bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Mas‐related gene family: structural and functional conservation of human and rhesus MrgX receptors
Authors: Burstein Ethan S , Ott Thomas R , Feddock Michele , Ma Jian‐Nong , Fuhs Steve , Wong Steven , Schiffer Hans H , Brann Mark R , Nash Norman R 
Published: November 2005

Recently, a large family of G‐protein‐coupled receptors called Mas‐related genes (Mrgs), which is selectively expressed in small‐diameter sensory neurons of dorsal root ganglia, was described. A subgroup of human Mrg receptors (MrgX1–X4) is not found in rodents and this has hampered efforts to define the physiological roles of these receptors.
MrgX receptors were cloned from rhesus monkey and functionally characterized alongside their human orthologs. Most of the human and rhesus MrgX receptors displayed high constitutive activity in a cellular proliferation assay. Proliferative responses mediated by human or rhesus MrgX1, or rhesus MrgX2 were partially blocked by pertussis toxin (PTX). Proliferative responses mediated by rhesus MrgX3 and both human and rhesus MrgX4 were PTX insensitive. These results indicate that human and rhesus MrgX1 and MrgX2 receptors activate both Gq‐ and Gi‐regulated pathways, while MrgX3 and MrgX4 receptors primarily stimulate Gq‐regulated pathways.
Peptides known to activate human MrgX1 and MrgX2 receptors activated the corresponding rhesus receptors in cellular proliferation assays, Ca2+‐mobilization assays, and GTP‐γS‐binding assays. Cortistatin‐14 was selective for human and rhesus MrgX2 receptors over human and rhesus MrgX1 receptors. BAM22 and related peptides strongly activated human MrgX1 receptors, but weakly activated rhesus MrgX1, human MrgX2, and rhesus MrgX2 receptors.
These data suggest that the rhesus monkey may be a suitable animal model for exploring the physiological roles of the MrgX receptors.

British Journal of Pharmacology (2006) 147, 73–82. doi:10.1038/sj.bjp.0706448
Multidrug resistance 1 gene polymorphisms are not associated with inflammatory bowel disease and response to therapy in Italian patients
Authors: PALMIERI O. , LATIANO A. , VALVANO R. , D'INCÀ R. , VECCHI M. , STURNIOLO G. C. , SAIBENI S. , BOSSA F. , LATIANO T. , DEVOTO M. , ANDRIULLI A. , ANNESE V. 
Published: November 2005

SummaryBackground : Host genetic factors may be important in determining not only disease susceptibility, but also disease behaviour and response to therapy in inflammatory bowel disease. Two polymorphisms (C3435T and G2677T/A) of the multidrug resistance 1 gene have been correlated with the altered P‐glycoprotein expression and function in humans, and associated with predisposition to ulcerative colitis and Crohn's disease.Aim : To investigate the contribution of these polymorphisms to disease susceptibility and response to medical therapy.Methods : A total of 946 inflammatory bowel disease patients (478 Crohn's disease, 272 males, mean age 43 ± 14 years and 468 ulcerative colitis, 290 males, mean age 48 ± 15 years) and 450 healthy controls were genotyped for the single nucleotide polymorphisms C3435T and G2677T/A. Patients were also classified on the basis of response to medical therapy (mesalazine, steroids, immunosuppressives and infliximab).Results : Both single nucleotide polymorphisms were in Hardy–Weinberg equilibrium and significant linkage disequilibrium. No significant difference in the allele, genotype, and haplotype frequencies was found in both Crohn's disease and ulcerative colitis patients compared with the controls. No correlation with clinical features was found, except for a reduced frequency of extra‐intestinal manifestations in Crohn's disease patients with the G2677T genotype (40%) compared with GG2677 and 2677TT genotypes (54% and 58%, respectively) (P = <0.02). No significant difference was also found after stratifying the patients on the basis of their response to medical therapy.Conclusion : The investigated polymorphisms of the multidrug resistance 1 gene have no significant role in disease susceptibility and response to medical therapy in our Italian population of inflammatory bowel disease patients.
Thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome: a new index predicting response to plasma exchange
Authors: Wyllie B. F. , Garg A. X. , Macnab J. , Rock G. A. , Clark W. F. ,   Members of the Canadian Apheresis Group
Published: November 2005

