bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Screening of Arabidopsis Mutants Suggests the Lysine Histidine Transporter 1 to Be Involved in Plant Uptake of Amino Acids
Authors: Svennerstam Henrik , Ganeteg Ulrika , Bellini Catherine , Näsholm Torgny
Published: February 2007

Plant nitrogen (N) uptake is a key process in the global N cycle and is usually considered a “bottleneck” for biomass production in land ecosystems. Earlier, mineral N was considered the only form available to plants. Recent studies have questioned this dogma and shown that plants may access organic N sources such as amino acids. The actual mechanism enabling plants to access amino acid N is still unknown. However, a recent study suggested the Lysine Histidine Transporter 1 (LHT1) to be involved in root amino acid uptake. In this study, we isolated mutants defective in root amino acid uptake by screening Arabidopsis (Arabidopsis thaliana) seeds from ethyl methanesulfonate-treated plants and seeds from amino acid transporter T-DNA knockout mutants for resistance against the toxic d-enantiomer of alanine (Ala). Both ethyl methanesulfonate and T-DNA knockout plants identified as d-Ala resistant were found to be mutated in the LHT1 gene. LHT1 mutants displayed impaired capacity for uptake of a range of amino acids from solutions, displayed impaired growth when N was supplied in organic forms, and acquired substantially lower amounts of amino acids than wild-type plants from solid growth media. LHT1 mutants grown on mineral N did not display a phenotype until at the stage of flowering, when premature senescence of old leaf pairs occurred, suggesting that LHT1 may fulfill an important function at this developmental stage. Based on the broad and unbiased screening of mutants resistant to d-Ala, we suggest that LHT1 is an important mediator of root uptake of amino acids. This provides a molecular background for plant acquisition of organic N from the soil.
The MtMMPL1 Early Nodulin Is a Novel Member of the Matrix Metalloendoproteinase Family with a Role in Medicago truncatula Infection by Sinorhizobium meliloti
Authors: Combier Jean-Philippe , Vernié Tatiana , de Billy Françoise , El Yahyaoui Fikri , Mathis René , Gamas Pascal
Published: February 2007

We show here that MtMMPL1, a Medicago truncatula nodulin gene previously identified by transcriptomics, represents a novel and specific marker for root and nodule infection by Sinorhizobium meliloti. This was established by determining the spatial pattern of MtMMPL1 expression and evaluating gene activation in the context of various plant and bacterial symbiotic mutant interactions. The MtMMPL1 protein is the first nodulin shown to belong to the large matrix metalloendoproteinase (MMP) family. While plant MMPs are poorly documented, they are well characterized in animals as playing a key role in a number of normal and pathological processes involving the remodeling of the extracellular matrix. MtMMPL1 represents a novel MMP variant, with a substitution of a key amino acid residue within the predicted active site, found exclusively in expressed sequence tags corresponding to legume MMP homologs. An RNA interference approach revealed that decreasing MtMMPL1 expression leads to an accumulation of rhizobia within infection threads, whose diameter is often significantly enlarged. Conversely, MtMMPL1 ectopic overexpression under the control of a constitutive (35S) promoter led to numerous abortive infections and an overall decrease in the number of nodules. We discuss possible roles of MtMMPL1 during Rhizobium infection.
Overexpression of an R1R2R3 MYB Gene, OsMYB3R-2, Increases Tolerance to Freezing, Drought, and Salt Stress in Transgenic Arabidopsis
Authors: Dai Xiaoyan , Xu Yunyuan , Ma Qibin , Xu Wenying , Wang Tai , Xue Yongbiao , Chong Kang
Published: February 2007

We used a cDNA microarray approach to monitor the expression profile of rice (Oryza sativa) under cold stress and identified 328 cold-regulated genes. Thirteen such genes encoding MYB, homeodomain, and zinc finger proteins with unknown functions showed a significant change in expression under 72-h cold stress. Among them, OsMYB3R-2 was selected for further study. Unlike most plant R2R3 MYB transcription factors, OsMYB3R-2 has three imperfect repeats in the DNA-binding domain, the same as in animal c-MYB proteins. Expression of OsMYB3R-2 was induced by cold, drought, and salt stress. The Arabidopsis (Arabidopsis thaliana) transgenic plants overexpressing OsMYB3R-2 showed increased tolerance to cold, drought, and salt stress, and the seed germination of transgenic plants was more tolerant to abscisic acid or NaCl than that of wild type. The expression of some clod-related genes, such as dehydration-responsive element-binding protein 2A, COR15a, and RCI2A, was increased to a higher level in OsMYB3R-2-overexpressing plants than in wild type. These results suggest that OsMYB3R-2 acts as a master switch in stress tolerance.
Specific Roles of α- and γ-Tocopherol in Abiotic Stress Responses of Transgenic Tobacco
Authors: Abbasi Ali-Reza , Hajirezaei Mohamad , Hofius Daniel , Sonnewald Uwe , Voll Lars M.
Published: February 2007

Tocopherols are lipophilic antioxidants that are synthesized exclusively in photosynthetic organisms. In most higher plants, α- and γ-tocopherol are predominant with their ratio being under spatial and temporal control. While α-tocopherol accumulates predominantly in photosynthetic tissue, seeds are rich in γ-tocopherol. To date, little is known about the specific roles of α- and γ-tocopherol in different plant tissues. To study the impact of tocopherol composition and content on stress tolerance, transgenic tobacco (Nicotiana tabacum) plants constitutively silenced for homogentisate phytyltransferase (HPT) and γ-tocopherol methyltransferase (γ-TMT) activity were created. Silencing of HPT lead to an up to 98% reduction of total tocopherol accumulation compared to wild type. Knockdown of γ-TMT resulted in an up to 95% reduction of α-tocopherol in leaves of the transgenics, which was almost quantitatively compensated for by an increase in γ-tocopherol. The response of HPT and γ-TMT transgenics to salt and sorbitol stress and methyl viologen treatments in comparison to wild type was studied. Each stress condition imposes oxidative stress along with additional challenges like perturbing ion homeostasis, desiccation, or disturbing photochemistry, respectively. Decreased total tocopherol content increased the sensitivity of HPT:RNAi transgenics toward all tested stress conditions, whereas γ-TMT-silenced plants showed an improved performance when challenged with sorbitol or methyl viologen. However, salt tolerance of γ-TMT transgenics was strongly decreased. Membrane damage in γ-TMT transgenic plants was reduced after sorbitol and methyl viologen-mediated stress, as evident by less lipid peroxidation and/or electrolyte leakage. Therefore, our results suggest specific roles for α- and γ-tocopherol in vivo.
Involvement of the Histone Acetyltransferase AtHAC1 in the Regulation of Flowering Time via Repression ofFLOWERING LOCUS Cin Arabidopsis
Authors: Deng WeiWei , Liu ChunYan , Pei YanXi , Deng Xian , Niu LiFang , Cao XiaoFeng
Published: February 2007

Histone acetylation is an important posttranslational modification correlated with gene activation. In Arabidopsis (Arabidopsis thaliana), the histone acetyltransferase AtHAC1 is homologous to animal p300/CREB (cAMP-responsive element-binding protein)-binding proteins, which are the main histone acetyltransferases participating in many physiological processes, including proliferation, differentiation, and apoptosis. The functions of p300/CREB-binding proteins in animals are well characterized, whereas little is known about the roles of AtHAC1 in developmental control in Arabidopsis. Lesions in AtHAC1 caused pleiotropic developmental defects, including delayed flowering, a shortened primary root, and partially reduced fertility. Analysis of the molecular basis of late flowering in hac1 mutants showed that the hac1 plants respond normally to day length, gibberellic acid treatment, and vernalization. Furthermore, the expression level of the flowering repressor FLOWERING LOCUS C (FLC) is increased in hac1 mutants, indicating that the late-flowering phenotype of hac1 mutants is mediated by FLC. Since histone acetylation is usually associated with the activation of gene expression, histone modifications of FLC chromatin are not affected by mutations in HAC1 and expression levels of all known autonomous pathway genes are unchanged in hac1 plants, we propose that HAC1 affects flowering time by epigenetic modification of factors upstream of FLC.
Histone Deacetylases and ASYMMETRIC LEAVES2 Are Involved in the Establishment of Polarity in Leaves ofArabidopsis
Authors: Ueno Yoshihisa , Ishikawa Takaaki , Watanabe Keiro , Terakura Shinji , Iwakawa Hidekazu , Okada Kiyotaka , Machida Chiyoko , Machida Yasunori
Published: February 2007

We show that two Arabidopsis thaliana genes for histone deacetylases (HDACs), HDT1/HD2A and HDT2/HD2B, are required to establish leaf polarity in the presence of mutant ASYMMETRIC LEAVES2 (AS2) or AS1. Treatment of as1 or as2 plants with inhibitors of HDACs resulted in abaxialized filamentous leaves and aberrant distribution of microRNA165 and/or microRNA166 (miR165/166) in leaves. Knockdown mutations of these two HDACs by RNA interference resulted in phenotypes like those observed in the as2 background. Nuclear localization of overproduced AS2 resulted in decreased levels of mature miR165/166 in leaves. This abnormality was abolished by HDAC inhibitors, suggesting that HDACs are required for AS2 action. A loss-of-function mutation in HASTY, encoding a positive regulator of miRNA levels, and a gain-of-function mutation in PHABULOSA, encoding a determinant of adaxialization, suppressed the generation of abaxialized filamentous leaves by inhibition of HDACs in the as1 or as2 background. AS2 and AS1 were colocalized in subnuclear bodies adjacent to the nucleolus where HDT1/HD2A and HDT2/HD2B were also found. Our results suggest that these HDACs and both AS2 and AS1 act independently to control levels and/or patterns of miR165/166 distribution and the development of adaxial-abaxial leaf polarity and that there may be interactions between HDACs and AS2 (AS1) in the generation of those miRNAs.
Dominant-Negative Modification Reveals the Regulatory Function of the Multimeric Cysteine Synthase Protein Complex in Transgenic Tobacco
Authors: Wirtz Markus , Hell Rüdiger
Published: February 2007

