bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structure of GOPC PDZ domain and its interaction with the C‐terminal motif of neuroligin
Authors: Li Xiang , Zhang Jiahai , Cao Zanxia , Wu Jihui , Shi Yunyu 
Published: August 2006

AbstractGOPC (Golgi‐associated PDZ and coiled‐coil motif‐containing protein) represents a PDZ domain‐containing protein associated with the Golgi apparatus, which plays important roles in vesicular trafficking in secretory and endocytic pathways. GOPC interacts with many other proteins, such as the Wnt receptors Frizzled 8 and neuroligin via its PDZ domain. Neuroligin is a neural cell‐adhesion molecule of the post‐synapse, which binds to the presynapse molecule neurexin to form a heterotypic intercellular junction. Here we report the solution structure of the GOPC PDZ domain by NMR. Our results show that it is a canonical class I PDZ domain, which contains two α‐helices and six β‐strands. Using chemical shift perturbation experiments, we further studied the binding properties of the GOPC PDZ domain with the C‐terminal motif of neuroligin. The observations showed that the ensemble of the interaction belongs to fast exchange with low affinity. The 3D model of the GOPC PDZ domain/neuroligin C‐terminal peptide complex was constructed with the aid of the molecular dynamics simulation method. Our discoveries provide insight into the specific interaction of the GOPC PDZ domain with the C‐terminal peptide of Nlg and also provide a general insight about the possible binding mode of the interaction of Nlg with other PDZ domain‐containing proteins.
Peptide deformylase is a potential target for anti‐Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X‐ray crystallography validation
Authors: Cai Jianhua , Han Cong , Hu Tiancen , Zhang Jian , Wu Dalei , Wang Fangdao , Liu Yunqing , Ding Jianping , Chen Kaixian , Yue Jianmin , Shen Xu , Jiang Hualiang 
Published: August 2006

AbstractColonization of human stomach by the bacterium Helicobacter pylori is a major causative factor for gastrointestinal illnesses and gastric cancer. However, the discovery of anti‐H. pylori agents is a difficult task due to lack of mature protein targets. Therefore, identifying new molecular targets for developing new drugs against H. pylori is obviously necessary. In this study, the in‐house potential drug target database (PDTD, http://www.dddc.ac.cn/tarfisdock/) was searched by the reverse docking approach using an active natural product (compound 1) discovered by anti‐H. pylori screening as a probe. Homology search revealed that, among the 15 candidates discovered by reverse docking, only diaminopimelate decarboxylase (DC) and peptide deformylase (PDF) have homologous proteins in the genome of H. pylori. Enzymatic assay demonstrated compound 1 and its derivative compound 2 are the potent inhibitors against H. pylori PDF (HpPDF) with IC50 values of 10.8 and 1.25 μM, respectively. X‐ray crystal structures of HpPDF and the complexes of HpPDF with 1 and 2 were determined for the first time, indicating that these two inhibitors bind well with HpPDF binding pocket. All these results indicate that HpPDF is a potential target for screening new anti‐H. pylori agents. In addition, compounds 1 and 2 were predicted to bind to HpPDF with relatively high selectivity, suggesting they can be used as leads for developing new anti‐H. pylori agents. The results demonstrated that our strategy, reverse docking in conjunction with bioassay and structural biology, is effective and can be used as a complementary approach of functional genomics and chemical biology in target identification.
Residue centrality, functionally important residues, and active site shape: Analysis of enzyme and non‐enzyme families
Authors: del Sol Antonio , Fujihashi Hirotomo , Amoros Dolors , Nussinov Ruth 
Published: August 2006

