4,620 research outputs found
Morse homology for the heat flow
We use the heat flow on the loop space of a closed Riemannian manifold to
construct an algebraic chain complex. The chain groups are generated by
perturbed closed geodesics. The boundary operator is defined in the spirit of
Floer theory by counting, modulo time shift, heat flow trajectories that
converge asymptotically to nondegenerate closed geodesics of Morse index
difference one.Comment: 89 pages, 3 figure
Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium
Microbial consortia constitute a majority of the earthâs biomass, but little is known about how these cooperating
communities persist despite competition among community members. Theory suggests that non-random spatial structures
contribute to the persistence of mixed communities; when particular structures form, they may provide associated
community members with a growth advantage over unassociated members. If true, this has implications for the rise and
persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances
of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a
synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a
biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable
growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes
in the initial environment; in other words, the structure enhances the ability of the consortium to survive
environmental disruptions. Second, when the layered structure forms in downstream environments the consortium
accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the
global productivity of the consortium. We also observed that the layered structure only assembles in downstream
environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for
self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques
of synthetic biology in elucidating fundamental biological principles
Evolutionary Analysis of Mitogenomes from Parasitic and Free-Living Flatworms
Copyright: © 2015 SolĂ et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article
Notch signaling during human T cell development
Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse
Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells
LFA-1 is a leukocyte specific ÎČ2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.Peer ReviewedPostprint (published version
Molecular motors robustly drive active gels to a critically connected state
Living systems often exhibit internal driving: active, molecular processes
drive nonequilibrium phenomena such as metabolism or migration. Active gels
constitute a fascinating class of internally driven matter, where molecular
motors exert localized stresses inside polymer networks. There is evidence that
network crosslinking is required to allow motors to induce macroscopic
contraction. Yet a quantitative understanding of how network connectivity
enables contraction is lacking. Here we show experimentally that myosin motors
contract crosslinked actin polymer networks to clusters with a scale-free size
distribution. This critical behavior occurs over an unexpectedly broad range of
crosslink concentrations. To understand this robustness, we develop a
quantitative model of contractile networks that takes into account network
restructuring: motors reduce connectivity by forcing crosslinks to unbind.
Paradoxically, to coordinate global contractions, motor activity should be low.
Otherwise, motors drive initially well-connected networks to a critical state
where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages,
8 figure
Sensitivity of diffusion MRI to perilesional reactive astrogliosis in focal ischemia
Reactive astrogliosis is a response to injury in the central nervous system that plays an essential role in inflammation and tissue repair. It is characterized by hypertrophy of astrocytes, alterations in astrocyte gene expression and astrocyte proliferation. Reactive astrogliosis occurs in multiple neuropathologies, including stroke, traumatic brain injury and Alzheimer's disease, and it has been proposed as a possible source of the changes in diffusion magnetic resonance imaging (dMRI) metrics observed with these diseases. In this study, the sensitivity of dMRI to reactive astrogliosis was tested in an animal model of focal acute and subacute ischemia induced by the vasoconstricting peptide, endothelin-1. Reactive astrogliosis in perilesional cortex was quantified by calculating the astrocyte surface density as determined with a glial fibrillary acidic protein (GFAP) antibody, whereas perilesional diffusion changes were measured in vivo with diffusional kurtosis imaging. We found substantial changes in the surface density of GFAP-positive astrocyte processes and modest changes in dMRI metrics in the perilesional motor cortex following stroke. Although there are time point-specific correlations between dMRI and histological measures, there is no definitive evidence for a causal relationship.postprin
Expansion and Harvesting of hMSC-TERT
The expansion of human mesenchymal stem cells as suspension culture by means of spinner flasks and microcarriers, compared to the cultivation in tissue culture flasks, offers the advantage of reducing the requirements of large incubator capacities as well as reducing the handling effort during cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of hMSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d-1. The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin-accutase mix was most effective. After spinner expansion and harvesting the cells were successfully differentiated to adipocytes
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