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Tomasini MD, Johnson DS, Mincer JS, Simon SM
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Modeling the dynamics and kinetics of HIV-1 Gag during viral assembly
PLOS ONE 2018 APR 20; 13(4):? Article e0196133
We report a computational model for the assembly of HIV-1 Gag into immature viral particles at the plasma membrane. To reproduce experimental structural and kinetic properties of assembly, a process occurring on the order of minutes, a coarse-grained representation consisting of a single particle per Gag molecule is developed. The model uses information relating the functional interfaces implicated in Gag assembly, results from cryo electrontomography, and biophysical measurements from fluorescence microscopy, such as the dynamics of Gag assembly at single virions. These experimental constraints eliminated many classes of potential interactions, and narrowed the model to a single interaction scheme with two non-equivalent interfaces acting to form Gags into a hexamer, and a third interface acting to link hexamers together. This model was able to form into a hexameric structure with correct lattice spacing and reproduced biologically relevant growth rates. We explored the effect of genomic RNA seeding punctum growth, finding that RNA may be a factor in locally concentrating Gags to initiate assembly. The simulation results infer that completion of assembly cannot be governed simply by Gag binding kinetics. However the addition of membrane curvature suggests that budding of the virion from the plasma membrane could factor into slowing incorporation of Gag at an assembly site resulting in virions of the same size and number of Gag molecules independent of Gag concentration or the time taken to complete assembly. To corroborate the results of our simulation model, we developed an analytic model for Gag assembly finding good agreement with the simulation results.
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Measurement of normalized differential t(t)over-bar cross sections in the dilepton channel from pp collisions at root s=13 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2018 APR 11; ?(4):? Article 060
Normalized differential cross sections for top quark pair production are measured in the dilepton (e(+)e(-), mu(+)mu(-), and mu(-/+),e(+/-)) decay channels in proton-proton collisions at a center-of-mass energy of 13 TeV. The measurements are performed with data corresponding to an integrated luminosity of 2.1 fb(-1) using the CMS detector at the LHC. The cross sections are measured differentially as a function of the kinematic properties of the leptons, jets from bottom quark hadronization, top quarks, and top quark pairs at the particle and parton levels. The results are compared to several Monte Carlo generators that implement calculations up to next-to-leading order in perturbative quantum chromodynamics interfaced with parton showering, and also to fixed-order theoretical calculations of top quark pair production up to next-to-next-to-leading order.
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Measurement of the Lambda(b) polarization and angular parameters in Lambda(b) -> J/psi Lambda decays from pp collisions at root s=7 and 8 TeV
PHYSICAL REVIEW D 2018 APR 17; 97(7):? Article 072010
An analysis of the bottom baryon decay Lambda(b) -> J/psi(-> mu(+)mu(-))Lambda( -> p pi(-)) is performed to measure the Lambda(b) polarization and three angular parameters in data from pp collisions at root s = 7 and 8 TeV, collected by the CMS experiment at the Large Hadron Collider. The Lambda(b) polarization is measured to be 0.00 +/- 0.06(stat) +/- 0.06(syst) and the parity-violating asymmetry parameter is determined to be 0.14 +/- 0.14(stat) +/- 0.10(syst). The measurements are compared to various theoretical predictions, including those from perturbative quantum chromodynamics.
Abe K, Irie K, Nakanishi H, Suzuki H, Fujiyoshi Y
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Crystal structures of the gastric proton pump
NATURE 2018 APR 12; 556(7700):214-218
The gastric proton pump-the H+, K+-ATPase-is a P-type ATPase responsible for acidifying the gastric juice down to pH 1. This corresponds to a million-fold proton gradient across the membrane of the parietal cell, the steepest known cation gradient of any mammalian tissue. The H+, K+-ATPase is an important target for drugs that treat gastric acid-related diseases. Here we present crystal structures of the H+, K+-ATPase in complex with two blockers, vonoprazan and SCH28080, in the luminal-open state, at 2.8 angstrom resolution. The drugs have partially overlapping but clearly distinct binding modes in the middle of a conduit running from the gastric lumen to the cation-binding site. The crystal structures suggest that the tight configuration at the cation-binding site lowers the pK(a) value of Glu820 sufficiently to enable the release of a proton even into the pH 1 environment of the stomach.
Hegele RA
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GENETICS AND MOLECULAR BIOLOGY introduction
CURRENT OPINION IN LIPIDOLOGY 2018 APR; 29(2):?
Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Grossmann J, Hormann N, Hrubec J, Jeitler M, Konig A, Kratschmer I, Liko D, Madlener T, Matsushita T, Mikulec I, Pree E, Rabady D, Rad N, Rohringer H, Schieck J, Spanring M, Spitzbart D, Strauss J, Waltenberger W, Wittmann J, Wulz CE, Zarucki M, Chekhovsky V, Mossolov V, Gonzalez JS, Shumeiko N, De Wolf EA, Janssen X, Lauwers J, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Abu Zeid S, Blekman F, D'Hondt J, De Bruyn I, De Clercq J, Deroover K, Flouris G, Lowette S, Moortgat S, Moreels L, Olbrechts A, Python Q, Skovpen K, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Karapostoli G, Lenzi T, Luetic J, Maerschalk T, Marinov A, Randle-conde A, Seva T, Vander Velde C, Vanlaer P, Vannerom 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F, Clarke C, Harr R, Karchin PE, Sturdy J, Zaleski S, Belknap DA, Buchanan J, Caillol C, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Pierro GA, Polese G, Ruggles T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Measurement of associated Z plus charm production in proton-proton collisions at root s=8TeV
EUROPEAN PHYSICAL JOURNAL C 2018 APR 9; 78(4):? Article 287
A study of the associated production of a Z boson and a charm quark jet (Z + c), and a comparison to production with a b quark jet (Z + b), in pp collisions at a centre-of-mass energy of 8 TeV are presented. The analysis uses a data sample corresponding to an integrated luminosity of 19.7 fb(-1), collected with the CMS detector at the CERN LHC. The Z boson candidates are identified through their decays into pairs of electrons or muons. Jets originating from heavy flavour quarks are identified using semileptonic decays of c or b flavoured hadrons and hadronic decays of charm hadrons. The measurements are performed in the kinematic region with two leptons with pT(l) > 20 GeV, vertical bar eta(l)vertical bar < 2.1, 71 < m(ll) < 111 GeV, and heavy flavour jets with p(T)(jet) > 25 GeV and vertical bar eta(jet)vertical bar < 2.5. The Z + c production cross section is measured to be sigma(pp -> Z + c + X) B(Z -> l(+)l(-)) = 8.8 +/- 0.5 (stat)+/- 0.6 (syst) pb. The ratio of the Z+c and Z+b production cross sections is measured to be sigma(pp -> Z+c+X)/sigma (pp -> Z+b+X) = 2.0 +/- 0.2 (stat)+/- 0.2 (syst). The Z+c production cross section and the cross section ratio are also measured as a function of the transverse momentum of theZ boson and of the heavy flavour jet. The measurements are compared with theoretical predictions.
Rosenthal L, Earnshaw VA, Moore JM, Ferguson DN, Lewis TT, Reid AE, Lewis JB, Stasko EC, Tobin JN, Ickovics JR
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Intergenerational Consequences: Women's Experiences of Discrimination in Pregnancy Predict Infant Social-Emotional Development at 6 Months and 1 Year
JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS 2018 APR; 39(3):228-237
Objective: Racial/ethnic and socioeconomic disparities in infant development in the United States have lifelong consequences. Discrimination predicts poorer health and academic outcomes. This study explored for the first time intergenerational consequences of women's experiences of discrimination reported during pregnancy for their infants' social-emotional development in the first year of life. Methods: Data come from a longitudinal study with predominantly Black and Latina, socioeconomically disadvantaged, urban young women (N = 704, M-age = 18.53) across pregnancy through 1 year postpartum. Women were recruited from community hospitals and health centers in a Northeastern US city. Linear regression analyses examined whether women's experiences of everyday discrimination reported during pregnancy predicted social-emotional development outcomes among their infants at 6 months and 1 year of age, controlling for potentially confounding medical and sociodemographic factors. Path analyses tested if pregnancy distress, anxiety, or depressive symptoms mediated significant associations. Results: Everyday discrimination reported during pregnancy prospectively predicted greater inhibition/separation problems and greater negative emotionality, but did not predict attention skills or positive emotionality, at 6 months and 1 year. Depressive symptoms mediated the association of discrimination with negative emotionality at 6 months, and pregnancy distress, anxiety, and depressive symptoms mediated the association of discrimination with negative emotionality at 1 year. Conclusion: Findings support that there are intergenerational consequences of discrimination, extending past findings to infant social-emotional development outcomes in the first year of life. It may be important to address discrimination before and during pregnancy and enhance support to mothers and infants exposed to discrimination to promote health equity across the life span.
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Search for new physics in events with a leptonically decaying Z boson and a large transverse momentum imbalance in proton-proton collisions at root s=13 TeV
EUROPEAN PHYSICAL JOURNAL C 2018 APR 11; 78(4):? Article 291
A search for new physics in events with a Z boson produced in association with large missing transverse momentum at the LHC is presented. The search is based on the 2016 data sample of proton-proton collisions recorded with the CMS experiment at root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). The results of this search are interpreted in terms of a simplified model of dark matter production via spin-0 or spin-1 mediators, a scenario with a standard-model-like Higgs boson produced in association with the Z boson and decaying invisibly, a model of unparticle production, and a model with large extra spatial dimensions. No significant deviations from the background expectations are found, and limits are set on relevant model parameters, significantly extending the results previously achieved in this channel.
Galea S, Vaughan RD
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The Invisible Forces That Create the Health of Populations: A Public Health of Consequence, April 2018
AMERICAN JOURNAL OF PUBLIC HEALTH 2018 APR; 108(4):445-446
Kara EE, Nussenzweig MC
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Redemption for self-reactive antibodies Antibody self-reactivity is repaired through antibody gene mutation in B cells
SCIENCE 2018 APR 13; 360(6385):152-153
Immunity to pathogens and tolerance to self are cardinal features of immune systems. Immunological specificity is encoded by receptors expressed on the surface of lymphocytes that are generated through random assembly of variable, diversity, and joining (VDJ) gene segments during B and T lymphocyte development. In addition, B lymphocytes further diversify this initial repertoire through somatic hypermutation of antibody genes in germinal centers (transient structures that form in lymphoid organs in which high-affinity antibodies arise). On page 223 of this issue, Burnett et al. (1) devise a strategy to track the fate of self-reactive B cells in germinal centers elicited by a foreign antigen that structurally mimics a self-antigen (antigen mimicry). The authors provide evidence that hypermutation of antibody genes in germinal centers can repair self-reactive antibodies. These results have implications for how broadly neutralizing antibodies to HIV-1 may be formed.