Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth-seventh century BC, central Italy).

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.

Emergency surgery preoperative delays: realities, economic impacts and gains of a second emergency operating theatre.

INTRODUCTION: Time-to-theatre (TTT) is a key performance indicator of theatre efficiency and delayed TTT incurs significant costs and poor clinical outcomes. An increasing Irish population in conjunction with an ageing population puts increasing pressure on emergency surgical services across Ireland. We examined our institution's experience with introducing a second emergency theatre and semi-elective theatre lists for acute surgical patients. METHODS: A retrospective review of electronic, prospectively maintained databases was performed between 1 February 2018 and 31 January 2020. A cost analysis was conducted to assess the economic impact of delayed TTT. The cost-saving benefit of introducing a second emergency theatre and semi-elective Kaizen lists was then calculated and compared with 2012-2014 figures from our institution. RESULTS: In total, 6,679 procedures were performed. Overall mean TTT was 16h, 10h shorter than before the introduction of a second emergency theatre and Kaizen theatre lists (p < 0.001). Patients aged >65 years, who are historically a significantly disadvantaged group, had a shorter TTT following the introduction of a second emergency theatre. The economic advantage of a second emergency theatre resulted in a cost saving of €3,674,538 over 24 months. CONCLUSION: Investment in emergency surgical services resulted in more efficient access to emergency theatres. There was a reduction in out-of-hours operating across all specialties and across the more at-risk groups such as those over the age of 65, who had an overall reduction in TTT. This had significant financial benefits and likely reduced the clinical risk associated with delayed TTT and out-of-hours operating.

Extreme seasonal water-level changes and hydraulic modeling of deep, high-altitude, glacial-carved, Himalayan lakes.

Himalayan lakes represent critical water resources, culturally important waterbodies, and potential hazards. Some of these lakes experience dramatic water-level changes, responding to seasonal monsoon rains and post-monsoonal draining. To address the paucity of direct observations of hydrology in retreating mountain glacial systems, we describe a field program in a series of high altitude lakes in Sagarmatha National Park, adjacent to Ngozumba, the largest glacier in Nepal. In situ observations find extreme (>12 m) seasonal water-level changes in a 60-m deep lateral-moraine-dammed lake (lacking surface outflow), during a 16-month period, equivalent to a 5 [Formula: see text] m[Formula: see text] volume change annually. The water column thermal structure was also monitored over the same period. A hydraulic model is constructed, validated against observed water levels, and used to estimate hydraulic conductivities of the moraine soils damming the lake and improves our understanding of this complex hydrological system. Our findings indicate that lake level compared to the damming glacier surface height is the key criterion for large lake fluctuations, while lakes lying below the glacier surface, regulated by surface outflow, possess only minor seasonal water-level fluctuations. Thus, lakes adjacent to glaciers may exhibit very different filling/draining dynamics based on presence/absence of surface outflows and elevation relative to retreating glaciers, and consequently may have very different fates in the next few decades as the climate warms.

Fast, accurate, and racially unbiased pan-cancer tumor-only variant calling with tabular machine learning.

Accurately identifying somatic mutations is essential for precision oncology and crucial for calculating tumor-mutational burden (TMB), an important predictor of response to immunotherapy. For tumor-only variant calling (i.e., when the cancer biopsy but not the patient's normal tissue sample is sequenced), accurately distinguishing somatic mutations from germline variants is a challenging problem that, when unaddressed, results in unreliable, biased, and inflated TMB estimates. Here, we apply machine learning to the task of somatic vs germline classification in tumor-only solid tumor samples using TabNet, XGBoost, and LightGBM, three machine-learning models for tabular data. We constructed a training set for supervised classification using features derived exclusively from tumor-only variant calling and drawing somatic and germline truth labels from an independent pipeline using the patient-matched normal samples. All three trained models achieved state-of-the-art performance on two holdout test datasets: a TCGA dataset including sarcoma, breast adenocarcinoma, and endometrial carcinoma samples (AUC > 94%), and a metastatic melanoma dataset (AUC > 85%). Concordance between matched-normal and tumor-only TMB improves from R2 = 0.006 to 0.71-0.76 with the addition of a machine-learning classifier, with LightGBM performing best. Notably, these machine-learning models generalize across cancer subtypes and capture kits with a call rate of 100%. We reproduce the recent finding that tumor-only TMB estimates for Black patients are extremely inflated relative to that of white patients due to the racial biases of germline databases. We show that our approach with XGBoost and LightGBM eliminates this significant racial bias in tumor-only variant calling.

The stoned age: Sex differences in the effects of adolescent cannabinoid exposure on prefrontal cortex structure and function in animal models.

Cannabis is the most used drug during adolescence, which is a period of enhanced cortical plasticity and synaptic remodeling that supports behavioral, cognitive, and emotional maturity. In this chapter, we review preclinical studies indicating that adolescent exposure to cannabinoids has lasting effects on the morphology and synaptic organization of the prefrontal cortex and associated circuitry, which may lead to cognitive dysfunction later in life. Additionally, we reviewed sex differences in the effects of adolescent cannabinoid exposure with a focus on brain systems that support cognitive functioning. The body of evidence indicates enduring sex-specific effects in behavior and organization of corticolimbic circuitry, which appears to be influenced by species, strain, drug, route of administration, and window/pattern of drug exposure. Caution should be exercised when extrapolating these results to humans. Adopting models that more closely resemble human cannabis use will provide more translationally relevant data concerning the long-term effects of cannabis use on the adolescent brain.

Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release.

Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small 'extinction burst', further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

Clostridium chrysemydis sp. nov., isolated from the faecal material of a painted turtle.

A strict anaerobic, Gram-stain-positive rod-shaped bacterium, designated PTT, was isolated from the faecal material of a painted turtle (Chrysemys picta). Based on a comparative 16S rRNA gene sequence analysis, the isolate was assigned to Clostridium sensu stricto with the highest sequence similarities to Clostridium moniliforme (97.4 %), Clostridium sardiniense (97.2 %) and the misclassified organism Eubacterium multiforme (97.1 %). The predominant cellular fatty acids of strain PTT were C14 : 0, C16 : 0 and an unidentified product with an equivalent chain length of 14.969. The G+C content determined from the genome was 28.8 mol%. The fermentation end products from glucose were acetate and butyrate with no alcohols detected and trace amounts of CO2 and H2 also detected; no respiratory quinones were detected. Based on biochemical, phylogenetic, genotypic and chemotaxonomic criteria, the isolate represents a novel species of the genus Clostridium for which the name Clostridium chrysemydis sp. nov. is proposed. The type strain is strain PTT (=CCUG 74180T=ATCC TSD-219T).

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer.

BACKGROUND: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. METHODS: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P < 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P < 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P < 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P < 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Disease recurrence and oncological outcome of patients treated surgically with curative intent for estrogen receptor positive, lymph node negative breast cancer.

BACKGROUND: The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses. AIMS: To describe clinicopathologic features, oncological outcome and relapse patterns in LABC. METHODS: Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses. RESULTS: Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07-2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21-4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25-2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49-4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19-8.22, P = 0.020) predicted OS. CONCLUSION: Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.

Membrane and Actin Tethering Transitions Help IQGAP1 Coordinate GTPase and Lipid Messenger Signaling.

The coordination of lipid messenger signaling with cytoskeletal regulation is central to many organelle-specific regulatory processes. This coupling often depends on the function of multidomain scaffolds that orchestrate transient interactions among multiple signaling intermediates and regulatory proteins on organelles. The number of possible scaffold interaction partners and the ability for these interactions to occur at different timescales makes investigations of scaffold functions challenging. This work employs live cell imaging to probe how the multidomain scaffold IQ motif containing GTPase activating protein 1 (IQGAP1) coordinates the activities of proteins affecting local actin polymerization, membrane processing, and phosphoinositide signaling. Using endosomes that are confined by a local actin network as a model system, we demonstrate that IQGAP1 can transition between different actin and endosomal membrane tethered states. Fast scaffold binding/disassociation transitions are shown to be driven by interactions between C-terminal scaffold domains and Rho GTPases at the membrane. Fluctuations in these binding modes are linked to negative regulation of actin polymerization. Although this control governs core elements of IQGAP1 dynamics, actin binding by the N-terminal calponin homology domain of the scaffold is shown to help the scaffold track the temporal development of endosome membrane markers, implying actin associations bolster membrane and actin coordination. Importantly, these effects are not easily distilled purely through standard (static) co-localization analyses or traditional pathway perturbations methods and were resolved by performing dynamic correlation and multiple regression analyses of IQGAP1 scaffold mutants. Using these capabilities with pharmacological inhibition, we provide evidence that membrane tethering is dependent on the activities of the lipid kinase phosphoinositide 3-kinase in addition to the Rho GTPases Rac1 and Cdc42. Overall, these methods and results point to a scaffold tethering mechanism that allows IQGAP1 to help control the amplitude of phosphoinositide lipid messenger signaling by coordinating signaling intermediate activities with the development and disassembly of local actin cytoskeletal networks.

Patients' attitude towards travelling for breast services versus waiting longer for local services

Geographical access is a cornerstone of health care provision. However, prolonged waiting for breast clinic appointments in local services results in delayed diagnosis and excessive anxiety for patients. In this study, we present a patient satisfaction survey results of an initiative to offer out-patient clinic appointments for non-urgent patients referred to the breast unit in Letterkenny General Hospital (LGH), Ireland, and exceeded the recommended waiting period of 12 weeks. These patients were offered appointment in University Hospital Galway (UCHG), which is an average travel time of about 3.5-4.5 hours away from LGH. 163 patients out of 336 (48.5%) patients actively waiting more than 12 weeks for appointments in LGH accepted alternative appointments in UCHG. Despite the long travel distance for these patients, 100% of them reported high satisfaction and 97.3% said they would accept further UCHG appointments if a similar situation of prolonged waiting in LGH arises. None of these patients were diagnosed with cancer, and only one had a benign lumpectomy. This study showed that if offered alternative appointments, just under half of the patients would accept. The initiative provides a feasible solution for long waiters, and the survey shows that patients' satisfaction remains high despite long travel.

Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Antibody MEDI3902, Are Conserved Among Diverse Global Clinical Isolates.

Background: Bispecific antibody MEDI3902, targeting the Pseudomonas aeruginosa type 3 secretion system (PcrV) and Psl exopolysaccharide, is currently in phase 2b development for prevention of nosocomial pneumonia in patients undergoing mechanical ventilation. We surveyed a diverse collection of isolates to study MEDI3902 epitope conservation and protective activity. Methods: P. aeruginosa clinical isolates (n = 913) were collected from diverse patients and geographic locations during 2003-2014. We conducted whole-genome sequencing; performed PcrV and Psl expression analyses via immunoblotting and enzyme-linked immunosorbent assay, respectively; performed crystallography to determine the MEDI3902 PcrV epitope, using anti-PcrV Fab and PcrV components (resolved at 2.8 Å); and evaluated MEDI3902 protective activity against select isolates in vitro and in vivo. Results: Intact psl operon and pcrV genes were present in 94% and 99% of isolates, respectively, and 99.9% of isolates contained at least one of the genetic elements. Anti-Psl binding was confirmed in tested isolates harboring a complete Psl operon or lacking nonessential psl genes. We identified 46 PcrV variant sequences, and MEDI3902-PcrV contact residues were preserved. MEDI3902 maintained potent in vivo activity against various strains, including strains expressing only a single target. Conclusions: Psl and PcrV are highly prevalent in global clinical isolates, suggesting MEDI3902 can mediate broad coverage against P. aeruginosa.

Correction to: Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

It has been highlighted that the original manuscript [1] contains a typesetting error regarding the authorship.

Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

BACKGROUND: Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options. METHODS: Patient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence. RESULTS: One hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options. CONCLUSION: Discordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.

Role of glucocorticoid receptor-mediated mechanisms in cocaine memory enhancement.

The basolateral amygdala (BLA) is a critical site for the reconsolidation of labile contextual cocaine memories following retrieval-induced reactivation/destabilization. Here, we examined whether glucocorticoid receptors (GR), which are abundant in the BLA, mediate this phenomenon. Rats were trained to lever press for cocaine reinforcement in a distinct environmental context, followed by extinction training in a different context. Rats were then briefly exposed to the cocaine-paired context (to elicit memory reactivation and reconsolidation) or their home cages (no reactivation control). Exposure to the cocaine-paired context elicited greater serum corticosterone concentrations than home cage stay. Interestingly, the GR antagonist, mifepristone (3-10 ng/hemisphere), administered into the BLA after memory reactivation produced a further, dose-dependent increase in serum corticosterone concentrations during the putative time of cocaine-memory reconsolidation but produced an inverted U-shaped dose-effect curve on subsequent cocaine-seeking behavior 72 h later. This effect was anatomically selective, dependent on memory reactivation (i.e., not observed after home cage exposure), and did not reflect protracted hyperactivity. However, the effect was also observed when mifepristone was administered after novelty stress that mimics drug context-induced hypothalamic-pituitary-adrenal (HPA) axis activation without explicit memory reactivation. Together, these findings suggest that, similar to explicit memory retrieval, a stressful event is sufficient to destabilize cocaine memories and permit their manipulation. Furthermore, BLA GR stimulation exerts inhibitory feedback upon HPA axis activation and thus suppresses cocaine-memory reconsolidation.

