Miracle-dz/UniFAR-FTUs huggingface dataset:
Complexity of spatio-temporal plantar pressure patterns during everyday behaviours

The human foot sole is the primary interface with the external world during balance and walking, and also provides important tactile information on the state of contact. However, prior studies on plantar pressure have focused mostly on summary metrics such as overall force or centre of pressure under limited conditions. Here, we recorded spatiotemporal plantar pressure patterns with high spatial resolution while participants completed a wide range of daily activities, including balancing, locomotion, and jumping tasks. Contact area differed across task categories, but was only moderately correlated with the overall force experienced by the foot sole. The centre of pressure was often located outside the contact area or in locations experiencing relatively low pressure, and therefore a result of disparate contact regions spread widely across the foot. Non-negative matrix factorisation revealed low-dimensional spatial complexity that increased during interaction with unstable surfaces. Additionally, pressure patterns at the heel and metatarsals decomposed into separately located and robustly identifiable components, jointly capturing most variance in the signal. These results suggest optimal sensor placements to capture task-relevant spatial information and provide insight into how pressure varies spatially on the foot sole during a wide variety of natural behaviours.
Structural study of UFL1-UFC1 interaction uncovers the importance of UFL1 N-terminal helix for ufmylation

Ufmylation, a protein modification by Ubiquitin-like (UBL) protein UFM1, plays a crucial role in several cellular processes including DNA damage response, protein translation and ER homeostasis. To date, little is known how the enzymes responsible for this modification coordinate their action. Here we have studied the details of UFL1 (E3) activity, its binding to UFC1 (E2), and its relation to UBA5 (E1), using a combination of structural modeling with Alphafold2, X-ray crystallography, NMR, and in vitro biochemical activity assays. Guided by an Alphafold2 model, we generated an active UFL1 fusion construct that includes its cofactor DDRGK1, and solved the first crystal structure of this critical interaction. This fusion construct also unveiled the importance of the N-terminal helix of UFL1 for its binding to UFC1, which was validated by ITC and NMR experiments. Importantly, the binding site suggested by our structural model of the UFL1-UFC1 interaction reveals a conserved interface, and suggests a competition for binding to UFC1 between UFL1 and UBA5, which we reconfirmed by NMR. Altogether, our study reveals a novel, terminal helix-mediated regulatory mechanism which coordinates the cascade of E1-E2-E3 mediated transfer of UFM1 to its substrate, and provides new leads to target this important modification. Significance statement Ufmylation is an important post-translational modification, but little is known about the mechanistic details of its machinery, and in particular how the UFM1 E3 ligase (UFL1) binds and functions together with the E2 conjugating enzyme (UFC1). We combined AlphaFold2 modeling, X-ray crystallography, NMR and biochemical experiments to reveal crucial elements that govern UFL1 activity and ufmylation. We discover a crucial role for the UFL1 N-terminal helix in binding to UFC1 and productive ufmylation. This helix competes with the E1 (UBA5) C-terminal helix for binding to UFC1. Altogether, our findings uncover a new, helix-mediated regulatory mechanism in ufmylation.
A conserved, non-canonical insert in FIS1 is required for mitochondrial fission and recruitment of DRP1 and TBC1D15

Mitochondrial fission protein 1 (FIS1) is conserved in all eukaryotes yet its activity in metazoans is thought divergent from lower eukaryotes like fungi. To address this discrepancy, structure-based sequence alignments revealed a conserved but non-canonical, three-residue insert in a turn of FIS1, suggesting conserved activity. In vertebrate FIS1 this insert is serine (S45), lysine (K46), and tyrosine (Y47). To determine the biological role of this “SKY insert”, three variants were evaluated for their fold, and tested in HCT116 cells for altered mitochondrial morphology and recruitment of effectors, DRP1 and TBC1D15. Substitution of the SKY insert with three alanine residues (AAA), or deletion of the insert (ΔSKY), did not substantially alter the fold or thermal stability of the protein. Replacing SKY with a canonical turn (ΔSKYD49G) introduced significant conformational heterogeneity by NMR that was removed upon deletion of a known regulatory region, the FIS1 arm. Expression of AAA fragmented mitochondria into perinuclear clumps associated with increased mitochondrial DRP1 similar to the wild-type protein. In contrast, expression of ΔSKY variants elongated mitochondrial networks and reduced mitochondrial DRP1. Co-expression of YFP-TBC1D15 partially rescued mitochondrial morphology and DRP1 recruitment for ΔSKY variants, although ΔSKY variants were markedly unable to support TBC1D15 assembly into punctate structures found upon co-expression with wildtype FIS1 or the AAA variant. Collectively these results show that FIS1 activity can be modulated by conserved residues supporting a generalized model whereby FIS1 is governed by intramolecular interactions between the regulatory FIS1 arm and SKY insert that may be conserved across species.
Extracellular vesicles and co-isolated endogenous retroviruses differently affect dendritic cells

Cells secrete membrane-enclosed extracellular vesicles (EVs) and non-vesicular nanoparticles (ENPs) that may play a role in intercellular communication. Tumor-derived EVs have been proposed either to induce immune priming of antigen presenting cells, or, to be immuno-suppressive agents promoting tumor immune escape. We suspect that such disparate functions are due to variable composition in EV subtypes and ENPs of the analyzed EV preparations. We aimed to exhaustively characterize the array of secreted EVs and ENPs of murine tumor cell lines. Unexpectedly, we identified virus-like particles (VLPs) from endogenous murine leukemia virus in preparations of EVs produced by tumor cells. We established a robust protocol to separate small (s)EVs from VLPs and ENPs. We compared their protein composition and analyzed their functional interaction with target dendritic cells (DCs). ENPs were poorly captured and did not affect DCs. sEVs specifically induced DC death. A mixed EV/VLP preparation was the most efficient to induce DC maturation and antigen presentation. Our results call for systematic re-evaluation of the respective proportions and functions of non-viral EVs and VLPs produced by tumors and their contribution to anti-tumor immune responses and to tumor progression.
Rapid genome functional annotation pipeline anchored to the house sparrow (Passer domesticus, Linnaeus 1758) genome reannotation

House sparrow (Passer domesticus) is an important avian model for both laboratory and field-based studies of evolutionary genetics, development, neurobiology, physiology, behavior, and ecology. The current annotation of the P. domesticus genome is available at Ensembl Rapid Release site, which currently only focuses on gene set building. Here, we provide the first functional reannotation of the P. domesticus genome based on enrichment with intestinal Illumina RNA-Seq libraries. This revised annotation describes 38592 transcripts, compared to 23574 currently for Ensembl, and 14717 predicted protein-coding genes, with 96.4% complete Passeriformes lineage BUSCOs. A key improvement in this revised annotation is the definition of untranslated region (UTR) sequences, with 82.7% and 93.8% of transcripts containing 5’ and 3’ UTRs, respectively. Our reannotation highlights the benefits to genome annotation improvement when additional specific RNA-Seq data is available for analysis and rapid data throughput (>200 Mb h−1) is used.
Identification of potent and selective N-myristoyltransferase inhibitors of Plasmodium vivax liver stage hypnozoites and schizonts

New drugs targeting multiple stages of the malaria-causing parasite, Plasmodium, are needed to reduce and eliminate malaria worldwide. N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme, and a validated chemically tractable drug target for malaria. Previous efforts have failed to target NMT owing to the low selectivity for the Plasmodium enzyme compared with human NMTs. Herein, we applied a structure-guided approach using previously reported NMT inhibitors as scaffolds to develop a new generation of Plasmodium vivax NMT (PvNMT) targeting compounds. We report a series of compounds with IC50 values in the nM range and an order of magnitude improved selectivity to Plasmodium NMT over human NMT (HsNMT). X-ray co-crystallization of PvNMT with a representative lead compound, 12b, supported the prevailing hypothesis that a conformational difference in a key tyrosine residue of PvNMT and HsNMT drives the selectivity between these enzymes. The compounds were triaged based on their selectivity for PvNMT. They significantly decreased P. falciparum blood-stage parasite load, with IC50 values ranging from 0.36 μM to 1.25 μM. The compounds exhibited a dose-dependent inhibition of P. vivax liver stage schizont and hypnozoite infection, consistently, in three different P. vivax isolates with IC50 values ranging from 2.2 μM to 6 μM and from 1.2 μM to 12 μM. Our data provide evidence that NMT inhibitors could be multistage antimalarials, targeting both dormant and developing liver stage parasites, which is essential for malaria elimination. One Sentence Summary Potent and selective N-myristoyltransferase inhibitors of Plasmodium vivax hypnozoites and schizonts were synthesized and tested.
A new compact representation of morphological profiles: report on first massive VHR image processing at the JRC

A new compact representation of dierential morphological prole (DMP) vector elds is presented. It is referred to as the CSL model and is conceived to radically reduce the dimensionality of the DMP descriptors. The model maps three characteristic parameters, namely scale, saliency and level, into the RGB space through a HSV transform. The result is a a medium abstraction semantic layer used for visual exploration, image information mining and pattern classication. Fused with the PANTEX built-up presence index, the CSL model converges to an approximate building footprint representation layer in which color represents building class labels. This process is demonstrated on the rst high resolution (HR) global human settlement layer (GHSL) computed from multi-modal HR and VHR satellite images. Results of the rst massive processing exercise involving several thousands of scenes around the globe are reported along with validation gures.
A better brain? Alternative spliced STIM2 in hominoids arises with synapse formation and creates a gain-of-function variant

