bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA identification based on sequence and structure alignment
Authors: Wang Xiaowo , Zhang Jing , Li Fei , Gu Jin , He Tao , Zhang Xuegong , Li Yanda
Published: July 2005

Motivation: MicroRNAs (miRNA) are ∼22 nt long non-coding RNAs that are derived from larger hairpin RNA precursors and play important regulatory roles in both animals and plants. The short length of the miRNA sequences and relatively low conservation of pre-miRNA sequences restrict the conventional sequence-alignment-based methods to finding only relatively close homologs. On the other hand, it has been reported that miRNA genes are more conserved in the secondary structure rather than in primary sequences. Therefore, secondary structural features should be more fully exploited in the homologue search for new miRNA genes.

Results: In this paper, we present a novel genome-wide computational approach to detect miRNAs in animals based on both sequence and structure alignment. Experiments show this approach has higher sensitivity and comparable specificity than other reported homologue searching methods. We applied this method on Anopheles gambiae and detected 59 new miRNA genes.

Availability: This program is available at http://bioinfo.au.tsinghua.edu.cn/miralign

Contact:  daulyd@tsinghua.edu.cn

Supplementary information: Supplementary information is available at http://bioinfo.au.tsinghua.edu.cn/miralign/supplementary.htm
Type 2 Diabetes in Children is Frequently Associated with Elevated Alanine Aminotransferase
Authors: Nadeau Kristen J , Klingensmith Georgeanna , Zeitler Phillip
Published: July 2005

Background:

Nonalcoholic fatty liver disease, a cause of chronic liver disease in obese adults also occurs in obese children. In susceptible populations, fatty liver progresses to nonalcoholic steatohepatitis and eventually to fibrosis and cirrhosis. Nonalcoholic steatohepatitis is associated with elevation of alanine aminotransferase, although the aminotransferases can also be normal. The prevalence of nonalcoholic fatty liver disease in type 2 diabetes is unclear in adults and unknown in children.

Objectives:

The aim of this study was to estimate the prevalence of elevated serum aminotransferases as a marker of nonalcoholic fatty liver disease in pediatric type 2 diabetes and to identify correlates of aminotransferase elevation.

Methods:

A chart review was completed on 115 children with type 2 diabetes at a pediatric diabetes clinic. The prevalence of elevated alanine aminotransferase was calculated from the 42% of patients with available aminotransferase measurements and correlations with fasting lipids, hemoglobin A‐1c, body mass index, age and diabetes therapy were sought.

Results:

The prevalence of elevated alanine aminotransferase was 48%. There was no association between elevations and other variables. Among subjects with elevated alanine aminotransferase, 39% were one to two times above normal, 26% were two to three times normal and 35% were greater than three times above normal. Several patients experienced improvement in aminotransferase elevations after using insulin‐sensitizing medications.

Conclusions:

There is a high prevalence of elevated serum aminotransferases among children with type 2 diabetes unrelated to age, body mass index, glycemic control, blood lipids or diabetic therapy. The significance of this abnormality and its relationship to nonalcoholic fatty liver disease requires further evaluation.
Influence of CARD15 Mutations on Disease Activity and Response to Therapy in 65 Pediatric Crohn Patients from Saxony, Germany
Authors: Roesler Joachim , Thürigen Anett , Sun Liping , Koch Rainer , Winkler Ulf , Laass Martin W , Gahr Manfred , Rösen‐Wolff Angela , Henker Jobst
Published: July 2005

Objectives:

Certain genetic variants in the CARD15 gene are accompanied by an enhanced risk to develop Crohn disease with the main activity in the terminal ileum and ensuing stricturing early in life. The objective of this study was to evaluate the relation between CARD15 mutations and overall disease activity and response to therapy in pediatric patients.

Methods:

65 genomic DNA samples from such patients were tested for the presence of three main Crohn associated mutations in CARD15 by direct genomic sequencing. The number of mutations (none, one or two alleles affected) was correlated with body mass index and height, Pediatric Crohn Disease Activity Index, therapy and therapeutical success in terms of body mass index and Pediatric Crohn Disease Activity Index improvement.

Results:

The authors found a nonsignificant trend of a lower body mass index and higher Pediatric Crohn Disease Activity Index in patients with CARD15 mutations. Physicians uninformed about their CARD15 status prescribed significantly more budesonide and prednisolone intermittently and more alimentary supplementation to these patients. The average improvement in terms of body mass index and Pediatric Crohn Disease Activity Index after 2 years of therapy was roughly similar in all patient groups.

Conclusions:

Pediatric Crohn patients with CARD15 mutations have a higher disease activity and need a more intensive therapy. With some exceptions, their medium‐term response to therapy is nevertheless satisfying.
Chronic Childhood Constipation Is Associated with Impaired Quality of Life: A Case‐Controlled Study
Authors: Youssef Nader N , Langseder Annette L , Verga Barbara J , Mones Richard L , Rosh Joel R
Published: July 2005

Objective:

The objective of this study was to investigate the effect of chronic constipation on children's quality of life.

