HIV Vaccine Efficacy Trials: RV144 and Beyond.
Authors: Heger E, Schuetz A, Vasan S Abstract Despite progress in antiretroviral therapy, pre-exposure prophylaxis, microbicides, and other preventive strategies, a vaccine to prevent HIV-1 infection remains desperately needed. Development of an effective vaccine is challenged by several immunologic features of HIV-1 evidenced by the failure of five of the six HIV-1 candidate vaccine efficacy trials to date. This chapter reviews these efficacy trials with a focus on the Phase 3 RV144 trial in Thailand, the only HIV-1 vaccine efficacy trial to show a moderate protective effect of 31% with respect to placebo administ...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

HIV T-Cell Vaccines.
Authors: Mothe B, Brander C Abstract Some of the strongest immune correlates of controlled HIV infection include markers related to antiviral T-cell responses, especially responses mediated by CD8+ cytotoxic T lymphocytes (CTL). These observations and lessons learned from other viral infections have motivated the development of T-cell vaccine candidates to HIV in the preventive and especially in the therapeutic setting. While none of the T-cell vaccine concepts tested to date have shown sufficient efficacy, the last few years have seen some advances indicating that strategies activating the cellular adaptive immune...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

HIV Broadly Neutralizing Antibodies: VRC01 and Beyond.
Authors: Wu X Abstract Developing an effective prophylaxis HIV-1 vaccine is likely to require the elicitation of broadly neutralizing antibodies (bnAbs). As the HIV-1 envelope (Env) glycoprotein - the sole target of bnAbs - has evolved multiple mechanisms to evade antibody neutralization, the processes for bnAb generation are highly selective and time-consuming. Benefiting from antibody isolation technologies of single B cell culturing and direct single B cell sorting and cloning, a new generation of monoclonal bnAbs has been isolated since 2009, exhibiting remarkable breadths and potencies, thus bre...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Structural Features of Broadly Neutralizing Antibodies and Rational Design of Vaccine.
Authors: Zhou T, Xu K Abstract Despite sequence diversity, glycosylation, and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), antibodies that neutralize diverse HIV-1 strains develop in selected HIV-1-infected individuals. The application of single B cell-based approaches has identified many broad and potent human antibodies from infected donors. Structural studies on antibody recognition of HIV Env have revealed that these broadly reactive antibodies target epitopes covering entire exposed and glycosylated surface on the viral spike; several classes of antibodies recog...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Monkey Models and HIV Vaccine Research.
Authors: Chen Z Abstract Since the discovery of acquired immunodeficiency syndrome (AIDS) in 1981, it has been extremely difficult to develop an effective vaccine or a therapeutic cure despite over 36 years of global efforts. One of the major reasons is due to the lack of an immune-competent animal model that supports live human immunodeficiency virus (HIV) infection and disease progression such that vaccine-induced correlates of protection and efficacy can be determined clearly before human trials. Nevertheless, rhesus macaques infected with simian immunodeficiency virus (SIV) and chimeric simian human i...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Treatment of HIV for the Prevention of Transmission in Discordant Couples and at the Population Level.
Authors: Kumi Smith M, Jewell BL, Hallett TB, Cohen MS Abstract The scientific breakthrough proving that antiretroviral therapy (ART) can halt heterosexual HIV transmission came in the form of a landmark clinical trial conducted among serodiscordant couples. Study findings immediately informed global recommendations for the use of treatment as prevention in serodiscordant couples. The extent to which these findings are generalizable to other key populations or to groups exposed to HIV through nonsexual transmission routes (i.e., anal intercourse or unsafe injection of drugs) has since driven a large body of researc...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

HIV Persistence on Antiretroviral Therapy and Barriers to a Cure.
Authors: Marsh Sung J, M Margolis D Abstract HIV persists within the body despite successful suppression of virus replication with antiretroviral therapy (ART). HIV lurks in latent and active reservoirs, leading to rebound of virus spread if ART is interrupted. The latent HIV reservoir is a natural consequence of the life cycle of HIV, with integration of HIV into the genomes of cells that are or later enter the resting state, resulting in transcriptionally quiescent provirus. Resting CD4 T cells comprise the majority of the latent reservoir, although new evidence points to additional, smaller cellular reservoirs o...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Molecular Biology of HIV Latency.
