bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper in xylem and phloem saps from rice (Oryza sativa): the effect of moderate copper concentrations in the growth medium on the accumulation of five essential metals and a speciation analysis of copper-containing compounds
Authors: Ando Yuko , Nagata Shinji , Yanagisawa Schuichi , Yoneyama Tadakatsu
Published: November 2012

Copper (Cu) is an essential element for cereals, playing important roles as a cofactor of several enzymes. Copper and four other metals (Fe, Mn, Zn and Mo) taken up by roots are efficiently delivered to the shoots via xylem and phloem. Here we investigated the concentrations of Cu, Fe, Mn, Zn and Mo in the xylem and phloem saps as well as in tissues of rice (Oryza sativa L.) seedlings when they were grown under different Cu levels in culture solution. Although the Cu concentrations in the roots and the Mn concentrations in the mature shoot tissues were increased with the increase of the Cu level in the culture solution, the concentrations of Cu and the other four metals in the xylem and phloem saps and the Cu contents in the shoot tissues were only slightly affected by moderate increases in the Cu medium level. The results of our analyses using membrane filtration, size-exclusion chromatography and electrospray ionisation time-of-flight mass spectrometry indicate that Cu in the xylem sap is dominantly complexed by 2′-deoxymugineic acid, whereas Cu in the phloem sap is bound to several compounds, i.e. nicotianamine, histidine and other >3-kDa compounds.
Annonas: soursop and Rollinia.
Authors: Paull R. E. , Duarte O.
Published: November 2012

This chapter on soursop (Annona muricata) and Rollinia (R. mucosa) provides information on taxonomy, areas of origin and distribution, environmental requirements for cultivation (soil physical and chemical properties, rainfall, air temperature, light and photoperiod, and wind), morphology (flowers, stems and fruits), development (flowering, pollination, fruit set, and fruit growth and ripening), cytology (chromosome number) and genetic improvement, cultivar development, propagation (through seeds and clonal propagation), cultural practices (field preparation, transplanting and spacing, irrigation, pruning, and fertilizer application), bacterial and fungal disease management (mainly through cultural control), insect pest management (through chemical and biological control), weed management (through chemical, physical and cultural control), harvesting and postharvest handling, and utilization and processing.
Breadfruit, jackfruit, chempedak and marang.
Authors: Paull R. E. , Duarte O.
Published: November 2012

This chapter on breadfruit (Artocarpus altilis), jackfruit (A. heterophyllus), chempedak (A. integer) and marang (A. odoratissimus) covers the following: taxonomy, geographical distribution, environmental requirements for growth (climate, and soil chemical and physical properties), plant morphology (whole tree, flowers and fruits) and development (pollination, and fruit set, growth and ripening), cultivar development and genetic improvement, cultural practices (propagation and nursery management, transplanting and plant spacing, irrigation, pruning and fertilizer application), diseases and insect pests, weed management (cultural control), orchard protection, harvesting, postharvest handling, and utilization.
Passion fruit and giant passion fruit.
Authors: Paull R. E. , Duarte O.
Published: November 2012

This chapter on passion fruits (Passiflora edulis and P. edulis f. flavicarpa) and giant passion fruit (P. quadrangularis) covers the following: taxonomy, areas of origin and distribution, environmental requirements for cultivation (climate, and soil chemical and physical properties), plant morphology (vine, flowers and fruits) and development (pollination, and fruit set, growth and ripening), cultivar development and selection, cultural practices (propagation, transplanting and spacing, hand pollination, pruning and training, irrigation, and fertilizer application), diseases and insect pests, harvesting, postharvest handling, and utilization.
Modeling Disaster: The Failure of the Management of the New England Groundfish Industry
Authors: Acheson James M. , Gardner Roy
Published: November 2012

Most of the world's marine fisheries are overexploited or endangered, including the Gulf of Maine groundfish fishery, once one of the world's most prolific. After 35 years of management, groundfish stock sizes and catches are lower than when management began. We argue that in New England, the groundfishing industry is caught in a prisoner's dilemma caused by a large number of interactive social, political, and economic variables. These factors have (1) motivated fishermen to oppose the rules promulgated by the government (which we call the “harvest game”) and (2) lowered the benefits of investing in rules to conserve fish stocks (which we call the “rule game”). In both games, fishermen are motivated to play their dominant strategy to the detriment of the industry, conservation, and fish stocks. We suggest that the dilemma will only be solved by a change in the culture of the industry that would lead to support for a conservation ethic. Unfortunately, the current institutional framework of management does not support the development of such an ethic. Rational-choice theory and concepts from evolutionary game theory add to our understanding of the dilemma facing those concerned with groundfish management in this region.

Received March 3, 2010; accepted June 16, 2011
Performance of Surplus Production Models with Time-Varying Parameters for Assessing Multispecies Assemblages
Authors: Nesslage Geneviève M. , Wilberg Michael J.
Published: November 2012

Single-species surplus production models are often used to assess multispecies assemblages in data-poor situations where catch and effort data are insufficient to perform individual species assessments. We examined the performance of single-species surplus production models applied to aggregated multispecies assemblages and explored the incorporation of time-varying parameters to improve model estimates. We simulated the dynamics of three species with different intrinsic growth rates and survey catchabilities over 50 years in the presence of fishing and a single fishery-independent survey. Schaefer surplus production models with and without time-varying growth rate and catchability were fitted to simulated data. We then compared the ability of each model to accurately estimate multispecies maximum sustainable yield and terminal year biomass and to accurately reflect overall trends in individual component stocks. All models produced biased estimates, but the accuracy of multispecies assemblage maximum sustainable yield was improved with the incorporation of time-varying parameters. The terminal biomass of the assemblage was best estimated by a basic production model in two of three scenarios. Multispecies assemblage trends were not reflective of all individual component species, resulting in situations in which some species were overexploited and others underexploited. Although the incorporation of time-varying parameters improved the accuracy of some estimates in this application, the direction and magnitude of bias may not be predictable unless the relative differences in growth rate and catchability among species in the assemblage are known. If single-species surplus production models are the only viable option for modeling assemblages, precautionary reference points should be adopted. Scaling the level of precaution to the range of growth rates among species in the assemblage is recommended.

Received February 19, 2012; accepted August 8, 2012
Utilizing Fishermen Knowledge and Expertise: Keys to Success for Collaborative Fisheries Research
Authors: Yochum Noëlle , Starr Richard M , Wendt Dean E
Published: November 2012

Collaborative fisheries research provides a mechanism for integrating the unique knowledge, experience, and skills of fishermen and scientists. It is a joint intellectual endeavor that begins with the inception of a project and continues until its final stages, with each group having mutual investment in—and ownership of—the project. Collaborative fisheries research promotes communication and trust among fishermen, scientists, and managers and can provide much-needed scientifically valid data for fisheries management. It can enhance federal and state management data collection programs, which span broad sections of coastline, by increasing the ability to detect changes in local metapopulations that may be overfished or underutilized. We describe a methodology for conducting collaborative fisheries surveys and apply it to marine protected areas along the central California coast. During a series of workshops in 2006, attended by members of the fishing, academic, environmental, and management communities, protocols were established for conducting hook-and-line surveys collaboratively with commercial passenger fishing vessel captains and volunteer recreational anglers. The protocols have been implemented annually since 2007. This case study highlights the effectiveness of—and the essential steps in—developing our collaborative fisheries research and monitoring projects.

RESUMEN

La investigación pesquera colaborativa brinda un mecanismo para integrar el conocimiento, experiencia y habilidades de pescadores y científicos. Representa una tarea intelectual conjunta que comienza con una propuesta de proyecto y hacia sus etapas finales, los grupos cuentan con una inversion mutua en -y siendo propietarios del- proyecto mismo. La investigación pesquera colaborativa promueve la comunicación y confianza entre pescadores, científicos y manejadores así como también puede proveer los tan necesitados dates, científicamente validados, para el manejo pesquero. Esto también puede mejorar los programas federales y estatales de colección y manejo de datos, los cuales abarcan grandes extensiones de la línea costera, a través del mejoramiento de las habilidades para detectar los cambios en metapoblaciones locales que pueden estar sobre-explotadas o subutilizadas. Se describe la metodología para llevar a cabo sondeos colaborativos en pesquerías y su aplicación en Areas Marinas Protegidas a lo largo de la porción central de California. Durante una serie de talleres de trabajo realizados en 2006, a los que atendieron miembros del sector pesquero, académico, ambiental y de manejo de comunidades, se establecieron los protocolos para conducir de forma conjunta encuestas a los capitanes de embarcaciones pesqueras y pescadores voluntarios de embarcaciones recreativas. Los protocolos se han implementado anualmente desde 2007. Este caso de estudio destaca la efectividad del -y los pasos funda-mentales para el- desarrollo de la investigación pesquera colaborativa y de proyectos de monitoreo.
Theoretical analysis of polymeric and crystalline thick films melting with a single gold nanoparticle embedded in a transparent matrix under nanosecond pulsed laser excitation
Authors: Rahimi L , Bahrampour A R , Pepe G P
Published: November 2012

Optothermal properties of noble metal nanoparticles can be used in a wide range of applications. This paper presents the results of a theoretical study on the utilization of laser-induced heating of a gold nanoparticle (GNP) to melt a region of a transparent material with sub-wavelength spatial resolution. The considered system consists of a 10 or 15 nm diameter GNP fixed inside a silica substrate. The silica surface is covered with a thick film of the transparent polymeric or crystalline material. The heating and melting processes are studied under a 7.5 ns pulsed laser illumination. Calculations are conducted under three temperature limits, on the maximum temperature of the free electrons, the maximum temperature of the GNP and the maximum temperature of the film layer. The temperature limits lead to the limiting of the average laser power. The maximum allowable value of the average laser power and the effect of various parameters on spatial characteristics of the molten region are considered.
Transapical 29-mm Edwards SAPIEN-XT Aortic Valve in a 34-mm Mitral Annuloplasty Ring
Authors: Dahle Gry , Fiane Arnt E. , Rein Kjell-Arne
Published: November 2012

A 71-year-old woman with severe congestive heart failure and failed mitral valve repair was referred for surgery. Because of her low ejection fraction, a valve-in-ring procedure was suggested. There was a great difference in the given size for the 34-mm Carpentier-Edwards-Physio-Ring and the biggest available transcatheter valve of 29 mm from Edwards. Therefore, we did a “bench test.” We expanded a 29-mm Edwards SAPIEN-XT aortic valve in a 34-mm Carpentier-Edwards-Physio-Ring. It fitted well and turned out circular with good coaptation of the leaflets. Thereafter, a successful transapical mitral valve-in-ring implantation on cardiopulmonary bypass was performed, and additional leads for cardiac resynchronization was placed.
“Kissing Stents” as an Adjunct to Thoracic Endovascular Aortic Repair Warts and All
Authors: Karmy-Jones Riyad , Nicholls Stephen C.
Published: November 2012

A 75-year-old man presented with symptomatic thoracic aneurysm involving the origin of the left subclavian artery. To obtain an adequate landing zone, a simultaneous stent was placed in the left common carotid artery. Until fenestrated and branch graft technology is more available, snorkel approaches may be an acceptable approach for patients with contraindications to open repair.
Effects of Percutaneous Stimulation of Both Sympathetic and Parasympathetic Cardiac Autonomic Nerves on Cardiac Function in Dogs
Authors: Kobayashi Mariko , Sakurai Seiichiro , Takaseya Tohru , Shiose Akira , Kim Hyun-Il , Fujiki Masako , Karimov Jamshid H. , Dessoffy Raymond , Massiello Alex , Borowski Allen G. , Van Wagoner David R. , Jung Eugene , Fukamachi Kiyotaka
Published: November 2012

Objective

Augmentation of left ventricular (LV) contractility and heart rate (HR) by sympathetic nerve stimulation and amelioration of heart failure by vagal nerve stimulation has been reported. However, the effects of concomitant electrical stimulation of both sympathetic and parasympathetic cardiac nerves in tissues such as those of the cardiac plexus remain unclear. This study sought to assess acute changes in cardiac function and hemodynamics in response to endovascular cardiac plexus stimulation (CPS).

Methods

Twelve dogs received endovascular CPS via a bipolar catheter within the right pulmonary artery. Stimulation frequency (20 Hz) and pulse width (4 milliseconds) were fixed; voltage varied (range, 15–60 V).

Results

Results fell into three categories: 1, no response (n = 4); 2, an increase in systemic arterial pressure that was dependent on electrode placement (n = 4); and 3, a very reproducible and stable increase in aortic pressure (n = 4). In the third group, mean systolic aortic pressures, maximum value of the first derivative of LV pressure, and LV stroke work increased with stimulation (P < 0.02 for all parameters) as did cardiac output, end-systolic elastance, and preload recruitable stroke work (P = 0.03). Systemic and pulmonary vascular resistance, central venous pressure, pulmonary arterial pressure, and HR remained unchanged (P > 0.05).

Conclusions

In contrast to conventional inotropic agents, endovascular CPS induced significant and selective increases in LV contractility without increasing HR. Efforts to optimize electrode placement and fixation will improve the reproducibility of endovascular CPS treatment.
Ten Years’ Follow-Up of Single-Surgeon Minimally Invasive Reparative Surgery for Degenerative Mitral Valve Disease
Authors: D'Alfonso Alessandro , Capestro Filippo , Zingaro Carlo , Matteucci Sacha , Rescigno Giuseppe , Torracca Lucia
Published: November 2012

Objective

Granted that minimally invasive mitral valve (MV) surgery short-term results were found to be equivalent to those achieved with traditional sternotomy with respect to perioperative morbidity and echocardiographic outcomes, little is known about the long-term efficacy of this approach. This report analyzes a 10-year single-surgeon experience with minimally invasive MV surgery through a right minithoracotomy with peripheral cannulation and external aortic cross-clamping and MV repair (MVR) by direct vision.

Methods

We studied 179 patients (48% female) who underwent MVR between December 1999 and December 2010. Mean age was 40.2 ± 10.1 years (range, 15–67 years). One hundred seventy patients (95.0%) had degenerative diseases, and nine patients (5.0%) had endocarditic diseases. Repair techniques for degenerative disease with posterior leaflet prolapse (74 patients, 43.5%) consisted of quadrangular resection (QR) and annuloplasty (AP) combined with sliding plasty (49 patients, 58.1%); for anterior leaflet prolapse (28 patients, 16.5%) and bileaflet prolapse (66 patients, 38.8%), edge-to-edge repair (EE) and AP; in 2 patients (1.2%), annular dilatation alone consisting of AP. Repair techniques for endocarditic disease consisted of EE in six patients (66.7%), perforation closure in two patients (22.2%), and QR combined with AP in one patient (11.1%).

Results

All patients survived the operation and were discharged with MV regurgitation (MR) less than 2+/4+. At 10 years’ follow-up, overall survival was 98.7% ± 1.2%, freedom from redo was 98.5% ± 1.1%, freedom from MR recurrence (>2+/4+) in QR and in EE repair were, respectively, 91.7% ± 2.2% and 90.0% ± 2.4% (P = not significant). The linearized rates of overall mortality, MR recurrence (>2+/4+), and redo at follow-up are 0.10% ± 0.10% per year, 0.63% ± 0.26% per year, and 0.21% ± 0.15% per year, respectively.

Conclusions

Minimally invasive MVR can be performed with very good perioperative and long-term results. Freedom from MR greater than 2+/4+ recurrence for patients with QR is equivalent to that with EE repair in our patient cohort.
The Application of Robotic Surgery in Vascular Medicine
Authors: Štádler Petr , Dvořáček Libor , Vitásek Petr , Matouš Pavel
Published: November 2012

Objective

The feasibility of robotically assisted laparoscopic aortic surgery has already been adequately demonstrated. Our clinical experience with robot-assisted aortoiliac reconstruction for occlusive diseases, aneurysms, and hybrid procedures performed using the Da Vinci system is described below.

Methods

Between November 2005 and November 2011, we performed 225 robot-assisted laparoscopic aortoiliac procedures. One hundred seventy-four patients were prospectively evaluated for occlusive diseases, 43 patients for abdominal aortic aneurysm, two for common iliac artery aneurysm, two for splenic artery aneurysm, three for hybrid procedures, and one for endoleak II treatment after endovascular aneurysm repair. The robotic system was applied to construct the vascular anastomosis for thromboendarterectomy, for aortoiliac reconstruction with a closure patch, for dissection of the splenic artery, and for posterior peritoneal suturing. A combination of conventional laparoscopic surgeries and robotic surgeries was routinely included. A modified fully robotic approach without laparoscopic surgery was used in the last 55 cases in our series.

Results

Two hundred seventeen cases (96%) were successfully completed robotically; one patient's surgery was discontinued during laparoscopy because of heavy aortic calcification. In seven patients (3%), conversion was necessary. The 30-day mortality rate was 0.4%, and nonlethal postoperative complications were observed in 10 patients (4.4%).

Conclusions

Our experience with robot-assisted laparoscopic surgery has demonstrated the feasibility of this technique for aortoiliac vascular and hybrid procedures. Compared with purely laparoscopic techniques, the Da Vinci robotic system facilitated the creation of the aortic anastomosis and shortened the aortic clamping time.
Video-Assisted Thymectomy with Contralateral Surveillance Camera a Means to Minimize the Risk of Contralateral Phrenic Nerve Injury
Authors: Nesher Nahum , Pevni Dmitry , Aviram Galit , Kramer Amir , Mohr Rephael , Uretzky Gideon , Ben-Gal Yanai , Paz Yosef
Published: November 2012

Objective

Thymectomy for thymoma has traditionally been performed through midsternotomy that provides excellent exposure for a complete and safe resection. Minimally invasive alternatives have not been extensively evaluated for this disease process because data regarding the long-term oncologic effectiveness of these techniques remain to be established. Furthermore, video-assisted surgery as a unilateral approach may compromise the extension of the resection and could cause irreversible damage to the phrenic nerve of the opposite side. We evaluated the clinical feasibility and safety of a bilateral concomitant video-assisted approach with contralateral surveillance camera in patients undergoing thymectomy for thymoma.

Methods

Four patients (3 females, 1 male) with thymoma causing myasthenia gravis (MG) were operated thoracoscopically at our institute under general anesthesia with double-lumen endotracheal intubation. The patients were placed in a supine position, and a 5-mm 30-degree lens thoracoscope was introduced into the left pleural space. Two other 10-mm working channels were applied. En bloc thymectomy was then performed, including mediastinal and pericardial fat pads, other tissue, and pleura from the level of the thoracic inlet to the diaphragm. A second 5-mm thoracoscope was inserted into the right hemithorax, and it was kept inside during the entire procedure to allow lateral surveillance of the extension and safety of the resection. Carbon dioxide insufflation and valved ports were used.

Results

The duration of the operation was 90 ± 72 minutes. Complete resection was achieved in all patients without any nerve injury. There were no perioperative adverse events. Gradual remission from extremity and ocular weakness was achieved after recovery.

Conclusions

The ultimate surgical goal of thymectomy is to completely remove the gland and anterior mediastinal tissue without nerve injury. Bilateral concomitant video-assisted thoracic thymectomy with a contralateral surveillance camera was found feasible and safe. Given the capability of our technique to perform a complete and extensive thymectomy associated with less invasiveness and beneficial effects, there seems to be a role for minimally invasive thymectomy in the treatment of thymoma.
Augmented Reality Image Guidance Improves Navigation for Beating Heart Mitral Valve Repair
Authors: Chu Michael W.A. , Moore John , Peters Terry , Bainbridge Daniel , McCarty David , Guiraudon Gerard M. , Wedlake Chris , Lang Pencilla , Rajchl Martin , Currie Maria E. , Daly Richard C. , Kiaii Bob
Published: November 2012

Objective

Emerging off-pump beating heart valve repair techniques offer patients less invasive alternatives for mitral valve (MV) repair. However, most of these techniques rely on the limited spatial and temporal resolution of transesophageal echocardiography (TEE) alone, which can make tool visualization and guidance challenging.

Methods

Using a magnetic tracking system and integrated sensors, we created an augmented reality (AR) environment displaying virtual representations of important intracardiac landmarks registered to biplane TEE imaging. In a porcine model, we evaluated the AR guidance system versus TEE alone using the transapically delivered NeoChord DS1000 system to perform MV repair with chordal reconstruction.

Results

Successful tool navigation from left ventricular apex to MV leaflet was achieved in 12 of 12 and 9 of 12 (P = 0.2) attempts with AR imaging and TEE alone, respectively. The distance errors of the tracked tool tip from the intended midline trajectory (5.2 ± 2.4 mm vs 16.8 ± 10.9 mm, P = 0.003), navigation times (16.7 ± 8.0 seconds vs 92.0 ± 84.5 seconds, P = 0.004), and total path lengths (225.2 ± 120.3 mm vs 1128.9 ± 931.1 mm, P = 0.003) were significantly shorter in the AR-guided trials compared with navigation with TEE alone. Furthermore, the potential for injury to other intracardiac structures was nearly 40-fold lower when using the AR imaging for tool navigation. The AR guidance also seemed to shorten the learning curve for novice surgeons.

