Insights and strategies for improving equity in graduate school admissions.

Applying to graduate school can be particularly challenging for students from historically minoritized backgrounds due to a hidden curriculum in the graduate admissions process. To address this issue, a team of volunteer STEM trainees established the Científico Latino Graduate Student Mentorship Initiative (CL-GSMI) in 2019 to support applicants from historically minoritized backgrounds. CL-GSMI is designed to improve access to critical resources, including information, mentorship, and financial support, and has assisted 443 students in applying and matriculating to graduate school. Using program evaluation data from 2020 to 2021, we highlight areas in graduate school admissions that can be improved to promote equity and inclusion.

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification.

Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C. elegans nervous system. To probe homeobox function, we make use of a number of reporter gene tools, including a novel multicolor reporter transgene, NeuroPAL, which permits simultaneous monitoring of the execution of multiple differentiation programs throughout the entire nervous system. Using these tools, we add to the previous characterization of homeobox gene function by identifying neuronal differentiation defects for 14 homeobox genes in 24 distinct neuron classes that are mostly unrelated by location, function and lineage history. 12 of these 24 neuron classes had no homeobox gene function ascribed to them before, while in the other 12 neuron classes, we extend the combinatorial code of transcription factors required for specifying terminal differentiation programs. Furthermore, we demonstrate that in a particular lineage, homeotic identity transformations occur upon loss of a homeobox gene and we show that these transformations are the result of changes in homeobox codes. Combining the present with past analyses, 113 of the 118 neuron classes of C. elegans are now known to require a homeobox gene for proper execution of terminal differentiation programs. Such broad deployment indicates that homeobox function in neuronal identity specification may be an ancestral feature of animal nervous systems.

Visualizing the organization and differentiation of the male-specific nervous system of C. elegans.

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode Caenorhabditis elegans, where male animals contain a little-studied set of 93 male-specific neurons. To make these neurons amenable for future study, we describe here how a multicolor reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male-specific neurons. We used NeuroPAL to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes and for cellular fate analysis by analyzing the effect of removal of several developmental patterning genes on neuronal identity acquisition. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage. This coordinated wave of differentiation, which we call 'just-in-time' differentiation, couples neuronal maturation programs with the appearance of sexual organs.

Pan-pox-specific T-cell responses in HIV-1-infected individuals after JYNNEOS vaccination.

People living with human immunodeficiency virus (HIV) are the individuals most affected by the current Monkeypox virus outbreak that was first announced in May 2022. Here we report Pan-pox-specific T-cell responses in a cohort of HIV-1-infected individuals after receiving the nonreplicative, attenuated smallpox vaccine JYNNEOS from Bavarian Nordic. Intradermal (i.d.) and subcutaneous (s.c.) vaccination was safe without major side effects. Dose-sparing i.d. vaccination was superior to s.c. vaccination and promoted T-cell polyfunctionality, and the expression of the gut-homing marker α4ß7 integrin on lymphocytes. HIV-1-infected individuals with CD4 T-cell counts ≤500/mm3 blood required at least a booster vaccination to exhibit efficient virus-specific T-cell responses. The magnitude of the Th1 response after this booster directly correlated with the CD4 T-cell count of the vaccinees. Further studies with a larger number of participants are warranted to confirm and expand our observations.

Increased Expression of the RBPMS Splice Variants Inhibits Cell Proliferation in Ovarian Cancer Cells.

