What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.     

Britton and bernstein on vygotsky: divergent views on mind and language in the pedagogic context

In recent influential work in language and social cognition relevant to pedagogical contexts, references to Basil Bernstein's work are notably absent, despite renewed recognition of the significance of his continued contribution to theories of classroom practices, sociolinguistics and the sociology of education. This article discusses several historical and ideological factors that have contributed to this lacuna. It reconsiders the organisation of the intellectual field of English education in Britain during the 1970s within which Bernstein's theorising about language took place. Within that field, it pays particular attention to the divergent readings of Vygotsky by James Britton and Bernstein with respect to power and the discursive regulation of 'legitimate' meanings in the pedagogic context. Finally, it considers the relevance in the post-Vygotskian field of social cognition of Bernstein's early attention to the relationship between social/institutional factors and individual functioning.     

Pretreatment social relations, therapeutic alliance, and improvements in parenting practices in parent management training.

The authors examined the parent-therapist alliance in parent management training for children (N = 218; 53 girls and 165 boys, ages 2-14) referred clinically for oppositional, aggressive, and antisocial behavior. The interrelations of pretreatment parent social relationships, the parent-therapist alliance over the course of treatment, and improvements in parenting practices at the end of treatment were evaluated by different raters. As expected, the better the quality of the parent-therapist alliance, the greater the improvements in parenting practices by the end of treatment. Social relations of the parents prior to treatment were associated with the parent-therapist alliance during treatment and parental improvements at the end of treatment. The relation between the therapeutic alliance and improvement in parenting practices was partially explained by pretreatment parent social relations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in histamine and microbiological analyses in fresh and frozen tuna muscle during temperature abuse

Temperature abuse of tuna (Thunnus alalunga) was carried out in order to assess the histamine buildup in fish-processing facilities where fish can be exposed to high temperatures for short periods of time. Histamine production was studied in tuna loins under different storage and abuse conditions. Tuna was stored at 0-2°C, 3-4°C, and 6-7°C, and abused for 2 h daily at 20°C and 30°C for 7-12 days. Loins abused at 30°C for 2 h daily contained potentially toxic histamine concentrations (67-382 mg kg^-1) when stored at a low refrigeration temperature (0-2°C), whereas when stored at 6-7°C, the loins contained highly toxic histamine concentrations (544.5-4156.6 mg kg^-1). Lower histamine concentrations (23-48 mg kg^-1 in loins stored at 0-2°C and 124.7-2435.8 mg kg^-1 in loins stored at 6-7°C) were observed in temperature-abused loins that were initially frozen. An increase over time was observed in most microbial counts tested. Bacteria isolated from the temperature-abused loins showed a varied ability of histamine production, with Morganella morganii, Klebsiella oxytoca, Staphylococcus hominis, and Enterococcus hirae being the most active histamine-producing bacteria.     

Specific impairments of emotion perception in multiple sclerosis.

Objective: Multiple sclerosis (MS) often results in demyelination of a network of frontal-subcortical tracts involved in processing emotional information. We investigated the effect of MS on the ability to identify emotional and nonemotional information from static and dynamic stimuli and determined whether difficulties in emotion perception related to quality of life. Method: 32 MS and 33 control participants, matched for age and education, identified emotions and nonemotional information from static images of faces and dynamic videos of people interacting. They also completed cognitive assessment and quality of life ratings. Results: On the static face perception tasks, participants with MS performed more poorly than healthy controls on emotion perception, t(63) = 3.30, p     

Spatial learning based on the shape of the environment is influenced by properties of the objects forming the shape.

In 3 experiments rats had to find a submerged platform that was located in a corner of a kite-shaped pool. The color of the walls creating this corner provided an additional cue for finding the platform in the shape + color condition but not the shape-only condition. During tests in a pool with walls of a uniform color but no platform, more time was spent in the corner where the platform was originally located after training in the shape + color than in the shape-only condition. The results challenge theories that assume either that learning about the shape of the environment takes place in a dedicated module or that cues compete for the control they acquire over behavior. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Violence with a conscience: Religiosity and moral certainty as predictors of support for violent warfare.

Objective: Emerging research on the moral licensing effect implies that increasing a person's moral certainty may decrease concerns about the moral consequences of violent warfare. Therefore, if religion increases moral certainty, then it may also contribute to support for violent warfare. The present experiment tested the extent to which religion's contribution to moral certainty explains participants' support for the United States' war in the Middle East. Method: Ninety-three predominantly Catholic and Protestant participants from a university setting completed the present study. The study was completed across two separate days. On the first day of the experiment, individual differences in a variety of types of religiosity (e.g., prayer), and moral certainty were measured. On the second day of the experiment, the perception that the United States' war in the Middle East is a religious or geopolitical conflict was experimentally manipulated, and support for violent warfare was measured. Results: Regression analyses and an analysis of variance yielded support for the moral certainty hypothesis. As predicted, greater religiosity relates to greater moral certainty, and greater moral certainty strengthens the (positive) relation between religiosity and support for violent warfare. Furthermore, moral certainty is a stronger predictor of support for violent warfare in religious conflict than it is in geopolitical conflict. Conclusion: The results support the moral certainty hypothesis and suggest that stronger moral certainty (1) predicts greater support for violent warfare, (2) is an underlying moderator of the relation between religiosity and support for violent warfare, and (3) is particularly influential in religious conflict. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Potentiation, overshadowing, and blocking of spatial learning based on the shape of the environment.

Rats were trained in Experiment 1 to find a submerged platform in 1 corner of either a rectangular or a kite-shaped pool. When the walls creating this corner were a different color than the opposite walls, then learning about the shape of the pool was potentiated in the kite but not in the rectangle. Experiments 2-4 revealed that learning about the rectangle can be overshadowed and blocked when information about the wall color indicates the location of the platform. The results mimic findings that have been obtained with Pavlovian conditioning, and they challenge the claim that learning about the shape of the environment takes places in a dedicated geometric module. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of cytotoxic perirhinal cortex lesions on spatial learning by rats: A comparison of the dark Agouti and Sprague-Dawley strains.

The effects of perirhinal cortex lesions in rats on spatial memory might depend on the choice of strain. The present study, therefore, compared perirhinal lesions in Sprague-Dawley rats (associated with deficits) with Dark Agouti rats (associated with null effects). Tests of reference memory and working memory in the water maze failed to provide evidence that perirhinal lesions disrupt overall levels of performance (irrespective of strain) or that these lesions have differential effects on the rates of spatial learning in these 2 strains. Strain differences were, however, found, as the Dark Agouti strain was often superior. Furthermore, the perirhinal lesions did have differential effects in the 2 strains, but these did not appear to relate directly to changes in spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short-chain fatty acid analysis—A comparison between two gas-chromatography methods

The compositions of a number of known mixtures of volatile fatty acids in aqueous solution and of volatile fatty acids in samples of rumen liquor were estimated by two gas-liquid chromatographic procedures, one of which operated in conjunction with an automatic titrating device and the other with a flame-ionisation detector. It was found that the method using flame-ionisation as the system of detection was more accurate and yielded results more rapidly than did that in which automatic titration was employed.