Top 10 Biorxiv Papers Today


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#1. The Developing Human Connectome Project: typical and disrupted functional connectivity across the perinatal period
Michael Eyre, Sean P Fitzgibbon, Judit Ciarrusta, Lucilio Cordero-Grande, Anthony N Price, Tanya Poppe, Andreas Schuh, Emer Hughes, Camilla O'Keeffe, Jakki Brandon, Daniel Cromb, Katy Vecchiato, Jesper Andersson, Eugene P Duff, Serena J Counsell, Stephen M Smith, Daniel Rueckert, Joseph V Hajnal, Tomoki Arichi, Jonathan O'Muircheartaigh, Dafnis Batalle, A David Edwards
The Developing Human Connectome Project (dHCP) is an Open Science project which provides the first large sample of neonatal functional MRI (fMRI) data with high temporal and spatial resolution. This data enables mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organisation in humans. Here, we characterise in unprecedented detail the maturation and integrity of resting-state networks (RSNs) at normal term age in 337 infants (including 65 born preterm). First, we applied group independent component analysis (ICA) to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was...
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biorxiv_neursci: The Developing Human Connectome Project: typical and disrupted functional connectivity across the perinatal period https://t.co/QbsaROulFH #biorxiv_neursci
biorxivpreprint: The Developing Human Connectome Project: typical and disrupted functional connectivity across the perinatal period https://t.co/0Z95BdYyEs #bioRxiv
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Authors: 22
Total Words: 11845
Unqiue Words: 3605

