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- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Journal article (peer-reviewed)
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6. |
- Ho, Joshua W. K., et al.
(author)
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Comparative analysis of metazoan chromatin organization
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Journal article (peer-reviewed)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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- Sodergren, Erica, et al.
(author)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Journal article (peer-reviewed)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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- Belov, Vladimir, et al.
(author)
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Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
- 2024
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In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Journal article (peer-reviewed)abstract
- Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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- Crowe, S., et al.
(author)
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Near-infrared observations of outflows and young stellar objects in the massive star-forming region AFGL 5180
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Journal article (peer-reviewed)abstract
- Context. Massive stars play important roles throughout the universe; however, their formation remains poorly understood. Observations of jets and outflows in high-mass star-forming regions, as well as surveys of young stellar object (YSO) content, can help test theoretical models of massive star formation. Aims. We aim at characterizing the massive star-forming region AFGL 5180 in the near-infrared (NIR), identifying outflows and relating these to sub-mm/mm sources, as well as surveying the overall YSO surface number density to compare to massive star formation models. Methods. Broad- and narrow-band imaging of AFGL 5180 was made in the NIR with the Large Binocular Telescope, in both seeing-limited (~0.5′) and high angular resolution (~0.09′) Adaptive Optics (AO) modes, as well as with the Hubble Space Telescope. Archival continuum data from the Atacama Millimeter/Submillimeter Array (ALMA) was also utilized. Results. At least 40 jet knots were identified via NIR emission from H2 and [FeII] tracing shocked gas. Bright jet knots outflowing from the central most massive protostar, S4 (estimated mass ~11 M⊙, via SED fitting), are detected towards the east of the source and are resolved in fine detail with the AO imaging. Additional knots are distributed throughout the field, likely indicating the presence of multiple driving sources. Sub-millimeter sources detected by ALMA are shown to be grouped in two main complexes, AFGL 5180 M and a small cluster ~15′ (0.15 pc in projection) to the south, AFGL 5180 S. From our NIR continuum images we identify YSO candidates down to masses of ~0.1 M⊙. Combined with the sub-mm sources, this yields a surface number density of such YSOs of N* ~ 103pc-2 within a projected radius of about 0.1 pc. Such a value is similar to those predicted by models of both core accretion from a turbulent clump environment and competitive accretion. The radial profile of N* is relatively flat on scales out to 0.2 pc, with only modest enhancement around the massive protostar inside 0.05 pc, which provides additional constraints on these massive star formation models. Conclusions. This study demonstrates the utility of high-resolution NIR imaging, in particular with AO, for detecting outflow activity and YSOs in distant regions. The presented images reveal the complex morphology of outflow-shocked gas within the large-scale bipolar flow of a massive protostar, as well as clear evidence for several other outflow driving sources in the region. Finally, this work presents a novel approach to compare the observed YSO surface number density from our study against different models of massive star formation.
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- Martínez-Sánchez, Noelia, et al.
(author)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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In: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Journal article (peer-reviewed)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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15. |
- Mussbacher, G., et al.
(author)
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The Relevance of Model-Driven Engineering Thirty years from Now
- 2014
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In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 8767, s. 183-200
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Journal article (peer-reviewed)abstract
- Although model-driven engineering (MDE) is now an established approach for developing complex software systems, it has not been universally adopted by the software industry. In order to better understand the reasons for this, as well as to identify future opportunities for MDE, we carried out a week-long design thinking experiment with 15 MDE experts. Participants were facilitated to identify the biggest problems with current MDE technologies, to identify grand challenges for society in the near future, and to identify ways that MDE could help to address these challenges. The outcome is a reflection of the current strengths of MDE, an outlook of the most pressing challenges for society at large over the next three decades, and an analysis of key future MDE research opportunities.
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