Neural processing as causal inference

Perception is about making sense, that is, understanding what events in the outside world caused the sensory observations. Consistent with this intuition, many aspects of human behavior confronting noise and ambiguity are well explained by principles of causal inference. Extending these insights, recent studies have applied the same powerful set of tools to perceptual processing at the neural level. According to these approaches, microscopic neural structures solve elementary probabilistic tasks and can be combined to construct hierarchical predictive models of the sensory input. This framework suggests that variability in neural responses reflects the inherent uncertainty associated with sensory interpretations and that sensory neurons are active predictors rather than passive filters of their inputs. Causal inference can account parsimoniously and quantitatively for non-linear dynamical properties in single synapses, single neurons and sensory receptive fields.     

Targeting age‐specific changes in CD4+ T cell metabolism ameliorates alloimmune responses and prolongs graft survival

Age impacts alloimmunity. Effects of aging on T‐cell metabolism and the potential to interfere with immunosuppressants have not been explored yet. Here, we dissected metabolic pathways of CD4⁺ and CD8⁺ T cells in aging and offer novel immunosuppressive targets. Upon activation, CD4⁺ T cells from old mice failed to exhibit adequate metabolic reprogramming resulting into compromised metabolic pathways, including oxidative phosphorylation (OXPHOS) and glycolysis. Comparable results were also observed in elderly human patients. Although glutaminolysis remained the dominant and age‐independent source of mitochondria for activated CD4⁺ T cells, old but not young CD4⁺ T cells relied heavily on glutaminolysis. Treating young and old murine and human CD4⁺ T cells with 6‐diazo‐5‐oxo‐l‐norleucine (DON), a glutaminolysis inhibitor resulted in significantly reduced IFN‐γ production and compromised proliferative capacities specifically of old CD4⁺ T cells. Of translational relevance, old and young mice that had been transplanted with fully mismatched skin grafts and treated with DON demonstrated dampened Th1‐ and Th17‐driven alloimmune responses. Moreover, DON diminished cytokine production and proliferation of old CD4⁺ T cells in vivo leading to a significantly prolonged allograft survival specifically in old recipients. Graft prolongation in young animals, in contrast, was only achieved when DON was applied in combination with an inhibition of glycolysis (2‐deoxy‐d‐glucose, 2‐DG) and OXPHOS (metformin), two alternative metabolic pathways. Notably, metabolic treatment had not been linked to toxicities. Remarkably, immunosuppressive capacities of DON were specific to CD4⁺ T cells as adoptively transferred young CD4⁺ T cells prevented immunosuppressive capacities of DON on allograft survival in old recipients. Depletion of CD8⁺ T cells did not alter transplant outcomes in either young or old recipients. Taken together, our data introduce an age‐specific metabolic reprogramming of CD4⁺ T cells. Targeting those pathways offers novel and age‐specific approaches for immunosuppression.     

The Genus Isolaimium Cobb, 1920 (Order Isolaimida,Isolaimiidae New Family)

Five species of lsolaimium Cobb, 1920 are described and illustrated: I. nigeriense n. sp., I. multipapillatum n. sp., I. caliIornicum, n. sp., I. papillatum Cobb, 1920, and I stictochroum Timm, 1961. A unique feature in lsolaimium, not found in any other nematode, is the presence of six cuticularized tubes surrounding the stoma and opening on the head. Order Isolaimida Cobb, 1920 is emended to accommodate this genus, which is considered to lie between the mermithoids and the dorylaimoids.     

Effects of competition and shading in planktonic communities

A model for several algal species which compete both for light and for nutrients, and which are also subject to settling and diffusion, is considered. The settling speeds and diffusion coefficients are assumed to be small, in a sense to be made precise later, and a singular perturbation argument is used. In certain cases vertical segregation of the algal species is observed, and the mechanism for this is interpreted biologically.Supported by the Danish Natural Science Research Council (Grant No. 11-8321)     

Tetra-acetylenic metabolites from Mycena viridimarginata

The structures of two new acetylenic compounds from Mycena viridimarginata were elucidated by spectroscopic methods and some chemical transformations. The major metabolite was 10-hydroxyundeca-2,4,6,8-tetraynamide and the minor one was 3,4,13-trihydroxytetradeca-5,7,9,11-tetraynoic acid γ-lactone. Another compound, methyl-3,4,13-trihydroxytetradeca-5,7,9,11-tetraynoate, was found to be an artifact from the γ-lactone produced on the Sephadex LH-20 column. Furthermore, model compounds were prepared to establish the chromophoric system of the major metabolite.