Conclusions

Augmented reality–enhanced TEE facilitates more direct and safe intracardiac navigation of the NeoChord DS tool from left ventricular apex to MV leaflet. Tracked tool path results demonstrate fourfold improved accuracy, fivefold shorter navigation times, and overall improved safety with AR imaging guidance.
Minimal-Access Left Ventricular Assist Device Explantation
Authors: Cheung Anson , Soon Jia-Lin
Published: November 2012

Patients on left ventricular assist device (LVAD) support can be successfully bridged to recovery. A novel explantation technique is reviewed. Six HeartMate II patients were successfully explanted off-pump through a combination of a left anterior minithoracotomy and a subxiphoid incision. A retrospective review of the institutional LVAD database was performed. The median LVAD support duration was 191 days (range, 69–307 days). There was no procedural or 30-day mortality associated with the LVAD explantation, and all patients are in New York Heart Association I to II at a median follow-up of 688 days (range, 127–1033 days). This procedure was associated with minimal blood transfusion and short intensive care unit stay (median, 1 day; range, 1–5 days) and hospitalization (median, 4.5 days; range, 3–19 days). One postexplant embolic cerebral infarct occurred. The HeartMate II LVAD can be safely explanted through a less conventional minimal-access approach.
A Type III restriction–modification system in
Mycoplasma mycoides
subsp.
capri
Authors: Algire Mikkel A. , Montague Michael G. , Vashee Sanjay , Lartigue Carole , Merryman Chuck
Published: November 2012

The sequenced genome of
Mycoplasma mycoides
subsp.
capri
revealed the presence of a Type III restriction–modification system (MmyCI). The methyltransferase (modification) subunit of MmyCI (M.MmyCI) was shown to recognize the sequence 5′-TGAG-3′ and methylate the adenine. The coding region of the methyltransferase gene contains 12 consecutive AG dinucleotide repeats that result in a translational termination at a TAA codon immediately beyond the repeat region. This strain does not have MmyCI activity. A clone was found with 10 AG repeats such that the gene is in frame, and this strain has MmyCI activity, suggesting that the expression of the MmyCI methyltransferase may be phase variable.
Biogeographic partitioning of Southern Ocean microorganisms revealed by metagenomics
Authors: Wilkins David , Lauro Federico M. , Williams Timothy J. , Demaere Matthew Z. , Brown Mark V. , Hoffman Jeffrey M. , Andrews‐Pfannkoch Cynthia , Mcquaid Jeffrey B. , Riddle Martin J. , Rintoul Stephen R. , Cavicchioli Ricardo
Published: November 2012

We performed a metagenomic survey (6.6 Gbp of 454 sequence data) of Southern Ocean (SO) microorganisms during the austral summer of 2007–2008, examining the genomic signatures of communities across a latitudinal transect from Hobart (44°S) to the Mertz Glacier, Antarctica (67°S). Operational taxonomic units (OTUs) of the SAR11 and SAR116 clades and the cyanobacterial genera Prochlorococcus and Synechococcus were strongly overrepresented north of the Polar Front (PF). Conversely, OTUs of the Gammaproteobacterial Sulfur Oxidizer‐EOSA‐1 (GSO‐EOSA‐1) complex, the phyla Bacteroidetes and Verrucomicrobia and order Rhodobacterales were characteristic of waters south of the PF. Functions enriched south of the PF included a range of transporters, sulfur reduction and histidine degradation to glutamate, while branched‐chain amino acid transport, nucleic acid biosynthesis and methionine salvage were overrepresented north of the PF. The taxonomic and functional characteristics suggested a shift of primary production from cyanobacteria in the north to eukaryotic phytoplankton in the south, and reflected the different trophic statuses of the two regions. The study provides a new level of understanding about SO microbial communities, describing the contrasting taxonomic and functional characteristics of microbial assemblages either side of the PF.
Endothelial FOS expression and pre‐eclampsia
Authors: Mackenzie RM , Sandrim VC , Carty DM , McClure JD , Freeman DJ , Dominiczak AF , McBride MW , Delles C
Published: November 2012

Please cite this paper as: Mackenzie RM, Sandrim VC, Carty DM, McClure JD, Freeman DJ, Dominiczak AF, McBride MW, Delles C. Endothelial FOS expression and pre‐eclampsia. BJOG 2012;119:1564–1571.

Objective  To study gene expression profiles in human endothelial cells incubated with plasma from women who developed pre‐eclampsia and women with normotensive pregnancies.

Design  A case–control study.

Setting  A longitudinal nested case–control study within three maternity units.

Population  A mixed obstetric population attending maternity hospitals in Glasgow.

Methods  Plasma was obtained at both 16 and 28 weeks of gestation from 12 women: six women subsequently developed pre‐eclampsia (cases) and six women, matched for age, body mass index (BMI) and parity, remained normotensive (controls). Human umbilical vein endothelial cells (HUVECs) were incubated with plasma for 24 hour before RNA isolation.

Main outcome measures  Gene expression profiles were compared between the two gestational time points using Illumina® HumanHT‐12 v4 Expression BeadChips. Differential mRNA expression observed in microarray experiments were validated using quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR), and gene networks were analysed using Ingenuity® pathway analysis.

Results  There was a significant difference in the expression of 25 genes following incubation with plasma from controls, and an increase in the expression of 11 genes following incubation with plasma from cases, with no overlap between the two groups (false discovery rate, FDR < 0.05). There was a 3.74‐fold (FDR < 0.001) increase in the expression of the c‐Fos gene (FOS) when HUVECs were incubated with control plasma from 16 and 28 weeks of gestation, with no significant difference between the two time points with plasma from cases. Similar findings for FOS were obtained by qRT‐PCR.

Conclusions  Plasma from women who subsequently develop pre‐eclampsia appears to contain factors that lead to the dysregulation of FOS in endothelial cells during pregnancy. Reduced expression of c‐Fos may lead to impaired vasculogenesis, and thereby contribute to the development of pre‐eclampsia.
Rescue corticosteroids in twin pregnancies and short‐term neonatal outcomes
Authors: Bibbo C , Deluca L , Gibbs KA , Saltzman DH , Rebarber A , Green RS , Fox NS
Published: November 2012

Objective  To estimate the efficacy of a rescue course of antenatal corticosteroids in twin pregnancies.

Design  Retrospective cohort study.

Setting  Tertiary‐care centre.

Population  Twins born from 24 to <34 weeks of gestation in a single maternal and fetal medicine practice from 2006 to 2011.

Methods  We compared neonatal outcomes in 88 twins exposed to a single course of corticosteroids with outcomes in 42 twins exposed to two courses of corticosteroids: the initial course and a single rescue course. Analyses were adjusted to control for correlation between twins born to the same mother.

Main outcome measure  Short‐term neonatal respiratory morbidity.

Results  Rescue corticosteroids were associated with fewer days of mechanical ventilation (7.3 ± 3.3 versus 33.9 ± 25.3 days, P = 0.003), fewer days with a fraction of inspired oxygen of >21% (6.3 ± 4.3 versus 33.3 ± 25.8 days, P = 0.003), a lower incidence of mechanical ventilation >14 days or death while on mechanical ventilation (0 versus 12.5%, P = 0.016), and a lower incidence of retinopathy of prematurity (0 versus 12.5%, P = 0.016). The proportion of neonates with respiratory distress syndrome did not differ between the groups (adjusted odds ratio 1.28, 95% confidence interval 0.50–3.26). There were no differences found for birthweight, head circumference and length.

Conclusions  In twins born before 34 weeks of gestation, exposure to rescue corticosteroids may be associated with improved neonatal outcomes. Further studies are warranted to assess the effect of rescue corticosteroids in twin pregnancies.
The implementation effects of expanded consolidation: the case of consolidating special purpose entities
Authors: Luo Ting , Warfield Terry
Published: November 2012

This article examines the impact of FASB Interpretation No. 46 (Revised), FIN 46(R), on perceived earnings informativeness of companies with special purpose entities (SPEs). We find that the impact depends on the pre‐FIN 46(R) incentives for using SPEs. The implementation of FIN 46(R) improves perceived earnings informativeness of companies that previously used SPEs less for the manipulation of financial reporting, but does not generate the same improvement for those otherwise. Furthermore, these differential effects are more pronounced when companies reacted to FIN 46(R) by restructuring their SPEs to keep them off financial statements.
When U.S. venture capital ventures abroad
Authors: Abdou Khaled , Varela Oscar
Published: November 2012

Older, more experienced and smaller U.S. venture capital firms are most probable to sacrifice proximate distance for new opportunities in foreign, and mostly mature, portfolio companies. These companies are treated differently than the domestic ones, as U.S. venture capital firms collaborate with and delegate monitoring to foreign partners, rather than stage or syndicate. Successful outcomes mostly occur in more mature, non‐hi‐tech, portfolio companies that receive more financing per round. Our results are robust to the investee country's openness and industry classification, stage of the investment and possible sample selection problems.
Character distribution maps: a visualization method for comparative cladistics
Authors: Whitlock John A. , Wilson Jeffrey A.
Published: November 2012

The rise of computational methods and widespread availability of phylogenetic software packages has resulted in a dramatic increase in the number of phylogenetic analyses published each year. We anticipate that as the number of workers and the number of analyses continues to increase, interest in so‐called ‘meta‐analyses’ that compare not just the resultant trees, but the data themselves, will also increase. Here, we demonstrate a simple method for authors to facilitate such comparisons by visually representing the character data included in their analyses, the Character Distribution Map (CDM).
Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity
Authors: Boughton C K , Murphy K G
Published: November 2012

Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti‐obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin‐concentrating hormone, orexins, relaxin‐3 and galanin‐like peptide or stimulating anorectic signalling pathways used by peptides such as the melanocortins, ciliary neurotrophic factor and brain‐derived neurotrophic factor, are approaches that have shown some promise, but which have also highlighted possible concerns. Manipulation of central peptidergic systems poses a number of therapeutic problems, including brain access and side effects. Given that the homeostatic defence of body weight may limit the effectiveness of any single‐target therapy developed, a combination therapy approach may offer the best hope for the effective prevention and treatment of obesity.

