bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sleep deprivation on central auditory processing
Authors: Liberalesso Paulo Breno Noronha , D’Andrea Karlin Fabianne Klagenberg , Cordeiro Mara L , Zeigelboim Bianca Simone , Marques Jair Mendes , Jurkiewicz Ari Leon
Published: September 2012

Background

Sleep deprivation is extremely common in contemporary society, and is considered to be a frequent cause of behavioral disorders, mood, alertness, and cognitive performance. Although the impacts of sleep deprivation have been studied extensively in various experimental paradigms, very few studies have addressed the impact of sleep deprivation on central auditory processing (CAP). Therefore, we examined the impact of sleep deprivation on CAP, for which there is sparse information. In the present study, thirty healthy adult volunteers (17 females and 13 males, aged 30.75 ± 7.14 years) were subjected to a pure tone audiometry test, a speech recognition threshold test, a speech recognition task, the Staggered Spondaic Word Test (SSWT), and the Random Gap Detection Test (RGDT). Baseline (BSL) performance was compared to performance after 24 hours of being sleep deprived (24hSD) using the Student’s t test.

Results

Mean RGDT score was elevated in the 24hSD condition (8.0 ± 2.9 ms) relative to the BSL condition for the whole cohort (6.4 ± 2.8 ms; p = 0.0005), for males (p = 0.0066), and for females (p = 0.0208). Sleep deprivation reduced SSWT scores for the whole cohort in both ears [(right: BSL, 98.4 % ± 1.8 % vs. SD, 94.2 % ± 6.3 %. p = 0.0005)(left: BSL, 96.7 % ± 3.1 % vs. SD, 92.1 % ± 6.1 %, p < 0.0001)]. These effects were evident within both gender subgroups [(right: males, p = 0.0080; females, p = 0.0143)(left: males, p = 0.0076; females: p = 0.0010).

Conclusion

Sleep deprivation impairs RGDT and SSWT performance. These findings confirm that sleep deprivation has central effects that may impair performance in other areas of life.
Integrating genome annotation and QTL position to identify candidate genes for productivity, architecture and water-use efficiency in Populus spp
Authors: Monclus Romain , Leplé Jean-Charles , Bastien Catherine , Bert Pierre-François , Villar Marc , Marron Nicolas , Brignolas Franck , Jorge Véronique
Published: September 2012

Background

Hybrid poplars species are candidates for biomass production but breeding efforts are needed to combine productivity and water use efficiency in improved cultivars. The understanding of the genetic architecture of growth in poplar by a Quantitative Trait Loci (QTL) approach can help us to elucidate the molecular basis of such integrative traits but identifying candidate genes underlying these QTLs remains difficult. Nevertheless, the increase of genomic information together with the accessibility to a reference genome sequence (Populus trichocarpa Nisqually-1) allow to bridge QTL information on genetic maps and physical location of candidate genes on the genome. The objective of the study is to identify QTLs controlling productivity, architecture and leaf traits in a P. deltoides x P. trichocarpa F1 progeny and to identify candidate genes underlying QTLs based on the anchoring of genetic maps on the genome and the gene ontology information linked to genome annotation. The strategy to explore genome annotation was to use Gene Ontology enrichment tools to test if some functional categories are statistically over-represented in QTL regions.

Results

Four leaf traits and 7 growth traits were measured on 330 F1 P. deltoides x P. trichocarpa progeny. A total of 77 QTLs controlling 11 traits were identified explaining from 1.8 to 17.2% of the variation of traits. For 58 QTLs, confidence intervals could be projected on the genome. An extended functional annotation was built based on data retrieved from the plant genome database Phytozome and from an inference of function using homology between Populus and the model plant Arabidopsis. Genes located within QTL confidence intervals were retrieved and enrichments in gene ontology (GO) terms were determined using different methods. Significant enrichments were found for all traits. Particularly relevant biological processes GO terms were identified for QTLs controlling number of sylleptic branches: intervals were enriched in GO terms of biological process like ‘ripening’ and ‘adventitious roots development’.

Conclusion

Beyond the simple identification of QTLs, this study is the first to use a global approach of GO terms enrichment analysis to fully explore gene function under QTLs confidence intervals in plants. This global approach may lead to identification of new candidate genes for traits of interest.
Swirl sign in intracerebral haemorrhage: definition, prevalence, reliability and prognostic value
Authors: Selariu Eufrozina , Zia Elisabet , Brizzi Marco , Abul-Kasim Kasim
Published: September 2012

Background

Swirl sign has previously been described in epidural hematomas as areas of low attenuation, radiolucency or irregular density. The aims of this study were to describe swirl sign in ICH, study its prevalence, study the reliability of the subjective evaluation on computed tomography (CT), and to explore its prognostic value.

Methods

CTs of 203 patients with ICH were retrospectively evaluated for the presence of swirl sign. Association between swirl sign and different clinical and radiological variables was studied.

