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Search Results: 1 - 10 of 298317 matches for " Lukas J. Neukomm "
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Two PI 3-Kinases and One PI 3-Phosphatase Together Establish the Cyclic Waves of Phagosomal PtdIns(3)P Critical for the Degradation of Apoptotic Cells
Nan Lu,Qian Shen,Timothy R. Mahoney,Lukas J. Neukomm,Ying Wang,Zheng Zhou
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001245
Abstract: Phosphatidylinositol 3-phosphate (PtdIns(3)P) is a signaling molecule important for many membrane trafficking events, including phagosome maturation. The level of PtdIns(3)P on phagosomes oscillates in two waves during phagosome maturation. However, the physiological significance of such oscillation remains unknown. Currently, the Class III PI 3-kinase (PI3K) Vps34 is regarded as the only kinase that produces PtdIns(3)P in phagosomal membranes. We report here that, in the nematode C. elegans, the Class II PI3K PIKI-1 plays a novel and crucial role in producing phagosomal PtdIns(3)P. PIKI-1 is recruited to extending pseudopods and nascent phagosomes prior to the appearance of PtdIns(3)P in a manner dependent on the large GTPase dynamin (DYN-1). PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3)P on phagosomes. Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3)P and disables phagosomes from recruiting multiple essential maturation factors, resulting in a complete arrest of apoptotic-cell degradation. We have further identified MTM-1, a PI 3-phosphatase that antagonizes the activities of PIKI-1 and VPS-34 by down-regulating PtdIns(3)P on phagosomes. Remarkably, persistent appearance of phagosomal PtdIns(3)P, as a result of inactivating mtm-1, blocks phagosome maturation. Our findings demonstrate that the proper oscillation pattern of PtdIns(3)P on phagosomes, programmed by the coordinated activities of two PI3Ks and one PI 3-phosphatase, is critical for phagosome maturation. They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.
Two PI 3-Kinases and One PI 3-Phosphatase Together Establish the Cyclic Waves of Phagosomal PtdIns(3)P Critical for the Degradation of Apoptotic Cells
Nan Lu,Qian Shen,Timothy R. Mahoney,Lukas J. Neukomm,Ying Wang,Zheng Zhou
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001245
Abstract: Phosphatidylinositol 3-phosphate (PtdIns(3)P) is a signaling molecule important for many membrane trafficking events, including phagosome maturation. The level of PtdIns(3)P on phagosomes oscillates in two waves during phagosome maturation. However, the physiological significance of such oscillation remains unknown. Currently, the Class III PI 3-kinase (PI3K) Vps34 is regarded as the only kinase that produces PtdIns(3)P in phagosomal membranes. We report here that, in the nematode C. elegans, the Class II PI3K PIKI-1 plays a novel and crucial role in producing phagosomal PtdIns(3)P. PIKI-1 is recruited to extending pseudopods and nascent phagosomes prior to the appearance of PtdIns(3)P in a manner dependent on the large GTPase dynamin (DYN-1). PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3)P on phagosomes. Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3)P and disables phagosomes from recruiting multiple essential maturation factors, resulting in a complete arrest of apoptotic-cell degradation. We have further identified MTM-1, a PI 3-phosphatase that antagonizes the activities of PIKI-1 and VPS-34 by down-regulating PtdIns(3)P on phagosomes. Remarkably, persistent appearance of phagosomal PtdIns(3)P, as a result of inactivating mtm-1, blocks phagosome maturation. Our findings demonstrate that the proper oscillation pattern of PtdIns(3)P on phagosomes, programmed by the coordinated activities of two PI3Ks and one PI 3-phosphatase, is critical for phagosome maturation. They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.
