bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine deaminase activity, trypsin inhibitory capacity and total antioxidant capacity in psoriasis
Authors: Hashemi M , Mehrabifar H , Daliri M , Ghavami S
Published: September 2009

Background  Psoriasis is a chronic inflammatory skin disease characterized by pathological skin lesions because of various exogenous and endogenous factors and associated with a number of biochemical and immunological disturbances.

Objective  The aim of the present study was to determine the level of adenosine deaminase activity, serum trypsin inhibitory capacity and total antioxidant capacity of plasma in psoriatic patients.

Subjects and methods  The study was performed in controls (n = 46) and in psoriatic patients (n = 40). The patients were scored with PASI (psoriasis area and severity index). The serum ADA activity was determined using Aguisti and Galanti method and serum trypsin inhibitory capacity (sTIC) were measured by enzymatic assay. Besides, serum total antioxidant capacity was measured using ferric reducing ability of plasma.

Results  The serum ADA activity of the psoriatic patients was found to be significantly higher (P < 0.001) than that of the healthy control. We also found that the trypsin inhibitory capacity was significantly higher in patients than in control group (P < 0.001). Total antioxidant capacity of plasma was significantly lower in psoriatic patients than in healthy controls (P = 0.025). There were no significant correlations among ADA, TAC and TIC.

Conclusion  Serum ADA activity and sTIC were increased in psoriatic patients. In parallel, serum total anti‐oxidant activity was decreased in these patients.
Binomial Mixture Model‐based Association Tests under Genetic Heterogeneity
Authors: Zhou Hui , Pan Wei
Published: September 2009

Most of the existing association tests for population‐based case‐control studies are based on comparing the mean genotype scores between the case and control groups, which may not be efficient under genetic heterogeneity. Given that most common diseases are genetically heterogeneous, caused by mutations in multiple loci, it may be beneficial to fully account for genetic heterogeneity in an association test. Here we first propose a binomial mixture model for such a purpose and develop a corresponding mixture likelihood ratio test (MLRT) for a single locus. We also consider two methods to combine single‐locus‐based MLRTs across multiple loci in linkage disequilibrium to boost power when causal SNPs are not genotyped. We show with a wide spectrum of numerical examples that under genetic heterogeneity the proposed tests are more powerful than some commonly used association tests.
Ca2+/calmodulin‐dependent transcriptional pathways: potential mediators of skeletal muscle growth and development
Authors: Al‐Shanti Nasser , Stewart Claire E.
Published: September 2009

The loss of muscle mass with age and disuse has a significant impact on the physiological and social well‐being of the aged; this is an increasingly important problem as the population becomes skewed towards older age. Exercise has psychological benefits but it also impacts on muscle protein synthesis and degradation, increasing muscle tissue volume in both young and older individuals. Skeletal muscle hypertrophy involves an increase in muscle mass and cross‐sectional area and associated increased myofibrillar protein content. Attempts to understand the molecular mechanisms that underlie muscle growth, development and maintenance, have focused on characterising the molecular pathways that initiate, maintain and regenerate skeletal muscle. Such understanding may aid in improving targeted interventional therapies for age‐related muscle loss and muscle wasting associated with diseases. Two major routes through which skeletal muscle development and growth are regulated are insulin‐like growth factor I (IGF‐I) and Ca2+/calmodulin‐dependent transcriptional pathways. Many reviews have focused on understanding the signalling pathways of IGF‐I and its receptor, which govern skeletal muscle hypertrophy. However, alternative molecular signalling pathways such as the Ca2+/calmodulin‐dependent transcriptional pathways should also be considered as potential mediators of muscle growth. These latter pathways have received relatively little attention and the purpose herein is to highlight the progress being made in the understanding of these pathways and associated molecules: calmodulin, calmodulin kinases (CaMKs), calcineurin and nuclear factor of activated T‐cell (NFAT), which are involved in skeletal muscle regulation. We describe: (1) how conformational changes in the Ca2+ sensor calmodulin result in the exposure of binding pockets for the target proteins (CaMKs and calcineurin). (2) How Calmodulin consequently activates either the Ca2+/calmodulin‐dependent kinases pathways (via CaMKs) or calmodulin‐dependent serine/threonine phosphatases (via calcineurin). (3) How calmodulin kinases alter transcription in the nucleus through the phosphorylation, deactivation and translocation of histone deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. (4) How calcineurin transmits signals to the nucleus through the dephosphorylation and translocation of NFAT from the cytoplasm to the nucleus.
Mistrust of Health Care Organizations Is Associated with Underutilization of Health Services
Authors: LaVeist Thomas A. , Isaac Lydia A. , Williams Karen Patricia
Published: September 2009

Purpose. We report the validation of an instrument to measure mistrust of health care organizations and examine the relationship between mistrust and health care service underutilization.

Methods. We conducted a telephone survey of a random sample of households in Baltimore City, MD. We surveyed 401 persons and followed up with 327 persons (81.5 percent) 3 weeks after the baseline interview. We conducted tests of the validity and reliability of the Medical Mistrust Index (MMI) and then conducted multivariate modeling to examine the relationship between mistrust and five measures of underutilization of health services.

Results. Using principle components analysis, we reduced the 17‐item MMI to 7 items with a single dimension. Test–retest reliability was moderately strong, ranging from Pearson correlation of 0.346–0.697. In multivariate modeling, the MMI was predictive of four of five measures of underutilization of health services: failure to take medical advice (b=1.56, p<.01), failure to keep a follow‐up appointment (b=1.11, p=.01), postponing receiving needed care (b=0.939, p=.01), and failure to fill a prescription (b=1.48, p=.002). MMI was not significantly associated with failure to get needed medical care (b=0.815, p=.06).

