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Colouring Australia is a digital platform for collecting and visualising building level information across several Australian cities. It provides a valuable resource for bringing together data on building age, material, sustainability ratings, walkability and other key metrics as we plan for net zero cities. Colouring Australia comprises part of the international Colouring Cities Research Programme, which supports the development of open-source platforms that provide open data on national building stocks. In this paper we outline the technical architecture of the platform, and the development and visualisation of a building level walkability metric based on pedestrian access to destinations. This platform provides a useful digital tool for planners to understand which parts of the city are walkable and in turn this can support future active transport programs and policies. Future research will be to validate this novel walkability index through a series of stakeholder and public workshops using the Colouring Australia platform in an interactive tabletop environment where usability testing can be undertaken.

Summary: Nutritional equivalency feeding studies with diets containing genetically modified grain continue to be required by some regulatory agencies as part of the safety assessment of new events. These studies have long been conducted using broiler chickens, as they are very sensitive to nutritional deficiencies and antinutrients in the diet owing to their very rapid growth rate. A new transgenic maize product containing event DP-2Ø2216-6 (DP202216) with enhanced grain yield potential and an herbicide-tolerance trait has been developed. The nutritional equivalency of grain produced from maize containing this event with conventional grain was evaluated in a 42-D feeding trial with male and female Ross 708 broiler chickens. Broilers consuming diets produced with grain from DP202216 maize plants performed as well and produced similar organ, carcass, and parts yields as broilers consuming diets produced with nontransgenic near-isogenic control grain. In addition, the ranges of observed performance and carcass and organ yield trait values from DP202216 and control groups were similar to the respective ranges observed for broilers fed diets containing nontransgenic commercially available maize grains. Based on these results, it is concluded that grain from DP202216 maize is nutritionally equivalent to grain from nontransgenic near-isogenic maize, consistent with previously published reports on whole-food (where the edible crop tissue is incorporated in the feed) animal feeding studies for other genetically modified events.

The molecular mechanisms underlying deficits in Down syndrome remain unclear. Here, the authors show that copy number restoration of a chromatin remodeler in trisomic mice is sufficient to rescue epigenomic, physiological and cognitive deficits.

Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of DYRK1A, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of Dyrk1a and treatment with ~9 mg/kg/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice. Treatment of individuals with DS with green tea extract (GTE) containing EGCG also showed some weight loss in individuals with DS, and we hypothesized that weights would be affected in Ts65Dn mice after EGCG treatment. Treatment with ~20 mg/kg/day EGCG for seven weeks showed no improvements in male Ts65Dn trabecular bone and only limited improvements in cortical measures. Comparing skeletal analyses after ~20mg/kg/day EGCG treatment with previously published treatments with ~9, 50, and 200 mg/kg/day EGCG showed that increased dosage and treatment time increased cortical structural deficits leading to weaker appendicular bones in male mice. Weight was not affected by treatment in mice, except for those given a high dose of EGCG by oral gavage. These data indicate that high doses of EGCG, similar to those reported in some treatment studies of DS and other disorders, may impair long bone structure and strength. Skeletal phenotypes should be monitored when high doses of EGCG are administered therapeutically.

Abstract Any hypothesis aiming to explain the social organisation of Eurasian badgers Meles meles has to consider its wide inter-population variability. We used radiotracking techniques to investigate the spatial organisation and the pattern of space-use by badger in Luxembourg, where badger density can be considered moderate compared to most of Europe. Eight badgers belonging to five social groups were caught and radio-collared. The size of individual home ranges, as assesses by 100% minimum convex polygons in spring-summer 2002 and 2003, varied from 42.5 ha to 171.8 ha. Core areas corresponded to the 50-70% kernel isopleths and covered an average of 10.1% of individual home ranges. The home ranges of badgers caught at the same sett overlapped largely (average 83.3%), whilst the overlap between neighbouring ranges did not exceed 13.8%. Altogether six boundary latrines were found at the intersection of group ranges. Overall, the spatial system of the Luxembourg badgers is quite flexible, with the boundaries of some group ranges remaining constant over the years, while others may expand or contract. Riassunto Organizzazione spaziale del tasso (Meles meles) in una popolazione a media densità del Lussemburgo. Qualsiasi ipotesi che voglia spiegare l’organizzazione sociale del tasso Meles meles, deve tener conto della sua ampia variabilità tra le popolazioni. Tramite la radiotelemetria e il monitoraggio delle latrine, la struttura territoriale e l’uso dello spazio da parte del tasso sono stati analizzati in una popolazione del Lussemburgo, dove la densità della specie può essere considerata intermedia rispetto ai valori noti per il resto dell’Europa. Sono stati marcati con radio-collari otto tassi, appartenenti a cinque diversi gruppi sociali. Le dimensioni delle aree vitali, stimate con il minimo poligono convesso al 100% per il periodo primaverile-estivo del 2002 e 2003, sono risultate comprese tra 42.5 e 171.8 ha. Le core areas, delimitate dalle isoplete al 50-70% ottenute con il metodo kernel, includevano, in media, il 10,1% delle aree vitali individuali. Le aree vitali di individui appartenenti allo stesso gruppo sociale sono risultate nettamente sovrapposte (media: 83.3%), mentre la massima sovrapposizione di home range confinanti è stata pari al 13,8%. In totale sono state individuate sei latrine, posizionate ai margini delle aree vitali di tre gruppi sociali tra loro confinanti. Nel complesso, i risultati ottenuti suggeriscono che anche in Lussemburgo la struttura spaziale del tasso è basata sulla territorialità, benché tale struttura sia probabilmente abbastanza flessibile, potendosi riscontrare sia confini territoriali stabili nel tempo sia contrazioni o espansioni delle aree vitali dei gruppi sociali. doi:10.4404/hystrix-21.1-4482