Balanced Ca2+ homeostasis is essential for cellular functions. STIM2 mediated Store-Operated Ca2+ Entry (SOCE) regulates cytosolic and ER Ca2+ concentrations, stabilizes dendritic spine formation and drives presynaptic spontaneous transmission and ER stress in neurons. Recently identified alternative spliced variants expand the STIM protein repertoire, uncover unique functions and facilitate our understanding of tissue specific regulation of SOCE. Here, we describe an addition to this repertoire, a unique short STIM2 variant (STIM2.3/STIM2G) present only in old world monkeys and humans with expression in humans starting with the beginning of brainwave activity and upon synapse formation within the cerebral cortex. In contrast to the short STIM1B variant, STIM2.3/STIM2G increases SOCE upon stimulation independently of specific spliced in residues. Basal cluster formation is reduced and analyses of several additional deletion and point mutations delineate the role of functional motifs for Ca2+ entry, NFAT activation and changes in neuronal gene expression. In addition, STIM2.3/STIM2G shows reduced binding and activation of the energy sensor AMPK. In the context of reduced STIM2.3 splicing seen in postmortem brains of patients with Huntington’s disease, our data suggests that STIM2.3/STIM2G is an important regulator of neuronal Ca2+ homeostasis, potentially involved in synapse formation/maintenance and evolutionary expansion of brain complexity.
Congruence and Simultaneity Judgment with a Single Multisensory Target: Preliminary Results

The presence of congruent features may suggest to the brain that stimuli in different modalities are due to a common cause. Previous work has presented conflicting results regarding the impact of congruence on simultaneity judgments, widely thought to be related to judgments of common cause. Here, a novel experimental paradigm using a single changing multi-sensory object is described, with the goal of contrasting results obtained using a single multi-sensory target with those obtained from previous work using arrays of moving dots and staggered asynchronous pairs of targets. Some preliminary results from a pilot validating the experimental procedure are discussed.
Influences of boundary layer scale separation on the vorticity transport contribution to turbulent inertia

In the flows of interest, the mean effect of turbulent inertia can be expressed as the difference of two velocity vorticity correlations. This difference must be sufficiently non-zero if turbulent inertia is to have a net influence on the mean dynamics. One of the correlations is physically related to change of scale effects, while the other is related to advective vorticity transport. The vorticity transport mechanism is studied under the influence of increasing scale separation. Through the use of both laboratory and field data, the scale separation between the fluctuations of wall-normal velocity, v, and spanwise vorticity ωz, are shown to increase with distance from the wall and Reynolds number. Time-delayed correlations between these quantities reveal that only slight variations in their average phase would cause significant variations in the mean transport of momentum. Spectra are used to explore previous observations of scale selection between v and ωz. The wavelengths corresponding to the peaks in.
Editorial: Body composition assessment techniques in clinical and epidemiological settings: Development, validation and use in dietary programs, physical training and sports

COPYRIGHT © 2023 Costa, Nogueira, Fisberg and Ferrari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Body composition assessment techniques in clinical and epidemiological settings: Development, validation and use in dietary programs, physical training and sports
Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer

Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, has been studied in some tumors except BC. This study has explored that PKMYT1 functional role by bioinformatics methods combined with local clinical samples and experiments. Comprehensive analysis showed that PKMYT1 expression was higher in BC tissues, especially in advanced patients than that in normal breast tissues. The expression of PKMYT1 was an independent determinant for BC patients’ prognosis when combined with the clinical features. In addition, based on multi-omics analysis, we found that the PKMYT1 expression was closely relevant to several oncogenic or tumor suppressor gene variants. The analysis of single-cell sequencing indicated that PKMYT1 expression was upregulated in triple-negative breast cancer (TNBC), consistent with the results of bulk RNA-sequencing. High PKMYT1 expression was correlated with a poor prognosis. Functional enrichment analysis revealed that PKMYT1 expression was associated with cell cycle-related, DNA replication-related, and cancer-related pathways. Further research revealed that PKMYT1 expression was linked to immune cell infiltration in the tumor microenvironment. Additionally, loss-of-function experiments in vitro were performed to investigate the role of PKMYT1. TNBC cell lines’ proliferation, migration, and invasion were inhibited when PKMYT1 expression was knock-down. Besides, the down-regulation of PKMYT1 induced apoptosis in vitro. As a result, PKMYT1 might be a biomarker for prognosis and a therapeutic target for TNBC.
Transcriptomic analysis reveals the potential crosstalk genes and immune relationship between IgA nephropathy and periodontitis

Background It is well known that periodontitis has an important impact on systemic diseases. The aim of this study was to investigate potential crosstalk genes, pathways and immune cells between periodontitis and IgA nephropathy (IgAN). Methods We downloaded periodontitis and IgAN data from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify shared genes. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the shared genes. Hub genes were further screened using least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was drawn according to the screening results. Finally, single-sample GSEA (ssGSEA) was used to analyze the infiltration level of 28 immune cells in the expression profile and its relationship with shared hub genes. Results By taking the intersection of WGCNA important module genes and DEGs, we found that the SPAG4, CCDC69, KRT10, CXCL12, HPGD, CLDN20 and CCL187 genes were the most important cross-talk genes between periodontitis and IgAN. GO analysis showed that the shard genes were most significantly enriched in kinase regulator activity. The LASSO analysis results showed that two overlapping genes (CCDC69 and CXCL12) were the optimal shared diagnostic biomarkers for periodontitis and IgAN. The immune infiltration results revealed that T cells and B cells play an important role in the pathogenesis of periodontitis and IgAN. Conclusion This study is the first to use bioinformatics tools to explore the close genetic relationship between periodontitis and IgAN. The SPAG4, CCDC69, KRT10, CXCL12, HPGD, CLDN20 and CCL187 genes were the most important cross-talk genes between periodontitis and IgAN. T-cell and B-cell-driven immune responses may play an important role in the association between periodontitis and IgAN.
The diagnostic performance of radiomics-based MRI in predicting microvascular invasion in hepatocellular carcinoma: A meta-analysis

Objective The aim of this study was to assess the diagnostic performance of radiomics-based MRI in predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Method The databases of PubMed, Cochrane library, Embase, Web of Science, Ovid MEDLINE, Springer, and Science Direct were searched for original studies from their inception to 20 August 2022. The quality of each study included was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2 and the radiomics quality score. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic accuracy. Sensitivity analysis and subgroup analysis were performed to explore the source of the heterogeneity. Deeks’ test was used to assess publication bias. Results A total of 15 studies involving 981 patients were included. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.79 (95%CI: 0.72–0.85), 0.81 (95%CI: 0.73–0.87), 4.1 (95%CI:2.9–5.9), 0.26 (95%CI: 0.19–0.35), 16 (95%CI: 9–28), and 0.87 (95%CI: 0.84–0.89), respectively. The results showed great heterogeneity among the included studies. Sensitivity analysis indicated that the results of this study were statistically reliable. The results of subgroup analysis showed that hepatocyte-specific contrast media (HSCM) had equivalent sensitivity and equivalent specificity compared to the other set. The least absolute shrinkage and selection operator method had high sensitivity and specificity than other methods, respectively. The investigated area of the region of interest had high specificity compared to the volume of interest. The imaging-to-surgery interval of 15 days had higher sensitivity and slightly low specificity than the others. Deeks’ test indicates that there was no publication bias (P=0.71). Conclusion Radiomics-based MRI has high accuracy in predicting MVI in HCC, and it can be considered as a non-invasive method for assessing MVI in HCC.
Quality control practices in FMRI analysis: Philosophy, methods and examples using AFNI

Quality control (QC) is a necessary, but often an under-appreciated, part of FMRI processing. Here we describe procedures for performing QC on acquired or publicly available FMRI datasets using the widely used AFNI software package. This work is part of the Research Topic, “Demonstrating Quality Control (QC) Procedures in fMRI. ” We used a sequential, hierarchical approach that contained the following major stages: (1) GTKYD (getting to know your data, esp. its basic acquisition properties), (2) APQUANT (examining quantifiable measures, with thresholds), (3) APQUAL (viewing qualitative images, graphs, and other information in systematic HTML reports) and (4) GUI (checking features interactively with a graphical user interface); and for task data, and (5) STIM (checking stimulus event timing statistics). We describe how these are complementary and reinforce each other to help researchers stay close to their data. We processed and evaluated the provided, publicly available resting state data collections (7 groups, 139 total subjects) and task-based data collection (1 group, 30 subjects). As specified within the Topic guidelines, each subject’s dataset was placed into one of three categories: Include, exclude or uncertain. The main focus of this paper, however, is the detailed description of QC procedures: How to understand the contents of an FMRI dataset, to check its contents for appropriateness, to verify processing steps, and to examine potential quality issues. Scripts for the processing and analysis are freely available.