Osmosis as nature's method for establishing optical alignment.

For eyes to maintain optimal focus, precise coordination is required between lens optics and retina position, a mechanism that in vertebrates is governed by genetics, visual feedback, and possibly intraocular pressure (IOP).1 While the underlying processes have been intensely studied in vertebrates, they remain elusive in arthropods, though visual feedback may be unimportant.2 How do arthropod eyes remain functional while undergoing substantial growth? Here, we test whether a common physiological process, osmoregulation,3 could regulate growth in the sophisticated camera-type eyes of the predatory larvae of Thermonectus marmoratus diving beetles. Upon molting, their eye tubes elongate in less than an hour, and osmotic pressure measurements reveal that this growth is preceded by a transient increase in hemolymph osmotic pressure. Histological evaluation of support cells that determine the lens-to-retina spacing reveals swelling rather than the addition of new cells. In addition, as expected, treating larvae with hyperosmotic media post-molt leads to far-sighted (hyperopic) eyes due to a failure of proper lengthening of the eye tube and results in impaired hunting success. This study suggests that osmoregulation could be of ubiquitous importance for properly focused eyes.

Effect of fibre fortification of low FODMAP pasta.

Irritable bowel syndrome (IBS) is a condition affecting the digestive system and can be triggered by several different factors, including diet. To ease symptoms of IBS, a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) is often recommended. Pasta, as a staple food in the Western World, is naturally high in FODMAPs. This study investigates the impact of insoluble and soluble dietary fibre ingredients in low-FODMAPs pasta. The assessment included physicochemical, sensory, and nutritional quality. Soluble fibre strengthened gluten network, which caused a lower cooking loss and a lower release of sugars during in vitro starch digestion. Insoluble fibre interfered with the gluten network development to a higher extent causing a higher sugar release during digestion. This study reveals the most suitable fibre ingredients for the development of pasta with elevated nutritional value and sensory characteristics compared to commercial products on the market. This type of pasta has a high potential of being suitable for IBS patients.

Enhancing the Techno-Functional Properties of Lentil Protein Isolate Dispersions Using In-Line High-Shear Rotor-Stator Mixing.

In response to global challenges such as climate change and food insecurity, plant proteins have gained interest. Among these, lentils have emerged as a promising source of proteins due to their good nutritional profile and sustainability considerations. However, their widespread use in food products has been impeded by limited solubility. This study aimed to investigate the potential of high-shear mixing, a resource-efficient technique, to enhance lentil protein solubility and its functional properties. Red lentil protein isolate powders were rehydrated and subjected to a semi-continuous in-line high-shear treatment at 10,200 rpm for a timespan ranging from 0 to 15 min. The results highlighted a significant (p < 0.05) increase in solubility from 46.87 to 68.42% after 15 min of shearing and a reduction in particle size as a result of the intense shearing and disruption provided by the rotor and forced passage through the perforations of the stator. The volume-weighted mean diameter decreased from 5.13 to 1.72 µm after 15 min of shearing, also highlighted by the confocal micrographs which confirmed the breakdown of larger particles into smaller and more uniform particles. Rheological analysis indicated consistent Newtonian behaviour across all dispersions, with apparent viscosities ranging from 1.69 to 1.78 mPa.s. Surface hydrophobicity increased significantly (p < 0.05), from 830 to 1245, indicating exposure of otherwise buried hydrophobic groups. Furthermore, colloidal stability of the dispersion was improved, with separation rates decreasing from 71.23 to 24.16%·h-1. The significant enhancements in solubility, particle size reduction, and colloidal stability, highlight the potential of in-line high-shear mixing in improving the functional properties of lentil protein isolates for formulating sustainable food products with enhanced techno-functional properties.

Commercial Egg Replacers in Pound Cake Systems: A Comprehensive Analysis of Market Trends and Application.

Replacing eggs without influencing pound cakes' texture, appearance, and taste is challenging. Ovalbumin, the major protein in egg white, contributes to the structures of cakes by providing SH Groups that form a firm gel during baking. However, there is a shift in the consumers' behaviour regarding health, well-being, animal welfare standards, and environmental concerns. To meet upcoming trends and consumer needs, 102 egg replacement products were launched globally to the best of the authors' knowledge, with 20 of them advertised as suitable for baking applications. Ten locally available commercial egg replacers with a range of protein contents were chosen and applied in a pound cake model system to evaluate their functionality by evaluating cake and cake batter quality. Three different categories of egg replacements were chosen: replacers containing no protein (R1-R3), a low amount of protein (1-10 g/100 g; R4-R5), and a high amount of protein (>10 g/100 g; R6-R10). Those were compared to three control cakes containing powdered whole egg, fresh egg, and liquid whole egg. All the analysed egg replacers significantly differed from the control cakes, including low-protein egg replacement R4. Despite R4 achieving the highest specific volume (1.63 ± 0.07 mL/g) and comparable texture values, none of the examined egg replacers compared favourably with the egg control cakes regarding appearance, physical and textural properties, and nutritional value.

Myelin protein zero mutation-related hereditary neuropathies: Neuropathological insight from a new nerve biopsy cohort.

Myelin protein zero (MPZ/P0) is a major structural protein of peripheral nerve myelin. Disease-associated variants in the MPZ gene cause a wide phenotypic spectrum of inherited peripheral neuropathies. Previous nerve biopsy studies showed evidence for subtype-specific morphological features. Here, we aimed at enhancing the understanding of these subtype-specific features and pathophysiological aspects of MPZ neuropathies. We examined archival material from two Central European centers and systematically determined genetic, clinical, and neuropathological features of 21 patients with MPZ mutations compared to 16 controls. Cases were grouped based on nerve conduction data into congenital hypomyelinating neuropathy (CHN; n = 2), demyelinating Charcot-Marie-Tooth (CMT type 1; n = 11), intermediate (CMTi; n = 3), and axonal CMT (type 2; n = 5). Six cases had combined muscle and nerve biopsies and one underwent autopsy. We detected four MPZ gene variants not previously described in patients with neuropathy. Light and electron microscopy of nerve biopsies confirmed fewer myelinated fibers, more onion bulbs and reduced regeneration in demyelinating CMT1 compared to CMT2/CMTi. In addition, we observed significantly more denervated Schwann cells, more collagen pockets, fewer unmyelinated axons per Schwann cell unit and a higher density of Schwann cell nuclei in CMT1 compared to CMT2/CMTi. CHN was characterized by basal lamina onion bulb formation, a further increase in Schwann cell density and hypomyelination. Most late onset axonal neuropathy patients showed microangiopathy. In the autopsy case, we observed prominent neuromatous hyperinnervation of the spinal meninges. In four of the six muscle biopsies, we found marked structural mitochondrial abnormalities. These results show that MPZ alterations not only affect myelinated nerve fibers, leading to either primarily demyelinating or axonal changes, but also affect non-myelinated nerve fibers. The autopsy case offers insight into spinal nerve root pathology in MPZ neuropathy. Finally, our data suggest a peculiar association of MPZ mutations with mitochondrial alterations in muscle.

Exploring the molecular makeup of support cells in insect camera eyes.

Animals typically have either compound eyes, or camera-type eyes, both of which have evolved repeatedly in the animal kingdom. Both eye types include two important kinds of cells: photoreceptor cells, which can be excited by light, and non-neuronal support cells (SupCs), which provide essential support to photoreceptors. At the molecular level deeply conserved genes that relate to the differentiation of photoreceptor cells have fueled a discussion on whether or not a shared evolutionary origin might be considered for this cell type. In contrast, only a handful of studies, primarily on the compound eyes of Drosophila melanogaster, have demonstrated molecular similarities in SupCs. D. melanogaster SupCs (Semper cells and primary pigment cells) are specialized eye glia that share several molecular similarities with certain vertebrate eye glia, including Müller glia. This led us to question if there could be conserved molecular signatures of SupCs, even in functionally different eyes such as the image-forming larval camera eyes of the sunburst diving beetle Thermonectus marmoratus. To investigate this possibility, we used an in-depth comparative whole-tissue transcriptomics approach. Specifically, we dissected the larval principal camera eyes into SupC- and retina-containing regions and generated the respective transcriptomes. Our analysis revealed several common features of SupCs including enrichment of genes that are important for glial function (e.g. gap junction proteins such as innexin 3), glycogen production (glycogenin), and energy metabolism (glutamine synthetase 1 and 2). To evaluate similarities, we compared our transcriptomes with those of fly (Semper cells) and vertebrate (Müller glia) eye glia as well as respective retinas. T. marmoratus SupCs were found to have distinct genetic overlap with both fly and vertebrate eye glia. These results suggest that T. marmoratus SupCs are a form of glia, and like photoreceptors, may be deeply conserved.