Results

Inter- and intraobserver agreement with regard to the occurrence of swirl sign was substantial (К 0.80) and almost perfect (К 0.87), respectively. Swirl sign was found in 30% of the study population. 61% of patients with swirl sign were dead at one month compared with 21% of those with no swirl sign (p < 0.001). Only 19% of patients with swirl sign exhibited favorable outcome at three months compared with 53% of those with no swirl sign (p < 0.001). Patients with swirl sign exhibited larger ICHs with average ICH-volume 52 ± 50 ml (median 42 ml) compared with 15 ± 25 ml (median 6) in patients whose CT did not show swirl sign (p < 0.001). Swirl sign was independent predictor of death at one month (p = 0.03; adjusted odds ratio 2.6, 95% CI 1.1 – 6), and functional outcome at three months (p = 0.045; adjusted odds ratio 2.6, 95% CI 1.02 – 6.5).

Conclusions

As swirl sign showed to be an ominous sign, we recommend identification of this sign in cases of ICHs.
Targeting of CD34+CD38-cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia
Authors: Jawad Mays , Yu Ning , Seedhouse Claire , Tandon Karuna , Russell Nigel H , Pallis Monica
Published: September 2012

Background

The CD34+CD38- subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment.

Methods

Chemosensitivity in phenotypically defined subsets from 34 primary AML samples was measured by flow cytometry following 48 hr in vitro treatment with gemtuzumab ozogamicin (GO, Mylotarg) and the farnesyltransferase inhibitor tipifarnib/zarnestra. The DNA damage response was measured using flow cytometry, immunofluorescence and immunohistochemistry.

Results

Using a previously validated in vitro minimal residual disease model, we now show that the combination of GO (10 ng/ml) and tipifarnib (5 μM) targets the CD34+CD38- subset resulting in 65% median cell loss compared to 28% and 13% CD34+CD38- cell loss in GO-treated and tipifarnib-treated cells, respectively. Using phosphokinome profiling and immunofluorescence in the TF-1a cell line, we demonstrate that the drug combination is characterised by the activation of a DNA damage response (induction of γH2A.X and thr68 phosphorylation of chk2). Higher induction of γH2AX was found in CD34+CD38- than in CD34+CD38+ patient cells. In a model system, we show that dormancy impairs damage resolution, allowing accumulation of γH2AX foci.

Conclusions

The chemosensitivity of the CD34+CD38- subset, combined with enhanced damage indicators, suggest that this subset is primed to favour programmed cell death as opposed to repairing damage. This interaction between tipifarnib and GO suggests a potential role in the treatment of AML.
Insight, psychopathology, explanatory models and outcome of schizophrenia in India: a prospective 5-year cohort study
Authors: Johnson Shanthi , Sathyaseelan Manoranjitham , Charles Helen , Jeyaseelan Visalakshi , Jacob Kuruthukulangara Sebastian
Published: September 2012

Background

The sole focus of models of insight on bio-medical perspectives to the complete exclusion of local, non-medical and cultural constructs mandates review. This study attempted to investigate the impact of insight, psychopathology, explanatory models of illness on outcome of first episode schizophrenia.

Method

Patients diagnosed to have DSM IV schizophrenia (n = 131) were assessed prospectively for insight, psychopathology, explanatory models of illness at baseline, 6, 12 and 60 months using standard instruments. Multiple linear and logistic regression and generalized estimating equations (GEE) were employed to assess predictors of outcome.

Results

We could follow up 95 (72.5%) patients. Sixty-five of these patients (68.4%) achieved remission. There was a negative relationship between psychosis rating and insight scores. Urban residence, fluctuating course of the initial illness, and improvement in global functioning at 6 months and lower psychosis rating at 12 months were significantly related to remission at 5 years. Insight scores, number of non-medical explanatory models and individual explanatory models held during the later course of the illness were significantly associated with outcome. Analysis of longitudinal data using GEE showed that women, rural residence, insight scores and number of non-medical explanatory models of illness held were significantly associated with BPRS scores during the study period.

Conclusions

Insight, the disease model and the number of non-medical model positively correlated with improvement in psychosis arguing for a complex interaction between the culture, context and illness variables. These finding argue that insight and explanatory models are secondary to psychopathology, course and outcome of the illness. The awareness of mental illness is a narrative act in which people make personal sense of the many challenges they face. The course and outcome of the illness, cultural context, acceptable cultural explanations and the prevalent social stigma interact to produce a complex and multifaceted understanding of the issues. This complexity calls for a nuanced framing of insight.
Observation of strain effect on the suspended graphene by polarized Raman spectroscopy
Authors: Huang Cheng-Wen , Lin Bing-Jie , Lin Hsing-Ying , Huang Chen-Han , Shih Fu-Yu , Wang Wei-Hua , Liu Chih-Yi , Chui Hsiang-Chen
Published: September 2012