AbstractThe representation of protein structures as small‐world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the performance of residue centrality, viewed as a family fold characteristic, in identifying functionally important residues in protein families. Our study is based on 46 families, including 29 enzyme and 17 non‐enzyme families. A total of 80% of these central positions corresponded to active site residues or residues in direct contact with these sites. For enzyme families, this percentage increased to 91%, while for non‐enzyme families the percentage decreased substantially to 48%. A total of 70% of these central positions are located in catalytic sites in the enzyme families, 64% are in hetero‐atom binding sites in those families binding hetero‐atoms, and only 16% belong to protein–protein interfaces in families with protein–protein interaction data. These differences reflect the active site shape: enzyme active sites locate in surface clefts, hetero‐atom binding residues are in deep cavities, while protein–protein interactions involve a more planar configuration. On the other hand, not all surface cavities or clefts are comprised of central residues. Thus, closeness centrality identifies functionally important residues in enzymes. While here we focus on binding sites, we expect to identify key residues for the integration and transmission of the information to the rest of the protein, reflecting the relationship between fold and function. Residue centrality is more conserved than the protein sequence, emphasizing the robustness of protein structures.
Long‐term survival in post‐transplant lymphoproliferative disorders with a dose‐adjusted ACVBP regimen
Authors: Fohrer Cécile , Caillard Sophie , Koumarianou Argyro , Ellero Bernard , Woehl‐Jaeglé Marie‐Lorraine , Meyer Carole , Epailly Eric , Chenard Marie‐Pierre , Lioure Bruno , Natarajan‐Ame Shanti , Maloisel Frédéric , Lutun Philippe , Kessler Romain , Moulin Bruno , Bergerat Jean‐Pierre , Wolf Philippe , Herbrecht Raoul 
Published: August 2006

SummaryPost‐transplant lymphoproliferative disorders (PTLD) are severe complications after solid organ transplantation with no consensus on best treatment practice. Chemotherapy is a therapeutic option with a high response and a significant relapse rate leading to a low long‐term tolerance rate. Currently, most centres use anthracycline‐based drug combinations, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). We assessed the efficacy and safety of a dose‐adjusted ACVBP (doxorubicin reduced to 50 mg/m2, cyclophosphamide adjusted to renal function, vindesine, bleomycin, prednisone) regimen in patients failing to respond to a reduction in immunosuppressive therapy. Favourable responses were observed in 24 (73%) of the 33 treated patients. Fourteen (42%) patients died, mostly from PTLD progression. Actuarial survival was 60% at 5 years and 55% at 10 years. Survival prognostic factors were: number of involved sites (P = 0·007), clinical stage III/IV (P = 0·004), bulky tumour (P < 0·0001), B symptoms (P = 0·03), decreased serum albumin (P = 0·03) and poor performance status (P = 0·06). Both the international and the PTLD prognostic index were predictive for survival (P = 0·001 and P = 0·002, respectively). Overall 128 cycles were given. Grade 3 or 4 neutropenia was recorded after 26 (20%) chemotherapy cycles in 19 (58%) patients. Forty‐one (32%) infections were recorded in 26 (79%) patients. This study demonstrated that an individual dose‐adjustment of ACVBP regimen was manageable in PTLD patients and favourably impacted on long‐term survival.
Diagnosis of iodinated contrast media hypersensitivity: results of a 6‐year period
Authors: Kvedariene V. , Martins P. , Rouanet L. , Demoly P. 
Published: August 2006

SummaryBackground
Iodinated contrast media (ICM) hypersensitivity reactions represent a serious problem. Very few clinical data concerning systematic skin testing to ICM are available.Objective
To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity.Material and methods
All patients referred over a 6‐year period for ICM hypersensitivity past reactions were skin tested for (a) the implicated ICM, or (b) a set of ICM if they were positive for the implicated ICM or if its name was unknown.Results
Forty‐four patients, with a median age of 56 years, were studied (15 males, 29 females). The ICM skin tests were positive in 10 patients (23%): one had a positive skin prick test, seven an immediate positive intradermal test (IDT) and two a delayed positive IDT. Skin tests were more often positive in patients with immediate (9/32) as compared with those with non‐immediate reactions (1/11). The time interval between the reaction and skin testing was shorter for those patients with an immediate ICM reaction and a positive skin test result (3 months [2.5–174.0]) as compared with those with an immediate ICM reaction and a negative skin test (48 months [6.8–159.0]), (P<0.05). Respiratory allergy was more frequent in the positive group (6/10 vs. 7/34, P<0.05).Conclusions
Skin tests with ICM are positive in a subgroup of patients with ICM hypersensitivity and may play an important role in the diagnosis of ICM allergy.
Pathophysiology of nasal obstruction and meta‐analysis of early and late effects of levocetirizine
Authors: Patou J. , De Smedt H. , Van Cauwenberge P. , Bachert C. 
Published: August 2006

SummaryNasal obstruction, also referred to as congestion, blockage or stuffiness, is a crucial symptom in allergic rhinitis (AR) and may affect sleep as well as quality of life. Early‐ and late‐phase‐allergic reactions both contribute to nasal obstruction, although it primarily represents a major symptom in the chronic allergic reaction. A complex network of inflammatory and neurogenic phenomena relates to chronic nasal obstruction, including the subepithelial accumulation of inflammatory cells, particularly mast cells and eosinophils, and the release of neuropeptides. Nasal obstruction is a difficult‐to‐treat symptom. Vasoconstrictors (decongestants) and intranasal corticosteroids, due to their anti‐inflammatory properties, have mainly been used for relieving the nasal passages from the congested mucosa. However, there is accumulating evidence recently that the latest‐generation potent antihistamines have decongestant properties in AR. This paper aims to review the pathophysiologic background of nasal obstruction and the evidence for an antihistamine, levocetirizine, in relieving nasal congestion. A meta‐analysis on the early and late effects of levocetirizine on nasal obstruction under artificial and natural allergen exposure conditions is presented, demonstrating convincingly that levocetirizine shows a consistent effect on nasal obstruction as early as over the first 2 h and sustained over 6 weeks.
A reproducible method for the enumeration of functional (cytokine producing)versusnon-functional peptide-specific cytotoxic T lymphocytes in human peripheral blood
Authors: Markovic S N , Nevala W K , Uhl C B , Celis E , McKean D J 
Published: August 2006

SummaryOne of the most difficult laboratory challenges in the field of therapeutic cancer vaccines has been the development of uncomplicated/reproducible methods for the quantification of vaccine immunization efficacy in peripheral blood of cancer patients. Existing methods are limited by lack of functional information (tetramers), difficulties with standardization/reproducibility [enzyme-linked immunosorbent spot (ELISPOT)] and reliance on endogenous (sample-specific) antigen presentation (cytokine flow cytometry). Herein we present a reproducible method utilizing an artificial antigen-presenting cell platform for flow cytometry-based quantification of the frequency and activation status of peptide-specific cytotoxic T lymphocytes. The methodology [currently presented for cytomegalovirus human leucocyte antigen (HLA)-A2 cognant peptide antigens] allows simultaneous ex vivo quantification of activated (cytokine-producing) and inactive tetramer-positive T cells following HLA class I/peptide/CD28 stimulation independent of endogenous antigen presentation. The simplicity and reliability of the assay provide for high-throughput applications and automation. The utility and application of this method are discussed.
Survival in patients with pulmonary arterial hypertension treated with first‐line bosentan
Authors: McLaughlin V. V. 
Published: August 2006

AbstractBackground  Pulmonary arterial hypertension (PAH) is a devastating disease of the small pulmonary arteries and arterioles, characterized by intimal fibrosis, medial hypertrophy and plexiform lesions. When untreated both the idiopathic form (IPAH, formerly termed primary pulmonary hypertension, PPH) and PAH related to various other conditions such as scleroderma (SSc) often take a progressive course with high mortality. There is ongoing search for disease‐specific treatments that are able to improve survival in these patients. The oral dual endothelin (ETA/ETB) antagonist bosentan has been shown to improve exercise capacity, time to clinical worsening, haemodynamics and quality of life in short‐term studies.Materials and methods  To determine the long‐term effects of bosentan on survival, patients from the two double‐blind, randomized trials and their open‐label extensions, treated with first‐line bosentan, were followed for up to 3 years. Data on survival were collected between September 1999 (first patient included in the placebo‐controlled trials) and December 2002. Vital status was verified in each patient. The survival cohorts of these patients were compared with either the predicted survival for each patient based on an equation from the National Institutes of Health (NIH) PPH registry or with historical controls.Results  Observed survival up to 36 months was reported as a Kaplan‐Meier estimate in three cohorts: (1) In 169 PPH patients treated with first‐line bosentan, 1‐ and 2‐year survival was 96% and 89%, respectively, vs. predicted untreated survival at 1 and 2 years of 69% and 57%, respectively; (2) in 50 patients with PAH associated with SSc (PAH‐SSc), 1‐, 2‐ and 3‐year survival was 82%, 67% and 64%, respectively, vs. ∼45%, ∼35% and ∼28%, respectively, from registry data of untreated PAH‐SSc patients; and (3) in 139 PPH patients in WHO functional class III, 1‐ and 2‐year survival was 97% and 91%, respectively, vs. 91% and 84% in a historical cohort of 346 patients treated with epoprostenol in five major referral centres.Conclusions  The present analyses suggest that first‐line bosentan therapy, followed by the addition of other disease‐specific therapies as required, improves survival in patients with advanced PAH.
Role of endothelin and endothelin receptor antagonists in renal disease
Authors: Neuhofer W. , Pittrow D. 
Published: August 2006

AbstractEndothelin (ET)‐1 is a potent vasoconstrictor peptide with pro‐inflammatory, mitogenic, and pro‐fibrotic properties that is closely involved in both normal renal physiology and pathology. ET‐1 exerts a wide variety of biological effects, including constriction of cortical and medullary vessels, mesangial cell contraction, stimulation of extracellular matrix production, and inhibition of sodium and water reabsorption along the collecting duct, effects that are primarily mediated in an autocrine/paracrine manner. Increasing evidence indicates that the ET system is involved in an array of renal disorders. These comprise chronic proteinuric states associated with progressive glomerular and tubulointerstitial fibrosis, including diabetic and hypertensive nephropathy, glomerulonephritis and others. In addition, ET‐1 is causally linked to renal disorders characterized by increased renal vascular resistance, including acute ischaemic renal failure, calcineurin inhibitor toxicity, endotoxaemia, hepatorenal syndrome and others. Furthermore, derangement of the ET system may be involved in conditions associated with inappropriate sodium and water retention; for example, in congestive heart failure and hepatic cirrhosis. Both selective and non‐selective ET receptor antagonist have been developed and tested in animal models with promising results. As key events in progressive renal injury like inflammation and fibrosis are mediated via both ETA and ETB receptors, while constrictor effects are primarily transduced by ETA receptors, dual ET receptor blockade may be superior over selective ETA antagonism. Several compounds have been developed with remarkable effects in several models of acute and progressive renal injury. Thus, clinical studies are required to assess whether these results can be confirmed in humans, hopefully leading to novel and effective therapeutic options with few side effects.
SOME SARAWAK SOILS
Authors: WOOD T. W. W. , BECKETT P. H. T. 
Published: August 2006

SummaryThe sub‐mature landscape of the country rock (Miocene fine sandstones and shales) along the coast north of Bintulu gives rise under a mean annual rainfall of 150 in. to highly leached yellow soils, comparable to Kellogg's Red‐Yellow Latosols, associated with lowland Dipterocarp rain forest. Areas of level or nearly level coarse‐textured marine or estuarine deposits marking successive stages of the fall in sea‐level during the Pleistocene are associated with ground‐water podzols supporting various forms of the characteristic kerangas forest, which give rise to ‘blackwater’ streams
DETERMINATION OF MOISTURE CONTENT WITH A GAMMA BACKSCATTER DENSITY GAUGE
Authors: CIFTCIOGLU O. , BYATT D. A. , TAYLOR D. 
Published: August 2006

SummaryGamma‐radiation, backscatter gauges, as normally employed for the determina‐tion of the bulk density of soils, use integral mode counting. They are relatively insensitive to the presence of soil moisture and hence not generally suitable for monitoring soil moisture content, particularly, if the soil type effect is minimized by counting only gamma‐photons of energy > 0.400 MeV for a 137Cs source. However, using differential mode counting with the window set at about 0.08 MeV, the phenomenon is one of multiple instead of single scattering. With a source‐detector Separation of the order of 20 cm, about eight Compton in‐teractions are obtained and, as a multiplying factor of ZjA is involved at each interaction, the increased response with hydrogen‐containing material is easily observable. The value of Z/A for hydrogen is 1.0, and for materials not containing hydrogen about 0.5; therefore for water it is 5/9. Hence under these conditions, the response for water compared with non‐hydrogen‐containing materials is [(s/9)/(1/2)]8= 2.32 times, an increase of 132 per cent. This method can therefore be exploited to measure the moisture content of soils. The sensitivity is high, and the accuracy is better than ± 5 per cent, which is not as good as can be achieved with a separate thermal neutron detector, but is useful for many purposes and, of course, only one instrument is required.
Studies on the rate of decomposition of plant residues in soil by following the changes in sugar components
Authors: CHESHIRE M. V. , INKSON R. H. E. , MUNDIE C. M. , SPARLING G. P. 
Published: August 2006

SUMMARYUniformly 14C labelled straw and ryegrass leaf were incubated in soil in the proportions 0.5 and 1% w/w, respectively at 12°C for various periods up to 5 years.Samples were hydrolysed with 2.5 m H2SO4 under reflux for 20 min to release non‐cellulosic sugars and subsequently with 12 M/0.5 m H2SO4 to release glucose from cellulose‐like polymers. Total radioactivity was determined in whole soil and hydrolysates and in individual sugars.Fitting the data to simple exponential equations, total and 2.5 m H2SO4 hydrolysate radioactivity were best expressed by three part exponential functions, whereas radioactivity in 12M/0.5M H2SO4 hydrolysates and sugars were best expressed by two part functions, except for arabinose from the straw, for which a three‐part function was better.A comparison of the fit was made with that using the single‐term exponential expressions devised by Janssen, 1984 and Weibull, 1951 and with a modification of the two part exponential expression by the substitution of one term by the Weibull expression. Apart from the Weibull expression on its own, there was no significant difference between the expressions.It is suggested that, even for well defined carbohydrate components of the substrate, the decomposability changes with time because of their increasing inaccessibility to microorganisms, rather than that several components are present each with a different constant rate of decomposition.
One‐dimensional biophysical modelling of fish egg vertical distributions in shelf seas
Authors: PETITGAS PIERRE , MAGRI STÉPHANIE , LAZURE PASCAL 
Published: August 2006

AbstractModelling the vertical distribution of fish eggs is important when assessing fish stocks with egg production methods and for monitoring the reproductive potential of fish populations. Fish eggs are passive particles and their vertical distribution is determined by a few parameters such as egg density, egg diameter, wind‐ and tide‐induced turbulence, and vertical hydrographic structure. A one‐dimensional vertical biophysical, numerical model was developed which was adapted to the hydrography of shelf seas under the influence of tidal currents, wind‐induced circulation, and river discharges. The biological part of the model parameterized the ascent velocity of the egg as a function of egg properties (diameter, density) and water properties (density, viscosity, turbulence). The model contains a turbulence closure which makes the model dynamic. The model parameters were surface wind, tidal currents, T‐S profile, and egg diameter and density, which were kept constant in time. The model has the capacity to generate sub‐surface egg maxima in different hydrographic conditions, e.g. in areas under the influence of river plumes, and can also homogenize the egg distribution under wind and tide forcing. Sensitivity tests were carried out to study the response of the model to variations in the model parameters for a variety of hydrographic conditions. The modelled egg vertical distributions were validated by comparison of the model results with egg distributions sampled in the field. The analysis highlighted variability in fish egg density of anchovy, sardine, and sprat across years and areas, with a potential link between egg density and surface sea water density. The validated model is a tool for the analysis of shelf seas fish egg vertical distributions.
Robust salivary gland‐specific transgene expression in Anopheles stephensi mosquito
Authors: Yoshida S. , Watanabe H. 
Published: August 2006

AbstractMalaria sporozoites invade the mosquito salivary glands and wait in the salivary duct until the next blood feeding. The mechanisms of the process and molecules involved in the salivary gland invasion remain largely unknown. To establish a robust salivary gland‐specific transgene expression in Anopheles stephensi, we obtained a salivary gland‐specific promoter for a gene encoding anopheline antiplatelet protein (AAPP). The aapp promoter is a female salivary gland‐specific and blood meal‐inducible strong promoter. Using this promoter, we generated a transgenic An. stephensi expressing abundant Discosoma sp. red fluorescent protein (DsRed) in the distal‐lateral lobes of the glands, where the sporozoites invade preferentially. These results open up the possibilities of elucidating salivary gland–parasite interactions and generating transgenic mosquitoes refractory to parasites.