What aspects of development are influenced by neurotrophins?

Neurotrophins - an overview ScienceDirect Topic

Neurotrophins and neurodegeneration - PubMe

a thin layer of extra cellular matrix material (primarily collagen, laminin, and fibronectin) that surrounds muscle cells and Schwann cells. Also underlies all epithelial sheets. AKA basment membrane. BDNF; one member of a family of neurotrophic factors, the best known constituent of which is nerve growth factor (NGF) Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, a group of structurally related polypeptide growth factors. The family also includes nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4/5) [ The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons and have since been shown to control a number of aspects of survival, development, and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving.

The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons, and have since been shown to control a number of aspects of survival, development and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving. Nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 all influence sensory neurons derived from the dorsal root ganglia. Traditionally these neurotrophins have been thought of as survival factors for sensory neurons during their development. Recent evidence from experiments where the in viv Neurotrophins, normally noted for their role in sensory neuron survival, are now known to affect almost every aspect of peripheral nociceptor development well into postnatal life

A role for neurotrophins in mature primary sensory neurons persists, extending beyond that of promoting survival during development, to one of maintaining phenotypic and functional properties. Many adaptive changes that occur after peripheral axotomy and in axonal repair are believed to be influenced by altered availability of neurotrophic molecules to the neuron in this state discovered neurotrophin in mammals, and the least well understood, several aspects distinguish NT-4 from other members of the neurotrophin family. It is the most divergent member and, in contrast to the other neurotrophins, its expression is ubiquitous and appears to be less influenced by environmental signals development and in the adaptive responses of the brain such as learning. A number of recent observations suggest that neurotrophins, identified initially as regulators of neuronal differentiation and survival, mediate important aspects of activity-dependent cortical plasticity. The notion that trophic factors are involved in sculptin And then the influence of neurotrophins. uncoordinated activity between synaptic partners, would weaken their synaptic connections. Well, these aspects of Hebb's Postulate, I think is very aptly summed up by my late, great colleague here at Duke, Dr Larry Catts. a child with ongoing development and construction of neural circuits, or an.

Neurotrophins can retrogradely influence the development of presynaptic neurons and anterogradely influence the development of postsynaptic cells (von Bartheld et al., 2001). Moreover, neurotrophins secreted by one neuron can exert both autocrine influences on that neuron itself as well as paracrine influences on nearby neurons Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play a fundamental role in brain function and neuroprotection and are affected by stress, are good candidates for the transduction of the effects of adverse events to changes in brain function - Frontiers inUnexpectedly, the pre-reproductive maternal rearing conditions did not influence neurotrophin levels in neocortical and hippocampal regions, despite the high sensitivity of these regions to parental experiences (Arai et al., 2009;Roth et al., 2009;Mychasiuk et al., 2012) and environmental enrichment (Pham et al., 1999(Pham et al.

Studies of neurotrophin biology in the developing

  1. Although the response properties and synaptic projections of muscle sensory neurons have been studied extensively, relatively little is known about how these sensory neurons develop their unique phenotypes during embryonic life. The explosion of new information on neurotrophins, however, has revealed that neurotrophin 3 (NT3) is critically involved in several aspects of this development.
  2. Recent evidence suggests that the NFATc family of transcription factors plays an important role in neuronal activity-dependent gene expression. This chapter reviews these data, focusing on activation of NFAT-dependent transcription by neurotrophins, signaling molecules involved in many aspects of neuronal development and plasticity
  3. development, but also for plastic circuit rearrangements and fiber regeneration following injury. Interestingly, many of these ligands are also present at synapses in the adult nervous system, where they influence synaptic plasticity and learning. Axon guidance molecules, such as ephrins, netrins, as well as neurotrophins an
  4. Neurotrophic factors are proteins that are traditionally known to influence survival and function of neurons in the central and peripheral nervous systems. Recent studies, however, have shown that specific neurotrophic factors may cause neuronal death instead of survival, depending upon which receptors and signaling pathways are activated
  5. Cellular growth, and development and function of nervous and endocrine systems were also closely related to PCOS (Fig. 4d). Enriched GO terms in differentially expressed gene clusters of the PCOS group involved brain development, and proliferation and differentiation of neural precursor cells, neurons, and neuroblast

The accessibility of the primary sensory neurons of the trigeminal system at stages throughout their development in avian and mammalian embryos and the ease with which these neurons can be studied in vivo has facilitated investigation of several fundamental aspects of neurotrophin biology For example, neurotrophins and their receptors influence many aspects of neuronal activity that result in the generation of new synaptic connections, which can be long lasting 3. Alterations in.

Neurotrophin receptors regulate synaptic development in

Freud (1905) stated that events in our childhood have a great influence on our adult lives, shaping our personality. He thought that parenting is of primary importance to a child's development, and the family as the most important feature of nurture was a common theme throughout twentieth-century psychology (which was dominated by environmentalists theories) Neurotrophins and neurotrophin receptors in neural crest, sympathetic nervous system and adrenal development. Neurotrophins (NTs) and NT receptors (NTRs) are critical for the development and maintenance of the vertebral CNS and PNS [47-50], NTs and NTRs are also expressed by human NBs and have been implicated in both NB regression and malignant. Abstract Despite considerable evidence that neuronal activity influences the organization and function of circuits in the developing and adult brain, the molecular signals that translate activity into structural and functional changes in connections remain largely obscure.This review discusses the evidence implicating neurotrophins as molecular mediators of synaptic and morphological plasticity


Ch. 23 Neuro Flashcards Quizle

  1. o acid sequences: neurotrophins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), NT-4, glial factor.
  2. In addition, there are aspects of neurotrophin action that do not conform with the classic neurotrophic hypothesis. For example, the dependence of some populations of sensory neurons on particular neurotrophins before significant neuronal death takes place raises the possibility that the supply of these neurotrophins is not limiting for.
  3. ed in a rat model. Our investigations suggest that a suitable combination of neurotrophins will attenuate both neural and non-neural (glial cells and endothelial cells) damage in SCI leading.
  4. Neurotrophin 4/5 is required for the normal development of the slow muscle fiber phenotype in the rat soleus Injections were made through the skin,along the dorsolateral aspect of the left hind limb, at the line of demarcation between the lateral gastrocnemius and the soleus muscle. all the muscle-derived neurotrophins could influence.
  5. In contrast, transgenic Unexpectedly, the pre-reproductive maternal rearing condi- mice with deficient release of BDNF and neurotrophin-3 show tions did not influence neurotrophin levels in neocortical and severe impairment in cerebellar development, both at structural hippocampal regions, despite the high sensitivity of these regions (survival.

Environmental enrichment is usually applied immediately after weaning or in adulthood, with strong effects on CNS anatomy and behavior. To examine the hypothesis that a pre-reproductive environmental enrichment of females could affect the motor development of their offspring, female rats were reared in an enriched environment from weaning to sexual maturity, while other female rats used as. Methods and kits are provided for manipulating and predicting the reproductive capacity of a female subject. The presence of endogenous neurotrophins and addition of exogenous neurotrophins, particularly BDNF, NT-4/5, and NGF, increase the reproductive capacity of a female patient by binding to receptors on the oocytes and stimulating maturation of the oocytes Other approaches include the development of mutant neurotrophins 12 by which specific ligands might influence p75 NTR in a aspects of modulating neurotrophin receptors and outline the. Neurotrophins promote growth during development and throughout life. Some studies suggest brain-derived neurotrophic factor (BDNF) helps the brain generate new neurons in the hippocampus, a region involved in learning and memory. This image shows new cells (pictured in purple) in the hippocampus of an adult mouse

An Overview of Brain-Derived Neurotrophic Factor and

Functionally Reduced Sensorimotor Connections Form with Normal Specificity Despite Abnormal Muscle Spindle Development: The Role of Spindle-Derived Neurotrophin 3. Download. Related Papers. Sensorimotor function is modulated by the serotonin receptor 1d, a novel marker for gamma motor neurons Few studies have focused on the relationship of neurotrophins and infant neurodevelopment . Rather than a simple interface, this relationship is likely to be a complex one in which various aspects are correlated and influence each other. Until now, the genesis of this matter and how much one component influences another has been unknown Basic Neurochemistry had its origin in the Conference on Neurochemistry Curriculum initiated and organized by R. Wayne Albers, Robert Katzman and George J. Siegel under the sponsorship of the National Institute for Neurological Diseases and Stroke, June 19 and 20, 1969, Bronx, New York. At this conference, a group of 30 neuroscientists constructed a syllabus outline delineating the scope of a. By virtue of their extensive axonal arborization and perisomatic synaptic targeting, cortical inhibitory parvalbumin (PV) cells strongly regulate principal cell output and plasticity and modulate experience-dependent refinement of cortical circuits during development. An interesting aspect of PV cell connectivity is its prolonged maturation time course, which is completed only by end of.

