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  • 1
    Language: English
    In: Science (New York, N.Y.), 09 September 2016, Vol.353(6304)
    Description: We directly measured at the single-molecule level the forces and lifetimes of DNA base-pair stacking interactions for all stack sequence combinations. Our experimental approach combined dual-beam optical tweezers with DNA origami components to allow positioning of blunt-end DNA helices so that the weak stacking force could be isolated. Base-pair stack arrays that lacked a covalent backbone connection spontaneously dissociated at average rates ranging from 0.02 to 500 per second, depending on the sequence combination and stack array size. Forces in the range from 2 to 8 piconewtons that act along the helical direction only mildly accelerated the stochastic unstacking process. The free-energy increments per stack that we estimate from the measured forward and backward kinetic rates ranged from -0.8 to -3.4 kilocalories per mole, depending on the sequence combination. Our data contributes to understanding the mechanics of DNA processing in biology, and it is helpful for designing the kinetics...
    Subject(s): Base Pairing ; Nucleic Acid Conformation ; DNA -- Chemistry
    ISSN: 0036-8075
    E-ISSN: 1095-9203
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  • 2
    Language: English
    In: The Journal of biological chemistry, 29 December 2017, Vol.292(52), pp.21490-21503
    Description: The Ig-like cell adhesion molecule (IgCAM) BT-IgSF (brain- and testis-specific Ig superfamily protein) plays a major role in male fertility in mice. However, the molecular mechanism by which BT-IgSF supports fertility is unclear. Here, we found that it is localized in Sertoli cells at the blood-testis barrier (BTB) and at the apical ectoplasmic specialization. The absence of BT-IgSF in Sertoli cells in both global and conditional mouse mutants ( AMHCre and Rosa26CreERT2 lines) resulted in male infertility, atrophic testes with vacuolation, azoospermia, and spermatogenesis arrest. Although transcripts of junctional proteins such as connexin43, ZO-1, occludin, and claudin11 were up-regulated in the absence of BT-IgSF, the functional integrity of the BTB was impaired, as revealed by injection of a BTB-impermeable component into the testes under conditions. Disruption of the BTB coincided with mislocalization of connexin43, which was present throughout the seminiferous epithelium and not restricted...
    Subject(s): Bt-Igsf (Igsf11) ; Igcam ; Igcam Bt-Igsf (Igsf11) ; Blood–Testis Barrier ; Cell Adhesion ; Connexin43 ; Male Fertility ; Spermatogenesis ; Testis ; Blood-Testis Barrier -- Physiology ; Immunoglobulins -- Physiology ; Spermatogenesis -- Genetics
    ISSN: 0021-9258
    E-ISSN: 1083-351X
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  • 3
    Language: English
    In: Organometallics, 14 February 2011, Vol.30(3), pp.383-385
    Description: Imidazolium salts react with HgO to give mono-NHC dihalomercury(II) complexes in acceptable yields. The solid-state structures of several examples were determined by X-ray diffraction. The complexes consist of monomeric (NHC)HgX2 units, which feature tricoordinated mercury atoms, a structural arrangement rarely found for mercury compounds.
    Subject(s): Chemistry;
    ISSN: 02767333
    E-ISSN: 15206041
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 27 November 2012, Vol.109(48), pp.19679-84
    Description: Mechanical forces are important signals for cell response and development, but detailed molecular mechanisms of force sensing are largely unexplored. The cytoskeletal protein filamin is a key connecting element between the cytoskeleton and transmembrane complexes such as integrins or the von Willebrand receptor glycoprotein Ib. Here, we show using single-molecule mechanical measurements that the recently reported Ig domain pair 20-21 of human filamin A acts as an autoinhibited force-activatable mechanosensor. We developed a mechanical single-molecule competition assay that allows online observation of binding events of target peptides in solution to the strained domain pair. We find that filamin force sensing is a highly dynamic process occurring in rapid equilibrium that increases the affinity to the target peptides by up to a factor of 17 between 2 and 5 pN. The equilibrium mechanism we find here can offer a general scheme for cellular force sensing.
    Subject(s): Contractile Proteins -- Chemistry ; Microfilament Proteins -- Chemistry
    ISSN: 0027-8424
    E-ISSN: 1091-6490
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  • 5
    In: Stroke, 2013, Vol.44(9), pp.e115-e115
    Description: To the Editor: We read with interest the 2 recent articles by Zhu et al1,2 regarding the usefulness of computed tomography perfusion (CTP) studies for predicting outcomes in acute stroke patients. We are puzzled by the analysis of data from the same group of patients being interpreted in such diametrically opposite ways by the same authors. In the first article,1 the authors conclude that a cerebral blood flow/cerebral blood volume mismatch or demonstration of an ischemic penumbra on CTP maps alone cannot predict functional outcome unless recanalization status …
    Subject(s): Medicine;
    ISSN: 0039-2499
    E-ISSN: 15244628
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  • 6
    In: Journal for the Scientific Study of Religion, May 2015, Vol.54(2), pp.380-401
    Description: The political environment for evangelical Protestants has changed substantially since the Christian Right reached its apex, as a more issue and ideologically diffuse political environment has emerged. The present study tests two different theoretical perspectives on whether these contextual changes may have altered Millennial evangelicals’ political perspectives vis‐à‐vis those of previous generations of evangelicals. On the one hand, theoretical perspectives related to differential political socialization processes across generations would lead to expectations of generational change among evangelicals. On the other hand, theoretical perspectives related to social identity theory would suggest far less change across generations. Using Pew's 2007 U.S. Religious Landscape Survey, we test these expectations by comparing the relationships between religiosity and political attitudes across three generations of evangelicals. Ordered probit and logistic regression models estimate the impact of religiosity on various political attitudes. These models reveal that Millennial evangelical religiosity continues to be strongly related to Republican Party identification and opposition toward abortion, which is largely consistent with the social identity perspective. Generational change is most evident in a variety of nonsocial issues in which religiosity is associated with less conservatism among Millennials. Additional analysis using the 2012 Religion and Politics Survey with a smaller sample of Millennial evangelicals confirms these results.
    Subject(s): Millennial Evangelicals ; Religiosity ; Public Opinion
    ISSN: 0021-8294
    E-ISSN: 1468-5906
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  • 7
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 05 November 2013, Vol.110(45), pp.18156-61
    Description: In this study we expand the accessible dynamic range of single-molecule force spectroscopy by optical tweezers to the microsecond range by fast sampling. We are able to investigate a single molecule for up to 15 min and with 300-kHz bandwidth as the protein undergoes tens of millions of folding/unfolding transitions. Using equilibrium analysis and autocorrelation analysis of the time traces, the full energetics as well as real-time kinetics of the ultrafast folding of villin headpiece 35 and a stable asparagine 68 alanine/lysine 70 methionine variant can be measured directly. We also performed Brownian dynamics simulations of the response of the bead-DNA system to protein-folding fluctuations. All key features of the force-dependent deflection fluctuations could be reproduced: SD, skewness, and autocorrelation function. Our measurements reveal a difference in folding pathway and cooperativity between wild-type and stable variant of headpiece 35. Autocorrelation force spectroscopy pushes...
    Subject(s): Chevron Plot ; Langevin Equation ; Markov Model ; Optical Trapping ; Thermodynamics ; Models, Biological ; Protein Folding ; Microfilament Proteins -- Chemistry ; Spectrum Analysis -- Methods
    ISSN: 0027-8424
    E-ISSN: 1091-6490
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  • 8
    In: Stroke, 2012, Vol.43(3), pp.e32-e32
    Subject(s): Carotid Stenosis -- Surgery ; Endarterectomy, Carotid -- Adverse Effects ; Intracranial Hemorrhages -- Etiology ; Reperfusion -- Adverse Effects ; Stents -- Adverse Effects;
    ISSN: 0039-2499
    E-ISSN: 15244628
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  • 9
    Language: English
    In: The Journal of biological chemistry, 18 March 2011, Vol.286(11), pp.8999-9008
    Description: The Helicobacter pylori protein CagA (cytotoxin-associated gene A) is associated with an increased risk for gastric cancer formation. After attachment to epithelial cells, the bacteria inject CagA via a type IV secretion apparatus into host cells, where it exerts its biological activity. Host cell responses to intracellular CagA have been linked exclusively to signaling motifs in the C terminus of the CagA protein. Little is known about the functional role of the remaining CagA protein. Using transgenic expression of CagA mutants in epithelial cells, we were able to identify a novel CagA inhibitory domain at the N terminus consisting of the first 200 amino acids. This domain localizes to cell-cell contacts and increases the rate and strength of cell-cell adhesion in epithelial cells. Thus, it compensates for the loss of cell-cell adhesion induced by the C terminus of the CagA protein. Consistent with its stabilizing role on cell-cell adhesion, the CagA N terminus domain reduces the CagA-induced β-catenin transcriptional activity in the nucleus. Furthermore, it inhibits apical surface constriction and cell elongations, host cell phenotypes induced by the C terminus in polarized epithelia. Therefore, our study suggests that CagA contains an intrinsic inhibitory domain that reduces host cell responses to CagA, which have been associated with the formation of cancer.
    Subject(s): Host-Pathogen Interactions ; Signal Transduction ; Antigens, Bacterial -- Metabolism ; Bacterial Proteins -- Metabolism ; Epithelial Cells -- Microbiology ; Helicobacter Pylori -- Physiology
    ISSN: 00219258
    E-ISSN: 1083-351X
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  • 10
    Language: English
    In: Applied Physics Letters, 14 June 2010, Vol.96(24)
    Description: Four-terminal ambipolar ballistic electron emission microscopy studies are conducted on Au/Si and Cu/Si Schottky contacts fabricated on back-gated silicon-on-insulator wafers, allowing the electric field to be varied so that both electron (n)- and hole (p)-Schottky barrier heights can be measured at the same sample location. While the individual n- and p-Schottky barrier heights varied by more than 200 meV between the Au/Si and Cu/Si contacts, for a given sample they sum to within 15 meV of the same value, indicating that the individual variations are due to variations in a local surface dipole as compared with tip effects or variations in local composition.
    Subject(s): Electronic Transport And Semiconductors;
    ISSN: 00036951
    E-ISSN: 10773118
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