Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases.

MutY adenine glycosylases prevent DNA mutations by excising adenine from promutagenic 8-oxo-7,8-dihydroguanine (OG):A mismatches. Here, we describe structural features of the MutY active site bound to an azaribose transition state analog which indicate a catalytic role for Tyr126 and approach of the water nucleophile on the same side as the departing adenine base. The idea that Tyr126 participates in catalysis, recently predicted by modeling calculations, is strongly supported by mutagenesis and by seeing close contact between the hydroxyl group of this residue and the azaribose moiety of the transition state analog. NMR analysis of MutY methanolysis products corroborates a mechanism for adenine removal with retention of stereochemistry. Based on these results, we propose a revised mechanism for MutY that involves two nucleophilic displacement steps akin to the mechanisms accepted for 'retaining' O-glycosidases. This new-for-MutY yet familiar mechanism may also be operative in related base excision repair glycosylases and provides a critical framework for analysis of human MutY (MUTYH) variants associated with inherited colorectal cancer

Flavonoids: Classification, Biosynthesis and Chemical Ecology

Flavonoids are natural products widely distributed in the plant kingdom and form one of the main classes of secondary metabolites. They display a large range of structures and ecological significance (e.g., such as the colored pigments in many flower petals), serve as chemotaxonomic marker compounds and have a variety of biological activities. Therefore, they have been extensively investigated but the interest in them is still increasing. The topics that will be discussed in this chapter describe the regulation of flavonoid biosynthesis, the roles of flavonoids in flowers, fruits and roots and mechanisms involved in pollination and their specific functions in the plant

Linhagem celular RC-IAL: sensibilidade de crescimento do vírus da rubéola

OBJECTIVE: The rapid growth of the rubella virus in RC-IAL² with development of cytopathic effect, in response to rubella virus infection, is described. For purposes of comparison, the rubella virus RA-27/3 strain was titered simultaneously in the RC-IAL, Vero, SIRC and RK13 cell lines. METHODS: Rubella virus RA-27/3 strain are inoculated in the RC-IAL cell line (rabbit Kidney, Institute Adolfo Lutz). Plates containing 1.5x10(5) cells/ml of RC-IAL line were inoculated with 0.1ml s RA-27/3 strain virus containing 1x 10(4)TCID50/0.1ml. A 25% cytopathic effect was observed after 48 hours and 100% after 96 hours. The results obtained were compared to those observed with the SIRC, Vero and RK13 cell lines. Rubella virus was detected by immunohistochemistry. RESULTS: With the results, it was possible to conclude that the RC-IAL cell line is a very good substrate for culturing rubella virus. The cells inoculated with rubella virus were examined by phase contrast microscopy and showed the characteristic rounded, bipolar and multipolar cells. The CPE in RC-IAL was observed in the first 48 hours and the curve of the increased infectivity was practically the same as observed in other cell lines. CONCLUSIONS: These findings are important since this is one the few cell lines described in the literature with a cytopathic effect. So it can be used for antigen preparation and serological testing for the diagnosis of specific rubella antibodies.OBJETIVO: Descreve-se o crescimento do vírus-padrão da rubéola RA-27/3 na linhagem celular RC-IAL, com desenvolvimento de efeito citopático em resposta à infecção viral. Para este propósito, o vírus-padrão foi titulado simultaneamente nas linhagens celulares Vero, SIRC e RK13. MÉTODOS: O vírus-padrão da rubéola RA-27/3 foi inoculado na linhagem celular RC-IAL (rim de coelho, Instituto Adolfo Lutz). Placas contendo 1,5x10(5) células/ml foram inoculadas com 0,1 ml do vírus contendo 1x10(4) DICT50/0,1 ml. O efeito citopático correspondente a 25% foi observado após 48 h e 100% após 96 h. Os resultados obtidos foram comparados com o crescimento do vírus nas linhagens celulares SIRC, Vero e RK13. O vírus da rubéola na linhagem celular RC-IAL foi detectado por imuno-histoquímica. RESULTADOS: As células inoculadas com o vírus da rubéola apresentaram efeito citopático nas primeiras 48h. As células apresentaram aspecto arredondado, com formação de alguns prolongamentos citoplasmáticos e sincícios, produzindo células multinucleadas. A curva do crescimento da infectividade do vírus foi praticamente a mesma que a observada nas outras linhagens celulares. CONCLUSÃO: Os resultados obtidos mostram que a linhagem celular RC-IAL é um ótimo substrato para crescimento do vírus da rubéola, pois poucas linhagens celulares descritas na literatura apresentam efeito citopático considerável e podem ser utilizadas para preparação de antígenos e nos testes de diagnóstico sorológico para o vírus da rubéola

