bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal body composition in relation to infant birth weight and subcutaneous adipose tissue
Authors: Forsum Elisabet , Löf Marie , Olausson Hanna , Olhager Elisabeth
Published: August 2006

Infant birth weight has increased recently, representing an obstetric and potentially a public health problem since high birth weight involves a risk of obesity later in life. Maternal nutritional status is important for fetal growth and therefore relationships between maternal body weight and composition v. birth weight and infant subcutaneous adipose tissue were investigated in twenty-three healthy women and their newborn infants using multiple and simple linear regression analysis. Furthermore, using previously published data for nineteen infants, it was demonstrated that an anthropometric method could provide useful estimates of the amount of subcutaneous adipose tissue. Birth weight was correlated with the maternal content of total body fat (TBF) both before pregnancy and in gestational week 32 and, together with gestational age at birth, TBF (%) before pregnancy explained 45% of the variation in birth weight. This figure was not increased when gestational gains in weight or TBF were added to the model. Furthermore, in infants, birth weight correlated with the amount of their subcutaneous adipose tissue. Together maternal TBF (%) and amount of subcutaneous adipose tissue in infants explained 61–63% of the variation in birth weight while the amount of infant subcutaneous adipose tissue alone explained only 55%. The maternal TBF content is likely to be important for the recent increase in birth weight. This factor probably causes a general augmentation in fetal growth rather than a specific stimulation of adipose tissue growth.
Neutrophils from p40phox−/− mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing
Authors: Ellson Chris D. , Davidson Keith , Ferguson G. John , O'Connor Rod , Stephens Len R. , Hawkins Phillip T.
Published: August 2006

The generation of reactive oxygen species (ROS) by the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex plays a critical role in the antimicrobial functions of the phagocytic cells of the immune system. The catalytic core of this oxidase consists of a complex between gp91phox, p22phox, p47phox, p67phox, p40phox, and rac-2. Mutations in each of the phox components, except p40phox, have been described in cases of chronic granulomatous disease (CGD), defining their essential role in oxidase function. We sought to establish the role of p40phox by investigating the NADPH oxidase responses of neutrophils isolated from p40phox−/− mice. In the absence of p40phox, the expression of p67phox is reduced by ∼55% and oxidase responses to tumor necrosis factor α/fibrinogen, immunoglobulin G latex beads, Staphylococcus aureus, formyl-methionyl-leucyl-phenylalanine, and zymosan were reduced by ∼97, 85, 84, 75, and 30%, respectively. The defect in ROS production by p40phox−/− neutrophils in response to S. aureus translated into a severe, CGD-like defect in the killing of this organism both in vitro and in vivo, defining p40phox as an essential component in bacterial killing.
Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1
Authors: Abraham Sonya M. , Lawrence Toby , Kleiman Anna , Warden Paul , Medghalchi Mino , Tuckermann Jan , Saklatvala Jeremy , Clark Andrew R.
Published: August 2006

Glucocorticoids (GCs), which are used in the treatment of immune-mediated inflammatory diseases, inhibit the expression of many inflammatory mediators. They can also induce the expression of dual specificity phosphatase 1 (DUSP1; otherwise known as mitogen-activated protein kinase [MAPK] phosphatase 1), which dephosphorylates and inactivates MAPKs. We investigated the role of DUSP1 in the antiinflammatory action of the GC dexamethasone (Dex). Dex-mediated inhibition of c-Jun N-terminal kinase and p38 MAPK was abrogated in DUSP1−/− mouse macrophages. Dex-mediated suppression of several proinflammatory genes (including tumor necrosis factor, cyclooxygenase 2, and interleukin 1α and 1β) was impaired in DUSP1−/− mouse macrophages, whereas other proinflammatory genes were inhibited by Dex in a DUSP1-independent manner. In vivo antiinflammatory effects of Dex on zymosan-induced inflammation were impaired in DUSP1−/− mice. Therefore, the expression of DUSP1 is required for the inhibition of proinflammatory signaling pathways by Dex in mouse macrophages. Furthermore, DUSP1 contributes to the antiinflammatory effects of Dex in vitro and in vivo.
Nemo: an evolutionary and population genetics programming framework
Authors: Guillaume Frédéric , Rougemont Jacques
Published: August 2006

Summary: Nemo is an individual-based, genetically explicit and stochastic population computer program for the simulation of population genetics and life-history trait evolution in a metapopulation context. It comes as both a C++ programming framework and an executable program file. Its object-oriented programming design gives it the flexibility and extensibility needed to implement a large variety of forward-time evolutionary models. It provides developers with abstract models allowing them to implement their own life-history traits and life-cycle events. Nemo offers a large panel of population models, from the Island model to lattice models with demographic or environmental stochasticity and a variety of already implemented traits (deleterious mutations, neutral markers and more), life-cycle events (mating, dispersal, aging, selection, etc.) and output operators for saving data and statistics. It runs on all major computer platforms including parallel computing environments.

Availability: The source code, binaries and documentation are available under the GNU General Public License at .

Contact: guillaum@zoology.ubc.ca
SEPARATE AND UNEQUAL: THE EFFECT OF UNEQUAL ACCESS TO EMPLOYMENT‐BASED HEALTH INSURANCE ON SAME‐SEX AND UNMARRIED DIFFERENT‐SEX COUPLES
Authors: ASH MICHAEL A. , LEE BADGETT M. V.
Published: August 2006

Employers' health insurance coverage for legal spouses places unmarried couples at a disadvantage for obtaining coverage. Data from the Current Population Survey confirm that people with same‐sex or different‐sex unmarried partners are two to three times more likely to be uninsured than married people, even after controlling for factors influencing coverage. Universal partner coverage would cut that uninsured rate by as much as 50%. Employers offering domestic partner benefits would see a small enrollment increase: 0.1%–0.3% for gay and lesbian partners and 1.3%–1.8% for heterosexual partners. We find no evidence of adverse selection. (JEL J32, J38, J71)
Fungal Speciation Using Quantitative Polymerase Chain Reaction (QPCR) in Patients With and Without Chronic Rhinosinusitis
Authors: Murr Andrew H. , Goldberg Andrew N. , Vesper Stephen
Published: August 2006

Objectives/Hypothesis: The objectives of this study were to determine the mycology of the middle meatus using an endoscopically guided brush sampling technique and polymerase chain reaction laboratory processing of nasal mucous; to compare the mycology of the middle meatus in patients with sinus disease with subjects without sinus disease; to compare the responses on two standardized quality‐of‐life survey forms between patients with and without sinusitis; and to determine whether the presence of fungi in the middle meatus correlates with responses on these data sets.

Study Design: The authors conducted a single‐blind, prospective, cross‐sectional study.

Methods: Patients with sinus disease and a control group without sinus disease were enrolled in the study. A disease‐specific, validated Sinonasal Outcomes Test survey (SNOT‐20) was completed by the subjects and a generalized validated Medical Outcomes Short Form 36 Survey (SF‐36) was also completed. An endoscopically guided brush sampling of nasal mucous was obtained from the middle meatus. Fungal specific quantitative polymerase chain reaction (QPCR) was performed on the obtained sample to identify one of 82 different species of fungus in the laboratory. Statistical analysis was used to categorize the recovered fungal DNA and to crossreference this information with the outcomes surveys.

Results: The fungal recovery rate in the study was 45.9% in patients with sinus disease and 45.9% in control subjects. Patients with chronic rhinosinusitis had a mean SNOT‐20 score of 1.80 versus the control group mean score of 0.77 (P < .0001). SF‐36 data similarly showed a statistically significant difference between diseased and control populations with controls scoring a mean of 80.37 and patients with chronic rhinosinusitis scoring a mean of 69.35 for a P value of .02. However, no statistical significance could be ascribed to the presence or absence of fungi recovered, the type of fungi recovered, or the possible impact of fungi on the quality‐of‐life survey results.

Conclusion: The recovery rate of fungi from the middle meatus of patients with chronic rhinosinusitis and a control population without chronic rhinosinusitis is 45.9% using QPCR techniques. No direct causation with regard to fungal species or presence was proven; however, a species grouping for future studies is proposed based on trends in this data and other reports. Disease‐specific outcomes surveys revealed a statistically significant difference between the two groups.
Improved Infant Swallowing After Gastroesophageal Reflux Disease Treatment: A Function of Improved Laryngeal Sensation?
Authors: Suskind Dana L. , Thompson Dana M. , Gulati Martha , Huddleston Penny , Liu Donald C. , Baroody Fuad M.
Published: August 2006

Objective: The objective of this study was to describe improvements in pediatric swallowing after gastroesophageal reflux treatment.

Study Design: The authors conducted a retrospective database and chart review at two tertiary care children's hospitals.

Participants: Patients (21 males, 7 females) ranged in age from 1 to 32 months. All patients had clinical evidence of gastroesophageal reflux disease (GERD) as well as evidence of dysphagia with aspiration (laryngeal vestibule and/or trachea) or hypopharyngeal pooling on flexible endoscopic evaluation of swallowing and sensation testing (FEESST) or videofluoroscopic swallow study (VSS).

Intervention: Each child underwent either medical or surgical intervention for control of their GERD.

Outcome Measures: Outcome measures were change in laryngopharyngeal sensation and swallowing function with repeat swallow evaluation after GERD treatment.

Results: A significant improvement in both swallow function and sensory testing was demonstrated after GERD treatment.

Conclusions: GERD may result in decreased laryngopharyngeal sensitivity, which may contribute to pediatric swallowing dysfunction. Control of GERD may improve swallow function. These findings have important clinical implications that need further study.
Two Temporal Bone Computed Tomography Measurements Increase Recognition of Malformations and Predict Sensorineural Hearing Loss
Authors: Purcell Derk D. , Fischbein Nancy J. , Patel Andrew , Johnson Jacob , Lalwani Anil K.
Published: August 2006

Objectives/Hypothesis: The objectives of this prospective study were to assess the reproducibility of the measurements of the cochlea and lateral semicircular canal (LSCC) and to determine if abnormal measurements predict sensorineural hearing loss (SNHL).

Methods: Two readers independently measured the cochlear height on coronal section and the LSCC bony island width on axial section on 109 temporal bone computed tomography scans; audiologic data on these patients were collected independently from medical records. Inter‐ and intrareader variability was evaluated using intraclass correlation coefficients (ICCs) based on a random‐effects model. The positive and negative predictive values of abnormal measurement for hearing loss were determined.

Results: There was excellent inter‐ and intraobserver agreement for both measurements (ICC >80%). The average cochlear height was 5.1 mm (normal range, 4.4–5.9 mm) and average LSCC bony island width was 3.7 mm (normal range, 2.6–4.8 mm). Review of the original radiology reports demonstrated that both cochlear hypoplasia and LSSC dysplasia were overlooked in >50% of patients with both abnormal measurements and SNHL. Cochlear hypoplasia (<4.4 mm) had a positive predictive value of 100% for SNHL, whereas cochlear hyperplasia and bony island dysplasia were less predictive.

Conclusion: The measurements of coronal cochlear height and axial LSCC bony width have excellent reproducibility and identify bony labyrinth abnormalities missed by visual inspection alone. In addition, cochlear hypoplasia is highly predictive of SNHL. To reliably identify inner ear malformations, measurement of the cochlear height and LSCC bony island width, in addition to the vestibular aqueduct, should be routinely performed on all temporal bone studies.
Optimal control and anti-control of the nonlinear dynamics of a rigid block
Authors: Lenci Stefano , Rega Giuseppe
Published: August 2006

This paper deals with control and anti-control of overturning of a rigid block subjected to a generic periodic excitation. Attention is focused on two relevant thresholds, corresponding to heteroclinic bifurcation and immediate overturning, and representing lower and upper bounds of the region where toppling can occur. The two opposite problems of increasing (control) or decreasing (anti-control) of these two curves by properly modifying the shape of the excitation are investigated in depth and the optimal excitations permitting their maximum variations are determined. The notions of ‘global’ and ‘one-side’ control (anti-control) are utilized and their different importance for the various cases is discussed. The effects of control (anti-control) of one curve on the uncontrolled (non-anti-controlled) curve are also investigated, both analytically and with numerical overturning charts. A good agreement is seen to occur.
Minimal control synthesis adaptive control of nonlinear systems: utilizing the properties of chaos
Authors: di Bernardo M , Stoten D.P
Published: August 2006

This paper discusses a novel approach to the control of chaos based on the use of the adaptive minimal control synthesis algorithm. The strategies presented are based on the explicit exploitation of different properties of chaotic systems including the boundedness of the chaotic attractors and their topological transitivity (or ergodicity). It is shown that chaos can be exploited to synthesize more efficient control techniques for nonlinear systems. For instance, by using the ergodicity of the chaotic trajectory, we show that a local adaptive control strategy can be used to synthesize a global controller. An application is to the swing-up control of a double inverted pendulum.
Control of chaos and its relevancy to spacecraft steering
Authors: Macau Elbert E.N , Grebogi Celso
Published: August 2006

In 1990, a seminal work named controlling chaos showed that not only the chaotic evolution could be controlled, but also the complexity inherent in the chaotic dynamics could be exploited to provide a unique level of flexibility and efficiency in technological uses of this phenomenon. Control of chaos is also making substantial contribution in the field of astrodynamics, especially related to the exciting issue of low-energy transfer. The purpose of this work is to bring up the main ideas regarding the control of chaos and targeting, and to show how these techniques can be extended to Hamiltonian situations. We give realistic examples related to astrodynamics problems, in which these techniques are unique in terms of efficiency related to low-energy spacecraft transfer and in-orbit stabilization.
Phase space warping: nonlinear time-series analysis for slowly drifting systems
Authors: Chelidze D , Cusumano J.P
Published: August 2006

A new general dynamical systems approach to data analysis is presented that allows one to track slowly evolving variables responsible for non-stationarity in a fast subsystem. The method is based on the idea of
phase space warping
, which refers to the small distortions in the fast subsystem's phase space that results from the slow drift, and uses short-time reference model prediction error as its primary measurement of this phenomenon. The basic theory is presented and the issues associated with its implementation in a practical algorithm are discussed. A vector-tracking version of the procedure, based on
smooth orthogonal decomposition
analysis, is applied to the study of a nonlinear vibrating beam experiment in which a crack propagates to complete fracture. Our method shows that the damage evolution is governed by a scalar process, and we are able to give real-time estimates of the current damage state and identify the governing damage evolution model. Using a final recursive estimation step based on this model, the time to failure is continuously and accurately predicted well in advance of actual failure.
Extracellular regulators of axonal growth in the adult central nervous system
Authors: Liu Betty P , Cafferty William B.J , Budel Stephane O , Strittmatter Stephen M
Published: August 2006

Robust axonal growth is required during development to establish neuronal connectivity. However, stable fibre patterns are necessary to maintain adult mammalian central nervous system (CNS) function. After adult CNS injury, factors that maintain axonal stability limit the recovery of function. Extracellular molecules play an important role in preserving the stability of the adult CNS axons and in restricting recovery from pathological damage. Adult axonal growth inhibitors include a group of proteins on the oligodendrocyte, Nogo-A, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein and ephrin-B3, which interact with axonal receptors, such as NgR1 and EphA4. Extracellular proteoglycans containing chondroitin sulphates also inhibit axonal sprouting in the adult CNS, particularly at the sites of astroglial scar formation. Therapeutic perturbations of these extracellular axonal growth inhibitors and their receptors or signalling mechanisms provide a degree of axonal sprouting and regeneration in the adult CNS. After CNS injury, such interventions support a partial return of neurological function.
Semaphorins in axon regeneration: developmental guidance molecules gone wrong?
Authors: Pasterkamp R. Jeroen , Verhaagen Joost
Published: August 2006

Semaphorins are developmental axon guidance cues that continue to be expressed during adulthood and are regulated by neural injury. During the formation of the nervous system, repulsive semaphorins guide axons to their targets by restricting and channelling their growth. They affect the growth cone cytoskeleton through interactions with receptor complexes that are linked to a complicated intracellular signal transduction network. Following injury, regenerating axons stop growing when they reach the border of the glial-fibrotic scar, in part because they encounter a potent molecular barrier that inhibits growth cone extension. A number of secreted semaphorins are expressed in the glial-fibrotic scar and at least one transmembrane semaphorin is upregulated in oligodendrocytes surrounding the lesion site. Semaphorin receptors, and many of the signal transduction components required for semaphorin signalling, are present in injured central nervous system neurons. Here, we review evidence that supports a critical role for semaphorin signalling in axon regeneration, and highlight a number of challenges that lie ahead with respect to advancing our understanding of semaphorin function in the normal and injured adult nervous system.
In vivo commitment to yeast cotranscriptional splicing is sensitive to transcription elongation mutants
Authors: Lacadie Scott A. , Tardiff Daniel F. , Kadener Sebastian , Rosbash Michael
Published: August 2006

Spliceosome assembly in the budding yeast Saccharomyces cerevisiae was recently shown to occur at the site of transcription. However, evidence for cotranscriptional splicing as well as for coupling between transcription and splicing is still lacking. Using modifications of a previously published chromatin immunoprecipitation (ChIP) assay, we show that cotranscriptional splicing occurs ∼1 kb after transcription of the 3′ splice site (3′SS). This pathway furthermore protects most intron-containing nascent transcripts from the effects of cleavage by an intronic hammerhead ribozyme. This suggests that a high percentage of introns are recognized cotranscriptionally. This observation led us to screen a small deletion library for strains that sensitize a splicing reporter to ribozyme cleavage. Characterization of the Δmud2 strain indicates that the early splicing factor Mud2p functions with U1 snRNP to form a cross-intron bridging complex on nascent pre-mRNA. The complex helps protect the transcript from ribozyme-mediated destruction and suggests an intron-definition event early in the spliceosome assembly process. The transcription elongation mutant strains Δdst1 and Δpaf1 show different cotranscriptional splicing phenotypes, suggesting that different transcription pathways differentially impact the efficiency of nascent intron definition.
Histone trimethylation and the maintenance of transcriptional ONand OFF states by trxG and PcG proteins
Authors: Papp Bernadett , Müller Jürg
Published: August 2006

Polycomb group (PcG) and trithorax group (trxG) proteins act as antagonistic regulators to maintain transcriptional OFF and ON states of HOX and other target genes. To study the molecular basis of PcG/trxG control, we analyzed the chromatin of the HOX gene Ultrabithorax (Ubx) in UbxOFFand UbxONcells purified from developing Drosophila. We find that PcG protein complexes PhoRC, PRC1, and PRC2 and the Trx protein are all constitutively bound to Polycomb response elements (PREs) in the OFF and ON state. In contrast, the trxG protein Ash1 is only bound in the ON state; not at PREs but downstream of the transcription start site. In the OFF state, we find extensive trimethylation at H3-K27, H3-K9, and H4-K20 across the entire Ubx gene; i.e., throughout the upstream control, promoter, and coding region. In the ON state, the upstream control region is also trimethylated at H3-K27, H3-K9, and H4-K20, but all three modifications are absent in the promoter and 5′ coding region. Our analyses of mutants that lack the PcG histone methyltransferase (HMTase) E(z) or the trxG HMTase Ash1 provide strong evidence that differential histone lysine trimethylation at the promoter and in the coding region confers transcriptional ON and OFF states of Ubx. In particular, our results suggest that PRE-tethered PcG protein complexes act over long distances to generate Pc-repressed chromatin that is trimethylated at H3-K27, H3-K9, and H4-K20, but that the trxG HMTase Ash1 selectively prevents this trimethylation in the promoter and coding region in the ON state.
Stability of recent and remote contextual fear memory
Authors: Frankland Paul W. , Ding Hoi-Ki , Takahashi Eiki , Suzuki Akinobu , Kida Satoshi , Silva Alcino J.
Published: August 2006

Following initial encoding, memories undergo a prolonged period of reorganization. While such reorganization may occur in many different memory systems, its purpose is not clear. Previously, we have shown that recall of recent contextual fear memories engages the dorsal hippocampus (dHPC). In contrast, recall of remote contextual fear memories engages a number of different cortical regions, including the anterior cingulate cortex (ACC). To examine whether this reorganization leads to greater memory stability, we examined reconsolidation of 1 d-old (recent) and 36 d-old (remote) contextual fear memory in mice. We infused the protein synthesis inhibitor, anisomycin (ANI), into either the dHPC or ACC immediately following retrieval of either a recent or remote contextual fear memory. In the dHPC, ANI infusions disrupted subsequent expression of recent, but not remote, contextual fear memory. Similar infusions into the ACC had no effect on either recent or remote contextual fear memories, whereas systemically applied ANI blocked subsequent remote memory expression when long re-exposure durations were used. Together, these data suggest that as memories mature they become increasingly stable. Furthermore, the dissociation between the effects of systemically and centrally administered ANI on remote memory suggests that stability is due, in part, to the distributed nature of remote contextual fear memories.
Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: a single‐centre experience in 303 patients
Authors: Zervas Kostas , Verrou Evgenia , Teleioudis Zisis , Vahtsevanos Konstantinos , Banti Anastasia , Mihou Dimitra , Krikelis Dimitris , Terpos Evangelos
Published: August 2006

