bluuebunny/crossref_metadata_2025 huggingface dataset:
Expressed sequence tags from the flower pathogen Claviceps purpurea
Authors: OESER BIRGITT , BEAUSSART FRANÇOIS , HAARMANN THOMAS , LORENZ NICOLE , NATHUES EVA , ROLKE YVONNE , SCHEFFER JAN , WEINER JANUARY , TUDZYNSKI PAUL
Published: June 2009

The ascomycete Claviceps purpurea (ergot) is a biotrophic flower pathogen of rye and other grasses. The deleterious toxic effects of infected rye seeds on humans and grazing animals have been known since the Middle Ages. To gain further insight into the molecular basis of this disease, we generated about 10 000 expressed sequence tags (ESTs)—about 25% originating from axenic fungal culture and about 75% from tissues collected 6–20 days after infection of rye spikes. The pattern of axenic vs. in planta gene expression was compared. About 200 putative plant genes were identified within the in planta library. A high percentage of these were predicted to function in plant defence against the ergot fungus and other pathogens, for example pathogenesis‐related proteins. Potential fungal pathogenicity and virulence genes were found via comparison with the pathogen–host interaction database (PHI‐base; http://www.phi‐base.org) and with genes known to be highly expressed in the haustoria of the bean rust fungus. Comparative analysis of Claviceps and two other fungal flower pathogens (necrotrophic Fusarium graminearum and biotrophic Ustilago maydis) highlighted similarities and differences in their lifestyles, for example all three fungi have signalling components and cell wall‐degrading enzymes in their arsenal. In summary, the analysis of axenic and in planta ESTs yielded a collection of candidate genes to be evaluated for functional roles in this plant–microbe interaction.
Interferon‐induced retinopathy and its risk in patients with diabetes and hypertension undergoing treatment for chronic hepatitis C virus infection
Authors: PANETTA J. D. , GILANI N.
Published: June 2009

Background  Ocular complications are amongst many side‐effects of interferon based therapy for hepatitis C virus (HCV) infection. Some suggest that diabetic and hypertensive patients are at increased risk of these complications.

Aim  To determine the frequency of ophthalmological complications related to interferon use.

Methods  Retrospective analysis of patients undergoing HCV treatment with pegylated interferon α‐2a, α‐2b or consensus interferon plus ribavirin between 2005 and 2007. All patients underwent a baseline eye examination and any visual complaints during treatment prompted a repeat examination. Data recorded included HCV genotype, treatment duration, interferon type, pre‐treatment and on treatment visual complaints, known ocular pathology, and retinal findings at baseline and at follow‐up.

Results  Of 183 patients, 29 (16%) had diabetes and 85 (46%) had hypertension. Seventy‐one (38%) received interferon α‐2a, 100 (55%) α‐2b, and 12 (7%) consensus interferon. Seven (3.8%) had retinal changes on follow‐up and treatment was discontinued in 3 (1.6%). Of seven with ocular changes two had hypertension and one had both hypertension and diabetes.

Conclusion  The incidence of symptomatic retinopathy in HCV patients undergoing interferon therapy appears low and treatment cessation is rarely needed. Furthermore, patients with hypertension and diabetes may not be at higher risk for interferon‐induced retinopathy.
Review article: the current and evolving treatment of colonic diverticular disease
Authors: TURSI A. , PAPAGRIGORIADIS S.
Published: June 2009

Background  Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis and consequently diverticular disease. Diverticular disease can be associated with numerous debilitating abdominal and gastrointestinal symptoms (including pain, bloating, nausea, constipation and diarrhoea).

Aims  To review the state of treatment for diverticular disease and its complications, and briefly discuss potential future therapies.

Methods  PubMed and recent conference abstracts were searched for articles describing the treatment of diverticular disease.

Results  Many physicians will recommend alterations to lifestyle and increasing fibre consumption. Empirical antibiotics remain the mainstay of therapy for patients with diverticular disease and rifaximin seems to be the best choice. In severe or relapsing disease, surgical intervention is often the only remaining treatment option. Although novel treatment options are yet to become available, the addition of therapies based on mesalazine (mesalamine) and probiotics may enhance treatment efficacy.

Conclusions  Data suggest that diverticular disease may share many of the hallmarks of other, better‐characterized inflammatory bowel diseases; however, treatment options for patients with diverticular disease are scarce, revolving around antibiotic treatment and surgery. There is a need for a better understanding of the fundamental mechanisms of diverticular disease to design treatment regimens accordingly.
Clinoform migration patterns of a Late Miocene delta complex in the Danish Central Graben; implications for relative sea‐level changes
Authors: Møller L. K. , Rasmussen E. S. , Clausen O. R.
Published: June 2009

A Late Miocene delta complex is located in the Danish Central Graben. The delta complex provides the opportunity to study the spatial development of a wave‐fluvial dominated delta complex in three dimensions. Based on 3D seismic data (seismic sections and amplitude maps) and well data the complex has been investigated. The delta was developed during an initial rise and then a significant fall (approximately 90 m) in relative sea‐level. The prograding clinoformal package of the delta complex has clinoform dips of 2–3° and a thickness of maximum 115 m. The sediments are deposited in five elongated depositional units with the long axis parallel to the delta slope, and progradation occurred in a south‐westerly direction. The grain size of the units vary from muddy to coarse‐grained sand. Incised canyons running parallel to the depositional direction tend to be straight or have low sinuosity and incise approximately 90 m into the top of the delta. The delta complex has been subdivided into two systems tracts based on a study of clinoform migration patterns: (1) Rising trajectory in Unit 1–4 of the complex, the sea‐level was rising as documents a highstand systems tract (HST). (2) Descending trajectory in Unit 5 documenting a forced regression wedge systems tract (FRWST) as the sea‐level was falling, creating incised canyons.
Structural controls on facies distribution in a small half‐graben basin: Luanping basin, northeast China
Authors: Cope Tim , Ping Luo , Xingyang Zhang , Xuanjie Zhang , Jinmin Song , Gang Zhou , Shultz Michael R.
Published: June 2009

Luanping basin is one of many small rift basins that developed in northeast China during mid‐Cretaceous time. It is filled by alluvial, fan‐deltaic and lacustrine strata of the Lower Cretaceous (post 130 Ma) Xiguayuan Formation. Distribution of facies and stacking patterns are controlled by position within the basin with respect to fault‐bounded basin margins. Luanping basin is bounded by a normal fault consisting of two segments that are perpendicular to each other in map view; one or both of these faults probably accommodates a component of strike‐slip. This geometry gave rise to three distinct depozones within the basin: (1) a region of maximum sediment thickness located near the intersection of these two basin‐bounding fault segments; (2) a shallower part of the basin, located near the tip of the normal fault segment bounding the basin to the north; and (3) a low‐gradient, north‐dipping ramp. The facies found in each of these settings are different. Coarse sublacustrine sediment gravity flows interfinger with profundal black shale near the basin depocentre at the intersection of the two basin‐bounding fault segments. Fan delta and shallow lacustrine sedimentation dominated in the shallower part of the basin near the northeastern tip of the master‐bounding fault. Fine‐grained shallow lacustrine sedimentation predominated along the low‐gradient ramp. The facies in Luanping basin are different from those found in basins of similar size elsewhere in the northeastern China extensional tract. Specifically, profundal, organic‐rich black shales are found in Luanping basin but are largely lacking in neighbouring basins. We suggest that this is due to higher rates of subsidence along more steeply dipping normal faults in Luanping basin, as opposed to the other basins.
Steering of experimental channels by lateral basin tilting
Authors: Kim Wonsuck , Sheets Ben A. , Paola Chris
Published: June 2009

A major issue in tectonics and sedimentation is the role of cross‐stream tectonic tilting in steering channels. The general idea is that channels will be attracted to lateral maxima in subsidence rate. A physical experiment performed in 1999 at the St. Anthony Falls Laboratory, however, was in conflict with the idea and showed that fluvial channels and resulting stratigraphy can be insensitive to even relatively strong lateral variation in subsidence. Here, we present results from an experiment which uses a simplified relay‐ramp geometry with laterally variable uplift and subsidence to test a hypothesis developed from the earlier experiment: Tectonic tilting steers channels only when the ratio of the time scales describing lateral channel mobility to tectonic deformation is sufficiently large. Occupation time by experimental channels and sand fraction in the deposit (a proxy for channel deposition) both increase with subsidence rate indicating strong steering of channels by tectonic forcing. We also found that, due to local incision, uplift lengthened the time scale for lateral channel migration relative to subsidence. Comparing channel mobility at the beginning of the experiment, with no tectonic forcing, to later tectonic stages of the experiment indicates that active tectonics increased the channel time scale. The interplay of channel steering with uplift and subsidence led to cyclic appearance and disappearance of an autogenic lake in the hanging‐wall basin. This lake was associated with alternation between channels going around vs. across the adjoining upstream uplifted footwall region. This creation and filling of the lake under constant tectonic forcing (constant fault slip rate) in the hanging wall created subaerial fan‐delta parasequences separated by fluvial deposits.
Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in combination with paracetamol)
Authors: Tavassoli Neda , Lapeyre‐Mestre Maryse , Sommet Agnès , Montastruc Jean‐Louis ,   the French Association of Regional Pharmacovigilance Centres
Published: June 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Three ‘weak’ opioid analgesics are marketed in France and other European countries in association with paracetamol.

• They are very largely used, but to our knowledge there is no large study comparing the reporting rate of adverse drug reactions (ADRs) between these different step 2 analgesic combinations to determine the safest one.

WHAT THIS STUDY ADDS

• The aim of this study was to compare reporting rate of ADRs with three step 2 combinations according to their consumption in France.

• The results show that among these combinations, reporting rate and ‘seriousness’ of reported ADRs are the highest with tramadol/paracetamol (TRM+P) and the lowest with codeine/paracetamol.

• The safety of TRM+P needs to be urgently investigated with more methodologically rigorous studies.

AIMS

Three ‘weak’ opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare the reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol (COD+P) and dextropropoxyphene/paracetamol (DXP+P).