RNA-Binding Protein with Multiple Splicing (RBPMS) is a member of family proteins that bind to nascent RNA transcripts and regulate their splicing, localization, and stability. Evidence indicates that RBPMS controls the activity of transcription factors associated with cell growth and proliferation, including AP-1 and Smads. Three major RBPMS protein splice variants (RBPMSA, RBPMSB, and RBPMSC) have been described in the literature. We previously reported that reduced RBPMS levels decreased the sensitivity of ovarian cancer cells to cisplatin treatment. However, little is known about the biological role of the RBPMS splice variants in ovarian cancer cells. We performed RT-PCR and Western blots and observed that both RBPMSA and RBPMSC are reduced at the mRNA and protein levels in cisplatin resistant as compared with cisplatin sensitive ovarian cancer cells. The mRNA and protein levels of RBPMSB were not detectable in any of the ovarian cancer cells tested. To better understand the biological role of each RBPMSA and RBPMSC, we transfected these two splice variants in the A2780CP20 and OVCAR3CIS cisplatin resistant ovarian cancer cells and performed cell proliferation, cell migration, and invasion assays. Compared with control clones, a significant reduction in the number of colonies, colony size, cell migration, and invasion was observed with RBPMSA and RBPMSC overexpressed cells. Moreover, A2780CP20-RBPMSA and A2780CP20-RBPMSC clones showed reduced senescence-associated ß-galactosidase (ß-Gal)-levels when compared with control clones. A2780CP20-RBPMSA clones were more sensitive to cisplatin treatment as compared with A2780CP20-RBPMSC clones. The A2780CP20-RBPMSA and A2780CP20-RBPMSC clones subcutaneously injected into athymic nude mice formed smaller tumors as compared with A2780CP20-EV control group. Additionally, immunohistochemical analysis showed lower proliferation (Ki67) and angiogenesis (CD31) staining in tissue sections of A2780CP20-RBPMSA and A2780CP20-RBPMSC tumors compared with controls. RNAseq studies revealed many common RNA transcripts altered in A2780CP20-RBPMSA and A2780CP20-RBPMSC clones. Unique RNA transcripts deregulated by each RBPMS variant were also observed. Kaplan-Meier (KM) plotter database information identified clinically relevant RBPMSA and RBPMSC downstream effectors. These studies suggest that increased levels of RBPMSA and RBPMSC reduce cell proliferation in ovarian cancer cells. However, only RBPMSA expression levels were associated with the sensitivity of ovarian cancer cells to cisplatin treatment.

Upregulation of the Long Noncoding RNA CASC10 Promotes Cisplatin Resistance in High-Grade Serous Ovarian Cancer.

Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC.

Reduced RBPMS Levels Promote Cell Proliferation and Decrease Cisplatin Sensitivity in Ovarian Cancer Cells.

Worldwide, the number of cancer-related deaths continues to increase due to the ability of cancer cells to become chemotherapy-resistant and metastasize. For women with ovarian cancer, a staggering 70% will become resistant to the front-line therapy, cisplatin. Although many mechanisms of cisplatin resistance have been proposed, the key mechanisms of such resistance remain elusive. The RNA binding protein with multiple splicing (RBPMS) binds to nascent RNA transcripts and regulates splicing, transport, localization, and stability. Evidence indicates that RBPMS also binds to protein members of the AP-1 transcription factor complex repressing its activity. Until now, little has been known about the biological function of RBPMS in ovarian cancer. Accordingly, we interrogated available Internet databases and found that ovarian cancer patients with high RBPMS levels live longer compared to patients with low RBPMS levels. Similarly, immunohistochemical (IHC) analysis in a tissue array of ovarian cancer patient samples showed that serous ovarian cancer tissues showed weaker RBPMS staining when compared with normal ovarian tissues. We generated clustered regularly interspaced short palindromic repeats (CRISPR)-mediated RBPMS knockout vectors that were stably transfected in the high-grade serous ovarian cancer cell line, OVCAR3. The knockout of RBPMS in these cells was confirmed via bioinformatics analysis, real-time PCR, and Western blot analysis. We found that the RBPMS knockout clones grew faster and had increased invasiveness than the control CRISPR clones. RBPMS knockout also reduced the sensitivity of the OVCAR3 cells to cisplatin treatment. Moreover, ß-galactosidase (ß-Gal) measurements showed that RBPMS knockdown induced senescence in ovarian cancer cells. We performed RNAseq in the RBPMS knockout clones and identified several downstream-RBPMS transcripts, including non-coding RNAs (ncRNAs) and protein-coding genes associated with alteration of the tumor microenvironment as well as those with oncogenic or tumor suppressor capabilities. Moreover, proteomic studies confirmed that RBPMS regulates the expression of proteins involved in cell detoxification, RNA processing, and cytoskeleton network and cell integrity. Interrogation of the Kaplan-Meier (KM) plotter database identified multiple downstream-RBPMS effectors that could be used as prognostic and response-to-therapy biomarkers in ovarian cancer. These studies suggest that RBPMS acts as a tumor suppressor gene and that lower levels of RBPMS promote the cisplatin resistance of ovarian cancer cells.

Cellular Expression and Functional Roles of All 26 Neurotransmitter GPCRs in the C. elegans Egg-Laying Circuit.

Maps of the synapses made and neurotransmitters released by all neurons in model systems, such as Caenorhabditis elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter GPCRs of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. Receptor knockouts reveal few egg-laying defects under standard laboratory conditions, suggesting that the receptors function redundantly or regulate egg-laying only in specific conditions; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.SIGNIFICANCE STATEMENT Neurotransmitters signal through GPCRs to modulate activity of neurons, and changes in such signaling can underlie conditions such as depression and Parkinson's disease. To determine how neurotransmitter GPCRs together help regulate function of a neural circuit, we analyzed the simple egg-laying circuit in the model organism C. elegans We identified all the cells that express every neurotransmitter GPCR and genetically analyzed how each GPCR affects the behavior the circuit produces. We found that many neurotransmitter GPCRs are expressed in each neuron, that neurons also appear to use these receptors to communicate with other cell types, and that GPCRs appear to often act redundantly or only under specific conditions to regulate circuit function.

Rapid antigen tests for the detection of SARS-CoV-2: A narrative review.

The rapid identificationand isolation of COVID-19 patients has become the cornerstone for the control of the recent outbreak. Real-time quantitative polymerase chain reaction is routinely used to confirm COVID-19 diagnosis and is considered the gold standard due to high sensitivity and specificity. Nevertheless, it usually takes several days and a relatively higher cost. Antigen tests based have emerged to cope with such disadvantages, by offering rapid results, an easy-to-use procedure, and low costs. The objective of the narrative review was to provide up-to-date data about CE-marked rapid antigen tests (RATs) for COVID-19. Given their large number, the study only focused on representative and widely used in Spain (Standard Q, Nadal, Panbio, CerTest, and Wondfo). RATs have become a very useful and validated tool for controlling the spread of COVID-19 allowing the rapid identification of active infection and isolation of positive patients. The present revision of the literature has demonstrated that sensitivity and specificity of all available RATs in Spain are high and accomplish European regulations and WHO recommendations.

Bone density, microarchitecture and tissue quality after 1 year of treatment with dolutegravir/abacavir/lamivudine.

BACKGROUND: Bone mineral density (BMD) decreases with ART initiation with a tenofovir disoproxil fumarate-containing regimen, although bone tissue quality increases. The impact of dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC)-based ART initiation on bone health parameters is not clear. OBJECTIVES: To study the impact of DTG/ABC/3TC-based therapy on bone health parameters in ART-naive individuals with HIV after 48 weeks of treatment. METHODS: An observational, prospective and analytical study of treatment-naive patients with HIV undergoing a DTG/ABC/3TC-based regimen at 48 week follow-up. Changes in bone strength parameters (BMD, bone microarchitecture and bone tissue quality) were assessed with non-parametric methods. RESULTS: Sixteen HIV-infected ART-naive patients starting DTG/ABC/3TC were included. BMD in the lumbar spine showed a significant decrease of -2.25% (P = 0.007) and -4.1% in the femoral neck (P = 0.007). Bone microarchitecture, as measured by trabecular bone score, also decreased significantly by -2.5% (P = 0.03). In contrast, bone quality [bone material strength index (BMi)], as measured by microindentation, significantly increased with respect to baseline after 48 weeks of treatment, showing better bone properties of +6.53% (P < 0.001). No significant changes were found in bone turnover markers. In addition, a positive significant correlation between the CD4/CD8 cell count ratio at baseline and changes in BMSi after 48 weeks of treatment was observed (Spearman's rho = 0.4974; P = 0.04). CONCLUSIONS: After a 48 week treatment with DTG/ABC/3TC-based ART, BMD and trabecular bone score decreased while bone tissue quality, as measured by microindentation, improved significantly. The state of the immune system at ART initiation is related to bone quality recovery. An overarching approach to assess bone toxicity in ART-treated patients is needed.

Serum albumin is a strong predictor of sepsis outcome in elderly patients.

The incidence of sepsis is disproportionately higher in elderly adults, and age is an independent predictor of mortality. Retrospective analysis was conducted among patients admitted to the emergency department in a tertiary teaching hospital from January 2016 to June 2017. To study the prognosis determinants of sepsis among elderly patients attended in the emergency room of a tertiary care hospital. As secondary objectives, we aimed to describe the causes of sepsis, the general outcome, and the general characteristics of these patients. Two hundred thirty-five episodes data of patients admitted throughout the 15-month study period who were diagnosed with sepsis, severe sepsis or septic shock, were included. Throughout the study cohort, 51 patients (21.7%) fulfilled the criteria of severe sepsis or septic shock. All-cause mortality was 11 patients (4.7%) on day 14 and 27 (11.5%) on day 30. Prognosis factors associated with 30-day mortality were the following: albumin level < 2.6 g/dl (first quartile of the overall population), odds ratio (OR 3.26, 95% CI 12-9.41; p = 0.029), Charlson comorbidity index (OR 1.23, 95% CI 1.04-1.45; p = 0.012), C-reactive protein on admission (OR 1.04, 95% CI 0.99-1.08; p = 0.062), and non-adequacy of the initial antimicrobial therapy (OR 3.3, 95% CI 1.06-10.4; p = 0.039). Among elderly patients with sepsis, strong predictors of mortality such as albumin could be considered as part of prognosis and future potential interventions. Adequacy of antimicrobial therapy at admission must be one of the objectives in the treatment of sepsis, also in the elderly, since it is an independent predictor of mortality.

Modulation of social space by dopamine in Drosophila melanogaster, but no effect on the avoidance of the Drosophila stress odorant.

Appropriate response to others is necessary for social interactions. Yet little is known about how neurotransmitters regulate attractive and repulsive social cues. Using genetic and pharmacological manipulations in Drosophila melanogaster, we show that dopamine is contributing the response to others in a social group, specifically, social spacing, but not the avoidance of odours released by stressed flies (dSO). Interestingly, this dopamine-mediated behaviour is prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation. Furthermore, alteration of dopamine levels has no effect on dSO avoidance regardless of sex, which suggests that a different neurotransmitter regulates this response.

Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.

Prevalence and trends of markers of hepatitis B virus, hepatitis C virus and human Immunodeficiency virus in Argentine blood donors.

BACKGROUND: Transfusion-transmitted infections are a major problem associated with blood transfusion. The aim of this study was to determine prevalence and trends of HBV, HCV and HIV in blood donors in Argentina. METHODS: A retrospective study was carried out in blood donors of 27 transfusion centers covering the whole country over a period of eight years (2004-2011). Serologic screening assays for HBsAg, anti-HBc, anti-HCV, and anti-HIV were performed in all centers and nucleic acid amplification testing (NAT) was performed in 2 out of the 27 centers. RESULTS: The 2,595,852 samples tested nationwide from 2004 to 2011 showed that the prevalence of HBsAg decreased from 0.336% to 0.198% (p < 0.0001), that of anti-HBc from 2.391% to 2.007% (p < 0.0001), that of anti-HCV from 0.721% to 0.460%, (p < 0.0001) and that of anti-HIV from 0.208% to 0.200 (p = 0.075). The prevalence of HBV, HCV and HIV was unevenly distributed among the different regions of the country. Two out of 74,838 screening- negative samples were positive in NAT assays (1 HIV-RNA and 1 HCV-RNA); moreover, HBV-DNA, HCV-RNA and HIV-RNA were detected in 60.29, 24.54 and 66.67% of screening-positive samples of the corresponding assays. As regards donors age, positive HBV-DNA and HCV-RNA donors were significantly older than healthy donors (46.6, 50.5 and 39.5 y respectively, p < 0.001). CONCLUSIONS: Argentina has a low prevalence of HBsAg, anti-HCV and anti-HIV in blood donors, with a decreasing trend for HBsAg, anti-HBc and anti-HCV but not for anti-HIV over the last 8 years. The uneven distribution of transfusion-transmitted infections prevalence among the different regions of the country highlights the need to implement regional awareness campaigns and prevention. The discrepancy between samples testing positive for screening assays and negative for NAT assays highlights the problem of blood donors who test repeatedly reactive in screening assays but are not confirmed as positive upon further testing. The uneven distribution of age between healthy donors and NAT-positive donors could be related to changes in risks of these pathogens in the general population and might be attributed to a longer exposure to transmission risk factors in elderly people.

An X across the Chest: A Rare Case of a Criss-crossed Sternalis Muscle.

OBJECTIVE: The present case study aims at drawing attention to a very rare presentation of the sternalis muscle noticed during routine dissection, and is intended to highlight the clinical significance and usefulness of this unique muscle in reconstructive surgeries, especially of the breast. CASE REPORT: Though many morphological variants of the muscle have been reported, we came across a unique bilateral sternalis muscle during routine dissection for undergraduate medical teaching, in an 80-year-old male cadaver. The muscle originates on both sides from the external oblique aponeurosis from the fleshy belly, and after becom-ing tendinous, converges in the midline to form a common tendon at the level of the sternal angle, and then splits again into two tendons which become continuous with the ipsilateral sternocleidomastoid. CONCLUSION: Notwithstanding the fact that the presence of a sternalis can be misdiagnosed as a wide range of anterior chest wall lesions and tumors, especially with misdiag-nosis of breast masses in routine mammograms, it has great use as a muscular flap for reconstructive surgeries of the anterior chest wall, head, neck and breast.

The metabolic baton: conducting the dance of N6-methyladenosine writing and erasing.

The modification N6-methyladenosine (m6A) plays an important role in determining the functional output of gene expression programs. Throughout the transcriptome, the levels of m6A are tightly regulated by the opposing activities of methyltransferases and demethylases, as well as the interaction of modified transcripts with m6A-dependent RNA-binding proteins that modulate transcript stability, often referred to as writers, erasers, and readers. The enzymatic activities of both writers and erasers are tightly linked to the cellular metabolic environment, as these enzymatic reactions rely on metabolism intermediaries as cofactors. In this review, we highlight the examples of intersection between metabolism and m6A-dependent gene regulation and discuss the different contexts where this interaction plays important roles.

Evaluation of a Lung Ultrasound Score in Hospitalized Adult Patients with COVID-19 in Barcelona, Spain.

Background/Objectives: During the COVID-19 pandemic and the burden on hospital resources, the rapid categorization of high-risk COVID-19 patients became essential, and lung ultrasound (LUS) emerged as an alternative to chest computed tomography, offering speed, non-ionizing, repeatable, and bedside assessments. Various LUS score systems have been used, yet there is no consensus on an optimal severity cut-off. We assessed the performance of a 12-zone LUS score to identify adult COVID-19 patients with severe lung involvement using oxygen saturation (SpO2)/fractional inspired oxygen (FiO2) ratio as a reference standard to define the best cut-off for predicting adverse outcomes. Methods: We conducted a single-centre prospective study (August 2020-April 2021) at Hospital del Mar, Barcelona, Spain. Upon admission to the general ward or intensive care unit (ICU), clinicians performed LUS in adult patients with confirmed COVID-19 pneumonia. Severe lung involvement was defined as a SpO2/FiO2 ratio <315. The LUS score ranged from 0 to 36 based on the aeration patterns. Results: 248 patients were included. The admission LUS score showed moderate performance in identifying a SpO2/FiO2 ratio <315 (area under the ROC curve: 0.71; 95%CI 0.64-0.77). After adjustment for COVID-19 risk factors, an admission LUS score ≥17 was associated with an increased risk of in-hospital death (OR 5.31; 95%CI: 1.38-20.4), ICU admission (OR 3.50; 95%CI: 1.37-8.94) and need for IMV (OR 3.31; 95%CI: 1.19-9.13). Conclusions: Although the admission LUS score had limited performance in identifying severe lung involvement, a cut-off ≥17 score was associated with an increased risk of adverse outcomes. and could play a role in the rapid categorization of COVID-19 pneumonia patients, anticipating the need for advanced care.

The neuropeptidergic connectome of C. elegans.

Efforts are ongoing to map synaptic wiring diagrams, or connectomes, to understand the neural basis of brain function. However, chemical synapses represent only one type of functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles in all nervous systems. By integrating single-cell anatomical and gene-expression datasets with biochemical analysis of receptor-ligand interactions, we have generated a draft connectome of neuropeptide signaling in the C. elegans nervous system. This network is characterized by high connection density, extended signaling cascades, autocrine foci, and a decentralized topology, with a large, highly interconnected core containing three constituent communities sharing similar patterns of input connectivity. Intriguingly, several key network hubs are little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate that the C. elegans neuropeptidergic connectome will serve as a prototype to understand how networks of neuromodulatory signaling are organized.