bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of Proliferative Defects Associated with Processing-defective Lamin A Mutants by hTERT or Inactivation of p53
Authors: Kudlow Brian A. , Stanfel Monique N. , Burtner Christopher R. , Johnston Elijah D. , Kennedy Brian K.
Published: October 2008

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, debilitating disease with early mortality and rapid onset of aging-associated pathologies. It is linked to mutations in LMNA, which encodes A-type nuclear lamins. The most frequent HGPS-associated LMNA mutation results in a protein, termed progerin, with an internal 50 amino acid deletion and, unlike normal A-type lamins, stable farnesylation. The cellular consequences of progerin expression underlying the HGPS phenotype remain poorly understood. Here, we stably expressed lamin A mutants, including progerin, in otherwise identical primary human fibroblasts to compare the effects of different mutants on nuclear morphology and cell proliferation. We find that expression of progerin leads to inhibition of proliferation in a high percentage of cells and slightly premature senescence in the population. Expression of a stably farnesylated mutant of lamin A phenocopied the immediate proliferative defects but did not result in premature senescence. Either p53 inhibition or, more surprisingly, expression of the catalytic subunit of telomerase (hTERT) suppressed the early proliferative defects associated with progerin expression. These findings lead us to propose that progerin may interfere with telomere structure or metabolism in a manner suppressible by increased telomerase levels and possibly link mechanisms leading to progeroid phenotypes to those of cell immortalization.
Ca2+-regulated Pool of Phosphatidylinositol-3-phosphate Produced by Phosphatidylinositol 3-Kinase C2α on Neurosecretory Vesicles
Authors: Wen Peter J. , Osborne Shona L. , Morrow Isabel C. , Parton Robert G. , Domin Jan , Meunier Frederic A.
Published: October 2008

Phosphatidylinositol-3-phosphate [PtdIns(3)P] is a key player in early endosomal trafficking and is mainly produced by class III phosphatidylinositol 3-kinase (PI3K). In neurosecretory cells, class II PI3K-C2α and its lipid product PtdIns(3)P have recently been shown to play a critical role during neuroexocytosis, suggesting that two distinct pools of PtdIns(3)P might coexist in these cells. However, the precise characterization of this additional pool of PtdIns(3)P remains to be established. Using a selective PtdIns(3)P probe, we have identified a novel PtdIns(3)P-positive pool localized on secretory vesicles, sensitive to PI3K-C2α knockdown and relatively resistant to wortmannin treatment. In neurosecretory cells, stimulation of exocytosis promoted a transient albeit large increase in PtdIns(3)P production localized on secretory vesicles sensitive to PI3K-C2α knockdown and expression of PI3K-C2α catalytically inactive mutant. Using purified chromaffin granules, we found that PtdIns(3)P production is controlled by Ca2+. We confirmed that PtdIns(3)P production from recombinantly expressed PI3K-C2α is indeed regulated by Ca2+. We provide evidence that a dynamic pool of PtdIns(3)P synthesized by PI3K-C2α occurs on secretory vesicles in neurosecretory cells, demonstrating that the activity of a member of the PI3K family is regulated by Ca2+in vitro and in living neurosecretory cells.
Posttranslational Regulation of the Scaffold for Fe-S Cluster Biogenesis, Isu
Authors: Andrew Amy J. , Song Ji-Yoon , Schilke Brenda , Craig Elizabeth A.
Published: October 2008

Isu, the scaffold protein on which Fe-S clusters are built in the mitochondrial matrix, plays a central role in the biogenesis of Fe-S cluster proteins. We report that the reduction in the activity of several components of the cluster biogenesis system, including the specialized Hsp70 Ssq1, causes a 15–20-fold up-regulation of Isu. This up-regulation results from changes at both the transcriptional and posttranslational level: an increase in ISU mRNA levels and in stability of ISU protein. Its biological importance is demonstrated by the fact that cells lacking Ssq1 grow poorly when Isu levels are prevented from rising above those found in wild-type cells. Of the biogenesis factors tested, Nfs1, the sulfur donor, was unique. Little increase in Isu levels occurred when Nfs1 was depleted. However, its presence was required for the up-regulation caused by reduction in activity of other components. Our results are consistent with the existence of a mechanism to increase the stability of Isu, and thus its level, that is dependent on the presence of the cysteine desulfurase Nfs1.
Efficient mapping of Applied Biosystems SOLiD sequence data to a reference genome for functional genomic applications
Authors: Ondov Brian D. , Varadarajan Anjana , Passalacqua Karla D. , Bergman Nicholas H.
Published: October 2008

Summary: Here, we report the development of SOCS (short oligonucleotide color space), a program designed for efficient and flexible mapping of Applied Biosystems SOLiD sequence data onto a reference genome. SOCS performs its mapping within the context of ‘color space’, and it maximizes usable data by allowing a user-specified number of mismatches. Sequence census functions facilitate a variety of functional genomics applications, including transcriptome mapping and profiling, as well as ChIP-Seq.

Availability: Executables, source code, and sample data are available at http://socs.biology.gatech.edu/

Contact:  nickbergman@gatech.edu

Supplementary information:  Supplementary data are available at Bioinformatics Online.
Systems-level modeling of cellular glycosylation reaction networks: O-linked glycan formation on natural selectin ligands
Authors: Liu Gang , Marathe Dhananjay D. , Matta Khushi L. , Neelamegham Sriram
Published: October 2008

Motivation: The emerging field of Glycomics requires the development of systems-based modeling strategies to relate glycosyltransferase gene expression and enzyme activity with carbohydrate structure and function.

Results: We describe the application of object oriented programming concepts to define glycans, enzymes, reactions, pathways and compartments for modeling cellular glycosylation reaction networks. These class definitions are combined with current biochemical knowledge to define potential reaction networks that participate in the formation of the sialyl Lewis-X (sLeX) epitope on O-glycans linked to a leukocyte cell-surface glycoprotein, P-selectin Glycoprotein Ligand-1 (PSGL-1). Subset modeling, hierarchical clustering, principal component analysis and adjoint sensitivity analysis are applied to refine the reaction network and to quantify individual glycosyltransferase rate constants. Wet-lab experiments validate estimates from computer modeling. Such analysis predicts that sLeX expression varies directly with sialyltransferase α2,3ST3Gal-IV expression and inversely with α2,3ST3Gal-I/II.

Availability: SBML files for all converged models are available at http://www.eng.buffalo.edu/~neel/bio_reaction_network.html

Contact:  neel@eng.buffalo.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
CNVDetector: locating copy number variations using array CGH data
Authors: Chen Peng-An , Liu Hsiao-Fei , Chao Kun-Mao
Published: October 2008

Summary: CNVDetector is a program for locating copy number variations (CNVs) in a single genome. CNVDetector has several merits: (i) it can deal with the array comparative genomic hybridization data even if the noise is not normally distributed; (ii) it has a linear time kernel; (iii) its parameters can be easily selected; (iv) it evaluates the statistical significance for each CNV calling.

Availability: CNVDetector (for Windows platform) can be downloaded from http:www.csie.ntu.edu.tw/~kmchao/tools/CNVDetector/. The manual of CNVDetector is also available.

Contact:  kmchao@csie.ntu.edu.tw

Supplementary information:  Supplementary data are available at Bioinformatics online.
A novel method for comparing topological models of protein structures enhanced with ligand information
Authors: Veeramalai Mallika , Gilbert David
Published: October 2008

We introduce TOPS+ strings, a highly abstract string-based model of protein topology that permits efficient computation of structure comparison, and can optionally represent ligand information. In this model, we consider loops as secondary structure elements (SSEs) as well as helices and strands; in addition we represent ligands as first class objects. Interactions between SSEs and between SSEs and ligands are described by incoming/outgoing arcs and ligand arcs, respectively; and SSEs are annotated with arc interaction direction and type. We are able to abstract away from the ligands themselves, to give a model characterized by a regular grammar rather than the context sensitive grammar of the original TOPS model. Our TOPS+ strings model is sufficiently descriptive to obtain biologically meaningful results and has the advantage of permitting fast string-based structure matching and comparison as well as avoiding issues of Non-deterministic Polynomial time (NP)-completeness associated with graph problems. Our structure comparison method is computationally more efficient in identifying distantly related proteins than BLAST, CLUSTALW, SSAP and TOPS because of the compact and abstract string-based representation of protein structure which records both topological and biochemical information including the functionally important loop regions of the protein structures. The accuracy of our comparison method is comparable with that of TOPS. Also, we have demonstrated that our TOPS+ strings method out-performs the TOPS method for the ligand-dependent protein structures and provides biologically meaningful results.

Availability: The TOPS+ strings comparison server is available from http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/topsplus.html.

Contact:  mallikav@burnham.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
A better block partition and ligation strategy for individual haplotyping
Authors: Zhao Yuzhong , Xu Yun , Wang Zhihao , Zhang Hong , Chen Guoliang
Published: October 2008

Motivation: Haplotype played an important role in the association studies of disease gene and drug responsivity over the past years, but the low throughput of expensive biological experiments largely limited its application. Alternatively, some efficient statistical methods were developed to deduce haplotypes from genotypes directly. Because these algorithms usually needed to estimate the frequencies of numerous possible haplotypes, the partition and ligation strategy was widely adopted to reduce the time complexity. The haplotypes were usually partitioned uniformly in the past, but recent studies showed that the haplotypes had their own block structure, which may be not uniform. More reasonable block partition and ligation strategy according to the haplotype structure may further improve the accuracy of individual haplotyping.

Results: In this article, we presented a simple algorithm for block partition and ligation, which provided better accuracy for individual haplotyping. The block partition and ligation could be completed within O(m2 logm+m2n) time complexity, where m represented the length of genotypes and n represented the number of individuals. We tested the performance of our algorithm on both real and simulated dataset. The result showed that our algorithm yielded better accuracy with short running time.

Availability: The software is publicly available at http://mail.ustc.edu.cn/~zyzh.

Contact:  xuyun@ustc.edu.cn
The Burkholderia Genome Database: facilitating flexible queries and comparative analyses
Authors: Winsor Geoffrey L. , Khaira Bhavjinder , Van Rossum Thea , Lo Raymond , Whiteside Matthew D. , Brinkman Fiona S. L.
Published: October 2008

Summary: As the genome sequences of multiple strains of a given bacterial species are obtained, more generalized bacterial genome databases may be complemented by databases that are focused on providing more information geared for a distinct bacterial phylogenetic group and its associated research community. The Burkholderia Genome Database represents a model for such a database, providing a powerful, user-friendly search and comparative analysis interface that contains features not found in other genome databases. It contains continually updated, curated and tracked information about Burkholderia cepacia complex genome annotations, plus other Burkholderia species genomes for comparison, providing a high-quality resource for its targeted cystic fibrosis research community.

Availability:  http://www.burkholderia.com. Source code: GNU GPL.

Contact:  brinkman@sfu.ca.
Faster exact Markovian probability functions for motif occurrences: a DFA-only approach
Authors: Ribeca Paolo , Raineri Emanuele
Published: October 2008

Background: The computation of the statistical properties of motif occurrences has an obviously relevant application: patterns that are significantly over- or under-represented in genomes or proteins are interesting candidates for biological roles. However, the problem is computationally hard; as a result, virtually all the existing motif finders use fast but approximate scoring functions, in spite of the fact that they have been shown to produce systematically incorrect results. A few interesting exact approaches are known, but they are very slow and hence not practical in the case of realistic sequences.

Results: We give an exact solution, solely based on deterministic finite-state automata (DFA), to the problem of finding the whole relevant part of the probability distribution function of a simple-word motif in a homogeneous (biological) sequence. Out of that, the z-value can always be computed, while the P-value can be obtained either when it is not too extreme with respect to the number of floating-point digits available in the implementation, or when the number of pattern occurrences is moderately low. In particular, the time complexity of the algorithms for Markov models of moderate order (0≤m≤2) is far better than that of Nuel, which was the fastest similar exact algorithm known to date; in many cases, even approximate methods are outperformed.

Conclusions: DFA are a standard tool of computer science for the study of patterns; previous works in biology propose algorithms involving automata, but there they are used, respectively, as a first step to write a generating function, or to build a finite Markov-chain imbedding (FMCI). In contrast, we directly rely on DFA to perform the calculations; thus we manage to obtain an algorithm which is both easily interpretable and efficient. This approach can be used for exact statistical studies of very long genomes and protein sequences, as we illustrate with some examples on the scale of the human genome.

Contact:  paolo.ribeca@gmail.com
Stochastic dynamics of genetic networks: modelling and parameter identification
Authors: Cinquemani Eugenio , Milias-Argeitis Andreas , Summers Sean , Lygeros John
Published: October 2008

Motivation: Identification of regulatory networks is typically based on deterministic models of gene expression. Increasing experimental evidence suggests that the gene regulation process is intrinsically random. To ensure accurate and thorough processing of the experimental data, stochasticity must be explicitly accounted for both at the modelling stage and in the design of the identification algorithms.

Results: We propose a model of gene expression in prokaryotes where transcription is described as a probabilistic event, whereas protein synthesis and degradation are captured by first-order deterministic kinetics. Based on this model and assuming that the network of interactions is known, a method for estimating unknown parameters, such as synthesis and binding rates, from the outcomes of multiple time-course experiments is introduced. The method accounts naturally for sparse, irregularly sampled and noisy data and is applicable to gene networks of arbitrary size. The performance of the method is evaluated on a model of nutrient stress response in Escherichia coli.

Contact:  cinquemani@control.ee.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
FABSIM: a software for generating F
ST distributions with various ascertainment biases
Authors: Ramírez-Soriano Anna , Calafell Francesc
Published: October 2008

Summary: We have developed a software that applies ascertainment bias on simulated DNA sequences and calculates FST on them, so they can be used to generate neutral distributions that are appropriate to test whether the genetic differentiation of a particular gene between populations is compatible with neutral evolution, or, on the contrary, suggests local adaptation by natural selection.

Availability: FABSIM is available from http://www.snpator.com/public/downloads/aRamirez/FABSIM/.

Contact:  francesc.calafell@upf.edu.

Supplementary information:  Supplementary data are available at Bioinformatics online. The data from which figures are built can be dowloaded from http://www.snpator.com/public/downloads/aRamirez/.
An International Comparison of Attitudes Toward Traditional and Modern Medicine in a Chinese and an American Clinic Setting
Authors: Burke Adam , Kuo Tony , Harvey Rick , Wang Jun
Published: October 2008

Introduction. International comparative research on traditional medicine (TM) offers a useful method for examining differences in patient characteristics and can provide insight into: (i) more universal characteristics which may cross cultures and international borders; (ii) unique characteristics influenced by regional/national factors; and (iii) cultural values of immigrant populations. To explore these issues TM patients from the United States and China were compared. Methods. Data collection took place at two TM college clinics. A convenience sample of 128 patients in China and 127 patients in the United States completed a 28‐item questionnaire. Results. There was a marked similarity between the two patient groups in terms of the biological characteristics of age and gender. Musculoskeletal issues were the most common presenting complaints in the United States; while in China TM was used for a more diverse array of conditions. The majority of patients in both countries had initially used allopathic medicine (AM); significantly, more of the United States respondents stopped allopathic treatment after beginning traditional treatment. In comparing the two countries, patients in China were significantly more satisfied with AM and American patients significantly more satisfied with TM. In comparing the two medicines, the patient samples in both countries were significantly more satisfied with TM than AM. Discussion. Although treatment often originated with allopathic providers, many patients sought alternatives presumably to find the best solution to their problems. This tendency toward self‐assignment suggests that a pluralistic healthcare system may provide the greatest satisfaction resulting from personal choice and improved outcomes.
OSPAR Ecological Quality Objectives: the utility of health indicators for the North Sea
Authors: Heslenfeld Peter , Enserink E. Lisette
Published: October 2008

Heslenfeld, P., and Enserink, E. L. 2008. OSPAR Ecological Quality Objectives: the utility of health indicators for the North Sea. – ICES Journal of Marine Science, 65: 1392–1397. Committed to the ecosystem approach to management, OSPAR has accumulated 15 years of experience in developing a conceptual framework for ecological indicators and objectives, and in applying the framework to the North Sea as a test case. These Ecological Quality Objectives (EcoQOs) have become a model for the implementation of the new European Marine Strategy Framework Directive. We describe the history of EcoQO development, its current status, and future needs. We also present our positive and negative experiences in developing the approach, and conclude that regional sea conventions and marine research institutes in Europe should join forces to accelerate the development of ecosystem indicators and objectives, using existing concepts.
Use of a Phytoplankton Community Index to assess the health of coastal waters
Authors: Tett P. , Carreira C. , Mills D. K. , van Leeuwen S. , Foden J. , Bresnan E. , Gowen R. J.
Published: October 2008

Tett, P., Carreira, C., Mills, D. K., van Leeuwen, S., Foden, J., Bresnan, E., and Gowen, R. J. 2008. Use of a Phytoplankton Community Index to assess the health of coastal waters. – ICES Journal of Marine Science, 65: 1475–1482. Monitoring of marine-ecosystem status and health requires indicators of community structure and function. As a structural indicator, we propose a Phytoplankton Community Index (PCI) based on the abundance of “life-forms” such as “pelagic diatoms” or “medium-sized autotrophic dinoflagellates”. To calculate the PCI, data showing seasonal variation in these abundances are plotted in “life-form space” of two or more dimensions. Data from a “type-specific reference condition” are then enclosed within a reference envelope. Comparison data are plotted into the same coordinate system, and the PCI is the proportion (between 0 and 1) of these new data that fall within the reference envelope. Results from initial applications of this method are shown for UK coastal waters in the northern North Sea (near Stonehaven), a Scottish fjord (Loch Creran), and the eastern Irish Sea (including Liverpool Bay). The Stonehaven data (1997–2005) were used to compare values obtained from weekly sampling with those from monthly sampling. A spatial comparison between more- and less-nutrient-enriched waters in the eastern Irish Sea (1991–2003) showed little difference in phytoplankton community structure. Loch Creran has experienced a large change in the “balance of organisms”, and hence a reduction in the PCI, between 1979–1981 and 2006/2007, associated with a decrease in chlorophyll but no apparent change in nutrients. These results are discussed in relation to the intended uses of the PCI as an index of biological quality for the Water Framework Directive (WFD) and an index of ecosystem health in the context of eutrophication. Although the method only measures change, it can also be used as an indicator of biological quality if the reference conditions are those defined for a WFD waterbody, and as an indicator of health if appropriately calibrated. Suggestions are made for further development.
Movement patterns of four coral reef fish species in a fragmented habitat in New Caledonia: implications for the design of marine protected area networks
Authors: Chateau Olivier , Wantiez Laurent
Published: October 2008

Chateau, O., and Wantiez, L. 2009. Movement patterns of four coral reef fish species in a fragmented habitat in New Caledonia: implications for the design of marine protected area networks. – ICES Journal of Marine Science, 66: 50–55. Acoustic telemetry was used to examine the patterns of fish movements between a marine reserve and two unprotected reefs separated by large areas of lagoon soft bottoms (900–2000 m) in the South Lagoon Marine Park of New Caledonia. Four commercial fish species (Epinephelus maculatus, Plectropomus leopardus, Chlorurus microrhinos, and Scarus ghobban) were studied for 17 months (45 fish). Nine fish (20%) were detected on reefs other than the reef onto which they were released. Four patterns of inter-reef movement were identified during the survey, including home range relocations, movements larger than the scale of the study, many inter-reef movements within the study area, and punctual excursions outside the daily home range. The information gathered in this study demonstrates the ability of the fish to carry out medium-scale movements in a fragmented habitat. Consequently, the effectiveness of the reserve to protect the entire population is probably limited for these species. Because all the identified patterns implied at least one movement across the reserve boundaries, our results support the hypothesis that the Larégnère Marine Reserve, part of the South Lagoon Marine Park, could benefit the adjacent fished area through spillover.
Lack of Correlation Between Fecal Elastase‐1 Levels and Fecal Nitrogen Excretion in Preterm Infants
Authors: Corvaglia Luigi , Paoletti Vittoria , Battistini Barbara , Simoni Patrizia , Faldella Giacomo
Published: October 2008

We measured fecal elastase‐1 (FE1) levels in 34 preterm newborns (15 small‐for‐gestational‐age and 19 appropriate‐for‐gestational‐age) during the first 2 months of life and evaluated whether they were correlated with nitrogen loss in stools. FE1 increased over time, and values were similar in both groups of newborns. Fecal nitrogen was significantly higher in small‐for‐gestational‐age infants. There was no correlation between FE1 levels and fecal nitrogen excretion. Pancreatic proteolytic function was efficient at an early stage in enterally fed preterm newborns. Despite the similar FE1 values, fecal nitrogen loss was significantly higher in small‐for‐gestational‐age preterm infants than in appropriate‐for‐gestational‐age preterm infants.
Comparison of a Novel Whole Blood Transglutaminase‐based ELISA With a Whole Blood Rapid Antibody Test and Established Conventional Serological Celiac Disease Assays
Authors: Raivio Tiina , Korponay‐Szabó Ilma R , Paajanen Tuula , Ashorn Merja , Iltanen Sari , Collin Pekka , Laurila Kaija , Nemes Éva , Kovács Judit B , Carrard Géraldine , Saramäki Mika , Mäki Markku , Kaukinen Katri
Published: October 2008

Objectives:

Serum immunoglobulin A–class tissue transglutaminase (tTG‐ab) and endomysial antibody (EMA) tests play a key role in the diagnostic evaluation of celiac disease. Recently, a novel whole blood rapid test based on self‐tissue transglutaminase (tTG) was developed for celiac disease case finding. Based on the same principle, a whole blood self‐tTG enzyme‐linked immunosorbent assay (ELISA), especially applicable to large‐scale screening of celiac disease, has been produced. We assessed the value of this new test in celiac disease antibody detection.

Patients and Methods:

The new test uses endogenous tTG found in red blood cells of whole blood in IgA‐class tTG‐ab measurement by detecting tTG–tTG‐ab complexes formed after hemolysis of the whole blood sample. Stored whole blood samples from 150 untreated celiac disease patients and 107 control individuals without celiac disease were evaluated, and the test results were compared with those of the whole blood rapid test, 2 conventional serum‐based tTG‐ab ELISA tests, and 2 EMA tests.

Results:

A total of 15 whole blood samples were found to be clotted or dried after storage and were excluded from further evaluation. The whole blood ELISA test had a specificity (98%) comparable to that of the conventional serological tests, the sensitivity (91%) being slightly lower. The test was concordant with the whole blood rapid test in 92% of cases, with 2 serological ELISA tests in 91% and 94% of cases and with EMA tests in 94% and 93% of cases.

Conclusions:

Whole blood self‐tTG–based testing is accurate in celiac antibody detection, also when an ELISA method is applied. The testing requires no serum separation or external tTG.
Long‐Term Outcome in Patients With Short Bowel Syndrome After Longitudinal Intestinal Lengthening and Tailoring
Authors: Reinshagen K , Kabs C , Wirth H , Hable N , Brade J , Zahn K , Hagl C , Jester I , Waag KL
Published: October 2008

Objectives:

Longitudinal intestinal lengthening and tailoring (LILT) is a well‐established surgical treatment for short bowel syndrome. It has been shown to enhance peristalsis, decrease bacterial overgrowth, and extend mucosal contact time for nutrients. We present the results of a long‐term follow‐up of patients who underwent LILT and define prognostic parameters for the survival of these patients.

Patients and Methods:

Between 1987 and 2006, 53 patients underwent LILT in our institution. The main diagnoses were gastroschisis, intestinal volvulus, intestinal atresias, and necrotizing enterocolitis. LILT was performed at a mean age of 24 months (range 4−144 months). The follow‐up time was 79.76 months (range 6−234 months).

Results:

After LILT, 41 of 53 patients survived, and 36 of 41 surviving patients were successfully weaned from parenteral nutrition (PN). In long‐term follow‐up 79% stayed free of PN. The overall survival rate was 77.36%. Weight gain occurred in 58% of the patients after LILT. The quality of life after LILT is on a high level, with most patients having normal physical strength and participating in normal social life and education. Prognostic factors for survival after LILT in short bowel syndrome are length of small intestine (0.06582 + 0.0131 × bowel cm), length of large bowel (P = 0.039), preoperative liver function, and successful weaning from PN within 18 months postoperatively (P = 0.0032).

Conclusions:

Patients undergoing LILT in short bowel syndrome have a high survival rate, weight gain, and a high quality of life. Autologous gastrointestinal reconstruction remains therefore the first choice in the treatment of patients with short bowel syndrome.
A Dietary Fiber Mixture versus Lactulose in the Treatment of Childhood Constipation: A Double‐blind Randomized Controlled Trial
Authors: Kokke Freddy TM , Scholtens Petra AMJ , Alles Martine S , Decates Tom S , Fiselier Theo JW , Tolboom Jules JM , Kimpen Jan LL , Benninga Marc A
Published: October 2008

Background:

Constipation is a common problem in children. As first‐line treatment, increased dietary fiber is often advocated. To our knowledge, however, no large studies evaluating the effect of dietary fibers in childhood constipation have been published.

Patients and Methods:

A randomized, double‐blind, prospective controlled study was performed. Patients received either a fiber mixture or lactulose in a yogurt drink. After a baseline period of 1 week, patients were treated for 8 weeks followed by 4 weeks of weaning. Polyethylene glycol 3350 was added if no clinical improvement was observed after 3 weeks. Using a standardized bowel diary, parents recorded defecation frequency during the treatment period. In addition, incontinence frequency, stool consistency, presence of abdominal pain and flatulence, necessity for step‐up medication, and dry weight of feces were recorded, as were adverse effects.

Results:

A total of 147 children were eligible; 12 children wished not to participate. Of the remaining children, 65 were randomized to treatment with fiber mixture and 70 to treatment with lactulose. In all, 97 children completed the study. No difference was found between the groups after the treatment period concerning defecation frequency (P = 0.481) and fecal incontinence frequency (P = 0.084). However, consistency of stools was softer in the lactulose group (P = 0.01). Abdominal pain and flatulence scores were comparable (P = 0.395 and P = 0.739, respectively). The necessity of step‐up medication during the treatment period was comparable (P = 0.996), as were taste scores (P = 0.657). No serious adverse effects were registered.

Conclusions:

A fluid fiber mixture and lactulose give comparable results in the treatment of childhood constipation.
Ferrous Gluconate and Ferrous Sulfate Added to a Complementary Food Distributed by the Mexican Nutrition Program Oportunidades Have a Comparable Efficacy to Reduce Iron Deficiency in Toddlers
Authors: Shamah‐Levy Teresa , Villalpando Salvador , Rivera‐Dommarco Juan A , Mundo‐Rosas Verónica , Cuevas‐Nasu Lucia , Jiménez‐Aguilar Alejandra
Published: October 2008

Objective:

To assess the efficacy of ferrous sulfate (FS) and ferrous gluconate (FG) as fortificants for a complementary baby food (Nutrisano) to improve the iron status and to reduce the prevalence of anemia in toddlers.

Patients and Methods:

Toddlers 12 to 30 months old were randomly assigned to receive either of 3 versions of Nutrisano fortified with FS or FG or not fortified (CG) for 6 months. In final blood samples, the concentrations of hemoglobin, serum ferritin, and soluble transferrin receptors (sTfR) were determined. The effects of treatment on final hemoglobin, ferritin, and sTfR were assessed by multivariate analysis.

Results:

No significant changes in hemoglobin were observed within or among treatment groups. The prevalence of high sTfR decreased 7.1 percentage points in FG, increased 13.1 percentage points in FS, and increased 0.7 percentage points in CG (P > 0.05). In an interaction between treatment and total intake of Nutrisano on the concentration of ferritin, sTfR, and total iron body stores, adjusted means of serum ferritin in the medium tertiles of intake of Nutrisano for FS (P = 0.05) and in the higher and medium tertiles for FG were higher (P = 0.001), and adjusted means of sTfR were significantly lower (P < 0.001), than the respective lower tertile of intake.

Conclusions:

Fortification of Nutrisano with FG has an acceptable level of beneficial effect on markers of iron status. The satisfactory efficacy and other sensory data has led to the political decision to substitute hydrogen‐reduced iron, used formerly as a fortificant, with FG. Studies to assess the effectiveness of the reformulated Nutrisano are in order.
The Constipated Child: Is There a Correlation Between Symptoms and Manometric Findings?
Authors: Feinberg Lisa , Mahajan Lori , Steffen Rita
Published: October 2008

Purpose:

The aim of our study was to evaluate patients referred for care of chronic constipation. We compared results of the anorectal manometry studies with a patient/guardian questionnaire about the patients' constipation.

Patients and Methods:

From patients seen for constipation in the department of pediatric gastroenterology, 123 were prospectively enrolled and they completed symptom questionnaires. These patients already were treated with stool softeners, either by the referring primary care physician or by the referring gastroenterologist. Anorectal manometry was performed per standard protocol.

Results:

Of the 123 patients enrolled in the study, 57.7% were male. Patient age ranged from 0.2 to 17.8 years, and the mean age was 7.5 years. The average duration of constipation was 4.84 years. The average number of stools per week was 3.6. Average time spent in the defecation process was 13.3 minutes. The incidence of hematochezia was 30%. Delayed passage of meconium was reported in 45 of 99 patients (45.5%). Significant correlation was found between frequency of soiling and threshold for rectoanal inhibitory reflex (P = 0.029). The volume of first urge also was positively correlated with frequency of soiling (P = 0.034). There was significant correlation of withholding behavior and the maximum volume tolerated (P = 0.020). The presence of blood in stool was inversely correlated with the maximum volume tolerated (P = 0.004). No correlation was found between severity of complaints and the presence of paradoxical puborectalis contraction. Of the patients, 90.5% had paradoxical puborectalis contraction.

Conclusions:

Significant correlation was found between frequency of soiling and rectoanal inhibitory reflex, as well as soiling and volume of first urge. There was correlation between withholding behaviors and maximum volume tolerated. The presence of blood inversely correlated with maximum volume tolerated. Anorectal manometry continues to provide additional new information and to assist in managing patients with this common chronic pediatric affliction.
Outcomes After Liver Transplantation in Young Infants
Authors: Sundaram Shikha S , Alonso Estella M , Anand Ravinder ,   Study of Pediatric Liver Transplantation Research Group
Published: October 2008

Background:

Liver transplantation in infants younger than 90 days is increasingly common. These infants typically arrive for transplantation in fragile medical condition. It is commonly assumed that they may experience high complication rates, difficult postoperative courses, and poor graft and patient survival.

Objectives:

We sought to understand whether graft and patient survival rates in these young infants were lower than in older children, these patients experienced more complications than older children, and health care resource utilization was higher in this population.

Patients and Methods:

Data queried from the Study of Pediatric Liver Transplantation (SPLIT) database were limited to infants ages 0 to 90 days who had received their primary liver transplant between February 1996 and May 2004. Patients older than 90 days registered in the SPLIT database were used for comparison.

Results:

Thirty‐eight patients, ages 0 to 90 days, were included in the analysis. Their severity of illness was reflected by a median calculated Pediatric Endstage Liver Disease score of 34.8 at transplant. A majority (89.5%) of infants received cadaveric liver grafts, of which 47% were reduced organs. The infants experienced prolonged hospitalizations, spending an average of 50.9 ± 7.6 days in the hospital after transplant. Long stays in the intensive care unit (average 22.1 ± 1.5 days) and need for mechanical ventilation (average 16.2 ± 2.7 days) also occurred. Length of hospitalization, intensive care, and mechanical ventilation were significantly higher than in older children (P < 0.0001). The reoperation rate (60.5%) was high and significantly greater than in older children (P = 0.007), with 10 patients (26.3%) needing 3 or more early reoperations. Reoperations occurred for bleeding, wound complications, biliary complications, and sepsis. There was no difference in vascular or biliary tract complications compared with older children. Bacterial infections were also common (52.6%) and were seen with greater frequency than in older children (P < 0.04). This infant cohort had an overall graft survival of 76.1% and overall patient survival of 87.8% at 1 year, with median follow‐up of 12.5 months (range 0.6–84.0 months). Graft and patient survival in infants younger than 90 days was similar to that in older infants and children (P = NS).

Conclusions:

Young infants experience graft and patient survival similar to that in older cohorts of liver transplant recipients. Posttransplant complication rates, including the reoperation rate, were higher in this younger group, and the duration of hospitalization and intensive support were significantly longer. Future studies to better examine the factors, including age, that may contribute to the need for reoperation in children are warranted. Recognition and further analysis of the cost of care in this age group is also needed.
Gluten‐dependent Small Bowel Mucosal Transglutaminase 2–specific IgA Deposits in Overt and Mild Enteropathy Coeliac Disease
Authors: Koskinen Outi , Collin Pekka , Korponay‐Szabo Ilma , Salmi Teea , Iltanen Sari , Haimila Katri , Partanen Jukka , Mäki Markku , Kaukinen Katri
Published: October 2008

Objectives:

In coeliac disease, immunoglobulin (Ig)A–class autoantibodies against transglutaminase‐2 are produced in the small intestinal mucosa, where they are deposited extracellularly. It remains unclear whether positive intestinal transglutaminase‐2‐targeted IgA deposits in subjects having normal small bowel mucosal morphology are signs of early‐stage coeliac disease. We evaluated the gluten dependency of these deposits in overt and mild enteropathy coeliac disease.

Patients and Methods:

All together 48 subjects suspected of coeliac disease but having normal small bowel mucosal villi were enrolled; 28 of them had latent coeliac disease. The remaining 20 having positive intestinal IgA deposits adopted a gluten‐free diet before villous atrophy had developed. For comparison, 13 patients with overt coeliac disease and 42 noncoeliac controls were studied. Small bowel mucosal transglutaminase‐2–specific autoantibodies were compared with villous morphology, intraepithelial lymphocyte densities, and serum coeliac autoantibodies.

Results:

Intestinal IgA deposits were seen in all but 1 of the patients with latent coeliac disease, when the morphology was still intact; the intensity of these deposits increased as villous atrophy developed and decreased again on a gluten‐free diet. In 20 patients with intestinal IgA deposits in normal villi, the intensity of the deposits decreased with the diet similarly to that seen in patients with overt coeliac disease. Mucosal IgA deposits were seen initially only in 5% of noncoeliac controls and in 8% after extended gluten consumption.

Conclusions:

The response of small bowel mucosal transglutaminase‐2–specific IgA deposits for dietary intervention was similar in overt and mild enteropathy coeliac disease. Detection of such IgA deposits thus offers a good diagnostic tool to uncover early‐stage coeliac disease.
Diversity and depletions in continental carnivore guilds: implications for prioritizing global carnivore conservation
Authors: Dalerum F , Cameron E.Z , Kunkel K , Somers M.J
Published: October 2008

Large carnivores are important ecosystem components but are extinction prone due to small populations, slow growth rates and large area requirements. Consequently, there has been a surge of carnivore conservation efforts. Such efforts typically target local populations, with limited attention to the effects on the ecosystem function of predator guilds. Also, there is no framework for prioritizing these efforts globally. We compared taxonomic and functional diversity of continental carnivore guilds, compared them with the corresponding guilds during the Late Pleistocene and synthesized our results into suggestions for global prioritizations for carnivore conservation. Recent extinctions have caused taxonomically and functionally depleted carnivore guilds in Europe and North and South America, contrasting with guilds in Africa and Asia, which have retained a larger proportion of their carnivores. However, Asia is at higher risk of suffering further extinctions than other continents. We suggest three priorities of contrasting urgency for global carnivore conservation: (i) to promote recovery of the threatened Asian species, (ii) to prevent species in the depleted guilds in Europe and North and South America from becoming threatened, and (iii) to reconstruct functionally intact sympatric guilds of large carnivores at ecologically effective population sizes.
Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history
Authors: Kim Philip M. , Lam Hugo Y.K. , Urban Alexander E. , Korbel Jan O. , Affourtit Jason , Grubert Fabian , Chen Xueying , Weissman Sherman , Snyder Michael , Gerstein Mark B.
Published: October 2008

