bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactions of simple aromatic heterocycles with niobium cluster ions (n≤30)
Authors: Pfeffer Britta , Jaberg Stephanie , Niedner-Schatteburg Gereon
Published: November 2009

Prior work on benzene activation by size selected niobium cluster cations and anions of up to 30 atoms is extended systematically through studying aromatic poly- and heterocyclic molecules such as naphthalene, pyridine, thiophene, pyrrole, furan, and benzofuran. Naphthalene is found to act much like benzene when reacting under single collision conditions with individual clusters. The most likely process is carbidization through complete dehydrogenation. Some clusters of particular sizes (most notably n=19) fail to activate both homocyclic molecules. Instead seemingly intact adsorption is observed which proves that activation is kinetically hindered at some point. All of the five studied heterocyclic aromatic molecules react unconditionally and by complete dehydrogenation with cationic niobium clusters, while they only attach to or react with anionic clusters larger than a minimum size of n=19–21. These findings are taken as strong evidence for initial coordination to the metal clusters of the heterocycles through their lone pair orbitals. The paper comprehends the observations in terms of cluster surface structure and reactivity.
All-atom ab initio native structure prediction of a mixed fold (1FME): A comparison of structural and folding characteristics of various ββα miniproteins
Authors: Kim Eunae , Jang Soonmin , Pak Youngshang
Published: November 2009

We performed an all-atom ab initio native structure prediction of 1FME, which is one of the computationally challenging mixed fold ββα miniproteins, by combining a novel conformational search algorithm (multiplexed Q-replica exchange molecular dynamics scheme) with a well-balanced all-atom force field employing a generalized Born implicit solvation model (param99MOD5/GBSA). The nativelike structure of 1FME was identified from the lowest free energy minimum state and in excellent agreement with the NMR structure. Based on the interpretation of the free energy landscape, the structural properties as well as the folding behaviors of 1FME were compared with other ββα miniproteins (1FSD, 1PSV, and BBA5) that we have previously studied with the same force field. Our simulation showed that the 28-residue ββα miniproteins (1FME, 1FSD, and 1PSV) share a common feature of the free energy topography and exhibit the three local minimum states on each computed free energy map, but the 23-residue miniprotein (BBA5) follows a downhill folding with a single minimum state. Also, the structure and stability changes resulting from the two point mutation (Gln1→Glu1 and Ile7→Tyr7) of 1FSD were investigated in details for direct comparison with the experiment. The comparison shows that upon mutation, the experimentally observed turn type switch from an irregular turn (1FSD) to type I′ turn (1FME) was well reproduced with the present simulation.
Four discrete Hall resistance states in single-layer Fe film for quaternary memory devices
Authors: Yoo Taehee , Khym S. , Yea Sun-young , Chung Sunjae , Lee Sanghoon , Liu X. , Furdyna J. K.
Published: November 2009

We report the realization of four distinct magnetic states using single layers of Fe at room temperature. When the Fe film was grown on the vicinal surface of GaAs, the fourfold-symmetric magnetization along crystallographic direction give rise to four distinct Hall resistance values due to the different combination of planar and anomalous Hall effects for the given direction. Each Hall resistance state can be written reproducibly by the sequence of field pulses and was remained constant at the written state for more than 2 h, which brings the idea of a quaternary memory device much closer to practical implementation.
Dynamical and quasistatic structural relaxation paths in Pd40Ni40P20 glass
Authors: Kahl A. , Koeppe T. , Bedorf D. , Richert R. , Lind M. L. , Demetriou M. D. , Johnson W. L. , Arnold W. , Samwer K.
Published: November 2009

By sequential heat treatment of a Pd40Ni40P20 metallic glass at temperatures and durations for which α-relaxation is not possible, dynamic, and quasistatic relaxation paths below the glass transition are identified via ex situ ultrasonic measurements following each heat treatment. The dynamic relaxation paths are associated with hopping between nonequilibrium potential energy states of the glass, while the quasistatic relaxation path is associated with reversible β-relaxation events toward quasiequilibrium states. These quasiequilibrium states are identified with secondary potential energy minima that exist within the inherent energy minimum of the glass, thereby supporting the concept of the sub-basin/metabasin organization of the potential-energy landscape.
Preserved Striate Cortex is Not Sufficient to Support the McCollough Effect: Evidence from two Patients with Cerebral Achromatopsia
Authors: Mullin Caitlin R , Démonet Jean François , Kentridge Robert W , Heywood Charles A , Goodale Melvyn A , Steeves Jennifer K E
Published: November 2009

The McCollough effect (ME) is a colour aftereffect contingent on pattern orientation. This effect is generally thought to be mediated by primary visual cortex (V1) although this has remained the subject of some debate. To determine whether V1 is in fact sufficient to subserve the ME, we compared McCollough adaptation in controls to adaptation in two patients with damage to ventrotemporal cortex, resulting in achromatopsia, but who have spared V1. Each of these patients has some residual colour abilities of which he is unaware. Participants performed a 2AFC orientation-discrimination task for pairs of oblique and vertical/horizontal gratings both before and after adaptation to red/green oblique induction gratings. Successful ME induction would manifest itself as an improvement in oblique-orientation discrimination owing to the additional colour cue after adaptation. Indeed, in controls oblique grating discrimination improved post-adaptation. Further, a subdivision of our control group demonstrated successful ME induction despite a lack of conscious awareness of the added colour cue, indicating that conscious colour awareness is not required for ME induction. The patients, however, did not show improvement in oblique-orientation discrimination, indicating a lack of ME induction. This suggests that V1 must be connected to higher cortical colour areas to drive ME induction.
The AAAA·DDDD Hydrogen Bond Dimer. Synthesis of a Soluble Sulfurane as AAAA Domain and Generation of a DDDD Counterpart
Authors: Taubitz Jörg , Lüning Ulrich
Published: November 2009

Sulfurane 5b with solubility enhancing substituents has been synthesized to be used as an AAAA recognition site in quadruple hydrogen bond heterodimers. A complementary DDDD partner [4b + H+] has been generated from a DDAD domain 4b by protonation. The association constant for the heterodimer complex formation has been determined by NMR titration in chloroform.
Control of Particle Morphology in Ab Initio RAFT Mediated Emulsion Polymerization
Authors: Sprong Ewan , De Bruyn Hank , Such Christopher H. , Hawkett Brian S.
Published: November 2009

Recent advances in the use of reversible addition–fragmentation chain transfer (RAFT) polymerization in dispersed phase systems have paved the way for the fine control of the morphology of latex particles that was not possible by conventional free radical polymerization techniques. With this approach, living amphiphilic block copolymers are synthesized that self-assemble to form micelles. The hydrophilic segment is formed from a water-soluble monomer which stabilizes the latex particles as polymerization proceeds and the latex particles grow. The hydrophobic ends of the RAFT diblocks ultimately grow into the polymer that forms the body of the particles. This paper presents examples of ways in which these advances can be used to engineer latex particles with unique morphologies that exhibit specific application properties.
Reversible Chain Transfer Catalyzed Polymerization of Methyl Methacrylate with In-Situ Formed Alkyl Iodide Initiator
Authors: Goto Atsushi , Nagasawa Koji , Shinjo Ayaka , Tsujii Yoshinobu , Fukuda Takeshi
Published: November 2009

A method utilizing generation of an alkyl iodide (low-mass dormant species) in situ formed in polymerization was adopted to reversible chain transfer catalyzed polymerizations (RTCP) (living radical polymerizations) with several nitrogen and phosphorus catalysts. The polymerization of methyl methacrylate afforded low-polydispersity polymers (Mw/Mn ~1.2–1.4), with Mn values predicted to high conversions; where Mn and Mw are the number- and weight-average molecular weights respectively. This method is robust and would enhance the utility of RTCP.
The Power of RAFT for Creating Polymers Having Imbedded Side-Chain Functionalities: Norbornenyl-Functionalized Polymers and their Transformations via ROMP and Thiol-ene Reactions
Authors: Ma Jun , Cheng Chong , Wooley Karen L.
Published: November 2009

Robust, efficient and orthogonal chemistries are becoming increasingly important tools for the construction of increasingly sophisticated materials. In this article, the selectivity of reversible addition–fragmentation chain transfer (RAFT)-based radical polymerization of bifunctional monomers is exploited for the preparation of statistical and block copolymers that contain imbedded side-chain functionalities, which are then shown to exhibit two different orthogonal types of chemical reactivity to afford discrete nanoscale objects and functional derivative structures. Based on the radical reactivity ratios calculated from Alfrey–Price theory, a bifunctional monomer 4-(5′-norbornene-2′-methoxy)-2,3,5,6-tetrafluorostyrene (1) was designed and synthesized, for its highly reactive tetrafluorostyrenyl group relative to its norbornene (Nb) group. Selective RAFT copolymerization of 1 with styrene (St) afforded copolymers with over 50 mol-% structural units having a pendent norbornenyl functionality while maintaining narrow molecular weight distribution (polydispersity index (PDI) = 1.23). Diblock copolymers (PDI = 1.09–1.23) with Nb side-chain substituents regioselectively placed along one segment of the block copolymer structure were also prepared by RAFT copolymerizations of 1 with St or 2,3,4,5,6-pentafluorostyrene, using either polystyrene or poly(styrene-alt-maleic anhydride)-based macro chain-transfer agents. A well-defined star block copolymer (PDI = 1.23) having a poly(norbornene)-based core and polystyrene arms was obtained by ring-opening metathesis polymerization using the regioselective diblock copolymer PSt-b-P(1-co-St) as the multifunctional macromonomer and Grubbs’ catalyst (first generation) as the initiator. Photo-induced thiol-ene reactions of Nb-functionalized polymers with thiols were fast and efficient, yielding polymers with new side-chain structures.
Bis(allyl)ruthenium(iv)-initiated S - S and C - S Bond Cleavages in Tetraalkylthiuram Sulfides. Formation and X-ray Crystal Structures of Dithiocarbamato Complexes
Authors: Xu Chang , Pullarkat Sumod A. , Goh Lai Yoong
Published: November 2009

The direct reaction of [{Ru(η3:η3-C10H16)(μ-Cl)Cl}2] (1) with tetraalkyldithiuram disulfides [R2NC(S)S-]2 (R = Me, iPr) and monosulfide [Me2NC(S)]2S led to the formation of orange solids of [Ru(η3:η3-C10H16)(η2-S2CNR2)Cl] (2a, R = Me; 2b, R =iPr) in high yields. Reaction of 1 with KPF6 and monosulfide [Me2NC(S)]2S resulted in [Ru(η3:η3-C10H16)(η2-S2CNMe2)(CH3CN)](PF6) (3). The treatment of 2a with KPF6 also yielded 3 in quantitative yield. Compounds 2–3 have been spectroscopically and crystallographically characterized.
The polychromatic
Helitron
landscape of the maize genome
Authors: Du Chunguang , Fefelova Nadezhda , Caronna Jason , He Limei , Dooner Hugo K.
Published: November 2009

Maize
Helitron
transposons are intriguing because of their notable ability to capture gene fragments and move them around the genome. To document more extensively their variability and their contribution to the remarkable genome structure variation of present-day maize, we have analyzed their composition, copy number, timing of insertion, and chromosomal distribution. First, we searched 2.4 Gb of sequences generated by the Maize Genome Sequencing Project with our HelitronFinder program. We identified 2,791 putative nonautonomous
Helitrons
and manually curated a subset of 272. The predicted
Helitrons
measure 11.9 kb on average and carry from zero to nine gene fragments, captured from 376 different genes. Although the diversity of
Helitron
gene fragments in maize is greater than in other species, more than one-third of annotated
Helitrons
carry fragments derived from just one of two genes. Most members in these two subfamilies inserted in the genome less than one million years ago. Second, we conducted a BLASTN search of the maize sequence database with queries from two previously described agenic
Helitrons
not detected by HelitronFinder. Two large subfamilies of
Helitrons
or
Helitron
-related transposons were identified. One subfamily, termed
Cornucopious
, consists of thousands of copies of an ≈1.0-kb agenic
Helitron
that may be the most abundant transposon in maize. The second subfamily consists of >150 copies of a transposon-like sequence, termed
Heltir
, that has terminal inverted repeats resembling
Helitron
3′ termini. Nonautonomous
Helitrons
make up at least 2% of the maize genome and most of those tested show +/− polymorphisms among modern inbred lines.
Amyloid-β42signals tau hyperphosphorylation and compromises neuronal viability by disrupting alkylacylglycerophosphocholine metabolism
Authors: Ryan Scott D. , Whitehead Shawn N. , Swayne Leigh Anne , Moffat Tia C. , Hou Weimin , Ethier Martin , Bourgeois André J. G. , Rashidian Juliet , Blanchard Alexandre P. , Fraser Paul E. , Park David S. , Figeys Daniel , Bennett Steffany A. L.
Published: November 2009

Perturbation of lipid second messenger networks is associated with the impairment of synaptic function in Alzheimer disease. Underlying molecular mechanisms are unclear. Here, we used an unbiased lipidomic approach to profile alkylacylglycerophosphocholine second messengers in diseased tissue. We found that specific isoforms defined by a palmitic acid (16:0) at thesn-1 position, namely 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0 PAF) and 1-O-hexadecyl-sn-glycero-3-phosphocholine (C16:0lyso-PAF), were elevated in the temporal cortex of Alzheimer disease patients, transgenic mice expressing human familial disease-mutant amyloid precursor protein, and human neurons directly exposed to amyloid-β42oligomers. Acute intraneuronal accumulation of C16:0 PAF but not C16:0lyso-PAF initiated cyclin-dependent kinase 5-mediated hyperphosphorylation of tau on Alzheimer disease-specific epitopes. Chronic elevation caused a caspase 2 and 3/7-dependent cascade resulting in neuronal death. Pharmacological inhibition of C16:0 PAF signaling, or molecular strategies increasing hydrolysis of C16:0 PAF to C16:0lyso-PAF, protected human neurons from amyloid-β42toxicity. Together, these data provide mechanistic insight into how disruptions in lipid metabolism can determine neuronal response to accumulating oligomeric amyloid-β42.
Ubiquitous internal gene duplication and intron creation in eukaryotes
Authors: Gao Xiang , Lynch Michael
Published: November 2009

Duplication of genomic segments provides a primary resource for the origin of evolutionary novelties. However, most previous studies have focused on duplications of complete protein-coding genes, whereas little is known about the significance of duplication segments that are entirely internal to genes. Our examination of six fully sequenced genomes reveals that internal duplications of gene segments occur at a high frequency (0.001–0.013 duplications/gene per million years), similar to that of complete gene duplications, such that 8–17% of the genes in a genome carry duplicated intronic and/or exonic regions. At least 7–30% of such genes have acquired novel introns, either because a prior intron in the same gene has been duplicated, or more commonly, because a spatial change has activated a latent splice site. These results strongly suggest a major evolutionary role for internal gene duplications in the origin of genomic novelties, particularly as a mechanism for intron gain.
Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response
Authors: Saitoh Tatsuya , Fujita Naonobu , Hayashi Takuya , Takahara Keigo , Satoh Takashi , Lee Hanna , Matsunaga Kohichi , Kageyama Shun , Omori Hiroko , Noda Takeshi , Yamamoto Naoki , Kawai Taro , Ishii Ken , Takeuchi Osamu , Yoshimori Tamotsu , Akira Shizuo
Published: November 2009

Microbial nucleic acids are critical for the induction of innate immune responses, a host defense mechanism against infection by microbes. Recent studies have indicated that double-stranded DNA (dsDNA) induces potent innate immune responses via the induction of type I IFN (IFN) and IFN-inducible genes. However, the regulatory mechanisms underlying dsDNA-triggered signaling are not fully understood. Here we show that the translocation and assembly of the essential signal transducers, stimulator of IFN genes (STING) and TANK-binding kinase 1 (TBK1), are required for dsDNA-triggered innate immune responses. After sensing dsDNA, STING moves from the endoplasmic reticulum (ER) to the Golgi apparatus and finally reaches the cytoplasmic punctate structures to assemble with TBK1. The addition of an ER-retention signal to the C terminus of STING dampens its ability to induce antiviral responses. We also show that STING co-localizes with the autophagy proteins, microtubule-associated protein 1 light chain 3 (LC3) and autophagy-related gene 9a (Atg9a), after dsDNA stimulation. The loss of Atg9a, but not that of another autophagy-related gene (Atg7), greatly enhances the assembly of STING and TBK1 by dsDNA, leading to aberrant activation of the innate immune response. Hence Atg9a functions as a regulator of innate immunity following dsDNA stimulation as well as an essential autophagy protein. These results demonstrate that dynamic membrane traffic mediates the sequential translocation and assembly of STING, both of which are essential processes required for maximal activation of the innate immune response triggered by dsDNA.
Depressive symptoms and outcomes in patients with heart failure: data from the COACH study
Authors: Lesman‐Leegte Ivonne , van Veldhuisen Dirk J. , Hillege Hans L. , Moser Debra , Sanderman Robbert , Jaarsma Tiny
Published: November 2009

Aims

To study the prognostic value of depressive symptoms on heart failure (HF) readmission and mortality, in a large and clinically relevant population of hospitalized HF patients adjusted for disease severity by B‐type natriuretic peptide (BNP) level.

Methods and results

We studied 958 patients enrolled after hospitalization for HF; 37% female; mean age 71 ± 11 years; New York Heart Association class II (51%) or III/IV (49%). Left ventricular ejection fraction: 33% ± 14%, and median BNP level: 454 pg/mL (75% CI, 195–876 pg/mL). In total, 377 patients (39%) had depressive symptoms [Centre for Epidemiological Studies Depression Scale (CES‐D) score ≥16] and 200 (21%) had severe depressive symptoms (score ≥24). During 18 months of follow‐up, 386 (40%) patients reached the primary endpoint of death or readmission for HF. In multivariate analyses, CES‐D was significantly associated with the primary endpoint [hazard ratio (HR) 1.13, P = 0.02], and also with both individual components of the primary endpoint [HF readmission (HR 1.165, P = 0.02) and mortality (HR 1.169, P = 0.02)]. Patients with severe depressive symptoms had a >40% higher risk for HF readmission or death.

Conclusion

In patients with HF, depression is independently associated with poor outcomes. These findings highlight the need for continued exploration of whether improvements in depression lead to better cardiovascular outcomes.

The study was registered at clinical trial (www.trialregister.nl): NCT 98675639.
Finding Jumps in Otherwise Smooth Curves: Identifying Critical Events in Political Processes
Authors: Ratkovic Marc T. , Eng Kevin H.
Published: November 2009

Many social processes are stable and smooth in general, with discrete jumps. We develop a sequential segmentation spline method that can identify both the location and the number of discontinuities in a series of observations with a time component, while fitting a smooth spline between jumps, using a modified Bayesian Information Criterion statistic as a stopping rule. We explore the method in a large-n, unbalanced panel setting with George W. Bush's approval data, a small-ntime series with median DW-NOMINATE scores for each Congress over time, and a series of simulations. We compare the method to several extant smoothers, and the method performs favorably in terms of visual inspection, residual properties, and event detection. Finally, we discuss extensions of the method.
Epidemiological typing of meticillin-resistant Staphylococcus aureus isolates from Pakistan and India
Authors: Shabir Sahida , Hardy Katherine J. , Abbasi Waseem S. , McMurray Claire L. , Malik Salman A. , Wattal Chand , Hawkey Peter M.
Published: November 2009

The levels of meticillin-resistantStaphylococcus aureus(MRSA) in Pakistan and India are known to be high, but few studies have described the epidemiology of the different MRSA clones present. In order to gain an understanding of the epidemiology of MRSA within this region, 60 MRSA isolates from Pakistan (49) and India (11) were genotyped. All isolates were typed using PFGE, staphylococcal interspersed repeat units (SIRUs), a restriction–modification method and staphylococcal cassette chromosomemec(SCCmec) typing. A subset of isolates that were distinct by PFGE and SIRUs were typed using multilocus sequence typing (MLST). Clonal complex (CC) 8 was the dominant clonal complex (57/60) and was present in both Pakistan and India. Within CC8, there were 10 SIRU profiles and 24 PFGE profiles. Two SIRU profiles were present in isolates from both India and Pakistan, whilst seven were distinct for Pakistan and one for India. All PFGE profiles were distinct for each of the two countries. Thirty-four of the 57 isolates carried SCCmectype III/IIIa and the remainder carried type IV SCCmec. MLST analysis of 14 CC8 isolates with diverse SIRU and PFGE profiles showed that all were single-locus variants, with nine belonging to sequence type (ST) 239, three to ST8 and two to ST113. From a single hospital in Pakistan, three isolates belonged to CC30 and all were indistinguishable by PFGE and SIRUs and carried the Panton–Valentine leukocidin gene. Thus, epidemiological typing of strains from three distinct locations in India and Pakistan revealed the predominance of one clonal complex and highly related STs. The ability of SIRUs and PFGE to differentiate within ST239 demonstrates their utility in defining local epidemiology in these countries.
The Pseudomonas aeruginosa oxidative stress regulator OxyR influences production of pyocyanin and rhamnolipids: protective role of pyocyanin
Authors: Vinckx Tiffany , Wei Qing , Matthijs Sandra , Cornelis Pierre
Published: November 2009

The LysR-type transcriptional regulator (LTTR) OxyR orchestrates the defence of the opportunistic pathogen Pseudomonas aeruginosa against reactive oxygen species. In previous work we also demonstrated that OxyR is needed for the utilization of the ferrisiderophore pyoverdine, stressing the importance of this regulator. Here, we show that an oxyR mutant is unable to swarm on agar plates, probably as a consequence of absence of production of rhamnolipid surfactant molecules. Another obvious phenotypic change was the increased production of the phenazine redox-active molecule pyocyanin in the oxyR mutant. As already described, the oxyR mutant could not grow in LB medium, unless high numbers of cells (>108 ml−1) were inoculated. However, its growth in Pseudomonas P agar (King's A), a medium inducing pyocyanin production, was like that of the wild-type, suggesting a protective action of this redox-active phenazine compound. This was confirmed by the restoration of the capacity to grow in LB medium upon addition of pure pyocyanin. Although both rhamnolipid and pyocyanin production are controlled by quorum sensing, no obvious changes were observed in the production of N-acylhomoserine lactones or the Pseudomonas quinolone signal (PQS). Complementation of rhamnolipid production and motility, and restoration of normal pyocyanin levels, was only possible when the oxyR gene was in single copy, while pyocyanin levels were increased when oxyR was present in a multicopy vector. Conversely, plating efficiency was increased only when the oxyR gene was present in multicopy, but not when in single copy in the chromosome, due to lower expression of oxyR compared with the wild-type, suggesting that some phenotypes are differently affected in function to the levels of OxyR molecules in the cell. Analysis of transcripts of oxidative stress-response enzymes showed a strong decrease of katB, ahpC and ahpB expression in the oxyR mutant grown in LB, but this was not the case when the mutant was grown on P agar, suggesting that the OxyR dependency for the transcription of these genes is not total.
Genotyping of Mycobacterium avium complex organisms using multispacer sequence typing
Authors: Cayrou Caroline , Turenne Christine , Behr Marcel A. , Drancourt Michel
Published: November 2009

Mycobacterium aviumcomplex (MAC) currently comprises eight species of environmental and animal-associated, slowly-growing mycobacteria:Mycobacterium avium,Mycobacterium intracellulare,Mycobacterium chimaera,Mycobacterium colombiense,Mycobacterium arosiense,Mycobacterium bouchedurhonense,Mycobacterium marseillenseandMycobacterium timonense. In humans, MAC organisms are responsible for opportunistic infections whose unique epidemiology remains poorly understood, in part due to the lack of a genotyping method applicable to all eight MAC species. In this study we developed multispacer sequence typing (MST), a sequencing-based method, for the genotyping of MAC organisms. An alignment of the genome sequence ofM. aviumsubsp.hominissuisstrain104 andM. aviumsubsp.paratuberculosisstrain K-10 revealed621 intergenic spacers <1000 bp. From these, 16 spacers were selected that ranged from 300 to 800 bp and contained a number of variable bases, <50 within each of the 16 spacers. Four spacers were successfully PCR-amplified and sequenced in 11 reference strains. Combining the sequence of these four spacers in 106 MAC organisms, including 83M. avium, 11M. intracellulare, sixM. chimaera, twoM. colombienseand one each ofM. arosiense,M. bouchedurhonense,M. marseillenseandM. timonense, yielded a total of 45 spacer types, with an index of discrimination of 0.94. Each spacer type was specific for a species and certain spacer types were specific for subspecies ofM. avium. MST is a new method for genotyping of organisms belonging to any one of the eight MAC species tested in this study.
Metabolism of conjugated linoleic acids and 18 : 1 fatty acids by ruminal bacteria: products and mechanisms
Authors: McKain Nest , Shingfield Kevin J. , Wallace R. John
Published: November 2009

Cultures of ruminal bacteria known to metabolize unsaturated fatty acids were grown in medium containing 50 μg ml−1of geometric and positional isomers of conjugated linoleic acid (CLA) or 18 : 1 fatty acids and 37.4 % deuterium oxide to investigate the mechanisms responsible for fatty acid metabolism.Butyrivibrio fibrisolvensJW11 convertedcis-9,trans-11-18 : 2 andtrans-9,trans-11-18 : 2 totrans-11-18 : 1 as the main product, labelled at C-9, and metabolizedtrans-10,cis-12-18 : 2 totrans-10-18 : 1, labelled at C-13, and smaller amounts oftrans-12-18 : 1 andcis-12-18 : 1.Butyrivibrio proteoclasticusP-18 did not grow in the presence ofcis-9,trans-11-18 : 2 ortrans-10,cis-12-18 : 2, but grew in medium containingtrans-9,trans-11-18 : 2, forming 18 : 0.Propionibacterium acnes, a ruminal species that isomerizes linoleic acid totrans-10,cis-12-18 : 2, did not metabolize CLA isomers further.B. fibrisolvensmetabolized small amounts oftrans-10-18 : 1,trans-11-18 : 1 andcis-9-18 : 1, but the products formed were not detected.B. proteoclasticus, on the other hand, carried out substantial conversion of 18 : 1 substrates to 18 : 0.P. acneshydratedcis-9-18 : 1 andtrans-11-18 : 1 to 10-OH-18 : 0, which was further oxidized to yield 10-O-18 : 0. The deuterium enrichment in the intermediates formed during incubations with 9,11 geometric isomers of CLA was about half that of the products fromtrans-10,cis-12 CLA and 18 : 1 isomers, suggesting that the reduction of 9,11 geometric isomers CLA by ruminal bacteria occurs via different mechanisms compared with the metabolism of other unsaturated fatty acids.
Systematic review: the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome
Authors: SPIEGEL B. , SCHOENFELD P. , NALIBOFF B.
Published: November 2009

Background Chronic abdominal pain syndromes may increase the risk of suicidal behaviour – a feature well described in non‐visceral pain syndromes.

Aim To perform a systematic review to summarize and interpret published data linking chronic abdominal pain syndromes and suicidal behaviour.

Methods We performed a structured search to identify studies pertaining to the following questions: (i) What is the prevalence of suicidal behaviour in patients with chronic abdominal pain syndromes, including bowel syndrome (IBS)? (ii) Is the prevalence of suicidal behaviour in chronic abdominal pain syndromes higher than in matched controls? And (iii) is suicidal behaviour in abdominal pain syndromes simply due to psychiatric co‐morbidities?

Results Thirty‐two relevant titles were identified, of which six manuscripts, describing eight studies, met inclusion criteria. Patients with non‐IBS syndromes were 3–11 times more likely to demonstrate suicidal behaviour vs. controls, while patients with IBS were two to four times more likely to have suicidal behaviour. Chronic abdominal pain was an independent predictor of suicidal behaviour after adjusting for co‐morbid psychiatric conditions.

Conclusions Chronic abdominal pain syndromes increase the risk for suicidal behaviours. This relationship may exist independently of co‐morbid depression, although additional research is needed to better understand this link. These data indicate that clinicians should survey for suicidal behaviour in chronic abdominal pain patients.
13C‐methacetin breath test as a quantitative liver function test in patients with chronic hepatitis C infection: continuous automatic molecular correlation spectroscopy compared to isotopic ratio mass spectrometry
Authors: GOETZE O. , SELZNER N. , FRUEHAUF H. , FRIED M. , GERLACH T. , MULLHAUPT B.
Published: November 2009

Background  The 13C‐methacetin breath test (MBT) has been proposed for the non‐invasive evaluation of hepatic microsomal activity.

Aim  To test a new continuous breath analysis system (BreathID) in comparison with gold‐standard isotopic ratio mass spectrometry (IRMS) in patients with chronic hepatitis C infection and to assess the diagnostic performance of these validation data compared with liver biopsy for the quantification of liver fibrosis.

Methods  Fifty patients at different METAVIR stages received 75 mg of 13C‐methacetin. Breath isotopic ratio was analysed over 90 min by BreathID (one sample/3 min; BreathID) and IRMS (one sample/10 min). Results were expressed as delta over baseline [DOB (%)] at each time interval and maximal DOB [DOBmax(%)].

Results  A high linear association between both methods was observed (R2 = 0.95, P < 0.001). For all DOB and DOBmax, the limits of agreement by Bland–Altman analysis were within the predefined maximal width of s.d. <2.5%. MBT parameters in patients with high‐grade fibrosis were different from patients with low‐grade fibrosis (P < 0.001).

Conclusion  The MBT obtained by an easy to operate, automated BreathID provides results comparable with standard IRMS and differentiates fibrosis grades in patients with chronic hepatitis C infection.
A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol
Authors: HEARD K. , GREEN J. L. , BAILEY J. E. , BOGDAN G. M. , DART R. C.
Published: November 2009

Background Previous studies have suggested that therapeutic doses of paracetamol (acetaminophen) are safe in alcoholic patients when administered for up to 3 days. However, 14 days of therapeutic doses of paracetamol has been associated with an increase in serum transaminases.

Aim To determine the effect of 10 days of the maximal therapeutic dose of paracetamol on serum alanine aminotransferase (ALT) activity in subjects who consume 1 to 3 alcoholic beverages per day.

Methods This was a randomized, double blind, placebo‐controlled trial. Subjects took 4 g of paracetamol (or placebo) daily for 10 days. Serum aspartate aminotransferase (AST), ALT, bilirubin and INR were measured at baseline, day 4 and day 11. Symptoms potentially related to liver injury were also recorded.

Results Paracetamol and placebo groups had no change from baseline values at day 4, but the paracetamol group had an increase in mean ALT at day 11 of 8.7 IU/L. No subject developed symptoms of liver injury or met predefined criteria for hepatotoxicity or liver failure.

Conclusion Therapeutic dosing of paracetamol administered for 10 days appears to elevate serum ALT in moderate drinkers, but does not produce clinically evident liver injury.
Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain
Authors: NYROP K. A. , PALSSON O. S. , LEVY R. L. , KORFF M. VON , FELD A. D. , TURNER M. J. , WHITEHEAD W. E.
Published: November 2009

Aim To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment.

Methods We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out‐of‐pocket expenses were assessed by questionnaires.

Results Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out‐of‐pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In‐patient care accounted for 17.5% of total costs (15.2% IBS).

Conclusion Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).
Review article: the pathophysiology of gastro‐oesophageal reflux disease
Authors: BOECKXSTAENS G. E. E.
Published: November 2009

Background Gastro‐oesophageal reflux disease (GERD) is a common condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications.

Aim To review the current knowledge on the underlying factors contributing to GERD, with particular emphasis on the most recent research.

Methods Literature searches were conducted in Medline and EMBASE. The abstracts from recent large congresses were also reviewed to ensure coverage of the latest findings.

Results The pathophysiological factors causing GERD can be split into those inducing greater exposure of the oesophagus to stomach contents, and those that provide increased perception of reflux or increased mucosal damage. Transient lower oesophageal sphincter relaxations, which are likely to be triggered by gastric distension, appear to be a key physiological cause of GERD. Excessive reflux may also be provoked by impaired oesophageal or gastric clearance mechanisms. Pre‐epithelial, epithelial and post‐epithelial defences all normally protect the oesophagus from injury, and may be compromised in individuals with GERD. Heartburn could also be caused by oesophageal hypersensitivity as a result of visceral neural pathway dysfunction.

Conclusion The pathophysiology of GERD is multifactorial, and abnormalities in the gastro‐oesophageal junction, the stomach, the oesophagus and the nervous system may all contribute to this disease state.
Oral pantoprazole in the form of granules or tablets are pharmacodynamically equivalent in suppressing acid output in patients with gastro‐oesophageal reflux disease and a history of erosive oesophagitis
Authors: HOGAN D. , PRATHA V. , RIFF D. , DUCKER S. , SCHWARTZ H. , SOFFER E. , WANG W. , RATH N. , COMER G. M.
Published: November 2009

Aim To demonstrate the pharmacodynamic comparability between oral 40 mg pantoprazole delayed‐release granules and tablets.

Methods This was a multicentre, randomized, open‐label, 2‐period, 2‐sequence, 9‐week crossover study in patients aged 18–65 years with gastro‐oesophageal reflux disease and documented erosive oesophagitis. The primary endpoint was a comparison of the inhibition of pentagastrin‐stimulated maximum acid output (MAO) at steady state after once daily dosing for 1 week and 23 h after the last dose of pantoprazole granules and tablets. Basal acid output was measured prior to MAO. Standard safety evaluations were performed. The one‐sided t‐test was used to test the null hypothesis that granules – 1.2 × tablet ≥ 0 against the alternative hypothesis that this difference was <0 for both MAO and basal acid output values.

Results Sixty patients completed the study. The mean MAO values were 7.11 ± 4.98 and 7.29 ± 4.77 mmol/h, while the mean basal acid output values were 0.74 ± 0.91 and 0.58 ± 0.63 mmol/h for the granules and tablets, respectively. The two formulations were shown statistically to be pharmacodynamically equivalent in suppressing MAO (P = 0.006), safe and well tolerated.

Conclusion Patients with gastro‐oesophageal reflux disease who are unable to swallow the tablet may safely be prescribed the pantoprazole sodium granules.
Transcriptional regulation of tumor suppressor p53 by cAMP‐responsive element‐binding protein/AMP‐activated protein kinase complex in response to glucose deprivation
Authors: Okoshi Rintaro , Ando Kiyohiro , Suenaga Yusuke , Sang Meixiang , Kubo Natsumi , Kizaki Harutoshi , Nakagawara Akira , Ozaki Toshinori
Published: November 2009

Tumor suppressor p53 plays a pivotal role in the regulation of cell fate determination in response to a variety of cellular stress including carbon source depletion. In this study, we found that cAMP‐responsive element‐binding protein (CREB) collaborates with AMP‐activated protein kinase α (AMPKα) to regulate the transcription of p53. Luciferase reporter assays showed that the genomic fragment spanning from −531 to −239 of human p53 gene is required for the transactivation of p53 in response to glucose deprivation. Within this region, we found out a putative CREB‐binding site. siRNA‐mediated knockdown of CREB resulted in a significant inhibition of the up‐regulation of p53 and apoptosis under glucose deprivation. Consistent with these observations, glucose deprivation induced the transcription of p53 and CREB. Additionally, glucose deprivation led to an efficient recruitment of CREB onto the promoter region of p53 gene carrying the canonical CREB‐binding site, indicating that CREB has an ability to bind to the promoter region of p53 gene and transactivate p53. Furthermore, the amounts of CREB/phospo‐AMPKα complex increased in response to glucose deprivation. Taken together, our present findings suggest that p53 is transcriptionally regulated by CREB/phospho‐AMPKα complex and thereby contributing to the induction of apoptosis under carbon source depletion.
An analysis of levels of infectious pancreatic necrosis virus in Atlantic salmon, Salmo salar L., broodstock in Scotland between 1990–2002
Authors: Munro E S , Millar C P , Hastings T S
Published: November 2009

Throughout this study period the prevalence of infectious pancreatic necrosis virus (IPNV) in Scottish farmed Atlantic salmon was high in the marine environment but relatively low in fresh water. In order to minimize the risk of vertical transmission of infection from parent to progeny, all IPNV infected broodstock populations had to undergo testing of all fish for the virus at the time of stripping and eggs from positive parents were destroyed. Between 1990 and 2002 over 68 000 Atlantic salmon broodfish were individually screened for IPNV by cell culture isolation and enzyme linked immunosorbent assay. Generalized linear mixed models were used to assess the influence of geographical region, age, sex and year on IPNV prevalence in Atlantic salmon broodstock. This analysis determined that the age and sex of the broodfish and the geographical region of the broodstock stripping site did not have a statistically significant influence on IPNV prevalence within the broodstock parental population. However, there was a statistically significant temporal increase in IPNV prevalence from 1990 to 2002.
Recommendations for assessing Patient‐Reported Outcomes and Health‐Related quality of life in clinical trials on allergy: a GA2LEN taskforce position paper
Authors: Baiardini I. , Bousquet P. J. , Brzoza Z. , Canonica G. W. , Compalati E. , Fiocchi A. , Fokkens W. , Van Wijk R. G. , La Grutta S. , Lombardi C. , Maurer M. , Pinto A. M. , Ridolo E. , Senna G. E. , Terreehorst I. , Bom A. Todo , Bousquet J. , Zuberbier T. , Braido F.
Published: November 2009

To cite this article: Baiardini I, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, van Wijk RG, La Grutta S, Lombardi C, Maurer M, Pinto AM, Ridolo E, Senna GE, Terreehorst I, Todo Bom A, Bousquet J, Zuberbier T, Braido F. Recommendations for assessing Patient‐Reported Outcomes and Health‐Related quality of life in clinical trials on allergy: a GA2LEN taskforce position paper. Allergy 2010; 65: 290–295.

The aim of this Global Allergy and Asthma European Network (GA2LEN) consensus report is to provide recommendations for patient‐reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients’ subjective assessment with respect to elements concerning their health condition. They include all health‐related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease‐specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient‐related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors’ indications without modification and performing a cross‐cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre–post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health‐related quality of life, and clinical data.
Molecular analysis of CYP21A2 can optimize the follow‐up of positive results in newborn screening for congenital adrenal hyperplasia
Authors: Silveira EL , Elnecave RH , Dos Santos EP , Moura V , Pinto EM , Van Der Linden Nader I , Mendonca BB , Bachega TASS
Published: November 2009

Neonatal screening for congenital adrenal hyperplasia (CAH) is useful in diagnosing salt wasting form (SW). However, there are difficulties in interpreting positive results in asymptomatic newborns. The main objective is to analyze genotyping as a confirmatory test in children with neonatal positive results. Patients comprised 23 CAH children and 19 asymptomatic infants with persistently elevated 17‐hydroxyprogesterone (17OHP) levels. CYP21A2 gene was sequenced and genotypes were grouped according to the enzymatic activity of the less severe allele: A1 null, A2 < 2%, B 3–7%, C > 20%. Twenty‐one children with neonatal symptoms and/or 17OHP levels > 80 ng/ml carried A genotypes, except two virilized girls (17OHP < 50 ng/ml) without CAH genotypes. Patients carrying SW genotypes (A1, A2) and low serum sodium levels presented with neonatal 17OHP > 200 ng/ml. Three asymptomatic boys carried simple virilizing genotypes (A2 and B): in two, the symptoms began at 18 months; another two asymptomatic boys had nonclassical genotypes (C). The remaining 14 patients did not present CAH genotypes, and their 17OHP levels were normalized by 14 months of age. Molecular analysis is useful as a confirmatory test of CAH, mainly in boys. It can predict clinical course, identify false‐positives and help distinguish between clinical forms of CAH.
Spatial distribution of colonizing Listronotus maculicollis populations: implications for targeted management and host preference
Authors: McGraw B. A. , Koppenhöfer A. M.
Published: November 2009

We characterized the spatio‐temporal distribution of emerging overwintered adult Listronotus maculicollis populations colonizing golf course fairways with Spatial Analyses by Distance IndicEs (SADIE) with the goal to better target management tactics and to test assumptions for weevil preference for annual bluegrass (Poa annua). Adults randomly colonized and moved throughout fairways. However, cumulative captures were significantly aggregated along fairway edges closest to overwintering sites demonstrating progressive movement through the edges. Spatial association analyses suggest that the spatial patterns of cumulative captures of adults rather than weekly patterns were strongly associated with larvae, indicating that the adults enter fairways from the edges and deposit eggs over the course of several weeks. We did not observe an effect of host species on the distribution of either adult or larval L. maculicollis which leads us to question traditional assumptions of host preference for short mown P. annua. Instead, we propose that the aggregated distribution of larvae is generated by a low encounter rate of short mown hosts, rather than preference for species or cultivar. This study indicates that caution need to be applied when using preference‐performance criteria in host preference studies. Future behavioural studies need to address the contributions of encounter rate and host species on L. maculicollis host selection and oviposition.