Molecular characterization of autophagic and apoptotic signaling induced by sorafenib in liver cancer cells

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5′AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P-JNK1/2/JNK1/2, Thr172P-AMPKα, Ser413P-Foxo3a, Thr308P-AKt/AKt and Thr32P-Foxo3a/Foxo3a ratios, and reduction of Ser2481P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL, Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308P-AKt/AKt and Ser473P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation.Ministerio de Economía y Competitividad BFU2016‐75352‐PInstituto de Salud Carlos III PI15/00034, PI13/ 00021, PI16/00090, PI14/01349Ministerio de Educación FPU16/05127, FPU12/01433, FPU13/01237Junta de Andalucía CTS-6264, PI-00025-2013, PI-0127-2013, PI-0198-201

Composición, propiedades, estabilidad y comportamiento térmico del aceite de semilla de tamarindo (Tamarindus indica)

The composition, thermal stability and phase behavior of tamarind (Tamarindus indica) seed oil were analyzed to contribute to the exploration of their potential uses. The oil was extracted from the kernel of the tamarind seed with hexane, and its main physical, chemical and thermal properties were analyzed by infrared spectrometry, gas chromatography-mass spectrometry, DSC, and TGA. The results showed that the tamarind seed had a 3.76 ± 0.20% oil with a saponification index of 174.80 ± 9.87 mg KOH/g and the major fatty acids were lignoceric (20.15%), oleic (18.99%) and palmitic (11.99%). Stearic, behenic, linoleic, arachidic, and other fatty acids were also present. TGA and DSC showed that in an inert atmosphere, the triacylglycerols of tamarind seed oil (TSO) are decomposed in a single stage that starts at 224.1 °C and in an air atmosphere in three stages, initiating its decomposition at 218 °C. The TSO showed crystallization and fusion curves with a single maximum peak with Tonset and Toffset of 20.16 and ?38.8 °C and ?22.2 and 28.6 °C, respectively. The solid fat profile of the oil showed a semi-solid and liquid consistency in the ambient temperature range. The composition, thermal and phase behavior showed that TSO is potentially useful for alimentary, pharmacological, and cosmetological purposes.La composición, estabilidad y comportamiento térmico del aceite de semilla de tamarindo (Tamarindus indica) fueron analizadas con el fin de contribuir al conocimiento de sus potenciales usos. El aceite fue extraído del núcleo de la semilla con hexano y analizado mediante sus principales propiedades físicas, químicas y térmicas mediante espectrometría infrarroja, cromatografía de gases, espectroscopia de masas, calorimetría (DSC) y termogravimetría (TGA). Los resultados mostraron que las semillas del tamarindo tuvieron un contenido de aceite de 3,76 ± 0,20%, con un índice de saponificación de 174,80 ± 9,87mg KOH/g y ácidos grasos mayoritarios: Lignocérico (20,15%), oleico (18,99%), palmítico (11,99%) y en cantidades menores los ácidos esteárico, behénico, linoleico y araquídico, entre otros. El análisis mediante TGA y DSC mostró que la temperatura inicial de descomposición del aceite fue de 224,1 °C en una sola etapa en atmósfera inerte y en atmósfera de aire fue a 218 °C en tres etapas. El aceite mostró curvas de cristalización y fusión con un solo máximo, iniciándose y finalizando estos cambios de fase a 20,16 y -38,8 °C, and -22,2 y 28,6 °C, respectivamente. Estas propiedades mostraron que el aceite de la semilla de tamarindo tiene potenciales aplicaciones en alimentos y productos farmacológicos y cosméticos

The Effects of the Transition from Home-based Childcare to Childcare Centers on Children's Health and Development in Colombia

Colombia’s national early childhood strategy launched in 2011 aimed at improving the quality of childcare services offered to socio-economically vulnerable children, and included the possibility that children and their childcare providers could transfer from nonparental family daycare units to large childcare centers in urban areas. This study seeks to understand whether the offer to transfer and the actual transfer from one program to the other had an impact on child cognitive and socioemotional development, and nutrition, using a cluster-randomized control trial with a sample of 2,767 children between the ages of 6 and 60 months located in 14 cities in Colombia. The results indicate a negative effect of this initiative on cognitive development, a positive effect on nutrition and no statistically significant effect of the intervention on socioemotional development. We also explored the extent to which these impacts might be explained by differences in the quality of both services during the transition, and report that quality indicators are low in both programs but are significantly worse in centers compared to community nurseries

Examining the relationship between semiquantitative methods analysing concentration-time and enhancement-time curves from dynamic-contrast enhanced magnetic resonance imaging and cerebrovascular dysfunction in small vessel disease

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to examine the distribution of an intravenous contrast agent within the brain. Computational methods have been devised to analyse the contrast uptake/washout over time as reflections of cerebrovascular dysfunction. However, there have been few direct comparisons of their relative strengths and weaknesses. In this paper, we compare five semiquantitative methods comprising the slope and area under the enhancement-time curve, the slope and area under the concentration-time curve ( SlopeCon and AUCCon ), and changes in the power spectrum over time. We studied them in cerebrospinal fluid, normal tissues, stroke lesions, and white matter hyperintensities (WMH) using DCE-MRI scans from a cohort of patients with small vessel disease (SVD) who presented mild stroke. The total SVD score was associated with AUCCon in WMH ( p0.05 ) and WMH burden ( p>0.05 ). Our results show the potential of different measures extracted from concentration-time curves extracted from the same DCE examination to demonstrate cerebrovascular dysfunction better than those extracted from enhancement-time curves

The onset and growth of the 2018 Martian Global Dust Storm

We analyze the onset and initial expansion of the 2018 Martian Global Dust Storm (GDS 2018) using ground-based images in the visual range. This is the first case of a confirmed GDS initiating in the Northern Hemisphere. A dusty area extending about 1.4x10e5 km^2 and centered at latitude +31.7{\deg} $\pm$ 1.8{\deg} and west longitude 18{\deg} $\pm$ 5{\deg}W in Acidalia Planitia was captured on 30 and 31 May 2018 (Ls = 184.9{\deg}). From 1 to 8 June, daily image series showed the storm expanding southwards along the Acidalia corridor with velocities of 5 m/s, and simultaneously progressing eastwards and westwards with horizontal velocities ranging from 5 to 40 m/s. By 8 June the dust reached latitude -55{\deg} and later penetrated in the South polar region, whereas in the North the dust progression stopped at latitude +46{\deg}. We compare the onset and expansion stage of this GDS with the previous confirmed storms.Comment: Accepted in Geophysical Research Letters. Main article and Supporting Informatio

High dosage thermoluminescence diamond dosimeters

Diamond thin films have been irradiated with high doses (up to 12.8 kGy) of ⁹⁰Sr beta particles. The diamond thin films have been synthesized from commercial Tequila as a precursor using pulsed liquid injection by chemical vapor deposition technique reported recently. Thermoluminescence phenomena at these doses exhibit peak curve shift to higher temperatures (from 370 to 440 K) in the glow curve and the integrated thermoluminescence curve show a linear behavior. Therefore, it has been considered that diamond thin films could be used as high doses dosimeters.Алмазні тонкі плівки, які було синтезовано хімічним осадженням парів з промислово виробленої Текіли в якості прекурсору з використанням методу імпульсного упорскування рідини, про який було нещодавно повідомлено, опромінювали високими (до 12,8 кГр) дозами бета-частинок ⁹⁰Sr. При таких дозах опромінення максимум кривої термолюмінесценції зсувається до більш високих (від 370 до 440 K) температур і залежність інтегрованої термолюмінесценції від дози опромінювання є лінійною. Тому алмазні тонкі плівки можуть бути використані як дозиметри при високих дозах опромінювання.Алмазные тонкие пленки, которые были синтезированы химическим осаждением паров из промышленно произведенной Текилы в качестве прекурсора при использовании метода импульсного впрыскивания жидкости, о котором недавно было сообщено, облучали высокими (до 12,8 кГр) дозами бета-частиц ⁹⁰Sr. При таких дозах облучения максимум кривой термолюминесценции сдвигается в область более высоких (от 370 до 440 K) температур и зависимость интегрированной термолюминесценции от дозы облучения является линейной. Поєтому алмазные тонкие пленки могут быть использованы как дозиметры при высоких дозах облучения

Analysis of dynamic texture and spatial spectral descriptors of dynamic contrast-enhanced brain magnetic resonance images for studying small vessel disease

Cerebral small vessel disease (SVD) comprises various pathological processes affecting small brain vessels and damaging white and grey matter. In this paper, we propose a framework comprising region of interest sampling, dynamic spectral and texture description, functional principal component analysis, and statistical analysis to study exogenous contrast agent distribution over time in various brain regions in patients with recent mild stroke and SVD features.We compared our results against current semi-quantitative surrogates of dysfunction such as signal enhancement area and slope. Biological sex, stroke lesion type and overall burden of white matter hyperintensities (WMH) were significant predictors of intensity, spectral, and texture features extracted from the ventricular region (p-value < 0.05), explaining between a fifth and a fourth of the data variance (0.20 ≤Adj.R2 ≤ 0.25). We observed that spectral feature reflected more the dysfunction compared to other descriptors since the overall WMH burden explained consistently the power spectra variability in blood vessels, cerebrospinal fluid, deep grey matter and white matter. Our preliminary results show the potential of the framework for the analysis of dynamic contrast-enhanced brain magnetic resonance imaging acquisitions in SVD since significant variation in our metrics was related to the burden of SVD features. Therefore, our proposal may increase sensitivity to detect subtle features of small vessel dysfunction. A public version of the code will be released on our research website

U B V R I Photometry of Stellar Structures throughout the Disk of the Barred Galaxy NGC 3367

We report new detailed surface U, B, V, R, and I photometry of 81 stellar structures in the disk of the barred galaxy NGC 3367. The images show many different structures indicating that star formation is going on in the most part of the disk. NGC 3367 is known to have a very high concentration of molecular gas distribution in the central regions of the galaxy and bipolar synchrotron emission from the nucleus with two lobes (at 6 kpc) forming a triple structure similar to a radio galaxy. We have determined the U, B, V, R, and I magnitudes and U - B, B - V, U - V, and V - I colors for the central region (nucleus), a region which includes supernovae 2003 AA, and 79 star associations throughout NGC 3367. Estimation of ages of star associations is very difficult due to several factors, among them: filling factor, metallicity, spatial distribution of each structure and the fact that we estimated the magnitudes with a circular aperture of 16 pixels in diameter, equivalent to $6''.8\sim1.4$ kpc. However, if the colors derived for NGC 3367 were similar to the colors expected of star clusters with theoretical evolutionary star tracks developed for the LMC and had a similar metallicity, NGC 3367 show 51 percent of the observed structures with age type SWB I (few tens of Myrs), with seven sources outside the bright surface brightness visible disk of NGC 3367.Comment: Accepted for publication (abr 2007) in The Astronomical Journal (July 2007 issue