bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis
Authors: Chen Daliang , Janganan Thamarai K. , Chen Gongyou , Marques Everaldo R. , Kress Marcia R. , Goldman Gustavo H. , Walmsley Adrian R. , Borges‐Walmsley M. Inês 
Published: July 2007

Summary Paracoccidioides brasiliensis is a human pathogenic fungus that switches from a saprobic mycelium to a pathogenic yeast. Consistent with the morphological transition being regulated by the cAMP‐signalling pathway, there is an increase in cellular cAMP levels both transiently at the onset (< 24 h) and progressively in the later stages (> 120 h) of the transition to the yeast form, and this transition can be modulated by exogenous cAMP. We have cloned the cyr1 gene encoding adenylate cyclase (AC) and established that its transcript levels correlate with cAMP levels. In addition, we have cloned the genes encoding three Gα (Gpa1–3), Gβ (Gpb1) and Gγ (Gpg1) G proteins. Gpa1 and Gpb1 interact with one another and the N‐terminus of AC, but neither Gpa2 nor Gpa3 interacted with Gpb1 or AC. The interaction of Gpa1 with Gpb1 was blocked by GTP, but its interaction with AC was independent of bound nucleotide. The transcript levels for gpa1, gpb1 and gpg1 were similar in mycelium, but there was a transient excess of gpb1 during the transition, and an excess of gpa1 in yeast. We have interpreted our findings in terms of a novel signalling mechanism in which the activity of AC is differentially modulated by Gpa1 and Gpb1 to maintain the signal over the 10 days needed for the morphological switch.
Rheumatic Fever and Rheumatic Heart Disease: Genetics and Pathogenesis
Authors: Guilherme L. , Ramasawmy R. , Kalil J. 
Published: July 2007

AbstractMolecular mimicry between streptococcal and human proteins is considered as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). Here, we present a review of the genetic susceptibility markers involved in the development of RF/RHD and the major immunopathological events underlying the pathogenesis of RF and RHD. Several human leucocyte antigen (HLA) class II alleles are associated with the disease. Among these alleles, HLA‐DR7 is predominantly observed in different ethnicities and is associated with the development of valvular lesions in RHD patients. Cardiac myosin is one of the major autoantigens involved in rheumatic heart lesions and several peptides from the LMM (light meromyosin) region were recognized by peripheral and intralesional T‐cell clones from RF and RHD patients. The production of TNF‐α and IFN‐γ from heart‐infiltrating mononuclear cells suggests that Th‐1 type cytokines are the mediators of RHD heart lesions while the presence of few interleukin‐4 producing cells in the valve tissue contributes to the maintenance and progression of the valvular lesions.
New Vaccines Require Potent Adjuvants like AFPL1 and AFCo1
Authors: Pérez O. , Lastre M. , Cabrera O. , Del Campo J. , Bracho G. , Cuello M. , Balboa J. , Acevedo R. , Zayas C. , Gil D. , Mora N. , González D. , Pérez R. , González E. , Barberá R. , Fajardo E. M. , Sierra G. , Solís R. L. , Campa C. 
Published: July 2007

Abstract Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative‐Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen‐associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non‐related antigens. AFPL1 is a detergent‐extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co‐administrated antigens; inducing type I IFN‐γ and IL‐12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4+, TCD8+, cross‐presentation and cytotoxic T‐lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1–AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co‐administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.
Concordant expression of proto‐oncogene promyelocytic leukemia and major histocompatibility antigen HLA class I in human hepatocellular carcinoma
Authors: Xia M. , Zhang J. Q. , Shen Y.‐Q. , Xu L. H. , Chen A. Q. , Miao F. Q. , Xie W. 
Published: July 2007

AbstractMany malignant cancer cells downregulate human leukocyte antigen (HLA) class I antigen expression to evade T cell recognition. However, hepatocellular carcinoma (HCC) is exceptional to the general findings in cancer cells, and the mechanisms for its upregulation remain unclear. It has been reported that promyelocytic leukemia (PML) proto‐oncogene controls the transcription of multiple class I antigen presentation genes in murine cancer cells. To find out the functional role of PML gene on the increased HLA class I antigen expression in HCC cells, we analyzed the expression of proto‐oncogene PML and multiple class I antigen presentation genes in HCC specimens obtained in China. The results showed concordant changes of proto‐oncogene PML and cell surface HLA‐A expression in 44 paraffin‐embedded HCC tissues. Furthermore, co‐upregulated expression of PML genes and class I antigen presentation genes could be detected in 9 of 15 fresh HCC tissues by reverse transcription polymerase chain reaction (RT‐PCR). In addition, studies using HCC cell lines showed that increased expression of HLA class I molecules paralleled with PML upregulation were detected in QGY‐7701 HCC cell line with RT‐PCR, western blot, and flow cytometry, and that the overexpression of exogenous PML in a low‐expression class I cell line BEL‐7405 could induce the expression of multiple class I antigen‐presenting molecule genes and slightly but significantly increase the expression of cell surface HLA class I molecules. In conclusion, the expression of proto‐oncogene PML and HLA class I molecules were concordantly upregulated and the expression of PML gene might be one of the mechanisms that leads to the increased expression of class I antigen in HCC.
Genetic analyses of celiac disease in a Spanish population confirm association with CELIAC3 but not with CELIAC4
Authors: Capilla A. , Donat E. , Planelles D. , Espinós C. , Ribes‐Koninckx C. , Palau F. 
Published: July 2007