SummaryDespite the favourable response of thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS) to plasma exchange, an early level of mortality persists. Non‐response has been associated with a low frequency of exchange. The Rose index of TTP/HUS severity, occasionally used to predict the response of TTP/HUS to plasma exchange, remains unsatisfactory. The purpose of this study was to develop a new index predicting response of TTP/HUS to plasma exchange and to compare it with the Rose index. Retrospective analysis of 171 cases of TTP/HUS from 39 apheresis units across Canada between 1980 and 2001 was conducted. Logistic regression analysis was used to derive a model predicting 6‐month mortality from presenting characteristics. The reduced model contained age >40 years, haemoglobin <9·0 g/dl and the presence of a fever at presentation. Gender, platelet count, creatinine and neurological signs were not part of the final model. This model predicted 13·4% of outcome variance. Predictive scores of 0, 2, 4 and 6 correlated with 6‐month mortality rates of 12·5%, 14·0%, 31·3% and 61·5% respectively in our source population. This simple model may help identify those patients who would benefit from higher treatment intensity.
Identification and expression analysis of putative mRNA‐like non‐coding RNA in Drosophila
Authors: Inagaki Sachi , Numata Koji , Kondo Takefumi , Tomita Masaru , Yasuda Kunio , Kanai Akio , Kageyama Yuji 
Published: November 2005

One of the most surprising results to emerge from mammalian cDNA sequencing projects is that thousands of mRNA‐like non‐coding RNAs (ncRNAs) are expressed and constitute at least 10% of poly(A)+ RNAs. In most cases, however, the functions of these RNA molecules remain unclear. To clarify the biological significance of mRNA‐like ncRNAs, we computationally screened 11 691 Drosophila melanogaster full‐length cDNAs. After eliminating presumable protein‐coding transcripts, 136 were identified as strong candidates for mRNA‐like ncRNAs. Although most of these putative ncRNAs are found throughout the Drosophila genus, predicted amino acid sequences are not conserved even in related species, suggesting that these transcripts are actually non‐coding RNAs. In situ hybridization analyses revealed that 35 of the transcripts are expressed during embryogenesis, of which 27 were detected only in specific tissues including the tracheal system, midgut primordial cells, visceral mesoderm, germ cells and the central and peripheral nervous system. These highly regulated expression patterns suggest that many mRNA‐like ncRNAs play important roles in multiple steps of organogenesis and cell differentiation in Drosophila. This is the first report that the majority of mRNA‐like ncRNAs in a model organism are expressed in specific tissues and cell types.
Bile acids stimulate biofilm formation in Vibrio cholerae
Authors: Hung Deborah T. , Zhu Jun , Sturtevant Derek , Mekalanos John J. 
Published: November 2005

Summary Vibrio cholerae is a Gram‐negative bacterium that causes the acute diarrhoeal disease cholera. After the bacterium is ingested, it passes through the digestive tract, encountering various environmental stresses including the acidic milieu of the stomach and the toxic effects of bile in the duodenum. While these stresses serve as part of a host defence system, V. cholerae has evolved resistance mechanisms that allow it to evade these defences and establish infection. We examined the expression profiles of V. cholerae in response to bile or bile acids and found an induction of biofilm genes. We found that V. cholerae shows significantly enhanced biofilm formation in response to bile acids, and that bacteria within the biofilm are more resistant to the toxicity of bile acids compared with planktonic cells. Bile acid induction of biofilms was found to be dependent on the vps genes (Vibriopolysaccharidesynthesis) and their transcriptional activator VpsR, but VpsT is not required. These results contribute to the developing picture of a complex relationship between V. cholerae and its environment within the host during infection.
Transcriptional regulation of fatty acid biosynthesis in Streptococcus pneumoniae
Authors: Lu Ying‐Jie , Rock Charles O. 
Published: November 2005

