The Use of Electrophysiology in the Study of Early Development

    ERIC Educational Resources Information Center

    Szucs, Denes

    2005-01-01

    Electrophysiology is a timely and important tool in the study of early cognitive development. This commentary polishes the definition of event-related potential (ERP) components; often interpreted as expressions of mental processes. Further, attention is drawn to time-frequency analysis of the electroencephalogram (EEG) which conveys much more…

  6. HIV Infection: Transmission, Effects on Early Development, and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1997-01-01

    Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

  7. Development and Implementation of an Effective Early Childhood Handicapped Program.

    ERIC Educational Resources Information Center

    Condon, Kathryn; Dahlstrom, Mark

    The paper describes the Early Childhood Handicapped Program of Kenosha (WI). The program focuses on receptive and expressive language, fine and gross motor skills, self-help skills, cognitive skills, perceptual skills, and social/emotional skills development. For admission into the program, children must exhibit significant delays in two or more…

  8. Early Journals and Their Influences on the Development of Gerontology

    ERIC Educational Resources Information Center

    Mercer, Lorraine; Carter, Lorraine

    2012-01-01

    This examination of early gerontology journals identifies the multidisciplinary backgrounds of contributors, methods of investigation, nascent theory development, and formative themes and controversies. Through use of content, thematic, and critical analyses of second year issues of "The Gerontologist," "Educational Gerontology," "Research on…

  9. Regionalism and Development in Early Nineteenth Century Spanish America.

    ERIC Educational Resources Information Center

    Friedman, Douglas

    An understanding of regionalism in early 19th century Spanish America is crucial to any understanding of this region's economic development. Regionalism became the barrier to the kind of integrated national economy that some writers claim could have been implemented had it not been for the imposition of dependency by external forces. This…

  10. Technology and Early Childhood Professional Development: A Policy Discussion.

    ERIC Educational Resources Information Center

    McMaken, Jessica; Kauerz, Kristie; DeCesare, Dale; Hale, Genevieve

    In July 2002, Knowledge Works Foundation and the Education Commission of the States assembled key stakeholders to focus on the policy opportunities, needs, and challenges of utilizing technology for coordinated early childhood professional development across the nation. This report summarizes the presentations and discussions held at the meeting…

  11. Developing Early Undergraduate Research at a Two-Year College

    ERIC Educational Resources Information Center

    Sibbernsen, Kendra

    2013-01-01

    Two-year college (TYC) physics teachers are not often required to provide student research experiences as a part of their contracted duties. However, some TYC physics faculty members are interested in developing research opportunities for their freshman- and sophomore-level students, often called "early undergraduate research" (EUR).…

  12. Early Childhood Traumatic Brain Injuries: Effects on Development and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1998-01-01

    Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…

  13. An Analysis of Early Childhood Education Research and Development.

    ERIC Educational Resources Information Center

    Scott, Myrtle; And Others

    This volume organizes information on research and development in early childhood education. Goals and objectives of the 77 programs reviewed are described, and the strategies for implementing the programs are discussed. Organizational factors and the problems encountered in the programs and projects are considered. There is a short discussion of…

  14. Brain Development & Early Childhood: An Arkansas Kids Count Special Report.

    ERIC Educational Resources Information Center

    Rule, J. Chris

    Using recent economic data on state spending and information about childhood brain development, this Kids Count mini-report offers a snapshot of where Arkansas stands on early education and spending on such programs. The report examines the next steps, challenging conventional wisdom in order to explore the best path for improving child outcomes…

  15. Identification of the Social Development in Early Childhood in Pakistan

    ERIC Educational Resources Information Center

    Malik, Asif; Sarwar, Muhammad; Khan, Naeemullah

    2010-01-01

    This study was conducted to identify the social development in early childhood years. It was delimited to eight private schools of Lahore City from the area of Faisal Town and Shadman. Forty students (male and female) were randomly selected as the sample. Five students from Nursery, Prep and grade one were selected from each school. A checklist…

  16. Pennsylvania Child Care/Early Childhood Development Training System.

    ERIC Educational Resources Information Center

    Pennsylvania State Dept. of Public Welfare, Harrisburg. Office of Children, Youth, and Families.

