Oncogenic IDH mutations increase heterochromatin-related replication stress without impacting homologous recombination.

Oncogenic mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) produce 2-hydroxyglutarate (2HG), which inhibits dioxygenases that modulate chromatin dynamics. The effects of 2HG have been reported to sensitize IDH tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors. However, unlike PARP-inhibitor-sensitive BRCA1/2 tumors, which exhibit impaired homologous recombination, IDH-mutant tumors have a silent mutational profile and lack signatures associated with impaired homologous recombination. Instead, 2HG-producing IDH mutations lead to a heterochromatin-dependent slowing of DNA replication accompanied by increased replication stress and DNA double-strand breaks. This replicative stress manifests as replication fork slowing, but the breaks are repaired without a significant increase in mutation burden. Faithful resolution of replicative stress in IDH-mutant cells is dependent on poly-(ADP-ribosylation). Treatment with PARP inhibitors increases DNA replication but results in incomplete DNA repair. These findings demonstrate a role for PARP in the replication of heterochromatin and further validate PARP as a therapeutic target in IDH-mutant tumors.

De novo inference of systems-level mechanistic models of development from live-imaging-based phenotype analysis.

Elucidation of complex phenotypes for mechanistic insights presents a significant challenge in systems biology. We report a strategy to automatically infer mechanistic models of cell fate differentiation based on live-imaging data. We use cell lineage tracing and combinations of tissue-specific marker expression to assay progenitor cell fate and detect fate changes upon genetic perturbation. Based on the cellular phenotypes, we further construct a model for how fate differentiation progresses in progenitor cells and predict cell-specific gene modules and cell-to-cell signaling events that regulate the series of fate choices. We validate our approach in C. elegans embryogenesis by perturbing 20 genes in over 300 embryos. The result not only recapitulates current knowledge but also provides insights into gene function and regulated fate choice, including an unexpected self-renewal. Our study provides a powerful approach for automated and quantitative interpretation of complex in vivo information.

Structural and developmental principles of neuropil assembly in C. elegans.

Neuropil is a fundamental form of tissue organization within the brain1, in which densely packed neurons synaptically interconnect into precise circuit architecture2,3. However, the structural and developmental principles that govern this nanoscale precision remain largely unknown4,5. Here we use an iterative data coarse-graining algorithm termed 'diffusion condensation'6 to identify nested circuit structures within the Caenorhabditis elegans neuropil, which is known as the nerve ring. We show that the nerve ring neuropil is largely organized into four strata that are composed of related behavioural circuits. The stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create neural structures that cage the strata within the nerve ring. We use high resolution light-sheet microscopy7,8 coupled with lineage-tracing and cell-tracking algorithms9,10 to resolve the developmental sequence and reveal principles of cell position, migration and outgrowth that guide stratified neuropil organization. Our results uncover conserved structural design principles that underlie the architecture and function of the nerve ring neuropil, and reveal a temporal progression of outgrowth-based on pioneer neurons-that guides the hierarchical development of the layered neuropil. Our findings provide a systematic blueprint for using structural and developmental approaches to understand neuropil organization within the brain.

Impact of participation as a peer change agent on peer change agents themselves: a quantitative study of a peer-led, social media-based PrEP promotion intervention.

Despite the adoption of pre-exposure prophylaxis (PrEP) as a crucial HIV intervention, uptake remains suboptimal among men who have sex with men, a sexual minority group, due to barriers like cost and stigma. Peer change agents (PCAs) disseminate PrEP information within their social networks. This study explores the reciprocal effects of an online community-based participatory intervention on PCAs, focusing on their transformed PrEP uptake perceptions-leadership efficacy, social network dynamics, attitudes, perceived benefits and barriers and self-efficacy. Leveraging insights from the PrEP Chicago Study, our research addresses a key gap in community-based participatory interventions for PrEP uptake: the transformative experiences and perception shifts of PCAs involved in these interventions. We engaged 20 men who have sex with men, aged 18-45, as PCAs in a one-group pretest-posttest design intervention, which disseminated PrEP communications within their preferred online networks. We utilized the PrEP Chicago Study's 45 Likert items, tailored to reveal the PCAs' transformative potential. Data on PrEP uptake perceptions, sociodemographics and social media use were captured and analyzed using the Wilcoxon matched-pairs signed-rank test, a nonparametric method. PCAs demonstrated significant changes in their PrEP uptake perceptions, including leadership capacity, social network dynamics, attitudes toward PrEP, perceived benefits, barriers and self-efficacy. Our intervention highlights the reciprocal transformation PCAs undergo when disseminating PrEP information. This study adds a new dimension to community-based PrEP interventions and underscores the need for continued refinement of peer-led strategies to optimize the transformative potential of PCAs.

Dental Care Utilization of Hospitalized Persons Living with HIV and Substance Use.

People living with HIV (PLWH) who use drugs experience worse health outcomes than their non-using counterparts. Little is known about how often they seek dental care and the factors that influence their utilization. PLWH with substance use disorders who were inpatients at 11 urban hospitals (n = 801) participated in a National Institute on Drug Abuse Clinical Trials Network study to improve engagement in HIV outcomes. Dental care utilization at each time point during the study period (baseline, 6 months and/or 12 months) was assessed (n = 657). Univariate analysis and logistic regression were used to examine factors associated with dental care utilization. Over half (59.4%) reported not having received any dental care at any timepoint. Participants with less than high school education had lower odds of reporting dental care utilization than those with more than education (aOR = 0.60 [95% CI 0.37-0.99], p = 0.0382). Participants without health insurance also had lower odds of reporting dental care utilization than those with insurance (aOR = 0.50 [95% CI 0.331-0.76], p = 0.0012). Higher food insecurity was associated with having recent dental care utilization (OR = 1.03 [95% CI 1.00, 1.05], p = 0.0359). Additionally, those from Southern states were less likely to report dental care utilization (aOR = 0.55 [95% CI 0.38, 0.79], p = 0.0013). Having health insurance and education are key factors associated with use of dental care for PLWH with substance use disorders. The association between food insecurity and dental care utilization among this population suggests the need for further exploration.

Prevalence and protective factors of HIV and syphilis infection among men who have sex with men in Northwest China.

BACKGROUND: Men who have sex with men (MSM) continue to be disproportionately impacted by human immunodeficiency virus (HIV) and syphilis in China. Little is known about HIV and syphilis infections among MSM in Xi'an, a developing city in Northwest China. A cross-sectional study with recruitment via snowball sampling was conducted to collect HIV and syphilis infection status and risk factors among MSM in Xi'an between April 2013 to December 2016. Among the 5000 participants, the mean age was 29.0 years (SD 7.7) and the prevalence of HIV, syphilis, and coinfection was 6.5%, 2.2%, and 0.4%, respectively. There was no significant change in HIV prevalence from 2013 to 2016, while the prevalence of syphilis and coinfection showed a downward trend. Multiple logistic regression analyses found that being over 25 years old (OR = 1.647), junior high school/middle school education and below (OR = 3.085), with a sexual role of passive or versatile (OR = 3.300; OR = 2.337), rush poppers use during the last 6 months (OR = 1.660) and syphilis infection (OR = 2.235) were more likely to acquire HIV infection, whereas used condoms in the last episode of anal sex (OR = 0.572) and tested HIV antibody previously (OR = 0.252) were protective factors for HIV infection. HIV prevalence among MSM in Xi'an was stable, whereas the prevalence of syphilis and coinfection showed a downward trend. Interventions to promote HIV and sexually transmitted disease testing and condom use should be strengthened, especially for MSM with low education.

HIV testing in the dental setting: A global perspective of feasibility and acceptability.

HIV is no longer a death sentence with early diagnosis and effective treatment contributing to a good prognosis. Surveillance data, however, suggest that one in four people globally living with HIV are unaware of their HIV infection and remains at risk of transmitting their infection if having unprotected sex. A wider array of testing opportunities and settings are thus needed to address this issue of public health significance. Evidence suggests there is a role for the dental team, particularly dentists, in offering chairside point-of-care HIV screening to patients during their dental appointments. Dentists, dental hygienists, and other members of the dental team may still have a role in helping to identify new cases of HIV with the goal of improving health outcomes, addressing health inequalities and improving the quality and quantity of life. This paper reviews the global epidemiology of HIV/AIDS, summarizes the point-of-care HIV testing process, highlights key findings of international studies (from high-, middle-, and low-income countries) on the role of dental professionals in point-of-care HIV testing, and offers suggestions for what additional evidence is needed to make point-of-care HIV testing a routine part of dental care.

HIV testing: What, where and how?

Globally, one in four people living with HIV are unaware of their status. Current HIV testing services' strategies are falling short of reaching all, and thus, HIV testing should be offered in more decentralized and non-traditional settings such as the dental and community settings. The workshop titled "HIV Testing: What, Where, and How?" provided an overview of concepts and advances in HIV point of care and self-testing diagnostics and a discussion on the implementation of HIV self-test interventions in different healthcare settings and its impact thereof. We also described how to build layperson capacity to deliver HIV testing in community settings. Additionally, we discussed what we have learned from expanding HIV testing beyond the specialist setting. We also noted considerations (i.e. provider willingness, test selection, training and preparing testing environment) dentists and other non-specialist providers need to account for if they are planning to conduct HIV testing. Finally, we highlighted facilitators and barriers to implementing HIV testing in the dental setting on a global scale. These considerations are critical to meeting the UNAIDS 90-90-90 target to help end the HIV/AIDS epidemic.

The role of patient and public involvement in oral health and HIV/AIDS research, practice and policy.

Patient and public involvement (PPI) is a process whereby patients, caregivers, service users and other relevant stakeholders, including the general public, are actively involved and engaged in activities to develop research. The dental research agenda has traditionally been driven by clinicians, where patients and the public have participated in research as subjects; patient and public involvement can contribute to the research agenda including the design and conduct of research by providing unique perspectives gained through lived experience. This panel of the 8th World Workshop on Oral Health and Diseases in AIDS considered the role of people living with HIV (PLHIV) to contribute to oral health and HIV research and policy through a process of involvement and empowerment. The panel introduced the concepts of PPI, described the purpose of PPI, reflected upon the logistic and ethical considerations thereof and considered how PPI had been utilised effectively in HIV research and policy change. The audience discussion focused on ways in which PPI could more readily and consistently be encouraged within oral health research involving PLHIV.

HIV and stigma in the healthcare setting.

People living with HIV (PLHIV) continue to endure stigma and discrimination in the context of health care despite global improvements in health outcomes. HIV stigma persists within healthcare settings, including dental settings, manifesting itself in myriad, intersecting ways, and has been shown to be damaging in the healthcare setting. Stigmatising practices may include excessive personal protective equipment, delaying the provision of care or unnecessary referral of PLHIV to specialist services in order to access care. The workshop entitled "HIV and Stigma in the Healthcare Setting" provided an overview of the concept and manifestation of HIV stigma and explored the disproportionate burden it places on groups that face additional disadvantages in accessing care. The final part of the workshop concluded with a review of institutional and community-based interventions that worked to reduce HIV stigma and group discussion of the ways in which these strategies might be adapted to the dental workforce.

Effect of early highly active antiretroviral therapy on viral suppression among newly diagnosed men who have sex with men living with human immunodeficiency virus in Xi'an, China.

BACKGROUND: The number of men who have sex with men (MSM) living with human immunodeficiency virus (HIV) in China has increased rapidly and thus immediate highly active antiretroviral therapy (HAART) after diagnosis was implemented as a strategy to reduce the HIV transmission. METHODS: MSM who were diagnosed with HIV and received HAART between 2013 to 2015 in Xi'an were divided into three groups (>350, 200-350, and <200 cell/µL) according to their baseline CD4+ T cell count. The time of follow-up was calculated from the first date of receiving HAART to December 31, 2016. The CD4+ T cell count was detected with 1 week before or after HAART. The plasma viral loads were tested after 1, 2, and 3 years of treatment. RESULTS: Of 1442 subjects who received HAART, 690 (47.9%) cases were in >350 cell/µL group, whereas 400 (27.7%) cases and 352 (24.4%) cases were in the 200-350 cell/µL group and <200 cell/µL group, respectively. After 1 year of treatment, the viral suppression rate in the <200 cell/µL group was 91.1%, which was significantly lower than the other two groups. The logistic regression results show that the >350 cell/µL group and 200-350 cell/µL group predicted higher viral suppression rates. CONCLUSIONS: Baseline CD4+ T cell count more than 350 cell/µL can improve viral suppression among MSM living with HIV. Furthermore, to reduce the transmission risk, the treatment compliance of people living with HIV with high CD4+ T cell levels should be improved, and their diagnosis to the treatment time should be decreased.

Self-Justifications for Unsafe Sex Among Incarcerated Young Men Who Have Sex with Men and Are Living with HIV: Results from a New York City Jail-Based Pilot Intervention.

Young men who have sex with men (YMSM), especially African American and Latinx YMSM, accounted for the highest proportion of new HIV diagnoses in 2016. Minorities and persons living with HIV are over-represented in correctional settings. To influence risk behaviors of incarcerated YMSM who are living with HIV, New York City Health + Hospitals adapted, implemented, and evaluated an evidence-based intervention (EBI)-Personalized Cognitive Counseling-as a pilot program for YMSM, aged 20-29 in New York City jails from May 2015 to July 2016. Thirty-four participants recalled a memorable episode of unprotected anal intercourse (UAI), discussed the episode and resulting thoughts and feelings, identified the self-justifications that facilitated the episode, and discussed possible behavior modifications when presented with similar situations in the future. The top endorsed self-justifications for UAI included that they already had UAI with this person, condomless sex feels more natural, not wanting to lose the opportunity for sex, that substance use influenced their thinking, and not wanting to think about HIV transmission. HIV knowledge improved slightly, as measured by the 18 item HIV-KQ-18 HIV Knowledge Questionnaire, from a pre-intervention average of 15.17 (SD = 3.05) to post-intervention average of 16.48 (SD = 1.64) (p < 0.05). Learning the self-justifications that justice-involved MSM have for having UAI is beneficial for targeting future health promotion interventions. Despite challenges inherent in the jail setting, HIV behavioral EBIs are feasible and they can improve HIV knowledge and encourage exploration of self-justifications for risky behavior.

AceTree: a major update and case study in the long term maintenance of open-source scientific software.

BACKGROUND: AceTree, a software application first released in 2006, facilitates exploration, curation and editing of tracked C. elegans nuclei in 4-dimensional (4D) fluorescence microscopy datasets. Since its initial release, AceTree has been continuously used to interact with, edit and interpret C. elegans lineage data. In its 11 year lifetime, AceTree has been periodically updated to meet the technical and research demands of its community of users. This paper presents the newest iteration of AceTree which contains extensive updates, demonstrates the new applicability of AceTree in other developmental contexts, and presents its evolutionary software development paradigm as a viable model for maintaining scientific software. RESULTS: Large scale updates have been made to the user interface for an improved user experience. Tools have been grouped according to functionality and obsolete methods have been removed. Internal requirements have been changed that enable greater flexibility of use both in C. elegans contexts and in other model organisms. Additionally, the original 3-dimensional (3D) viewing window has been completely reimplemented. The new window provides a new suite of tools for data exploration. CONCLUSION: By responding to technical advancements and research demands, AceTree has remained a useful tool for scientific research for over a decade. The updates made to the codebase have extended AceTree's applicability beyond its initial use in C. elegans and enabled its usage with other model organisms. The evolution of AceTree demonstrates a viable model for maintaining scientific software over long periods of time.

C. elegans SoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types.

Neurogenesis involves deeply conserved patterning molecules, such as the proneural basic helix-loop-helix transcription factors. Sox proteins and specifically members of the SoxB and SoxC groups are another class of conserved transcription factors with an important role in neuronal fate commitment and differentiation in various species. In this study, we examine the expression of all five Sox genes of the nematode C. elegans and analyze the effect of null mutant alleles of all members of the SoxB and SoxC groups on nervous system development. Surprisingly, we find that, unlike in other systems, neither of the two C. elegans SoxB genes sox-2 (SoxB1) and sox-3 (SoxB2), nor the sole C. elegans SoxC gene sem-2, is broadly expressed throughout the embryonic or adult nervous system and that all three genes are mostly dispensable for embryonic neurogenesis. Instead, sox-2 is required to maintain the developmental potential of blast cells that are generated in the embryo but divide only postembryonically to give rise to differentiated neuronal cell types. Moreover, sox-2 and sox-3 have selective roles in the terminal differentiation of specific neuronal cell types. Our findings suggest that the common themes of SoxB gene function across phylogeny lie in specifying developmental potential and, later on, in selectively controlling terminal differentiation programs of specific neuron types, but not in broadly controlling neurogenesis.

Digital development: a database of cell lineage differentiation in C. elegans with lineage phenotypes, cell-specific gene functions and a multiscale model.

Developmental systems biology is poised to exploit large-scale data from two approaches: genomics and live imaging. The combination of the two offers the opportunity to map gene functions and gene networks in vivo at single-cell resolution using cell tracking and quantification of cellular phenotypes. Here we present Digital Development (http://www.digital-development.org), a database of cell lineage differentiation with curated phenotypes, cell-specific gene functions and a multiscale model. The database stores data from recent systematic studies of cell lineage differentiation in the C. elegans embryo containing ∼ 200 conserved genes, 1400 perturbed cell lineages and 600,000 digitized single cells. Users can conveniently browse, search and download four categories of phenotypic and functional information from an intuitive web interface. This information includes lineage differentiation phenotypes, cell-specific gene functions, differentiation landscapes and fate choices, and a multiscale model of lineage differentiation. Digital Development provides a comprehensive, curated, multidimensional database for developmental biology. The scale, resolution and richness of biological information presented here facilitate exploration of gene-specific and systems-level mechanisms of lineage differentiation in Metazoans.

A Qualitative Study of Rapid HIV Testing and Lesbian, Gay, Bisexual, Transgender, and Queer Competency in the Oral Health Setting: Practices and Attitudes of New York State Dental Directors.

PURPOSE: Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) cultural competency and awareness in healthcare settings have been recognized for minimizing health disparities, yet their integration within the oral health community has been minimal. Furthermore, despite evidence showing the compatibility of rapid HIV testing (RHT) in the oral health setting, actual uptake by dentists has been limited. The purpose of this qualitative study was to document New York State dental directors' perspectives and attitudes regarding issues relevant to the LGBTQ patient care and RHT. MATERIALS AND METHODS: Semi-structured interviews (N=10) were conducted with New York State dental directors practicing in areas of high HIV prevalence. A deductive and inductive qualitative approach was used to develop an interview guide, in accordance with the Theory of Planned Behavior, that elicited their perspectives, attitudes, and perspectives on RHT and LGBTQ issues. RESULTS: Thematic analysis of the interviews revealed that many dentists cited limited, if any, training and experience in RHT and LGBTQ patient care. Additionally, there was also an evident dichotomy between dentists who were offering RHT and dentists who were knowledgeable and well-versed in LGBTQ issues. Barriers to implementation included time constraints and minimal training and knowledge. CONCLUSIONS: While potential facilitators such as test kit reimbursement and patient referral sources could enable LGBTQ and RHT training and uptake, actual implementation in the oral health setting will likely require additional trainings, more involved collaboration with primary care providers, and an overall cultural change amongst the dental profession.

Cell cycle features of C. elegans germline stem/progenitor cells vary temporally and spatially.

Many organisms accumulate a pool of germline stem cells during development that is maintained in later life. The dynamics of establishment, expansion and homeostatic maintenance of this pool are subject to both developmental and physiological influences including the availability of a suitable niche microenvironment, nutritional status, and age. Here, we investigated the dynamics of germline proliferation during stages of expansion and homeostasis, using the C. elegans germ line as a model. The vast majority of germ cells in the proliferative zone are in interphase stages of mitosis (G1, S, G2) rather than in the active mitotic (M) phase. We examined mitotic index and DNA content, comparing different life stages, mutants, and physiological conditions. We found that germ cells in larval stages cycle faster than in adult stages, but that this difference could not be attributed to sexual fate of the germ cells. We also found that larval germ cells exhibit a lower average DNA content compared to adult germ cells. We extended our analysis to consider the effects of distance from the niche and further found that the spatial pattern of DNA content differs between larval and adult stages in the wild type and among mutants in pathways that interfere with cell cycle progression, cell fate, or both. Finally, we characterized expansion of the proliferative pool of germ cells during adulthood, using a regeneration paradigm (ARD recovery) in which animals are starved and re-fed. We compared adult stage regeneration and larval stage expansion, and found that the adult germ line is capable of rapid accumulation but does not sustain a larval-level mitotic index nor does it recapitulate the larval pattern of DNA content. The regenerated germ line does not reach the number of proliferative zone nuclei seen in the continuously fed adult. Taken together, our results suggest that cell cycle dynamics are under multiple influences including distance from the niche, age and/or maturation of the germ line, nutrition and, possibly, latitude for physical expansion.

Willingness of Certified Health Education Specialists to Conduct Rapid HIV Testing: Results From the Promoting Research on Methods in Screening Expertise Study.

BACKGROUND: Approximately 16% of people living with HIV are not aware of their infection. Health education specialists, with their training in health program design, implementation, evaluation, and work with vulnerable communities, may have the necessary expertise to conduct rapid HIV testing (RHT). METHOD: A national, cross-sectional, online survey of Certified Health Education Specialists (CHES) and Master CHES (MCHES) was conducted from April to October 2013, with participants recruited through the National Commission on Health Education Credentialing. We surveyed CHES/MCHES on HIV knowledge and attitudes as well as willingness to conduct RHT. RESULTS: A total of 1,421 CHES/MCHES completed the survey, with a median age of 32 years and median level of 7 years of experience. The majority were White (70.3%), female (91.7%), and heterosexual (93.1%). The majority of respondents had high knowledge of HIV (69.7%), thought that CHES/MCHES should offer RHT (75.2%), and was willing to get trained/certified to conduct RHT (80.3%). Those willing to get trained/certified were more likely to feel comfortable educating clients about HIV prevention methods (p < .001) and planning health promotion programs for people living with HIV (p < .001). Perceived barriers to conducting RHT were related to lack of knowledge of RHT counseling (34.8%) and procedures (25%). CONCLUSIONS: CHES/MCHES have the potential to play a significant role in increasing the availability of HIV testing, and the majority of respondents expressed a willingness to become involved. However, training and implementation barriers were identified. Piloting such an approach should be considered to further evaluate the optimum ways in which expanding HIV testing can be achieved.

Willingness of Australian health educators and health promotion officers to conduct rapid HIV testing.

Issue addressed: Rapid HIV tests were recently approved by the Australian government. This paper examines the attitudes and willingness to conduct rapid HIV testing (RHT) of Australian health educators and health promotion officers (HE/HPO) from various settings and disciplines.Methods: The aim of the Promoting Research on Methods in Screening Expertise study was to explore knowledge of HIV, attitudes towards people living with HIV, and willingness to conduct RHT among HE/HPO in Australia; this information was attained via an online survey of HE/HPO. Descriptive statistics, χ2 tests, t-tests, and multivariate logistic regression were then conducted.Results: Data from 156 HE/HPOs were analysed. Overall, 60% of participants believed that HE/HPO should offer RHT. Additionally, 70% were personally willing to undergo training in conducting RHT. Fifty-nine percent of participants scored as having 'high' HIV knowledge (at least 12 out of 13 correct answers), with 32% answering all questions correctly. Knowledge was strongly associated with willingness to be trained to conduct RHT.Conclusions: HE/HPO with advanced training in developing evidence-based approaches to improve the health and wellbeing of marginalised and disadvantaged groups may be an appropriate workforce to train to conduct RHT and counselling.So what?: As government agencies and community-based organisations plan to expand RHT, HE/HPO, including those who work outside of sexual health, should be considered as a viable workforce to upskill.

WormGUIDES: an interactive single cell developmental atlas and tool for collaborative multidimensional data exploration.

BACKGROUND: Imaging and image analysis advances are yielding increasingly complete and complicated records of cellular events in tissues and whole embryos. The ability to follow hundreds to thousands of cells at the individual level demands a spatio-temporal data infrastructure: tools to assemble and collate knowledge about development spatially in a manner analogous to geographic information systems (GIS). Just as GIS indexes items or events based on their spatio-temporal or 4D location on the Earth these tools would organize knowledge based on location within the tissues or embryos. Developmental processes are highly context-specific, but the complexity of the 4D environment in which they unfold is a barrier to assembling an understanding of any particular process from diverse sources of information. In the same way that GIS aids the understanding and use of geo-located large data sets, software can, with a proper frame of reference, allow large biological data sets to be understood spatially. Intuitive tools are needed to navigate the spatial structure of complex tissue, collate large data sets and existing knowledge with this spatial structure and help users derive hypotheses about developmental mechanisms. RESULTS: Toward this goal we have developed WormGUIDES, a mobile application that presents a 4D developmental atlas for Caenorhabditis elegans. The WormGUIDES mobile app enables users to navigate a 3D model depicting the nuclear positions of all cells in the developing embryo. The identity of each cell can be queried with a tap, and community databases searched for available information about that cell. Information about ancestry, fate and gene expression can be used to label cells and craft customized visualizations that highlight cells as potential players in an event of interest. Scenes are easily saved, shared and published to other WormGUIDES users. The mobile app is available for Android and iOS platforms. CONCLUSION: WormGUIDES provides an important tool for examining developmental processes and developing mechanistic hypotheses about their control. Critically, it provides the typical end user with an intuitive interface for developing and sharing custom visualizations of developmental processes. Equally important, because users can select cells based on their position and search for information about them, the app also serves as a spatially organized index into the large body of knowledge available to the C. elegans community online. Moreover, the app can be used to create and publish the result of exploration: interactive content that brings other researchers and students directly to the spatio-temporal point of insight. Ultimately the app will incorporate a detailed time lapse record of cell shape, beginning with neurons. This will add the key ability to navigate and understand the developmental events that result in the coordinated and precise emergence of anatomy, particularly the wiring of the nervous system.