19 research outputs found
Housing conditions differentially affect physiological and behavioural stress responses of zebrafish, as well as the response to anxiolytics
PMCID: PMC3324417This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Hemoglobin E Disorders in South Gujarat – A Study Of 35 Cases
Background:Among the inherited disorders of blood, hemoglobinopathies and thalassemia constitute a major bulk of non-communicable genetic disease in India. Most commonly found abnormal hemoglobins in India are hemoglobin S (Hb S), hemoglobin E (Hb E) and hemoglobin D (Hb D). The distribution of Hb E (α2β226Glu< Lys) is mostly restricted to north-eastern India and it is relatively rare in rest of the country. Identification of this disorder is immensely important epidemiologically and aid in prevention of more serious hemoglobin disorder.
Aims:Thepurpose of the study is to highlight importance of identification of Hb E disorders and prevention of doubly heterozygous state for Hb E and β-thalassemia which may be falsely characterized clinically by thalassemia major.
Material and Method:This study is a part of the work done under Sickle Cell Anemia Control Programme, under which samples are tested for various routine as well as specific tests such as dithionite tube turbidity test (DTT Test), hemoglobin electrophoresis and High Performance Liquid Chromatography (HPLC) to diagnose Sickle cell disorders along with other hemoglobinopathies.
Result and Conclusion: Total 70308 cases were analyzed during the period ofJune 2007 to October 2011 out of these 35 cases of Hb E variant were identified. Among these 29 cases of Hb E trait, 1 case of Hb E disease and 5 cases of Hb E β-thalassemia were identified. Hb E trait and Hb E disease were asymptomatic while 5 cases of Hb E β-thalassemia were suffering from haemolytic anemia. Detection of this asymptomatic abnormal hemoglobin will help in the prevention of more serious doubly heterozygous hemoglobinopathy
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD
Jatropha curcas biodiesel production in Kenya: economics and potential value chain development for smallholder farmers.
Temporal Changes in Inflammatory Mitochondria-Enriched MicroRNAs Following Traumatic Brain Injury and Effects of miR-146a Nanoparticle Delivery
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function. We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation (i.e., miR-142-3p, miR-142-5p, and miR-146a) are altered in the hippocampus at 3–12 hours following a severe traumatic brain injury. In the present study, we investigated the temporal expression profile of these inflammatory miRNAs in mitochondria and cytosol fractions at more chronic post-injury times following severe controlled cortical impact injury in rats. In addition, several inflammatory genes were analyzed in the cytosol fractions. The analysis showed that while elevated levels were observed in cytoplasm, the mitochondria-enriched miRNAs, miR-142-3p and miR-142-5p continued to be significantly reduced in mitochondria from injured hippocampi for at least 3 days and returned to near normal levels at 7 days post-injury. Although not statistically significant, miR-146a also remained at reduced levels for up to 3 days following controlled cortical impact injury, and recovered by 7 days. In contrast, miRNAs that are not enriched in mitochondria, including miR-124a, miR-150, miR-19b, miR-155, and miR-223 were either increased or demonstrated no change in their levels in mitochondrial fractions for 7 days. The one exception was that miR-223 levels were reduced in mitochondria at 1 day following injury. No major alterations were observed in sham operated animals. This temporal pattern was unique