    The Pennsylvania Child Care/Early Childhood Development Training System offers comprehensive training opportunities to the Pennsylvania Department of Public Welfare's licensed and registered child care providers, including center-based staff, school-age child care staff, and home-based providers. This booklet outlines state-mandated training…

  17. Cognitive and Cultural Determinants of Early IE Development.

    ERIC Educational Resources Information Center

    Stephens, Mark W.

    Results of several studies of cognitive and cultural correlates and determinants of early IE development are discussed, and some implications of the findings are pointed out. In studies of correlations between IE and intelligence test scores, results show that the scores increase regularly with age, from age 4 through 8, and there are fairly…

  18. Reflecting on Early Literacy Development in the Context of Vanuatu

    ERIC Educational Resources Information Center

    Hughes, Desma

    2004-01-01

    A low level of literacy development plagues many parts of the Pacific region despite the fact that parents are very keen for their children to become literate in order to embrace the modern world. Issues concerning early education and the attainment of literacy are still a challenge in the Pacific. In order to understand the reasons for the low…

  19. Predictors of Early versus Later Spelling Development in Danish

    ERIC Educational Resources Information Center

    Nielsen, Anne-Mette Veber; Juul, Holger

    2016-01-01

    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  20. Predictors of Early versus Later Spelling Development in Danish

    ERIC Educational Resources Information Center

    Nielsen, Anne-Mette Veber; Juul, Holger

    2016-01-01

    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  1. Early Childhood Traumatic Brain Injuries: Effects on Development and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1998-01-01

    Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…

  2. Applying cognitive training to target executive functions during early development

    PubMed Central

    Wass, Sam V.

    2015-01-01

    Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

  3. Learning Workers: Young New Zealanders and Early Career Development

    ERIC Educational Resources Information Center

    Vaughan, Karen

    2010-01-01

    Young adults' early career development is an increasingly important field of inquiry. With the complexity of modern transitions from school and the lifelong learning demands of emerging knowledge societies, governments are concerned to improve learning pathways into, and through, tertiary education and work. Young adults are exploring new learning…

  4. Family Concepts in Early Learning and Development Standards

    ERIC Educational Resources Information Center

    Walsh, Bridget A.; Sanchez, Claudia; Lee, Angela M.; Casillas, Nicole; Hansen, Caitlynn

    2016-01-01

    This exploratory study investigated the use of concepts related to families, parents, and the home in 51 state-level early learning and development standards documents. Guidelines from six national family involvement, engagement, and school-partnership models were used to create the Family Involvement Models Analysis Chart (FIMAC), which served as…

  5. Rethinking Early Learning and Development Standards in the Ugandan Context

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2013-01-01

    Concerns that the African child is being tailored to be a "global child," alongside other homogenizing and dominating projections, such as early learning and development standards (ELDS), have increased. African communities need to be assured that global standards and global indicators will not further homogenize nations and thereby risk…

  6. Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

    ERIC Educational Resources Information Center

    Hawley, Theresa

    Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

  7. Participation as a Basis for Developing Early Intervention Outcomes

    ERIC Educational Resources Information Center

    Wilcox, M. Jeanne; Woods, Juliann

    2011-01-01

    Purpose: This article describes how participation in activities/routines can be used as a basis for understanding children's communication and language skills and how that knowledge can be extended to collaborate with families and caregivers to develop meaningful early intervention outcomes. Method: The approach is centered on children's use of…

  8. Early Retinoic acid deprivation in developing zebrafish results in microphthalmia

    PubMed Central

    Le, Hong-Gam T.; Dowling, John E.; Cameron, D. Joshua

    2013-01-01

    Vitamin A deficiency causes impaired vision and blindness in millions of children around the world. Previous studies in zebrafish have demonstrated that retinoic acid (RA), the acid form of vitamin A, plays a vital role in early eye development. The objective of this study was to describe the effects of early RA deficiency by treating zebrafish with diethylaminobenzaldehyde (DEAB), a potent inhibitor of the enzyme retinaldehyde dehydrogenase (Raldh) that converts retinal to RA. Zebrafish embryos were treated for 2 hours beginning at 9 hours post-fertilization (hpf). Gross morphology and retinal development were examined at regular intervals for 5 days after treatment. The optokinetic reflex (OKR) test, visual background adaptation (VBA) test, and the electroretinogram (ERG) were performed to assess visual function and behavior. Early treatment of zebrafish embryos with 100 μM DEAB (9hr) resulted in reduced eye size and this microphthalmia persisted through larval development. Retinal histology revealed that DEAB eyes, had significant developmental abnormalities but had relatively normal retinal lamination by 5.5 days post-fertilization (dpf). However, the fish showed neither, an OKR or VBA response. Further, the retina did not respond to light as measured by the ERG. We conclude that early deficiency of RA during eye development causes microphthalmia as well as other visual defects, and that timing of the RA deficiency is critical to the developmental outcome. PMID:23013828