We report the strain effect of suspended graphene prepared by micromechanical method. Under a fixed measurement orientation of scattered light, the position of the 2D peaks changes with incident polarization directions. This phenomenon is explained by a proposed mode in which the peak is effectively contributed by an unstrained and two uniaxial-strained sub-areas. The two axes are tensile strain. Compared to the unstrained sub-mode frequency of 2,672 cm−1, the tension causes a red shift. The 2D peak variation originates in that the three effective sub-modes correlate with the light polarization through different relations. We develop a method to quantitatively analyze the positions, intensities, and polarization dependences of the three sub-peaks. The analysis reflects the local strain, which changes with detected area of the graphene film. The measurement can be extended to detect the strain distribution of the film and, thus, is a promising technology on graphene characterization.
Some new common fixed point results through generalized altering distances on partial metric spaces
Authors: Ahmad Abd Ghafur Bin , Fadail Zaid Mohammed , Nashine Hemant Kumar , Kadelburg Zoran , Radenović Stojan
Published: September 2012

We establish common fixed point results for two pairs of weakly compatible mappings on a partial metric space, satisfying a weak contractive condition involving generalized control functions. The presented theorems extend and unify various known fixed point results. Examples are given to show that our results are proper extensions of the known ones.

MSC:47H10, 54H25, 54H10.
Prostaglandin Metabolite Induces Inhibition of TRPA1 and Channel-Dependent Nociception
Authors: Weng Yingqi , Batista-Schepman Patricia A , Barabas Marie E , Harris Eli Q , Dinsmore Thomas B , Kossyreva Elena A , Foshage Audra M , Wang Michelle H , Schwab Matthew J , Wang Victoria M , Stucky Cheryl L , Story Gina M
Published: September 2012

Background:

The Transient Receptor Potential (TRP) ion channel TRPA1 is a key player in pain pathways. Irritant chemicals activate ion channel TRPA1 via covalent modification of N-terminal cysteines. We and others have shown that 15-Deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) similarly activates TRPA1 and causes channel-dependent nociception. Paradoxically, 15d-PGJ2 can also be anti-nociceptive in several pain models. Here we hypothesized that activation and subsequent desensitization of TRPA1 in dorsal root ganglion (DRG) neurons underlies the anti-nociceptive property of 15d-PGJ2. To investigate this, we utilized a battery of behavioral assays and intracellular Ca2+ imaging in DRG neurons to test if pre-treatment with 15d-PGJ2 inhibited TRPA1 to subsequent stimulation.

Results:

Intraplantar pre-injection of 15d-PGJ2, in contrast to mustard oil (AITC), attenuated acute nocifensive responses to subsequent injections of 15d-PGJ2 and AITC, but not capsaicin (CAP). Intraplantar 15d-PGJ2—administered after the induction of inflammation—reduced mechanical hypersensitivity in the Complete Freund's Adjuvant (CFA) model for up to 2 h post-injection. The 15d-PGJ2-mediated reduction in mechanical hypersensitivity is dependent on TRPA1, as this effect was absent in TRPA1 knockout mice. Ca2+ imaging studies of DRG neurons demonstrated that 15d-PGJ2 pre-exposure reduced the magnitude and number of neuronal responses to AITC, but not CAP. AITC responses were not reduced when neurons were pre-exposed to 15d-PGJ2 combined with HC-030031 (TRPA1 antagonist), demonstrating that inhibitory effects of 15d-PGJ2 depend on TRPA1 activation. Single daily doses of 15d-PGJ2, administered during the course of 4 days in the CFA model, effectively reversed mechanical hypersensitivity without apparent tolerance or toxicity.

Conclusions:

Taken together, our data support the hypothesis that 15d-PGJ2 induces activation followed by persistent inhibition of TRPA1 channels in DRG sensory neurons in vitro and in vivo. Moreover, we demonstrate novel evidence that 15d-PGJ2 is analgesic in mouse models of pain via a TRPA1-dependent mechanism. Collectively, our studies support that TRPA1 agonists may be useful as pain therapeutics.
A single-institution study of stereotactic body radiotherapy for patients with unresectable visceral pulmonary or hepatic oligometastases
Authors: Fumagalli Ingrid , Bibault Jean-Emmanuel , Dewas Sylvain , Kramar Andrew , Mirabel Xavier , Prevost Bernard , Lacornerie Thomas , Jerraya Hajer , Lartigau Eric
Published: September 2012

Purpose

The purpose of this study is to evaluate the feasibility, efficacy and toxicity of SBRT for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients who received prior systemic chemotherapy.

Methods and materials

Between July 2007 and June 2010, 90 patients were treated with the CyberKnife® SBRT system for hepatic or pulmonary metastatic lesions. Medical records were retrospectively reviewed. The endpoints of this study were local control, overall survival (OS), disease-free survival (DFS), local relapse free-survival (LRFS), and treatment toxicity.

