Kinase-independent function of RIP1, critical for mature T-cell survival and proliferation.

The death receptor, Fas, triggers apoptotic death and is essential for maintaining homeostasis in the peripheral lymphoid organs. RIP1 was originally cloned when searching for Fas-binding proteins and was later shown to associate also with the signaling complex of TNFR1. Although Fas exclusively induces apoptosis, TNFR1 primarily activates the pro-survival/pro-inflammatory NF-κB pathway. Mutations in Fas lead to lymphoproliferative (lpr) diseases, and deletion of TNFR1 results in defective innate immune responses. However, the function of RIP1 in the adult lymphoid system has not been well understood, primarily owing to perinatal lethality in mice lacking the entire RIP1 protein in germ cells. This current study investigated the requirement for RIP1 in the T lineage using viable RIP1 mutant mice containing a conditional and kinase-dead RIP1 allele. Disabling the kinase activity of RIP1 had no obvious impact on the T-cell compartment. However, T-cell-specific deletion of RIP1 led to a severe T-lymphopenic condition, owing to a dramatically reduced mature T-cell pool in the periphery. Interestingly, the immature T-cell compartment in the thymus appeared intact. Further analysis showed that mature RIP1(-/-) T cells were severely defective in antigen receptor-induced proliferative responses. Moreover, the RIP1(-/-) T cells displayed greatly increased death and contained elevated caspase activities, an indication of apoptosis. In total, these results revealed a novel, kinase-independent function of RIP1, which is essential for not only promoting TCR-induced proliferative responses but also in blocking apoptosis in mature T cells

Assessing direct contributions of morphological awareness and prosodic sensitivity to children’s word reading and reading comprehension

We examined the independent contributions of prosodic sensitivity and morphological awareness to word reading, text reading accuracy, and reading comprehension. We did so in a longitudinal study of English-speaking children (N = 70). At 5 to 7 years of age, children completed the metalinguistic measures along with control measures of phonological awareness and vocabulary. Children completed the reading measures two years later. Morphological awareness, but not prosodic sensitivity made a significant independent contribution to word reading, text reading accuracy and reading comprehension. The effects of morphological awareness on reading comprehension remained after controls for word reading. These results suggest that morphological awareness needs to be considered seriously in models of reading development and that prosodic sensitivity might have primarily indirect relations to reading outcomes. Keywords: Morphological Awareness; Prosody; Word Reading; Reading Comprehension

RIPK1 protects from TNF-α-mediated liver damage during hepatitis

Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-alpha) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-alpha-dependent signaling pathway. We took advantage of two different deficient mouse lines, the RIPK1 kinase dead knock-in mice (Ripk1K45A) and the conditional knockout mice lacking RIPK1 only in liver parenchymal cells (Ripk1LPC-KO), to characterize the role of RIPK1 and TNF-alpha in hepatitis induced by concanavalin A (ConA). Our results show that RIPK1 is dispensable for liver homeostasis under steady-state conditions but in contrast, RIPK1 kinase activity contributes to caspase-independent cell death induction following ConA injection and RIPK1 also serves as a scaffold, protecting hepatocytes from massive apoptotic cell death in this model. In the Ripk1LPC-KO mice challenged with ConA, TNF-alpha triggers apoptosis, responsible for the observed severe hepatitis. Mechanism potentially involves both TNF-independent canonical NF-kappa B activation, as well as TNF-dependent, but canonical NF-kappa B-independent mechanisms. In conclusion, our results suggest that RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases

A systematic review of the effects of arbuscular mycorrhizal fungi on root-lesion nematodes Pratylenchus spp.