Cys synthesis in plants constitutes the entry of reduced sulfur from assimilatory sulfate reduction into metabolism. The catalyzing enzymes serine acetyltransferase (SAT) and O-acetylserine (OAS) thiol lyase (OAS-TL) reversibly form the heterooligomeric Cys synthase complex (CSC). Dominant-negative mutation of the CSC showed the crucial function for the regulation of Cys biosynthesis in vivo. An Arabidopsis thaliana SAT was overexpressed in the cytosol of transgenic tobacco (Nicotiana tabacum) plants in either enzymatically active or inactive forms that were both shown to interact efficiently with endogenous tobacco OAS-TL proteins. Active SAT expression resulted in a 40-fold increase in SAT activity and strong increases in the reaction intermediate OAS as well as Cys, glutathione, Met, and total sulfur contents. However, inactive SAT expression produced much greater enhancing effects, including 30-fold increased Cys levels, attributable, apparently, to the competition of inactive transgenic SAT with endogenous tobacco SAT for binding to OAS-TL. Expression levels of tobacco SAT and OAS-TL remained unaffected. Flux control coefficients suggested that the accumulation of OAS and Cys in both types of transgenic plants was accomplished by different mechanisms. These data provide evidence that the CSC and its subcellular compartmentation play a crucial role in the control of Cys biosynthesis, a unique function for a plant metabolic protein complex.
Cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in England and Wales
Authors: Hickman Matthew , Vickerman Peter , Macleod John , Kirkbride James , Jones Peter B.
Published: February 2007

Aims  To estimate long‐term trends in cannabis use and projections of schizophrenia assuming a causal relation between cannabis use and schizophrenia.

Methods  Trends in cannabis use were estimated from a national survey, 2003; and incidence of schizophrenia was derived from surveys in three English cities, 1997–99. A difference equation cohort model was fitted against estimates of schizophrenia incidence, trends in cannabis exposure and assumptions on association between cannabis and schizophrenia. The model projects trends in schizophrenia incidence, prevalence and attributable fraction of cannabis induced schizophrenia.

Results  Between 1970 and 2002 cannabis exposure increased: incidence by fourfold; period prevalence by 10‐fold; and use among under 18‐year‐olds by 18‐fold. In 1997–99 incidence and prevalence of schizophrenia were 17 per 100 000 and 0.63% among men and 7.3 per 100 000 and 0.23% among women, respectively. If cannabis use causes schizophrenia, earlier increases in cannabis use would lead to increases in overall schizophrenia incidence and prevalence of 29% and 12% among men between 1990 and 2010. By 2010 model projections which assume an association between schizophrenia and light and heavy users suggest that approximately one‐quarter of new schizophrenia cases could be due to cannabis, whereas if the association is twofold and confined to heavy cannabis users, then approximately 10% of schizophrenia cases may be due to cannabis.

Conclusions  If cannabis use causes schizophrenia, and assuming other causes are unchanged, then relatively substantial increases in both prevalence and incidence of schizophrenia should be apparent by 2010. More accurate data on cannabis consumption and future monitoring of schizophrenia are critical.
Transcriptional responses to exposure to the brassicaceous defence metabolites camalexin and allyl‐isothiocyanate in the necrotrophic fungus Alternaria brassicicola
Authors: SELLAM ADNANE , DONGO ANITA , GUILLEMETTE THOMAS , HUDHOMME PIÉTRICK , SIMONEAU PHILIPPE
Published: February 2007

Alternaria brassicicola is the causative agent of black spot disease of Brassicaceae belonging to the genera Brassica and Raphanus. During host infection, A. brassicicola is exposed to high levels of antimicrobial defence compounds such as indolic phytoalexins and glucosinolate breakdown products. To investigate the transcriptomic response of A. brassicicola when challenged with brassicaceous defence metabolites, suppression subtractive hybridization (SSH) was performed to generate two cDNA libraries from germinated conidia treated either with allyl isothiocyanate (Al‐ITC) or with camalexin. Following exposure to Al‐ITC, A. brassicicola displayed a response similar to that experienced during oxidative stress. Indeed, a substantial subset of differentially expressed genes was related to cell protection against oxidative damage. Treatment of A. brassicicola conidia with the phytoalexin camalexin appeared to activate a compensatory mechanism to preserve cell membrane integrity and, among the camalexin‐elicited genes, several were involved in sterol and sphingolipid biosynthesis. The transcriptomic analysis suggested that protection against the two tested compounds also involved mechanisms aimed at limiting their intracellular accumulation, such as melanin biosynthesis (in the case of camalexin exposure only) and drug efflux. From the Al‐ITC and the camalexin differentially expressed genes identified here, 25 were selected to perform time‐course studies during interactions with brassicaceous hosts. In planta, up‐regulation of all the selected genes was observed during infection of Raphanus sativus whereas only a subset were over‐expressed during the incompatible interaction with Arabidopsis thaliana ecotype Columbia.
Traditional treatment of malaria in Mbarara District, western Uganda
Authors: Katuura E. , Waako P. , Ogwal‐Okeng J. , Bukenya‐Ziraba R.
Published: February 2007

An ethnobotanical survey on traditional treatment of malaria was carried out in Mbarara District, western Uganda, a malaria‐endemic area. From this study, traditional healers understood malaria symptoms. Malaria was reported to be the most common condition treated by traditional healers in this area. Plants were the single most important source of natural products used for malaria treatment. Most of the plants used in malaria treatment belong to the family Asteraceae. The most commonly used plant parts were the leaves. Water was the most common solvent and the oral route was the most commonly used. From this study there are a number of plants in Mbarara district that can be used as sources of herbal remedies for malaria. A number of these plants can be incorporated in the national primary healthcare package after scientific studies on safety and efficacy are done.
An investigation into Fusarium spp. associated with coffee and banana plants as potential pathogens of robusta coffee
Authors: Serani S. , Taligoola H. K. , Hakiza G. J.
Published: February 2007

Studies were conducted on fungi isolated from coffee trees affected by Fusarium xylarioides (Heim & Saccas) Steyaert to establish their pathogenicity and identify possible alternate hosts. Coffee and banana plant samples were collected from individual coffee farmers from the coffee growing districts of Mukono, Mpigi, Mubende, Kabarole and Kibaale. The studies were aimed at isolating the type of Fusarium species affecting coffee trees, identifying and characterizing them. Various Fusarium species were found associated with robusta coffee berries, stems and roots. These included Fusarium xylarioides, F. stilboides Wollen‐webber & Reiking, F. solani (Mart.) Saccas, F. lateritium Nees, F.semitectum Berk & Rav, F. oxysporum Schlecht, F. moniliforme Sheldon and F. acuminatum Ell. & Ev. Also recovered from banana roots and pseudo‐stem were F. xylarioides, F. oxysporum, F. solani, F. acuminatum and F. moniliforme. Fusarium xylarioides, F. oxysporum and F. solani were isolated most frequently from roots followed by stems and rarely on berries. Both F. stilboides and F. lateritium were next in abundance and were isolated mostly from berries. In culture, F. xylarioides isolates showed two types of colonies: one was soft, slimy and smooth, while the other was wrinkled. The two F. xylarioides isolates were not compatible. The five commonly isolated Fusarium species from robusta coffee produced symptoms on inoculated robusta coffee clones but F. xylarioides isolates induced the more severe symptoms, killing the greatest number of shoots.
Ecological, environmental and socioeconomic aspects of the Lake Victoria's introduced Nile perch fishery in relation to the native fisheries and the species culture potential: lessons to learn
Authors: Balirwa John S.
Published: February 2007

Inland fishery ecosystems in Africa are characterized by patterns of overexploitation, environmental degradation and exotic species introductions. Ecological complexity and diversity of aquatic habitats dictate that fishes in general are not evenly distributed in a water body. However, fisheries management regimes tend to ignore this basic principle, assume generalized conditions in a water body, and focus more on ‘desired’ objectives such as maximizing catch. The result is to disregard fish habitat boundaries and anthropogenic influences from the catchment that influence fish production. Overexploitation and environmental degradation disrupt sustainable socioeconomic benefits from the fisheries, create uncertainty among investors, but leave some managers calling for more information with the expectation that the fisheries will recover with time. Open access to the fisheries and full control of fishing effort remain challenges for managers. Exotic species introductions and fish farming can increase production, but such interventions require firm commitment to sound ecological principles and strict enforcement of recommended conservation and co‐management measures in capture fisheries. The general tendency to downplay fishing effort issues, other ecosystem values and functions or rely on temperate fisheries models until a new cycle of overexploitation emerges, characterizes many management patterns in inland fisheries. Aquaculture is not an option to challenges in capture fisheries management. Aquaculture should be developed to increase fish production but even this practice may have negative environmental impacts depending on practice and scale. Decades of information on Lake Victoria fisheries trends and aquaculture development did not stop the collapse of native fisheries. The successfully introduced Nile perch (Lates niloticus) has shown signs of overexploitation and aquaculture has again been considered as the option. By reviewing significant trends associated with Nile perch and its feasibility in aquaculture this paper uses Lake Victoria to illustrate ‘special interest management’ targeting selected species of fish rather than the fisheries.
Awake fibrecapnic intubation in head and neck cancer patients with difficult airways: new findings and refinements to the technique*
Authors: Huitink J. M. , Balm A. J. M. , Keijzer C. , Buitelaar D. R.
Published: February 2007

Recently, we described an adaptation of awake fibreoptic intubation that we call awake fibrecapnic intubation. The aim of this study was to evaluate the efficacy and risk of complications with this novel technique in a consecutive case series of head and neck cancer patients known to have difficult airways. We prospectively studied 40 consecutive intubations in head and neck cancer patients prior to a diagnostic or surgical procedure. Following topical anaesthesia, a flexible bronchoscope was introduced into the pharynx; spontaneous respiration was maintained in all patients. A special suction catheter was advanced into the airway through the suction channel of the bronchoscope for carbon dioxide measurements. When four capnograms were obtained, the bronchoscope was railroaded over the catheter and a tracheal tube was placed. All adverse events and complications were recorded. There were no complications associated with the technique. The median (range) time to intubation was 3 min (1.5–15 min). All patients were intubated successfully, 39 (98%) of them using awake fibrecapnic intubation. There was one patient with severe tumour bleeding and acute airway obstruction caused by advancement of the tube over the bronchoscope. This was not considered to be a complication of the fibrecapnic technique. Awake fibrecapnic intubation is a safe and valuable technique in head and neck cancer patients with a difficult airway.
Cost evaluation in the intensive care units of Trinidad applying the cost‐blocks method – an international comparison*
Authors: Hariharan S. , Chen D. , Merritt‐Charles L.
Published: February 2007

This study evaluated the costs of intensive care in Trinidad applying the cost‐blocks method. Data regarding demographics, severity of illness, therapeutic interventions and length of stay were prospectively recorded for 111 patients admitted to four intensive care units during a 3‐month period. Annual costs, cost per admission, cost per patient‐day and cost per therapeutic intervention score point were derived. The cost‐block for staff, especially medical staff, was the largest proportion of the expenditure. Process of care and outcome were comparable, whereas costs were lower than the developed countries. The median cost per intensive care unit bed per year and cost per patient per day in Trinidad were £133 117 and £366, respectively, in comparison with £265 163 and £904 in the UK. The cost‐blocks method is a useful framework for evaluating the costs of intensive care and for comparing costs between countries.
Carisoprodol use and abuse in Norway. A pharmacoepidemiological study
Authors: Bramness Jørgen G. , Furu Kari , Engeland Anders , Skurtveit Svetlana
Published: February 2007

What is already known about this subject

• Carisoprodol was developed to create a drug with less abuse potential than meprobamate.

• Case reports have established carisoprodol as a drug of abuse, but no systematic studies have been published about the extent of abuse.

What this study adds

• A large number of patients used more carisoprodol than recommended.

• High use of carisoprodol was associated with high use of benzodiazepines and opiates.

• Compared with other medicinal drugs, carisoprodol showed many prescription database signals of being a potential drug of abuse.

Aim

Carisoprodol was developed to create a drug with less potential for abuse than meprobamate. However, case reports have established carisoprodol as a drug of abuse. This paper explores the extent of potential abuse of this drug in Norway.

Methods

The Norwegian Prescription Database contains information on prescription drugs dispensed to individuals in Norway. Patients can be followed over time. High levels of carisoprodol use could indicate use for pleasurable effects or development of tolerance. Concomitant use of other potential drugs of abuse was also studied. We studied drug‐seeking behaviour by looking at patients who received carisoprodol from many different pharmacies and doctors or from high‐prescribing doctors. Carisoprodol was compared with a series of other medicinal drugs with or without known potential for abuse.

Results

Some 53 889 Norwegian women (2.4%) and 29 824 men (1.3%) ≥18 years old received carisoprodol at least once in 2004. Prescribing of carisoprodol was skewed. As many as 32% of the patients received more than 15 defined daily doses (DDDs) of carisoprodol and >11 000 patients (15%) received ≥75 DDDs in 2004. High users of carisoprodol also received more benzodiazepines and opioids. Few patients used three or more doctors for prescriptions, but carisoprodol‐abusing patients more often received their prescription from high‐prescribing doctors.

Conclusions

Carisoprodol was widely used and the skewedness in use indicated that it is a potential drug of abuse. A large number of patients used more carisoprodol than recommended in the guidelines. The high level of use and abuse of carisoprodol should be of concern in Norway.
Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases
Authors: Howell C. , Wilson A. D. , Waring W. S.
Published: February 2007

What is already known about this subject

• Recent concerns about lack of cardiovascular safety have led to restrictions in the use of venlafaxine in the UK.

• Venlafaxine may predispose to arrhythmia in high‐risk individuals.

What this study adds

• Venlafaxine ingestion gave rise to sympathomimetic cardiovascular features and QTc prolongation in previously healthy young adults.

• These findings suggest plausible mechanisms by which venlafaxine might predispose to arrhythmia, and require further consideration.

Aims

Venlafaxine may increase the risk of arrhythmia in certain patients. We sought to characterize the cardiovascular effects of venlafaxine overdose in adults.

Methods

A retrospective casenote review of patients admitted to the Royal Infirmary of Edinburgh between January 2000 and June 2006. Haemodynamic and electrocardiographic data were examined in the whole group and a subset that ingested venlafaxine alone.

Results

Two hundred and thirty‐five patients (65 men) with median (interquartile range) age 34 years (27–43 years) had ingested venlafaxine 1500 mg (919–2800 mg). Tachycardia (40.0%), high blood pressure (28.4%) and mydriasis (36.6%) were common. Corrected QT >450 ms occurred in seven men (11.1%) and 17 women (10.5%) and transient arrhythmia in three patients. There was a positive correlation between stated quantity of venlafaxine ingested and heart rate [ρ = 0.195, 95% confidence interval (CI) 0.054, 0.328] and QTc (ρ = 0.314, 95% CI 0.089, 0.509).

Conclusions

Venlafaxine overdose is associated with sympathomimetic cardiovascular effects and prolonged QTc, irrespective of coingested drugs. These mechanisms might pose an increased risk of arrhythmia and require further exploration.
Filter selection for five color flow cytometric analysis with a single laser
Authors: BRAUN R. K. , RUDNICKI M. A. , SEKALY R. P. , FILION L. G.
Published: February 2007

Flow cytometry has evolved from single‐ and two‐color analysis to the current use of 11–16 colors. The relatively bright excitation spectra of most fluorochromes have made color compensation a challenge especially when performed manually. We describe how by choosing filters with narrower bandwidths results in the color compensation values between FITC, PE, PE‐TxR (ECD), PE‐Cy5, and PE‐Cy7 that range from 0 % to 50% depending on the combination of fluorochromes. Peripheral blood mononuclear cells were stained with α‐CD4‐FITC, α‐CD27‐PE, α‐CD62L‐ECD, α‐CD45RA‐PE‐Cy5 and α‐CD3‐PE‐Cy7. The samples were acquired on a MO Flo. The initial (first) and second filter sets for our experiments consisted of 530/30 or 519/20 for FITC, 580/30 or 575/20for PE, 630/30 or 630/22 for PE‐TxR (ECD), 670/30 or 675/20 for PE‐Cy5 and 740LP or 780/40 for PE‐Cy7. Nonstained cells were used to adjust the threshold values of detection for each photo multiplier tube (PMT) for each filter set. The mean fluorescent intensity (MFI) of each fluorochrome was not reduced to any great extent by either filter set. However, the compensation value between PE and PE‐TxR (ECD) with the first filter selection ranged from 84% to 89% and with the second set of filters it was 25–36%. In addition, the compensation between PE‐TxR (ECD) and PE‐Cy5 were reduced to 30.2% from 44.2% with the second filter set. The reduction of filter bandwidths that results in minimizing spectral overlaps without lost of signal provides a method by which discrimination of signals between PE containing fluorochromes can be achieved.
Expression of activin and inhibin subunits, receptors and binding proteins in human pheochromocytomas: a study based on mRNA analysis and immunohistochemistry
Authors: Hofland J. , Van Nederveen F. H. , Timmerman M. A. , Korpershoek E. , De Herder W. W. , Lenders J. W. , Verhofstad A. A. , De Krijger R. R. , De Jong F. H.
Published: February 2007

Objective  Pheochromocytomas are uncommon tumours arising from chromaffin cells of the adrenal medulla and related paraganglia. So far, one of the few reported markers to discriminate malignant from benign tumours is the βB‐subunit of inhibin and activin, members of the transforming growth factor (TGF)‐β superfamily of growth and differentiation factors.

Design  We investigated the expression of the mRNAs coding for activin and inhibin subunits, their receptors and binding proteins by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) and studied the presence of the inhibin βB‐subunit in human pheochromocytomas by immunohistochemistry.

Patients  Samples from resected pheochromocytomas of patients operated between 1973 and 2003 were used for experiments.

Results  The immunohistochemical investigations revealed that staining of the inhibin βB‐subunit was positive in 12 of 36 (33%) benign and 5 of 34 (15%) malignant pheochromocytomas (P > 0·05). Therefore, it was not possible to discriminate between benign and malignant tumours solely on the basis of inhibin βB‐subunit immunohistochemistry. Quantitative real‐time RT‐PCR in nine benign and four malignant tumours showed expression of inhibin α‐, βA‐ and βB‐subunits, the activin receptors Alk‐4, ActRIIA, and ActRIIB, and the inhibin‐ and activin‐binding proteins betaglycan and follistatin in all samples. No correlations were detected between individually coupled expression of mRNAs of these activin‐ and inhibin‐related genes in the 13 pheochromocytomas. Only inhibin βA‐subunit expression was different in malignant compared to benign pheochromocytomas (P = 0·020).

Conclusions  No clear role for activin and inhibin was found in discriminating between benign and malignant pheochromocytomas.
Gender differences in plasma ghrelin and its relations to body composition and bone – an opposite‐sex twin study
Authors: Makovey Joanna , Naganathan Vasi , Seibel Markus , Sambrook Philip
Published: February 2007

Background  Ghrelin, a peptide hormone that plays a role in the regulation of appetite and body adiposity, may also play a role in bone metabolism.

Objectives  We used the opposite‐sex twin model to study associations of plasma ghrelin levels with measures of bone mass and body composition, and determine how such associations were influenced by gender and age.

Patients and measurements  We measured total plasma ghrelin by radioimmunoassay (RIA) and bone mass/body composition parameters by dual energy X‐ray absorptiometry in 79 pairs of opposite sex twins (n = 158 subjects). To examine the effect of age, the study population was divided by median age into two groups: under 51·2 years (38 pairs) and over 51·2 years (41 pairs).

Results  Women had higher plasma ghrelin levels than men (median 1063 vs. 869 ng/l, P < 0·01). Age was a significant predictor of plasma ghrelin levels after adjustment for gender, fat mass and body size. In the older age group, plasma ghrelin levels were inversely associated with fat mass measures in men and women, but there were gender differences in the nature of these associations. In women, plasma ghrelin correlated inversely with body mass index (BMI, r = −0·32), total fat mass (r = −0·30) and fat mass/lean mass ratio (r = −0·42), whereas in men associations with abdominal fat mass (r = −0·31) and fat distribution index (r = −0·33) were observed. Plasma ghrelin was associated with alcohol consumption in older men and women. In the obese subgroup (BMI > 30) no significant gender differences in plasma ghrelin were found. Plasma ghrelin levels were not significantly associated with bone mineral density (BMD) generally, except for hip BMD in younger women (r = −0·39).

Conclusion  Plasma ghrelin levels are associated with age, gender, alcohol intake and fat mass measures but only weakly to bone mass measures.
Well‐being, health‐related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease – a community‐based study
Authors: Bell Robin J. , Rivera‐Woll Livia , Davison Sonia L. , Topliss Duncan J. , Donath Susan , Davis Susan R.
Published: February 2007

Objectives  The aim of this study was to evaluate whether subclinical thyroid disease is associated with impaired health‐related quality of life and a more adverse cardiovascular disease risk profile.

Design  A community‐based cross‐sectional study.

Setting and participants  A total of 1423 non‐healthcare‐seeking women, aged 18–75 years were randomly recruited from the community via the electoral roll from April 2002 to August 2003.

Main outcome measures  These were the scores for the Short‐Form 36 (SF‐36), the Psychological General Well‐being Index (PGWI), thyroid hormone levels, serum lipids and high sensitivity C‐reactive protein (hsCRP). Subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCHyper) were defined as serum TSH > 4·0 mIU/l and < 0·5 mIU/l, respectively, with a normal free thyroxine (free T4) level.

Results  Evaluable data were available for all participants. 10·7% of all women had an abnormal TSH value. The prevalence of a low TSH level by age group ranged from 1·2% to 6·4%, whereas the prevalence of an elevated TSH level ranged from 2·8% to 9·2% and increased with age (P = 0·002). There were no significant differences between women with SCH or SCHyper and age‐matched controls for the total PGWI score or the Mental and Physical Component Scores of the SF‐36. Women with SCH were no different from controls for serum lipids or hsCRP. Using linear regression, SCH vs. euthyroidism did not make an independent contribution to variation in either total cholesterol or triglycerides, with or without adjustment for age ± age2 ± BMI.

Conclusions  Our data indicate that subclinical thyroid disease in women in the community is not associated with lower well‐being or impaired health‐related quality of life and SCH is not associated with increased serum markers of CVD risk.
Range size in North AmericanEnallagmadamselflies correlates with wing size
Authors: RUNDLE SIMON D. , BILTON DAVID T. , ABBOTT JOHN C. , FOGGO ANDREW
Published: February 2007

1. Cross‐species macroecological comparisons in freshwater invertebrates have been restricted by a lack of large‐scale distributional data, and robust phylogenies. Here, we use data from theOdonataCentraldatabase to explore body length–range size and wing length–range size relationships in damselflies from the genusEnallagma; the recent publication of a phylogeny for this group meant that, as well as a cross‐species analysis, we were able to assess relationships in a phylogenetically controlled manner.

2. For cross‐species comparisons, only wing length showed significant (positive) regression relationships with range size and occupancy, although the inclusion of body length in multiple regressions increased the fit of the models. Damselflies with larger wings relative to their body length had larger distributions, a result confirmed by a significant positive relationship between range size and residuals from the regression of wing size on body size.

3. For the phylogenetically controlled analyses, only wing length contrast scores were significantly related to distribution patterns and entered into regression models; the significant positive relationships between wing length contrasts and both range size and occupancy contrasts suggested that evolutionary increases in wing length had occurred alongside range expansions.

4. Together these results suggest that species ofEnallagmawith larger wings (both absolute and relative to body length) tend to be more widely distributed in North America and that the evolution of wing size may have played a role in range expansion. No such relationships were evident for body size. We discuss the potential importance of wing morphometrics for studying the evolutionary ecology of freshwater insects.
The stress sensitivity of shaley sandstones
Authors: MacBeth Colin , Ribeiro Christophe
Published: February 2007

The link between the stress sensitivity of shaley sandstones and their porosity and clay content is investigated. This is achieved by firstly fitting a compliance‐based stress‐sensitivity law to laboratory measurements of ultrasonic velocity taken from four sets of reservoir sandstones, extracted from a variety of depositional settings. Correlations are then sought between the independent parameters of this law and the porosity or clay fraction of the rocks, which are then subsequently interpreted in terms of framework or pore‐space‐related microstructural clay models. The general conclusion drawn from the results is that both of the parameters defining the stress‐sensitivity law (the asymptotic modulus and the stress‐dependent excess compliance) clearly vary with porosity. However, only the asymptotic modulus shows a convincing trend with clay and there is little observed variation of the stress‐dependent compliance with clay. There is therefore a resultant variation of stress sensitivity with clay, but it is controlled only by the asymptotic modulus. The analysis also concludes that all four data sets fall into a framework‐related category of clay model.
Estimation of the apertures of water‐saturated fractures by nuclear magnetic resonance well logging
Authors: Nakashima Yoshito , Kikuchi Tsuneo
Published: February 2007

Fracture aperture is an important transport property in subsurface hydrology because it influences well productivity and the volume of the water resource. Nuclear magnetic resonance (NMR) well logging measures the hydrogen‐bearing fluid molecules in porous or fractured strata, and the NMR signal intensity increases with the amount of fluid in the sensed region of the NMR sonde. Fluid confined in a large fracture of >>0.2 mm in aperture has T2 (i.e. spin‐spin relaxation time) values as long as those of the bulk fluid. The bulk‐fluid porosity (i.e. porosity calculated using this long T2 component in a T2 histogram data) increases linearly with aperture. Therefore, NMR logging enables quantitative estimation of fracture apertures of >>0.2 mm using the bulk‐fluid porosity data if the calibration of the NMR sonde is performed adequately. We applied NMR logging to a borehole in a Holocene andesite lava at Sumikawa, Japan, to estimate the aperture of open fractures within the lava. A test well of 100 m depth and 20 cm diameter, filled with bentonite drilling mud, was scanned with an NMR sonde to obtain a profile of the porosity and the T2 histogram of the andesite. The bulk‐fluid porosity was calculated from the T2 histogram data, as the porosity at which the T2 value is larger than or equal to a threshold T2 of bulk bentonite mud. The bulk‐fluid porosity of a specific inclined fracture responsible for the total loss of circulation at 61.2 m depth during drilling was calculated assuming a threshold or T2 cut‐off of 33 ms, and again for a cut‐off of 100 ms. Calibration of the NMR sensor in a laboratory and measurement of the fracture dip angle by electrical microimaging logging enabled us to estimate the fracture aperture as 1.7 cm, assuming a T2 cut‐off of 33 ms, or 1.6 cm for a T2 cut‐off of 100 ms. The method of aperture determination described in this study is independent of fluid species and lithology, and is applicable to various hydrogen‐bearing borehole fluids (clean water, mud and oil) and geological settings.
Numerical study of seismic scattering and waveguide excitation in faulted coal seams
Authors: Greenhalgh S.A. , Zhou B. , Pant D.R. , Green A.
Published: February 2007

Finite‐difference P‐SV simulations of seismic scattering characteristics of faulted coal‐seam models have been undertaken for near‐surface P‐ and S‐wave sources in an attempt to understand the efficiency of body‐wave to channel‐wave mode conversion and how it depends on the elastic parameters of the structure. The synthetic seismograms clearly show the groups of channel waves generated at the fault: one by the downgoing P‐wave and the other by the downgoing S‐wave. These modes travel horizontally in the seam at velocities less than the S‐wavespeed of the rock. A strong Airy phase is generated for the fundamental mode.

The velocity contrast between the coal and the host rock is a more important parameter than the density contrast in controlling the amplitude of the channel waves. The optimal coupling from body‐wave energy to channel‐wave energy occurs at a velocity contrast of 1.5. Strong guided waves are produced by the incident S‐sources for source angles of 75° to 90° (close to the near‐side face of the fault). As the fault throw increases, the amplitude of the channel wave also increases. The presence of a lower‐velocity clay layer within the coal‐seam sequence affects the waveguiding characteristics. The displacement amplitude distribution is shifted more towards the lower‐wavespeed layer. The presence of a ‘washout’ zone or a brecciated zone surrounding the fault also results in greater forward scattering and channel‐wave capture by the coal seam.
3D magnetotelluric modelling including surface topography
Authors: Nam Myung Jin , Kim Hee Joon , Song Yoonho , Lee Tae Jong , Son Jeong‐Sul , Suh Jung Hee
Published: February 2007

An edge finite‐element method has been applied to compute magnetotelluric (MT) responses to three‐dimensional (3D) earth topography. The finite‐element algorithm uses a single edge shape function at each edge of hexahedral elements, guaranteeing the continuity of the tangential electric field while conserving the continuity of magnetic flux at boundaries. We solve the resulting system of equations using the biconjugate gradient method with a Jacobian preconditioner. The solution gives electric fields parallel to the slope of a surface relief that is often encountered in MT surveys. The algorithm is successfully verified by comparison with other numerical solutions for a 3D‐2 model for comparison of modelling methods for EM induction and a ridge model. We use a 3D trapezoidal‐hill model to investigate 3D topographic effects, which are caused mainly by galvanic effects, not only in the Zxy mode but also in the Zyx mode. If a 3D topography were approximated by a two‐dimensional topography therefore errors occurring in the transverse electric mode would be more serious than those in the transverse magnetic mode.
Candida albicans and filtrates interfere with human spermatozoal motility and alter the ultrastructure of spermatozoa: an in vitro study
Authors: Tian Yong‐Hong , Xiong Jin‐Wen , Hu Lian , Huang Dong‐Hui , Xiong Cheng‐Liang
Published: February 2007

The in vitro effects of Candida albicans and its filtrates on the motility and ultrastructure of human spermatozoa from healthy donors were studied. A significant reduction in sperm progressive motility and signs of membrane alteration, directly related to contact time were observed. Distinct adhesion of spermatozoa to C. albicans and agglutination were observed. Light and transmission electron microscopy examinations showed that spermatozoa attached to C. albicans mainly via the head. Multiple ultrastructural lesions were present, which were the possible morphological reasons for spermatozoan immobilization observed in the present study. It is concluded that C. albicans as well as its filtrates had an inhibitory effect on human sperm motility and impaired the ultrastructure of human spermatozoa, which could be associated with male infertility.
Changes in the expression of P‐cadherin in the normal, cryptorchid and busulphan‐treated rat testis
Authors: Pospechova K. , Kopecky M. , Nachtigal P. , Pospisilova N. , Jamborova G. , Semecky V.
Published: February 2007

Adhesion between Sertoli cells and germ cells is important for spermatogenesis. Cadherins are Ca2+‐dependent transmembrane proteins that mediate cell–cell adhesion. The aim of this study was to compare the expression of P‐cadherin in unilaterally cryptorchid and busulphan‐treated rat testes using immunohistochemistry. The pattern of expression of P‐cadherin in the seminiferous epithelium changed with the stage of the seminiferous epithelium. The membranes of round spermatids and membranes and cytoplasm of spermatocytes were strongly positive. Our experiments revealed that busulphan treatment (2 doses – 10 mg/kg of body weight – 21 days apart) and cryptorchism led to destructive changes in the structure of seminiferous tubules, together with the decrease in P‐cadherin expression. The expression of P‐cadherin disappeared in the spermatids segregated from the epithelium while segregated spermatocytes remained still positive for P‐cadherin during the 3‐ to 11‐day cryptorchid period. In busulphan‐treated animals, the expression of P‐cadherin was dependent on the presence or absence of the spermatocytes and spermatids in the tubules. Strong positivity for P‐cadherin was observed in the spermatocytes that re‐appeared in the regenerating seminiferous epithelium. We suggest that P‐cadherin participates in the architecture of adherens junctions in testis, plays an important role in maintaining normal spermatogenesis and that cryptorchism and busulphan treatment lead to adherens junction disintegration.