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Rebecca S. Bart Mawsheng Chern Miguel E. Vega-Sánchez Patrick Canlas Pamela C. Ronald 《PLoS genetics》2010,6(9)
Rice NH1 (NPR1 homolog 1) is a key mediator of innate immunity. In both plants and animals, the innate immune response is often accompanied by rapid cell death at the site of pathogen infection. Over-expression of NH1 in rice results in resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo), constitutive expression of defense related genes and enhanced benzothiadiazole (BTH)- mediated cell death. Here we describe a forward genetic screen that identified a suppressor of NH1-mediated lesion formation and resistance, snl6. Comparative genome hybridization and fine mapping rapidly identified the genomic location of the Snl6 gene. Snl6 is a member of the cinnamoyl-CoA reductase (CCR)-like gene family. We show that Snl6 is required for NH1-mediated resistance to Xoo. Further, we show that Snl6 is required for pathogenesis-related gene expression. In contrast to previously described CCR family members, disruption of Snl6 does not result in an obvious morphologic phenotype. Snl6 mutants have reduced lignin content and increased sugar extractability, an important trait for the production of cellulosic biofuels. These results suggest the existence of a conserved group of CCR-like genes involved in the defense response, and with the potential to alter lignin content without affecting development. 相似文献
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Channel functions of the neuronal α4β2 nicotinic acetylcholine receptor (nAChR), one of the most widely expressed subtypes in the brain, can be inhibited by volatile anesthetics. Our Na+ flux experiments confirmed that the second transmembrane domains (TM2) of α4 and β2 in 2:3 stoichiometry, (α4)2(β2)3, could form pentameric channels, whereas the α4 TM2 alone could not. The structure, topology, and dynamics of the α4 TM2 and (α4)2(β2)3 TM2 in magnetically aligned phospholipid bicelles were investigated using solid-state NMR spectroscopy in the absence and presence of halothane and isoflurane, two clinically used volatile anesthetics. 2H NMR demonstrated that anesthetics increased lipid conformational heterogeneity. Such anesthetic effects on lipids became more profound in the presence of transmembrane proteins. PISEMA experiments on the selectively 15N-labeled α4 TM2 showed that the TM2 formed transmembrane helices with tilt angles of 12° ± 1° and 16° ± 1° relative to the bicelle normal for the α4 and (α4)2(β2)3 samples, respectively. Anesthetics changed the tilt angle of the α4 TM2 from 12° ± 1° to 14° ± 1°, but had only a subtle effect on the tilt angle of the (α4)2(β2)3 TM2. A small degree of wobbling motion of the helix axis occurred in the (α4)2(β2)3 TM2. In addition, a subset of the (α4)2(β2)3 TM2 exhibited counterclockwise rotational motion around the helix axis on a time scale slower than 10- 4 s in the presence of anesthetics. Both helical tilting and rotational motions have been identified computationally as critical elements for ion channel functions. This study suggested that anesthetics could alter these motions to modulate channel functions. 相似文献
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MARIA E. MCNAMARA PATRICK J. ORR TOM MANZOCCHI LUIS ALCALÁ PERE ANADÓN ENRIQUE PEÑALVER 《Lethaia: An International Journal of Palaeontology and Stratigraphy》2012,45(2):210-226
McNamara, M.E., Orr, P.J., Manzocchi, T., Alcalá, L., Anadón, P. & Peñalver, E. 2011: Biological controls upon the physical taphonomy of exceptionally preserved salamanders from the Miocene of Rubielos de Mora, northeast Spain. Lethaia, Vol. 45, pp. 210–226. The middle Miocene Rubielos de Mora Konservat‐Lagerstätte of northeast Spain is hosted within profundal, finely laminated, lacustrine mudstones. The diverse biota includes abundant salamanders. Most individuals died during separate episodes and sank rapidly postmortem. Specimens are typically preserved in dorso‐ventral aspect, the most hydrodynamically stable orientation. The near‐cylindrical morphology of the body, however, allowed some carcasses to settle in or subsequently re‐orientate into, lateral orientations. Loss of skeletal elements (i.e. reduced completeness) reflects their location within the body and followed a distal to proximal trend. Two stages are identified: initial loss of a small number of phalanges, followed by loss of more proximal limb bones plus additional phalanges. Disarticulation is more complex: it occurred via several mechanisms (notably, abdominal rupture and re‐orientation of part of the body and limbs during decay) and shows no consistent pattern among specimens. The physical taphonomy of the salamanders is controlled predominantly by intrinsic biological factors, i.e. the geometry of the body and of individual skeletal elements, the orientation, inherent strength and location of specific joints and the extent to which soft tissues, particularly the skin, persist during decay. These biological factors probably control patterns of physical taphonomy of other fossil tetrapods with a similar skeletal configuration. □Articulation, completeness, Konservat‐Lagerstätten, orientation, quantitative taphonomy, salamanders. 相似文献
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Steve Horvath Abu NM Nazmul-Hossain Rodney PE Pollard Frans GM Kroese Arjan Vissink Cees GM Kallenberg Fred KL Spijkervet Hendrika Bootsma Sara A Michie Sven U Gorr Ammon B Peck Chaochao Cai Hui Zhou David TW Wong 《Arthritis research & therapy》2012,14(6):1-13
Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. 相似文献
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Ma D Brandon NR Cui T Bondarenko V Canlas C Johansson JS Tang P Xu Y 《Biophysical journal》2008,94(11):4454-4463
The four-α-helix bundle mimics the transmembrane domain of the Cys-loop receptor family believed to be the protein target for general anesthetics. Using high resolution NMR, we solved the structure (Protein Data Bank ID: 2I7U) of a prototypical dimeric four-α-helix bundle, (Aα2-L1M/L38M)2, with designed specific binding pockets for volatile anesthetics. Two monomers of the helix-turn-helix motif form an antiparallel dimer as originally designed, but the high-resolution structure exhibits an asymmetric quaternary arrangement of the four helices. The two helices from the N-terminus to the linker (helices 1 and 1′) are associated with each other in the dimer by the side-chain ring stacking of F12 and W15 along the long hydrophobic core and by a nearly perfect stretch of hydrophobic interactions between the complementary pairs of L4, L11, L18, and L25, all of which are located at the heptad e position along the helix-helix dimer interface. In comparison, the axes of the two helices from the linker to the C-terminus (helices 2 and 2′) are wider apart from each other, creating a lateral access pathway around K47 from the aqueous phase to the center of the designed hydrophobic core. The site of the L38M mutation, which was previously shown to increase the halothane binding affinity by ∼3.5-fold, is not part of the hydrophobic core presumably involved in the anesthetic binding but shows an elevated transverse relaxation (R2) rate. Qualitative analysis of the protein dynamics by reduced spectral density mapping revealed exchange contributions to the relaxation at many residues in the helices. This observation was confirmed by the quantitative analysis using the Modelfree approach and by the NMR relaxation dispersion measurements. The NMR structures and Autodock analysis suggest that the pocket with the most favorable amphipathic property for anesthetic binding is located between the W15 side chains at the center of the dimeric hydrophobic core, with the possibility of two additional minor binding sites between the F12 and F52 ring stacks of each monomer. The high-resolution structure of the designed anesthetic-binding protein offers unprecedented atomistic details about possible sites for anesthetic-protein interactions that are essential to the understanding of molecular mechanisms of general anesthesia. 相似文献
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Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer
Elizabeth A. Bowling Jarey H. Wang Fade Gong William Wu Nicholas J. Neill Ik Sun Kim Siddhartha Tyagi Mayra Orellana Sarah J. Kurley Rocio Dominguez-Vidaña Hsiang-Ching Chung Tiffany Y.-T. Hsu Julien Dubrulle Alexander B. Saltzman Heyuan Li Jitendra K. Meena Gino M. Canlas Srinivas Chamakuri Thomas F. Westbrook 《Cell》2021,184(2):384-403.e21
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Eight Danish Holstein cows were milked with a 1-mm thick specially designed soft liner on their right rear teat and a standard
liner mounted under extra high tension on their left rear teat. Four of the animals were overmilked for 5 min. Rear teats
were subjected to ultrasound examination on the first day and to infrared thermography on the second day. Teats were submersed
in ethanol 20 min post-milking on the second day. Ultrasonography measurements showed that teat canal length increased by
30–41% during milking. Twenty minutes after milking, teats milked with modified standard liners still had elongated teat canals
while teats milked with the soft liner were normalized. Overmilking tended to increase teat wall thickness. Approximately
80% of variability in teat canal length, from before teat preparation to after milking, could be explained by changes during
teat preparation. Thermography indicated a general drop in teat temperature during teat preparation. Teat temperature increased
during milking and continued to increase until the ethanol challenge induced a significant drop. Temperatures approached pre-challenge
rather than pre-milking temperatures within 10 minutes after challenge. Teat temperatures were dependent on type of liner.
Mid-teat temperatures post-challenge relative to pre-teat preparation were dependent on overmilking. Thermography and ultrasound
were considered useful methods to indirectly and non invasively evaluate teat tissue integrity. 相似文献