Syringyl lignin production in conifers: Proof of concept in a Pine tracheary element system.

Conifers (softwoods) naturally lack syringyl units in their lignins, rendering lignocellulosic materials from such species more difficult to process than syringyl-rich hardwood species. Using a transformable Pinus radiata tracheary element (TE) system as an experimental platform, we investigated whether metabolic engineering can be used to create syringyl lignin in conifers. Pyrolysis-GC/MS and 2D-NMR analysis of P.

Multibeam seeded brillouin sidescatter in inertial confinement fusion experiments.

We present the first observations of multibeam weakly seeded Brillouin sidescatter in indirect-drive inertial confinement fusion (ICF) experiments. Two seeding mechanisms have been identified and quantified: specular reflections ("glint") from opposite hemisphere beams, and Brillouin backscatter from neighboring beams with a different angle of incidence. Seeded sidescatter can dominate the overall coupling losses, so understanding this process is crucial for proper accounting of energy deposition and drive symmetry.

Small glycosylated lignin oligomers are stored in Arabidopsis leaf vacuoles.

Lignin is an aromatic polymer derived from the combinatorial coupling of monolignol radicals in the cell wall. Recently, various glycosylated lignin oligomers have been revealed in Arabidopsis thaliana. Given that monolignol oxidation and monolignol radical coupling are known to occur in the apoplast, and glycosylation in the cytoplasm, it raises questions about the subcellular localization of glycosylated lignin oligomer biosynthesis and their storage.

Tricin, a flavonoid monomer in monocot lignification.

Tricin was recently discovered in lignin preparations from wheat (Triticum aestivum) straw and subsequently in all monocot samples examined. To provide proof that tricin is involved in lignification and establish the mechanism by which it incorporates into the lignin polymer, the 4'-O-β-coupling products of tricin with the monolignols (p-coumaryl, coniferyl, and sinapyl alcohols) were synthesized along with the trimer that would result from its 4'-O-β-coupling with sinapyl alcohol and then coniferyl alcohol. Tricin was also found to cross couple with monolignols to form tricin-(4'-O-β)-linked dimers in biomimetic oxidations using peroxidase/hydrogen peroxide or silver (I) oxide.

Introduction of chemically labile substructures into Arabidopsis lignin through the use of LigD, the Cα-dehydrogenase from Sphingobium sp. strain SYK-6.

Bacteria-derived enzymes that can modify specific lignin substructures are potential targets to engineer plants for better biomass processability. The Gram-negative bacterium Sphingobium sp. SYK-6 possesses a Cα-dehydrogenase (LigD) enzyme that has been shown to oxidize the α-hydroxy functionalities in β-O-4-linked dimers into α-keto analogues that are more chemically labile.

Hohlraum glint and laser pre-pulse detector for NIF experiments using velocity interferometer system for any reflector.

Laser pre-pulse and early-time laser reflection from the hohlraum wall onto the capsule (termed "glint") can cause capsule imprint and unwanted early-time shocks on indirect drive implosion experiments. In a minor modification to the existing velocity interferometer system for any reflector diagnostic on NIF a fast-response vacuum photodiode was added to detect this light. The measurements show evidence of laser pre-pulse and possible light reflection off the hohlraum wall and onto the capsule.

Polarimetry of uncoupled light on the NIF.

Polarimetry has been added to the full aperture backscatter diagnostic on the NIF. Wollaston prisms are used to sample a small region of a beam's backscatter, effectively separating it into two linear polarizations, one of which is parallel to the incident beam. A time-averaged measurement of each polarization is obtained by imaging the separated spots off of a scatter plate.

Quantitative ultrasound of denervated hand muscles.

Introduction: Presentations to the neuromuscular clinic commonly involve hand muscle denervation, but few studies have evaluated hand muscle ultrasound.

Methods: Ultrasound studies of abductor pollicis brevis, first dorsal interosseous, and abductor digit minimi were prospectively performed in a cohort of 34 patients (77 muscles) with electromyography (EMG)-confirmed denervation, compared with 58 healthy control subjects.

Results: In control subjects, muscle thickness was highly reproducible [intraclass correlation coefficient (ICC) = 0.

Mutation of the inducible ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE2 alters lignin composition and improves saccharification.

ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE1 (ATR1) and ATR2 provide electrons from NADPH to a large number of CYTOCHROME P450 (CYP450) enzymes in Arabidopsis (Arabidopsis thaliana). Whereas ATR1 is constitutively expressed, the expression of ATR2 appears to be induced during lignin biosynthesis and upon stresses. Therefore, ATR2 was hypothesized to be preferentially involved in providing electrons to the three CYP450s involved in lignin biosynthesis: CINNAMATE 4-HYDROXYLASE (C4H), p-COUMARATE 3-HYDROXYLASE1 (C3H1), and FERULATE 5-HYDROXYLASE1 (F5H1).

A highly diastereoselective oxidant contributes to Ligninolysis by the white rot basidiomycete Ceriporiopsis subvermispora.

The white rot basidiomycete Ceriporiopsis subvermispora delignifies wood selectively and has potential biotechnological applications. Its ability to remove lignin before the substrate porosity has increased enough to admit enzymes suggests that small diffusible oxidants contribute to delignification. A key question is whether these unidentified oxidants attack lignin via single-electron transfer (SET), in which case they are expected to cleave its propyl side chains between Cα and Cβ and to oxidize the threo-diastereomer of its predominating β-O-4-linked structures more extensively than the corresponding erythro-diastereomer.

Phenylcoumaran benzylic ether reductase prevents accumulation of compounds formed under oxidative conditions in poplar xylem.

Phenylcoumaran benzylic ether reductase (PCBER) is one of the most abundant proteins in poplar (Populus spp) xylem, but its biological role has remained obscure. In this work, metabolite profiling of transgenic poplar trees downregulated in PCBER revealed both the in vivo substrate and product of PCBER. Based on mass spectrometry and NMR data, the substrate was identified as a hexosylated 8-5-coupling product between sinapyl alcohol and guaiacylglycerol, and the product was identified as its benzyl-reduced form.

A group of sequence-related sphingomonad enzymes catalyzes cleavage of β-aryl ether linkages in lignin β-guaiacyl and β-syringyl ether dimers.

Lignin biosynthesis occurs via radical coupling of guaiacyl and syringyl hydroxycinnamyl alcohol monomers (i.e., "monolignols") through chemical condensation with the growing lignin polymer.

A click chemistry strategy for visualization of plant cell wall lignification.

Bioorthogonal click chemistry was commissioned to visualize the plant cell wall lignification process in vivo. This approach uses chemical reporter-tagged monolignol mimics that can be metabolically incorporated into lignins and subsequently derivatized via copper-assisted or copper-free click reactions.

Laccases direct lignification in the discrete secondary cell wall domains of protoxylem.

Plants precisely control lignin deposition in spiral or annular secondary cell wall domains during protoxylem tracheary element (TE) development. Because protoxylem TEs function to transport water within rapidly elongating tissues, it is important that lignin deposition is restricted to the secondary cell walls in order to preserve the plasticity of adjacent primary wall domains. The Arabidopsis (Arabidopsis thaliana) inducible VASCULAR NAC DOMAIN7 (VND7) protoxylem TE differentiation system permits the use of mutant backgrounds, fluorescent protein tagging, and high-resolution live-cell imaging of xylem cells during secondary cell wall development.

First trimester vitamin D status and placental epigenomics in preeclampsia among Northern Plains primiparas.

Aims: As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to determine variations in DNA methylation patterns and associated protein expression in placental genes regulating vitamin D metabolism.

Main Methods: A convenience sample of 48 pregnant nulliparous women, including 11 later diagnosed with preeclampsia, were recruited in this prospective study. Using a case-control design in two groups of women, we administered a food frequency questionnaire to determine vitamin D dietary intake.

Influence of Populus genotype on gene expression by the wood decay fungus Phanerochaete chrysosporium.

We examined gene expression patterns in the lignin-degrading fungus Phanerochaete chrysosporium when it colonizes hybrid poplar (Populus alba × tremula) and syringyl (S)-rich transgenic derivatives. A combination of microarrays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) allowed detection of a total of 9,959 transcripts and 793 proteins. Comparisons of P.

A comparison of ultrasonographic and electrophysiologic 'inching' in ulnar neuropathy at the elbow.

Objective: The present study aimed to clarify the relationship between structural ulnar nerve changes and electrophysiological nerve dysfunction in patients with ulnar neuropathy at the elbow (UNE).

Methods: High-resolution ultrasonography of the ulnar nerve was performed on 17 limbs with clinically and electrophysiologically confirmed UNE, and 52 control subjects at four standardised sites proximal and distal to the medial epicondyle (P2, P1, D1, D2), corresponding to segments of ulnar short-segment nerve conduction studies ("inching studies").

Results: Ulnar nerve cross-sectional area (CSA) and hypoechoic fraction were significantly increased in patients with UNE immediately distal (D1) and proximal (P1) to the medial epicondyle (p<0.

Determination of the Structure and Catalytic Mechanism of Sorghum bicolor Caffeic Acid O-Methyltransferase and the Structural Impact of Three brown midrib12 Mutations.

Using S-adenosyl-methionine as the methyl donor, caffeic acid O-methyltransferase from sorghum (Sorghum bicolor; SbCOMT) methylates the 5-hydroxyl group of its preferred substrate, 5-hydroxyconiferaldehyde. In order to determine the mechanism of SbCOMT and understand the observed reduction in the lignin syringyl-to-guaiacyl ratio of three brown midrib12 mutants that carry COMT gene missense mutations, we determined the apo-form and S-adenosyl-methionine binary complex SbCOMT crystal structures and established the ternary complex structure with 5-hydroxyconiferaldehyde by molecular modeling. These structures revealed many features shared with monocot ryegrass (Lolium perenne) and dicot alfalfa (Medicago sativa) COMTs.

Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development.

We recently reported the discovery of GSK2606414 (1), a selective first in class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), which inhibited PERK activation in cells and demonstrated tumor growth inhibition in a human tumor xenograft in mice. In continuation of our drug discovery program, we applied a strategy to decrease inhibitor lipophilicity as a means to improve physical properties and pharmacokinetics. This report describes our medicinal chemistry optimization culminating in the discovery of the PERK inhibitor GSK2656157 (6), which was selected for advancement to preclinical development.

Transient hyperckemia in the setting of neuromyelitis optica (NMO).

Introduction: Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerves from an autoimmune response against water channel aquaporin-4 (AQP4). We report 2 patients with transient hyperCKemia associated with NMO suggesting possible skeletal muscle damage.

Methods: Patient 1 was a 72-year-old man who presented with muscle soreness and elevated serum creatine kinase (CK) preceding an initial attack of NMO.