Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells' activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm.     

Global cell sorting is mediated by local cell-cell interactions in the C. elegans embryo

The Caenorhabditis elegans embryo achieves pattern formation by sorting cells into coherent regions before morphogenesis is initiated. The sorting of cells is coupled to their fate. Cells move extensively relative to each other to reach their correct position in the body plan. Analyzing the mechanism of cell sorting in in vitro culture experiments using 4D microscopy, we show that all AB-derived cells sort only according to their local neighbors, and that all cells are able to communicate with each other. The directions of cell movement do not depend on a cellular polarity but only on local cell-cell interactions; in experimental situations, this allows even the reversal of the polarity of whole regions of the embryo. The work defines a new mechanism of pattern formation we call "cell focusing".     

Human serum albumin supported lipid patterns for the targeted recognition of microspheres coated by membrane based on ss-DNA hybridization

Human serum albumin (HSA) patterns have been successfully fabricated for the deposition of lipid bilayer, 1,2-dimyristoyl-sglycerophosphate (DMPA), by making use of the micro-contact printing (microCP) technique and liposome fusion. Confocal laser scanning microscopy (CLSM) results indicate that lipid bilayer has been assembled in HSA patterns with a good stability. Such well-defined lipid patterns formed on HSA surface create possibility to incorporate specific components like channels or receptors for specific recognition. In view of this, microspheres coated with lipid membranes were immobilized in HSA-supported lipid patterns via the hybridization of complementary ss-DNAs. This procedure enables to transfer solid materials to a soft surface through a specific recognition.     

Resonant neurons and bushcricket behaviour

The resonant properties of the intrinsic dynamics of single neurons could play a direct role in behaviour. One plausible role is in the recognition of temporal patterns, such as that seen in the auditory communication systems of Orthoptera. Recent behavioural data from bushcrickets suggests that this behaviour has interesting resonance properties, but the underlying mechanism is unknown. Here we show that a very simple and general model for neural resonance could directly account for the different behavioural responses of bushcrickets to different song patterns.     

The mechanism of sudden stripe formation during dorso-ventral patterning in <Emphasis Type="Italic">Drosophila</Emphasis>

The front and back (ventral and dorsal part respectively) of arthropods and chordates are defined by a highly conserved mechanism during early embryonic development [De Robertis and Kuroda in Annu. Rev. Cell Dev. Biol. 20, 285–308 (2004)]. An important feature is the sudden formation of a narrow midline peak of signaling. Mathematical models have helped to improve our understanding of the underlying mechanism [Eldar et al. in Nature 419(6904), 304–308 (2002); Mizutani in Dev. Cell 8(6), 915–924 (2005); Shimmi et al. in Cell 120(6), 873–886, (2005)]. In particular, the most recent model shows that diffusion and receptor-dependent degradation of the morphogen together with protease-mediated cleavage of a carrier protein for the morphogen are sufficient for the sudden generation of a sharp midline peak [Mizutani in Dev. Cell 8(6), 915–924 (2005)]. How these processes give rise to the observed pattern and how sensitive the model is to changes in parameter values has, however, not been resolved by this numerical study. By analysing the model in detail, we find that the sudden formation of a signaling peak is the consequence of the inversion of the gradient of the morphogen-carrier complex in the dorsal domain. As a consequence ligand is suddenly transported into rather than out of the midline, and a midline peak forms. We further show that a two-component carrier complex, consisting of Sog and Tsg, is required for abrupt peak formation. We derive quantitative conditions for the time and concentration at which the peak forms. We identify the receptor concentration, the ligand production and degradation rates, and the carrier production, diffusion, and cleavage rates as parameters to which the model is sensitive. Numerical studies confirm our analysis.      

Spontaneous Patchiness in a Host-Parasitoid Integrodifference Model

Observations of a host-parasitoid interaction in which victims are significantly less motile than their exploiters suggest the possibility of stable spatial pattern in a fairly homogeneous environment. Findings of pattern formation in continuous-time models are not fully able to account for this behavior. Those findings often rely on questionable biological conditions, and more fundamentally, the continuous nature of time in such models does not reflect the reality of the observed interaction. In this paper, we introduce a discrete-time spatial model of the interaction. The final state of our model is often a striking spatial pattern, similar to those observed. We analyze the model, describe its transient behavior, and find the conditions under which these spatial patterns occur, as well as an estimate of maximum possible patch size under those conditions. We also discuss the existence of such conditions in the natural system.     