Methods:

From October 2002 to November 2003, 224 children (140 male, 84 female, aged 10.6 ± 2.9 years) and 224 parents were evaluated by a health related quality of life tool during initial outpatient consultation. Children with constipation (n = 80) were compared with controls with inflammatory bowel disease (n = 42), controls with gastroesophageal reflux disease (n = 56), and with healthy children (n = 46).

Results:

Children with constipation had lower quality of life scores than did those with inflammatory bowel disease (70 versus 84; P < 0.05), gastroesophageal reflux disease (70 versus 80; P < 0.05), and healthy children (70 versus 88; P < 0.05). Children with constipation reported lower physical scores than did inflammatory bowel disease patients (75 versus 85; P < 0.02), gastroesophageal reflux disease patients (75 versus 85; P < 0.05), or healthy children (75 versus 87; P < 0.05). Parents of children with constipation reported lower scores than did their children (61 versus 70; P < 0.05). Children with constipation had longer duration of symptoms than did the controls with inflammatory bowel disease and gastroesophageal reflux disease (43.8 months versus 14.2 months; P < 0.001). Prolonged duration of symptoms for children with constipation correlated with lower parent‐reported scores (P < 0.002).

Conclusions:

At initial evaluation, children with constipation have a lower quality of life than do children with inflammatory bowel disease or gastroesophageal reflux disease. Self‐reported lower scores may be a reflection of impaired physical ability. Parental perceptions of low quality of life are probably impacted by the duration of their child's symptoms and by family members with similar complaints. Practitioners should be aware of the high level of parental concern and the relatively low self‐reported and parent‐reported quality of life in children with chronic constipation as they plan therapy.
A two-fluid model for avalanche and debris flows
Authors: Pitman E. Bruce , Le Long
Published: July 2005

Geophysical mass flows—debris flows, avalanches, landslides—can contain
O
(10
6
–10
10
) m
3
or more of material, often a mixture of soil and rocks with a significant quantity of interstitial fluid. These flows can be tens of meters in depth and hundreds of meters in length. The range of scales and the rheology of this mixture presents significant modelling and computational challenges. This paper describes a depth-averaged ‘thin layer’ model of geophysical mass flows containing a mixture of solid material and fluid. The model is derived from a ‘two-phase’ or ‘two-fluid’ system of equations commonly used in engineering research. Phenomenological modelling and depth averaging combine to yield a tractable set of equations, a hyperbolic system that describes the motion of the two constituent phases. If the fluid inertia is small, a reduced model system that is easier to solve may be derived.
Blowing snow at Mizuho station, Antarctica
Authors: Nishimura Kouichi , Nemoto Masaki
Published: July 2005

Blowing snow observations were carried out at Mizuho station, Antarctica, from October to November 2000. A blowing snow observation system including snow particle counters, which can sense not only the number of snow particles, but also their diameters, was situated on a 30 m tower. All instruments worked correctly and the data obtained revealed profiles of mass flux and particle size distributions as a function of the friction velocity. Measurements were compared with a blowing snow model that accounted for most physical processes including aerodynamic entrainment, grain/bed collisions, wind modification, particle size distribution and turbulent fluctuations on the particle trajectories. Simulated and measured results showed close agreement, and the validity of the model was demonstrated. Vertical profiles of horizontal mass flux from saltation to suspension, as well as the particle size distributions were expressed precisely, which could not be achieved using the previous models.
A hybrid Petri nets model of networked manufacturing systems and its control system architecture
Authors: Wang Zheng , Zhang Jie , Chan Felix T.S.
Published: July 2005

Purpose

To introduce a Petri nets model that describes a networked manufacturing system and its dynamics.

Design/methodology/approach

A hybrid Petri nets model is constructed, the continuous part of which is to describe the dynamics of the production process within a manufacturing system and the discrete part of which is to describe the dynamics of the ordering and delivering process between every two manufacturing systems. In addition, the mathematical formulation of the dynamics of networked manufacturing systems is proposed to describe its behaviors in detail. Based on the model, the control system architecture of networked manufacturing systems is constructed to make and execute the production plan, solve the conflicts among manufacturing systems and realize the reconfiguration of the network.

Findings

There are two key aspects in the dynamics of this hybrid system: first, in the continuous part of this hybrid system, the production process, the variables are discrete. Accordingly, the change of the systems states is not always continuous. Second, in the discrete part of this hybrid system the control variables are actually the safety and objective inventory levels and the minimum quantity of cumulative orders to trigger deliveries which determine the time and quantities of ordering or delivery. However, the relations between them are non‐linear.

Originality/value

Based on the model, the control system architecture of networked manufacturing systems can be constructed to make and execute the production plan, solve the conflicts among manufacturing systems and realize the reconfiguration of the network.
Model‐supported supply chains for cost‐efficient intelligent enterprises
Authors: Esra Aslanertik B.
Published: July 2005

Purpose

The twentieth century brought great competition and complexity to business life. Advanced technologies and new production techniques resulted in shortening product life cycles. Firms that wanted to survive began to implement different strategies directly focused on customer satisfaction. Supply chain management, as a management philosophy, highlighted a new area that has the potential to reduce cost further than production costs. This paper promotes the supply chains for cost‐efficient intelligent enterprises.

Design/methodology/approach

Promotes the use of supply chains by means of simulation and allocating the results to solver in Excel for decision modelling in order to integrate the supplier and manufacturer relationship for the cost‐efficient enterprise.

Findings

Finds that a manufacturing firm really needs to develop effective co‐ordination within and beyond its boundaries in order to maximise the potential for converting competitive advantage into profitability. Good co‐ordination with the key suppliers especially will increase product availability.

Originality/value

The synchronisation of activities in supply will create value to both its members (supplier and manufacturer) and in addition it will create value to the end customer by satisfying delivery dates.
Integrated modeling of the major events in the MHC class I antigen processing pathway
Authors: Dönnes Pierre , Kohlbacher Oliver
Published: June 2005

Rational design of epitope‐driven vaccines is a key goal of immunoinformatics. Typically, candidate selection relies on the prediction of MHC–peptide binding only, as this is known to be the most selective step in the MHC class I antigen processing pathway. However, proteasomal cleavage and transport by the transporter associated with antigen processing (TAP) are essential steps in antigen processing as well. While prediction methods exist for the individual steps, no method has yet offered an integrated prediction of all three major processing events. Here we present WAPP, a method combining prediction of proteasomal cleavage, TAP transport, and MHC binding into a single prediction system. The proteasomal cleavage site prediction employs a new matrix‐based method that is based on experimentally verified proteasomal cleavage sites. Support vector regression is used for predicting peptides transported by TAP. MHC binding is the last step in the antigen processing pathway and was predicted using a support vector machine method, SVMHC. The individual methods are combined in a filtering approach mimicking the natural processing pathway. WAPP thus predicts peptides that are cleaved by the proteasome at the C terminus, transported by TAP, and show significant affinity to MHC class I molecules. This results in a decrease in false positive rates compared to MHC binding prediction alone. Compared to prediction of MHC binding only, we report an increased overall accuracy and a lower rate of false positive predictions for the HLA‐A*0201, HLA‐B*2705, HLA‐A*01, and HLA‐A*03 alleles using WAPP. The method is available online through our prediction server at http://www‐bs.informatik.uni‐tuebingen.de/WAPP.
Seasonal, diel and ontogenetic variation in feeding patterns of small yellow croaker in the central Yellow Sea
Authors: Xue Y. , Jin X. , Zhang B. , Liang Z.
Published: July 2005

Stomach contents of 1603 small yellow croaker Pseudosciaena polyactis, sampled from seasonal bottom trawl surveys in the central Yellow Sea between March 2001 and January 2002, were examined. The results showed that small yellow croaker was a carnivorous predator and >30 prey species were identified from stomach contents analysis. Crustaceans (mainly euphausiids and decapods) were the most important prey, occurring in 93·1% of the stomachs containing food, and accounting for 77·6% of the total food by mass. Feeding activity was highest in autumn and lowest in spring and winter. Decapods were more important in summer, whereas euphausiids were more important during other seasons. Ontogenetic differences were found in the diet composition and feeding activity within the range of size (standard length, LS) studied. The importance of fishes and decapods increased with LS, whereas euphausiids, copepods and amphipods decreased in importance with LS. Dietary breadth increased markedly for adults. A positive relationship was found between LS and prey size. In each season the maximum diel feeding activity occurred at 0800 and 2400 hours, indicating that there was crepuscular and nocturnal feeding by small yellow croaker.
Effect of caudal fin height on swimming kinematics in the mackerel Scomber scombrus L.
Authors: He P. , Wardle C. S.
Published: July 2005

Geometry of the caudal fin of the mackerel Scomber scombrus was modified to examine the effect of the height of the fin on swimming kinematics. Mackerel with reduced caudal fin height had significantly shorter stride length and higher tail beat amplitude compared with the control having an intact caudal fin (P < 0·005).
Summer habitat relationships of barbels in south‐west Spain
Authors: Morán‐López R. , Pérez‐Bote J. L. , Da Silva Rubio E. , Corbacho Amado C.
Published: July 2005

An analysis was made of the associations with local habitat features of barbels (Barbus sp.) of a Mediterranean river basin. The analysis was based on the presence data from sampling the upper, middle, and lower reaches of 31 rivers in the middle Guadiana River basin (south‐west Spain). Numerous local habitat variables were determined, including the river's size and substratum, physicochemical variables of water, and the aquatic and riparian vegetation. For each species, a univariate analysis was performed using preference indices, and logistic regression was used to construct a parsimonious multivariate model and Gaussian response models with the most influential variables, quantifying the species’ limits of tolerance. Distinct habitat associations for every species were obtained, mainly relating Barbus comiza to the larger habitats and higher water levels, Barbus microcephalus to the maintenance of lotic conditions and Barbus sclateri to more fluctuating rivers. Barbus steindachneri showed a different habitat relationship from that of the genetically almost identical B. comiza. Cover played a significant role in all but B. comiza.
Spawning aggregations of Lutjanus cyanopterus(Cuvier) on the Belize Barrier Reef over a 6 year period
Authors: Heyman W. D. , Kjerfve B. , Graham R. T. , Rhodes K. L. , Garbutt L.
Published: July 2005

