Publications by authors named "Sujith Sebastian"

Skeletal muscle stem cells (MuSC) are crucial for tissue homoeostasis and repair after injury. Following activation, they proliferate to generate differentiating myoblasts. A proportion of cells self-renew, re-enter the MuSC niche under the basal lamina outside the myofiber and become quiescent.

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An automated platform for cell culture combines robotics and artificial intelligence to optimize cell culture protocols and reliably produce specific cell types that could be used for regenerative medicine treatments.

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Cell-based therapies must achieve clinical efficacy and safety with reproducible and cost-effective manufacturing. This study addresses process development issues using the exemplar of a human pluripotent stem cell-based dopaminergic neuron cell therapy product. Early identification and correction of risks to product safety and the manufacturing process reduces the expensive and time-consuming bridging studies later in development.

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Human pluripotent stem cells (hPSCs) have the potential to transform medicine. However, hurdles remain to ensure safety for such cellular products. Science-based understanding of the requirements for source materials is required as are appropriate materials.

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This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early.

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Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM.

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Background: The traditional problems of performing skeletal muscle cell cultures derived from mammalian or avian species are limited myotube differentiation, and transient myotube persistence which greatly restricts the ability of myotubes to undergo phenotypic maturation. We report here on a major technical breakthrough in the establishment of a simple and effective method of extended porcine myotube cultures (beyond 50 days) in two-dimension (2D) that recapitulates key features of postnatal fibre types.

Results: Primary porcine muscle satellite cells (myoblasts) were isolated from the longissimus dorsi of 4 to 6 weeks old pigs for 2D cultures to optimise myotube formation, improve surface adherence and characterise myotube maturation.

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Unlabelled: Skeletal muscle, at 30 to 40% of body mass, is the most abundant soft tissue in the body. Besides its primary function in movement and posture, skeletal muscle is a significant innate immune organ with the capacity to produce cytokines and chemokines and respond to proinflammatory cytokines. Little is known about the role of skeletal muscle during systemic influenza A virus infection in any host and particularly avian species.

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Highly pathogenic avian influenza (HPAI) H5N1 viruses cause severe infection in chickens at near complete mortality, but corresponding infection in ducks is typically mild or asymptomatic. To understand the underlying molecular differences in host response, primary chicken and duck lung cells, infected with two HPAI H5N1 viruses and a low pathogenicity avian influenza (LPAI) H2N3 virus, were subjected to RNA expression profiling. Chicken cells but not duck cells showed highly elevated immune and pro-inflammatory responses following HPAI virus infection.

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Insects successfully occupy most environmental niches and this success depends on surviving a broad range of environmental stressors including temperature, desiccation, xenobiotic, osmotic and infection stress. Epithelial tissues play key roles as barriers between the external and internal environments and therefore maintain homeostasis and organismal tolerance to multiple stressors. As such, the crucial role of epithelia in organismal stress tolerance cannot be underestimated.

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The capa peptide family exists in a very wide range of insects including species of medical, veterinary and agricultural importance. Capa peptides act via a cognate G-protein coupled receptor (capaR) and have a diuretic action on the Malpighian tubules of Dipteran and Lepidopteran species. Capa signaling is critical for fluid homeostasis and has been associated with desiccation tolerance in the fly, Drosophila melanogaster.

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Memories are classified as consolidated (stable) or labile according to whether they withstand amnestic treatment, or not. In contrast to the general prevalence of this classification, its neuronal and molecular basis is poorly understood. Here, we focused on consolidated and labile memories induced after a single cycle training in the Drosophila aversive olfactory conditioning paradigm and we used mutants to define the impact of cAMP signals.

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Background: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses.

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The success of insects is in large part due to their ability to survive environmental stress, including heat, cold, and dehydration. Insects are also exposed to infection, osmotic or oxidative stress, and to xenobiotics or toxins. The molecular mechanisms of stress sensing and response have been widely investigated in mammalian cell lines, and the area of stress research is now so vast to be beyond the scope of a single review article.

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Receptorguanylate cyclases (rGCs) modulate diverse physiological processes including mammalian cardiovascular function and insect eclosion. The Drosophila genome encodes several receptor and receptor-like GCs, but no ligand for any Drosophila rGC has yet been identified. By screening peptide libraries in Drosophila S2 cells, the Drosophila peptide NPLP1-VQQ (NLGALKSSPVHGVQQ) was shown to be a ligand for the rGC, Gyc76C (CG42636, previously CG8742, l(3)76BDl, DrGC-1).

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Article Synopsis
  • Point mutations in the ZRS region of the Lmbr1 gene are linked to polydactyly (extra toes) in humans, cats, and mice, highlighting its role in limb development.
  • Recent research has pinpointed a specific single nucleotide polymorphism (SNP) in chickens that is responsible for a form of polydactyly in Silkie chickens, further demonstrating the ZRS's significance.
  • Experiments using Silkie chicken legs show that increased Sonic hedgehog (Shh) expression in certain areas leads to changes in toe formation and causes preaxial polydactyly.
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