Authors: Khoury G, Darcis G, Lee MY, Bouchat S, Van Driessche B, Purcell DFJ, Van Lint C Abstract HIV remains incurable due to the existence of a reservoir of cells that harbor intact integrated genomes of the virus in the absence of viral replication. This population of infected cells remains invisible to the immune system and is not targeted by the drugs used in the current antiretroviral therapies (cART). Reversal of latency by the use of inhibitors of chromatin-remodeling enzymes has been studied extensively in an attempt to purge this reservoir of latent HIV but has thus far not shown any success in clini...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cellular Determinants of HIV Persistence on Antiretroviral Therapy.
Authors: Mikhailova A, Valle-Casuso JC, Sáez-Cirión A Abstract The era of antiretroviral therapy has made HIV-1 infection a manageable chronic disease for those with access to treatment. Despite treatment, virus persists in tissue reservoirs seeded with long-lived infected cells that are resistant to cell death and immune recognition. Which cells contribute to this reservoir and which factors determine their persistence are central questions that need to be answered to achieve viral eradication. In this chapter, we describe how cell susceptibility to infection, resistance to cell death, and immune-med...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

In Vitro and In Vivo Models of HIV Latency.
Authors: Whitney JB, Brad Jones R Abstract Latently infected cells are very infrequent in CD4+ T cells from antiretroviral (ARV) treated individuals, with only approximately one in a million infected CD4+ T cells in blood. Given the low frequency of infected cells in vivo, multiple in vitro latency models have been developed to facilitate investigations into mechanisms of HIV latency, as well as to enable the evaluation of pharmacological and immunological interventions aimed at depleting latently infected cells. These in vitro models include clones of transformed cell lines with integrated HIV proviruses or primar...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Measuring HIV Persistence on Antiretroviral Therapy.
Authors: Horsburgh BA, Palmer S Abstract In order to determine if an eradication strategy for HIV is effective, it will be important to measure persistent replication-competent virus, the current barrier to a cure. Various assays are available that measure persistent virus, each with advantages and disadvantages that must be balanced in order to select the best assay for the experimental aim. Assays of free virus do not measure the latent form of the virus but can be utilised in conjunction with other assays in order to better understand HIV persistence on ART. The quantitative viral outgrowth assay (QVOA) is the g...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Clinical Interventions in HIV Cure Research.
Authors: Rasmussen TA, Søgaard OS Abstract Research over the past decade has resulted in a much-improved understanding of how and where HIV persists in patients on otherwise suppressive antiretroviral therapy (ART). It has become clear that the establishment of a latent infection in long-lived cells is the key barrier to curing HIV or allowing for sustained ART-free remission. Informed by in vitro and ex vivo studies, several therapeutic approaches aimed at depleting the pool of latently infected cells have been tested in small-scale experimental clinical trials including studies of ART intensification, geno...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Introduction to Molecular Mechanisms in Notch Signal Transduction and Disease Pathogenesis.
Authors: Giaimo BD, Borggrefe T Abstract The Notch signaling pathway plays a pivotal role in development, physiology and diseases such as cancer. In this chapter, we first give an overview of the different molecular mechanisms that regulate Notch signaling. Each subject is covered in more depth in the subsequent chapters of this book. Next, we will use the inflammatory system as an example to discuss the physiological function of Notch signaling. This is followed by a discussion of recent advances in the different pathophysiological roles of Notch signaling in leukemia as well as a wide range of solid cancers. Fina...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Structural Insights into Notch Receptor-Ligand Interactions.
Authors: Handford PA, Korona B, Suckling R, Redfield C, Lea SM Abstract Pioneering cell aggregation experiments from the Artavanis-Tsakonas group in the late 1980's localized the core ligand recognition sequence in the Drosophila Notch receptor to epidermal growth factor-like (EGF) domains 11 and 12. Since then, advances in protein expression, structure determination methods and functional assays have enabled us to define the molecular basis of the core receptor/ligand interaction and given new insights into the architecture of the Notch complex at the cell surface. We now know that Notch EGF11 and 12 interact with...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Molecular Mechanism of Notch Activation.
