The selectivity of neuronal responses arises from the architecture of excitatory and inhibitory connections. In the primary visual cortex, the selectivity of a neuron in layer 2/3 for stimulus ...orientation and direction is thought to arise from intracortical inputs that are similarly selective
. However, the excitatory inputs of a neuron can have diverse stimulus preferences
, and inhibitory inputs can be promiscuous
and unselective
. Here we show that the excitatory and inhibitory intracortical connections to a layer 2/3 neuron accord with its selectivity by obeying precise spatial patterns. We used rabies tracing
to label and functionally image the excitatory and inhibitory inputs to individual pyramidal neurons of layer 2/3 of the mouse visual cortex. Presynaptic excitatory neurons spanned layers 2/3 and 4 and were distributed coaxial to the preferred orientation of the postsynaptic neuron, favouring the region opposite to its preferred direction. By contrast, presynaptic inhibitory neurons resided within layer 2/3 and favoured locations near the postsynaptic neuron and ahead of its preferred direction. The direction selectivity of a postsynaptic neuron was unrelated to the selectivity of presynaptic neurons, but correlated with the spatial displacement between excitatory and inhibitory presynaptic ensembles. Similar asymmetric connectivity establishes direction selectivity in the retina
. This suggests that this circuit motif might be canonical in sensory processing.
Context. The circular polarization of light that planets reflect is often neglected because it is very small compared to the linear polarization. It could, however, provide information on a planet’s ...atmosphere and surface, and on the presence of life, because homochiral molecules that are the building blocks of life on Earth are known to reflect circularly polarized light. Aims. We compute Pc, the degree of circular polarization, of light that is reflected by rocky (exo)planets to provide insight into the viability of circular spectropolarimetry for characterizing (exo)planetary atmospheres. Methods. We compute the Pc of light that is reflected by rocky (exo)planets with liquid water or sulfuric acid solution clouds, both spatially resolved across the planetary disk and, for planets with patchy clouds, integrated across the planetary disk, for various planetary phase angles α. Results. The optical thickness and vertical distribution of the atmospheric gas and clouds, the size parameter and refractive index of the cloud particles, and α all influence Pc. Spatially resolved, Pc varies between ± 0.20% (the sign indicates the polarization direction). Only for small gas optical thicknesses above the clouds do significant sign changes (related to cloud particle properties) across the planets’ hemispheres occur. For patchy clouds, the disk-integrated Pc is typically smaller than ± 0.025%, with maximum for α between 40° and 70°, and 120° to 140°. As expected, the disk-integrated Pc is virtually zero at α = 0° and 180°. The disk-integrated Pc is also very small at α ≈ 100°. Conclusions. Measuring circular polarization signals appears to be challenging with current technology. The small atmospheric circular polarization signal could, however, allow the detection of circular polarization due to homochiral molecules such as those associated with life on Earth. Confirmation of the detectability of such signals requires better knowledge of the strength of circular polarization signals of biological sources and in particular of the angular distribution of their scattering.
Natural extracts are frequently adopted as a valuable alternative to antibiotics in intensive animal farming. Their diverse bioactive constituents such as phytosterols, glucosinolates, carotenoids ...and polyphenols have shown antioxidant, anti-inflammatory and antibacterial effects. Tannins are the largest class of polyphenol compounds of plant extracts, which can be classified into two hydrolysable or condensed subgroups. Poultry and swine nutrition are the most important sectors in which tannins have been used, firstly adopting tannin-rich feedstuffs and more recently, using tannin extracts from different plants. Several commercial products are available containing tannins extracted from the European chestnut tree (Castanea sativa Mill.) and the American quebracho (Schinopsis spp.). Tannins extracted from these plants have been applied on intensive swine farms due to their ability to improve animal performance and health. These positive and prominent effects are frequently associated with the antinutritional effects in reducing feed palatability, digestibility and protein utilization of feed. Some criticisms and contrasting results regarding pig performance and intestinal health have been reported. This paper provides an overview of the effects of chestnut and quebracho tannins on growth performance and intestinal health of pigs in order to clarify the appropriate dosage and response in the various physiological stages.
Context. Clouds have already been detected in exoplanetary atmospheres. They play crucial roles in a planet’s atmosphere and climate and can also create ambiguities in the determination of ...atmospheric parameters such as trace gas mixing ratios. Knowledge of cloud properties is required when assessing the habitability of a planet. Aims. We aim to show that various types of cloud cover such as polar cusps, subsolar clouds, and patchy clouds on Earth-like exoplanets can be distinguished from each other using the polarization and flux of light that is reflected by the planet. Methods. We have computed the flux and polarization of reflected starlight for different types of (liquid water) cloud covers on Earth-like model planets using the adding-doubling method, that fully includes multiple scattering and polarization. Variations in cloud-top altitudes and planet-wide cloud cover percentages were taken into account. Results. We find that the different types of cloud cover (polar cusps, subsolar clouds, and patchy clouds) can be distinguished from each other and that the percentage of cloud cover can be estimated within 10%. Conclusions. Using our proposed observational strategy, one should be able to determine basic orbital parameters of a planet such as orbital inclination and estimate cloud coverage with reduced ambiguities from the planet’s polarization signals along its orbit.
