bluuebunny/crossref_metadata_2025 huggingface dataset:
Clathrin Hub Expression Affects Early Endosome Distribution with Minimal Impact on Receptor Sorting and Recycling
Authors: Bennett Elizabeth M. , Lin Sharron X. , Towler Mhairi C. , Maxfield Frederick R. , Brodsky Frances M.
Published: July 2013

Clathrin-coated vesicles execute receptor-mediated endocytosis at the plasma membrane. However, a role for clathrin in later endocytic trafficking processes, such as receptor sorting and recycling or maintaining the organization of the endocytic pathway, has not been thoroughly characterized. The existence of clathrin-coated buds on endosomes suggests that clathrin might mediate later endocytic trafficking events. To investigate the function of clathrin-coated buds on endosomal membranes, endosome function and distribution were analyzed in a HeLa cell line that expresses the dominant-negative clathrin inhibitor Hub in an inducible manner. As expected, Hub expression reduced receptor-mediated endocytosis at the plasma membrane. Hub expression also induced a perinuclear aggregation of early endosome antigen 1-positive early endosomes, such that sorting and recycling endosomes were found tightly concentrated in the perinuclear region. Despite the dramatic redistribution of endosomes, Hub expression did not affect the overall kinetics of receptor sorting or recycling. These data show that clathrin function is necessary to maintain proper cellular distribution of early endosomes but does not play a prominent role in sorting and recycling events. Thus, clathrin's role on endosomal membranes is to influence organelle localization and is distinct from its role in trafficking pathways at the plasma membrane and trans-Golgi network.
Mammalian Dynamin-like Protein DLP1 Tubulates Membranes
Authors: Yoon Yisang , Pitts Kelly R. , McNiven Mark A.
Published: July 2013

Dynamins are large GTPases with mechanochemical properties that are known to constrict and tubulate membranes. A recently identified mammalian dynamin-like protein (DLP1) is essential for the proper cellular distribution of mitochondria and the endoplasmic reticulum in cultured cells. In this study, we investigated the ability of DLP1 to remodel membranes similar to conventional dynamin. We found that the expression of a GTPase-defective mutant, DLP1-K38A, in cultured cells led to the formation of large cytoplasmic aggregates. Electron microscopy (EM) of cells expressing DLP1-K38A revealed that these aggregates were comprised of membrane tubules of a consistent diameter. High-magnification EM revealed the presence of many regular striations along individual membrane tubules, and immunogold labeling confirmed the association of DLP1 with these structures. Biochemical experiments with the use of recombinant DLP1 and labeled GTP demonstrated that DLP1-K38A binds but does not hydrolyze or release GTP. Furthermore, the affinity of DLP1-K38A for membrane is increased compared with wild-type DLP1. To test whether DLP1 could tubulate membrane in vitro, recombinant DLP1 was combined with synthetic liposomes and nucleotides. We found that DLP1 protein alone assembled into sedimentable macromolecular structures in the presence of guanosine-5′-O-(3-thio)triphosphate (GTPγS) but not GTP. EM of the GTPγS-treated DLP1 revealed clusters of stacked helical ring structures. When liposomes were included with DLP1, formation of long membrane tubules similar in size to those formed in vivo was observed. Addition of GTPγS greatly enhanced membrane tubule formation, suggesting the GTP-bound form of DLP1 deforms liposomes into tubules as the DLP1-K38A does in vivo. These results provide the first evidence that the dynamin family member, DLP1, is able to tubulate membranes both in living cells and in vitro. Furthermore, these findings also indicate that despite the limited homology to conventional dynamins (35%) these proteins remodel membranes in a similar manner.
An integrative approach to understanding the combinatorial histone code at functional elements
Authors: Lai William K. M. , Buck Michael J.
Published: July 2013

Summary: The rapid advancement of genomic technology has revealed the enormous complexity and combinatorial nature of chromatin modifications. To facilitate interpretation of the combinatorial nature of chromatin, we have developed a novel method to integrate all chromatin datasets into distinct nucleosome types (nucleosome alphabet). We have applied this approach to Saccharomyces cerevisiae, generating a nucleosome alphabet, which forms chromatin motifs when mapped back to the genome. By applying novel chromatin alignment and global word search approaches, we have defined distinctive chromatin motifs for introns, origins of replication, tRNAs, antisense transcripts, double-strand-break hotspots and DNase hypersensitive sites, and can distinguish genes by expression level. We have also uncovered strong associations between transcription factor binding and specific types of nucleosomes. Our results demonstrate the uses and functionality of defining a chromatin alphabet and provide a unique and novel framework for exploring chromatin architecture.

Contact: mjbuck@buffalo.edu

Supplementary Information: Supplementary data are available at Bioinformatics online.
Attachment site recognition and regulation of directionality by the serine integrases
Authors: Rutherford Karen , Yuan Peng , Perry Kay , Sharp Robert , Van Duyne Gregory D.
Published: July 2013

Serine integrases catalyze the integration of bacteriophage DNA into a host genome by site-specific recombination between ‘attachment sites’ in the phage ( attP ) and the host ( attB ). The reaction is highly directional; the reverse excision reaction between the product attL and attR sites does not occur in the absence of a phage-encoded factor, nor does recombination occur between other pairings of attachment sites. A mechanistic understanding of how these enzymes achieve site-selectivity and directionality has been limited by a lack of structural models. Here, we report the structure of the C-terminal domains of a serine integrase bound to an attP DNA half-site. The structure leads directly to models for understanding how the integrase-bound attP and attB sites differ, why these enzymes preferentially form attP × attB synaptic complexes to initiate recombination, and how attL × attR recombination is prevented. In these models, different domain organizations on attP vs. attB half-sites allow attachment-site specific interactions to form between integrase subunits via an unusual protruding coiled-coil motif. These interactions are used to preferentially synapse integrase-bound attP and attB and inhibit synapsis of integrase-bound attL and attR . The results provide a structural framework for understanding, testing and engineering serine integrase function.
Minimizing the risk of cancer: tissue architecture and cellular replication limits
Authors: Rodriguez-Brenes Ignacio A. , Wodarz Dominik , Komarova Natalia L.
Published: July 2013

Normal somatic cells are capable of only a limited number of divisions, which prevents unlimited cell proliferation and the onset of tumours. Cancer cells find ways to circumvent this obstacle, typically by expressing the enzyme telomerase and less often by alternative recombination strategies. Given this fundamental link between cellular replication limits and cancer, it is important to understand how a tissue's architecture affects the replicative capacity of a cell population. We define this as the average number of remaining divisions at equilibrium. The lower the replication capacity, the lower the chances to escape the replication limit during abnormal growth when a tumour develops. In this paper, we examine how the replication capacity is influenced by defining characteristics of cell lineages, such as the number of intermediate cell compartments, self-renewal capability of cells and division rates. We describe an optimal tissue architecture that minimizes the replication capacity of dividing cells and thus the risk of cancer. Interestingly, some of the features that define an optimal tissue architecture have been documented in a variety of tissues, suggesting that they may have evolved as a cancer-protecting strategy in multicellular organisms.
Improving cytocompatibility of Co28Cr6Mo by TiO
2
coating: gene expression study in human endothelial cells
Authors: Tsaryk R. , Peters K. , Unger R. E. , Feldmann M. , Hoffmann B. , Heidenau F. , Kirkpatrick C. J.
Published: July 2013

Cobalt-based materials are widely used for coronary stents, as well as bone and joint implants. However, their use is associated with high corrosion incidence. Titanium alloys, by contrast, are more biocompatible owing to the formation of a relatively inactive titanium oxide (TiO
2
) layer on their surface. This study was aimed at improving Co28Cr6Mo alloy cytocompatibility via sol–gel TiO
2
coating to reduce metal corrosion and metal ion release. Owing to their role in inflammation and tissue remodelling around an implant, endothelial cells present a suitable
in vitro
model for testing the biological response to metallic materials. Primary human endothelial cells seeded on Co28Cr6Mo showed a stress phenotype with numerous F-actin fibres absent on TiO
2
-coated material. To investigate this effect at the gene expression level, cDNA microarray analysis of in total 1301 genes was performed. Compared with control cells, 247 genes were expressed differentially in the cells grown on Co28Cr6Mo, among them genes involved in proliferation, oxidative stress response and inflammation. TiO
2
coating reduced the effects of Co28Cr6Mo on gene expression in endothelial cells, with only 34 genes being differentially expressed. Quantitative real-time polymerase chain reaction and protein analysis confirmed microarray data for selected genes. The effect of TiO
2
coating can be, in part, attributed to the reduced release of Co
2+
, because addition of CoCl
2
resulted in similar cellular responses. TiO
2
coating of cobalt-based materials, therefore, could be used in the production of cobalt-based devices for cardiovascular and skeletal applications to reduce the adverse effects of metal corrosion products and to improve the response of endothelial and other cell types.
Label-free Raman monitoring of extracellular matrix formation in three-dimensional polymeric scaffolds
Authors: Kunstar Aliz , Leferink Anne M. , Okagbare Paul I. , Morris Michael D. , Roessler Blake J. , Otto Cees , Karperien Marcel , van Blitterswijk Clemens A. , Moroni Lorenzo , van Apeldoorn Aart A.
Published: July 2013

Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional scaffolds for regenerative medicine and clinical purposes. Raman spectroscopy can be used for non-invasive sensing of cellular and ECM biochemistry. We have investigated the use of conventional (confocal and semiconfocal) Raman microspectroscopy and fibre-optic Raman spectroscopy for
in vitro
monitoring of ECM formation in three-dimensional poly(ethylene oxide terephthalate)–poly(butylene terephthalate) (PEOT/PBT) scaffolds. Chondrocyte-seeded PEOT/PBT scaffolds were analysed for ECM formation by Raman microspectroscopy, biochemical analysis, histology and scanning electron microscopy. ECM deposition in these scaffolds was successfully detected by biochemical and histological analysis and by label-free non-destructive Raman microspectroscopy. In the spectra collected by the conventional Raman set-ups, the Raman bands at 937 and at 1062 cm
−1
which, respectively, correspond to collagen and sulfated glycosaminoglycans could be used as Raman markers for ECM formation in scaffolds. Collagen synthesis was found to be different in single chondrocyte-seeded scaffolds when compared with microaggregate-seeded samples. Normalized band-area ratios for collagen content of single cell-seeded samples gradually decreased during a 21-day culture period, whereas collagen content of the microaggregate-seeded samples significantly increased during this period. Moreover, a fibre-optic Raman set-up allowed for the collection of Raman spectra from multiple pores inside scaffolds in parallel. These fibre-optic measurements could give a representative average of the ECM Raman signal present in tissue-engineered constructs. Results in this study provide proof-of-principle that Raman microspectroscopy is a promising non-invasive tool to monitor ECM production and remodelling in three-dimensional porous cartilage tissue-engineered constructs.
Stokes flow singularities in a two-dimensional channel: a novel transform approach with application to microswimming
Authors: Crowdy Darren G. , Davis Anthony M. J.
Published: July 2013

A transform method for determining the flow generated by the singularities of Stokes flow in a two-dimensional channel is presented. The analysis is based on a general approach to biharmonic boundary value problems in a simply connected polygon formulated by Crowdy & Fokas in this journal. The method differs from a traditional Fourier transform approach in entailing a simultaneous spectral analysis in the independent variables both along and across the channel. As an example application, we find the evolution equations for a circular treadmilling microswimmer in the channel correct to third order in the swimmer radius. Significantly, the new transform method is extendible to the analysis of Stokes flows in more complicated polygonal microchannel geometries.
Can terrestrial ectotherms escape the heat of climate change by moving?
Authors: Buckley Lauren B. , Tewksbury Joshua J. , Deutsch Curtis A.
Published: July 2013

Whether movement will enable organisms to alleviate thermal stress is central to the biodiversity implications of climate change. We use the temperature-dependence of ectotherm performance to investigate the fitness consequences of movement. Movement to an optimal location within a 50 km radius will only offset the fitness impacts of climate change by 2100 in 5 per cent of locations globally. Random movement carries an 87 per cent risk of further fitness detriment. Mountainous regions with high temperature seasonality (i.e. temperate areas) not only offer the greatest benefit from optimal movement but also the most severe fitness consequences if an organism moves to the wrong location. Doubling dispersal capacity would provide modest benefit exclusively to directed dispersers in topographically diverse areas. The benefits of movement for escaping climate change are particularly limited in the tropics, where fitness impacts will be most severe. The potential of movement to lessen climate change impacts may have been overestimated.
Spatial and temporal escape from fungal parasitism in natural communities of anciently asexual bdelloid rotifers
Authors: Wilson Christopher G. , Sherman Paul W.
Published: July 2013

Sexual reproduction is costly, but it is nearly ubiquitous among plants and animals, whereas obligately asexual taxa are rare and almost always short-lived. The Red Queen hypothesis proposes that sex overcomes its costs by enabling organisms to keep pace with coevolving parasites and pathogens. If so, the few cases of stable long-term asexuality ought to be found in groups whose coevolutionary interactions with parasites are unusually weak. In theory, antagonistic coevolution will be attenuated if hosts disperse among patches within a metapopulation separately from parasites and more rapidly. We examined whether these conditions are met in natural communities of bdelloid rotifers, one of the longest-lived asexual lineages. At any life stage, these microscopic invertebrates can tolerate the complete desiccation of their ephemeral freshwater habitats, surviving as dormant propagules that are readily carried by the wind. In our field experiments, desiccation and wind transport enabled bdelloids to disperse independently of multiple fungal parasites, in both time and space. Surveys of bdelloid communities in unmanipulated moss patches confirmed that fungal parasitism was negatively correlated with extended drought and increasing height (exposure to wind). Bdelloid ecology therefore matches a key condition of models in which asexuals persist through spatio-temporal decoupling from coevolving enemies.
Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks
Authors: Saini Camille , Liani André , Curie Thomas , Gos Pascal , Kreppel Florian , Emmenegger Yann , Bonacina Luigi , Wolf Jean-Pierre , Poget Yves-Alain , Franken Paul , Schibler Ueli
Published: July 2013

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.
Control of Reproductive Floral Organ Identity Specification inArabidopsisby the C Function Regulator AGAMOUS
Authors: Ó’Maoiléidigh Diarmuid S. , Wuest Samuel E. , Rae Liina , Raganelli Andrea , Ryan Patrick T. , Kwaśniewska Kamila , Das Pradeep , Lohan Amanda J. , Loftus Brendan , Graciet Emmanuelle , Wellmer Frank
Published: July 2013

The floral organ identity factor AGAMOUS (AG) is a key regulator of Arabidopsis thaliana flower development, where it is involved in the formation of the reproductive floral organs as well as in the control of meristem determinacy. To obtain insights into how AG specifies organ fate, we determined the genes and processes acting downstream of this C function regulator during early flower development and distinguished between direct and indirect effects. To this end, we combined genome-wide localization studies, gene perturbation experiments, and computational analyses. Our results demonstrate that AG controls flower development to a large extent by controlling the expression of other genes with regulatory functions, which are involved in mediating a plethora of different developmental processes. One aspect of this function is the suppression of the leaf development program in emerging floral primordia. Using trichome initiation as an example, we demonstrate that AG inhibits an important aspect of leaf development through the direct control of key regulatory genes. A comparison of the gene expression programs controlled by AG and the B function regulators APETALA3 and PISTILLATA, respectively, showed that while they control many developmental processes in conjunction, they also have marked antagonistic, as well as independent activities.
Phase determination of the crystal structure factor by measuring rocking curves from a polar crystal
Authors: Negishi Riichirou , Fukamachi Tomoe , Jongsukswat Sukswat , Hirano Kenji , Hirano Keiichi , Kawamura Takaaki
Published: July 2013

A novel phase determination approach comparing FWHMs with intensities of rocking curves from the top and bottom surfaces of a polar crystal is proposed. The approach is applied to GaAs ±333 reflections in Bragg mode and the phases are determined with good accuracy. This approach is potentially very useful for determining the phase of a polar crystal, including that for a nearly perfect crystal.
GBgeom: a computer program for visualizing texture parameters and simulating grain boundary structures in cubic crystals
Authors: Karthikeyan Thangaraj , Saroja Saibaba
Published: July 2013

GBgeom is a computer graphics program developed for unraveling the relations between different texture parameters and for simulating the basic unrelaxed atomic structures at grain boundary planes in body- and face-centered cubic crystalline materials. It could be a useful tool to materials researchers for interpreting texture data and for deciphering the possible ordered structures at grain boundaries. The software has been developed using the Visual C++ language, and OpenGL routines have been used for rendering various outputs and implementing an intuitive user interface.
Improved asymmetric peak parameter refinement
Authors: Hester James R.
Published: July 2013

New expressions for the calculation of axial asymmetry peak shape parameter derivatives in the Finger, Cox and Jephcoat model [J. Appl. Cryst. (1994), 27, 892–900] are presented. Code utilizing the new expressions shows an improved range of convergence for powder diffraction peak shape refinements, particularly when the parameters are transformed to A = H + S and B = H − S.
Evidence for Dualism in Inquisitorial Registers of the 1240s: A Contribution to a Debate
Authors: Taylor Claire
Published: July 2013

In theChristian middle ages, people who refused to accept what they were supposed to believe about God or HisChurch were labelled ‘heretics’. But who decided whether their views were ‘orthodox’ or ‘heretical'? ‘Heretics’ typically saw themselves as the trueChristians. Most did not dispute the central doctrines ofChristianity itself, but challenged theChurch as it was constituted in their day. In this they clashed with the vested interests of clerics, and as a result they typically had doctrinal and moral crimes attributed to them in the sources. These possibly bore little relationship to what they actually believed. Given this, how can we know that they were heretics in the first place? Through examining the testimony of witnesses giving evidence to inquisitors in southernFrance in the 1240s, this article demonstrates not only that the role of theRomanChurch was contested, but also that core orthodox doctrines, such as belief in one God, in His creation of the world, and in HisSonJesus suffering and dying in human form, were disputed. Such concepts were not simply imposed on the written record by inquisitors. We have evidence of sincerely held dissenting beliefs, which were often the result of discussion and debate between three competing religious systems prevalent in the region:Catholicism, what historians now call ‘Catharism’, and ‘Waldensianism’. Inquisitors did not simply impose an externally constructed or stereotypical ‘heretic’ onto its records. The evidence indicates that ‘Catharism’ was both real and antithetical to other belief systems.
Churchill's Black Dog at the Home Office, 1910–1911: The Evidential Reliability of Psychiatric Inference
Authors: Attenborough Wilfred
Published: July 2013

This is a case study of what passes for the evidential basis of psychological and psychiatric generalizations within popular historical accounts of, and widely publicized conceptions of, Winston Churchill. There are two objectives. First, to sift and evaluate textual evidence concerning Black Dog's actual manifestations and impact during Churchill's term at the Home Office – a period often suggested as one in which he experienced significant mental ill‐health – utilizing, wherever possible, information and clues Churchill himself left behind. The second objective, interwoven with the first, is to subject to test and challenge the evidence relied on for diagnostic pronouncements from the dominant Storr/Ghaemi perspective, while being alert for indications of the alternative apprehension perspective identified, though not consistently adhered to, by Lord Moran. The overall conclusion is that, although clinical precision is unobtainable, the likelihood is that Black Dog at the Home Office manifested as, not melancholia, but worry and other forms of anxiety disorder.
Making Gibraltar British in the Eighteenth Century
Authors: Plank Geoffrey
Published: July 2013

The conquest and retention of Gibraltar was a challenge for Britain in the eighteenth century, not only militarily and diplomatically, but also in the context of domestic politics and culture. Gibraltar was a British imperial possession on the edge of Europe, an imposing but isolated outpost, and the centre of a trade network dominated by Muslim Africans and Sephardic Jews. Its largest ethnic group was Catholic and Genoese. Never well understood by most Britons, Gibraltar became an object of fantasy. The British fantasies are revealing, providing evidence, for example, on popular understandings of Anglo‐Muslim relations, the place of Jews within the British empire and Britain's relationship with the European continent. Gibraltar defied easy classification and forced the Britons who commanded there, resided there, or contemplated the outpost from afar to reconsider the importance of Protestantism, European heritage and British identity within the framework of the empire. Before 1748 most British commentary on Gibraltar associated the place with Africans, but after the middle of the century it was increasingly viewed as a bastion defending one frontier of Europe. Following the unsuccessful Spanish siege of 1779–83, Gibraltar became a symbol of British strength and endurance, with Britons standing alone against the rest of the world.
Hypnosis Antenatal Training for Childbirth: a randomised controlled trial
Authors: Cyna AM , Crowther CA , Robinson JS , Andrew MI , Antoniou G , Baghurst P
Published: July 2013

Objective

To determine the use of pharmacologic analgesia during childbirth when antenatal hypnosis is added to standard care.

Design

Randomised controlled clinical trial, conducted from December 2005 to December 2010.

Setting

The largest tertiary referral centre for maternity care in South Australia.

Population

A cohort of 448 women at >34 weeks of gestation, with a singleton pregnancy and cephalic presentation, planning a vaginal birth. Exclusions were: the need for an interpreter; pre‐existing pain; psychiatric illness; younger than 18 years; and previous experience of hypnosis for childbirth.

Methods

All participants received usual care. The group of women termedHypnosis + CD(hypnotherapist guided) were offered three antenatal live hypnosis sessions plus each session's corresponding audioCDfor further practise, as well as a final fourthCDto listen to during labour. The group of women termedCDonly (nurse administered) were played the same antenatal hypnosisCDs as group 1, but did not receive live hypnosis training. The control group participants were given no additional intervention orCDs.

Main outcome measure

Use of pharmacological analgesia during labour and childbirth.

Results

No difference in the use of pharmacological analgesia during labour and childbirth was found comparing hypnosis + CDwith control (81.2 versus 76.2%; relative risk,RR1.07; 95% confidence interval, 95% CI0.95–1.20), or comparingCDonly with control (76.9 versus 76.2%,RR1.01, 95% CI0.89–1.15).

Conclusions

Antenatal group hypnosis using the Hypnosis Antenatal Training for Childbirth (HATCh) intervention in late pregnancy does not reduce the use of pharmacological analgesia during labour and childbirth.
Randomized Pilot Trial Between Prostaglandin I2 Analog and Anti‐Platelet Drugs on Peripheral Arterial Disease in Hemodialysis Patients
Authors: Ohtake Takayasu , Sato Motoyoshi , Nakazawa Ryoichi , Kondoh Morihiro , Miyaji Takehiko , Moriya Hidekazu , Hidaka Sumi , Kobayashi Shuzo
Published: July 2013

The effect of the prostaglandin I2 analog, beraprost sodium (BPS), on hemodialysis (HD) patients with peripheral arterial disease (PAD) has not been fully elucidated. The effect of BPS was compared to that of PAD drugs in HD patients with PAD in a multicenter randomized prospective interventional pilot study (J‐PADD). Seventy‐two PAD patients on HD were entered and randomly divided into two groups; that is, BPS group (Group A: n = 35) and PAD drug (cilostazol or sarpogrelate) group (Group B: n = 37). Primary endpoint was changes in skin perfusion pressure (SPP). Kidney Disease Quality of Life (KDQOL) score, cardiovascular events, PAD events, and adverse events were also evaluated. SPP increased significantly in both groups at 24 weeks from their basal levels. The absolute increase of SPP in Group A and Group B were 15.4 ± 30.0 mm Hg (P < 0.0001) and 20.2 ± 22.1 mm Hg (P = 0.025) (instep), and 13.8 ± 19.3 mm Hg (P < 0.0001) and 9.2 ± 16.3 mm Hg (P = 0.041) (sole), respectively. Changes of KDQOL score showed significantly better result in the role of physical score in Group A compared with Group B. Although heart rate was unchanged in Group A, 9.3/min increase was seen in Group B patients who received cilostazol. There was no intergroup difference in cardiovascular events and/or PAD events between the two groups during the study period. This exploratory pilot study suggested BPS was as effective as anti‐platelet drugs in improving microcirculation in HD patients.
Efficacy of Intra‐Arterial Treatment for Massive Gastrointestinal Bleeding in Hemodialysis Patients
Authors: Banshodani Masataka , Kawanishi Hideki , Moriishi Misaki , Shintaku Sadanori , Sato Tomoyasu , Tsuchiya Shinichiro
Published: July 2013

The incidence of acute nonvariceal massive gastrointestinal bleeding (GIB) is higher in hemodialysis (HD) patients than in healthy individuals, and this is often a life‐threatening event. We evaluated the efficacy of intra‐arterial treatment for GIB in HD patients. Between January 2006 and June 2012, eight HD patients with GIB were treated with superselective transarterial embolization. Of the eight cases, one was duodenal bleeding, two were jejunal bleeding, one was ileocecum bleeding, two were ascending colonic bleeding, and two were sigmoid colonic bleeding. After examining the site of bleeding by endoscopy or contrast‐enhanced computed tomography (CT), embolizations with microcoils, gelatin sponges, or N‐butyl cyanoacrylate were performed through interventional radiology (IVR). In all cases, blood transfusions were frequently administered. Six of the eight patients with GIB were successfully salvaged by transarterial embolization. In one case, duodenal bleeding was refractory to endoscopic treatment. Embolization was performed twice in this case; however, the patient died of an aneurysm rupture at the embolization site 24 days after the embolizations. In another case, massive jejunal bleeding and disseminated intravascular coagulation were identified at the time of the first examination, and the patient died of multiorgan failure 26 days after the embolization. On the basis of our experience, we established an effective treatment strategy for HD patients with acute nonvariceal massive GIB, by immediately identifying the exact site and degree of bleeding using contrast‐enhanced computed tomography and performing early treatment with transarterial embolization.
Plasma Adiponectin Levels for Prediction of Cardiovascular Risk Among Hemodialysis Patients
Authors: El‐Shafey Eid M , Shalan Mohamed
Published: July 2013

Adiponectin (ADPN) is an endogenous insulin sensitizing and anti‐inflammatory hormone, released by the adipose tissue. We investigated the clinical and biochemical correlates of plasma ADPN levels and the predictive value of ADPN with respect to survival rates and cardiovascular (CV) events was tested prospectively in a cohort of hemodialysis (HD) patients. We measured baseline ADPN in 110 HD patients, in addition to, 34 healthy subjects to serve as reference group. ADPN levels, were related to different clinical and biochemical cardiovascular risk factors such as increased body mass index (BMI), serum triglycerides (TG), duration of HD, smoking, mean arterial blood pressure (MBP), heart rate (HR), high density (HDL) cholesterol, low density (LDL) cholesterol, serum glucose, hemoglobulin and C‐reactive protein (CRP) levels in HD patients. Plasma ADPN levels were higher (P = 0.000) among HD patients (15.06 ± 3.54 μg/mL) than among reference subjects (6.52 ± 1.07 μg/mL), were independent of age, and higher among women (16.13 ± 3.09 μg/mL) than among men (13.94 ± 3.65 μg/mL). Plasma ADPN levels were inversely related to BMI, TG, CRP and glucose levels. Furthermore, plasma ADPN levels were directly related to HDL‐cholesterol and Kt/V. Plasma ADPN levels were lower (P = 0.000) among patients who experienced new CV events (11.13 ± 2.15 μg/mL) than among event‐free patients (16.82 ± 2.45 μg/mL), and seem to predict cardiovascular outcomes. The inverse relationships between ADPN and several cardiovascular risk factors indicate that ADPN may have a protective role in the prevention of CV events.
Mixing of Isaria fumosorosea with enhanced diatomaceous earth and bitterbarkomycin for control of Rhyzopertha dominica
Authors: Riasat Tahira , Wakil Waqas , Yasin Muhammad , Kwon Yong Jung
Published: July 2013

The virulence of Isaria fumosorosea alone and integrated with an enhanced formulation of diatomaceous earth (diatomaceous earth + bitterbarkomycin, DEBBM) was tested against the lesser grain borer Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) under laboratory conditions on stored wheat. The fungus was applied to wheat grains at various concentrations of 3.60 × 106, 3.60 × 108, and 3.60 × 1010 conidia/kg alone, or in combination with 15 and 30 ppm of DEBBM. R. dominica was held at 20, 25 and 30°C and two RH regimes (56 and 75%) and mortality was registered after 5, 10 and 15 d. Generally, I. fumosorosea was most effective at 25°C caused the highest mortality of R. dominica at 56% RH. The increase of temperature, concentration and exposure interval increased the insecticidal effect of DEBBM at low RH level. The DE alone suppressed the progeny emergence at higher dose rate as compared I. fumosorosea alone, but their simultaneous use further reduced the progeny production of R. dominica. The integrated use of both tested bio control agents synergized the effect of each other and caused the highest mortality at 25°C and 56% RH. The results clearly demonstrated that I. fumosorosea and new enhanced DEBBM can be integrated to be an effective control measure for R. dominica in stored wheat.
A systematic review of attachment and psychosis: measurement, construct validity and outcomes
Authors: Gumley A. I. , Taylor H. E. F. , Schwannauer M. , MacBeth A.
Published: July 2013

Objective

This review sought to identify, summarise and critically evaluate studies that investigated attachment amongst individuals with psychosis.

Method

The following computerised databases searched were CINAHL < 1980 to December 2012; EMBASE < 1980 to December 2012; Ovid MEDLINE (R) < 1980 to December 2012; PsychINFO < 1980 to December 2012; and Google Scholar < 1980 to December 2012.

Results

We identified 22 papers describing 21 studies comprising 1453 participants, with a mean age of 35.0 years (range of 12–71 years), of whom 68.4% (n = 994) were male. Of our sample, 1112 (76.5%) had a diagnosis of schizophrenia. We found small to moderate associations between greater attachment insecurity (as reflected in anxiety and avoidance) and poorer engagement with services, more interpersonal problems, more avoidant coping strategies, more negative appraisals of parenting experiences and more severe trauma. We also found small to modest associations between attachment insecurity and more positive and negative symptoms and greater affective symptom problems.

Conclusion

Attachment theory may be useful as a means of understanding the developmental and interpersonal basis of recovery and adaptation in the context of psychosis. However, further research comprising more representative samples in their first episode and using prospective designs is required.
Extracorporeal Detoxification for Hepatic Failure Using Molecular Adsorbent Recirculating System: Depurative Efficiency and Clinical Results in a Long‐Term Follow‐Up
Authors: Donati Gabriele , La Manna Gaetano , Cianciolo Giuseppe , Grandinetti Valeria , Carretta Elisa , Cappuccilli Maria , Panicali Laura , Iorio Mario , Piscaglia Fabio , Bolondi Luigi , Colì Luigi , Stefoni Sergio
Published: July 2013

Acute liver failure and acute‐on‐chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty‐four patients with life‐threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23–82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32–62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36–54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1‐year follow‐up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17–29); direct bilirubin RRs was 28% (21–35), and indirect bilirubin RRs was 8% (3–21). Ammonia RRs was 34% (12–86). Conjugated cholic acid RRs was 58% (48–61); chenodeoxycholic acid RRs was 34% (18–48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9–7.9) versus 7.9 ng/mL (3.2–14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End‐stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan–Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.
Economic evaluation of bariatric surgery to combat morbid obesity: A study from the West of Scotland
Authors: Karim Muhammad Ali , Clifton Edward , Ahmed Jamil , Mackay Gordon William , Ali Abdulmajid
Published: July 2013

Introduction

The increasing prevalence of obesity has now become a global concern. Forecasts of its health and financial ramifications have prompted the need for effective interventions. Bariatric surgery is an effective measure to control obesity and its related comorbidities, but its high upfront costs have raised questions about its cost‐effectiveness. In this study we evaluated the health care‐related direct cost savings after bariatric surgery.

Methods

Data were prospectively obtained from patients who underwent bariatric surgery between May 2008 and April 2011, and a review was performed. These patients' annual cost of regular medications, hospital admissions and outpatient clinic visits were compared with the postoperative costs of these services. Data were collected from January 2005 to April 2012.

Results

The analysis included 88 patients, 17 of whom were men and 71 were women. The procedures included 36 laparoscopic adjustable gastric banding, 33 sleeve gastrectomies and 19 Roux‐en‐Y gastric bypasses. All procedures were laparoscopic. Data were collected from patients during a median preoperative period of 60 months (range, 42–75 months) and a median postoperative period of 24 months (range, 12–45 moths). Annual savings were £11 452 on medications, £16 420 on hospital admissions and £2532 on outpatient clinic visits. Total annual savings were £30 404.

Conclusion

Given the rising prevalence of morbid obesity, bariatric surgery is a cost‐effective treatment for morbid obesity and should be made available to morbidly obese patients.
An analysis of a decade of research in 10 instructional design and technology journals
Authors: West Richard Edward , Borup Jered
Published: July 2013

In this paper, we review findings from an analysis of the past decade (2001–10) of research in 10 major journals in the field of instructional design and technology. Each research paper published in these journals during this decade was categorized according to its focus or methodology, topical keywords, authorship and citation trends; and the findings were aggregated across all of the journals to show trends over the last decade. We found there is a strong emphasis on technology‐related issues, distance education, communication strategies and instructional methods over cognitive‐related topics and learning issues. There is a strong history of theoretical inquiry and a fairly even balance of qualitative and quantitative research being published, with other research methods emerging. However, there are distinct differences in methodological stances among the journals. We also found some evidence that the Institute for Scientific Information Impact Factor may not be the best indicator of impact quality for journals in our field.
Late Ordovician, deep‐water gravity‐flow deposits, palaeogeography and tectonic setting, Tarim Basin, Northwest China
Authors: Lin C. , Liu J. , Eriksson K. , Yang H. , Cai Z. , Li H. , Yang Z. , Rui Z.
Published: July 2013

The Upper Ordovician in the Tarim Basin contains 5000–7000 m of siliciclastic and calciclastic deep‐water, gravity‐flow deposits. Their depositional architecture and palaeogeographical setting are documented in this investigation based on an integrated analysis of seismic, borehole and outcrop data. Six gravity‐flow depositional–palaeogeomorphological elements have been identified as follows: submarine canyon or deeply incised channels, broad and shallow erosional channels, erosional–depositional channel and levee–overbank complexes, frontal splays‐lobes and nonchannelized sheets, calciclastic lower slope fans and channel lobes or sheets, and debris‐flow complexes. Gravity‐flow deposits of the Sangtamu and Tierekeawati formations comprise a regional transgressive‐regressive megacycle, which can be further classified into six sequences bounded by unconformities and their correlative conformities. A series of incised valleys or canyons and erosional–depositional channels are identifiable along the major sequence boundaries which might have been formed as the result of global sea‐level falls. The depositional architecture of sequences varies from the upper slope to abyssal basin plain. Palaeogeographical patterns and distribution of the gravity‐flow deposits in the basin can be related to the change in tectonic setting from a passive continental margin in the Cambrian and Early to Middle Ordovician to a retroarc foreland setting in the Late Ordovician. More than 3000 m of siliciclastic submarine‐fan deposits accumulated in south‐eastern Tangguzibasi and north‐eastern Manjiaer depressions. Sedimentary units thin onto intrabasinal palaeotopographical highs of forebulge origin and thicken into backbulge depocentres. Sediments were sourced predominantly from arc terranes in the south‐east and the north‐east. Slide and mass‐transport complexes and a series of debris‐flow and turbidite deposits developed along the toes of unstable slopes on the margins of the deep‐water basins. Turbidite sandstones of channel‐fill and frontal‐splay origin and turbidite lobes comprise potential stratigraphic hydrocarbon reservoirs in the basin.
Inverse correlation between Thr‐669 and constitutive tyrosine phosphorylation in the asymmetric epidermal growth factor receptor dimer conformation
Authors: Sato Kanae , Shin Myoung‐Sook , Sakimura Ayaka , Zhou Yue , Tanaka Tomohiro , Kawanishi Miho , Kawasaki Yuki , Yokoyama Satoru , Koizumi Keiichi , Saiki Ikuo , Sakurai Hiroaki
Published: July 2013

We have recently identified tumor necrosis factor (TNF)‐α‐induced phosphorylation of epidermal growth factor receptor (EGFR) at Thr‐669 and Ser‐1046/1047 via ERK and p38 pathways, respectively. In the present study, we investigated the roles of ligand‐induced phosphorylation of serine and threonine residues in EGFR‐overexpressing MDA‐MB‐468 breast cancer cells. Epidermal growth factor and heregulin, an ErbB3 ligand, induced the phosphorylation of Thr‐669 and Ser‐1046/1047. Inversely, constitutive tyrosine phosphorylation of the C‐terminal domain, including Tyr‐1068, was significantly downregulated on ligand stimulation. Inhibition of the ERK pathway by U0126 blocked ligand‐induced Thr‐669 phosphorylation as well as Tyr‐1068 dephosphorylation. Downregulation of constitutive tyrosine phosphorylation of EGFR in HEK293 cells stably expressing the wild type was abolished by substitution of Thr‐669 for Ala. In an asymmetric EGFR homodimer structure, one Thr‐669 in the receiver kinase of the dimer was involved in downregulation. Similarly, Thr‐669 in an EGFR‐ErbB3 heterodimer also participated in tyrosine dephosphorylation. These results indicate that ERK‐mediated Thr‐669 phosphorylation suppresses constitutive tryrosine phosphosphorylation in the homo‐ and heterodimer asymmetric conformations of the EGFR.
Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis
Authors: Wisniewski J. A. , Agrawal R. , Minnicozzi S. , Xin W. , Patrie J. , Heymann P. W. , Workman L. , Platts‐Mills T. A. , Song T. W. , Moloney M. , Woodfolk J. A.
Published: July 2013

Background

Atopic dermatitis (AD) is common in children; however, persistence of AD with or without asthma is less common. Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship with asthma.

Objective

To use a cross‐sectional study design of children with active AD to analyse age‐related differences in IgE antibodies and relation to wheeze.

Methods

IgE antibodies to food and inhalant allergens were measured in children with active AD (5 months to 15 years of age, n = 66), with and without history of wheeze.

Results

Whereas IgE antibodies to foods persisted at a similar prevalence and titre throughout childhood, IgE antibodies to all aeroallergens rose sharply into adolescence. From birth, the chance of sensitization for any aeroallergen increased for each 12‐month increment in age (OR ≥ 1.21, P < 0.01), with the largest effect observed for dust mite (OR = 1.56, P < 0.001). A steeper age‐related rise in IgE antibody titre to dust mite, but no other allergen was associated with more severe disease. Despite this, sensitization to cat was more strongly associated with wheeze (OR = 4.5, P < 0.01), and linked to Fel d 1 and Fel d 4, but not Fel d 2. Comparison of cat allergic children with AD to those without, revealed higher IgE levels to Fel d 2 and Fel d 4 (P < 0.05), but not Fel d 1.

Conclusions and Clinical Relevance

Differences in sensitization to cat and dust mite among young children with AD may aid in identifying those at increased risk for disease progression and development of asthma. Early sensitization to cat and risk for wheeze among children with AD may be linked to an increased risk for sensitization to a broader spectrum of allergen components from early life. Collectively, our findings argue for early intervention strategies designed to mitigate skin inflammation in children with AD.