bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Reproductive Isolation between Sympatric Lineages of Fall Chinook Salmon in White Salmon River, Washington
Authors: Smith Christian T. , Engle Rod
Published: June 2011

Populations of fall Chinook salmon Oncorhynchus tshawytscha in the Columbia River are divided among two evolutionarily significant units: lower Columbia River fall Chinook salmon (or “tules”) in the lower portion of the river and upriver “brights” (URBs) in the upper portion. The two lineages migrate together through portions of the lower Columbia River but spawn allopatrically. Little White Salmon National Fish Hatchery has been releasing URBs adjacent to what was historically exclusively tule spawning habitat in the White Salmon River for approximately 22 years. Tules and URBs now spawn in sympatry in the adjacent White Salmon River, and potential introgression between these two lineages has been identified as a genetic risk of the hatchery program. To assess the extent of introgression, we analyzed 13 microsatellite loci in juveniles taken from the White Salmon River in three consecutive years. Assignment tests revealed that juveniles leaving the White Salmon River from March to early May resembled tules, while those leaving from late May to June resembled URBs. Model‐based hybrid detection revealed that between 4.3% and 15.0% of the juveniles in each year were tule × URB hybrids. No hybrid adults were detected in any of the collections examined. The divergence between the tule and URB populations in the White Salmon River was comparable to that between allopatric populations representing the two lineages. Although hybrid juveniles are produced in the wild, we found no evidence that they survive to return as adults or successfully cross back into the parental populations. The separation between the two fall Chinook salmon lineages thus appears to be based on intrinsic as well as extrinsic factors.
Population Genetic Structure and Life History Variability inOncorhynchus nerkafrom the Snake River Basin
Authors: Waples Robin S. , Aebersold Paul B. , Winans Gary A.
Published: June 2011

We used the variation at 64 allozyme loci to examine genetic relationships among 32 samples of sockeye salmonOncorhynchus nerkaand kokanee (resident sockeye salmon) from the Snake River basin and other North American locations. The genetic differentiation among populations was pronounced: Wright'sFSTwas higher (0.244) than has been reported in any other study of Pacific salmon. A detailed examination of theO. nerkafrom lakes in the Sawtooth Valley of Idaho was undertaken to help guide recovery planning for the endangered Redfish Lake population and to help resolve the relationships between the resident and anadromous forms. In Redfish Lake, adult sockeye salmon that returned in 1991–1993 were genetically distinct from local kokanee but similar to a small group of “residual” sockeye salmon discovered in the lake in 1992. This result is consistent with the hypothesis that the original sockeye salmon population was not extirpated by Sunbeam Dam early in this century. Populations ofO. nerkathat appear to be native to the Snake River were also found in Alturas Lake, Stanley Lake, and Warm Lake, although the latter two lakes also showed evidence of nonnative gene pools. Kokanee sampled from Pettit Lake are clearly the result of an introduction of late‐spawning kokanee from northern Idaho, and we found evidence of twoO. nerkagene pools in Wallowa Lake, both traceable to introductions of nonnative kokanee.
Single‐Nucleotide Polymorphic Genotypes Reveal Patterns of Early Juvenile Migration of Sockeye Salmon in the Eastern Bering Sea
Authors: Seeb Lisa W. , Seeb James E. , Habicht Christopher , Farley Edward V. , Utter Fred M.
Published: June 2011

We estimate patterns of nearshore migration in the eastern Bering Sea for out‐migrating Bristol Bay sockeye salmon Oncorhynchus nerka in their first year at sea. Over 3,000 juveniles were collected during the late summer of 2005–2007 as part of the Bering–Aleutian Salmon International Survey and tested with a regional genetic baseline of 45 single‐nucleotide polymorphisms. Population‐specific and westward migrations from natal rivers were evident. Populations from Wood River and northwestward predominated in the northern latitudes of Bristol Bay and the eastern Bering Sea and populations from the Egegik River and southwestward in the southern latitudes, while the populations spawning at the head of Bristol Bay had the highest proportions in the middle latitudes. These patterns were stable across years, apparently unaffected by marine productivity and temperature. This continuum of marine migratory patterns most likely reflects stable and population‐specific adaptations to buffer the distribution of dynamically shifting marine resources. As monitoring continues, these juvenile surveys will accumulate information to refine predictions of the magnitude of adult returns to their respective rivers of origin and thereby assist in the management of this valuable resource.
Spawning Habitat and Geography Influence Population Structure and Juvenile Migration Timing of Sockeye Salmon in the Wood River Lakes, Alaska
Authors: McGlauflin Molly T. , Schindler Daniel E. , Seeb Lisa W. , Smith Christian T. , Habicht Christopher , Seeb James E.
Published: June 2011

The strict homing of sockeye salmon Oncorhynchus nerka results in reproductively isolated populations that often spawn in close proximity and share rearing habitat. High spawning fidelity enables these populations to adapt to local conditions, resulting in a wide range of life history characteristics and genetic variation within individual watersheds. The Wood River system in southwestern Alaska provides a pristine, well‐studied system in which to examine fine‐scale population structure and its influences on juvenile life histories. Adult sockeye salmon spawn in lake beaches, rivers, and small tributaries throughout this watershed, and juveniles rear in five nursery lakes. We genotyped 30 spawning populations and 6,066 migrating smolts at 45 single nucleotide polymorphism loci, two of which are candidates for positive selection in the study system. We show that there is significant genetic structure (FST = 0.032) in the Wood River lakes and that divergence is generally related to spawning rather than nursery habitat (hierarchical analysis of molecular variance; P < 0.05). Four groups of populations were identified based on genetic structure and used to determine the composition of unknown mixtures of migrating smolts using a Bayesian modeling framework. We demonstrate that smolt migration timing is related to genetic structure; stream and river populations dominate catches in early June, while beach spawners and the populations in Lake Kulik are more prevalent from mid‐June to early September. Age‐2 smolts are primarily produced by the Lake Kulik and beach spawning populations, showing that genetic differences may reflect divergent freshwater and migration life history strategies. These results indicate that local adaptation to spawning habitat influences genetic divergence in the Wood River lakes, affecting both adult and juvenile life stages of sockeye salmon.
Resolving Adaptive and Demographic Divergence among Chinook Salmon Populations in the Columbia River Basin
Authors: Matala Andrew P. , Hess Jon E. , Narum Shawn R.
Published: June 2011

Chinook salmon Oncorhynchus tshawytscha in the Columbia River basin (CRB) comprise three lineages—lower Columbia River and sympatric interior ocean and stream types—each with distinct biological attributes. To evaluate the adaptive and neutral genetic variation of this species in the CRB, we genotyped 54 Chinook salmon populations using a panel of 96 single‐nucleotide polymorphism (SNP) loci. All three lineages were represented among the collections and were widely distributed across locations, ranging from the upper Salmon River to near the Columbia River estuary. Our goal was to explore local adaptation as a process shaping the population structure and genetic variation among Chinook salmon beyond the inferences possible with neutral marker data. In our analyses with putatively neutral SNPs, the population structure of Chinook salmon throughout the CRB was generally concordant with that of previous studies using microsatellites. Regression analyses and outlier methods identified 28, 17, and 29 candidate SNP loci for positive selection among stream‐type, ocean‐type, and lower‐river Chinook salmon, respectively. The candidate SNP markers were tested for association with seven environmental variables using multiple methods. We identified unambiguous markers, including nine candidates in the stream‐type lineage and seven in the ocean‐type lineage that were significantly correlated with elevation and/or temperature. The association of six candidates markers in the lower‐river lineage could not be confirmed by population structure analyses and remained ambiguous. We observed a significant association of isolation by distance for the ocean‐ and stream‐type lineages with our SNP panel; however, there was also a significant relationship between pairwise FST and several habitat variables. In all cases, the apparent adaptive variation complemented the results of demographic genetic structure but with higher resolution of population differentiation.
A Microsatellite Genome Screen Identifies Chromosomal Regions under Differential Selection in Steelhead and Rainbow Trout
Authors: Martínez Andrés , Garza John Carlos , Pearse Devon E.
Published: June 2011

Novel genetic resources now make it possible to directly assess the effects of natural selection on specific regions of the salmonid genome. Natural selection on specific genetic loci will also affect the variation in linked flanking regions through “hitchhiking” effects, causing greater differentiation between populations than would be expected from purely neutral processes. Here we identify candidate genomic regions for the effects of differential natural selection in two closely related populations of steelhead–rainbow trout Oncorhynchus mykiss separated for the last century following anthropogenic introduction above a barrier waterfall in a coastal California stream. A set of 110 expressed sequence tag (EST)‐linked and 188 anonymous microsatellite loci, most of which are mapped, were chosen to provide distributed coverage of all linkage groups in the O. mykiss genome. A genome screen was then performed to identify genomic regions under divergent selection. Multiple complementary statistical methods were used to detect outlier loci, and loci identified by more than one method were considered strong candidates for genomic regions affected by recent natural selection and genomic adaptation to the environment above the waterfall. We identified six strongly supported outlier loci, including one linked to an EST and two located in a genomic region that contains quantitative trait loci associated with egg development, spawning time, and other life history variation. Identification of regions in the genome that are potentially under selection provides valuable information about the genetic basis of selection in novel habitats and the genetic architecture of salmonid life history variation.
Relative Genetic Diversity Estimates among Four Pacific Salmonids
Authors: Campbell Nathan R. , Narum Shawn R.
Published: June 2011

The genetic diversity within a species is a reflection of its evolutionary past and ongoing mutation, drift, and adaptation. Species that occupy a diverse range of habitats and that have adapted for generations under selective pressures will carry a genetic imprint of that adaptation within specific functional genes. Alternatively, genetic diversity may be reduced owing to historical bottlenecks and genetic drift. In this study, genetic diversity was estimated in four species of Pacific salmon (rainbow trout, steelhead [anadromous rainbow trout] Oncorhynchus mykiss, Chinook salmon O. tshawytscha, coho salmon O. kisutch, and sockeye salmon, kokanee [lacustrine sockeye salmon] O. nerka) using 563–608 kilo–base pairs of DNA sequence data from 32 individuals per species. Individual samples were chosen to represent the major lineages of each species across their natural ranges. The results show the highest genetic diversity estimates for rainbow trout and the lowest for sockeye salmon. Statistically significant differences were observed between the species with the highest genetic diversity (rainbow trout) and the three remaining species. Loci with the highest genetic diversity within each species are listed as potentially being influenced by balancing selection.
Candidate Genetic Markers Associated with Anadromy in Oncorhynchus mykiss of the Klickitat River
Authors: Narum Shawn R. , Zendt Joseph S. , Frederiksen Chris , Campbell Nate , Matala Andrew , Sharp William R.
Published: June 2011

