1 6784 87 [CHRONIC STRESS AND EPIGENETICS. RELATION BETWEEN ACADEMIC SCIENCES AND THEOLOGY]. THE AUTHOR GIVES A SHORT ACCOUNT ON THE PRINCIPLES OF SELYE'S STRESS THEORY, AND DISCUSSES SIMILARITIES AND DISSIMILARITIES OF ACUTE AND CHRONIC STRESS. BOTH THE EXTERNAL, AND THE INTERNAL ENVIRONMENT, AS WELL AS THE PSYCHO-MENTAL STATUS ARE INVOLVED IN THE NOTION OF THE ENVIRONMENT. BASIC PRINCIPLES OF EPIGENETICS ARE REVIEWED: INTERACTION BETWEEN ENVIRONMENT AND GENES, NEUROENDOCRINE AND ENZYMATIC MECHANISMS INVOLVED IN SILENCING AND ACTIVATION OF GENES, NOTIONS OF PHENOTYPIC PLASTICITY, AND EPIGENETIC REPROGRAMMING ARE DISCUSSED. EPIGENETIC MECHANISMS OF INTERRELATION BETWEEN PATHOLOGICAL CLINICAL STATES (DISEASES) AND THE CHARACTERISTIC PHENOTYPES, CAUSATIVE ROLE OF PSYCHO-MENTAL STATUS IN EVOKING PATHOLOGICAL SOMATIC ALTERATIONS, AND THE POTENTIAL THERAPEUTIC CONSEQUENCES ARE BRIEFLY DISCUSSED. THE ETIOLOGICAL ROLE OF CHRONIC, CIVILIZATION STRESS IN PRODUCING THE WORLDWIDE INCREMENT OF CARDIOVASCULAR MORBIDITY IS CITED, ARGUMENTATION AND CRITICISM OF THE CURRENT THERAPEUTICAL PRACTICE IS DISCUSSED. THE AUTHOR CONCLUDES THAT RECENT ADVANCES IN EPIGENETIC KNOWLEDGE SEEM TO SOLVE THE CONTROVERSY BETWEEN THE ACADEMIC AND THEOLOGICAL SCIENCES. 2012 2 760 18 CASZ1: CURRENT IMPLICATIONS IN CARDIOVASCULAR DISEASES AND CANCERS. CASTOR ZINC FINGER 1 (CASZ1) IS A C2H2 ZINC FINGER FAMILY PROTEIN THAT HAS TWO SPLICING VARIANTS, CASZ1A AND CASZ1B. IT IS INVOLVED IN MULTIPLE PHYSIOLOGICAL PROCESSES, SUCH AS TISSUE DIFFERENTIATION AND ALDOSTERONE ANTAGONISM. GENETIC AND EPIGENETIC ALTERNATIONS OF CASZ1 HAVE BEEN CHARACTERIZED IN MULTIPLE CARDIOVASCULAR DISORDERS, SUCH AS CONGENITAL HEART DISEASES, CHRONIC VENOUS DISEASES, AND HYPERTENSION. HOWEVER, LITTLE IS KNOWN ABOUT HOW CASZ1 MECHANICALLY PARTICIPATES IN THE PATHOGENESIS OF THESE DISEASES. OVER THE PAST DECADES, AT FIRST GLANCE, PARADOXICAL INFLUENCES ON CELL BEHAVIORS AND PROGRESSIONS OF DIFFERENT CANCER TYPES HAVE BEEN DISCOVERED FOR CASZ1, WHICH MAY BE EXPLAINED BY A "DOUBLE-AGENT" ROLE FOR CASZ1. IN THIS REVIEW, WE DISCUSS THE PHYSIOLOGICAL FUNCTION OF CASZ1, AND FOCUS ON THE ASSOCIATION OF CASZ1 ABERRATIONS WITH THE PATHOGENESIS OF CARDIOVASCULAR DISEASES AND CANCERS. 2023 3 2796 12 FBW7 MEDIATES SENESCENCE AND PULMONARY FIBROSIS THROUGH TELOMERE UNCAPPING. TISSUE STEM CELLS UNDERGO PREMATURE SENESCENCE UNDER STRESS, PROMOTING AGE-RELATED DISEASES; HOWEVER, THE ASSOCIATED MECHANISMS REMAIN UNCLEAR. HERE, WE REPORT THAT IN RESPONSE TO RADIATION, OXIDATIVE STRESS, OR BLEOMYCIN, THE E3 UBIQUITIN LIGASE FBW7 MEDIATES CELL SENESCENCE AND TISSUE FIBROSIS THROUGH TELOMERE UNCAPPING. FBW7 BINDING TO TELOMERE PROTECTION PROTEIN 1 (TPP1) FACILITATES TPP1 MULTISITE POLYUBIQUITINATION AND ACCELERATES DEGRADATION, TRIGGERING TELOMERE UNCAPPING AND DNA DAMAGE RESPONSE. OVEREXPRESSING TPP1 OR INHIBITING FBW7 BY GENETIC ABLATION, EPIGENETIC INTERFERENCE, OR PEPTIDOMIMETIC TELOMERE DYSFUNCTION INHIBITOR (TELODIN) REDUCES TELOMERE UNCAPPING AND SHORTENING, EXPANDING THE PULMONARY ALVEOLAR AEC2 STEM CELL POPULATION IN MICE. TELODIN, SYNTHESIZED FROM THE SEVENTH BETA STRAND BLADE OF FBW7 WD40 PROPELLER DOMAIN, INCREASES TPP1 STABILITY, LUNG RESPIRATORY FUNCTION, AND RESISTANCE TO SENESCENCE AND FIBROSIS IN ANIMALS CHRONICALLY EXPOSED TO ENVIRONMENTAL STRESS. OUR FINDINGS ELUCIDATE A PIVOTAL MECHANISM UNDERLYING STRESS-INDUCED PULMONARY EPITHELIAL STEM CELL SENESCENCE AND FIBROSIS, PROVIDING A FRAMEWORK FOR AGING-RELATED DISORDER INTERVENTIONS. 