Results

A total of 113 liver and 26 lung metastatic lesions in 52 men (58%) and 38 women (42%) were treated. Median follow-up was 17 months. Median age at treatment was 65 years (range, 23–84 years). Primary cancers were 63 GI, three lung, eight breast, four melanoma, three neuro-endocrine tumors, and three sarcomas. Median diameter of the lesions was 28 mm (range, 7–110 mm) for liver and 12.5 mm (range, 5–63.5 mm) for lung. Local control rates at 1 and 2 years were 84.5% and 66.1%, respectively. Two-year overall survival rate was 70% (95% CI: 55–81%). The 1 and 2-year disease-free survival rates were 27% (95% CI: 18–37%) and 10% (95% CI: 4–20%), respectively. Median duration of disease-free survival was 6.7 months (95% CI: 5.1–9.5 months). Observed toxicities included grade 1–3 acute toxicities. One grade 3 and no grade 4 toxicity were reported.

Conclusion

High-dose SBRT for metastatic lesions is both feasible and effective with high local control rates. Overall survival is comparable with other available techniques. Treatment is well tolerated with low toxicity rates. It could represent an interesting treatment option for oligometastatic patients not amenable to surgery, even when patients had been pre-treated with chemotherapy.

Stereotactic body radiotherapy (SBRT) has previously been successfully used in the treatment of metastatic lesions. It could be considered as a curative option for oligometastatic patients. This retrospective study involved 90 patients, designed to test potential effectiveness of SBRT in the treatment of oligometastases irrespective of primary. Results suggest SBRT could be an effective treatment extending patients’ life span. This treatment appears to be more effective when used prior to multiple systemic treatment regimens.
Enhanced DPPH radical scavenging activity and DNA protection effect of litchi pericarp extract by Aspergillus awamoribioconversion
Authors: Lin Sen , Yang Bao , Chen Feng , Jiang Guoxiang , Li Qing , Duan Xuewu , Jiang Yueming
Published: September 2012

Background

Litchi (Litchi chinensis Sonn.) pericarp is a major byproduct which contains a significant amount of polyphenol. This study was designed to biotransformation litchi pericarp extract (LPE) by Aspergillus awamori to produce more bioactive compounds with stronger antioxidant activities.

Results

The study exhibited that the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities significantly (p < 0.05) increased from 15.53% to 18.23% in the water-extracted fraction and from 25.41% to 36.82% in the ethyl acetate-extracted fraction. Application of DNA cleavage assay further demonstrated the enhanced protection effect of the fermented phenolics on DNA damage. It is also noted that the water-extracted fraction of the fermented LPE possessed a much stronger capacity than the ethyl acetate-extracted fraction to prevent from damage of supercoiled DNA. Interestingly, it was found that some new compounds such as catechin and quercetin appeared after of A. awamori fermentation of LPE, which could account for the enhanced antioxidant activity.

Conclusion

The DPPH radical scavenging activity and DNA protection effect of LPE were increased by Aspergillus awamori bioconversion while some compounds responsible for the enhanced antioxidant activity were identified. This study provided an effective way of utilizing fruit pericarp as a readily accessible source of the natural antioxidants in food industry and, thus, extended the application area such as fruit by-products.
Predicting the difficulty of pure, strict, epistatic models: metrics for simulated model selection
Authors: Urbanowicz Ryan J , Kiralis Jeff , Fisher Jonathan M , Moore Jason H
Published: September 2012

Background

Algorithms designed to detect complex genetic disease associations are initially evaluated using simulated datasets. Typical evaluations vary constraints that influence the correct detection of underlying models (i.e. number of loci, heritability, and minor allele frequency). Such studies neglect to account for model architecture (i.e. the unique specification and arrangement of penetrance values comprising the genetic model), which alone can influence the detectability of a model. In order to design a simulation study which efficiently takes architecture into account, a reliable metric is needed for model selection.

Results

We evaluate three metrics as predictors of relative model detection difficulty derived from previous works: (1) Penetrance table variance (PTV), (2) customized odds ratio (COR), and (3) our own Ease of Detection Measure (EDM), calculated from the penetrance values and respective genotype frequencies of each simulated genetic model. We evaluate the reliability of these metrics across three very different data search algorithms, each with the capacity to detect epistatic interactions. We find that a model’s EDM and COR are each stronger predictors of model detection success than heritability.

Conclusions

This study formally identifies and evaluates metrics which quantify model detection difficulty. We utilize these metrics to intelligently select models from a population of potential architectures. This allows for an improved simulation study design which accounts for differences in detection difficulty attributed to model architecture. We implement the calculation and utilization of EDM and COR into GAMETES, an algorithm which rapidly and precisely generates pure, strict, n-locus epistatic models.
Interactions of the CpxA sensor kinase and cognate CpxR response regulator from Yersinia pseudotuberculosis
Authors: Thanikkal Edvin J , Mangu Jagadish C K , Francis Matthew S
Published: September 2012

Background

The CpxA sensor kinase-CpxR response regulator two-component regulatory system is a sentinel of bacterial envelope integrity. Integrating diverse signals, it can alter the expression of a wide array of components that serve to shield the envelope from damage and to promote bacterial survival. In bacterial pathogens such as Yersinia pseudotuberculosis, this also extends to pathogenesis. CpxR is thought to dimerize upon phosphorylation by the sensor kinase CpxA. This phosphorylation enables CpxR binding to specific DNA sequences where it acts on gene transcription. As Cpx pathway activation is dependent on protein-protein interactions, we performed an interaction analysis of CpxR and CpxA from Y. pseudotuberculosis.

Results

CpxR full-length and truncated versions that either contained or lacked a putative internal linker were all assessed for their ability to homodimerize and interact with CpxA. Using an adenylate cyclase-based bacterial two hybrid approach, full-length CpxR readily engaged with CpxA. The CpxR N-terminus could also homodimerize with itself and with a full-length CpxR. A second homodimerization assay based upon the λcI repressor also demonstrated that the CpxR C-terminus could homodimerize. While the linker was not specifically required, it enhanced CpxR homodimerization. Mutagenesis of cpxR identified the aspartate at residue 51, putative N-terminal coiled-coil and C-terminal winged-helix-turn-helix domains as mediators of CpxR homodimerization. Scrutiny of CpxA full-length and truncated versions revealed that dimerization involved the N-terminus and an internal dimerization and histidine phosphotransfer domain.

Conclusions

This interaction analysis mapped regions of CpxR and CpxA that were responsible for interactions with self or with each other. When combined with other physiological and biochemical tests both hybrid-based assays can be useful in dissecting molecular contacts that may underpin Cpx pathway activation and repression.
Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H ß-synuclein
Authors: Sekigawa Akio , Fujita Masayo , Sekiyama Kazunari , Takamatsu Yoshiki , Hatano Taku , Rockenstein Edward , La Spada Albert R , Masliah Eliezer , Hashimoto Makoto
Published: September 2012

Background

Axonopathy is critical in the early pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Axonal swellings such as globules and spheroids are a distinct feature of axonopathy and our recent study showed that transgenic (tg) mice expressing DLB-linked P123H β-synuclein (P123H βS) were characterized by P123H βS-immunoreactive axonal swellings (P123H βS-globules). Therefore, the objectives of this study were to evaluate α-synuclein (αS)-immunoreactive axonal swellings (αS-globules) in the brains of tg mice expressing human wild-type αS and to compare them with the globules in P123H βS tg mice.

Results

In αS tg mice, αS-globules were formed in an age-dependent manner in various brain regions, including the thalamus and basal ganglia. These globules were composed of autophagosome-like membranous structures and were reminiscent of P123H βS-globules in P123H βS tg mice. In the αS-globules, frequent clustering and deformation of mitochondria were observed. These changes were associated with oxidative stress, based on staining of nitrated αS and 4-hydroxy-2-nonenal (4-HNE). In accord with the absence of mitochondria in the P123H βS-globules, staining of nitrated αS and 4-HNE in these globules was weaker than that for αS-globules. Leucine-rich repeat kinase 2 (LRRK2), the PARK8 of familial PD, was detected exclusively in αS-globules, suggesting a specific role of this molecule in these globules.

Conclusions

Lysosomal pathology was similarly observed for both αS- and P123H βS-globules, while oxidative stress was associated with the αS-globules, and to a lesser extent with the P123H βS-globules. Other pathologies, such as mitochondrial alteration and LRRK2 accumulation, were exclusively detected for αS-globules. Collectively, both αS- and P123H βS-globules were formed through similar but distinct pathogenic mechanisms. Our findings suggest that synuclein family members might contribute to diverse axonal pathologies.
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Authors: Morgan Xochitl C , Tickle Timothy L , Sokol Harry , Gevers Dirk , Devaney Kathryn L , Ward Doyle V , Reyes Joshua A , Shah Samir A , LeLeiko Neal , Snapper Scott B , Bousvaros Athos , Korzenik Joshua , Sands Bruce E , Xavier Ramnik J , Huttenhower Curtis
Published: September 2012

Background

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status.

Results

Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways.

Conclusions

This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.
Gas hydrate and free gas petroleum system in 3D seismic data, offshore Angola
Authors: Nyamapfumba Martin , McMechan George A.
Published: September 2012

Evidence of gas hydrate and free gas occurrences in a 3D seismic volume from the West-Central Coastal Province of the Congo Fan, offshore Angola, illustrates all the components of a complete petroleum system. Analysis and interpretation are based on the information in attributes calculated from three 3D time-migrated common-angle seismic volumes; the attributes include seismic amplitude, spectral components, dip magnitude, amplitude variation with angle, and instantaneous frequency. The source is organic-rich muds associated with late Cretaceous to early Tertiary channels, the migration paths are along growth faults, and the traps are partly defined by the gas hydrate stability zone (for the gas hydrate), partly by the bottom-simulating reflector (for the subhydrate free gas), and partly by faults (for both). The spatial distribution of free gas is further supported by the associated seismic bright spots, and also by the attenuation of high frequencies of P-waves that traverse the gas-saturated zone. Locally higher temperatures, associated with upward fluid circulation along fault zones, facilitate gas transmission through the gas hydrate and forms gas chimneys that extend to the sea floor.
Molecular anatomy of tunicate senescence: reversible function of mitochondrial and nuclear genes associated with budding cycles
Authors: Kawamura Kaz , Kitamura Seigo , Sekida Satoko , Tsuda Masayuki , Sunanaga Takeshi
Published: September 2012

Zooids of the asexual strain of Polyandrocarpa misakiensis have a lifespan of 4-5 months; before dying, they produce many buds, enabling continuation of the strain. This study was designed to investigate the nature of gene inactivation and reactivation during this continuous process of senescence and budding. During senescence, the zooidal epidermis showed acid β-galactosidase activity, lost proliferating cell nuclear antigen immunoreactivity and became ultrastructurally worn, indicating that the epidermis is a major tissue affected by the ageing process. Semi-quantitative PCR analysis showed that the genes encoding mitochondrial respiratory chains (MRCs) engaged in decreased transcriptional activity in senescent adults compared with younger adults. The results of in situ hybridization showed that the epidermis dramatically attenuates MRC expression during ageing but restores gene activity when budding commences. During budding and ageing, the nuclear gene Eed (a polycomb group component) was activated and inactivated in a pattern similar to that observed in MRCs. In buds, RNA interference (RNAi) of Eed attenuated Eed transcripts but did not affect the gene expression of pre-activated MRCs. A tunicate humoral factor, TC14-3, could induce Eed, accompanying the reactivation of MRC in adult zooids. When RNAi of Eed and Eed induction were performed simultaneously, zooidal cells and tissues failed to engage in MRC reactivation, indicating the involvement of Eed in MRC activation. Results of this study provide evidence that the mitochondrial gene activities of Polyandrocarpa can be reversed during senescence and budding, suggesting that they are regulated by nuclear polycomb group genes.
Achilles tendon stiffness is unchanged one hour after a marathon
Authors: Peltonen Jussi , Cronin Neil J. , Stenroth Lauri , Finni Taija , Avela Janne
Published: September 2012

Overuse-induced injuries have been proposed as a predisposing factor for Achilles tendon (AT) ruptures. If tendons can be overloaded, their mechanical properties should change during exercise. Because there data are lacking on the effects of a single bout of long-lasting exercise on AT mechanical properties, the present study measured AT stiffness before and after a marathon. AT stiffness was determined as the slope of the force–elongation curve between 10 and 80% of maximum voluntary force. AT force–elongation characteristics were measured in an ankle dynamometer using simultaneous motion-capture-assisted ultrasonography. Oxygen consumption and ankle kinematics were also measured on a treadmill at the marathon pace. All measurements were performed before and after the marathon. AT stiffness did not change significantly from the pre-race value of 197±62 N mm−1 (mean ± s.d.) to the post-race value of 206±59 N mm−1 (N=12, P=0.312). Oxygen consumption increased after the race by 7±10% (P<0.05) and ankle kinematic data revealed that in nine out of 12 subjects, the marathon induced a change in their foot strike technique. The AT of the physically active individuals seems to be able to resist mechanical changes under physiological stress. We therefore suggest that natural loading, like in running, may not overstress the AT or predispose it to injury. In addition, decreased running economy, as well as altered foot strike technique, was probably attributable to muscle fatigue.
Perception of dimethyl sulfide (DMS) by loggerhead sea turtles: a possible mechanism for locating high-productivity oceanic regions for foraging
Authors: Endres Courtney S. , Lohmann Kenneth J.
Published: September 2012

During their long-distance migrations, sea turtles of several species feed on jellyfish and other invertebrates that are particularly abundant in ocean regions characterized by high productivity. An ability to distinguish productive oceanic regions from other areas, and to concentrate foraging activities in locations where prey density is highest, might therefore be adaptive. The volatile compound dimethyl sulfide (DMS) accumulates in the air above productive ocean areas such as upwelling and frontal zones. In principle, DMS might therefore serve as an indicator of high prey density for turtles. To determine whether turtles perceive DMS, juvenile loggerhead sea turtles (Caretta caretta) were placed into a water-filled arena in which DMS and other odorants could be introduced to the air above the water surface. Turtles exposed to air that had passed over a cup containing 10 nmol l−1 DMS spent more time at the surface with their noses out of the water than control turtles, which were exposed to air that had passed over a cup containing distilled water. Odors that do not occur in the sea (cinnamon, jasmine and lemon) did not elicit increased surface time, implying that the response to DMS is unlikely to reflect a generalized response to any novel odor. The results demonstrate for the first time that sea turtles can detect DMS, an ability that might enable the identification of favorable foraging areas.
The Geography of Conflicts and Regional Trade Agreements
Authors: Martin Philippe , Mayer Thierry , Thoenig Mathias
Published: September 2012

In addition to standard trade gains, regional trade agreements (RTAs) can promote peaceful relations by increasing the opportunity cost of conflicts. Country pairs with large trade gains from RTAs and a high probability of conflict should be more likely to sign an RTA. Using data from 1950 to 2000, we show that this complementarity between economic and politics determines the geography of RTAs. We disentangle trade gains from political factors by a theory-driven empirical estimation and find that country pairs with higher frequency of past wars are more likely to sign RTAs, the more so the larger the trade gains. (JEL D72, D74, F15, N70)
Intrinsic flexibility of snRNA hairpin loops facilitates protein binding
Authors: Rau Michael , Stump W. Tom , Hall Kathleen B.
Published: September 2012