Exploring the molecular makeup of support cells in insect camera eyes.

Animals generally have either compound eyes, which have evolved repeatedly in different invertebrates, or camera eyes, which have evolved many times across the animal kingdom. Both eye types include two important kinds of cells: photoreceptor cells, which can be excited by light, and non-neuronal support cells (SupCs), which provide essential support to photoreceptors. Despite many examples of convergence in eye evolution, similarities in the gross developmental plan and molecular signatures have been discovered, even between phylogenetically distant and functionally different eye types. For this reason, a shared evolutionary origin has been considered for photoreceptors. In contrast, only a handful of studies, primarily on the compound eyes of Drosophila melanogaster , have demonstrated molecular similarities in SupCs. D. melanogaster SupCs (Semper cells and primary pigment cells) are specialized eye glia that share several molecular similarities with certain vertebrate eye glia, including Müller glia. This led us to speculate whether there are conserved molecular signatures of SupCs, even in functionally different eyes such as the image-forming larval camera eyes of the sunburst diving beetle Thermonectus marmoratus . To investigate this possibility, we used an in-depth comparative whole-tissue transcriptomics approach. Specifically, we dissected the larval principal camera eyes into SupC- and retina-containing regions and generated the respective transcriptomes. Our analysis revealed several conserved features of SupCs including enrichment of genes that are important for glial function (e.g. gap junction proteins such as innexin 3), glycogen production (glycogenin), and energy metabolism (glutamine synthetase 1 and 2). To evaluate the extent of conservation, we compared our transcriptomes with those of fly (Semper cells) and vertebrate (Müller glia) eye glia as well as respective retinas. T. marmoratus SupCs were found to have distinct genetic overlap with both fly and vertebrate eye glia. These results provide molecular evidence for the deep conservation of SupCs in addition to photoreceptor cells, raising essential questions about the evolutionary origin of eye-specific glia in animals.

Impact of different fibre ingredients on a low-FODMAP biscuit model system.

Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) are carbohydrates which can cause symptoms of irritable bowel syndrome (IBS). Cereal-based products are high in FODMAPs, as they are part of the carbohydrate fraction in flour. Low-FODMAP products are starch-based which leads to a low dietary fibre content. Hence, the fortification with dietary fibre ingredients low in FODMAPs is essential. This study reveals the impact of three different fibre ingredients, resistant starch, cellulose, and arabinoxylan, and their interactions with each other in a low-FODMAP biscuit model system using response surface methodology. All fibre ingredients have an affinity to water which was further increased by their coexistence in the model system. Fibersym RW affected the biscuit hardness by its morphology and potential to recrystallise leading to a maximum inclusion level of 40%. VITACEL L 600-30 also increased biscuit hardness due to its plasticising character leading to a maximum inclusion of 20%. AgriFiber BFG mainly impacted the colour of the product restricting its inclusion to 2.3%. Additionally, it reduced the degree of starch digestibility of the biscuit by the formation of a film imbedding the starch granules and reducing enzyme attack. This research provides an in-depth insight into the integration potential of these fibre ingredients into a low-FODMAP biscuit, their interactions within the system and inclusion levels which allow their coexistence.

Brewers' Spent Grain: An Unprecedented Opportunity to Develop Sustainable Plant-Based Nutrition Ingredients Addressing Global Malnutrition Challenges.

There is an urgent requirement to minimize food waste and create more sustainable food systems that address global increases in malnutrition and hunger. The nutritional value of brewers' spent grain (BSG) makes it attractive for upcycling into value-added ingredients rich in protein and fiber having a lower environmental impact than comparable plant-based ingredients. BSG is predictably available in large quantities globally and can therefore play a role in addressing hunger in the developing world via the fortification of humanitarian food aid products. Moreover, addition of BSG-derived ingredients can improve the nutritional profile of foods commonly consumed in more developed regions, which may aid in reducing the prevalence of dietary-related disease and mortality. Challenges facing the widespread utilization of upcycled BSG ingredients include regulatory status, variability of raw material composition, and consumer perception as low-value waste products; however, the rapidly growing upcycled food market suggests increasing consumer acceptability and opportunities for significant market growth via effective new product innovation and communication strategies.

Probing the conserved roles of cut in the development and function of optically different insect compound eyes.

