The neural coding of properties shared by faces, bodies and objects

Previous studies have identified relatively separated regions of the brain that respond strongly when participants view images of either faces, bodies or objects. The aim of this thesis was to investigate how and where in the brain shared properties of faces, bodies and objects are processed. We selected three properties that are shared by faces and bodies, shared categories (sex and weight), shared identity and shared orientation (i.e. facing direction). We also investigated one property shared by faces and objects, the tendency to process a face or object as a whole rather than by its parts, which is known as holistic processing. We hypothesized that these shared properties might be encoded separately for faces, bodies and objects in the previously defined domain-specific regions, or alternatively that they might be encoded in an overlapping or shared code in those or other regions. In all of studies in this thesis, we used fMRI to record the brain activity of participants viewing images of faces and bodies or objects that showed differences in the shared properties of interest. We then investigated the neural responses these stimuli elicited in a variety of specifically localized brain regions responsive to faces, bodies or objects, as well as across the whole-brain. Our results showed evidence for a mix of overlapping coding, shared coding and domain-specific coding, depending on the particular property and the level of abstraction of its neural coding. We found we could decode face and body categories, identities and orientations from both face- and body-responsive regions showing that these properties are encoded in overlapping brain regions. We also found that non-domain specific brain regions are involved in holistic face processing. We identified shared coding of orientation and weight in the occipital cortex and shared coding of identity in the early visual cortex, right inferior occipital cortex, right parahippocampal cortex and right superior parietal cortex, demonstrating that a variety of brain regions combine face and body information into a common code. In contrast to these findings, we found evidence that high-level visual transformations may be predominantly processed in domain-specific regions, as we could most consistently decode body categories across image-size and body identity across viewpoint from body-responsive regions. In conclusion, this thesis furthers our understanding of the neural coding of face, body and object properties and gives new insights into the functional organisation of occipitotemporal cortex

The neural coding of face and body orientation in occipitotemporal cortex

Face and body orientation convey important information for us to understand other people's actions, intentions and social interactions. It has been shown that several occipitotemporal areas respond differently to faces or bodies of different orientations. However, whether face and body orientation are processed by partially overlapping or completely separate brain networks remains unclear, as the neural coding of face and body orientation is often investigated separately. Here, we recorded participants’ brain activity using fMRI while they viewed faces and bodies shown from three different orientations, while attending to either orientation or identity information. Using multivoxel pattern analysis we investigated which brain regions process face and body orientation respectively, and which regions encode both face and body orientation in a stimulus-independent manner. We found that patterns of neural responses evoked by different stimulus orientations in the occipital face area, extrastriate body area, lateral occipital complex and right early visual cortex could generalise across faces and bodies, suggesting a stimulus-independent encoding of person orientation in occipitotemporal cortex. This finding was consistent across functionally defined regions of interest and a whole-brain searchlight approach. The fusiform face area responded to face but not body orientation, suggesting that orientation responses in this area are face-specific. Moreover, neural responses to orientation were remarkably consistent regardless of whether participants attended to the orientation of faces and bodies or not. Together, these results demonstrate that face and body orientation are processed in a partially overlapping brain network, with a stimulus-independent neural code for face and body orientation in occipitotemporal cortex

Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro-inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single-nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell-cycle, and senescence-associated pathways in naturally aged mice. Long-term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases

A novel fusion protein scaffold 18/12/TxM activates the IL-12, IL-15, and IL-18 receptors to induce human memory-like natural killer cells

Natural killer (NK) cells are cytotoxic innate lymphoid cells that are emerging as a cellular immunotherapy for various malignancies. NK cells are particularly dependent on interleukin (IL)-15 for their survival, proliferation, and cytotoxic function. NK cells differentiate into memory-like cells with enhanced effector function after a brief activation with IL-12, IL-15, and IL-18. N-803 is an IL-15 superagonist composed of an IL-15 mutant (IL-15N72D) bound to the sushi domain of IL-15Rα fused to the Fc region of IgG1, which results in physiological trans-presentation of IL-15. Here, we describe the creation of a novel triple-cytokine fusion molecule, 18/12/TxM, using the N-803 scaffold fused to IL-18 via the IL-15N72D domain and linked to a heteromeric single-chain IL-12 p70 by the sushi domain of the IL-15Rα. This molecule displays trispecific cytokine activity through its binding and signaling through the individual cytokine receptors. Compared with activation with the individual cytokines, 18/12/TxM induces similar short-term activation and memory-like differentiation of NK cells on both the transcriptional and protein level and identica

