Diseño de 1600 ML de adoquinado, ubicado en los barrios: anexo a la villa Victoria de julio, Antonio Mendoza y Rubén Ulloa; en el casco urbano de Tipitapa, municipio de Managua

El desarrollo de nuestro país se basa en elementos fundamentales, como: agricultura industria, ganadería, comercio, turismo, etc. Pero el factor determinante entre estos es el sistema nacional de transporte es decir: transporte terrestre, transporte aéreo, transporte marítimo, etc. el cual es el enlace principal para el desarrollo de la sociedad. En Nicaragua el transporte terrestre es el más utilizado por la población, y debido al aumento de la movilización de vehículos con motores más potentes por las vías, obliga a la modernización de la infraestructura vial, permitiendo un tránsito más seguro y eficiente. El incremento de la red vial está vinculado directamente con la economía de nuestro país, pues su papel es primordial en las actividades que se realizan a diario en los diferentes sectores que aportan a la economía nacional. Actualmente la construcción de nuevas vías de comunicación, rehabilitación de carreteras y mejoras de los caminos ya existentes debe ser una necesidad para los gobiernos, ya que constituyen un componente fundamental para el bienestar y desarrollo de la sociedad, además su diseño debe adoptar las condiciones necesarias para obtener una obra de calidad; cumpliéndose en el todos los principios y normas correspondientes al diseño de carreteras. El presente trabajo denominado ‘‘Diseño de 1600 ML de calle, ubicados en los barrios: Anexo la Villa Rubén Ulloa, Villa Victoria de Julio y Antonio Mendoza localizados en el casco urbano de Tipitapa, municipio de Managua’’. Muestra en su contenido los estudios, métodos y normas aplicables para elaborar: el diseño geométrico de la vía, diseño hidráulico y de la estructura de pavimento, tomando en cuenta las especificaciones correspondientes al diseño de carreteras en Nicaragua

Allelic Gene Structure Variations in Anopheles gambiae Mosquitoes

Allelic gene structure variations and alternative splicing are responsible for transcript structure variations. More than 75% of human genes have structural isoforms of transcripts, but to date few studies have been conducted to verify the alternative splicing systematically.The present study used expressed sequence tags (ESTs) and EST tagged SNP patterns to examine the transcript structure variations resulting from allelic gene structure variations in the major human malaria vector, Anopheles gambiae. About 80% of 236,004 available A. gambiae ESTs were successfully aligned to A. gambiae reference genomes. More than 2,340 transcript structure variation events were detected. Because the current A. gambiae annotation is incomplete, we re-annotated the A. gambiae genome with an A. gambiae-specific gene model so that the effect of variations on gene coding could be better evaluated. A total of 15,962 genes were predicted. Among them, 3,873 were novel genes and 12,089 were previously identified genes. The gene completion rate improved from 60% to 84%. Based on EST support, 82.5% of gene structures were predicted correctly. In light of the new annotation, we found that approximately 78% of transcript structure variations were located within the coding sequence (CDS) regions, and >65% of variations in the CDS regions have the same open-reading-frame. The association between transcript structure isoforms and SNPs indicated that more than 28% of transcript structure variation events were contributed by different gene alleles in A. gambiae.We successfully expanded the A. gambiae genome annotation. We predicted and analyzed transcript structure variations in A. gambiae and found that allelic gene structure variation plays a major role in transcript diversity in this important human malaria vector

Targeting AKT induced Ferroptosis through FTO/YTHDF2-dependent GPX4 m6A methylation up-regulating and degradating in colorectal cancer

Ferroptosis is a new type of iron-dependent programmed cell death induced by lipid peroxidation. However, the underlying mechanisms and function in tumor therapy still remain undisclosed especially in post-transcription regulation. Here, we found that targeting AKT significantly induced GPX4 dependent ferroptosis and suppressed colorectal cancer growth both in vitro and in vivo. During this process, demethylase FTO was downregulated, which increased the m6A methylation level of GPX4, subsequently recognized by YTHDF2 and degraded. Prediction results showed that there are three potential methylated sites (193/647/766), and 193 site was identified as the right one, which was demethylated by FTO and read by YTHDF2. In parallel, AKT inhibition caused the accumulation of ROS which had a negative feedback on GPX4 expression. In addition, protective autophagy was initiated by MK2206 stimulation, while blocking autophagy further increased ferroptosis and markedly enhanced the anti-tumor activity of MK2206. In a word, inhibiting AKT activated ferroptosis through FTO/YTHDF2/GPX4 axis to suppress colon cancer progression, which raised FTO/GPX4 as potential biomarkers and targets in colorectal cancer therapy.</p

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor.

Tetrahydroprotoberberines (THPBs) are isoquinoline alkaloids isolated from the Chinese herb Corydalis yanhusuo. In the present study, we performed competitive binding assays to examine the binding of l-THBr to neurotransmitter receptors known to be involved in sedation, hypnosis and anxiety. Our results show that l-THBr does not interact with GABAergic receptors but has binding affinities for dopamine and serotonin receptors. In addition, cAMP and [35S]GTPγS assays were used to determine the agonist or antagonist properties of l-THBr at dopamine (D1, D2) or serotonin (5-HT) receptors. Our results show that l-THBr displays D1 and D2 antagonist and 5-HT1A agonist properties. Moreover, l-THBr-treated rodents exhibit anxiolytic-like effects in the light/dark box and elevated plus-maze tests, and the anxiolytic effect of l-THBr can be reduced by WAY-100635, a selective 5-HT1A receptor antagonist. Our results suggest that l-THBr may produce potent anxiolytic-like effects mainly through serotonin receptors

Cyclin-dependent kinase inhibitor flavopiridol promotes remyelination in a cuprizone induced demyelination model

<p>The cuprizone (CPZ) model has been widely used for the studies of de-and remyelination. The CPZ-exposed mice show oligodendrocyte precursor cells (OPCs) increase and mature oligodendrocytes decrease, suggesting an imbalance between proliferation and differentiation of OPCs. In the first experiment of this study, we examined the expression of cell cycle related genes in brains of mice following CPZ administration for 5 weeks by means of microarray assay. In addition, we performed a double labeling of BrdU and Ki-67 to calculate cell cycle exit index in the mice. Our results showed that CPZ administration up-regulated the expression of 16 cell cycle related genes, but down-regulated the expression of only one in the prefrontal cortex (PFC) of mice compared to control group. The treatment inhibited potential precursor cells exit from cell cycle. In the second experiment, we evaluated effects of a CDK inhibitor flavopiridol (FLA) on CPZ-induced neuropathological changes and spatial working memory impairment in mice.FLA treatment for one week effectively attenuated the CPZ-induced increases in NG2 positive cells, microglia and astrocytes, alleviated the concurrent mature oligodendrocyte loss and myelin breakdown, and improved spatial working memory deficit in the CPZ-exposed mice. These results suggest that CPZ-induced neuropathological changes involve in dysregulation of cell cycle related genes. The therapeutic effects of FLA on CPZ-exposed mice may be related to its ability of cell cycle inhibition.</p

Effects of <i>l</i>-THBr on locomotor activity in mice.

<p>(A) The distance traveled within a 10 min interval. (B) The total distance traveled within 60 min. The data are represented as the means ± S.E.M.</p

Recovery Sleep Reverses Impaired Response Inhibition due to Sleep Restriction: Evidence from a Visual Event Related Potentials Study

<div><p>Objective</p><p>To investigate response inhibition after total sleep deprivation (TSD) and the restorative effects of one night of recovery sleep (RS).</p><p>Methods</p><p>Fourteen healthy male participants performed a visual Go/NoGo task, and electroencephalogram recordings were conducted at five time points: (1) baseline, (2) after 12 h of TSD, (3) after 24 h of TSD, (4) after 36 h of TSD, and (5) following 8 h of RS. The dynamic changes in response inhibition during TSD and after 8 h of RS were investigated by examining the NoGo-N2 and NoGo-P3 event-related potential components.</p><p>Results</p><p>Compared with baseline, NoGo-P3 amplitudes were decreased, while the NoGo-N2 latency increased along with the awake time prolonged. NoGo anteriorization, which was minimized after 24 h of TSD, progressively decreased with increasing TSD. After 8 h of RS, recoveries of both the NoGo-P3 amplitude and NoGo-N2 latency in the prefrontal cortex were observed compared with the values after 36 h of TSD.</p><p>Conclusion</p><p>TSD induced a dose-dependent functional decline in the response inhibition of NoGo-N2 and NoGo-P3 on prefrontal cortex activation, and 8 h of RS resulted in recovery or maintenance of the response inhibition. However, it was not restored to baseline levels.</p><p>Limitations</p><p>Participants were chosen male college students only, thus the findings cannot be generalized to older people and women. Additionally, the sample size was small, and, thus, speculations on the meaning of the results of this study should be cautious. The EEG continuous recording should be employed to monitor the decline of alertness following TSD.</p></div

<i>l</i>-THBr acts as an antagonist at D₁ dopamine receptors.

<p>(A) The effects of the D₁ receptor agonist SKF 38393 and <i>l</i>-THBr on cAMP formation in CHO cells expressing the D₁ receptor. The EC₅₀ of SKF 38393 was calculated. (B) The inhibition of cAMP formation induced by SKF 38393 (10 μM) by the D₁ receptor antagonist SKF 23390 and <i>l</i>-THBr in CHO cells expressing the D₁ receptor. Curves were fitted by non-linear regression analysis. The half maximal inhibitory concentration (IC₅₀) was calculated. The means ± S.E.M. from three independent experiments performed in duplicate are shown.</p

Chemical structure of levo-tetrahydroberberrubine (<i>l</i>-THBr).

<p>Chemical structure of levo-tetrahydroberberrubine (<i>l</i>-THBr).</p

<i>l</i>-THBr acts as an antagonist at D₂ dopamine receptors.

<p>(A) Dose-response curves of quinpirole- or l-THBr–induced [³⁵S]GTPγS binding in HEK293 cells expressing the human D₂ dopamine receptor. (B) <i>l</i>-THBr significantly attenuates the binding of [³⁵S]GTPγS to D₂ receptors induced by quinpirole (10 μM). Curves were fitted by non-linear regression analysis. The means ± S.E.M from three independent experiments in duplicate are shown.</p