bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equivalent binding sites reveal convergently evolved interaction motifs
Authors: Henschel Andreas , Kim Wan Kyu , Schroeder Michael 
Published: November 2005

Abstract
Motivation: Much research has been devoted to the characterization of interaction interfaces found in complexes with known structure. In this context, the interactions of non-homologous domains at equivalent binding sites are of particular interest, as they can reveal convergently evolved interface motifs. Such motifs are an important source of information to formulate rules for interaction specificity and to design ligands based on the common features shared among diverse partners.
Results: We develop a novel method to identify non-homologous structural domains which bind at equivalent sites when interacting with a common partner. We systematically apply this method to all pairs of interactions with known structure and derive a comprehensive database for these interactions. Of all non-homologous domains, which bind with a common interaction partner, 4.2% use the same interface of the common interaction partner (excluding immunoglobulins and proteases). This rises to 16% if immunoglobulin and proteases are included. We demonstrate two applications of our database: first, the systematic screening for viral protein interfaces, which can mimic native interfaces and thus interfere; and second, structural motifs in enzymes and its inhibitors. We highlight several cases of virus protein mimicry: viral M3 protein interferes with a chemokine dimer interface. The virus has evolved the motif SVSPLP, which mimics the native SSDTTP motif. A second example is the regulatory factor Nef in HIV which can mimic a kinase when interacting with SH3. Among others the virus has evolved the kinase’s PxxP motif. Further, we elucidate motif resemblances in Baculovirus p35 and HIV capsid proteins. Finally, chymotrypsin is subject to scrutiny wrt. its structural similarity to subtilisin and wrt. its inhibitor’s similar recognition sites.
Contact: ah@biotec.tu-dresden.de
Supplementary informaton: A database is online at
2SNP: scalable phasing based on 2-SNP haplotypes
Authors: Brinza Dumitru , Zelikovsky Alexander 
Published: November 2005

Abstract
Summary: 2SNP software package implements a new very fast scalable algorithm for haplotype inference based on genotype statistics collected only for pairs of SNPs. This software can be used for comparatively accurate phasing of large number of long genome sequences, e.g. obtained from DNA arrays. As an input 2SNP takes genotype matrix and outputs the corresponding haplotype matrix. On datasets across 79 regions from HapMap 2SNP is several orders of magnitude faster than GERBIL and PHASE while matching them in quality measured by the number of correctly phased genotypes, single-site and switching errors. For example, 2SNP requires 41 s on Pentium 4 2 Ghz processor to phase 30 genotypes with 1381 SNPs (ENm010.7p15:2 data from HapMap) versus GERBIL and PHASE requiring more than a week and admitting no less errors than 2SNP.
Availability: 2SNP software package is publicly available at
Contact: alexz@cs.gsu.edu
Association of the C677T methylenetetrahydrofolate reductase mutation with congenital heart diseases
Authors: Lee Chien‐Nan , Su Yi‐Ning , Cheng Wen‐Fang , Lin Ming‐Tai , Wang Jou‐Kou , Wu Mei‐Hwan , Hsieh Fon‐Jou 
Published: November 2005

Background.  To investigate whether the cytosine‐to‐thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with congenital heart diseases (CHD), using high throughput heteroduplex analysis based upon the powerful technique of denaturing high‐performance liquid chromatography.Methods.  We investigated the MTHFR genotype of a cytosine‐to‐thymine mutation at base 677 for 213 patients of CHDs as confirmed by cardiac catheterization and also for 195 healthy controls.Results.  The overall genotype frequencies of the MTHFR C677T polymorphism were not significantly different between the CHD patients and the healthy control (P = 0.345). Furthermore, taking various subgroups of CHD patients into consideration, we noted a significantly increased proportion of homozygous TT genotypes for patients suffering from valvular pulmonary stenosis (PS) or pulmonary atresia with an intact ventricular septum (PA + IVS) (p = 0.0005). For patients revealing heterotaxy syndrome, a conotruncal anomaly including tetralogy of Fallot, an interruption of the aortic arch, persistent truncus arteriosus, and aortopulmonary window, no statistically significant difference existed.Conclusions.  The discrepancy in the distribution of MTHFR genotypes amongst various subtypes of CHD reflects some heterogeneity in the developmental mechanism of CHD. The increased percentage of homozygous TT genotypes might contribute to the pathogenesis of valvular PS and PA + IVS.
Increased granulocyte chemotactic protein‐2 concentrations in peritoneal fluid of women with endometriosis
Authors: Suzumori Nobuhiro , Zhao Xaio Xi , Suzumori Kaoru 
Published: November 2005

