Beta Response Research Articles

Response of CaSO4:Dy Teflon embedded thermoluminescent dosimeter badge on different ISO phantoms for photons and beta sources using FLUKA and GEANT4

In this study, Monte Carlo codes FLUKA and GEANT4 were used to assess the angular variation in the response of CaSO4:Dy Teflon disc based TLD badge. These badges were positioned on various ISO phantoms to simulate the angular exposures ranging from 0° to 60° for photons within the energy range of 12.3 keV to 1.25 MeV, as well as for 90Sr/90Y and 106Rh/106Ru beta sources. Plots showing the TL response of the discs in terms of Hp(10), Hp(3), and Hp(0.07) as a function of photon energy were obtained for ISO slab, cylindrical, and pillar phantoms, respectively. Additionally, the study estimated the angular variation in the response of disc ratios (R12 and R32) with respect to both photon and beta energies. The simulation results revealed that the response of the open disc (D3) was higher for lower X-ray energies, attributed to an increase in the photoelectric effect. Conversely, the response of the disc under the metal filter (D1) was observed to increase with the angle, indicating the Compton scattering from the cassette body and phantom, especially at lower X-ray energies. Beta response of both disc D2 (under PMMA filter) and D3 found to be decreasing with the angle of incidence while R32 ratio found to be increasing with the angle of incidence for both 90Sr/90Y and 106Rh/106Ru beta sources. Notably, the simulated results demonstrated good agreement with experimental observations, reinforcing the reliability of the Monte Carlo simulations for complex interactions and responses of TLD badges under different irradiation conditions.

Simultaneous whole-head electrophysiological recordings using EEG and OPM-MEG

Abstract Electroencephalography (EEG) and magnetoencephalography (MEG) non-invasively measure human brain electrophysiology. They differ in nature; MEG offers better performance while EEG (a wearable platform) is more practical. They are also complementary, with studies showing that concurrent MEG/EEG provides advantages over either modality alone, and consequently clinical guidelines for MEG in epilepsy recommend simultaneous acquisition of MEG and EEG. In recent years, new instrumentation—the optically pumped magnetometer (OPM)—has had a significant impact on MEG, offering improved performance, lifespan compliance, and wearable MEG systems. Nevertheless, the ability to carry out simultaneous EEG/OPM-MEG remains critical. Here, we investigated whether simultaneous, wearable, whole-head EEG and OPM-MEG measurably degrades signal quality in either modality. We employed two tasks: a motor task known to modulate beta oscillations, and an eyes-open/closed task known to modulate alpha oscillations. In both, we characterised the performance of EEG alone, OPM-MEG alone, and concurrent EEG/OPM-MEG. Results show that the signal to noise ratio (SNR) of the beta response was similar, regardless of whether modalities were used individually or concurrently. Likewise, our alpha band recordings demonstrated that signal contrast was stable, regardless of the concurrent recording. We also demonstrate significant advantages of OPM-MEG; specifically, the OPM-MEG signal is less correlated across channels and less susceptible to interference from non-brain sources. Our results suggest that there are no barriers to simultaneous wearable EEG/OPM-MEG, and consequently this technique is ripe for neuroscientific and clinical adoption. This will be important in the clinic where simultaneous EEG and OPM-MEG recordings will facilitate better interpretation of OPM-MEG data in patients.

An Improved Pedotransfer Function for Soil Hydrological Properties in New Zealand

This paper describes a new pedotransfer function (PTF) for the soil water content of New Zealand soils at seven specific tensions (0, −5, −10, −20, −40, −100, −1500 kPa) using explanatory variables derived from the S-map soil mapping system. The model produces unbiased and physically plausible estimates of the response at each tension, as well as unbiased and physically plausible estimates of the response differences that define derived properties (e.g., macroporosity and total available water content). The PTF is a development of an earlier model using approximately double the number of sites compared with the earlier study, a change in fitting methodology to a semi-parametric GAM Beta response, and the inclusion of sample depth. The results show that the new model has resulted in significant improvements for the soil water content estimates and derived quantities using standard goodness-of-fit measures, based on validation data. A comparison with an international PTF using explanatory variables compatible with variables available from S-map (EUPTF2) suggests that the model is better for prediction of soil water content using the limited information available from the S-map system.

Neurotoxic effects of home radon exposure on oscillatory dynamics serving attentional orienting in children and adolescents

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6–14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3–7 Hz, 300–800 ms), alpha (9–13 Hz, 400–900 ms), and beta responses (14–24 Hz, 400–900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued – validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition.

Frontotemporal lobar degeneration changes neuronal beta-frequency dynamics during the mismatch negativity response

The consequences of frontotemporal lobar degeneration include changes in prefrontal cortical neurophysiology, with abnormalities of neural dynamics reported in the beta frequency range (14–30 Hz) that correlate with functional severity. We examined beta dynamics in two clinical syndromes associated with frontotemporal lobar degeneration: the behavioral variant of frontotemporal dementia (bvFTD) and progressive supranuclear palsy (PSP). Whilst these two syndromes are partially convergent in cognitive effects, they differ in disease mechanisms such as molecular pathologies and prefrontal atrophy. Whether bvFTD and PSP also differ in neurophysiology remains to be fully investigated. We compared magnetoencephalography from 20 controls, 23 people with bvFTD and 21 people with PSP (Richardson’s syndrome) during an auditory roving oddball paradigm. We measured changes in low and high total beta power responses (14–22 and 22–30 Hz respectively) over frontotemporal cortex in the period of the mismatch negativity response (100–250 ms post-stimulus). In controls, we found increased 14–22 Hz beta power following unexpected sensory events (i.e. increased deviant versus standard response), from right prefrontal cortex. Relative to controls, PSP reversed the mismatch response in this time–frequency window, reflecting reduced responses to the deviant stimuli (relative to standard stimuli). Abnormal beta at baseline in PSP could account for the reduced task-modulation of beta. Across bvFTD and PSP groups, the beta response to deviant stimuli (relative to standard stimuli) correlated with clinical severity, but not with atrophy of the prefrontal source region. These findings confirm the proposed importance of higher-order cortical regions, and their beta-power generators, in sensory change detection and context-updating during oddball paradigms. The physiological effects are proposed to result from changes in synaptic density, cortical neurotransmitters and subcortical connections, rather than merely atrophy. Beta-power changes may assist clinical stratification and provide intermediate outcomes for experimental medicine studies of novel therapeutic strategies.

Regular cannabis use alters the neural dynamics serving complex motor control.

Cannabis is the most widely used recreational drug in the United States and regular use has been linked to deficits in attention and memory. However, the effects of regular use on motor control are less understood, with some studies showing deficits and others indicating normal performance. Eighteen users and 23 nonusers performed a motor sequencing task during high-density magnetoencephalography (MEG). The MEG data was transformed into the time-frequency domain and beta responses (16-24 Hz) during motor planning and execution phases were imaged separately using a beamformer approach. Whole-brain maps were examined for group (cannabis user/nonuser) and time window (planning/execution) effects. As expected, there were no group differences in task performance (e.g., reaction time, accuracy, etc.). Regular cannabis users exhibited stronger beta oscillations in the contralateral primary motor cortex compared to nonusers during the execution phase of the motor sequences, but not during the motor planning phase. Similar group-by-time window interactions were observed in the left superior parietal, right inferior frontal cortices, right posterior insular cortex, and the bilateral motor cortex. We observed differences in the neural dynamics serving motor control in regular cannabis users compared to nonusers, suggesting regular users may employ compensatory processing in both primary motor and higher-order motor cortices to maintain adequate task performance. Future studies will need to examine more complex motor control tasks to ascertain whether this putative compensatory activity eventually becomes exhausted and behavioral differences emerge.

The Dirichlet Dual Response Model: An Item Response Model for Continuous Bounded Interval Responses

Standard response formats such as rating or visual analogue scales require respondents to condense distributions of latent states or behaviors into a single value. Whereas this is suitable to measure central tendency, it neglects the variance of distributions. As a remedy, variability may be measured using interval-response formats, more specifically the dual-range slider (RS2). Given the lack of an appropriate item response model for the RS2, we develop the Dirichlet dual response model (DDRM), an extension of the beta response model (BRM; Noel & Dauvier in Appl Psychol Meas, 31:47–73, 2007). We evaluate the DDRM’s performance by assessing parameter recovery in a simulation study. Results indicate overall good parameter recovery, although parameters concerning interval width (which reflect variability in behavior or states) perform worse than parameters concerning central tendency. We also test the model empirically by jointly fitting the BRM and the DDRM to single-range slider (RS1) and RS2 responses for two Extraversion scales. While the DDRM has an acceptable fit, it shows some misfit regarding the RS2 interval widths. Nonetheless, the model indicates substantial differences between respondents concerning variability in behavior. High correlations between person parameters of the BRM and DDRM suggest convergent validity between the RS1 and the RS2 interval location. Both the simulation and the empirical study demonstrate that the latent parameter space of the DDRM addresses an important issue of the RS2 response format, namely, the scale-inherent interdependence of interval location and interval width (i.e., intervals at the boundaries are necessarily smaller).

Mentalizing and self-other distinction in visual perspective taking: the analysis of temporal neural processing using high-density EEG.

This high density EEG report dissects the neural processing in the visual perspective taking using four experimental comparisons (Arrow, Avatar and Self, Other). Early activation differences occurred between the Avatar and the Arrow condition in primary visual pathways concomitantly with alpha and beta phase locked responses predominant in the Avatar condition. In later time points, brain activation was stronger for the Avatar condition in paracentral lobule of frontal lobe. When taking the other's perspective, there was an increased recruitment of generators in the occipital and temporal lobes and later on in mentalizing and salience networks bilaterally before spreading to right frontal lobe subdivisions. Microstate analysis further supported late recruitment of the medial frontal gyrus and precentral lobule in this condition. Other perspective for the Avatar only showed a strong beta response located first in left occipito-temporal and right parietal areas, and later on in frontal lobes. Our EEG data support distinct brain processes for the Avatar condition with an increased recruitment of brain generators that progresses from primary visual areas to the anterior brain. Taking the other's perspective needs an early recruitment of neural processors in posterior areas involved in theory of mind with later involvement of additional frontal generators.

Epigenetic signals that direct cell type-specific interferon beta response in mouse cells.

The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes (ISGs) across human and mouse tissues but varies between cell types. However, the links between the underlying epigenetic features and the ISG profile are not well understood. We mapped ISGs, binding sites of the STAT1 and STAT2 transcription factors, chromatin accessibility, and histone H3 lysine modification by acetylation (ac) and mono-/tri-methylation (me1, me3) in mouse embryonic stem cells and fibroblasts before and after IFNβ treatment. A large fraction of ISGs and STAT-binding sites was cell type specific with promoter binding of a STAT1/2 complex being a key driver of ISGs. Furthermore, STAT1/2 binding to putative enhancers induced ISGs as inferred from a chromatin co-accessibility analysis. STAT1/2 binding was dependent on the chromatin context and positively correlated with preexisting H3K4me1 and H3K27ac marks in an open chromatin state, whereas the presence of H3K27me3 had an inhibitory effect. Thus, chromatin features present before stimulation represent an additional regulatory layer for the cell type-specific antiviral response.

Zika virus infection of mature neurons from immunocompetent mice generates a disease-associated microglia and a tauopathy-like phenotype in link with a delayed interferon beta response

BackgroundZika virus (ZIKV) infection at postnatal or adult age can lead to neurological disorders associated with cognitive defects. Yet, how mature neurons respond to ZIKV remains substantially unexplored.MethodsThe impact of ZIKV infection on mature neurons and microglia was analyzed at the molecular and cellular levels, in vitro using immunocompetent primary cultured neurons and microglia, and in vivo in the brain of adult immunocompetent mice following intracranial ZIKV inoculation. We have used C57BL/6 and the genetically diverse Collaborative Cross mouse strains, displaying a broad range of susceptibility to ZIKV infection, to question the correlation between the effects induced by ZIKV infection on neurons and microglia and the in vivo susceptibility to ZIKV.ResultsAs a result of a delayed induction of interferon beta (IFNB) expression and response, infected neurons displayed an inability to stop ZIKV replication, a trait that was further increased in neurons from susceptible mice. Alongside with an enhanced expression of ZIKV RNA, we observed in vivo, in the brain of susceptible mice, an increased level of active Iba1-expressing microglial cells occasionally engulfing neurons and displaying a gene expression profile close to the molecular signature of disease-associated microglia (DAM). In vivo as well as in vitro, only neurons and not microglial cells were identified as infected, raising the question of the mechanisms underlying microglia activation following brain ZIKV infection. Treatment of primary cultured microglia with conditioned media from ZIKV-infected neurons demonstrated that type-I interferons (IFNs-I) secreted by neurons late after infection activate non-infected microglial cells. In addition, ZIKV infection induced pathological phosphorylation of Tau (pTau) protein, a hallmark of neurodegenerative tauopathies, in vitro and in vivo with clusters of neurons displaying pTau surrounded by active microglial cells.ConclusionsWe show that ZIKV-infected mature neurons display an inability to stop viral replication in link with a delayed IFNB expression and response, while signaling microglia for activation through IFNs-I secreted at late times post-infection. In the brain of ZIKV-infected susceptible mice, uninfected microglial cells adopt an active morphology and a DAM expression profile, surrounding and sometimes engulfing neurons while ZIKV-infected neurons accumulate pTau, overall reflecting a tauopathy-like phenotype.

Influence of Rising Water Temperature on the Temperate Seagrass Species Eelgrass (Zostera marina L.) in the Northeast USA

Sea surface temperature (SST) has increased worldwide since the beginning of the 20th century, a trend which is expected to continue. Changes in SST can have significant impacts on marine biota, including population-level shifts and alterations in community structure and diversity, and changes in the timing of ecosystem events. Seagrasses are a group of foundation species that grow in shallow coastal and estuarine systems, where they provide many ecosystem services. Eelgrass, Zostera marina L., is the dominant seagrass species in the Northeast United States of America (USA). Multiple factors have been cited for losses in this region, including light reduction, eutrophication, and physical disturbance. Warming has the potential to exacerbate seagrass loss. Here, we investigate regional changes in eelgrass presence and abundance in relation to local water temperature using monitoring data from eight sites in the Northeastern USA (New Hampshire to Maryland) where a consistent monitoring protocol, SeagrassNet, has been applied. We use a hurdle model consisting of a generalized additive mixed model (GAMM) with binomial and beta response distributions for modeling eelgrass presence and abundance, respectively, in relation to the local summer average water temperature. We show that summer water temperature one year prior to monitoring is a significant predictor of eelgrass presence, but not abundance, on a regional scale. Above average summer temperatures correspond to a decrease in probability of eelgrass presence (and increased probability of eelgrass absence) the following year. Cooler than average temperatures in the preceding year, down to approximately 0.5°C below the site average, are associated with the highest predicted probability of eelgrass presence. Our findings suggest vulnerability in eelgrass meadows of the Northeast USA and emphasize the value of unified approaches to seagrass monitoring, conservation and management at the seascape scale.

Spinal cord microstructural changes are connected with the aberrant sensorimotor cortical oscillatory activity in adults with cerebral palsy

Previous animal models have illustrated that reduced cortical activity in the developing brain has cascading activity-dependent effects on the microstructural organization of the spinal cord. A limited number of studies have attempted to translate these findings to humans with cerebral palsy (CP). Essentially, the aberrations in sensorimotor cortical activity in those with CP could have an adverse effect on the spinal cord microstructure. To investigate this knowledge gap, we utilized magnetoencephalographic (MEG) brain imaging to quantify motor-related oscillatory activity in fourteen adults with CP and sixteen neurotypical (NT) controls. A subset of these participants also underwent cervical-thoracic spinal cord MRI. Our results showed that the strength of the peri-movement beta desynchronization and the post-movement beta rebound were each weaker in the adults with CP relative to the controls, and these weakened responses were associated with poorer task performance. Additionally, our results showed that the strength of the peri-movement beta response was associated with the total cross-sectional area of the spinal cord and the white matter cross-sectional area. Altogether these results suggest that the altered sensorimotor cortical activity seen in CP may result in activity-dependent plastic changes within the spinal cord microstructure, which could ultimately contribute to the sensorimotor deficits seen in this population.

P005 The solute carrier LC22A4/Organic Cation Transporter (OCTN)-1 as a novel Inflammatory Bowel Disease determinant at the microbe-host interface

Abstract Background The putative Ergothioneine Transporter, SLC22A4/OCTN1, is expressed in the intestine and monocytes/macrophages, and its widely represented missense variant L503F (0.4 Minor Allele Frequency in Caucasians) has been found to be associated with Crohn’s disease, sporadic colorectal cancer in early age and ulcerative colitis (UC) patients. The leucine-to-phenylalanine substitution at amino acid 503 affects OCTN1 capacity to transport ergothioneine, acetylcholine and likely other substrates of endogenous or microbial origin; however, whether this defect contributes to inflammatory bowel disease (IBD) pathogenesis, and the mechanistic underpinnings, remain elusive. Methods In order to gain mechanistic insight on the role of SLC22A4 in IBD, we first analyzed primary monocytes from healthy donors and UC patients of varying OCTN1 genotypes. Then we stably knocked down or overexpressed OCTN1 and its disease-associated variant in the monocytic cell line THP-1. Finally, we compared wild-type and OCTN1 knockout C57BL/6 mice in a chemical colitis paradigm in vivo. Results Primary adherent monocytes from healthy donors homozygous for the IBD-associated allele (TT) displayed a significant enhancement of interleukin 1 beta (IL-1β) response to peptidoglycan (PGN) compared to the other genotypes. Likewise, cells from UC patients bearing the 503F variant released more IL-1β in response to live bacteria and displayed reduced expression of autophagy markers (e.g. p62, LC3), compared to patients negative for the variant. In agreement with these findings, OCTN1-deficient THP-1 macrophages secreted reduced amounts of IL-1β when challenged in vitro with PGN or live bacteria. Most relevant, THP1 cells engineered to overexpress the 503F variant of OCTN1 displayed a much stronger IL-1β response to muramyl dipeptide and PGN challenge, compared to cells transduced with the “wild type” transporter. Also consistent with a role for OCTN1 variants in inflammatory cascades relevant to IBD, in vivo studies revealed milder DSS-induced colitis in OCTN1 knockout mice compared to wild-type animals, both at the peak of disease severity and at the end of the recovery period. Conclusion Collectively our initial evidence supports the view that OCTN1 may have a causative role in IBD via deranged bacterial sensing and cytokine production, with 503F likely behaving as a gain-of-function variant. Thus, targeting OCTN1 variant may provide unprecedented opportunities for the personalized treatment of IBD patients and a better understanding of disease pathogenesis.

The human olfactory bulb processes odor valence representation and cues motor avoidance behavior

Determining the valence of an odor to guide rapid approach-avoidance behavior is thought to be one of the core tasks of the olfactory system, and yet little is known of the initial neural mechanisms supporting this process or of its subsequent behavioral manifestation in humans. In two experiments, we measured the functional processing of odor valence perception in the human olfactory bulb (OB)-the first processing stage of the olfactory system-using a noninvasive method as well as assessed the subsequent motor avoidance response. We demonstrate that odor valence perception is associated with both gamma and beta activity in the human OB. Moreover, we show that negative, but not positive, odors initiate an early beta response in the OB, a response that is linked to a preparatory neural motor response in the motor cortex. Finally, in a separate experiment, we show that negative odors trigger a full-body motor avoidance response, manifested as a rapid leaning away from the odor, within the time period predicted by the OB results. Taken together, these results demonstrate that the human OB processes odor valence in a sequential manner in both the gamma and beta frequency bands and suggest that rapid processing of unpleasant odors in the OB might underlie rapid approach-avoidance decisions.

Distinct brain oscillatory responses for the perception and identification of one's own body from other's body.

The body recognition process includes complex visual processing, the sensation, perception, and distinction stages of the stimulus. This study examined this process by using the time-frequency analysis of EEG signals and analyzed the obtained data by using the event-related oscillations method. This study aimed to examine the oscillatory brain responses and distinguish one's own body from other's body. In the present study, 17 young adults were included and the EEGs were recorded with 32 electrodes placed in different locations. Event-related power spectrum and phase-locking analyzes were performed. ITC and ERSP data were analyzed using 2 (condition) × 11 (location) × 2 (hemisphere) ANOVA Design. As we observed a prolonged response in the theta band in the grand averages, we included the time variable in the overall model. As a result, we found that the phase-locking and the event-related power spectrum of the theta response in recognizing one's own body were higher when compared to the phase-locking and the event-related power spectrum of the theta response in recognizing others' body (p < 0.05). When the time variable was included, the early theta response was more phase-locked and had a higher power spectrum compared to the late theta response (p < 0.05). As a result of the power spectrum analysis, the condition × hemisphere interaction effect in the beta band was higher in the left hemisphere regarding increased responses in recognizing one's own body (p < 0.05). As a result of ITC, the main effect of the condition was higher in the recognition of the stimulus of one's own body (p < 0.05). Finally, the theta oscillator response stood out in distinguishing one's own body from other's body. Similarly, the power spectrum in the beta response was higher in the left hemisphere, and this finding is consistent with the literature.

An Extension of the Beta Response Model for Continuous Responses and Parameter Estimation via an EM Algorithm

An Extension of the Beta Response Model for Continuous Responses and Parameter Estimation via an EM Algorithm

Abstract 6681: Inhibition of LSD1 using the reversible inhibitor SP2577 promotes Interferon dependent anti-tumor response in adrenocortical carcinoma

Abstract Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive disease with poor prognosis. The first line of treatment is surgery followed by chemotherapy (Mitotane), though these therapies still result in a dismal 15-44% survival rate after 5 years. Currently, there is no effective second line of treatment. Efforts have been made to treat ACC with immune therapy agents such as Avelumab, a PD-L1 antibody, but a recent study showed that there was only an overall response rate of 6% in a phase 1 clinical trial, further exhibiting a need for the development of novel therapeutics. Further research suggests that the current first line ACC treatments may benefit from the addition of immune therapies that induce an Interferon Beta (IFN-β) response in the tumor microenvironment. Previous studies have shown that treatment with IFN-β induces cell death and sensitizes human ACC lines to Mitotane, implying that combination of therapies that induce an IFN-β response may improve the anti-tumor response to Mitotane. Recently, inhibition of Lysine-Specific histone Demethylase 1 (LSD-1) was shown to stimulate an IFN-dependent anti-tumor response driven by the expression of Endogenous Retroviral Elements (ERVs) in a variety of cancer types. In addition, PD-L1 expression has also been shown to increase after LSD-1 inhibition. Yang, et al. reported that SP-2509, a preclinical analog of SP-2577 (Seclidemstat, currently in clinical phase I trials, Salarius Pharmaceuticals, Houston, TX) was able to induce the expression and release of interferons and cytokines in triple negative breast cancer models. In this study we investigate the ability of SP-2577 to promote the expression of IFN-β in human ACC cell lines, resulting in an anti-tumor immune response. Experimental Design: qRT-PCR was performed on ACC cell lines H295R and SW-13 at 48 and 72 hours post treatment to verify the ability of SP-2577 to promote IFN-β expression. ACC cells were co-cultured with peripheral blood mononuclear cells (PBMCs) in a 3D platform to evaluate lymphocyte infiltration following SP-2577 treatment. Interferons, chemokines, and cytokines were quantified in the culture supernatant after treatment with SP-2577 using the Meso Scale Discovery platform. Results: qRT-PCR showed that SP-2577 promotes ERV-mediated immune response in ACC cell lines via the expression and release of interferons, chemokines, and cytokines. Additionally, SP-2577 stimulates lymphocyte infiltration in an ACC derived 3D-spheroid platform further resulting in a cytotoxic effect. Conclusion: Our data suggests that the LSD-1 inhibitor SP-2577 can be used as a single agent in ACC patients to promote immune response and can potentially sensitize the tumor to first line of therapy, Mitotane. This study was supported by funding from the TGen Foundation. Citation Format: Sunil Sharma, Raffaella Soldi, Alexis Weston, Samuel Sampson, Sherin Daniel Ampanattu, Scott Celinski, Haiyong Han, Mohan Kaadige, Michael Berens, Jeffrey Trent. Inhibition of LSD1 using the reversible inhibitor SP2577 promotes Interferon dependent anti-tumor response in adrenocortical carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6681.