SummaryThe transcriptional regulation of membrane fatty acid composition in the human pathogen Streptococcus pneumoniae is distinct from the systems utilized in the model organisms Escherichia coli and Bacillus subtilis. The genes encoding the components of type II fatty acid biosynthesis cluster at a single location within the S. pneumoniae genome, and the second gene in this cluster (SPR0376) encodes a transcription factor (FabT) that belongs to the MarR superfamily. Derivatives of S. pneumoniae strain D39 were constructed that lacked functional FabT. This strain had significantly elevated levels of saturated fatty acids and longer chain lengths than the control strain, was unable to grow at pH 5.5 and had increased sensitivity to detergent. Eliminating FabT function increased the expression levels of all of fab genes with the notable exception of fabM. FabT was purified and bound to the DNA palindrome located within the promoter regions of the fabT and fabK genes within the cluster. The analysis of cells with increased expression of individual genes leads to a model where the physical properties of the S. pneumoniae membrane is controlled primarily by the activity of FabK, the enoyl reductase, which diverts intermediates to saturated fatty acid formation, in contrast to E. coli where FabB, an elongation condensing enzyme, pulls the pathway in the direction of unsaturated acid synthesis.
A theoretical study of intraocular lens tilt and decentration on perceptual image quality
Authors: Turuwhenua Jason 
Published: November 2005

AbstractMaps of perceptual image quality were generated for a range of intraocular (IOL) tilts and decentrations, using a perceptually based metric i.e. the square integral (SQRI) metric. Maps were generated for a well‐corrected eye, and for hyperopic (−0.1 mm) and myopic (+0.1 mm) image planes (for 2 and 4 mm pupils). These perceptually based results were compared with a standard optical measure (i.e. the equivalent SQRI for given spectacle power added at the cornea). The image quality changes in maps were small, but detectable (exceeding the perceptual just noticeable difference (jnd) or 1 jnd threshold). Clockwise (negative) tilt combined with decenter fell below the ‘contrast reserve’ modulation transfer functions (MTFs) for 0.25 and 0.5 D defocus, 4 mm pupil. These errors were larger than those found previously, probably because of the shape‐factor of the IOL used. Pupil size contributed the largest drop in SQRI value, followed by clockwise tilt combined with decenter. Anticlockwise tilt with decenter produced image quality improvements for the hyperopic eye. Spot diagrams confirmed defocus and the balance of coma‐like aberration and astigmatism as causes of the changes in SQRI values. The SQRI maps conveniently summarize imaging, and may be a useful tool in assessing image quality in eye modelling applications.
Visual function assessment and metamorphopsia after macular hole surgery*,†
Authors: Wittich Walter , Overbury Olga , Kapusta Michael A. , Faubert Jocelyn 
Published: November 2005

AbstractThe purpose of this study was to develop a new resolution acuity measure for patients after macular hole surgery. Fifty eyes of 44 patients who had undergone successful treatment were tested. Visual acuity was measured with the Snellen, Early Treatment of Diabetic Retinopathy Study and Landolt‐C charts. A Line Resolution Test was performed as part of their follow‐up exam where a vertical line was presented. Participants were categorized by their perception of the line as solid, bent or broken. The line could be distorted into a sine‐wave pattern in order to determine the participants’ detection threshold for the distortion. Chart acuities did not differ among the three groups, as categorized by their line perception. Only the distortion measure was sensitive enough to differentiate the solid‐ from the broken‐line group. The distortion measure assesses resolution power of the macula in smaller increments than acuity charts. This hyperacuity approach is more appropriate in the assessment of functional outcome after microsurgery.
Accuracy of accommodation in heterophoric patients: testing an interaction model in a large clinical sample
Authors: Hasebe Satoshi , Nonaka Fumitaka , Ohtsuki Hiroshi 
Published: November 2005

AbstractA model of the cross‐link interactions between accommodation and convergence predicted that heterophoria can induce large accommodation errors (Schor, Ophthalmic Physiol. Opt. 1999;19:134–150). In 99 consecutive patients with intermittent tropia or decompensated phoria, we tested these interactions by comparing their accommodative responses to a 2.50‐D target under binocular fused conditions (BFC) and monocular occluded conditions (MOC). The accommodative response in BFC frequently differed from that in MOC. The magnitude of the accommodative errors in BFC, ranging from an accommodative lag of 1.80 D (in an esophoric patient) to an accommodative lead of 1.56 D (in an exophoric patient), was correlated with distance heterophoria and uncorrected refractive errors. These results indicate that heterophoria affects the accuracy of accommodation to various degrees, as the model predicted, and that an accommodative error larger than the depth of focus of the eye occurs in exchange for binocular single vision in some heterophoric patients.
Increase in central corneal thickness in dry and normal eyes with application of artificial tears: a new diagnostic and follow‐up criterion for dry eye*
Authors: Karadayi Koray , Ciftci Ferda , Akin Tugrul , Bilge Ahmet Hamdi 
Published: November 2005

AbstractAims:  To investigate the effect of artificial tear application on central corneal thickness (CCT) in dry and normal eyes.Methods:  Forty eyes of 40 patients with symptomatic dry eyes and 20 eyes of 20 controls were included in the study. A combination artificial tear therapy was given to both groups for 1 week. The CCT was measured with ultrasonic pachymetry before and after the therapy. In addition, at the beginning of the study, 11 dry eye patients and eight control patients were evaluated separately as a subgroup: they received artificial tears every 10 min for an hour to determine whether this might constitute a diagnostic criterion. Results were analysed with a Wilcoxon test, accepting p < 0.01 as significant.Results:  The mean CCT in the dry eye group before and after 1‐week therapy was 531.5 ± 16.5 and 559.6 ± 26.1 μm, respectively (p < 0.0001); thus yielding an average CCT increase of 28.1 ± 9.4 μm (=5.30%: 1.65% minimum; 7.03% maximum) from baseline. The mean CCT in the control group before and after 1‐week therapy was 549.2 ± 37.8 and 552.3 ± 39.8 μm, respectively (p = 0.001); thus, yielding an average CCT increase of 3.1 ± 1.9 μm (=0.56%: 0.00% minimum; 1.18% maximum) from baseline. When the subgroup was evaluated separately, the average increase from baseline in 11 dry eye patients was 10.4 ± 4.0 μm (=1.89%: 0.60% minimum; 4.26% maximum) after 1 h of artificial tear application, while it was 2.9 ± 2.0 μm (=0.51%: 0.00% minimum; 0.58% maximum) in eight control patients (p < 0.0001).Conclusion:  The CCT in dry eyes increases rapidly and significantly compared to normal eyes after application of artificial tears. It is suggested that this increase could be used as a criterion in the diagnosis and follow up of dry eyes, and that this increase in thickness should be considered in intra‐ocular pressure measurements as well as in refractive surgical procedures.
Compensation of aniseikonia in astigmatic pseudophakic eyes*
Authors: MacKenzie Graeme E. 
Published: November 2005

AbstractPurpose:  A recently published manuscript addressed the problem of compensating for aniseikonia between pseudophakic astigmatic eyes using a least‐squares calculation scheme. The purpose of this paper is to revisit this topic with the specific aim of providing explicit formulae for the determination of the intra‐ocular lens required to produce a specified transverse image size at the plane of the retina and the characteristics of the contact or spectacle lens required to realize some desired refractive outcome.Methods:  The 4 × 4 ray transference is central to the development of all formulae presented in this paper. Specifically, the formula for the determination of the power of the intra‐ocular lens required to achieve some transverse image size at the retina is derived directly from the disjugacy of the pseudophakic eye.Results:  The formula is applicable to both stigmatic and astigmatic systems without restriction. A detailed numerical example for an unusual eye is provided.Conclusion:  A formula for the determination of the intra‐ocular lens required to produce any given transverse image size at the retina is derived. This approach does not require the application of the Moore‐Penrose pseudo‐inverse and one is able to work rather with the properties of the optical system directly without further modification.
Evaluation of retinal function using the Dynamic Focal Cone ERG
Authors: Binns Alison , Margrain Tom H. 
Published: November 2005

AbstractThe development of effective means of assessing visual function in retinal disease holds the key to improved understanding of pathogenesis, and better monitoring of treatment outcomes. In diseases such as age‐related macular degeneration, in which the primary locus of dysfunction is the outer retina, tests which provide a direct measure of the functional integrity of the photoreceptor/retinal pigment epithelium (RPE) complex are of great importance. Recovery of retinal function following adaptation to a bright light requires the healthy function of photoreceptors, RPE, Bruch's membrane and choroidal circulation, making an assessment of this recovery a potentially useful clinical tool. However, current techniques are either subjective in nature, or are influenced by post‐retinal processing of visual information. This report describes a novel technique, the ‘Dynamic Focal Cone Electro‐retinogram (ERG)’, which allows direct, objective assessment of the recovery of macular function following photopigment bleach. A series of 41 Hz ERGs was recorded, and ERG amplitude was plotted as a function of time following cessation of the bleach. Normative data was collected from 10 healthy subjects. For all subjects, there was no measurable ERG immediately after the bleach, but the amplitude had returned to a pre‐bleach level within 4 min. The amplitude recovery data were adequately described both by an exponential recovery function and by a model based on a rate‐limited recovery process. We conclude that this technique provides a clinically applicable, objective measure of outer retinal recovery.
Multi‐family treatment for patients with persistent auditory hallucinations and their relatives: a pilot study
Authors: Jenner J. A. , van de Willige G. , Wiersma D. 
Published: November 2005

Objective:  To test feasibility and effectiveness of multi‐family treatment (MFT) for patients with persistent auditory hallucinations.Method:  A naturalistic pilot study with 6‐month follow‐up of 12 patients and 10 relatives. Pre‐ and post‐treatment assessment concerned compliance, satisfaction, subjective burden, and control of voices, psychopathology, quality of life, social functioning and burden on the family.Results:  Significant improvements were found in all domains. Compliance and satisfaction with treatment were satisfactory. Self‐help contacts outside treatment sessions increased over time.Conclusion:  MFT may be considered a potentially effective form of additional treatment for refractory voice hearers.
Adaptation of muscle size and myofascial force transmission: a review and some new experimental results
Authors: Huijing P. A. , Jaspers R. T. 
Published: November 2005

This paper considers the literature and some new experimental results important for adaptation of muscle fiber cross‐sectional area and serial sarcomere number. Two major points emerge: (1) general rules for the regulation of adaptation (for in vivo immobilization, low gravity conditions, synergist ablation, tenotomy and retinaculum trans‐section experiments) cannot be derived. As a consequence, paradoxes are reported in the literature. Some paradoxes are resolved by considering the interaction between different levels of organization (e.g. muscle geometrical effects), but others cannot. (2) An inventory of signal transduction pathways affecting rates of muscle protein synthesis and/or degradation reveals controversy concerning the pathways and their relative contributions.A major explanation for the above is not only the inherently limited control of the experimental conditions in vivo, but also of in situ experiments.Culturing of mature single Xenopus muscle fibers at high and low lengths (allowing longitudinal study of adaptation for periods up to 3 months) did not yield major changes in the fiber cross‐sectional area or the serial sarcomere number. This is very different from substantial effects (within days) of immobilization in vivo. It is concluded that overall strain does not uniquely regulate muscle fiber size.Force transmission, via pathways other than the myotendinous junctions, may contribute to the discrepancies reported: because of substantial serial heterogeneity of sarcomere lengths within muscle fibers creating local variations in the mechanical stimuli for adaptation. For the single muscle fiber, mechanical signalling is quite different from the in vivo or in vitro condition. Removal of tensile and shear effects of neighboring tissues (even of antagonistic muscle) modifies or removes mechanical stimuli for adaptation.It is concluded that the study of adaptation of muscle size requires an integrative approach taking into account fundamental mechanisms of adaptation, as well as effects of higher levels of organization. More attention should be paid to adaptation of connective tissues within and surrounding the muscle and their effects on muscular properties.
Debugging "level"
Authors: Hamlet Dick 
Published: November 2005

Debugging techniques originated with low-level programming languages, where the memory dump and interactive word-by-word examination of memory were the primary tools. "High-level" debugging is often no more than low-level techniques adapted to high-level languages. For example, to examine the execution of an operational specification one state at a time by setting breakpoints, is superior to doing the same thing to a machine-language program, but only because the language level has improved; the debugging remains primitive. This paper attempts a radical definition of debugging level, and illustrates it with a technique for ordering the execution of concurrent processes in a way that follows their design structure.
Division of a program into a collection of cooperating processes is a means of controlling the complexity of each process. However, in execution the program--development structure is ignored, with the result that the advantages of decomposition are lost. What the designer has divided and conquered, the debugger sees as an overwhelming monolith. The technique proposed here causes the focus of execution to follow the design structure, in a way that does not require detailed user direction.