bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of adversity and perceived social support on the outcome of major depressive disorder in subjects with different levels of depressive symptoms
Authors: LESKELÄ ULLA , RYTSÄLÄ HEIKKI , KOMULAINEN ERKKI , MELARTIN TARJA , SOKERO PETTERI , LESTELÄ-MIELONEN PAULA , ISOMETSÄ ERKKI 
Published: March 2006

Background. Adverse life events and social support may influence the outcome of major depressive disorder (MDD). We hypothesized that outcome would depend on the level of depressive symptoms present at the outset, with those in partial remission being particularly vulnerable.Method. In the Vantaa Depression Study (VDS), patients with DSM-IV MDD were interviewed at baseline, and at 6 and 18 months. Life events were investigated with the Interview for Recent Life Events (IRLE) and social support with the Interview Measure of Social Relationships (IMSR) and the Perceived Social Support Scale – Revised (PSSS-R). The patients were divided into three subgroups at 6 months, those in full remission (n=68), partial remission (n=75) or major depressive episode (MDE) (n=50). The influence of social support and negative life events during the next 12 months on the level of depressive symptoms, measured by the Hamilton Rating Scale for Depression (HAMD), was investigated at endpoint.Results. The severity of life events and perceived social support influenced the outcome of depression overall, even after adjusting for baseline level of depression and neuroticism. In the full remission subgroup, both severity of life events and subjective social support significantly predicted outcome. However, in the partial remission group, only the severity of events, and in the MDE group, the level of social support were significant predictors.Conclusions. Adverse life events and/or poor perceived social support influence the medium-term outcome of all psychiatric patients with MDD. These factors appear to have the strongest predictive value in the subgroup of patients currently in full remission.
Clinical and neuropsychological characteristics of child and adolescent bipolar disorder
Authors: KYTE ZOË A. , CARLSON GABRIELLE A. , GOODYER IAN M. 
Published: March 2006

Background. The diagnosis of bipolar disorder in pre-pubertal populations remains difficult and often controversial. Consequently, the clinical and neuropsychological characteristics of mania in the child and adolescent years remain poorly defined. This review provides a clinical account of childhood and adolescent bipolar disorder and compares the neuropsychology and neuroanatomy of young BPD patients compared with adult BPD and childhood syndromes of attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD).Method. Literature review based on Pubmed searches.Results. Early- and adult-onset mania and BPD may share a common pattern of neurobiological characteristics despite developmental variations in the clinical presentation. In contrast, important distinctions are apparent between the child-onset syndromes of BPD, ADHD and CD, specifically at the neural level.Conclusions. Disorders of affect dysregulation in childhood deserve closer neuroscientific and phenotypic scrutiny than given hitherto.
Lack of ceramide generation and altered sphingolipid composition are associated with drug resistance in human ovarian carcinoma cells
Authors: Prinetti Alessandro , Millimaggi Danilo , D'Ascenzo Sandra , Clarkson Matilda , Bettiga Arianna , Chigorno Vanna , Sonnino Sandro , Pavan Antonio , Dolo Vincenza 
Published: March 2006

PTX (Paclitaxel®) is an antimitotic agent used in the treatment of a number of major solid tumours, particularly in breast and ovarian cancer. This study was undertaken to gain insight into the molecular alterations producing PTX resistance in ovarian cancer. PTX treatment is able to induce apoptosis in the human ovarian carcinoma cell line, CABA I. PTX-induced apoptosis in CABA I cells was accompanied by an increase in the cellular Cer (ceramide) levels and a decrease in the sphingomyelin levels, due to the activation of sphingomyelinases. The inhibition of acid sphingomyelinase decreased PTX-induced apoptosis. Under the same experimental conditions, PTX had no effect on Cer and sphingomyelin levels in the stable PTX-resistant ovarian carcinoma cell line, CABA-PTX.
The acquisition of the PTX-resistant phenotype is accompanied by unique alterations in the complex sphingolipid pattern found on lipid extraction. In the drug-resistant cell line, the levels of sphingomyelin and neutral glycosphingolipids were unchanged compared with the drug-sensitive cell line. The ganglioside pattern in CABA I cells is more complex compared with that of CABA-PTX cells. Specifically, we found that the total ganglioside content in CABA-PTX cells was approximately half of that in CABA I cells, and GM3 ganglioside content was remarkably higher in the drug-resistant cell line.
Taken together our findings indicate that: i) Cer generated by acid sphingomyelinase is involved in PTX-induced apoptosis in ovarian carcinoma cells, and PTX-resistant cells are characterized by their lack of increased Cer upon drug treatment, ii) PTX resistance might be correlated with an alteration in metabolic Cer patterns specifically affecting cellular ganglioside composition.
The CD38-independent ADP-ribosyl cyclase from mouse brain synaptosomes: a comparative study of neonate and adult brain
Authors: Ceni Claire , Pochon Nathalie , Villaz Michel , Muller-Steffner Hélène , Schuber Francis , Baratier Julie , De Waard Michel , Ronjat Michel , Moutin Marie-Jo 
Published: March 2006

cADPR (cADP-ribose), a metabolite of NAD+, is known to modulate intracellular calcium levels and to be involved in calcium-dependent processes, including synaptic transmission, plasticity and neuronal excitability. However, the enzyme that is responsible for producing cADPR in the cytoplasm of neural cells, and particularly at the synaptic terminals of neurons, remains unknown. In the present study, we show that endogenous concentrations of cADPR are much higher in embryonic and neonate mouse brain compared with the adult tissue. We also demonstrate, by comparing wild-type and Cd38−/− tissues, that brain cADPR content is independent of the presence of CD38 (the best characterized mammalian ADP-ribosyl cyclase) not only in adult but also in developing tissues. We show that Cd38−/− synaptosome preparations contain high ADP-ribosyl cyclase activities, which are more important in neonates than in adults, in line with the levels of endogenous cyclic nucleotide. By using an HPLC method and adapting the cycling assay developed initially to study endogenous cADPR, we accurately examined the properties of the synaptosomal ADP-ribosyl cyclase. This intracellular enzyme has an estimated Km for NAD+ of 21 μM, a broad optimal pH at 6.0–7.0, and the concentration of free calcium has no major effect on its cADPR production. It binds NGD+ (nicotinamide–guanine dinucleotide), which inhibits its NAD+-metabolizing activities (Ki=24 μM), despite its incapacity to cyclize this analogue. Interestingly, it is fully inhibited by low (micromolar) concentrations of zinc. We propose that this novel mammalian ADP-ribosyl cyclase regulates the production of cADPR and therefore calcium levels within brain synaptic terminals. In addition, this enzyme might be a potential target of neurotoxic Zn2+.
Adaptation of enterocytic Caco-2 cells to glucose modulates triacylglycerol-rich lipoprotein secretion through triacylglycerol targeting into the endoplasmic reticulum lumen
Authors: Pauquai Thomas , Bouchoux Julien , Chateau Danielle , Vidal Romain , Rousset Monique , Chambaz Jean , Demignot Sylvie 
Published: March 2006

Enterocytes are responsible for the absorption of dietary lipids, which involves TRL [TG (triacylglycerol)-rich lipoprotein] assembly and secretion. In the present study, we analysed the effect on TRL secretion of Caco-2 enterocyte adaptation to a differential glucose supply. We showed that TG secretion in cells adapted to a low glucose supply for 2 weeks after confluence was double that of control cells maintained in high-glucose-containing medium, whereas the level of TG synthesis remained similar in both conditions. This increased secretion resulted mainly from an enlargement of the mean size of the secreted TRL. The increased TG availability for TRL assembly and secretion was not due to an increase in the MTP (microsomal TG transfer protein) activity that is required for lipid droplet biogenesis in the ER (endoplasmic reticulum) lumen, or to the channelling of absorbed fatty acids towards the monoacylglycerol pathway for TG synthesis. Interestingly, by electron microscopy and subcellular fractionation studies, we observed, in the low glucose condition, an increase in the TG content available for lipoprotein assembly in the ER lumen, with the cytosolic/microsomal TG levels being verapamil-sensitive. Overall, we demonstrate that Caco-2 enterocytes modulate TRL secretion through TG partitioning between the cytosol and the ER lumen according to the glucose supply. Our model will help in identifying the proteins involved in the control of the balance between TRL assembly and cytosolic lipid storage. This mechanism may be a way for enterocytes to regulate TRL secretion after a meal, and thus impact on our understanding of post-prandial hypertriglyceridaemia.
Tumour necrosis factor α-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family members
Authors: Hermey Guido , Sjøgaard Susanne S. , Petersen Claus Munck , Nykjær Anders , Gliemann Jørgen 
Published: March 2006

Several transmembrane molecules are cleaved at juxtamembrane extracellular sites leading to shedding of ectodomains. We analysed shedding of members of the Vps10p-D (Vps10p domain; where Vps is vacuolar protein sorting) family of neuronal type-I receptors with partially overlapping functions, and additional proteolytic events initiated by the shedding. When transfected into CHO (Chinese-hamster ovary) cells (CHO-K1), sorCS1a–sorCS1c isoforms were shed at high rates (∼0.61%·min−1) that were increased approx. 3-fold upon stimulation with phorbol ester. sorCS1c identified in the cultured neuroblastoma cell line SH-SY5Y was shed similarly. In CHO-K1 transfectants, constitutive and stimulated shedding of sorCS3 also occurred at high rates (0.29% and 1.03%·min−1). By comparison, constitutive and stimulated shedding of sorLA occurred at somewhat lower rates (0.07% and 0.48%·min−1), whereas sorCS2 and sortilin were shed at very low rates even when stimulated (∼0.01%·min−1). Except for sorCS2, shedding of the receptors was dramatically reduced in mutant CHO cells (CHO-M2) devoid of active TACE (tumour necrosis factor α-converting enzyme), demonstrating that this enzyme accounts for most sheddase activity. The release of sorCS1 and sorLA ectodomains initiated rapid cleavage of the membrane-tethered C-terminal stubs that accumulated only in the presence of γ-secretase inhibitors. Purified shed sorLA bound several ligands similarly to the entire luminal domain of the receptor, including PDGF-BB (platelet-derived growth factor-BB) and amyloid-β precursor protein. In addition, PDGF-BB also bound to the luminal domains of sorCS1 and sorCS3. The results suggest that ectodomains shed from a subset of Vps10p-D receptors can function as carrier proteins.
rhEPO (recombinant human eosinophil peroxidase): expression inPichia pastorisand biochemical characterization
Authors: Ciaccio Chiara , Gambacurta Alessandra , Sanctis Giampiero DE , Spagnolo Domenico , Sakarikou Christina , Petrella Giovanni , Coletta Massimo 
Published: March 2006

A Pichia pastoris expression system has for the first time been successfully developed to produce rhEPO (recombinant human eosinophil peroxidase). The full-length rhEPO coding sequence was cloned into the pPIC9 vector in frame with the yeast α-Factor secretion signal under the transcriptional control of the AOX (acyl-CoA oxidase) promoter, and transformed into P. pastoris strain GS115. Evidence for the production of rhEPO by P. pastoris as a glycosylated dimer precursor of approx. 80 kDa was determined by SDS/PAGE and gel filtration chromatography. Recombinant hEPO undergoes proteolytic processing, similar to that in the native host, to generate two chains of approx. 50 and 20 kDa. A preliminary biochemical characterization of purified rhEPO demonstrated that the spectral and kinetic properties of the recombinant wild-type EPO are comparable with those of the native enzyme and are accompanied by oxidizing activity towards several physiological anionic substrates such as SCN−, Br− and Cl−. On the basis of the estimated Km and kcat values it is evident that the pseudohalide SCN− is the most specific substrate for rhEPO, consistent with the catalytic properties of other mammalian EPOs purified from blood.
Characterization of Schistosoma mansoni Sds homologue, a leucine-rich repeat protein that interacts with protein phosphatase type 1 and interrupts a G2/M cell-cycle checkpoint
Authors: Daher Wassim , Cailliau Katia , Takeda Kojiro , Pierrot Christine , Khayath Naji , Dissous Colette , Capron Monique , Yanagida Mitsuhiro , Browaeys Edith , Khalife Jamal 
Published: March 2006

The suppressor of the dis2 mutant (sds22+) has been shown to be an essential regulator in cell division of fission and budding yeast where its deletion causes mitotic arrest. Its role seems to take place through the activation of PP1 (protein phosphatase type 1) in Schizosaccharomyces pombe. In the trematode Schistosoma mansoni, we have identified the Sds22 homologue (SmSds), and the PP1 (SmPP1). We showed by using a GST (glutathione S-transferase) pull-down assay that the SmSds gene product interacts with SmPP1 and that the SmSds–SmPP1 complex is present in parasite extracts. Furthermore, we observed that SmSds inhibited PP1 activity. Functional studies showed that the microinjection of SmSds into Xenopus oocytes interacted with the Xenopus PP1 and disrupted the G2/M cell-cycle checkpoint by promoting progression to GVBD (germinal vesicle breakdown). Similar results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies. Taken together, these observations suggest that SmSds can regulate the cell cycle by binding to PP1.
The ABC transporter BmrA from Bacillus subtilis is a functional dimer when in a detergent-solubilized state
Authors: Ravaud Stéphanie , Do Cao Marie-Ange , Jidenko Marie , Ebel Christine , Le Maire Marc , Jault Jean-Michel , Di Pietro Attilio , Haser Richard , Aghajari Nushin 
Published: March 2006

BmrA from Bacillus subtilis is a half-size ABC (ATP-binding cassette) transporter involved in multidrug resistance. Although its supramolecular organization has been investigated after reconstitution in a lipid bilayer environment, and shows a dimeric and possibly a tetrameric form, the precise quaternary structure in a detergent-solubilized state has never been addressed. In the present study, BmrA was purified from Escherichia coli membranes using an optimized purification protocol and different detergents. Furthermore, the ATPase activity of BmrA and the quantity of bound lipids and detergent were determined, and the oligomeric state was analysed using SEC (size-exclusion chromatography) and analytical ultracentrifugation. The activity and the quaternary structure of BmrA appeared to be strongly influenced by the type and concentration of the detergent used. SEC data showed that BmrA could be purified in a functional form in 0.05 and 0.01% DDM (n-dodecyl-β-D-maltoside) and was homogeneous and monodisperse with an Rs (Stokes radius) of 5.6 nm that is compatible with a dimer structure. Sedimentation-velocity and equilibrium experiments unequivocally supported that BmrA purified in DDM is a dimer and excluded the presence of other oligomeric states. These observations, which are discussed in relation to results obtained in proteoliposomes, also constitute an important first step towards crystallographic studies of BmrA structure.
Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine–homocysteine S-methyltransferase
Authors: Sparks Janet D. , Collins Heidi L. , Chirieac Doru V. , Cianci Joanne , Jokinen Jenny , Sowden Mark P. , Galloway Chad A. , Sparks Charles E. 
Published: March 2006

We have previously reported a positive correlation between the expression of BHMT (betaine–homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639–645]. To examine whether a similar relationship occurs in vivo, hepatic BHMT expression was induced by feeding rats a Met (L-methionine)-restricted betaine-containing diet, and parameters of ApoB metabolism were evaluated. There were no generalized metabolic abnormalities associated with Met restriction for 7 days, as evidenced by control levels of serum glucose, ketones, alanine aminotransferase and L-homocysteine levels. Betaine plus the Met restriction resulted in lower serum insulin and non-esterified fatty acid levels. Betaine plus Met restriction induced hepatic BHMT 4-fold and ApoB mRNA 3-fold compared with Met restriction alone. No changes in percentage of edited ApoB mRNA were observed on the test diets. An increase in liver ApoB mRNA correlated with an 82% and 46% increase in ApoB and triacylglycerol production respectively using in vivo Triton WR 1339. Increased secretion of VLDL (very-low-density lipoprotein) with Met restriction plus betaine was associated with a 45% reduction in liver triacylglycerol compared with control. Nuclear run-off assays established that transcription of both bhmt and apob genes was also increased in Met-restricted plus betaine diets. No change in ApoB mRNA stability was detected in BHMT-transfected McA cells. Hepatic ApoB and BHMT mRNA levels were also increased by 1.8- and 3-fold respectively by betaine supplementation of Met-replete diets. Since dietary betaine increased ApoB mRNA, VLDL ApoB and triacylglycerol production and decreased hepatic triacylglycerol, results suggest that induction of apob transcription may provide a potential mechanism for mobilizing hepatic triacylglycerol by increasing ApoB available for VLDL assembly and secretion.
Finding regions of significance in SELDI measurements for identifying protein biomarkers
Authors: Tan Chuen Seng , Ploner Alexander , Quandt Andreas , Lehtiö Janne , Pawitan Yudi 
Published: March 2006

AbstractMotivation: There is a well-recognized potential of protein expression profiling using the surface-enhanced laser desorption and ionization technology for discovering biomarkers that can be applied in clinical diagnosis, prognosis and therapy prediction. The pre-processing of the raw data, however, is still problematic.Methods: We focus on the peak detection step, where the standard method is marked by poor specificity. Currently, scientists need to inspect individual spectra visually and laboriously in order to verify that spectral peaks identified by the standard method are real. Motivated by this multi-spectral process, we investigate an analytical approach—called RS for ‘regions of significance’—that reduces the data to a single spectrum of F-statistics capturing significant variability between spectra. To account for multiple testing, we use a false discovery rate criterion for identifying potentially interesting proteins.Results: We show that RS has better operating characteristics than several existing methods and demonstrate routine applications on a number of large datasets.Availability: RS is implemented in an R package called ProSpect which is available atContact: yudi.pawitan@ki.seSupplementary information: Supplementary data are available at Bioinformatics online.
GBPM: GRID-based pharmacophore model: concept and application studies to protein–protein recognition
Authors: Ortuso Francesco , Langer Thierry , Alcaro Stefano 
Published: March 2006

Abstract
Motivation: Automatic procedures to obtain pharmacophore models from experimentally determined macromolecular complexes can help in the drug discovery process, especially when protein–protein recognition plays an important biological role.
Results: The GRID-based pharmacophore model (GBPM) is a fully objective method for defining most relevant interaction areas in complexes deriving pharmacophore models from three-dimensional (3D) molecular structure information. It is based on logical and clustering operations with 3D maps computed by the GRID program on structurally known molecular complexes. In this manuscript we describe the concept and discuss application examples regarding protein–protein recognition. In particular two complexes selected in the Protein Data Bank have been tested to evaluate the GBPM capability to identify interaction areas. The results obtained show the capabilities of this new bioinformatic method.
Availability: The GBPM method has not been developed as a new computational code. It is based on the combination of existing scientific programs.
Contact: alcaro@unicz.it
Heart Rate Variability–guided Prophylactic Treatment of Severe Hypotension after Subarachnoid Block for Elective Cesarean Delivery
Authors: Hanss Robert , Bein Berthold , Francksen Helga , Scherkl Wiebke , Bauer Martin , Doerges Volker , Steinfath Markus , Scholz Jens , Tonner Peter H. 
Published: March 2006

Background
Baseline low-to-high frequency ratio (LF/HF) of heart rate variability predicted hypotension after subarachnoid block (SAB). LF/HF-guided treatment of hypotension with vasopressors or colloids was investigated.

Methods
In 80 women scheduled to undergo cesarean delivery during SAB, LF/HF and systolic blood pressure (SBP) were analyzed. Patients were randomly assigned to a control group (n = 40) or a treatment group (n = 40). Control patients were assigned by their baseline LF/HF to one of two subgroups: LF/HF less than 2.5 or LF/HF greater than 2.5. Treatment patients with baseline LF/HF greater than 2.5 were treated with vasopressor infusion right after SAB (n = 20) or colloid prehydration until LF/HF decreased below 2.5 (n = 20). The incidences of hypotension (SBP < 80 mmHg) and hypertension (SBP > 140 mmHg) were investigated. LF/HF is presented as median and range, and SBP is presented as mean +/- SD.

Results
Three of 17 control patients with low baseline LF/HF (1.7 [1.3/1.8]) demonstrated hypotension, and mean SBP remained stable (lowest SBP = 105 +/- 14 mmHg). In contrast, 20 of 23 control patients with high baseline LF/HF (3.8 [3.3/4.8]; P < 0.0001 vs. low baseline LF/HF) demonstrated hypotension after SAB: lowest SBP = 78 +/- 15 mmHg (P < 0.0001 vs. lowest SBP of control group with low baseline LF/HF). LF/HF-guided vasopressor therapy prevented hypotension in 19 of 20 patients: baseline SBP = 123 +/- 15 mmHg, lowest SBP = 116 +/- 17 mmHg. Mean prophylactic colloid infusion of 1,275 +/- 250 ml reduced elevated baseline LF/HF from 5.4 (4.1/7.5) to 1.3 (0.8/1.59) (P < 0.0001). Hypotension was prevented in 17 of 20 patients: baseline SBP = 115 +/- 13 mmHg, lowest SBP = 104 +/- 19 mmHg. No hypertensive episode was recognized.

Conclusions
LF/HF may be a tool to guide prophylactic therapy of patients at high risk for hypotension after SAB. Vasopressor therapy tended to be more effective compared with colloid prehydration.