The incidence, characteristics and risk factors for the development of osteonecrosis of the jaw (ONJ) were evaluated among 303 myeloma patients. Only patients who received bisphosphonates developed ONJ (28/254; 11%). Zoledronic acid produced 9·5‐fold greater risk for developing ONJ than pamidronate alone (P = 0·042) and 4·5‐fold greater risk than subsequent use of pamidronate + zoledronic acid (P = 0·018). Use of thalidomide and number of bisphosphonate infusions also increased the risk for ONJ by 2·4‐fold (P = 0·043), and 4·9‐fold respectively (P = 0·012). ONJ developed earlier among patients receiving zoledronic acid. Our data indicates that administration of zoledronic acid for more than 2 years or in combination with thalidomide requires caution in myeloma.
Bosentan in Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension
Authors: Kourouklis S. , Christopoulos A. , Liagkas K. , Paradellis G. , Kyriakides Z. S.
Published: August 2006

Background  Bosentan, a dual endothelin receptor antagonist, has been used for symptomatic improvement of patients with idiopathic pulmonary arterial hypertension (PAH) and specific types of secondary (e.g. scleroderma and human immunodeficiency virus infection) PAH, but its efficacy in patients with congenital heart disease and chronic thromboembolic pulmonary hypertension is still under evaluation. In this study two patients are presented, one with common atrioventricular canal and pulmonary hypertension and the other with recurrent pulmonary thromboembolism; both improved significantly after bosentan administration.

Materials and methods  The first patient was a 38‐year‐old female with trisomy 21, common atrioventricular canal and pulmonary hypertension (Eisenmenger syndrome). The second patient was a 57‐year‐old male, who was on anticoagulant therapy owing to an episode of pulmonary embolism that had been diagnosed 3 years earlier. Recurrent pulmonary thromboembolism was considered the most probable diagnosis. Chest spiral computed tomography examination excluded pulmonary endarterectomy as a therapeutic approach. At admission, the two patients were on New York Heart Association class IV, diagnosed by progressive rest dyspnea. Bosentan was administered to patients 1 and 2 for 6 and 9 months, respectively (62·5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.).

Results  Bosentan therapy resulted in significant clinical improvement in both patients. No hepatic dysfunction nor any other side‐effect was observed.

Conclusions  Bosentan could be an effective therapy for pulmonary hypertension owing to congenital heart disease and chronic thromboembolic disease.
Bosentan therapy for pulmonary arterial hypertension associated with hereditary haemorrhagic telangiectasia
Authors: Bonderman D. , Nowotny R. , Skoro‐Sajer N. , Adlbrecht C. , Lang I. M.
Published: August 2006

Hereditary haemorrhagic telangiectasia (HHT) is a disorder of arteriovenous malformations and telangiectases. In rare cases affected individuals may develop typical pulmonary arterial hypertension (PAH). Vasodilator therapy has not been recommended because of a potential increase in arteriovenous shunt volume.

This report is on two patients with severe HHT‐associated PAH who were treated with bosentan, an oral endothelin ETA/ETB receptor antagonist. After 1 year, symptomatic and functional improvements were confirmed by haemodynamic evaluation demonstrating a significant decrease of mean pulmonary artery pressures and an increase in cardiac index, without evidence for an increase in effective shunt volume.
Clinical outcomes of bosentan in pulmonary arterial hypertension do not correlate with levels of TIMPs
Authors: Giannelli G. , Iannone F. , Marinosci F. , Lapadula G. , Antonaci S.
Published: August 2006

Background Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), are involved in tissue inflammation and fibrotic processes. Treatment with bosentan has been shown to improve the clinical outcome of patients with pulmonary arterial hypertension (PAH) with and without association with systemic sclerosis (SSc), and also to modulate the serum levels of matrix metalloproteases‐9. We measured TIMP‐1 and TIMP‐2 in the serum of patients with SSc with and without PAH treated with long‐term bosentan compared with healthy donors (HD).

Materials and methods Serum samples from HD (n = 16) and patients with SSc (n = 35), including patients with SSc without PAH (n = 23) and patients with PAH (n = 12), were analyzed using enzyme‐linked immunosorbent assays (ELISAs) for total TIMP‐1 and TIMP‐2.

Results Both mean TIMP‐1 and TIMP‐2 levels were significantly increased in patients with SSc compared with HD, but no differences were observed between patients with SSc with and without PAH. In the eight bosentan‐treated patients, TIMP‐1 and TIMP‐2 levels did not change during 1 year of treatment, while bosentan increased the 6‐min walking distance by 136 meters after 1 year, as well as clinical outcomes.

Conclusions Increased levels of TIMP‐1 and TIMP‐2 in patients with SSc compared with HD suggest that the inhibition of proteolysis allows the accumulation of ECM proteins. As bosentan does not stimulate TIMPs, it appears to favour proteolytic imbalance and to increase the turnover of ECM proteins.
Dual ETA/ETBvs. selective ETAendothelin receptor antagonism in patients with pulmonary hypertension
Authors: Opitz C. F. , Ewert R.
Published: August 2006

Since the identification of endothelin as a key mediator in the pathogenesis of several diseases, including pulmonary arterial hypertension (PAH), the pharmacologic control of the activated endothelin system with endothelin receptor antagonists (ETRA) has been a major therapeutic achievement for the treatment of patients with PAH. To date, dual ETA/ETBand selective ETAreceptor antagonists have clinically been evaluated. To answer the question of whether selective or dual ETRA is preferable in patients with PAH, experimental and clinical data with relevance to the pulmonary circulation are reviewed in this article.