This paper describes a multiagent architecture integrated system designed to supervise infrastructures in solar farms. The system enables monitoring the environment by means of sensor networks that are in charge of collecting data. It is designed using a hybrid model composed of an inference engine and an ontology. The former makes the system intelligent, while the latter structures knowledge. We have also developed a tool to configure and use the multiagent system in a simple and intuitive way.

Social animals regularly face consensus decisions whereby they choose, collectively, between mutually exclusive actions. Such decisions often involve conflicts of interest between group members with respect to preferred action. Conflicts could, in principle, be resolved, either by sharing decisions between members (‘shared decisions’) or by one ‘dominant’ member making decisions on behalf of the whole group (‘unshared decisions’). Both, shared and unshared decisions, have been observed. However, it is unclear as to what favours the evolution of either decision type. Here, after a brief literature review, we present a novel method, involving a combination of self-organizing system and game theory modelling, of investigating the evolution of shared and unshared decisions. We apply the method to decisions on movement direction. We find that both, shared and unshared, decisions can evolve without individuals having a global overview of the group's behaviour or any knowledge about other members' preferences or intentions. Selection favours unshared over shared decisions when conflicts are high relative to grouping benefits, and vice versa. These results differ from those of group decision models relating to activity timings. We attribute this to fundamental differences between collective decisions about modalities that are disjunct (here, space) or continuous (here, time) with respect to costs/benefits. [ABSTRACT FROM AUTHOR]

1. The distribution and density of Eurasian badgers Meles meles in Luxembourg was estimated by gathering information about the location of badger setts with a questionnaire survey, by visiting 708 setts in order to classify them as ‘main setts’ or ‘outliers’, and by estimating social group size by directly counting emerging badgers. 2. Badgers were found to be widely distributed in Luxembourg, with a minimum main sett density of 0.17 setts/km2. Setts were sited preferentially in forest habitat. The mean minimum group size was 4.6 badgers. 3. The Luxembourg badger population was conservatively estimated to contain at least 2010 adult and young badgers (95% CI 1674–2347) in spring 2002, equivalent to a density of 0.78 adult and young badgers/km2 (95% CI 0.65–0.91). This is moderate compared to most of continental Europe. [ABSTRACT FROM AUTHOR]

(1) The Shetland Islands lie between Scotland and Norway and this study describes the vegetation types found there with reference to both British/Continental and Scandinavian communities. (2) A conspectus of the main plant communities was obtained by recording vegetation plots from fifteen of the islands, from shingle beaches, sand dunes, salt-marshes, wet meadows, grasslands, blanket peat and heaths. (3) Sixty-five noda were identified and their general characteristics described. These noda were assigned to both recognized and new taxa within seventeen phytosociological classes. (4) A new association of grazed low altitude blanket bogs, the Empetrum- Rhytidiadelphus loreus Association is outlined. (5) The factors influencing plant and vegetation distribution in Shetland are discussed: geographical position and physical isolation from seed sources provide the historical basis. (6) While climatic and topographic interaction on the flora have determined the natural vegetation communities, the impact of land use, particularly grazing, has been to confine these communities to areas inaccessible to sheep. The majority of Shetland's vegetation composition has been determined by grazing. (7) The absence of comparative taxonomic studies, the Islands' geographical position and climate, the influence of salt-spray and intensive land-use produce a merging of community boundaries and difficulties in delimiting discrete associations. [ABSTRACT FROM AUTHOR]

We report a case of angioedema caused by angiotensin-converting enzyme inhibitor and topical lignocaine spray, administered during nasendoscopy.Angioedema induced by angiotensin-converting enzyme inhibitors is a rare but well known entity. Allergy to topical lignocaine has been acknowledged as a rare phenomenon when used for dental surgery and for skin anaesthesia, but it has not previously been reported after topical administration prior to nasendoscopy. In the reported case, our patient was unfortunate enough to be allergic to both lisinopril and lignocaine. The result was life-threatening airway obstruction, and the continued use of lignocaine spray sustained the laryngeal oedema. We advise that patients are asked about any and every allergy – specifically, any previous problems with dental procedures – before administration of local anaesthetic spray to the upper aerodigestive tract. [ABSTRACT FROM AUTHOR]

DYRK1A syndrome results from a reduction in copy number of the DYRK1A gene, which resides on human chromosome 21 (Hsa21). DYRK1A has been implicated in the development of cognitive phenotypes associated with many genetic disorders, including Down syndrome (DS) and Alzheimer’s disease (AD). Additionally, overexpression of DYRK1A in DS has been implicated in the development of abnormal skeletal phenotypes in these individuals. Analyses of mouse models with Dyrk1a dosage imbalance (overexpression and underexpression) show skeletal deficits and abnormalities. Normalization of Dyrk1a copy number in an otherwise trisomic animal rescues some skeletal health parameters, and reduction of Dyrk1a copy number in an otherwise euploid (control) animal results in altered skeletal health measurements, including reduced bone mineral density (BMD) in the femur, mandible, and skull. However, little research has been conducted thus far on the implications of DYRK1A reduction on human skeletal health, specifically in individuals with DYRK1A syndrome. This review highlights the skeletal phenotypes of individuals with DYRK1A syndrome, as well as in murine models with reduced Dyrk1a copy number, and provides potential pathways altered by a reduction of DYRK1A copy number, which may impact skeletal health and phenotypes in these individuals. Understanding how decreased expression of DYRK1A in individuals with DYRK1A syndrome impacts bone health may increase awareness of skeletal traits and assist in the development of therapies to improve quality of life for these individuals.

Abstract The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has highlighted the threat that viral outbreaks pose to global health. A key tool in the arsenal to prevent and control viral disease outbreaks is disinfection of equipment and surfaces with formulations that contain virucidal agents (VA). However, assessment of the efficacy of virus inactivation often requires live virus assays or surrogate viruses such as Modified Vaccinia Virus Ankara (MVA), which can be expensive, time consuming and technically challenging. Therefore, we have developed a pseudo-typed virus (PV) based approach to assess the inactivation of enveloped viruses with a fast and quantitative output that can be adapted to emerging viruses. Additionally, we have developed a method to completely remove the cytotoxicity of virucidal agents while retaining the required sensitivity to measure PV infectivity. Our results indicated that the removal of cytotoxicity was an essential step to accurately measure virus inactivation. Further, we demonstrated that there was no difference in susceptibility to virus inactivation between PVs that express the envelopes of HIV-1, SARS-CoV-2, and Influenza A/Indonesia. Therefore, we have developed an effective and safe alternative to live virus assays that enables the rapid assessment of virucidal activity for the development and optimization of virucidal reagents.

Abstract The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.

Aberrant neurodevelopment in Down syndrome (DS)—caused by triplication of human chromosome 21—is commonly attributed to gene dosage imbalance, linking overexpression of trisomic genes with disrupted developmental processes, with DYRK1A particularly implicated. We hypothesized that regional brain DYRK1A protein overexpression in trisomic mice varies over development in sex-specific patterns that may be distinct from Dyrk1a transcription, and reduction of Dyrk1a copy number from 3 to 2 in otherwise trisomic mice reduces DYRK1A, independent of other trisomic genes. DYRK1A overexpression varied with age, sex, and brain region, with peak overexpression on postnatal day (P) 6 in both sexes. Sex-dependent differences were also evident from P15-P24. Reducing Dyrk1a copy number confirmed that these differences depended on Dyrk1a gene dosage and not other trisomic genes. Trisomic Dyrk1a mRNA and protein expression were not highly correlated. Sex-specific patterns of DYRK1A overexpression during trisomic neurodevelopment may provide mechanistic targets for therapeutic intervention in DS.

Porcine respiratory disease is multifactorial and most commonly involves pathogen co-infections. Major contributors include swine influenza A (swIAV) and porcine reproductive and respiratory syndrome (PRRSV) viruses. Experimental co-infection studies with these two viruses have shown that clinical outcomes can be exacerbated, but how innate and adaptive immune responses contribute to pathogenesis and pathogen control has not been thoroughly evaluated. We investigated immune responses following experimental simultaneous co-infection of pigs with swIAV H3N2 and PRRSV-2. Our results indicated that clinical disease was not significantly exacerbated, and swIAV H3N2 viral load was reduced in the lung of the co-infected animals. PRRSV-2/swIAV H3N2 co-infection did not impair the development of virus-specific adaptive immune responses. swIAV H3N2-specific IgG serum titers and PRRSV-2-specific CD8β+ T-cell responses in blood were enhanced. Higher proportions of polyfunctional CD8β+ T-cell subset in both blood and lung washes were found in PRRSV-2/swIAV H3N2 co-infected animals compared to the single-infected groups. Our findings provide evidence that systemic and local host immune responses are not negatively affected by simultaneous swIAV H3N2/PRRSV-2 co-infection, raising questions as to the mechanisms involved in disease modulation.

The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

Abstract Studying medulloblastoma, the most common malignant paediatric brain tumour, requires simple yet realistic in vitro models. In this study, we optimised a robust, reliable, three-dimensional (3D) culture method for medulloblastoma able to recapitulate the spatial conformation, cell–cell and cell–matrix interactions that exist in vivo and in patient tumours. We show that, when grown under the same stem cell enriching conditions, SHH subgroup medulloblastoma cell lines established tight, highly reproducible 3D spheroids that could be maintained for weeks in culture and formed pathophysiological oxygen gradients. 3D spheroid culture also increased resistance to standard-of-care chemotherapeutic drugs compared to 2D monolayer culture. We exemplify how this model can enhance in vitro therapeutic screening approaches through dual-inhibitor studies and continual monitoring of drug response. Next, we investigated the initial stages of metastatic dissemination using brain-specific hyaluronan hydrogel matrices. RNA sequencing revealed downregulation of cell cycle genes and upregulation of cell movement genes and key fibronectin interactions in migrating cells. Analyses of these upregulated genes in patients showed that their expression correlated with early relapse and overall poor prognosis. Our 3D spheroid model is a significant improvement over current in vitro techniques, providing the medulloblastoma research community with a well-characterised and functionally relevant culture method.

We present results on the morphological and structural evolution of a total of 3956 galaxies observed with JWST at 1.5 < z < 6.5 in the JWST CEERS observations that overlap with the CANDELS EGS field. This is the biggest visually classified sample observed with JWST yet, ∼20 times larger than previous studies, and allows us to examine in detail how galaxy structure has changed over this critical epoch. All sources were classified by six individual classifiers using a simple classification scheme aimed at producing disk/spheroid/peculiar classifications, whereby we determine how the relative number of these morphologies has evolved since the Universe’s first billion years. Additionally, we explore structural and quantitative morphology measurements using Morfometryka , and show that galaxies with M _* > 10 ^9 M _⊙ at z > 3 are not dominated by irregular and peculiar structures, either visually or quantitatively, as previously thought. We find a strong dominance of morphologically selected disk galaxies up to z = 6 in this mass range. We also find that the stellar mass and star formation rate densities are dominated by disk galaxies up to z ∼ 6, demonstrating that most stars in the Universe were likely formed in a disk galaxy. We compare our results to theory to show that the fraction of types we find is predicted by cosmological simulations, and that the Hubble Sequence was already in place as early as one billion years after the Big Bang. Additionally, we make our visual classifications public for the community.

Food limitation may interact with nest predation and influence nesting patterns, such as breeding season length and renesting intervals. If so, reproductive effort should change with food availability. Thus, when food is limited, birds should have fewer attempts and shorter seasons than when food is not limiting. Here we experimentally test that increased food availability results in increased reproductive effort in a fragmented landscape in the Variable Antshrike (Thamnophilus caerulescens) in southern Brazil. We followed nesting pairs in a naturally fragmented habitat and experimentally supplemented food for half of those pairs. Birds were seen, but evidence of nesting was never found in two small fragments, even though these fragments were larger than individual territories. Pairs with supplemented food were more likely to increase clutch size from two to three eggs and tended to renest sooner (20 d on average) than control pairs. Also, fragment size was associated with breeding patterns, although fragment replicates were unavailable. Nest duration, nest success and breeding season length were all greater, while renesting intervals were shorter, in the largest fragments. Simulations showed that only the largest fragments were able to have a net production of young. Food availability clearly influenced reproductive effort and as a consequence, because of the interaction with predation risk, forest fragments of varying sizes will have complex reproductive dynamics.

ABSTRACT The island rule suggests that, when mainland animals are isolated on islands, large animals tend to become smaller, while small animals tend to become larger. A small frog in eastern Brazil, Phyllodytes luteolus (Wied-Neuwied, 1824), is widely distributed in association with bromeliads. At the end of the last glaciation, parts of the mainland became islands due to rising sea levels, thereby isolating frog populations on these islands. If the island rule holds, we predicted that frogs on islands would tend to be larger than frogs on the mainland. We compared sizes (weight and length) of 30 randomly selected male frogs from the mainland with 30 from an island in the state of Espírito Santo, Brazil. We also sampled population density on the island and mainland because concurrent with changing sizes, depending on the causal relationship, density may also change. As predicted, island frogs tended to be larger (both in snout-vent length and weight) and were much more abundant. While not specifically addressed in this study, the absence of predators and interspecific competitors may explain both of these trends.

Down syndrome (trisomy 21, or DS) is the most common live-born aneuploidy in humans, occurring in approximately 1 in 700 live births.

Populations of Asterina stellifera Möbius, 1859 are declining in southern Brazil and today the species is on the Brazilian list of endangered species. Here we experimentally investigate the ecological role played by A. stellifera as a predator on the rocky substrate community by increasing densities of this species. Starfish taken from other, nearby, locations were added to three replicate plots and their density was maintained every 15 days. None of the total of 32 species that were identified in the encrusting community appeared to be influenced by the experiment. Two species, the barnacle Chthamalus bisinuatus Pilsbry, 1916 and the algae Gracilaria verrucosa (Hudson), showed small apparent responses to predation. We found that A. stellifera only exerts weak predation pressure on the community, even at high densities. This result is strikingly different from that observed for similar species in the northern hemisphere and in Australia.

Sexual and asexual reproduction and associated population dynamics were investigated in the colonial ascidian Didemnum rodriguesi Rocha & Monniot, 1993 (Didemnidae) in southern Brazil. Investment in sexual (production of new individuals) and asexual (colony growth) reproduction was compared between seasons. Permanently marked quadrats were repeatedly photographed to measure changes in colonies. Eggs and larvae were counted monthly in collected colonies. This species alternates seasonally between sexual (summer) and asexual (winter) reproduction. In summer, colonies were smaller, brooded eggs and larvae and recruitment rates were greater, while in winter, colony size was larger and eggs and larvae were absent. There is a relationship between fecundity and colony area. Fragmentation and fusion of colonies were similar in summer and winter, as well as mortality. In conclusion, D. rodriguesi has a lifecycle usual for high latitude ascidians with a limited time length for sexual reproduction and alternate investment in sexual and asexual reproduction along the year.Reprodução sexuada e assexuada, mortalidade e a dinâmica de fusões e fissões de colônias de Didemnum rodriguesi Rocha & Monniot, 1993 foram investigados e comparados no sul do Brasil, no inverno e verão. Tais eventos foram analisados por fotografias de áreas permanentemente demarcadas e coletas mensais de colônias. Os resultados indicam que esta espécie alterna sazonalmente a reprodução sexuada (verão) e assexuada (inverno). Durante o verão as colônias são mais abundantes e menores, com ovos e larvas incubados e taxas de recrutamento maiores. No inverno há um menor número de colônias, porém de maior tamanho e inférteis. Existe uma relação entre fecundidade e tamanho da colônia. Não foram encontradas diferenças estatísticas no número de eventos de fragmentação e fusão entre o verão e inverno, bem como para mortalidade. Conclui-se que esta espécie tem um ciclo de vida típico de espécies de maiores latitudes, com tempo limitado para a reprodução sexuada e alternância no investimento entre reprodução sexuada e assexuada.

Down syndrome is a collection of features that are caused by trisomy for human Chromosome 21. While elevated transcript levels of the more than 350 genes on the chromosome are primarily responsible, it is likely that multiple genetic mechanisms underlie the numerous ways in which development and function diverge in individuals with trisomy 21 compared to euploid individuals. We consider genotype-phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy.