bluuebunny/crossref_metadata_2025 huggingface dataset:
The BRCA1 Ashkenazi founder mutations occur on common haplotypes and are not highly correlated with anonymous single nucleotide polymorphisms likely to be used in genome-wide case-control association studies
Authors: Pereira Lutécia H Mateus , Pineda Marbin A , Rowe William H , Fonseca Libia R , Greene Mark H , Offit Kenneth , Ellis Nathan A , Zhang Jinghui , Collins Andrew , Struewing Jeffery P
Published: October 2007

Background

We studied linkage disequilibrium (LD) patterns at the BRCA1 locus, a susceptibility gene for breast and ovarian cancer, using a dense set of 114 single nucleotide polymorphisms in 5 population groups. We focused on Ashkenazi Jews in whom there are known founder mutations, to address the question of whether we would have been able to identify the 185delAG mutation in a case-control association study (should one have been done) using anonymous genetic markers. This mutation is present in approximately 1% of the general Ashkenazi population and 4% of Ashkenazi breast cancer cases. We evaluated LD using pairwise and haplotype-based methods, and assessed correlation of SNPs with the founder mutations using Pearson's correlation coefficient.

Results

BRCA1 is characterized by very high linkage disequilibrium in all populations spanning several hundred kilobases. Overall, haplotype blocks and pair-wise LD bins were highly correlated, with lower LD in African versus non-African populations. The 185delAG and 5382insC founder mutations occur on the two most common haplotypes among Ashkenazim. Because these mutations are rare, even though they are in strong LD with many other SNPs in the region as measured by D-prime, there were no strong associations when assessed by Pearson's correlation coefficient, r (maximum of 0.04 for the 185delAG).

Conclusion

Since the required sample size is related to the inverse of r, this suggests that it would have been difficult to map BRCA1 in an Ashkenazi case-unrelated control association study using anonymous markers that were linked to the founder mutations.
Genetic diversity of the obligate intracellular bacterium Chlamydophila pneumoniae by genome-wide analysis of single nucleotide polymorphisms: evidence for highly clonal population structure
Authors: Rattei Thomas , Ott Stephan , Gutacker Michaela , Rupp Jan , Maass Matthias , Schreiber Stefan , Solbach Werner , Wirth Thierry , Gieffers Jens
Published: October 2007

Background

Chlamydophila pneumoniae is an obligate intracellular bacterium that replicates in a biphasic life cycle within eukaryotic host cells. Four published genomes revealed an identity of > 99 %. This remarkable finding raised questions about the existence of distinguishable genotypes in correlation with geographical and anatomical origin.

Results

We studied the genetic diversity of C. pneumoniae by analysing synonymous single nucleotide polymorphisms (sSNPs) that are under reduced selection pressure. We conducted an in silico analysis of the four sequenced genomes, chose 232 representative sSNPs and analysed the loci in 38 C. pneumoniae isolates. We identified 15 different genotypes that were separated in four major clusters. Clusters were not associated with anatomical or geographical origin. However, animal lineages are basal on the C. pneumomiae phylogeny, suggesting a recent transmission to humans through successive bottlenecks some 150,000 years ago. A lack of detectable variation in 17 isolates emphasizes the extraordinary genetic conservation of this species and the high clonality of the population. Moreover, the largest cluster, which encompasses 80% of all analysed strains, is an extremely young clade, that went through an important population expansion some 3,300 years ago.

Conclusion

sSNPs have proven useful as a sensitive marker to gain new insights into genetic diversity, population structure and evolutionary history of C. pneumoniae.
Wide diversity in structure and expression profiles among members of the Caenorhabditis elegans globin protein family
Authors: Hoogewijs David , Geuens Eva , Dewilde Sylvia , Vierstraete Andy , Moens Luc , Vinogradov Serge , Vanfleteren Jacques R
Published: October 2007

Background

The emergence of high throughput genome sequencing facilities and powerful high performance bioinformatic tools has highlighted hitherto unexpected wide occurrence of globins in the three kingdoms of life. In silico analysis of the genome of C. elegans identified 33 putative globin genes. It remains a mystery why this tiny animal might need so many globins. As an inroad to understanding this complexity we initiated a structural and functional analysis of the globin family in C. elegans.

Results

All 33 C. elegans putative globin genes are transcribed. The translated sequences have the essential signatures of single domain bona fide globins, or they contain a distinct globin domain that is part of a larger protein. All globin domains can be aligned so as to fit the globin fold, but internal interhelical and N- and C-terminal extensions and a variety of amino acid substitutions generate much structural diversity among the globins of C. elegans. Likewise, the encoding genes lack a conserved pattern of intron insertion positioning. We analyze the expression profiles of the globins during the progression of the life cycle, and we find that distinct subsets of globins are induced, or repressed, in wild-type dauers and in daf-2(e1370)/insulin-receptor mutant adults, although these animals share several physiological features including resistance to elevated temperature, oxidative stress and hypoxic death. Several globin genes are upregulated following oxygen deprivation and we find that HIF-1 and DAF-2 each are required for this response. Our data indicate that the DAF-2 regulated transcription factor DAF-16/FOXO positively modulates hif-1 transcription under anoxia but opposes expression of the HIF-1 responsive globin genes itself. In contrast, the canonical globin of C. elegans, ZK637.13, is not responsive to anoxia. Reduced DAF-2 signaling leads to enhanced transcription of this globin and DAF-16 is required for this effect.

Conclusion

We found that all 33 putative globins are expressed, albeit at low or very low levels, perhaps indicating cell-specific expression. They show wide diversity in gene structure and amino acid sequence, suggesting a long evolutionary history. Ten globins are responsive to oxygen deprivation in an interacting HIF-1 and DAF-16 dependent manner. Globin ZK637.13 is not responsive to oxygen deprivation and regulated by the Ins/IGF pathway only suggesting that this globin may contribute to the life maintenance program.
Comparative genomic analysis of Campylobacter jejuni associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity
Authors: Taboada Eduardo N , van Belkum Alex , Yuki Nobuhiro , Acedillo Rey R , Godschalk Peggy CR , Koga Michiaki , Endtz Hubert P , Gilbert Michel , Nash John HE
Published: October 2007

Background

Campylobacter jejuni infection represents the most frequent antecedent infection triggering the onset of the neuropathic disorders Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Although sialylated ganglioside-mimicking lipo-oligosaccharide (LOS) structures are the strongest neuropathogenic determinants in C. jejuni, they do not appear to be the only requirement for a neuropathic outcome since strains capable of their production have been isolated from patients with uncomplicated cases of enteritis. Consequently, other pathogen and/or host-related factors contribute to the onset of neurological complications. We have used comparative genomic hybridization to perform a detailed genomic comparison of strains isolated from GBS/MFS and enteritis-only patients. Our dataset, in which the gene conservation profile for 1712 genes was assayed in 102 strains, including 56 neuropathogenic isolates, represents the largest systematic search for C. jejuni factors associated with GBS/MFS to date and has allowed us to analyze the genetic background of neuropathogenic C. jejuni strains with an unprecedented level of resolution.

Results

The majority of GBS/MFS strains can be assigned to one of six major lineages, suggesting that several genetic backgrounds can result in a neuropathogenic phenotype. A statistical analysis of gene conservation rates revealed that although genes involved in the sialylation of LOS structures were significantly associated with neuropathogenic strains, still many enteritis-control strains both bear these genes and share remarkable levels of genomic similarity with their neuropathogenic counterparts. Two capsule biosynthesis genes (Cj1421c and Cj1428c) showed higher conservation rates among neuropathogenic strains compared to enteritis-control strains. Any potential involvement of these genes in neuropathogenesis must be assessed. A single gene (HS:3 Cj1135) had a higher conservation rate among enteritis-control strains. This gene encodes a glucosyltransferase that is found in some of the LOS classes that do not express ganglioside mimics.

Conclusion

Our findings corroborate that neuropathogenic factors may be transferred between unrelated strains of different genetic background. Our results would also suggest that the failure of some strains isolated from uncomplicated cases of enteritis to elicit a neuropathic clinical outcome may be due to subtle genetic differences that silence their neuropathogenic potential and/or due to host-related factors.

The microarray data has been deposited in NCBI's Gene Expression Omnibus under accession number GSE3579.
Impact of delayed initiation of erythropoietin in critically ill patients
Authors: Duby Jeremiah J , Erstad Brian L , Abarca Jacob , Camamo James M , Huckleberry Yvonne , Bramblett Stuart N
Published: October 2007

Background

The purpose of this study was to evaluate the impact of recombinant human erythropoietin (rHuEPO) use for anemia of critical illness at a practice site where delayed initiation is common.

Methods

Retrospective medical record review involving patients treated with rHuEPO for anemia of critical illness. Those patients given rHuEPO or diagnosed with end-stage renal disease (ESRD) prior to ICU admission were excluded. The primary endpoints were rHuEPO use and RBC transfusion patterns.

Results

Complete data were collected for consecutive admissions of 126 patients. Average age (SD) and APACHE II score were 56.5 (18.6) years and 25 (7.8), respectively. The median ICU (IQR) and hospital length of stay (LOS) were 24 (11.25, 39) and 29 (17, 44.75) days, respectively. Treatment with rHuEPO was started an average of 12.5 +/- 10.5 days after ICU admission and given for 3.8 +/- 3.8 doses. Eighty percent of patients were transfused with an average total of 5.42 +/- 5.08 units received. RBC exposure inversely correlated with a lower mean hemoglobin response to rHuEPO. ICU LOS (p < 0.0001), hemoglobin at 24 hours (p = 0.055), transfusion within 48 hours of admit (p < 0.0001), and postoperative status (p = 0.019) were the best predictors of transfusion requirements (r2 = 0.37).

Conclusion

Delayed initiation of rHuEPO for anemia of critical illness resulted in comparable hemoglobin and transfusion benefits. Future studies are needed to establish clinical benefit and role in therapy. RBC exposure may blunt the erythropoietic effects of rHuEPO, potentially frustrating benefits to those of greatest apparent need.
Trinucleotide cassettes increase diversity of T7 phage-displayed peptide library
Authors: Krumpe Lauren RH , Schumacher Kathryn M , McMahon James B , Makowski Lee , Mori Toshiyuki
Published: October 2007

Background

Amino acid sequence diversity is introduced into a phage-displayed peptide library by randomizing library oligonucleotide DNA. We recently evaluated the diversity of peptide libraries displayed on T7 lytic phage and M13 filamentous phage and showed that T7 phage can display a more diverse amino acid sequence repertoire due to differing processes of viral morphogenesis.

Methods

In this study, we evaluated and compared the diversity of a 12-mer T7 phage-displayed peptide library randomized using codon-corrected trinucleotide cassettes with a T7 and an M13 12-mer phage-displayed peptide library constructed using the degenerate codon randomization method.

Results

We herein demonstrate that the combination of trinucleotide cassette amino acid codon randomization and T7 phage display construction methods resulted in a significant enhancement to the functional diversity of a 12-mer peptide library. This novel library exhibited superior amino acid uniformity and order-of-magnitude increases in amino acid sequence diversity as compared to degenerate codon randomized peptide libraries. Comparative analyses of the biophysical characteristics of the 12-mer peptide libraries revealed the trinucleotide cassette-randomized library to be a unique resource.

Conclusion

The combination of T7 phage display and trinucleotide cassette randomization resulted in a novel resource for the potential isolation of binding peptides for new and previously studied molecular targets.
Elastic intramedullary nailing and DBM-Bone marrow injection for the treatment of simple bone cysts
Authors: Kanellopoulos Anastasios D , Mavrogenis Andreas F , Papagelopoulos Panayiotis J , Soucacos Panayotis N
Published: October 2007

Background

Simple or unicameral bone cysts are common benign fluid-filled lesions usually located at the long bones of children before skeletal maturity.

Methods

We performed demineralized bone matrix and iliac crest bone marrow injection combined with elastic intramedullary nailing for the treatment of simple bone cysts in long bones of 9 children with a mean age of 12.6 years (range, 4 to 15 years).

Results

Two of the 9 patients presented with a pathological fracture. Three patients had been referred after the failure of previous treatments. Four patients had large lesions with impending pathological fractures that interfered with daily living activities. We employed a ratio to ascertain the severity of the lesion. The extent of the lesion on the longitudinal axis was divided with the normal expected diameter of the long bone at the site of the lesion. The mean follow-up was 77 months (range, 5 to 8 years). All patients were pain free and had full range of motion of the adjacent joints at 6 weeks postoperatively. Review radiographs showed that all 7 cysts had consolidated completely (Neer stage I) and 2 cysts had consolidated partially (Neer stage II). Until the latest examination there was no evidence of fracture or re-fracture.

Conclusion

Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to the normal activities of the pre-teen patients.
A genetic code alteration generates a proteome of high diversity in the human pathogen Candida albicans
Authors: Gomes Ana C , Miranda Isabel , Silva Raquel M , Moura Gabriela R , Thomas Benjamin , Akoulitchev Alexandre , Santos Manuel AS
Published: October 2007

Background

Genetic code alterations have been reported in mitochondrial, prokaryotic, and eukaryotic cytoplasmic translation systems, but their evolution and how organisms cope and survive such dramatic genetic events are not understood.

Results

Here we used an unusual decoding of leucine CUG codons as serine in the main human fungal pathogen Candida albicans to elucidate the global impact of genetic code alterations on the proteome. We show that C. albicans decodes CUG codons ambiguously and tolerates partial reversion of their identity from serine back to leucine on a genome-wide scale.

Conclusion

Such codon ambiguity expands the proteome of this human pathogen exponentially and is used to generate important phenotypic diversity. This study highlights novel features of C. albicans biology and unanticipated roles for codon ambiguity in the evolution of the genetic code.
PAZAR: a framework for collection and dissemination of cis-regulatory sequence annotation
Authors: Portales-Casamar Elodie , Kirov Stefan , Lim Jonathan , Lithwick Stuart , Swanson Magdalena I , Ticoll Amy , Snoddy Jay , Wasserman Wyeth W
Published: October 2007

PAZAR is an open-access and open-source database of transcription factor and regulatory sequence annotation with associated web interface and programming tools for data submission and extraction. Curated boutique data collections can be maintained and disseminated through the unified schema of the mall-like PAZAR repository. The Pleiades Promoter Project collection of brain-linked regulatory sequences is introduced to demonstrate the depth of annotation possible within PAZAR. PAZAR, located at http://www.pazar.info, is open for business.
All duplicates are not equal: the difference between small-scale and genome duplication
Authors: Hakes Luke , Pinney John W , Lovell Simon C , Oliver Stephen G , Robertson David L
Published: October 2007

Background

Genes in populations are in constant flux, being gained through duplication and occasionally retained or, more frequently, lost from the genome. In this study we compare pairs of identifiable gene duplicates generated by small-scale (predominantly single-gene) duplications with those created by a large-scale gene duplication event (whole-genome duplication) in the yeast Saccharomyces cerevisiae.

Results

We find a number of quantifiable differences between these data sets. Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts. At first sight, either of these latter two features could provide a plausible mechanism by which the difference in dispensability might arise. However, we uncover no evidence suggesting that this is the case. We find that the difference in dispensability observed between the two duplicate types is limited to gene products found within protein complexes, and probably results from differences in the relative strength of the evolutionary pressures present following each type of duplication event.

Conclusion

Genes, and the proteins they specify, originating from small-scale and whole-genome duplication events differ in quantifiable ways. We infer that this is not due to their association with different functional categories; rather, it is a direct result of biases in gene retention.
Perturbation of gene expression of the chromatin remodeling pathway in premature newborns at risk for bronchopulmonary dysplasia
Authors: Cohen Jennifer , Van Marter Linda J , Sun Yao , Allred Elizabeth , Leviton Alan , Kohane Isaac S
Published: October 2007

Background

One-third to one-half of all infants born before the 28th week of gestation develop bronchopulmonary dysplasia (BPD). Inflammatory regulators appear to be involved in the pathogenesis of BPD, possibly beginning in fetal life. To evaluate the feasibility of using expression profiling in umbilical cord tissue to discover molecular signatures for developmental staging and for determining risk of BPD, we conducted a cross-sectional study of infants born at less than 28 weeks of gestation (n = 54). Sections of umbilical cord were obtained at birth from 20 infants who later developed BPD and from 34 of their peers who did not develop BPD.

Results

Umbilical cord expression profiles at birth exhibited systematic differences in bioenergetic pathways with respect to gestational age. Infants who subsequently developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways, which have previously been implicated in several adult onset lung diseases. These findings are consistent with prior work on inflammatory processes and bioenergetics in prematurity.

Conclusion

This study of gene expression of the newborn umbilical cord implicates the chromatin remodeling pathways in those premature infants who subsequently develop BPD. Larger sample sizes will be required to generate prognostic markers from umbilical cord profiles.
Divergent evolution of arrested development in the dauer stage of Caenorhabditis elegans and the infective stage of Heterodera glycines
Authors: Elling Axel A , Mitreva Makedonka , Recknor Justin , Gai Xiaowu , Martin John , Maier Thomas R , McDermott Jeffrey P , Hewezi Tarek , McK Bird David , Davis Eric L , Hussey Richard S , Nettleton Dan , McCarter James P , Baum Thomas J
Published: October 2007

Background

The soybean cyst nematode Heterodera glycines is the most important parasite in soybean production worldwide. A comprehensive analysis of large-scale gene expression changes throughout the development of plant-parasitic nematodes has been lacking to date.

Results

We report an extensive genomic analysis of H. glycines, beginning with the generation of 20,100 expressed sequence tags (ESTs). In-depth analysis of these ESTs plus approximately 1,900 previously published sequences predicted 6,860 unique H. glycines genes and allowed a classification by function using InterProScan. Expression profiling of all 6,860 genes throughout the H. glycines life cycle was undertaken using the Affymetrix Soybean Genome Array GeneChip. Our data sets and results represent a comprehensive resource for molecular studies of H. glycines. Demonstrating the power of this resource, we were able to address whether arrested development in the Caenorhabditis elegans dauer larva and the H. glycines infective second-stage juvenile (J2) exhibits shared gene expression profiles. We determined that the gene expression profiles associated with the C. elegans dauer pathway are not uniformly conserved in H. glycines and that the expression profiles of genes for metabolic enzymes of C. elegans dauer larvae and H. glycines infective J2 are dissimilar.

Conclusion

Our results indicate that hallmark gene expression patterns and metabolism features are not shared in the developmentally arrested life stages of C. elegans and H. glycines, suggesting that developmental arrest in these two nematode species has undergone more divergent evolution than previously thought and pointing to the need for detailed genomic analyses of individual parasite species.
Host origin of plastid solute transporters in the first photosynthetic eukaryotes
Authors: Tyra Heather M , Linka Marc , Weber Andreas PM , Bhattacharya Debashish
Published: October 2007

Background

It is generally accepted that a single primary endosymbiosis in the Plantae (red, green (including land plants), and glaucophyte algae) common ancestor gave rise to the ancestral photosynthetic organelle (plastid). Plastid establishment necessitated many steps, including the transfer and activation of endosymbiont genes that were relocated to the nuclear genome of the 'host' followed by import of the encoded proteins into the organelle. These innovations are, however, highly complex and could not have driven the initial formation of the endosymbiosis. We postulate that the re-targeting of existing host solute transporters to the plastid fore-runner was critical for the early success of the primary endosymbiosis, allowing the host to harvest endosymbiont primary production.

Results

We tested this model of transporter evolution by conducting a comprehensive analysis of the plastid permeome in Arabidopsis thaliana. Of 137 well-annotated transporter proteins that were initially considered, 83 that are broadly distributed in Plantae were submitted to phylogenetic analysis. Consistent with our hypothesis, we find that 58% of Arabidopsis transporters, including all carbohydrate transporters, are of host origin, whereas only 12% arose from the cyanobacterial endosymbiont. Four transporter genes are derived from a Chlamydia-like source, suggesting that establishment of the primary plastid likely involved contributions from at least two prokaryotic sources.

Conclusion

Our results indicate that the existing plastid solute transport system shared by Plantae is derived primarily from host genes. Important contributions also came from the cyanobacterial endosymbiont and Chlamydia-like bacteria likely co-resident in the first algae.
Human Chorionic Gonadotropin Induces Nestin Expression in Endothelial Cells of the Ovary via Vascular Endothelial Growth Factor Signaling
Authors: Takahashi Noriyuki , Itoh Masanori T. , Ishizuka Bunpei
Published: October 2007

The intermediate filament protein nestin was originally found to be expressed in neuronal progenitor cells, but recent studies have shown that other cell types, including endocrine and vascular endothelial cells, express nestin. In the present study, we examined the expression and localization of nestin in the ovaries of developing, peripubertal, and adult rats. RT-PCR and Western blot analyses revealed that nestin mRNA and proteins were expressed in adult rat ovaries. Immunohistochemical analyses using adult rat ovaries showed that nestin was mainly localized to capillary endothelial cells of theca interna in follicles with more than two layers of granulosa cells and that its expression increased with follicle growth. Ontogenetically, ovarian nestin expression started at the peripubertal period when the first gonadotropin surge occurs. To test the possibility that gonadotropins induce nestin expression, prepubertal (postnatal d 21) rats were sc injected with equine chorionic gonadotropin (eCG) and/or human chorionic gonadotropin (hCG). A single injection of hCG, but not eCG, was sufficient to induce nestin expression in follicles, mainly in capillary endothelial cells of theca interna. Furthermore, pretreatment with an inhibitor of vascular endothelial growth factor receptor prevented the induction of the nestin expression by hCG. These findings demonstrate that the endogenous LH surge induces nestin expression in capillary endothelial cells of theca interna via the vascular endothelial growth factor signaling pathway. Nestin may be involved in angiogenesis in growing follicles, which is followed by follicle maturation and subsequent ovulation.
Visually guided obstacle avoidance in the box jellyfish Tripedalia cystophora and Chiropsella bronzie
Authors: Garm A. , O'Connor M. , Parkefelt L. , Nilsson D.-E.
Published: October 2007

Box jellyfish, cubomedusae, possess an impressive total of 24 eyes of four morphologically different types. Two of these eye types, called the upper and lower lens eyes, are camera-type eyes with spherical fish-like lenses. Compared with other cnidarians, cubomedusae also have an elaborate behavioral repertoire, which seems to be predominantly visually guided. Still, positive phototaxis is the only behavior described so far that is likely to be correlated with the eyes. We have explored the obstacle avoidance response of the Caribbean species Tripedalia cystophora and the Australian species Chiropsella bronzie in a flow chamber. Our results show that obstacle avoidance is visually guided. Avoidance behavior is triggered when the obstacle takes up a certain angle in the visual field. The results do not allow conclusions on whether color vision is involved but the strength of the response had a tendency to follow the intensity contrast between the obstacle and the surroundings (chamber walls). In the flow chamber Tripedalia cystophora displayed a stronger obstacle avoidance response than Chiropsella bronzie since they had less contact with the obstacles. This seems to follow differences in their habitats.
Circadian timed episodic-like memory – a bee knows what to do when,and also where
Authors: Pahl Mario , Zhu Hong , Pix Waltraud , Tautz Juergen , Zhang Shaowu
Published: October 2007

This study investigates how the colour, shape and location of patterns could be memorized within a time frame. Bees were trained to visit two Y-mazes, one of which presented yellow vertical (rewarded) versushorizontal (non-rewarded) gratings at one site in the morning, while another presented blue horizontal (rewarded) versus vertical (non-rewarded)gratings at another site in the afternoon. The bees could perform well in the learning tests and various transfer tests, in which (i) all contextual cues from the learning test were present; (ii) the colour cues of the visual patterns were removed, but the location cue, the orientation of the visual patterns and the temporal cue still existed; (iii) the location cue was removed, but other contextual cues, i.e. the colour and orientation of the visual patterns and the temporal cue still existed; (iv) the location cue and the orientation cue of the visual patterns were removed, but the colour cue and temporal cue still existed; (v) the location cue, and the colour cue of the visual patterns were removed, but the orientation cue and the temporal cue still existed. The results reveal that the honeybee can recall the memory of the correct visual patterns by using spatial and/or temporal information. The relative importance of different contextual cues is compared and discussed. The bees' ability to integrate elements of circadian time, place and visual stimuli is akin to episodic-like memory; we have therefore named this kind of memory circadian timed episodic-like memory.
Linkage mechanics and power amplification of the mantis shrimp's strike
Authors: Patek S. N. , Nowroozi B. N. , Baio J. E. , Caldwell R. L. , Summers A. P.
Published: October 2007

Mantis shrimp (Stomatopoda) generate extremely rapid and forceful predatory strikes through a suite of structural modifications of their raptorial appendages. Here we examine the key morphological and kinematic components of the raptorial strike that amplify the power output of the underlying muscle contractions. Morphological analyses of joint mechanics are integrated with CT scans of mineralization patterns and kinematic analyses toward the goal of understanding the mechanical basis of linkage dynamics and strike performance. We test whether a four-bar linkage mechanism amplifies rotation in this system and find that the rotational amplification is approximately two times the input rotation, thereby amplifying the velocity and acceleration of the strike. The four-bar model is generally supported, although the observed kinematic transmission is lower than predicted by the four-bar model. The results of the morphological, kinematic and mechanical analyses suggest a multi-faceted mechanical system that integrates latches, linkages and lever arms and is powered by multiple sites of cuticular energy storage. Through reorganization of joint architecture and asymmetric distribution of mineralized cuticle, the mantis shrimp's raptorial appendage offers a remarkable example of how structural and mechanical modifications can yield power amplification sufficient to produce speeds and forces at the outer known limits of biological systems.
Search for hepatopancreatic ecdysteroid-responsive genes during the crayfish molt cycle: from a single gene to multigenicity
Authors: Shechter Assaf , Tom Moshe , Yudkovski Yana , Weil Simy , Chang Sharon A. , Chang Ernest S. , Chalifa-Caspi Vered , Berman Amir , Sagi Amir
Published: October 2007

The expression of the vitellogenin gene of the red-claw crayfish Cherax quadricarinatus (CqVg) was previously demonstrated in male crayfish during an endocrinologically induced molt cycle. The hypothesis that this expression is under the direct control of ecdysteroids was tested in this study both in vivo and in vitro. Unlike vitellogenin of insects, CqVg was not found to be ecdysteroid-responsive. Thus, a multigenic approach was employed for the identification of other hepatopancreatic ecdysteroid-responsive genes by a cDNA microarray. For the purposes of this study, a multi-parametric molt-staging technique, based on X-ray detection of gastrolith growth, was developed. To identify ecdysteroid-responsive genes during premolt, the molt cycle was induced by two manipulations, 20-hydroxyecdysone administration and X-organ–sinus gland complex removal; both resulted in significant elevation of ecdysteroids. Two clusters of affected genes (129 and 122 genes, respectively) were revealed by the microarray. It is suggested that only genes belonging to similarly responsive (up- or downregulated) gene clusters in both manipulations (102 genes) could be considered putative ecdysteroid-responsive genes. Some of these ecdysteroid-responsive genes showed homology to genes controlling chitin metabolism, proteases and other cellular activities, while 56.8% were unknown. The majority of the genes were downregulated, presumably by an energetic shift of the hepatopancreas prior to ecdysis. The effect of 20-hydroxyecdysone on representative genes from this group was confirmed in vitro using a hepatopancreas tissue culture. This approach for ecdysteroid-responsive gene identification could also be implemented in other tissues for the elucidation of ecdysteroid-specific signaling pathways during the crustacean molt cycle.
Anatomy of the hind legs and actions of their muscles during jumping in leafhopper insects
Authors: Burrows Malcolm
Published: October 2007

The rapid and simultaneous depression of the trochantera about the coxae of both hind legs of leafhoppers are the key joint movements powering a jump. The present study analyses the structure of these joints and the actions of the muscles that move them. The hind coxae are huge and are linked to each other at the midline by a protrusion from one coxa that inserts in a socket of the other and acts like a press-stud (popper) fastener. This asymmetry is not reflected in any left- or right-handed preference either within one species or between species. The movements of the joints in a jump are monitored by a number of possible proprioceptors that should be activated when a hind leg is fully levated in preparation for a jump: a hair row and two hair plates on the coxa, a hair plate on a trochanteral pivot with a coxa, and femoral spines at the femoro-tibial joint. The depressor and levator muscles that move the trochanter are of similar size and together occupy the greater part of the metathorax. Their lever arms are similar when the leg is fully levated, but the lever arm of the depressor increases with initial depression of the coxo-trochanteral joint while that of the levator declines. A jump is preceded by activity in the trochanteral depressor and levator muscles, which results in a forward movement of the coxa and metathorax with the trochanter fully levated. This period of co-contraction could result in storage of energy in skeletal structures in the thorax. Just before the rapid depression of the trochanter in the jump movement the frequency of depressor spikes increases while that in the levator declines, releasing any force stored by the preceding muscle contractions. These bursts of depressor spikes occur at the same time in the left and right muscles but none of the individual motor spikes appeared to be synchronous on the two sides.
The sensory basis of roost finding in a forest bat,Nyctalus noctula
Authors: Ruczyński Ireneusz , Kalko Elisabeth K. V. , Siemers Björn M.
Published: October 2007

Tree cavities are a critical resource for most forest-dwelling bats. Yet,it is not known how bats search for new sites and, in particular, find entrances to cavities. Here, we evaluated the importance of different sensory channels for the detection of tree roosts by the noctule bat Nyctalus noctula. Specifically, we tested the role of three non-social cues (echo information, visual information and temperature-related cues) and two social sensory cues (conspecific echolocation calls and the presence of bat olfactory cues). We set up an experiment in a flight room that mimicked natural conditions. In the flight room, we trained wild-caught bats kept in captivity for a short while to find the entrance to an artificial tree cavity. We measured the bats' hole-finding performance based on echolocation cues alone and then presented the bat with one of four additional sensory cues. Our data show that conspecific echolocation calls clearly improved the bats'performance in finding tree holes, both from flying (long-range detection) and when they were crawling on the trunk (short range detection). The other cues we presented had no, or only weak, effects on performance, implying that detection of new cavities from a distance is difficult for noctules if no additional social cues, in particular calls from conspecifics, are present. We conclude that sensory constraints strongly limit the effectiveness of finding new cavities and may in turn promote sociality and acoustic information transfer among bats. As acoustic cues clearly increased the bats' detection performance, we suggest that eavesdropping is an important mechanism for reducing the costs of finding suitable roosts.
Detailed Technical Analysis of Urine RNA-Based Tumor Diagnostics Reveals ETS2/Urokinase Plasminogen Activator to Be a Novel Marker for Bladder Cancer
Authors: Hanke Merle , Kausch Ingo , Dahmen Gerlinde , Jocham Dieter , Warnecke Jens M
Published: October 2007

Background: The noninvasive detection of RNA tumor markers in body fluids represents an attractive diagnostic option, but diagnostic performance of tissue-derived markers is often poorer when measured in body fluids rather than in tumors. We aimed to develop a procedure for measurement of tumor RNA in urine that would minimize donor-dependent influences on the results.

Methods: RNA isolated from urinary cell pellet, cell-depleted fraction, and whole urine was quantified by reverse transcription quantitative–PCR. The donor-dependent influence of urine background on individual steps of the standardized procedure was analyzed using an external RNA standard. Using a test set of samples from 61 patients with bladder cancer and 37 healthy donors, we compared 4 putative RNA tumor markers identified in whole urine with 5 established, tissue-derived RNA tumor markers for the detection of bladder cancer.

Results: Of the markers analyzed by this system, the RNA ratio of v-ets erythroblastosis virus E26 oncogene homolog 2 (avian; ETS2) to urokinase plasminogen activator (uPA) enabled the most specific (100%) and sensitive (75.4%) detection of bladder cancer from whole urine, with an area under the curve of 0.929 (95% CI 0.882–0.976).

Conclusions: The described methodology for RNA marker detection in urine appears to be clinically applicable. The ratio of ETS2 mRNA to uPA mRNA in urine is a potential marker for bladder cancer.
Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration
Authors: Goodwin Robert S , Wilkins Diana G , Averin Olga , Choo Robin E , Schroeder Jennifer R , Jasinski Donald R , Johnson Rolley E , Jones Hendrée E , Huestis Marilyn A
Published: October 2007

Background: Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid dependence in pregnant women. We hypothesized that there would be a relationship between the cumulative maternal dose of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair.

Methods: This study examined buprenorphine and norbuprenorphine concentrations in hair obtained from 9 buprenorphine-maintained pregnant women and 4 of their infants. Specimens were analyzed by liquid chromatography-tandem mass spectrometry with limits of quantification of 3.0 pg/mg. All maternal hair specimens were washed with methylene chloride before analysis, and when sufficient amounts of maternal hair were available, specimens also were analyzed without washing. Infant hair specimens were not washed.

Results: Buprenorphine concentrations were significantly greater in unwashed hair than washed hair (P = 0.031). Norbuprenorphine concentrations were significantly greater than buprenorphine concentrations in both maternal (P = 0.0097) and infant hair (P = 0.0033). There were statistically significant associations between the cumulative maternal dose of buprenorphine administered and the concentrations of buprenorphine (washed, P <0.0001; unwashed, P = 0.0004), norbuprenorphine (washed, P <0.0001; unwashed, P = 0.0005), and buprenorphine plus norbuprenorphine (washed, P <0.0001; unwashed, P = 0.0005) for both washed and unwashed maternal hair specimens. There was a significant positive association between concentrations of buprenorphine and norbuprenorphine in maternal hair (washed, P <0.0001; unwashed, P = 0.0003), a trend for this association in infant hair (P = 0.08), and an association between buprenorphine concentrations in maternal unwashed hair and infant hair (P = 0.0002). The buprenorphine:norbuprenorphine ratio increased in distal segments.

Conclusion: Buprenorphine treatment during gestation provides an opportunity for monitoring drug disposition in maternal and fetal tissues under controlled conditions.
Effects of 7 Hemoglobin Variants on the Measurement of Glycohemoglobin by 14 Analytical Methods
Authors: Lee Seung-Tae , Weykamp Cas W , Lee Yong-Wha , Kim Jong-Won , Ki Chang-Seok
Published: October 2007

Background: Hemoglobin variants (HbVAR) are not uncommon in the Korean population, with Hb G-Coushatta and Hb Queens being the 2 most common HbVAR. Hb G-Coushatta is also the most common HbVAR in Chinese people from the Silk Road region, as well as in some North American Indian tribes. However, data are scarce on the effect of these HbVAR on the different methods used for analyzing HbA1c.

Methods: Specimens from 24 individuals with 7 HbVAR (Hb G-Coushatta, Hb Queens, Hb G-Hsi-Tsou, Hb Ube-4, Hb G-Waimanalo, Hb Inglewood, and Hb Bologna-St.Orsola) were collected and tested using the International Federation of Clinical Chemistry primary reference method as well as 14 routine HbA1c assay methods.

Results: Hb G-Coushatta showed a clinically significant effect on the measured HbA1c, particularly when analysis was performed with ion-exchange HPLC methods with short elution times. This interference could be resolved by measuring the HbA1c using other methods such as HPLC with a long elution time, immunoassay, boronate affinity chromatography, and enzymatic assay. Hb Queens showed a clinically significant difference, defined as a >10% deviation from regression lines, in results from the 2 HPLC methods but not in the other methods. The remaining 5 rare HbVAR showed different HbA1c results in the different assays.

Conclusion: Hb G-Coushatta, Hb Queens, and other rare HbVAR can interfere with glycohemoglobin assays, including ion-exchange HPLC methods with short elution times, but the interference can be resolved using other unaffected methods. It is important to identify these HbVAR through a careful inspection of the chromatograms and apply other noninterfering methods for accurate measurements of the HbA1c.
Energy Savings Resulting from Building Envelope Upgrades in Mid-Rise Construction—A Case Study
Authors: Peterson J. Eric , Blodgett William H.
Published: October 2007

The Bice House Dormitory on the campus “Grounds” of the University of Virginia was constructed in the mid-1970s as a dormitory for the nursing school. The building was an eight-story, concrete framed, residential facility with brick veneer cladding over steel stud framing systems. After more than 25 years of service, deficiencies in the brick façade, coupled with inadequate exterior wall framing, required removal and replacement of the entire exterior wall system from the interior drywall, up to and including the brick veneer. As part of the exterior wall replacement, window systems and insulation materials were upgraded. The building was also refitted with an air barrier system over the new exterior gypsum sheathing. Because existing individual packaged terminal air conditioning units were temporarily removed and reinstalled after renovation, the heating and cooling systems for the building remained unchanged, providing a unique opportunity to measure the true energy savings realized in a building strictly as a result of upgrading the building envelope. When the total heating and cooling costs after the first two full years of service were compared to the costs from years prior to the renovation (normalized for the temperature variations), a distinct reduction in energy costs were recognized from the improvements made during the renovation. The yearly energy consumption for the building was reduced by roughly 14 %, yielding a savings of roughly $12,800 per year based on current energy costs. Based on a payback period method of analysis, the improvements will have paid for themselves in roughly 14 years.
Los temas de salud en la Unión Europea: su impacto en la sanidad española
Authors: Guimarães Luisa , Freire José-Manuel
Published: October 2007

El texto revisa el impacto de la integración europea en el sector salud (salud pública y servicios sanitarios), estudiando instituciones, funcionamiento y competencias de la Unión Europea (UE), a partir de literatura, documentos y observaciones coyunturales. La UE no tiene competencias directas en salud, pero su legislación ejerce importante impacto en las políticas sanitarias de todos los Estados Miembros. Esta influencia se manifiesta en la protección de la salud y seguridad de los consumidores, regulación de medicamentos y aparatos médicos, homologación de títulos profesionales, libertad de movimiento de profesionales y pacientes, compras y contratación, e investigación biomédica. Estudiando la evolución de la política de salud en la UE se constata un refuerzo progresivo de sus políticas sanitarias y que el objetivo de alcanzar un alto nivel de protección de la salud, tiene importantes implicaciones en todas las políticas europeas. Tomando como caso de estudio las repercusiones de la integración europea en el sistema sanitario español, se destacan sus aspectos más influyentes, retos actuales y perspectivas, así como lecciones para que procesos de integración regional sean factores de equidad y eficiencia en salud.
Coesão social e integração regional: a agenda social do MERCOSUL e os grandes desafios das políticas sociais integradas
Authors: Draibe Sônia Miriam
Published: October 2007

As políticas sociais se encontram em estágio ainda embrionário nos processos constitutivos do MERCOSUL. Entretanto, desde a segunda metade dos anos 1990, acelerou-se o processo de construção das instituições a elas dedicadas no interior do sistema institucional do mercado comum. Tendo por foco a política de saúde e mais amplamente o sistema de políticas sociais, o artigo rastreia as razões do desequilíbrio através de três movimentos: a reconstituição da trajetória de construção institucional do MERCOSUL social; a identificação e confronto das sucessivas estratégias de formulação e implantação da agenda social da integração; e a reflexão sobre os dilemas e desafios que hoje cercam o tema. O estudo permite afirmar que o MERCOSUL opera com estratégias de difícil conciliação. No plano institucional, orienta-se por uma estratégia minimalista, enquanto que no plano conceitual/discursivo, maneja a estratégia maximalista da unificação supranacional das políticas sociais. O fato é que opera uma estratégia minimalista de políticas sociais, uma vez que abdica de trazer para o campo da integração social o debate e a proposição de modelos de desenvolvimento econômico e social que possam sustentar o processo efetivo de constituição da cidadania social regional.
Recursos humanos e trabalho em saúde: os desafios de uma agenda de pesquisa
Authors: Assunção Ada Ávila , Belisário Soraya Almeida , Campos Francisco Eduardo , D'Ávila Luciana Souza
Published: October 2007

Neste artigo são apresentados elementos conceituais considerados chave para as políticas dirigidas aos recursos humanos em saúde no contexto latino-americano. Foram focalizados os conceitos de integração, enfatizando-se os temas integração regional e integração conceitual. São apresentados os conceitos sobre recursos humanos e trabalho, para, ao final, serem debatidos os desafios postos diante do objeto de pesquisa compartilhado, tendo como cenário o contexto das reformas setoriais em curso na América Latina. Concluindo, afirma-se a necessidade, já debatida pelos autores, de se desenvolver um sistema de pesquisa e de tecnologia capaz de sustentar a agenda de intercâmbio entre os países membros do MERCOSUL.