The coordinating role of IQGAP1 in the regulation of local, endosome-specific actin networks.

IQGAP1 is a large, multi-domain scaffold that helps orchestrate cell signaling and cytoskeletal mechanics by controlling interactions among a spectrum of receptors, signaling intermediates, and cytoskeletal proteins. While this coordination is known to impact cell morphology, motility, cell adhesion, and vesicular traffic, among other functions, the spatiotemporal properties and regulatory mechanisms of IQGAP1 have not been fully resolved. Herein, we describe a series of super-resolution and live-cell imaging analyses that identified a role for IQGAP1 in the regulation of an actin cytoskeletal shell surrounding a novel membranous compartment that localizes selectively to the basal cortex of polarized epithelial cells (MCF-10A). We also show that IQGAP1 appears to both stabilize the actin coating and constrain its growth. Loss of compartmental IQGAP1 initiates a disassembly mechanism involving rapid and unconstrained actin polymerization around the compartment and dispersal of its vesicle contents. Together, these findings suggest IQGAP1 achieves this control by harnessing both stabilizing and antagonistic interactions with actin. They also demonstrate the utility of these compartments for image-based investigations of the spatial and temporal dynamics of IQGAP1 within endosome-specific actin networks.

Prospective comparison of outcome after treatment for triple-negative and non-triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancers (TNBC) are associated with a poor prognosis owing to an aggressive phenotype. We aimed to carry out a prospective study comparing management strategies and response to therapy in TNBC and non-TNBC patients. METHODS: Data were obtained from a prospectively maintained database of patients treated for breast cancer. RESULTS: A total of 142 TNBC and 142 age-, stage- and NPI-matched non-TNBC patients were treated. The difference in overall survival between the 2 groups was statistically significant (77% of TNBC patients alive at a mean follow-up of 32 months, versus 92% of non-TNBC patients at a mean follow-up of 38 months, P = 0.0 Log rank test). This survival difference was found to be independent of NPI (P = 0.0 Log rank test). Locoregional recurrence rates were similar between TNBC patients who were treated with wide local excision versus mastectomy (P = 0.449 Log rank test). A significant difference in survival was noted between TNBC patients who responded differentially to neoadjuvant chemotherapy (P = 0.035 Log rank test). CONCLUSION: Patients with TNBC have adverse outcomes despite aggressive treatment. The development of effective targeted therapies is essential for this breast cancer subtype.

Note: A portable laser induced breakdown spectroscopy instrument for rapid sampling and analysis of silicon-containing aerosols.

A portable instrument has been developed for measuring silicon-containing aerosols in near real-time using laser-induced breakdown spectroscopy (LIBS). The instrument uses a vacuum system to collect and deposit airborne particulate matter onto a translatable reel of filter tape. LIBS is used to analyze the deposited material, determining the amount of silicon-containing compounds present. In laboratory testing with pure silica (SiO2), the correlation between LIBS intensity for a characteristic silicon emission and the concentration of silica in a model aerosol was determined for a range of concentrations, demonstrating the instrument's plausibility for identifying hazardous levels of silicon-containing compounds.

Human islets and dendritic cells generate post-translationally modified islet autoantigens.

The initiation of type 1 diabetes (T1D) requires a break in peripheral tolerance. New insights into neoepitope formation indicate that post-translational modification of islet autoantigens, for example via deamidation, may be an important component of disease initiation or exacerbation. Indeed, deamidation of islet autoantigens increases their binding affinity to the T1D highest-risk human leucocyte antigen (HLA) haplotypes HLA-DR3/DQ2 and -DR4/DQ8, increasing the chance that T cells reactive to deamidated autoantigens can be activated upon T cell receptor ligation. Here we investigated human pancreatic islets and inflammatory and tolerogenic human dendritic cells (DC and tolDC) as potential sources of deamidated islet autoantigens and examined whether deamidation is altered in an inflammatory environment. Islets, DC and tolDC contained tissue transglutaminase, the key enzyme responsible for peptide deamidation, and enzyme activity increased following an inflammatory insult. Islets treated with inflammatory cytokines were found to contain deamidated insulin C-peptide. DC, heterozygous for the T1D highest-risk DQ2/8, pulsed with native islet autoantigens could present naturally processed deamidated neoepitopes. HLA-DQ2 or -DQ8 homozygous DC did not present deamidated islet peptides. This study identifies both human islets and DC as sources of deamidated islet autoantigens and implicates inflammatory activation of tissue transglutaminase as a potential mechanism for islet and DC deamidation.