Miracle-dz/UniFAR-FTUs huggingface dataset:
Topographic Divergence of Atypical Cortical Asymmetry and Regional Atrophy Patterns in Temporal Lobe Epilepsy: A Worldwide ENIGMA Study

Temporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.
Enhancing and inhibitory motifs have coevolved to regulate CD4 activity

CD4+ T cells use T cell receptor (TCR)-CD3 complexes, and CD4, to respond to peptide antigens within MHCII molecules (pMHCII). We report here that, through ∼435 million years of evolution in jawed vertebrates, purifying selection has shaped motifs in the extracellular, transmembrane, and intracellular domains of eutherian CD4 that both enhance pMHCII responses and are coevolving with residues in an intracellular motif that inhibits pMHCII responses. Importantly, while CD4 interactions with the Src kinase, Lck, are classically viewed as the key determinant of CD4’s contribution to pMHCII responses, we found that without the inhibitory motif CD4-Lck interactions are not necessary for robust responses to pMHCII. In summary, motifs that mediate events on the outside and inside of CD4+ T cells coevolved to finetune the relay of pMHCII-specific information across the membrane. These results have implications for the evolution and function of complex transmembrane receptors and for biomimetic engineering.
Single-molecule mechanical unfolding kinetics of unmodified Saccharomyces cerevisiae tRNAPhe: a hint to the tRNA chaperone-tRNA interaction mechanism

The biological activity of tRNA is closely related to its mechanical folding properties. Although previous studies focused on the folding and unfolding mechanism of tRNA, its kinetics are largely unknown. In this study, combining optical tweezers and molecule dynamics simulations, we characterized the mechanical folding and unfolding processes of a single unmodified Saccharomyces cerevisiae tRNAphe. We identified the intermediates and pathways for tRNA mechanical folding and unfolding in the presence of Mg2+, discovering that the folding/unfolding kinetics of D stem-loop and T stem-loop but not the anti-codon stem-loop significantly affected by their upstream and downstream structures. The cooperative unfolding of the tRNA in the presence of Mg2+ lead to a large hysteresis between the folding and unfolding pathway, and such hysteresis and unfolding cooperativity are significantly reduced by lowering the Mg2+ concentration or mutating the nucleotides forming the ‘elbow’ structure. Moreover, both steered molecular dynamics simulation and optical tweezers experiment results support that, formation of tertiary interactions in the elbow region increases energy barriers of the mechanical unfolding pathway, including those in between intermediates, and determines the overall unfolding cooperativity. Our studies may shed light on the detailed tRNA chaperone mechanism of TruB and TrmA.
Context free and context-dependent conceptual representation in the brain

How concepts are coded in the brain is a core issue in cognitive neuroscience. Studies have focused on how individual concepts are processed, but the way in which conceptual representation changes to suit the context is unclear. We parametrically manipulated the association strength between words, presented in pairs one word at a time using a slow event-related fMRI design. We combined representational similarity analysis and computational linguistics to probe the neurocomputational content of these trials. Individual word meaning was maintained in supramarginal gyrus (associated with verbal short-term memory) when items were judged to be unrelated, but not when a linking context was retrieved. Context-dependent meaning was instead represented in left lateral prefrontal gyrus (associated with controlled retrieval), angular gyrus and ventral temporal lobe (regions associated with integrative aspects of memory). Analyses of informational connectivity, examining the similarity of activation patterns across trials between sites, showed that control network regions had more similar multivariate responses across trials when association strength was weak, reflecting a common controlled retrieval state when the task required more unusual associations. These findings indicate that semantic control and representational sites amplify contextually-relevant meanings in trials judged to be related.
Experimental evidence for delayed post-conflict management behaviour in wild dwarf mongooses

In many species, within-group conflict leads to immediate avoidance of potential aggressors or increases in affiliation, but no studies have investigated delayed post-conflict management behaviour. Here, we experimentally test that possibility using wild dwarf mongooses (Helogale parvula). First, we used natural and playback-simulated foraging displacements to demonstrate that bystanders take notice of the vocalisations produced during such within-group conflict events. We then used another playback experiment to assess delayed effects of within-group conflict on grooming interactions. Overall, fewer individuals groomed on evenings following an afternoon of simulated conflict, but those that did groomed more than on control evenings. Subordinate bystanders groomed with the simulated aggressor significantly less, and groomed more with one another, on conflict compared to control evenings. Our study provides experimental evidence that dwarf mongooses acoustically obtain information about within-group contests (including protagonist identity), retain that information and use it to inform conflict-management decisions with a temporal delay.
The representation of priors and decisions in parietal cortex

Animals actively sample their environment through orienting actions such as saccadic eye movements. Saccadic targets are selected based both on sensory evidence immediately preceding the saccade, and a ‘salience map’ or prior built up over multiple saccades. In the primate cortex, the selection of each individual saccade depends on competition between target-selective cells that ramp up their firing rate to saccade release. However it is less clear how a cross-saccade prior might be represented, either in neural firing or through an activity-silent mechanism such as modification of synaptic weights on sensory inputs. Here we present evidence from magnetoencephalography for two distinct processes underlying the selection of the current saccade, and the representation of the prior, in human parietal cortex. While the classic ramping decision process for each saccade was reflected in neural firing rates (measured as event related field), a prior built up over multiple saccades was represented via modulation of the gain on sensory inputs from the preferred target, as evidenced by rapid frequency tagging. A cascade of computations over time (initial representation of the prior, followed by evidence accumulation and then updating) provides a mechanism by which a salience map may be built up across saccades in parietal cortex. It also provides insight into why evidence accumulation signals are present in parietal cortex, when inactivation of the region has been shown not to affect performance on single-trial tasks.
Low-bias ncRNA libraries using ordered two-template relay: Serial template jumping by a modified retroelement reverse transcriptase

Significance Retrotransposons are noninfectious, mobile genetic elements that proliferate in host genomes via an RNA intermediate that is copied into DNA by a reverse transcriptase (RT) enzyme. RTs are important for biotechnological applications involving information capture from RNA since RNA is first converted into complementary DNA for detection or sequencing. Here, we biochemically characterized RTs from two retroelements and uncovered several activities that allowed us to design a streamlined, efficient workflow for determining the inventory of RNA sequences in processed RNA pools. The unique properties of nonretroviral RT activities obviate many technical issues associated with current methods of RNA sequence analysis, with wide applications in research, biotechnology, and diagnostics. Selfish, non-long terminal repeat (non-LTR) retroelements and mobile group II introns encode reverse transcriptases (RTs) that can initiate DNA synthesis without substantial base pairing of primer and template. Biochemical characterization of these enzymes has been limited by recombinant expression challenges, hampering understanding of their properties and the possible exploitation of their properties for research and biotechnology. We investigated the activities of representative RTs using a modified non-LTR RT from Bombyx mori and a group II intron RT from Eubacterium rectale. Only the non-LTR RT supported robust and serial template jumping, producing one complementary DNA (cDNA) from several templates each copied end to end. We also discovered an unexpected terminal deoxynucleotidyl transferase activity of the RTs that adds nucleotide(s) of choice to 3′ ends of single- and/or double-stranded RNA or DNA. Combining these two types of activity with additional insights about nontemplated nucleotide additions to duplexed cDNA product, we developed a streamlined protocol for fusion of next-generation sequencing adaptors to both cDNA ends in a single RT reaction. When benchmarked using a reference pool of microRNAs (miRNAs), library production by Ordered Two-Template Relay (OTTR) using recombinant non-LTR retroelement RT outperformed all commercially available kits and rivaled the low bias of technically demanding home-brew protocols. We applied OTTR to inventory RNAs purified from extracellular vesicles, identifying miRNAs as well as myriad other noncoding RNAs (ncRNAs) and ncRNA fragments. Our results establish the utility of OTTR for automation-friendly, low-bias, end-to-end RNA sequence inventories of complex ncRNA samples.
Hierarchical, Memory-based Movement Models for Translocated Elk (Cervus canadensis)

The use of spatial memory is well documented in many animal species and has been shown to be critical for the emergence of spatial learning. Adaptive behaviors based on learning can emerge thanks to an interdependence between the acquisition of information over time and movement decisions. The study of how spatio-ecological knowledge is constructed throughout the life of an individual has not been carried out in a quantitative and comprehensive way, hindered by the lack of knowledge of the information an animal already has of its environment at the time monitoring begins. Identifying how animals use memory to make beneficial decisions is fundamental to developing a general theory of animal movement and space use. Here we propose several mobility models based on memory and perform hierarchical Bayesian inference on 11-month trajectories of 21 elk after they were released in a completely new environment. Almost all the observed animals exhibited preferential returns to previously visited patches, such that memory and random exploration phases occurred. Memory decay was mild or negligible over the study period. The fact that individual elk rapidly become used to a relatively small number of patches was consistent with the hypothesis that they seek places with predictable resources and reduced mortality risks such as predation.
The Arabidopsis thaliana PeptideAtlas; harnessing world-wide proteomics data for a comprehensive community proteomics resource

We developed a new resource, the Arabidopsis PeptideAtlas (www.peptideatlas.org/builds/arabidopsis/), to solve central questions about the Arabidopsis proteome, such as the significance of protein splice forms, post-translational modifications (PTMs), or simply obtain reliable information about specific proteins. PeptideAtlas is based on published mass spectrometry (MS) analyses collected through ProteomeXchange and reanalyzed through a uniform processing and metadata annotation pipeline. All matched MS-derived peptide data are linked to spectral, technical and biological metadata. Nearly 40 million out of ∼143 million MSMS spectra were matched to the reference genome Araport11, identifying ∼0.5 million unique peptides and 17858 uniquely identified proteins (only isoform per gene) at the highest confidence level (FDR 0.0004; 2 non-nested peptides ≥ 9 aa each), assigned canonical proteins, and 3543 lower confidence proteins. Physicochemical protein properties were evaluated for targeted identification of unobserved proteins. Additional proteins and isoforms currently not in Araport11 were identified, generated from pseudogenes, alternative start, stops and/or splice variants and sORFs; these features should be considered for updates to the Arabidopsis genome. Phosphorylation can be inspected through a sophisticated PTM viewer. This new PeptideAtlas is integrated with community resources including TAIR, tracks in JBrowse, PPDB and UniProtKB. Subsequent PeptideAtlas builds will incorporate millions more MS data. One sentence summary A new web resource providing the global community with mass spectrometry-based Arabidopsis proteome information and its spectral, technical and biological metadata integrated with TAIR and JBrowse
Post-Stroke Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Attenuates Chronic Changes in Brain Metabolism, Increases Neurotransmitter Levels, and Improves Recovery

The aim of this study was to test whether poststroke oral administration of a small molecule p75 neurotrophin receptor (p75NTR) modulator (LM11A-31) can augment neuronal survival and improve recovery in a mouse model of stroke. Mice were administered LM11A-31 for up to 12 weeks, beginning 1 week after stroke. Metabolomic analysis revealed that after 2 weeks of daily treatment, mice that received LM11A-31 were distinct from vehicle-treated mice by principal component analysis and had higher levels of serotonin, acetylcholine, and dopamine in their ipsilateral hemisphere. LM11A-31 treatment also improved redox homeostasis by restoring reduced glutathione. It also offset a stroke-induced reduction in glycolysis by increasing acetyl-CoA. There was no effect on cytokine levels in the infarct. At 13 weeks after stroke, adaptive immune cell infiltration in the infarct was unchanged in LM11A-31–treated mice, indicating that LM11A-31 does not alter the chronic inflammatory response to stroke at the site of the infarct. However, LM11A-31–treated mice had less brain atrophy, neurodegeneration, tau pathology, and microglial activation in other regions of the ipsilateral hemisphere. These findings correlated with improved recovery of motor function on a ladder test, improved sensorimotor and cognitive abilities on a nest construction test, and less impulsivity in an open field test. These data support small molecule modulation of the p75NTR for preserving neuronal health and function during stroke recovery. SIGNIFICANCE STATEMENT The findings from this study introduce the p75 neurotrophin receptor as a novel small molecule target for promotion of stroke recovery. Given that LM11A-31 is in clinical trials as a potential therapy for Alzheimer’s disease, it could be considered as a candidate for assessment in stroke or vascular dementia studies.
Application of random forest and multi-linear regression methods in downscaling GRACE derived groundwater storage changes

ABSTRACT The advent of Gravity Recovery and Climate Experiment (GRACE) has opened the doors for remote monitoring of gravitational changes and its derivatives across the globe, but received less attention due to poor spatial and temporal representation. Statistical models of varying complexity are commonly employed to downscale the GRACE datasets for use with local to regional applications. This study presents the application of two commonly employed machine learning models, multi-linear regression (MLR) and random forest (RF), in spatially downscaling (from 1° to 0.25°) the GRACE-derived terrestrial water storage anomalies (TWSA) by establishing a correlation with various land surface and hydroclimatic variables. The downscaled TWSA was further converted into groundwater storage anomalies. Applicability of the proposed methods was tested on four contrasting hydrogeological basins of India. For each basin, the significant predictor variables were considered to establish the relations. Seasonal groundwater levels observed in 236 wells during 2006–2015 were used for method validation and accuracy assessment. We observed a close match between GRACE-derived groundwater levels and the measurements for three of the four basins (r = 0.40–0.92, Root mean square error (RMSE) = 3.6–10.5 cm). Our results indicate that the predictor variables to downscale TWSA should be considered cautiously based on the hydrogeological, topographical, and meteorological characteristics of the basin.
40 Years of Multiple Social Categorization: A Tool for Social Inclusivity

ABSTRACT We review a 40-year corpus of research that we collectively name “Multiple Categorisation Theory” (MCT). From early illustrations using the minimal group paradigm, through a focus on how people cognitively represent social diversity, to recent models of outgroup “re-humanisation”, this work has revealed much about how we think about inclusivity, exclusion, and intergroup differences. We review research that assessed ways to reduce intergroup bias by attenuating the reliance on simple categorisation via “crossed categorisation”. We describe how this research evolved from a focus on intergroup differences to incorporate self-categorisation, through processes of decategorisation and increased social identity complexity. Finally, we consider contemporary models that reveal the generalised benefits of multiple categorisation in promoting outgroup “re-humanisation” through “cognitive liberalisation”. We conclude by highlighting the theoretical and practical implications of this research programme.
Effect of sintering treatment time on the sintering behaviour and thermal shock resistance of Li2O-Al2O3-SiO2 glass-ceramics

ABSTRACT In order to determine the correlation of flexural strength and thermal shock resistance properties, the sintering behavior of Li2O-Al2O3-SiO2 (LAS) glass-ceramics at different sintering treatment times and the effect of thermal shock cycles on LAS glass-ceramics were investigated. The LAS glass-ceramics were isothermally treated at 1100°C from 1.5 to 4.5 h. Phase transformation of major crystalline of β-spodumene and minor crystalline of ZrTiO4 revealed unchanged as sintering treatment time increased. The physical properties of LAS glass-ceramics that were sintered for 3.5 h demonstrated an increased density (2.45 g/cm3) and less porosity percentage (0.62%). The prolonged sintering treatment affected the microstructure whereby the mean grain size increased from 0.55 to 0.67 µm which also demonstrated the increase of microhardness in the range between 3.90 and 5.47 GPa. The flexural strength of LAS glass-ceramics revealed an enhancement of 158 MPa when sintered for 3.5 h. The thermal shock resistance properties were assessed at 500°C from one to seven cycles via thermal shock tests. After four thermal shock cycles, LAS glass-ceramics showed an improvement of 82% of residual strength from its original strength, due to a decrease in the formation of pores and an increase in the crystallinity and percentage of β-spodumene.
Thermal stability and decomposition paths of MoAlB ceramic

ABSTRACT The thermal stability of MoAlB powder was studied. The effects of vacuum, Ar protection, molten salt treatment, and additives (B and C) on its thermal stability were studied. Results showed that MoAlB powder would react with a small amount of O2 in the furnace under vacuum and low temperature to form MoB, Al3Mo, B2O3, and Al2O3. At higher temperature, MoAlB first decomposed into MoB and Al. Al was oxidized to Al2O3. The thermal stability of MoAlB powder was better under the protection of Ar. However, molten salt heat treatment and additives such as B and C could promote the decomposition of MoAlB
Keynes on Economic Stagnation and Debt

Abstract The purpose of this article is to explain how the failure of neoclassical economics to embrace Keynes’ arguments with regard to the long-run tendency of the economic system to trend toward stagnation and to ignore the problems endemic in the economics of debt facilitated the adoption of economic policies in the United States that contributed to the economic, political, and social problems we face today.
Is “accredited crowdfunding” a lemons market? Evidence from 506(c) filings

ABSTRACT The United States Congress passed the JOBS Act of 2012, which allowed small private companies to advertise the sale of their securities to accredited investors. However, this new fundraising method is subject to criticism that it might lead to a lemons market in crowdfunding platforms due to limited information disclosure requirements. This article thus examines this concern, and the results do not support the development of a lemons market. Conversely, we identify a separating equilibrium in which quality companies choose to raise capital from the accredited investors. Firms’ operating characteristics and VC monitoring provide effective signals in the accredited crowdfunding markets.
Barriers to and enablers of sustainable practices: insights from ethnic minority migrants

ABSTRACT Migration from the Global South to Global North is a major feature of contemporary population movements, and provides a lived experiment of the implications of moving from less resource-intensive modes of living towards more resource-intensive ones. Pre-migration practices come together in complex ways post-migration with established norms and infrastructures in destination countries. Here we examine the barriers to and enablers of sustainable practices, synthesising in-depth research from nine different studies in south-eastern Australia in relation to household water use, food growing and transport. The total sample includes 323 migrants from 33 countries. The main barriers include infrastructure and broader patterns of work and society. The main enablers are cultural norms of frugality and preferences for public transport. Barriers and enablers interact in diverse ways. We show that migrants are important contributors to inadvertent sustainabilities, but their contributions may be weakened by infrastructural, structural and cultural barriers. Addressing the diverse capacities of migrants would enhance system change for everyone.