Miracle-dz/UniFAR-FTUs huggingface dataset:
Side chain contributions to the interconversion of the topological isomers of guanylin‐like peptides

The peptide hormones guanylin and uroguanylin are ligands of the intestinal guanylyl cyclase‐C (GC‐C) that is involved in the regulation of epithelial water and electrolyte transport. The small peptides contain 15 and 16 amino acids, respectively, and two disulfide bonds with a 1–3/2–4 connectivity. This structural feature causes the unique existence of two topological isoforms for each peptide in an approximate 3:2 ratio, with only one of the isoforms exhibiting GC‐C‐activating potential. The two uroguanylin isomers can be separated by HPLC and are of sufficient stability to be studied separately at ambient temperatures while the two guanylin isomers are rapidly interconverting even at low temperatures. Both isomers show clearly distinguishable 1H chemical shifts. To investigate the influence of certain amino acid side chains on this isomerism and interconversion kinetics, derivatives of guanylin and uroguanylin (L‐alanine scan and chimeric peptides) were designed and synthesized by Fmoc solid‐phase chemistry and compared by HPLC and 2D 1H NMR spectroscopy. Amino acid residues with the most significant effects on the interconversion kinetics were predominantly identified in the COOH‐terminal part of both peptides, whereas amino acids in the central part of the peptides only moderately affected the interconversion. Thus, the conformational conversion among the isomers of both peptides is under the control of a COOH‐terminal sterical hindrance, providing a detailed model for this dynamic isomerism. Our results demonstrate that kinetic control of the interconversion process can be achieved by the introduction of side chains with a defined sterical profile at suitable sequence positions. This is of potential impact for the future development of GC‐C peptide agonists and antagonists. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Flow mediated dilation with photoplethysmography as a substitute for ultrasonic imaging

Flow mediated dilation (FMD) is a non-invasive method for endothelial function assessment providing an index extracted from ultrasonic B-mode images. Although utilized in the research community, the difficulty of its application and high cost of ultrasonic devices prevent it from being widely used in clinical settings. In this study we show that substituting the ultrasonic device with more easily handled and low cost photoplethysmography and electrocardiography is possible. We introduce new indices based on the photoplethysmogram (PPG) and electrocardiogram (ECG) and show that they are correlated with the ultrasound-based FMD Index. To this end, a conventional ultrasound FMD test was carried out whereas PPG and ECG were simultaneously recorded from 20 healthy volunteers (13 M, 7 F) in the age range of 23–32 years. Our results show a significant correlation between our proposed index and ultrasound FMD when using the ECG in conjunction with the PPG (R = 0.77, p < 0.000 01). Using the PPG alone produces a lower correlation (R = 0.72, p < 0.0001). Compared to conventional FMD, the proposed method is low cost and does not require any special operator skills. Hence it may be easily utilized as a screening tool in locations deprived of high-end ultrasound imaging devices.
Investigation of the mechanism of the dominant negative effect of mutations in the tyrosine kinase domain of the insulin receptor.

Mutations in the tyrosine kinase domain of the insulin receptor cause insulin resistance in a dominant fashion. It has been proposed that formation of hybrid dimers between normal and mutant receptors may explain the dominant negative effect of these mutations. To investigate this mechanism, we expressed two types of human insulin receptors in NIH‐3T3 cells; wild type and the tyrosine kinase‐deficient Ile1153 mutant. To distinguish the two types of receptors, 43 amino acids were deleted from the C‐terminus of the wild type receptor (delta 43 truncation). If mutant and wild type receptors assemble in a random fashion, 50% of the receptors would be hybrid oligomers (alpha 2 beta beta mut). However, alpha 2 beta beta mut hybrids were undetectable. Nevertheless, insulin stimulated the kinase competent delta 43 receptors to transphosphorylate the kinase‐deficient Ile1153 mutant receptor in co‐transfected cells via an intermolecular mechanism. Furthermore, transphosphorylation of the Ile1153 mutant receptor is sufficient to trigger insulin‐stimulated endocytosis. Despite the absence of alpha 2 beta beta mut hybrids, expression of the Ile1153 mutant receptor inhibited the ability of the delta 43 truncated receptor to mediate insulin‐stimulated phosphorylation of insulin receptor substrate‐1 (IRS‐1). Evidence is presented to support the hypothesis that the Ile1153 mutant receptor retains the ability to bind IRS‐1, and that sequestration of substrate may explain the dominant negative effect of the mutant receptor to inhibit phosphorylation of IRS‐1.
Characterization of the uptake of 16 alpha-([18F]fluoro)-17 beta-estradiol in DMBA-induced mammary tumors.

In order to investigate possible correlations between the uptake of 16 alpha-([18F]fluoro)-17 beta-estradiol (18F-ES) by 7,12-dimethylbenz(a) anthracene (DMBA)-induced tumors in rats and the estrogen receptor (ER) content of these tumors, a comprehensive study was performed in which the tissue distribution of 18F-ES was measured in tumor-bearing rats, together with simultaneous measurements of blood volume (by technetium-labeled red blood cells) and blood flow (by iodoantipyrine infusion). In addition, the time course of 18F-ES metabolism and the tissue distribution of the metabolites was studied. Metabolism of 18F-ES is very rapid, and after 2 h, most of the activity in blood and nontarget tissues is due to metabolites; target tissue activity, however, is due mainly to unmetabolized compound. Most of the circulating activity, both 18F-ES and its metabolites, is strongly associated with macromolecules or cells, and while the metabolites are not taken up selectively by target tissues, they do enter nontarget tissues. Tumor blood volume and blood flow vary widely, but not in a way that appears related to tumor necrosis. The uptake of 18F-ES by the uterus and DMBA-induced mammary tumors of adult rats reaches maximum levels (ca 0.35 and 0.10% I.D./g X kg, respectively) at early times (0-1 h), and drops slowly thereafter. The uterus to nontarget or tumour to nontarget tissue ratios, however, start low and continue to increase, reaching maximum levels (ca 20 and 15, respectively) at 2-3 h. There does not, however, appear to be a simple relationship between tumor uptake (either as % I.D./g X kg or tumor to nontarget ratio) measured at a single 3 h time point and tumor ER content, even considering differences in tumor blood flow. This suggests that an estimation of tumor ER content will require the application of more complex pharmacodynamic models that involve the measurement of the complete profile of receptor lignad uptake, retention, and washout from target to nontarget areas. The application of such models will be assisted by the development of estrogen receptor binding ligands that are not converted to circulating metabolites.
Expression Pattern Similarities Support the Prediction of Orthologs Retaining Common Functions after Gene Duplication Events1[OPEN]

Expressologs identify functional orthologs and will be a powerful tool in future orthology assignment. The identification of functionally equivalent, orthologous genes (functional orthologs) across genomes is necessary for accurate transfer of experimental knowledge from well-characterized organisms to others. This frequently relies on automated, coding sequence-based approaches such as OrthoMCL, Inparanoid, and KOG, which usually work well for one-to-one homologous states. However, this strategy does not reliably work for plants due to the occurrence of extensive gene/genome duplication. Frequently, for one query gene, multiple orthologous genes are predicted in the other genome, and it is not clear a priori from sequence comparison and similarity which one preserves the ancestral function. We have studied 11 organ-dependent and stress-induced gene expression patterns of 286 Arabidopsis lyrata duplicated gene groups and compared them with the respective Arabidopsis (Arabidopsis thaliana) genes to predict putative expressologs and nonexpressologs based on gene expression similarity. Promoter sequence divergence as an additional tool to substantiate functional orthology only partially overlapped with expressolog classification. By cloning eight A. lyrata homologs and complementing them in the respective four Arabidopsis loss-of-function mutants, we experimentally proved that predicted expressologs are indeed functional orthologs, while nonexpressologs or nonfunctionalized orthologs are not. Our study demonstrates that even a small set of gene expression data in addition to sequence homologies are instrumental in the assignment of functional orthologs in the presence of multiple orthologs.
Stronger Neo‐Minophagen C™, a glycyrrhizin‐containing preparation, protects liver against carbon tetrachloride‐induced oxidative stress in transgenic mice expressing the hepatitis C virus polyprotein

Background/Aim: Stronger Neo‐Minophagen C™ (SNMC), a glycyrrhizin‐containing preparation, has been used as a treatment for chronic hepatitis for more than 30 years in Japan, and shown to be effective in preventing the development of hepatocellular carcinoma in chronic hepatitis C patients, but its underlying mechanisms remain elusive. The aim of this study was to investigate if SNMC had an anti‐oxidative effect, as oxidative stress has been proposed to be one of the mechanisms of liver injury in hepatitis C virus (HCV)‐associated chronic liver diseases.
CRTH2 Is A Critical Regulator of Neutrophil Migration and Resistance to Polymicrobial Sepsis

Although arachidonic acid cascade has been shown to be involved in sepsis, little is known about the role of PGD2 and its newly found receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), on the septic response. Severe sepsis is associated with the failure of neutrophil migration. To investigate whether CRTH2 influences neutrophil recruitment and the lethality during sepsis, sepsis was induced by cecal ligation and puncture (CLP) surgery in mice. CRTH2 knockout (CRTH2−/−) mice were highly resistant to CLP-induced sepsis, which was associated with lower bacterial load and lower production of TNF-α, IL-6, and CCL3. IL-10, an anti-inflammatory cytokine, was higher in CRTH2−/− mice, blunting CLP-induced lethality in CRTH2−/− mice. Neutrophil accumulation in the peritoneum was more pronounced after CLP in CRTH2−/− mice, which was associated with higher CXCR2 levels in circulating neutrophils. Furthermore, sepsis caused a decrease in the level of acetylation of histone H3, an activation mark, at the CXCR2 promoter in wild-type neutrophils, suggesting that CXCR2 expression levels are epigenetically regulated. Finally, both pharmacological depletion of neutrophils and inhibition of CXCR2 abrogated the survival benefit in CRTH2−/− mice. These results demonstrate that genetic ablation of CRTH2 improved impaired neutrophil migration and survival during severe sepsis, which was mechanistically associated with epigenetic-mediated CXCR2 expression. Thus, CRTH2 is a potential therapeutic target for polymicrobial sepsis.
Redefining the boundaries of the hippocampal CA2 subfield in the mouse using gene expression and 3‐dimensional reconstruction

The morphology of neurons in the main divisions of the hippocampal complex allow the easy identification of granule cells in the dentate gyrus and pyramidal cells in the CA1 and CA3 regions of Ammon's horn. However, neurons in the CA2 subfield have been much more difficult to reliably identify. We have recently identified a set of genes whose expression is restricted to either the dentate gyrus, CA1, CA2, or CA3. Here we show that these genes have an essentially nonoverlapping distribution throughout the entire septotemporal extent of the hippocampus. 3‐Dimensional reconstruction of serial sections processed for in situ hybridization of mannosidase 1, alpha (CA1), bcl‐2‐related ovarian killer protein (CA3), and Purkinje cell protein 4 (dentate gyrus + CA2) was used to define the boundaries of each subregion throughout the entire hippocampus. The boundaries observed for these three genes are recapitulated across a much larger set of genes similarly enriched in specific hippocampal subregions. The extent of CA2 defined on the basis of gene expression is somewhat larger than that previously described on the basis of structural anatomical criteria, particularly at the rostral pole of the hippocampus. These results indicate that, at least at the molecular level, there are robust, consistent genetic boundaries between hippocampal subregions CA1, CA2, CA3, and the dentate gyrus, allowing a redefinition of their boundaries in order to facilitate functional studies of different neuronal subtypes in the hippocampus. J. Comp. Neurol. 485:1–10, 2005. © 2005 Wiley‐Liss, Inc.
Tubal factor infertility, with special regard to chlamydial salpingitis

Purpose of review This article will highlight recent research into tubal factor infertility as one of the main causes of involuntary childlessness in women. There will be a focus on chlamydial infections. Recent findings The most common cause of tubal factor infertility is occlusion of the fallopian tubes due to an infection by a sexually transmitted agent, by Chlamydia trachomatis or Neisseria gonorrhoeae.The prevalence of diagnosed cases of tubal factor infertility (TFI) can be correlated to the epidemiological situation regarding these agents that was prevailing several years ago. This is partly due to the trend seen in many Western countries that women often postpone to try to get pregnant. Therefore, there is often a time lag between the acute primary pelvic inflammatory disease (PID) and when women first consult because of fertility problems. Sub-clinical salpingitis is today regarded as even more common than symptomatic PID. Persistent tubal infections by C. trachomatis are also a common feature, even despite courses of antibiotic therapy. The current focus on TFI has been on the immunopathology of tubal chlamydial infections, for which differences in host factors, such as genetic polymorphism in cytokine response and human leukocyte antigen type, may play a role in the outcome of pelvic inflammatory disease. Hysterosonography is a more convenient mode for diagnosing tubal occlusion than hysterosalpingography. The use of new species-specific antibody tests for C. trachomatis has decreased previous specificity problems found when used to detect tubal occlusion in work-up of women consulting because of infertility. Summary Infection by C. trachomatis is a major cause of TFI. Many cases of chlamydial salpingitis have a more or less subclinical course. The tubal infection may become chronic in spite of antibiotic therapy. Immunological processes may continue after microbiological cure, which stresses the importance of screening for C. trachomatis in order to detect and treat carriers to hinder spread to still uninfected women.
Performance evaluation of different allocation algorithms using FPGA platforms

The communication between processing elements are suffering challenges due to latency. The arbitration algorithm used inside an arbitration unit of a network-on-chip based router plays a significant role in determining the performance of the whole network-on-chip based mesh. This paper revaluates some of the standard forms of the arbitration algorithms and presents the synthesis and implementation on FPGA platforms. The work will help NoC designers to suitable allocation algorithms for their FPGA design The implementation is carried out using various arbitration algorithms responsible for scheduling 12-bit request vector. The implementation targets Virtex5 FPGA family. The analysis concludes that the iSlip allocation algorithm shows lower power delay product and lower resource utilization and a reasonably lower area delay product when implemented for speed optimization goal. Hence it can be best used for high speed low power NoC based systems.
Organic Cultivation of Triticum turgidum subsp. durum Is Reflected in the Flour-Sourdough Fermentation-Bread Axis

ABSTRACT Triticum turgidum subsp. durum was grown according to four farming systems: conventional (CONV), organic with cow manure (OMAN) or green manure (OLEG), and without inputs (NOINPUT). Some chemical and technological characteristics differed between CONV and organic flours. As shown by two-dimensional electrophoresis (2-DE) analysis, OMAN and OLEG flours showed the highest number of gliadins, and OMAN flour also had the highest number of high-molecular-mass glutenins. Type I sourdoughs were prepared at the laboratory level through a back-slopping procedure, and the bacterial ecology during sourdough preparation was described by 16S rRNA gene pyrosequencing. Before fermentation, the dough made with CONV flour showed the highest bacterial diversity. Flours were variously contaminated by genera belonging to the Proteobacteria, Firmicutes, and Actinobacteria. Mature sourdoughs were completely and stably dominated by lactic acid bacteria. The diversity of Firmicutes was the highest for mature sourdoughs made with organic and, especially, NOINPUT flours. Beta diversity analysis based on the weighted UniFrac distance showed differences between doughs and sourdoughs. Those made with CONV flour were separated from the other with organic flours. Lactic acid bacterium microbiota structure was qualitatively confirmed through the culturing method. As shown by PCR-denaturing gradient gel electrophoresis (DGGE) analysis, yeasts belonging to the genera Saccharomyces, Candida, Kazachstania, and Rhodotorula occurred in all sourdoughs. Levels of bound phenolic acids and phytase and antioxidant activities differed depending on the farming system. Mature sourdoughs were used for bread making. Technological characteristics were superior in the breads made with organic sourdoughs. The farming system is another determinant affecting the sourdough microbiota. The organic cultivation of durum wheat was reflected along the flour-sourdough fermentation-bread axis.
A survey of attitudes of glaucoma subspecialists in England and Wales to visual field test intervals in relation to NICE guidelines

Objectives To establish the attitudes of glaucoma specialists to the frequency of visual field (VF) testing in the UK, using the NICE recommendations as a standard for ideal practice. Design Interview and postal survey. Setting UK and Eire Glaucoma Society national meeting 2011 in Manchester, UK, with a second round of surveys administered by post. Participants All consultant glaucoma specialists in England and Wales were invited to complete the survey. Primary and secondary outcome measures (1) Compliance of assigned follow-up VF intervals with NICE guidelines for three hypothetical patient scenarios, with satisfactory treated intraocular pressure and (a) no evidence of VF progression; (b) evidence of VF progression and (c) uncertainty about VF progression, and respondents were asked to provide typical follow-up intervals representative of their practice; (2) attitudes to research recommendations for six VF in the first 2 years for newly diagnosed patients with glaucoma. Results 70 glaucoma specialists completed the survey. For each of the clinical scenarios a, b and c, 14 (20%), 33 (47%) and 28 (40%) responses, respectively, fell outside the follow-up interval recommended by NICE. Nearly half of the specialists (46%) agreed that 6 VF tests in the first 2 years was ideal practice, while 16 (28%) said this was practice ‘not possible’, with many giving resources within the NHS setting as a limiting factor. Conclusions The results from this survey suggest that there is a large variation in attitudes to follow-up intervals for patients with glaucoma in the UK, with assigned intervals for VF testing which are, in many cases, inconsistent with the guidelines from NICE.
The Effects of Staff-rotation in Public Administration on the Decision to Bribe or be Bribed

Periodic rotation of staff in public administration may lead to lower corruption, as it disrupts long-term relationships between public officials and potential bribers. This paper proposes an experimental design that tests the anti-corruption effect of staff rotation in situations where public officials have committed to reciprocating bribes. We find that staff rotation does not influence the proportion of firms offering bribes but does reduce the~share of bribe acceptance and inefficient decisions owing to bribery. The~outcome of the~staff-rotation treatment, in which firms offered bribes even though they were rarely accepted by officials, is consistent with the game having a quantal response equilibria.
Expression and prognostic value of the retinoblastoma tumour suppressor gene (RB‐1) in childhood acute lymphoblastic leukaemia

In a retrospective analysis, acute lymphoblastic leukaemia (ALL) blast cells of 102 children were investigated for the expression of the retinoblastoma susceptibility (RB)‐1 gene at mRNA level by dot blot hybridization and semiquantitative RT‐PCR. 56 patients were analysed by dot blot hybridization and 35 representative patients out of this group by semiquantitative RT‐PCR. Two additional groups of patients (23 patients with initial and 23 patients with relapsed ALL) were also investigated by semiquantitative RT‐PCR. RB‐1 gene expression was detectable in all investigated ALL at different levels. According to the relative mRNA expression the patients were discriminated by the median value in groups with low or high RB‐1 expression. The Kaplan‐Meier estimates showed that patients with low RB‐1 expression had a lower probability of remaining in first remission (P=0.03) and a significantly higher risk to succumb to their disease (P=0.03). Furthermore, the comparison of the results between initial and relapsed ALL showed that the relapses had significantly lower RB‐1 mRNA expression (P=0.02). The overall survival of the patients was shorter in both groups when RB‐1 gene expression was low. A multivariate analysis, including age, sex, immunological subtype, initial white blood cell count and RB‐1 expression, identified RB‐1 as an independent prognostic predictor (P=0.017) in addition to the initial white blood cell count (P=0.00001). In conclusion, low RB‐1 expression is an unfavourable prognostic predictor in initial and relapsed childhood ALL. The RB‐1 gene expression in relapsed ALL is significantly lower than in initial ALL.