Electrical spin injection from an organic-based ferrimagnet in a hybrid organic/inorganic heterostructure

We report the successful extraction of spin polarized current from the organic-based room temperature ferrimagnetic semiconductor V[TCNE]x (x~2, TCNE: tetracyanoethylene; TC ~ 400 K, EG ~ 0.5 eV, s ~ 10-2 S/cm) and its subsequent injection into a GaAs/AlGaAs light-emitting diode (LED). The spin current tracks the magnetization of V[TCNE]x~2, is weakly temperature dependent, and exhibits heavy hole / light hole asymmetry. This result has implications for room temperature spintronics and the use of inorganic materials to probe spin physics in organic and molecular systems

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Functional Conservation of the Drosophila gooseberry Gene and Its Evolutionary Alleles

The Drosophila Pax gene gooseberry (gsb) is required for development of the larval cuticle and CNS, survival to adulthood, and male fertility. These functions can be rescued in gsb mutants by two gsb evolutionary alleles, gsb-Prd and gsb-Pax3, which express the Drosophila Paired and mouse Pax3 proteins under the control of gooseberry cis-regulatory region. Therefore, both Paired and Pax3 proteins have conserved all the Gsb functions that are required for survival of embryos to fertile adults, despite the divergent primary sequences in their C-terminal halves. As gsb-Prd and gsb-Pax3 uncover a gsb function involved in male fertility, construction of evolutionary alleles may provide a powerful strategy to dissect hitherto unknown gene functions. Our results provide further evidence for the essential role of cis-regulatory regions in the functional diversification of duplicated genes during evolution

Calibration of ionic and cellular cardiac electrophysiology models

© 2020 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. Cardiac electrophysiology models are among the most mature and well-studied mathematical models of biological systems. This maturity is bringing new challenges as models are being used increasingly to make quantitative rather than qualitative predictions. As such, calibrating the parameters within ion current and action potential (AP) models to experimental data sets is a crucial step in constructing a predictive model. This review highlights some of the fundamental concepts in cardiac model calibration and is intended to be readily understood by computational and mathematical modelers working in other fields of biology. We discuss the classic and latest approaches to calibration in the electrophysiology field, at both the ion channel and cellular AP scales. We end with a discussion of the many challenges that work to date has raised and the need for reproducible descriptions of the calibration process to enable models to be recalibrated to new data sets and built upon for new studies. This article is categorized under: Analytical and Computational Methods > Computational Methods Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Cellular Models

SUMOylation by Pias1 Regulates the Activity of the Hedgehog Dependent Gli Transcription Factors

Hedgehog (Hh) signaling, a vital signaling pathway for the development and homeostasis of vertebrate tissues, is mediated by members of the Gli family of zinc finger transcription factors. Hh signaling increases the transcriptional activity of Gli proteins, at least in part, by inhibiting their proteolytic processing. Conversely, phosphorylation by cAMP-dependent protein kinase (PKA) inhibits Gli transcriptional activity by promoting their ubiquitination and proteolysis. Whether other post-translational modifications contribute to the regulation of Gli protein activity has been unclear.Here we provide evidence that all three Gli proteins are targets of small ubiquitin-related modifier (SUMO)-1 conjugation. Expression of SUMO-1 or the SUMO E3 ligase, Pias1, increased Gli transcriptional activity in cultured cells. Moreover, PKA activity reduced Gli protein SUMOylation. Strikingly, in the embryonic neural tube, the forced expression of Pias1 increased Gli activity and induced the ectopic expression of the Gli dependent gene Nkx2.2. Conversely, a point mutant of Pias1, that lacks ligase activity, blocked the endogenous expression of Nkx2.2.Together, these findings provide evidence that Pias1-dependent SUMOylation influences Gli protein activity and thereby identifies SUMOylation as a post-translational mechanism that regulates the hedgehog signaling pathway

CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections