59 research outputs found

    Spatial Frequency Tuning of Body Inversion Effects

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    Body inversion effects (BIEs) reflect the deployment of the configural processing of body stimuli. BIE modulates the activity of body-selective areas within both the dorsal and the ventral streams, which are tuned to low (LSF) or high spatial frequencies (HSF), respectively. The specific contribution of different bands to the configural processing of bodies along gender and posture dimensions, however, is still unclear. Seventy-two participants performed a delayed matching-to-sample paradigm in which upright and inverted bodies, differing for gender or posture, could be presented in their original intact form or in the LSF- or HSF-filtered version. In the gender discrimination task, participants’ performance was enhanced by the presentation of HSF images. Conversely, for the posture discrimination task, a better performance was shown for either HSF or LSF images. Importantly, comparing the amount of BIE across spatial-frequency conditions, we found greater BIEs for HSF than LSF images in both tasks, indicating that configural body processing may be better supported by HSF information, which will bias processing in the ventral stream areas. Finally, the exploitation of HSF information for the configural processing of body postures was lower in individuals with higher autistic traits, likely reflecting a stronger reliance on the local processing of body-part details

    “Left and right prefrontal routes to action comprehension”

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    Successful action comprehension requires the integration of motor information and semantic cues about objects in context. Previous evidence suggests that while motor features are dorsally encoded in the fronto-parietal action observation network (AON); semantic features are ventrally processed in temporal structures. Importantly, these dorsal and ventral routes seem to be preferentially tuned to low (LSF) and high (HSF) spatial frequencies, respectively. Recently, we proposed a model of action comprehension where we hypothesized an additional route to action understanding whereby coarse LSF information about objects in context is projected to the dorsal AON via the prefrontal cortex (PFC), providing a prediction signal of the most likely intention afforded by them. Yet, this model awaits for experimental testing. To this end, we used a perturb-and-measure continuous theta burst stimulation (cTBS) approach, selectively disrupting neural activity in the left and right PFC and then evaluating the participant's ability to recognize filtered action stimuli containing only HSF or LSF. We find that stimulation over PFC triggered different spatial-frequency modulations depending on lateralization: left-cTBS and right-cTBS led to poorer performance on HSF and LSF action stimuli, respectively. Our findings suggest that left and right PFC exploit distinct spatial frequencies to support action comprehension, providing evidence for multiple routes to social perception in humans

    Neutrophils in cancer: neutral no more

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    Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

    Peripersonal space representation develops independently from visual experience

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    Our daily-life actions are typically driven by vision. When acting upon an object, we need to represent its visual features (e.g. shape, orientation, etc.) and to map them into our own peripersonal space. But what happens with people who have never had any visual experience? How can they map object features into their own peripersonal space? Do they do it differently from sighted agents? To tackle these questions, we carried out a series of behavioral experiments in sighted and congenitally blind subjects. We took advantage of a spatial alignment effect paradigm, which typically refers to a decrease of reaction times when subjects perform an action (e.g., a reach-To-grasp pantomime) congruent with that afforded by a presented object. To systematically examine peripersonal space mapping, we presented visual or auditory affording objects both within and outside subjects' reach. The results showed that sighted and congenitally blind subjects did not differ in mapping objects into their own peripersonal space. Strikingly, this mapping occurred also when objects were presented outside subjects' reach, but within the peripersonal space of another agent. This suggests that (the lack of) visual experience does not significantly affect the development of both one's own and others' peripersonal space representation

    MET is required for the recruitment of anti-tumoural neutrophils

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    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential ‘Achilles’ heel’ of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases

    International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

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    Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice

    The COGs (context, object, and goals) in multisensory processing

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    Our understanding of how perception operates in real-world environments has been substantially advanced by studying both multisensory processes and “top-down” control processes influencing sensory processing via activity from higher-order brain areas, such as attention, memory, and expectations. As the two topics have been traditionally studied separately, the mechanisms orchestrating real-world multisensory processing remain unclear. Past work has revealed that the observer’s goals gate the influence of many multisensory processes on brain and behavioural responses, whereas some other multisensory processes might occur independently of these goals. Consequently, other forms of top-down control beyond goal dependence are necessary to explain the full range of multisensory effects currently reported at the brain and the cognitive level. These forms of control include sensitivity to stimulus context as well as the detection of matches (or lack thereof) between a multisensory stimulus and categorical attributes of naturalistic objects (e.g. tools, animals). In this review we discuss and integrate the existing findings that demonstrate the importance of such goal-, object- and context-based top-down control over multisensory processing. We then put forward a few principles emerging from this literature review with respect to the mechanisms underlying multisensory processing and discuss their possible broader implications

    Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

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    Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.This work was supported by the Medical Research Council (MRC) Clinical Training Fellowship (awards G0802255 and MR/K023845/1 to A.A.R.T. and R.S.D., respectively), a National Institute for Health Research (NIHR) Clinical Lectureship and an Academy of Medical Sciences starter grant (to A.A.R.T.), a Wellcome Trust postdoctoral clinical fellowship (110086 to A.M.), a Wellcome Trust Senior Clinical Fellowship award (098516 to S.R.W.), a Wellcome Trust Senior Clinical Fellowship award (076945 to D.H.D.), a British Lung Foundation Fellowship (F05/7 to H.M.M.), a Wellcome Trust New Investigator Award (WT100981MA to N.M.M.), and a British Heart Foundation Senior Basic Science Research Fellowship (FS/13/48/30453 to A.L.). E.R.C. and A.S.C. are supported by the NIHR Cambridge Biomedical Research Centre. R.H.S. is supported by the MRC. R.R.M. is supported by MRC (MC_PC_U127574433), Biotechnology and Biological Sciences Research Council, and European Chemical Industry Council grants. M.M. is supported by the European Research Council (OxyMO). The MRC/University of Edinburgh Centre for Inflammation Research is supported by an MRC Centre Grant

    Neutrophils in cancer: neutral no more

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