  9. Early development of synchrony in cortical activations in the human

    PubMed Central

    Koolen, N.; Dereymaeker, A.; Räsänen, O.; Jansen, K.; Vervisch, J.; Matic, V.; Naulaers, G.; De Vos, M.; Van Huffel, S.; Vanhatalo, S.

    2016-01-01

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  10. [Bacterial proteases and bacterial resistance against human innate immunity factors].

    PubMed

    Tiurin, Iu A; Mustafin, I G; Fassakhov, R S

    2011-01-01

    The molecular and cell-mediated mechanisms that are developed by certain opportunistic and pathogenic bacteria and were obtained over the course of evolution to preserve resistance against principal components of human body innate immunity are summarized.

  11. Ontogenetic profile of innate immune related genes and their tissue-specific expression in brown trout, Salmo trutta (Linnaeus, 1758).

    PubMed

    Cecchini, Stefano; Paciolla, Mariateresa; Biffali, Elio; Borra, Marco; Ursini, Matilde V; Lioi, Maria B

    2013-09-01

    The innate immune system is a fundamental defense weapon of fish, especially during early stages of development when acquired immunity is still far from being completely developed. The present study aims at looking into ontogeny of innate immune system in the brown trout, Salmo trutta, using RT-PCR based approach. Total RNA extracted from unfertilized and fertilized eggs and hatchlings at 0, 1 h and 1, 2, 3, 4, 5, 6, 7 weeks post-fertilization was subjected to RT-PCR using self-designed primers to amplify some innate immune relevant genes (TNF-α, IL-1β, TGF-β and lysozyme c-type). The constitutive expression of β-actin was detected in all developmental stages. IL-1β and TNF-α transcripts were detected from 4 week post-fertilization onwards, whereas TGF-β transcript was detected only from 7 week post-fertilization onwards. Lysozyme c-type transcript was detected early from unfertilized egg stage onwards. Similarly, tissues such as muscle, ovary, heart, brain, gill, testis, liver, intestine, spleen, skin, posterior kidney, anterior kidney and blood collected from adult brown trout were subjected to detection of all selected genes by RT-PCR. TNF-α and lysozyme c-type transcripts were expressed in all tissues. IL-1β and TGF-β transcripts were expressed in all tissues except for the brain and liver, respectively. Taken together, our results show a spatial-temporal expression of some key innate immune-related genes, improving the basic knowledge of the function of innate immune system at early stage of brown trout. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Innate Immune Evasion by Filoviruses

    PubMed Central

    Basler, Christopher F.

    2015-01-01

    Ebola viruses and Marburg viruses, members of the filovirus family, cause severe hemorrhagic fever. The ability of these viruses to potently counteract host innate immune responses is thought to be an important component of viral pathogenesis. Several mechanisms of filoviral innate immune evasion have been defined and are reviewed here. These mechanisms inclue suppression of type I interferon (IFN) production; inhibition of IFN-signaling and mechanisms that either prevent cell stress responses or allow the virus to replication in the face of such responses. A greater understanding these innate immune evasion mechanisms may suggest novel therapeutic approaches for these deadly pathogens. PMID:25843618

  13. Early development of Xenopus embryos is affected by simulated gravity

    NASA Technical Reports Server (NTRS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-01-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  14. Early development of Xenopus embryos is affected by simulated gravity

    NASA Technical Reports Server (NTRS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-01-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  15. Early development of Xenopus embryos is affected by simulated gravity

    NASA Astrophysics Data System (ADS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-08-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) ``morphological patterning'' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) ``the timing of embryonic events'' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  16. Developing International Collaborations for Early Career Researchers in Psychology

    PubMed Central

    Flanagan, Julianne C.; Barrett, Emma L.; Crome, Erica; Forbes, Miriam

    2015-01-01

    International collaboration is becoming increasingly vital as the emphasis on unmet need for mental health across cultures and nations grows. Opportunities exist for early career researchers to engage in international collaboration. However, little information is provided about such opportunities in most current psychology training models. The authors are early career researchers in psychology from U.S. and Australia who have developed a collaborative relationship over the past two years. Our goal is to increase awareness of funding opportunities to support international research and to highlight the benefits and challenges associated with international collaboration based on our experience. PMID:27453624

  17. Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus.

