Synergistic Activation of RD29A Via Integration of Salinity Stress and Abscisic Acid in Arabidopsis thaliana.

Plants perceive information from the surroundings and elicit appropriate molecular responses. How plants dynamically respond to combinations of external inputs is yet to be revealed, despite the detailed current knowledge of intracellular signaling pathways. We measured dynamics of Response-to-Dehydration 29A (RD29A) expression induced by single or combined NaCl and ABA treatments in Arabidopsis thaliana. RD29A expression in response to a combination of NaCl and ABA leads to unique dynamic behavior that cannot be explained by the sum of responses to individual NaCl and ABA. To explore the potential mechanisms responsible for the observed synergistic response, we developed a mathematical model of the DREB2 and AREB pathways based on existing knowledge, where NaCl and ABA act as the cognate inputs, respectively, and examined various system structures with cross-input modulation, where non-cognate input affects expression of the genes involved in adjacent signaling pathways. The results from the analysis of system structures, combined with the insights from microarray expression profiles and model-guided experiments, predicted that synergistic activation of RD29A originates from enhancement of DREB2 activity by ABA. Our analysis of RD29A expression profiles demonstrates that a simple mathematical model can be used to extract information from temporal dynamics induced by combinatorial stimuli and produce experimentally testable hypotheses

Regulation of scleral cell contraction by transforming growth factor-β and stress competing roles in myopic growth

Reduced extracellular matrix accumulation in the sclera of myopic eyes leads to increased ocular extensibility and is related to reduced levels of scleral transforming growth factor-β (TGF-β). The current study investigated the impact of this extracellular environment on scleral cell phenotype and cellular biomechanical characteristics. Scleral cell phenotype was investigated in vivo in a mammalian model of myopia using the myofibroblast marker, α-smooth muscle actin (α-SMA). In eyes developing myopia α-SMA levels were increased, suggesting increased numbers of contractile myofibroblasts, and decreased in eyes recovering from myopia. To understand the factors regulating this change in scleral phenotype, the competing roles of TGF-β and mechanical stress were investigated in scleral cells cultured in three-dimensional collagen gels. All three mammalian isoforms of TGF-β altered scleral cell phenotype to produce highly contractile, α-SMA-expressing myofibroblasts (TGF-β3 > TGF-β2 > TGF-β1). Exposure of cells to the reduced levels of TGF-β found in the sclera in myopia produced decreased cell-mediated contraction and reduced α-SMA expression. These findings are contrary to the in vivo gene expression data. However, when cells were exposed to both the increased stress and the reduced levels of TGF-β found in myopia, increased α-SMA expression was observed, replicating in vivo findings. These results show that although reduced scleral TGF-β is a major contributor to the extracellular matrix remodeling in the myopic eye, it is the resulting increase in scleral stress that dominates the competing TGF-β effect, inducing increased α-SMA expression and, hence, producing a larger population of contractile cells in the myopic eye

Flexible entangled state generation in linear optics

Fault-tolerant quantum computation can be achieved by creating constant-sized, entangled resource states and performing entangling measurements on subsets of their qubits. Linear optical quantum computers can be designed based on this approach, even though entangling operations at the qubit level are non-deterministic in this platform. Probabilistic generation and measurement of entangled states must be pushed beyond the required threshold by some combination of scheme optimisation, introduction of redundancy and auxiliary state assistance. We report progress in each of these areas. We explore multi-qubit fusion measurements on dual-rail photonic qubits and their role in measurement-based resource state generation, showing that it is possible to boost the success probability of photonic GHZ state analysers with single photon auxiliary states. By incorporating generators of basic entangled "seed" states, we provide a method that simplifies the process of designing and optimising generators of complex, encoded resource states by establishing links to ZX diagrams.Comment: Comments welcom

High photon-loss threshold quantum computing using GHZ-state measurements

We propose fault-tolerant architectures based on performing projective measurements in the Greenberger-Horne-Zeilinger (GHZ) basis on constant-sized, entangled resource states. We present linear-optical constructions of the architectures, where the GHZ-state measurements are encoded to suppress the errors induced by photon loss and the probabilistic nature of linear optics. Simulations of our constructions demonstrate high single-photon loss thresholds compared to the state-of-the-art linear-optical architecture realized with encoded two-qubit fusion measurements performed on constant-sized resource states. We believe this result shows a resource-efficient path to achieving photonic fault-tolerant quantum computing

Reduced scleral TIMP-2 expression is associated with myopia development: TIMP-2 supplementation stabilizes scleral biomarkers of myopia and limits myopia development

Purpose: The purpose of this study was to determine the endogenous regulation pattern of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the tree shrew sclera during myopia development and investigate the capacity of exogenous TIMP-2 to inhibit matrix metalloproteinase-2 (MMP-2) in vitro and both scleral collagen degradation and myopia development in vivo. Methods: TIMP-2 expression in the sclera during myopia development was assessed using polymerase chain reaction. In vitro TIMP-2 inhibition of MMP-2 was investigated using a gelatinase activity plate assay and zymography. Tree shrews were injected with a collagen precursor before undergoing monocular form deprivation and concurrent daily subconjunctival injections of either TIMP-2 or vehicle to the form-deprived eye. In vivo ocular biometry changes were monitored, and scleral tissue was collected after 12 days and assayed for collagen degradation. Results: The development of myopia was associated with a mean reduction in TIMP-2 mRNA expression after 5 days of form deprivation (P < 0.01). Both activation and activity of MMP-2 were inhibited by TIMP-2 with an IC50 of 10 to 20 and 2 nM, respectively. In vivo exogenous addition of TIMP-2 significantly reduced myopia development (P < 0.01), due to reduced vitreous chamber elongation (P < 0.01). In vivo TIMP-2 treatment also significantly inhibited posterior scleral collagen degradation relative to vehicle-treated eyes (P < 0.01), with levels similar to those in control eyes. Conclusions: Myopia development in mammals is associated with reduced expression of TIMP-2, which contributes to increased degradative activity in the sclera. It follows that replenishment of this TIMP-2 significantly reduced the rate of both scleral collagen degradation and myopia development

Rapid neurogenesis through transcriptional activation in human stem cells

Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems-level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types

Going for GOLD! Greater Manchester Growing Older with Learning Disabilities: An inclusive research project to reduce social isolation amongst older adults with learning disabilities

This research was part of the Greater Manchester Growing Older with Learning Disabilities (GM GOLD) project, which was carried out by a team of 16 older people with learning disabilities. The aim was to reduce social isolation amongst older adults (aged 50+) with learning disabilities and to find out what makes somewhere an age-friendly place to live for older adults with learning disabilities. The team was supported by 'research buddies' from Manchester Metropolitan University and the partner organisations to conduct interviews and focus groups with 59 older people (aged 50-79 years) with learning disabilities from eight Greater Manchester areas (Bolton, Bury, Manchester, Oldham, Rochdale, Salford, Tameside, Wigan). Later life transitions for people with learning disabilities are particularly disruptive, and they are at particular risk of social isolation and loneliness. People with learning disabilities have the same rights to relationships and to participate in the cultural life of the community as the rest of society. If society, neighbourhoods and communities do not become more inclusive of people with learning disabilities, in addition to the legal, moral and ethical implications, this is likely to result in additional demand for public services