AbstractGenetic predisposition to celiac disease (CD) is determined primarily by the human leukocyte antigen (HLA) genes (CELIAC1 region; 6p21), although many loci are involved in disease susceptibility. First, we have analysed a large series of CD patients from the Spanish Mediterranean region who had previously been characterised for the HLA complex. We have investigated how relevant regions contribute to CD susceptibility: CELIAC3 (CD28/CTLA4/ICOS region on 2q33) and CELIAC4 (19p13) as well as the tumour necrosis factor α (TNF‐α) and the linfotoxin loci by case–control and association analyses. We highlight the association with the +49*A allele of cytotoxic T‐lymphocyte‐associated antigen 4 locus (P = 0.01), and the −308*A of TNF‐α locus (P = 0.0008) in DQ2 individuals, although an independent role for TNF‐α as risk factor has not been proven. Moreover, we do not confirm the association with the CELIAC4 region polymorphisms described in other populations.
Competitive inhibition of the auxin‐induced elongation by α‐D‐oligogalacturonides in pea stem segments
Authors: Branca C. , Lorenzo G. De , Cervone F. 
Published: July 2007

Branca, C, De Lorenzo, G. and Cervone, F. 1988. Competitive inhibition of the auxin‐induced elongation by α‐D‐oligogalacturonides in pea stem segments. ‐ Physiol. Plant. 72: 499–504.α‐D‐galacturonide oligomers (OG) were prepared by partial hydrolysis of sodium polypectate with an homogeneous Aspergillus niger endopolygalacturonase (EC 3.2.1.15). OG, obtained after digestion for 10, 20, 30, 60, 120 min and 24 h, were assayed for their ability to interfere with the IAA‐induced elongation of pea (Pisum sativum L. cv. Alaska) stems. Maximum inhibiting activity was exhibited by oligomers with an approximate degree of polymerization higher than 8. Inhibition by longer OG was much lower, and the products of the 24 h digestion and the unhydrolysed polypectate were ineffective. The addition of OG to pea stems caused a parallel shift to the right of the IAA dose‐effect curve. The shift depended on the amount of OG used, showing that oligogalacturonides behave as competitive antagonists of IAA. The presence of OG caused the disappearance of the second maximum of the elongation rate and reduced the first maximum. OG were also tested for their ability to inhibit IAA‐induced ethylene evolution of pea stem segments. Maximal inhibition was obtained with OG of the same size as those that interfered with IAA‐induced elongation. Inhibition of the auxin action seemed to be specific as OG did not interfere with the activity of gibberellic acid (GA3) or kinetin. It was concluded that oligogalacturonides strongly interfere with the activity of IAA, although they are by themselves incapable to influence the elongation of pea stem segments directly.
Temperature gradient between brain tissue and arterial blood mirrors the flow‐metabolism relationship in uninjured brain: an experimental study
Authors: Soukup J. , Rieger A. , Holz C. , Miko I. , Nemeth N. , Menzel M. 
Published: July 2007

Background:  The purpose of the present experimental study was to determine the feasibility and usefulness of brain temperature measurement (Tbr) and the calculated difference between brain temperature and arterial blood temperature (ΔTbr‐a) in uninjured brain during variations of cerebral perfusion pressure (CPP) and concomitant changes of the regional cerebral blood flow (rCBF).Methods:  Nine anaesthetized pigs were subjected to controlled CPP decrease to assess the lower cerebral autoregulation threshold. A parenchymal intracranial pressure (ICP) sensor combined with a microthermistor for temperature measurement, a miniaturized Clark‐type electrode measuring brain tissue oxygenation (ptiO2), a small flexible intraparenchymal thermodilution probe for measuring rCBF and cerebral microdialysis were inserted carefully in the frontal white matter.Results:  Analysing the ptiO2 during controlled CPP decrease, we found significant breakpoints of ptiO2 at a CPP of 40 mmHg and 20 mmHg, related to an rCBF of 20 ml/100 g/min and approximately 10 ml/100 g/min. Similarly, the relationship between ΔTbr‐a, and CPP or rCBF revealed a characteristic increase of ΔTbr‐a in the negative direction up to more than –0.30 °C assuming a strong flow dependency.Conclusion:  The temperature difference between brain tissue and arterial blood ΔTbr‐a mainly reflects the cerebral blood flow–brain tissue oxygenation–metabolism relationship as far as the estimation of the individual lower cerebral autoregulation threshold.
Prospective peer‐review audit of paediatric upper gastrointestinal endoscopy
Authors: O’Loughlin Edward V , Dutt Shoma , Kamath Ramananda , Gaskin Kevin , Dorney Stuart 
Published: July 2007