Cubera snapper Lutjanus cyanopterus aggregated to spawn at Gladden Spit, a salient sub‐surface reef promontory seaward of the emergent reef and near the continental shelf edge of Belize. Their spawning aggregations typically formed 2 days before to 12 days after full moon from March to September 1998–2003 within a 45 000 m2 reef area. Peak abundance of 4000 to 10 000 individuals was observed between April and July each year, while actual spawning was most frequently observed in May. Spawning was observed consistently from 40 min before to 10 min after sunset within a confined area ≤1000 m2. Data suggested that cubera snapper consistently formed seasonal spawning aggregations in relation to location, photoperiod, water temperature and lunar cycle, and that spawning was cued by time of day but not tides. The cubera snapper aggregation site was included within the Gladden Spit Marine Reserve, a conditional no‐take fishing zone.
Reproductive cycle and growth of Phyllopteryx taeniolatus
Authors: Sanchez‐Camara J. , Booth D. J. , Turon X.
Published: July 2005

In this study, 36 males, 33 females and 15 juveniles of the common or weedy seadragon Phyllopteryx taeniolatus, a syngnathid fish endemic to the waters of southern Australia, were identified using visual implant fluorescent elastomer tags and pattern of appendages and their reproductive cycle and growth was studied from May 2001 to June 2002. Brooding males were present for a period of >6 months, from June–July to early‐January. The percentage of males that were pregnant in the studied areas peaked in November–December, near the end of the breeding season. Two pregnancies were reported for some males. Ten recruits were identified from November to June. Growth rates for young‐of‐the‐year, young of the previous year, males and females were measured. The von Bertalanffy growth constant K was estimated at 0·098 month−1.
Seasonal growth of Atlantic cod: effects of temperature, feeding and reproduction
Authors: Mello L. G. S. , Rose G. A.
Published: July 2005

Growth of 2659 Atlantic cod Gadus morhua aged 4 to 9 years examined in Placentia Bay, Newfoundland, peaked in most cases in June and was at a minimum in October or November. Water temperature, partial fullness index (IP) and gonado‐somatic index (IG) explained between 31 and 52% of the monthly variability in growth. Temperature and IP of capelin Mallotus villosus had significant effects on growth of all age groups and explained most of the variance for ages 6–8 and 4–5 years, respectively. The IP of large invertebrates (ages 4 to 7 years), sandlance (Ammodytes sp. age 6 years) and demersal fishes (age 9 years) had age‐specific effects in the model. Overall, amphipods, decapods and echinoderms dominated the Atlantic cod diet in most seasons, but fish consumption by Atlantic cod was high in June and July, particularly on capelin. The rapid increase in somatic mass during June and July occurred despite cold water temperatures ( < 3° C at 50 m) and moderate to high gonado‐somatic index. The findings of this study suggest that when food was not a limiting factor, growth tended to increase even when Atlantic cod occupied colder waters, but when food was limiting, the opposite may have occured.
The rate of uptake of sex steroids from water by Tinca tinca is influenced by their affinity for sex steroid binding protein in plasma
Authors: Scott A. P. , Pinillos M. L. , Huertas M.
Published: July 2005

Two experiments were carried out in which male and female tench Tinca tinca were placed in individual containers and tritiated steroids then added to the water. Water samples were collected over the next 6 or 7 h and the fish then sacrificed, bled and the gall bladder removed. Radioactivity was counted in all the samples. Over the course of the exposure period in the first experiment (7 h), radioactivity of 11‐ketotestosterone (11‐KT) in the water was depleted by 11%, 17,20β‐dihydroxypregn‐4‐en‐3‐one (17,20ß‐P) and 17,20α‐dihydroxypregn‐4‐en‐3‐one (17,20α‐P) by 28%, testosterone (T) by 56% and androstenedione (AD) by 68%. HPLC analysis of water samples at 3 h indicated that none of the steroids was extensively metabolized during the experiment. Females had a faster rate of uptake of AD than males. In the second experiment (6 h), radioactivity of cortisol in the water was depleted by 5%, 11‐KT by 7%, 17‐hydroxypregnen‐4‐ene (17‐P) by 17%, 17β‐oestradiol (E2) by 35%, T by 37% and AD by 44%. In both experiments, the amounts of radioactivity that were recovered from the gall bladder and plasma were positively correlated with the rate of disappearance of radioactivity from the water. The ability of the steroids to bind to sex steroid binding protein (SBP) of tench plasma was tested by incubating plasma with radioactive steroids and then separating bound and free with ice cold dextran‐coated charcoal. When plasma at a final dilution of 1 : 60 (v/v) was incubated with 5 nM of each steroid, the percentage of radiolabel bound to SBP was: T 48% AD 44%, E2 30%, 17‐P 17%, 11‐KT 13·2%, 17,20α‐P 10·3%, 17,20β‐P 4·5% and cortisol 0%. Saturation analysis established dissociation constants (Kd; mean ± s.e.) of 3·4 ± 0·4, 2·2 ± 0·2, 4·0 ± 0·3. 9·0 ± 2·8 and 51·8 nM and binding capacities (Bmax) of 201 ± 29, 201 ± 33, 165 ± 3, 187 ± 15 and 13·4 nM for T, AD, E2,17‐P and 17,20β‐P respectively. The ability of steroids to displace tritiated T and AD from SBP was in the rank order AD > T > E2 > 17,20αP = 17,20β‐P = 11‐KT = 17‐P > cortisol. Thus, the ability of tench plasma to bind certain steroids showed a relatively strong correlation with the ability of the fish to take up these steroids from water. Modelling of data for AD and 17,20β‐P helped to show why and how plasma binding had a strong influence on the rate of uptake (and hence release) of the steroids.
Underlying physiological control of reproduction in urban and forest‐dwelling European blackbirds Turdus merula
Authors: Partecke Jesko , J. Van't Hof Thomas , Gwinner Eberhard
Published: June 2005

