a b s t r a c tWe examined whether people spontaneously represent the partner's viewpoint in spatial memory when it is available in advance and whether they adapt their spontaneous descriptions accordingly. In 18 pairs, Directors studied arrays of objects while: (1) not knowing about having to describe the array to a Matcher, (2) knowing about the subsequent description, and (3) knowing the Matcher's subsequent viewpoint, which was offset by 90°, 135°, or 180°. In memory tests preceding descriptions, Directors represented the Matcher's viewpoint when it was known during study, taking longer to imagine orienting to perspectives aligned with it and rotating their drawings of arrays toward it. Conversely, when Directors didn't know their Matcher's viewpoint, they encoded arrays egocentrically, being faster to imagine orienting to and to respond from perspectives aligned with their own. Directors adapted their descriptions flexibly, using partner-centered spatial expressions more frequently when misaligned by 90°and egocentric ones when misaligned by 135°. Knowing their misalignment in advance helped partners recognize when descriptions would be most difficult for Directors (at 135°) and to mutually agree on using their perspective. Thus, in collaborative tasks, people don't rely exclusively on their spatial memory but also use other pertinent perceptual information (e.g., their misalignment from their partner) to assess the computational demands on each partner and select strategies that maximize the efficiency of communication.

Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Although lactobacilli and bifidobacteria produce beneficial lactic and short-chain fatty acids in the mammalian gut, the significance of intestinal Escherichia coli producing these acids is debatable. Taking a Koch’s postulates approach in reverse, we define Escherichia coli as health-promoting for naturally colonizing the gut of healthy mice and protecting them against intestinal colonization and concomitant mortality by Pseudomonas aeruginosa. Reintroduction of faecal bacteria and E. coli in antibiotic-treated mice establishes a high titre of E. coli in the host intestine and increases defence against P. aeruginosa colonization and mortality. Strikingly, high sugar concentration favours E. coli fermentation to lactic and acetic acid and inhibits P. aeruginosa growth and virulence in aerobic cultures and in a model of aerobic metabolism in flies, while dietary vegetable fats - not carbohydrates or proteins - favour E. coli fermentation and protect the host in the anaerobic mouse gut. Thus E. coli metabolic output is an important indicator of resistance to infection. Our work may also suggest that the lack of antimicrobial bacterial metabolites in mammalian lungs and wounds allows P. aeruginosa to be a formidable microbe at these sites.

BackgroundBereavement research has traditionally focused on the negative sequel of loss. Recently, however, research has begun to focus on the positive outcomes following loss: post-traumatic growth (PTG).PurposeTo synthesise studies which directly examine PTG following bereavement.DesignThis is the first systematic review which synthesises studies into directly examining PTG following bereavement.Data sourcesFrom the 70 published journal articles reviewed from PubMed, PsychINFO, IsiWeb of Knowledge Google Scholar, Science Direct, Springer Link, Taylor & Francis online, Sage Journals and Wiley Online Library, only 15 studies were directly examining PTG following bereavement and thus, included in this review.ResultsFindings of this systematic review suggest that PTG can indeed occur following bereavement and that certain factors can act as mediators for such growth to emerge. Key factors are: (1) The age of the bereaved; (2) social support; (3) time since death; (4) religion; and (5) active cognitive coping strategies.ConclusionsFurther research should include comparative-longitudinal studies controlling for maturational growth with non-trauma comparisons, as well as meta-analytic studies designed to examine effect sizes for associations among variables theorised to predict PTG following bereavement. Potential clinical applications include therapists becoming better positioned to recognise when PTG is likely to occur and its mediating factors, in order to more effectively facilitate it.

Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.

Immunotherapy efficacy depends on T cell trafficking to tumors and migrating to malignant cells to kill them. One barrier to T cell homing is the tumor blood vessel wall, which inhibits T cell attachment and transmigration through the endothelin B receptor, but antagonizing this receptor has not led to a clinically approved drug. One reason may be tumor hypo‐perfusion, which limits the area of perfused vessels for T cell attachment. If collapsed vessels can be decompressed and re‐perfused by alleviating tumor stiffness, then endothelin B receptor antagonism can improve immunotherapy. Here, it is tested whether the nonselective endothelin receptor blocker, bosentan, by simultaneously interfering with endothelin A receptor induced fibrosis, can normalize the tumor microenvironment thereby acting as a “mechanotherapeutic.” Tumor stiffness is monitored with ultrasound elastography and nanomechanical properties with atomic force microscopy to find an optimal dose, which reprograms cancer‐associated fibroblasts resulting in reduced collagen thereby decompressing vessels. Through this mechanism, T cell association with tumor vessels increases and immunosuppressive hypoxia is reduced. Additionally, bosentan increases the CD8+ T cells proliferating fraction. Ultrasound stiffness measurements correlate well with response to immunotherapy, suggesting the potential role of ultrasound elastography as a predictive biomarker of response to immune checkpoint inhibitors.