Aim:  To describe the findings of paediatric upper gastrointestinal endoscopy (UGE) and to reduce the rate of normal findings in children undergoing diagnostic UGE.Methods:  Upper gastrointestinal endoscopy were performed at a single tertiary referral children’s hospital over a 3‐year period by four endoscopists. Patients were subgrouped into diagnostic categories (recurrent abdominal pain syndrome (RAP), oesophagitis, coeliac disease and enteropathy/inflammatory bowel disease) and endoscopists recorded their clinical diagnosis as above before each procedure. Endoscopic and biopsy findings were compared with clinical diagnosis. After the first year of audit each endoscopist was appraised of their practice and strategies implemented to reduce the normal UGE. In years 2 and 3 all endoscopists were audited by their peers on a monthly basis.Results:  A total of 1172 UGE were performed over a 3‐year period. Ninety per cent were diagnostic procedures, of which 48% were normal, 16% identified oesophagitis, 11% coeliac disease, 6% gastritis, 3%Helicobacter pylori and 1% peptic ulcer disease. Peer‐review audit significantly reduced the number of normal findings in coeliac disease, RAP and overall (P < 0.01) but not in the groups with presumed oesophagitis or investigation of enteropathy/inflammatory bowel disease.Conclusions:  A high proportion of patients undergoing UGE have normal procedures. Peer‐review audit can reduce the number of normal procedures particularly in RAP and in the diagnosis of coeliac disease.
Portability of Tag SNPs Across Isolated Population Groups: An Example from India
Authors: Roy N. Sarkar , Farheen S. , Roy N. , Sengupta S. , Majumder P. P. 
Published: July 2007

SummaryIsolated population groups are useful in conducting association studies of complex diseases to avoid various pitfalls, including those arising from population stratification. Since DNA resequencing is expensive, it is recommended that genotyping be carried out at tagSNP (tSNP) loci. For this, tSNPs identified in one isolated population need to be used in another. Unless tSNPs are highly portable across populations this strategy may result in loss of information in association studies. We examined the issue of tSNP portability by sampling individuals from 10 isolated ethnic groups from India. We generated DNA resequencing data pertaining to 3 genomic regions and identified tSNPs in each population. We defined an index of tSNP portability and showed that portability is low across isolated Indian ethnic groups. The extent of portability did not significantly correlate with genetic similarity among the populations studied here. We also analyzed our data with sequence data from individuals of African and European descent. Our results indicated that it may be necessary to carry out resequencing in a small number of individuals to discover SNPs and identify tSNPs in the specific isolated population in which a disease association study is to be conducted.
Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability
Authors: Hirsch Lawrence J. , Arif Hiba , Buchsbaum Richard , Weintraub David , Lee Jeansun , Chang Jennifer T. , Resor Stanley R. , Bazil Carl W. 
Published: July 2007

Summary: Purpose:To compare pharmacokinetics and tolerability of levetiracetam (LEV) in older versus younger adults.Methods:As part of the Columbia Antiepileptic Drug Database, we retrospectively studied the pharmacokinetics and tolerability of LEV in patients who had been seen as an outpatient at our center during a 4‐year period. We compared apparent clearance (CL) of LEV in the youngest (16–31 years; n = 151) and oldest (55–88 years; n = 157) quartile of 629 adult outpatients who had taken LEV. We also analyzed the frequency of adverse effects leading to dose change or discontinuation (“intolerability”) and specific adverse effects in the younger versus older adults. One‐year retention was determined for younger and older adults newly started on LEV at our center.Results:Mean LEV CL differed significantly between older (46.5 ml/h/kg) and younger adults (78.3 ml/h/kg). On average, older patients had a 40% lower LEV CL than younger patients. Comedication with an enzyme‐inducing antiepileptic drug (EIAED; mostly carbamazepine) was associated with a 24% higher clearance of LEV compared to those who were not on EIAEDs. This difference was 37% in a subgroup of patients whose LEV CL was compared while they were on and off EIAEDs. Stepwise linear regression identified younger age and comedication with an EIAED as significant predictors of increased LEV CL. A total of 34.3% of the 629 patients (31.7% of younger vs. 40.7% of older patients; p = 0.16) reported intolerability to LEV on at least one occasion. This difference in tolerability reached significance in the group of patients newly started on LEV (26.3% vs. 41.0%; p = 0.017). Drowsiness and psychiatric/behavioral side effects were the most common adverse effects associated with LEV use in both age groups. One‐year retention was 72% in the older group vs. 54% in the younger group (not significant).Conclusion:Older adults have lower CL than younger adults and require a mean 40% lower dose of LEV to achieve the same serum level. Comedication with an EIAED increases LEV CL by 24–37%. Younger adults tolerate LEV better than older adults, but 1‐year retention was (nonsignificantly) higher in the older group.
Discovery of the strongly eccentric, short-period binary nature of the B-type system HD 313926 by the MOST satellite
Authors: Rucinski Slavek M. , Kuschnig Rainer , Matthews Jaymie M. , Dimitrov Wojtek , Pribulla Theodor , Guenther David B. , Moffat Anthony F. J. , Sasselov Dimitar , Walker Gordon A. H. , Weiss Werner W. 
Published: July 2007

Abstract
The MOST photometric space mission discovered an eclipsing binary among its guide stars in 2006 June which combines a relatively large eccentricity e= 0.20 with an orbital period of only 2.27 d. HD 313926 appears to consist of two early-type stars of spectral type B3–B7. It has the largest eccentricity among known early-type binaries with periods less than 3.5 d. Despite the large components indicated by its spectral type and light curve model, and its short period, the orbit of HD 313926 has not yet circularized so it is probably very young, even compared with other young B stars.
Shared Decision-Making and the Lower Literate Patient
Authors: Shalowitz David I. , Wolf Michael S. 
Published: July 2007

In recent years, shared decision-making has become entrenched in the medical literature and the law as the ideal method for involving patients in decisions related to their health care. Shared decision-making represents a compromise between the opposed extremes of paternalistic interactions that limit patients’ control of their health care, and “informed choice” interactions that require physicians to provide technical expertise only, leaving patients to make all treatment decisions on their own. An implicit goal of shared decision-making is to improve medical care by promoting joint participation of patients and physicians in clinical consultations. The model of shared decision-making may, however, inadequately address the health care needs of lower literate patients, a significant portion of the general population.As shared decision-making is widely held as a clinical ideal, we highlight the difficulties that physicians might have in implementing shared decision-making with lower literate patients.
Nonlinear Vibrations
of an Extensible Flexible Marine Riser Carrying a Pulsatile
Flow
Authors: Monprapussorn T. , Athisakul C. , Chucheepsakul S. 
Published: July 2007

Abstract
The influence of transported fluid on static and dynamic behaviors of marine risers is investigated. The internal flow of the transported fluid could have a constant, a linear, or a wave velocity. The riser pipe may possibly experience the conditions of high extensibility, flexibility, and large displacements. Accordingly, the mathematical riser models should be governed by the large strain formulations of extensible flexible pipes transporting fluid. Nonlinear hydrodynamic dampings due to ocean wave–pipe interactions implicate the high degree of nonlinearity in the riser vibrations, for which numerical solutions are determined by the state–space–finite-element method. It is revealed that the impulsive acceleration of internal flow could seriously relocate the vibrational equilibrium positions of the riser pipe. The fluctuation of the pulsatile flow relatively introduces the expansion of amplitudes and the reduction of frequencies of the riser vibrations. The pulsatile frequencies of the internal flow in wave aspect could reform the oscillation behavior of the conveyor pipe.
Genetic diversity and phylogenetic relationships in Vigna Savi germplasm revealed by DNA amplification fingerprinting
Authors: Simon M.V. , Benko-Iseppon A.-M. , Resende L.V. , Winter P. , Kahl G. 
Published: July 2007

The pantropical genus Vigna (Leguminosae) comprises 7 cultivated species that are adapted to a wide range of extreme agroclimatic conditions. Few data are available on the relationships among these cultivated species or on their importance as sources of resistance against biotic and abiotic stresses. Therefore, we optimized DNA amplification fingerprinting (DAF) to estimate the genetic diversity within, and genetic relationships among, a representative core collection of cowpea, as compared with 16 accessions representing cultivars from 6 Vigna species. A set of 26 primers was selected from 262 tested random primers and used for the characterization of 85 Vigna accessions (6 V. angularis , 4 each of V. mungo and V. radiata , 2 V. umbellata , 1 V. aconitifolia , and 68 V. unguiculata ), with Phaseolus vulgaris subsp. vulgaris as outgroup. A total of 212 polymorphic bands were used for maximum parsimony analysis. Our results clearly distinguished Brazilian from African V. unguiculata genotypes. At the species level, V. angularis was the most related and V. radiata the most divergent species relative to V. unguiculata. DAF markers were also informative at the intraspecific level, detecting a large diversity between cowpea cultivars. The implications of the presented results for cowpea breeding programs are discussed.