2020 4 5814 17 STRESS AND FELINE HEALTH. IN THE HEALTH SCIENCES, STRESS OFTEN IS DEFINED IN TERMS OF STRESSORS; EVENTS THAT ARE PERCEIVED AS THREATS TO ONE'S PERCEPTION OF CONTROL. FROM THIS PERSPECTIVE, A STRESSOR IS ANYTHING THAT ACTIVATES THE CENTRAL THREAT RESPONSE SYSTEM (CTRS). RECENT RESEARCH SHOWS THAT THE CTRS CAN BE SENSITIZED TO ENVIRONMENTAL EVENTS THROUGH EPIGENETIC MODULATION OF GENE EXPRESSION. WHEN CTRS ACTIVATION IS CHRONIC, HEALTH AND WELFARE MAY BE HARMED. ENVIRONMENTAL MODIFICATION CAN MITIGATE THE HARMFUL EFFECTS OF CHRONIC CTRS ACTIVATION BY REDUCING THE INDIVIDUAL'S PERCEPTION OF THREAT AND INCREASING ITS PERCEPTION OF CONTROL, WHICH IMPROVES HEALTH AND WELFARE. 2020 5 3862 19 ISOPATHIC USE OF AUTO-SARCODE OF DNA AS ANTI-MIASMATIC HOMEOPATHIC MEDICINE AND MODULATOR OF GENE EXPRESSION? INTRODUCTION: IN ADDITION TO THE FOUR PILLARS OF HOMEOPATHY, VITALISM AND THE MIASMATIC THEORY ARE OFTEN USED TO EXPLAIN THE HEALTH-DISEASE PROCESS. ACCORDING TO HAHNEMANN'S CONCEPTS, HOMEOPATHIC MIASMS ARE THE MAIN OBSTACLE TO THE CURE OF CHRONIC DISEASES, WITH PSORA BEING THE FUNDAMENTAL CAUSE OF ALL FORMS OF DISEASES. ACCORDING TO MODERN GENETICS, THE DISEASE-PROMOTING EPIGENETIC ALTERATIONS ARE THE FUNDAMENTAL CAUSE OF THE MANIFESTATION OF CHRONIC DISEASES. OBJECTIVE: THIS ARTICLE DEVELOPS A PHILOSOPHICAL-SCIENTIFIC CORRELATION BETWEEN CHRONIC MIASMS AND DISEASE-PROMOTING EPIGENETIC MODIFICATIONS, AIMING TO JUSTIFY THE ISOPATHIC USE OF AUTO-SARCODE OF AN INDIVIDUAL'S DNA AS HOMEOPATHIC MEDICINE. RESULTS: BASED ON THE STUDY OF HOMEOPATHIC DOCTRINE AND EPIGENETICS, A CONCEPTUAL AND FUNCTIONAL CORRELATION IS OBSERVED BETWEEN HOMEOPATHIC CHRONIC MIASMS AND DISEASE-PROMOTING EPIGENETIC MODIFICATIONS. ADDITIONALLY, SEVERAL EXPERIMENTAL STUDIES SUGGEST THAT HOMEOPATHY'S MECHANISM OF ACTION MAY BE BY MODULATING GENE EXPRESSION. CONCLUSIONS: BY THE PHILOSOPHICAL-SCIENTIFIC CORRELATIONS DESCRIBED, IT IS INFERRED THAT DISEASE-PROMOTING EPIGENETIC ALTERATIONS ARE THE BIOLOGICAL REPRESENTATION OF THE CHRONIC MIASMS, SUGGESTING THE ISOPATHIC USE OF AUTO-SARCODE OF DNA AS HOMEOPATHIC THERAPEUTIC MODULATOR OF GENE EXPRESSION FOR THE MANAGEMENT OF CHRONIC DISEASES. 2019 6 608 17 BEYOND HOMEOSTASIS: UNDERSTANDING THE IMPACT OF PSYCHOSOCIAL FACTORS ON APPETITE USING NONHUMAN PRIMATE MODELS. ANIMAL MODELS HAVE PROVEN TO BE EXCEPTIONALLY INFORMATIVE IN DEFINING NEUROPEPTIDE REGULATION OF APPETITE AND ENERGY HOMEOSTASIS (GAO AND HORVATH 2007, BERTHOUD 2012, WILLIAMS AND ELMQUIST 2012). MORE RECENT STUDIES USING A RANGE OF ANIMAL MODELS AND MOLECULAR TOOLS ARE ELUCIDATING HOW EPIGENETIC CHANGES RESULTING FROM SPECIFIC PRENATAL AND POSTNATAL DIETARY ENVIRONMENTS OR EXPERIENCES AFFECT METABOLIC PROCESSES AND APPETITE REGULATION (LEVIN 2008, ZAMBRANO AND NATHANIELSZ 2013, BURDGE AND LILLYCROP 2014). TAKEN TOGETHER, THESE APPROACHES ARE HELPING TO DEFINE POSSIBLE TREATMENT INTERVENTIONS FOR EATING DISORDERS IN PEOPLE (CASPER, SULLIVAN, AND TECOTT 2008, FOLTIN 2012, VAN GESTEL ET AL. 2014, LUTTER, CROGHAN, AND CUI 2016). THE CHOICE OF ANIMAL USED IS BEST DICTATED BY THE QUESTION BEING ADDRESSED. BECAUSE OF SIMILARITIES IN PHYSIOLOGY AND NEUROBIOLOGY, STUDIES OF CAPTIVE NONHUMAN PRIMATES HAVE BEGUN TO CONTRIBUTE SIGNIFICANTLY TO OUR UNDERSTANDING OF APPETITE REGULATION (SEE WILSON ET AL. 2014 FOR A REVIEW). IMPORTANTLY, THE USE OF NONHUMAN PRIMATE MODELS PROVIDES THE UNIQUE OPPORTUNITY TO EXTEND ANALYSES BEYOND A FOCUS ON THE HOMEOSTATIC REGULATION OF APPETITE. THIS IS PARTICULARLY RELEVANT GIVEN THE WELL-ESTABLISHED NOTION THAT A NUMBER OF PSYCHOSOCIAL FACTORS INFLUENCE FOOD INTAKE IN PEOPLE (BRUCE AND RICCIARDELLI 2015), INCLUDING CHRONIC STRESSOR EXPOSURE (TSENKOVA, BOYLAN, AND RYFF 2013), EVEN IN CHILDREN (NGUYEN-RODRIGUEZ, UNGER, AND SPRUIJT-METZ 2009). WHILE THE IMPORTANCE OF PSYCHOSOCIAL FACTORS CAN BE MODELED IN NONPRIMATE ANIMALS (TAMASHIRO, HEGEMAN, AND SAKAI 2006), SOCIALLY HOUSED NONHUMAN PRIMATES SHARE MANY CHARACTERISTICS IN ADDITION TO PHYSIOLOGY AND NEUROBIOLOGY, WITH HUMANS INCREASING THE TRANSLATIONAL VALUE OF THESE PRE-CLINICAL STUDIES. 