Quantitative FLIM-FRET Microscopy to Monitor Nanoscale Chromatin Compaction In Vivo Reveals Structural Roles of Condensin Complexes

How metazoan genomes are structured at the nanoscale in living cells and tissues remains unknown. Here, we adapted a quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) approach to assay nanoscale chromatin compaction in living organisms. Caenorhabditis elegans was chosen as a model system. By measuring FRET between histone-tagged fluorescent proteins, we visualized distinct chromosomal regions and quantified the different levels of nanoscale compaction in meiotic cells. Using RNAi and repetitive extrachromosomal array approaches, we defined the heterochromatin state and showed that its architecture presents a nanoscale-compacted organization controlled by Heterochromatin Protein-1 (HP1) and SETDB1 H3-lysine-9 methyltransferase homologs in vivo. Next, we functionally explored condensin complexes. We found that condensin I and condensin II are essential for heterochromatin compaction and that condensin I additionally controls lowly compacted regions. Our data show that, in living animals, nanoscale chromatin compaction is controlled not only by histone modifiers and readers but also by condensin complexes

Vizualni identitet Koprivničko-križevačke županije

BackgroundPrevious studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient.MethodsHere we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology.ResultsConnectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions.ConclusionThese results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the 'dysconnectivity hypothesis' of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes.C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGR

The genome sequence of segmental allotetraploid peanut Arachis hypogaea

Like many other crops, the cultivated peanut (Arachis hypogaea L.) is of hybrid origin and has a polyploid genome that contains essentially complete sets of chromosomes from two ancestral species. Here we report the genome sequence of peanut and show that after its polyploid origin, the genome has evolved through mobile-element activity, deletions and by the flow of genetic information between corresponding ancestral chromosomes (that is, homeologous recombination). Uniformity of patterns of homeologous recombination at the ends of chromosomes favors a single origin for cultivated peanut and its wild counterpart A. monticola. However, through much of the genome, homeologous recombination has created diversity. Using new polyploid hybrids made from the ancestral species, we show how this can generate phenotypic changes such as spontaneous changes in the color of the flowers. We suggest that diversity generated by these genetic mechanisms helped to favor the domestication of the polyploid A. hypogaea over other diploid Arachis species cultivated by humans

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Abstract Number ‐ 193: Endovascular Thrombectomy for Basilar Artery Occlusion: Systematic Review and Meta‐analysis

Introduction Basilar artery occlusion (BAO), accounting for approximately 1% of all ischemic strokes and 5–10% of all proximal intracranial occlusions, usually causes devastating neurologic sequelae, poor prognosis and even death [1‐2]. Endovascular thrombectomy (EVT) has been recommended for anterior circulation stroke with large vessel occlusion (LVO) [3‐6]. During the past decade, there has been emerging interests in whether EVT could provide similar overwhelming benefits in posterior circulation stroke, especially BAO [7‐8]. The goal of our study is to compare EVT with conservative medical treatment (CMT) about the efficacy and the safety in patients with BAO. Methods All relevant literature comparing the outcomes of EVT versus CMT in patients with BAO were recruited via PubMed, Embase and the Cochrane Library until April 2022. Random‐effects model was adopted to pool estimates regrading favorable/good functional outcome, symptomatic intracranial hemorrhage (sICH) and the mortality. The heterogeneity of outcomes was assessed using the Cochran Q test (reported as a Cochran Q p value) and I2 statistics. Results Of the eight studies, a total of 3733 patients with pure BAO were enrolled. EVT was conducted in 2573 patients, and the others received CMT. Compared with CMT group, EVT group with or without intravenous thrombolytic therapy achieved more favorable functional outcome (OR 1.26, 95% CI 1.03 to 1.55, I2 = 54%, p = 0.05; Figure 1A) in patients with BAO. Similar trend was also noted in the good functional outcome (OR 1.23, 95% CI 0.97 to 1.57, I2 = 63%, p = 0.02; Figure 1B). Even though EVT group tended to provoke more sICH (OR 2.91, 95% CI 1.38 to 6.18, I2 = 22%, p = 0.27; Figure 1C), it reduced the mortality (OR 0.81, 95% CI 0.70 to 0.93, I2 = 31%, p = 0.19; Figure 1D) in patients with BAO, originally a devastating condition. Conclusions Our study worked in concert with the recent climate in the endovascular era [9] that EVT in BAO provides superior functional outcomes and less mortality compared with CMT. Despite the tendency of developing sICH after reperfusion, EVT still brought a dawn to posterior circulation stroke. We are no more at our wits’ end with BAO and its grave prognosis. Furthermore, we still need more future randomized control trials [10] or large‐scale cohorts for conclusive evidence

Clover v3 assembly

We present an assembly of the genome of subterranean clover, Trifolium subterraneum, an important pasture legume. Specifically, in situ Hi-C data (48X) was used to correct misjoins and anchor, order, and orient scaffolds in a previously published genome assembly (TSUd_r1.1; scaffold N50: 287kb). This resulted in an improved genome assembly (TrSub3; scaffold N50: 56Mb) containing eight chromosome-length scaffolds that span 95% of the sequenced bases in the input assembly

Abstract 022: Acute Kidney Injury in Subarachnoid Hemorrhage: Exploring its Clinical Significance and Prognostic Implications

Introduction Subarachnoid Hemorrhage (SAH) resulting from the spontaneous rupture of an aneurysm is a rare and highly debilitating condition. Despite its severity, patients with aneurysmal SAH remain understudied, particularly concerning the evaluation of the incidence and consequences of subsequent acute kidney injury (AKI). Thus, the objective of this study was to explore the predictors and ramifications of AKI in patients with aneurysmal SAH. Further research and attention to this area are crucial for improving patient outcomes and guiding clinical interventions in this challenging condition. Methods ICD‐10‐CM codes were used to query the National Inpatient Sample (NIS) for patients with AIS between 2010 and 2019. Subgroup analysis was stratified by the presence of a definitive AKI diagnosis. The AKI and non‐AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score‐matching were all performed using IBM SPSS 28. Results 76,553 patients within the NIS were diagnosed with nontraumatic SAH between 2010 and 2019, of which 10,634 (13.89%) had a comorbid diagnosis of AKI. Patients with AKI were on average older (63.29 vs 61.07, p < 0.01), more often obese (12.15% vs 9.32%, p < 0.01), of the white race (55.82% vs 51%, p < 0.01), and considered long‐term users of anticoagulants (8.12% vs 5.34%, p < 0.01) when compared to the non‐AKI group. In terms of complications, patients within the AKI cohort had lower rates of decompressive hemicraniectomy (1.37% vs. 2.38%, p = 0.52) and, interestingly, cerebral vasospasms (4.47% vs. 8.22%, p < 0.01). However, AKI patients had higher rates of deep vein thrombosis (6.36% vs. 3.54%, p < 0.01), pulmonary embolism (4.22% vs. 1.42%, p < 0.01), pneumonia (21.39% vs. 8.84%, p < 0.01), urinary tract infection (19.07% vs. 13.32%, p < 0.01), sepsis (20.27% vs. 4.18%, p < 0.01), acute myocardial infarction (12.14% vs. 3.21%, p < 0.01), and cardiac arrest (10.25% vs. 3.23%, p < 0.01). In a multivariate regression assessing the impact of AKI on SAH outcome, this diagnosis was found to be independently correlated with poor functional outcome (OR: 3.306, CI: 3.11 – 3.513, p < 0.001) above average LOS (OR: 1.503, CI: 1.438 ‐ 1.571, p <0.001), and in‐hospital mortality (OR: 2.434, CI: 2.323 ‐ 2.55, p <0.001), when controlling for admission age, SAH severity, and other significant comorbidities. Conclusion The findings of this national database evaluation reveal a significant association between AKI and adverse outcomes in patients with aneurysmal SAH. Specifically, the study highlights a strong correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. These results emphasize the importance of early detection and proactive management of AKI in SAH patients to improve their overall prognosis and enhance their chances of recovery