Procrastination and Occupational Stress of Teachers in Philippine Public Schools

This descriptive-correlational study aimed to determine the extent of procrastination and level of occupational stress of teachers in the Schools Division of Himamaylan City, Negros Occidental, Philippines, when taken as a whole and when classified according to key stages (grade level taught), teaching position, educational attainment, years in service, and take- home pay. The study's respondents were the 284 public school teachers selected using stratified random sampling. The adopted research instrument contains the demographic profile of the respondents and the statements on procrastination and occupational stress. The results revealed that the respondents' procrastination and occupational stress were low when taken as a whole. Furthermore, there were no significant differences in the respondents' procrastination and occupational stress when grouped according to the abovementioned variables. Finally, data revealed a significant relationship between the respondents' extent of procrastination and their level of occupational stress. The findings of this study may provide relevant and significant information which would serve as a baseline for all the policymakers in devising, crafting, and designing activities such as training, workshops, seminars, and stress intervention programs. Furthermore, this study may help the teachers better establish and develop themselves to become adaptive to the demands and trends of the present educational landscape

Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity

Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease

Topiramate-associated acute glaucoma in a migraine patient receiving concomitant citalopram therapy: a case-report

We describe the case of a 34 year-old man with diagnosis of migraine with and without aura that developed myopia and acute glaucoma after 7 days of treatment with topiramate. The patient had also been taking citalopram daily for two months. Both topiramate and citalopram have been related to the increase of intraocular pressure and the development of glaucoma. We can't exclude that in this patient citalopram caused an increase of the ocular pressure in dose-dependent manner, facilitating topiramate-induced glaucoma. We recommend to pay particular attention in prescribing of topiramate in migraine patients who are already under treatment with citalopram or other antidepressants with a similar mechanisms of action

No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity

Myelinated axons are endowed with a specialized domain structure that is essential for saltatory action potential conduction. The paranodal domain contains the axoglial junctions and displays a unique ultrastructure that resembles the invertebrate septate junctions (SJs). Biochemical characterizations of the paranodal axoglial SJs have identified several molecular components that include Caspr and contactin (Cont) on the axonal side and neurofascin 155 kDa (NF155) isoform on the glial side. All these proteins are essential for the formation of the axoglial SJs. Based on the interactions between Caspr and Cont and their colocalization in the CA1 synaptic areas, it was proposed that the synaptic function of Cont requires Caspr. Here we have extended the phenotypic analysis of CASPR mutants to address further the role of Caspr at the axoglial SJs and also in axonal orientation and synaptic plasticity. We report that, in CASPR mutants, the smooth endoplasmic reticulum (SER) forms elongated membranous complexes that accumulate at the nodal/ paranodal region and stretch into the juxtaparanodal region, a defect that is consistent with the paranodal disorganization. We show that the cerebellar microorganization is unaffected in CASPR mutants. We also demonstrate that Caspr function is not essential for normal CA1 synaptic transmission and plasticity. Taken together with previous findings, our results highlight that the Caspr/ Cont complex is essential for the formation of axoglial SJs, whereas Cont may regulate axonal orientation and synaptic plasticity independent of its association with Caspr