Both environmental and genetic factors influence anadromy in rainbow trout Oncorhynchus mykiss, but the genetic mechanisms that contribute to migratory selection are not well understood. In this study, we used a limited genome scan approach to identify candidate genetic markers associated with anadromy in 10 populations of O. mykiss from the Klickitat River, Washington. From an initial panel of 96 single‐nucleotide polymorphism (SNP) markers, we identified 3 SNPs that were significantly associated with anadromy after accounting for underlying population structure and selective environmental conditions. Univariate logistic regression of allele frequencies and residency/anadromy were also significant, and thus three SNPs were considered candidate markers associated with anadromy (Omy_IL6–320, Omy_LDHB‐2_i6, and Omy_ndk‐152). A multivariate logistic model was developed from the allele frequencies of these three markers to predict the potential for anadromy in natural populations. This model was applied to eight additional populations of O. mykiss to evaluate its utility. The results of this study indicate that these markers are strong candidates for association with anadromy in O. mykiss in the Klickitat River, but further testing is needed to evaluate this association across more of this species’ range. Common‐garden experiments may also help clarify the association of these candidate markers with the smoltification phenotypes of individual fish.
The failure of the fixed point property for unbounded sets in 𝑐₀
Authors: Benavides T.
Published: June 2011

In this paper we prove that for every unbounded convex closed set

C
C

in

c
0

c_0

there exists a nonexpansive mapping

T
:
C
→
C

T:C\to C

which is fixed point free. This result solves in a negative sense a question that has remained open for some time in Metric Fixed Point Theory.
Immune system simulation online
Authors: Rapin Nicolas , Lund Ole , Castiglione Filippo
Published: June 2011

Motivation: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way.

Results: We have equipped an agent-based model of the immune system with immuno-informatics methods to allow the simulation of the cardinal events of the antigenic recognition, going from single peptides to whole proteomes.

The recognition process accounts for B cell-epitopes prediction through Parker-scale affinity estimation, class I and II HLA peptide prediction and binding through position-specific scoring matrices based on information from known HLA epitopes prediction tools, and TCR binding to HLA–peptide complex calculated as the averaged sum of a residue–residue contact potential.

These steps are executed for all lymphocytes agents encountering the antigen in a wide-reaching Monte Carlo simulation.

Availability:  http://www.cbs.dtu.dk/services/C-ImmSim-10.1/

Contact:  f.castiglione@iac.cnr.it
A tree-based approach for motif discovery and sequence classification
Authors: Yan Rui , Boutros Paul C. , Jurisica Igor
Published: June 2011

Motivation: Pattern discovery algorithms are widely used for the analysis of DNA and protein sequences. Most algorithms have been designed to find overrepresented motifs in sparse datasets of long sequences, and ignore most positional information. We introduce an algorithm optimized to exploit spatial information in sparse-but-populous datasets.

Results: Our algorithm Tree-based Weighted-Position Pattern Discovery and Classification (T-WPPDC) supports both unsupervised pattern discovery and supervised sequence classification. It identifies positionally enriched patterns using the Kullback–Leibler distance between foreground and background sequences at each position. This spatial information is used to discover positionally important patterns. T-WPPDC then uses a scoring function to discriminate different biological classes. We validated T-WPPDC on an important biological problem: prediction of single nucleotide polymorphisms (SNPs) from flanking sequence. We evaluated 672 separate experiments on 120 datasets derived from multiple species. T-WPPDC outperformed other pattern discovery methods and was comparable to the supervised machine learning algorithms. The algorithm is computationally efficient and largely insensitive to dataset size. It allows arbitrary parameterization and is embarrassingly parallelizable.

Conclusions: T-WPPDC is a minimally parameterized algorithm for both pattern discovery and sequence classification that directly incorporates positional information. We use it to confirm the predictability of SNPs from flanking sequence, and show that positional information is a key to this biological problem.

Contacts:  ruiyan@cs.toronto.edu; paul.boutros@oicr.on.ca; juris@ai.toronto.edu

Availability: The algorithm, code and data are available at: http://www.cs.utoronto.ca/~juris/data/TWPPDC

Supplementary information:  Supplementary data are available at Bioinformatics online.
CHASM and SNVBox: toolkit for detecting biologically important single nucleotide mutations in cancer
Authors: Wong Wing Chung , Kim Dewey , Carter Hannah , Diekhans Mark , Ryan Michael C. , Karchin Rachel
Published: June 2011

Summary: Thousands of cancer exomes are currently being sequenced, yielding millions of non-synonymous single nucleotide variants (SNVs) of possible relevance to disease etiology. Here, we provide a software toolkit to prioritize SNVs based on their predicted contribution to tumorigenesis. It includes a database of precomputed, predictive features covering all positions in the annotated human exome and can be used either stand-alone or as part of a larger variant discovery pipeline.

Availability and Implementation: MySQL database, source code and binaries freely available for academic/government use at http://wiki.chasmsoftware.org, Source in Python and C++. Requires 32 or 64-bit Linux system (tested on Fedora Core 8,10,11 and Ubuntu 10), 2.5*≤ Python <3.0*, MySQL server >5.0, 60 GB available hard disk space (50 MB for software and data files, 40 GB for MySQL database dump when uncompressed), 2 GB of RAM.