to mitochondria-enriched miRNAs and correlated with injury-induced changes in mitochondrial bioenergetics as well as expression levels of several inflammatory markers. These observations suggested a potential compartmental re-distribution of the mitochondria-enriched inflammatory miRNAs and may reflect an intracellular mechanism by which specific miRNAs regulate injury-induced inflammatory signaling. To test this, we utilized a novel peptide-based nanoparticle strategy for in vitro and in vivo delivery of a miR-146a mimic as a potential therapeutic strategy for targeting nuclear factor-kappaB inflammatory modulators in the injured brain. Nanoparticle delivery of miR-146a to BV-2 or SH-SY5Y cells significantly reduced expression of TNF receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1), two important modulators of the nuclear factor-kappaB (NF-κB) pro-inflammatory pathway. Moreover, injections of miR-146a containing nanoparticles into the brain immediately following controlled cortical impact injury significantly reduced hippocampal TNF receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1 levels. Taken together, our studies demonstrate the subcellular alteration of inflammatory miRNAs after traumatic brain injury and establish proof of principle that nanoparticle delivery of miR-146a has therapeutic potential for modulating pro-inflammatory effectors in the injured brain. All of the studies performed were approved by the University of Kentucky Institutional Animal Care and Usage Committee (IACUC protocol # 2014-1300) on August 17, 2017
Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing
In addition to its essential functions within the cytoskeleton, actin also localizes to the cell nucleus, where it is linked to many important nuclear processes from gene expression to maintenance of genomic integrity. However, the molecular mechanisms by which actin operates in the nucleus remain poorly understood. Here, we have used two complementary mass spectrometry (MS) techniques, AP-MS and BioID, to identify binding partners for nuclear actin. Common high-confidence interactions highlight the role of actin in chromatin-remodeling complexes and identify the histone-modifying complex human Ada-Two-A-containing (hATAC) as a novel actin-containing nuclear complex. Actin binds directly to the hATAC subunit KAT14, and modulates its histone acetyl transferase activity in vitro and in cells. Transient interactions detected through BioID link actin to several steps of transcription as well as to RNA processing. Alterations in nuclear actin levels disturb alternative splicing in minigene assays, likely by affecting the transcription elongation rate. This interactome analysis thus identifies both novel direct binding partners and functional roles for nuclear actin, as well as forms a platform for further mechanistic studies on how actin operates during essential nuclear processes. This article has an associated First Person interview with the first author of the paper.Peer reviewe
Proapoptotic regimes for HTLV-I-transformed cells: targeting Tax and the NF-κB pathway
[No abstract available]Adams J, 2003, CANCER TREAT REV, V29, P3, DOI 10.1016-S0305-7372(03)00081-1; Arnulf B, 2002, BLOOD, V100, P4129, DOI 10.1182-blood-2001-12-0372; BAEUERLE PA, 1994, ANNU REV IMMUNOL, V12, P141, DOI 10.1146-annurev.immunol.12.1.141; Baldwin AS, 1996, ANNU REV IMMUNOL, V14, P649, DOI 10.1146-annurev.immunol.14.1.649; BALLARD DW, 1988, SCIENCE, V241, P1652, DOI 10.1126-science.2843985; Bangham CRM, 2000, CURR OPIN IMMUNOL, V12, P397, DOI 10.1016-S0952-7915(00)00107-2; Bazarbachi A, 1999, BLOOD, V93, P278; Bazarbachi A, 2001, VIRUS RES, V78, P79, DOI 10.1016-S0168-1702(01)00286-6; Bazarbachi A, 2004, CANCER RES, V64, P2039, DOI 10.1158-0008-5472.CAN-03-2390; Bazarbachi A, 2004, LANCET ONCOL, V5, P664, DOI 10.1016-S1470-2045(04)01608-0; BERAUD C, 1996, J ACQ IMMUN DEF SYND, V13, P76; Bex F, 1998, MOL CELL BIOL, V18, P2392; Bex F, 1997, J VIROL, V71, P3484; BOES B, 1994, J EXP MED, V179, P901, DOI 10.1084-jem.179.3.901; Brauweiler A, 1997, VIROLOGY, V231, P135, DOI 10.1006-viro.1997.8509; Burton M, 2000, J VIROL, V74, P2351, DOI 10.1128-JVI.74.5.2351-2364.2000; Caamano JH, 1996, MOL CELL BIOL, V16, P1342; Cascio P, 2002, EMBO J, V21, P2636, DOI 10.1093-emboj-21.11.2636; Chen GQ, 1996, BLOOD, V88, P1052; Chen ZJ, 1996, CELL, V84, P853, DOI 10.1016-S0092-8674(00)81064-8; Chiari E, 2004, J VIROL, V78, P11823, DOI 10.1128-JVI.78.21.11823-11832.2004; Chu ZL, 1998, J BIOL CHEM, V273, P15891, DOI 10.1074-jbc.273.26.15891; Ciechanover A, 2004, TRENDS CELL BIOL, V14, P103, DOI 10.1016-j.tcb.2004.01.004; Dewan MZ, 2003, J VIROL, V77, P5286, DOI 10.1128-JVI.77.9.5286-5294.2003; El-Sabban ME, 2002, BLOOD, V99, P3383, DOI 10.1182-blood.V99.9.3383; El-Sabban ME, 2000, BLOOD, V96, P2849; Fu DX, 2003, J BIOL CHEM, V278, P1487, DOI 10.1074-jbc.M210631200; Gabet AS, 2003, ONCOGENE, V22, P3734, DOI 10.1038-sj.onc.1206468; GESSAIN A, 1985, LANCET, V2, P407; Gessain A, 1996, ADV VIRUS RES, V47, P377, DOI 10.1016-S0065-3527(08)60740-X; Good LF, 1996, J VIROL, V70, P2730; GRASSMANN R, 1989, P NATL ACAD SCI USA, V86, P3351, DOI 10.1073-pnas.86.9.3351; Harhaj EW, 1998, J BIOL CHEM, V273, P25185, DOI 10.1074-jbc.273.39.25185; Hemelaar J, 2001, J VIROL, V75, P11106, DOI 10.1128-JVI.75.22.11106-11115.2001; HENKEL T, 1992, CELL, V68, P1121, DOI 10.1016-0092-8674(92)90083-O; Hermine O, 2004, HEMATOL J, V5, P130, DOI 10.1038-sj.thj.6200374; Hershko A, 1998, ANNU REV BIOCHEM, V67, P425, DOI 10.1146-annurev.biochem.67.1.425; HINUMA Y, 1982, GAN TO KAGAKU RYOHO, V8, P1313; HIRAI H, 1994, P NATL ACAD SCI USA, V91, P3584, DOI 10.1073-pnas.91.9.3584; HIRAI H, 1992, ONCOGENE, V7, P1737; Huang GJ, 2002, FEBS LETT, V531, P494, DOI 10.1016-S0014-5793(02)03590-1; Ikeda K, 1999, INT J CANCER, V82, P599, DOI 10.1002-(SICI)1097-0215(19990812)82:4599::AID-IJC213.0.CO;2-R; INOUE J, 1992, CELL, V68, P1109, DOI 10.1016-0092-8674(92)90082-N; Jeang KT, 2004, J BIOL CHEM, V279, P31991, DOI 10.1074-jbc.R400009200; JEANG KT, 1990, SCIENCE, V247, P1082, DOI 10.1126-science.2309119; JENTSCH S, 1995, CELL, V82, P881, DOI 10.1016-0092-8674(95)90021-7; Kawakami A, 1999, BLOOD, V94, P3847; Lallemand-Breitenbach V, 2001, J EXP MED, V193, P1361, DOI 10.1084-jem.193.12.1361; LANOIX J, 1994, ONCOGENE, V9, P841; Lau A, 1998, BLOOD, V91, P2467; LEBAIL O, 1993, EMBO J, V12, P5043; Lomas M, 2002, J GEN VIROL, V83, P641; Lonard DM, 2000, MOL CELL, V5, P939, DOI 10.1016-S1097-2765(00)80259-2; Mahieux R, 2000, AIDS RES HUM RETROV, V16, P1677, DOI 10.1089-08892220050193137; MERCURIO F, 1993, GENE DEV, V7, P705, DOI 10.1101-gad.7.4.705; Mesnard JM, 1999, VIROLOGY, V257, P277, DOI 10.1006-viro.1999.9685; Mitra-Kaushik S, 2004, BLOOD, V104, P802, DOI 10.1182-blood-2003-11-3967; Mori N, 2002, BLOOD, V100, P1828, DOI 10.1182-blood-2002-01-0151; Mori N, 2001, VIRUS GENES, V22, P279, DOI 10.1023-A:1011158021749; Mortreux F, 2003, LEUKEMIA, V17, P26, DOI 10.1038-sj.leu.2402777; Nakano H, 1998, P NATL ACAD SCI USA, V95, P3537, DOI 10.1073-pnas.95.7.3537; Nasr R, 2003, BLOOD, V101, P4576, DOI 10.1182-blood-2002-09-2986; Nasr R, 2005, ONCOGENE, V24, P419, DOI 10.1038-sj.onc.1208212; NERENBERG M, 1987, SCIENCE, V237, P1324, DOI 10.1126-science.2888190; Neuveut C, 1998, MOL CELL BIOL, V18, P3620; NOLAN GP, 1993, MOL CELL BIOL, V13, P3557; Pahl HL, 1999, ONCOGENE, V18, P6853, DOI 10.1038-sj.onc.1203239; PALOMBELLA VJ, 