We computed proper motions of a selected sample of globular clusters projected on the central bulge, employing CCD images gathered along the last 25 yr at the ESO-New Technology Telescope, ESO-Danish ...and Hubble Space Telescope telescopes. We presented a method to derive their proper motions, and a set of coordinate transformations to obtain 3D Galactic velocity vectors of the clusters. We analysed 10 globular clusters, namely Terzan 1, Terzan 2, Terzan 4, Terzan 9, NGC 6522, NGC 6558, NGC 6540, AL 3, ESO456-SC38 and Palomar 6. For comparison purposes, we also studied the outer bulge cluster NGC 6652. We discuss the general properties of the proper-motion-cleaned colour-magnitude Diagrams, derived for the first time for most of them. A general conclusion is that the inner bulge globular clusters have clearly lower transverse motions (and spatial velocities) than halo clusters, and appear to be trapped in the bulge bar.
Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in ...the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatmentsare desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options.
The Asian lineage of Zika virus (ZIKV) has recently caused epidemics and severe disease. Unraveling the mechanisms causing increased viral transmissibility and disease severity requires experimental ...systems. We report an infectious cDNA clone of ZIKV that was generated using a clinical isolate of the Asian lineage. The cDNA clone-derived RNA is infectious in cells, generating recombinant ZIKV. The recombinant virus is virulent in established ZIKV mouse models, leading to neurological signs relevant to human disease. Additionally, recombinant ZIKV is infectious for Aedes aegypti and thus provides a means to examine virus transmission. The infectious cDNA clone was further used to generate a luciferase ZIKV that exhibited sensitivity to a panflavivirus inhibitor, highlighting its potential utility for antiviral screening. This ZIKV reverse genetic system, together with mouse and mosquito infection models, may help identify viral determinants of human virulence and mosquito transmission as well as inform vaccine and therapeutic strategies.
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•An infectious cDNA clone of Zika virus and a luciferase reporter virus were developed•Recombinant Zika virus is virulent in A129 and AG129 mice•Recombinant Zika virus is highly infectious for Aedes aegypti mosquitos•The luciferase Zika virus can be used for antiviral drug discovery
Zika virus (ZIKV) is causing devastating epidemics with severe disease. Shan et al. generated an infectious cDNA clone of ZIKV as well as a luciferase reporter virus. Recombinant ZIKV is virulent in mice and infectious in Aedes aegypti and thus may help identify viral determinants of virulence and transmission.
The high-throughput analysis of microRNAs (miRNAs) circulating within the blood of healthy and diseased individuals is an active area of biomarker research. Whereas quantitative real-time reverse ...transcription polymerase chain reaction (qPCR)-based methods are widely used, it is yet unresolved how the data should be normalized. Here, we show that a combination of different algorithms results in the identification of candidate reference miRNAs that can be exploited as normalizers, in both discovery and validation phases. Using the methodology considered here, we identify normalizers that are able to reduce nonbiological variation in the data and we present several case studies, to illustrate the relevance in the context of physiological or pathological scenarios. In conclusion, the discovery of stable reference miRNAs from high-throughput studies allows appropriate normalization of focused qPCR assays.
•Strontium is incorporated into bone mineral during treatment with strontium ranelate.•The incorporation of strontium into the nanocrystals may change their properties.•The structure and composition ...of the mineral need to be evaluated at the nanoscale.•Advanced microscopy and microanalytical methods show great potential for this analysis.
The interest in effects of strontium (Sr) on bone has greatly increased in the last decade due to the development of the promising drug strontium ranelate. This drug is used for treating osteoporosis, a major bone disease affecting hundreds of millions of people worldwide, especially postmenopausal women. The novelty of strontium ranelate compared to other treatments for osteoporosis is its unique effect on bone: it simultaneously promotes bone formation by osteoblasts and inhibits bone resorption by osteoclasts. Besides affecting bone cells, treatment with strontium ranelate also has a direct effect on the mineralized bone matrix. Due to the chemical similarities between Sr and Ca, a topic that has long been of particular interest is the incorporation of Sr into bones replacing Ca from the mineral phase, which is composed by carbonated hydroxyapatite nanocrystals. Several groups have analyzed the mineral produced during treatment; however, most analysis were done with relatively large samples containing numerous nanocrystals, resulting thus on data that represents an average of many crystalline domains. The nanoscale analysis of the bone apatite crystals containing Sr has only been described in a few studies. In this study, we review the current knowledge on the effects of Sr on bone mineral and discuss the methodological approaches that have been used in the field. In particular, we focus on the great potential that advanced microscopy and microanalytical techniques may have on the detailed analysis of the nanostructure and composition of bone apatite nanocrystals produced during treatment with strontium ranelate.
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