bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel mutations in abetalipoproteinaemia and homozygous familial hypobetalipoproteinaemia
Authors: Vongsuvanh R. , Hooper A. J. , Coakley J. C. , Macdessi J. S. , O'Loughlin E. V. , Burnett J. R. , Gaskin K. J. 
Published: November 2007

SummaryAbetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)‐containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat‐soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB‐30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in‐frame deletion of MTP exon 15 (c.2076‐39_2303+52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat‐soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.
Transcriptional activity of the RHOB gene is influenced by regulatory polymorphisms in its promoter region
Authors: Mahr Sandra , Müller-Hilke Brigitte 
Published: November 2007

Abstract
Osteoarthritis (OA) is a chronic joint disease with genetic as well as environmental factors contributing to its etiology. We recently identified RHOB as a gene overexpressed in osteoarthritis. Interestingly, RHOB harbors numerous polymorphisms in its promoter region and genotyping of OA patients and healthy controls revealed an association of the single nucleotide polymorphism (SNP) rs585017 with the disease. We here set out to investigate the influence of RHOB promoter polymorphisms on the transcriptional activity of the gene and we found evidence that the SNPs rs2602160 and rs585017 cooperate in regulating RHOB expression. In addition, a variable number of tandem repeats (VNTR) impacts on the RHOB transcriptional activity in a cell type restricted manner. These results mechanistically link our previous finding of an elevated RHOB expression to the disease associated SNP rs585017 and confirm a role for regulatory polymorphisms in osteoarthritis.
Population dynamics and intra-litter transmission patterns ofIsospora suisin suckling piglets under on-farm conditions
Authors: SOTIRAKI S. , ROEPSTORFF A. , NIELSEN J. P. , MADDOX-HYTTEL C. , ENøE C. , BOES J. , MURRELL K. D. , THAMSBORG S. M. 
Published: November 2007

SUMMARYThe aim of this study was to investigate the intra-litter infection dynamics ofIsospora suisunder natural conditions, and to study any association between parasite transmission and the contamination level of the farrowing pen by applying different interventions in order to reduce the transmission ofI. suisinfection within the litter. The study was divided in 2 trials including in total 22 litters (254 piglets). The first trial included 4 litters (where standard procedures practiced routinely on the farm piglets were applied) and the piglets were followed coprologically from farrowing until 2 weeks after weaning. The sows of those litters were also examined at various intervals before and after farrowing. The second trial included the application of 3 different management procedures: (A) standard farm hygiene and management procedures, (B) standard farm hygiene and management procedures+the first piglets found to excreteI. suisoocysts in each pen were removed from the pen, and (C) reduced cleaning. Each procedure was studied in 2 litters. This was replicated 3 times to yield a total of 18 litters. The results suggested that (i) the sow does not play an important role in transmission ofI. suisin the farrowing pen; (ii) in natural infections, both the age of the piglet age at onset of oocyst excretion and the oocyst excretion patterns may vary considerably; (iii) the course of oocyst excretion or development of diarrhoea is related to the time of initial infection and (iii) piglets, which are heavy at birth, are more prone to acquireI. suisinfection. Moreover, it was demonstrated that cleaning could be an effective means of restricting the spread of the parasite within the litter and thus the development of diarrhoea.
Reversal of an immunity associated plant cell death program by the growth regulator auxin
Authors: Gopalan Suresh 
Published: November 2007

AbstractOne form of plant immunity against pathogens involves a rapid host programmed cell death at the site of infection accompanied by resistance, termed the hypersensitive response (HR). Here it is shown that the HR programmed cell death program initiated by the bacterial type III secretion system dependent proteinaceous elicitor harpin from Erwinia amylovora can be reversed till very late in the process by the plant growth regulator auxin. Early inhibition or late reversal of this cell death program does not affect marker genes tightly correlated with local and systemic resistance. Cross-regulation between cell death programs and growth regulators is prevalent in different kingdoms. Thus, the concept that cell death program can be reversed till late provides a framework for further investigation of such phenomena, in addition to having utility in choosing better targets and strategies for treating mammalian and agricultural diseases.
Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6‐drug interactions
Authors: Maréchal J‐D , Kemp C A , Roberts G C K , Paine M J I , Wolf C R , Sutcliffe M J 
Published: November 2007

The cytochromes P450 (CYPs) comprise a vast superfamily of enzymes found in virtually all life forms. In mammals, xenobiotic metabolizing CYPs provide crucial protection from the effects of exposure to a wide variety of chemicals, including environmental toxins and therapeutic drugs. Ideally, the information on the possible metabolism by CYPs required during drug development would be obtained from crystal structures of all the CYPs of interest. For some years only crystal structures of distantly related bacterial CYPs were available and homology modelling techniques were used to bridge the gap and produce structural models of human CYPs, and thereby obtain useful functional information. A significant step forward in the reliability of these models came seven years ago with the first crystal structure of a mammalian CYP, rabbit CYP2C5, followed by the structures of six human enzymes, CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6 and CYP3A4, and a second rabbit enzyme, CYP2B4. In this review we describe as a case study the evolution of a CYP2D6 model, leading to the validation of the model as an in silico tool for predicting binding and metabolism. This work has led directly to the successful design of CYP2D6 mutants with novel activity—including creating a testosterone hydroxylase, converting quinidine from inhibitor to substrate, creating a diclofenac hydroxylase and creating a dextromethorphan O‐demethylase. Our modelling‐derived hypothesis‐driven integrated interdisciplinary studies have given key insight into the molecular determinants of CYP2D6 and other important drug metabolizing enzymes.British Journal of Pharmacology (2008) 153, S82–S89; doi:10.1038/sj.bjp.0707570; published online 19 November 2007
AS601245, a c‐Jun NH2‐terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils
Authors: Carboni S , Boschert U , Gaillard P , Gotteland J‐P , Gillon J‐Y , Vitte P‐A 
Published: November 2007

Background and purpose.Based on their proven ability, in animal models of stroke, to reduce damage to brain grey matter, many drugs have been tested in clinical trials but without success. Failure to save axons from injury and to protect functional outcome has been proposed as the major reason for this lack of success. We have previously demonstrated in two rodent models of cerebral ischaemia, that AS601245 (1,3‐benzothiazol‐2‐yl (2‐{[2‐(3‐pyridinyl) ethyl] amino}‐4 pyrimidinyl) acetonitrile), an inhibitor of the c‐Jun NH2‐terminal kinase (JNK), has neuroprotective properties. The aim of the present study was to further investigate if AS601245 in addition to its ability to protect neurons also could protect neurites and preserve memory after cerebral ischaemia, in gerbils.Experimental approach.Using immunohistochemical techniques and a behavioural test, we studied the effect of the compound AS601245 on neurodegeneration and cognitive deficits after global cerebral ischaemia in gerbils.Key results.At a dose of 80 mg kg−1, i.p., AS601245 reduced damage to neurites by 67% (P<0.001 versus controls) and activation of astrocytes by 84% (P<0.001 versus controls). In addition, AS601245 (80 mg kg−1, i.p.) prevented ischaemia‐induced impairment of memory in the inhibitory avoidance task model.Conclusions and implications.The present results suggest that AS601245 reduced damage to neurites and decreased astrogliosis following global ischaemia and also improved long‐term memory, supporting JNK inhibition as a promising therapeutic strategy for ischaemic insults to the CNS.British Journal of Pharmacology(2008)153, 157–163; doi:10.1038/sj.bjp.0707574; published online 19 November 2007
[Pt(O,O′‐acac)(γ‐acac)(DMS)], a new Pt compound exerting fast cytotoxicity in MCF‐7 breast cancer cells via the mitochondrial apoptotic pathway
Authors: Muscella A , Calabriso N , Fanizzi F P , De Pascali S A , Urso L , Ciccarese A , Migoni D , Marsigliante S 
Published: November 2007

Background and purpose:We showed previously that a new Pt complex containing an O,O′‐chelated acetylacetonate ligand (acac) and a dimethylsulphide in the Pt coordination sphere, [Pt(O,O′‐acac)(γ‐acac)(DMS)], induces apoptosis in HeLa cells. The objective of this study was to investigate the hypothesis that [Pt(O,O′‐acac)(γ‐acac)(DMS)] is also cytotoxic in a MCF‐7 breast cancer cell line relatively insensitive to cisplatin, and to gain a more detailed analysis of the cell death pathways.Experimental approach:Cells were treated with Pt compounds and cytotoxicity tests were performed, together with Western blotting of various proteins involved in apoptosis. The mitochondrial membrane potential was assessed by fluorescence microscopy and spectrofluorometry and the Pt bound to cell fractions was measured by atomic absorption spectrometry.Key results:In contrast to cisplatin, the cytotoxicity of [Pt(O,O′‐acac)(γ‐acac)(DMS)] correlated with cellular accumulation but not with DNA binding. Also, the Pt content in DNA bases was considerably higher for cisplatin than for [Pt(O,O′‐acac)(γ‐acac)(DMS)], thus excluding DNA as a target of [Pt(O,O′‐acac)(γ‐acac)(DMS)]. [Pt(O,O′‐acac)(γ‐acac)(DMS)] exerted high and fast apoptotic processes in MCF‐7 cells since it provoked: (a) mitochondria depolarization; (b) cytochrome c accumulation in the cytosol; (c) translocation of Bax and truncated‐Bid from cytosol to mitochondria and decreased expression of Bcl‐2; (d) cleavage of caspases ‐7 and ‐9, and PARP degradation; (e) chromatin condensation and DNA fragmentation.Conclusions and implications:[Pt(O,O′‐acac)(γ‐acac)(DMS)] is highly cytotoxic for MCF‐7 cells, cells relatively resistant to many chemotherapeutic agents, as it activates the mitochondrial apoptotic pathway. Hence, [Pt(O,O′‐acac)(γ‐acac)(DMS)] has the potential to provide us with new opportunities for therapeutic intervention.British Journal of Pharmacology (2008) 153, 34–49; doi:10.1038/sj.bjp.0707576; published online 19 November 2007
Analysis of sphingosine 1‐phosphate receptors involved in constriction of isolated cerebral arteries with receptor null mice and pharmacological tools
Authors: Salomone S , Potts E M , Tyndall S , Ip P C , Chun J , Brinkmann V , Waeber C 
Published: November 2007

Background and purpose:Sphingosine 1‐phosphate (S1P) selectively and potently constricts isolated cerebral arteries, but this response has not been pharmacologically characterized.Experimental approach:The receptor subtype(s) involved in S1P‐induced cerebrovascular constriction were characterized using genetic (S1P2 and S1P3 receptor null mice) and pharmacological tools (phospho‐FTY720, a S1P1/3/4/5 receptor agonist; SEW2871, a S1P1 receptor agonist, JTE‐013, a S1P2 receptor antagonist, VPC23019, a S1P1/3 receptor antagonist). Isolated basilar or peripheral (femoral, mesenteric resistance) arteries, from either rat or mouse, were studied in a wire myograph.Key results:S1P concentration‐dependently constricted basilar artery in rat, wild‐type (WT) and S1P2 null mice, but barely affected vascular tone in S1P3 null mice. Vasoconstriction to U46619 (a thromboxane analogue) or to endothelin‐1 did not differ between WT, S1P2 and S1P3 null mice. JTE‐013 inhibited not only S1P‐induced vasoconstriction, but also KCl‐, U46619‐ and endothelin‐1‐induced constriction. This effect was observed in WT as well as in S1P2 null mice. VPC23019 increased the concentration‐dependent vasoconstriction to S1P in both rat and mouse basilar arteries with intact endothelium, but not in rat basilar artery without endothelium. Phospho‐FTY720 concentration‐dependently constricted rat basilar arteries, but not femoral or mesenteric resistance arteries, while SEW2871 did not induce any response in the same arteries.Conclusions and implications:S1P constricts cerebral arteries through S1P3 receptors. The purported S1P2 receptor antagonist JTE‐013 does not appear to be selective, at least in rodents. Enhancement of S1P‐induced contraction by VPC23019 might be related to blockade of S1P1 receptors and NO generation.British Journal of Pharmacology (2008) 153, 140–147; doi:10.1038/sj.bjp.0707581; published online 19 November 2007
Endocannabinoids and cannabinoid receptors in ischaemia–reperfusion injury and preconditioning
Authors: Pacher P , Haskó G 
Published: November 2007

Ischaemia–reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB1/CB2receptor‐dependent and ‐independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB1receptor agonists or knockout mice demonstrated CB1receptor‐dependent protection against cerebral I/R injury in various animal models. In contrast, several follow‐up reports have shown protection afforded by CB1receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB2receptor agonists and/or knockout mice have provided compelling evidence that CB2receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB2receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R‐induced tissue damage.British Journal of Pharmacology(2008)153, 252–262; doi:10.1038/sj.bjp.0707582; published online 19 November 2007
Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi‐site prospective cohort study
Authors: Davoli Marina , Bargagli Anna M. , Perucci Carlo A. , Schifano Patrizia , Belleudi Valeria , Hickman Matthew , Salamina Giuseppe , Diecidue Roberto , Vigna‐Taglianti Federica , Faggiano Fabrizio ,   for the VEdeTTE Study Group
Published: November 2007

ABSTRACTBackground  Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality.Methods  Prospective cohort study of 10 454 heroin users entering treatment 1998–2001 in Italy followed‐up for 10 208 person‐years in treatment and 2914 person‐years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment.Results  There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8–5.4] and 21.4 (16.7–27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04–0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6–61.1) in the month immediately following treatment and 7.3 (3.3–16.2) in the subsequent period.Conclusions  We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short‐term therapies for opiate use.
Fluidized Bed Assisted Abrasive Jet Machining (FB-AJM): Precision
Internal Finishing of Inconel 718 Components
Authors: Barletta M. , Ceccarelli D. , Guarino S. , Tagliaferri V. 
Published: November 2007

Abstract
The relatively new technique of fluidized bed assisted abrasive jet machining (FB-AJM) is applied to finishing the inner surfaces of tubular Inconel 718 components. The effects of abrasive size, jet pressure, and machining cycle were evaluated, and the behavior of abrasive cutting edges acting against the surface during the process to remove material is accounted for. The finished surface was found to be highly dependent on jet pressure because it affects the abrasive contact against the surface as well as the finishing force acting on the abrasive, on the abrasive grain size, which controls the depth of cut, and on machining cycle, which controls the interaction time between the abrasives and the surface being finished. By altering these conditions, this process achieves surface roughness (Ra) as fine as 0.1μm and imparts minimal additional residual stress on the surface. This study also reveals the mechanisms that determine the smoothing of the inner surface of Inconel 718 tubes and improve the form accuracy, i.e., the internal roundness of the Inconel 718 tube.
Metal Transfer in Double-Electrode Gas Metal Arc Welding
Authors: Li Kehai , Zhang YuMing 
Published: November 2007

Abstract
Gas metal arc welding (GMAW) is the most widely used process for metal joining because of its high productivity and good quality, but analysis shows that the fundamental characteristic restricts conventional GMAW from further increasing the welding productivity. A novel GMAW process, refereed to as double-electrode GMAW or DE-GMAW, thus has been developed to make it possible to increase the melting current while the base metal current can still be controlled at a desired level. This fundamental change provides an effective method to allow manufacturers to use high melting currents to achieve high melting speed and low base metal heat input. A series of experiments have been conducted to uncover the basic characteristics of this novel process. Results obtained from analyses of high-speed image sequences and recorded current signals suggest that DE-GMAW can lower the critical current for achieving the desired spray transfer, shift the droplet trajectory, reduce the diameter of the droplet, and increase the speed and (generation) rate of the droplets.
yadBC
of
Yersinia pestis
, a New Virulence Determinant for Bubonic Plague
Authors: Forman Stanislav , Wulff Christine R. , Myers-Morales Tanya , Cowan Clarissa , Perry Robert D. , Straley Susan C. 
Published: November 2007

ABSTRACT

In all
Yersinia pestis
strains examined, the adhesin/invasin
yadA
gene is a pseudogene, yet
Y. pestis
is invasive for epithelial cells. To identify potential surface proteins that are structurally and functionally similar to YadA, we searched the
Y. pestis
genome for open reading frames with homology to
yadA
and found three: the bicistronic operon
yadBC
(YPO1387 and YPO1388 of
Y. pestis
CO92; y2786 and y2785 of
Y. pestis
KIM5), which encodes two putative surface proteins, and YPO0902, which lacks a signal sequence and likely is nonfunctional. In this study we characterized
yadBC
regulation and tested the importance of this operon for
Y. pestis
adherence, invasion, and virulence. We found that loss of
yadBC
caused a modest loss of invasiveness for epithelioid cells and a large decrease in virulence for bubonic plague but not for pneumonic plague in mice.
The effects of crown ratio on the transition from juvenile to mature wood production in lodgepole pine in western Canada
Authors: Mansfield Shawn D. , Parish Roberta , Goudie James W. , Kang Kyu-Young , Ott Peter 
Published: November 2007

Crown depth, tree spacing, and stand density have major effects on wood quality and fibre characteristics of trees. Lodgepole pine ( Pinus contorta Doug. ex Loud.) trees from a mixture of plantation and fire origin stands were employed to determine how crown ratio, a surrogate for stand density, affected mature wood production. In total, 104 trees were sampled, ranging from 24 to 110 years of age, from stands in western Alberta and interior British Columbia, Canada. Samples taken along the bole were measured for wood density, which was subject to segmented regression analysis to identify the transition point from juvenile to mature wood production. On average, the lodgepole pine trees were 31 (±17 SD) years old before mature wood production began. A mixed-effects model, in which combination of fixed effects (tree age, height of the sample disc relative to crown base, and crown length) and random effects (site, trees nested in sites, and discs nested in both trees and sites) proved to be the best predictor of years of mature wood production along the bole. The transition from juvenile to mature wood was shown to be below the crown base in trees <50 years old with deep crowns, and above the crown base otherwise.