TY - JOUR
AB - Chemokines are the main guidance cues directing leukocyte migration. Opposed to early assumptions, chemokines do not necessarily act as soluble cues but are often immobilized within tissues, e.g., dendritic cell migration toward lymphatic vessels is guided by a haptotactic gradient of the chemokine CCL21. Controlled assay systems to quantitatively study haptotaxis in vitro are still missing. In this chapter, we describe an in vitro haptotaxis assay optimized for the unique properties of dendritic cells. The chemokine CCL21 is immobilized in a bioactive state, using laser-assisted protein adsorption by photobleaching. The cells follow this immobilized CCL21 gradient in a haptotaxis chamber, which provides three dimensionally confined migration conditions.
AU - Schwarz, Jan
AU - Sixt, Michael K
ID - 1597
JF - Methods in Enzymology
TI - Quantitative analysis of dendritic cell haptotaxis
VL - 570
ER -
TY - JOUR
AB - The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.
AU - Kiermaier, Eva
AU - Moussion, Christine
AU - Veldkamp, Christopher
AU - Gerardy Schahn, Rita
AU - De Vries, Ingrid
AU - Williams, Larry
AU - Chaffee, Gary
AU - Phillips, Andrew
AU - Freiberger, Friedrich
AU - Imre, Richard
AU - Taleski, Deni
AU - Payne, Richard
AU - Braun, Asolina
AU - Förster, Reinhold
AU - Mechtler, Karl
AU - Mühlenhoff, Martina
AU - Volkman, Brian
AU - Sixt, Michael K
ID - 1599
IS - 6269
JF - Science
TI - Polysialylation controls dendritic cell trafficking by regulating chemokine recognition
VL - 351
ER -
TY - JOUR
AB - We show that the Anderson model has a transition from localization to delocalization at exactly 2 dimensional growth rate on antitrees with normalized edge weights which are certain discrete graphs. The kinetic part has a one-dimensional structure allowing a description through transfer matrices which involve some Schur complement. For such operators we introduce the notion of having one propagating channel and extend theorems from the theory of one-dimensional Jacobi operators that relate the behavior of transfer matrices with the spectrum. These theorems are then applied to the considered model. In essence, in a certain energy region the kinetic part averages the random potentials along shells and the transfer matrices behave similar as for a one-dimensional operator with random potential of decaying variance. At d dimensional growth for d>2 this effective decay is strong enough to obtain absolutely continuous spectrum, whereas for some uniform d dimensional growth with d<2 one has pure point spectrum in this energy region. At exactly uniform 2 dimensional growth also some singular continuous spectrum appears, at least at small disorder. As a corollary we also obtain a change from singular spectrum (d≤2) to absolutely continuous spectrum (d≥3) for random operators of the type rΔdr+λ on ℤd, where r is an orthogonal radial projection, Δd the discrete adjacency operator (Laplacian) on ℤd and λ a random potential.
AU - Sadel, Christian
ID - 1608
IS - 7
JF - Annales Henri Poincare
TI - Anderson transition at 2 dimensional growth rate on antitrees and spectral theory for operators with one propagating channel
VL - 17
ER -
TY - JOUR
AB - We prove that whenever A is a 3-conservative relational structure with only binary and unary relations,then the algebra of polymorphisms of A either has no Taylor operation (i.e.,CSP(A)is NP-complete),or it generates an SD(∧) variety (i.e.,CSP(A)has bounded width).
AU - Kazda, Alexandr
ID - 1612
IS - 1
JF - Algebra Universalis
TI - CSP for binary conservative relational structures
VL - 75
ER -
TY - JOUR
AB - In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells.
In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD.
AU - Mungenast, Alison
AU - Siegert, Sandra
AU - Tsai, Li
ID - 1613
JF - Molecular and Cellular Neuroscience
TI - Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells
VL - 73
ER -
TY - JOUR
AB - The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.
AU - Kowalski, Janina
AU - Gan, Jian
AU - Jonas, Peter M
AU - Pernia-Andrade, Alejandro
ID - 1616
IS - 5
JF - Hippocampus
TI - Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats
VL - 26
ER -
TY - JOUR
AB - We study the discrepancy of jittered sampling sets: such a set P⊂ [0,1]d is generated for fixed m∈ℕ by partitioning [0,1]d into md axis aligned cubes of equal measure and placing a random point inside each of the N=md cubes. We prove that, for N sufficiently large, 1/10 d/N1/2+1/2d ≤EDN∗(P)≤ √d(log N) 1/2/N1/2+1/2d, where the upper bound with an unspecified constant Cd was proven earlier by Beck. Our proof makes crucial use of the sharp Dvoretzky-Kiefer-Wolfowitz inequality and a suitably taylored Bernstein inequality; we have reasons to believe that the upper bound has the sharp scaling in N. Additional heuristics suggest that jittered sampling should be able to improve known bounds on the inverse of the star-discrepancy in the regime N≳dd. We also prove a partition principle showing that every partition of [0,1]d combined with a jittered sampling construction gives rise to a set whose expected squared L2-discrepancy is smaller than that of purely random points.
AU - Pausinger, Florian
AU - Steinerberger, Stefan
ID - 1617
JF - Journal of Complexity
TI - On the discrepancy of jittered sampling
VL - 33
ER -
TY - JOUR
AB - We consider the Bardeen–Cooper–Schrieffer free energy functional for particles interacting via a two-body potential on a microscopic scale and in the presence of weak external fields varying on a macroscopic scale. We study the influence of the external fields on the critical temperature. We show that in the limit where the ratio between the microscopic and macroscopic scale tends to zero, the next to leading order of the critical temperature is determined by the lowest eigenvalue of the linearization of the Ginzburg–Landau equation.
AU - Frank, Rupert
AU - Hainzl, Christian
AU - Seiringer, Robert
AU - Solovej, Jan
ID - 1620
IS - 1
JF - Communications in Mathematical Physics
TI - The external field dependence of the BCS critical temperature
VL - 342
ER -
TY - JOUR
AB - We prove analogues of the Lieb–Thirring and Hardy–Lieb–Thirring inequalities for many-body quantum systems with fractional kinetic operators and homogeneous interaction potentials, where no anti-symmetry on the wave functions is assumed. These many-body inequalities imply interesting one-body interpolation inequalities, and we show that the corresponding one- and many-body inequalities are actually equivalent in certain cases.
AU - Lundholm, Douglas
AU - Nam, Phan
AU - Portmann, Fabian
ID - 1622
IS - 3
JF - Archive for Rational Mechanics and Analysis
TI - Fractional Hardy–Lieb–Thirring and related Inequalities for interacting systems
VL - 219
ER -
TY - JOUR
AB - Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ## rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models.
AU - Kelleher, Jerome
AU - Etheridge, Alison
AU - Véber, Amandine
AU - Barton, Nicholas H
ID - 1631
JF - Theoretical Population Biology
TI - Spread of pedigree versus genetic ancestry in spatially distributed populations
VL - 108
ER -