Segmental duplications (SDs) are operationally defined as >1 kb stretches of duplicated DNA with high sequence identity. They arise from copy number variants (CNVs) fixed in the population. To investigate the formation of SDs and CNVs, we examine their large-scale patterns of co-occurrence with different repeats. Alu elements, a major class of genomic repeats, had previously been identified as prime drivers of SD formation. We also observe this association; however, we find that it sharply decreases for younger SDs. Continuing this trend, we find only weak associations of CNVs with Alus. Similarly, we find an association of SDs with processed pseudogenes, which is decreasing for younger SDs and absent entirely for CNVs. Next, we find that SDs are significantly co-localized with each other, resulting in a highly skewed “power-law” distribution and chromosomal hotspots. We also observe a significant association of CNVs with SDs, but find that an SD-mediated mechanism only accounts for some CNVs (<28%). Overall, our results imply that a shift in predominant formation mechanism occurred in recent history: ∼40 million years ago, during the “Alu burst” in retrotransposition activity, non-allelic homologous recombination, first mediated by Alus and then the by newly formed CNVs themselves, was the main driver of genome rearrangements; however, its relative importance has decreased markedly since then, with proportionally more events now stemming from other repeats and from non-homologous end-joining. In addition to a coarse-grained analysis, we performed targeted sequencing of 67 CNVs and then analyzed a combined set of 270 CNVs (540 breakpoints) to verify our conclusions.
Symmetry determination following structure solution inP1
Authors: Palatinus L. , van der Lee A.
Published: October 2008

A new method for space-group determination is described. It is based on a symmetry analysis of the structure-factor phases resulting from a structure solution in space groupP1. The output of the symmetry analysis is a list of all symmetry operations compatible with the lattice. Each symmetry operation is assigned a symmetry agreement factor that is used to select the symmetry operations that are the elements of the space group of the structure. On the basis of the list of the selected operations the complete space group of the structure is constructed. The method is independent of the number of dimensions, and can also be used in solution of aperiodic structures. A number of cases are described where this method is particularly advantageous compared with the traditional symmetry analysis.
Factors affecting seasonal variations in demersal fish assemblages at an ecocline in a tropical–subtropical estuary
Authors: Barletta M. , Amaral C. S. , Corrêa M. F. M. , Guebert F. , Dantas D. V. , Lorenzi L. , Saint‐Paul U.
Published: October 2008

Seasonal changes of fish species composition in terms of biomass, density and number of species in three areas of the main channel of the Paranaguá Estuary (axis east–west) are described in relation to seasonal fluctuations in salinity, water temperature and dissolved oxygen in the main channel. Two hundred and thirty‐four samples were collected monthly, between July 2000 and June 2001, in the main channel. Seventy‐nine species of 29 families were captured with a total estimated mean density and biomass of 1513 individuals ha−1 and 34 kg ha−1, respectively. The number of species and total mean density differed significantly among areas and seasons, but the total mean biomass differed only significantly throughout the ecocline (areas) of the Paranaguá Estuary. For the most abundant species, the mean densities of Stellifer rastrifer, Aspistor luniscutis, Menticirrhus americanus, Sphoeroides testudineus, Cynoscion leiarchus and Symphurus tesselatus (with the exception of Cathorops spixii and Genidens genidens) differed significantly among seasons. The mean biomass of these species, with the exception of G. genidens, S. rastrifer, A. luniscutis and S. testudineus, also differed significantly for the factor seasons. Area was a significant factor for the eight most abundant species (density and biomass), except S. testudineus (density), G. genidens, C. leiarchus and S. tesselatus (biomass). The season v. area interaction term was significant for C. leiarchus (density). Most of these differences occurred during the rainy season when fishes concentrated principally in the middle of the estuary, where the salinity remained stable. It is suggested that the salinity stability in the middle of the estuary is the main reason why the most estuarine resident fish species move downstream and remain there, regardless of the increased freshwater runoff. Moreover, canonical correspondent analysis output detected that during the late rainy season, the variable dissolved oxygen (P < 0·01) was the most important environmental variable, responsible for structuring patterns of fishes assemblages in the west–east axis of Paranaguá Estuary. During the end of the dry season, both salinity (P < 0·01) and dissolved oxygen (P < 0·05) were responsible for this ecological feature in the estuary. Finally, it was possible to detect that juveniles and adults of some important species respond differently to seasonal fluctuations of the ecocline‐determining environmental factors. This behaviour is suggested as a strategy to avoid competition and predation during the rainy season in the middle estuary. The Paranaguá Estuary did not fit with the pre‐existing models described in the tropical and subtropical estuarine fish literature since its main channel fish assemblages remained within its bounds even during the rainy season.