1. The neurotrophins play an important role during development to stimulate and guide axonal growth for the establishment of a correctly wired and functional neural system. Neurotrophins can also regulate adult nervous system plasticity by promoting neuronal survival and stimulating nerve regrowth following injury Neurotrophins such as nerve growth factor (NGF) and to provide adequate incentives to offspring in the first months of brain-derived neurotrophic factor (BDNF), which play a funda- life, the chance of a significant loss in neurobiological and mental role in brain function and neuroprotection and are affected psychological development increases [2] sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively Each of these neurotrophins has been previously shown to regulate the survival of about half of the geniculate ganglion neurons, with additive losses observed in newborn mice lacking both BDNF and NT-4 [3,4]. Recently, it was also established that BDNF and NT-4 influence geniculate neuron survival at different developmental stages

The neurotrophin family of neurotrophic factors: an

The Biology of Neurotrophins, Signalling Pathways, and

Previous studies indicated that nerve growth factor (NGF) and proNGF differentially regulate the phenotype of macrophages and microglia via actions at tropomyosin receptor kinase A (TrkA) and p75 neurotrophin receptors (p75NTR), respectively. The ability of HIV gp120 and virions to induce the secretion of factors toxic to neurons was suppressed by NGF and enhanced by proNGF, suggesting the. Molecular Aspects of Concussion and Chronic Traumatic Encephalopathy. C H A P T E R 8 Molecular Aspects of Concussion and Chronic Traumatic Encephalopathy INTRODUCTION Boxers and players of contact sports such as Americ... Download PDF . 3MB Sizes 0 Downloads 15 Views. Report Neurotrophins BDNF and NT4 influence the development of the rodent gustatory system. Despite binding to the same receptor, TrkB, they have different roles. BDNF is chemo-attractive for gustatory neurons and regulates gustatory neuron targeting and number during development MCQs for Essentials of Oral Histology and Embryology [1 ed.] 9780702068980, 9780702069819, 0702069817. For students, a good way to test their understanding and knowledge about a particular subject and to prepare for exams

Neurotrophins and the Specification of Neuronal Phenotyp

  1. o acid transporter JhI-21 coevolves with glutamate receptors, impacts NMJ physiology, and influences locomotor activity in Drosophila larvae. Sci Rep 6: 19692. PubMed ID: 26805723 Summary: Changes in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development
  2. Neurotrophins are important in regulating aspects of later sensory neuron development that, in some instances, control important aspects of neuronal phenotype. For example, NGF-responsive sensory neurons primarily convey nociceptive information and extend either unmyelinated C-fibers or thinly myelinated A δ fibers
  3. Neurotrophins can influence the development of thalamocortical connections The discovery that neuronal activity can regulate the expression of neurotrophins, together with the known growth-promoting effects of neurotrophins in the peripheral nervous system, suggested that neurotrophins participate in the activity-dependent rearrangement of.
  4. physiological aspects in mammals. If we can dissect how these pathways are activated, then maybe we can generate druggable targets specific for desired effects. Beyond Development Tessarollo uses genetically modified mice as his model of choice for understanding the physiological functions of neurotrophins and their receptors. I like to loo

Neurotrophin signaling Neurotrophin signaling uses a two-receptor system. Neurotrophins bind to two different classes of transmembrane receptor proteins, the Trks and the neurotrophin receptor p75 (Fig.1).This dual system allows the transduction of very different signals following ligand binding, which can be as contrasted as signaling cell death through p75 or cell survival through the Trk. regarding the influence of neurotrophins on dendritic development in cortical slice cultures. In their initial study [6], the authors reported that cells in different layers of the cortex respond differentially to neurotrophin stimulation. For example, BDNF promotes the growth of dendrites of layer 4 and 5 neurons, but suppresses the development of For example, neurotrophins might function as long term mediators of changes in cellular shapes under the influence of electrical activity, as well as in pathological situations when axonal elongation is needed to restore connections, or to maintain the well-being of neurons that are eliminated during the course of neurodegenerative diseases investigated different aspects of these three elements and revealed novel interactions of brain neurotrophins, environmental influences and emotional behaviour in mice. In the first two studies, we used C57BL6 mice housed in standard or enriched conditions to investigate anxiety- and fear-related behaviour and neurotrophin levels i To the Editors: Asthma is the most common chronic disease in childhood and is characterised by chronic airway inflammation, reversible airflow obstruction and hyperresponsiveness of the airways. Among the substantial pathophysiological aspects of asthma are neuroimmune interaction mechanisms; neurotrophins are mediators of the interactions providing links between immune, structural and.

The process of early brain development is constantly modified by environmental influences. Child abuse and neglect constitute one aspect of these environmental influences, which present the maturing child's brain with experiences that will crucially and potentially adversely affect the child's future development and functioning Example 1: If you live in a complex and elaborate enviroment you need an elaborate nervous system vs if you were a lab rat living in a small grey cage; Example 2: Measurable expansion of neurons has also been shown in humans as a function of physical activity; Example 3: The thickness of the cerebral cortex declines in old age but much less in those that are physically active

The development of nociceptive circuits Nature Reviews

Recent studies suggest that endogenous neurotrophins play a central role in the patterning of cortical connections and in cortical synaptic physiology. Do these effects of neurotrophins reflect independent cellular events, or are they manifestations of a single cellular mechanism central to developmental plasticity Neurotrophin-4 (NT-4) is a member of a family of neurotrophic factors, the neurotrophins, that control survival and differentiation of vertebrate neurons (2-4). Besides being the most recently discovered neurotrophin in mammals, and the least well understood, several aspects distinguish NT-4 from other members of the neurotrophin family. It is the most divergent member and, in contrast to. Neurotrophins and their respective tropomyosin related kinase (Trk) receptors (TrkA, TrkB, and TrkC) and the p75 neurotrophin receptor (p75NTR) play a fundamental role in the development and maintenance of the nervous system making them important targets for treatment of neurodegenerative diseases. Whereas Trk receptors are directly activated by specific neurotrophins, the p75NTR is a.

Neurotrophins constitute a small family of growth factors that play a key role in several different aspects of the development and maintenance of the nervous system. The first factor that was discovered in 1951 and subsequently purified was the nerve growth factor (NGF), which was initiall A general role for p75 in neural development is supported by the ability of p75 to bind all neurotrophins (Rodrı́guez-Tébar et al., 1990, 1992) along with its broad expression in all classes of sensory neurons (Yan and Johnson, 1988; Wright and Snider, 1995), Schwann cells (Taniuchi et al., 1988), and target tissues (Wheeler and Bothwell.

Neurotrophins and Nerve Injury in the Adult - NASA/AD

which cells differentiate during development reflect the actions of specific growth factors. One example is the formation of post-mitotic neurons which occurs in response to specific growth factors such as members of the neurotrophin family. Note that in this instance, as in many cases of differentiation, tha BDNF is a key member of the neurotrophin family which also includes nerve growth factor, neurotrophin 3, and neurotrophin 4 [1]. BDNF has a high expression levels in the brain and it plays an important role in the survival, differentiation and synaptic formation of several classes of neurons [2,3]. It also influence Neurotrophins have thus become prototypic retrograde factors for both long-term and acute actions on presynaptic neurons. In addition to neurotrophins, other families of growth factors and cytokines can also regulate the survival and growth of presynaptic neurons as well as modulate neuronal and synaptic functions (24 280). However, it remains.

Neurotrophins In Developmental Plasticity - The Changing

BDNF as a Neurotrophin Lion's Mane has peculiar neurotrophic qualities It exceeds BDNF & NGF in healing peripheral neuron injuries. And is alluded to improve cognitive function for dementia patients. More specifically, Neurotrophins are a family of signaling proteins that promote the survival, development, and improved function of neurons Diffusible cues secreted by target tissues impinge on nerve terminals to influence diverse aspects of neural development, including survival, axon growth and guidance, target innervation and synapse formation. The family of neurotrophins provides one of the best examples of these target-derived instructive cues

Serum NGF, BDNF and IL-6 Levels in Postpartum Mothers As

examined to verify whether the various aspects of motor behav-iors were influenced to a similar extent by the maternal rearing condition. Furthermore, given the critical role of neurotrophins in survival, maintenance, and maturation of neurons (Lindsay et al., 1994;Lewin and Barde, 1996),the expression ofBDNF an The development of local, layer-specific visual cortical axons in the absence of extrinsic influences and intrinsic activity. J. Neurosci. 18 , 4145-4154 (1998)

(PDF) Pre-reproductive maternal enrichment influences

  1. A role for neurotrophins in mature primary sensory neurons persists, extending beyond that of promoting survival during development, to one of maintaining phenotypic and functional properties. Many..
  2. ed whether NGF-associated increased ACh release could be modified by activity level. An identical NGF treatment in sister.
  3. Neurotrophins inferred. One possibility is that BDNF or NT-4/5 acts are small, secreted proteins that have been found to play principally to regulate the growth of thalamic axons within important roles in various aspects of nervous system layer 4. Neurotrophin infusion may lead to an increased development
  4. The development of the fetal nervous system mirrors general fetal development, comprising a combination of genetic resources and effects of the intrauterine environment. Our aim was to assess the 2 nd trimester amniotic fluid levels of brain-derived neurotrophic factor (BDNF) and to investigate its association with fetal growth. In accordance with our study design, samples of amniotic fluid.
  5. Thus many neurons receive less excitation and neurotrophins than normal and they undergo apoptosis. Cocaine or cigarettes (ADHD, behavioural deficits) Antidepressants (increased risk of heart problems) The immature brain is highly responsive to influences from the mother eg stress and fear
  6. e hypothesis, impairment of the hipotalamic-pituitary.
  7. Development of nerve growth factor for diabetic neuropathy was discontinued because phase 3 results did not confirm efficacy. Neurotrophin-3. As a neurotrophin like the brain-derived neurotrophic factor, neurotrophin-3 is a candidate for clinical trials in diabetic neuropathy

Our results demonstrate that the secondary hyperalgesia can be prevented by intramuscular injection of neurotrophin-3 (NT-3). Because of the importance of gender in widespread pain syndromes associated with secondary hyperalgesia, it is plausible that estrogen strongly influences the development of these conditions The temporal and spatial distributions of several growth factors suggest roles in the regulation of neuronal differentiation in the neocortex. Among such growth factors, the insulin-like growth factors (IGF-I and -II) are of particular interest because they are available to neurons from multiple sources under independent control. IGF-I is produced by many neurons throughout the brain and also. Neurotrophins (nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4/5)) constitute a family of molecules (Thoenen, 1991) that have assumed a central role in studies of recovery after spinal cord injury.This emerged from evaluation of their role during development where they act as differentiation and survival factors for sensory. Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity. Molecular and cellular aspects of patterning sensory neurone connections in the vertebrate nervous system. Role of neurotrophins in mouse neural development. The trophic influence of specific nerve supply as revealed by prolonged observations of denervated and reinnervated organs

Development and specification of muscle sensory neurons

Cellular growth, and development and function of nervous and endocrine systems were also closely related to PCOS (Fig. 4d). Enriched GO terms in differentially expressed gene clusters of the PCOS group involved brain development, and proliferation and differentiation of neural precursor cells, neurons, and neuroblast There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive. Delineation of these and other aspects of the biology of microbes as immunomodulators might lead to the development of new avenues of allergy prevention and treatment in near future. Conclusion In this article we have reviewed the role of allergens, viruses, and endotoxin in the development of allergy and asthma Synapse and axon development are influenced by many underlying phenomena. Axon growth is influenced by the presence of synapses [15] and trophic factors models suggests that it is the qualitative aspects of these (e.g., neurotrophins and pro-neurotrophins) influenced the growth and retraction of axons and the local growth of synapses on. NEUROPHYSIOLOGICAL ASPECTS OF PLASTICITY OF THE BRAIN Bindu M Kutty, B.S. Shankaranarayana Rao and T.R. Raju Synapse formation during development is thought to be depended upon both the genetic and environmental influences. This initial stages of synapse formation occurs There is an increasing evidence that neurotrophins (NTs) are.

The classic neurotrophins Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) and Neurotrophins NT-3 and NT-4 are well known to regulate various aspects of neuronal differentiation, survival and growth. They do this by binding to their cognate receptors, members of the Tropomyosin-related kinase (Trk) receptor tyrosine kinase family, namely TrkA, TrkB, and TrkC regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development. History Runt related (Runx) genes are evolutionarily conserve CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): ii The enteric nervous system (ENS) continues its development after birth, with formation of ganglia and functional synapses; plasticity is also demonstrated in significant axon growth that occurs after experimental colitis in the adult colon. However, little is known about factors in the postnatal intestine that. Traditionally, the primary function of oligodendrocytes (OLGs) in the CNS has been considered to be myelination. Here, we investigated whether OLGs may play a trophic role, particularly during development. Neurotrophin expression was assessed in postnatal day 7 basal forebrain (BF) OLGs, using in situ hybridization and detection of myelin basic protein Runt-related (Runx) transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and.

Identification and targeting of signaling networks that influence a broad spectrum of tau pathogenic mechanisms might prevent or reverse synaptic degeneration and modify disease outcomes. The p75 neurotrophin receptor (p75NTR) modulates such networks, including activation of multiple tau kinases, calpain and rhoA-cofilin activity Traumatic brain injury (TBI) may be due to a bump, blow, or jolt to the head or a penetrating head injury that disrupts normal brain function; it presents an ever-growing, serious public health problem that causes a considerable number of fatalities and cases of permanent disability annually. Physical exercise restores the healthy homeostatic regulation of stress, affect and the regulation of. A number of environmental factors can affect the development and severity of allergy and asthma; however, it can be argued that the most significant inhaled agents that modulate the development of these conditions are biologics. Sensitization to environmental allergens is an important risk factor for the development of asthma

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