    PubMed

    Cowan, Jennifer E; McCarthy, Nicholas I; Parnell, Sonia M; White, Andrea J; Bacon, Andrea; Serge, Arnauld; Irla, Magali; Lane, Peter J L; Jenkinson, Eric J; Jenkinson, William E; Anderson, Graham

    2014-08-01

    αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.

  18. Evaluation of early stimulation programs for enhancing brain development.

    PubMed

    Bonnier, Christine

    2008-07-01

    The term 'early intervention' designates educational and neuroprotection strategies aimed at enhancing brain development. Early educational strategies seek to take advantage of cerebral plasticity. Neuroprotection, a term initially used to characterize substances capable of preventing cell death, now encompasses all interventions that promote normal development and prevent disabilities, including organisational, therapeutic and environment-modifying measures, such as early stimulation programs. Early stimulation programs were first devised in the United States for vulnerable children in low-income families; positive effects were recorded regarding school failure rates and social problems. Programs have also been implemented in several countries for premature infants and low-birth-weight infants, who are at high risk for neurodevelopmental abnormalities. The programs target the child, the parents or both. The best evaluated programs are the NIDCAP (Newborn Individualized Developmental Care and Assessment Program) in Sweden for babies<1500 g in neonatal intensive care units and the longitudinal multisite program IHDP (Infant Health and Development Program) created in the United States for infants<37 weeks or <2500 g. Although the NIDCAP and the IHDP targeted different populations, they produced similar effects in several regards: efficacy was greatest with programs involving both the parents and the child; long-term stimulation improved cognitive outcomes and child-parent interactions; cognition showed greater improvements than motor skills and larger benefits were obtained in families that combined several risk factors including low education attainment by the mothers.

  19. Germination and early plant development of ten plant species ...

    EPA Pesticide Factsheets

    Ten agronomic plant species were exposed to different concentrations of nano titanium dioxide (nTiO2) or nano cerium oxide (nCeO2) (0, 250, 500 and 1000 mg/L) to examine potential effects on germination and early seedling development. We modified a standard test protocol developed for soluble chemicals (OPPTS 850.4200) to determine if such an approach might be useful for screening engineered nanomaterials (ENMs) and whether there were differences in response across a range of commercially important plant species to two common metal oxide ENMs. Eight of 10 species responded to nTiO2, and 5 species responded to nCeO2. Overall, it appeared that early root growth may be a more sensitive indicator of potential effects from ENM exposure than germination. The observed effects did not always relate to the exposure concentration, indicating that mass-based concentration may not fully explain developmental effects of these two ENMs. The results suggest that nTiO2 and nCeO2 have different effects on early plant growth of agronomic species, which may alter the timing of specific developmental events during their life cycle. In addition, standard germination tests, which are commonly used for toxicity screening of new materials, may not detect the subtle but potentially more important changes associated with early growth and development in terrestrial plants. Engineered nanoparticles (ENMs) have been recognized as valuable components of new technologies and are current

  20. Is matching innate?

    PubMed

    Gallistel, C R; King, Adam Philip; Gottlieb, Daniel; Balci, Fuat; Papachristos, Efstathios B; Szalecki, Matthew; Carbone, Kimberly S

    2007-03-01

    Experimentally naive mice matched the proportions of their temporal investments (visit durations) in two feeding hoppers to the proportions of the food income (pellets per unit session time) derived from them in three experiments that varied the coupling between the behavioral investment and food income, from no coupling to strict coupling. Matching was observed from the outset; it did not improve with training. When the numbers of pellets received were proportional to time invested, investment was unstable, swinging abruptly from sustained, almost complete investment in one hopper, to sustained, almost complete investment in the other-in the absence of appropriate local fluctuations in returns (pellets obtained per time invested). The abruptness of the swings strongly constrains possible models. We suggest that matching reflects an innate (unconditioned) program that matches the ratio of expected visit durations to the ratio between the current estimates of expected incomes. A model that processes the income stream looking for changes in the income and generates discontinuous income estimates when a change is detected is shown to account for salient features of the data.