bluuebunny/crossref_metadata_2025 huggingface dataset:
An econometric analysis of the Spanish fresh fish market
Authors: Castillo-Manzano José I. , López-Valpuesta Lourdes , Gonzalez-Laxe Fernando , Pedregal Diego J.
Published: November 2013

This article seeks to analyse the factors that determine the dynamics of the balance between supply and demand in the Spanish fresh fish market. For this, the time-series of fresh fish landed in the 1973–2009 period is analysed through an estimation of the series of transfer function models. Among other things, the findings in the Spanish case show a complex relationship between the amount of fish landed and price; a clear substitution relationship between fresh fish and aquaculture; a negative impact of labour costs in a manual labour-intensive sector such as fishing, which in developed countries is being affected by an exodus of manpower to other sectors where there is less uncertainty surrounding labour conditions; the impact of Spain being barred from international fishing grounds a result of the delimitation of exclusive economic zones (EEZs); and the dwindling importance of fisheries traffic as a result of the port devolution process begun in Spain in the early 1990s. The non-significance of a priori key factors, such as the price of oil and Spain's entry into the EEC, can be explained by widespread energy subsidies and contradictions in the objectives of the Common Fisheries Policy, respectively.
Glitch recoveries in radio-pulsars and magnetars
Authors: Haskell B. , Antonopoulou D.
Published: November 2013

Pulsar glitches are sudden increases in the spin frequency of an otherwise steadily spinning down neutron star. These events are thought to represent a direct probe of the dynamics of the superfluid interior of the star. However glitches can differ significantly from one another, not only in size and frequency, but also in the post-glitch response of the star. Some appear as simple steps in frequency, while others also display an increase in spin-down rate after the glitch. Others still show several exponentially relaxing components in the post-glitch recovery. We show that if glitches are indeed due to large-scale unpinning of superfluid vortices, the different regions in which this occurs and respective time-scales on which they recouple can lead to the various observed signatures. Furthermore, we show that this framework naturally accounts for the peculiar relaxations of glitches in Anomalous X-ray Pulsars.
Cycling of the E. coli lagging strand polymerase is triggered exclusively by the availability of a new primer at the replication fork
Authors: Yuan Quan , McHenry Charles S.
Published: November 2013

Two models have been proposed for triggering release of the lagging strand polymerase at the replication fork, enabling cycling to the primer for the next Okazaki fragment—either collision with the 5′-end of the preceding fragment (collision model) or synthesis of a new primer by primase (signaling model). Specific perturbation of lagging strand elongation on minicircles with a highly asymmetric G:C distribution with ddGTP or dGDPNP yielded results that confirmed the signaling model and ruled out the collision model. We demonstrated that the presence of a primer, not primase per se, provides the signal that triggers cycling. Lagging strand synthesis proceeds much faster than leading strand synthesis, explaining why gaps between Okazaki fragments are not found under physiological conditions.
Translation rate is controlled by coupled trade-offs between site accessibility, selective RNA unfolding and sliding at upstream standby sites
Authors: Espah Borujeni Amin , Channarasappa Anirudh S. , Salis Howard M.
Published: November 2013

The ribosome’s interactions with mRNA govern its translation rate and the effects of post-transcriptional regulation. Long, structured 5′ untranslated regions (5′ UTRs) are commonly found in bacterial mRNAs, though the physical mechanisms that determine how the ribosome binds these upstream regions remain poorly defined. Here, we systematically investigate the ribosome’s interactions with structured standby sites, upstream of Shine–Dalgarno sequences, and show that these interactions can modulate translation initiation rates by over 100-fold. We find that an mRNA’s translation initiation rate is controlled by the amount of single-stranded surface area, the partial unfolding of RNA structures to minimize the ribosome’s binding free energy penalty, the absence of cooperative binding and the potential for ribosomal sliding. We develop a biophysical model employing thermodynamic first principles and a four-parameter free energy model to accurately predict the ribosome’s translation initiation rates for 136 synthetic 5′ UTRs with large structures, diverse shapes and multiple standby site modules. The model predicts and experiments confirm that the ribosome can readily bind distant standby site modules that support high translation rates, providing a physical mechanism for observed context effects and long-range post-transcriptional regulation.
Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny
Authors: Kumar Satyendra , Wuerffel Robert , Achour Ikbel , Lajoie Bryan , Sen Ranjan , Dekker Job , Feeney Ann J. , Kenter Amy L.
Published: November 2013

V(D)J joining is mediated by RAG recombinase during early B-lymphocyte development in the bone marrow (BM). Activation-induced deaminase initiates isotype switching in mature B cells of secondary lymphoid structures. Previous studies questioned the strict ontological partitioning of these processes. We show that pro-B cells undergo robust switching to a subset of immunoglobulin H (IgH) isotypes. Chromatin studies reveal that in pro-B cells, the spatial organization of the Igh locus may restrict switching to this subset of isotypes. We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE phenotype of Omenn syndrome.
Building the mammalian testis: origins, differentiation, and assembly of the component cell populations
Authors: Svingen Terje , Koopman Peter
Published: November 2013

Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial cells arise from bipotential precursors present in the precursor tissue, the genital ridge. These cell types do not differentiate independently but depend on signals from Sertoli cells that differentiate under the influence of transcription factors SRY and SOX9. While these steps are becoming better understood, the origins and roles of many testicular cell types and structures—including peritubular myoid cells, the tunica albuginea, the arterial and venous blood vasculature, lymphatic vessels, macrophages, and nerve cells—have remained unclear. This review synthesizes current knowledge of how the architecture of the testis unfolds and highlights the questions that remain to be explored, thus providing a roadmap for future studies that may help illuminate the causes of XY disorders of sex development, infertility, and testicular cancers.
Modification of Plasma Membrane Organization in Tobacco Cells Elicited by Cryptogein
Authors: Gerbeau-Pissot Patricia , Der Christophe , Thomas Dominique , Anca Iulia-Andra , Grosjean Kevin , Roche Yann , Perrier-Cornet Jean-Marie , Mongrand Sébastien , Simon-Plas Françoise
Published: November 2013

Lipid mixtures within artificial membranes undergo a separation into liquid-disordered and liquid-ordered phases. However, the existence of this segregation into microscopic liquid-ordered phases has been difficult to prove in living cells, and the precise organization of the plasma membrane into such phases has not been elucidated in plant cells. We developed a multispectral confocal microscopy approach to generate ratiometric images of the plasma membrane surface of Bright Yellow 2 tobacco (Nicotiana tabacum) suspension cells labeled with an environment sensitive fluorescent probe. This allowed the in vivo characterization of the global level of order of this membrane, by which we could demonstrate that an increase in its proportion of ordered phases transiently occurred in the early steps of the signaling triggered by cryptogein and flagellin, two elicitors of plant defense reactions. The use of fluorescence recovery after photobleaching revealed an increase in plasma membrane fluidity induced by cryptogein, but not by flagellin. Moreover, we characterized the spatial distribution of liquid-ordered phases on the membrane of living plant cells and monitored their variations induced by cryptogein elicitation. We analyze these results in the context of plant defense signaling, discuss their meaning within the framework of the “membrane raft” hypothesis, and propose a new mechanism of signaling platform formation in response to elicitor treatment.
Bis(5-hydroxyisophthalato-κO1)bis[4-(pyridine-3-carboxamido-κN3)pyridinium]copper(II) tetrahydrate
Authors: O'Donovan Megan E. , LaDuca Robert L.
Published: November 2013

In the title compound, [Cu(C11H10N3O)2(C8H4O5)2]·4H2O, the CuIIion, located on a crystallographic inversion center, is coordinated in a square-planar environment by twotrans-O atoms belonging to two monodentate 5-hydroxyisophthalate (hip) dianions and twotransnicotinamide pyridyl N-donor atoms from monodentate protonated pendantN-(pyridin-4-yl)nicotinamide (4-pnaH) ligands. The protonated 4-pyridylamine groups engage in N—H+...O−hydrogen-bond donation to unligated hip O atoms to construct supramolecular chain motifs parallel to [100]. Water molecules of crystallization, situated between the chains, engage in O—H...O hydrogen bonding to form supramolecular layers and the overall three-dimensional network structure.
2,9-Dimethyl-1,10-phenanthrolin-1-ium 2,4,5-tricarboxybenzoate monohydrate
Authors: Zhong Kai-Long
Published: November 2013

In the preparation of the title hydrated salt, C14H13N2+·C10H5O8−·H2O, a proton has been transfered to the 2,9-dimethyl-1,10-phenanthrolinium cation, forming a 2,4,5-tricarboxybenzoate anion. In the anion, the mean planes of the protonated carboxylate groups form dihedral angles of 11.0 (5), 4.4 (5) and 80.3 (4)° with the benzene ring to which they are attached. The mean plane of the deprotonated carboxylate group forms a dihedral angle of 10.6 (5)° with the benzene ring. In the crystal, the anions are involved in carboxylic acid O—H...Ocarboxylhydrogen bonds, generating a two-dimensional network parallel to (001) containingR44(28) andR44(32) motifs. The 2,9-dimethyl-1,10-phenanthrolinium cations and water molecules reside between the anion layers and are connected to the anionsviaN—H...Owaterand Owater—H...Ocarboxylhydrogen bonds. An intramolecular O—H...O hydrogen bond is also observed in the anion.
(1S,3R,8R,10R)-2,2-Dibromo-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodecan-9-one
Authors: Benharref Ahmed , Mazoir Noureddine , Daran Jean-Claude , Berraho Moha
Published: November 2013

The title compound, C16H24Br2O was synthesized by three steps from β-himachalene (3,5,5,9-tetramethyl-2,4a,5,6,7,8-hexahydro-1H-benzocycloheptene), which was isolated from essential oil of the Atlas cedar (Cedrus atlantica). The molecule is built up from a seven-membered ring to which a six- and a three-membered ring are fused. The six-membered ring shows a chair conformation. One C atom in the seven-membered ring and two methyl groups attached to the ring are disordered over two sets of sites, with an occupancy ratio of 0.658 (7):0.342 (7).
(E)-1-[2-(4-Fluoro-2-nitrostyryl)-1-phenylsulfonyl-1H-indol-3-yl]propan-1-one
Authors: Umadevi M. , Saravanan V. , Yamuna R. , Mohanakrishnan A. K. , Chakkaravarthi G.
Published: November 2013

In the title compound, C25H19FN2O5S, the substituted phenyl ring makes a dihedral angle of 12.26 (9)° with the indole ring system. The nitro group is twisted at an angle of 26.92 (8)° out of the plane of the ring to which it is attached. The molecular structure is stabilized by weak C—H...O hydrogen bonds. In the crystal, weak C—H...O, C—H...F and π–π [centroid–centroid distance = 3.6645 (11) Å] interactions link the molecules, forming a three-dimensional network.
Bacterial communities and syntrophic associations involved in anaerobic oxidation of methane process of the Sonora Margin cold seeps, Guaymas Basin
Authors: Vigneron Adrien , Cruaud Perrine , Pignet Patricia , Caprais Jean‐Claude , Gayet Nicolas , Cambon‐Bonavita Marie‐Anne , Godfroy Anne , Toffin Laurent
Published: November 2013

The Sonora Margin cold seeps present on the seafloor a patchiness pattern of white microbial mats surrounded by polychaete and gastropod beds. These surface assemblages are fuelled by abundant organic inputs sedimenting from the water column and upward‐flowing seep fluids. Elevated microbial density was observed in the underlying sediments. A previous study on the same samples identified anaerobic oxidation of methane (AOM) as the potential dominant archaeal process in these Sonora Margin sediments, probably catalysed by three clades of archaeal anaerobic methanotrophs (ANME‐1, ANME‐2 and ANME‐3) associated with bacterial syntrophs. In this study, molecular surveys and microscopic observations investigating the diversity of Bacteria involved in AOM process, as well as the environmental parameters affecting the composition and the morphologies of AOM consortia in the Sonora Margin sediments were carried out. Two groups of Bacteria were identified within the AOM consortia, the Desulfosarcina/Desulfococcus SEEP SRB‐1a group and a Desulfobulbus‐related group. These bacteria showed different niche distributions, association specificities and consortia architectures, depending on sediment surface communities, geochemical parameters and ANME‐associated phylogeny. Therefore, the syntrophic AOM process appears to depend on sulphate‐reducing bacteria with different ecological niches and/or metabolisms, in a biofilm‐like organic matrix.
Functions of the nicotinamide adenine dinucleotide phosphate oxidase family in Ganoderma lucidum: an essential role in ganoderic acid biosynthesis regulation, hyphal branching, fruiting body development, and oxidative‐stress resistance
Authors: Mu Dashuai , Li Chenyang , Zhang Xuchen , Li Xiongbiao , Shi Liang , Ren Ang , Zhao Mingwen
Published: November 2013

Ganoderma lucidum has drawn worldwide interest with regard to its secondary metabolism and pharmaceutical activity. However, the development of such research has been limited because of a lack of basic biological knowledge. Nicotinamide adenine dinucleotide phosphate oxidases (Nox) have recently been highlighted because of the many important biological roles in plants and animals; however, the exact functions of Nox are still not fully understood in fungi. In this study, we identified two Nox isoforms (NoxA and NoxB) and a regulator, NoxR. RNA interference was used, and silencing of the Nox isoforms and NoxR expression indicated a central role for these genes in hyphal branching, fruiting body development, reactive oxygen species (ROS) generation, ROS resistance and ganoderic acid biosynthesis regulation. Further mechanistic investigation revealed that Nox‐generated ROS elevated cytosolic Ca2+ levels by activating a plasma membrane Ca2+ influx pathway, thereby inducing the Ca2+ signal pathway to regulate ganoderic acid biosynthesis and hyphal branching. Importantly, our results highlight the Nox functions in signal crosstalk between ROS and Ca2+, and these findings provide an excellent opportunity to identify the potential pathway linking ROS networks to calcium signalling in fungi and suggest that plants, animals and fungi share a conserved signal‐crosstalk mechanism.
Phylogenetic constraints on elemental stoichiometry and resource allocation in heterotrophic marine bacteria
Authors: Zimmerman Amy E. , Allison Steven D. , Martiny Adam C.
Published: November 2013

The objective of this study was to evaluate the contribution of evolutionary history to variation in the biomass stoichiometry and underlying biochemical allocation patterns of heterotrophic marine bacteria. We hypothesized that phylogeny significantly constrains biochemical allocation strategy and elemental composition among taxa of heterotrophic marine bacteria. Using a ‘common‐garden’ experimental design, we detected significant interspecific variation in stoichiometry, macromolecule allocation and growth rate among 13 strains of marine Proteobacteria. However, this variation was not well explained by 16S rRNA phylogenetic relationships or differences in growth rate. Heterotrophic bacteria likely experience C‐limitation when consuming resources in Redfield proportions, which consequently decouples growth rate from allocation to rRNA and biomass P content. Accordingly, overall bacterial C : nutrient ratios (C : P = 77, C : N = 4.9) were lower than Redfield proportions, whereas the average N : P ratio of 17 was consistent with the Redfield ratio. Our results suggest that strain‐level diversity is an important driver of variation in the C : N : P ratios of heterotrophic bacterial biomass and that the potential importance of non‐nucleic acid pools of P warrants further investigation. Continued work clarifying the range and controls on the stoichiometry of heterotrophic marine bacteria will help improve understanding and predictions of global ocean C, N and P dynamics.
Identification accuracy and diversity reproducibility associated with internal transcribed spacer‐based fungal taxonomic library preparation
Authors: Yamamoto Naomichi , Dannemiller Karen C. , Bibby Kyle , Peccia Jordan
Published: November 2013

This study investigated analytical parameters that are inherently relevant to identifying and quantifying fungal communities based on polymerase chain reaction amplicons. Specifically, we evaluated the accuracy of the BLASTn‐based identification for internal transcribed spacer (ITS) sequences generated from pure cultures, and quantified the reproducibility of relative abundances as well as α and β diversity measurements using duplicated environmental samples. The BLASTn‐based method produced accurate fungal identification for the pure culture sequences at the genus rank. Percentages of the sequences assigned to correct genera were 99.8%, 99.8% and 99.9% for Alternaria alternata, Cladosporium cladosporioides and Epicoccum nigrum respectively. These fractions were smaller for Aspergillus fumigatus and Penicillium chrysogenum, which have dual nomenclatures or sibling species that are indistinguishable by ITS sequences. Our duplicate environmental analyses demonstrated that α diversity and relative abundance levels were reproducible (r2 > 0.9), that variability decreases with increased sequence quantity, and that the differences in distinct environmental samples were larger than differences in replicate samples (β diversity). These results serve to better characterize the identification and quantification limits of ITS‐based fungal taxonomic studies, and demonstrate that while diversity quantification is reproducible, limitations in ITS‐based taxonomic identification and dual nomenclature conventions are current barriers to identification accuracy.
‘Why don't those lazy priests answer the book?’MatthewTindal, Censorship, Freedom of the Press and Religious Debate in Early Eighteenth‐CenturyEngland
Authors: Barber Alex
Published: November 2013

This article engages with recent work on the consequences of the lapse of licensing (1695) that has emphasized that many people embraced the new opportunities offered by the end of pre‐publication censorship. It is argued here, instead, that many people opposed the press and lobbied enthusiastically for books and authors to be prosecuted. Far from the lapse of licensing being an important precursor to the emergence of a self‐confident and modern nation it initiated a period of political and religious turbulence. Nevertheless, the intention here is not to revise a simplistic view of censorship as a series of discrete moments devoid of ideological importance. Rather, this article contends that the consequences of the lapse of licensing can only be understood by considering the interaction between acts of censorship and theories of the freedom of the press. To this end the article considers the disputes between freethinkers and clerics to establish the answers to a series of vital questions: why and when should authors, books and publishers be prosecuted? Who had responsibility to initiate prosecutions – government, church or public? How much publicity should be given to censorship trials so that they acted as forms of deterrence? This article, then, by considering both the promotion of a free press and the subsequent clerical responses, sheds new light on the vitality of the confrontation between freethinker and cleric in the early eighteenth century.
Video‐assisted thoracoscopic lobectomy with a single utility port is feasible in the treatment of elderly patients with peripheral lung cancer
Authors: Li Chang , Xu Chun , Ma Haitao , Ni Bin , Chen Jun , Chen Tengfei , Zhang Hongtao , Zhao Jun
Published: November 2013

Background

Video‐assisted thoracoscopic (VATS) lobectomy with a single utility port has emerged as a new technology in recent years. The aim of this study is to review the technology in the treatment of elderly patients with peripheral lung cancer.

Methods

We retrospectively analyzed the clinical data of 21 elderly patients with peripheral lung cancer who underwent single utility port VATS lobectomy from February 2011 to February 2013 in the First Affiliated Hospital of Soochow University (VATS group). The clinical outcomes and postoperative complications were then compared to data from 32 elderly patients who underwent lobectomy by thoracotomy (TL group).

Results

No mortality occurred during the postoperative period in either group. There was no statistical difference in surgery duration, the quantity of lymph node dissection or intraoperative blood loss between the VATS and TL groups. However, significant differences existed in the postoperative hospital stay (6.19 ± 1.69 days vs. 8.22 ± 2.55 days), time to first activity out of bed (20.57 ± 7.72 hours vs. 26.81 ± 9.27 hours), chest drainage duration (4.24 ± 1.04 days vs. 5.22 ± 1.29 days), and total postoperative drainage volume (642.86 ± 158.18 mL vs. 787.81 ± 211.55 mL) between the VATS and TL groups (P < 0.05). The percentage of patients with no complications in the VATS group (85.71%) is significantly higher when compared with the TL group (56.25%, P < 0.05).