The Wnt Pathway Controls Cell Death Engulfment, Spindle Orientation, and Migration through CED-10/Rac
Juan Cabello,Lukas J. Neukomm,Ufuk Günesdogan,Katharina Burkart,Steve J. Charette,Günter Lochnit,Michael O. Hengartner,Ralf Schnabel
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000297
Abstract: Wnt signalling pathways have extremely diverse functions in animals, including induction of cell fates or tumours, guidance of cell movements during gastrulation, and the induction of cell polarity. Wnt can induce polar changes in cellular morphology by a remodelling of the cytoskeleton. However, how activation of the Frizzled receptor induces cytoskeleton rearrangement is not well understood. We show, by an in depth 4-D microscopy analysis, that the Caenorhabditis elegans Wnt pathway signals to CED-10/Rac via two separate branches to regulate modulation of the cytoskeleton in different cellular situations. Apoptotic cell clearance and migration of the distal tip cell require the MOM-5/Fz receptor, GSK-3 kinase, and APC/APR-1, which activate the CED-2/5/12 branch of the engulfment machinery. MOM-5 (Frizzled) thus can function as an engulfment receptor in C. elegans. Our epistatic analyses also suggest that the two partially redundant signalling pathways defined earlier for engulfment may act in a single pathway in early embryos. By contrast, rearrangement of mitotic spindles requires the MOM-5/Fz receptor, GSK-3 kinase, and β-catenins, but not the downstream factors LIT-1/NLK or POP-1/Tcf. Taken together, our results indicate that in multiple developmental processes, CED-10/Rac can link polar signals mediated by the Wnt pathway to rearrangements of the cytoskeleton.
The Wnt Pathway Controls Cell Death Engulfment, Spindle Orientation, and Migration through CED-10/Rac
Juan Cabello,Lukas J. Neukomm,Ufuk Günesdogan,Katharina Burkart,Steve J. Charette,Günter Lochnit,Michael O. Hengartner,Ralf Schnabel
PLOS Biology , 2010, DOI: 10.1371/journal.pbio.1000297
Abstract: Wnt signalling pathways have extremely diverse functions in animals, including induction of cell fates or tumours, guidance of cell movements during gastrulation, and the induction of cell polarity. Wnt can induce polar changes in cellular morphology by a remodelling of the cytoskeleton. However, how activation of the Frizzled receptor induces cytoskeleton rearrangement is not well understood. We show, by an in depth 4-D microscopy analysis, that the Caenorhabditis elegans Wnt pathway signals to CED-10/Rac via two separate branches to regulate modulation of the cytoskeleton in different cellular situations. Apoptotic cell clearance and migration of the distal tip cell require the MOM-5/Fz receptor, GSK-3 kinase, and APC/APR-1, which activate the CED-2/5/12 branch of the engulfment machinery. MOM-5 (Frizzled) thus can function as an engulfment receptor in C. elegans. Our epistatic analyses also suggest that the two partially redundant signalling pathways defined earlier for engulfment may act in a single pathway in early embryos. By contrast, rearrangement of mitotic spindles requires the MOM-5/Fz receptor, GSK-3 kinase, and β-catenins, but not the downstream factors LIT-1/NLK or POP-1/Tcf. Taken together, our results indicate that in multiple developmental processes, CED-10/Rac can link polar signals mediated by the Wnt pathway to rearrangements of the cytoskeleton.
Classification-related approach in the surgical treatment of thoracolumbar fractures
Lukas R,Sram J
Indian Journal of Orthopaedics , 2007,
Abstract: Background: Advanced diagnostic tools, classification systems and accordingly selected surgical approaches are essential requirements for the prevention of failure of surgical treatment of thoracolumbar fractures. The present study is designed to evaluate the contribution of classification to the choice of a surgical approach using the current fracture classification systems. Materials and Methods: We studied prospectively a group of 64 patients (22 females, 42 males) of an average age of 43 years, all operated on for thoracolumbar fractures during the year 2001. The AO-ASIF classification was used preoperatively with all imaging studies (X-ray, computed tomography (CT) and magnetic resonance imaging (MRI)). When the damage was detected only in the anterior column (A type), an isolated anterior stabilization (n=22) was preferred. If the MRI study disclosed an injury in the posterior column, a posterior approach (n=20) using the internal fixator was chosen. Injuries involving the posterior column (B or C type) were classified additionally according to the load-sharing classification (LSC). If LSC gave six or more points, treatment was completed with an anterior fusion.. The combined postero-anterior procedure was carried out 22 times.. The minimum follow-up period was 22 months. Results: Neither implant failure and nor significant loss of correction were observed in patients treated with anterior or combined procedures. The average loss of correction (increase of kyphosis) in simple posterior stabilization was 3.1 degree. Conclusion: Complex fracture classification helps in the selection of the surgical approach and helps to decrease the chances of treatment failure.
NJL breaking of supersymmetric GUTs
E. J. Chun,A. Lukas
Physics , 1993, DOI: 10.1016/0550-3213(93)90451-T
Abstract: We analyze the breakdown of SUSY GUTs driven by Nambu--Jona--Lasinio condensates. Starting with the most general gauge invariant and pure K\"ahlerian Lagrangian up to quartic order we solve the one loop gap equation and determine the breaking direction. This is done for various classes of groups and spectra of fundamental particles which especially cover the most promising unifying groups $SU(5)$, $SO(10)$ and $E_6$. Heavy masses for the fundamental as well as for the composite particles are calculated. The results are used to single out candidates which may lead to an acceptable low energy theory. In these models we discuss some phenomenological aspects and point out the difficulties in constructing phenomenological viable theories in our scenario.
Axino Mass in Supergravity Models
E. J. Chun,A. Lukas
Physics , 1995, DOI: 10.1016/0370-2693(95)00881-K
Abstract: We analyze the mass of the axino, the fermionic superpartner of the axion, in general supergravity models incorporating a Peccei--Quinn--symmetry and determine the cosmological constraints on this mass. In particular, we derive a simple criterion to identify models with an LSP--axino which has a mass of $O(m_{3/2}^2/f_{PQ})=O($keV) and can serve as a candidate for (warm) dark matter. We point out that such models have very special properties and in addition, the small axino mass has to be protected against radiative corrections by demanding small couplings in the Peccei--Quinn--sector. Generically, we find an axino mass of order $m_{3/2}$. Such masses are constrained by the requirement of an axino decay which occurs before the decoupling of the ordinary LSP. Especially, for a large Peccei--Quinn--scale $f_{PQ}>10^{11}$ GeV this constraint might be difficult to fulfill.
Discrete Gauge Symmetries in Axionic Extensions of the SSM
E. J. Chun,A. Lukas
Physics , 1992, DOI: 10.1016/0370-2693(92)91266-C
Abstract: We examine discrete gauge symmetries in axionic extensions of the SSM which provide a solution of the $\mu$-problem. Automatic-PQ symmetry and proton stability are shown to be guaranteed by certain discrete symmetries. Focusing on the L-violating discrete symmetries we discuss two sources of neutrino masses and their relevance for the solar neutrino problem.
Quark and Lepton Mass Matrices from Horizontal U(1) Symmetry
E. J. Chun,A. Lukas
Physics , 1996, DOI: 10.1016/0370-2693(96)01015-5
Abstract: In the simplest model of horizontal U(1) symmetry with one singlet added to the supersymmetric standard model, we systematically reconstruct quark mass matrices from the low-energy data to prove that there are only two mass matrices found by Binetruy et.~al.. The same U(1) symmetry constrains the hierarchical structure of L-violating couplings, from which we build radiative neutrino mass matrices accommodating the solar and hot dark matter neutrino masses and mixing. We find a few patterns of acceptable charged lepton and neutrino mass matrices, most of which are consistent with large $\tan\beta \simeq m_t/m_b$ only.
An Information-Theoretic Approach for Evaluating Probabilistic Tuning Functions of Single Neurons
Lukas Brostek,Thomas Eggert,Michael J. Mustari
Frontiers in Computational Neuroscience , 2011, DOI: 10.3389/fncom.2011.00015
Abstract: Neuronal tuning functions can be expressed by the conditional probability of observing a spike given any combination of explanatory variables. However, accurately determining such probabilistic tuning functions from experimental data poses several challenges such as finding the right combination of explanatory variables and determining their proper neuronal latencies. Here we present a novel approach of estimating and evaluating such probabilistic tuning functions, which offers a solution for these problems. By maximizing the mutual information between the probability distributions of spike occurrence and the variables, their neuronal latency can be estimated, and the dependence of neuronal activity on different combinations of variables can be measured. This method was used to analyze neuronal activity in cortical area MSTd in terms of dependence on signals related to eye and retinal image movement. Comparison with conventional feature detection and regression analysis techniques shows that our method offers distinct advantages, if the dependence does not match the regression model.
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