2017 7 582 20 BEHAVIORAL AND PHYSIOLOGICAL EFFECTS OF ACUTE AND CHRONIC KAVA EXPOSURE IN ADULT ZEBRAFISH. KAVA KAVA (PIPER METHYSTICUM) IS A MEDICINAL PLANT CONTAINING KAVALACTONES THAT EXERT POTENT SEDATIVE, ANALGESIC AND ANTI-STRESS ACTION. HOWEVER, THEIR PHARMACOLOGICAL EFFECTS AND MOLECULAR TARGETS REMAIN POORLY UNDERSTOOD. THE ZEBRAFISH (DANIO RERIO) HAS RECENTLY EMERGED AS A POWERFUL NEW MODEL ORGANISM FOR NEUROSCIENCE RESEARCH AND DRUG DISCOVERY. HERE, WE EVALUATE THE EFFECTS OF ACUTE AND CHRONIC EXPOSURE TO KAVA AND KAVALACTONES ON ADULT ZEBRAFISH ANXIETY, AGGRESSION AND SOCIALITY, AS WELL AS ON THEIR NEUROCHEMICAL, NEUROENDOCRINE AND GENOMIC RESPONSES. SUPPORTING EVOLUTIONARILY CONSERVED MOLECULAR TARGETS, ACUTE KAVA AND KAVALACTONES EVOKED DOSE-DEPENDENT BEHAVIORAL INHIBITION, UPREGULATED BRAIN EXPRESSION OF EARLY PROTOONCOGENES C-FOS AND C-JUN, ELEVATED BRAIN MONOAMINES AND LOWERED WHOLE-BODY CORTISOL. CHRONIC 7-DAY KAVA EXPOSURE EVOKED SIMILAR BEHAVIORAL EFFECTS, DID NOT ALTER CORTISOL LEVELS, AND FAILED TO EVOKE WITHDRAWAL-LIKE STATES UPON DISCONTINUATION. HOWEVER, CHRONIC KAVA UPREGULATED SEVERAL MICROGLIAL (INOS, EGR-2, CD11B), ASTROCYTAL (C3, C4B, S100A), EPIGENETIC (NCOA-1) AND PRO-INFLAMMATORY (IL-1BETA, IL-6, TNFA) BIOMARKER GENES, DOWNREGULATED CD206 AND IL-4, AND DID NOT AFFECT MAJOR APOPTOTIC GENES IN THE BRAIN. COLLECTIVELY, THIS STUDY SUPPORTS ROBUST, EVOLUTIONARILY CONSERVED BEHAVIORAL AND PHYSIOLOGICAL EFFECTS OF KAVA AND KAVALACTONES IN ZEBRAFISH, IMPLICATES BRAIN MONOAMINES IN THEIR ACUTE EFFECTS, AND PROVIDES NOVEL IMPORTANT INSIGHTS INTO POTENTIAL ROLE OF NEUROGLIAL AND EPIGENETIC MECHANISMS IN LONG-TERM KAVA USE. 2020 8 2649 13 EPIGENOMIC, GENOMIC, AND TRANSCRIPTOMIC LANDSCAPE OF SCHWANNOMATOSIS. SCHWANNOMATOSIS (SWNTS) IS A GENETIC CANCER PREDISPOSITION SYNDROME THAT MANIFESTS AS MULTIPLE AND OFTEN PAINFUL NEURONAL TUMORS CALLED SCHWANNOMAS (SWNS). WHILE GERMLINE MUTATIONS IN SMARCB1 OR LZTR1, PLUS SOMATIC MUTATIONS IN NF2 AND LOSS OF HETEROZYGOSITY IN CHROMOSOME 22Q HAVE BEEN IDENTIFIED IN A SUBSET OF PATIENTS, LITTLE IS KNOWN ABOUT THE EPIGENOMIC AND GENOMIC ALTERATIONS THAT DRIVE SWNTS-RELATED SWNS (SWNTS-SWNS) IN A MAJORITY OF THE CASES. WE PERFORMED MULTIPLATFORM GENOMIC ANALYSIS AND ESTABLISHED THE MOLECULAR SIGNATURE OF SWNTS-SWNS. WE SHOW THAT SWNTS-SWNS HARBOR DISTINCT GENOMIC FEATURES RELATIVE TO THE HISTOLOGICALLY IDENTICAL NON-SYNDROMIC SPORADIC SWNS (NS-SWNS). WE DEMONSTRATE THE EXISTENCE OF FOUR DISTINCT DNA METHYLATION SUBGROUPS OF SWNTS-SWNS THAT ARE ASSOCIATED WITH SPECIFIC TRANSCRIPTIONAL PROGRAMS AND TUMOR LOCATION. WE SHOW SEVERAL NOVEL RECURRENT NON-22Q DELETIONS AND STRUCTURAL REARRANGEMENTS. WE DETECTED THE SH3PXD2A-HTRA1 GENE FUSION IN SWNTS-SWNS, WITH PREDOMINANCE IN LZTR1-MUTANT TUMORS. IN ADDITION, WE IDENTIFIED SPECIFIC GENETIC, EPIGENETIC, AND ACTIONABLE TRANSCRIPTIONAL PROGRAMS ASSOCIATED WITH PAINFUL SWNTS-SWNS INCLUDING PIGF, VEGF, MEK, AND MTOR PATHWAYS, WHICH MAY BE HARNESSED FOR MANAGEMENT OF THIS SYNDROME. 2021 9 3598 14 IMPLICATIONS ON HYPNOTHERAPY: NEUROPLASTICITY, EPIGENETICS AND PAIN. WE PROVIDE A BRIEF REVIEW ABOUT THE SIGNIFICANCE OF HYPNOSIS WITH RESPECT TO APPLICATIONS AND PHYSIOLOGICAL PROCESSES IN HYPNOTHERAPY. OUR REVIEW CONCLUDES THAT HYPNOSIS IS A PROMISING METHOD TO MANAGE ACUTE AND CHRONIC PAIN. IN ADDITION, WE DISCUSS INDICATIONS POINTING TOWARD THE VIEW THAT HYPNOSIS CAN INDUCE CHANGES IN NEUROPLASTICITY POSSIBLY INVOLVING EPIGENETIC MECHANISMS. 2021 10 1679 21 DRUG RESISTANCE IN GIARDIA DUODENALIS. GIARDIA DUODENALIS IS A MICROAEROPHILIC PARASITE OF THE HUMAN GASTROINTESTINAL TRACT AND A MAJOR CONTRIBUTOR TO DIARRHEAL AND POST-INFECTIOUS CHRONIC GASTROINTESTINAL DISEASE WORLD-WIDE. TREATMENT OF G. DUODENALIS INFECTION CURRENTLY RELIES ON A SMALL NUMBER OF DRUG CLASSES. NITROHETEROCYCLICS, IN PARTICULAR METRONIDAZOLE, HAVE REPRESENTED THE FRONT LINE TREATMENT FOR THE LAST 40 YEARS. NITROHETEROCYCLIC-RESISTANT G. DUODENALIS HAVE BEEN ISOLATED FROM PATIENTS AND CREATED IN VITRO, PROMPTING CONSIDERABLE RESEARCH INTO THE BIOMOLECULAR MECHANISMS OF RESISTANCE. THESE COMPOUNDS ARE REDOX-ACTIVE AND ARE BELIEVED TO DAMAGE PROTEINS AND DNA AFTER BEING ACTIVATED BY OXIDOREDUCTASE ENZYMES IN METABOLICALLY ACTIVE CELLS. IN THIS REVIEW, WE EXPLORE THE MOLECULAR PHENOTYPES OF NITROHETEROCYCLIC-RESISTANT G. DUODENALIS DESCRIBED TO DATE IN THE CONTEXT OF THE PROTIST'S UNUSUAL GLYCOLYTIC AND ANTIOXIDANT SYSTEMS. WE PROPOSE THAT RESISTANCE MECHANISMS ARE LIKELY TO EXTEND WELL BEYOND CURRENTLY DESCRIBED RESISTANCE-ASSOCIATED ENZYMES (I.E., PYRUVATE FERREDOXIN OXIDOREDUCTASES AND NITROREDUCTASES), TO INCLUDE NAD(P)H- AND FLAVIN-GENERATING PATHWAYS, AND POSSIBLY REDOX-SENSITIVE EPIGENETIC REGULATION. MECHANISMS THAT ALLOW G. DUODENALIS TO TOLERATE OXIDATIVE STRESS MAY LEAD TO RESISTANCE AGAINST BOTH OXYGEN AND NITROHETEROCYCLICS, WITH IMPLICATIONS FOR CLINICAL CONTROL. THE PRESENT REVIEW HIGHLIGHTS THE POTENTIAL FOR SYSTEMS BIOLOGY TOOLS AND ADVANCED BIOINFORMATICS TO FURTHER INVESTIGATE THE MULTIFACETED MECHANISMS OF NITROHETEROCYCLIC RESISTANCE IN THIS IMPORTANT PATHOGEN. 2015 11 967 14 CHRONIC NICOTINE EXPOSURE AUGMENTS RENAL OXIDATIVE STRESS AND INJURY THROUGH TRANSCRIPTIONAL ACTIVATION OF P66SHC. BACKGROUND: CHRONIC NICOTINE (CH-NIC) EXPOSURE EXACERBATES ISCHEMIA/REPERFUSION (I/R)-INDUCED OXIDATIVE STRESS AND ACUTE KIDNEY INJURY (AKI), AND MITOCHONDRIAL PRODUCTION OF REACTIVE OXYGEN SPECIES (ROS) IN CULTURED RENAL PROXIMAL TUBULE CELLS (RPTCS). BECAUSE SER36-PHOSPHORYLATED P66SHC MODULATES MITOCHONDRIAL ROS PRODUCTION AND INJURY OF RPTCS, WE HYPOTHESIZED THAT CH-NIC EXACERBATES AKI BY INCREASING STRESS-INDUCED PHOSPHORYLATION OF P66SHC. METHODS: WE FIRST TESTED WHETHER CH-NIC AUGMENTS I/R-AKI-INDUCED EXPRESSION AND PHOSPHORYLATION OF P66SHC IN VIVO. WE THEN EXAMINED WHETHER KNOCKING DOWN P66SHC, OR IMPAIRING ITS SER36 PHOSPHORYLATION OR BINDING TO CYTOCHROME C, ALTERS THE EFFECTS OF CH-NIC ON OXIDATIVE STRESS (H(2)O(2))-INDUCED PRODUCTION OF ROS, MITOCHONDRIAL DEPOLARIZATION AND INJURY IN RPTCS IN VITRO. RESULTS: WE FOUND THAT CH-NIC INCREASED THE EXPRESSION OF P66SHC IN THE CONTROL AND ISCHEMIC KIDNEYS, BUT ONLY INCREASED ITS SER36 PHOSPHORYLATION AFTER RENAL I/R. KNOCKING DOWN P66SHC OR IMPAIRING PHOSPHORYLATION OF ITS SER36 RESIDUE, VIA THE S36A MUTATION (BUT NOT THE PHOSPHOMIMETIC S36D MUTATION), BLUNTED CH-NIC + H2O2-DEPENDENT ROS PRODUCTION, MITOCHONDRIAL DEPOLARIZATION AND INJURY IN RPTCS. ADDITIONALLY, CH-NIC + H2O2-DEPENDENT BINDING OF P66SHC TO MITOCHONDRIAL CYTOCHROME C WAS ATTENUATED BY S36A MUTATION OF P66SHC, AND IMPAIRING CYTOCHROME C BINDING (VIA W134F MUTATION) ABOLISHED ROS PRODUCTION, MITOCHONDRIAL DEPOLARIZATION AND INJURY, WHILE ECTOPIC OVEREXPRESSION OF P66SHC (WHICH MIMICS CH-NIC TREATMENT) AUGMENTED OXIDANT INJURY. WE DETERMINED THAT CH-NIC STIMULATES THE P66SHC PROMOTER THROUGH P53- AND EPIGENETIC MODIFICATION (PROMOTER HYPOMETHYLATION). CONCLUSIONS: CH-NIC WORSENS OXIDATIVE STRESS-DEPENDENT ACUTE RENAL INJURY BY INCREASING EXPRESSION AND CONSEQUENT OXIDATIVE STRESS-DEPENDENT SER36 PHOSPHORYLATION OF P66SHC. THUS, TARGETING THIS PATHWAY MAY HAVE THERAPEUTIC RELEVANCE IN PREVENTING/AMELIORATING TOBACCO-RELATED KIDNEY INJURY. 2013 12 2819 18 FILARIAL AND WOLBACHIA GENOMICS. FILARIAL NEMATODE PARASITES, THE CAUSATIVE AGENTS FOR A SPECTRUM OF ACUTE AND CHRONIC DISEASES INCLUDING LYMPHATIC FILARIASIS AND RIVER BLINDNESS, THREATEN THE WELL-BEING AND LIVELIHOOD OF HUNDREDS OF MILLIONS OF PEOPLE IN THE DEVELOPING REGIONS OF THE WORLD. THE 2007 PUBLICATION ON A DRAFT ASSEMBLY OF THE 95-MB GENOME OF THE HUMAN FILARIAL PARASITE BRUGIA MALAYI- REPRESENTING THE FIRST HELMINTH PARASITE GENOME TO BE SEQUENCED - HAS BEEN FOLLOWED IN RAPID SUCCESSION BY PROJECTS THAT HAVE RESULTED IN THE GENOME SEQUENCING OF SIX ADDITIONAL FILARIAL SPECIES, SEVEN NONFILARIAL NEMATODE PARASITES OF ANIMALS AND NEARLY 30 PLANT PARASITIC AND FREE-LIVING SPECIES. PARALLEL TO THE GENOMIC SEQUENCING, TRANSCRIPTOMIC AND PROTEOMIC PROJECTS HAVE FACILITATED GENOME ANNOTATION, EXPANDED OUR UNDERSTANDING OF STAGE-ASSOCIATED GENE EXPRESSION AND PROVIDED A FIRST LOOK AT THE ROLE OF EPIGENETIC REGULATION OF FILARIAL GENOMES THROUGH MICRORNAS. THE EXPANSION IN FILARIAL GENOMICS WILL ALSO PROVIDE A SIGNIFICANT ENRICHMENT IN OUR KNOWLEDGE OF THE DIVERSITY AND VARIABILITY IN THE GENOMES OF THE ENDOSYMBIOTIC BACTERIUM WOLBACHIA LEADING TO A BETTER UNDERSTANDING OF THE GENETIC PRINCIPLES THAT GOVERN FILARIAL-WOLBACHIA MUTUALISM. THE GOAL HERE IS TO PROVIDE AN OVERVIEW OF THE TRENDS AND ADVANCES IN FILARIAL AND WOLBACHIA GENOMICS. 2012 13 5763 16 SOME COMMENTS ON MASOCHISM AND THE DELUSION OF OMNIPOTENCE FROM A DEVELOPMENTAL PERSPECTIVE. THIS PAPER EXPLORES THE RELATION OF THE DELUSION OF OMNIPOTENCE TO MASOCHISM AND SUGGESTS THAT THIS FANTASY CONSTITUTES A MAJOR COMPONENT OF THE RESISTANCE SO PROMINENT IN WORK WITH MASOCHISTIC PATIENTS. THE CONNECTIONS AMONG MASOCHISM, OMNIPOTENCE, NEGATIVE THERAPEUTIC REACTION, AND CLINGING TO PAIN ARE DISCUSSED. THE CLASSICAL VIEW HAS BEEN THAT THE FAILURE OF INFANTILE OMNIPOTENCE FORCES THE CHILD TO TURN TO REALITY. OUR EXPERIENCE WITH MASOCHISTIC PATIENTS SUGGESTS THAT IT IS THE REAL FAILURE TO ACHIEVE COMPETENT INTERACTIONS WITH OTHERS THAT FORCES THE CHILD TO TURN TO OMNIPOTENT SOLUTIONS. THE DISTINCTION IS MADE BETWEEN FANTASIES THAT ENHANCE THE REAL CAPACITIES OF THE SELF AND THOSE AIMED AT DENYING AND TRANSFORMING THE PAIN AND INADEQUACY OF THE MOTHER-CHILD RELATIONSHIP. THE EPIGENETIC TRANSFORMATIONS OF OMNIPOTENT FANTASIES THROUGH ALL LEVELS OF DEVELOPMENT ARE DESCRIBED. THE PATIENT'S NEED TO PROTECT THE OMNIPOTENT FANTASY IS DISCUSSED IN RELATION TO RESISTANCE AT EACH PHASE OF ANALYSIS. 1991 14 3570 15 IMPACT OF JUVENILE HORMONE ANALOGUE INSECTICIDES ON THE WATER FLEA MOINA MACROCOPA: GROWTH, REPRODUCTION AND TRANSGENERATIONAL EFFECT. THE INCREASING QUANTITIES OF INSECTICIDES THAT LEACH INTO WATER BODIES SEVERELY AFFECT THE HEALTH OF THE AQUATIC ENVIRONMENT. JUVENILE HORMONE ANALOGUE (JHA) INSECTICIDES ARE ENDOCRINE DISRUPTERS THAT INTERFERE WITH HORMONAL ACTIVITY IN INSECTS BY MIMICKING JUVENILE HORMONES (JHS). BECAUSE THE STRUCTURE AND FUNCTIONS OF METHYL FARNESOATE IN CRUSTACEANS ARE SIMILAR TO THE INSECT JHS, EXOGENOUS JHA INSECTICIDES MAY CAUSE ADVERSE EFFECTS ON THE GROWTH AND REPRODUCTION IN CRUSTACEANS SIMILAR TO THOSE OBSERVED IN INSECTS. THIS STUDY EXAMINED THE TOXIC EFFECTS OF TWO JHA INSECTICIDES, METHOPRENE AND FENOXYCARB, ON THE WATER FLEA MOINA MACROCOPA. THE 24-H AND 48-H LC(50) VALUES FOR FENOXYCARB AND METHOPRENE WERE 0.53 AND 0.32 MG/L AND 0.70 AND 0.54 MG/L, RESPECTIVELY. CHRONIC EXPOSURE TO THE TWO JHAS CAUSED A SERIES OF TOXIC EFFECTS IN M. MACROCOPA, INCLUDING SHORTENING OF LIFE EXPECTANCY, REPRESSION OF BODY GROWTH, REDUCTION IN FECUNDITY, AND DISTURBED THE EXPRESSION OF GENES INVOLVED IN THE JH SIGNALING PATHWAY, IN CUTICLE DEVELOPMENT, AND IN THE CARBOHYDRATE, AMINO ACID, AND ATP METABOLIC PROCESSES. MOREOVER, JHA EXPOSURE IMPAIRED THE GROWTH AND REPRODUCTION OF THE OFFSPRING OF M. MACROCOPA EXPOSED TO JHAS, EVEN WHEN THE NEONATES WERE NOT EXPOSED TO THE CHEMICALS. IN ADDITION, CHANGES IN THE EXPRESSION OF GENES RELATED TO HISTONE METHYLATION INDICATE THAT EPIGENETIC CHANGES MAY PROMOTE TRANSGENERATIONAL IMPAIRMENT IN M. MACROCOPA. THESE RESULTS DEMONSTRATE THE TOXIC EFFECTS OF FENOXYCARB AND METHOPRENE ON NON-TARGET AQUATIC ORGANISMS. THE DAMAGES DONE BY THESE JHA INSECTICIDES TO THE AQUATIC ENVIRONMENT IS WORTHY OF OUR ATTENTION AND FURTHER STUDIES. 2020 15 35 18 A CHROMATIN ACTIVITY-BASED CHEMOPROTEOMIC APPROACH REVEALS A TRANSCRIPTIONAL REPRESSOME FOR GENE-SPECIFIC SILENCING. IMMUNE CELLS DEVELOP ENDOTOXIN TOLERANCE (ET) AFTER PROLONGED STIMULATION. ET INCREASES THE LEVEL OF A REPRESSION MARK H3K9ME2 IN THE TRANSCRIPTIONALLY SILENT CHROMATIN SPECIFICALLY ASSOCIATED WITH PRO-INFLAMMATORY GENES. HOWEVER, IT IS NOT CLEAR WHAT PROTEINS ARE FUNCTIONALLY INVOLVED IN THIS PROCESS. HERE WE SHOW THAT A NOVEL CHROMATIN ACTIVITY-BASED CHEMOPROTEOMIC (CHAC) APPROACH CAN DISSECT THE FUNCTIONAL CHROMATIN PROTEIN COMPLEXES THAT REGULATE ET-ASSOCIATED INFLAMMATION. USING UNC0638 THAT BINDS THE ENZYMATICALLY ACTIVE H3K9-SPECIFIC METHYLTRANSFERASE G9A/GLP, CHAC REVEALS THAT G9A IS CONSTITUTIVELY ACTIVE AT A G9A-DEPENDENT MEGA-DALTON REPRESSOME IN PRIMARY ENDOTOXIN-TOLERANT MACROPHAGES. G9A/GLP BROADLY IMPACTS THE ET-SPECIFIC REPROGRAMMING OF THE HISTONE CODE LANDSCAPE, CHROMATIN REMODELLING AND THE ACTIVITIES OF SELECT TRANSCRIPTION FACTORS. WE DISCOVER THAT THE G9A-DEPENDENT EPIGENETIC ENVIRONMENT PROMOTES THE TRANSCRIPTIONAL REPRESSION ACTIVITY OF C-MYC FOR GENE-SPECIFIC CO-REGULATION OF CHRONIC INFLAMMATION. CHAC MAY ALSO BE APPLICABLE TO DISSECT OTHER FUNCTIONAL PROTEIN COMPLEXES IN THE CONTEXT OF PHENOTYPIC CHROMATIN ARCHITECTURES. 2014 16 3157 16 GLYCEMIC MEMORY. PURPOSE OF REVIEW: THE MISTAKE OF PREDICTING THE FUTURE IS PERHAPS NOT TENDING TO REPRESSED OR PAST MEMORIES. HAMLET'S 17TH-CENTURY SOLILOQUY 'THE HEARTACHE AND THE THOUSAND NATURAL SHOCKS, THAT FLESH IS HEIR TO', (3.1. 7-8) IS A TALE THAT LOOKS BEYOND THE PRESENT BY LINKING THE PAST WITH THE FUTURE. THE PRESENT ARTICLE EXAMINES THE RESURGENCE IN THE FIELD TO UNDERSTAND GENE-REGULATING EPIGENETIC CHANGES CONFERRING GLYCEMIC MEMORY. RECENT FINDINGS: CHROMATIN MODIFICATIONS ARE CRITICAL IN REGULATING GENOME STRUCTURE AND FUNCTION AND DESPITE THE SIGNIFICANT ADVANCES OF RECENT YEARS IN IDENTIFYING THE ENZYMES-MEDIATING CHEMICAL CHANGES TO HISTONE TAILS AND THE DNA TEMPLATE, THE PRECISE REGULATION OF GENE EXPRESSION REMAINS INCOMPLETE IN MODELS OF HEALTH AND DIABETIC COMPLICATIONS. SUMMARY: DISPELLING THE MYTH THAT ALL GENOMES ARE DRIVEN AND RESPOND EQUALLY, EXPERIMENTAL RESEARCH IS NOW UNCOVERING THE FUNCTION OF ENZYMES CONFERRING CHROMATIN MODIFICATIONS. WHATEVER THE ROLE OF THE EPIGENOME, SHOWING ITS INVOLVEMENT IN GLYCEMIC SIGNALING IS THE FIRST STEP TO NEW STRATEGIES AND TARGETS TO DEVELOP THERAPIES THAT PREVENT, RETARD OR REVERSE THE LONG-TERM DELETERIOUS END-ORGAN EFFECTS OF CHRONIC, INTERMITTENT AND PRIOR HYPERGLYCEMIA. 2012 17 4669 20 NEW INSIGHTS INTO PATHOPHYSIOLOGY OF VESTIBULAR MIGRAINE. VESTIBULAR MIGRAINE (VM) IS A COMMON DISORDER IN WHICH GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS PROBABLY CONTRIBUTE TO ITS DEVELOPMENT. THE PATHOPHYSIOLOGY OF VM IS UNKNOWN; NEVERTHELESS IN THE LAST FEW YEARS, SEVERAL STUDIES ARE CONTRIBUTING TO UNDERSTAND THE NEUROPHYSIOLOGICAL PATHWAYS INVOLVED IN VM. THE CURRENT HYPOTHESES ARE MOSTLY BASED ON THE KNOWLEDGE OF MIGRAINE ITSELF. THE EVIDENCE OF TRIGEMINAL INNERVATION OF THE LABYRINTH VESSELS AND THE LOCALIZATION OF VASOACTIVE NEUROPEPTIDES IN THE PERIVASCULAR AFFERENT TERMINALS OF THESE TRIGEMINAL FIBERS SUPPORT THE INVOLVEMENT OF THE TRIGEMINO-VASCULAR SYSTEM. THE NEUROGENIC INFLAMMATION TRIGGERED BY ACTIVATION OF THE TRIGEMINAL-VESTIBULOCOCHLEAR REFLEX, WITH THE SUBSEQUENT INNER EAR PLASMA PROTEIN EXTRAVASATION AND THE RELEASE OF INFLAMMATORY MEDIATORS, CAN CONTRIBUTE TO A SUSTAINED ACTIVATION AND SENSITIZATION OF THE TRIGEMINAL PRIMARY AFFERENT NEURONS EXPLAINING VM SYMPTOMS. THE RECIPROCAL CONNECTIONS BETWEEN BRAINSTEM VESTIBULAR NUCLEI AND THE STRUCTURES THAT MODULATE TRIGEMINAL NOCICEPTIVE INPUTS (ROSTRAL VENTROMEDIAL MEDULLA, VENTROLATERAL PERIAQUEDUCTAL GRAY, LOCUS COERULEUS, AND NUCLEUS RAPHE MAGNUS) ARE CRITICAL TO UNDERSTAND THE PATHOPHYSIOLOGY OF VM. ALTHOUGH CORTICAL SPREADING DEPRESSION CAN AFFECT CORTICAL AREAS INVOLVED IN PROCESSING VESTIBULAR INFORMATION, FUNCTIONAL NEUROIMAGING TECHNIQUES SUGGEST A DYSMODULATION IN THE MULTIMODAL SENSORY INTEGRATION AND PROCESSING OF VESTIBULAR AND NOCICEPTIVE INFORMATION, RESULTING FROM A VESTIBULO-THALAMO-CORTICAL DYSFUNCTION, AS THE PATHOGENIC MECHANISM UNDERLYING VM. THE ELEVATED PREVALENCE OF VM SUGGESTS THAT MULTIPLE FUNCTIONAL VARIANTS MAY CONFER A GENETIC SUSCEPTIBILITY LEADING TO A DYSREGULATION OF EXCITATORY-INHIBITORY BALANCE IN BRAIN STRUCTURES INVOLVED IN THE PROCESSING OF SENSORY INFORMATION, VESTIBULAR INPUTS, AND PAIN. THE INTERACTIONS AMONG SEVERAL FUNCTIONAL AND STRUCTURAL NEURAL NETWORKS COULD EXPLAIN THE PATHOGENIC MECHANISMS OF VM. 2015 18 5340 18 QUORUM SENSING AND VIRULENCE OF PSEUDOMONAS AERUGINOSA DURING LUNG INFECTION OF CYSTIC FIBROSIS PATIENTS. PSEUDOMONAS AERUGINOSA IS THE PREDOMINANT MICROORGANISM IN CHRONIC LUNG INFECTION OF CYSTIC FIBROSIS PATIENTS. THE CHRONIC LUNG INFECTION IS PRECEDED BY INTERMITTENT COLONIZATION. WHEN THE CHRONIC INFECTION BECOMES ESTABLISHED, IT IS WELL ACCEPTED THAT THE ISOLATED STRAINS DIFFER PHENOTYPICALLY FROM THE INTERMITTENT STRAINS. DOMINATING CHANGES ARE THE SWITCH TO MUCOIDITY (ALGINATE OVERPRODUCTION) AND LOSS OF EPIGENETIC REGULATION OF VIRULENCE SUCH AS THE QUORUM SENSING (QS). TO ELUCIDATE THE DYNAMICS OF P. AERUGINOSA QS SYSTEMS DURING LONG TERM INFECTION OF THE CF LUNG, WE HAVE INVESTIGATED 238 ISOLATES OBTAINED FROM 152 CF PATIENTS AT DIFFERENT STAGES OF INFECTION RANGING FROM INTERMITTENT TO LATE CHRONIC. ISOLATES WERE CHARACTERIZED WITH REGARD TO QS SIGNAL MOLECULES, ALGINATE, RHAMNOLIPID AND ELASTASE PRODUCTION AND MUTANT FREQUENCY. THE GENETIC BASIS FOR CHANGE IN QS REGULATION WERE INVESTIGATED AND IDENTIFIED BY SEQUENCE ANALYSIS OF LASR, RHLR, LASI AND RHLI. THE FIRST QS SYSTEM TO BE LOST WAS THE ONE ENCODED BY LAS SYSTEM 12 YEARS (MEDIAN VALUE) AFTER THE ONSET OF THE LUNG INFECTION WITH SUBSEQUENT LOSS OF THE RHL ENCODED SYSTEM AFTER 17 YEARS (MEDIAN VALUE) SHOWN AS DEFICIENCIES IN PRODUCTION OF THE 3-OXO-C12-HSL AND C4-HSL QS SIGNAL MOLECULES RESPECTIVELY. THE CONCOMITANT DEVELOPMENT OF QS MALFUNCTION SIGNIFICANTLY CORRELATED WITH THE REDUCED PRODUCTION OF RHAMNOLIPIDS AND ELASTASE AND WITH THE OCCURRENCE OF MUTATIONS IN THE REGULATORY GENES LASR AND RHLR. ACCUMULATION OF MUTATIONS IN BOTH LASR AND RHLR CORRELATED WITH DEVELOPMENT OF HYPERMUTABILITY. INTERESTINGLY, A HIGHER NUMBER OF MUCOID ISOLATES WERE FOUND TO PRODUCE C4-HSL SIGNAL MOLECULES AND RHAMNOLIPIDS COMPARED TO THE NON-MUCOID ISOLATES. AS SEEN FROM THE PRESENT DATA, WE CAN CONCLUDE THAT P. AERUGINOSA AND PARTICULARLY THE MUCOID STRAINS DO NOT LOSE THE QS REGULATION OR THE ABILITY TO PRODUCE RHAMNOLIPIDS UNTIL THE LATE STAGE OF THE CHRONIC INFECTION. 2010 19 2596 24 EPIGENETICS OF STRESS ADAPTATIONS IN THE BRAIN. RECENT FINDINGS IN EPIGENETICS SHED NEW LIGHT ON THE REGULATION OF GENE EXPRESSION IN THE CENTRAL NERVOUS SYSTEM (CNS) DURING STRESS. THE MOST FREQUENTLY STUDIED EPIGENETIC MECHANISMS ARE DNA METHYLATION, HISTONE MODIFICATIONS AND MICRORNA ACTIVITY. THESE MECHANISMS STABLY DETERMINE CELL PHENOTYPE BUT CAN ALSO BE RESPONSIBLE FOR DYNAMIC MOLECULAR ADAPTATIONS OF THE CNS TO STRESSORS. THE LIMBIC-HYPOTHALAMIC-PITUITARY-ADRENAL AXIS (LHPA) IS THE PRIMARY CIRCUIT THAT INITIATES, REGULATES AND TERMINATES A STRESS RESPONSE. THE SAME BRAIN AREAS THAT CONTROL STRESS ALSO REACT TO STRESS DYNAMICALLY AND WITH LONG-TERM CONSEQUENCES. ONE OF THE BIOLOGICAL PROCESSES EVOKING POTENT ADAPTIVE CHANGES IN THE CNS SUCH AS CHANGES IN BEHAVIOR, GENE ACTIVITY OR SYNAPTIC PLASTICITY IN THE HIPPOCAMPUS IS PSYCHOGENIC STRESS. THIS REVIEW SUMMARIZES THE CURRENT DATA REGARDING THE EPIGENETIC BASIS OF MOLECULAR ADAPTATIONS IN THE BRAIN INCLUDING GENOME-WIDE EPIGENETIC CHANGES OF DNA METHYLATION AND PARTICULAR GENES INVOLVED IN EPIGENETIC RESPONSES THAT PARTICIPATE IN THE BRAIN RESPONSE TO CHRONIC PSYCHOGENIC STRESSORS. IT IS CONCLUDED THAT SPECIFIC EPIGENETIC MECHANISMS IN THE CNS ARE INVOLVED IN THE STRESS RESPONSE. 2013 20 4048 18 MAINTENANCE AND PHARMACOLOGIC TARGETING OF ROR1 PROTEIN LEVELS VIA UHRF1 IN T(1;19) PRE-B-ALL. EXPRESSION OF THE TRANSMEMBRANE PSEUDOKINASE ROR1 IS REQUIRED FOR SURVIVAL OF T(1;19)-PRE-B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T(1;19) PRE-B-ALL), CHRONIC LYMPHOCYTIC LEUKEMIA, AND MANY SOLID TUMORS. HOWEVER, TARGETING ROR1 WITH SMALL-MOLECULES HAS BEEN CHALLENGING DUE TO THE ABSENCE OF ROR1 KINASE ACTIVITY. TO IDENTIFY GENES THAT REGULATE ROR1 EXPRESSION AND MAY, THEREFORE, SERVE AS SURROGATE DRUG TARGETS, WE EMPLOYED AN SIRNA SCREENING APPROACH AND DETERMINED THAT THE EPIGENETIC REGULATOR AND E3 UBIQUITIN LIGASE, UHRF1, IS REQUIRED FOR T(1;19) PRE-B-ALL CELL VIABILITY IN A ROR1-DEPENDENT MANNER. UPON UHRF1 SILENCING, ROR1 PROTEIN IS REDUCED WITHOUT ALTERING ROR1 MRNA, AND ECTOPICALLY EXPRESSED UHRF1 IS SUFFICIENT TO INCREASE ROR1 LEVELS. ADDITIONALLY, PROTEASOME INHIBITION RESCUES LOSS OF ROR1 PROTEIN AFTER UHRF1 SILENCING, SUGGESTING A ROLE FOR THE PROTEASOME IN THE UHRF1-ROR1 AXIS. FINALLY, WE SHOW THAT ROR1-POSITIVE CELLS ARE TWICE AS SENSITIVE TO THE UHRF1-TARGETING DRUG, NAPHTHAZARIN, AND UNDERGO INCREASED APOPTOSIS COMPARED TO ROR1-NEGATIVE CELLS. NAPHTHAZARIN ELICITS REDUCED EXPRESSION OF UHRF1 AND ROR1, AND COMBINATION OF NAPHTHAZARIN WITH INHIBITORS OF PRE-B CELL RECEPTOR SIGNALING RESULTS IN FURTHER REDUCTION OF CELL SURVIVAL COMPARED WITH EITHER INHIBITOR ALONE. THEREFORE, OUR WORK REVEALS A MECHANISM BY WHICH UHRF1 STABILIZES ROR1, SUGGESTING A POTENTIAL TARGETING STRATEGY TO INHIBIT ROR1 IN T(1;19) PRE-B-ALL AND OTHER MALIGNANCIES. 2018