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New therapeutic targets for human placental angiogenesis diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194612 Year: Pages: 113 DOI: 10.3389/978-2-88919-461-2 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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A large number of publications have described impaired angiogenesis and vasculogenesis present in the feto-placental circulation after pregnancy diseases such as pre-eclamptic pregnancies, gestational diabetes, and intrauterine growth restriction, among others. Results suggest impaired secretion and activity of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), adenosine and nitric oxide, associates with compromised secretion and activity of anti-angiogenic factors such as soluble receptor of VEGF (sFlt-1), thrombospondin 2, endostatin among others. More recent evidences include the participation of endothelial progenitor cells (EPC), which circulating number is reduced infeto-placental circulation in pregnancies such as pre-eclampsia. Despite this knowledge, therapies for placental angiogenesis recovery during pathological pregnancies are far to be tested. However, from the cardiovascular field, it has been described the administration of EPC, alone or used as gene-transfer therapy; or it has been described the potential role of statins (HMGCoA inhibitors), or angiotensin-converter enzyme (ACE) inhibitors for enhancing angiogenesis. Finally, feto-placental tissue is an exceptional source of progenitor and stem cells, which could be used for treated other human diseases such as stroke, myocardial infarction, hypertension, or even cancer. In this research topic, authors highlight physiopatological and clinical importance of the impaired placental angiogenesis, and suggest potential targets for developing innovative therapies.

Brain Development and the Attention Spectrum

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194827 Year: Pages: 96 DOI: 10.3389/978-2-88919-482-7 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
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Early-onset and enduring developmental deficits in attention, especially if combined with increased hyperactivity, and impulsivity, may result in constant impairments in multiple domains of personal life. The full spectrum of symptoms is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity, which is maladaptive and inconsistent with a comparable level of developmental age known as Attention Deficit Hyperactivity Disorder (ADHD). ADHD is considered one of the most common neurobehavioral disorders and of childhood, and among the most prevalent chronic health conditions.Given the wide heterogeneity and complex manifestations of the disorder, there is an importance in a developmental perspective that views ADHD as a multi-factorial disorder with multiple, causal processes, and pathways. The symptoms of ADHD should be cast, not as static or fixed neurobehavioral deficits, but rather in terms of underlying developmental processes.Even experienced professional might minimize the prevalence of a disorder among certain groups of patients. Therefore, the existence of attention disorders might become ""transparent"" for both the patient and the professional. This might lead to a non-accurate diagnosis, harm the treatment aspects and has potential non beneficial prognostic aspects.The developmental approach can provide predictions as to how characteristics associated with attention develop over time and how multiple risk and protective factors transact to impact it's development, as well as the development of a broad range of associated co-morbid features.Among children with mental retardation, autistic spectrum disorders, children who were born premature, born with low birth weight, as well as among those who suffer from chronic disorders (such as epilepsy, diabetes, chronic kidney disease or asthma), as well as among otherwise healthy preschoolers - the assessment of attention performance might be very challenging. In this research topic, we explore the latest cutting edge research on the biological and neural pathways as well as on psychosocial and behavioral correlates of brain development and attention spectrum. In doing so we aim to highlight: what is currently known regarding this new conceptualization of attention as a spectrum; the mechanisms underlying this spectrum; and where this field is headed in terms of developing our understanding of the link between brain development and attention performance.

Keywords

ADHD --- Attention --- Brain --- autism --- Child --- Delay --- development --- fetal --- maturation --- spectrum --- visual

Experimental models of early exposure to alcohol: a way to unravel the neurobiology of mental retardation

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194728 Year: Pages: 104 DOI: 10.3389/978-2-88919-472-8 Language: English
Publisher: Frontiers Media SA
Subject: Pediatrics --- Psychiatry --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:33
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Excessive alcohol drinking represents a major social and public health problem for several countries. Alcohol abuse during pregnancy leads to a complex syndrome referred to as fetal alcohol spectrum disorders (FASD), chiefly characterized by mental retardation. The effects of early exposure to ethanol can be reproduced in laboratory animals and this helped to answer several key questions concerning the human pathology. The interest of experimental models of FASD is twofold. First, they increase our knowledge about the dose and modality of alcohol consumption able to induce damaging effects on the developing brain. Second, experimental models of FASD can provide useful hints to elucidate the basic mechanisms leading to the intellectual disability. In fact, experimental exposure to alcohol can be carried out during discrete, often very restricted, time windows. As a consequence, FASD models, though depending on the multifaceted interference of alcohol with several molecular pathways, can provide valuable information about which specific developmental periods and brain areas are critically involved in the genesis of mental retardation. Putting together data obtained through several experimental paradigms of alcohol exposure and those deriving from other genetic and non-genetic models, one can figure out to what extent different types of mental retardation share common pathogenetic mechanisms. The present Research Topic is aimed at establishing the state of the art of the current research on experimental FASD, focusing on differences and homologies with other types of intellectual disability. The ultimate goal is to find out a common roadmap in view of future therapeutical approaches.

Genetics and epigenetics of fetal alcohol spectrum disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195732 Year: Pages: 114 DOI: 10.3389/978-2-88919-573-2 Language: English
Publisher: Frontiers Media SA
Subject: Biology --- Science (General) --- Genetics
Added to DOAB on : 2016-02-05 17:24:33
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Women drinking during pregnancy can result in Fetal Alcohol Spectrum Disorder (FASD), which may feature variable neurodevelopmental deficits, facial dysmorphology, growth retardation, and learning disabilities. Research suggests the human brain is precisely formed through an intrinsic, genetic-cellular expression that is carefully orchestrated by an epigenetic program. This program can be influenced by environmental inputs such as alcohol. Current research suggests the genetic and epigenetic elements of FASD are heavily intertwined and highly dependent on one another. As such, now is the time for investigators to combine genetic, genomic and epigenetic components of alcohol research into a centralized, accessible platform for discussion. Genetic analyses inform gene sets which may be vulnerable to alcohol exposure during early neurulation. Prenatal alcohol exposure indeed alters expression of gene subsets, including genes involved in neural specification, hematopoiesis, methylation, chromatin remodeling, histone variants, eye and heart development. Recently, quantitative genomic mapping has revealed loci (QTLs) that mediate alcohol-induced phenotypes identified between two alcohol-drinking mouse strains. One question to consider is (besides the role of dose and stage of alcohol exposure) why only 5% of drinking women deliver newborns diagnosed with FAS (Fetal Alcohol Syndrome)? Studies are ongoing to answer this question by characterizing genome-wide expression, allele-specific expression (ASE), gene polymorphisms (SNPs) and maternal genetic factors that influence alcohol vulnerability. Alcohol exposure during pregnancy, which can lead to FASD, has been used as a model to resolve the epigenetic pathway between environment and phenotype. Epigenetic mechanisms modify genetic outputs through alteration of 3D chromatin structure and accessibility of transcriptional machinery. Several laboratories have reported altered epigenetics, including DNA methylation and histone modification, in multiple models of FASD. During development DNA methylation is dynamic yet orchestrated in a precise spatiotemporal manner during neurulation and coincidental with neural differentiation. Alcohol can directly influence epigenetics through alterations of the methionine pathway and subsequent DNA or histone methylation/acetylation. Alcohol also alters noncoding RNA including miRNA and transposable elements (TEs). Evidence suggests that miRNA expression may mediate ethanol teratology, and TEs may be affected by alcohol through the alteration of DNA methylation at its regulatory region. In this manner, the epigenetic and genetic components of FASD are revealing themselves to be mechanistically intertwined. Can alcohol-induced epigenomic alterations be passed across generations? Early epidemiological studies have revealed infants with FASD-like features in the absence of maternal alcohol, where the fathers were alcoholics. Novel mechanisms for alcohol-induced phenotypes include altered sperm DNA methylation, hypomethylated paternal allele and heritable epimutations. These studies predict the heritability of alcohol-induced epigenetic abnormalities and gene functionality across generations. We opened a forum to researchers and investigators the field of FASD to discuss their insights, hypotheses, fresh data, past research, and future research themes embedded in this rising field of the genetics and epigenetics of FASD. This eBook is a product of the collective sharing and debate among researchers who have contributed or reviewed each subject.

