Loss of SNAP29 Impairs Endocytic Recycling and Cell Motility

Intracellular membrane trafficking depends on the ordered formation and consumption of transport intermediates and requires that membranes fuse with each other in a tightly regulated and highly specific manner. Membrane anchored SNAREs assemble into SNARE complexes that bring membranes together to promote fusion. SNAP29 is a ubiquitous synaptosomal-associated SNARE protein. It interacts with several syntaxins and with the EH domain containing protein EHD1. Loss of functional SNAP29 results in CEDNIK syndrome (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma). Using fibroblast cell lines derived from CEDNIK patients, we show that SNAP29 mediates endocytic recycling of transferrin and β1-integrin. Impaired β1-integrin recycling affected cell motility, as reflected by changes in cell spreading and wound healing. No major changes were detected in exocytosis of VSVG protein from the Golgi apparatus, although the Golgi system acquired a dispersed morphology in SNAP29 deficient cells. Our results emphasize the importance of SNAP29 mediated membrane fusion in endocytic recycling and consequently, in cell motility

Jet Medium interactions at Quark Matter 09

The suppression of the yield of high transverse momentum $p_{T}$ hadrons in heavy-ion collisions, referred to as "jet-quenching", has now developed into a comprehensive science. Jets are now used as probes of a variety of properties of the dense medium through which they propagate. Major theoretical improvements include jet modification in a 3-D fluid dynamical medium, the first set of in-medium Monte-Carlo implementations, an understanding of multi-hadron observables and energy flow within perturbative QCD, along with improvements in the AdS/CFT description of energy loss. On the experimental side, high statistics data are allowing for the first discriminatory test of various theoretical models and approximations while the new measurements of full jet reconstruction pose a challenge to theory.Comment: 11 pages, 6 figures - To appear in the conference proceedings for Quark Matter 2009, March 30 - April 4, Knoxville, Tennessee, typos corrected, references adde

Can holography reproduce the QCD Wilson line?

Recently a remarkable agreement was found between lattice simulations of long Wilson lines and behavior of the Nambu Goto string in flat space-time. However, the latter fails to fit the short distance behavior since it admits a tachyonic mode for a string shorter than a critical length. In this paper we examine the question of whether a classical holographic Wilson line can reproduce the lattice results for Wilson lines of any length. We determine the condition on the the gravitational background to admit a Coulombic potential at short distances. We analyze the system using three different renormalization schemes. We perform an explicit best fit comparison of the lattice results with the holographic models based on near extremal D3 and D4 branes, non-critical near extremal AdS6 model and the Klebanov Strassler model. We find that all the holographic models examined admit after renormalization a constant term in the potential. We argue that the curves of the lattice simulation also have such a constant term and we discuss its physical interpretation

Drag and jet quenching of heavy quarks in a strongly coupled N=2* plasma

The drag of a heavy quark and the jet quenching parameter are studied in the strongly coupled N=2* plasma using the AdS/CFT correspondence. Both increase in units of the spatial string tension as the theory departs from conformal invariance. The description of heavy quark dynamics using a Langevin equation is also considered. It is found that the difference between the velocity dependent factors of the transverse and longitudinal momentum broadening of the quark admit an interpretation in terms of relativistic effects, so the distribution is spherical in the quark rest frame. When conformal invariance is broken there is a broadening of the longitudinal momentum distribution. This effect may be useful in understanding the jet distribution observed in experiments.Comment: 30 pages, 5 figures, references added, minor corrections. To be published in JHE

Five Easy Pieces: The Dynamics of Quarks in Strongly Coupled Plasmas

We revisit the analysis of the drag a massive quark experiences and the wake it creates at a temperature T while moving through a plasma using a gravity dual that captures the renormalisation group runnings in the dual gauge theory. Our gravity dual has a black hole and seven branes embedded via Ouyang embedding, but the geometry is a deformation of the usual conifold metric. In particular the gravity dual has squashed two spheres, and a small resolution at the IR. Using this background we show that the drag of a massive quark receives corrections that are proportional to powers of log T when compared with the drag computed using AdS/QCD correspondence. We use the perturbation produced by the quark strings to compute the wake and compare with the results obtained using AdS/QCD correspondence. We also study the shear viscosity with running couplings, analyze the viscosity to entropy ratio and compare the result with the known bound. In the presence of higher order curvature square corrections from the back-reactions of the embedded D7 branes, we argue the possibility of the entropy to viscosity bound being violated. Finally, we show that our set-up could in-principle allow us to study a family of gauge theories at the boundary by cutting off the dual geometry respectively at various points in the radial direction. All these gauge theories can have well defined UV completions, and more interestingly, we demonstrate that any thermodynamical quantities derived from these theories would be completely independent of the cut-off scale and only depend on the temperature at which we define these theories. Such a result would justify the holographic renormalisabilities of these theories which we, in turn, also demonstrate. We give physical interpretations of these results and compare them with more realistic scenarios.Comment: 130 pages, 12 eps figures, LaTex; v4: final version with corrected typos, numerous additional references and enlargement of some sections. The published version, that appears in Nucl. Phys. B, differs slightly in section 3 where there is more emphasis on holographic renormalisabilty and less on the wake, compared to this versio

Early-Time Energy Loss in a Strongly-Coupled SYM Plasma

We carry out an analytic study of the early-time motion of a quark in a strongly-coupled maximally-supersymmetric Yang-Mills plasma, using the AdS/CFT correspondence. Our approach extracts the first thermal effects as a small perturbation of the known quark dynamics in vacuum, using a double expansion that is valid for early times and for (moderately) ultrarelativistic quark velocities. The quark is found to lose energy at a rate that differs significantly from the previously derived stationary/late-time result: it scales like T^4 instead of T^2, and is associated with a friction coefficient that is not independent of the quark momentum. Under conditions representative of the quark-gluon plasma as obtained at RHIC, the early energy loss rate is a few times smaller than its late-time counterpart. Our analysis additionally leads to thermally-corrected expressions for the intrinsic energy and momentum of the quark, in which the previously discovered limiting velocity of the quark is found to appear naturally.Comment: 39 pages, no figures. v2: Minor corrections and clarifications. References added. Version to be published in JHE

Qualitative study of system-level factors related to genomic implementation

PURPOSE: Research on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects. METHODS: Up to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects, were interviewed using a semistructured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs. RESULTS: Key barriers included (1) limitations in integrating genomic data and clinical decision support tools into electronic health records, (2) physician reluctance toward genomic research participation and clinical implementation due to a limited evidence base, (3) inadequate reimbursement for genomic medicine, (4) communication among and between investigators and clinicians, and (5) lack of clinical and leadership engagement. CONCLUSION: Implementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice

Developing a Common Framework for Evaluating the Implementation of Genomic Medicine Interventions in Clinical Care: The IGNITE Network’s Common Measures Working Group

Purpose Implementation research provides a structure for evaluating the clinical integration of genomic medicine interventions. This paper describes the Implementing GeNomics In PracTicE (IGNITE) Network’s efforts to promote: 1) a broader understanding of genomic medicine implementation research; and 2) the sharing of knowledge generated in the network. Methods To facilitate this goal the IGNITE Network Common Measures Working Group (CMG) members adopted the Consolidated Framework for Implementation Research (CFIR) to guide their approach to: identifying constructs and measures relevant to evaluating genomic medicine as a whole, standardizing data collection across projects, and combining data in a centralized resource for cross network analyses. Results CMG identified ten high-priority CFIR constructs as important for genomic medicine. Of those, eight didn’t have standardized measurement instruments. Therefore, we developed four survey tools to address this gap. In addition, we identified seven high-priority constructs related to patients, families, and communities that did not map to CFIR constructs. Both sets of constructs were combined to create a draft genomic medicine implementation model. Conclusion We developed processes to identify constructs deemed valuable for genomic medicine implementation and codified them in a model. These resources are freely available to facilitate knowledge generation and sharing across the field

Holographic QCD: Past, Present, and Future

At the dawn of a new theoretical tool based on the AdS/CFT correspondence for nonperturbative aspects of quantum chromodynamics, we give an interim review on the new tool, holographic QCD, with some of its accomplishment. We try to give an A-to-Z picture of the holographic QCD, from string theory to a few selected top-down holographic QCD models with one or two physical applications in each model. We may not attempt to collect diverse results from various holographic QCD model studies.Comment: 80 pages, 18 figures, LaTeX; references added, published version + appendi