Understanding Body Language Does Not Require Matching the Body's Egocentric Map to Body Posture: A Brain Activation fMRI Study

Body language (BL) is a type of nonverbal communication in which the body communicates the message. We contrasted participants' cognitive processing of body representations or meanings versus body positions. Participants (N\u2009=\u200920) were shown pictures depicting body postures and were instructed to focus on their meaning (BL) or on the position of a body part relative to the position of another part (body structural description [BSD]). We examined activation in brain areas related to the two types of body representation\u2014body schema and BSD\u2014as modulated by the two tasks. We presumed that if understanding BL triggers embodiment of body posture, a matching procedure between the egocentric map coding the position of one's body segments in space and time should occur. We found that BL (vs. BSD) differentially activated the angular gyrus bilaterally, the anterior middle temporal gyrus, the temporal pole, and the right superior temporal gyrus, the inferior frontal gyrus, the superior medial gyrus, and the left superior frontal gyrus. BSD (vs. BL) differentially activated the superior parietal lobule (Area 7A) bilaterally, the posterior inferior temporal gyrus, the middle frontal gyrus, and the left precentral gyrus. Sensorimotor areas were differentially activated by BSD when compared with BL. Inclusive masking showed significant voxels in the superior colliculus and pulvinar, fusiform gyrus, inferior temporal gyrus, superior temporal gyrus, the intraparietal sulcus bilaterally, inferior frontal gyrus bilaterally, and precentral gyrus. These results indicate common brain networks for processing BL and BSD, for which some areas show differentially stronger or weaker processing of one task or the other, with the precuneus and the superior parietal lobule, the intraparietal sulcus, and sensorimotor areas most related to the BSD as activated by the BSD task. In contrast, the parietal operculum, an area related to the body schema, a representation crucial during embodiment of body postures, was not activated for implicit masking or for the differential contrasts

Identifying environmental sounds: a multimodal mapping study

Our environment is full of auditory events such as warnings or hazards, and their correct recognition is essential. We explored environmental sound (ES) recognition in a series of studies. In study 1 we performed an Activation Likelihood Estimation (ALE) meta-Analysis of neuroimaging studies addressing ES processing to delineate the network of areas consistently involved in ES processing. In study 2 we reported a series of 7 neurosurgical patients with lesions involving the areas found consistently activated by the ALE meta-analysis and tested their ES recognition abilities. In study 3 we investigated how the areas involved in ES might be functionally deregulated as an effect of lesion by performing an fMRI study on patients (in comparison to healthy controls). Areas found to be consistently activated in the ALE quantitative meta-analysis involved the STG/MTG, insula/rolandic operculum, parahippocampal gyrus and inferior frontal gyrus complex bilaterally. Some of these areas were found modulated by design choices, e.g., type of task, type of control condition, type of stimuli. Patients with lesions in these areas of the left and the right hemisphere had an impaired ES recognition. The most frequently lesioned area corresponded to the hippocampus/insula/superior temporal gyrus. For the most part, the patients’ responses were unrelated to the target sounds or were semantically related to the target sounds. The other type of responses were: auditorily related, semantically and auditorily related, and I don't Know answers. The fMRI evidenced deregulations of the activation reported in the right IFG and in the STG bilaterally and in the left insula. We showed that some of these clusters of activation truly reflect ES processing, whereas others are related to design choices. Our results allowed a parcelization of the activation found along the MTG/STG are

Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein

Tumors have evolved elaborate mechanisms for evading immune detection, such as production of immunoinhibitory cytokines and down-regulation of major histocompatibility complex (MHC) expression. We have studied PAX3-FKHR as an example of an oncogenic fusion protein associated with an aggressive metastatic cancer. We show that PAX3-FKHR alters expression of genes that are normally regulated by Janus kinase/signal transducer and activator of transcription (STAT) signaling pathways. This occurs as a result of a specific interaction between PAX3-FKHR and the STAT3 transcription factor, which results in a dramatic reduction in tumor MHC expression, and an alteration in local cytokine concentrations to inhibit surrounding inflammatory cells and immune detection. Collectively, these data show that an oncogenic transcription factor can promote tumor growth and tissue invasion while inhibiting local inflammatory and immune responses. This is the first time that an immunomodulatory role has been described for an oncogenic fusion protein

Innate lymphoid cell dysfunction during long-term suppressive antiretroviral therapy in an African cohort

BACKGROUND: Innate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. HIV associated destruction of mucosal lymphoid tissue depletes ILCs, among other immune dysfunctions. Studies have described limited restoration of ILCs during the first three years of combined antiretroviral therapy (cART). Little is known about restoration of ILCs during long-term cART, particularly in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART. RESULTS: We examined phenotypes and function of ILCs from peripheral blood mononuclear cells after 12 years of suppressive cART. We report that ILC1 frequencies (T-BET + CD127 + and CD161 +) were higher in cART-treated HIV-infected relative to age-matched health HIV-negative adults; P = 0.04 whereas ILC precursors (ILCP) were comparable in the two groups (P = 0.56). Interferon gamma (IFN-γ) secretion by ILC1 was higher among cART-treated HIV-infected relative to HIV-negative adults (P = 0.03). CONCLUSION: HIV associated alteration of ILC persisted during cART and may likely affect the quality of host innate and adaptive immune responses during long-term cART

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort.

BACKGROUND: We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/μl) and age-matched healthy-HIV-uninfected individuals from the same community. METHODS: Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56+/-CD16+/-). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production. RESULTS: CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals. CONCLUSION: NK cell activation and dysfunction persisted despite seven years of suppressive ART with "normalization" of peripheral CD4 counts

Monocyte Dysfunction, Activation, and Inflammation After Long-Term Antiretroviral Therapy in an African Cohort.

BACKGROUND: Monocyte dysfunction may persist during antiretroviral therapy (ART). METHODS: Frozen peripheral blood mononuclear cells of 30 human immunodeficiency virus (HIV)-infected ART-treated adults with sustained viral suppression and CD4 counts ≥500 cells/µL were consecutively analyzed for monocyte phenotypes and function. RESULTS: Nonclassical monocytes (CD14+, CD16++), interleukin (IL)-1β production, and expression of CD40 and CD86 were lower among ART-treated HIV-infected adults relative to age-matched HIV-negative adults (P = .01, P = .01, and P = .02, respectively). Intestinal fatty acid-binding protein, IL6, and soluble CD14 were higher among HIV-infected adults relative to HIV-negative adults (P = .0002, P = .04, and P = .0017, respectively). CONCLUSIONS: Further investigation is required to understand drivers of persistent monocyte activation and dysfunction

An Efficient Strategy to Induce and Maintain In Vitro Human T Cells Specific for Autologous Non-Small Cell Lung Carcinoma

BACKGROUND: The efficient expansion in vitro of cytolytic CD8+ T cells (CTLs) specific for autologous tumors is crucial both for basic and translational aspects of tumor immunology. We investigated strategies to generate CTLs specific for autologous Non-Small Cell Lung Carcinoma (NSCLC), the most frequent tumor in mankind, using circulating lymphocytes. PRINCIPAL FINDINGS: Classic Mixed Lymphocyte Tumor Cultures with NSCLC cells consistently failed to induce tumor-specific CTLs. Cross-presentation in vitro of irradiated NSCLC cells by autologous dendritic cells, by contrast, induced specific CTL lines from which we obtained a high number of tumor-specific T cell clones (TCCs). The TCCs displayed a limited TCR diversity, suggesting an origin from few tumor-specific T cell precursors, while their TCR molecular fingerprints were detected in the patient's tumor infiltrating lymphocytes, implying a role in the spontaneous anti-tumor response. Grafting NSCLC-specific TCR into primary allogeneic T cells by lentiviral vectors expressing human V-mouse C chimeric TCRalpha/beta chains overcame the growth limits of these TCCs. The resulting, rapidly expanding CD4+ and CD8+ T cell lines stably expressed the grafted chimeric TCR and specifically recognized the original NSCLC. CONCLUSIONS: This study defines a strategy to efficiently induce and propagate in vitro T cells specific for NSCLC starting from autologous peripheral blood lymphocytes

