Single-pulse Laue diffraction, stroboscopic data collection and femtosecond flash photolysis on macromolecules

We review the time structure of synchrotron radiation and its use for fast time-resolved diffraction experiments in macromolecular photo-cycles using flash photolysis to initiate the reaction. The source parameters and optics for ID09 at ESRF are presented together with the phase-locked chopper and femtosecond laser. The chopper can set up a 900 Hz pulse train of 100 ps pulses from the hybrid bunch-mode and, in conjunction with a femtosecond laser, it can be used for stroboscopic data collection with both monochromatic and polychromatic beams. Single-pulse Laue data from Cutinase, a 22 kD lipolic enzyme, are presented which show that the quality of single-pulse Laue patterns is sufficient to refine the excited state(s) in a reaction pathway from a known ground state. The flash photolysis technique is discussed and an example is given for heme proteins. The radiation damage from a laser pulse in the femto and picosecond range can be reduced by triggering at a wavelength where the interaction is strong. We propose the use of microcrystals between 25–50 μm for efficient photolysis with femto and picosecond pulses. The performance of circular storage rings is compared with the predicted performance of an X-ray free electron laser (XFEL). The combination of micro beams, a gain of 105105 photons per pulse and an ultrashort pulse length of 100 fs is likely to improve pulsed diffraction data very substantially. It may be used to image coherent nuclear motion at atomic resolution in ultrafast uni-molecular reactions. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87418/2/267_1.pd

British Ornithologists’ Union Records Committee (BOURC): 49th Report (October 2018)

No abstract available

Isolation, Characterization, and Mapping of a Human Acid β-Galactosidase cDNA

A λgt11 human testicular cDNA library was screened with degenerate oligonucleotide probe mixtures based on amino acid sequence data generated from cyanogen bromide fragments and tryptic fragments of purified human β-galactosidase.Six positive clones were identified after screening 2 x 106 plaques. The sequences of these six clones were determined and found to be derived from two different cDNAs. The sequence of the longest of these cDNAs is nearly identical to that recently determined by Oshima et al. (1988). It codes for a 76-kD protein and all 11 peptides that were generated from the purified enzyme. The second clone is shorter by 393 bp in the central portion of the coding region. Analysis by Northern blotting revealed the presence of a single mRNA species of 2.45 kb in lymphoblasts and testicular tissue. It is deduced from the amino acid sequence data that proteolytic processing of the precursor form of β-galactosidase must occur by cleavage in the carboxy-terminal portion of the polypeptide perhaps around amino acid 530 at a uniquely hydrophilic sequence. Using a probe generated from the 3\u27 region of the cDNA, we have mapped the locus coding for human β-galactosidase to chromosome 3p21-3pter

Identification of epitopes recognised by mucosal CD4+ T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7

Additional file 5. Sequence alignment of Intimin epitopes against Intimin sequences from non-O157 EHEC serotypes. Alignment of Intimin CD4+ T-cell epitope sequences with representative Intimin sequences from EHEC serotypes O145, O127, O26, O103, O121, O45 and O111. Percentage values indicate % similarity to the EHEC O157:H7 reference sequence

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effectiveness of a targeted exercise intervention in reversing older peoples mild balance dysfunction: A randomised controlled trail

Background: Previous research has mainly targeted older people with high risk of falling. The effectiveness of exercise interventions in older people with mild levels of balance dysfunction remains unexplored. Objective: This study evaluated the effectiveness of a home balance and strength exercise intervention in older people systematically screened as having mild balance dysfunction. Design: This was a community-based, randomized controlled trial with assessors blinded to group allocation. Participants: Study participants were older people who reported concerns about their balance but remained community ambulant (n=225). After a comprehensive balance assessment, those classified as having mild balance dysfunction (n=165) were randomized into the trial. Intervention: Participants in the intervention group (n=83) received a 6-month physical therapist–prescribed balance and strength home exercise program, based on the Otago Exercise Program and the Visual Health Information Balance and Vestibular Exercise Kit. Participants in the control group (n=82) continued with their usual activities. Outcome Measures: Laboratory and clinical measures of balance, mobility, and strength were assessed at baseline and at a 6-month reassessment.Results: After 6 months, the intervention group (n=59) significantly improved relative to the control group (n=62) for: the Functional Reach Test (mean difference=2.95 cm, 95% confidence interval [CI]=1.75 to 4.15), the Step Test (2.10 steps/15 seconds, 95% CI=1.17 to 3.02), hip abductor strength (0.02, 95% CI=0.01 to 0.03), and gait step width (2.17 cm, 95% CI=1.23 to 3.11). There were nonsignificant trends for improvement on most other measures. Fourteen participants in the intervention group (23.7%) achieved balance performance within the normative range following the exercise program, compared with 3 participants (4.8%) in the control group. Limitations: Loss to follow-up (26.6%) was slightly higher than in some similar studies but was unlikely to have biased the results. Conclusions: A physical therapist–prescribed home exercise program targeting balance and strength was effective in improving a number of balance and related outcomes in older people with mild balance impairment

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented

State-building, war and violence : evidence from Latin America

In European history, war has played a major role in state‐building and the state monopoly on violence. But war is a very specific form of organized political violence, and it is decreasing on a global scale. Other patterns of armed violence now dominate, ones that seem to undermine state‐building, thus preventing the replication of European experiences. As a consequence, the main focus of the current state‐building debate is on fragility and a lack of violence control inside these states. Evidence from Latin American history shows that the specific patterns of the termination of both war and violence are more important than the specific patterns of their organization. Hence these patterns can be conceptualized as a critical juncture for state‐building. While military victories in war, the subordination of competing armed actors and the prosecution of perpetrators are conducive for state‐building, negotiated settlements, coexistence, and impunity produce instability due to competing patterns of authority, legitimacy, and social cohesion

Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway

Human genetic studies have revealed an association between GTP cyclohydrolase 1 polymorphisms, which decrease tetrahydrobiopterin (BH4) levels, and reduced pain in patients. We now show that excessive BH4 is produced in mice by both axotom- ized sensory neurons and macrophages infiltrating damaged nerves and inflamed tissue. Constitutive BH4 overproduction in sensory neurons increases pain sensitivity, whereas blocking BH4 production only in these cells reduces nerve injury-induced hy- persensitivity without affecting nociceptive pain. To minimize risk of side effects, we targeted sepiapterin reductase (SPR), whose blockade allows minimal BH4 production through the BH4 salvage pathways. Using a structure-based design, we developed a potent SPR inhibitor and show that it reduces pain hypersensitivity effectively with a concomitant decrease in BH4 levels in target tissues, acting both on sensory neurons and macrophages, with no development of tolerance or adverse effects. Finally, we demonstrate that sepiapterin accumulation is a sensitive biomarker for SPR inhibition in vivo

A Tale of Four “Carp”: Invasion Potential and Ecological Niche Modeling

. We assessed the geographic potential of four Eurasian cyprinid fishes (common carp, tench, grass carp, black carp) as invaders in North America via ecological niche modeling (ENM). These “carp” represent four stages of invasion of the continent (a long-established invader with a wide distribution, a long-established invader with a limited distribution, a spreading invader whose distribution is expanding, and a newly introduced potential invader that is not yet established), and as such illustrate the progressive reduction of distributional disequilibrium over the history of species' invasions.We used ENM to estimate the potential distributional area for each species in North America using models based on native range distribution data. Environmental data layers for native and introduced ranges were imported from state, national, and international climate and environmental databases. Models were evaluated using independent validation data on native and invaded areas. We calculated omission error for the independent validation data for each species: all native range tests were highly successful (all omission values <7%); invaded-range predictions were predictive for common and grass carp (omission values 8.8 and 19.8%, respectively). Model omission was high for introduced tench populations (54.7%), but the model correctly identified some areas where the species has been successful; distributional predictions for black carp show that large portions of eastern North America are at risk.ENMs predicted potential ranges of carp species accurately even in regions where the species have not been present until recently. ENM can forecast species' potential geographic ranges with reasonable precision and within the short screening time required by proposed U.S. invasive species legislation