Conclusion

VATS lobectomy with a single utility port is a safe and feasible surgical procedure for selected elderly patients with peripheral lung cancer.
Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome
Authors: Su Y.‐P. , Chang C.‐K. , Hayes R. D. , Harrison S. , Lee W. , Broadbent M. , Taylor D. , Stewart R.
Published: November 2013

Objective

To investigate the association between neuroleptic malignant syndrome (NMS) and levels of antipsychotic exposure.

Method

Electronic health record data systematically screened from a large mental health service provider in southeast London provided 67 NMS cases which were individually matched with 254 controls on age, gender, and primary psychiatric diagnosis. Data on psychotropic agents, combinations, dose, and dose change of antipsychotic prescriptions over the preceding 5 (oral agents) or 15 days (depot agents) were extracted and compared between groups using conditional logistic regression models.

Results

NMS was associated with higher number of antipsychotic agents used, use of first‐generation agents or aripiprazole, use of first‐generation agents only or cross‐generation agents, and higher mean and maximum daily doses. In further analyses, associations with antipsychotics type remained significant when adjusted for dose, but those with dose were attenuated following adjustment for type. The specific use of haloperidol, aripiprazole, depot flupentixol, and benzodiazepines was independently associated with NMS. Non‐white ethnicity was also found to be associated with NMS.

Conclusion

NMS was primarily associated with type of antipsychotic and polypharmacy rather than overall dose. Variation in risk by ethnicity requires further research.
Intravenous Immunoglobulin Treatment for Repeated IVF/ICSI Failure and Unexplained Infertility: A Systematic Review and a Meta‐Analysis
Authors: Li Jie , Chen Yang , Liu Chengjun , Hu Yanling , Li Liuming
Published: November 2013

Intravenous immunoglobulin (IVIG) has been introduced empirically into IVF/ICSI programs with the hopes of improving in vitro fertilization (IVF) success. However, the effects of IVIG have been inconsistent. We investigated the effects of IVIG on hard outcomes, including implantation rate, clinical pregnancy rate, live birth rate, miscarriage rate, and live birth rate per embryo transferred. The PubMed, EMBASE, and CNKI databases were searched up to June of 2013 and 10 studies were included. Case‐controlled studies comparing IVIG with placebo in IVF/ICSI women and/or unexplained infertility were included. Using fixed and random effects models, the pooled risk ratios (RR) with 95% confidence intervals (CIs) were calculated. The use of IVIG was significantly associated with a higher implantation rate and RR was 2.708 (95%CI: 1.302–5.629) compared with the placebo. The clinical pregnancy rate and the live birth rate were significantly increased in patients randomized to IVIG; RR was 1.475 (95%CI: 1.191–1.825) for the clinical pregnancy rate and RR was 1.616 (95%CI: 1.243–2.101) for the live birth rate. Moreover, the miscarriage rate was significantly less in patients randomized to IVIG (0.352, 95%CI: 0.168–0.738), but the live birthrate per embryo transferred was not (2.893; 95%CI: 0.810–10.331) less. Our results strongly support that IVIG is a useful treatment option for women undergoing repeated IVF failure.
IL‐23 Induces IL‐22 and IL‐17 Production in Response to Chlamydia muridarum Genital Tract Infection, but the Absence of these Cytokines does not Influence Disease Pathogenesis
Authors: Frazer Lauren C. , Scurlock Amy M. , Zurenski Matthew A. , Riley Melissa M. , Mintus Margaret , Pociask Derek A. , Sullivan Jeanne E. , Andrews Charles W. , Darville Toni
Published: November 2013

Objective

Chlamydia trachomatis infections are a significant cause of reproductive tract pathology. Protective and pathological immune mediators must be differentiated to design a safe and effective vaccine.

Methods

Wild‐type mice and mice deficient in IL‐22 and IL‐23 were infected intravaginally with Chlamydia muridarum, and their course of infection and oviduct pathology were compared. Local genital tract and draining lymph node immune responses were also examined in IL‐23‐deficient mice.

Results

IL‐22‐ and IL‐23‐deficient mice exhibited normal susceptibility to infection and oviduct pathology. IL‐23 was required for the development of a Chlamydia‐specific Th17 response in the lymph nodes and for production of IL‐22 and IL‐17 in the genital tract. However, influx of Th1 and innate immune cells was not compromised in the absence of IL‐23.

Conclusion

IL‐22 and IL‐23 play either redundant or minimal roles in the pathogenesis of Chlamydia infection in the mouse model. Induction of Th17‐associated cytokines by a Chlamydia vaccine should be avoided as these responses are not central to resolution of infection and have pathologic potential.
Comparative Effects of Pulsatile and Nonpulsatile Flow on Plasma Fibrinolytic Balance in Pediatric Patients Undergoing Cardiopulmonary Bypass
Authors: Aĝirbaşli Mehmet A. , Song Jianxun , Lei Fengyang , Wang Shigang , Kunselman Allen R. , Clark Joseph B. , Myers John L. , Ündar Akif
Published: November 2013

In the brain, the components of the fibrinolytic system, tissue plasminogen activator (tPA) and its endogenous inhibitor plasminogen activator inhibitor‐1 (PAI‐1), regulate various neurophysiological and pathological responses. Fibrinolytic balance depends on PAI‐1 and tPA concentrations. The objective of this study is to compare the effects of pulsatile and nonpulsatile perfusion on fibrinolytic balance in children undergoing pediatric cardiopulmonary bypass (CPB). Plasma PAI‐1 antigen and tPA antigen were measured in 40 children (n = 20 pulsatile and n = 20 nonpulsatile group). Plasma samples (1.5 mL) were collected (i) prior to incision, (ii) 1 h after CPB, and (iii) 24 h after CPB. PAI‐1 and tPA levels were measured at each time point. PAI‐1 and tPA levels were significantly increased at 1 h after CPB, followed by a decrease at 24 h. Nonpulsatile but not pulsatile CPB lowered PAI‐1 : tPA ratio significantly at 24 h (median PAI‐1 : tPA ratio 4.63 ± 0.83:1.98 ± 0.48, P = 0.03, for the nonpulsatile group and 4.50 ± 0.92:3.56 ± 1.28, P = 0.2, for the pulsatile group). These results suggest that pulsatile flow maintains endogenous fibrinolytic balance after pediatric cardiopulmonary bypass. Further studies are needed to define the clinical significance of these differences.
Paediatric patients with inflammatory bowel disease who received infliximab experienced improved growth and bone health
Authors: Pichler Judith , Hanslik Andreas , Dietrich Huber Wolf , Aufricht Christoph , Bidmon‐Fliegenschnee Bettina
Published: November 2013

Aim

Children with inflammatory bowel disease (IBD) have a high prevalence of growth retardation and low bone mineral density (BMD). This retrospective study investigated whether the start of infliximab treatment (IFX) was associated with improvement of growth and bone health.

Methods

Anthropometry, BMD and bone markers were measured 1 year before and after the start of IFX treatment in 33 patients (51% males), with a median age of 13.5 years at baseline. Outcomes were growth with treatment and indicators of improved bone health.

Results

Twenty‐one children (64%) experienced a positive catch‐up growth after IFX. Height standard deviation scores (SDS) were significantly higher in children in remission. Treatment with IFX was associated with a statistically significant increase in 25‐hydroxycholecalciferol (25‐OHD, p = 0.01). IFX had no influence on BMD. Children with low BMD < −2 had significantly higher inflammation scores, lower body mass index, weight, height SDS and 25‐ODH after IFX.

Conclusion

After treatment with IFX, children with IBD improved significantly in weight, with the majority achieving positive catch‐up growth. Bone mass tended to remain static with time of treatment with IFX, despite a significant increase in 25‐OHD. Improved nutritional status positively predicts improved bone mineralisation.
Long‐term follow‐up of sacral neuromodulation for lower urinary tract dysfunction
Authors: Peeters Karlien , Sahai Arun , De Ridder Dirk , Van Der Aa Frank
Published: November 2013

Objective

To report our long‐term experience of sacral neuromodulation (SNM) for various lower urinary tract dysfunctions but with a focus on efficacy, safety, re‐interventions and degree of success.

Patients and Methods

This is a single tertiary referral centre study that included 217 patients (86% female) who received an implantable pulse generator (IPG) (Interstim™, Medtronic, Minneapolis, USA) between 1996 and 2010.

Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline, but was further stratified.

Results

The mean duration of follow‐up was 46.88 months.

Success and cure rates were ≈70% and 20% for urgency incontinence, 68% and 33% for urgency frequency syndrome and 73% and 58% for idiopathic retention.

In those patients with an unsuccessful therapy outcome, the mean time to failure was 24.6 months after implantation.

There were 88 (41%) patients who had at least one device or treatment related surgical re‐intervention.

The re‐intervention rate was 1.7 per patient with most of them (47%) occurring ≤2 years of follow‐up.

Conclusions

SNM appears effective in the long‐term with a success rate after definitive IPG implant of ≈70% and complete cure rates ranging between 20% and 58% depending on indication.

Patients with idiopathic retention appear to do best.

The re‐intervention rate is high with most occurring ≤2 years of implantation. It is likely that with the newer techniques used, efficacy and re‐intervention rates will improve.
MINIMUM WAGE HIKES AND THE WAGE GROWTH OF LOW‐WAGE WORKERS
Authors: Swaffield Joanna K.
Published: November 2013

This paper presents difference‐in‐differences estimates of the impact of the British minimum wage on the wage growth of low‐wage employees. Estimates of the probability of low‐wage employees receiving positive wage growth have been significantly increased by the minimum wage upratings or hikes. However, whether the actual wage growth of these workers has been significantly raised or not depends crucially on the magnitude of the minimum wage hike considered. Findings are consistent with employers complying with the legally binding minimum wage but holding down or offsetting the wage growth that they might have awarded in periods of relatively low minimum wage hikes.
GluN2C/GluN2D subunit‐selective NMDA receptor potentiator CIQ reverses MK‐801‐induced impairment in prepulse inhibition and working memory in Y‐maze test in mice
Authors: Suryavanshi P S , Ugale R R , Yilmazer‐Hanke D , Stairs D J , Dravid S M
Published: November 2013

Background and Purpose

Despite ample evidence supporting the N‐methyl‐d‐aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, progress in the development of effective therapeutics based on this hypothesis has been limited. Facilitation of NMDA receptor function by co‐agonists (d‐serine or glycine) only partially alleviates the symptoms in schizophrenia; other means to facilitate NMDA receptors are required. NMDA receptor sub‐types differ in their subunit composition, with varied GluN2 subunits (GluN2A‐GluN2D) imparting different physiological, biochemical and pharmacological properties. CIQ is a positive allosteric modulator that is selective for GluN2C/GluN2D‐containing NMDA receptors (Mullasseril et al.).

Experimental Approach

The effect of systemic administration of CIQ was tested on impairment in prepulse inhibition (PPI), hyperlocomotion and stereotypy induced by i.p. administration of MK‐801 and methamphetamine. The effect of CIQ was also tested on MK‐801‐induced impairment in working memory in Y‐maze spontaneous alternation test.

Key Results

We found that systemic administration of CIQ (20 mg·kg−1, i.p.) in mice reversed MK‐801 (0.15 mg·kg−1, i.p.)‐induced, but not methamphetamine (3 mg·kg−1, i.p.)‐induced, deficit in PPI. MK‐801 increased the startle amplitude to pulse alone, which was not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK‐801‐ and methamphetamine‐induced hyperlocomotion and stereotyped behaviours. Additionally, CIQ reversed the MK‐801‐induced working memory deficit in spontaneous alternation in a Y‐maze.

Conclusion and Implications

Together, these results suggest that facilitation of GluN2C/GluN2D‐containing receptors may serve as an important therapeutic strategy for treating positive and cognitive symptoms in schizophrenia.
Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats
Authors: Lopez‐Rodriguez Ana Belen , Llorente‐Berzal Alvaro , Garcia‐Segura Luis M , Viveros Maria‐Paz
Published: November 2013

Background and Purpose

Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long‐term effects of Δ9‐tetrahydrocannabinol (THC) and 3,4‐methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers.

Experimental Approach

Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex.

Key Results

THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba‐1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a ‘normalization’ to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA.

Conclusions and Implications

Adolescent exposure of rats to THC and/or MDMA induced long‐term, sex‐dependent neurochemical and glial alterations, and revealed interactions between the two drugs.

Linked Articles

This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐6
Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men
Authors: Lisulo M M , Kapulu M C , Banda R , Sinkala E , Kayamba V , Sianongo S , Kelly P
Published: November 2013

There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of α4β7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10 nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3 h after 10 mg ATRA. We then evaluated the effect of 10 mg ATRA given 1 h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] Cmax was 26·2 (11·7–39·5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P = 0·02) and protein (P = 0·04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant.
Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus
Authors: Neumann Thomas , Hofbauer Lorenz C. , Rauner Martina , Lodes Sabine , Kästner Bettina , Franke Sybille , Kiehntopf Michael , Lehmann Thomas , Müller Ulrich A. , Wolf Gunter , Hamann Christine , Sämann Alexander
Published: November 2013

Aim

Type 1 diabetes mellitus (T1DM) increases fragility fractures due to low bone mass, micro‐architectural alterations and decreased bone formation. Sclerostin is expressed by osteocytes and inhibits osteoblastic bone formation. We evaluated serum sclerostin levels in T1DM and their association with bone mineral density (BMD), bone turnover, glycaemic control and physical activity.

Patients and Methods

In a cross‐sectional study, 128 men and premenopausal women with long‐standing T1DM (mean age 43·4 ± 8·8 years, diabetes duration 22·4 ± 9·5 years) and 77 age‐, BMI (Body Mass Index) and gender‐matched healthy individuals were evaluated.

Results

Serum sclerostin levels were higher in T1DM compared with controls, irrespective of gender (male 0·55 ± 0·17 vs 0·49 ± 0·12 ng/ml, P = 0·046; female 0·52 ± 0·19 ng/ml vs 0·43 ± 0·12 ng/ml, P = 0·012). Partial correlation analysis adjusted for age and gender revealed a positive correlation between serum sclerostin levels and BMD at lumbar spine and femoral neck in T1DM and between BMD at lumbar spine, femoral neck and total hip in controls. Bone turnover markers, parathyroid hormone, calcium and vitamin D did not correlate with serum sclerostin levels in T1DM or controls. Physical activity was not associated with serum sclerostin levels. A multivariate analysis revealed that only the interaction of T1DM and age affects serum sclerostin levels but not T1DM alone. The influence of age on serum sclerostin levels was more pronounced in T1DM compared with controls.

Conclusions

Sclerostin serum levels were increased in patients with T1DM, and the positive correlation of age with serum sclerostin levels was stronger in T1DM. There was no effect of serum sclerostin levels on markers of bone metabolism and they do not explain the detrimental effects of T1DM on BMD.
Roles of Sema4A in multiple sclerosis and interferon‐β therapy efficacy
Authors: Nakatsuji Yuji , Okuno Tatsusada , Koda Toru , Takata Kazushiro , Honorat Josephe A. , Mochizuki Hideki , Kumanogoh Atsushi
Published: November 2013

The early initiation of appropriate treatment is important for a better prognosis for patients with multiple sclerosis (MS). Although interferon (IFN‐β) has been the most prescribed therapy for MS, some patients are poor responders to this therapy. Therefore, finding biomarkers to predict treatment responsiveness is required. Some patients with MS have high serum Sema4A and concurrently have characteristics of Th17‐skewing conditions, and do not respond well to IFN‐β therapy. In the present review, we discuss Sema4A and responsiveness to IFN‐β therapy. In addition, we review biomarkers relevant to IFN‐β therapy responsiveness.
Adolescent onset cognitive regression and neuropsychiatric symptoms associated with the A140V MECP2 mutation
Authors: Venkateswaran Sunita , McMillan Hugh J , Doja Asif , Humphreys Peter
Published: November 2013

The phenotype attributed to MECP2 mutations continues to expand. In addition to classic and variant Rett syndrome, phenotypes include non‐specific intellectual disability and autism spectrum disorder in females, and fatal neonatal encephalopathy in males. One particular phenotype of parkinsonism, pyramidal signs, and neuropsychiatric symptoms (PPM‐X) has been described only in males. We report on the first female with the A140V MECP2 mutation presenting with late onset cognitive regression, pyramidal symptoms, parkinsonism, and bipolar symptoms. This finding emphasizes the need to consider MECP2 sequencing in females with non‐classic Rett phenotypes, particularly those with intellectual disability and neuropsychiatric features.
The roles of top and intermediate predators in herbivore suppression: contrasting results from the field and laboratory
Authors: HOGG BRIAN N. , DAANE KENT M.
Published: November 2013

Intraguild predators can have unpredictable effects in food webs: they can either disrupt or enhance herbivore suppression, depending on their direct effects on herbivores. Furthermore, intraguild predation is not always unidirectional, with top predators eating more effective intermediate predators.

In a vineyard field experiment and a series of laboratory experiments, the effect of intraguild interactions between a likely top predator (the spiderCheiracanthium mildei) and an intermediate predator (the spiderAnyphaena pacifica) on suppression of their shared leafhopper prey (Erythroneuraspp.) was examined.

In the field experiment,C. mildeidrove the suppression of leafhoppers while reducing numbers of the other spiderA. pacifica. The results of laboratory experiments confirmed the predatory impacts ofC. mildeion both leafhoppers andA. pacifica. As a top intraguild predator,C. mildeiappears to dominate predator–prey interactions in the vineyard ecosystem, although results indicate that its impact may be dampened by cannibalism.

By contrast,A. pacificapreyed on leafhoppers and smallerC. mildeiin laboratory experiments, but had no measurable impacts in the field experiment.

The larger average size and wide‐ranging hunting mode ofC. mildeimay provide a predatory advantage in the field that did not emerge over short time periods in small laboratory cages.

These results highlight the pitfalls of extrapolating from the controlled setting of the laboratory to more heterogeneous conditions in the field.
Posterior parietal cortex is critical for the encoding, consolidation, and retrieval of a memory that guides attention for learning
Authors: Schiffino Felipe L. , Zhou Vivian , Holland Peter C.
Published: November 2013

Within most contemporary learning theories, reinforcement prediction error, the difference between the obtained and expected reinforcer value, critically influences associative learning. In some theories, this prediction error determines the momentary effectiveness of the reinforcer itself, such that the same physical event produces more learning when its presentation is surprising than when it is expected. In other theories, prediction error enhances attention to potential cues for that reinforcer by adjusting cue‐specific associability parameters, biasing the processing of those stimuli so that they more readily enter into new associations in the future. A unique feature of these latter theories is that such alterations in stimulus associability must be represented in memory in an enduring fashion. Indeed, considerable data indicate that altered associability may be expressed days after its induction. Previous research from our laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event, and to the subsequent expression of that altered associability in more rapid learning. Here, for the first time, we identified a brain region, the posterior parietal cortex, as a potential site for a memorial representation of altered stimulus associability. In three experiments using rats and a serial prediction task, we found that intact posterior parietal cortex function was essential during the encoding, consolidation, and retrieval of an associability memory enhanced by surprising omissions. We discuss these new results in the context of our previous findings and additional plausible frontoparietal and subcortical networks.