The development and the continual expansion of urban areas have not only destroyed natural habitats, but also have drastically changed the environmental and ecological conditions of these areas. Consequently, species that have settled in these new man‐made ecosystems are exposed to considerable alternations in environmental conditions compared to their ‘wild’ conspecifics. To understand the impact of human‐induced environmental changes on life history events such as reproduction, we compared the timing of the reproductive season and its underlying endocrine control in free‐living European blackbirds Turdus merula inhabiting urban and nearby forest areas. Body mass, fat score, gonadal size, luteinizing hormone (LH), testosterone (T), and estradiol (E2) were measured. Urban blackbirds developed their gonads approximately three weeks earlier than forest birds, whereas the timing of gonadal regression did not differ. There are several factors (e.g. artificial light, temperature, food availability, and social cues) which may have caused the differences in the temporal organization of gonadal growth between the urban and forest‐living populations. The advanced gonadal development of urban blackbirds did not coincide with an earlier secretion of reproductive hormones. In contrast, urban males had lower plasma LH and T levels during testicular growth than forest males. Differences in social interactions and environmental conditions may explain the contrast of gonadal development and the timing of hormone secretion between urban and forest blackbirds.
Benefits and costs of rapid growth in common murre chicksUria aalge
Authors: Benowitz‐Fredericks Z Morgan , Kitaysky Alexander S.
Published: June 2005

While accelerated growth can be advantageous to nestling birds, there may be a tradeoff between rapid growth and resistance to food shortages. Common murresUria aalge are colonial seabirds that benefit from reproductive synchrony. Individuals that lay eggs late should benefit if they produce chicks capable of growing quickly and fledging synchronously with their neighbors. In this study, we controlled food provisioning of captive‐hatched common murre chicks from a single subcolony and examined differences in growth between early‐hatched individuals and their later‐hatched neighbors. We assessed potential costs of rapid growth by comparing growth of chicks fedad libitumwith their growth under food restricted conditions. Chicks that hatched later were heavier, ate more and gained body mass more quickly than chicks that hatched earlier. Late‐hatched chicks grew quickly enough to reach the same mass as their early‐hatched neighbors in five days. However, chicks that grew more quickly underad libitumfood conditions grew more slowly when food was restricted. We conclude that murres that lay eggs late may synchronize their reproduction with early‐laying neighbors by producing rapidly growing chicks. However, the ability to compensate for late hatching by growing quickly can be costly when food becomes limited.
Factors affecting avian cross‐species microsatellite amplification
Authors: R. Primmer Craig , N. Painter Jodie , T. Koskinen Mikko , U. Palo Jukka , Merilä Juha
Published: June 2005

Compilation and analysis of information from the literature regarding cross‐species microsatellite amplification and polymorphism success, and relating this to source‐target species genetic distance as estimated by pairwise cytochrome b (cytb) divergence, enabled an in‐depth investigation of factors affecting avian cross‐species microsatellite amplification. Source‐target species cytb distances provided accurate estimates of cross‐species microsatellite amplification/polymorphism success rates not only in birds, but also in taxa where microsatellites cross‐amplify across contrasting levels of taxonomic classification (frogs and cetaceans). As cytb is one of the most commonly sequenced DNA regions, pairwise cytb genetic distances should therefore be useful for predicting cross‐species microsatellite success across a range of taxonomic groups. While the most important factor affecting cross‐species microsatellite amplification/polymorphism success was a negative association with source‐target species genetic distance, associations with additional features affecting cross‐species amplification/polymorphism success included: decreasing PCR annealing temperature significantly increasing the chance of successful cross‐species amplification, and a significant positive association between source species polymorphism and the proportion of target species in which a locus revealed polymorphism. No association between cross‐species amplification and repeat motif (di‐, tri‐, or tetranucelotide) or repeat structure (perfect, imperfect, or compound) was observed. A set of nine loci which cross‐amplified across an unusually broad range of passerine bird species were also identified, and could serve as a good starting point for cross‐species amplification testing in passerine species for which insufficient loci are available.
Hypoxia aggravates lipopolysaccharide-induced lung injury
Authors: Vuichard D , Ganter M T , Schimmer R C , Suter D , Booy C , Reyes L , Pasch T , Beck-Schimmer B
Published: July 2005

The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non-pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin-induced lung injury. Lipopolysaccharide, 150 µg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide-animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor-α and macrophage inflammatory protein-1β, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein-B showed enhanced concentrations in lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage-depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia-induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.
Regulation of Toll-like receptor (TLR)2 and TLR4 on CD14dimCD16+ monocytes in response to sepsis-related antigens
Authors: Skinner N A , MacIsaac C M , Hamilton J A , Visvanathan K
Published: July 2005

Rapid overproduction of proinflammatory cytokines are characteristic of sepsis. CD14dimCD16+ monocytes are thought to be major producers of cytokine and have been shown to be elevated in septic patients. Toll-like receptors (TLR) are pattern recognition receptors important in mediating the innate immune response and their activation can lead to production of cytokines. Using whole blood culture and flow cytometry we have investigated TLR2 and TLR4 regulation after stimulation with sepsis-relevant antigens [lipopolysaccharide (LPS), Staphylococcal enterotoxin B (SEB) and peptidoglycan (PGN)]. The percentage of CD14dimCD16+ monocyte population expanded at 20 h post-stimulation, after a rise in tumour necrosis factor (TNF)-α and interleukin (IL)-6 at 2 h. A strong positive correlation between the percentage of CD14dimCD16+ monocytes and secreted TNF-α was demonstrated (r = 0·72). Furthermore, we were able to induce expansion of the CD14dimCD16+ population to approximately 35% of all monocytes with the addition of recombinant TNF-α to the whole blood culture. TLR4 was found to be expressed 2·5 times higher on CD14dimCD16+ compared to CD14+ CD16– monocytes, while TLR2 expression was similar in both subpopulations. The CD14dimCD16+ and CD14+ CD16– monocyte populations were different in their response to various antigens. LPS down-regulated TLR4 by 4·9 times in CD16+ monocytes compared to only 2·3 times in CD16– monocytes at 2 h. LPS was able to up-regulate TLR2 by 6·2 times after 2 h, with no difference between the subpopulations. LPS further up-regulated TLR2 by 18·4 times after 20 h only in the CD14+ CD16– population. PGN and SEB induced no significant changes in TLR2 or TLR4 expression. We hypothesize that following exposure to bacterial antigens, subsequent TNF-α drives a differentiation of monocytes into a CD14dimCD16+ subpopulation.
Use of pro‐atrial natriuretic peptide in the detection of myocardial ischaemia
Authors: Bocek T. , Morgenthaler N. G. , Staub D. , Nusbaumer C. , Christ A. , Zellweger M. J. , Mueller‐Brand J. , Mueller B. , Perruchoud A. P. , Mueller C.
Published: July 2005

Background  Because of its unique storage and release mechanisms allowing a very rapid response to haemodynamic changes, pro‐atrial natriuretic peptide (proANP) may be a helpful cardiac marker in the detection of myocardial ischaemia.

Materials and methods  A total of 260 consecutive patients with suspected myocardial ischaemia referred for rest/ergometry myocardial perfusion single‐photon emission computed tomography (SPECT) were enrolled. Levels of plasma proANP were determined before and 1 min after maximal exercise.

Results  Baseline proANP and peak exercise proANP were significantly higher in patients with myocardial ischaemia as compared to those without ischaemia (median, 82 [IQR, 57–112] vs. 67 [IQR, 50–106] pmol L−1, P = 0·007; and 89 [IQR, 65–121] vs. 78 [IQR, 57–116] pmol L−1, P = 0·033). The area under the ROC curve for baseline proANP was 0·597 (95% CI, 0·527–0·667), as compared to 0·577 (95% CI, 0·507–0·648) for peak exercise proANP. Exercise‐induced changes in proANP were similar in patients with and without myocardial ischaemia, and showed no correlation with the extent of myocardial ischaemia.

Conclusions  Baseline proANP and peak exercise proANP are significantly higher in patients with myocardial ischaemia. However, because of considerable overlap in proANP levels between patients with and without myocardial ischaemia, neither measurement seems helpful in the detection of myocardial ischaemia in clinical practice.
Dental erosion in 12‐year‐old schoolchildren: a cross‐sectional study in Southern Brazil
Authors: PERES K. G. , ARMÊNIO M. F. , PERES M. A. , TRAEBERT J. , DE LACERDA J. T.
Published: June 2005

Objective. The aim of this study was to assess the prevalence and severity of dental erosion among 12‐year‐old schoolchildren in Joaçaba, southern Brazil, and to compare prevalence between boys and girls, and between public and private school students.

Methods.  A cross‐sectional study was carried out involving all of the municipality's 499, 12‐year‐old schoolchildren. The dental erosion index proposed by O'Sullivan was used for the four maxillary incisors. Data analysis included descriptive statistics, location, distribution, and extension of affected area and severity of dental erosion.

Results.  The prevalence of dental erosion was 13·0% (95% confidence interval = 9·0–17·0). There was no statistically significant difference in prevalence between boys and girls, but prevalence was higher in private schools (21·1%) than in public schools (9·7%) (P < 0·001). Labial surfaces were less often affected than palatal surfaces. Enamel loss was the most prevalent type of dental erosion (4·86 of 100 incisors). Sixty‐three per cent of affected teeth showed more than a half of their surface affected.

Conclusion.  The prevalence of dental erosion in 12‐year‐old schoolchildren living in a small city in southern Brazil appears to be lower than that seen in most of epidemiological studies carried out in different parts of the world. Further longitudinal studies should be conducted in Brazil in order to measure the incidence of dental erosion and its impact on children's quality of life.
Finding more meaning: the antecedents of uncertainty revisited
Authors: Wallace Meredith
Published: June 2005

Aims and objectives.  The objective of this study was to explore the extent to which several antecedents explained the uncertainty of men who were undergoing the watchful waiting management option for prostate cancer.

Background.  Uncertainty plays a significant role in explaining various outcomes in the chronically ill. However, little is known about the factors that accompany and modify uncertainty. For uncertainty to predict the outcomes of individuals coping with illness, it is imperative to understand its accompanying antecedents.

Design.  The study used a correlational single group non‐experimental design.

Methods.  The convenience sample completed a one‐time mailed questionnaire aimed at measuring the antecedents of uncertainty.

Results.  A total of 19 participants completed questionnaires. The results revealed significant relationships between level of education and length of time with illness and uncertainty. Stepwise multiple regression indicated that education explained 52% of the variance in uncertainty.

Conclusions.  This study strengthens the relationship between both education and length of time with illness, and uncertainty. It further supports the Uncertainty in Illness Model and enhances the understanding of the factors that influence uncertainty in the sample.

Relevance to clinical practice.  This study assisted in the identification of factors that influence uncertainty in men undergoing the watchful waiting management option for prostate cancer. Future study should examine the role of antecedents in explaining uncertainty in additional populations and using alternative measures, when necessary.
Nursing students’ perception of group supervision during clinical training
Authors: Lindgren Barbro , Brulin Christine , Holmlund Kristina , Athlin Elsy
Published: June 2005

Aim.  The aim of this study was to investigate nursing students’ perception of and satisfaction with clinical group supervision based on a special model, used in nursing training.

Background.  Long‐standing efforts have been made to create supervision models in nursing training that promote personal and professional development and prepare nursing students to cope with the complex and demanding situations they will face as registered nurses.

Methods.  Data were collected from nursing students (n = 43) during their clinical training by means of two questionnaires. Most questions were concerned with the importance of factors involved in the contract and the students’ experiences of how these factors were covered during the clinical group supervision.

Findings.  The findings showed that, before starting the supervision programme, most all the students expressed positive attitudes towards group supervision, but 25% had negative expectations as well. At the end of the programme all students thought that group supervision had been an important support to them during their training and almost everyone wanted to participate in group supervision in the future as registered nurses. The findings showed that both the structure and the climate were important for the success of the group supervision.

Relevance to clinical practice.  The findings will strengthen the model and confirm its usefulness in clinical training for nursing students. Using this supervision model, which includes reflection about feelings, thoughts and actions, the students will be well prepared for demanded situations in their future role as a registered nurse. A replication of this study addressed to trained nurses would be valuable.
Preschool children with and without developmental delay: behaviour problems, parents’ optimism and well‐being
Authors: Baker B. L. , Blacher J. , Olsson M. B.
Published: June 2005

Background  Children with intellectual disability are at heightened risk for behaviour problems, and these are known to increase parenting stress. This study explored the relation of behaviour problems to less child‐related domains of parent well‐being (depression and marital adjustment), as well as the moderating effect of a personality trait, dispositional optimism.

Method  Participating children (N = 214) were classified as developmentally delayed, borderline, or nondelayed. Mothers’ and fathers’ well‐being and child behaviour problems were assessed at child ages 3 and 4 years.

Results  Parents of delayed and nondelayed preschoolers generally did not differ on depression or marital adjustment, but child behaviour problems were strongly related to scores on both measures. Optimism moderated this relationship, primarily for mothers. When child behaviour problems were high, mothers who were less optimistic reported lower scores on measures of well‐being than did mothers who were more optimistic.

Conclusions  Interventions for parents that aim to enhance both parenting skills and psycholog‐ ical well‐being should be available in preschool. It may be beneficial for such programmes to focus not only on behaviour management strategies aimed at child behaviour change, but also on parents’ belief systems, with the aim of increasing dispositional optimism.
Effect of IL‐2 on hepatitis C virus RNA levels in patients co‐infected with human immunodeficiency virus receiving HAART
Authors: Tedaldi E. M. , Chen L. , Markowitz N. , Kelly L. , Abrams D. ,   the CPCRA Hepatitis Working Group
Published: June 2005

Summary.  The effect of interleukin‐2 (IL‐2) on the plasma levels of hepatitis C RNA (HCV‐RNA) has varied in published reports. We measured the impact of IL‐2 on plasma HCV RNA levels in 54 human immunodeficiency virus (HIV)/HCV coinfected patients enrolled in a randomized trial of 512 participants designed to compare the virologic and immunologic effects of cycled IL‐2 plus antiretroviral therapy (ART) vs ART alone in the treatment of HIV in patients with CD4 cell counts ≥300 cells/mm3. The mean decreases in average HCV RNA levels (copies/mL, log 10) were 0.28 log in the IL‐2 group (n = 26) and 0.04 log in the ART alone group (n = 28) at 12 months (P = 0.18). The changes in HCV RNA level were not associated with baseline or nadir CD4 cell counts, baseline aspartate aminotransferanse, CD4 cell response to IL‐2, or changes in plasma HIV RNA values. Compared with those participants who only had HIV, the HIV/HCV co‐infected patients did not have a significantly different CD4 cell response to IL‐2 therapy. Intermittent IL‐2 therapy does not produce a significant sustained decrease in plasma HCV RNA levels among patients co‐infected with HIV/HCV who are on highly active ART.
SEN virus infection in patients with hepatocellular carcinoma
Authors: Momosaki S. , Umemura T. , Scudamore C. H. , Kojiro M. , Alter H. J. , Tabor E.
Published: June 2005

Summary.  Although most cases of hepatocellular carcinoma (HCC) are associated with either the hepatitis B or C viruses (HBV, HCV), about 10–20% of HCCs occur in patients with chronic hepatitis that is aetiologically undefined. The aim of the present study was to determine the prevalence of the transfusion‐transmitted SEN virus (SEN‐V) in patients with HCC, including those patients who do not otherwise appear to be infected with HBV or HCV.

Fragments of SEN‐V subtypes D and H were amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues from eight of the Canadian patients.

SEN‐V DNA was found in the serum of 10 of 31 (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of 50 (36%) HCC patients]. SEN‐V DNA was detected in the serum of 10 of 23 (43%) HCC patients with antibody to HCV (anti‐HCV), six of 11 (55%) with hepatitis B surface antigen (HBsAg), and two of 16 (12%) without detectable anti‐HCV or HBsAg. Twenty‐three HCC patients in this study had ‘silent HBV,’ characterized by the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had SEN‐V infections.

SEN‐V DNA was detected in HCC patients most typically in those with coexistent HBV or HCV infection. SEN‐V was found in only one of seven HCC patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear to be an important cause of ‘cryptogenic’ HCC.
Sitosterolaemia in Switzerland: molecular genetics links the US Amish‐Mennonites to their European roots
Authors: Solcà C , Stanga Z , Pandit B , Diem P , Greeve J , Patel SB
Published: July 2005

Sitosterolaemia is a rare autosomal recessive disease characterized by increased intestinal absorption of plant sterols, decreased hepatic excretion into bile and elevated concentrations in plasma phytosterols. Homozygous or compound heterozygous loss of function mutations in either of the ATP‐binding cassette (ABC) proteins ABCG5 and ABCG8 explain the increased absorption of plant sterols. Here we report a Swiss index patient with sitosterolaemia, who presented with the classical symptoms of xanthomas, but also had mitral and aortic valvular heart disease. Her management over the last 20 years included a novel therapeutic approach of high‐dose cholesterol feeding that was semi‐effective. Mutational and extended haplotype analyses showed that our patient shared this haplotype with that of the Amish‐Mennonite sitosterolaemia patients, indicating they are related ancestrally.
Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart‐hand syndrome?
Authors: Šinkovec M , Petrovič D , Volk M , Peterlin B
Published: July 2005

We identified a family with 10 affected members in four generations suffering from adult‐onset progressive sinoatrial and atrioventricular conduction disease, sudden death due to ventricular tachyarrhythmia, dilated cardiomyopathy, and a unique type of brachydactyly with mild hand involvement (short distal, middle, proximal phalanges and clinodactyly) and more severe foot involvement (short distal, proximal phalanges and metatarsal bones, short or absent middle phalanges, terminal symphalangism, duplication of the bases of the second metatarsals, extra ossicles, and syndactyly). The phenotype differences from other reported genetic abnormalities and linkage exclusion of Holt–Oram syndrome, ulnar–mammary syndrome, brachydactyly type B or Robinow syndrome, and cardiac conduction disease or Brugada syndrome loci suggest that we report on a new hereditary heart‐hand syndrome.
Genetic regulation of stem cell origins in the mouse embryo
Authors: Ralston A , Rossant J
Published: July 2005

‘Stem cell’ has practically become a household term, but what is a stem cell and where does it come from? Insight into these questions has come from the early mouse embryo, or blastocyst, from which three kinds of stem cells have been derived: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extraembryonic endoderm (XEN) cells. These stem cells appear to derive from three distinct tissue lineages within the blastocyst: the epiblast, the trophectoderm, and the extraembryonic endoderm. Understanding how these lineages arise during development will illuminate efforts to understand the establishment and maintenance of the stem cell state and the mechanisms that restrict stem cell potency. Genetic analysis has enabled the identification of several genes important for lineage decisions in the mouse blastocyst. Among these, Oct4, Nanog, Cdx2, and Gata6 encode transcription factors required for the three lineages of the blastocyst and for the maintenance their respective stem cell types. Interestingly, genetic manipulation of several of these factors can cause lineage switching among these stem cells, suggesting that knowledge of key lineage‐determining genes could help control differentiation of stem cells more generally. Pluripotent stem cells have also been isolated from the human blastocyst, but the relationship between these cells and stem cells of the mouse blastocyst remains to be explored. This review describes the genetic regulation of lineage allocation during blastocyst formation and discusses similarities and differences between mouse and human ES cells.