Authors: Lovendahl KN, Blacklow SC, Gordon WR Abstract Research in the last several years has shown that Notch proteolysis, and thus Notch activation, is conformationally controlled by the extracellular juxtamembrane NRR of Notch, which sterically occludes the S2 protease site until ligand binds. The question of how conformational exposure of the protease site is achieved during physiologic activation, and thus how normal activation is bypassed in disease pathogenesis, has been the subject of intense study in the last several years, and is the subject of this chapter. Here, we summarize the structural features of t...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Regulation of Notch Function by O-Glycosylation.
Authors: Harvey BM, Haltiwanger RS Abstract The Notch receptor initiates a unique intercellular signaling pathway that is evolutionarily conserved across all metazoans and contributes to the development and maintenance of numerous tissues. Consequently, many diseases result from aberrant Notch signaling. Emerging roles for Notch in disease are being uncovered as studies reveal new information regarding various components of this signaling pathway. Notch activity is regulated at several levels, but O-linked glycosylation of Epidermal Growth Factor (EGF) repeats in the Notch extracellular domain has emerged as a majo...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Modeling the Notch Response.
Authors: Binshtok U, Sprinzak D Abstract NOTCH signaling regulates developmental processes in all tissues and all organisms across the animal kingdom. It is often involved in coordinating the differentiation of neighboring cells into different cell types. As our knowledge on the structural, molecular and cellular properties of the NOTCH pathway expands, there is a greater need for quantitative methodologies to get a better understanding of the processes controlled by NOTCH signaling. In recent years, theoretical and computational approaches to NOTCH signaling and NOTCH mediated patterning are gaining popularity. Ma...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Endocytic Trafficking of the Notch Receptor.
Authors: Schnute B, Troost T, Klein T Abstract The endosomal pathway plays an important role in several aspects of Notch signalling ranging from ligand-dependent to independent activation and also degradation of the Notch receptor. Here, we will focus on its role during receptor degradation and describe the endosomal pathway with the components that are important for Notch degradation and the molecular machinery that orchestrates these events. Subsequently, we will describe the journey of Notch through the endosomal system and discuss the role of the genes involved. Mechanisms of the recently discovered ligand-inde...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Notch Interactome: Complexity in Signaling Circuitry.
Authors: Ho DM, Guruharsha KG, Artavanis-Tsakonas S Abstract The Notch pathway controls a very broad spectrum of cell fates in metazoans during development, influencing proliferation, differentiation and cell death. Given its central role in normal development and homeostasis, misregulation of Notch signals can lead to various disorders including cancer. How the Notch pathway mediates such pleiotropic and differential effects is of fundamental importance. It is becoming increasingly clear through a number of large-scale genetic and proteomic studies that Notch interacts with a staggeringly large number of other gen...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Integration of Drosophila and Human Genetics to Understand Notch Signaling Related Diseases.
Authors: Salazar JL, Yamamoto S Abstract Notch signaling research dates back to more than one hundred years, beginning with the identification of the Notch mutant in the fruit fly Drosophila melanogaster. Since then, research on Notch and related genes in flies has laid the foundation of what we now know as the Notch signaling pathway. In the 1990s, basic biological and biochemical studies of Notch signaling components in mammalian systems, as well as identification of rare mutations in Notch signaling pathway genes in human patients with rare Mendelian diseases or cancer, increased the significance of this pathway...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Mechanisms of Non-canonical Signaling in Health and Disease: Diversity to Take Therapy up a Notch?
Authors: Alfred V, Vaccari T Abstract Non-canonical Notch signaling encompasses a wide range of cellular processes, diverging considerably from the established paradigm. It can dispense of ligand, proteolytic or nuclear activity. Non-canonical Notch signaling events have been studied mostly in the fruit fly Drosophila melanogaster, the organism in which Notch was identified first and a powerful model for understanding signaling outcomes. However, non-canonical events are ill-defined and their involvement in human physiology is not clear, hampering our understanding of diseases arising from Notch signaling alteratio...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Notch3 Receptor and Its Intracellular Signaling-Dependent Oncogenic Mechanisms.