Linked Articles

This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue‐7
Characterization of AQX‐1125, a small‐molecule SHIP1 activator
Authors: Stenton Grant R , Mackenzie Lloyd F , Tam Patrick , Cross Jennifer L , Harwig Curtis , Raymond Jeffrey , Toews Judy , Chernoff David , MacRury Thomas , Szabo Csaba
Published: November 2012

Background

The efficacy of AQX‐1125, a small‐molecule SH2‐containing inositol‐5′‐phosphatase 1 (SHIP1) activator and clinical development candidate, is investigated in rodent models of inflammation.

Experimental Approach

AQX‐1125 was administered orally in a mouse model of passive cutaneous anaphylaxis (PCA) and a number of rodent models of respiratory inflammation including: cigarette smoke, LPS and ovalbumin (OVA)‐mediated airway inflammation. SHIP1 dependency of the AQX‐1125 mechanism of action was investigated by comparing the efficacy in wild‐type and SHIP1‐deficient mice subjected to an intrapulmonary LPS challenge.

Results

AQX‐1125 exerted anti‐inflammatory effects in all of the models studied. AQX‐1125 decreased the PCA response at all doses tested. Using bronchoalveolar lavage (BAL) cell counts as an end point, oral or aerosolized AQX‐1125 dose dependently decreased the LPS‐mediated pulmonary neutrophilic infiltration at 3–30 mg kg−1 and 0.15–15 μg kg−1 respectively. AQX‐1125 suppressed the OVA‐mediated airway inflammation at 0.1–10 mg kg−1. In the smoke‐induced airway inflammation model, AQX‐1125 was tested at 30 mg kg−1 and significantly reduced the neutrophil infiltration of the BAL fluid. AQX‐1125 (10 mg kg−1) decreased LPS‐induced pulmonary neutrophilia in wild‐type mice but not in SHIP1‐deficient mice.

Conclusions

The SHIP1 activator, AQX‐1125, suppresses leukocyte accumulation and inflammatory mediator release in rodent models of pulmonary inflammation and allergy. As shown in the mouse model of LPS‐induced lung inflammation, the efficacy of the compound is dependent on the presence of SHIP1. Pharmacological SHIP1 activation may have clinical potential for the treatment of pulmonary inflammatory diseases.

Linked Article

This article is accompanied by Stenton et al., pp. 1506–1518 of this issue. To view this article visit http://dx.doi.org/10.1111/bph.12039
GPCR heterodimers: asymmetries in ligand binding and signalling output offer new targets for drug discovery
Authors: Goupil Eugénie , Laporte Stéphane A , Hébert Terence E
Published: November 2012

This article is a commentary on the research paper by Siddiquee et al., pp. 1104‐1117 of this issue.
Inhibition of endothelial cell Ca2+ entry and transient receptor potential channels by Sigma‐1 receptor ligands
Authors: Amer Mohamed S , McKeown Lynn , Tumova Sarka , Liu Ruifeng , Seymour Victoria AL , Wilson Lesley A , Naylor Jacqueline , Greenhalgh Katriona , Hou Bing , Majeed Yasser , Turner Paul , Sedo Alicia , O'Regan David J , Li Jing , Bon Robin S , Porter Karen E , Beech David J
Published: November 2012

Background and Purpose

The Sigma‐1 receptor (Sig1R) impacts on calcium ion signalling and has a plethora of ligands. This study investigated Sig1R and its ligands in relation to endogenous calcium events of endothelial cells and transient receptor potential (TRP) channels.

Experimental Approach

Intracellular calcium and patch clamp measurements were made from human saphenous vein endothelial cells and HEK 293 cells expressing exogenous human TRPC5, TRPM2 or TRPM3. Sig1R ligands were applied and short interfering RNA was used to deplete Sig1R. TRP channels tagged with fluorescent proteins were used for subcellular localization studies.

Key Results

In endothelial cells, 10–100 μM of the Sig1R antagonist BD1063 inhibited sustained but not transient calcium responses evoked by histamine. The Sig1R agonist 4‐IBP and related antagonist BD1047 were also inhibitory. The Sig1R agonist SKF10047 had no effect. Sustained calcium entry evoked by VEGF or hydrogen peroxide was also inhibited by BD1063, BD1047 or 4‐IBP, but not SKF10047. 4‐IBP, BD1047 and BD1063 inhibited TRPC5 or TRPM3, but not TRPM2. Inhibitory effects of BD1047 were rapid in onset and readily reversed on washout. SKF10047 inhibited TRPC5 but not TRPM3 or TRPM2. Depletion of Sig1R did not prevent the inhibitory actions of BD1063 or BD1047 and Sig1R did not co‐localize with TRPC5 or TRPM3.

Conclusions and Implications

The data suggest that two types of Sig1R ligand (BD1047/BD1063 and 4‐IBP) are inhibitors of receptor‐ or chemically activated calcium entry channels, acting relatively directly and independently of the Sig1R. Chemical foundations for TRP channel inhibitors are suggested.
Mesenchymal stem cells regulate epithelial–mesenchymal transition and tumor progression of pancreatic cancer cells
Authors: Kabashima‐Niibe Ayano , Higuchi Hajime , Takaishi Hiromasa , Masugi Yohei , Matsuzaki Yumi , Mabuchi Yo , Funakoshi Shinsuke , Adachi Masayuki , Hamamoto Yasuo , Kawachi Shigeyuki , Aiura Koichi , Kitagawa Yuko , Sakamoto Michiie , Hibi Toshifumi
Published: November 2012

Cancer‐associated fibroblasts contribute to cancer progression that is caused by epithelial–mesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs) were found to be the major candidate involved in the development of tumor‐promoting cancer stroma. Here we report that α‐smooth muscle actin‐positive myofibroblast‐like cells originating from MSCs contribute to inducing EMT in side population cells of pancreatic cancer. More importantly, MSC‐derived myofibroblasts function to maintain tumor‐initiating stem cell‐like characteristics, including augmenting expression levels of various stemness‐associated genes, enhancing sphere‐ forming activity, promoting tumor formation in a mouse xenograft model, and showing resistance to anticancer drugs. Furthermore, both γ‐secretase inhibitor and siRNA directed against Jagged‐1 attenuated MSC‐associated E‐cadherin suppression and sphere formation in pancreatic cancer side population cells. Thus, our results suggest that MSC‐derived myofibroblasts play important roles in regulating EMT and tumor‐initiating stem cell‐like properties of pancreatic cancer cells through an intermediating Notch signal.
A novel mass spectrometry‐based method for determining insulin‐like growth factor 1: assessment in a cohort of subjects with newly diagnosed acromegaly
Authors: Kay Richard , Halsall David J. , Annamalai Anand K. , Kandasamy Narayanan , Taylor Kevin , Fenwick Susanna , Webb Alison , Wark Gwen , Pleasance Steve , Gurnell Mark
Published: November 2012

Objective

To develop an alternative method to immunoassay for the quantitative analysis of insulin‐like growth factor 1 (IGF‐1) using a mass spectrometry (MS)‐based approach.

Study design and patients

A stable isotope dilution Ultra High Performance Liquid Chromatography tandem MS (uHPLC‐MS/MS)‐based method for the quantification of IGF‐1 was developed. The method employed Selected Reaction Monitoring (SRM) of two tryptic peptides derived from IGF‐1, and utilised solid phase extraction for enrichment of the peptide fraction containing IGF‐1 rather than immunocapture, so was less susceptible to assay interference. Plasma samples from 25 consecutive unselected patients with newly diagnosed acromegaly, collected both before and after 24 weeks of primary medical therapy with Lanreotide Autogel®, were analysed by a widely used commercial immunoassay (Siemens Immulite 2000®) and by uHPLC‐MS/MS.

Results

The uHPLC‐MS/MS method showed good correlation with the immunoassay over a wide range of IGF‐1 concentrations. The Passing and Bablock regression was: uHPLC‐MS/MS (nmol/l) = 1·37 (95% confidence interval: 1·26–1·46) × immunoassay (nmol/l) + 3·14 (95% confidence interval: –2·71 to 10·32). Six patients had discordant growth hormone (GH) and IGF‐1 levels following primary medical therapy, and in all six the immunoassay and uHPLC‐MS/MS platforms returned comparable results. The method was not affected by concentrations of IGFBP3 up to 12 500 ng/ml.

Conclusions

uHPLC‐MS/MS offers an independent method for determining/validating IGF‐1 in subjects with acromegaly. Further studies, including the establishment of age‐ and sex‐matched reference ranges and calibration to the new International IGF‐1 standard IS 02/254, are now required to allow its introduction in to routine clinical use.
Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features
Authors: Bonnet Fabrice , Velayoudom Cephise Fritz‐Line , Gautier Alain , Dubois Séverine , Massart Catherine , Camara Alioune , Larifla Laurent , Balkau Beverley , Ducluzeau Pierre‐Henri
Published: November 2012

Background

SHBG and liver enzymes levels are both associated with the risk of type 2 diabetes. However, the relationship between SHBG with liver enzymes and intrahepatic fat content remain poorly understood.

Objective

To investigate whether SHBG is correlated with glucose and lipids levels and whether this association depends on fatty liver content, liver enzymes or sex hormone concentrations.

Design and Patients

We studied 233 dysmetabolic men with measures of plasma SHBG, total testosterone, 17β‐oestradiol, glucose, adiponectin, liver enzymes and hepatokines. Intrahepatic liver fat and visceral fat contents were measured by magnetic resonance imaging in 108 of these individuals.

Results

After adjustment for age, SHBG concentration was inversely correlated with fasting glucose (βstandardized = −0·21, P = 0·0007), HbA1c (βstandardized = −0·27, P < 0·0001), triglycerides (βstandardized = −0·19, P = 0·003) and positively correlated with HDL‐Cholesterol (βstandardized = 0·14, P = 0·03). These correlations persisted after adjustment for either total testosterone or 17β‐oestradiol levels. SHBG was not related to either fetuin A or FGF 21 concentrations. The inverse association of SHBG with HbA1c and glycaemia was not altered after adjusting for liver markers but was no longer significant after adjustment for hepatic fat content.

Conclusion

The significant association between SHBG and fasting glycaemia, HbA1c and lipid levels in dysmetabolic men was not related to either sex hormones or markers of liver function, but was dependent on intrahepatic fat. This suggests that intrahepatic fat, but not alterations in liver function markers, may be involved in the association between SHBG and glucose and lipid metabolism.
To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening
Authors: Delatycki MB , Wolthuizen M , Aitken MA , Hickerton C , Metcalfe SA , Allen KJ
Published: November 2012

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.