Stem–loop II of U1 snRNA and Stem–loop IV of U2 snRNA typically have 10 or 11 nucleotides in their loops. The fluorescent nucleobase 2-aminopurine was used as a substitute for the adenines in each loop to probe the local and global structures and dynamics of these unusually long loops. Using steady-state and time-resolved fluorescence, we find that, while the bases in the loops are stacked, they are able to undergo significant local motion on the picosecond/nanosecond timescale. In addition, the loops have a global conformational change at low temperatures that occurs on the microsecond timescale, as determined using laser T-jump experiments. Nucleobase and loop motions are present at temperatures far below the melting temperature of the hairpin stem, which may facilitate the conformational change required for specific protein binding to these RNA loops.
METHODS—One-Switch Conditions for Multiattribute Utility Functions
Authors: Abbas Ali E. , Bell David E.
Published: September 2012

We introduce a variety of new independence conditions for multiattribute utility functions that permit preference dependencies among the attributes of a decision problem. The hierarchy of new conditions varies in the degree to which it specifies the functional form, ranging from more general solutions with weaker constraints, to more specific solutions with stronger constraints. This formulation provides a wealth of new functional forms that a decision maker may use in a multiattribute decision problem. In addition, it may be used to tailor the utility elicitation process to the comfort level of the decision maker. The new conditions, and the corresponding functional forms, are based on the idea of limiting the number of switches that a decision maker may make between two decision alternatives as a parameter of the problem varies. We show how this formulation also relates many widely used concepts in single and multiattribute utility theory.
Does the posterolateral bundle influence rotational movement more than the anteromedial bundle in anterior cruciate ligament reconstruction?
Authors: Komzák M. , Hart R. , Okál F. , Safi A.
Published: September 2012

The biomechanical function of the anteromedial (AM) and posterolateral (PL) bundles of the anterior cruciate ligament (ACL) remains controversial. Some studies report that the AM bundle stabilises the knee joint in anteroposterior (AP) translation and rotational movement (both internal and external) to the same extent as the PL bundle. Others conclude that the PL bundle is more important than the AM in controlling rotational movement.

The objective of this randomised cohort study involving 60 patients (39 men and 21 women) with a mean age of 32.9 years (18 to 53) was to evaluate the function of the AM and the PL bundles of the ACL in both AP and rotational movements of the knee joint after single-bundle and double-bundle ACL reconstruction using a computer navigation system. In the double-bundle group the patients were also randomised to have the AM or the PL bundle tensioned first, with knee laxity measured after each stage of reconstruction. All patients had isolated complete ACL tears, and the presence of a meniscal injury was the only supplementary pathology permitted for inclusion in the trial. The KT-1000 arthrometer was used to apply a constant load to evaluate the AP translation and the rolimeter was used to apply a constant rotational force. For the single-bundle group deviation was measured before and after ACL reconstruction. In the double-bundle group deviation was measured for the ACL-deficient, AM- or PL-reconstructed first conditions and for the total reconstruction.

We found that the AM bundle in the double-bundle group controlled rotation as much as the single-bundle technique, and to a greater extent than the PL bundle in the double-bundle technique. The double-bundle technique increases AP translation and rotational stability in internal rotation more than the single-bundle technique.
Evaluation of the relationship between anteroposterior translation of a posterior cruciate ligament-retaining total knee replacement and functional outcome
Authors: Seah R. B. , Pang H. N. , Lo N. N. , Chong H. C. , Chin P. L. , Chia S. L. , Yeo S. J.
Published: September 2012

The success of total knee replacement (TKR) depends on optimal soft-tissue balancing, among many other factors. The objective of this study is to correlate post-operative anteroposterior (AP) translation of a posterior cruciate ligament-retaining TKR with clinical outcome at two years. In total 100 patients were divided into three groups based on their AP translation as measured by the KT-1000 arthrometer. Group 1 patients had AP translation < 5 mm, Group 2 had AP translation from 5 mm to 10 mm, and Group 3 had AP translation >  10 mm. Outcome assessment included range of movement of the knee, the presence of flexion contractures, hyperextension, knee mechanical axes and functional outcome using the Knee Society score, Oxford knee score and the Short-Form 36 questionnaire.

At two years, patients in Group 2 reported significantly better Oxford knee scores than the other groups (p = 0.045). A positive correlation between range of movement and AP translation was noted, with patients in group 3 having the greatest range of movement (mean flexion: 117.9° (106° to 130°)) (p < 0.001). However, significantly more patients in Group 3 developed hyperextension > 10° (p = 0.01).

In this study, the best outcome for cruciate-ligament retaining TKR was achieved in patients with an AP translation of 5 mm to 10 mm.
Mobile-bearing lateral unicompartmental knee replacement with the Oxford domed tibial component
Authors: Streit M. R. , Walker T. , Bruckner T. , Merle C. , Kretzer J. P. , Clarius M. , Aldinger P. R. , Gotterbarm T.
Published: September 2012

The Oxford mobile-bearing unicompartmental knee replacement (UKR) is an effective and safe treatment for osteoarthritis of the medial compartment. The results in the lateral compartment have been disappointing due to a high early rate of dislocation of the bearing. A series using a newly designed domed tibial component is reported.

The first 50 consecutive domed lateral Oxford UKRs in 50 patients with a mean follow-up of three years (2.0 to 4.3) were included. Clinical scores were obtained prospectively and Kaplan-Meier survival analysis was performed for different endpoints. Radiological variables related to the position and alignment of the components were measured.

One patient died and none was lost to follow-up. The cumulative incidence of dislocation was 6.2% (95% confidence interval (CI) 2.0 to 17.9) at three years. Survival using revision for any reason and aseptic revision was 94% (95% CI 82 to 98) and 96% (95% CI 85 to 99) at three years, respectively. Outcome scores, visual analogue scale for pain and maximum knee flexion showed a significant improvement (p < 0.001). The mean Oxford knee score was 43 (sd 5.3), the mean Objective American Knee Society score was 91 (sd 13.9) and the mean Functional American Knee Society score was 90 (sd 17.5). The mean maximum flexion was 127° (90° to 145°). Significant elevation of the lateral joint line as measured by the proximal tibial varus angle (p = 0.04) was evident in the dislocation group when compared with the non-dislocation group.

Clinical results are excellent and short-term survival has improved when compared with earlier series. The risk of dislocation remains higher using a mobile-bearing UKR in the lateral compartment when compared with the medial compartment. Patients should be informed about this complication. To avoid dislocations, care must be taken not to elevate the lateral joint line.
The role of the sensory nerve response in ultrasound accelerated fracture repair
Authors: Lam W-L. , Guo X. , Leung K-S. , Kwong K. S. C.
Published: September 2012

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology.

Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing.
The adverse effect of elevated body mass index on outcome after autologous chondrocyte implantation
Authors: Jaiswal P. K. , Bentley G. , Carrington R. W. J. , Skinner J. A. , Briggs T. W. R.
Published: September 2012

We analysed whether a high body mass index (BMI) had a deleterious effect on outcome following autologous chondrocyte implantation (ACI) or matrix-carried autologous chondrocyte implantation (MACI) for the treatment of full-thickness chondral defects of the knee from a subset of patients enrolled in the ACI vs MACI trial at The Royal National Orthopaedic Hospital.

The mean Modified Cincinnati scores (MCS) were significantly higher (p < 0.001) post-operatively in patients who had an ideal body weight (n = 53; 20 to 24.9 kg/m2) than in overweight (n = 63; 25 to 30 kg/m2) and obese patients (n = 22; > 30 kg/m2). At a follow-up of two years, obese patients demonstrated no sustained improvement in the MCS. Patients with an ideal weight experienced significant improvements as early as six months after surgery (p = 0.007). In total, 82% of patients (31 of 38) in the ideal group had a good or excellent result, compared with 49% (22 of 45) of the overweight and 5.5% (one of 18) in the obese group (p < 0.001). There was a significant negative relationship between BMI and the MCS 24 months after surgery (r = -0.4, p = 0.001).

This study demonstrates that obese patients have worse knee function before surgery and experience no sustained benefit from ACI or MACI at two years after surgery. There was a correlation between increasing BMI and a lower MCS according to a linear regression analysis. On the basis of our findings patient selection can be more appropriately targeted.
The incidence of post operative venous thromboembolism in patients undergoing varicose vein surgery recorded in Hospital Episode Statistics
Authors: Sutton PA , El-Duhwaib Y , Dyer J , Guy AJ
Published: September 2012

INTRODUCTION

The aim of this study was to establish the incidence of post-operative venous thromboembolism (VTE) following varicose vein treatment.

METHODS

Hospital Episode Statistics (HES) data were obtained for all patients undergoing varicose vein treatment between April 2006 and April 2007 to identify those reattending with either deep vein thrombosis or pulmonary embolism within 12 months.

RESULTS

The incidence of VTE was 0.51%, which was comparable with the incidence for those undergoing open surgery (0.54%), sclerotherapy (0.19%) and endovenous laser therapy (EVLT) (0.47%). The incidence of VTE in those undergoing combined EVLT and phlebectomy was 1.26% (p=0.01). In contrast to unilateral treatment (all modalities), where bilateral treatment was performed an increase in the incidence of VTE was seen in those undergoing redo (1.62%) and short saphenous system (1.16%) treatments.Overall, 1.02% of cases were performed under local anaesthesia with zero incidence of VTE in this cohort.

CONCLUSIONS

The overall incidence of VTE recorded in HES was 0.51% and appears to be highest in those undergoing bilateral redo or short saphenous system surgery as well as those undergoing a combination of EVLT and phlebectomy. The use of VTE prophylaxis, particularly in these groups, is recommended.