75 research outputs found
Talk, text or tag?:the development of a self-annotation app for activity recognition in smart environments
Exercise training improves long-term memory in obese mice
Obesity has been linked to a range of pathologies, including dementia. In contrast, regular physical activity is associated with the prevention or reduced progression of neurodegeneration. Specifically, physical activity can improve memory and spatial cognition, reduce age-related cognitive decline, and preserve brain volume, but the mechanisms are not fully understood. Accordingly, we investigated whether any detrimental effects of high-fat diet (HFD)-induced obesity on cognition, motor behavior, adult hippocampal neurogenesis, and brain-derived neurotrophic factor (BDNF) could be mitigated by voluntary exercise training in male C57Bl/6 mice. HFD-induced impairment of motor function was not reversed by exercise. Importantly, voluntary wheel running improved long-term memory and increased hippocampal neurogenesis, suggesting that regular physical activity may prevent cognitive decline in obesity
Talk, text, tag? Understanding self-annotation of smart home data from a user’s perspective
Delivering effortless interactions and appropriate interventions through pervasive systems requires making sense of multiple streams of sensor data. This is particularly challenging when these concern people’s natural behaviours in the real world. This paper takes a multidisciplinary perspective of annotation and draws on an exploratory study of 12 people, who were encouraged to use a multi-modal annotation app while living in a prototype smart home. Analysis of the app usage data and of semi-structured interviews with the participants revealed strengths and limitations regarding self-annotation in a naturalistic context. Handing control of the annotation process to research participants enabled them to reason about their own data, while generating accounts that were appropriate and acceptable to them. Self-annotation provided participants an opportunity to reflect on themselves and their routines, but it was also a means to express themselves freely and sometimes even a backchannel to communicate playfully with the researchers. However, self-annotation may not be an effective way to capture accurate start and finish times for activities, or location associated with activity information. This paper offers new insights and recommendations for the design of self-annotation tools for deployment in the real world
CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold
The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity
CD8+ T-Âcell specificity is compromised at a defined major histocompatibility complex class I/CD8 affinity threshold
The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity
CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold
The CD8 coreceptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR) binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~ 1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~ 10-fold). In this study, we used a panel of MHCI mutants with altered CD8 binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity.
The pMHCI/CD8 interaction controls specificit
Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection
Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems
Measurement of messenger RNA encoding the α-chain, polymeric immunoglobulin receptor, and J-chain in duodenal mucosa from dogs with and without chronic diarrhea by use of quantitative real-time reverse transcription-polymerase chain reaction assays
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