ON/OFF domains shape receptive fields in mouse visual cortex

In higher mammals, thalamic afferents to primary visual cortex (area V1) segregate according to their responses to increases (ON) or decreases (OFF) in luminance1–4. This organization induces columnar, ON/OFF domains postulated to provide a scaffold for the emergence of orientation tuning2,5–15. To further test this idea, we asked whether ON/OFF domains exist in mouse V1 – a species containing orientation tuned, simple cells, like those found in other mammals16–19. Here we show that mouse V1 is indeed parceled into ON/OFF domains. Revealingly, fluctuations in the relative density ON/OFF neurons on the cortical surface mirror fluctuations in the relative density of ON/OFF receptive field centers on the visual field. In each cortical volume examined, the average of simple-cell receptive fields correlates with the difference between the average of ON and OFF receptive fields7. Moreover, the local diversity of simple-cell receptive fields is explained by a model in which neurons linearly combine a small number of ON and OFF signals available in their cortical neighborhoods15,20. Altogether, these findings indicate that ON/OFF domains originate in fluctuations of the spatial density of ON/OFF inputs on the visual field which, in turn, shapes the structure of receptive fields10–13,21–23.

Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation

Bladder cancer constitutes one of the deadliest genitourinary diseases, especially when diagnosed at late stages. These tumours harbour microenvironmental niches characterized by low levels of oxygen (hypoxia) and limited glucose supply due to poor vascularization. However, the synergic contribution of these features to disease development is poorly understood. Here, we demonstrated that cells with distinct histopathological and molecular backgrounds responded similarly to such stimuli. Cancer cells arrested proliferation, significantly increased invasive capacity in vitro and enhanced tolerance to cisplatin-based chemotherapy. Reoxygenation and access to glucose restored basal proliferation and invasion levels without triggering stress-induced apoptosis, denoting significant cellular plasticity in adapting to microenvironmental cues. Whole transcriptomics showed major molecular reprogramming, supporting main functional alterations. Metabolomics evidenced fatty acids β-oxidation as main bioenergetic pathway rather than anaerobic glycolysis generally adopted by hypoxic cells. Joint pathway analysis also suggested relevant alterations in mucin-type O-glycan biosynthesis. Glycomics confirmed a major antagonization of O-glycosylation pathways, leading to simple cell glycophenotypes characterized by the accumulation of immature short-chain O-glycans such as Tn and STn antigens at the cell surface. Glycoengineered models reflecting simple cell glycophenotypes were developed and functional studies in vitro and in vivo showed that Tn and STn overexpression decreased proliferation and promoted chemoresistance, reinforcing their close link with tumour aggressiveness. Collectively, we have demonstrated that hypoxia and glucose deprivation trigger more aggressive cell behaviours, in what appears to be an escape mechanism from microenvironmental stress. We propose that, altered glycosylation may be used to target these subpopulations, paving the way for precision oncology.

How simple cell to cell communication rules can generate and maintain scale invariant gradients of signalling activity across a multicellular population

This paper shows computationally and conceptually how gradients of signalling activity can be generated and dynamically maintained across a population of cells using very simple cell to cell communication rules. The rules work on the basis of cells regulating their production rate of a signalling molecule according to the production rates of their immediate neighbours. Highly stable, scale invariant signalling gradients can be formed across the population, with highest rates at the centre and lowest at the periphery.The cell to cell communication behaviour that causes gradient formation is first explained in a descriptive, thought experiment type manner. It is then defined more formally using a conceptual, mathematically discrete computational model, which provides a network or graph type framework in which it is easy to analyse and control discrete signals that are sent between neighbouring cells. This provides an intuitive method of explaining how the signalling gradient emerges as a result of local cell to cell communication. Finally, examples of gradient formation are shown using software implementations of the model.

Lateral Crushing and Energy Absorption Behavior of Multicellular Tube Structures

Thin-walled metallic tubular elements are extensively employed as an impact energy attenuator in modern vehicles owing to light weight, easy fabrication and average cost. Besides, the novel multi-cell tubular structures have superior energy absorption characteristics related to a conventional simple cell tube. In this research article, the finite element simulation of thin-walled aluminium alloy extruded multicellular structure under lateral impact loading is investigated. Nonlinear impact simulations were performed on multicellular tubes of various configurations using finite element ABAQUS/CAE explicit code. From the outcomes attained, the energy absorption capability of various multicellular tube structures were compared and it shows that multicellular tubes have more remarkable than that of traditional simple cell tubes. Moreover, square shaped multicellular structure tube were retained as most prominent for higher energy absorption. This type of multicellular tubes was found to be effective one to improve the lateral crashworthiness performance

The Sizable Difficulty in Recognizing Unfamiliar Faces Differing Only Moderately in Orientation in Depth is a Function of Image Dissimilarity

Attempting to match unfamiliar faces at moderate differences in orientation in depth is surprisingly difficult. No general account of these costs has been offered. We assessed the effects of orientation disparity in a match-to-sample paradigm of a triangular display of three faces. Two lower test faces, a matching face and a foil, were always at the same orientation and differed by 0° to 20° from the sample on top. The similarity of the images was scaled by a model based on simple cell tuning that correlates almost perfectly with psychophysical similarity. Two measures of face similarity accounted for matching performance: a) the decrease in similarity between the images of the matching and sample faces produced by increases in their orientation disparity, and b) the similarity between the matching face and the selection of a particular foil. The two images of the same face at a 20° difference in orientation revealed a previously unappreciated marked increase in dissimilarity that was so high that it could be equivalent to the image dissimilarity between two faces at the same orientation, but differing in race, sex, and expression. The 20° orientation disparity was thus sufficient to yield a sizeable 301 msec increase in reaction time.