bluuebunny/crossref_metadata_2025 huggingface dataset:
Concordance between ecotypes and macroinvertebrate assemblages in Mediterranean streams
Authors: SÁNCHEZ‐MONTOYA MARIA DEL MAR , PUNTÍ TURA , SUÁREZ MARIA LUISA , VIDAL‐ABARCA MARIA DEL ROSARIO , RIERADEVALL MARIA , POQUET JOSÉ MANUEL , ZAMORA‐MUÑOZ CARMEN , ROBLES SANTIAGO , ÁLVAREZ MARUXA , ALBA‐TERCEDOR JAVIER , TORO MANUEL , PUJANTE ANA MARIA , MUNNÉ ANTONI , PRAT NARCÍS
Published: July 2007

1. According to the guidelines of the European Water Framework Directive, assessment of the ecological quality of streams and rivers should be based on ecotype‐specific reference conditions. Here, we assess two approaches for establishing a typology for Mediterranean streams: a top‐down approach using environmental variables and bottom‐up approach using macroinvertebrate assemblages.

2. Classification of 162 sites using environmental variables resulted in five ecotypes: (i) temporary streams; (ii) evaporite calcareous streams at medium altitude; (iii) siliceous headwater streams at high altitude; (iv) calcareous headwater streams at medium to high altitude and (v) large watercourses.

3. Macroinvertebrate communities of minimally disturbed sites (n = 105), grouped using UPGMA (unweighted pair‐group method using arithmetic averages) on Bray–Curtis similarities, were used to validate four of the five ecotypes obtained using environmental variables; ecotype 5, large watercourses, was not included as this group had no reference sites.

4. Analysis of similarities (anosim) showed that macroinvertebrate assemblage composition differed among three of the four ecotypes, resulting in differences between the bottom‐up and top‐down classification approaches. Siliceous streams were clearly different from the other three ecotypes, evaporite and calcareous ecotypes did not show large differences in macroinvertebrate assemblages and temporary streams formed a very heterogeneous group because of large variability in salinity and hydrology.

5. This study showed that stream classification schemes based on environmental variables need to be validated using biological variables. Furthermore, our findings indicate that special attention should be given to the classification of temporary streams.
Utilization of recombinant activated factor VII in southern Ontario in 85 patients with and without haemophilia
Authors: WEBERT K. E. , ARNOLD D. M. , CARRUTHERS J. , MOLNAR L. , ALMONTE T. , DECKER K. , SEROSKI W. , REED J. , CHAN A. K. , PAI M. , WALKER I. R.
Published: July 2007

Summary.  Recombinant activated factor VII (rFVIIa) is licensed for the treatment of bleeding in individuals with haemophilia and inhibitors. The use of rFVIIa appears to be increasing, and an increase in unlicensed use is suspected. There are currently few data about the specific indications for its use.

The aim of this study was to describe the patterns of utilization of rFVIIa.

We performed a retrospective cohort study using rFVIIa infusion data collected prospectively and clinical data collected retrospectively. Patients were identified using a tracking system designed to account for use of all coagulation factor concentrates issued in southern Ontario.

Between 1 January 2001 and 31 December 2005, 85 patients received rFVIIa. 1164 infusions were given (8246.4 mg). Haemophilia patients with inhibitors accounted for 82.9% of rFVIIa infused and represented 8.2% of patients. The total amount of rFVIIa used increased each year from 2001 to 2004 and then decreased in 2005. The total number of infusions of rFVIIa administered annually increased. Both on‐label and off‐label use of rFVIIa increased. The number of patients with haemophilia receiving rFVIIa remained small and constant. The number of patients receiving rFVIIa for off‐label indications increased markedly.

Most rFVIIa infusions were given for licensed indications; however, these infusions represented <10% of patients treated. Overall, the utilization of rFVIIa is increasing, mostly for approved indications; however, the number of patients being prescribed rFVIIa for off‐label indications has increased. The tracking system used in this study is a valuable tool to describe ongoing utilization patterns of rFVIIa.
Compound heterozygosity for two novel mutations (1203insG/Y1456X) in the von Willebrand factor gene causing type 3 von Willebrand disease
Authors: XIE F. , WANG X. , COOPER D. N. , LAN F. , FANG Y. , CAI X. , WANG Z. , WANG H.
Published: July 2007

Summary.  A 23‐year‐old Chinese woman with severe von Willebrand factor (VWF) deficiency and her parents were investigated by PCR/direct sequencing of the VWF gene. The patient was found to be compound heterozygous for two novel null mutations. The first was a microinsertion in exon 8 (1203insG) that introduced a frameshift at codon 298 leading to premature translational termination at codon 302. The second was a C to A transversion in exon 28 which resulted in the replacement of tyrosine 562 by a stop codon (Y1456X). The failure to amplify VWF cDNA from the patient by semi‐nested PCR is consistent with the induction of nonsense‐mediated mRNA decay.
Effect of boron on the expression of aluminium toxicity in Phaseolus vulgaris
Authors: Stass Angelika , Kotur Zorica , Horst Walter J.
Published: July 2007

The interaction of boron (B) and aluminium (Al) was investigated in 5‐day‐old seedlings of soybean cv. Maple Arrow. Al treatment inhibited root elongation and callose formation in root tips particularly after 4‐h Al treatment. After 10 and 24 h, both parameters indicated increasing recovery from Al stress. B deficiency aggravated Al toxicity compared with B sufficiency. B deficiency did lead to an increase in unmethylated pectin in the first 3 mm of the root tip. This increase in potential binding sites is reflected in generally higher Al contents in root tips of B‐deficient plants. A fractionated extraction of Al from the root tips showed that citrate‐exchangeable and non‐exchangeable Al steeply increased up to 4 h, but then decreased after 10‐ and 24‐h Al treatment faster in B‐sufficient than in B‐deficient plants. This decrease of Al contents can be explained by an Al‐enhanced release of citrate from the root tips after 10‐h Al treatment. However, the citrate exudation rate was the same (after 10 h) or even lower (after 24 h) in B‐sufficient plants and thus cannot explain the faster decrease in Al contents of the root tips compared with the B‐deficient plants. We, therefore, propose that under B deficiency, Al is more strongly bound by the pectic network of the cell wall of the root tips, which delays or prevents the recovery from initial Al stress through exudation of citrate, and thus explains the greater Al sensitivity of B‐deficient common bean roots.
Intramural duodenal haematoma presenting as a complication after endoscopic biopsy
Authors: Borsaru AD , Nandurkar D
Published: July 2007

Intramural duodenal haematoma is an uncommon lesion, usually a complication of blunt abdominal trauma in children and young adults. We present a case of intramural duodenal haematoma following endoscopic biopsy, which caused partial duodenal obstruction and pancreatitis and resolved with conservative management.
Management options for echogenic intracardiac focus and choroid plexus cysts: A review including Australian Association of Obstetrical and Gynaecological Ultrasonologists consensus statement
Authors: Bethune M
Published: July 2007

Echogenic intracardiac focus and choroid plexus cysts are common findings at the midtrimester ultrasound. These findings have been linked with an increased risk of Down syndrome and trisomy 18. Most fetuses with these findings will, however, not have chromosomal abnormalities, especially when these findings are isolated. Patients experience considerable anxiety when informed of these findings and require extensive counselling in order to minimize anxiety not only about aneuploidy but also about the structure and development of the heart and brain. Although early studies showed an association with aneuploidies, several recent studies have cast doubt on this association. Many of the early studies were carried out in high‐risk populations or in populations that had not had the benefit of other screening tests. Many Australian and New Zealand patients will access screening tests designed to detect these aneuploidies before presenting for a midtrimester ultrasound. Patients who have been screened by nuchal translucency, maternal serum screening or some combination of the two will already have had most cases of Down syndrome and trisomy 18 detected, and any soft marker found will almost certainly be a false positive. It is time to rethink the management of these markers. Recent evidence indicates that if these markers are found in isolation in an otherwise low‐risk pregnancy, then there is minimal or no increase in the risk of Down syndrome or trisomy 18: these markers should be considered normal variants.The Australian Association of Obstetrical and Gynaecological Ultrasonologists consensus statement on these markers is included.
Capillary haemangioma involving the middle and external ear: Radiotherapy as a treatment method
Authors: Pavamani SP , Surendrababu NRS , Ram TS , Thomas M , Viswanathan PN , Viswanathan FR
Published: July 2007

Capillary haemangiomas rarely occur in the auditory canal and have mainly been managed with surgical excision or kept on close follow up for development of symptoms. Radiotherapy, as a treatment method, has not been reported previously in the published work. We describe a study of a capillary haemangioma in the auditory canal of a 26‐year‐old woman who presented with bleeding. She was treated with radiotherapy, after the lesion was found to be unsuitable for surgery and embolization. The patient remains well 5 years after completion of treatment.
Lactate quantification by proton magnetic resonance spectroscopy using a clinical MRI machine: A basic study
Authors: Isobe T , Matsumura A , Anno I , Kawamura H , Shibata Y , Muraishi H , Minami M
Published: July 2007

The purpose of this study was to establish quantification method of lactate concentration by proton magnetic resonance spectroscopy (MRS) carried out using a conventional 1.5‐T MRI machine. We used a lactate phantom with known concentrations (1, 1.5, 3, 6, 12 and 14 mmol/L). As a clinical example, a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) was evaluated. Proton MRS was carried out using a clinical 1.5‐T super‐conducting magnetic resonance whole‐body system. Data were acquired by point resolved spectroscopy. A coupling constant of J = 7.35 Hz (2/J = 272 ms) and two long in‐phase echo time of 272 ms and 544 ms were used to calculate the T2 relaxation time. The tissue water signal was used as an internal standard to quantify lactate. The correlation coefficient R between the calculated lactate concentrations and the known concentration of lactate was 0.99 with a constant factor of 0.32 (1/3.14). In patients with MELAS, the lactate concentration measured by MRS was 6.2 mmol/kg wet weight, which is similar to the value obtained in previous studies. In the present study, we have established a reliable method for lactate quantification in a phantom study and have shown a sample of clinical case of MELAS.
Infusion of 50% glucose solution before injection of ethanolamine oleate during balloon‐occluded retrograde transvenous obliteration
Authors: Yamagami T , Kato T , Hirota T , Yoshimatsu R , Matsumoto T , Nishimura T
Published: July 2007

The feasibility of infusion of 50% glucose solution before balloon‐occluded retrograde transvenous obliteration (BRTO) to occlude collateral vessels draining gastric varices other than gastrorenal shunt was evaluated. In five patients with such collateral vessels, 50% glucose solution was infused from the balloon catheter inflated within the gastrorenal shunt. The degree of collateral vessels had decreased when BRTO was carried out so that sclerotic agents sufficiently occupied the gastric varices in all patients. In three patients, embolization of collateral vessels with coils was unnecessary. There were no complications. In conclusion, retrograde infusion of 50% glucose solution assists in effectively carrying out BRTO.
New radiological typing system for rhinosinusitis and comparison with existing system: Initial finding
Authors: Rustogi R , Coucher JR , Malan JF
Published: July 2007

The objective of this study was to determine whether the proposed Malan radiological sinusitis typing (RST) system facilitated a level of agreement and ease of use comparable with the Lund–Mackay (LM) system for chronic rhinosinusitis. Ten observers (one otolaryngologist and nine radiologists), in two separate centres (regional and tertiary), blinded to all clinical data, used these two systems to independently and randomly score and type 15 sets of scans, recording the time to score each film. Using unweighted kappa scores, both methods facilitated a moderate level of agreement, slightly better with the LM system. The Malan system is more time efficient. Preliminarily, this study shows that the Malan RST system is easy to apply with a comparable level of agreement. The Malan RST system is a focused attempt at classifying disease extent radiologically and correlating it to a surgical approach. It emphasizes that scoring systems are vulnerable and proves to be superior to the LM system as a surgical planning tool. To score sinus disease, a Quality‐of‐Life questionnaire in association with this typing method is more appropriate.
Alveolar hydatid disease of the liver: Brief review and spectrum of adjacent organ invasion
Authors: Demir MK , Kilicoğlu G , Akinci O
Published: July 2007

The purpose of this study is to show the spectrum of adjacent organ invasion and to make a brief review of hepatic alveolar hydatid disease (AHD), using CT and MR imaging. We retrospectively reviewed CT and MR images of three patients with various adjacent organ invasions surgically and histologically proven to be AHD. Local invasion to right kidney and adrenal, right hemidiaphragm and lung were detected in one patient, right adrenal in another patient and gall bladder, duodenum, gastric wall and pancreas invasion in the other. AHD may rarely extend to the gall bladder, stomach, duodenum, pancreas, right adrenal and kidney, diaphragm, pleura and lung. The extension of the disease outside the liver is usually encountered in patients with large, peripherally located masses in the advanced stage of the disease.
Fluoroscopic‐guided balloon dilatation and stenting in tracheal stenosis with metallic self‐expandable stents and long‐term follow‐up results
Authors: Bodhey NK , Gupta AK , Neelakandhan KS , Neema PK , Kapilamoorthy TR , Purkayastha S , Thomas B , Krishnamoorthy T , Kesavadas C
Published: July 2007

The purpose of this study was to assess the safety and long‐term efficacy of self‐expandable stents in the treatment of benign tracheal stenosis. Nine patients (seven men) with tracheal stenosis (including one with fistula) of varied cause were treated by fluoroscopically guided balloon dilatation and stenting with self‐expandable metallic stents. The procedure was carried out under topical spray in eight patients and under general anaesthesia in one patient. The patients were followed up for a period ranging between 13 and 60 months. In eight of the nine patients, satisfactory positioning of the stent was achieved at the first instance, with immediate relief of dyspnoea. One patient with innominate artery aneurysm died 16 days after the procedure because of renal failure. At 1 month of follow up, six out of eight (75%) of our live patients were without any respiratory embarrassment. This dyspnoea‐free result reached almost 90% by the end of 1 year especially so in the fibrous strictures. Four out of the eight live patients (50%) had cough for 2 months and two (25%) had mild blood‐tinged sputum treated by inhalation and mucolytic agents. Secondary intervention was required in one patient at 1 month because of recurrent symptoms. The patient with tracheo‐oesophageal fistula required surgical intervention because of fracture of the stent. Fluoroscopically guided balloon dilatation and stenting of the tracheal stenosis is an effective non‐surgical therapy resulting in cure of fibrous strictures and palliation in cases of malignancy.
Is rural radiation oncology practice quality as good as the big smoke? Results of the Australian radiotherapy single machine unit trial
Authors: Shakespeare TP , Turner M , Chapman A
Published: July 2007

Radiotherapy utilization rates in rural Australia are suboptimal, with one solution being the building of single machine units (SMUs). One concern raised with such an approach is the quality of care delivered in SMUs. The Australian and Victorian governments have established two SMUs in the state of Victoria, with each SMU operated as a satellite service of a major ‘hub’ site. We report on the planned evaluation of practice quality. Radiation oncologist (RO) clinical practice was externally audited using the Royal Australian and New Zealand College of Radiologists Peer Review Audit instrument. This tool splits RO clinical practice into documentation/quality assurance (QA) criteria and decision‐making criteria. Over the four sites, 130 patients were randomly selected for audit. At hub sites, 79.6% of all criteria audited were adequate, compared with 84.4% of criteria audited at SMUs (P = 0.0002). This difference was largely because of better adherence to documentation/QA criteria at the SMU sites. RO decision‐making and protocol adherence were routinely very high and consistent with other clinical practice audits. There were no significant differences between hubs and SMUs for adherence to decision‐making criteria; however, the few potential deficiencies in patient care identified occurred only at the hub sites. In at least one of these cases, potential suboptimal management was as a direct result of inadequate documentation. This audit found that SMUs provide as high a standard of radiotherapeutic care as larger hub departments. The findings also emphasize the need for all departments to target clinical documentation.
Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome
Authors: CHAN TAK MAO , LIN AI WU , TANG SYDNEY CW , QIAN JIA QI , LAM MAN FAI , HO YIU WING , TSE KAI CHUNG , CHAN KWOK WAH , LAI KAR NENG , TANG COLIN SO
Published: July 2007

Background:  Retrospective and anecdotal data suggest that mycophenolate mofetil (MMF) might be effective when given as rescue therapy for membranous nephropathy (MN). Prospective controlled data on MMF and prednisolone as primary therapy are lacking.

Methods:  A prospective, randomized, controlled, open‐label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome. MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients, with follow up of 15 months.

Results:  MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction, despite a lower cumulative prednisolone dose in the MMF group (3.80 ± 0.28 vs 9.93 ± 0.25 g, P < 0.001). Remission (composite of ‘complete’ and ‘partial’) rates were 63.6% and 66.7% in the MMF group and control group, respectively (P = 1.000). Serum creatinine and creatinine clearance remained stable during follow up. Cumulative relapse rate was 23.1% at 2 years. Chlorambucil resulted in more leucopenia compared with MMF.

Conclusion:  Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid‐sparing and having less adverse effects compared with other commonly used cytotoxic agents.
Vascular calcification and arterial stiffness in chronic kidney disease: Implications and management
Authors: TOUSSAINT NIGEL D , KERR PETER G
Published: July 2007

SUMMARY:  Cardiovascular (CV) disease is the commonest cause of mortality in patients with chronic kidney disease (CKD). Vascular calcification (VC), induced by calcium and phosphate excess and uraemia, is a major risk factor and is independently associated with CV events and death. Local and systemic calcium‐regulatory proteins as well as inhibitory extracellular factors are involved in the pathogenesis of VC. In CKD the balance becomes dysregulated leading to differentiation of vascular smooth muscle cells into phenotypically distinct osteoblast‐like cells with subsequent ossification of the arterial wall. Associated with imbalances in mineral metabolism, VC has intimate interactions with bone mineralization and enhanced bone resorption. Arterial stiffness represents the functional disturbance of VC, with reduced compliance of large arteries, and predominantly results from greater medial calcification. As with VC, arterial stiffness is an independent predictor of CV mortality and patients with CKD have greater arterial stiffness than the general population resulting in the principal consequences of left ventricular hypertrophy and altered coronary perfusion. Both VC and arterial stiffness can be measured through non‐invasive techniques involving computed tomography, ultrasound, echocardiography, and pulse wave velocity. Management in CKD is difficult but detection, prevention and treatment is crucial to reduce CV mortality. The optimal control of mineral metabolism, especially hyperphosphatemia with non‐calcium based phosphate binders, has been shown to be effective to reduce VC, and attenuation of arterial stiffness, especially with good blood pressure control, can have a favourable effect with regression of left ventricular hypertrophy. The use of bisphosphonates, calcimimetics, vitamin D therapy and newer experimental treatments, as well as nocturnal dialysis, may have potential benefit.
Chinese herbal formula Qilong‐Lishui granule improves puromycin aminonucleoside‐induced renal injury through regulation of bone morphogenetic proteins
Authors: LI PING , YAN JING , SUN YU , BURCZYNSKI FRANK J , GONG YUEWEN
Published: July 2007

Background:  The Chinese herbal formula Qilong‐Lishui granule (QLG) is an effective natural product for treatment of renal disorder. It was composed of six Chinese herbs according to our clinical practice in the treatment of patients with kidney disease. However, molecular and cellular mechanisms of QLG are still unclear. Therefore, the objective of the current study is to investigate molecular and cellular mechanisms of QLG in puromycin aminonucleoside (PAN)‐induced nephrotic syndrome.

Method:  Wistar rats were divided into six groups of sham operation, PAN model, PAN model with high‐dosage QLG (QLG‐H), PAN model with median‐dosage QLG (QLG‐M), PAN model with low‐dosage QLG (QLG‐L), and PAN model with fosinopril (FP). The PAN model was induced by jugular vein injection of PAN at a dose of 5 mg/100 g body weight. Quantities of 24 h urinary protein excretion were examined on days 5, 10, 15, 20, 25 and 30. All rats were sacrificed on day 31 for blood biochemistry, kidney histology and reverse transcriptase‐polymerase chain reaction analysis.

Results:  PAN‐induced nephrotic syndrome was successfully produced in rats. Treatment of QLG significantly reduced protein excretion and blood urea nitrogen and creatinine. QLG and FP treatments also improved protein content in blood, and reduced total cholesterol and triglyceride in blood. Moreover, QLG and FP improved the damage of interstitial induced by PAN. Furthermore, CYP and FP were able to reverse BMPRII and Smad1 mRNAs abundance caused by PAN.

Conclusion:  QLG attenuates PAN‐induced kidney injury possibly through the bone morphogenetic protein signal transduction pathway.
Exposure to predation generates personality in threespined sticklebacks (Gasterosteus aculeatus)
Authors: Bell Alison M. , Sih Andrew
Published: July 2007

A perplexing new question that has emerged from the recent surge of interest in behavioural syndromes or animal personalities is – why do individual animals behave consistently when behavioural flexibility is advantageous? If individuals have a tendency to be generally aggressive, then a relatively aggressive individual might be overly aggressive towards offspring, mates or even predators. Despite these costs, studies in several taxa have shown that individuals that are more aggressive are also relatively bold. However, the behavioural correlation is not universal; even within a species, population comparisons have shown that boldness and aggressiveness are correlated in populations of sticklebacks that are under strong predation pressure, but not in low predation populations. Here, we provide the first demonstration that an environmental factor can induce a correlation between boldness and aggressiveness. Boldness under predation risk and aggressiveness towards a conspecific were measured before and after sticklebacks were exposed to predation by trout, which predated half the sticklebacks. Exposure to predation generated the boldness–aggressiveness behavioural correlation. The behavioural correlation was produced by both selection by predators and behavioural plasticity. These results support the hypothesis that certain correlations between behaviours might be adaptive in some environments.
Collection of fungi samples from nails: comparative study of curettage and drilling techniques
Authors: Shemer A , Trau H , Davidovici B , Grunwald MH , Amichai B
Published: July 2007

Background  Onychomycosis is a common problem. Obtaining a positive laboratory test before treatment is important in clinical practice because the treatment of onychomycosis requires expensive oral antifungal therapy with potentially serious side‐effects.

Objective  The purpose of this study was to compare curettage and subungual drilling techniques of nail sampling in the diagnosis of onychomycosis.

Methods  We evaluated 194 patients suffering from distal and lateral subungual onychomycosis and lateral subungual onychomycosis using curettage and subungual drilling sampling techniques. Nail samples were obtained in each case from proximal, medial and distal parts of the nail. KOH examination and fungal culture were used for detection and identification of fungal infection.

Results  With each technique, the culture sensitivity improved as the location of the sample was more proximal (drilling proximal vs. distal, χ2 = 5.15, P = 0.023; curettage proximal vs. distal, χ2 = 4.2, P = 0.041). In each sample location, the drilling technique has a better culture sensitivity (drilling vs. curettage proximal, χ2 = 11.9, P = 0.001; drill vs. curettage distal, χ2 = 13.7, P < 0.0001). Trichophyton rubrum was by far the most common pathogen detected by both techniques from all sampling sites.

Conclusion  The drilling technique was found to be statistically better than curettage at each site of sampling. With each technique, we found that the culture sensitivity improved as the location of the sample was more proximal. More types of pathogens were detected in samples taken by both methods from proximal parts of the affected nails.
Occipital Neuralgia As a Presenting Symptom of Cervicomedullary Dural Arteriovenous Fistula
Authors: Hashiguchi Akihito , Mimata Chikara , Ichimura Homare , Kuratsu Jun‐Ichi
Published: July 2007

Dural arteriovenous fistulas (DAVFs) at the cervicomedullary junction are rare and have a wide variation in presentation. We report a case of occipital neuralgia (ON) as a rare presenting symptom of cervicomedullary DAVF causing intramedullary hemorrhage at the C1 level. It is important to consider the underlying causes of ON, and precise neurological examinations and radiological evaluations are needed.
Food WebSpecific Biomagnification of Persistent Organic Pollutants
Authors: Kelly Barry C. , Ikonomou Michael G. , Blair Joel D. , Morin Anne E. , Gobas Frank A. P. C.
Published: July 2007

Substances that accumulate to hazardous levels in living organisms pose environmental and human-health risks, which governments seek to reduce or eliminate. Regulatory authorities identify bioaccumulative substances as hydrophobic, fat-soluble chemicals having high octanol-water partition coefficients (
K
OW
)(≥100,000). Here we show that poorly metabolizable, moderately hydrophobic substances with a
K
OW
between 100 and 100,000, which do not biomagnify (that is, increase in chemical concentration in organisms with increasing trophic level) in aquatic food webs, can biomagnify to a high degree in food webs containing air-breathing animals (including humans) because of their high octanol-air partition coefficient (
K
OA
) and corresponding low rate of respiratory elimination to air. These low
K
OW
–high
K
OA
chemicals, representing a third of organic chemicals in commercial use, constitute an unidentified class of potentially bioaccumulative substances that require regulatory assessment to prevent possible ecosystem and human-health consequences.
DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7)
Authors: Ünal Elçin , Heidinger-Pauli Jill M. , Koshland Douglas
Published: July 2007

Faithful chromosome segregation and repair of DNA double-strand breaks (DSBs) require cohesin, the protein complex that mediates sister-chromatid cohesion. Cohesion between sister chromatids is thought to be generated only during ongoing DNA replication by an obligate coupling between cohesion establishment factors such as Eco1 (Ctf7) and the replisome. Using budding yeast, we challenge this model by showing that cohesion is generated by an Eco1-dependent but replication-independent mechanism in response to DSBs in G
2
/M. Furthermore, our studies reveal that Eco1 has two functions: a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. Finally, the DSB-induced cohesion is not limited to broken chromosomes but occurs also on unbroken chromosomes, suggesting that the DNA damage checkpoint through Eco1 provides genome-wide protection of chromosome integrity.
Scattering and Interference in Epitaxial Graphene
Authors: Rutter G. M. , Crain J. N. , Guisinger N. P. , Li T. , First P. N. , Stroscio J. A.
Published: July 2007

A single sheet of carbon, graphene, exhibits unexpected electronic properties that arise from quantum state symmetries, which restrict the scattering of its charge carriers. Understanding the role of defects in the transport properties of graphene is central to realizing future electronics based on carbon. Scanning tunneling spectroscopy was used to measure quasiparticle interference patterns in epitaxial graphene grown on SiC(0001). Energy-resolved maps of the local density of states reveal modulations on two different length scales, reflecting both intravalley and intervalley scattering. Although such scattering in graphene can be suppressed because of the symmetries of the Dirac quasiparticles, we show that, when its source is atomic-scale lattice defects, wave functions of different symmetries can mix.
Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World
Authors: Salay G. , Dorta M. L. , Santos N. M. , Mortara R. A. , Brodskyn C. , Oliveira C. I. , Barbiéri C. L. , Rodrigues M. M.
Published: July 2007

We evaluated whether four recombinant antigens previously used for vaccination against experimental infection withLeishmania(Leishmania)majorcould also induce protective immunity against a challenge withLeishmania(Viannia)braziliensis, the species responsible for 90% of the 28,712 annual cases of cutaneous and mucocutaneous leishmaniasis recorded in Brazil during the year of 2004. Initially, we isolated the homolog genes encoding fourL. (V.)braziliensisantigens: (i) homologue of receptor for activated C kinase, (ii) thiol-specific antioxidant, (iii)Leishmaniaelongation and initiation factor, and (iv)L. (L.)majorstress-inducible protein 1. At the deduced amino acid level, all four open reading frames had a high degree of identity with the previously described genes ofL. (L.)majorbeing expressed on promastigotes and amastigotes ofL. (V.)braziliensis. These genes were inserted into the vector pcDNA3 or expressed as bacterial recombinant proteins. After immunization with recombinant plasmids or proteins, BALB/c mice generated specific antibody or cell-mediated immune responses (gamma interferon production). After an intradermal challenge withL. (V.)braziliensisinfective promastigotes, no significant reduction on the lesions was detected. We conclude that the protective immunity afforded by these four vaccine candidates against experimental cutaneous leishmaniasis caused byL. (L.)majorcould not be reproduced against a challenge withL. (V.)braziliensis. Although negative, we consider our results important since they suggest that studies aimed at the development of an effective vaccine againstL. (V.)braziliensis, the main causative agent of cutaneous leishmaniasis in the New World, should be redirected toward distinct antigens or different vaccination strategies.
Changes in the Clonal Nature and Antibiotic Resistance Profiles of Methicillin-Resistant
Staphylococcus aureus
Isolates Associated with Spread of the EMRSA-15 Clone in a Tertiary Care Portuguese Hospital
Authors: Amorim M. L. , Faria N. A. , Oliveira D. C. , Vasconcelos C. , Cabeda J. C. , Mendes A. C. , Calado E. , Castro A. P. , Ramos M. H. , Amorim J. M. , de Lencastre H.
Published: July 2007

Two hundred eighty methicillin-resistant
Staphylococcus aureus
(MRSA) clinical isolates recovered from a tertiary care hospital in Oporto, Portugal, between 2003 and 2005 were studied by a combination of molecular typing techniques in order to investigate the genetic backgrounds associated with the changes in the resistance phenotypes observed since 2001 and compare them to those previously found in the hospital. All MRSA isolates were grouped into resistance profiles for a panel of seven antibiotics and characterized by pulsed-field gel electrophoresis (PFGE) and SCC
mec
(
s
taphylococcal
c
assette
c
hromosome
mec
) typing. Representative isolates of PFGE types were further studied by
spa
typing and multilocus sequence typing. Our findings clearly document that the increasing isolation of nonmultiresistant MRSA strains was associated with the decline (from 69% in 1996 to 2000 to 12% in 2003 to 2005) and massive replacement of the multiresistant Brazilian clone (ST239-IIIA) by the epidemic EMRSA-15 clone (ST22-IV), in which resistance to antibiotics other than β-lactams is very rare, as the major clone (80% of isolates). The Iberian clone (ST247-IA), a major clone in 1992 to 1993, was represented in the present study by just one isolate. Two other pandemic MRSA clones were detected, as sporadic isolates, for the first time in our hospital: the New York/Japan (ST5-II) and the EMRSA-16 (ST36-II) clones. Furthermore, the pattern of susceptibility of MRSA isolates both to gentamicin and to trimethoprim-sulfamethoxazole was shown to be an excellent phenotypic marker for the discrimination of the EMRSA-15 clone from other nonmultiresistant MRSA clones present in our hospital.
Performance of the BD GeneOhm Methicillin-Resistant
Staphylococcus aureus
Test before and during High-Volume Clinical Use
Authors: Paule Suzanne M. , Hacek Donna M. , Kufner Bridget , Truchon Karine , Thomson Richard B. , Kaul Karen L. , Robicsek Ari , Peterson Lance R.
Published: July 2007

We evaluated the use of the BD GeneOhm MRSA real-time PCR assay (BD Diagnostics, San Diego, CA) for the detection of nasal colonization with methicillin-resistant
Staphylococcus aureus
(MRSA). The initial evaluation consisted of 403 paired nasal swabs and was done using the specimen preparation provided with the kit and an in-house lysis method that was specifically developed to accommodate large-volume testing using a minimal amount of personnel time. One swab was placed in an achromopeptidase (ACP) lysis solution, and the other was first used for culture and then prepared according to the kit protocol. PCR was performed on both lysates, and results were compared to those for culture. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PCR assay were 98%, 96%, 77%, and 99.7% with the kit lysate and 98%, 95%, 75%, and 99.7% with the ACP lysate (
P
, not significant), respectively. The second evaluation was done after implementation of all-admission surveillance using PCR with ACP lysis and a sampling of 1,107 PCR-negative samples and 215 PCR-positive samples that were confirmed by culture. The results of this sampling showed an NPV of 99.9% and a PPV of 73.5% (prevalence, 6%), consistent with our initial findings. The BD GeneOhm MRSA assay is an accurate and rapid way to detect MRSA nasal colonization. When one is dealing with large specimen numbers, the ACP lysis method offers easier processing without negatively affecting the sensitivity or specificity of the PCR assay.
Deletion of the MeningococcalfetAGene Used for Antigen Sequence Typing of Invasive and Commensal Isolates from Germany: Frequencies and Mechanisms
Authors: Claus Heike , Elias Johannes , Meinhardt Christine , Frosch Matthias , Vogel Ulrich
Published: July 2007

Antigen sequence typing (ST) of FetA is part of the molecular typing scheme ofNeisseria meningitidis. Among invasive meningococcal isolates from 2,201 patients in Germany, we identified 11 strains lacking thefetAgene because of deletions mediated by repeat arrays flanking the gene, i.e., Correia elements, repeat sequence 13 (RS13), and duplicated RS3. Geographic mapping and multilocus ST of invasive isolates revealed thatfetAdeletion was a sporadic event without genetic fixation. Among 821 carrier strains, 12 strains lackedfetA, suggesting thatfetAis maintained during asymptomatic carriage. Interestingly, most of these isolates belonged to the multilocus ST-35 clonal complex (cc). ST-35 cc strains and the recently published ST-192 strains from Burkina Faso may benefit from loss offetA, but their infrequent occurrence among invasive isolates currently does not affectfetAantigen ST.
Diversity of Mutations in the
atpC
Gene Coding for the
c
Subunit of F
0
F
1
ATPase in Clinical Isolates of Optochin-Resistant
Streptococcus pneumoniae
from Brazil
Authors: Dias Cícero A. , Agnes Grasiela , Frazzon Ana Paula G. , Kruger Filipe D. , d'Azevedo Pedro A. , Carvalho Maria da Glória S. , Facklam Richard R. , Teixeira Lúcia M.
Published: July 2007

We report the characteristics of four optochin-resistant (Opt
r
)
Streptococcus pneumoniae
isolates from Brazil. All four Opt
r
isolates presented mutations in the nucleotide sequence coding for the
c
subunit of F
0
F
1
ATPase. Two isolates showed mutations in codons 23 (leading to the deduced amino acid substitution isoleucine instead of alanine) and 49 (serine instead of alanine, a novel type of mutation detected at this position), respectively. Two additional novel mutations, both located in codon 45, were detected in the other two isolates, corresponding to leucine or valine (instead of phenylalanine). The data indicate that three previously unrecognized alterations were detected in the
atpC
gene of
S. pneumoniae
and that Opt resistance among Brazilian pneumococcal isolates is not related to a specific pneumococcal serotype, antimicrobial-resistance profile, or clonal group.
Dengue Virus (DV) Replication in Monocyte-Derived Macrophages Is Not Affected by Tumor Necrosis Factor Alpha (TNF-α), and DV Infection Induces Altered Responsiveness to TNF-α Stimulation
Authors: Wati Satiya , Li Peng , Burrell Christopher J. , Carr Jillian M.
Published: July 2007

Tumor necrosis factor alpha (TNF-α) is believed to play a significant role in the pathogenesis of dengue virus (DV) infection, with elevated levels of TNF-α in the sera of DV-infected patients paralleling the severity of disease and TNF-α release being coincident with the peak of DV production from infected monocyte-derived macrophages (MDM) in vitro. Since macrophages are a primary cell target in vivo for DV infection, we investigated the potential antiviral role of TNF-α in regulating DV replication in MDM. While pretreatment of MDM with TNF-α had a minor inhibitory effect, addition of TNF-α to MDM with established DV infection had no effect on DV replication as measured by DV RNA levels or progeny virus production. Blocking endogenous TNF-α using short interfering RNA or inhibitory TNF-α antibodies also had no effect on infectious DV production or viral RNA synthesis. Together, these results demonstrate that DV replication in MDM is not affected by TNF-α. Additionally, normal cellular TNF-α signaling, measured by quantitation of TNF-α-induced stimulation of transcription from an NF-κB-responsive reporter plasmid or NF-κB protein nuclear translocation, was blocked in DV-infected MDM and Huh7 cells. Thus, DV replication in MDM is not affected by TNF-α, and infected cells do not respond normally to TNF-α stimulation. It is therefore unlikely that the increased production of TNF-α seen in DV infection directly effects DV clearance by reducing DV replication, and the ability of DV to alter TNF-α responsiveness highlights another example of viral subversion of cellular functions.
Epstein-Barr Virus Exploits BSAP/Pax5 To Achieve the B-Cell Specificity of Its Growth-Transforming Program
Authors: Tierney Rosemary , Nagra Jasdeep , Hutchings Isabel , Shannon-Lowe Claire , Altmann Markus , Hammerschmidt Wolfgang , Rickinson Alan , Bell Andrew
Published: July 2007

Epstein-Barr virus (EBV) can infect various cell types but limits its classical growth-transforming function to B lymphocytes, the cells in which it persists in vivo. Transformation initiates with the activation of Wp, a promoter present as tandemly repeated copies in the viral genome. Assays with short Wp reporter constructs have identified two promoter-activating regions, one of which (UAS2) appears to be lineage independent, while the other (UAS1) was B-cell specific and contained two putative binding sites for the B-cell-specific activator protein BSAP/Pax5. To address the physiologic relevance of these findings, we first used chromosome immunoprecipitation assays and found that BSAP is indeed bound to Wp sequences on the EBV genome in transformed cells. Thereafter, we constructed recombinant EBVs carrying two Wp copies, both wild type, with UAS1 or UAS2 deleted, or mutated in the BSAP binding sites. All the viruses delivered their genomes to the B-cell nucleus equally well. However, the BSAP binding mutant (and the virus with UAS1 deleted) showed no detectable activity in B cells, whether measured by early Wp transcription, expression of EBV latent proteins, or outgrowth of transformed cells. This was a B-cell-specific defect since, on entry into epithelial cells, an environment where Wp is not the latent promoter of choice, all the Wp mutant viruses initiated infection as efficiently as wild-type virus. We infer that EBV ensures the B-cell specificity of its growth-transforming function by exploiting BSAP/Pax5 as a lineage-specific activator of the transforming program.
The Cytoplasmic Tail of Glycoprotein M (gpUL100) Expresses Trafficking Signals Required for Human Cytomegalovirus Assembly and Replication
Authors: Krzyzaniak Magdalena , Mach Michael , Britt William J.
Published: July 2007

The virion envelope of human cytomegalovirus (HCMV) is complex and consists of an incompletely defined number of glycoproteins. The gM/gN protein complex is the most abundant protein component of the envelope. Studies have indicated that deletion of the viral gene encoding either gM or gN is a lethal mutation. Analysis of the amino acid sequence of gM disclosed a C-terminal acidic cluster of amino acids and a tyrosine-containing trafficking motif, both of which are well-described trafficking/sorting signals in the cellular secretory pathway. To investigate the roles of these signals in the trafficking of the gM/gN complex during virus assembly, we made a series of gM (UL100 open reading frame) mutants in the AD169 strain of HCMV. Mutant viruses that lacked the entire C-terminal cytoplasmic tail of gM were not viable, suggesting that the cytoplasmic tail of gM is essential for virus replication. In addition, the gM mutant protein lacking the cytoplasmic domain exhibited decreased protein stability. Mutant viruses with a deletion of the acidic cluster or alanine substitutions in tyrosine-based motifs were viable but exhibited a replication-impaired phenotype suggestive of a defect in virion assembly. Analysis of these mutant gMs using static immunofluorescence and fluorescence recovery after photobleaching demonstrated delayed kinetics of intracellular localization of the gM/gN protein to the virus assembly compartment compared to the wild-type protein. These data suggest an important role of the glycoprotein gM during virus assembly, particularly in the dynamics of gM trafficking during viral-particle assembly.
Although Macrophage-Tropic Simian/Human Immunodeficiency Viruses Can Exhibit a Range of Pathogenic Phenotypes, a Majority of Isolates Induce No Clinical Disease in Immunocompetent Macaques
Authors: Igarashi Tatsuhiko , Donau Olivia K. , Imamichi Hiromi , Nishimura Yoshiaki , Theodore Theodore S. , Iyengar Ranjini , Erb Christopher , Buckler-White Alicia , Buckler Charles E. , Martin Malcolm A.
Published: July 2007

Unlike prototypical lentiviruses like visna and caprine arthritis-encephalitis viruses, which are mainly macrophage tropic (M-tropic), primate lentiviruses primarily target CD4+T lymphocytes. We previously reported that during the late phase of highly pathogenic chimeric simian/human immunodeficiency virus (SHIV) infections of rhesus macaques, when CD4+T cells have been systemically eliminated, high levels of viremia are maintained from productively infected macrophages. The availability of several different M-tropic SHIVs from such late-stage immunocompromised animals provided the opportunity to assess whether they might contribute to the immune deficiency induced by their T-cell-tropic parental viruses or possibly cause a distinct disease based on their capacity to infect macrophages. Pairs of rhesus monkeys were therefore inoculated intravenously with six different M-tropic SHIV preparations, and their plasma viral RNA loads, circulating lymphocyte subset numbers, and eventual disease outcomes were monitored. Only one of these six M-tropic SHIVs induced any disease; the disease phenotype observed was the typical rapid, complete, and irreversible depletion of CD4+T cells induced by pathogenic SHIVs. An analysis of two asymptomatic monkeys, previously inoculated with an M-tropic SHIV recovered directly from alveolar macrophages, revealed that this inoculum targeted alveolar macrophages in vivo, compared to a T-cell-tropic virus, yet no clinical disease occurred. Although one isolate did, in fact, induce the prototypical rapid, irreversible, and complete loss of CD4+T cells, indicating that M-tropism and pathogenicity may not be inversely related, the majority of M-tropic SHIVs induced no clinical disease in immunocompetent macaques.