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Darnell James E Jr
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Joys and surprises of a career studying eukaryotic gene expression.
The Journal of biological chemistry 2013 2013-May-3; 288(18):12957-66
In this Reflections, I review a few early and very lucky events that gave me a running start for the rest of a long and wonderfully enjoyable career. For the main part, a discussion is provided of what I recall as the main illuminating results that my many dozens of students and postdoctoral fellows (approximately 140 in all) provided to our biochemical/molecular biological world.
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R, Herndon M, Herve A, Klabbers P, Klukas J, Lanaro A, Lazaridis C, Leonard J, Loveless R, Mohapatra A, Ojalvo I, Palmonari F, Pierro GA, Ross I, Savin A, Smith WH, Swanson J
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Measurement of the ZZ production cross section and search for anomalous couplings in 2l2l' final states in pp collisions at root s=7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2013 JAN; ?(1):? Article 063
A measurement is presented of the ZZ production cross section in the ZZ -> 2l2l' decay mode with l = e, mu and l' = e, mu, tau in proton-proton collisions at root s = 7 TeV with the CMS experiment at the LHC. Results are based on data corresponding to an integrated luminosity of 5.0 fb(-1). The measured cross section sigma(pp -> ZZ) = 6.24(-080)(+0.86) (stat.)(-0.32)(+0.41) (syst.) +/- 0.14 (lumi.) pb is consistent with the standard model predictions. The following limits on ZZZ and ZZ-gamma anomalous trilinear gauge couplings are set at 95% confidence level: -0.011 < f(4)(Z) < 0.012, -0.012 < f(5)(Z) < 0.012, -0.013 < f(4)(gamma) < 0.015, and -0.014 < f(5)(gamma) < 0.014.
Yovel Galit, Freiwald Winrich A
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Face recognition systems in monkey and human: are they the same thing?
F1000prime reports 2013 2013 Apr 02; 5(?):10-10
Primate societies are based on face recognition. Face recognition mechanisms have been studied most extensively in humans and macaque monkeys. In both species, multiple brain areas specialized for face processing have been found, and their functional properties are characterized with increasing detail, so we can now begin to address questions about similarities and differences of face-recognition systems across species with 25 million years of separate evolution. Both systems are organized into multiple face-selective cortical areas in spatial arrangements and with functional specializations, implying both hierarchical and parallel modes of information processing. Yet open questions about homologies remain. To address these, future studies employing similar techniques and experimental designs across multiple species are needed to identify a putative core primate face processing system and to understand its differentiations into the multiple branches of the primate order.
Dhingra Nikhil, Suarez-Farinas Mayte, Fuentes-Duculan Judilyn, Gittler Julia K, Shemer Avner, Raz Assaf, Fischetti Vincent A, Krueger James G, Guttman-Yassky Emma
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Attenuated neutrophil axis in atopic dermatitis compared to psoriasis reflects TH17 pathway differences between these diseases.
The Journal of allergy and clinical immunology 2013 2013-Aug; 132(2):498-501.e3
Han L, Wang Y, Sangaletti R, D'Urso G, Lu Y, Shaham S, Bianchi L
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Two Novel DEG/ENaC Channel Subunits Expressed in Glia Are Needed for Nose-Touch Sensitivity in Caenorhabditis elegans
JOURNAL OF NEUROSCIENCE 2013 JAN 16; 33(3):936-949
Neuronal DEG/ENaC (degenerin and epithelial Na+ channel) Na+ channels have been implicated in touch sensation. For example, MEC-4 is expressed in touch neurons in Caenorhabditis elegans and mediates gentle-touch response. Similarly, homologous mammalian ASIC2 and ASIC3 are expressed in sensory neurons and produce touch phenotypes when knocked out in mice. Here, we show that novel DEG/ENaC subunits DELM-1 and DELM-2 (degenerin-like channel mechanosensory linked-1 and degenerin-like channel mechanosensory linked-2) are expressed in glia associated with touch neurons in C. elegans and that their knock-out causes defects in mechanosensory behaviors related to nose touch and foraging, which are mediated by OLQ and IL1 sensory neurons. Cell-specific rescue supports that DELM-1 and DELM-2 are required cell-autonomously in glia to orchestrate mechanosensory behaviors. Electron microscopy reveals that in delm-1 knock-outs, OLQ and IL1 sensory neurons and associated glia are struct!
Foley EA, Kapoor TM
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Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore
NATURE REVIEWS MOLECULAR CELL BIOLOGY 2013 JAN; 14(1):25-37
In eukaryotes, chromosome segregation during cell division is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric DNA. The kinetochore attaches chromosomes to spindle microtubules, modulates the stability of these attachments and relays the microtubule-binding status to the spindle assembly checkpoint (SAC), a cell cycle surveillance pathway that delays chromosome segregation in response to unattached kinetochores. Recent studies are shaping current thinking on how each of these kinetochore-centred processes is achieved, and how their integration ensures faithful chromosome segregation, focusing on the essential roles of kinase-phosphatase signalling and the microtubule-binding KMN protein network.
Diaz Leslie L, Lepherd Michelle, Scott Joseph
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Enteric Infection and Subsequent Septicemia due to Attaching and Effacing Escherichia coli in a Chinchilla.
Comparative medicine 2013 2013; 63(6):503-7
An adult male chinchilla (Chinchilla lanigera) presented with severe lethargy and tachypnea; the physical examination was otherwise unremarkable. Due to the animal's clinical condition, it was submitted for necropsy but died immediately prior to euthanasia. Clinicopathologic findings included leukocytosis with a left-shift neutrophilia and lymphopenia, azotemia, hyperphosphatemia, hyperglycemia, hyperlipemia, electrolyte imbalance, cholestasis, and hepatocellular damage. Neutrophilic enteritis with gramnegative bacterial colonization, hepatic lipidosis, interstitial pneumonia, suppurative tubulonephritis, erosive gastritis, cerebral edema, and lymphoid depletion were present microscopically. Attaching and effacing, eae-positive, Escherichia coli characterized by the presence of the intimin virulence factor was isolated from both the kidney and spleen. The cause of death was attributed to acute E. coli septicemia and subsequent disseminated intravascular coagulation.
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Belknap D, Borrello L, Carlsmith D, Cepeda M, Dasu S, Friis E, Gray L, Grogg KS, Grothe M, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Klukas J, Lanaro A, Lazaridis C, Leonard J, Loveless R, Mohapatra A, Ojalvo I, Palmonari F, Pierro GA, Ross I, Savin A, Smith WH, Swanson J
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Search for supersymmetry in final states with missing transverse energy and 0, 1, 2, or >= 3 b-quark jets in 7 TeV pp collisions using the variable alpha(T)
JOURNAL OF HIGH ENERGY PHYSICS 2013 JAN; ?(1):? Article 077
A search for supersymmetry in final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of root s = 7 TeV. The data sample corresponds to an integrated luminosity of 4.98 fb(-1) collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, alpha(T), is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. The search is performed in a signal region that is binned in the scalar sum of the transverse energy of jets and the number of jets identified as originating from a bottom quark. No excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of the constrained minimal supersymmetric extension of the standard model, and also in simplified models, with a special emphasis on compressed spectra and third-generation scenarios.
Knepp AM, Sakmar TP, Huber T
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Homogeneous Time-Resolved Fluorescence Assay to Probe Folded G Protein-Coupled Receptors
G PROTEIN COUPLED RECEPTORS: MODELING, ACTIVATION, INTERACTIONS AND VIRTUAL SCREENING 2013; 522(?):169-189
Continued advances in G protein-coupled receptor (GPCR) structural biology and biochemistry depend in part on strategies to stabilize these polytopic membrane proteins in purified systems. New methods to measure properly folded GPCRs are needed to facilitate the identification of suitable conditions and ensure sample quality. Most GPCRs do not contain an intrinsic reporter on their functionality, so probes must be introduced. Here, we describe a fluorescence-based approach to quantitatively measure the chemokine receptor CCR5 with labeled antibodies. The assay is exceptionally sensitive and high-throughput. We detail procedures to label antibodies, characterize the system, and process data. We also describe several useful applications, including optimization of incorporation into nanoscale apolipoprotein bound bilayers (NABBs or nanodiscs), measurement of receptor stability, and competition binding assays.
Kelly H, Mandraju R, Coelho-dos-Reis JGA, Tsuji M
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Effects of HIV-1-induced CD1c and CD1d modulation and endogenous lipid presentation on CD1c-restricted T-cell activation
BMC IMMUNOLOGY 2013 JAN 24; 14(?):? Article 4
Background: It has been shown that human immunodeficiency virus (HIV)-1 infection induces the production of endogenous lipids required for effective viral production, and the cluster of differentiation (CD) 1 molecule CD1d is downregulated by HIV-1 infection. However, the role of endogenous lipid presentation and the implications of CD1 downregulation by HIV-1 infection have not yet been characterized. Results: In this study, we observed downregulation of both CD1c and CD1d expression through a Vpu-dependent and Nef-independent mechanism, and the concomitant HIV-1-induced production of host cholesterol decreased the extent of CD1c and CD1d modulation. While the modest downregulation of CD1c by HIV-1 infection decreased the ability of CD1c-restricted T cells to respond and secrete interferon-gamma, the cholesterol upregulation in the same cells by HIV-1 infection appears to limit the downregulation of CD1c. Conclusions: The two conflicting HIV-1-mediated changes in CD1c expression appear to minimize the modulation of CD1c expression, thus leading the host to maintain a CD1c-restricted T-cell response against HIV-1.