A case study of transport of tropical marine boundary layer and lower tropospheric air masses to the northern midlatitude upper troposphere

Low-ozone (<20 ppbv) air masses were observed in the upper troposphere in northern midlatitudes over the eastern United States and the North Atlantic Ocean on several occasions in October 1997 during the NASA Subsonic Assessment, Ozone and Nitrogen Oxide Experiment (SONEX) mission. Three cases of low-ozone air masses were shown to have originated in the tropical Pacific marine boundary layer or lower troposphere and advected poleward along a warm conveyor belt during a synoptic-scale disturbance. The tropopause was elevated in the region with the low-ozone air mass. Stratospheric intrusions accompanied the disturbances. On the basis of storm track and stratospheric intrusion climatologies, such events appear to be more frequent from September through March than the rest of the year. Copyright 2000 by the American Geophysical Union

Biotransformation of doxycycline by \u3ci\u3eBrevundimonas naejangsanensis\u3c/i\u3e and \u3ci\u3eSphingobacterium mizutaii\u3c/i\u3e strains

The fate of doxycycline (DC), a second generation tetracycline antibiotic, in the environment has drawn increasing attention in recent years due to its wide usage. Little is known about the biodegradability of DC in the environment. The objective of this study was to characterize the biotransformation of DC by pure bacterial strains with respect to reaction kinetics under different environmental conditions and biotransformation products. Two bacterial strains, Brevundimonas naejangsanensis DD1 and Sphingobacterium mizutaii DD2, were isolated from chicken litter and characterized for their biotransformation capability of DC. Results show both strains rely on cometabolism to biotransform DC with tryptone as primary growth substrate. DD2 had higher biotransformation kinetics than DD1. The two strains prefer similar pHs (7 and 8) and temperature (30 °C), however, they exhibited opposite responses to increasing background tryptone concentration. While hydrolysis converted DC to its isomer or epimer, the two bacterial strains converted DC to various biotransformation products through a series of demethylation, dehydration, decarbonylation and deamination. Findings from the study can be used to better predict the fate of DC in the environment

Structure-guided engineering of Lactococcus lactis alcohol dehydrogenase LlAdhA for improved conversion of isobutyraldehyde to isobutanol

We have determined the X-ray crystal structures of the NADH-dependent alcohol dehydrogenase LlAdhA from Lactococcus lactis and its laboratory-evolved variant LlAdhA^(RE1) at 1.9 Å and 2.5 Å resolution, respectively. LlAdhA^(RE1), which contains three amino acid mutations (Y50F, I212T, and L264V), was engineered to increase the microbial production of isobutanol (2-methylpropan-1-ol) from isobutyraldehyde (2-methylpropanal). Structural comparison of LlAdhA and LlAdhA^(RE1) indicates that the enhanced activity on isobutyraldehyde stems from increases in the protein's active site size, hydrophobicity, and substrate access. Further structure-guided mutagenesis generated a quadruple mutant (Y50F/N110S/I212T/L264V), whose K_M for isobutyraldehyde is ∼17-fold lower and catalytic efficiency (k_(cat)/K_M) is ∼160-fold higher than wild-type LlAdhA. Combining detailed structural information and directed evolution, we have achieved significant improvements in non-native alcohol dehydrogenase activity that will facilitate the production of next-generation fuels such as isobutanol from renewable resources

Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation

Heterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an α subunit with intrinsic GTPase activity and a βγ heterodimer, the trimeric complex dissociates upon receptor-mediated nucleotide exchange on the α subunit, enabling each component to engage downstream effector targets for either activation or inhibition as dictated in a particular pathway. To mitigate excessive effector engagement and concomitant signal transmission, the Gα subunit's intrinsic activation timer (the rate of GTP hydrolysis) is regulated spatially and temporally by a class of GTPase accelerating proteins (GAPs) known as the regulator of G protein signaling (RGS) family. The array of G protein-coupled receptors, Gα subunits, RGS proteins and downstream effectors in mammalian systems is vast. Understanding the molecular determinants of specificity is critical for a comprehensive mapping of the G protein system. Here, we present the 2.9 Å crystal structure of the enigmatic, neuronal G protein Gαo in the GTP hydrolytic transition state, complexed with RGS16. Comparison with the 1.89 Å structure of apo-RGS16, also presented here, reveals plasticity upon Gαo binding, the determinants for GAP activity, and the structurally unique features of Gαo that likely distinguish it physiologically from other members of the larger Gαi family, affording insight to receptor, GAP and effector specificity

Crystal structure of the Nogo-receptor-2

The inhibition of axon regeneration upon mechanical injury is dependent on interactions between Nogo receptors (NgRs) and their myelin-derived ligands. NgRs are composed of a leucine-rich repeat (LRR) region, thought to be structurally similar among the different isoforms of the receptor, and a divergent “stalk” region. It has been shown by others that the LRR and stalk regions of NgR1 and NgR2 have distinct roles in conferring binding affinity to the myelin associated glycoprotein (MAG) in vivo . Here, we show that purified recombinant full length NgR1 and NgR2 maintain significantly higher binding affinity for purified MAG as compared to the isolated LRR region of either NgR1 or NgR2. We also present the crystal structure of the LRR and part of the stalk regions of NgR2 and compare it to the previously reported NgR1 structure with respect to the distinct signaling properties of the two receptor isoforms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83453/1/597_ftp.pd

Constraints on T-Odd, P-Even Interactions from Electric Dipole Moments

We construct the relationship between nonrenormalizable,effective, time-reversal violating (TV) parity-conserving (PC) interactions of quarks and gauge bosons and various low-energy TVPC and TV parity-violating (PV) observables. Using effective field theory methods, we delineate the scenarious under which experimental limits on permanent electric dipole moments (EDM's) of the electron, neutron, and neutral atoms as well as limits on TVPC observables provide the most stringent bounds on new TVPC interactions. Under scenarios in which parity invariance is restored at short distances, the one-loop EDM of elementary fermions generate the most severe constraints. The limits derived from the atomic EDM of $^{199}$Hg are considerably weaker. When parity symmetry remains broken at short distances, direct TVPC search limits provide the least ambiguous bounds. The direct limits follow from TVPC interactions between two quarks.Comment: 43 pages, 9 figure

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

Interventions for treating depression after stroke

Background: Depression is an important consequence of stroke that impacts on recovery yet is often not detected or inadequately treated. This is an update of a Cochrane review first published in 2004. Objectives: To determine whether pharmaceutical, psychological, or electroconvulsive treatment (ECT) of depression in patients with stroke can improve outcome. Search strategy: We searched the trials registers of the Cochrane Stroke Group (last searched October 2007) and the Cochrane Depression Anxiety and Neurosis Group (last searched February 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2008), MEDLINE (1966 to May 2006), EMBASE (1980 to May 2006), CINAHL (1982 to May 2006), PsycINFO (1967 to May 2006) and other databases. We also searched reference lists, clinical trials registers, conference proceedings and dissertation abstracts, and contacted authors, researchers and pharmaceutical companies. Selection criteria: Randomised controlled trials comparing pharmaceutical agents with placebo, or various forms of psychotherapy or ECT with standard care (or attention control), in patients with stroke, with the intention of treating depression. Data collection and analysis: Two review authors selected trials for inclusion and assessed methodological quality; three review authors extracted, cross-checked and entered data. Primary analyses were the prevalence of diagnosable depressive disorder at the end of treatment. Secondary outcomes included depression scores on standard scales, physical function, death, recurrent stroke and adverse effects. Main results: Sixteen trials (17 interventions), with 1655 participants, were included in the review. Data were available for 13 pharmaceutical agents, and four trials of psychotherapy. There were no trials of ECT. The analyses were complicated by the lack of standardised diagnostic and outcome criteria, and differing analytic methods. There was some evidence of benefit of pharmacotherapy in terms of a complete remission of depression and a reduction (improvement) in scores on depression rating scales, but there was also evidence of an associated increase in adverse events. There was no evidence of benefit of psychotherapy. Authors' conclusions: A small but significant effect of pharmacotherapy (not psychotherapy) on treating depression and reducing depressive symptoms was found, as was a significant increase in adverse events. More research is required before recommendations can be made about the routine use of such treatments

Folding Mechanism of Beta-Hairpin Trpzip2: Heterogeneity, Transition State and Folding Pathways

We review the studies on the folding mechanism of the β-hairpin tryptophan zipper 2 (trpzip2) and present some additional computational results to refine the picture of folding heterogeneity and pathways. We show that trpzip2 can have a two-state or a multi-state folding pattern, depending on whether it folds within the native basin or through local state basins on the high-dimensional free energy surface; Trpzip2 can fold along different pathways according to the packing order of tryptophan pairs. We also point out some important problems related to the folding mechanism of trpzip2 that still need clarification, e.g., a wide distribution of the computed conformations for the transition state ensemble

Focused ultrasound-mediated brain genome editing.

Gene editing in the brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches mainly rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain