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  • Oxford University Press  (11)
  • American Association for the Advancement of Science (AAAS)  (4)
  • 2015-2019  (15)
  • 1965-1969
  • 1940-1944
  • 2019  (15)
Collection
Publisher
Years
  • 2015-2019  (15)
  • 1965-1969
  • 1940-1944
Year
  • 1
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    A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) is a key Ras activator that is autoinhibited in the cytosol and activates upon membrane recruitment. Autoinhibition release involves structural rearrangements of the protein at the membrane and thus introduces a delay between initial recruitment and activation. In this study, we designed a single-molecule assay to resolve the time between initial receptor-mediated membrane recruitment and the initiation of GEF activity of individual SOS molecules on microarrays of Ras-functionalized supported membranes. The rise-and-fall shape of the measured SOS activation time distribution and the long mean time scale to activation (~50 seconds) establish a basis for kinetic proofreading in the receptor-mediated activation of Ras. We further demonstrate that this kinetic proofreading is modulated by the LAT (linker for activation of T cells)–Grb2–SOS phosphotyrosine-driven phase transition at the membrane.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    A metagenomic strategy for harnessing the chemical repertoire of the human microbiome (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Extensive progress has been made in determining the effects of the microbiome on human physiology and disease, but the underlying molecules and mechanisms governing these effects remain largely unexplored. Here, we combine a new computational algorithm with synthetic biology to access biologically active small molecules encoded directly in human microbiome–derived metagenomic sequencing data. We discover that members of a clinically used class of molecules are widely encoded in the human microbiome and that they exert potent antibacterial activities against neighboring microbes, implying a possible role in niche competition and host defense. Our approach paves the way toward a systematic unveiling of the chemical repertoire encoded by the human microbiome and provides a generalizable platform for discovering molecular mediators of microbiome-host and microbiome-microbiome interactions.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Lateral variation of crustal attenuation properties from southern Tibet to eastern Nepal Himalaya (2019)
    Oxford University Press
    Details
    Publication Date: 2019
    Description: 〈span〉〈div〉SUMMARY〈/div〉Lateral variations of body wave, coda wave, intrinsic and scattering attenuation have been investigated using 114 local earthquakes which were recorded in eastern Nepal Himalaya and southern Tibet from October 2001 to March 2003. The extended coda normalization method and single isotropic scattering model are used to estimate the quality factor of body waves (〈span〉Qp〈/span〉, 〈span〉Qs〈/span〉) and coda wave (〈span〉Qc〈/span〉), respectively. We have divided the entire area into two zones such as eastern Nepal Himalaya and southern Tibet to explore the attenuation characteristics laterally. We have used all crustal events within hypocentral distance of 100 km. The observations are made at six different central frequencies such as 2, 4, 6, 8, 10 and 12 Hz. For both regions 〈span〉Q〈/span〉 values are found to be frequency dependent. Subsequently, we separate out the contributions of both intrinsic (〈span〉Qi〈/span〉) and scattering (〈span〉Qsc〈/span〉) attenuation parameters using the Wennerberg approach. It is observed that the intrinsic attenuation prevails over scattering attenuation in eastern Nepal Himalaya at all the frequency ranges while for southern Tibet scattering attenuation dominates at higher frequencies (〉8Hz). The similarity between 〈span〉Qc〈/span〉 and 〈span〉Qi〈/span〉 is noted for both areas, which confirms that the decay of coda wave is primarily due to the intrinsic dissipation. Intrinsic attenuation is found to be higher in southern Tibet, which could be associated with the partial melting, fluid trapped in the crust or high heat flow that exists below the region. The results correlate with the underlying geo-tectonical model as well as with the structural complexities present beneath the study area. The obtained values in this study are well comparable with other results reported for similar tectonic regime.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 4
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    A new metal transfer process for van der Waals contacts to vertical Schottky-junction transition metal dichalcogenide photovoltaics (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Two-dimensional transition metal dichalcogenides are promising candidates for ultrathin optoelectronic devices due to their high absorption coefficients and intrinsically passivated surfaces. To maintain these near-perfect surfaces, recent research has focused on fabricating contacts that limit Fermi-level pinning at the metal-semiconductor interface. Here, we develop a new, simple procedure for transferring metal contacts that does not require aligned lithography. Using this technique, we fabricate vertical Schottky-junction WS〈sub〉2〈/sub〉 solar cells, with Ag and Au as asymmetric work function contacts. Under laser illumination, we observe rectifying behavior and open-circuit voltage above 500 mV in devices with transferred contacts, in contrast to resistive behavior and open-circuit voltage below 15 mV in devices with evaporated contacts. One-sun measurements and device simulation results indicate that this metal transfer process could enable high specific power vertical Schottky-junction transition metal dichalcogenide photovoltaics, and we anticipate that this technique will lead to advances for two-dimensional devices more broadly.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    A metagenomic strategy for harnessing the chemical repertoire of the human microbiome (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Remarkable progress has been made in determining the effects of the microbiome on human physiology and disease, but the underlying molecules and mechanisms governing these effects remain largely unexplored. Here, we combine a new computational algorithm with synthetic biology to access biologically active small molecules encoded directly in human microbiome-derived metagenomic sequencing data. We discover that members of a clinically used class of molecules are widely encoded in the human microbiome, and that they exert potent antibacterial activities against neighboring microbes, implying a possible role in niche competition and host defense. Our approach paves the way toward a systematic unveiling of the chemical repertoire encoded by the human microbiome and provides a generalizable platform for discovering molecular mediators of microbiome-host and microbiome-microbiome interactions.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Lateral variation of crustal attenuation properties from southern Tibet to eastern Nepal Himalaya (2019)
    Oxford University Press
    Details
    Publication Date: 2019
    Description: 〈span〉〈div〉Summary〈/div〉Lateral variations of body wave, coda wave, intrinsic and scattering attenuation have been investigated using 114 local earthquakes which were recorded in eastern Nepal Himalaya and southern Tibet from October 2001 to March 2003. The extended coda normalization method and single isotropic scattering model are used to estimate the quality factor of body waves (〈span〉Qp, Qs〈/span〉) and coda wave (〈span〉Qc〈/span〉) respectively. We have divided the entire area into two zones such as eastern Nepal Himalaya and southern Tibet to explore the attenuation characteristics laterally. We have used all crustal events within hypocentral distance of 100 km. The observations are made at six different central frequencies such as 2, 4, 6, 8, 10 and 12 Hz. For both regions 〈span〉Q〈/span〉 values are found to be frequency dependent. Subsequently we separate out the contributions of both intrinsic (〈span〉Qi〈/span〉) and scattering (〈span〉Qsc〈/span〉) attenuation parameters using usingWennerberg (1993) approach. It is observed that the intrinsic attenuation prevails over scattering attenuation in eastern Nepal Himalaya at all the frequency ranges while for southern Tibet scattering attenuation dominates at higher frequencies (〉8Hz). The similarity between 〈span〉Qc〈/span〉 and 〈span〉Qi〈/span〉 is noticed for both areas which confirms that the decay of coda wave is primarily due to the intrinsic dissipation. Intrinsic attenuation is found to be higher in southern Tibet which could be associated with the partial melting, fluid trapped in the crust, or high heat flow that exists below the region. The results correlate with the underlying geo-tectonical model as well as with the structural complexities present beneath the study area. The obtained values in this study are well comparable with other results reported for similar tectonic regime.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 7
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    Small nucleolar RNAs controlling rRNA processing in Trypanosoma brucei (2019)
    Oxford University Press
    Details
    Publication Date: 2019-01-03
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Targeted DNA oxidation and trajectory of radical DNA using DFT based QM/MM dynamics (2019)
    Oxford University Press
    Details
    Publication Date: 2019-02-18
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Multifunctional transcriptional coactivator PC4 is a global co-regulator of p53-dependent stress response and gene regulation (2019)
    Oxford University Press
    Details
    Publication Date: 2019-06-24
    Description: Human positive coactivator 4 (PC4), a multifunctional chromatin-associated protein, is known to directly interact with p53 and modulate expressions of a few p53-dependent genes. However, the role of PC4 in p53's myriad of other regulatory functions is not known. The p53–PC4 interaction was selectively perturbed by a small peptide which led to abrogation of genotoxic stress-induced up-regulation of many p53-dependent genes and reduction of apoptosis in A549 cells. Over-expression of a PC4 point mutant, incapable of binding p53, recapitulated many of the effects of the peptide. Global gene expression profiling in A549 cells, upon peptide treatment, revealed PC4's involvement in the regulation of many p53-dependent pathways, including the Hippo pathway. Introduction of the peptide in neuronal cells significantly reduced its amyloid-β-induced death. Thus, PC4 emerges as a global co-regulator of p53 and a therapeutic target against pathogeneses where the p53-dependent cell death process plays a crucial role.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
    Published by Oxford University Press on behalf of Japanese Biochemical Society.
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  • 10
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    Comparison of haplotype-based tests for detecting gene–environment interactions with rare variants (2019)
    Oxford University Press
    Details
    Publication Date: 2019-04-18
    Description: Dissecting the genetic mechanism underlying a complex disease hinges on discovering gene–environment interactions (GXE). However, detecting GXE is a challenging problem especially when the genetic variants under study are rare. Haplotype-based tests have several advantages over the so-called collapsing tests for detecting rare variants as highlighted in recent literature. Thus, it is of practical interest to compare haplotype-based tests for detecting GXE including the recent ones developed specifically for rare haplotypes. We compare the following methods: haplo.glm, hapassoc, HapReg, Bayesian hierarchical generalized linear model (BhGLM) and logistic Bayesian LASSO (LBL). We simulate data under different types of association scenarios and levels of gene–environment dependence. We find that when the type I error rates are controlled to be the same for all methods, LBL is the most powerful method for detecting GXE. We applied the methods to a lung cancer data set, in particular, in region 15q25.1 as it has been suggested in the literature that it interacts with smoking to affect the lung cancer susceptibility and that it is associated with smoking behavior. LBL and BhGLM were able to detect a rare haplotype–smoking interaction in this region. We also analyzed the sequence data from the Dallas Heart Study, a population-based multi-ethnic study. Specifically, we considered haplotype blocks in the gene ANGPTL4 for association with trait serum triglyceride and used ethnicity as a covariate. Only LBL found interactions of haplotypes with race (Hispanic). Thus, in general, LBL seems to be the best method for detecting GXE among the ones we studied here. Nonetheless, it requires the most computation time.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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