Conclusions. The MMI is a robust predictor of underutilization of health services. Greater attention should be devoted to building greater trust among patients.
Serum lactate dehydrogenase activity in canine malignancies
Authors: Marconato L. , Crispino G. , Finotello R. , Mazzotti S. , Salerni F. , Zini E.
Published: September 2009

Lactate dehydrogenase (LDH) is commonly used in human cancer patients for prognostic purposes. Aim of this study was to determine the magnitude of serum LDH elevation in dogs with cancer compared with healthy dogs and dogs with non‐neoplastic disease, and to verify whether it may support the diagnosis of specific malignancies. About 128 healthy dogs, 211 diseased dogs and 188 cancer dogs were enrolled. Dogs with cancer had significantly higher LDH than diseased (P< 0.001) and healthy dogs (P< 0.001), but large overlap was found. Dogs with lymphoma showed significantly higher LDH compared with dogs with carcinoma (P< 0.001) or mast cell tumour (MCT;P< 0.05) but not compared with other malignancies. When considering lymphoma and MCT, LDH levels were not different between early and advanced clinical stages. Measuring LDH levels may not be useful as a screening tool for cancer detection. More studies are needed to define its role in specific tumours.
The combination of a blood test and Fibroscan improves the non‐invasive diagnosis of liver fibrosis
Authors: Boursier Jérôme , Vergniol Julien , Sawadogo Apollinaire , Dakka Taoufiq , Michalak Sophie , Gallois Yves , Le Tallec Véronique , Oberti Frédéric , Fouchard‐Hubert Isabelle , Dib Nina , Rousselet Marie Christine , Konaté Anselme , Amrani Naïma , De Ledinghen Victor , Calès Paul
Published: September 2009

Background and aims: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm.

Methods: Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included. Five blood fibrosis tests were evaluated: APRI, FIB‐4, Hepascore, Fibrotest and FibroMeter. The reference was fibrosis Metavir staging.

Results: Diagnosis of significant fibrosis (Metavir F≥2). The most accurate synchronous combination was FibroMeter+LSE, which provided a significantly higher area under the receiver operating characteristic curve (0.892) than LSE alone (0.867, P=0.011) or Fibrometer (0.834, P<10−3). An algorithm using the FibroMeter+LSE combination and then a liver biopsy in indeterminate cases had 91.9% diagnostic accuracy and required significantly fewer biopsies (20.2%) than previously published Bordeaux algorithm (28.6%, P=0.02) or sequential algorithm for fibrosis evaluation (SAFE) (55.7%, P<10−3). The Angers algorithm performance was not significantly different between viral hepatitis and other causes. Diagnosis of cirrhosis. The most accurate synchronous combination was LSE+FibroMeter, which provided ≥90% predictive values for cirrhosis in 90.6% of patients vs 87.4% for LSE (P=0.02) and 57.9% for FibroMeter (P<10−3). An algorithm including the LSE+FibroMeter combination, and then a liver biopsy in indeterminate cases, had a significantly higher diagnostic accuracy than the SAFE algorithm (91.0 vs 79.8%, P<10−3), and required significantly fewer biopsies than the Bordeaux algorithm (9.3 vs 25.3%, P<10−3).

Conclusion: The synchronous combination of a blood test plus LSE improves the accuracy of the non‐invasive diagnosis of liver fibrosis and, consequently, markedly decreases the biopsy requirement in the diagnostic algorithm, notably to <10% in cirrhosis diagnosis.
Serum cystatin C level is a good prognostic marker in patients with cirrhotic ascites and normal serum creatinine levels
Authors: Seo Yeon Seok , Jung Eun Suk , An Hyonggin , Kim Jeong Han , Jung Young Kul , Kim Ji Hoon , Yim Hyung Joon , Yeon Jong Eun , Byun Kwan Soo , Kim Chang Duck , Ryu Ho Sang , Um Soon Ho
Published: September 2009

Background/Aims: Serum creatinine (Cr) is not a reliable marker for early detection of renal dysfunction in patients with cirrhotic ascites. Several reports have suggested that cystatin C (CysC) is more sensitive than Cr for detecting reduced renal function in these patients. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and a normal serum Cr level.

Methods: We enrolled patients with ascites and a normal serum Cr level (<1.2 mg/dl). Liver function tests, international normalized ratio (INR) and serum Cr and CysC levels were measured on the same day for all patients. CysC levels were measured using the automated latex‐enhanced immunonephelometric method. The endpoint of follow‐up was the development of hepatorenal syndrome (HRS) or mortality.

Results: Seventy‐eight patients with cirrhotic ascites were enrolled in the study (58 men and 30 women; age, 53±11 years). The underlying liver diseases in these patients were chronic hepatitis B (37%), chronic hepatitis C (4%), alcoholic liver disease (53%) and others (6%). Forty‐six (59%) and 32 (41%) patients were in Child–Pugh classes B and C respectively. HRS developed in 14 patients during the follow‐up period (349±241 days), with cumulative incidences of 10.2% and 20.4% at 6 and 12 months respectively. The CysC level was the only independent predictive factor for HRS. Twenty‐three patients died during the follow‐up period. CysC level and INR were independent factors for predicting mortality.

Conclusion: Serum CysC level is a good marker for predicting HRS and survival in patients with cirrhotic ascites and a normal Cr level.
Intrathecal Therapy: What Has Changed With the Introduction of Ziconotide
Authors: Kress Hans G. , Simpson Karen H. , Marchettini Paolo , Ver Donck Ann , Varrassi Giustino
Published: September 2009

Administering drugs into the intrathecal space is becoming more popular in the treatment of patients with intractable pain or intolerable side effects of systemic analgesic treatments. Although morphine and ziconotide are the only intrathecal analgesics currently approved by regulatory authorities in the U.S. (Food and Drug Administration) and Europe (national‐level approval by individual countries for morphine and European Agency for the Evaluation of Medicinal Products approval for ziconotide), a wide variety of opioid and non‐opioid drugs are being used in this way. There is no official guidance concerning the selection of these drugs or their use in combinations and a paucity of efficacy and safety data from randomized controlled trials. The polyanalgesic initiative aims to summarize the current knowledge and to facilitate rational choices of intrathecal drug and drug combinations for the management of chronic pain. The most recent polyanalgesic consensus recommendations were published in 2007. In this review, we shall examine these recommendations, which are tailored toward those practicing intrathecal analgesia in the U.S., and discuss how they should be implemented in Europe, where the healthcare systems and regulations of the medical authorities are different.
The Window of Epileptogenesis: Looking beyond the Latent Period
Authors: Wong Michael
Published: September 2009

Development of Spontaneous Recurrent Seizures after Kainate-Induced Status Epilepticus. Williams PA, White AM, Clark S, Ferraro DJ, Swiercz W, Staley KJ, Dudek FE. J Neurosci 2009;29:2103–2112. Acquired epilepsy (i.e., after an insult to the brain) is often considered to be a progressive disorder, and the nature of this hypothetical progression remains controversial. Antiepileptic drug treatment necessarily confounds analyses of progressive changes in human patients with acquired epilepsy. Here, we describe experiments testing the hypothesis that development of acquired epilepsy begins as a continuous process of increased seizure frequency (i.e., proportional to probability of a spontaneous seizure) that ultimately plateaus. Using nearly continuous surface cortical and bilateral hippocampal recordings with radiotelemetry and semiautomated seizure detection, the frequency of electrographically recorded seizures (both convulsive and nonconvulsive) was analyzed quantitatively for 100 d after kainate-induced status epilepticus in adult rats. The frequency of spontaneous recurrent seizures was not a step function of time (as implied by the “latent period”); rather, seizure frequency increased as a sigmoid function of time. The distribution of interseizure intervals was nonrandom, suggesting that seizure clusters (i.e., short interseizure intervals) obscured the early stages of progression, and may have contributed to the increase in seizure frequency. These data suggest that ( 1 ) the latent period is the first of many long interseizure intervals and a poor measure of the time frame of epileptogenesis, ( 2 ) epileptogenesis is a continuous process that extends much beyond the first spontaneous recurrent seizure, ( 3 ) uneven seizure clustering contributes to the variability in occurrence of epileptic seizures, and ( 4 ) the window for antiepileptogenic therapies aimed at suppressing acquired epilepsy probably extends well past the first clinical seizure.
Severe Symptoms in Mid and Apical Hypertrophic Cardiomyopathy
Authors: Shah Ajay , Duncan Karl , Winson Glenda , Chaudhry Farooq A. , Sherrid Mark V
Published: September 2009

Background: We analyzed the clinical and quantitative echocardiographic characteristics of patients with sub‐basal hypertrophic cardiomyopathy (HCM) to define the characteristics of patients (pts) with severe symptoms. Methods: Of 444 pts in a referral‐based HCM program, 22 (5%) had midventricular or apical HCM. Quality of life (QoL) questionnaire was administered as an independent confirmer of symptomatic state. Results: Ten pts were NYHA III and IV, and 12 pts were NYHA I and II; QoL scores (41 ± 26 vs. 10 ± 13, P = 0.001) confirmed a priori division of two groups based on NYHA classification. Pts with more severe symptoms were more likely female (70% vs. 25%, P = 0.001) with atrial fibrillation (40% vs. 0%, P = 0.02). They more frequently had midventricular HCM 60% versus 8% (P = 0.01) (mid‐LV thickness 17 ± 6 vs. 12 ± 2 mm, P = 0.03) and had much smaller LV diastolic volumes 68 ± 12 versus 102 ± 22 ml (39 ± 4 vs. 53 ± 12 ml/m2, P = 0.001). Septal E/E’ was higher in the severely symptomatic pts (15 ± 5 vs. 7 ± 3, P = 0.001) indicating higher estimated LV filling pressure. Midobstruction with apical akinetic chamber was noted in 4/10 pts who developed refractory symptoms. Cardiac mortality was higher in the severely symptomatic patients, 4/10 who had midventricular HCM as compared to 0/12 in the mildly symptomatic apical HCM group (P = 0.03). Conclusions: In subbasal HCM, pts with severe symptoms have midventricular hypertrophy, with encroachment of the LV cavity and consequent very small LV volumes that may be complicated by mid‐LV obstruction. Pts with mid‐LV hypertrophy are more symptomatic than those with apical HCM, are often refractory to therapy, and have higher mortality.
Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Evaluation of Mitral and Aortic Valve Prosthetic Paravalvular Regurgitation
Authors: Singh Preeti , Manda Jayaprakash , Hsiung Ming Chon , Mehta Anjlee , Kesanolla Saritha Kumari , Nanda Navin C. , Tsai Shen‐Kou , Jeng‐Wei   M.D., Ph.D.  , Yin Wei‐Hsian
Published: September 2009

Thirteen patients already scheduled for surgery for repair of prosthetic paravalvular regurgitation underwent intraoperative real time two‐dimensional transesophageal echocardiography (2D TEE) and live/real time three‐dimensional transesophageal echocardiography (3D TEE). In all patients, 3D TEE was able to provide more information regarding the location and size of the paravalvular defect as compared to 2D TEE. 3D TEE resulted in a more accurate localization of the defect and an estimation of the size of the defect that correlated much more closely with surgical findings when compared with 2D TEE. Our preliminary results demonstrate the superiority of 3D TEE over 2D TEE in the evaluation of paravalvular prosthetic regurgitation. 3D TEE not only provides an accurate assessment of the exact site of the leakage, but also gives a more accurate estimate of its size. This information could be valuable to surgeons who may encounter difficulty when localizing and estimating the size of paraprosthetic leaks while the heart is devoid of blood during surgery.
Adaptive Regulation at the Cell Surface by N‐Glycosylation
Authors: Dennis James W. , Lau Ken S. , Demetriou Michael , Nabi Ivan R.
Published: September 2009

The association of receptors and solute transporters with components of the endocytic machinery regulates their surface levels, and thereby cellular sensitivity to cytokines, ligands and nutrients in the extracellular environment. Most transmembrane receptors and solute transporters are glycoproteins, and the Asn (N)‐linked oligosaccharides (N‐glycans) can bind animal lectins, forming multivalent lattices or microdomains that regulate glycoprotein mobility in the plane of membrane. The N‐glycan number (sequence‐encoded NXS/T) and context‐dependent Golgi N‐glycan branching cooperate to regulate glycoprotein affinities for the galectin family of lectins. Galectin‐3 binding reduces EGF receptor trafficking into clathrin‐coated pits and caveolae lipid rafts, decreases ligand‐independent receptor activation and promotes α5β1 integrin remodelling in focal adhesions. N‐glycan branching in the medial Golgi increases glycan affinity for galectins, and the Golgi pathway is sensitive to uridine diphosphate‐N‐acetylglucosamine (UDP‐GlcNAc) supply, in turn hexosamine pathway metabolites (fructose‐6‐P, glutamine and acetyl‐CoA). Thus, lattice avidity and cellular responsiveness to extracellular cues are regulated in an adaptive manner by metabolism and Golgi modification to glycoproteins. Computational modelling of the hexosamine/Golgi/lattice has provided new insight on cell surface adaptation in cancer and autoimmune disease.
Spatial variability of above‐ground net primary production in Uruguayan grasslands: a remote sensing approach
Authors: Baeza S. , Lezama F. , Piñeiro G. , Altesor A. , Paruelo J. M.
Published: September 2009

Question: How does above‐ground net primary production (ANPP) differ (estimated from remotely sensed data) among vegetation units in sub‐humid temperate grasslands?

Location: Centre‐north Uruguay.

Methods: A vegetation map of the study area was generated from LANDSAT imagery and the landscape configuration described. The functional heterogeneity of mapping units was analysed in terms of the fraction of photosynthetically active radiation absorbed by green vegetation (fPAR), calculated from the normalized difference vegetation index (NDVI) images provided by the moderate resolution imaging spectroradiometer (MODIS) sensor. Finally, the ANPP of each grassland class was estimated using NDVI and climatic data.

Results: Supervised classification presented a good overall accuracy and moderate to good average accuracy for grassland classes. Meso‐xerophytic grasslands occupied 45% of the area, Meso‐hydrophytic grasslands 43% and Lithophytic steppes 6%. The landscape was shaped by a matrix of large, unfragmented patches of Meso‐xerophytic and Meso‐hydrophytic grasslands. The region presented the lowest anthropic fragmentation degree reported for the Rio de la Plata grasslands. All grassland units showed bimodal annual fPAR seasonality, with spring and autumn peaks. Meso‐hydrophytic grasslands showed a radiation interception 10% higher than the other units. On an annual basis, Meso‐hydrophytic grasslands produced 3800 kg dry matter (DM) ha−1 yr−1 and Meso‐xerophytic grasslands and Lithophytic steppes around 3400 kg·DM·ha−1·yr−1. Meso‐xerophytic grasslands had the largest spatial variation during most of the year. The ANPP temporal variation was higher than the fPAR variability.

Conclusions: Our results provide valuable information for grazing management (identifying spatial and temporal variations of ANPP) and grassland conservation (identifying the spatial distribution of vegetation units).
Evolutionary changes to transthyretin: structure–function relationships
Authors: Prapunpoj P. , Leelawatwattana L.
Published: September 2009

Transthyretin is one of the three major thyroid hormone‐binding proteins in plasma and/or cerebrospinal fluid of vertebrates. It transports retinol via binding to retinol‐binding protein, and exists mainly as a homotetrameric protein of ∼ 55 kDa in plasma. The first 3D structure of transthyretin was an X‐ray crystal structure from human transthyretin. Elucidation of the structure–function relationship of transthyretin has been of significant interest since its highly conserved structure was shown to be associated with several aspects of metabolism and with human diseases such as amyloidosis. Transthyretin null mice do not have an overt phenotype, probably because transthyretin is part of a network with other thyroid hormone distributor proteins. Systematic study of the evolutionary changes of transthyretin structure is an effective way to elucidate its function. This review summarizes current knowledge about the evolution of structural and functional characteristics of vertebrate transthyretins. The molecular mechanism of evolutionary change and the resultant effects on the function of transthyretin are discussed.
The role of Tyr71 in Streptomyces trypsin on the recognition mechanism of structural protein substrates
Authors: Uesugi Yoshiko , Usuki Hirokazu , Iwabuchi Masaki , Hatanaka Tadashi
Published: September 2009

Studies of substrate recognition by serine proteases have focused on specificities at the primary S1–Sn sites, but topological specificities (i.e. recognition at distinct three‐dimensional structural motifs) have not been established. This is the first report to identify the key amino acid residue conferring topological specificity. A serine protease from Streptomyces omiyaensis (SOT), which is a trypsin‐like enzyme, was chosen as a model enzyme to clarify the recognition mechanism of structural protein substrates in serine proteases. We have found previously that the topological specificities of SOT and S. griseus trypsin (SGT) for high molecular mass substrates differ greatly, even though the enzymes have similar primary structures. In this study, we constructed chimeras between SOT and SGT using an in vivo DNA shuffling system and several mutants to identify the key residues involved in topological specificities. By comparing the substrate specificities of chimeras and mutants, we found that residue 71 of SOT, which is separate from the catalytic triad, contributes to the topological specificity. Using site‐directed mutagenesis, residue 71 of SOT was also found to be crucial for catalytic efficiency and enzyme conformation.
Common G102S polymorphism in chitotriosidase differentially affects activity towards 4‐methylumbelliferyl substrates
Authors: Bussink Anton P. , Verhoek Marri , Vreede Jocelyne , Ghauharali‐van der Vlugt Karen , Donker‐Koopman Wilma E. , Sprenger Richard R. , Hollak Carla E. , Aerts Johannes M. F. G. , Boot Rolf G.
Published: September 2009

Chitotriosidase (CHIT1) is a chitinase that is secreted by activated macrophages. Plasma chitotriosidase activity reflects the presence of lipid‐laden macrophages in patients with Gaucher disease. CHIT1 activity can be conveniently measured using fluorogenic 4‐methylumbelliferyl (4MU)–chitotrioside or 4MU–chitobioside as the substrate, however, nonsaturating concentrations have to be used because of apparent substrate inhibition. Saturating substrate concentrations can, however, be used with the newly designed substrate 4MU–deoxychitobioside. We studied the impact of a known polymorphism, G102S, on the catalytic properties of CHIT1. The G102S allele was found to be common in type I Gaucher disease patients in the Netherlands (∼ 24% of alleles). The catalytic efficiency of recombinant Ser102 CHIT1 was ∼ 70% that of wild‐type Gly102 CHIT1 when measured with 4MU–chitotrioside at a nonsaturating concentration. However, the activity was normal with 4MU–deoxychitobioside as the substrate at saturating concentrations, consistent with predictions from molecular dynamics simulations. In conclusion, interpretation of CHIT1 activity measurements with 4MU–chitotrioside with respect to CHIT1 protein concentrations depends on the presence of Ser102 CHIT1 in an individual, complicating estimation of the body burden of storage macrophages. Use of the superior 4MU–deoxychitobioside substrate avoids such complications because activity towards this substrate under saturating conditions is not affected by the G102S substitution.
Suppression of nuclear factor‐κB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles
Authors: De Pascale Clara , Graham Valerie , Fowkes Robert C. , Wheeler‐Jones Caroline P. D. , Botham Kathleen M.
Published: September 2009

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor‐κB (NF‐κB) has been implicated. In this study, the influence of CMR on the activity of NF‐κB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP‐1 and CMR‐like particles (CRLPs). Incubation of THP‐1 macrophages with CRLPs caused decreased NF‐κB activation and downregulated the expression of phospho‐p65–NF‐κB and phospho‐IκBα (pIκBα). Secretion of the inflammatory cytokines tumour necrosis factor α, interleukin‐6 and monocyte chemoattractant protein‐1, which are under NF‐κB transcriptional control, was inhibited and mRNA expression for cyclooxygenase‐2, an NF‐κB target gene, was reduced. CRLPs enriched in polyunsaturated fatty acids compared with saturated or monounsaturated fatty acids had a markedly greater inhibitory effect on NF‐κB binding to DNA and the expression of phospho‐p65–NF‐κB and pIκB. Lipid loading of macrophages with CRLPs enriched in polyunsaturated fatty acids compared with monounsaturated fatty acids or saturated fatty acids also increased the subsequent rate of cholesterol efflux, an effect which may be linked to the inhibition of NF‐κB activity. These findings demonstrate that CMR suppress NF‐κB activity in macrophages, and that this effect is modulated by their fatty acid composition. This downregulation of inflammatory processes in macrophages may represent a protective effect of CMR which is enhanced by dietary polyunsaturated fatty acids.
LIN54 is an essential core subunit of the DREAM/LINC complex that binds to the cdc2 promoter in a sequence‐specific manner
Authors: Schmit Fabienne , Cremer Sarah , Gaubatz Stefan
Published: September 2009

Recently, the conserved human LINC/DREAM complex has been described as an important regulator of cell cycle genes. LINC consists of a core module that dynamically associates with E2F transcription factors, p130 and the B‐MYB transcription factor in a cell cycle‐dependent manner. In this study, we analyzed the evolutionary conserved LIN54 subunit of LINC. We found that LIN54 is required for cell cycle progression. Protein interaction studies demonstrated that a predicted helix–coil–helix motif is required for the interaction of LIN54 with p130 and B‐MYB. In addition, we found that the cysteine‐rich CXC domain of LIN54 is a novel DNA‐binding domain that binds to the cdc2 promoter in a sequence‐specific manner. We identified two binding sites for LIN54 in the cdc2 promoter, one of which overlaps with the cell cycle homology region at the transcriptional start site. Gel shift assays suggested that, in quiescent cells, the binding of LIN54 at the cell cycle homology region is stabilized by the binding of E2F4 to the adjacent cell cycle‐dependent element. Our data demonstrate that LIN54 is an important and integral subunit of LINC.

Structured digital abstract

 MINT‐7239362: LIN54 (uniprotkb:Q6MZP7) physically interacts (MI:0915) with p130 (uniprotkb:Q08999) by anti tag coimmunoprecipitation (MI:0007)

 MINT‐7239376: LIN54 (uniprotkb:Q6MZP7) physically interacts (MI:0915) with B‐Myb (uniprotkb:P10244) by anti tag coimmunoprecipitation (MI:0007)
An E3 ubiquitin ligase, Synoviolin, is involved in the degradation of immature nicastrin, and regulates the production of amyloid β‐protein
Authors: Maeda Tomoji , Marutani Toshihiro , Zou Kun , Araki Wataru , Tanabe Chiaki , Yagishita Naoko , Yamano Yoshihisa , Amano Tetsuya , Michikawa Makoto , Nakajima Toshihiro , Komano Hiroto
Published: September 2009

The presenilin complex, consisting of presenilin, nicastrin, anterior pharynx defective‐1 and presenilin enhancer‐2, constitutes γ‐secretase, which is required for the generation of amyloid β‐protein. In this article, we show that Synoviolin (also called Hrd1), which is an E3 ubiquitin ligase implicated in endoplasmic reticulum‐associated degradation, is involved in the degradation of endogenous immature nicastrin, and affects amyloid β‐protein generation. It was found that the level of immature nicastrin was dramatically increased in synoviolin‐null cells as a result of the inhibition of degradation, but the accumulation of endogenous presenilin, anterior pharynx defective‐1 and presenilin enhancer‐2 was not changed. This was abolished by the transfection of exogenous Synoviolin. Moreover, nicastrin was co‐immunoprecipitated with Synoviolin, strongly suggesting that nicastrin is the substrate of Synoviolin. Interestingly, amyloid β‐protein generation was increased by the overexpression of Synoviolin, although the nicastrin level was decreased. Thus, Synoviolin‐mediated ubiquitination is involved in the degradation of immature nicastrin, and probably regulates amyloid β‐protein generation.

Structured digital abstract

 MINT‐7255352: Synoviolin (uniprotkb:Q9DBY1) physically interacts (MI:0915) with NCT (uniprotkb:P57716) by anti tag coimmunoprecipitation (MI:0007)

 MINT‐7255377: Ubiquitin (uniprotkb:P62991) physically interacts (MI:0915) with NCT (uniprotkb:P57716) by anti bait coimmunoprecipitation (MI:0006)

 MINT‐7255363: NCT (uniprotkb:P57716) physically interacts (MI:0915) with Synoviolin (uniprotkb:Q9DBY1) by anti bait coimmunoprecipitation (MI:0006)
Biochemical analysis of the human EVL domains in homologous recombination
Authors: Takaku Motoki , Machida Shinichi , Nakayama Shugo , Takahashi Daisuke , Kurumizaka Hitoshi
Published: September 2009

EVL is a member of the ENA/VASP family, which is involved in actin‐remodeling processes. Previously, we reported that human EVL directly interacts with RAD51, which is an essential protein in the homologous recombinational repair of DNA double‐strand breaks, and stimulates RAD51‐mediated recombination reactions in vitro. To identify the EVL domain required for the recombination function, we purified the EVL fragments EVL(1–221) and EVL(222–418), which contain the EVH1 and Pro‐rich domains and the EVH2 domain, respectively. We found that EVL(222–418) possesses DNA‐binding and RAD51‐binding activities, and also stimulates RAD51‐mediated homologous pairing. In contrast, EVL(1–221) did not exhibit any of these activities. Therefore, the EVH2 domain, which is highly conserved among the ENA/VASP family proteins, may be responsible for the recombination function of EVL.

Structured digital abstract

 MINT‐7239394: EVL (uniprotkb:Q9UI08) binds (MI:0407) to RAD51 (uniprotkb:Q06609) by pull down (MI:0096)
CHANGES IN MUSCLE PROPERTIES DURING POSTMORTEM STORAGE OF FARMED SEA BREAM (SPARUS AURATA)
Authors: SUÁREZ M.D. , MARTÍNEZ T.F. , SÁEZ M.I. , ALFÉREZ B. , GARCÍA‐GALLEGO M.
Published: September 2009

This study assesses the effects of storage temperature on postmortem changes in textural parameters (firmness, water holding capacity), and their relationship with biochemical and electrophoretic determinations (muscle collagen content and solubility, amount and integrity of sarcoplasmic and myofibrillar proteins) in sea bream muscle. Storage at 1C resulted in a prolongation of the firmness compared with 4C, with no noticeable changes in water holding capacity. This delay in muscle softening at 1C could be partially explained by a limited proteolysis of some myofibrillar proteins, although inconsistent tendency was observed for other fractions. In contrast, the rate of muscle collagen degradation was higher at 4C compared with 1C, this becoming the main contributing factor to firmness losses. The great variety of protein fractions separated electrophoretically, and the relatively minor and contradictory changes observed suggest the unfeasibility of electrophoresis as a routine procedure for studying freshness in stored sea bream.

PRACTICAL APPLICATIONS

According to the results obtained, it is strongly recommended that the storage of sea bream (Sparus aurata) throughout the commercial chain is carried out at 1C, instead of the usual temperature of 4C. This modification clearly delays the process of muscle softening, thus improving objective quality in this species.

The electrophoretic separation of muscle proteins has been previously proposed as a suitable procedure for assessing the freshness of fish during cold storage. However, the results obtained here indicate that the attempts aimed to the development of an electrophoretic procedure for detecting modifications in muscle proteins that could be correlated with flesh textural properties were unsuccessful. This is especially true if short‐term deterioration is assessed.
THERMAL INACTIVATION OF LACTOBACILLUS PLANTARUM IN A MODEL LIQUID FOOD
Authors: AUGUSTO PEDRO E.D. , TRIBST ALLINE A.L. , CRISTIANINI MARCELO
Published: September 2009

Thermal process is one of the safest and most frequently used methods for food preservation. The use of model food in thermal treatment studies has several experimental advantages and enables reproducibility. Correct physical characterization of the model food and determination of thermal resistance of microorganisms are essential requirements in thermal treatments experiments. The present work determined the rheological characteristics of a 0.3% (w/w) carboxymethylcellulose (CMC) suspension, used as model liquid food, and the thermal resistance of Lactobacillus plantarum, a target microorganism in pasteurization processes. The rheological characterization was conducted using a double wall concentric‐cylinder rheometer with controlled stress, at various temperatures ranging from 25 to 80C. The L. plantarum thermal resistance was evaluated using the three‐neck flask method, at 52, 55, 58 and 61C. The rheological behavior of the model food was adjusted to the power law, with pseudoplastic behavior, consistency index (k) of 0.09Pa·sn and behavior index (n) of 0.80 at 25C. The parameters Ak and the activation energy (Eak) of the Arrhenius model were 0.0003Pa·sn and 14,140.7 J/mol/K, respectively. The values of D52C, D55C, D58C and D61C of L. plantarum were 76.3, 36.7, 16.4 and 7.3 s, respectively, with a z of 8.9C. The results showed that the model food system evaluated in this work represents several types of fruit juices. The use of well‐characterized model food systems could greatly improve experimental consistency and reproducibility of thermal process studies, which are characteristics highly desirable but still scarce in the literature.

PRACTICAL APPLICATIONS

The use of model food in the study of thermal process is highly desirable, but there is limited information in the literature on the characterization of model food systems associated with inactivation kinetics of microorganisms. The carboxymethylcellulose suspension described in this work can be used as a fruit juice model. The thermal inactivation of Lactobacillus plantarum proposed in this model is suitable for thermal process studies and design. The data on the model liquid food system and thermobacteriology described in this work are potentially useful for future studies on food thermal processes and represent a contribution to the development of efficacious food processing protocols.
FEASIBILITY OF USING A MINIATURE FIBER OPTIC UV‐VIS‐NIR SPECTROMETER TO ASSESS TOTAL POLYPHENOL INDEX, COLOR INTENSITY AND VOLUMIC MASS IN RED WINE FERMENTATIONS
Authors: FERNÁNDEZ‐NOVALES JUAN , SÁNCHEZ MARÍA‐TERESA , LÓPEZ MARÍA‐ISABEL , GARCÍA‐MESA JOSÉ‐ANTONIO , RAMÍREZ PILAR
Published: September 2009

This study sought to assess the feasibility of using ultraviolet‐visible‐near infrared (UV‐VIS‐NIR) spectroscopy to monitor changes in total polyphenol index, color intensity and volumic mass, three indicators of quality during red wine fermentation. Samples (n = 68) collected from eleven tanks during fermentation were scanned in three types of quartz flow cells, path lengths 0.1, 2 and 50 mm, in the UV‐VIS‐NIR region (200–1,100 nm), using a fiber spectrometer system in transmission mode. Principal component analysis and partial least squares regression were used to interpret spectra and develop calibrations for predicting wine composition during fermentation. Models for the prediction of total polyphenol index displayed coefficients of determination (r2) ranging between 0.21–0.98, whereas values for the standard error of cross‐validation (SECV) ranged from 2.29 to 14.91, depending on the spectral region used. Values for the prediction of color intensity were: r2 = 0.56–0.98 and SECV = 0.43–1.88. Corresponding values for volumic mass were r2 = 0.31–0.94 and SECV = 8.71–30.20 g/dm3. These results suggest that UV‐VIS‐NIR spectroscopy using a miniature fiber optic spectrometer as a promising tool could be used as an alternative method for the rapid monitoring of quality parameters during red wine fermentation.

PRACTICAL APPLICATIONS

The study develops ultraviolet‐visible‐near infrared calibrations to monitor changes in total polyphenol index, color intensity and volumic mass, main indicators of quality during red‐wine fermentation, taking into account and responding to the requirements of the enological industry that looks for a swift, efficient, economical and – particularly – nondestructive analytical technique for measuring quality parameters during fermentation process with a single instrument and in a matter of seconds, saving time and enhancing the decision‐making process. The work also evaluates the efficacy of a simple, efficient and low‐cost instrument that belongs to so called new near infrared spectroscopy (NIRS) generation, which are most suitable to be implemented for on‐line analysis in the winemaking industry. The results suggest that the miniature fiber optic NIR spectrometer is a promising tool for monitoring the red wine fermentation process, allowing the instantaneous prediction of the main parameters to be controlled. At the same time, suitable wavelengths for these parameters are also proposed according to x‐loading weights and regression coefficients.
The Systematic Development of a Nursing Intervention Aimed at Increasing Enrollment in Cardiac Rehabilitation for Acute Coronary Syndrome Patients
Authors: Cossette Sylvie , D'Aoust Louis‐Xavier , Morin Magali , Heppell Sonia , Frasure‐Smith Nancy
Published: September 2009

Acute coronary syndrome (ACS) is a leading cause of morbidity worldwide. Although cardiac rehabilitation (CR) programs can decrease recurrence of coronary events by as much as 25%, few patients engage in CR after a cardiac event. Current therapeutic procedures for ACS are provided quickly after the onset of symptoms, resulting in briefer hospital stays. Therefore, within this shorter time frame, the education of patients about ACS risk factors and their reduction presents a new nursing challenge. The purpose of this paper is to describe the systematic pathway in the development of a nursing intervention which addresses these new challenges in ACS risk factor reduction. The intervention aims to increase enrollment in CR, and enhance illness perceptions and medication adherence, while decreasing anxiety, risk factors, and emergency revisits.
Assurance de soins de santé au Japon: au‐delà de la vision binaire entre Etat et famille
Authors: Naïto Kusuto
Published: September 2009

La prise en charge des personnes âgées et à charge au Japon fut considérée comme une activité exclusive à la sphère familiale. Cette conception a prévalu en dépit de toutes les diversités régionales dans les structures familiales, d'une part, et l'existence jadis simultanée de solidarités extrafamiliales, d'autre part. L'évolution sociodémographique depuis le milieu du 20e siècle a amené non seulement les autorités politiques, mais aussi l'opinion publique, à la création d'une assurance publique de soins de santé. Instaurée en 2000, elle vise à«socialiser» ces activités à priori familiales et féminines. Cet article propose une analyse critique du système ainsi que du contexte dans lequel l'assurance a vu sa genèse. Le système répond‐il aux besoins des personnes âgées et de leurs entourages (familiaux et non familiaux)? Par ailleurs, tient‐il compte des diversités régionales, notamment en ce qui touche les situations des ménages, au‐delà des soucis financiers et des présuppositions sociétales? Le processus de vieillissement démographique connu par les sociétés industrialisées invite à revisiter leurs cheminements socio‐historiques, afin d'adapter continuellement les comportements et lieux de vie à des contextes socio‐économiques en importante évolution.
Zur freiwilligen Mitgliedschaft in Perus Rentensystem mit Individualkonten
Authors: Li Carmen A. , Olivera Javier
Published: September 2009

Auszug

Ein wichtiger Aspekt bei der Gestaltung des Sozialschutzes ist die Deckung. Wie in den meisten lateinamerikanischen Ländern ist die Deckung durch die soziale Sicherheit in Peru nur für Arbeitnehmer im formellen Sektor obligatorisch. Dieser Beitrag untersucht die Faktoren für eine freiwillige Mitgliedschaft in Perus Individualkonten‐Rentensystem. Es wurde festgestellt, dass Angehörige folgender Personengruppe eher als andere Personen dem System freiwillig beitreten: verheiratete Männer mit höherer Schulbildung und in Haushalten mit höheren Einkommen sowie mit Familienmitgliedern, die bereits Mitglied in einem Rentensystem mit Individualkonten sind. Die Ergebnisse zeigen, dass familiengestützte Sicherheitsnetze zwar einen Ersatz für die freiwillige Mitgliedschaft in Individualkonten‐Rentensystemen darstellen können, die Ausdehnung der Rentendeckung und die Armutsbekämpfung jedoch als Herausforderungen für den Staat bestehen bleiben.
Pflegeversicherung in Japan: Abschied von der binären Vision Staat‐Familie
Authors: Naïto Kusuto
Published: September 2009

Auszug

Die Betreuung älterer pflegebedürftiger Personen in Japan galt als eine ausschließlich der Familie obliegende Aufgabe, und dies trotz einer nicht zu vernachlässigenden regionalen Unterschiedlichkeit bei Familienstrukturen einerseits und bereits früher parallel dazu bestehender Solidaritätseinrichtungen außerhalb der Familien andererseits. Die soziodemografische Entwicklung seit Mitte des 20. Jahrhunderts bewog nicht nur die politischen Instanzen, sondern auch die öffentliche Meinung zur Schaffung einer öffentlichen Pflegeversicherung, die im Jahr 2000 eingeführt wurde und die vorher meist den Familien und den Frauen obliegenden Aufgaben sozialisieren sollte. Der vorliegende Artikel bietet eine kritische Analyse des Systems sowie des Kontextes, in dem die Versicherung entstand. Entspricht das System den Bedürfnissen der älteren Menschen und ihres (familiären und nicht familiären) Umfelds? Berücksichtigt es auch die regionalen Unterschiede, die Unterschiede in den Situationen der Haushalte, die über rein finanzielle Belange hinausgehen, sowie die gesellschaftlichen Werte und Glaubensvorstellungen? Wir kommen zum Schluss, dass der demografische Alterungsprozess nach einer gesellschaftlichen Reaktion verlangt auf die laufenden Veränderungen von Verhalten und Lebensformen.
Afiliación voluntaria al sistema de pensiones de cuentas individuales del Perú
Authors: Li Carmen A. , Olivera Javier
Published: September 2009

La cobertura es un aspecto importante en el diseño de la protección social. En el Perú, al igual que en la mayor parte de los países de América Latina, la cobertura de la seguridad social sólo es obligatoria para los trabajadores del sector formal. El presente artículo investiga los factores que determinan la afiliación voluntaria al sistema de pensiones de cuentas individuales del Perú. Se ha comprobado que hay un grupo selecto de personas que presenta una mayor probabilidad de afiliación voluntaria; se trata del formado por hombres casados con un nivel de estudios superior a la educación secundaria que viven en hogares de ingresos elevados y en cuya familia hay miembros que ya están afiliados al sistema de pensiones de cuentas individuales. A pesar de que los resultados sugieren que las redes familiares de seguridad pueden sustituir a la participación voluntaria en el sistema de pensiones de cuentas individuales, ampliar la cobertura de las pensiones y erradicar la pobreza siguen siendo retos para la participación del gobierno.