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Gustatory receptors (GRs) are critical for insect chemosensation and are potential targets for controlling pests and disease vectors, making their structural investigation a vital step toward such applications. We present structures of Bombyx mori Gr9 (BmGr9), a fructose-gated cation channel, in agonist-free and fructo... | [{'text': 'Bombyx mori Gr9', 'coordinates': [133, 5, 381, 43]}, {'text': 'Ligand-binding pocket', 'coordinates': [599, 2, 916, 43]}, {'text': 'polar', 'coordinates': [582, 437, 667, 480]}, {'text': 'aliphatic', 'coordinates': [690, 434, 819, 482]}, {'text': 'oaromatic', 'coordinates': [827, 439, 975, 475]}, {'text': 'P... |
Thalamocortical loops have a central role in cognition and motor control, but precisely how they contribute to these processes is unclear. Recent studies showing evidence of plasticity in thalamocortical synapses indicate a role for the thalamus in shaping cortical dynamics through learning. Since signals undergo a com... | [{'text': 'Stimulus', 'coordinates': [404, 2, 526, 34]}, {'text': 'error', 'coordinates': [140, 184, 208, 210]}, {'text': 'Behavior', 'coordinates': [740, 200, 866, 232]}, {'text': 'pre lpost|', 'coordinates': [115, 257, 251, 298]}, {'text': 'Cortex', 'coordinates': [422, 324, 518, 356]}, {'text': 'Local plasticity', ... |
Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome hyperactivation contributes to many human chronic inflammatory diseases, and understanding how NLRP3 inflammasome is regulated can provide strategies to treat inflammatory diseases. Here, we demonstrate that NLRP3 Cys126 is palmitoylat... | [{'text': 'Priming', 'coordinates': [34, 43, 157, 92]}, {'text': '126 KKKK PI4P 1', 'coordinates': [761, 85, 867, 187]}, {'text': 'trans-Golgi network localization', 'coordinates': [516, 192, 720, 242]}, {'text': 'Palmitoyl CoA ZDHHC7', 'coordinates': [194, 206, 340, 292]}, {'text': '126 1 KKKK', 'coordinates': [405, 1... |
Nitric oxide (NO) is a gasotransmitter required in a broad range of mechanisms controlling plant development and stress conditions. However, little is known about the specific role of this signaling molecule during lipid storage in the seeds. Here, we show that NO is accumulated in developing embryos and regulates the ... | [{'text': 'NITRATION', 'coordinates': [443, 21, 657, 65]}, {'text': 'ONOO', 'coordinates': [305, 57, 431, 99]}, {'text': 'NOz-Linolenic acid', 'coordinates': [713, 52, 974, 147]}, {'text': 'PRX', 'coordinates': [203, 227, 289, 269]}, {'text': 'PRX', 'coordinates': [445, 227, 531, 271]}, {'text': 'SNO', 'coordinates': [... |
Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse ... | [{'text': 'Molecular recording', 'coordinates': [37, 23, 301, 61]}, {'text': 'Lineage Tracing in Trunk-like Structures', 'coordinates': [326, 18, 673, 108]}, {'text': 'Embryoids mESCs', 'coordinates': [759, 23, 905, 116]}, {'text': 'Casg', 'coordinates': [56, 84, 114, 110]}, {'text': 'Lineage barcode', 'coordinates': [... |
Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing, yet there is currently no therapeutic means to correct this mis-splicing. Here, we utilize synthetic introns uniquely responsive to mutant SF3B1 to identify trans factors req... | [{'text': 'Synthetic intron reporter unveils major trans factor required for mutant SF3B1 aberrant RNA splicing activity SF3B1-WT mEm erald', 'coordinates': [8, 0, 914, 87]}, {'text': 'GPATCH8', 'coordinates': [813, 59, 875, 75]}, {'text': 'positive enrichment for genePRhoseeoss corrects SF3B1 mutation-dependent mis-sp... |
Although oligodendrocytes (OLs) synthesize laminin-γ1, the most widely used γ subunit, its functional significance in the CNS remains unknown. To answer this important question, we generated a conditional knockout mouse line with laminin-γ1 deficiency in OL lineage cells (γ1-OKO). γ1-OKO mice exhibit weakness/paralysis... | [{'text': 'BBB integrity', 'coordinates': [586, 36, 879, 99]}, {'text': 'Oligodendrocyte- derived laminin-V1', 'coordinates': [62, 380, 404, 480]}, {'text': 'Proliferation', 'coordinates': [67, 653, 305, 701]}, {'text': 'Myelination', 'coordinates': [708, 654, 932, 708]}, {'text': 'Differentiation', 'coordinates': [252... |
The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice ... | [{'text': 'RS: recovery sleep High sleep pressure', 'coordinates': [119, 19, 405, 95]}, {'text': 'SD', 'coordinates': [176, 134, 226, 166]}, {'text': '2 200 2', 'coordinates': [30, 144, 103, 284]}, {'text': 'POA', 'coordinates': [818, 206, 884, 238]}, {'text': '3 100', 'coordinates': [30, 284, 103, 363]}, {'text': 'sin... |
Interferon (IFN) contributes to the host’s antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and the mechanism of action remain elusive. Here, we report that one such ISG, TRIM21, interacts with and degrades the TRPV2 channel in myeloid cells, reducing its expression and prov... | [{'text': 'JAKI IFNAR TYk2 STAT1 STAT2 Trim21 UAYOA', 'coordinates': [675, 307, 788, 520]}, {'text': 'TRPV2', 'coordinates': [97, 343, 139, 357]}, {'text': 'IFNs', 'coordinates': [413, 349, 443, 361]}, {'text': 'TRPV2', 'coordinates': [929, 411, 971, 425]}, {'text': 'TRIM2I', 'coordinates': [71, 425, 115, 439]}, {'text... |
Mouse embryonic stem cells (mESCs) in the primed pluripotency state, which resembles the post-implantation epiblast, can be de-differentiated in culture to a naive state that resembles the pre-implantation inner cell mass. We report that primed-to-naive mESC transition entails a significant slowdown of DNA replication ... | [{'text': 'PRIMED-TO-NAIVE TRANSITION', 'coordinates': [189, 13, 806, 57]}, {'text': 'naive mESCs', 'coordinates': [57, 97, 197, 185]}, {'text': 'MREI1', 'coordinates': [245, 179, 385, 221]}, {'text': 'SLOW FORKS', 'coordinates': [503, 203, 763, 247]}, {'text': '2i', 'coordinates': [439, 317, 479, 357]}, {'text': 'prim... |
Proteotoxic stress drives numerous degenerative diseases. Cells initially adapt to misfolded proteins by activating the unfolded protein response (UPR), including endoplasmic-reticulum-associated protein degradation (ERAD). However, persistent stress triggers apoptosis. Enhancing ERAD is a promising therapeutic approac... | [{'text': 'ZIP7 and Zn2t promote ERAD', 'coordinates': [54, 14, 330, 124]}, {'text': 'ZIP7 mitigates ER stress', 'coordinates': [455, 13, 903, 73]}, {'text': 'endoplasmic reticulum (ER)', 'coordinates': [117, 126, 368, 220]}, {'text': 'without ZIP7 TER Stress', 'coordinates': [415, 116, 636, 219]}, {'text': 'with ZIP7 ... |
Assembly of TopBP1 biomolecular condensates triggers activation of the ataxia telangiectasia-mutated and Rad3-related (ATR)/Chk1 signaling pathway, which coordinates cell responses to impaired DNA replication. Here, we used optogenetics and reverse genetics to investigate the role of sequence-specific motifs in the for... | [{'text': 'Optogenetics (DNA damage-free) DNA damage NN', 'coordinates': [16, 14, 248, 126]}, {'text': 'TopBP1 biomolecular condensates', 'coordinates': [582, 14, 982, 46]}, {'text': 'Clients', 'coordinates': [880, 78, 970, 108]}, {'text': 'N STOP', 'coordinates': [259, 87, 325, 167]}, {'text': 'FANCJ', 'coordinates': ... |
