21,106 research outputs found
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Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase.
In meiotic prophase, chromosomes are organized into compacted loop arrays to promote homolog pairing and recombination. Here, we probe the architecture of the mouse spermatocyte genome in early and late meiotic prophase using chromosome conformation capture (Hi-C). Our data support the established loop array model of meiotic chromosomes, and infer loops averaging 0.8-1.0 megabase pairs (Mb) in early prophase and extending to 1.5-2.0 Mb in late prophase as chromosomes compact and homologs undergo synapsis. Topologically associating domains (TADs) are lost in meiotic prophase, suggesting that assembly of the meiotic chromosome axis alters the activity of chromosome-associated cohesin complexes. While TADs are lost, physically separated A and B compartments are maintained in meiotic prophase. Moreover, meiotic DNA breaks and interhomolog crossovers preferentially form in the gene-dense A compartment, revealing a role for chromatin organization in meiotic recombination. Finally, direct detection of interhomolog contacts genome-wide reveals the structural basis for homolog alignment and juxtaposition by the synaptonemal complex
Actin at cell-cell junctions is composed of two dynamic and functional populations
The ability of epithelial cells to polarize requires cell-cell adhesion mediated by cadherin receptors. During cell-cell contact, the mechanism via which a flat, spread cell shape is changed into a tall, cuboidal epithelial morphology is not known. We found that cadherin-dependent adhesion modulates actin dynamics by triggering changes in actin organization both locally at junctions and within the rest of the cell. Upon induction of cell-cell contacts, two spatial actin populations are distinguishable: junctional actin and peripheral thin bundles. With time, the relative position of these two populations changes and becomes indistinguishable to form a cortical actin ring that is characteristic of mature, fully polarized epithelial cells. Junctional actin and thin actin bundles differ in their actin dynamics and mechanism of formation, and interestingly, have distinct roles during epithelial polarization. Whereas junctional actin stabilizes clustered cadherin receptors at cell-cell contacts, contraction of peripheral actin bundle is essential for an increase in the maximum height at the lateral domain during polarization (cuboidal morphology). Thus, both junctional actin and thin bundles are necessary, and cooperate with each other to generate a polarized epithelial morphology
Construction and Application of an AMR Algorithm for Distributed Memory Computers
While the parallelization of blockstructured adaptive mesh refinement techniques is relatively straight-forward on shared memory architectures, appropriate distribution strategies for the emerging generation of distributed
memory machines are a topic of on-going research. In this paper, a locality-preserving domain decomposition is proposed that partitions the entire AMR hierarchy from the base level on. It is shown that the approach reduces the
communication costs and simplifies the implementation. Emphasis is put on the effective parallelization of the flux correction procedure at coarse-fine boundaries, which is indispensable for conservative finite volume schemes. An
easily reproducible standard benchmark and a highly resolved parallel AMR
simulation of a diffracting hydrogen-oxygen detonation demonstrate the proposed
strategy in practice
Network structure determines patterns of network reorganization during adult neurogenesis
New cells are generated throughout life and integrate into the hippocampus
via the process of adult neurogenesis. Epileptogenic brain injury induces many
structural changes in the hippocampus, including the death of interneurons and
altered connectivity patterns. The pathological neurogenic niche is associated
with aberrant neurogenesis, though the role of the network-level changes in
development of epilepsy is not well understood. In this paper, we use
computational simulations to investigate the effect of network environment on
structural and functional outcomes of neurogenesis. We find that small-world
networks with external stimulus are able to be augmented by activity-seeking
neurons in a manner that enhances activity at the stimulated sites without
altering the network as a whole. However, when inhibition is decreased or
connectivity patterns are changed, new cells are both less responsive to
stimulus and the new cells are more likely to drive the network into bursting
dynamics. Our results suggest that network-level changes caused by
epileptogenic injury can create an environment where neurogenic reorganization
can induce or intensify epileptic dynamics and abnormal integration of new
cells.Comment: 28 pages, 10 figure
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Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.
BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers
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Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.
Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture
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