Novel mutation in the mitochondrial transfer RNACys gene in a child

Mitochondrial DNA (mtDNA) disorders are an important group of genetic diseases presenting with a multifacet array of clinical manifestations. Highly energy-dependent tissues such as central nervous system and skeletal and cardiac muscles are commonly involved either as multisystem or as isolated organ disease. Characteristic symptoms include epilepsy, myopathy, deafness and ophthalmoplegia, all associated with point mutations in the mtDNA. Pathogenic mtDNA mutations can be heteroplasmic or homoplasmic. Heteroplasmic mutations are typically associated with mutations in mt-tRNA genes. Mutations in mt-tRNAs genes are responsible for the majority of the presentations of a mitochondrial disease being associated with marked clinical heterogeneity. Although tRNA-encoding genes make up only 9% of the entire mitochondrial genome, over 40% of all point mutations reported in the mtDNA are located in tRNA genes. Here, we present a child with vomiting episodes and migraine in whom we found a novel variant in the mitochondrial tRNACys gene

Lathrophytoic acids A and B: two novel polyprenylated phloroglucinol derivatives from Kielmeyera lathrophyton

AbstractTwo novel polyprenylated phloroglucinol derivatives were isolated from the trunk of Kielmeyera lathrophyton (Clusiaceae). Lathrophytoic acid A presented an unusual caged carbon skeleton with a 1,3-dione-4-cyclopentanol moiety. Lathrophytoic acid B exhibited a highly substituted bicycle[3.3.1]nonane skeleton and an isopropylfuran system which was formed by unusual cyclization of a prenyloxy side chain

"Double trouble” or digenic disorder in Complex I deficiency

Complex I (CI) deficiency is a defect of OXPHOS caused by mutations in the mitochondrial or nuclear genomes. To date disease-causing mutations have been reported in all mitochondrial-encoded subunits and 22 nuclear genes. In about 50% of the patients no mutations are found, suggesting that undiscovered factors are an important cause of disease. In this study we report a consanguineous family from Southern Portugal with three affected children presenting with CI deficiency and 3-methylglutaconic aciduria type IV

Parâmetros De Qualidade Físico-químicos E Avaliação Da Atividade Antioxidante De Folhas De Plectranthus Barbatus Andr. (lamiaceae) Submetidas A Diferentes Processos De Secagem

This paper describes the physicochemical composition, the evaluation of the antioxidant activity by free DPPH radicals using the scavenging method, the determination of flavonoids and total phenolic compounds of ethanol, acetone and aqueous extracts of the medicinal plant Plectranthus barbatus Andr. (Lamiaceae), dehydrated in solar dryer and circulation oven at 60 °C. Water activity rates for two drying methods were below the minimum necessary for growth and toxin production of important food pathogens. Physicochemical results showed that both processes were effective in the dehydration of P. barbatus. The results demonstrated that the acetone (over) and ethanol (over and solar dryer) extracts showed the highest content of total phenols. The ethanol extract (over) showed the highest amount of flavonoids and better antioxidant activity (75.71 ± 10.57 µg L-1). © 2016, Instituto de Biociencias. All rights reserved.181485

Signatures of heavy Majorana neutrinos and HERA's isolated lepton events

The graph of neutrinoless double beta decay is applied to HERA and generalized to final states with any two charged leptons. Considered is the case in which one of the two escapes typical identification criteria and the case when a produced tau decays hadronically. Both possibilities give one isolated lepton with high transverse momentum, hadronic activity and an imbalance in transverse momentum. We examine the kinematical properties of these events and compare them with the high p_T isolated leptons reported by the H1 collaboration. Their positive charged muon events can be explained by the ``double beta'' process and we discuss possibilities for the precise determination which original final state produced the single isolated lepton. To confirm our hypothesis one should search in the data for high pseudorapidity and/or low p_T leptons or for additional separated jets.Comment: 19 pages with 14 figures, minor change

The cyclooxigenase-2 inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observations

Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant e cacy, but also considerable toxicity. This study addresses the chemopreventive e ect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16+/-, n = 10, parecoxib-treated); II (HPV16+/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/- n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn’t modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive e ects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.This work is supported by National Funds by FCT—Portuguese Foundation for Science and Technology, under the projects UID/AGR/04033/2019, UID/CVT/00772/2019 and UID/EQU/00511/2019 - Laboratory for Process Engineering, Environment, Biotechnology and Energy—LEPABE funded by national funds through FCT/MCTES (PIDDAC); Project “LEPABE-2-ECO-INNOVATION”—NORTE-01-0145-FEDER-000005, funded by Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund.info:eu-repo/semantics/publishedVersio

Portuguese Ministers, 1851-1999: Social Background and Paths to Power

Disponível em: http://193.136.113.6/Opac/Pages/Search/Results.aspx?SearchText=UID=bb8aa8d5-c6b6-466a-81bb-fe8a67693cee&DataBase=10449_UNLFCSHThis paper provides an empirical analysis of the impact of regime changes in the composition and patterns of recruitment of the Portuguese ministerial elite throughout the last 150 years. The ‘out-of-type’, violent nature of most regime transformations accounts for the purges in and the extensive replacements of the political personnel, namely of the uppermost officeholders. In the case of Cabinet members, such discontinuities did not imply, however, radical changes in their social profile. Although there were some significant variations, a series of salient characteristics have persisted over time. The typical Portuguese minister is a male in his midforties, of middle-class origin and predominantly urban-born, highly educated and with a state servant background. The two main occupational contingents have been university professors - except for the First Republic (1910-26) - and the military, the latter having only recently been eclipsed with the consolidation of contemporary democracy. As regards career pathways, the most striking feature is the secular trend for the declining role of parliamentary experience, which the democratic regime did not clearly reverse. In this period, a technocratic background rather than political experience has been indeed the privileged credential for a significant proportion of minister

Polymorphism In Lep And Lepr May Modify Leptin Levels And Represent Risk Factors For Thyroid Cancer

Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P A) polymorphism and disease susceptibility and cardiovascular disease in patients with rheumatoid arthritis (2011) Clinical and Experimental Rheumatology, 29 (2), pp. 293-298Jiang, Y., Wilk, J.B., Borecki, I., Common variants in the 5' region of the leptin gene are associated with bodymass index in men fromthe National Heart, Lung, and Blood Institute Family Heart Study (2004) The American Journal of Human Genetics, 75 (2), pp. 220-230He, J., Xi, B., Ruiter, R., Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: Evidence froma meta-analysis (2013) PLoS ONE, 8 (10)Furusawa, T., Naka, I., Yamauchi, T., The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders (2010) Human Genetics, 127 (3), pp. 287-294Saukko, M., Kesäniemi, Y.A., Ukkola, O., Leptin receptor Lys109Arg and Gln223Arg polymorphisms are associated with early atherosclerosis (2010) Metabolic Syndrome and Related Disorders, 8 (5), pp. 425-430Lucas, A., Granada, M.L., Olaizola, I., Leptin and thyrotropin relationship is modulated by smoking status in euthyroid subjects (2013) Thyroid, 23 (8), pp. 964-970Duntas, L.H., Biondi, B., The interconnections between obesity, thyroid function, and autoimmunity: Themultifold role of leptin (2013) Thyroid, 23 (6), pp. 646-653Marzullo, P., Minocci, A., Tagliaferri, M.A., Investigations of thyroid hormones and antibodies in obesity: Leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants (2010) Journal of Clinical Endocrinology and Metabolism, 95 (8), pp. 3965-3972Guzel, S., Seven, A., Guzel, E.C., Buyuk, B., Celebi, A., Aydemir, B., Visfatin, leptin, and TNF-α: Interrelated adipokines in insulin-resistant clinical and subclinical hypothyroidism (2013) Endocrine Research, 38 (3), pp. 184-194Mammès, O., Betoulle, D., Aubert, R., Herbeth, B., Siest, G., Fumeron, F., Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight (2000) Annals of Human Genetics, 64 (5), pp. 391-394Portoles, O., Sorli, J.V., Frances, F., Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain (2006) European Journal of Epidemiology, 21 (8), pp. 605-612Liu, C., Liu, L., Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: A metaanalysis (2011) Tumour Biology, 32 (6), pp. 1233-1240Hoffsted, J., Eriksson, P., Mottagui-Tabar, S., Arner, P., A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin (2002) Hormone and Metabolic Research, 34 (7), pp. 355-359Murugesan, D., Arunachalam, T., Ramamurthy, V., Subramanian, S., Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore (2010) Indian Journal of Human Genetics, 16 (2), pp. 72-77Quinton, N.D., Lee, A.J., Ross, R.J.M., Eastell, R., Blakemore, A.I.F., A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fatmass and leptin levels in postmenopausal Caucasian women (2001) Human Genetics, 108 (3), pp. 233-236Mattevi, V.S., Zembrzuski, V.M., Hutz, M.H., Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil (2002) International Journal of Obesity, 26 (9), pp. 1179-1185Yiannakouris, N., Yannakoulia, M., Melistas, L., Chan, J.L., Klimis-Zacas, D., Mantzoros, C.S., TheQ223Rpolymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of bodyweight and body composition variability (2001) Journal of Clinical Endocrinology and Metabolism, 86 (9), pp. 4434-4439Stefan, N., Vozarova, B., Del Parigi, A., The Gln223Arg polymorphism of the leptin receptor in Pima Indians: Influence on energy expenditure, physical activity and lipid metabolism (2002) International Journal of Obesity, 26 (12), pp. 1629-1632Chiu, K.C., Chu, A., Chuang, L.-M., Saad, M.F., Association of leptin receptor polymorphism with insulin resistance (2004) European Journal of Endocrinology, 150 (5), pp. 725-729Chu, A., Chuang, L.M., Saad, M., Chiu, K., Association of the Q223R polymorphism of the leptin receptor gene with insulin resistance and metabolic syndrome (2003) Diabetes, 52, p. 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Q223R leptin receptor polymorphism associated with obesity in Brazilianmultiethnic subjects (2006) The American Journal of Human Biology, 18 (4), pp. 448-453Wauters, M., Mertens, I., Chagnon, M., Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women (2001) International Journal of Obesity, 25 (5), pp. 714-720Ogawa, T., Hirose, H., Yamamoto, Y., Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population (2004) Metabolism: Clinical and Experimental, 53 (7), pp. 879-885Fairbrother, U.L., Tankó, L.B., Walley, A.J., Christiansen, C., Froguel, P., Blakemore, A.I.F., Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women (2007) Journal of Bone and Mineral Research, 22 (4), pp. 544-550Salopuro, T., Pulkkinen, L., Lindström, J., Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study (2005) International Journal of Obesity, 29 (10), pp. 1245-1251Wauters, M., Mertens, I., Rankinen, T., Chagnon, M., Bouchardt, C., Van Gaal, L., Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance (2001) Journal of Clinical Endocrinology and Metabolism, 86 (7), pp. 3227-3232Park, K.S., Shin, H.D., Park, B.L., Polymorphisms in the leptin receptor (LEPR)-putative association with obesity and T2DM (2006) Journal of Human Genetics, 51 (2), pp. 85-91Han, C.-Z., Du, L.-L., Jing, J.-X., Associations among lipids, leptin, and leptin receptor geneGin223Arg polymorphisms and breast cancer in China (2008) Biological Trace Element Research, 126 (1-3), pp. 38-48Okobia, M.N., Bunker, C.H., Garte, S.J., Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study (2008) BMC Cancer, 8He, B.-S., Pan, Y.-Q., Zhang, Y., Xu, Y.-Q., Wang, S.-K., Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: A meta-analysis (2012) Molecular Biology Reports, 39 (3), pp. 3117-3122Lin, D.W., Fitz Gerald, L.M., Fu, R., Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality (2011) Cancer Epidemiology, Biomarkers & Prevention, 20 (9), pp. 1928-1936Li, Y.L., Geng, J.L., Wang, Y., The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients (2012) Journal of Cancer Research and Clinical Oncology, 138 (2), pp. 311-316Wazir, U., Al Sarakbi, W., Jiang, W.G., Mokbel, K., Evidence of an autocrine role for leptin and leptin receptor in human breast cancer (2012) CancerGenomics and Proteomics, 9 (6), pp. 383-388Li, L., Lee, K.J., Choi, B.C., Baek, K.H., Relationshipbetween leptin receptor and polycystic ovary syndrome (2013) Gene, 527 (1), pp. 71-74Friedlander, Y., Li, G., Fornage, M., Candidate molecular pathway genes related to appetite regulatory neural network, adipocyte homeostasis and obesity: Results from the CARDIA Study (2010) Annals of Human Genetics, 74 (5), pp. 387-39