Authors: Bellavia D, Checquolo S, Palermo R, Screpanti I Abstract During evolution, gene duplication of the Notch receptor suggests a progressive functional diversification. The Notch3 receptor displays a number of structural differences with respect to Notch1 and Notch2, most of which have been reported in the transmembrane and in the intracellular regions, mainly localized in the negative regulatory region (NRR) and trans-activation domain (TAD). Targeted deletion of Notch3 does not result in embryonic lethality, which is in line with its highly restricted tissue expression pattern. Importantly, deregulated Notch...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Notch and Neurogenesis.
Authors: Engler A, Zhang R, Taylor V Abstract Neurogenesis is the process of forming neurons and is essential during vertebrate development to produce most of the neurons of the adult brain. However, neurogenesis continues throughout life at distinct locations in the vertebrate brain. Neural stem cells (NSCs) are the origin of both embryonic and adult neurogenesis, but their activity and fate are tightly regulated by their local milieu or niche. In this chapter, we will discuss the role of Notch signaling in the control of neurogenesis and regeneration in the embryo and adult. Notch-dependence is a common feature a...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Notch and Stem Cells.
Authors: Bigas A, Porcheri C Abstract The Notch pathway is crucial in the regulation of stem cells biology. Notch-mediated signalling controls several aspects of tissue homeostasis in both embryonic and adult tissues, balancing stem cells maintenance and differentiation. Although the major elements of the pathway are well conserved throughout evolution, its fine regulation varies among different systems. In this review, we are focusing at the differences and analogies of Notch activity in different animal models, comparing stem cells of various tissues in both adulthood and development. We summarize the major mode ...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Oscillatory Control of Notch Signaling in Development.
Authors: Kageyama R, Shimojo H, Isomura A Abstract The Notch effectors Hes1 and Hes7 and the Notch ligand Delta-like1 (Dll1) are expressed in an oscillatory manner during neurogenesis and somitogenesis. These two biological events exhibit different types of oscillations: anti-/out-of-phase oscillation in neural stem cells during neurogenesis and in-phase oscillation in presomitic mesoderm (PSM) cells during somitogenesis. Accelerated or delayed Dll1 expression by shortening or elongating the size of the Dll1 gene, respectively, dampens or quenches Dll1 oscillation at intermediate levels, a phenomenon known as "...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

CSL-Associated Corepressor and Coactivator Complexes.
Authors: Oswald F, Kovall RA Abstract The highly conserved Notch signal transduction pathway orchestrates fundamental cellular processes including, differentiation, proliferation, and apoptosis during embryonic development and in the adult organism. Dysregulated Notch signaling underlies the etiology of a variety of human diseases, such as certain types of cancers, developmental disorders and cardiovascular disease. Ligand binding induces proteolytic cleavage of the Notch receptor and nuclear translocation of the Notch intracellular domain (NICD), which forms a ternary complex with the transcription factor CSL and ...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Notch and Senescence.
Authors: Hoare M, Narita M Abstract Cellular senescence, previously thought of as an autonomous tumour suppressor mechanism, is emerging as a phenotype and effector present throughout the life of an organism from embryogenesis to senile decline. Senescent cells have powerful non-autonomous effects upon multiple players within their microenvironment mainly through their secretory phenotype. How senescent cells co-ordinate numerous, sometimes functionally contrasting outputs through their secretome had previously been unclear. The Notch pathway, originally identified for its involvement in Drosophila wing development...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Control of Blood Vessel Formation by Notch Signaling.
Authors: Tetzlaff F, Fischer A Abstract Blood vessels span throughout the body to nourish tissue cells and to provide gateways for immune surveillance. Endothelial cells that line capillaries have the remarkable capacity to be quiescent for years but to switch rapidly into the activated state once new blood vessels need to be formed. In addition, endothelial cells generate niches for progenitor and tumor cells and provide organ-specific paracrine (angiocrine) factors that control organ development and regeneration, maintenance of homeostasis and tumor progression. Recent data indicate a pivotal role for blood vesse...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Notch and T Cell Function - A Complex Tale.
Authors: Vijayaraghavan J, Osborne BA Abstract Notch drives critical decisions in a multitude of developmental decisions in many invertebrate and vertebrate organisms including flies, worms, fish, mice and humans. Therefore, it is not surprising that Notch family members also play a key role in cell fate choices in the vertebrate immune system. This review highlights the critical function of Notch in the development of mature T lymphocytes from hematopoietic precursors and describes the role of Notch in mature T cell activation, proliferation and differentiation. PMID: 30030835 [PubMed - in process] (Source: Ad...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Notch in Leukemia.
Authors: McCarter AC, Wang Q, Chiang M Abstract Notch is commonly activated in lymphoid malignancies through ligand-independent and ligand-dependent mechanisms. In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), ligand-independent activation predominates. Negative Regulatory Region (NRR) mutations trigger supraphysiological Notch1 activation by exposing the S2 site to proteolytic cleavage in the absence of ligand. Subsequently, cleavage at the S3 site generates the activated form of Notch, intracellular Notch (ICN). In contrast to T-ALL, in mature lymphoid neoplasms such as chronic lymphocytic leukemia (CLL),...
Source: Advances in Experimental Medicine and Biology - July 22, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Influenza: Underestimated in Children Below 2 Years of Age.
Authors: Wrotek A, Czajkowska M, Zawłocka E, Jackowska T Abstract Children under 2 years of age may receive antiviral therapy when influenza is suspected. Signs of influenza are frequently unclear and testing is indicated. The aim of the study was to assess the usefulness of clinical signs and the rapid influenza diagnostic test (RIDT) in diagnosing influenza and in choosing the appropriate treatment. In the 2015-2016 influenza season, 89 children under 2 years of age (56.7% of 157 children diagnosed with influenza) were hospitalized. There were 74 RIDT and 70 reverse transcription polymerase chain react...
Source: Advances in Experimental Medicine and Biology - July 12, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Knowledge Regarding Influenza and Influenza Vaccination in General Population: Results of a National Survey in Poland.
In conclusion, the knowledge on influenza vaccination is deficient in the general population. Education on immunization should be prioritized to increase vaccination coverage rate in Poland. PMID: 29995213 [PubMed - as supplied by publisher] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - July 12, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Epidemiology of Granulomatosis with Polyangiitis in Poland, 2011-2015.
In conclusion, the incidence and prevalence rates of GPA in Poland are similar to that reported in other European countries. The study provides recent epidemiological data on GPA in Poland, which may be useful for comparisons with other geographical regions. PMID: 29971682 [PubMed - as supplied by publisher] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - July 5, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

One-Carbon Metabolism and Lipid Metabolism in DOHaD.
Authors: Fukuoka H, Kubota T Abstract The predisposing factors to lifestyle-associated diseases are established in the early period of life with underlying gene-environment interaction. Epigenetics is a chemical modification-based genetic mechanism that is affected by various nutritional factors. One-carbon metabolism is a metabolic system associated with methyl residue that is supplied from folic acid. Therefore, from the epigenetic point of view, proper intake of folic acid is important for pregnant women not only to prevent congenital abnormalities such as neural tube defect but also to prevent various adult dis...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Novel Models of Epigenetic Gene Regulation in the Nutritional Environment.
Authors: Mochizuki K, Hariya N, Kubota T Abstract Epigenetic memories are acquired information included in the chromatin or DNA such as methylation and histone modifications. Recent studies suggest that epigenetic memories determine the types of differentiated cells in each tissue. Moreover, the development of metabolic diseases induced by environmental factors during development is controlled by epigenetic regulation rather than the genetic regulation such as DNA sequence-dependent transcriptional regulation. In general, the demethylation of CpG islands induces histone acetylation, associated changes from heteroch...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Epigenetic Switching and Neonatal Nutritional Environment.
Authors: Hashimoto K, Ogawa Y Abstract The hepatic metabolic function changes sequentially during early life in mammals to adapt to the drastic changes in the nutritional environment. Accordingly, hepatic fatty acid β-oxidation is activated after birth to produce energy from breast milk lipids. De novo lipogenesis is induced upon the onset of oral intake, when the major nutritional source switches to carbohydrate. However, how a particular metabolic pathway is activated during the liver maturation is poorly understood. We found that the expression of glycerol-3-phosphate acyltransferase 1 (GPAT1), a rate-limit...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Developmental Origins of Nonalcoholic Fatty Liver Disease (NAFLD).