1994, CELL, V78, P773, DOI 10.1016-S0092-8674(94)90482-0; PEPIN N, 1994, VIROLOGY, V204, P706, DOI 10.1006-viro.1994.1586; Pise-Masison CA, 2000, AIDS RES HUM RETROV, V16, P1669, DOI 10.1089-08892220050193128; Portis T, 2001, BLOOD, V98, P1200, DOI 10.1182-blood.V98.4.1200; Prajapati S, 2002, J BIOL CHEM, V277, P24331, DOI 10.1074-jbc.M201393200; Robek MD, 1999, J VIROL, V73, P4856; Rothwarf DM, 1998, NATURE, V395, P297; Rousset R, 1996, NATURE, V381, P328, DOI 10.1038-381328a0; RYSECK RP, 1992, MOL CELL BIOL, V12, P674; Satou Y, 2004, LEUKEMIA, V18, P1357, DOI 10.1038-sj.leu.2403400; Sun SC, 1999, ONCOGENE, V18, P6948, DOI 10.1038-sj.onc.1203220; SUN SC, 1994, MOL CELL BIOL, V14, P7377; Sun SC, 2003, CANCER METAST REV, V22, P405, DOI 10.1023-A:1023733231406; Suzuki T, 1999, VIROLOGY, V259, P384, DOI 10.1006-viro.1999.9760; SUZUKI T, 1995, ONCOGENE, V10, P1199; SUZUKI T, 1994, ONCOGENE, V9, P3099; Tamiya S, 1998, BLOOD, V91, P3935; Tan C, 2002, CANCER RES, V62, P1083; TANAKA A, 1990, P NATL ACAD SCI USA, V87, P1071, DOI 10.1073-pnas.87.3.1071; Thrower JS, 2000, EMBO J, V19, P94, DOI 10.1093-emboj-19.1.94; Tojima Y, 2000, NATURE, V404, P778; Uhlik M, 1998, J BIOL CHEM, V273, P21132, DOI 10.1074-jbc.273.33.21132; VERMA IM, 1995, GENE DEV, V9, P2723, DOI 10.1101-gad.9.22.2723; WALDMANN TA, 1993, BLOOD, V82, P1701; Whiteside ST, 1997, EMBO J, V16, P1413, DOI 10.1093-emboj-16.6.1413; Xiao GT, 2000, ONCOGENE, V19, P5198, DOI 10.1038-sj.onc.1203894; Xiao GT, 2001, EMBO J, V20, P6805, DOI 10.1093-emboj-20.23.6805; Yamaoka S, 1998, CELL, V93, P1231, DOI 10.1016-S0092-8674(00)81466-X; Yin MJ, 1998, CELL, V93, P875, DOI 10.1016-S0092-8674(00)81447-6; Yoshida M, 2001, ANNU REV IMMUNOL, V19, P475, DOI 10.1146-annurev.immunol.19.1.475; ZABEL U, 1990, CELL, V61, P255, DOI 10.1016-0092-8674(90)90806-P; Zhu J, 2001, ONCOGENE, V20, P7257, DOI 10.1038-sj.onc.120485223222
Examination of neuromuscular and tissue oxygenation characteristics during submaximal treadmill running with blood flow restriction
Click on the DOI link to access this article at the publishers website (may not be free).Purpose: The use of blood flow restricted (BFR) running may provide an alternative to lower the running speed without compromising physiological responses that often occur during high intensity running. The purpose of this investigation was to compare the acute effects of various submaximal treadmill running speeds with BFR relative to maximal treadmill running speed without BFR on surface electromyographic amplitude (sEMGAMP), surface electromyographic mean power frequency (sEMGMPF), and muscle tissue oxygenation (StO2) responses. Methods: Thirteen college-aged females randomly completed four, three-minute treadmill running bouts at 70%, 80%, and 90% of their top speed (achieved during a graded exercise test) with BFR (70%BFR, 80%BFR, and 90%BFR) and 100% of their top speed without BFR (100%NOBFR). The sEMGAMP, sEMGMPF, and StO2 responses were analyzed from the final minute of the treadmill running bouts. Results: Each treadmill running bout led to similar (zero present in each Bayesian 95% high-density interval) sEMGAMP, sEMGMPF, and StO2 responses (70%BFR = 80%BFR = 90%BFR = 100%NOBFR). The mean difference (Meandiff) between speeds ranged from 2.73% to 11.20% for sEMGAMP, 0.04% to 7.08% for sEMGMPF, and 0.02% to 1.03% for StO2. Conclusion: Despite reductions in treadmill running speed, sEMGAMP, sEMGMPF, and StO2 responses were similar among non-BFR maximal treadmill running and submaximal treadmill running with BFR. Thus, submaximal treadmill running with BFR may serve as a potential alternative when maximal intensity aerobic exercise is contraindicated. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025