Exploration of plant growth and development using the European Modular Cultivation System facility on the International Space Station

Space experiments provide a unique opportunity to advance our knowledge of how plants respond to the space environment, and specifically to the absence of gravity. The European Modular Cultivation System (EMCS) has been designed as a dedicated facility to improve and standardise plant growth in the International Space Station (ISS). The EMCS is equipped with two centrifuges to perform experiments in microgravity and with variable gravity levels up to 2.0 g. Seven experiments have been performed since the EMCS was operational on the ISS. The objectives of these experiments aimed to elucidate phototropic responses (experiments TROPI‐1 and ‐2), root gravitropic sensing (GRAVI‐1), circumnutation (MULTIGEN‐1), cell wall dynamics and gravity resistance (Cell wall/Resist wall), proteomic identification of signalling players (GENARA‐A) and mechanism of InsP₃ signalling (Plant signalling). The role of light in cell proliferation and plant development in the absence of gravity is being analysed in an on‐going experiment (Seedling growth). Based on the lessons learned from the acquired experience, three preselected ISS experiments have been merged and implemented as a single project (Plant development) to study early phases of seedling development. A Topical Team initiated by European Space Agency (ESA), involving experienced scientists on Arabidopsis space research experiments, aims at establishing a coordinated, long‐term scientific strategy to understand the role of gravity in Arabidopsis growth and development using already existing or planned new hardware.     

Toll-like Receptor 11 (TLR11) Prevents Salmonella Penetration into the Murine Peyer Patches

Toll-like receptors (TLRs) are key molecular sensors used by the mammalian innate immune system to detect microorganisms. Although TLR functions in colonic immune homeostasis and tolerance to commensal bacteria have been intensively researched, the precise roles of different TLRs in response to pathogen infection in the gut remain elusive. Peyer patches are the major entrance of Salmonella infection and antigen transportation in intestine. Here, we report that, in contrast to TLR5 as a “carrier of Salmonella,” TLR11 works as a “blocker of Salmonella” to prevent highly invasive Salmonella from penetrating into the murine Peyer patches and spreading systemically. TLR11 plays an important role in mediating TNF-α induction and systemic inflammation in response to Salmonella infection. Remarkably, in mice lacking TLR11, apparent hemorrhages at Peyer patches are induced by highly invasive Salmonella, a phenotype resembling human Salmonella infection. Therefore, our results indicate a potentially important role for TLR11 in preventing murine intestinal infection and modulating antigen transportation in the gut and imply an important role for various TLRs in cooperation with tight control of pathogens penetrating into Peyer patches. The TLR11 knock-out mouse can serve as a good animal model to study Salmonella infection.     

Pathogen sensing by nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is mediated by direct binding to muramyl dipeptide and ATP

Nucleotide binding and oligomerization domain-containing protein 2 (NOD2/Card15) is an intracellular protein that is involved in the recognition of bacterial cell wall-derived muramyl dipeptide. Mutations in the gene encoding NOD2 are associated with inherited inflammatory disorders, including Crohn disease and Blau syndrome. NOD2 is a member of the nucleotide-binding domain and leucine-rich repeat-containing protein gene (NLR) family. Nucleotide binding is thought to play a critical role in signaling by NLR family members. However, the molecular mechanisms underlying signal transduction by these proteins remain largely unknown. Mutations in the nucleotide-binding domain of NOD2 have been shown to alter its signal transduction properties in response to muramyl dipeptide in cellular assays. Using purified recombinant protein, we now demonstrate that NOD2 binds and hydrolyzes ATP. Additionally, we have found that the purified recombinant protein is able to bind directly to muramyl dipeptide and can associate with known NOD2-interacting proteins in vitro. Binding of NOD2 to muramyl dipeptide and homo-oligomerization of NOD2 are enhanced by ATP binding, suggesting a model of the molecular mechanism for signal transduction that involves binding of nucleotide followed by binding of muramyl dipeptide and oligomerization of NOD2 into a signaling complex. These findings set the stage for further studies into the molecular mechanisms that underlie detection of muramyl dipeptide and assembly of NOD2-containing signaling complexes.     

Mako: A Graph-based Pattern Growth Approach to Detect Complex Structural Variants

Complex structural variants (CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants. However, detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy. As a result, there has been limited progress for CSV discovery compared with simple structural variants. Here, we systematically analyzed the multi-breakpoint connection feature of CSVs, and proposed Mako, utilizing a bottom-up guided model-free strategy, to detect CSVs from paired-end short-read sequencing. Specifically, we implemented a graph-based pattern growth approach, where the graph depicts potential breakpoint connections, and pattern growth enables CSV detection without pre-defined models. Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms. Notably, validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%, where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp, respectively. Moreover, the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types, including two novel types of adjacent segment swap and tandem dispersed duplication. Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs. Mako is publicly available at https://github.com/xjtu-omics/Mako.