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"Ruiz, E."
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Barrio dreams : selected plays
\"The first-ever anthology of plays by Chicana playwright Silviana Wood\"--Provided by publisher.
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METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability
Oxaliplatin is the first-line regime for advanced gastric cancer treatment, while its resistance is a major problem that leads to the failure of clinical treatments. Tumor cell heterogeneity has been considered as one of the main causes for drug resistance in cancer. In this study, the mechanism of oxaliplatin resistance was investigated through in vitro human gastric cancer organoids and gastric cancer oxaliplatin-resistant cell lines and in vivo subcutaneous tumorigenicity experiments. The in vitro and in vivo results indicated that CD133+ stem cell-like cells are the main subpopulation and PARP1 is the central gene mediating oxaliplatin resistance in gastric cancer. It was found that PARP1 can effectively repair DNA damage caused by oxaliplatin by means of mediating the opening of base excision repair pathway, leading to the occurrence of drug resistance. The CD133+ stem cells also exhibited upregulated expression of N6-methyladenosine (m6A) mRNA and its writer METTL3 as showed by immunoprecipitation followed by sequencing and transcriptome analysis. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3′-untranslated Region (3′-UTR) of PARP1 mRNA. The CD133+ tumor stem cells can regulate the stability and expression of m6A to PARP1 through METTL3, and thus exerting the PARP1-mediated DNA damage repair ability. Therefore, our study demonstrated that m6A Methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity.
Journal Article
Progress in the determination of metalloids and non-metals by means of high-resolution continuum source atomic or molecular absorption spectrometry. A critical review
This work examines the new possibilities introduced with the arrival of commercially available high-resolution continuum source atomic absorption spectrometers for the determination of metalloids (B, Si, Ge, As, Se, Sb and Te) and non-metals (P, S, F, Cl, Br, I and N-based species), such as the improved potential to detect and correct for spectral overlaps and the strategies available to correct for matrix effects. In particular, and considering the increasing number of papers reporting on the use of molecular absorption spectrometry using graphite furnaces and flames as vaporizers, the work discusses in detail the advantages and limitations derived from the monitoring of molecular spectra from a practical point of view, in an attempt to guide future users of the technique.
Figure
Heating of a graphite furnace with platform
Journal Article
Cytokines in clinical cancer immunotherapy
Cytokines are soluble proteins that mediate cell-to-cell communication. Based on the discovery of the potent anti-tumour activities of several pro-inflammatory cytokines in animal models, clinical research led to the approval of recombinant interferon-alpha and interleukin-2 for the treatment of several malignancies, even if efficacy was only modest. These early milestones in immunotherapy have been followed by the recent addition to clinical practice of antibodies that inhibit immune checkpoints, as well as chimeric antigen receptor T cells. A renewed interest in the anti-tumour properties of cytokines has led to an exponential increase in the number of clinical trials that explore the safety and efficacy of cytokine-based drugs, not only as single agents, but also in combination with other immunomodulatory drugs. These second-generation drugs under clinical development include known molecules with novel mechanisms of action, new targets, and fusion proteins that increase half-life and target cytokine activity to the tumour microenvironment or to the desired effector immune cells. In addition, the detrimental activity of immunosuppressive cytokines can be blocked by antagonistic antibodies, small molecules, cytokine traps or siRNAs. In this review, we provide an overview of the novel trends in the cytokine immunotherapy field that are yielding therapeutic agents for clinical trials.
Journal Article
The intake of high-fat diets induces the acquisition of brown adipocyte gene expression features in white adipose tissue
Background/Objective:
White-to-brown adipose tissue remodeling (browning) in response to different stimuli constitutes an active research area for obesity treatment. The emergence in traditional white adipose tissue (WAT) depots of multilocular adipocytes that express uncoupling protein 1 (UCP1) and resemble brown adipocytes, the so called 'brite' adipocytes, could contribute to increased energy expenditure. In rodents, obesogenic stimuli such as the intake of hyperlipidic diets can increase brown adipose tissue (BAT) thermogenic capacity and contribute to maintaining body weight. The aim of this study was to investigate the potential of two different hyperlipidic diets, a commercial high-fat (HF) diet and a highly palatable cafeteria (CAF) diet, to induce WAT browning.
Methods:
We analyzed gene expression of a wide number of brown/brite adipocyte markers in different WAT depots, in BAT and in peripheral blood mononuclear cells (PBMCs) increasingly being used in nutrition studies as a potential source of biomarkers of physiological effects. We also performed morphological analysis of adipose tissue.
Results:
Both HF diets studied were able to increase the expression of the markers studied in WAT in a depot-specific manner, as well as in BAT; some of these changes were also reflected in PBMCs. This increased browning capacity was translated into the appearance of UCP1- and CIDE-A (cell death-inducing DFFA-like effector A)-positive brite adipocytes in retroperitoneal WAT. Administration of the CAF diet, associated with higher adiposity, produced the strongest impact on the parameters studied while its withdrawal restored basal conditions.
Conclusions:
Acquisition of brown adipocyte features in WAT could evidence an adaptation to try to counteract increased adiposity due to the intake of HF diets. Additionally, PBMCs could constitute an interesting easily obtainable material to assess the effect of nutritional interventions on browning capacity.
Journal Article
Swope Supernova Survey 2017a (SSS17a), the optical counterpart to a gravitational wave source
On 17 August 2017, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Virgo interferometer detected gravitational waves (GWs) emanating from a binary neutron star merger, GW170817. Nearly simultaneously, the Fermi and INTEGRAL (INTErnational Gamma-Ray Astrophysics Laboratory) telescopes detected a gamma-ray transient, GRB 170817A. At 10.9 hours after the GW trigger, we discovered a transient and fading optical source, Swope Supernova Survey 2017a (SSS17a), coincident with GW170817. SSS17a is located in NGC 4993, an S0 galaxy at a distance of 40 megaparsecs. The precise location of GW170817 provides an opportunity to probe the nature of these cataclysmic events by combining electromagnetic and GW observations.
Journal Article
An intrinsic temporal order of c-JUN N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment
Protein phosphorylation is a major regulatory mechanism of cellular signalling. The c-JUN proto-oncoprotein is phosphorylated at four residues within its transactivation domain (TAD) by the JNK family kinases, but the functional significance of c-JUN multisite phosphorylation has remained elusive. Here we show that c-JUN phosphorylation by JNK exhibits defined temporal kinetics, with serine63 and serine73 being phosphorylated more rapidly than threonine91 and threonine93. We identify the positioning of the phosphorylation sites relative to the kinase docking motif, and their primary sequence, as the main factors controlling phosphorylation kinetics. Functional analysis reveals three c-JUN phosphorylation states: unphosphorylated c-JUN recruits the MBD3 repressor, serine63/73 doubly-phosphorylated c-JUN binds to the TCF4 co-activator, whereas the fully phosphorylated form disfavours TCF4 binding attenuating JNK signalling. Thus, c-JUN phosphorylation encodes multiple functional states that drive a complex signalling response from a single JNK input.
Phosphorylation at multiple sites is a major regulatory mechanism in cellular signalling. Here, the authors show that multisite phosphorylation of the c-JUN transcription factor by the JNK kinase exhibits intrinsic kinetics that allow a precise and timed regulation of the transcriptional output.
Journal Article
Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella
Plastic degradation by biological systems with re-utilization of the by-products could be a future solution to the global threat of plastic waste accumulation. Here, we report that the saliva of
Galleria mellonella
larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours’ exposure at room temperature under physiological conditions (neutral pH). The wax worm saliva can overcome the bottleneck step in PE biodegradation, namely the initial oxidation step. Within the saliva, we identify two enzymes, belonging to the phenol oxidase family, that can reproduce the same effect. To the best of our knowledge, these enzymes are the first animal enzymes with this capability, opening the way to potential solutions for plastic waste management through bio-recycling/up-cycling.
The crucial first step in the biodegradation of polyethylene plastic is oxidation of the polymer. This has traditionally required abiotic pre-treatment, but now Bertocchini and colleagues report two wax worm enzymes capable of catalyzing this oxidation and subsequent degradation at room temperature.
Journal Article
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma
In patients with advanced renal-cell carcinoma, treatment with cabozantinib plus nivolumab and ipilimumab resulted in longer progression-free survival than treatment with nivolumab and ipilimumab alone.
Journal Article
Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance
Epithelial tissues require the removal and replacement of damaged cells to sustain a functional barrier. Dying cells provide instructive cues that can influence surrounding cells to proliferate, but how these signals are transmitted to their healthy neighbors to control cellular behaviors during tissue homeostasis remains poorly understood. Here we show that dying stem cells facilitate communication with adjacent stem cells by caspase-dependent production of Wnt8a-containing apoptotic bodies to drive cellular turnover in living epithelia. Basal stem cells engulf apoptotic bodies, activate Wnt signaling, and are stimulated to divide to maintain tissue-wide cell numbers. Inhibition of either cell death or Wnt signaling eliminated the apoptosis-induced cell division, while overexpression of Wnt8a signaling combined with induced cell death led to an expansion of the stem cell population. We conclude that ingestion of apoptotic bodies represents a regulatory mechanism linking death and division to maintain overall stem cell numbers and epithelial tissue homeostasis.
Damaged epithelial tissues are known to compensate for cell death through compensatory cell divisions to maintain epithelial integrity. Here, the authors show in living epithelia that dying cells stimulate adjacent stem cells to divide through caspase-dependent production of Wnt8a-containing apoptotic bodies.
Journal Article