Authors: Itoh H, Kanayama N Abstract Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Its prevalence is currently increasing not only in developed obese countries but also in developing countries. Recent findings from human cohorts and animal studies suggest that a nutritional imbalance in the early critical period is causatively associated with the incidence of NAFLD in later life. Based on the current theory of the developmental origins of health and disease (DOHaD), undernourishment and overnourishment in utero are both hypothesized to prime the predisposition for hepati...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Fetal Origins of Hypertension.
Authors: Arima Y, Nishiyama K, Izumiya Y, Kaikita K, Hokimoto S, Tsujita K Abstract Hypertension is a common noncommunicable disease. According to the World Health Organization, 1.13 billion people were suffering from hypertension in the year 2015. High blood pressure, hypertension, has a multifactorial etiology. Arterial atherosclerotic changes, systolic or diastolic dysfunction of the heart, and other noncardiac factors are involved. Epidemiological evidence has revealed that perinatal growth disturbance elevates the prevalence of hypertension. However, the specific effects of developmental disturbances on the pa...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Involvement of Noncoding RNAs in Stress-Related Neuropsychiatric Diseases Caused by DOHaD Theory : ncRNAs and DOHaD-Induced Neuropsychiatric Diseases.
Authors: Nemoto T, Kakinuma Y Abstract According to the DOHaD theory, low birth weight is a risk factor for various noncommunicable chronic diseases that develop later in life. Noncoding RNAs (ncRNAs), including miRNAs, siRNAs, piRNAs, and lncRNAs, are functional RNA molecules that are transcribed from DNA but that are not translated into proteins. In general, miRNAs, siRNAs, and piRNAs function to regulate gene expression at the transcriptional and posttranscriptional levels. Studying ncRNAs has provided opportunities for new diagnosis and therapeutic knowledge in the endocrinological and metabolic fields as well ...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Placental Development and Nutritional Environment.
Authors: Taniguchi K, Kawai T, Hata K Abstract The placenta is considered to have developed recently in mammalian evolution. While the fundamental function of the placenta, i.e., providing nutrients and oxygen to the fetus and receiving waste products, is the same in all mammals, the morphology of the placenta varies substantially in a species-dependent manner. Therefore, considerable interest exists in understanding placental development and function in mammals from a molecular biological viewpoint. Numerous recent studies have shown that various environmental factors before and during pregnancy, including nutriti...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Risk of Neurodevelopmental Disease by Paternal Aging: A Possible Influence of Epigenetic Alteration in Sperm.
This article will mainly discuss recent findings about the effects of the advanced paternal age on the next generation, in relation to the onset of psychiatric disorders such as autism spectrum disorder. We would like to advocate for further exploration on the DOHaD theory in a wider view. PMID: 29956196 [PubMed - in process] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Preemptive Epigenetic Medicine Based on Fetal Programming.
Authors: Kubota T Abstract The developmental origins of health and disease (DOHaD) refers to the concept that environmental stress during pregnancy alters the programmed fetal development and subsequently causes disorders, such as cardiovascular and metabolic diseases, in adulthood. Epigenetics is a gene regulation mechanism that does not depend on DNA sequence but on chemical modifications of DNA. Several lines of evidence suggest that environmental stress in the fetal period alters the epigenetic state of genes, leading to permanent gene dysregulation, which may be associated with disorders that emerge after birt...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Prognostic Impact of Extracapsular Lymph Node Invasion on Survival in Non-small-Cell Lung Cancer: A Systematic Review and Meta-analysis.
In conclusion, ECE has a significant impact on survival in NSCLC patients and should be considered in diagnostic and therapeutic decisions in addition to the current TNM staging. Postoperative radiotherapy may be an option in ECE-positive pN1 NSCLC patients. PMID: 29956198 [PubMed - as supplied by publisher] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Effects of Low-Level Laser Therapy in Autism Spectrum Disorder.