Astonishing functional diversity exists among arthropod eyes, yet eye development relies on deeply conserved genes. This phenomenon is best understood for early events, whereas fewer investigations have focused on the influence of later transcriptional regulators on diverse eye organizations and the contribution of critical support cells, such as Semper cells (SCs). As SCs in Drosophila melanogaster secrete the lens and function as glia, they are critical components of ommatidia. Here, we perform RNAi-based knockdowns of the transcription factor cut (CUX in vertebrates), a marker of SCs, the function of which has remained untested in these cell types. To probe for the conserved roles of cut, we investigate two optically different compound eyes: the apposition optics of D. melanogaster and the superposition optics of the diving beetle Thermonectus marmoratus. In both cases, we find that multiple aspects of ocular formation are disrupted, including lens facet organization and optics as well as photoreceptor morphogenesis. Together, our findings support the possibility of a generalized role for SCs in arthropod ommatidial form and function and introduces Cut as a central player in mediating this role.

Plant-Based Alternatives to Cheese Formulated Using Blends of Zein and Chickpea Protein Ingredients.

In this study, zein protein isolate (ZPI) and chickpea protein concentrate (CPC) ingredients were used to formulate five plant-based cheese alternatives. Ingredient ratios based on protein contributions of 0:100, 25:75, 50:50, 75:25 and 100:0 from ZPI and CPC, respectively, were used. Formulations were developed at pH ~4.5, with a moisture target of 59%. Shea butter was used to target 15% fat, while tapioca starch was added to target the same carbohydrate content for all samples. Microstructural analysis showed differences among samples, with samples containing ZPI displaying a protein-rich layer surrounding the fat globules. Schreiber meltability and dynamic low amplitude oscillatory shear rheological analyses showed that increasing the proportion of ZPI was associated with increasing meltability and greater ability to flow at high temperatures. In addition, the sample containing only CPC showed the highest adhesiveness, springiness and cohesiveness values from the texture profile analysis, while the sample containing only ZPI exhibited the highest hardness. Furthermore, stretchability increased with increasing ZPI proportions. This work will help understanding of the role and potential of promising plant-protein-ingredient blends in formulating plant-based alternatives to cheese with desirable functional properties.

From Waste to Taste: Application of Fermented Spent Rootlet Ingredients in a Bread System.

The process of upcycling and incorporating food by-products into food systems as functional ingredients has become a central focus of research. Barley rootlets (BR) are a by-product of the malting and brewing industries that can be valorised using lactic acid bacteria fermentation. This research investigates the effects of the inclusion of unfermented (BR-UnF), heat-sterilised (BR-Ster), and five fermented BR ingredients (using Weissella cibaria MG1 (BR-MG1), Leuconostoc citreum TR116 (BR-TR116), Lactiplantibacillus plantarum FST1.7 (BR-FST1.7), Lactobacillus amylovorus FST2.11 (BR-FST2.11), and Limosilactobacillus reuteri R29 (BR-R29) in bread. The antifungal compounds in BR ingredients and the impact of BR on dough rheology, gluten development, and dough mixing properties were analysed. Additionally, their effects on the techno-functional characteristics, in vitro starch digestibility, and sensory quality of bread were determined. BR-UnF showed dough viscoelastic properties and bread quality comparable to the baker's flour (BF). BR-MG1 inclusion ameliorated bread specific volume and reduced crumb hardness. Breads containing BR-TR116 had comparable bread quality to BF, while the inclusion of BR-R29 substantially slowed microbial spoilage. Formulations containing BR-FST2.11 and BR-FST1.7 significantly reduced the amounts of sugar released from breads during a simulated digestion and resulted in a sourdough-like flavour profile. This study highlights how BR fermentation can be tailored to achieve desired bread characteristics.

Associating Compositional, Nutritional and Techno-Functional Characteristics of Faba Bean (Vicia faba L.) Protein Isolates and Their Production Side-Streams with Potential Food Applications.

Faba beans (Vicia faba L.) show exciting prospects as a sustainable source of protein and fibre, with the potential to transition to a more sustainable food production. This study reveals the compositional, nutritional and techno-functional characteristics of two protein isolates from faba beans (Vicia faba L.), a high-starch fraction and a high-fibre side-stream. During the analysis of those four ingredients, particular attention was paid to the isolates' protein profile and the side-streams' carbohydrate composition. The isoelectric precipitated protein isolate 1 showed a protein content of 72.64 ± 0.31% DM. It exhibited low solubility but superior digestibility and high foam stability. High foaming capacity and low protein digestibility were observed for protein isolate 2, with a protein content of 71.37 ± 0.93% DM. This fraction was highly soluble and consisted primarily of low molecular weight proteins. The high-starch fraction contained 83.87 ± 3.07% DM starch, of which about 66% was resistant starch. Over 65% of the high-fibre fraction was insoluble dietary fibre. The findings of this study provide a detailed understanding of different production fractions of faba beans, which is of great value for future product development.

Functional Properties of Brewer's Spent Grain Protein Isolate: The Missing Piece in the Plant Protein Portfolio.

Plant protein sources, as a part of developing sustainable food systems, are currently of interest globally. Brewer's spent grain (BSG) is the most plentiful by-product of the brewing industry, representing ~85% of the total side streams produced. Although nutritionally dense, there are very few methods of upcycling these materials. High in protein, BSG can serve as an ideal raw material for protein isolate production. This study details the nutritional and functional characteristics of BSG protein isolate, EverPro, and compares these with the technological performance of the current gold standard plant protein isolates, pea and soy. The compositional characteristics are determined, including amino acid analysis, protein solubility, and protein profile among others. Related physical properties are determined, including foaming characteristics, emulsifying properties, zeta potential, surface hydrophobicity, and rheological properties. Regarding nutrition, EverPro meets or exceeds the requirement of each essential amino acid per g protein, with the exception of lysine, while pea and soy are deficient in methionine and cysteine. EverPro has a similar protein content to the pea and soy isolates, but far exceeds them in terms of protein solubility, with a protein solubility of ~100% compared to 22% and 52% for pea and soy isolates, respectively. This increased solubility, in turn, affects other functional properties; EverPro displays the highest foaming capacity and exhibits low sedimentation activity, while also possessing minimal gelation properties and low emulsion stabilising activity when compared to pea and soy isolates. This study outlines the functional and nutritional properties of EverPro, a brewer's spent grain protein, in comparison to commercial plant protein isolates, indicating the potential for the inclusion of new, sustainable plant-based protein sources in human nutrition, in particular dairy alternative applications.

Nutrition-induced macular-degeneration-like photoreceptor damage in jumping spider eyes.

Age-related macular degeneration (AMD) is a leading cause of vision loss in humans. Despite its prevalence and medical significance, many aspects of AMD remain elusive and treatment options are limited. Here, we present data that suggest jumping spiders offer a unique opportunity for understanding the fundamentals underlying retinal degeneration, thereby shedding light on a process that impacts millions of people globally. Using a micro-ophthalmoscope and histological evidence, we demonstrate that significant photoreceptor damage can occur during development in the image-forming anterior lateral eyes of the jumping spider Phidippus audax. Furthermore, we find that this photoreceptor degeneration is exacerbated by inadequate nutrition and is most prevalent in the high-density region of the retina, like AMD in humans. This suggests that similar to those in vertebrates, the retinas in P. audax are challenged to meet high-energy cellular demands.

Co-fermentation of non-Saccharomyces yeasts with Lactiplantibacillus plantarum FST 1.7 for the production of non-alcoholic beer.

The non-alcoholic beer (NAB) sector has experienced steady growth in recent years, with breweries continuously seeking new ways to fulfil consumer demands. NAB can be produced by limited fermentation of non-Saccharomyces yeasts; however, beer produced in this manner is often critiqued for its sweet taste and wort-like off-flavours due to high levels of residual sugars and lack of flavour metabolites. The use of Lactobacillus in limited co-fermentation with non-Saccharomyces yeasts is a novel approach to produce NABs with varying flavour and aroma characteristics. In this study, lab-scale fermentations of Lachancea fermentati KBI 12.1 and Cyberlindnera subsufficiens C6.1 with Lactiplantibacillus plantarum FST 1.7 were performed and compared to a brewer's yeast, Saccharomyces cerevisiae WLP001. Fermentations were monitored for pH, TTA, extract reduction, alcohol production, and microbial cell count. The final beers were analysed for sugar and organic acid concentration, free amino nitrogen content (FAN), glycerol, and levels of volatile metabolites. The inability of the non-Saccharomyces yeasts to utilise maltotriose as an energy source resulted in extended fermentation times compared to S. cerevisiae WLP001. Co-fermentation of yeasts with lactic acid bacteria (LAB) resulted in a decreased pH, higher TTA and increased levels of lactic acid in the final beers. The overall acceptability of the NABs produced by co-fermentation was higher than or similar to that of the beers fermented with the yeasts alone, indicating that LAB fermentation did not negatively impact the sensory attributes of the beer. C. subsufficiens C6.1 and L. plantarum FST 1.7 NAB was characterised as fruity tasting with the significantly higher ester concentrations masking the wort-like flavours resulting from limited fermentation. NAB produced with L. fermentati KBI12.1 and L. plantarum FST1.7 had decreased levels of the undesirable volatile compound diacetyl and was described as 'fruity' and 'acidic', with the increased sourness masking the sweet, wort-like characteristics of the NAB. Moreover, this NAB was ranked as the most highly acceptable in the sensory evaluation. In conclusion, the limited co-fermentation of non-Saccharomyces yeasts with LAB is a promising strategy for the production of NAB.

Epithelial TGFß engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features.

The pro-tumourigenic role of epithelial TGFß signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFß signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFß signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFß signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFß signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC's with born to be bad traits.

Transcriptional comparison of adult human primary Retinal Pigment Epithelium, human pluripotent stem cell-derived Retinal Pigment Epithelium, and ARPE19 cells.

The therapeutic potential of pluripotent stem cells is great as they promise to usher in a new era of medicine where cells or organs may be prescribed to replace dysfunctional tissue. At the forefront are efforts in the eye to develop this technology as it lends itself to in vivo monitoring and sophisticated non-invasive imaging modalities. In the retina, retinal pigment epithelium (RPE) is the most promising replacement cell as it has a single layer, is relatively simple to transplant, and is associated with several eye diseases. However, after transplantation, the cells may transform and cause complications. This transformation may be partially due to incomplete maturation. With the goal of learning how to mature RPE, we compared induced pluripotent stem cell-derived RPE (iPSC-RPE) cells with adult human primary RPE (ahRPE) cells and the immortalized human ARPE-19 line. We cultured ARPE-19, iPSC-RPE, and ahRPE cells for one month, and evaluated morphology, RPE marker staining, and transepithelial electrical resistance (TEER) as quality control indicators. We then isolated RNA for bulk RNA-sequencing and DNA for genotyping. We genotyped ahRPE lines for the top age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR) risk allele polymorphisms. Transcriptome data verified that both adult and iPSC-RPE exhibit similar RPE gene expression signatures, significantly higher than ARPE-19. In addition, in iPSC-RPE, genes relating to stem cell maintenance, retina development, and muscle contraction were significantly upregulated compared to ahRPE. We compared ahRPE to iPSC-RPE in a model of epithelial-mesenchymal transition (EMT) and observed an increased sensitivity of iPSC-RPE to producing contractile aggregates in vitro which resembles incident reports upon transplantation. P38 inhibition was capable of inhibiting iPSC-RPE-derived aggregates. In summary, we find that the transcriptomic signature of iPSC-RPE conveys an immature RPE state which may be ameliorated by targeting "immature" gene regulatory networks.

EyeVolve, a modular PYTHON based model for simulating developmental eye type diversification.

Vision is among the oldest and arguably most important sensory modalities for animals to interact with their external environment. Although many different eye types exist within the animal kingdom, mounting evidence indicates that the genetic networks required for visual system formation and function are relatively well conserved between species. This raises the question as to how common developmental programs are modified in functionally different eye types. Here, we approached this issue through EyeVolve, an open-source PYTHON-based model that recapitulates eye development based on developmental principles originally identified in Drosophila melanogaster. Proof-of-principle experiments showed that this program's animated timeline successfully simulates early eye tissue expansion, neurogenesis, and pigment cell formation, sequentially transitioning from a disorganized pool of progenitor cells to a highly organized lattice of photoreceptor clusters wrapped with support cells. Further, tweaking just five parameters (precursor pool size, founder cell distance and placement from edge, photoreceptor subtype number, and cell death decisions) predicted a multitude of visual system layouts, reminiscent of the varied eye types found in larval and adult arthropods. This suggests that there are universal underlying mechanisms that can explain much of the existing arthropod eye diversity. Thus, EyeVolve sheds light on common principles of eye development and provides a new computational system for generating specific testable predictions about how development gives rise to diverse visual systems from a commonly specified neuroepithelial ground plan.