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#2. Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension
Gi Fay Mok, Leighton Folkes, Shannon Weldon, Eirini Maniou, Victor Martinez-Heredia, Alice Godden, Ruth Williams, Grant Nicholas Wheeler, Simon Moxon, Andrea Munsterberg
The development of multicellular organisms is exquisitely regulated through differential gene activity, which governs cell differentiation programs. However, many details of spatiotemporal control of gene regulation are still poorly understood. We used the accessibility of chick embryos to examine genome-wide signatures characterizing the progressive differentiation of paraxial mesoderm along the head-to-tail axis. Paraxial mesoderm becomes organized into repetitive units, termed somites, the hallmark of the segmented vertebrate body plan. New somite pairs form periodically as the axis extends at the posterior end. This process generates a developmental gradient within a single embryo, with anterior somites more advanced in their differentiation compared to posterior somites. Following somite formation, cell rearrangements generate compartments, comprising lineages of the musculoskeletal system, including cartilage of the vertebral column and ribs, and skeletal muscle cells of the trunk and limbs. To examine how paraxial mesoderm...
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Authors: 10
Total Words: 0
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#3. Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis
Francesco Atzeni, Laurynas Pasakarnis, Gabriella Moscsa, Richard Smith, Christof Aegerter, Damian Brunner
Tissue morphogenesis integrates cell type-specific biochemistry and architecture, cellular force generation and mechanisms coordinating forces amongst neighbouring cells and tissues. We use finite element-based modelling to explore the interconnections at these multiple biological scales in embryonic dorsal closure, where pulsed actomyosin contractility in adjacent Amnioserosa (AS) cells powers the closure of an epidermis opening. Based on our in vivo observations, the model implements F-actin nucleation periodicity that is independent of MyoII activity. Our model reveals conditions, where depleting MyoII activity nevertheless indirectly affects oscillatory F-actin behaviour, without the need for biochemical feedback. In addition, it questions the previously proposed role of Dpp-mediated regulation of the patterned actomyosin dynamics in the AS tissue, suggesting them to be emergent. Tissue-specific Dpp interference supports the model's prediction. The model further predicts that the mechanical properties of the surrounding...
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biorxivpreprint: Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis https://t.co/qb5sn3qfKF #bioRxiv
biorxiv_sysbio: Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis https://t.co/TN3LfqpPgR #biorxiv_sysbio
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Authors: 6
Total Words: 0
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#4. Lipid accumulation promotes scission of caveolae
Madlen Hubert, Elin Larsson, Naga Venkata Gayathri Vegesna, Maria Ahnlund, Annika I Johansson, Lindon W.K Moodie, Richard Lundmark
Caveolae, bulb-shaped invaginations of the plasma membrane (PM), show distinct behaviors of scission and fusion at the cell surface. Although it is known that caveolae are enriched in cholesterol and sphingolipids, exactly how lipid composition influences caveolae surface stability has not yet been elucidated. Accordingly, we inserted specific lipids into the PM of cells via membrane fusion and studied acute effects on caveolae dynamics. We demonstrate that cholesterol and glycosphingolipids specifically accumulate in caveolae, which decreases their neck diameter and drives their scission from the cell surface. The lipid-induced scission was counteracted by the ATPase EHD2. We propose that lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not balanced by the restraining force of EHD2 at the neck. Our work advances the understanding of how lipids contribute to caveolae dynamics, providing a mechanistic link between caveolae and their ability to sense the PM lipid composition.
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biorxivpreprint: Lipid accumulation promotes scission of caveolae https://t.co/1IEzcQ5C9O #bioRxiv
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Authors: 7
Total Words: 0
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#5. Phosphatidylinositol-4-kinase IIα licenses phagosomes for TLR4 signaling and MHC-II presentation in dendritic cells
Cynthia Lopez-Haber, Roni Levin-Konigsberg, Yueyao Zhu, Jing Bi-Karchin, Tamas Balla, Sergio Grinstein, Michael S. Marks, Adriana R. Mantegazza
Toll like receptor (TLR) recruitment to phagosomes in dendritic cells (DCs) and downstream TLR signaling are essential to initiate antimicrobial immune responses. However, the mechanisms underlying TLR localization to phagosomes are poorly characterized. We show herein that phosphatidylinositol-4-kinase IIα (PI4KIIα) plays a key role in initiating phagosomal TLR4 responses in murine DCs by generating a phosphatidylinositol-4-phosphate (PtdIns4P) platform conducive to the binding of the TLR sorting adaptor TIRAP. PI4KIIα is recruited to LPS-containing phagosomes in an adaptor protein AP-3 dependent manner, and both PI4KIIα and PtdIns4P are also detected on phagosomal membrane tubules. Knockdown of PI4KIIα - but not of the related PI4KIIβ - impairs TIRAP and TLR4 localization to phagosomes, reduces proinflammatory cytokine secretion, abolishes phagosomal tubule formation and impairs MHC-II presentation. Phagosomal TLR responses in PI4KIIα-deficient DCs are restored by reexpression of wild-type PI4KIIα, but not of variants lacking...
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biorxivpreprint: Phosphatidylinositol-4-kinase IIα licenses phagosomes for TLR4 signaling and MHC-II presentation in dendritic cells https://t.co/Nm3DLAXVe3 #bioRxiv
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Authors: 8
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#6. The role of maternal effects on offspring performance in familiar and novel environments
Milan Vrtílek, Pierre J. C. Chuard, Maider Iglesias-Carrasco, Michael D. Jennions, Megan L. Head
Stressful conditions, like novel host environment, can stimulate mothers to produce offspring with phenotypes that better suit the conditions they are likely to experience (i.e. adaptive maternal effects). However, mothers might vary in their ability to adjust their offspring's phenotype in response to environmental cues. This could generate a maternal-by-environment interaction (M×E) that inflates estimates of genotype-by-environment effects (G×E). Our main aim in this study was to test for M×E with a paternal full-sib/half-sib breeding design in the seed beetle Callosobruchus maculatus , where we split and reared offspring from the same mother on two different bean host types - original and novel. Partitioning of offspring phenotypic variation indicated that maternal effects were very small for all the measured life-history traits, prohibiting a formal test for M×Es. There was also little evidence that the degree of maternal preference to oviposit on one host type predicted her offspring's relative performance on this host....
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Authors: 5
Total Words: 0
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#7. Structural determinants of dynamic fluctuations between segregation and integration on the human connectome
Makoto Fukushima, Olaf Sporns
While segregation and integration of neural information in the neocortex are thought to be important for human behavior and cognition, the neural substrates enabling their dynamic fluctuations remain elusive. To tackle this problem, we aim to identify specific network features of the connectome (the complete set of structural brain connections) that are responsible for the emergence of dynamic fluctuations between segregated and integrated patterns in human resting-state fMRI functional connectivity. The contributions of network features to the dynamic fluctuations were examined by constructing randomly rewired surrogate connectome data in which network features of interest were selectively preserved, and then by assessing the magnitude of fluctuations simulated with these surrogates. Our analysis demonstrates significant contributions from spatial geometry and network topology of the connectome, as well as from localized structural connections involving visual areas. By providing a structural account of dynamic fluctuations in...
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Authors: 2
Total Words: 12503
Unqiue Words: 2663

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#8. NREM consolidation and increased spindle counts improve age-related memory impairments and hippocampal representations
Robin K. Yuan, Matthew Roberto Lopez, Mar E. Normandin, Arthur S. Thomas, Vanessa R. Cerda, Amandine E. Grenier, Matthew T. Wood, Celia M. Gagliardi, Isabel A. Muzzio
Age-related changes in sleep patterns have been linked to cognitive decline. Specifically, age is associated with increased fragmentation of sleep and wake cycles. Yet it remains unknown if improvements in sleep architecture can ameliorate cellular and cognitive deficits. We evaluated how changes in sleep architecture following sleep restriction affected hippocampal representations and memory in young and old mice. Following training in a hippocampus dependent object/place recognition task, control animals were allowed to sleep normally, while experimental animals underwent 5 hr of sleep restriction (SR). Interestingly, old SR mice exhibited proper object/place memory, similarly to young control mice, whereas young SR and old control mice did not. Successful memory correlated with the presence of two hippocampal cell types: 1) 'Context' cells, which remained stable throughout training and testing, and 2) 'Object' cells, which shifted their preferred firing location when objects were introduced to the context and moved during...
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biorxiv_neursci: NREM consolidation and increased spindle counts improve age-related memory impairments and hippocampal representations https://t.co/7BPuA9rQ7m #biorxiv_neursci
biorxivpreprint: NREM consolidation and increased spindle counts improve age-related memory impairments and hippocampal representations https://t.co/SFwnZ0btQ7 #bioRxiv
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Authors: 9
Total Words: 0
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#9. Super-Beacons: open-source probes with spontaneous tunable blinking compatible with live-cell super-resolution microscopy
Pedro M. Pereira, Nils Gustafsson, Mark Marsh, Musa M. Mhlanga, Ricardo Henriques
Localization based super-resolution microscopy relies on the detection of individual molecules cycling between fluorescent and non-fluorescent states. These transitions are commonly regulated by high-intensity illumination, imposing constrains to imaging hardware and producing sample photodamage. Here, we propose single-molecule self-quenching as a mechanism to generate spontaneous photoswitching independent of illumination. To demonstrate this principle, we developed a new class of DNA-based open-source Super-Resolution probes named Super-Beacons, with photoswitching kinetics that can be tuned structurally, thermally and chemically. The potential of these probes for live-cell friendly Super-Resolution Microscopy without high-illumination or toxic imaging buffers is revealed by imaging Interferon Inducible Transmembrane proteins (IFITMs) at sub-100nm resolutions.
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biorxivpreprint: Super-Beacons: open-source probes with spontaneous tunable blinking compatible with live-cell super-resolution microscopy https://t.co/R2o6Ry8AJ6 #bioRxiv
biorxiv_cellbio: Super-Beacons: open-source probes with spontaneous tunable blinking compatible with live-cell super-resolution microscopy https://t.co/fVKlfhH9Av #biorxiv_cellbio
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Authors: 5
Total Words: 7888
Unqiue Words: 2809

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#10. Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis
Wenfei Sun, Hua Dong, Miroslav Balaz, Michal Slyper, Eugene Drokhlyansky, Georgia Colleluori, Antonio Giordano, Zuzana Kovanicova, Patrik Stefanicka, Lianggong Ding, Gottfried Rudofsky, Jozef Ukropec, Saverio Cinti, Aviv Regev, Christian Wolfrum
Adipose tissue usually is classified as either white, brown or beige/brite, based on whether it functions as an energy storage or thermogenic organ. It serves as an important regulator of systemic metabolism, exemplified by the fact that dysfunctional adipose tissue in obesity leads to a host of secondary metabolic complications such as diabetes, cardiovascular diseases and cancer. In addition, adipose tissue is an important endocrine organ, which regulates the function of other metabolic tissues through paracrine and endocrine signals. Work in recent years has demonstrated that tissue heterogeneity is an important factor regulating the functionality of various organs. Here we used single nucleus analysis in mice and men to deconvolute adipocyte heterogeneity. We are able to identify a novel subpopulation of adipocytes whose abundance is low in mice (2~8%) and which is increased under higher ambient temperatures. Interestingly, this population is abundant in humans who live close to thermoneutrality. We demonstrate that this novel...
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biorxivpreprint: Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis https://t.co/Ag9qGicmJj #bioRxiv
biorxiv_cellbio: Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis https://t.co/H3cLcOq6A7 #biorxiv_cellbio
GLim2016: RT @biorxivpreprint: Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis https://t.co/Ag9qGicmJj #bioRxiv
RogerJDavis1: RT @biorxivpreprint: Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis https://t.co/Ag9qGicmJj #bioRxiv
AyalaTovy: RT @biorxivpreprint: Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis https://t.co/Ag9qGicmJj #bioRxiv
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Sample Sizes : [14, 2]
Authors: 15
Total Words: 12080
Unqiue Words: 4439

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