Background.  To evaluate the release of granulocyte chemotactic protein‐2 (GCP‐2) into peritoneal fluid in women with endometriosis, we measured its concentration with reference to the disease stage and the phase of the menstrual cycle.Methods.  Surgery was scheduled in the proliferative or secretory phase of the menstrual cycle for 64 women with endometriosis (n = 38) or cystadenomas (n = 26). GCP‐2 concentrations in the peritoneal fluid were measured using an enzyme‐linked immunosorbent assay.Result.  Our findings indicated elevated concentrations of GCP‐2 in peritoneal fluid from women with endometriosis during the proliferative phase, which were positively correlated with the stage of endometriosis.Conclusion.  Inflammation associated with endometriosis may be involved in the pathogenesis of the disease through increasing levels of peritoneal fluid GCP‐2.
Maternal underweight and the risk of spontaneous abortion
Authors: Helgstrand Stine , Andersen Anne‐Marie Nybo 
Published: November 2005

Background.  To evaluate the risk of spontaneous abortion in relation to maternal pre‐pregnant underweight.Methods.  The study was designed as a cohort study within the framework of the Danish National Birth Cohort (DNBC). The participants were a total of 23 821 women recruited consecutively to the DNBC from October 1, 1997 to March 31, 1999 and interviewed subsequently. The pregnant women were recruited in first half of pregnancy and interviewed about pre‐pregnant body size, obstetric history, exposures in pregnancy, and socio‐demographic factors. Pregnancies were followed‐up regarding spontaneous abortion. Relative risk of spontaneous abortion was calculated as Hazard Ratios using Cox regression with delayed entry.Results.  The outcome measure was spontaneous abortion. The hazard ratio for spontaneous abortion in women with a pre‐pregnant body mass index (BMI) below 18.5 was 1.24 (95% confidence limits 0.95–1.63) compared to women with pre‐pregnant BMI 18.5–24.9. Women with a BMI of 25 or more had a smaller increase in risk of spontaneous abortion. Adjustment for maternal age, parity, previous miscarriages, and lifestyle factors did not affect the estimates substantially, neither did exclusion of women with metabolic or eating disorders.Conclusion.  These results indicate that pre‐pregnant underweight may affect the risk of spontaneous abortion negatively.
A study of oligosaccharide variants of alpha‐fetoproteins produced by normal fetuses and fetuses with trisomy 21
Authors: Yamamoto Ritsu , Ohkouchi Toshihiro , Tabata Kouichi , Ebina Yasuhiko , Watari Hidemichi , Kudo Masataka , Shimizu Kayoko , Satomura Shinji , Minakami Hisanori , Sakuragi Noriaki 
Published: November 2005

Background.  The mechanisms of the increase in the percentage of alpha‐fetoproteins (AFPs) that strongly binds to Lens culinaris agglutinin (AFP‐L3) in pregnancies with a trisomy 21 fetus have not been analyzed. To investigate the oligosaccharide variants of AFP produced by normal fetuses and fetuses with trisomy 21, the lectin reactivity of AFP was analyzed.Methods.  Fetal liver tissue, amniotic fluid, and maternal serum were obtained from five normal pregnancies and five pregnancies with a trisomy 21 fetus. The percentages of AFP reactive to lectins were determined by lectin‐affinity electrophoresis coupled with antibody‐affinity blotting.Results.  The percentages of AFP‐L3 in the fetal liver and the maternal serum were 23.9 and 27.0%, respectively, in normal pregnancies, and 28.7 and 38.5%, respectively, in pregnancies with a trisomy 21 fetus. There was no statistically significant difference between the percentage in the fetal liver and the percentage in the maternal serum in normal pregnancies; however, a significant difference (P < 0.01) was found in pregnancies with a trisomy 21 fetus. In regard to the percentage of AFP‐L3 in the fetal liver, there was no significant difference; however, a significant difference (P < 0.05) was found in the maternal serum between normal pregnancies and pregnancies with a trisomy 21 fetus.Conclusions.  The transference of the AFP‐L3 fraction might be relatively high in the placentas of women carrying a trisomy 21 fetus, and this could be the one of the reasons for the increase in the percentage of AFP‐L3 in the maternal serum in pregnancies with a trisomy 21 fetus.
O3 2  Cumulative delivery rate from a single oocyte harvest
Authors: Hydén‐Granskog C , Unkila‐Kallio L , Ahola U , Halttunen M , Tiitinen A. 
Published: November 2005

Background.  There is an urgent need to evaluate the cumulative delivery rate (DR) from a single oocyte harvest after both fresh and frozen embryo transfers (ET). Elective single embryo transfer (eSET) in combination with embryo cryopreservation has reduced the multiple delivery rate (MDR) compared with transfer of two embryos (DET), but the effect of frozen embryo transfers (FET) on cumulative DR and multiple DR has not been evaluated. In cases of imminent risk of ovarian hyperstimulation syndrome (OHSS) fresh ET is not performed and all embryos are cryopreserved. However, little is known about the DR after later frozen ETs from these OHSS cycles.The aim was to find out the total reproductive potential from a single oocyte harvest i.e. DR after fresh transfer and one or several frozen embryo transfers performed after an unsuccesful fresh transfer.The FET cycles performed during 1.3.1998–30.6.2004 were as follows: in the eSET group 907 FETs, in eDET 516 FETs and in no ET 161 FETs. In FET cycles one or two embryos were transferred in the eSET group. The mean number of embryos transferred in FET cycles was 1.5/1.6/1.5 respectively.Methods.  All OPU‐cycles with ET and/or cryopreservation during 1998–2003.

Type of transfer
SET
eSET*
DET
eSET + cryo
eDET + cryo
No ET + cryo

Number
260
10
197
791
608
66

Mean age
33.6
36.2
34.5
32.3
34.1
31.9

mean n of cryo
0
0
0
6.4
3.4
12.4

embryos (range)

(1–31)
(1–24)
(1–39)

no cryopreservation due to poor quality of the other embryo

Findings.

Type of transfer
SET
eSET*
DET
eSET + cryo
eDET + cryo
No ET + cryo

DR in fresh cycles
15.4%
20.0%
23.5%
29.0%
30.9%
0

MDR
2.5%
0
10.9%
1.3%
26.6%
0

DR in FET cycles
0
0
0
24.9%
18.8%
24.2%

Cumulative DR
15.4%
20%
23.5%
52.6%
42.8%
54.5%

Cumulative MDR
2.5%
0
10.9%
6.7%
25.0%
16.7%

no cryopreservation due to poor quality of the other embryo

Interpretation.  Delivery rate in OPU cycles without cryopreservation was lower than in cycles with cryopreservation. In OPU cycles with cryopreservation the DR was not effected by the number of embryos transferred, but more twins were seen in cycles with eDET than with eSET (26.6% compared to 1.3%). The cumulative DR in the group with eSET in the fresh cycle exceeded that with eDET (52.6% vs 42.8%). In the eSET group only 6.7% of the deliveries were multiples compared to 25% in the group with eDET. Elective SET and cryopreservation is an effective tool not only to achieve a good cumulative delivery rate, but also to reduce multiple births. The possibility to cryopreserve all embryos in case of risk for OHSS is associated with good DR from frozen cycles, since at least one delivery has been achieved in 54.5% of these cycles.
Bacterial diversity of metagenomic and PCR libraries from the Delaware River
Authors: Cottrell Matthew T. , Waidner Lisa A. , Yu Liying , Kirchman David L. 
Published: November 2005

SummaryTo determine whether metagenomic libraries sample adequately the dominant bacteria in aquatic environments, we examined the phylogenetic make‐up of a large insert metagenomic library constructed with bacterial DNA from the Delaware River, a polymerase chain reaction (PCR) library of 16S rRNA genes, and community structure determined by fluorescence in situ hybridization (FISH). The composition of the libraries and community structure determined by FISH differed for the major bacterial groups in the river, which included Actinobacteria, beta‐proteobacteria and Cytophaga‐like bacteria. Beta‐proteobacteria were underrepresented in the metagenomic library compared with the PCR library and FISH, while Cytophaga‐like bacteria were more abundant in the metagenomic library than in the PCR library and in the actual community according to FISH. The Delaware River libraries contained bacteria belonging to several widespread freshwater clusters, including clusters of Polynucleobacter necessarius, Rhodoferax sp. Bal47 and LD28 beta‐proteobacteria, the ACK‐m1 and STA2‐30 clusters of Actinobacteria, and the PRD01a001B Cytophaga‐like bacteria cluster. Coverage of bacteria with > 97% sequence identity was 65% and 50% for the metagenomic and PCR libraries respectively. Rarefaction analysis of replicate PCR libraries and of a library constructed with re‐conditioned amplicons indicated that heteroduplex formation did not substantially impact the composition of the PCR library. This study suggests that although it may miss some bacterial groups, the metagenomic approach can sample other groups (e.g. Cytophaga‐like bacteria) that are potentially underrepresented by other culture‐independent approaches.
Fishing for biodiversity: novel methanopterin‐linked C1 transfer genes deduced from the Sargasso Sea metagenome
Authors: Kalyuzhnaya Marina G. , Nercessian Olivier , Lapidus Alla , Chistoserdova Ludmila 
Published: November 2005

