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Topological charges of nodal lines in a multigap system are represented by non-Abelian numbers, and the Euler class, a topological invariant, can be used to explain their topological phase transitions, such as pair-annihilation of nodal lines. Up until now, no discussion of phase transitions of nodal lines in photonic crystals using the Euler class has been reported, despite the fact that the Euler class and topological phase transition have recently been addressed in metallic or acoustic crystals. Here, we show how the deformation of a photonic crystal causes topological phase transitions in the nodal lines, and the Euler class can be used to theoretically predict the nodal lines’ stability based on the non-Abelian topological charge theory. Specifically, by manipulating the separation between the two single diamond structures and the extent of structural distortion, we numerically demonstrate the topological transition of nodal lines, e.g., from nodal lines to nodal rings. We then demonstrate that the range of surface states is strongly influenced by the topological phase transition of nodal lines. Moreover, the Zak phase was used to explain the surface states’ existence.

This review synthesizes findings from 117 studies that have manipulated various picture-word interference (PWI) task properties to establish whether semantic context effects reflect competitive word retrieval, or are driven by noncompetitive processes. Manipulations of several PWI task parameters (e.g., distractor visibility) have produced contradictory findings. Evidence derived from other manipulations (e.g., visual similarity between targets and distractors) has been scarce. Some of the manipulations that have furnished reliable effects (e.g., distractor taboo interference) do not discriminate between the rival theories. Interference from nonverbal distractors has been shown to be a genuine effect dependent on adequate lexicalization of interfering stimuli. This supports the swinging lexical network hypothesis and the selection-by-competition-with-competition-threshold hypothesis while undermining one of the assumptions of the response exclusion hypothesis. The contribution of pre-lexical processes, such as an interaction between distractor processing and conceptual encoding of the target to the overall semantic context effect is far from settled.

Conventional protein kinase C (cPKC) isozymes tune the signaling output of cells, with loss-of-function somatic mutations associated with cancer and gain-of-function germline mutations identified in neurodegeneration. PKC with impaired autoinhibition is removed from the cell by quality-control mechanisms to prevent the accumulation of aberrantly active enzyme. Here, we examine how a highly conserved residue in the C1A domain of cPKC isozymes permits quality-control degradation when mutated to histidine in cancer (PKCβ-R42H) and blocks down-regulation when mutated to proline in the neurodegenerative disease spinocerebellar ataxia (PKCγ-R41P). Using FRET-based biosensors, we determined that mutation of R42 to any residue, including lysine, resulted in reduced autoinhibition as indicated by higher basal activity and faster agonist-induced plasma membrane translocation. R42 is predicted to form a stabilizing salt bridge with E655 in the C-tail and mutation of E655, but not neighboring E657, also reduced autoinhibition. Western blot analysis revealed that whereas R42H had reduced stability, the R42P mutant was stable and insensitive to activator-induced ubiquitination and down-regulation, an effect previously observed by deletion of the entire C1A domain. Molecular dynamics (MD) simulations and analysis of stable regions of the domain using local spatial pattern (LSP) alignment suggested that P42 interacts with Q66 to impair mobility and conformation of one of the ligand-binding loops. Additional mutation of Q66 to the smaller asparagine (R42P/Q66N), to remove conformational constraints, restored degradation sensitivity. Our results unveil how disease-associated mutations of the same residue in the C1A domain can toggle between gain- or loss-of-function of PKC.

Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.