Basic information for the development of a toxicity assay in inactivated bacterial vaccines

This study dealt with the toxicity of inactivated bacteria intended for veterinary autogenous vaccines toward a suitable control assay. Two in vitro methods were used. The [3-(4, 5 -dimethylthiazol-2-yl) -2,5 -diphenyltetrazolium bromide] (MTT) test, based on the metabolic reaction of a tetrazolium salt in vital cells, was adopted on the basis of previous positive results. The Interleukin (IL)-1 beta release assay on monocyte-derived pig macrophages was carried out for comparative purposes, to evaluate the possible role of the inflammatory response. MTT and IL-1 beta responses showed a significant correlation (P < 0.05) at defined test dilutions of bacterial antigens, whereas no correlation was demonstrated using MTT responses normalized on bacterial cell concentration. Furthermore, the toxic effects shown in the MTT test were positively correlated to the extracellular protein content. On the whole, the above results could be a useful basis for the development of a toxicity assay on inactivated bacterial vaccines. Also, our data point at bacterial autolysis as a major component underlying toxicity.

Modulation of attention networks serving reorientation in healthy aging

Orienting attention to behaviorally relevant stimuli is essential for everyday functioning and mainly involves activity in the dorsal and ventral frontoparietal networks. Many studies have shown declines in the speed and accuracy of attentional reallocation with advancing age, but the underlying neural dynamics remain less understood. We investigated this age-related decline using magnetoencephalography (MEG) and a Posner task in 94 healthy adults (22-72 years old). MEG data were examined in the time-frequency domain, and significant oscillatory responses were imaged using a beamformer. We found that participants responded slower when attention reallocation was needed (i.e., the validity effect) and that this effect was positively correlated with age. We also found age-related validity effects on alpha activity in the left parietal and beta in the left frontal-eye fields from 350-950 ms. Overall, stronger alpha and beta responses were observed in younger participants during attention reallocation trials, but this pattern was reversed in the older participants. Interestingly, this alpha validity effect fully mediated the relationship between age and behavioral performance. In conclusion, older adults were slower in reorienting attention and exhibited age-related alterations in alpha and beta responses within parietal and frontal regions, which may reflect increased task demands depleting their compensatory resources.

Immune gene signature delineates a subclass of thyroid cancer with unfavorable clinical outcomes.

Thyroid cancer (THCA) is a heterogeneous disease with multiple clinical outcomes Immune cells regulate its progression. Three immunomolecular subtypes (C1, C2, C3) were identified in gene expression data sets from TCGA and GEO databases. Among them, subtype C3 had highest frequency of BRAF mutations, lowest frequency of RAS mutations, highest mutation load and shorter progression-free survival. Functional enrichment analysis for the genes revealed that C1 was up-regulated in the ERK cascade pathway, C2 was up-regulated in cell migration and proliferation pathways, while C3 was enriched in body fluid, protein regulation and response to steroid hormones functions. Notably, the three molecular subtypes exhibit differences in immune microenvironments as shown by timer database and analysis of immune expression signatures. The abundance of B_cell, CD4_Tcell, Neutrophil, Macrophage and Dendritic cells in C2 subtype were lower than in C1 and C3 subtypes Leukocyte fraction, proliferation macrophage regulation, lymphocyte infiltration, IFN gamma response and TGF beta response scores were significantly higher in C3 compared with C1 and C2 subtypes. Unlike C3 subtype, it was observed that C1 and C2 subtypes were significantly negatively correlated with most immune checkpoint genes in two different cohorts. The characteristic genes were differentially expressed between cancer cells, adjacent tissues, and metastatic tissues in different cohorts. In summary, THCA can be subclassified into three molecular subtypes with distinct histological types, genetic and transcriptional phenotypes, all of which have potential clinical implications.