SummaryThe recently generated database of microbial genes from an oligotrophic environment populated by a calculated 1800 major phylotypes (the Sargasso Sea metagenome – SSM) presents a great source for expanding local databases of genes indicative of a specific function. In this article we analyse the SSM for the presence of methanopterin‐linked C1 transfer genes that are signature for methylotrophy. We conclude that more than 10 phylotypes possessing genes of interest are present in this environment. The sequences representative of these major phylotypes do not appear to belong to any known microbial group capable of methanopterin‐linked C1 transfer. Instead, these sequences separate from all known sequences on phylogenetic trees, pointing toward their affiliation with novel microbial phyla. These data imply a broader distribution of methanopterin‐linked functions in the microbial world than has been previously known.
Putative novel photosynthetic reaction centre organizations in marine aerobic anoxygenic photosynthetic bacteria: insights from metagenomics and environmental genomics
Authors: Yutin Natalya , Béjà Oded 
Published: November 2005

SummaryPhotosynthetic core complexes of anoxygenic bacteria consist of reaction centres (RCs) surrounded by light‐harvesting complexes (LHC). The structural proteins of the RC–LHC1 complex are encoded by the puf‐operon. We find diverse operon organizations of puf‐operons that reflect structural differences of the core complex in marine aerobic anoxygenic photosynthetic bacteria (AAnP). By analysis of environmental DNA records coming from AAnP bacteria we find several unknown proteins downstream to the pufM, which were assigned as novel PufX proteins. As all known pufX genes belong to Rhodobacter strains which carry out anaerobic photosynthesis, this may be the first observation of a PufX‐containing RCs in aerobic anoxygenic photosynthetic bacteria. Phylogenetic analyses of PufM proteins from cultured as well as from uncultured bacteria show that PufM from operons containing putative novel pufX genes are grouped with Rhodobacter and not with Roseobacter strains.
Insights into the genomes of archaea mediating the anaerobic oxidation of methane
Authors: Meyerdierks Anke , Kube Michael , Lombardot Thierry , Knittel Katrin , Bauer Margarete , Glöckner Frank Oliver , Reinhardt Richard , Amann Rudolf 
Published: November 2005

SummaryThe anaerobic oxidation of methane is a globally significant process which is mediated by consortia of yet uncultivated methanotrophic archaea (ANME) and sulfate‐reducing bacteria. In order to gain deeper insights into genome characteristics of the different ANME groups, large‐insert genomic libraries were constructed using DNA extracted from a methanotrophic microbial mat growing in the anoxic part of the Black Sea, and from sediments above gas hydrates at the Hydrate Ridge off the coast of Oregon. Analysis of these fosmid libraries with respect to archaeal 16S rRNA gene diversity revealed a single ANME‐1b ribotype for the Black Sea libraries, whereas the sequences derived from the Hydrate Ridge library phylogenetically affiliated with the ANME‐2a, ANME‐2c and ANME‐3 group. Genome walking for ANME‐1b resulted in a contiguous 155 kb composite genome fragment. The comparison of a set of four genomic fragments belonging to the different ANME groups revealed differences in the rRNA operon structure and the average G+C content, with the ANME‐2c contig showing the highest divergence within the set. A detailed analysis of the ANME contigs with respect to genes putatively involved in the anaerobic oxidation of methane led to the identification of: (i) a putative N5,N10‐methenyltetrahydromethanopterin cyclohydrolase gene, (ii) a gene cluster supposedly encoding a novel type of heterodisulfide reductase/dehydrogenase complex and (iii) a gene cluster putatively encoding a new type of CO dehydrogenase/acetyl‐CoA synthase enzyme complex.
A wide host‐range metagenomic library from a waste water treatment plant yields a novel alcohol/aldehyde dehydrogenase
Authors: Wexler Margaret , Bond Philip L. , Richardson David J. , Johnston Andrew W. B. 
Published: November 2005