Contact:  karchin@jhu.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Noise reduction in genome-wide perturbation screens using linear mixed-effect models
Authors: Yu Danni , Danku John , Baxter Ivan , Kim Sungjin , Vatamaniuk Olena K. , Salt David E. , Vitek Olga
Published: June 2011

Motivation: High-throughput perturbation screens measure the phenotypes of thousands of biological samples under various conditions. The phenotypes measured in the screens are subject to substantial biological and technical variation. At the same time, in order to enable high throughput, it is often impossible to include a large number of replicates, and to randomize their order throughout the screens. Distinguishing true changes in the phenotype from stochastic variation in such experimental designs is extremely challenging, and requires adequate statistical methodology.

Results: We propose a statistical modeling framework that is based on experimental designs with at least two controls profiled throughout the experiment, and a normalization and variance estimation procedure with linear mixed-effects models. We evaluate the framework using three comprehensive screens of Saccharomyces cerevisiae, which involve 4940 single-gene knock-out haploid mutants, 1127 single-gene knock-out diploid mutants and 5798 single-gene overexpression haploid strains. We show that the proposed approach (i) can be used in conjunction with practical experimental designs; (ii) allows extensions to alternative experimental workflows; (iii) enables a sensitive discovery of biologically meaningful changes; and (iv) strongly outperforms the existing noise reduction procedures.

Availability: All experimental datasets are publicly available at www.ionomicshub.org. The R package HTSmix is available at http://www.stat.purdue.edu/~ovitek/HTSmix.html.

Contact:  ovitek@stat.purdue.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
KvSNP: accurately predicting the effect of genetic variants in voltage-gated potassium channels
Authors: Stead L. F. , Wood I. C. , Westhead D. R.
Published: June 2011

Motivation: Non-synonymous single nucleotide polymorphisms (nsSNPs) in voltage-gated potassium (Kv) channels cause diseases with potentially fatal consequences in seemingly healthy individuals. Identifying disease-causing genetic variation will aid presymptomatic diagnosis and treatment of such disorders. NsSNP-effect predictors are hypothesized to perform best when developed for specific gene families. We, thus, created KvSNP: a method that assigns a disease-causing probability to Kv-channel nsSNPs.

Results: KvSNP outperforms popular non gene-family-specific methods (SNPs&GO, SIFT and Polyphen) in predicting the disease potential of Kv-channel variants, according to all tested metrics (accuracy, Matthews correlation coefficient and area under receiver operator characteristic curve). Most significantly, it increases the separation of the median predicted disease probabilities between benign and disease-causing SNPs by 26% on the next-best competitor. KvSNP has ranked 172 uncharacterized Kv-channel nsSNPs by disease-causing probability.

Availability and Implementation:KvSNP, a WEKA implementation is available at www.bioinformatics.leeds.ac.uk/KvDB/KvSNP.html.

Contact:  d.r.westhead@leeds.ac.uk

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Decomposing flux distributions into elementary flux modes in genome-scale metabolic networks
Authors: Chan Siu Hung Joshua , Ji Ping
Published: June 2011

Motivation: Elementary flux mode (EFM) is a fundamental concept as well as a useful tool in metabolic pathway analysis. One important role of EFMs is that every flux distribution can be decomposed into a set of EFMs and a number of methods to study flux distributions originated from it. Yet finding such decompositions requires the complete set of EFMs, which is intractable in genome-scale metabolic networks due to combinatorial explosion.

Results: In this article, we proposed an algorithm to decompose flux distributions into EFMs in genome-scale networks. It is an iterative scheme of a mixed integer linear program. Unlike previous optimization models to find pathways, any feasible solutions can become EFMs in our algorithm. This advantage enables the algorithm to approximate the EFM of largest contribution to an objective reaction in a flux distribution. Our algorithm is able to find EFMs of flux distributions with complex structures, closer to the realistic case in which a cell is subject to various constraints. A case of Escherichia coli growth in the Lysogeny broth (LB) medium containing various carbon sources was studied. Essential metabolites and their syntheses were located. Information on the contribution of each carbon source not obvious from the apparent flux distribution was also revealed. Our work further confirms the utility of finding EFMs by optimization models in genome-scale metabolic networks.

Contact:  joshua.chan@connect.polyu.hk

Supplementary information:  Supplementary data are available at Bioinformatics online.
AMIGO, a toolbox for advanced model identification in systems biology using global optimization
Authors: Balsa-Canto Eva , Banga Julio R.
Published: June 2011

Motivation: Mathematical models of complex biological systems usually consist of sets of differential equations which depend on several parameters which are not accessible to experimentation. These parameters must be estimated by fitting the model to experimental data. This estimation problem is very challenging due to the non-linear character of the dynamics, the large number of parameters and the frequently poor information content of the experimental data (poor practical identifiability). The design of optimal (more informative) experiments is an associated problem of the highest interest.

Results: This work presents AMIGO, a toolbox which facilitates parametric identification by means of advanced numerical techniques which cover the full iterative identification procedure putting especial emphasis on robust methods for parameter estimation and practical identifiability analyses, plus flexible capabilities for optimal experimental design.

Availability: The toolbox and the corresponding documentation may be downloaded from: http://www.iim.csic.es/~amigo

Contact:  ebalsa@iim.csic.es
Diagnostic Performance and Therapeutic Consequence of Thromboelastometry Activated by Kaolin versus a Panel of Specific Reagents
Authors: Larsen Ole Halfdan , Fenger-Eriksen Christian , Christiansen Kirsten , Ingerslev Jørgen , Sørensen Benny
Published: June 2011

Background

Thromboelastography/metry (TEG®; Haemoscope, Niles, IL/ROTEM®; Tem International GmbH, Munich, Germany) is increasingly used to guide transfusion therapy. This study investigated the diagnostic performance and therapeutic consequence of using kaolin-activated whole blood compared with a panel of specific TEM®-reagents to distinguish: dilutional coagulopathy, thrombocytopenia, hyperfibrinolysis, and heparinization.

Methods

Blood was drawn from 11 healthy volunteers. Dilutional coagulopathy was generated by 50% dilution with hydroxyethyl starch 130/0.4 whereas thrombocytopenia (mean platelet count 20 ×10⁹/l) was induced using a validated model. Hyperfibrinolysis and heparin contamination were generated by tissue plasminogen activator 2 nM and unfractionated heparin 0.1U/ml, respectively. Coagulation tests were run on ROTEM® delta.

Results

Kaolin-activated whole blood showed no differences between dilutional coagulopathy and thrombocytopenia (mean clotting time 450 s vs. 516 s, α-angle 47.1° vs. 41.5°, maximum clot firmness 35.0 mm vs. 34.2 mm, all P values ≥0.14). Hyperfibrinolysis specifically disclosed an increased maximum lysis (median: 100%, all P values less than 0.001), and heparin induced a distinctly prolonged clotting time (2283 s, all P values less than 0.02). The coagulopathies were readily distinguishable using a panel of TEM-reagents. In particular, dilutional coagulopathy was separated from thrombocytopenia using FIBTEM (maximum clot firmness 1.9 mm vs. 11.2 mm, P < 0.001). The run time of analysis to achieve diagnostic data was shorter applying a panel of TEM-reagents. A transfusion algorithm based on kaolin suggested platelets in case of dilutional coagulopathy, whereas an algorithm applying TEM-reagents suggested fibrinogen.

Conclusion

Monoanalysis with kaolin was unable to distinguish coagulopathies caused by dilution from that of thrombocytopenia. Algorithms based on the use of kaolin may lead to unnecessary transfusion with platelets, whereas the application of TEM-reagents may result in goal-directed fibrinogen substitution.
Congenital Hepatic Fibrosis and Portal Hypertension in Autosomal Dominant Polycystic Kidney Disease
Authors: O'Brien Kevin , Font‐Montgomery Esperanza , Lukose Linda , Bryant Joy , Piwnica‐Worms Katie , Edwards Hailey , Riney Lauren , Garcia Angelica , Daryanani Kailash , Choyke Peter , Mohan Parvathi , Heller Theo , Gahl William A. , Gunay‐Aygun Meral
Published: June 2011

Objectives:

Autosomal dominant (ADPKD) and recessive (ARPKD) polycystic kidney diseases are the most common hepatorenal fibrocystic diseases (ciliopathies). Characteristics of liver disease of these disorders are quite different. All of the patients with ARPKD have congenital hepatic fibrosis (CHF) often complicated by portal hypertension. In contrast, typical liver involvement in ADPKD is polycystic liver disease, although rare atypical cases with CHF are reported. Our goal was to describe the characteristics of CHF in ADPKD.

Patients and Methods:

As a part of an intramural study of the National Institutes of Health on ciliopathies (www.clinicaltrials.gov, trial NCT00068224), we evaluated 8 patients from 3 ADPKD families with CHF. We present their clinical, biochemical, imaging, and PKD1 and PKHD1 sequencing results. In addition, we tabulate the characteristics of 15 previously reported patients with ADPKD‐CHF from 11 families.

Results:

In all of the 19 patients with ADPKD‐CHF (9 boys, 10 girls), portal hypertension was the main manifestation of CHF; hepatocelllular function was preserved and liver enzymes were largely normal. In all of the 14 families, CHF was not inherited vertically, that is the parents of the index cases had PKD but did not have CHF‐suggesting modifier gene(s). Our 3 families had pathogenic mutations in PKD1; sequencing of the PKHD1 gene as a potential modifier did not reveal any mutations.

Conclusions:

Characteristics of CHF in ADPKD are similar to CHF in ARPKD. ADPKD‐CHF is caused by PKD1 mutations, with probable contribution from modifying gene(s). Given that both boys and girls are affected, these modifier(s) are likely located on autosomal chromosome(s) and less likely X‐linked.
Decrease of Total Subcutaneous Adipose Tissue From Infancy to Childhood
Authors: Kaimbacher Petra S. , Dunitz‐Scheer Marguerite , Wallner‐Liebmann Sandra J. , Scheer Peter J.Z. , Sudi Karl , Schnedl Wolfgang J. , Tafeit Erwin
Published: June 2011

Objectives:

The observation and research of body composition is a topic of present interest. For the assessment of health and variables influencing growth and nutrition, it is of utmost interest to focus on the population of young children.

Subjects and Methods:

The measurements of subcutaneous body fat distribution in a sample of clinically healthy children ages 0 to 7 years were examined. The optical device LIPOMETER was applied to measure the thickness of subcutaneous adipose tissue layers (in millimeters) at 15 well‐defined body sites. This set of measurement points defines the subcutaneous adipose tissue topography. In the present study, subcutaneous adipose tissue topography was determined in 275 healthy children (128 girls and 147 boys) divided into 3 age groups.

Results:

The results of the measurements are presented in 3 levels: total subcutaneous adipose tissue, 4 body regions, and 15 body sites. Our results show a clear physiological decrease in subcutaneous body fat in boys (−43.8%) and girls (−39.8%). One interesting finding was that the decrease occurs mainly in the trunk, abdomen, and lower extremities, whereas the body fat distribution of the upper extremities did not differ. Furthermore, slight subcutaneous adipose tissue topography differences between both sexes were found.

Conclusions:

The present study provides basic documentation of subcutaneous adipose tissue topography in healthy children ages 0 to 7 years. An accurate description of subcutaneous adipose tissue topography in healthy subjects could help to characterize various diseases in relation to overnutrition and malnutrition throughout childhood.
Cost‐effectiveness Analysis of Adjunct VSL#3 Therapy Versus Standard Medical Therapy in Pediatric Ulcerative Colitis
Authors: Park K.T. , Perez Felipe , Tsai Raymond , Honkanen Anita , Bass Dorsey , Garber Alan
Published: June 2011

Background:

Inflammatory bowel diseases (IBDs) are costly chronic gastrointestinal diseases, with pediatric IBD representing increased costs per patient compared to adult disease. Health care expenditures for ulcerative colitis (UC) are >$2 billion annually. It is not clear whether the addition of VSL#3 to standard medical therapy in UC induction and maintenance of remission is a cost‐effective strategy.

Patients and Methods:

We performed a systematic review of the literature and created a Markov model simulating a cohort of 10‐year‐old patients with severe UC, studying them until 100 years of age or death. We compared 2 strategies: standard medical therapy versus medical therapy + VSL#3. For both strategies, we assumed that patients progressed through escalating therapies—mesalamine, azathioprine, and infliximab—before receiving a colectomy + ileal pouch anal anastamosis (IPAA) if the 3 medical therapy options were exhausted. The primary outcome measure was the incremental cost‐effectiveness ratio (ICER), defined as the difference of costs between strategies for each quality‐adjusted life‐year (QALY) gained. One‐way sensitivity analyses were performed on variables to determine the key variables affecting cost‐effectiveness.

Results:

Standard medical care accrued a lifetime cost of $203,317 per patient, compared to $212,582 per patient for medical therapy + VSL#3. Lifetime QALYs gained was comparable for standard medical therapy and medical therapy + VSL#3 at 24.93 versus 25.05, respectively. Using the definition of ICER <50,000/QALY as a cost‐effective intervention, medical therapy + VSL#3 produced an ICER of $79,910 per QALY gained, making this strategy cost‐ineffective. Sensitivity analyses showed that 4 key parameters could affect the cost‐effectiveness of the 2 strategies: cost of colectomy + IPAA, maintenance cost after surgery, probability of developing pouchitis after surgery, and the quality of life after a colectomy + IPAA. High surgical and postsurgical costs, a high probability of developing pouchitis, and a low quality of life after a colectomy + IPAA could make adjunct VSL#3 use a cost‐effective strategy.

Conclusions:

Given present data, adjunct VSL#3 use for pediatric UC induction and maintenance of remission is not cost‐effective, although several key parameters could make this strategy cost‐effective. The quality of life after an IPAA is the single most important variable predicting whether this procedure benefits patients over escalating standard medical therapy.
Heterogeneity of Lower Esophageal Sphincter Function in Children With Achalasia
Authors: Morera Claudio , Nurko Samuel
Published: June 2011

Background and Aim:

Achalasia is a rare esophageal motor disorder in children. The manometric hallmarks are esophageal body aperistalsis, lack of lower esophageal sphincter (LES) relaxation, and high LES pressure. However, LES relaxation and function may be heterogeneous, making the diagnosis difficult at times. The aim of the study was to describe LES function in children with achalasia.

Patients and Methods:

The present study is a retrospective review of manometric tracings of pediatric patients with achalasia and controls. LES response after each swallow was evaluated. LES parameters were defined as homogeneous (normal or abnormal) if the same response was observed in >75% of swallows. Otherwise, the LES parameters were considered heterogeneous.

Results:

Twenty‐nine patients with achalasia and 16 control patients were included. All of the controls had normal LES pressure and relaxation in all of the wet swallows. In the achalasia group, some LES relaxation was present in 74% of swallows and 25% of swallows had normal relaxation. Depending on the parameter, a heterogeneous LES (resting pressure, relaxation, residual pressure, and duration of relaxation) was observed in 27.6% to 34.5% of patients with achalasia versus 0% of the controls (P < 0.001). The rest of the patients with achalasia had homogeneous abnormal responses versus homogeneous normal responses in 100% of control patients (P < 0.001).

Conclusions:

The LES function in pediatric patients with achalasia is heterogeneous. The classic description of a nonrelaxing high‐pressure LES in patients with achalasia is rarely found in children. Partial relaxations are common, and normal relaxations may be present.
Medical ultrasound: imaging of soft tissue strain and elasticity
Authors: Wells Peter N. T. , Liang Hai-Dong
Published: June 2011

After X-radiography, ultrasound is now the most common of all the medical imaging technologies. For millennia, manual palpation has been used to assist in diagnosis, but it is subjective and restricted to larger and more superficial structures. Following an introduction to the subject of elasticity, the elasticity of biological soft tissues is discussed and published data are presented. The basic physical principles of pulse-echo and Doppler ultrasonic techniques are explained. The history of ultrasonic imaging of soft tissue strain and elasticity is summarized, together with a brief critique of previously published reviews. The relevant techniques—low-frequency vibration, step, freehand and physiological displacement, and radiation force (displacement, impulse, shear wave and acoustic emission)—are described. Tissue-mimicking materials are indispensible for the assessment of these techniques and their characteristics are reported. Emerging clinical applications in breast disease, cardiology, dermatology, gastroenterology, gynaecology, minimally invasive surgery, musculoskeletal studies, radiotherapy, tissue engineering, urology and vascular disease are critically discussed. It is concluded that ultrasonic imaging of soft tissue strain and elasticity is now sufficiently well developed to have clinical utility. The potential for further research is examined and it is anticipated that the technology will become a powerful mainstream investigative tool.
Proposal of Intrasporangium mesophilum sp. nov., and reclassification of

Humihabitans oryzae

Kageyama et al. 2007 as Intrasporangium oryzae comb. nov.
Authors: Yang Ling-Ling , Ao Tao , Wang Xing-Hong , He Jie , Klenk Hans-Peter , Tang Shu-Kun , Li Wen-Jun
Published: June 2011

A Gram-positive and aerobic bacterium, designated strain YIM 49065T, was isolated from rhizospheric soil of Jatropha curcas in Yunnan, China. This isolate formed branched and fragmented mycelia containing ll-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The major cellular fatty acid profile was characterized by iso-C14 : 0, iso-C15 : 0 and iso-C16 : 0, and the predominant menaquinone was MK-8(H4). The DNA G+C content was 69.6 mol%. A phylogenetic analysis based on 16S rRNA gene sequence demonstrated that strain YIM 49065T was closely associated with

Intrasporangium calvum

DSM 43043T and

Humihabitans oryzae

KV-657T, exhibiting 98.8 % and 98.6 % 16S rRNA gene sequence similarities, respectively. Furthermore, DNA–DNA hybridizations among strains YIM 49065T,

I. calvum

DSM 43043T and

H. oryzae

DSM 22331T indicated that this isolate represented a novel species in the genus

Intrasporangium

. On the basis of these data, we proposed one novel species, Intrasporangium mesophilum sp. nov., for strain YIM 49065T ( = DSM 23217T  = CCTCC AA 209077T). Additionally, the comparison of biochemical and phylogenetic characters supported the reclassification of

Humihabitans oryzae

as a separate species within the genus

Intrasporangium

, Intrasporangium oryzae comb. nov. (type strain KV-657T  = JCM 15924T  = NBRC 101802T  = NRRL B-24470T).
Gulosibacter

chungangensis sp. nov., an actinomycete isolated from a marine sediment, and emended description of the genus

Gulosibacter
Authors: Park Mi-Hak , Traiwan Jitsopin , Jung Min Young , Kim Wonyong
Published: June 2011

A Gram-positive, strictly aerobic, non-spore-forming, irregular short rod, strain CAU 9625T, was isolated from a sediment of the Yellow Sea in the Republic of Korea. Strain CAU 9625T grew optimally at 37 °C, at pH 8.0 and in the presence of 1 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CAU 9625T belonged to the genus

Gulosibacter

, which has one known member,

Gulosibacter molinativorax

. Strain CAU 9625T and

G. molinativorax

ON4T shared 97.8 % 16S rRNA gene sequence similarity and formed a distinct cluster (99 % bootstrap support) within the family

Microbacteriaceae

. DNA–DNA relatedness between strain CAU 9625T and

G. molinativorax

DSM 13485T was 35.4±0.9 %. The predominant menaquinone was MK-9. The major whole-cell sugars were ribose and glucose. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified lipid. The fatty acid composition was similar to that of

G. molinativorax

DSM 13485T, with anteiso-C15 : 0 as the predominant fatty acid. The DNA G+C content of strain CAU 9625T was 66.2 mol%. The phylogenetic and genetic distinctiveness and several differentiating phenotypic and chemotaxonomic properties revealed that strain CAU 9625T was distinguishable from

G. molinativorax

and other phylogenetic neighbours. On the basis of these data, strain CAU 9625T represents a novel species of the genus

Gulosibacter

, for which the name Gulosibacter chungangensis sp. nov. is proposed. The type strain is CAU 9625T ( = KCTC 13959T  = CCUG 60841T).
Salinimicrobium gaetbulicola sp. nov., isolated from tidal flat sediment
Authors: Lee Soo-Young , Park Sooyeon , Oh Tae-Kwang , Yoon Jung-Hoon
Published: June 2011

A Gram-stain-negative, aerobic, non-flagellated, non-gliding and short rod- or rod-shaped bacterial strain, designated BB-My20T, was isolated from tidal flat sediment taken from the southern coast of Korea. Strain BB-My20T grew optimally at 37 °C, at pH 7.0–7.5 and in the presence of 2 % (w/v) NaCl. A phylogenetic tree based on 16S rRNA gene sequences showed that strain BB-My20T fell within the clade comprising

Salinimicrobium

species, joining

Salinimicrobium catena

HY1T, with which it had a 16S rRNA gene sequence similarity value of 97.4 %. It exhibited 95.4–96.9 % sequence similarity to the type strains of other members of the genus

Salinimicrobium

. Strain BB-My20T contained MK-6 as the predominant menaquinone and iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH as the major fatty acids. The major polar lipids detected in strain BB-My20T and

S. catena

JCM 14015T were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of strain BB-My20T was 45.1 mol% and its mean DNA–DNA relatedness value with

S. catena

JCM 14015T was 4.5 %. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain BB-My20T can be distinguished from the four recognized species of the genus

Salinimicrobium

. On the basis of the data presented, strain BB-My20T is considered to represent a novel species of the genus

Salinimicrobium

, for which the name Salinimicrobium
gaetbulicola sp. nov. is proposed; the type strain is BB-My20T ( = KCTC 23579T = CCUG 60898T).
Inhella
fonticola sp. nov., isolated from spring water, and emended description of the genus Inhella
Authors: Chen Wen-Ming , Sheu Fu-Sian , Young Chiu-Chung , Sheu Shih-Yi
Published: June 2011

A yellow-pigmented bacterial strain designated TNR-25T was isolated from spring water in Taiwan and was characterized using a polyphasic taxonomic approach. Strain TNR-25T was Gram-negative, obligately aerobic, rod-shaped, non-motile and non-spore-forming. Growth occurred at 15–40 °C (optimum, 25 °C), at pH 6.0–10.0 (optimum, pH 7.0) and with 0–0.5 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TNR-25T belonged to the genus

Inhella

and its closest neighbour was

Inhella inkyongensis

IMCC1713T with 98.1 % sequence similarity. The major fatty acids (>10 %) of strain TNR-25T were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The major cellular hydroxy fatty acids were C10 : 0 3-OH and C12 : 0 3-OH. The isoprenoid quinone was Q-8 and the DNA G+C content was 69.6 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, diphosphatidylglycerol and several uncharacterized phospholipids. The DNA–DNA relatedness between strain TNR-25T and

I. inkyongensis

IMCC1713T was about 30.6–35.5 %. On the basis of the genotypic and phenotypic data, strain TNR-25T represents a novel species in the genus

Inhella

, for which the name Inhella
fonticola sp. nov. is proposed; the type strain is TNR-25T ( = BCRC 80211T = LMG 25721T).
A DNA damage checkpoint in Caulobacter crescentus inhibits cell division through a direct interaction with FtsW
Authors: Modell Joshua W. , Hopkins Alexander C. , Laub Michael T.
Published: June 2011

Following DNA damage, cells typically delay cell cycle progression and inhibit cell division until their chromosomes have been repaired. The bacterial checkpoint systems responsible for these DNA damage responses are incompletely understood. Here, we show that Caulobacter crescentus responds to DNA damage by coordinately inducing an SOS regulon and inhibiting the master regulator CtrA. Included in the SOS regulon is sidA (SOS-induced inhibitor of cell division A), a membrane protein of only 29 amino acids that helps to delay cell division following DNA damage, but is dispensable in undamaged cells. SidA is sufficient, when overproduced, to block cell division. However, unlike many other regulators of bacterial cell division, SidA does not directly disrupt the assembly or stability of the cytokinetic ring protein FtsZ, nor does it affect the recruitment of other components of the cell division machinery. Instead, we provide evidence that SidA inhibits division by binding directly to FtsW to prevent the final constriction of the cytokinetic ring.
Biological mechanisms, one molecule at a time
Authors: Tinoco Ignacio , Gonzalez Ruben L.
Published: June 2011

The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome.
The IDOL–UBE2D complex mediates sterol-dependent degradation of the LDL receptor
Authors: Zhang Li , Fairall Louise , Goult Benjamin T. , Calkin Anna C. , Hong Cynthia , Millard Christopher J. , Tontonoz Peter , Schwabe John W.R.
Published: June 2011

We previously identified the E3 ubiquitin ligase IDOL as a sterol-dependent regulator of the LDL receptor (LDLR). The molecular pathway underlying IDOL action, however, remains to be determined. Here we report the identification and biochemical and structural characterization of an E2–E3 ubiquitin ligase complex for LDLR degradation. We identified the UBE2D family (UBE2D1–4) as E2 partners for IDOL that support both autoubiquitination and IDOL-dependent ubiquitination of the LDLR in a cell-free system. NMR chemical shift mapping and a 2.1 Å crystal structure of the IDOL RING domain–UBE2D1 complex revealed key interactions between the dimeric IDOL protein and the E2 enzyme. Analysis of the IDOL–UBE2D1 interface also defined the stereochemical basis for the selectivity of IDOL for UBE2Ds over other E2 ligases. Structure-based mutations that inhibit IDOL dimerization or IDOL–UBE2D interaction block IDOL-dependent LDLR ubiquitination and degradation. Furthermore, expression of a dominant-negative UBE2D enzyme inhibits the ability of IDOL to degrade the LDLR in cells. These results identify the IDOL–UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake.