808 research outputs found

    Absence of the spindle assembly checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion

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    The fidelity of mitosis depends on cohesive forces that keep sister chromatids together. This is mediated by cohesin that embraces sister chromatid fibers from the time of their replication until the subsequent mitosis [1-3]. Cleavage of cohesin marks anaphase onset, where single chromatids are dragged to the poles by the mitotic spindle [4-6]. Cohesin cleavage should only occur when all chromosomes are properly bio-oriented to ensure equal genome distribution and prevent random chromosome segregation. Unscheduled loss of sister chromatid cohesion is prevented by a safeguard mechanism known as the spindle assembly checkpoint (SAC) [7, 8]. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates Drosophila wing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knockdown of the acetyltransferase separation anxiety (San)/Naa50, a cohesin complex stabilizer [9-12]. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key SAC proteins, Mad2 and Mpsl, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects, and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome biorientation at mitotic entry, coupled with slow engagement of error-correction reactions. Thus, in contrast to SAC's role as a safeguard mechanism for mitotic fidelity, removal of this checkpoint alleviates mitotic errors when sister chromatid cohesion is compromised.Lisboa Regional Operational Programme (Lisboa 2020) through the European Regional Development Fund (FEDER); Fundacao para a Ciencia e a Tecnologia (FCT; Portugal); FCT [SFRH/BPD/87482/2012, SFRH /BD/52438/2013, PD/BD/52428/2013, PD/00117/2012, CRM: 0027030, PTDC/BEX-BID/0395/2014, UID/BIM/04773/2013 CBMR 1334, IF/00851/2012/CP0185/CT0004]; Association for International Cancer Research [AICR 10-0553]; EMBO Installation Grant [IG2778]; European Research Council Starting Grant [ERC-2014-STG-638917]; [PPBI-POCI-01-0145-FEDER-022122]; [LISBOA-01-0145-FEDER-022170

    A fitotoxicidade de óxido de grafeno como base para nanofertilizantes

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    Apresentação em painelOs dados sobre a fitotoxicidade de compostos de grafeno na agricultura não são consensuais na literatura, pelo que o seu uso como base de desenvolvimento nanofertilizantes requer um aprofundamento do conhecimento sobre esta matéria. Assim, neste estudo pretendeu-se caracterizar as interações da concentração de oxido de grafeno, com a fitotoxicidade em Lepidium sativum L, por forma a aumentar a segurança no uso destes compostos na formulação de nanofertilizantes.info:eu-repo/semantics/publishedVersio

    L-Theanine promotes cultured human Sertoli cells proliferation and modulates glucose metabolism

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    L-Theanine is the major free amino acid present in tea (Camellia sinensis L.). The effects of several tea constituents on male reproduction have been investigated, but L-theanine has been overlooked. Sertoli cells (SCs) are essential for the physical and nutritional support of germ cells. In this study, we aimed to investigate the ability of L-theanine to modulate important mechanisms of human SCs (hSCs) metabolism, mitochondrial function and oxidative profile, which are essential to prevent or counteract spermatogenesis disruption in several health conditions.info:eu-repo/semantics/publishedVersio

    A dual-function SNF2 protein drives chromatid resolution and nascent transcripts removal in mitosis

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    Mitotic chromatin is largely assumed incompatible with transcription due to changes in the transcription machinery and chromosome architecture. However, the mechanisms of mitotic transcriptional inactivation and their interplay with chromosome assembly remain largely unknown. By monitoring ongoing transcription in Drosophila early embryos, we reveal that eviction of nascent mRNAs from mitotic chromatin occurs after substantial chromosome compaction and is not promoted by condensin I. Instead, we show that the timely removal of transcripts from mitotic chromatin is driven by the SNF2 helicase-like protein Lodestar (Lds), identified here as a modulator of sister chromatid cohesion defects. In addition to the eviction of nascent transcripts, we uncover that Lds cooperates with Topoisomerase 2 to ensure efficient sister chromatid resolution and mitotic fidelity. We conclude that the removal of nascent transcripts upon mitotic entry is not a passive consequence of cell cycle progression and/or chromosome compaction but occurs via dedicated mechanisms with functional parallelisms to sister chromatid resolution.info:eu-repo/semantics/publishedVersio

    Antioxidant activity and acute toxicity of Neoglaziovia variegata (Bromeliaceae)

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    Antioxidant activities of Neoglaziovia variegata were evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and β-carotene-linoleic acid bleaching and was compared with ascorbic acid, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The total phenolics content of the extracts was determined by the Folin-Ciocalteu method. Total flavonoid was also determined. The most significant total phenolic content was of 543.50 ± 9.38 mg of gallic acid equivalent/g for ethyl acetate extract (AcOEt), which presented the best antioxidant activity (IC50 5.08 ± 0.20 μg/ml) for DPPH scavenging. The acute toxicity of Nv-EtOH was performed 2.0 g/kg intraperitoneally and 5.0 g/kg orally in mice. No mortality and no toxicity signs were observed, indicating low toxicity of the extract. Blood was removed after 14 days for laboratory analysis of hematological and biochemical parameters. Alterations of aspartate aminotransferase (AST) and creatinine were observed. The data obtained showed that the doses induced microscopic alterations in the liver and kidney. In conclusion, the Nv-EtOH can be considered of low toxicity.Keywords: Antioxidant activity, acute toxicity, Neoglaziovia variegata, Bromeliacea
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