Gene repression by the Polycomb pathway is essential for metazoan development. Polycomb domains, characterized by trimethylation of histone H3 lysine 27 (H3K27me3), carry the memory of repression and hence need to be maintained to counter the dilution of parental H3K27me3 with unmodified H3 during replication. Yet, how... | [{'text': 'Polycomb domain maintenance across the cell cycle', 'coordinates': [9, 13, 990, 73]}, {'text': 'Recovery', 'coordinates': [25, 139, 208, 200]}, {'text': 'Dilution', 'coordinates': [801, 145, 949, 189]}, {'text': '2', 'coordinates': [330, 176, 356, 212]}, {'text': '2', 'coordinates': [608, 490, 632, 522]}, {'... |
Heterogeneity in gene expression is common among clonal cells in bacteria, although the sources and functions of variation often remain unknown. Here, we track cellular heterogeneity in the bacterium Pseudomonas aeruginosa during colony growth by focusing on siderophore gene expression (pyoverdine versus pyochelin) imp... | [{'text': '{', 'coordinates': [88, 57, 118, 136]}, {'text': '[', 'coordinates': [85, 134, 123, 289]}, {'text': 'Bacteria on agarose', 'coordinates': [176, 234, 366, 262]}, {'text': 'Imaging every 10 minutes', 'coordinates': [640, 292, 884, 320]}, {'text': 'L', 'coordinates': [90, 372, 122, 480]}, {'text': 'Single cell'... |
The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for β-glucan-induced trained immunity in... | [{'text': 'B-glucan Dectin-1', 'coordinates': [354, 36, 471, 83]}, {'text': 'Cholesterol Metabolism HMG-CoA Squalene Oz+ (NADPH SQLE NADP 2,3- Epoxysqualene Cholesterol ', 'coordinates': [403, 139, 597, 429]}, {'text': 'Glucose Glycolysis Pyruvate', 'coordinates': [125, 219, 246, 325]}, {'text': 'Inhibitors KDIKOI Y193... |
The red sea urchin (Mesocentrotus franciscanus) is one of the Earth’s longest-living animals, reported to live more than 100 years with indeterminate growth, life-long reproduction, and no increase in mortality rate with age. To understand the genetic underpinnings of longevity and negligible aging, we constructed a ch... | [{'text': 'Chromosome-level genome assembly', 'coordinates': [506, 38, 928, 70]}, {'text': 'Mesocentrotus franciscanus', 'coordinates': [18, 216, 406, 246]}, {'text': 'COMPARATIVE ANALYSES BETWEEN URCHINS WITH DIFFERENT LIFESPANS', 'coordinates': [512, 286, 886, 334]}, {'text': 'Expanded gene families Contracted gene f... |
Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Usi... | [{'text': 'Network Analyses of B Lineage Developmental States', 'coordinates': [198, 26, 804, 59]}, {'text': 'Blood cell scRNA-seq', 'coordinates': [42, 84, 290, 116]}, {'text': 'SJARACNe', 'coordinates': [366, 86, 506, 116]}, {'text': 'NetBID2', 'coordinates': [752, 86, 852, 116]}, {'text': 'B Cell Development and Leu... |
Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant... | [{'text': 'ScRNA-seq hGBM-IDHwt (n=40) hAstro-IDHmut (n=8) hOligo-IDHmut (n-3) mGBM-IDHmut (n=12', 'coordinates': [263, 28, 472, 170]}, {'text': 'Mo-TAM cluster gene signature', 'coordinates': [554, 26, 712, 80]}, {'text': 'Histo-transcriptome assignment', 'coordinates': [786, 26, 974, 80]}, {'text': '2', 'coordinates'... |
Narratives can synchronize neural and physiological signals between individuals, but the relationship between these signals, and the underlying mechanism, is unclear. We hypothesized a top-down effect of cognition on arousal and predicted that auditory narratives will drive not only brain signals but also peripheral ph... | [{'text': 'Bidirectional Brain-Body interaction', 'coordinates': [154, 0, 854, 50]}, {'text': 'Audio narrative', 'coordinates': [24, 98, 216, 128]}, {'text': 'Brain activity (EEG)', 'coordinates': [575, 95, 739, 160]}, {'text': 'Gaze variation', 'coordinates': [672, 482, 782, 544]}, {'text': 'Pupil size', 'coordinates'... |
Neuronal morphology influences synaptic connectivity and neuronal signal processing. However, it remains unclear how neuronal shape affects steady-state distributions of organelles like mitochondria. In this work, we investigated the link between mitochondrial transport and dendrite branching patterns by combining math... | [{'text': 'dendrite scaling = ra + Tzd', 'coordinates': [5, 56, 338, 161]}, {'text': 'Drosophila HS dendrite', 'coordinates': [631, 91, 969, 133]}, {'text': 'parent-daughter', 'coordinates': [39, 336, 272, 376]}, {'text': 'subtree size', 'coordinates': [90, 409, 285, 447]}, {'text': 'sister-sister', 'coordinates': [74,... |
The gut must perform a dual role of protecting the host against toxins and pathogens while harboring mutualistic microbiota. Previous studies suggested that the NADPH oxidase Duox contributes to intestinal homeostasis in Drosophila by producing reactive oxygen species (ROS) in the gut that stimulate epithelial renewal.... | [{'text': 'Oral infection', 'coordinates': [188, 74, 312, 98]}, {'text': 'Malpighian tubules Duox', 'coordinates': [603, 98, 776, 151]}, {'text': 'ROS', 'coordinates': [660, 206, 706, 230]}, {'text': 'Midgut Upd3', 'coordinates': [76, 246, 144, 306]}, {'text': 'Transport by Countercurrent flow', 'coordinates': [260, 23... |
Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular RNAs that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging and chromatin association remain poorly understood. Here, we address these questions in Drosophila. We find that cRNAs constitute a he... | [{'text': 'Heterochromatin', 'coordinates': [296, 48, 704, 104]}, {'text': 'Linker histone', 'coordinates': [23, 163, 163, 253]}, {'text': 'cRNA', 'coordinates': [291, 159, 397, 201]}, {'text': 'hrp48', 'coordinates': [612, 172, 726, 222]}, {'text': 'hrp36', 'coordinates': [765, 154, 883, 209]}, {'text': 'Decreased lin... |
Many studies infer the role of neurons by asking what information can be decoded from their activity or by observing the consequences of perturbing their activity. An alternative approach is to consider information flow between neurons. We applied this approach to the parietal reach region (PRR) and the lateral intrapa... | [{'text': 'PRR', 'coordinates': [48, 86, 148, 138]}, {'text': 'Reach plan', 'coordinates': [231, 71, 355, 176]}, {'text': 'Saccade plan', 'coordinates': [611, 77, 779, 184]}, {'text': 'LIP', 'coordinates': [848, 92, 924, 140]}, {'text': 'Sensory information', 'coordinates': [423, 444, 581, 523]}, {'text': 'LFP', 'coord... |
How cancer cells determine their shape in response to three-dimensional (3D) geometric and mechanical cues is unclear. We develop an approach to quantify the 3D cell shape of over 60,000 melanoma cells in collagen hydrogels using high-throughput stage-scanning oblique plane microscopy (ssOPM). We identify stereotypic a... | [{'text': '1. Stage scanning oblique plane microscopy Collagen hydrogel ,', 'coordinates': [13, 0, 910, 104]}, {'text': 'Light sheet imaging', 'coordinates': [35, 77, 284, 115]}, {'text': 'Lightsheet', 'coordinates': [731, 69, 869, 107]}, {'text': 'Deep', 'coordinates': [853, 107, 930, 148]}, {'text': '60,000+ cells an... |
Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonst... | [{'text': 'Wild-type_', 'coordinates': [188, 9, 339, 63]}, {'text': 'inner hair cell ribbon synapse', 'coordinates': [353, 16, 801, 57]}, {'text': 'Synaptic Ribbon Synaptic Vesicle', 'coordinates': [765, 91, 924, 174]}, {'text': 'GluR2 GluR3 GluR4 NMDAR PSD95', 'coordinates': [766, 204, 844, 448]}, {'text': 'Bai1 knock... |
The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child’s health. Here, we profiled at the single-cell level the placent... | [{'text': 'Single-cell census', 'coordinates': [672, 26, 913, 66]}, {'text': 'Early placental human explants', 'coordinates': [11, 73, 197, 162]}, {'text': 'Plasmodium falciparum', 'coordinates': [290, 116, 546, 144]}, {'text': 'Placental responses', 'coordinates': [829, 118, 950, 177]}, {'text': 'Toxoplasma gondii', '... |
TRP channels are implicated in various diseases, but high structural similarity between them makes selective pharmacological modulation challenging. Here, we study the molecular mechanism underlying specific inhibition of the TRPM7 channel, which is essential for cancer cell proliferation, by the anticancer agent CCT12... | [{'text': 'Cation channel TRPM7 in closed state', 'coordinates': [44, 14, 460, 44]}, {'text': 'Mg2+ Zn2+ Ca2+', 'coordinates': [654, 14, 826, 44]}, {'text': 'Out', 'coordinates': [932, 72, 972, 96]}, {'text': 'CCT_', 'coordinates': [444, 130, 502, 160]}, {'text': 'In', 'coordinates': [949, 227, 971, 247]}, {'text': 'J'... |
Muscle stem cells (MuSCs) contribute to a robust muscle regeneration process after injury, which is highly orchestrated by the sequential expression of multiple key transcription factors. However, it remains unclear how key transcription factors and cofactors such as the Mediator complex cooperate to regulate myogenesi... | [{'text': 'WT', 'coordinates': [27, 27, 87, 63]}, {'text': 'Med23 KO', 'coordinates': [523, 25, 699, 63]}, {'text': 'Ditt penes', 'coordinates': [387, 241, 442, 257]}, {'text': 'Elkt', 'coordinates': [565, 237, 591, 253]}, {'text': 'peno8 Prolll =', 'coordinates': [647, 256, 711, 285]}, {'text': 'Diff genes', 'coordina... |
High-penetrance mutations affecting mental health can involve genes ubiquitously expressed in the brain. Whether the specific patterns of dysfunctions result from ubiquitous circuit deficits or might reflect selective vulnerabilities of targetable subnetworks has remained unclear. Here, we determine how loss of ubiquit... | [{'text': 'Wild type', 'coordinates': [210, 30, 328, 60]}, {'text': 'Fmriyl-', 'coordinates': [680, 30, 780, 60]}, {'text': 'RSC', 'coordinates': [276, 104, 330, 134]}, {'text': 'RSC', 'coordinates': [758, 102, 812, 132]}, {'text': 'dH', 'coordinates': [188, 142, 224, 172]}, {'text': 'dH', 'coordinates': [670, 140, 706... |
Bone is highly susceptible to cancer metastasis, and both tumor and bone cells enable tumor invasion through a “vicious cycle” of biochemical signaling. Tumor metastasis into bone also alters biophysical cues to both tumor and bone cells, which are highly sensitive to their mechanical environment. However, the mechanob... | [{'text': 'Spheroid size and tumor cell proliferation', 'coordinates': [167, 33, 527, 101]}, {'text': 'Metastatic multicellular mineralized model', 'coordinates': [624, 32, 916, 96]}, {'text': 'Mechanical compression', 'coordinates': [804, 104, 961, 172]}, {'text': 'Growth into spheroids', 'coordinates': [70, 128, 222,... |
A common cause of deafness in humans is dysregulation of the endocochlear potential generated by the stria vascularis (SV). Thus, proper formation of the SV is critical for hearing. Using single-cell transcriptomics and a series of Shh signaling mutants, we discovered that the Shh receptor Patched1 (Ptch1) is essential... | [{'text': 'Differentiation of marginal cells and formation of stria vascularis in the developing cochlea', 'coordinates': [92, 8, 905, 93]}, {'text': 'WT', 'coordinates': [240, 116, 292, 146]}, {'text': 'Ptch1CKo', 'coordinates': [669, 111, 805, 149]}, {'text': '3', 'coordinates': [28, 178, 56, 256]}, {'text': 'Cross s... |
Mitochondrial dysfunction critically contributes to many major human diseases. The impact of specific gut microbial metabolites on mitochondrial functions of animals and the underlying mechanisms remain to be uncovered. Here, we report a profound role of bacterial peptidoglycan muropeptides in promoting mitochondrial f... | [{'text': 'isolation', 'coordinates': [296, 90, 410, 122]}, {'text': 'Peptidoglycan (PG)', 'coordinates': [669, 105, 859, 175]}, {'text': 'E coli', 'coordinates': [124, 232, 210, 264]}, {'text': 'lysozyme', 'coordinates': [573, 231, 705, 267]}, {'text': 'in vitro', 'coordinates': [366, 336, 460, 366]}, {'text': 'Bind, ... |
Current organoid technologies require intensive manual manipulation and lack uniformity in organoid size and cell composition. We present here an automated organoid platform that generates uniform organoid precursors in high-throughput. This is achieved by templating from monodisperse Matrigel droplets and sequentially... | [{'text': 'Drugs', 'coordinates': [145, 109, 244, 153]}, {'text': 'Personalized Medicine', 'coordinates': [468, 148, 665, 222]}, {'text': 'Organoids', 'coordinates': [165, 339, 327, 379]}, {'text': 'Organoid Printing', 'coordinates': [222, 651, 520, 702]}, {'text': 'Tumor', 'coordinates': [698, 748, 798, 780]}, {'text'... |
Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting millions of elder people due to the degeneration of dopamine neurons in the striatum and substantia nigra. The clinical manifestations of PD include tremor, rigidity, bradykinesia and postural instability. Studying PD is challenging ... | [{'text': 'A', 'coordinates': [0, 0, 37, 37]}, {'text': 'B', 'coordinates': [988, 2, 1018, 38]}, {'text': 'p.I723V (ATC GTC)', 'coordinates': [1040, 6, 1268, 36]}, {'text': 'Disease-related gene mutation', 'coordinates': [586, 56, 730, 106]}, {'text': 'Reprogramming method Sendai virual Sendai viral Retroviral Episomal... |
Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present stud... | [{'text': 'Chemotherapy', 'coordinates': [671, 65, 952, 128]}, {'text': '8', 'coordinates': [734, 150, 790, 246]}, {'text': 'Colorectal Liver Metastases', 'coordinates': [25, 263, 542, 315]}, {'text': 'Viability', 'coordinates': [83, 403, 236, 464]}, {'text': 'Single-cell RNAseq', 'coordinates': [739, 387, 936, 493]}, ... |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) mediates viral entry into cells and is critical for vaccine development against coronavirus disease 2019 (COVID-19). Structural studies have revealed distinct conformations of S, but real-time information that connects these structures is lackin... | [{'text': 'SARS-CoV-2', 'coordinates': [31, 44, 282, 88]}, {'text': 'spike', 'coordinates': [512, 46, 622, 96]}, {'text': '4 conformations', 'coordinates': [650, 44, 954, 92]}, {'text': 'spi e', 'coordinates': [358, 141, 499, 214]}, {'text': "Down'", 'coordinates': [669, 155, 794, 203]}, {'text': "'Intermediate'", 'coo... |
Mutations in the lipid transport protein ABCA12 cause the life-threatening skin condition harlequin ichthyosis (HI), which is characterized by the loss of skin barrier function, inflammation, and dehydration. Inflammatory responses in HI increase disease severity by impairing keratinocyte differentiation, suggesting am... | [{'text': 'Aminosalicylic Acid treatment of Harlequin Ichthyosis:', 'coordinates': [124, 4, 885, 124]}, {'text': 'Abca12+lt', 'coordinates': [101, 117, 291, 161]}, {'text': 'Abca12NA', 'coordinates': [351, 113, 544, 163]}, {'text': 'Abca12N4 4ASA', 'coordinates': [751, 113, 942, 201]}, {'text': '+', 'coordinates': [762... |
Methyl-CpG binding protein 2 (MeCP2) has historically been linked to heterochromatin organization, and in mouse cells it accumulates at pericentric heterochromatin (PCH), closely following major satellite (MajSat) DNA distribution. However, little is known about the specific function of MeCP2 in these regions. We descr... | [{'text': 'Pericentric heterochromatin organization in mESC-derived neurons', 'coordinates': [13, 31, 985, 75]}, {'text': 'Mecp2-ly neurons ~', 'coordinates': [38, 86, 321, 187]}, {'text': 'WT neurons upon MajSat-fw RNA KD MoCP2 UCCp2 Mecpe MCp MeCP2 NecP2 Mecp2 MeCP2 KaCp Nacpz Mecp2', 'coordinates': [689, 88, 955, 25... |
Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Not... | [{'text': 'A', 'coordinates': [219, 87, 237, 113]}, {'text': 'putative model for stress induced anti-bacterial immunity', 'coordinates': [244, 75, 808, 168]}, {'text': "5' 8", 'coordinates': [918, 254, 984, 310]}, {'text': 'GAPs open', 'coordinates': [592, 364, 674, 432]}, {'text': 'Farttication', 'coordinates': [725, ... |
Chromosomal translocations are prevalent among soft tissue tumors, including those of the vasculature such as pseudomyogenic hemangioendothelioma (PHE). PHE shows endothelial cell (EC) features and has a tumor-specific t(7;19)(q22;q13) SERPINE1-FOSB translocation, but is difficult to study as no primary tumor cell line... | [{'text': 'hiPSC-ECsWT', 'coordinates': [296, 70, 501, 114]}, {'text': 'hiPSC-ECs', 'coordinates': [601, 97, 773, 137]}, {'text': 'PHE model', 'coordinates': [783, 99, 965, 137]}, {'text': 'hiPSCWT', 'coordinates': [10, 226, 147, 268]}, {'text': 'Proliferation, tube formation', 'coordinates': [683, 241, 897, 319]}, {'t... |
Cellular identity is ultimately dictated by the interaction of transcription factors with regulatory elements (REs) to control gene expression. Advances in epigenome profiling techniques have significantly increased our understanding of cell-specific utilization of REs. However, it remains difficult to dissect the majo... | [{'text': 'OCT4', 'coordinates': [195, 142, 305, 184]}, {'text': 'TALE', 'coordinates': [9, 174, 112, 216]}, {'text': 'SOX2', 'coordinates': [307, 181, 419, 225]}, {'text': 'Nanog', 'coordinates': [648, 153, 804, 216]}, {'text': 'NANOG', 'coordinates': [201, 251, 356, 300]}, {'text': 'Nanog regulatory complex', 'coordi... |
Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CT... | [{'text': 'Combinatorial Checkpoint Blockade', 'coordinates': [212, 42, 776, 90]}, {'text': 'Combination', 'coordinates': [105, 109, 299, 147]}, {'text': 'MGDO19 PD-1 x CTLA-4 Bispecific', 'coordinates': [667, 111, 977, 192]}, {'text': 'PD-1 mAb', 'coordinates': [46, 158, 176, 188]}, {'text': 'CTLA-4 mAb', 'coordinates... |
The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment—the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a highly druggable and attractiv... | [{'text': 'Irecount2', 'coordinates': [469, 45, 656, 107]}, {'text': 'PHAROS', 'coordinates': [778, 50, 926, 98]}, {'text': 'Genomic and Clinical Features', 'coordinates': [19, 131, 280, 212]}, {'text': 'cBioPortal FOR CANCER GENOMICS', 'coordinates': [423, 140, 587, 193]}, {'text': 'TCGA CDR', 'coordinates': [652, 130... |
Pioneer transcription factors (pTFs) bind to target sites within compact chromatin, initiating chromatin remodeling and controlling the recruitment of downstream factors. The mechanisms by which pTFs overcome the chromatin barrier are not well understood. Here, we reveal, using single-molecule fluorescence, how the yea... | [{'text': 'Rap1', 'coordinates': [475, 9, 586, 65]}, {'text': 'Target search', 'coordinates': [658, 56, 802, 168]}, {'text': 'TF binding', 'coordinates': [12, 113, 205, 169]}, {'text': 'sites', 'coordinates': [13, 171, 101, 213]}, {'text': 'Chromatin invasion & opening', 'coordinates': [661, 270, 884, 447]}, {'text': '... |
Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted... | [{'text': "Altered cholesterol and bile acid metabolism in Alzheimer's disease", 'coordinates': [62, 5, 882, 101]}, {'text': 'Metabolic profile of Bile acids in brain', 'coordinates': [690, 117, 990, 203]}, {'text': 'Cholesterol', 'coordinates': [187, 169, 306, 197]}, {'text': 'Classical pathway CYPZA1 HSD3B7 CYPBB1 CA... |
Metastatic melanoma is an aggressive disease, despite recent improvements in therapy. Eradicating all melanoma cells even in drug-sensitive tumors is unsuccessful in patients because a subset of cells can transition to a slow-cycling state, rendering them resistant to most targeted therapy. It is still unclear what pat... | [{'text': 'DNA Damage, Targeted Therapy, Aging', 'coordinates': [97, 72, 622, 117]}, {'text': 'Wnt5A', 'coordinates': [250, 141, 348, 173]}, {'text': 'Extracellular Space', 'coordinates': [786, 214, 982, 244]}, {'text': '8', 'coordinates': [316, 246, 340, 304]}, {'text': 'Melanoma Cell', 'coordinates': [18, 296, 172, 3... |
Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on coh... | [{'text': 'anti-PD-(L)1', 'coordinates': [172, 16, 402, 70]}, {'text': 'TRM', 'coordinates': [715, 43, 787, 87]}, {'text': '(CD103-', 'coordinates': [786, 36, 938, 90]}, {'text': 'non-Trm (CD103)', 'coordinates': [462, 110, 786, 164]}, {'text': '3 3', 'coordinates': [494, 228, 520, 296]}, {'text': 'Anti-PD-(L)1 respons... |
In vitro spermatogenesis has been achieved by culturing mouse embryonic stem cells (ESCs) together with a cell suspension of male juvenile gonad. However, for human fertility treatment or preservation, patient-specific ESCs or juvenile gonad is not available. We therefore aim to achieve in vitro spermatogenesis using m... | [{'text': 'Active state of prophase checkpoints', 'coordinates': [411, 81, 597, 123]}, {'text': 'Active state of the spindle assembly checkpoint', 'coordinates': [666, 81, 942, 124]}, {'text': 'On', 'coordinates': [515, 233, 543, 253]}, {'text': 'Meiotic arrest', 'coordinates': [593, 245, 709, 265]}, {'text': 'Pachynem... |
The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1–DENV4) and protects against experimental challenge with DENV2 in humans. Here, we track vaccine viremia and B and T cell responses to this vaccination/challenge model to understa... | [{'text': 'Live Attenuated Tetravalent Dengue Vaccine stimulates B and T cell responses in humans', 'coordinates': [14, 9, 984, 42]}, {'text': 'No viremia No Rash Non-sterile protection Dengue 2 antibody boost) Sterile protection I(No DENV2 antibody boost)', 'coordinates': [671, 92, 942, 280]}, {'text': 'months', 'coor... |
Prevotella spp. are a dominant bacterial genus within the human gut. Multiple Prevotella spp. co-exist in some individuals, particularly those consuming plant-based diets. Additionally, Prevotella spp. exhibit variability in the utilization of diverse complex carbohydrates. To investigate the relationship between Prevo... | [{'text': 'Mouse', 'coordinates': [28, 8, 147, 49]}, {'text': 'Prevotella spp.', 'coordinates': [185, 29, 419, 71]}, {'text': 'MAGs', 'coordinates': [25, 83, 131, 121]}, {'text': 'Isolates', 'coordinates': [151, 85, 281, 121]}, {'text': '3 Species', 'coordinates': [374, 80, 540, 128]}, {'text': '8', 'coordinates': [652... |
Mutations in KCNH2 can lead to long QT syndrome type 2. Variable disease manifestation observed with this channelopathy is associated with the location and type of mutation within the protein, complicating efforts to predict patient risk. Here, we demonstrated phenotypic differences in cardiomyocytes derived from isoge... | [{'text': 'Introduce genetic variants:', 'coordinates': [124, 2, 584, 57]}, {'text': 'ULLLLL', 'coordinates': [338, 198, 466, 226]}, {'text': 'L', 'coordinates': [737, 196, 795, 226]}, {'text': 'KCNHZAS6ITIwt', 'coordinates': [168, 241, 343, 277]}, {'text': 'control hiPSC', 'coordinates': [476, 246, 650, 278]}, {'text'... |
In mammals, chromatin organization undergoes drastic reorganization during oocyte development. However, the dynamics of three-dimensional chromatin structure in this process is poorly characterized. Using low-input Hi-C (genome-wide chromatin conformation capture), we found that a unique chromatin organization graduall... | [{'text': 'Mouse oogenesis', 'coordinates': [364, 15, 632, 63]}, {'text': 'PGC', 'coordinates': [45, 139, 115, 175]}, {'text': 'GO |', 'coordinates': [264, 142, 334, 174]}, {'text': 'GO II', 'coordinates': [394, 142, 468, 174]}, {'text': 'FGO', 'coordinates': [532, 142, 602, 174]}, {'text': 'GVBD', 'coordinates': [706,... |
Pioneering microbial genomic surveys have revealed numerous untapped biosynthetic gene clusters, unveiling the great potential of new natural products. Here, using a combination of genome mining, mutasynthesis, and activity screening in an infection model comprising Caenorhabditis elegans and Pseudomonas aeruginosa, we... | [{'text': 'Genome mining', 'coordinates': [169, 27, 381, 65]}, {'text': 'CAya L C-AncLTE', 'coordinates': [395, 73, 515, 89]}, {'text': 'Anti-P aeruginosa agent', 'coordinates': [647, 80, 976, 119]}, {'text': 'C-Asa T-C-AtcT-TE', 'coordinates': [229, 109, 349, 127]}, {'text': 'CAtnTC- AlcTTE CAsT-C At-TTE', 'coordinate... |
The histone chaperone FACT and histone H2B ubiquitination (H2Bub) facilitate RNA polymerase II (Pol II) passage through chromatin, yet it is not clear how they cooperate mechanistically. We used genomics, genetic, biochemical, and microscopic approaches to dissect their interplay in Schizosaccharomyces pombe. We show t... | [{'text': 'FACT complex', 'coordinates': [261, 41, 489, 81]}, {'text': 'Pob3 8 8 1 1 8', 'coordinates': [166, 173, 304, 331]}, {'text': 'Pob9 (Spt16', 'coordinates': [399, 175, 591, 235]}, {'text': 'Spt16', 'coordinates': [742, 178, 837, 220]}, {'text': '% 1 2 1', 'coordinates': [652, 200, 770, 321]}, {'text': 'ub', 'c... |
Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These adaptations drive their recognition, nondestructive penetration, and elaborate reengineering of the host’s cells to promote their growth, dissemination,... | [{'text': 'evolution of novelty', 'coordinates': [67, 0, 437, 58]}, {'text': 'global spatial proteome', 'coordinates': [540, 0, 988, 58]}, {'text': 'free-living ancestor', 'coordinates': [60, 50, 197, 129]}, {'text': 'apicomplexan parasite', 'coordinates': [307, 57, 495, 133]}, {'text': 'cellular landscapes of function... |
Activating KRAS mutations are found in over 90% of pancreatic ductal adenocarcinomas (PDACs), yet KRAS has remained a difficult target to inhibit pharmacologically. Here, we demonstrate, using several human and mouse models of PDACs, rapid acquisition of tumor resistance in response to targeting KRAS or MEK, associated... | [{'text': 'Adaptive resistance', 'coordinates': [99, 30, 405, 70]}, {'text': 'Combination drug sensitivity', 'coordinates': [517, 26, 966, 75]}, {'text': 'AMG-51O/Trametinib', 'coordinates': [90, 116, 326, 144]}, {'text': 'AMG-51O/Trametinib', 'coordinates': [581, 116, 817, 144]}, {'text': 'KRASIMEK', 'coordinates': [1... |
Although obesity is known to be critical for cancer development, how obesity negatively impacts antitumor immune responses remains largely unknown. Here, we show that increased fatty acid oxidation (FAO) driven by activated STAT3 in CD8+ T effector cells is critical for obesity-associated breast tumor progression. Abla... | [{'text': 'Breast Adipocytes', 'coordinates': [79, 33, 357, 73]}, {'text': 'Tumor CD8+ T cells', 'coordinates': [555, 32, 851, 72]}, {'text': 'Leptin Fatty acids', 'coordinates': [413, 98, 536, 164]}, {'text': 'LEPR', 'coordinates': [622, 118, 686, 142]}, {'text': 'PDI', 'coordinates': [736, 118, 782, 142]}, {'text': '... |
Macrophages form a major cell population in the tumor microenvironment. They can be activated and polarized into tumor-associated macrophages (TAM) by the tumor-derived soluble molecules to promote tumor progression and metastasis. Here, we used comparative metabolomics coupled with biochemical and animal studies to sh... | [{'text': 'Cancer cell', 'coordinates': [4, 0, 208, 43]}, {'text': 'E-cadherin N-cadherin Vimentin', 'coordinates': [549, 13, 731, 133]}, {'text': 'Fumarate', 'coordinates': [97, 119, 253, 157]}, {'text': 'SDH', 'coordinates': [83, 169, 165, 205]}, {'text': 'Tumor metastasis', 'coordinates': [686, 155, 898, 247]}, {'te... |
The role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mut... | [{'text': 'Ctrl', 'coordinates': [266, 108, 320, 138]}, {'text': 'OB-Rdbldb', 'coordinates': [609, 104, 732, 137]}, {'text': 'iPSCs', 'coordinates': [134, 208, 204, 236]}, {'text': 'RNAseq', 'coordinates': [429, 195, 524, 228]}, {'text': '100', 'coordinates': [187, 325, 223, 345]}, {'text': 'Proteomics', 'coordinates':... |
Plasma dihydroceramides are predictors of type 2 diabetes and related to metabolic dysfunctions, but the underlying mechanisms are not characterized. We compare the relationships between plasma dihydroceramides and biochemical and hepatic parameters in two cohorts of diabetic patients. Hepatic steatosis, steatohepatiti... | [{'text': 'Plasma dihydroceramide (DhCer), a sphingolipid, is described long-term predictor of Type 2 diabetes onset', 'coordinates': [18, 6, 960, 105]}, {'text': 'as a', 'coordinates': [110, 68, 172, 96]}, {'text': 'Two cohorts of Type 2 diabetic patients (n=129 and n= 90)', 'coordinates': [5, 141, 319, 273]}, {'text'... |
Progressive lung fibrosis is a major cause of mortality in systemic sclerosis (SSc) patients, but the underlying mechanisms remain unclear. We demonstrate that immune complexes (ICs) activate human monocytes to promote lung fibroblast migration partly via osteopontin (OPN) secretion, which is amplified by autocrine mon... | [{'text': 'Immune', 'coordinates': [12, 56, 222, 110]}, {'text': 'complex', 'coordinates': [0, 115, 233, 191]}, {'text': 'IL6', 'coordinates': [450, 174, 536, 230]}, {'text': 'mono', 'coordinates': [225, 286, 361, 328]}, {'text': 'MCSF', 'coordinates': [484, 300, 647, 362]}, {'text': 'mac.', 'coordinates': [791, 303, 8... |
In this study, we incorporate analyses of genome-wide sequence and structural alterations with pre- and on-therapy transcriptomic and T cell repertoire features in immunotherapy-naive melanoma patients treated with immune checkpoint blockade. Although tumor mutation burden is associated with improved treatment response... | [{'text': 'Genomic features (tumor)', 'coordinates': [171, 38, 402, 108]}, {'text': 'Transcriptomic features (tumor)', 'coordinates': [528, 37, 833, 107]}, {'text': 'Clonal TMB Mutation signatures HLA variation Aneuploidy 8 po', 'coordinates': [272, 180, 468, 431]}, {'text': 'Expressed TMB PD-L1 expression CTLA-4 expre... |
The proteolytic turnover of mitochondrial proteins is poorly understood. Here, we used a combination of dynamic isotope labeling and mass spectrometry to gain a global overview of mitochondrial protein turnover in yeast cells. Intriguingly, we found an exceptionally high turnover of the NADH dehydrogenase, Nde1. This h... | [{'text': 'Mitochondrial Surface', 'coordinates': [210, 30, 682, 80]}, {'text': 'Healthy Cells', 'coordinates': [115, 321, 403, 381]}, {'text': 'Respiration-Deficient Cells', 'coordinates': [526, 324, 978, 422]}, {'text': 'Proteasome', 'coordinates': [148, 432, 396, 480]}, {'text': 'Cell Death', 'coordinates': [718, 46... |
CD4+ T follicular helper cells (Tfh) are key drivers of antibody development. During Plasmodium falciparum malaria in children, the activation of Tfh is restricted to the Th1 subset and not associated with antibody levels. To identify Tfh subsets that are associated with antibody development in malaria, we assess Tfh a... | [{'text': 'Malaria', 'coordinates': [98, 26, 190, 56]}, {'text': 'Treatment', 'coordinates': [305, 37, 435, 67]}, {'text': '0 Day', 'coordinates': [167, 125, 239, 167]}, {'text': '8 Day', 'coordinates': [335, 127, 405, 165]}, {'text': '14/15 Day', 'coordinates': [571, 127, 698, 165]}, {'text': 'end of study (Day 27-36)... |
Insulin is an essential growth factor for the survival and self-renewal of human embryonic stem cells (hESCs). Although it is best known as the principal hormone promoting glycolysis in somatic cells, insulin's roles in hESC energy metabolism remain unclear. In this report, we demonstrate that insulin is essential to s... | [{'text': 'Insulin', 'coordinates': [198, 26, 358, 76]}, {'text': 'IGF', 'coordinates': [386, 24, 474, 74]}, {'text': 'Insulin', 'coordinates': [411, 193, 537, 235]}, {'text': 'IGF Receptor', 'coordinates': [560, 190, 813, 242]}, {'text': 'Membrane', 'coordinates': [21, 341, 219, 383]}, {'text': 'PI3K', 'coordinates': ... |
H2S-producing enzymes in bacteria have been shown to be closely engaged in the process of microbial survival and antibiotic resistance. However, no inhibitors have been discovered for these enzymes, e.g., 3-mercaptopyruvate sulfurtransferase (MST). In the present study, we identified several classes of inhibitors for E... | [{'text': 'Compound Libraries ~26, 000 compounds)', 'coordinates': [383, 118, 622, 178]}, {'text': 'High-throughput Inhibitor Screening', 'coordinates': [408, 254, 592, 336]}, {'text': 'Bacterial Growth Homeostasis', 'coordinates': [112, 290, 320, 371]}, {'text': 'Bacterial Death Imbalance', 'coordinates': [712, 288, 9... |
DNA methylation and histone H1 mediate transcriptional silencing of genes and transposable elements, but how they interact is unclear. In plants and animals with mosaic genomic methylation, functionally mysterious methylation is also common within constitutively active housekeeping genes. Here, we show that H1 is enric... | [{'text': 'Histone HI increases nucleosome spacing', 'coordinates': [318, 6, 708, 34]}, {'text': 'Nucleosome spacing', 'coordinates': [63, 49, 191, 65]}, {'text': 'Nucleosome spacing', 'coordinates': [797, 49, 923, 65]}, {'text': 'Long linker DNA', 'coordinates': [521, 55, 621, 73]}, {'text': 'Short linker DNA', 'coord... |
Neural crest cells are an embryonic multipotent stem cell population. Recent studies in model organisms have suggested that neural crest cells are specified earlier than previously thought, at blastula stages. However, the molecular dynamics of early neural crest specification, and functional changes from pluripotent p... | [{'text': 'A', 'coordinates': [0, 0, 28, 30]}, {'text': 'ES', 'coordinates': [1651, 91, 1701, 127]}, {'text': 'NC-6h NC-12h', 'coordinates': [1650, 163, 1771, 267]}, {'text': 'NC-18h', 'coordinates': [1651, 305, 1771, 341]}, {'text': 'NC-D1 NC-D2 NC-D3 NC-D4 NC-D5', 'coordinates': [1650, 375, 1759, 685]}, {'text': 'B',... |
Mode of delivery strongly influences the early infant gut microbiome. Children born by cesarean section (C-section) lack Bacteroides species until 6–18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome. Here, we re-evaluate this hypothesis by comparing... | [{'text': 'Week 1', 'coordinates': [533, 35, 597, 55]}, {'text': 'Number of families by delivery mode: Vaginal 40 C-section = 35', 'coordinates': [38, 46, 240, 156]}, {'text': 'Delivery', 'coordinates': [247, 91, 324, 118]}, {'text': 'D2', 'coordinates': [503, 97, 531, 117]}, {'text': 'D3', 'coordinates': [619, 99, 645... |
R loops arising during transcription induce genomic instability, but how cells respond to the R loop-associated genomic stress is still poorly understood. Here, we show that cells harboring high levels of R loops rely on the ATR kinase for survival. In response to aberrant R loop accumulation, the ataxia telangiectasia... | [{'text': 'ATR', 'coordinates': [530, 260, 588, 288]}, {'text': 'Mitotic entry', 'coordinates': [862, 291, 954, 360]}, {'text': 'MUS81', 'coordinates': [258, 398, 352, 428]}, {'text': 'Further collisions', 'coordinates': [818, 462, 946, 522]}, {'text': 'RNAPII', 'coordinates': [287, 575, 383, 603]}, {'text': 'Fork reco... |
The acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Here, we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline or genetic downregulation of the enzyme prevents infec... | [{'text': 'Acid sphingomyelinase inhibition', 'coordinates': [24, 32, 245, 122]}, {'text': 'Acid sphingomyelinase inhibition', 'coordinates': [516, 32, 734, 122]}, {'text': 'No inhibition', 'coordinates': [304, 62, 458, 92]}, {'text': 'No inhibition', 'coordinates': [796, 60, 948, 90]}, {'text': 'pp-VSV-SARS-CoV-2 spik... |
Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll... | [{'text': 'Trained monocytes', 'coordinates': [789, 30, 968, 123]}, {'text': 'Primary stimulation', 'coordinates': [305, 58, 449, 128]}, {'text': 'Secondary stimulation', 'coordinates': [566, 59, 711, 128]}, {'text': '1 5 1', 'coordinates': [27, 68, 104, 212]}, {'text': 'Human monocytes', 'coordinates': [167, 204, 280,... |
Lymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity. Al... | [{'text': 'CD8+RA+', 'coordinates': [182, 312, 296, 344]}, {'text': 'Memory Tregs', 'coordinates': [365, 365, 478, 437]}, {'text': 'CD8+ROt', 'coordinates': [792, 368, 908, 398]}, {'text': 'CDA+ RA', 'coordinates': [88, 482, 194, 512]}, {'text': 'CDA+ ROt', 'coordinates': [566, 478, 684, 508]}, {'text': 'IL-22', 'coord... |
Constant neuroregeneration in adult olfactory epithelium maintains olfactory function by basal stem cell proliferation and differentiation to replace lost olfactory sensory neurons (OSNs). Understanding the mechanisms regulating this process could reveal potential therapeutic targets for stimulating adult olfactory neu... | [{'text': 'A', 'coordinates': [0, 9, 39, 53]}, {'text': 'B-gallDAPI', 'coordinates': [65, 7, 235, 49]}, {'text': 'OMPIDAPI', 'coordinates': [433, 9, 601, 45]}, {'text': 'B-gallOMFI431"', 'coordinates': [748, 8, 1007, 50]}, {'text': '50 um', 'coordinates': [12, 298, 98, 328]}, {'text': 'B', 'coordinates': [8, 386, 40, 4... |
While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear. We hypothesized that the local metabolic environment could be an important determinant. To this end, we compared metabolites released from WAT of 81 obese and non-obese women... | [{'text': 'LEAN', 'coordinates': [150, 16, 292, 66]}, {'text': 'OBESE', 'coordinates': [644, 14, 840, 68]}, {'text': 'Glutamine', 'coordinates': [62, 142, 204, 174]}, {'text': 'Inflammation', 'coordinates': [760, 186, 938, 218]}, {'text': 'CDA+ T cell M1 ATM', 'coordinates': [914, 256, 994, 376]}, {'text': 'High glutam... |
In animal models, time-restricted feeding (TRF) can prevent and reverse aspects of metabolic diseases. Time-restricted eating (TRE) in human pilot studies reduces the risks of metabolic diseases in otherwise healthy individuals. However, patients with diagnosed metabolic syndrome often undergo pharmacotherapy, and it h... | [{'text': 'BASELINE', 'coordinates': [388, 44, 630, 96]}, {'text': '6am', 'coordinates': [170, 180, 226, 208]}, {'text': 'Metabolic Syndrome Waist Circumference Blood Pressure Blood Glucose Triglycerides HDL Cholesterol', 'coordinates': [370, 189, 712, 406]}, {'text': '>14 hours eating $ <10 hours fasting On Medication... |
In 2014, an outbreak of avian A/H10N7 influenza virus occurred among seals along North-European coastal waters, significantly impacting seal populations. Here, we examine the cross-species transmission and mammalian adaptation of this influenza A virus, revealing changes in the hemagglutinin surface protein that increa... | [{'text': 'N-Europe AHIONZ outbreak', 'coordinates': [28, 29, 187, 153]}, {'text': '1/8', 'coordinates': [741, 57, 795, 93]}, {'text': 'LAvian]', 'coordinates': [394, 117, 514, 159]}, {'text': 'Early', 'coordinates': [391, 231, 481, 275]}, {'text': 'Avian A/HION7', 'coordinates': [645, 275, 885, 313]}, {'text': '1/4', ... |
Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACC... | [{'text': 'Physician-directed', 'coordinates': [284, 0, 634, 46]}, {'text': 'Patient-powered Gopn', 'coordinates': [668, 0, 980, 74]}, {'text': 'Two-arm enrollment', 'coordinates': [17, 39, 226, 134]}, {'text': 'Data collection', 'coordinates': [21, 225, 298, 269]}, {'text': 'Data curation', 'coordinates': [21, 391, 27... |
Phagocytosis is a key function in various cells throughout the body. A deficiency in photoreceptor outer segment (POS) phagocytosis by the retinal pigment epithelium (RPE) causes vision loss in inherited retinal diseases and possibly age-related macular degeneration. To date, there are no effective therapies available ... | [{'text': 'Human pluripotent derived RPE- based screening and validation platform', 'coordinates': [120, 0, 876, 30]}, {'text': 'Human PSC RPE inTranswell', 'coordinates': [80, 63, 222, 107]}, {'text': 'Hits Confirmation Dose Response', 'coordinates': [434, 91, 586, 139]}, {'text': 'Miniaturization', 'coordinates': [22... |
Mutations in CAPN3 cause limb girdle muscular dystrophy R1 (LGMDR1, formerly LGMD2A) and lead to progressive and debilitating muscle wasting. Calpain 3 deficiency is associated with impaired CaMKIIβ signaling and blunted transcriptional programs that encode the slow-oxidative muscle phenotype. We conducted a high-throu... | [{'text': 'Healthy WT muscle', 'coordinates': [10, 14, 320, 62]}, {'text': 'Capn3-/- muscle', 'coordinates': [371, 13, 642, 61]}, {'text': 'Capna-/- muscle +AMBMP', 'coordinates': [712, 14, 984, 99]}, {'text': 'exercise-', 'coordinates': [27, 319, 155, 355]}, {'text': 'exercise', 'coordinates': [389, 319, 515, 355]}, {... |
The SARS-CoV-2 spike employs mobile receptor-binding domains (RBDs) to engage the human ACE2 receptor and to facilitate virus entry, which can occur through low-pH-endosomal pathways. To understand how ACE2 binding and low pH affect spike conformation, we determined cryo-electron microscopy structures—at serological an... | [{'text': 'A', 'coordinates': [114, 16, 146, 56]}, {'text': 'pH-Dependent Switch Mediates Endosomal Positioning of SARS-CoV-2 Spike Receptor-Binding Domains', 'coordinates': [42, 7, 956, 189]}, {'text': 'SARS-CoV-2 virion', 'coordinates': [185, 223, 545, 267]}, {'text': 'antibody', 'coordinates': [21, 318, 196, 380]}, ... |
Theory and experiments suggest that organisms would benefit from pre-adaptation to future stressors based on reproducible environmental fluctuations experienced by their ancestors, but the mechanisms driving pre-adaptation remain enigmatic. We report that the [SMAUG+] prion allows yeast to anticipate nutrient repletion... | [{'text': 'Prion-based control of cell division strategies', 'coordinates': [54, 10, 962, 64]}, {'text': '[smaug]', 'coordinates': [438, 182, 594, 230]}, {'text': 'Mitotic proliferation', 'coordinates': [105, 224, 280, 302]}, {'text': 'Meiotic differentiation', 'coordinates': [713, 229, 907, 299]}, {'text': '[SMAUGt]',... |
Tracing DNA repair factors by fluorescence microscopy provides valuable information about how DNA damage processing is orchestrated within cells. Most repair pathways involve single-stranded DNA (ssDNA), making replication protein A (RPA) a hallmark of DNA damage and replication stress. RPA foci emerging during S phase... | [{'text': 'DNA lesion RPA Rad52', 'coordinates': [719, 45, 897, 161]}, {'text': 'intranuclear quality control compartment (INQ)', 'coordinates': [257, 157, 581, 283]}, {'text': 'MCM helicase', 'coordinates': [717, 161, 947, 203]}, {'text': 'postreplicative repair territories (PORTs)', 'coordinates': [34, 286, 314, 418]... |
RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA targets. FMRP ... | [{'text': 'Inactive translation', 'coordinates': [79, 97, 228, 117]}, {'text': 'YTHDF1 condensation', 'coordinates': [421, 97, 601, 117]}, {'text': 'Active translation', 'coordinates': [791, 97, 929, 117]}, {'text': 'Neuronal stimulation p-FMRP', 'coordinates': [247, 205, 409, 282]}, {'text': 'Protein co-condensation',... |
Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, with contradictory results stemming from experimental difficulties associated with accurate dosing and measuring H2S and the use of model systems that do not accurately represent the human gut environment. Here, we engineer ... | [{'text': 'Strain Engineering', 'coordinates': [209, 18, 329, 38]}, {'text': 'Engineered strains titrate H,S in human gut microphysiological system', 'coordinates': [643, 15, 903, 47]}, {'text': '!', 'coordinates': [385, 109, 399, 145]}, {'text': 'Human Intestinal', 'coordinates': [637, 189, 747, 203]}, {'text': 'Epith... |
Deletion of the obsessive-compulsive disorder (OCD)-associated gene SAP90/PSD-95-associated protein 3 (Sapap3), which encodes a postsynaptic anchoring protein at corticostriatal synapses, causes OCD-like motor behaviors in mice. While corticostriatal synaptic dysfunction is central to this phenotype, the striatum effic... | [{'text': 'Sapap3 !-', 'coordinates': [258, 26, 373, 63]}, {'text': 'cortex', 'coordinates': [794, 40, 870, 66]}, {'text': 'Sapap3', 'coordinates': [850, 124, 944, 156]}, {'text': 'compulsive grooming', 'coordinates': [49, 148, 182, 215]}, {'text': 'SPN', 'coordinates': [798, 212, 854, 240]}, {'text': 'dSPN', 'coordina... |
Promoters are essential tools for basic and translational neuroscience research. An ideal promoter should possess the shortest possible DNA sequence with cell-type selectivity. However, whether ultra-compact promoters can offer neuron-specific expression is unclear. Here, we report the development of an extremely short... | [{'text': 'Human CALMI gene TSS MBAMDOD Core promoter region (120 bp) +I(TSS) Ultra-compact pCALMI promoter', 'coordinates': [129, 69, 403, 277]}, {'text': 'Plasmid construction Genes of interest (GOI)', 'coordinates': [641, 65, 789, 111]}, {'text': 'PCALMI', 'coordinates': [557, 95, 613, 111]}, {'text': 'polyA', 'coor... |
Aerobic glycolysis is critical for cancer progression and can be exploited in cancer therapy. Here, we report that the human carboxymethylenebutenolidase homolog (carboxymethylenebutenolidase-like [CMBL]) acts as a tumor suppressor by reprogramming glycolysis in colorectal cancer (CRC). The anti-cancer action of CMBL i... | [{'text': 'CMBL proficiency', 'coordinates': [29, 31, 287, 71]}, {'text': 'CMBL deficiency', 'coordinates': [725, 26, 971, 71]}, {'text': 'CMBL', 'coordinates': [86, 116, 164, 144]}, {'text': 'Genotoxic Stress', 'coordinates': [440, 110, 558, 164]}, {'text': 'CMBL ~', 'coordinates': [818, 116, 899, 153]}, {'text': 'p53... |
Previous studies of the murine Ly49 and human KIR gene clusters implicated competing sense and antisense promoters in the control of variegated gene expression. In the current study, an examination of transcription factor genes defines an abundance of convergent and divergent sense/antisense promoter pairs, suggesting ... | [{'text': 'Competing promoter motif found', 'coordinates': [51, 8, 680, 64]}, {'text': 'in 18% of TFs', 'coordinates': [691, 11, 953, 55]}, {'text': 'Antisense Promoter', 'coordinates': [28, 138, 284, 168]}, {'text': 'TF Promoter', 'coordinates': [356, 138, 520, 168]}, {'text': 'Intronic Antisense Promoter', 'coordinat... |
Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin... | [{'text': 'Cell state change in myofibroblasts from progressive scarring in fibrotic disease', 'coordinates': [124, 94, 892, 127]}, {'text': 'Integrins', 'coordinates': [396, 196, 478, 220]}, {'text': 'cytoskeletal contractility', 'coordinates': [446, 358, 556, 402]}, {'text': 'PAKI', 'coordinates': [304, 394, 386, 426... |
Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2− breast cancer. We... | [{'text': 'OvERGROWTH', 'coordinates': [168, 24, 354, 56]}, {'text': 'CELL CYCLE WiTHDRAWAL STOP ', 'coordinates': [503, 11, 853, 94]}, {'text': 'CDK4/6 inhibitor (CDK4/6i)', 'coordinates': [64, 120, 158, 194]}, {'text': 'GO/G1 ARREST', 'coordinates': [212, 140, 362, 164]}, {'text': 'drug washout', 'coordinates': [421,... |
The phosphoinositide 3-kinase p110α is an essential mediator of insulin signaling and glucose homeostasis. We interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110α and found that the Hippo kinases phosphorylate p110α at T1061, which inhibits its activity. This inhibitory ... | [{'text': 'Fasting Epinephrine', 'coordinates': [127, 153, 291, 231]}, {'text': 'Feeding Insulin', 'coordinates': [465, 152, 576, 226]}, {'text': 'EPAC MST1/2el', 'coordinates': [310, 248, 456, 342]}, {'text': 'PKA', 'coordinates': [178, 310, 234, 340]}, {'text': 'PI3K', 'coordinates': [490, 310, 552, 340]}, {'text': '... |
Macroautophagy/autophagy plays a pivotal role in immune regulation. Its significance is evident in modulation of immune cell differentiation and maturation, physiologically and pathologically. Here, we investigate the role of macrophage autophagy on the development of atopic dermatitis (AD). By employing an MC903-induc... | [{'text': 'Atopic dermatitis Skin IL-25', 'coordinates': [239, 15, 789, 106]}, {'text': 'Macrophages', 'coordinates': [702, 142, 962, 194]}, {'text': 'Chemokines IL-4/13', 'coordinates': [495, 173, 707, 281]}, {'text': 'Dermal immune cells', 'coordinates': [23, 193, 423, 235]}, {'text': 'Autophagy complete', 'coordinat... |
Branching allows neurons to make synaptic contacts with large numbers of other neurons, facilitating the high connectivity of nervous systems. Neuronal arbors have geometric properties such as branch lengths and diameters that are optimal in that they maximize signaling speeds while minimizing construction costs. In th... | [{'text': 'Dendritic arbor', 'coordinates': [20, 2, 308, 50]}, {'text': 'Subtree dendrogram', 'coordinates': [542, 0, 940, 57]}, {'text': 'increasing subtree size', 'coordinates': [748, 52, 922, 163]}, {'text': 'Fly_nociceptor neuron_', 'coordinates': [29, 365, 341, 401]}, {'text': 'Subtree size is scale invariant', 'c... |
Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and they accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. Howev... | [{'text': '1.5 1 1.0 0.5 1 0.0', 'coordinates': [654, 52, 732, 234]}, {'text': 'Control', 'coordinates': [122, 130, 194, 154]}, {'text': 'Formaldehyde', 'coordinates': [303, 127, 438, 159]}, {'text': 'Phosphoproteome Ub-modified proteome Proteome', 'coordinates': [162, 240, 365, 309]}, {'text': 'Ribosome', 'coordinates... |
PRMT1 plays a vital role in breast tumorigenesis; however, the underlying molecular mechanisms remain incompletely understood. Herein, we show that PRMT1 plays a critical role in RNA alternative splicing, with a preference for exon inclusion. PRMT1 methylome profiling identifies that PRMT1 methylates the splicing facto... | [{'text': '1', 'coordinates': [388, 110, 416, 194]}, {'text': 'SRSF1 Exon 2', 'coordinates': [456, 146, 534, 244]}, {'text': '1', 'coordinates': [578, 98, 602, 190]}, {'text': 'Exon 1', 'coordinates': [334, 214, 410, 242]}, {'text': 'Exon 3', 'coordinates': [574, 212, 654, 244]}, {'text': 'RAD1, AURKA et: al', 'coordin... |
The inheritance of a functional endoplasmic reticulum (ER) is ensured by the ER stress surveillance (ERSU) pathway. Here, we made the unexpected discovery that reticulon 1 (Rtn1) and Yop1, well-known ER-curvature-generating proteins, each possess two sphingolipid-binding motifs within their transmembrane domains and th... | [{'text': 'mislocalized septin ring', 'coordinates': [644, 128, 788, 179]}, {'text': 'septin ring', 'coordinates': [187, 135, 316, 172]}, {'text': 'Rtn1', 'coordinates': [140, 266, 208, 296]}, {'text': 'Yopi', 'coordinates': [301, 268, 371, 306]}, {'text': 'Yop1', 'coordinates': [629, 301, 706, 344]}, {'text': 'directi... |
In autosomal dominant polycystic kidney disease (ADPKD), renal cyst lesions predominantly arise from collecting ducts (CDs). However, relevant CD cyst models using human cells are lacking. Although previous reports have generated in vitro renal tubule cyst models from human induced pluripotent stem cells (hiPSCs), ther... | [{'text': 'RAR agonists', 'coordinates': [676, 32, 826, 63]}, {'text': 'PKD1-+ hiPSCs', 'coordinates': [42, 134, 122, 184]}, {'text': 'UBOs', 'coordinates': [250, 136, 314, 160]}, {'text': 'CD cyst model', 'coordinates': [502, 293, 662, 323]}, {'text': 'UBTCs', 'coordinates': [244, 334, 320, 358]}, {'text': 'Passaging'... |
In the retina, rod and cone pathways mediate visual signals over a billion-fold range in luminance. AII (“A-two”) amacrine cells (ACs) receive signals from both pathways via different bipolar cells, enabling AIIs to operate at night and during the day. Previous work has examined luminance-dependent changes in AII gap j... | [{'text': 'Night', 'coordinates': [106, 26, 214, 78]}, {'text': 'Sunriselsunset', 'coordinates': [354, 24, 640, 72]}, {'text': 'scotopic vision (rods)', 'coordinates': [18, 144, 296, 246]}, {'text': 'mesopic vision (rods and cones)', 'coordinates': [336, 144, 656, 244]}, {'text': 'photopic vision (cones)', 'coordinates... |
Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1’s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss ... | [{'text': 'Patient derived iPSCs', 'coordinates': [82, 36, 302, 62]}, {'text': 'Neuronal aggregates and microcephalic organoids result from NGLY1 mutations', 'coordinates': [759, 102, 974, 204]}, {'text': 'WT NGLYI AAV', 'coordinates': [485, 131, 565, 145]}, {'text': 'Mut NGLY1 organoids', 'coordinates': [373, 285, 467... |
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