Authors: Leisman G, Machado C, Machado Y, Chinchilla-Acosta M Abstract The study examined the efficacy of low-level laser therapy, a form of photobiomodulation, for the treatment of irritability associated with autistic spectrum disorder in children and adolescents aged 5-17 years. Twenty-one of the 40 participants received eight 5-min procedures administered to the base of the skull and temporal areas across a 4-week period (test, i.e., active treatment participants). All the participants were evaluated with the Aberrant Behavior Checklist (ABC), with the global scale and five subscales (irritability/agitatio...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Virological Situation in Poland in the 2016/2017 Epidemic Season Based on Sentinel Data.
Authors: Cieślak K, Szymański K, Kowalczyk D, Hallmann-Szelińska E, Brydak LB Abstract The influenza Sentinel surveillance system is a source of valuable data about the dynamics of epidemic seasons in Poland. During the epidemic season 2016/2017, more than 1,000 samples were examined, of which 48% were positive for influenza diagnosis. The predominance of influenza A/H3N2/ was confirmed. Influenza B viruses were noted in only 1% of the samples tested. After the analysis in age groups, the highest number of positive samples was observed in the group of 26-44 years. Infections caused by influenza-like viruses...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Introduction.
Authors: Wong CC, Yu J Abstract Obesity is fast becoming a major disorder for mankind. Numerous lifestyle factors play a role in the rising obesity epidemic, including changes in the diet and the lack of physical activity. Unfortunately, more than two-thirds of the adult population in developed countries is considered overweight and more than a third of them are obese. In addition to the well-publicized association of obesity with type II diabetes and cardiovascular diseases, emerging evidence indicates that obesity represents a major risk factor for fatty liver diseases and fatty liver disease-associated hepatocel...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Epidemiology and Etiologic Associations of Non-alcoholic Fatty Liver Disease and Associated HCC.
Authors: Liu K, McCaughan GW Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world and will soon become the number one cause of hepatocellular carcinoma (HCC), liver transplantation and liver-related mortality. The disease often occurs in the setting of metabolic conditions such as obesity and type II diabetes mellitus. These same metabolic drivers are also risk factors for NAFLD associated HCC which can occur even in the absence of cirrhosis or advanced fibrosis and appears to be phenotypically different to HCCs arising from other chronic liver diseases. The frequ...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Pathogenesis of NASH: How Metabolic Complications of Overnutrition Favour Lipotoxicity and Pro-Inflammatory Fatty Liver Disease.
Authors: Farrell GC, Haczeyni F, Chitturi S Abstract Overnutrition, usually with obesity and genetic predisposition, lead to insulin resistance, which is an invariable accompaniment of nonalcoholic fatty liver disease (NAFLD). The associated metabolic abnormalities, pre- or established diabetes, hypertension and atherogenic dyslipidemia (clustered as metabolic syndrome) tend to be worse for nonalcoholic steatohepatitis (NASH), revealing it as part of a continuum of metabolic pathogenesis. The origins of hepatocellular injury and lobular inflammation which distinguish NASH from simple steatosis have intrigued invest...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Chemokines and Chemokine Receptors in the Development of NAFLD.
Authors: Roh YS, Seki E Abstract Chemokines are chemo-attractants for leukocyte trafficking, growth, and activation in injured and inflammatory tissues. The chemokine system is comprised of 50 chemokine ligands and 20 cognate chemokine receptors. In the context of liver diseases, leukocytes, hepatocytes, hepatic stellate cells, endothelial cells, and vascular smooth muscle cells are capable of producing chemokines. Chemokine receptors are typically expressed in various leukocyte subsets. Given that inflammation is a critical factor for the transition from simple steatosis to non-alcoholic steatohepatitis (NASH), an...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

NAFLD Related-HCC: The Relationship with Metabolic Disorders.
Authors: Zhang X Abstract Obesity increases death rates of all cancers including non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (NAFLD-HCC). NAFLD is considered as hepatic manifestation of metabolic syndrome and is a multi-system disease. Recent prevalence studies have intensively reported the association of obesity, metabolic risk factors and HCC incidence and mortality. Mechanistic studies suggested that immune response, PI3K/AKT/mTOR/PTEN pathway, mitochondrial dysfunction and genetic alterations are important mediators in the progression of NAFLD-HCC from metabolic disorder. In this ...
Source: Advances in Experimental Medicine and Biology - July 1, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research