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This prediction model is validated against 1,000 new candidate compounds. see more Different compounds despite driving specific modulation outcomes elicit a varying effect on cellular integrity. Strikingly, this confirms that phenotypic responses are not conserved that enables quantification of signaling heterogeneity. Agonist-antagonist signaling pairs demonstrate switch of the targets in the cascades hinting toward evidence of signaling plasticity. Quantitative analysis of the screen has enabled the identification of these underlying signatures. Together, these image-based profiling approaches can be employed for target identification in drug and diseased states and understand the hallmark of cellular response.Poliomyelitis is caused by poliovirus (PV), a positive strand non-enveloped virus. link= see more Since its discovery in the 1950s, several cell culture and molecular methods have been developed to detect and characterize the various strains of PV. Here, we provide an accurate and standardized protocol to differentiate human embryonic stem cells (hESCs) toward engineered neural tissue enriched with motor neurons (MN ENTs). These MN ENTs expressed markers of motor neuron CHAT and Hb-9 as revealed by immunofluorescence staining and quantitative RT-PCR. Interestingly, our results suggest that motor neurons are responsible for the permissiveness of poliovirus within the MN ENTs. Moreover, our study revealed the molecular events occurring upon PV-3 infection in the MN ENTs and highlighted the modulation of a set of genes involved in EGR-EP300 complex. Collectively, we report the development of a reliable in vitro model to investigate the pathophysiology of PV infection, allowing to both design and assess novel therapeutic approaches against PV infection.C-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet. Herein, we evaluate the expression and functions of CtBPs in postnatal NSCs from the subventricular zone (SVZ). We found that CtBPs were expressed in immature/progenitor cells, neurons and glial cells in the SVZ niche. Using the CtBPs modulator 4-methylthio 2-oxobutyric acid (MTOB), our results showed that 1 mM of MTOB induced cell death, while 5, 25, and 50 μM increased the number of proliferating neuroblasts, mature neurons, and oligodendrocytes. Interestingly, it also increased the dendritic complexity of immature neurons. Altogether, our results highlight CtBPs putative application for brain regenerative applications.Hair cells are heterogenous, enabling varied roles in sensory systems. An emerging hypothesis is that the transmembrane channel-like (Tmc) proteins of the hair cell's mechanotransduction apparatus vary within and between organs to permit encoding of different mechanical stimuli. Five anatomical variables that may coincide with different Tmc use by a hair cell within the ear are the containing organ, cell morphology, cell position within an organ, axis of best sensitivity for the cell, and the hair bundle's orientation within this axis. link2 Here, we test this hypothesis in the organs of the zebrafish ear using a suite of genetic mutations. Transgenesis and quantitative measurements demonstrate two morphologically distinct hair cell types in the central thickness of a vestibular organ, the lateral crista short and tall. In contrast to what has been observed, we find that tall hair cells that lack Tmc1 generally have substantial reductions in mechanosensitivity. In short hair cells that lack Tmc2 isoforms, mechanotransduction is largely abated. However, hair cell Tmc dependencies are not absolute, and an exceptional class of short hair cell that depends on Tmc1 is present, termed a short hair cell erratic. To further test anatomical variables that may influence Tmc use, we map Tmc1 function in the saccule of mutant larvae that depend just on this Tmc protein to hear. We demonstrate that hair cells that use Tmc1 are found in the posterior region of the saccule, within a single axis of best sensitivity, and hair bundles with opposite orientations retain function. Overall, we determine that Tmc reliance in the ear is dependent on the organ, subtype of hair cell, position within the ear, and axis of best sensitivity.Discussions about the responsible advancement of synthetic biology science are at fever pitch. Commentators from across the globe are calling for greater integrated science investments and more inclusive governance processes in the development and implementation of these potentially disruptive technologies. We take stock of the promises and realities of science integration by sharing our experiences of embarking on this very challenge in Australia. We conclude by offering suggestions for bringing about the enabling conditions for improved integration across the natural and social sciences. Four key actions are articulated to help pivot synthetic biology toward a more integrated scientific endeavor (a) formalizing inclusivity from inception to project conclusion; (b) valuing differing philosophical positions as a strength rather than a barrier; (c) accepting that integration takes persistence and communication but is immensely rewarding; and (d) promoting meaningful interactions, such as pursuing joint opportunities, co-designing and co-publishing research. We argue that these actions are key enablers for realizing science integration in synthetic biology.Although it is known that stronger cell-extracellular matrix interactions will be developed as neurons mature, how such change influences their response against traumatic injury remains largely unknown. In this report, by transecting axons with a sharp atomic force microscope tip, we showed that the injury-induced retracting motion of axon can be temporarily arrested by tight NCAM (neural cell adhesion molecule) mediated adhesion patches, leading to a retraction curve decorated with sudden bursts. Interestingly, although the size of adhesion clusters (~0.5-1 μm) was found to be more or less the same in mature and immature neurons (after 7- and 3-days of culturing, respectively), the areal density of such clusters is three times higher in mature axons resulting in a much reduced retraction in response to injury. A physical model was also adopted to explain the observed retraction trajectories which suggested that apparent adhesion energy between axon and the substrate increases from ~0.12 to 0.39 mJ/m2 as neural cell matures, in good agreement with our experiments.Currently, selective laser melting (SLM) has been thriving in implant dentistry for on-demand fabricating dental implants. Based on the coarse microtopography of SLM titanium surfaces, constructing nanostructure to form the hierarchical micro-nano topography is effective in enhancing osseointegration. Given that current nanomodification techniques of SLM implants, such as anodization and hydrothermal treatment, are facing the inadequacy in costly specific apparatus and reagents, there has been no recognized nanomodified SLM dental implants. link2 The present study aimed to construct hierarchical micro-nano topography on self-made SLM dental implants by a simple and safe inorganic chemical oxidation, and to evaluate its contribution on osteoblastic cells bioactivity and osseointegration. The surface chemical and physical parameters were characterized by FE-SEM, EDS, profilometer, AFM, and contact angle meter. The alteration on bioactivity of MG-63 human osteoblastic cells were detected by qRT-PCR. Then the osseointeied SLM implants was equal to untreated SLM implants and marketable TixOs implants. The overall findings indicated that the inorganic chemical oxidized hierarchical micro-nano topography could enhance the bioactivity of osteoblastic cells, and consequently promote the peri-implant bone formation and mineralization of SLM dental implants. This study sheds some light on improvements in additive manufactured dental implants.Microbial production of commodity chemicals has gained increasing attention and most of the focus has been on reducing the production cost. Selecting a suitable microorganism, which can grow rapidly on cheap feedstocks, is of key importance when developing an economically feasible bioprocess. We chose Lactococcus lactis, a well-characterized lactic acid bacterium, as our microbial host to produce pyruvate, which is a commodity chemical with various important applications. link3 Here we report the engineering of Lactococcus lactis into becoming an efficient microbial platform for producing pyruvate. The strain obtained, FS1076 (MG1363 Δ3ldh Δpta ΔadhE Δals), was able to produce pyruvate as the sole product. Since all the competitive pathways had been knocked out, we achieved growth-coupled production of pyruvate with high yield. More than 80 percent of the carbon flux was directed toward pyruvate, and a final titer of 54.6 g/L was obtained using a fed-batch fermentation setup. see more By introducing lactose catabolism into FS1076, we obtained the strain FS1080, which was able to generate pyruvate from lactose. We then demonstrated the potential of FS1080 for valorizing lactose contained in dairy side-streams, by achieving a high titer (40.1 g/L) and high yield (78.6%) of pyruvate using residual whey permeate (RWP) as substrate. The results obtained, show that the L. lactis platform is well-suited for transforming lactose in dairy waste into food-grade pyruvate, and the yields obtained are the highest reported in the literature. link3 These results demonstrate that it is possible to achieve sustainable bioconversion of waste products from the dairy industry (RWP) to valuable products.Microbial production of chemicals using renewable feedstocks such as glucose has emerged as a green alternative to conventional chemical production processes that rely primarily on petroleum-based feedstocks. The carbon footprint of such processes can further be reduced by using engineered cells that harness solar energy to consume feedstocks traditionally considered to be wastes as their carbon sources. Photosynthetic bacteria utilize sophisticated photosystems to capture the energy from photons to generate reduction potential with such rapidity and abundance that cells often cannot use it fast enough and much of it is lost as heat and light. Engineering photosynthetic organisms could enable us to take advantage of this energy surplus by redirecting it toward the synthesis of commercially important products such as biofuels, bioplastics, commodity chemicals, and terpenoids. In this work, we review photosynthetic pathways in aerobic and anaerobic bacteria to better understand how these organisms have naturally evolved to harness solar energy. We also discuss more recent attempts at engineering both the photosystems and downstream reactions that transfer reducing power to improve target chemical production. Further, we discuss different methods for the optimization of photosynthetic bioprocess including the immobilization of cells and the optimization of light delivery. We anticipate this review will serve as an important resource for future efforts to engineer and harness photosynthetic bacteria for chemical production.