In the past few years, 3D electron microscopy (3DEM) has undergone a revolution in instrumentation and methodology. One of the central players in this wide-reaching change is the continuous ...development of image processing software. Here we present Scipion, a software framework for integrating several 3DEM software packages through a workflow-based approach. Scipion allows the execution of reusable, standardized, traceable and reproducible image-processing protocols. These protocols incorporate tools from different programs while providing full interoperability among them. Scipion is an open-source project that can be downloaded from http://scipion.cnb.csic.es.
Summary
Aging contributes to the appearance of several retinopathies and is the largest risk factor for aged‐related macular degeneration, major cause of blindness in the elderly population. ...Accumulation of undegraded material as lipofuscin represents a hallmark in many pathologies of the aged eye. Autophagy is a highly conserved intracellular degradative pathway that plays a critical role in the removal of damaged cell components to maintain the cellular homeostasis. A decrease in autophagic activity with age observed in many tissues has been proposed to contribute to the aggravation of age‐related diseases. However, the participation of different autophagic pathways to the retina physiopathology remains unknown. Here, we describe a marked reduction in macroautophagic activity in the retina with age, which coincides with an increase in chaperone‐mediated autophagy (CMA). This increase in CMA is also observed during retinal neurodegeneration in the Atg5flox/flox; nestin‐Cre mice, a mouse model with downregulation of macroautophagy in neuronal precursors. In contrast to other cell types, this autophagic cross talk in retinal cells is not bi‐directional and CMA inhibition renders cone photoreceptor very sensitive to stress. Temporal and cell‐type‐specific differences in the balance between autophagic pathways may be responsible for the specific pattern of visual loss that occurs with aging. Our results show for the first time a cross talk of different lysosomal proteolytic systems in the retina during normal aging and may help the development of new therapeutic intervention for age‐dependent retinal diseases.
In this work, we present a configurable encryption system based on the Encryption by Synchronization in a Cellular Automata (ESCA) system, which is a symmetric key algorithm based on the ...synchronization phenomenon of Cellular Automata with rule-90. With the aim of producing a flexible system to trade-off power consumption and security level, we implemented a pseudo-random number generator (PRNG) that can be configured with three different key sizes. This variable-length PRNG, together with the capability of bypassing specific modules in the rest of the system, allow us to operate under a wide range of applications. In particular, it would enable online adjustments in IoT and power-constrained devices to fine-tune them between a low-power consumption and a maximum-security level. The system can be implemented with 5956gates, and it is designed to provide in a 0.5<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> CMOS process a throughput of 50Mbps @ 37mW, at the maximum-security level, and an energy consumption of less than 7mW @ 30Mbps at the lowest-security level, while still providing a satisfactory perceptual security metric.
The initial colonization of the Americas remains a highly debated topic
, and the exact timing of the first arrivals is unknown. The earliest archaeological record of Mexico-which holds a key ...geographical position in the Americas-is poorly known and understudied. Historically, the region has remained on the periphery of research focused on the first American populations
. However, recent investigations provide reliable evidence of a human presence in the northwest region of Mexico
, the Chiapas Highlands
, Central Mexico
and the Caribbean coast
during the Late Pleistocene and Early Holocene epochs. Here we present results of recent excavations at Chiquihuite Cave-a high-altitude site in central-northern Mexico-that corroborate previous findings in the Americas
of cultural evidence that dates to the Last Glacial Maximum (26,500-19,000 years ago)
, and which push back dates for human dispersal to the region possibly as early as 33,000-31,000 years ago. The site yielded about 1,900 stone artefacts within a 3-m-deep stratified sequence, revealing a previously unknown lithic industry that underwent only minor changes over millennia. More than 50 radiocarbon and luminescence dates provide chronological control, and genetic, palaeoenvironmental and chemical data document the changing environments in which the occupants lived. Our results provide new evidence for the antiquity of humans in the Americas, illustrate the cultural diversity of the earliest dispersal groups (which predate those of the Clovis culture) and open new directions of research.
Metal smelting and processing are highly polluting activities that have a strong influence on the levels of heavy metals in air, soil, and crops. We employ an atmospheric transport and dispersion ...model to predict the pollution levels originated from the second largest Cu-smelter in Europe. The model predicts that the concentrations of copper (Cu), zinc (Zn), and arsenic (As) in an urban area close to the Cu-smelter can reach 170, 70, and 30ngm−3, respectively. The model captures all the observed urban pollution events, but the magnitude of the elemental concentrations is predicted to be lower than that of the observed values; ~300, ~500, and ~100ngm−3 for Cu, Zn, and As, respectively. The comparison between model and observations showed an average correlation coefficient of 0.62±0.13. The simulation shows that the transport of heavy metals reaches a peak in the afternoon over the urban area. The under-prediction in the peak is explained by the simulated stronger winds compared with monitoring data. The stronger simulated winds enhance the transport and dispersion of heavy metals to the regional area, diminishing the impact of pollution events in the urban area. This model, driven by high resolution meteorology (2km in horizontal), predicts the hourly-interval evolutions of atmospheric heavy metal pollutions in the close by urban area of industrial hotspot.
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•Atmospheric heavy metals from a large Cu-smelter were predicted by the HYSPLIT.•The high-resolution predictions were evaluated with hourly measurement data.•The model captured all the urban pollution events during two measurement campaigns.•The transport of Cu-smelter pollutants peaked during the afternoon at the urban area.•The low-resolution global HYSPLIT predictions were further constrained.
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.
The early sorafenib‐induced endoplasmic reticulum (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 BimEL, which was associated with the shift from autophagy to apoptosis.
The impact of road dust emissions on PM10 and PM2.5 (atmospheric particulate matter with diameteer < 10 μm and 2.5 μm mass concentrations recorded from 2003 to 2010 at 11 locations (rural, urban and ...industrial) in southern Spain was estimated based on the chemical characterization of PM and the use of a constrained Positive Matrix Factorization, where the chemical profile of local road dust samples is used as a priori knowledge. Results indicate that road dust increased PM10 levels on average by 21–35% at traffic sites, 29–34% at urban background sites heavily affected by road traffic emissions, 17–22% at urban-industrial sites and 9–22% at rural sites. Road dust contributions to ambient PM levels show a marked seasonality with maxima in summer and minima in winter, likely due to the rainfall frequency. Decreasing concentration trends over the sampling years were found at some traffic and urban sites but in most cases the decreases were less significant than for vehicle exhaust emissions, while concentrations increased at industrial sites, probably due to local peculiarities. Concerning PM2.5, road dust contributions were lower than in PM10, as expected but still important (21–31%, 11–31%, 6–16% and 7% for traffic, urban background, urban-industrial and rural sites, respectively). In addition the three main sources of road dust (carbonaceous particles, brake wear and road wear/mineral) were identified and their contributions to road dust mass loadings estimated, supporting the idea that air quality managers should drive measures aimed at preventing the build-up of road dust particles on roads.
In many large cities of Europe standard air quality limit values of particulate matter (PM) are exceeded. Emissions from road traffic and biomass burning are frequently reported to be the major ...causes. As a consequence of these exceedances a large number of air quality plans, most of them focusing on traffic emissions reductions, have been implemented in the last decade. In spite of this implementation, a number of cities did not record a decrease of PM levels. Thus, is the efficiency of air quality plans overestimated? Do the road traffic emissions contribute less than expected to ambient air PM levels in urban areas? Or do we need a more specific metric to evaluate the impact of the above emissions on the levels of urban aerosols? This study shows the results of the interpretation of the 2009 variability of levels of PM, Black Carbon (BC), aerosol number concentration (N) and a number of gaseous pollutants in seven selected urban areas covering road traffic, urban background, urban-industrial, and urban-shipping environments from southern, central and northern Europe. The results showed that variations of PM and N levels do not always reflect the variation of the impact of road traffic emissions on urban aerosols. However, BC levels vary proportionally with those of traffic related gaseous pollutants, such as CO, NO2 and NO. Due to this high correlation, one may suppose that monitoring the levels of these gaseous pollutants would be enough to extrapolate exposure to traffic-derived BC levels. However, the BC/CO, BC/NO2 and BC/NO ratios vary widely among the cities studied, as a function of distance to traffic emissions, vehicle fleet composition and the influence of other emission sources such as biomass burning. Thus, levels of BC should be measured at air quality monitoring sites. During morning traffic rush hours, a narrow variation in the N/BC ratio was evidenced, but a wide variation of this ratio was determined for the noon period. Although in central and northern Europe N and BC levels tend to vary simultaneously, not only during the traffic rush hours but also during the whole day, in urban background stations in southern Europe maximum N levels coinciding with minimum BC levels are recorded at midday in all seasons. These N maxima recorded in southern European urban background environments are attributed to midday nucleation episodes occurring when gaseous pollutants are diluted and maximum insolation and O3 levels occur. The occurrence of SO2 peaks may also contribute to the occurrence of midday nucleation bursts in specific industrial or shipping-influenced areas, although at several central European sites similar levels of SO2 are recorded without yielding nucleation episodes. Accordingly, it is clearly evidenced that N variability in different European urban environments is not equally influenced by the same emission sources and atmospheric processes. We conclude that N variability does not always reflect the impact of road traffic on air quality, whereas BC is a more consistent tracer of such an influence. However, N should be measured since ultrafine particles (<100 nm) may have large impacts on human health. The combination of PM10 and BC monitoring in urban areas potentially constitutes a useful approach for air quality monitoring. BC is mostly governed by vehicle exhaust emissions, while PM10 concentrations at these sites are also governed by non-exhaust particulate emissions resuspended by traffic, by midday atmospheric dilution and by other non-traffic emissions.
Abstract Mouse models of retinal degeneration are useful tools to study therapeutic approaches for patients affected by hereditary retinal dystrophies. We have studied degeneration in the rd10 mice ...both by immunocytochemistry and TUNEL-labeling of retinal cells, and through electrophysiological recordings. The cell degeneration in the retina of rd10 mice produced appreciable morphological changes in rod and cone cells by P20. Retinal cell death is clearly observed in the central retina and it peaked at P25 when there were 800 TUNEL-positive cells per mm2 . In the central retina, only one row of photoreceptors remained in the outer nuclear layer by P40 and there was a remarkable deterioration of bipolar cell dendrites postsynaptic to photoreceptors. The axon terminals of bipolar cells also underwent atrophy and the inner retina was subject to further changes, including a reduction and disorganization of AII amacrine cell population. Glutamate sensitivity was tested in rod bipolar cells with the single cell patch-clamp technique in slice preparations, although at P60 no significant differences were observed with age-matched controls. Thus, we conclude that rod and cone degeneration in the rd10 mouse model is followed by deterioration of their postsynaptic cells and the cells in the inner retina. However, the functional preservation of receptors for photoreceptor transmission in bipolar cells may open new therapeutic possibilities.
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