Optogenetic actuators have revolutionized the resolution at which biological processes can be controlled. In plants, deployment of optogenetics is challenging due to the need for these light-responsive systems to function in the context of horticultural light environments. Furthermore, many available optogenetic actuators are based on plant photoreceptors that might crosstalk with endogenous signaling processes, while others depend on exogenously supplied cofactors. To overcome such challenges, we have developed Highlighter, a synthetic, light-gated gene expression system tailored for in planta function. Highlighter is based on the photoswitchable CcaS-CcaR system from cyanobacteria and is repurposed for plants as a fully genetically encoded system. Analysis of a re-engineered CcaS in Escherichia coli demonstrated green/red photoswitching with phytochromobilin, a chromophore endogenous to plants, but also revealed a blue light response likely derived from a flavin-binding LOV-like domain. We deployed Highlighter in transiently transformed Nicotiana benthamiana for optogenetic control of fluorescent protein expression. Using light to guide differential fluorescent protein expression in nuclei of neighboring cells, we demonstrate unprecedented spatiotemporal control of target gene expression. We implemented the system to demonstrate optogenetic control over plant immunity and pigment production through modulation of the spectral composition of broadband visible (white) light. Highlighter is a step forward for optogenetics in plants and a technology for high-resolution gene induction that will advance fundamental plant biology and provide new opportunities for crop improvement.

Human electrophysiological and related time series data are often acquired in complex, event-rich environments. However, the resulting recorded brain or other dynamics are often interpreted in relation to more sparsely recorded or subsequently-noted events. Currently a substantial gap exists between the level of event description required by current digital data archiving standards and the level of annotation required for successful analysis of event-related data across studies, environments, and laboratories. Manifold challenges must be addressed, most prominently ontological clarity, vocabulary extensibility, annotation tool availability, and overall usability, to allow and promote sharing of data with an effective level of descriptive detail for labeled events. Motivating data authors to perform the work needed to adequately annotate their data is a key challenge. This paper describes new developments in the Hierarchical Event Descriptor (HED) system for addressing these issues. We recap the evolution of HED and its acceptance by the Brain Imaging Data Structure (BIDS) movement, describe the recent release of HED-3G, a third generation HED tools and design framework, and discuss directions for future development. Given consistent, sufficiently detailed, tool-enabled, field-relevant annotation of the nature of recorded events, prospects are bright for large-scale analysis and modeling of aggregated time series data, both in behavioral and brain imaging sciences and beyond.

Cell homeostasis is perturbed when dramatic shifts in the external environment cause the physical-chemical properties inside the cell to change. Experimental approaches for dynamically monitoring these intracellular effects are currently lacking. Here, we leverage the environmental sensitivity and structural plasticity of intrinsically disordered protein regions (IDRs) to develop a FRET biosensor capable of monitoring rapid intracellular changes caused by osmotic stress. The biosensor, named SED1, utilizes the Arabidopsis intrinsically disordered AtLEA4-5 protein expressed in plants under water deficit. Computational modeling and in vitro studies reveal that SED1 is highly sensitive to macromolecular crowding. SED1 exhibits large and near-linear osmolarity-dependent changes in FRET inside living bacteria, yeast, plant, and human cells, demonstrating the broad utility of this tool for studying water-associated stress. This study demonstrates the remarkable ability of IDRs to sense the cellular environment across the tree of life and provides a blueprint for their use as environmentally-responsive molecular tools.

The investigation of merging galaxy clusters that exhibit radio relics is strengthening our understanding of the formation and evolution of galaxy clusters, the nature of dark matter, the intracluster medium, and astrophysical particle acceleration. Each merging cluster provides only a single view of the cluster formation process, and the variety of merging clusters is vast. Clusters hosting double radio relics are rare and extremely important because they allow tight constraints on the merger scenario. We present a weak-lensing and X-ray analysis of MACS J1752.0+4440 (z = 0.365) and ZWCL 1856.8+6616 (z = 0.304), two double radio relic clusters. Our weak-lensing mass estimates show that each cluster is a major merger with approximately 1:1 mass ratio. The total mass of MACS J1752.0+4440 (ZWCL 1856.8+6616) is M200 = 14.7-+3.33.8 ´ 1014 Me (M200 = 2.4-+0.70.9 ´ 1014 Me). We find that these two clusters have comparable features in their weak-lensing and gas distributions, even though the systems have vastly different total masses. From the likeness of the X-ray morphologies and the remarkable symmetry of the radio relics, we propose that both systems underwent nearly head-on collisions. However, revelations from the hot-gas features and our multiwavelength data analysis suggest that ZWCL 1856.8+6618 is likely at a later merger phase than MACS J1752.0+4440. We postulate that the SW radio relic in MACS J1752.0 +4440 is a result of particle reacceleration.

Homochiral membrane bilayers organize biological functions in all domains of life. The membrane's permeability-its key property-correlates with a molecule's lipophilicity, but the role of the membrane's rich and uniform stereochemistry as a permeability determinant is largely ignored in empirical and computational measurements. Here, we describe a new approach to measuring permeation using continuously generated microfluidic droplet interface bilayers (DIBs, generated at a rate of 480 per minute) and benchmark this system by monitoring fluorescent dye DIB permeation over time. Enantioselective permeation of alkyne-labelled amino acids (Ala, Val, Phe, Pro) and dipeptides through a chiral phospholipid bilayer was demonstrated using DIB transport measurements; the biological L enantiomers permeated faster than the D enantiomers (from 1.2-fold to 6-fold for Ala to Pro). Enantioselective permeation both poses a potentially unanticipated criterion for drug design and offers a kinetic mechanism for the abiotic emergence of homochirality via chiral transfer between sugars, amino acids and lipids.

Abstract Bioluminescent and fluorescent proteins are now used as tools for research in all organisms. There has been massive progress over the past 15 years in creating a palette of fluorescent proteins with a wide spectrum of specific properties. One of the big challenges is to decide which variant may be best for a certain application. A recent article by Mann et al. in BMC Biotechnology describes a new orange fluorescent protein in plants. See research article http://www.biomedcentral.com/1472-6750/12/17

The accumulation and propagation of hyperphosphorylated tau (p-Tau) is a neuropathological hallmark occurring with neurodegeneration of Alzheimer's disease (AD). Extracellular vesicles, exosomes, have been shown to initiate tau propagation in the brain. Notably, exosomes from human-induced pluripotent stem cell (iPSC) neurons expressing the AD familial A246E mutant form of presenilin 1 (mPS1) are capable of inducing tau deposits in the mouse brain after in vivo injection. To gain insights into the exosome proteome cargo that participates in propagating tau pathology, this study conducted proteomic analysis of exosomes produced by human iPSC neurons expressing A246E mPS1. Significantly, mPS1 altered the profile of exosome cargo proteins to result in (1) proteins present only in mPS1 exosomes and not in controls, (2) the absence of proteins in the mPS1 exosomes which were present only in controls, and (3) shared proteins which were upregulated or downregulated in the mPS1 exosomes compared to controls. These results show that mPS1 dysregulates the proteome cargo of exosomes to result in the acquisition of proteins involved in the extracellular matrix and protease functions, deletion of proteins involved in RNA and protein translation systems along with proteasome and related functions, combined with the upregulation and downregulation of shared proteins, including the upregulation of amyloid precursor protein. Notably, mPS1 neuron-derived exosomes displayed altered profiles of protein phosphatases and kinases involved in regulating the status of p-tau. The dysregulation of exosome cargo proteins by mPS1 may be associated with the ability of mPS1 neuron-derived exosomes to propagate tau pathology.

Protein kinase C (PKC) family members are multi-domain proteins whose function is exquisitely tuned by interdomain interactions that control the spatiotemporal dynamics of their signaling. Despite extensive mechanistic studies on this family of enzymes, no structure of a full-length enzyme that includes all domains has been solved. Here, we take into account the biochemical mechanisms that control autoinhibition, the properties of each individual domain, and previous structural studies to propose a unifying model for the general architecture of PKC family members. This model shows how the C2 domains of conventional and novel PKC isozymes, which have different topologies and different positions in the primary structure, can occupy the same position in the tertiary structure of the kinase. This common architecture of conventional and novel PKC isozymes provides a framework for understanding how disease-associated mutations impair PKC function.

Accumulation and propagation of hyperphosphorylated Tau (p-Tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating Tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-Tau pathology after injection into mouse brain. To gain an understanding of the mTau exosome cargo involved in Tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in 1) proteins uniquely present only in mTau, and not control exosomes, 2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and 3) shared proteins which were significantly upregulated or downregulated in mTau compared with control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-Tau. Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes. Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or downregulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-Tau neuropathology in mouse brain.

Greed and power have morphed into forms of capitalism unaddressed from a philosophical, moral or educative framework. This article seeks to address this important gap in the literature by first outlining how the financialisation of capital constitutes the new educational subject in primary, secondary and tertiary school. The author establishes how these new morphologies of power create an imagination that renders students and even the goal of education as a function of unending growth, extraction and disembodiment. In response, the author posits a different vision of habits, practices, postures and morals that root out power in education. Drawing from degrowth theory and an emphasis on simplicity, care, conviviality and the ritual destruction of accumulation, the author theorises what a pedagogy of degrowth may entail. Doing so answers an ever-important question--what is an educational good?--by conceiving of the 'value' of education beyond the bounds of capitalism.

Background: Cancer cachexia is prevalent in head and neck cancer patients. The L3 skeletal muscle index (SMI) is often used to assess sarcopenia and cachexia but is infrequently able to be measured in this population. Masseter muscle thickness (MT) may serve as an alternative predictor of cachexia. Methods: SMI and MT were calculated from 20 trauma (CTRL) and 40 cachectic (CA‐CX) and non‐cachectic (CA‐NCX) head and neck cancer patients. Area Under the Curve of the Receiver Operating Characteristics (AUC‐ROC) analysis was performed for SMI and MT. Results: Both SMI and MT were significantly decreased in CA‐CX patients (vs. CA‐NCX mean difference −19.5 cm2/m2 and −2.06 mm, respectively) and significant predictors of CA‐CX (AUC = 0.985 and 0.805, respectively). When analyzed by sex, the same findings were observed for MT in males and trended toward significance in females. Conclusions: Compared with SMI, MT is a good alternative prognostic biomarker to determine CA‐CX status in HNC patients. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that rhythmic temporal cues in the environment influence the encoding of information into long-term memory. Here, we test the hypothesis that these mnemonic effects of rhythm reflect the coupling of high-frequency (gamma) oscillations to entrained lower-frequency oscillations synchronized to the beat of the rhythm. In Study 1, we first test this hypothesis in the context of global effects of rhythm on memory, when memory is superior for visual stimuli presented in rhythmic compared with arrhythmic patterns at encoding [Jones, A., & Ward, E. V. Rhythmic temporal structure at encoding enhances recognition memory, Journal of Cognitive Neuroscience, 31, 1549–1562, 2019]. We found that rhythmic presentation of visual stimuli during encoding was associated with greater phase-amplitude coupling (PAC) between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. In Study 2, we next investigated cross-frequency PAC in the context of local effects of rhythm on memory encoding, when memory is superior for visual stimuli presented in-synchrony compared with out-of-synchrony with a background auditory beat [Hickey, P., Merseal, H., Patel, A. D., & Race, E. Memory in time: Neural tracking of low-frequency rhythm dynamically modulates memory formation. Neuroimage, 213, 116693, 2020]. We found that the mnemonic effect of rhythm in this context was again associated with increased cross-frequency PAC between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. Furthermore, the magnitude of gamma power modulations positively scaled with the subsequent memory benefit for in- versus out-of-synchrony stimuli. Together, these results suggest that the influence of rhythm on memory encoding may reflect the temporal coordination of higher-frequency gamma activity by entrained low-frequency oscillations. [ABSTRACT FROM AUTHOR]