Faktor Resiko Terjadinya Perdarahan Post Partum : Studi Literatur

Maternal mortality rate in Indonesia is relatively high. The most common cause of maternal death is bleeding. Post partum haemorrhage (PPH) is an unexpected cause and the fastest cause of maternal death worldwide. PPH is blood loss of 500 cc or more that occurs after the baby is born. Risk factors/predisposition for postpartum hemorrhage include: anemia, parity, gestational age, delivery distance, excessive uterine stretching (macrosomia, gemely, and polyhidramnions), precipitate parturition, oxytocin induction, history of cesarean section, ante partum bleeding, first stage of labor and the elongated II, and so on. This literature review aims to determine the risk factors/trigger factors of postpartum hemorrhage. Using literature study according to the topic. Literature studies were obtained from various sources, including from journals ranging from 2015-2020. Source articles from goggle scholars and Goggle Scholars. From several journals that have been reviewed, postpartum hemorrhage is one of the complications that has a high incidence. And there is a relationship between predisposing factors and the incidence of postpartum hemorrhageAbstrakAngka kematian ibu melahirkan di Indonesia relatif tinggi. Adapun penyebab terbanyak yang menyebabkan kematian ibu adalah perdarahan. Perdarahan post partum adalah penyebab tak terduga dan penyebab tercepat kematian ibu diseluruh dunia. Perdarahan post partum adalah hilangnya darah 500 cc atau lebih yang terjadi setelah bayi lahir. Faktor resiko/predisposisi terjadinya perdarahan post partum antara lain : anemia, paritas, umur kehamilan, jarak persalinan, peregangan uterus yang berlebihan (makrosomia, gemeli dan polihidramnion), partus presipitatus, induksi oksitosin, riwayat seksio secaria, perdarahan ante partum, persalinan kalan I dan II yang memanjang, dan lain-lain. literatur review ini bertujuan untuk mengetahui faktor resiko/faktor pencetus dari perdarahan post partum. menggunakan studi literatur sesuai dengan topik. Studi literatur didapat dari berbagai sumber, diantaranya dari jurnal berkisar tahun 2014-2018. Sumber artikel dari Pubmed, Portal Garuda dan goggle Scholar. dari beberapa jurnal yang telah ditelaah, perdarahan post partum merupakan salah satu komplikasi yang angka kejadiannya masih tinggi. Dan ada hubungan antara faktor predisposisi dengan kejadian perdarahan post partu

Faktor Resiko Terjadinya Perdarahan Post Partum : Studi Literatur

Maternal mortality rate in Indonesia is relatively high. The most common cause of maternal death is bleeding. Post partum haemorrhage (PPH) is an unexpected cause and the fastest cause of maternal death worldwide. PPH is blood loss of 500 cc or more that occurs after the baby is born. Risk factors/predisposition for postpartum hemorrhage include: anemia, parity, gestational age, delivery distance, excessive uterine stretching (macrosomia, gemely, and polyhidramnions), precipitate parturition, oxytocin induction, history of cesarean section, ante partum bleeding, first stage of labor and the elongated II, and so on. This literature review aims to determine the risk factors/trigger factors of postpartum hemorrhage. Using literature study according to the topic. Literature studies were obtained from various sources, including from journals ranging from 2015-2020. Source articles from goggle scholars and Goggle Scholars. From several journals that have been reviewed, postpartum hemorrhage is one of the complications that has a high incidence. And there is a relationship between predisposing factors and the incidence of postpartum hemorrhageAbstrakAngka kematian ibu melahirkan di Indonesia relatif tinggi. Adapun penyebab terbanyak yang menyebabkan kematian ibu adalah perdarahan. Perdarahan post partum adalah penyebab tak terduga dan penyebab tercepat kematian ibu diseluruh dunia. Perdarahan post partum adalah hilangnya darah 500 cc atau lebih yang terjadi setelah bayi lahir. Faktor resiko/predisposisi terjadinya perdarahan post partum antara lain : anemia, paritas, umur kehamilan, jarak persalinan, peregangan uterus yang berlebihan (makrosomia, gemeli dan polihidramnion), partus presipitatus, induksi oksitosin, riwayat seksio secaria, perdarahan ante partum, persalinan kalan I dan II yang memanjang, dan lain-lain. literatur review ini bertujuan untuk mengetahui faktor resiko/faktor pencetus dari perdarahan post partum. menggunakan studi literatur sesuai dengan topik. Studi literatur didapat dari berbagai sumber, diantaranya dari jurnal berkisar tahun 2014-2018. Sumber artikel dari Pubmed, Portal Garuda dan goggle Scholar. dari beberapa jurnal yang telah ditelaah, perdarahan post partum merupakan salah satu komplikasi yang angka kejadiannya masih tinggi. Dan ada hubungan antara faktor predisposisi dengan kejadian perdarahan post partu