Promiscuous functions of the prion protein gene family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196050 Year: Pages: 113 DOI: 10.3389/978-2-88919-605-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2016-08-16 10:34:25
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The cellular prion protein PrPC is a ubiquitous GPI-anchored protein. While PrPC has been the focus of intense research for its involvement in a group of neurodegenerative disorders known as transmissible spongiform encephalopathies (TSE), much less attention has been devoted to its physiological function. This notably relates to the lack of obvious abnormalities of mice, goat or cattle lacking PrPC. This apparently normal phenotype in these PrPC-deficient animals however contrasts with the very high degree of conservation of the prion protein gene (Prnp) in mammalian species (over 80%), and the presence of genes with similarities to Prnp in birds, reptiles, amphibians and fish. This high conservation together with its ubiquitous expression, - albeit at highest levels in the brain-, suggest that PrPC has major physiological functions. Dissecting PrPC function is further complicated by the occurrence, in mammals, of two potentially partially redundant homologues, Doppel, and Shadoo. The biological overlaps between members of the prion protein family are still under investigation and much debated. Similarly, although in vitro analyses have suggested various functions for PrPC, notably in cell death and survival processes, some have yielded conflicting results and/or discrepancies with in vivo studies. This Research Topic brings together the accumulated knowledge regarding the biological roles of the prion protein family, from the animal to the molecular scale.

Immune Interactions during the Reproductive Cycle

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195640 Year: Pages: 158 DOI: 10.3389/978-2-88919-564-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Mammalian pregnancy represents a unique immunological riddle in that the mother does not reject her allogeneic fetus. In part this is largely due to a general sequestration or diminution of T cell activity, and an increased involvement of the innate immune system. The field of immunology is concerned primarily with how innate and adaptive mechanisms collaborate to protect vertebrates from infection. Although many cellular and molecular actors have evidently important roles, antibodies and lymphocytes are considered to be the principal players. Yet despite their importance, it would be definitely simplistic to conclude that they are solely essential for immunity overall. A major distinction between adaptive and innate immunity is the spontaneity of the innate immune response, which utilizes an already pre-existing but limited repertoire of responding modules. The slower onset of adaptive immunity compensates by its ability to recognize a much broader repertory of foreign substances, and also by its power to constantly improve during a response, whereas innate immunity remains relatively unaffected. The interactions between the reproductive system and the immune system are of particular interest, since the reproductive system is unique in that its primary role is to assure the continuity of the species, while the immune system provides internal protection and thus facilitates continued health and survival. The modus operandi of these two morphologically diffuse systems involves widely distributed chemical signals in response to environmental input, and both systems must interact for the normal functioning of each. Furthermore, dysregulation of normal physiological interactions between the reproductive and immune systems can lead to severe pregnancy-related disorders or complications. On the other hand, by ameliorating auto-inflammatory conditions such as MS and RA, pregnancy may provide a unique insight into novel immune modulatory strategies. The scientific focus on reproductive–immune research has historically provided substantial insight into the interface between these two physiological systems. A translational research approach would involve a tight interaction between diverse scientific and clinical disciplines including immunology, obstetrics, haematology, haemostasis and endocrinology. With so much recent progress in the field, we believe that it is valuable and well-timed to review the broad variety of the relevant physiologic and pathologic aspects – from menstruation to fertilization and implantation, and from placentation and pregnancy per se to the post partum condition - in which the immune system takes part. We are looking forward to a wide and vivid discussion of these and related issues, and we sincerely expect that our readers profoundly benefit from new exciting insights and fruitful collaborations.

Bridging the gap before and after birth: Methods and technologies to explore the functional neural development in humans

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196876 Year: Pages: 114 DOI: 10.3389/978-2-88919-687-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Infant brain damage is a serious condition that affects millions of babies each year. The period from late gestation to the first year of life is the most critical one for the development of central and autonomous nervous systems. Medical conditions such as preterm birth may compromise brain function and the end result usually is that the baby may experience long-term neurological problems related to a wide range of psychological, physical and functional complications, with consequent life-long burdens for the individuals and their families, and a high socio-economic impact for the health care system and the whole of society. During the last years, several techniques have been employed to monitor the brain functional development in utero and after birth. As well, various analytical methods have been used to understand the functional maturation of the brain and the autonomous nervous system. However, in spite of the rapid improvement of diagnostic methods and procedures, there is still a widely recognized, severe shortage of clinically viable means for the high quality monitoring of the brain function in early life with a direct relevance to acute neurological illness and future neurocognitive outcomes. The studies collected in this e-book document the most recent advancements in monitoring systems, analytical methods and clinical diagnostic procedures that contribute to increase our knowledge of the functional development of the human brain and autonomous nervous system during pregnancy and after birth, with the ultimate goal of reducing fetal impairment and improving healthcare in the neonatal and infant period.

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