Memory-like differentiation enhances NK cell responses to melanoma

PURPOSE: Treatment of advanced melanoma is a clinical challenge. Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers, but are frequently deficient or dysfunctional in patients with melanoma. Thus, new strategies are needed to enhance NK-cell antitumor responses. Cytokine-induced memory-like (ML) differentiation overcomes many barriers in the NK-cell therapeutics field, resulting in potent cytotoxicity and enhanced cytokine production against blood cancer targets. However, the preclinical activity of ML NK against solid tumors remains largely undefined. EXPERIMENTAL DESIGN: Phenotypic and functional alterations of blood and advanced melanoma infiltrating NK cells were evaluated using mass cytometry. ML NK cells from healthy donors (HD) and patients with advanced melanoma were evaluated for their ability to produce IFNγ and kill melanoma targets RESULTS: NK cells in advanced melanoma exhibited a decreased cytotoxic potential compared with blood NK cells. ML NK cells differentiated from HD and patients with advanced melanoma displayed enhanced IFNγ production and cytotoxicity against melanoma targets. This included ML differentiation enhancing melanoma patients\u27 NK-cell responses against autologous targets. The ML NK-cell response against melanoma was partially dependent on the NKG2D- and NKp46-activating receptors. Furthermore, in xenograft NSG mouse models, human ML NK cells demonstrated superior control of melanoma, compared with conventional NK cells. CONCLUSIONS: Blood NK cells from allogeneic HD or patients with advanced melanoma can be differentiated into ML NK cells for use as a novel immunotherapeutic treatment for advanced melanoma, which warrants testing in early-phase clinical trials

Targeting histone lysine demethylase KDM4A in Aggressive Variant Prostate Cancer

View full abstracthttps://openworks.mdanderson.org/leading-edge/1054/thumbnail.jp

Crop Updates 2000 Cereals - part 3

This session covers eighteen papers from different authors: BARLEY AND OAT AGRONOMY 1. Unicorn barley must meet malting specifications to be a viable option, Roslyn Jettnerand Blakely Paynter, Agriculture Western Australia 2. Optimum oat seed rates, Glenn McDonald, Agriculture Western Australia 3. Production and Quality of export Oaten Hay (1998 and 1989), Pierre Fievez, Pierre Fievez and Associates FROST 4. Climatology of Frost in Southern Western Australia, Ian Foster, Agriculture Western Australia 5. Flowering calculator, David Tennant, Agriculture Western Australia 6. Some options for managing the risk of frost damage, Wal Anderson, Agriculture Western Australia PASTURE 7. TIMERITE® Control of redlegged earth mite in south western Australia with a spring spray to pastures, James Ridsdill-Smith and Celia Pavri, CSIRO Entomology, University of Western Australia 8. The pattern of seed softening in subterranean clover in relation to presicted false break risk, Ross Chapman and Senthold Asseng, CSIRO Plant Industry, Centre for Mediterranean Agricultural Research 9. Charano serradella – a viable option for 1:1 cropping, Steve Carr and Brad Nutt IAMA Agri-Services Western Australia and Centre for Legumes in Mediterranean Agriculture, University of Western Australia 10. Alfalfa mosaic virus in alternative annual pasture and forage legumes, Lindrea Latham and Roger Jones, Crop Improvement Institute, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture, University of Western Australia 11. Pasture mixture performs better than single-species-based pasture – 1999, Anyou Liu, Clinton Revell and David Ferris, Centre for Cropping Systems, Agriculture Western Australia 12. Better pasture management improves performance of following crops – 1999, Anyou Liu, Clinton Revell and David Ferris, Centre for Cropping Systems, Agriculture Western Australia 13. Lucerne Benefits Crop Production, Roy Latta1, Lisa-Jane Blacklow2, Chris Matthews1 1Agriculture Western Australia 2University of Western Australia 14. Does size count? Determining optimum release number of red apion for biocontrol of doublegee, Tim Woodburn and Paul Yeoh, CSIRO Entomology/CRC Weed Management Systems, Perth 15. Herbicide tolerance of some new cultivars of annual pasture legumes, Clinton Revell and Ian Rose, Centre for Cropping Systems, Agriculture Western Australia 16. Lucerne – crop rotations in the Esperance region, Anita Lyons, Roy Latta and Chris Matthews,Agriculture Western Australia PRECISION AGRICULTURE 17. Assessing the results of on-farm experiments using yield monitors, Simon Cook and Matthew Adams, CSIRO Land and Water 18. Achiever: A GIS based achievable yield and fertiliser recommendation system for precision agriculture, Robert J. Corner, Matthew L. Adams, Precision Agriculture Research Group CSIRO Land and Wate