Whereas experimental and clinical data provide unambiguous evidence that ETAreceptors mediate the detrimental effects of ET‐1, such as vasoconstriction and cell proliferation, the elucidation of the role of ETBreceptors has been more complex. It has been shown that there is a subpopulation of ETBreceptors on smooth muscle cells and fibroblasts mediating vasoconstriction and proliferation. On the contrary, there is clear evidence that endothelial ETBreceptors continue to mediate vasodilation, vasoprotection and ET‐1 clearance despite the pathology associated with pulmonary hypertension. More difficult to assess is the net effect of these mechanisms in patients to be treated with ETRA. When considering the available data from controlled clinical trials, nonselectivity does not appear to carry a relevant clinical benefit for the treatment of patients with PAH when compared with selective ETAreceptor antagonism.
Successful treatment of portopulmonary hypertension with bosentan: case report
Authors: Stähler G. , Von Hunnius P.
Published: August 2006

Pulmonary arterial hypertension (PAH) is found in 2–20% of cirrhosis patients who have portal hypertension (portopulmonary hypertension, PPHT). Endothelin (ET), a potent vasoconstrictor, is likely to play a role in the pathogenesis of portal hypertension. We describe the long‐term successful use of the dual ETA/ETB receptor antagonist bosentan in a 43‐year‐old male with alcohol‐related cirrhosis (Child‐Pugh A), right ventricular enlargement and dysfunction, respectively, and moderate PAH. Elevated pulmonary arterial pressure was substantially reduced and exercise capacity increased. Improvement was maintained over 2 years, and bosentan treatment continues in this patient. Our report is in line with a series of current reports in PPHT that support the use of bosentan in this subset of PAH patients.
Bosentan for severe pulmonary arterial hypertension related to systemic sclerosis with interstitial lung disease
Authors: Ahmadi‐Simab K. , Hellmich B. , Gross W. L.
Published: August 2006

Background  The oral dual endothelin (ET) antagonist bosentan has been established as a cornerstone in the treatment of pulmonary arterial hypertension (PAH). ET is believed to be a key pathogenic mediator in systemic sclerosis (scleroderma, SSc), causing fibrotic, hypertrophic and inflammatory processes. PAH is one of the resulting deleterious effects in approximately 15% of SSc patients.

Material and methods  This was an open‐label prospective observational study of 8 patients aged 34−73 years with symptomatic, severe PAH related to SSc (WHO class III or IV) and mostly, lung fibrosis. PAH diagnosis was ascertained with echocardiography or right heart catheterization. Patients were treated on top of diuretics and anticoagulants with bosentan 62·5 mg twice daily for 4 weeks followed by a maintenance dose of 125 mg twice daily.

Results  The mean 6‐minute walk distance (data available in 7 patients) increased from 71·9 (± 54·7) m at baseline to 191·9 (± 104·6) m after 3 months (P = 0·012) and to 202·6 (± 108·1) m after 6 months (P = 0·011), respectively. Six of 8 patients improved in the 6‐minute walk test, and these 6 patients also improved in World Health Organization functional class. Two patients did not sufficiently respond to bosentan therapy; one of them died. The tolerability of bosentan was good, and there were no discontinuations. Elevations of hepatic aminotransferases above 3 times the upper limit of normal were not recorded.

Conclusion  Bosentan treatment was well tolerated in this cohort of SSc patients with interstitial lung disease and was effective for treatment of severe PAH in the majority of patients.
THE MOISTURE REGIMES OF SIX SOIL SERIES OF THE CENTRAL LOWLANDS OF SCOTLAND
Authors: DUNCAN N. A.
Published: August 2006

In a study of the moisture regimes of some of the most commonly occurring soils of the Central Lowlands of Scotland, three field techniques are compared. Soil tensiometers were used to measure matric suction and results are presented for a brown forest soil, a gteyed brown forest soil and a surface water gley soil. Borehole water levels are given for the surface water gley soils (and gleyed brown forest soil) for the two years under study. A close relationship between matric suction and borehole levels was established but this was not maintained once a soil moisture deficit occurred. Piezometer data was recorded and is shown to give little useful information due to the low hydraulic conductivity of the subsoils.
Reduction of ecosystem productivity and respiration during the European summer 2003 climate anomaly: a joint flux tower, remote sensing and modelling analysis
Authors: REICHSTEIN M. , CIAIS P. , PAPALE D. , VALENTINI R. , RUNNING S. , VIOVY N. , CRAMER W. , GRANIER A. , OGÉE J. , ALLARD V. , AUBINET M. , BERNHOFER Chr. , BUCHMANN N. , CARRARA A. , GRÜNWALD T. , HEIMANN M. , HEINESCH B. , KNOHL A. , KUTSCH W. , LOUSTAU D. , MANCA G. , MATTEUCCI G. , MIGLIETTA F. , OURCIVAL J.M. , PILEGAARD K. , PUMPANEN J. , RAMBAL S. , SCHAPHOFF S. , SEUFERT G. , SOUSSANA J.‐F. , SANZ M.‐J. , VESALA T. , ZHAO M.
Published: August 2006

The European CARBOEUROPE/FLUXNET monitoring sites, spatial remote sensing observations via the EOS‐MODIS sensor and ecosystem modelling provide independent and complementary views on the effect of the 2003 heatwave on the European biosphere's productivity and carbon balance. In our analysis, these data streams consistently demonstrate a strong negative anomaly of the primary productivity during the summer of 2003. FLUXNET eddy‐covariance data indicate that the drop in productivity was not primarily caused by high temperatures (‘heat stress’) but rather by limitation of water (drought stress) and that, contrary to the classical expectation about a heat wave, not only gross primary productivity but also ecosystem respiration declined by up to more than to 80 gC m−2 month−1. Anomalies of carbon and water fluxes were strongly correlated. While there are large between‐site differences in water‐use efficiency (WUE, 1–6 kg C kg−1 H2O) here defined as gross carbon uptake divided by evapotranspiration (WUE=GPP/ET), the year‐to‐year changes in WUE were small (<1 g kg−1) and quite similar for most sites (i.e. WUE decreased during the year of the heatwave). Remote sensing data from MODIS and AVHRR both indicate a strong negative anomaly of the fraction of absorbed photosynthetically active radiation in summer 2003, at more than five standard deviations of the previous years. The spatial differentiation of this anomaly follows climatic and land‐use patterns: Largest anomalies occur in the centre of the meteorological anomaly (central Western Europe) and in areas dominated by crops or grassland. A preliminary model intercomparison along a gradient from data‐oriented models to process‐oriented models indicates that all approaches are similarly describing the spatial pattern of ecosystem sensitivity to the climatic 2003 event with major exceptions in the Alps and parts of Eastern Europe, but differed with respect to their interannual variability.
Effects of elevated carbon dioxide and ozone on aphid oviposition preference and birch bud exudate phenolics
Authors: PELTONEN PETRI A. , JULKUNEN‐TIITTO RIITTA , VAPAAVUORI ELINA , HOLOPAINEN JARMO K.
Published: August 2006

The effect of atmospheric change on birch aphid (Euceraphis betulae Koch) oviposition preference was examined and plant characteristics that are possibly responsible for the observed effects were investigated. It was hypothesized that the increasing concentrations of CO2 and O3 affect singly or in combination the oviposition of birch aphids via changes in host plant characteristics. Two genotypes of field‐growing silver birch (Betula pendula Roth) trees (clones 4 and 80), which were exposed to doubled ambient concentration of CO2 and O3, singly and in combination, in a 3‐year open‐top chamber experiment, were used in an aphid oviposition preference test. It was found that elevated CO2, irrespective of ozone concentration, increased the number of aphid eggs laid on clone 4, but not in clone 80. Several flavonoid aglycones were identified from the exudate coating of birch buds. Although elevated CO2 and O3 affected these phenolic compounds in clone 4, the effects did not correlate with the observed changes in aphid oviposition. It is suggested that neither bud length, which was not affected by the treatments, nor surface exudate phenolics mediate birch aphid oviposition preference.
Soil respiration in six temperate forests in China
Authors: WANG CHUANKUAN , YANG JINYAN , ZHANG QUANZHI
Published: August 2006

Scaling soil respiration (RS), the major CO2 source to the atmosphere from terrestrial ecosystems, from chamber‐based measurements to ecosystems requires studies on variations and correlations of RS from various biomes and across geographic regions. However, few studies on RS are available for Chinese temperate forest despite the importance of this forest in the national and global carbon budgets. In this study, we conducted 18‐month RS measurements during 2004–2005 in six temperate forest types, representing the typical secondary forest ecosystems across various site conditions in northeastern China: Mongolian oak (Quercus mongolica Fisch.), aspen‐birch (Populous davidiana Dode and Betula platyphylla Suk.), mixed deciduous (no dominant tree species), hardwood (dominated by Fraxinus mandshurica Rupr., Juglans mandshurica Maxim., and Phellodendron amurense Rupr.) forests, Korean pine (Pinus koraiensis Sieb. et Zucc.) and Dahurian larch (Larix gmelinii Rupr.) plantations. Our specific objectives were to: (1) explore relationships of RS against soil temperature and water content for the six forest ecosystems, (2) quantify annual soil surface CO2 flux and its relations to belowground carbon storage, (3) examine seasonal variations in RS and related environmental factors, and (4) quantify among‐ and within‐ecosystem variations in RS. The RS was positively correlated to soil temperature in all forest types, and was significantly influenced by the interactions of soil temperature and water content in the pine, larch, and mixed deciduous forests. The sensitivity of RS to soil temperature at 10 cm depth (Q10) ranged from 2.61 in the oak forest to 3.75 in the aspen‐birch forests. The Q10 tended to increase with soil water content until reaching a threshold, and then decline. The annual RS for the larch, pine, hardwood, oak, mixed deciduous, and aspen‐birch forests averaged 403, 514, 781, 785, 786, and 813 g C m−2 yr−1, respectively. The annual RS of the broadleaved forests was 72% greater than that of the coniferous forests. The annual RS was positively correlated to soil organic carbon (SOC) concentration at O horizon (R2=0.868) and total biomass of roots <0.5 cm in diameter (R2=0.748). The coefficient of variation (CV) of RS among forest types averaged 25% across the 18‐month measurements. The CV of RS within plots varied from 20% to 27%, significantly (P<0.001) greater than those among plots (9–15%), indicating the importance of the fine‐scaled heterogeneity in RS. This study emphasized that variations in soil respiration and potential sampling bias should be appropriately tackled for accurate soil CO2 flux estimates.
Expression of immune responsive genes in cell lines from two different Anopheline species
Authors: Luna C. , Hoa N. T. , Lin H. , Zhang L. , Nguyen H. L. A. , Kanzok S. M. , Zheng L.
Published: August 2006

Malaria infection results in increased expression of immune responsive genes, including those encoding antimicrobial peptides such as Gambicin (Gam1) and Cecropin A (Cec1). Understanding how these genes are regulated will provide insights how the mosquito immune system is activated by Plasmodium. We previously have shown that Cec1 was primarily regulated by the Imd‐Relish (REL2) pathway in the Anopheles gambiae Sua1B cell line. We show here that expression of Defensin A (Def1) and Gam1 was reduced after RNA interference against components of the Imd‐REL2 pathway in An. gambiae cell lines. Interestingly, promoter reporters of these antimicrobial peptides were expressed at very low level in the cell line MSQ43 from Anopheles stephensi. Surprisingly, over‐expression of either NF‐κB transcription factor REL1 or REL2 alone is sufficient to induce the expression of Cec1, Gam1 and Def1. These results suggest that expression of these antimicrobial peptides (AMP) in vivo may be regulated by both the Toll and Imd pathways. We also show here for the first time that Tep4, a gene encoding a thioester containing protein, is regulated by REL2. Taken together, these results suggest that there are significant overlaps of genes regulated by the Toll‐Rel1 and Imd‐Rel2 pathways. Further, the different expression patterns in two different Anopheline cell lines provide a platform to identify other key positive and negative regulators of the antimicrobial peptide genes.
Molecular, biochemical and histochemical characterization of two acetylcholinesterase cDNAs from the German cockroach Blattella germanica
Authors: Kim J. I. , Jung C. S. , Koh Y. H. , Lee S. H.
Published: August 2006

Full length cDNAs encoding two acetylcholinesterases (AChEs; Bgace1 and Bgace2) were cloned and characterized from the German cockroach, Blattella germanica. Sequence analyses showed that both genes possess all the typical features of ace, and that Bgace1 is orthologous to the insect ace1 whereas Bgace2 is to the insect ace2. Transcript level of Bgace1 was significantly higher (c. 10 fold) than that of Bgace2 in all 11 tissues examined, suggesting that Bgace1 likely encodes a predominant AChE. Multiple AChE bands were identified by native polyacrylamide gel electrophoresis and isoelectricfocusing from various tissue preparations, among which ganglia produced distinct two major and two minor AChE bands, indicative of the presence of at least two active AChEs. B. germanica AChEs appeared to be mainly localized in the central nervous system as demonstrated by histochemical activity staining, together with quantitative analysis of Bgace transcripts. Fluorescence in situ hybridization of the 1st thoracic ganglion confirmed that Bgace1 is predominantly transcribed and further showed that its transcript is found in almost entire region of inter or motor neurones including the cell bodies and axonal/dendritic branches. Bgace2 transcript is found only in the subset of neurones, particularly in the cell body. In addition, certain neurones were observed to express Bgace1 only.
Intact mariner‐like element in tobacco budworm, Heliothis virescens (Lepidoptera: Noctuidae)
Authors: Ren X. , Park Y. , Miller T. A.
Published: August 2006

An intact mariner‐like element was isolated from the genome of tobacco budworm, Heliothis virescens. This is the first report of an intact mariner element after the initial identification of Mos1 from Drosophila mauritiana. The full‐length Hvmar1 has 30 bp inverted terminal repeats and a complete 1065 bp open reading frame (ORF) encoding the transposase with a ‘D,D(34)D’ motif in the catalytic domain. Polymerase chain reaction results show that at least one insertion of the Hvmar1 element is conserved in this Heliothis strain. Phylogenetic analysis demonstrated that Hvmar1 belongs to the irritans subfamily.
A review of causal factors and control measures for bloat in farmed salmonids with a suggested mechanism for the development of the condition
Authors: Anderson C D
Published: August 2006

A mechanism for the development of bloat in salmonids is proposed and explained in terms of the physiology of digestion and osmoregulation in fish. Understanding the causal factors for bloat enables control measures to be identified. In farmed salmonids, the chyme produced during the digestion of nutrient‐rich pelleted foods that rapidly disintegrate in the stomach will be a potent activator of a negative feedback mechanism (enterogastric control), which slows stomach emptying to protect the small intestine from nutrient overload. In saline environments salmonids continuously drink sea water to replace fluid lost across the gills. Fluid loss is increased during periods of stress caused by factors such as low oxygen levels, elevated temperature or high salinity. When ingestion of nutrient‐rich food results in prolonged activation of enterogastric control, slowed stomach emptying leads to decreased absorption of water, thirst and increased drinking. This further exacerbates stomach distention. The proposed mechanism for the development of bloat is supported by on‐farm experience where measures to control bloat include reducing food intake, altering the composition of the diet and using appropriate strategies to reduce stress.