METHODS

All spontaneous reports submitted to the French Pharmacovigilance Database from 1 January 1987 to 31 December 2006 suspected to be induced by one of the three step 2 analgesic combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same period was obtained from the French Drug Agency. The number of ADRs, serious ADRs and different organ classes of ADRs were compared according to their consumption. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each variable using DXP+P as reference.

RESULTS

The reporting rate of ADRs was calculated as 24.9/100 000 person‐years for DXP+P, 44.5/100 000 person‐years for TRM+P and 12.5/100 000 person‐years for COD+P. The reporting rate (OR 0.56, 95% CI 0.50, 0.63) and ‘seriousness»’ (OR 0.65, 95% CI 0.53, 0.80) of ADRs were significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59, 4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and ‘seriousness’ (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with DXP+P than with COD+P.

CONCLUSIONS

Among the three step 2 analgesic combinations, reporting rate and ‘seriousness’ of ADRs are the highest with TRM+P and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is worst than that of COD+P.
Aminophospholipid translocase and phospholipid scramblase activities in sickle erythrocyte subpopulations
Authors: Barber Latorya A. , Palascak Mary B. , Joiner Clinton H. , Franco Robert S.
Published: June 2009

Phosphatidylserine (PS) externalization may contribute to Sickle Cell Disease (SCD) characteristics including thrombogenesis, endothelial adhesion and shortened red blood cell (RBC) lifespan. Aminophospholipid translocase (APLT) returns externalized PS to the inner membrane, and phospholipid scramblase (PLSCR) equilibrates phospholipids (PL) across the membrane. APLT inhibition and PLSCR activation appear to be important for PS externalization. We examined relationships between APLT, PLSCR and external PS in mature sickle RBC and reticulocytes. Normally‐hydrated sickle RBC without external PS had active APLT and inactive PLSCR. PS‐exposing sickle RBC had inhibited APLT and active PLSCR. Sickle reticulocytes had active APLT and active PLSCR independent of external PS. Sickle RBC dehydrated in vivo had the highest proportion of PS‐exposing RBC and markedly inhibited APLT. Normal and sickle RBC dehydrated in vitro had moderately decreased APLT. Rehydration resulted in significant recovery of APLT in RBC previously dehydrated in vitro, but not in sickle RBC dehydrated in vivo. These findings indicate that (i) PS externalization in mature sickle RBC depends on the balance between APLT and PLSCR activities, (ii) PS externalization in sickle reticulocytes depends primarily on PLSCR activation and (iii) APLT inhibition in sickle RBC dehydrated in vivo is due to dehydration itself and other factors.
The impact of risk stratification by early bone‐marrow response in childhood lymphoblastic leukaemia: results from the United Kingdom Medical Research Council trial ALL97 and ALL97/99
Authors: Mitchell Christopher , Payne Jeanette , Wade Rachel , Vora Ajay , Kinsey Sally , Richards Sue , Eden Tim
Published: June 2009

The 1997 acute lymphoblastic leukaemia (ALL) trial (ALL97) was a randomised comparison of prednisolone versus dexamethasone and of 6‐mercaptopurine versus 6‐thioguanine. During the first 2 years of the trial, review of survival data showed the preceding trial, UKALL XI, was no better than its predecessor and that survival for childhood ALL in the UK had not improved in the fashion witnessed by other cooperative treatment groups. The therapy template was therefore altered to an American Children’s Cancer Group (CCG) style regimen, including stratification by age, white cell count and early response to therapy by assessment of the bone marrow. This phase of the trial was designated ALL97/99. Comparison of the two phases showed that the event‐free survival (EFS) for both ALL97 and ALL97/99 was better than previous UKALL trials, as was overall survival (OS) for ALL97/99. Both EFS and OS were significantly better in ALL97/99 than in ALL97 (at five years, 80·0% vs. 74·0%, P = 0·002; and 88·0% vs. 83·5%, P = 0·005, respectively). Isolated central nervous system (CNS) relapse for patients in ALL97/99 was half that in ALL97 (3·0% vs. 4·9%), P = 0·03) and the overall CNS relapse rate was halved in ALL97/99 (4·4% vs. 9·6%, P < 0·00005). There were no significant differences for non‐CNS relapse, induction deaths or deaths in remission between the two phases of the trial.
Venous thromboembolism and ethnicity
Authors: Roberts Lara N. , Patel Raj K. , Arya Roopen
Published: June 2009

Venous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non‐Western countries, and the low incidence of hereditary thrombophilia in those of non‐Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non‐Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.
Timothy grass pollen major allergen Phl p 1 activates respiratory epithelial cells by a non‐protease mechanism
Authors: Röschmann K. , Farhat K. , König P. , Suck R. , Ulmer A. J. , Petersen A.
Published: June 2009

Background
Group 1 allergens from grass pollen (e.g. Phl p 1, the major allergen of timothy grass Phleum pratense) cause IgE reactivity in about 95% of allergic subjects and exist in all grass species. The respiratory epithelium represents a first line of contact of the immune system with airborne allergens, functions as physical barrier and is an important immunological regulation system.

Objective
The aim of this study was to investigate the interaction of Phl p 1 with human respiratory epithelium to elucidate the contribution of epithelial cells to the development of allergic reactions.

Methods
Purified Phl p 1 was used to stimulate A549 cells and transient transfected HEK293 cells. mRNA level of different mediators were investigated by real‐time PCR, release of the mediators was determined by ELISA. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) test and an ex vivo model of the murine trachea were used to investigate a potential proteolytic activity of Phl p 1.

Results
Phl p 1 activates respiratory epithelial cells as measured by induction of IL‐6, IL‐8 and TGF‐β mRNA and release. Phl p 1, in contrast to Der p 1 from the house dust mite, does not exert proteolytic activity, as investigated by microscopic observation and MTT test. In an ex vivo model of the murine trachea we were able to show that Der p 1, in contrast to Phl p 1, enhances the transportation velocity of particles by the trachea, presumably by ATP released from the injured epithelium.

Conclusion
We conclude that under physiological conditions Phl p 1 affects tracheal epithelial cells through a non‐proteolytic activity. Enhancement of TGF‐β expression induced by Phl p 1 together with the increased release of IL‐6 and IL‐8 might provide an indirect mechanism through which the allergen may cross the epithelial barrier and attracts immunocompetent cells.
Basophil activation tests for the diagnosis of food allergy in children
Authors: Ocmant A. , Mulier S. , Hanssens L. , Goldman M. , Casimir G. , Mascart F. , Schandené L.
Published: June 2009

Background
Positive skin prick tests (SPT) for food allergens and specific IgE (sIgE) in serum indicate sensitization but do not enable distinction between sensitized but tolerant and clinically allergic patients.

Objective
Herein, we evaluate the clinical relevance of basophil activation tests (BATs) for peanut or egg allergy diagnosis.

Methods
Thirty‐two peanut‐allergic, 14 peanut‐sensitized (sIgE+ and/or SPT+ to peanuts) but tolerant children and 29 controls with no history of an adverse reaction to peanuts were included. Similarly, 31 egg‐allergic, 14 egg‐sensitized children (sIgE+ and/or SPT+ to egg white) and 22 controls were studied. Flow cytometric analysis of CD63 expression or CD203c upregulation on basophils and the production of leukotrienes (LT) were performed in response to an in vitro crude peanut extract or ovalbumin (OVA) challenge.

Results
After in vitro peanut challenge, the basophils from peanut‐allergic children showed significantly higher levels of activation than those from controls (P<0.001). After OVA challenge, a similar distinction (P<0.001) was observed between egg‐allergics and controls. Interestingly, the majority of egg‐ or peanut‐sensitized children failed to activate basophils, respectively, in response to OVA and peanut challenge. The sensitivity of the CD63, CD203c and LT assay was 86.7%, 89.5% and 76.0% with a specificity of 94.1%, 97.1% and 94.6% for peanut allergy diagnosis. The corresponding performances of BATs applied to egg allergy diagnosis were 88.9%, 62.5% and 77.8% for the sensitivity and 100%, 96.4% and 96.4% for the specificity.

Conclusion
Neither conventional tests nor BATs are sensitive and specific enough to predict food allergy accurately. However, BATs may helpfully complete conventional tests, especially SPT, allowing improved discrimination between allergic and non‐allergic individuals.
Inhaled house dust mite induces pulmonary T helper 2 cytokine production
Authors: Gregory L. G. , Causton B. , Murdoch J. R. , Mathie S. A. , O'Donnell V. , Thomas C. P. , Priest F. M. , Quint D. J. , Lloyd C. M.
Published: June 2009

Background
Inhaled house dust mite (HDM) results in T‐helper (TH) 2 type pathology in unsensitized mice, in conjunction with airway hyperreactivity and airway remodelling. However, the pulmonary cytokine and chemokine profile has not been reported.

Methods
We have performed a time course analysis of the characteristic molecular mediators and cellular influx in the bronchoalveolar lavage (BAL) and lung in order to define the pulmonary inflammatory response to inhaled HDM extract. Mice were exposed five times a week to soluble HDM extract for 3 weeks. Lung function was measured in groups of mice at intervals following the final HDM challenge. Recruitment of inflammatory cells and inflammatory mediator production was then assessed in BAL and lungs of individual mice.

Results
We found that Th2 cytokines were significantly increased in BAL and lung after HDM challenge from as early as 2 h post‐final challenge. The levels of cytokines and chemokines correlated with the influx of eosinophils and Th2 cells to the different compartments of the lung. However, the production of key cytokines such as IL‐4, IL‐5 and IL‐13 preceded the increase in airways resistance.

Conclusion
Inhaled HDM challenge induces a classical Th2 inflammatory mediator profile in the BAL and lung. These data are important for studies determining the efficacy of novel treatment strategies for allergic airways disease.
Changes in asthma‐like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model
Authors: Zhang X. D. , Hubbs A. F. , Siegel P. D.
Published: June 2009

Background
Organic acid anhydride‐induced occupational asthma is considered to be IgE‐mediated. Airway and skin exposure are the two main routes of sensitization in the work place. Recently we developed an allergic asthmatic Brown Norway rat model sensitized by dermal exposure to trimellitic anhydride (TMA) using an occlusion patch application.

Objectives
The objectives of this study were (1) to develop a model of non‐occluded dermal exposure leading to allergic sensitization and (2) to examine the effect of extended removal from exposure on persistence of both specific IgE and TMA aerosol‐induced airway responses in this model.

Methods
TMA powder (4 or 40 mg) was applied, unoccluded, to the skin of rats for 4 h, once/week for 4 weeks. Rats were given a 10‐min aerosol challenge to 40 mg/m3 TMA 2 weeks after the last dermal exposure (day 35). Another group was challenged on day 35 and again 18–24 months later. Respiratory enhanced pause (Penh), pulmonary histopathology and inflammation and specific IgE titres were measured.

Results
Rats produced dose‐dependent specific IgE titres after exposure and developed early‐phase (EAR) and late‐phase airway responses (LAR) after airway challenge to TMA aerosol as well as airway eosinophilic inflammation. Specific airway responses were still manifested after a second TMA airway challenge given 18–24 months following the initial airway challenge. While persistent, airway inflammation, specific IgE and EAR were significantly attenuated following the second TMA challenge. LAR remained robust at 18–24 months and was not significantly different from the response on day 35.

Conclusions
These results demonstrate the persistence of chemical sensitization and further suggest that IgE is not essential for LAR.
Factors determining the remission of microprolactinomas after dopamine agonist withdrawal
Authors: Huda M. S. B. , Athauda N. B. , Teh M. M. , Carroll P. V. , Powrie J. K.
Published: June 2009

Background  Withdrawal of dopamine agonist (DA) therapy in the management of microprolactinoma is common practice, but it is unclear which patients are likely to attain long‐term remission.

Objective  To identify predictive factors for long‐term remission.

Design  Prospective cohort study.

Patients  Forty subjects (39 female, aged 24–60 years) with microprolactinoma; all had been normoprolactinaemic on DA therapy for at least 2 years [mean duration of therapy 9 years (range 2–27)].

Measurements  A pituitary magnetic resonance imaging (MRI) was performed on 36 (90%) subjects before DA withdrawal. Relapse was defined as prolactin greater than 480 mIU/l (22·8 μg/l) on two occasions.

Results  Nine out of 40 (22·5%) subjects were normoprolactinaemic 12 months after DA withdrawal. Amongst the relapse group, 24 of 31 subjects (79·4%) had already relapsed at 3 months. Normalization of MRI prior to DA withdrawal (P = 0·0006) and longer duration of DA treatment (P = 0·032) were significant predictors of remission. Age, pre‐treatment prolactin, nadir prolactin, previous failure of DA withdrawal, pregnancy, dose and type of DA were not significant predictors of remission. The nine patients who were in remission at 12 months were then followed up for 58·0 ± 5·8 months; all remained in remission.

Conclusions  As many as 22·5% of subjects with microprolactinoma remained normoprolactinaemic 12 months after DA withdrawal and these subjects stayed in remission for up to 5 years. Significant predictive factors were normalization of MRI prior to discontinuation, and duration of DA treatment. Our findings support intermittent DA withdrawal after a period of normoprolactinaemia, particularly where MRI appearances have normalized.
The adipokine zinc‐α2‐glycoprotein (ZAG) is downregulated with fat mass expansion in obesity
Authors: Mracek T. , Ding Q. , Tzanavari T. , Kos K. , Pinkney J. , Wilding J. , Trayhurn P. , Bing C.
Published: June 2009

Introduction  Zinc‐α2‐glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes.

Methods  Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson‐Golabi‐Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real‐time PCR and protein by Western blotting.

Results  In human subjects, ZAG mRNA level was negatively correlated with BMI (r = −0·61, P < 0·001, n = 23, visceral; r = −0·6, P < 0·05, n = 14, subcutaneous) and fat mass (r = −0·62, P < 0·01, visceral; r = −0·6, P < 0·05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = −0·65, P < 0·001, visceral; r = −0·55, P < 0·05, subcutaneous) and homeostasis model of insulin resistance (HOMA‐IR) (r = −0·65, P < 0·001, visceral; r = −0·52, P = 0·055, subcutaneous), and C reactive protein (CRP) (r = −0·46, P < 0·05, visceral; r = −0·53, P < 0·05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0·5, P < 0·05, visceral; r = 0·82, P < 0·001, subcutaneous) but negatively associated with leptin mRNA (r = −0·42, P < 0·05, visceral; r = −0·54, P < 0·05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes.

Conclusion  ZAG gene expression in adipose tissue is downregulated with increased adiposity and circulating insulin. ZAG mRNA is positively correlated with adiponectin mRNA, and ZAG enhances adiponectin production by human adipocytes. We suggest that ZAG is linked to obesity and obesity‐related insulin resistance.
Leptin secretion rate increases with higher CAG repeat number in Huntington’s disease patients
Authors: Ahmad Aziz N. , Pijl Hanno , Frölich Marijke , Maurits van der Graaf A.W. , Roelfsema Ferdinand , Roos Raymund A.C.
Published: June 2009

Background  Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown.

Objective  To perform a detailed analysis of adipose tissue function in HD patients as abnormal fat tissue function could contribute to the weight loss.

Design, setting and participants  In a clinical research laboratory, 24‐h plasma concentrations of leptin, adiponectin and resistin were studied in nine early‐stage, medication‐free HD patients and nine age‐, gender‐ and body mass index (BMI)‐matched controls.

Measurements  Leptin was measured every 20 min whereas adiponectin and resistin were measured hourly. Autodeconvolution and cosinor regression were applied to quantify secretion characteristics of leptin and diurnal variations in leptin, adiponectin and resistin levels.

Results  Plasma levels and diurnal rhythmicity of leptin, adiponectin and resistin were not significantly different between HD patients and controls. However, although leptin production increased with higher BMI and fat mass in controls, no such relation was present in HD patients. Moreover, when corrected for fat mass, mean plasma leptin concentration as well as basal, pulsatile and total secretion rates increased with the size of the CAG repeat mutation (r = +0·72 to r = +0·80; all P < 0·05). Both higher pulsatile leptin secretion and higher mean adiponectin levels were associated with a greater degree of motor and functional impairment in HD patients.

Conclusions  CAG‐repeat size‐dependent interference of the HD mutation with adipose tissue function may contribute to weight loss in HD patients.
How should the patient with multiple endocrine neoplasia type 1 (MEN 1) be followed?
Authors: Burgess John
Published: June 2009

Multiple endocrine neoplasia type 1 (MEN 1) is a complex multi‐system disease manifesting a diverse range of primary and secondary metabolic and neoplastic disorders. It is possible to improve patient prognosis by early disease detection and treatment. Regular biochemical and radiological screening for parathyroid, gastro‐enteropancreatic, pituitary, intrathorasic and adrenal lesions forms the basis of surveillance. The likelihood of adverse sequelea such as renal and bone disease resulting from hyperparathyroidism, severe peptic ulceration and gastric carcinoidosis secondary to hypergastrinaemia can be ameliorated by early detection and management.
Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated fromCelastrus regelii
Authors: Kim D. H. , Shin E. K. , Kim Y. H. , Lee B. W. , Jun J.‐G. , Park J. H. Y. , Kim J.‐K.
Published: June 2009

Background Celastrol, a quinone methide triterpenoid isolated from theCelastraceaefamily, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation.

Materials and methods Anti‐inflammatory effects of celastrol (0–1 μM) were examined in lipopolysaccharide (LPS)‐stimulated RAW 264·7 macrophages. To investigate the effects of celastrol (0–50 μg per mice)in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA)‐induced mouse ear oedema model.

Results Ourin vitroexperiments showed that celastrol suppressed not only LPS‐stimulated generation of nitric oxide and prostaglandin E2, but also expression of inducible nitric oxide synthase and cyclooxygenase‐2 in RAW264·7 cells. Similarly, celastrol inhibited LPS‐induced production of inflammatory cytokines, including tumour necrosis factor‐α and interleukin‐6. In an animal model, celastrol protected mice from TPA‐induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines.

Conclusions Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases.
Assessment of arsenic availability to roots in contaminated Tuscany soils by a diffusion gradient in thin films (DGT) method and uptake by Pteris vittata and Agrostis capillaris
Authors: Cattani I. , Capri E. , Boccelli R. , Del Re A.A.M.
Published: June 2009

A laboratory study was conducted to evaluate the availability of arsenic (As) to roots in nine soils from five fields in Tuscany (Italy). Concentrations of As in soils range from 200 to 1200 mg kg−1 as a result of human activities and natural deposition. In a first stage, potentially root‐available As and the risk of crop uptake were estimated using the diffusion gradient in thin films (DGT) technique. In a second stage, a glasshouse experiment was performed to compare As depletion in the rhizosphere by the hyperaccumulator Pteris vittata (ladder brake), and by the test plant Agrostis capillaris (colonial bentgrass). In this stage, DGT results were supported by a sequential extraction procedure. The main objectives were to study the root availability of As in old, contaminated soils and the modification of the available pool size over time. The phytoextraction efficiency of Pteris vittata as applied to this case study was also investigated. In all samples, concentrations of total and potentially root‐available As in soil solution were small compared with total As in soil (approximately 0.0003–0.03%, corresponding to 3.5–350 μg l−1, respectively). There was also little re‐supply of As from the solid phase to the soil solution. In the rhizosphere, despite uptake by Pteris and Agrostis, total and root available As in solution were sustained over time. It appeared that plants induced a re‐supply of As from the solid phase. Despite the uptake and translocation of As by Pteris (50.7 mg kg−1 and 6.6 mg As kg−1 in fronds and roots, respectively) together with plant biomass (17.2 g per plant), the success of phytoextraction appears unlikely. The results obtained demonstrated the sensitivity of DGT to root‐induced changes in soil and the suitability of the technique as an easy‐to‐use tool to predict assimilation by plants.
Shrinkage behaviour of transiently‐ and constantly‐loaded soils and its consequences for soil moisture release
Authors: Peng X. , Dörner J. , Zhao Y. , Horn R.
Published: June 2009

Soils under loaded conditions may have different shrinkage behaviour from that of load‐free soils. In this study, we applied two kinds of mechanical stress (σ) on repacked homogeneous soil samples: transient and constant stresses, simulating the traffic load during tillage and the overburden pressure, respectively. Three transient stresses were applied on the soil surface with 150, 400 and 1400 kPa, while the constant stresses ranged from 1.8, 3.8, 5.5, to 7.3 kPa. We hypothesized that the two stresses play different roles in soil shrinkage behaviour as depicted by void ratio (e) and moisture ratio (ϑ), as compared with load‐free soil. Thus, our aim was to build up the relationship between e, ϑ and σ. For a swelling soil, total pores can be divided into rigid and non‐rigid components according to their swelling and shrinkage capacity relative to soil moisture. The non‐rigid pores compacted by the transient stress can be regained in the subsequent wetting at load‐free conditions, whereas the compacted rigid pores do not recover. The reduction in rigid pores does not alter the soil pore shrinkage capacity. The shrinkage curves of transiently‐loaded soils are therefore parallel to each other with an identical coefficient of linear extensibility (COLE) and the same shrinkage slope, although their structural shrinkage phase narrows with an increase of stress. However, the constant stress compresses non‐rigid pores readily through suppressing their swelling capacity during wetting as well as compacting rigid pores. If the change of rigid pores is negligible, the shrinkage curves of constantly‐loaded soils converge at the zero shrinkage or the dry‐end point with the load‐free soil shrinkage. If the reductions of rigid and non‐rigid pores are both considered, the soil shrinkage combines the part of parallel shrinkage derived from the reduced rigid pores and the intersected shrinkage resulted from the altered non‐rigid pores. On the basis of different shrinkage behaviours resulting from the two mechanical stresses, we propose numerical formulae to illustrate a series of curves for the e‐ϑ‐σ relationship. The different changes in rigid and non‐rigid pores cause soil water release differently.
Delivery of hatching larvae to estuaries by an amphidromous river shrimp: tests of hypotheses based on larval moulting and distribution
Authors: ROME NICHOLAS E. , CONNER SARA L. , BAUER RAYMOND T.
Published: June 2009

1. Amphidromous shrimps live and breed in freshwater rivers and streams, but their larvae require development in sea water. Larvae may hatch upstream and then drift to the sea, although in some species females have been reported to migrate to the coast before larvae are released. Here, we tested the relative importance of larval drift and female migration in Macrobrachium ohione (Decapoda: Palaemonidae) in a distributary of the Mississippi River in Louisiana, U.S.A.

2. Newly hatched (stage‐1) larvae are nonfeeding and will not moult to stage 2 (first feeding stage) without encountering salt water. A factorial experiment was conducted in the laboratory to test the effects on moulting to stage 2 of (i) time spent by stage‐1 larvae in fresh water before (ii) exposure to and maintenance in water of different salinity. Larvae kept in fresh water for 1 or 3 days before a change to saline water at 6 or 10 ppt showed a greater frequency of moulting than those kept for longer (5 days) in fresh water or changed to less saline water (2 ppt). Non‐moulting larvae died or were moribund within 11 days of hatching.

3. The relative abundance of stage‐1 larvae was measured with plankton tows at two locations in the river c. 150 km apart, one near the sea and one upstream. Larval abundances near the sea were significantly greater than those upstream.

4. The results indicate that hatched larvae of M. ohione have a limited period in which to drift in fresh water before reaching water sufficiently saline to stimulate moulting to the first feeding stage. Female migrations may play an important role in delivering larvae of amphidromous species from large continental river systems in which distances to the sea are great, while larval drift alone may be sufficient in species living in short streams, like those found in many small mountainous tropical islands.
Extended lifespan traded for diapause in Daphnia
Authors: SLUSARCZYK MIROSŁAW
Published: June 2009

1. Most freshwater crustaceans of the genus Daphnia are cyclically parthenogenetic organisms that are well adapted to unstable habitats due to their short life cycle, wide phenotypic plasticity, and the ability to produce protective diapausing eggs in anticipation of environmental deterioration. Short lifespan and heterogonic reproduction are typical features of Daphnia in a broad spectrum of freshwater habitats, from small temporary pools to large permanent lakes. However, in some locations, departures may be observed from this typical life history pattern to obligate asexuality or extended lifespan.

2. A 3‐year field study in a deep ultraoligotrophic fish‐free alpine‐type lake (Czarny Staw in the Tatra mountains in southern Poland) revealed the coexistence of two closely related asexual lineages of Daphnia of the pulex complex, which differ in body colour (transparent versus orange) and in their strategies for surviving long winters.

3. The ‘transparent’ clone of European origin exhibits an ephemeral lifestyle. It completes its life cycle within a single season, forming two generations of active specimens during the short summer and producing diapausing eggs late in the season. Transparent individuals live no longer than 5–6 months in this cold lake and survive winter exclusively in the form of diapausing eggs.

4. Individuals of the ‘orange’ lineage, which are closely related to eastern Nearctic Daphnia pulicaria, exhibit a biennial lifestyle unique to this genus. They do not form diapausing eggs or produce them only occasionally. Instead, they are active throughout the year and live for up to 13–14 months. Reproduction is postponed until the second year of life when food conditions have improved. Rich lipid reserves accumulated in the first season fuel them during the long winter and permit early reproduction the following spring.

5. Possible reasons for the evolution of obligatory parthenogenesis and long lifespan in Daphnia are discussed.
Effects of body mass and huddling on resting metabolic rates of post‐weaned European rabbits under different simulated weather conditions
Authors: Seltmann Martin W. , Ruf Thomas , Rödel Heiko G.
Published: June 2009

1. During the early juvenile period, animals are especially prone to heat loss due to their high surface area to volume ratio. Consequently, adverse environmental conditions such as low ambient temperature and wetness affect the energy balance in juveniles more strongly than in adults.

2. Our main study goal was to experimentally measure the influence of low ambient temperatures and wet fur on resting metabolic rates (RMR) and on thermal conductance in young, pre‐weaned (wild‐type) European rabbits (Oryctolagus cuniculusL.), i.e. shortly after young rabbits in the wild usually leave the breeding burrow.

3. We predicted that a higher body mass and therefore a more favourable surface area to volume ratio might decrease the responses of the juveniles to adverse weather conditions. Furthermore, huddling with siblings might buffer the negative influences of low temperature and wet fur.

4. Using studies in field enclosures, we first evaluated the occurrence of huddling in juvenile European rabbits, and recorded the variation in ambient temperature experienced by the young. In laboratory experiments, we then measured RMR in single and pair‐housed (huddling) juveniles with dry and wet fur under different ambient temperatures reflecting the conditions experienced by same‐aged rabbits in the wild.

5. We found interacting effects of temperature and wetness on RMR and on thermal conductance, which increased more strongly with decreasing temperature when the animals were wet. In addition, RMR decreased significantly with increasing body mass, but only under wet conditions when the temperature was low.

6. Pre‐weaned juveniles in the field enclosures almost exclusively huddled in pairs but not in larger groups, probably because of the high juvenile mortality, which was strongly limiting the number of litter mates. In laboratory experiments, we did not find significantly lower RMR or thermal conductance in huddling pairs than in single juveniles. The occurrence of huddling, in the field and in the laboratory, was also not related to ambient temperature conditions.

7. Our study highlights the importance of a high juvenile body mass which helps to reduce maintenance costs under adverse environmental conditions. Such effects might have important implications for the individual’s pre‐weaning growth and development and may exert long‐term effects on fitness‐related traits.
Lag‐phase autophagy in the methylotrophic yeast Pichia pastoris
Authors: Yamashita Shun‐ichi , Yurimoto Hiroya , Murakami Dai , Yoshikawa Mari , Oku Masahide , Sakai Yasuyoshi
Published: June 2009

When microbes sense environmental changes, they often temporarily attenuate cell growth to adapt to the new situations, showing a lag phase. In this study, we report that the methylotrophic yeast, Pichia pastoris, induced autophagy during the lag phase after the cells were shifted from glucose to methanol medium. Through the autophagic process at least two proteins, aminopeptidase I precursor and cytosolic aldehyde dehydrogenase, were found to be transported into the vacuole, which was dependent on PpAtg11 and PpAtg17, respectively. Notably, PpAtg1 and PpAtg17 were required for early exit from the lag phase during the methanol adaptation. In accordance, phosphorylation states of elongation initiation factor 2α indicated reductions of intracellular amino‐acid pools in the atg mutant strains. Together, these data demonstrate the importance of amino acid recycling by autophagy during a cell‐remodeling process.
Dissection of σE‐dependent cell lysis in Escherichia coli: roles of RpoE regulators RseA, RseB and periplasmic folding catalyst PpiD
Authors: Noor Rashed , Murata Masayuki , Nagamitsu Hiroshi , Klein Gracjana , Raina Satish , Yamada Mamoru
Published: June 2009

To understand the mechanism of σE‐dependent cell lysis, we examined the consequences of deletion derivatives of rpoE regulators rseA, rseB and rseC on σE transcription, on levels of free versus membrane‐bound σE and on OMP‐biogenesis limiting factor(s) that could impact cell lysis. RT‐PCR showed that individual nonpolar ΔrseA and ΔrseB increased the rpoE expression to varying extents, with pronounced induction in ΔrseA. Significantly the ratio of soluble (free) versus membrane‐bound form of RpoE increased in ΔrseA, however without increase of its total amount, unraveling furthermore complexity in RpoE regulation. Significant characteristics of cell lysis, accompanied by a severe reduction in the levels of periplasmic OMP‐folding factor (PpiD), were observed in ΔrseA. The cell‐lysis phenotype of ΔrseA was suppressed by either rseA or ppiD plasmids, but neither by rseB nor by rseC clones. However, the cell lysis of the wild‐type strain was almost completely repressed not only by the rseA clone but also by the rseB clone, suggesting RseB might be limiting in vivo. Thus, increase in the ratio of free σE in rseA mutants with a concomitant reduction in PpiD levels can account for σE‐dependent lysis in concert with a potential role of small RNAs on the lysis process.