Photoexcitation of the blue light using FAD photoreceptor AppA results in ultrafast changes to the protein matrix.

Photoexcitation of the flavin chromophore in the BLUF photosensor AppA results in a conformational change that leads to photosensor activation. This conformational change is mediated by a hydrogen-bonding network that surrounds the flavin, and photoexcitation is known to result in changes in the network that include a strengthening of hydrogen bonding to the flavin C4═O carbonyl group. Q63 is a key residue in the hydrogen-bonding network, and replacement of this residue with a glutamate results in a photoinactive mutant.

Is TNF a link between aging-related reproductive endocrine dyscrasia and Alzheimer's disease?

This commentary addresses a novel mechanism by which aging-related changes in reproductive hormones could mediate their action in the brain. It presents the evidence that dyotic endocrine signals modulate the expression of tumor necrosis factor (TNF) and related cytokines, and that these cytokines are a functionally important downstream link mediating neurodegeneration and dysfunction. This convergence of dyotic signaling on TNF-mediated degeneration and dysfunction has important implications for understanding the pathophysiology of AD, stroke, and traumatic brain disease, and also for the treatment of these diseases.

Charge photoinjection in intercalated and covalently bound [Re(CO)3(dppz)(py)]+-DNA constructs monitored by time-resolved visible and infrared spectroscopy.

The complex [Re(CO)(3)(dppz)(py'-OR)](+) (dppz = dipyrido[3,2-a:2',3'-c]phenazine; py'-OR = 4-functionalized pyridine) offers IR sensitivity and can oxidize DNA directly from the excited state, making it a promising probe for the study of DNA-mediated charge transport (CT). The behavior of several covalent and noncovalent Re-DNA constructs was monitored by time-resolved IR (TRIR) and UV/visible spectroscopies, as well as biochemical methods, confirming the long-range oxidation of DNA by the excited complex. Optical excitation of the complex leads to population of MLCT and at least two distinct intraligand states.

Prevalence of anaerobic ammonium-oxidizing bacteria in contaminated groundwater.

Anaerobic ammonium-oxidizing (anammox) bacteria perform an important step in the global nitrogen cycle: anaerobic oxidation of ammonium and reduction of nitrite to form dinitrogen gas (N(2)). Anammox organisms appear to be widely distributed in natural and artificial environments. However, their roles in groundwater ammonium attenuation remain unclear and only limited biomarker-based data confirmed their presence prior to this study.

Metagenomic comparison of direct and indirect soil DNA extraction approaches.

Full pyrosequencing runs of both direct-extracted (high yield, low DNA size) and indirect-extracted DNA (low yield, high DNA size) from the same prairie soil show that the sequence distribution of the majority of the metabolic functions and species detected were statistically similar. Although some microbial functions differed at the 95% confidence interval in bootstrap analyses, the overall functional diversity was the same.

Vibrationally quantum-state-specific dynamics of the reactions of CN radicals with organic molecules in solution.

The dynamics of reactions of CN radicals with cyclohexane, d(12)-cyclohexane, and tetramethylsilane have been studied in solutions of chloroform, dichloromethane, and the deuterated variants of these solvents using ultraviolet photolysis of ICN to initiate a reaction. The H(D)-atom abstraction reactions produce HCN (DCN) that is probed in absorption with sub-picosecond time resolution using ∼500 cm(-1) bandwidth infrared (IR) pulses in the spectral regions corresponding to C-H (or C-D) and C≡N stretching mode fundamental and hot bands. Equivalent IR spectra were obtained for the reactions of CN radicals with the pure solvents.

Development of a real-time PCR assay for detection and quantification of Rhizobium leguminosarum bacteria and discrimination between different biovars in zinc-contaminated soil.

Primers were designed to target 16S rRNA and nodD genes of Rhizobium leguminosarum from DNA extracted from two different soil types contaminated with Zn applied in sewage sludge. Numbers of rhizobia estimated using 16S rRNA gene copy number showed higher abundance than those estimated by both nodD and the most-probable-number (MPN) enumeration method using a plant trap host. Both 16S rRNA gene copies and the MPN rhizobia declined with increased levels of Zn contamination, as did the abundance of the functional gene nodD, providing compelling evidence of a toxic effect of Zn on R.

TNF and leptin tell essentially the same story in Alzheimer's disease.

Both tumor necrosis factor (TNF) and leptin are, independently, under investigation as the central mechanism for Alzheimer's disease. The wider literature provides every indication that both mediators are part of the same pathways thought to cause functional loss in this condition. This association, which has not been specifically addressed in the Alzheimer's disease literature, may be a useful link to expedite future study into the pathogenesis of this condition.

Can an electronic prescribing system detect doctors who are more likely to make a serious prescribing error?

Objectives: We aimed to assess whether routine data produced by an electronic prescribing system might be useful in identifying doctors at higher risk of making a serious prescribing error.

Design: Retrospective analysis of prescribing by junior doctors over 12 months using an electronic prescribing information and communication system. The system issues a graded series of prescribing alerts (low-level, intermediate, and high-level), and warnings and prompts to respond to abnormal test results.

Transcriptome analysis shows differential gene expression in the saprotrophic to parasitic transition of Pochonia chlamydosporia.

Expression profiles were identified in the fungus Pochonia chlamydosporia, a biological control agent of plant parasitic nematodes, through a cDNA-amplified fragment length polymorphism approach. Two isolates with different host ranges, IMI 380407 and IMI 331547, were assayed in conditions of saprotrophic-to-parasitic transition, through in vitro assays. Gene expression profiles from three different nutritional conditions and four sampling times were generated, with eggs of host nematodes Globodera pallida and Meloidogyne incognita.

The war on malaria and Nora Heysen's documentation of Australian medical research through art between 1943 and 1945.

With the expansion of the Second World War into the Pacific in 1941, and due to the deleterious impact of malarial infection on fighting capacity, the Australian Army devoted significant resources to new research into the prevention and treatment of malaria between 1943 and 1945 by forming the Land Headquarters Medical Research Unit in Cairns, Queensland. The documentation of this research became a significant subject for leading Australian artist Nora Heysen, when she was commissioned as the first female war artist by the Australian War Memorial in 1943.

Phototriggering electron flow through Re(I)-modified Pseudomonas aeruginosa azurins.

The [Re(I)(CO)(3)(4,7-dimethyl-1,10-phenanthroline)(histidine-124)(tryptophan-122)] complex, denoted [Re(I)(dmp)(W122)], of Pseudomonas aeruginosa azurin behaves as a single photoactive unit that triggers very fast electron transfer (ET) from a distant (2 nm) Cu(I) center in the protein. Analysis of time-resolved (ps-μs) IR spectroscopic and kinetics data collected on [Re(I)(dmp)(W122)AzM] (in which M=Zn(II), Cu(II), Cu(I); Az=azurin) and position-122 tyrosine (Y), phenylalanine (F), and lysine (K) mutants, together with excited-state DFT/time-dependent (TD)DFT calculations and X-ray structural characterization, reveal the character, energetics, and dynamics of the relevant electronic states of the [Re(I)(dmp)(W122)] unit and a cascade of photoinduced ET and relaxation steps in the corresponding Re-azurins. Optical population of [Re(I)(imidazole-H124)(CO)(3)]→dmp (1)CT states (CT=charge transfer) is followed by around 110 fs intersystem crossing and about 600 ps structural relaxation to a (3)CT state.

Photochemistry of (η(6)-arene)Cr(CO)3 (arene = methylbenzoate, naphthalene, or phenanthrene) in n-heptane solution: population of two excited states following 400 nm excitation as detected by picosecond time-resolved infrared spectroscopy.

The photochemistry of (η(6)-methylbenzoate)Cr(CO)(3), (η(6)-naphthalene)Cr(CO)(3), and (η(6)-phenanthrene)Cr(CO)(3) in n-heptane solution was investigated by picosecond time-resolved infrared spectroscopy (TRIR). The observation of two transient IR features in the organic carbonyl region at 1681 and 1724 cm(-1) following 400 nm excitation of (η(6)-methylbenzoate)Cr(CO)(3) confirms formation of two excited states which are classified as metal-to-arene charge transfer (MACT) and metal-to-CO charge transfer (MCCT), respectively. Time-dependent density functional theory calculations have been used to support these assignments.

Ultrafast excited-state dynamics of rhenium(I) photosensitizers [Re(Cl)(CO)3(N,N)] and [Re(imidazole)(CO)3(N,N)]+: diimine effects.

Femto- to picosecond excited-state dynamics of the complexes [Re(L)(CO)(3)(N,N)](n) (N,N = bpy, phen, 4,7-dimethyl-phen (dmp); L = Cl, n = 0; L = imidazole, n = 1+) were investigated using fluorescence up-conversion, transient absorption in the 650-285 nm range (using broad-band UV probe pulses around 300 nm) and picosecond time-resolved IR (TRIR) spectroscopy in the region of CO stretching vibrations. Optically populated singlet charge-transfer (CT) state(s) undergo femtosecond intersystem crossing to at least two hot triplet states with a rate that is faster in Cl (∼100 fs)(-1) than in imidazole (∼150 fs)(-1) complexes but essentially independent of the N,N ligand. TRIR spectra indicate the presence of two long-lived triplet states that are populated simultaneously and equilibrate in a few picoseconds.

A comparative picosecond transient infrared study of 1-methylcytosine and 5'-dCMP that sheds further light on the excited states of cytosine derivatives.

The role of N1-substitution in controlling the deactivation processes in photoexcited cytosine derivatives has been explored using picosecond time-resolved IR spectroscopy. The simplest N1-substituted derivative, 1-methylcytosine, exhibits relaxation dynamics similar to the cytosine nucleobase and distinct from the biologically relevant nucleotide and nucleoside analogues, which have longer-lived excited-state intermediates. It is suggested that this is the case because the sugar group either facilitates access to the long-lived (1)n(O)π* state or retards its crossover to the ground state.

Bioattenuation in groundwater impacted by landfill leachate traced with δ13C.

The impact on groundwater imparted by the infiltration of high dissolved organic carbon (DOC) leachate from capped, unlined landfills can be attenuated by biogeochemical reactions beyond the waste source, although such reactive loss in the aquifer is difficult to distinguish from conservative advective dispersion. Compound-specific measurement of δ(13)C in carbon species, including CH(4), dissolved inorganic carbon (DIC), and the major DOC compounds (acetate, humic acid, and fulvic acid) provides a constraint in this assessment that can assist in exercises of modeling and prediction of leachate transport. The Trail Road municipal landfill near Ottawa, Ontario, Canada, hosts an unlined sector which produces a highly enriched leachate (DOC >4500 mg/L) that provides a good site to examine reactive attenuation within the receptor aquifer.

Vibrationally quantum-state-specific reaction dynamics of H atom abstraction by CN radical in solution.

Solvent collisions can often mask initial disposition of energy to the products of solution-phase chemical reactions. Here, we show with transient infrared absorption spectra obtained with picosecond time resolution that the nascent HCN products of reaction of CN radicals with cyclohexane in chlorinated organic solvents exhibit preferential excitation of one quantum of the C-H stretching mode and up to two quanta of the bending mode. On time scales of approximately 100 to 300 picoseconds, the HCN products undergo relaxation to the vibrational ground state by coupling to the solvent bath.

CCAAT/enhancer binding protein β expression is increased in the brain during HIV-1-infection and contributes to regulation of astrocyte tissue inhibitor of metalloproteinase-1.

Human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) associated with infection and activation of mononuclear phagocytes (MP) in the brain, occur late in disease. Infected/activated MP initiate neuroinflammation activating glial cells and ultimately disrupting neuronal function. Astrocytes secrete tissue inhibitor of metalloproteinase (TIMP)-1 in response to neural injury.

Ultrafast infrared spectroscopy of an isotope-labeled photoactivatable flavoprotein.

The blue light using flavin (BLUF) domain photosensors, such as the transcriptional antirepressor AppA, utilize a noncovalently bound flavin as the chromophore for photoreception. Since the isoalloxazine ring of the chromophore is unable to undergo large-scale structural change upon light absorption, there is intense interest in understanding how the BLUF protein matrix senses and responds to flavin photoexcitation. Light absorption is proposed to result in alterations in the hydrogen-bonding network that surrounds the flavin chromophore on an ultrafast time scale, and the structural changes caused by photoexcitation are being probed by vibrational spectroscopy.

Accessing the soil metagenome for studies of microbial diversity.

Soil microbial communities contain the highest level of prokaryotic diversity of any environment, and metagenomic approaches involving the extraction of DNA from soil can improve our access to these communities. Most analyses of soil biodiversity and function assume that the DNA extracted represents the microbial community in the soil, but subsequent interpretations are limited by the DNA recovered from the soil. Unfortunately, extraction methods do not provide a uniform and unbiased subsample of metagenomic DNA, and as a consequence, accurate species distributions cannot be determined.

ULTRA: A Unique Instrument for Time-Resolved Spectroscopy.

We report the development of a high-sensitivity time-resolved infrared and Raman spectrometer with exceptional experimental flexibility based on a 10-kHz synchronized dual-arm femtosecond and picosecond laser system. Ultrafast high-average-power titanium sapphire lasers and optical parametric amplifiers provide wavelength tuning from the ultraviolet (UV) to the mid-infrared region. Customized silicon, indium gallium arsenide, and mercury cadmium telluride linear array detectors are provided to monitor the probe laser intensity in the UV to mid-infrared wavelength range capable of measuring changes in sample absorbance of ΔOD ~ 10(-5) in 1 second.

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action.

Background: Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro.

Methods: Cross-sectional study conducted in a large population-based volunteer cohort of twins.

Excited state dynamics and activation parameters of remarkably slow photoinduced CO loss from (η⁶-benzene)Cr(CO)₃ in n-heptane solution: a DFT and picosecond-time-resolved infrared study.

The electronic structure of (η⁶-benzene)Cr(CO)₃ has been calculated using density functional theory and a molecular orbital interaction diagram constructed based on the Cr(CO)₃ and benzene fragments. The highest occupied molecular orbitals are mainly metal based. The nature of the lowest energy excited states were determined by time-dependent density functional theory, and the lowest energy excited state was found to have significant metal to carbonyl charge transfer character.

The Hammersmith Hospital hematopathology case of the month: paraspinal B lymphoblastic lymphoma – problems in diagnosis and initial indolent behavior.

We describe a young man who presented with neurological signs and symptoms, and with a paraspinal soft tissue mass involving the vertebral body at T4. The patient was treated with dexamethasone prior to neurosurgical decompression and debulking. Biopsy showed features of a small B-cell lymphoma possibly of follicle center cell origin.

The roles of TNF in brain dysfunction and disease.

Certain cytokines, the prototype being the highly pleiotropic TNF, have many homeostatic physiological roles, are involved in innate immunity, and cause inflammation when in excess. These cytokines have long been accepted to have central roles in the pathogenesis of systemic or local non-cerebral disease states, whether acute or chronic, and whether or not caused by infectious agents. Over the last decade they have also been appreciated to be broadly important in brain physiology.