SummaryUsing DNA obtained from the metagenome of an anaerobic digestor in a waste water treatment plant, we constructed a gene library cloned in the wide host‐range cosmid pLAFR3. One cosmid enabled Rhizobium leguminosarum to grow on ethanol as sole carbon and energy source, this being due to the presence of a gene, termed adhEMeta. The AdhEMeta protein most closely resembles the AdhE alcohol dehydrogenase of Clostridium acetobutylicum, where it catalyses the formation of ethanol and butanol in a two‐step reductive process. However, cloned adhEMeta did not confer ethanol utilization ability to Escherichia coli or to Pseudomonas aeruginosa, even though it was transcribed in both these hosts. Further, cell‐free extracts of E. coli and R. leguminosarum containing cloned adhEMeta had butanol and ethanol dehydrogenase activities when assayed in vitro. In contrast to the well‐studied AdhE proteins of C. acetobutylicum and E. coli, the enzyme specified by adhEMeta is not inactivated by oxygen and it enables alcohol to be catabolized. Cloned adhEMeta did, however, confer one phenotype to E. coli. AdhE– mutants of E. coli fail to ferment glucose and introduction of adhEMeta restored the growth of such mutants when grown under fermentative conditions. These observations show that the use of wide host‐range vectors enhances the efficacy with which metagenomic libraries can be screened for genes that confer novel functions.
Genetic and functional properties of uncultivated thermophilic crenarchaeotes from a subsurface gold mine as revealed by analysis of genome fragments
Authors: Nunoura Takuro , Hirayama Hisako , Takami Hideto , Oida Hanako , Nishi Shinro , Shimamura Shigeru , Suzuki Yohey , Inagaki Fumio , Takai Ken , Nealson Kenneth H. , Horikoshi Koki 
Published: November 2005

SummaryWithin a phylum Crenarchaeota, only some members of the hyperthermophilic class Thermoprotei, have been cultivated and characterized. In this study, we have constructed a metagenomic library from a microbial mat formation in a subsurface hot water stream of the Hishikari gold mine, Japan, and sequenced genome fragments of two different phylogroups of uncultivated thermophilic Crenarchaeota: (i) hot water crenarchaeotic group (HWCG) I (41.2 kb), and (ii) HWCG III (49.3 kb). The genome fragment of HWCG I contained a 16S rRNA gene, two tRNA genes and 35 genes encoding proteins but no 23S rRNA gene. Among the genes encoding proteins, several genes for putative aerobic‐type carbon monoxide dehydrogenase represented a potential clue with regard to the yet unknown metabolism of HWCG I Archaea. The genome fragment of HWCG III contained a 16S/23S rRNA operon and 44 genes encoding proteins. In the 23S rRNA gene, we detected a homing‐endonuclease encoding a group I intron similar to those detected in hyperthermophilic Crenarchaeota and Bacteria, as well as eukaryotic organelles. The reconstructed phylogenetic tree based on the 23S rRNA gene sequence reinforced the intermediate phylogenetic affiliation of HWCG III bridging the hyperthermophilic and non‐thermophilic uncultivated Crenarchaeota.
Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities
Authors: Janssen Dick B. , Dinkla Inez J. T. , Poelarends Gerrit J. , Terpstra Peter 
Published: November 2005

SummaryBacterial dehalogenases catalyse the cleavage of carbon‐halogen bonds, which is a key step in aerobic mineralization pathways of many halogenated compounds that occur as environmental pollutants. There is a broad range of dehalogenases, which can be classified in different protein superfamilies and have fundamentally different catalytic mechanisms. Identical dehalogenases have repeatedly been detected in organisms that were isolated at different geographical locations, indicating that only a restricted number of sequences are used for a certain dehalogenation reaction in organohalogen‐utilizing organisms. At the same time, massive random sequencing of environmental DNA, and microbial genome sequencing projects have shown that there is a large diversity of dehalogenase sequences that is not employed by known catabolic pathways. The corresponding proteins may have novel functions and selectivities that could be valuable for biotransformations in the future. Apparently, traditional enrichment and metagenome approaches explore different segments of sequence space. This is also observed with alkane hydroxylases, a category of proteins that can be detected on basis of conserved sequence motifs and for which a large number of sequences has been found in isolated bacterial cultures and genomic databases. It is likely that ongoing genetic adaptation, with the recruitment of silent sequences into functional catabolic routes and evolution of substrate range by mutations in structural genes, will further enhance the catabolic potential of bacteria toward synthetic organohalogens and ultimately contribute to cleansing the environment of these toxic and recalcitrant chemicals.
RESWITCHING AS A CAUSE OF INSTABILITY OF INTERTEMPORAL EQUILIBRIUM
Authors: Schefold Bertram 
Published: November 2005

ABSTRACTIt is generally recognized that the paradoxes of capital, of which reswitching is the most striking example, are a reason to question the existence of aggregate production functions. It is here shown that they affect intertemporal general equilibrium as well as causes of instabilities.