Root-lesion nematodes (Pratylenchus spp.) and arbuscular mycorrhizal fungi (AMF) occupy the same ecological niche in the phytobiome of many agriculturally important crops. Arbuscular mycorrhizal fungi can enhance the resistance or tolerance of a plant to Pratylenchus and previous studies have been undertaken to investigate the relationship between these organisms. A restructuring of the AMF phylum Glomeromycota has reallocated the species into genera according to molecular analysis. A systematic review of the literature was synthesized to assess the interaction between Pratylenchus spp. and AMF using the revised classification. Plants inoculated with AMF generally exhibited greater tolerance as demonstrated by increased biomass under Pratylenchus pressure. Species of AMF fromthe order Diversisporales tended to increase Pratylenchus population densities compared to those from the order Glomerales. Species from the genera Funneliformis and Glomus had a reductive effect on Pratylenchus population densities. The interaction between AMF and Pratylenchus spp. showed variation in responses as a result of cultivar, crop species, and AMF species. Putative mechanisms involved in these interactions are discussed

The Gisin-Percival stochastic Schrödinger equation from standard quantum filtering theory

We show that the quantum state diffusion equation of Gisin and Percival, driven by complex Wiener noise, is equivalent up to a global stochastic phase to quantum trajectory models. With an appropriate feedback scheme, we set up an analogue continuous measurement model with exactly simulates the Gisin-Percival quantum state diffusion.Comment: Originally submitted to a Theoretical Physics journal but rejected with the re-submission instructions to drop my discussion and references to the papers of Gisin and Percival, which I consider unethical. To be now submitted to an appropriate Mathematical Physics journal instea

Discourse or dialogue? Habermas, the Bakhtin Circle, and the question of concrete utterances

This is the author's accepted manuscript. The final publication is available at Springer via the link below.This article argues that the Bakhtin Circle presents a more realistic theory of concrete dialogue than the theory of discourse elaborated by Habermas. The Bakhtin Circle places speech within the “concrete whole utterance” and by this phrase they mean that the study of everyday language should be analyzed through the mediations of historical social systems such as capitalism. These mediations are also characterized by a determinate set of contradictions—the capital-labor contradiction in capitalism, for example—that are reproduced in unique ways in more concrete forms of life (the state, education, religion, culture, and so on). Utterances always dialectically refract these processes and as such are internal concrete moments, or concrete social forms, of them. Moreover, new and unrepeatable dialogic events arise in these concrete social forms in order to overcome and understand the constant dialectical flux of social life. But this theory of dialogue is different from that expounded by Habermas, who tends to explore speech acts by reproducing a dualism between repeatable and universal “abstract” discursive processes (commonly known as the ideal speech situation) and empirical uses of discourse. These critical points against Habermas are developed by focusing on six main areas: sentences and utterances; the lifeworld and background language; active versus passive understandings of language; validity claims; obligation and relevance in language; and dialectical universalism

CADMIUM GEOCHEMISTRY OF SOILS AND WILLOW IN A METAMORPHIC BEDROCK TERRAIN AND ITS POSSIBLE RELATION TO MOOSE HEALTH, SEWARD PENINSULA, ALASKA

The regional geochemistry of soil and willow over Paleozoic metamorphic rocks in the Seward Peninsula, Alaska is potentially high in cadmium (Cd), and willow, a preferred browse of moose, bioaccumulates Cd. Local moose show clinical signs of tooth wear and breakage and have been declining in population for unknown reasons. Willow leaves (all variants of Salix pulchra) and A-, B-, and C-horizon soils were sampled near 2 mining prospects suspected to be high in Cd. Although Al, Cd, Co, Cu, Fe, Mo, Ni, Pb, and Zn were examined, our focus in this exploratory study was on the level of Cd in the 3 soil horizons and willow between and within the 2 prospects and their vicinity. We used an unbalanced, one-way, hierarchical analysis of variance (ANOVA) to investigate the geochemistry of soils and willow at various distance scales across the 2 prospect areas that were separated by ~80 km; sites within a location were approximately 0.5 km apart and replicate samples were separated by ~0.05 km. Cd concentration was significantly different in willow between and within sites, and within sites for all soil horizons. Specifically, this exploratory study identified highly elevated levels of Cd in willow growing over Paleozoic bedrock in the Seward Peninsula at both prospects and over the Paleozoic geologic unit in general. Potential negative effects for moose are discussed