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vaccines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vaccination serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4(+) T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1 & beta;, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abrogated vaccine responses in communities with endemic infections.Author summarySchistosomiasis drives host immune responses for optimal pathogen survival, potentially altering host responses to vaccine-related antigen. Chronic schistosomiasis and co-infection with hepatotropic viruses are common in countries where schistosomiasis is endemic. We explored the impact of Schistosoma mansoni (S. mansoni) worm burden on Hepatitis B (HepB) vaccination of individuals from a fishing community in Uganda. We demonstrate that higher schistosome-specific antigen (circulating anodic antigen, CAA) concentration pre-vaccination, is associated with lower HepB antibody titers post-vaccination at month 7. We show higher pre-vaccination levels of CCL17 in instances of high CAA that negatively associate with HepB antibody titers month 12 post-vaccination and coincided with lower frequencies of circulating T follicular helper cell populations (cTfh), proliferating antibody secreting cells (ASCs), and higher frequencies of regulatory T cells (Tregs). We also show that monocyte function is important in HepB vaccine responses, and high CAA is associated with alterations in the early innate cytokine/chemokine microenvironment. Our findings suggest that in individuals with high CAA and likely high worm burden, schistosomiasis can create an environment that is polarized against optimal host immune responses to the vaccine, which puts many endemic communities at risk for infection against HepB and other diseases that are preventable by vaccines.Cancer Signaling networks and Molecular Therapeutic

Performance of the CMS High Granularity Calorimeter prototype to charged pion beams of 20−-300 GeV/c

The upgrade of the CMS experiment for the high luminosity operation of the LHC comprises the replacement of the current endcap calorimeter by a high granularity sampling calorimeter (HGCAL). The electromagnetic section of the HGCAL is based on silicon sensors interspersed between lead and copper (or copper tungsten) absorbers. The hadronic section uses layers of stainless steel as an absorbing medium and silicon sensors as an active medium in the regions of high radiation exposure, and scintillator tiles directly readout by silicon photomultipliers in the remaining regions. As part of the development of the detector and its readout electronic components, a section of a silicon-based HGCAL prototype detector along with a section of the CALICE AHCAL prototype was exposed to muons, electrons and charged pions in beam test experiments at the H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology as foreseen for the HGCAL but with much finer longitudinal segmentation. The performance of the calorimeters in terms of energy response and resolution, longitudinal and transverse shower profiles is studied using negatively charged pions, and is compared to GEANT4 predictions. This is the first report summarizing results of hadronic showers measured by the HGCAL prototype using beam test data.Comment: To be submitted to JINS

Attention to the other’s body sensations modulates the ventromedial prefrontal cortex

Theory of Mind (ToM) is involved in experiencing the mental states and/or emotions of others. A further distinction can be drawn between emotion and perception/sensation. We investigated the mechanisms engaged when participants’ attention is driven toward specific states. Accordingly, 21 right-handed healthy individuals performed a modified ToM task in which they reflected about someone’s emotion or someone’s body sensation, while they were in a functional magnetic resonance imaging scanner. The analysis of brain activity evoked by this task suggests that the two conditions engage a widespread common network previously found involved in affective ToM (temporo-parietal junction (TPJ), parietal cortex, dorso-lateral prefrontal cortex (DLPFC), medial- prefrontal cortex (MPFC), Insula). Critically, the key brain result is that body sensation implicates selectively ventromedial prefrontal cortex (VMPFC). The current findings suggest that only paying attention to the other’s body sensations modulates a self-related representation (VMPFC)