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In this paper, we discuss challenges emerging in connection to teaching for and with more-than-human values and stakeholder perspectives in human-computer interaction (HCI) curriculum. Recently, we have experienced a rise in interest in more-than-human perspectives in various HCI venues. However, there is still a lack of published work on how to teach such perspectives, as well as practical educational resources for supporting the more-than-human HCI in education. In this paper, we discuss challenges emerging in connection to teaching for and with more-than-human values and stakeholder perspectives in human-computer interaction (HCI) curriculum. Recently, we have experienced a rise in interest in more-than-human perspectives in various HCI venues. However, there is still a lack of published work on how to teach such perspectives, as well as practical educational resources for supporting the more-than-human HCI in education.

In this special interest group (SIG) we invite researchers, practitioners, and educators to share their perspectives and experiences on the expansion of human-centred perspective to more-than-human design orientation in human-computer interaction (HCI). This design for and with more-than-human perspectives and values cover a range of fields and topics, and comes with unique design opportunities and challenges.In this SIG, we propose a forum for exchange of concrete experiences and a range of perspectives, and to facilitate reflective discussions and the identification of possible future paths. In this special interest group (SIG) we invite researchers, practitioners, and educators to share their perspectives and experiences on the expansion of human-centred perspective to more-than-human design orientation in human-computer interaction (HCI). This design for and with more-than-human perspectives and values cover a range of fields and topics, and comes with unique design opportunities and challenges. In this SIG, we propose a forum for exchange of concrete experiences and a range of perspectives, and to facilitate reflective discussions and the identification of possible future paths.

Date Presented 04/02/2022 This research elicited experiences of practitioners in multiple African countries to elucidate critical factors they believed were conducive to creating a culturally responsive, effective, and sustainable global partnership. Results elucidate common challenges when developing these partnerships and identify recommended preparatory activities that may help create stronger partnerships. Results can assist OTs from the global north when establishing partnerships with practitioners from Africa. Primary Author and Speaker: Jackson Johnson Additional Authors and Speakers: Peter O. Ndaa, Delaney Batik, Jaime P. Muñoz, Anne Marie Hansen

The unique cell biology of Toll-like receptor 4 (TLR4) allows it to initiate two signal-transduction cascades: a signal dependent on the adaptors TIRAP (Mal) and MyD88 that begins at the cell surface and regulates proinflammatory cytokines, and a signal dependent on the adaptors TRAM and TRIF that begins in the endosomes and drives the production of type I interferons. Negative feedback circuits to limit TLR4 signals from both locations are necessary to balance the inflammatory response. We describe a negative feedback loop driven by autocrine-paracrine prostaglandin E2 (PGE2) and the PGE2 receptor EP4 that restricted TRIF-dependent signals and the induction of interferon-β through the regulation of TLR4 trafficking. Inhibition of PGE2 production or antagonism of EP4 increased the rate at which TLR4 translocated to endosomes and amplified TRIF-dependent activation of the transcription factor IRF3 and caspase-8. This PGE2-driven mechanism restricted TLR4-TRIF signaling in vitro after infection of macrophages by the Gram-negative pathogens Escherichia coli or Citrobacter rodentium and protected mice against mortality induced by Salmonella enteritidis serovar Typhimurium. Thus, PGE2 restricted TLR4-TRIF signaling specifically in response to lipopolysaccharide.

Enteropathogenic Escherichia coli (EPEC) use a type 3 secretion system (T3SS) for injection of effectors into host cells and intestinal colonization. Here, we demonstrate that the multicargo chaperone CesT has two strictly conserved tyrosine phosphosites, Y152 and Y153 that regulate differential effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine strongly attenuated EPEC type 3 effector injection into host cells, and limited Tir effector mediated intimate adherence during infection. EPEC expressing a CesT Y152F variant were deficient for NleA effector expression and exhibited significantly reduced translocation of NleA into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating phosphosites Y152 and Y153 in CesT functionality. A mouse infection model of intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for tandem tyrosine phosphosites within CesT. Therefore, CesT via its C-terminal tyrosine phosphosites, has relevant roles beyond typical type III secretion chaperones that interact and stabilize effector proteins.

TLR4 is unique in its capacity to initiate two qualitatively distinct transcriptional programs from two cellular locations. Cell surface TLR4/MyD88 complexes drive pro-inflammatory cytokine transcription through NF-κB, while endosomal TLR4/TRIF complexes activate IRF3 and a type I interferon response. Feedback circuits to limit signals from both locations are necessary to balance the inflammatory response to Gram negative bacteria, yet how endosomal TLR4/TRIF signals are terminated has remained an open question. We find that activation of TLR4 triggers rapid prostaglandin PGE2 production, necessary to limit the kinetics of endosomal TRIF, but not MyD88, signaling. Mechanistically, autocrine PGE2 activates the specific EP4 receptor to inhibit small GTPase mediated TLR4 trafficking to endosomes and to accelerate autophagic degradation of active TLR4/TRIF complexes. Inhibition of EP4 receptor function does not impair cell surface MyD88 signals, but leads to hyper TRIF dependent type I interferon production in response to bacterial LPS or to macrophage infection by live Gram negative pathogens.

Enteropathogenic Escherichia coli (EPEC) use a type 3 secretion system (T3SS) for injection of effectors into host cells and intestinal colonization. Here, we demonstrate that the multicargo chaperone CesT has two strictly conserved tyrosine phosphosites, Y152 and Y153 that regulate differential effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine strongly attenuated EPEC type 3 effector injection into host cells, and limited Tir effector mediated intimate adherence during infection. EPEC expressing a CesT Y152F variant were deficient for NleA effector expression and exhibited significantly reduced translocation of NleA into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating phosphosites Y152 and Y153 in CesT functionality. A mouse infection model of intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for tandem tyrosine phosphosites within CesT. Therefore, CesT via its C-terminal tyrosine phosphosites, has relevant roles beyond typical type III secretion chaperones that interact and stabilize effector proteins.

Enteropathogenic Escherichia coli (EPEC) are worldwide human enteric pathogens inflicting significant morbidity and causing large economic losses. A type 3 secretion system (T3SS) is critical for EPEC intestinal colonization, and injection of effectors into host cells contributes to cellular subversion and innate immune evasion. Here, we demonstrate that two strictly conserved C-terminal tyrosine residues, Y152 and Y153, within the multicargo T3SS chaperone CesT serve differential roles in regulating effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine attenuated EPEC type 3 effector injection into host cells, and significantly limited Tir effector mediated intimate adherence, a key feature of attaching and effacing pathogenesis. Whereas CesT Y153 supported normal levels of Tir translocation, CesT Y152 was strictly required for the effector NleA to be expressed and subsequently translocated into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y152, Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating Y152 in CesT functionality. A mouse infection model of EPEC intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for strictly conserved tandem tyrosine residues within CesT. Tyrosine 152 of CesT is implicated in NleA expression, providing functional relevance for localized amino acid conservation. Therefore, CesT via its novel C-terminal domain, has relevant roles beyond typical T3SC that interact and stabilize effector proteins.

Background & Aims Enterohemorrhagic Escherichia coli (EHEC) causes over 70,000 episodes of foodborne diarrhea annually in the United States. The early sequence of events that precede life-threatening hemorrhagic colitis and hemolytic uremic syndrome is not fully understood due to the initial asymptomatic phase of the disease and the lack of a suitable animal model. We determined the initial molecular events in the interaction between EHEC and human colonic epithelium. Methods Human colonoids derived from adult proximal colonic stem cells were developed into monolayers to study EHEC-epithelial interactions. Monolayer confluency and differentiation were monitored by transepithelial electrical resistance measurements. The monolayers were apically infected with EHEC, and the progression of epithelial damage over time was assessed using biochemical and imaging approaches. Results Human colonoid cultures recapitulate the differential protein expression patterns characteristic of the crypt and surface colonocytes. Mucus-producing differentiated colonoid monolayers are preferentially colonized by EHEC. Upon colonization, EHEC forms characteristic attaching and effacing lesions on the apical surface of colonoid monolayers. Mucin 2, a main component of colonic mucus, and protocadherin 24 (PCDH24), a microvillar resident protein, are targeted by EHEC at early stages of infection. The EHEC-secreted serine protease EspP initiates brush border damage through PCDH24 reduction. Conclusions Human colonoid monolayers are a relevant pathophysiologic model that allow the study of early molecular events during enteric infections. Colonoid monolayers provide access to both apical and basolateral surfaces, thus providing an advantage over three-dimensional cultures to study host–pathogen interactions in a controllable and tractable manner. EHEC reduces colonic mucus and affects the brush border cytoskeleton in the absence of commensal bacteria.

In the present paper, ToneInk, a prototype of a music based play scenario that investigates player collaboration, is introduced. ToneInk is an explorative sound environment that differs from the majority of music based games in that players can collaborate and be creative in the way they express themselves through melody and rhythm. The paper provides player interaction and navigation results and demonstrates how various affordances in the ToneInk design iterations make it hard or possible for players to engage with the system and with each other. From observations it was clear that players lost mutual awareness, and in general were more passive when they needed to monitor a screen interface that supported the sound environment. Player collaboration was strongest when players negotiated rhythm, while the negotiation of melody was temporally offset and consisted of long individual explorations.