bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic acid synthesis from n‐3 fatty acid precursors in rat hippocampal neurons
Authors: Kaduce Terry L. , Chen Yucui , Hell Johannes W. , Spector Arthur A. 
Published: February 2008

AbstractDocosahexaenoic acid (DHA), the most abundant n‐3 polyunsaturated fatty acid in the brain, has important functions in the hippocampus. To better understand essential fatty acid homeostasis in this region of the brain, we investigated the contributions of n‐3 fatty acid precursors in supplying hippocampal neurons with DHA. Primary cultures of rat hippocampal neurons incorporated radiolabeled 18‐, 20‐, 22‐, and 24‐carbon n‐3 fatty acid and converted some of the uptake to DHA, but the amounts produced from either [1‐14C]α‐linolenic or [1‐14C]eicosapentaenoic acid were considerably less than the amounts incorporated when the cultures were incubated with [1‐14C]22:6n‐3. Most of the [1‐14C]22:6n‐3 uptake was incorporated into phospholipids, primarily ethanolamine phosphoglycerides. Additional studies demonstrated that the neurons converted [1‐14C]linoleic acid to arachidonic acid, the main n‐6 fatty acid in the brain. These findings differ from previous results indicating that cerebral and cerebellar neurons cannot convert polyunsaturated fatty acid precursors to DHA or arachidonic acid. Fatty acid compositional analysis demonstrated that the hippocampal neurons contained only 1.1–2.5 mol% DHA under the usual low‐DHA culture conditions. The relatively low‐DHA content suggests that some responses obtained with these cultures may not be representative of neuronal function in the brain.
Ischemic post‐conditioning protects brain and reduces inflammation in a rat model of focal cerebral ischemia/reperfusion
Authors: Xing Bianzhi , Chen Hui , Zhang Min , Zhao Dongming , Jiang Rui , Liu Xiuheng , Zhang Suming 
Published: February 2008

AbstractIschemic post‐conditioning (Post‐cond) is a phenomenon in which intermittent interruptions of blood flow in the early phase of reperfusion can protect organ from ischemia/reperfusion (I/R) injury. Recent studies demonstrated ischemic Post‐cond reduced infarct size in cerebral I/R injury. However, the molecular mechanisms underlying this phenomenon are not completely understood. As inflammation is known to be detrimental to the neurological outcome during the acute phase after stroke, we investigated whether ischemic Post‐cond played its protective role in preventing post‐ischemic inflammation in the rat middle cerebral artery occlusion model. Rats were treated with ischemic Post‐cond after 60 min of occlusion (beginning of reperfusion). The infarct volume and myeloperoxidase activity were assessed at 24 h. The lipid peroxidation levels was evaluated by malondialdehyde assay and the expressions of interleukin‐1β, tumor necrosis factor‐α, and intercellular adhesion molecule 1 were studied by RT‐PCR or western blotting. Ischemic Post‐cond decreased myeloperoxidase activity and expressions of interleukin‐1β, tumor necrosis factor‐α, and intercellular adhesion molecule 1. Ischemic Post‐cond also reduced infarct volume and lipid peroxidation levels. These findings indicated that ischemic Post‐cond may be a promising neuroprotective approach for focal cerebral I/R injury and it is achieved, at least in part, by the inhibition of inflammation.
Parkin protects against tyrosinase‐mediated dopamine neurotoxicity by suppressing stress‐activated protein kinase pathways
Authors: Hasegawa Takafumi , Treis Angela , Patenge Nadja , Fiesel Fabienne C. , Springer Wolfdieter , Kahle Philipp J. 
Published: February 2008

AbstractParkinson’s disease (PD) motor symptoms are caused by degeneration of nigrostriatal dopaminergic (DAergic) neurons. The most common causes of hereditary PD are mutations in the PARKIN gene. The ubiquitin ligase parkin has been shown to mediate neuroprotection in cell culture and in vivo, but the molecular mechanisms are not well understood. We investigated the effects of parkin in a human SH‐SY5Y neuroblastoma cell culture model of PD, in which transcriptional induction of the enzyme tyrosinase causes a neurotoxic overproduction of cellular DA and its oxidative metabolites. Tyrosinase induction caused formation of reactive oxygen species in the cytosol and mitochondria, and neurotoxicity via activation of apoptotic stress‐activated protein kinases and caspase 3. Stable transfection of wild‐type parkin suppressed tyrosinase‐induced apoptosis, and PD‐associated mutations abolished the neuroprotective effect of parkin. Expression of wild‐type parkin did not affect reactive oxygen species production, but attenuated the tyrosinase‐induced activation of both c‐Jun N‐terminal kinase and p38 mitogen‐activated protein kinase as well as their cognate mitogen‐activated protein kinase kinases. PD‐associated mutations differentially affected the anti‐apoptotic signaling of parkin. Thus, parkin contributes to DAergic neuroprotection by suppression of apoptotic stress‐activated protein kinase pathways.
A role for p53 in the regulation of lysosomal permeability by Δ9‐tetrahydrocannabinol in rat cortical neurones: implications for neurodegeneration
Authors: Gowran Aoife , Campbell Veronica A. 
Published: February 2008

AbstractThe psychoactive ingredient of marijuana, Δ9‐tetrahydrocannabinol (Δ9‐THC), can evoke apoptosis in cultured cortical neurones. Whilst the intracellular mechanisms responsible for this apoptotic pathway remain to be fully elucidated, we have recently identified a role for the CB1 type of cannabinoid (CB) receptor and the tumour suppressor protein, p53. In the current study, we demonstrate the Δ9‐THC promotes a significant increase in lysosomal permeability in a dose‐ and time‐dependent manner. The increase in lysosomal permeability was blocked by the CB1 receptor antagonist, AM251. Δ9‐THC increased the localization of phospho‐p53Ser15 at the lysosome and stimulated the release of the lysosomal cathepsin enzyme, cathepsin‐D, into the cytosol. The p53 inhibitor, pifithrin‐α and small interfering RNA‐mediated knockdown of p53 prevented the Δ9‐THC‐mediated increase in lysosomal permeability. Furthermore, the Δ9‐THC ‐mediated induction of apoptosis was abrogated by a cell‐permeable cathepsin‐D inhibitor (10 μM). Thus, the study demonstrates that Δ9‐THC impacts on the lysosomal system, via p53, to evoke lysosomal instability as an early event in the apoptotic cascade. This provides evidence for a novel link between the CB1 receptor and the lysosomal branch of the apoptotic pathway which is crucial in regulating neuronal viability following exposure to Δ9‐THC.
Developmentally regulated alternative splicing of densin modulates protein–protein interaction and subcellular localization
Authors: Jiao Yuxia , Robison A. J. , Bass Martha A. , Colbran Roger J. 
Published: February 2008

AbstractDensin is a member of the leucine‐rich repeat (LRR) and PDZ domain (LAP) protein family that binds several signaling molecules via its C‐terminal domains, including calcium/calmodulin‐dependent protein kinase II (CaMKII). In this study, we identify several novel mRNA splice variants of densin that are differentially expressed during development. The novel variants share the LRR domain but are either prematurely truncated or contain internal deletions relative to mature variants of the protein (180 kDa), thus removing key protein–protein interaction domains. For example, CaMKIIα coimmunoprecipitates with densin splice variants containing an intact C‐terminal domain from lysates of transfected HEK293 cells, but not with variants that only contain N‐terminal domains. Immunoblot analyses using antibodies to peptide epitopes in the N‐ and C‐ terminal domains of densin are consistent with developmental regulation of splice variant expression in brain. Moreover, putative splice variants display different subcellular fractionation patterns in brain extracts. Expression of green fluorescent protein (GFP)‐fused densin splice variants in HEK293 cells shows that the LRR domain can target densin to a plasma membrane‐associated compartment, but that the splice variants are differentially localized and have potentially distinct effects on cell morphology. In combination, these data show that densin splice variants have distinct functional characteristics suggesting multiple roles during neuronal development.
The glutamate transporter GLT1b interacts with the scaffold protein PSD‐95
Authors: González‐González Inmaculada M. , García‐Tardón Noemí , Cubelos Beatriz , Giménez Cecilio , Zafra Francisco 
Published: February 2008

AbstractThe glutamate transporter (GLT1) regulates glutamate concentrations in glutamatergic synapses and it is expressed in at least two isoforms, GLT1a and GLT1b. In this work, we show that the C‐terminus of GLT1b is able to interact with the PDZ domains of a number of proteins. Notably, one of them might be the scaffold protein post‐synaptic density (PSD‐95). GLT1b formed co‐immunoprecipitable complexes with PSD‐95 in solubilizated rat brain extracts, complexes that also contained NMDA receptors. Co‐transfection of GLT1b, PSD‐95, and NMDA receptor subunits in heterologous expression systems recapitulated in vitro the interactions among these proteins that had been observed in the rat brain extracts and revealed the importance of the GLT1b C‐terminal PDZ binding motif in tethering this transporter to PSD‐95. Significantly, co‐expression of GLT1b and PSD‐95 increased the Vmax of the transporter by decreasing the rate of GLT1b endocytosis. Moreover, GLT1b transfected into primary cultured neurons or glia formed protein clusters that co‐localized with co‐transfected PSD‐95, clusters that in these neurons accumulated preferentially in dendritic spines. We hypothesize that the GLT1b/PSD‐95 interaction, characterized here in vitro, might anchor this transporter close to the post‐synaptic glutamate receptors, thereby permitting the fine regulation of glutamate concentrations in this microenvironment. This tight association might also facilitate the regulation of GLT1b through the signaling pathways initiated by the activation of glutamate receptors.
Advances in vertebrate aging research 2007
Authors: Austad Steven 
Published: February 2008

SummaryAmong this year's highlights in vertebrate aging research, we find a study in which, contrary to the oxidative stress hypothesis of aging, reduced expression of a major cellular antioxidant, glutathione peroxidase 4, led to a small increase in mouse lifespan. By contrast, a large comparative proteomic analysis discovered a remarkably robust and previous unsuspected inverse association between species lifespan and relative frequency of cysteine residues in mitochondrially encoded respiratory chain proteins only, which the authors attribute to cysteine's ease of oxidation. Another study evaluated more cleanly than any previous work the hypothesis that blood glucose concentration is a key mediator of aging, and concluded that it wasn't. Several new mouse longevity mutants were also reported this year, some (PAPP‐A, IRS‐1, and IRS‐2 knockouts) supporting previous work on the importance of insulin/insulin‐like growth factor‐1 signaling and aging. However, there were inconsistencies between laboratories in some of the results, which merit further investigation. Also, somewhat inconsistent with these findings, over‐expression of insulin‐like growth factor‐1 in heart only lengthened life. From a completely new direction, type 5 adenylyl cyclase knockout mice were observed to live more than 30% longer than controls. Finally, a new program for evaluating potential pharmaceutical interventions in aging and longevity made its appearance, and is notable at this point chiefly for the excellence of its experimental design. A similar program for the disinterested evaluation of reported longevity mutations in mice would be a service to the community of vertebrate aging researchers.
Left ventricular end‐diastolic geometrical adjustments during exercise in endurance athletes
Authors: Henriksen Egil , Sundstedt Milena , Hedberg Pär 
Published: February 2008

SummaryThe increase in left ventricular (LV) end‐diastolic volume has recently been shown to explain more than 70% of the increase in stroke volume during upright exercise in endurance athletes. As the end‐diastolic volume enhancement not could be explained by an increase in axial cavity length an augmentation in LV short‐axis diameters is to be expected. To investigate LV end‐diastolic geometrical alterations during exercise, 15 endurance athletes were examined using contrast exercise echocardiography. LV end‐diastolic short‐axis diameters were made from apical views at several LV cavity levels. From upright rest to upright exercise the LV end‐diastolic internal cavity measurements increased significantly. During exercise, the LV cavity became geometrically more spherical with the largest increase in the LV end‐diastolic short‐axis cavity diameters in the mid and apical parts of the left ventricle. The LV internal long axis showed significant increase from rest to exercise but the absolute increase was small.
Effects of local α2‐adrenergic receptor blockade on adipose tissue lipolysis during prolonged systemic adrenaline infusion in normal man
Authors: Simonsen Lene , Enevoldsen Lotte H. , Stallknecht Bente , Bülow Jens 
Published: February 2008

SummaryDuring prolonged adrenaline infusion, lipolysis peaks within 30 min and thereafter tends to decline, and we hypothesized that the stimulation of local adipose tissue α2‐adrenergic receptors accounts for this decline. The lipolytic effect of a prolonged intravenous adrenaline infusion combined with local infusion of the α2‐blocker phentolamine in superficial and deep abdominal subcutaneous adipose tissue and in preperitoneal adipose tissue was studied in seven healthy subjects. The interstitial glycerol concentration in the three adipose tissue depots was measured by the microdialysis method. Regional adipose tissue blood flow was measured by the 133Xe clearance technique. Regional glycerol output (lipolytic rate) was calculated from these measurements and simultaneous measurements of arterial glycerol concentrations. Adrenaline infusion increased lipolysis in all three depots (data previously published). Phentolamine infusion did not augment lipolysis in the subcutaneous depots while it increased the lipolytic rate in the preperitoneal depot. It is concluded that α2‐adrenergic receptors do not have a significant effect on subcutaneous adipose tissue lipolysis during high circulating adrenaline concentrations, and the decrease in lipolysis in subcutaneous adipose tissue under prolonged adrenaline stimulation is thus not attributed to α2‐adrenergic receptor inhibition of lipolysis. However, in the preperitoneal adipose tissue depot, α2‐adrenergic receptor tone plays a role for the lipolytic rate obtained during prolonged adrenaline stimulation.
Bone mineral density and single photon emission computed tomography changes after total knee arthroplasty: a 2‐year follow‐up study
Authors: Soininvaara Tarja , Nikola Tua , Vanninen Esko , Miettinen Hannu , Kröger Heikki 
Published: February 2008

SummaryDual X‐ray absorptionmetry (DXA) provides a highly reproducible method for quantitative analysis and monitoring periprosthetic bone mineral density (BMD) after total knee arthroplasty (TKA). Single photon emission computed tomography (SPECT) with bone avid radiopharmaceuticals reflects bone metabolic activity and circulation. We combined information from DXA and SPECT to assess the evaluation of the dynamic balance between BMD and bone turnover.Sixteen patients underwent serial DXA (Lunar Expert XL) and 99mTc‐methylene diphosphonate SPECT measurements until 2 years after TKA. A rapid bone loss, up to 25·5%, was detected in femur during the first six postoperative months. However, tibial periprosthetic BMD remained close to baseline. There was a significant correlation between 12‐month SPECT uptake and preceding BMD change in medial tibia (r = 0·5, P = 0·044). At 12 months, SPECT uptakes in the operated knee were notably higher compared with those of the control knee. SPECT uptakes showed statistically significant decreases from 12 months to 24 months, while SPECT uptake in the control knee remained stable. In tibia, the results are more complex; referring that increased bone remodelling is continuing below the tibial tray. Furthermore, femoral diaphyseal uptake remained elevated, while corresponding tibial uptake had levelled off at 2 years.Increased SPECT uptake during the first 2 years after uncomplicated TKA results most likely from normal postoperative bone remodelling. Levelling of SPECT uptake may indicate a new balance between bone loss and regain.
IGF‐1, IGFBP‐3, VEGF and MMP‐9 levels and their potential relationship with renal functions in patients with compensatory renal growth
Authors: Yildiz Bilal , Kural Nurdan , Colak Omer , Ak Ilknur , Akcar Nevbahar 
Published: February 2008

SummaryBackground:  Mechanisms of compensatory renal growth (CRG) still remain a mystery. Various growth factors, including growth hormone, insulin‐like growth factor‐1 (IGF‐1) have been implicated in different forms of CRG.Aims:  To investigate the serum levels of IGF‐1, vascular endothelial growth factor (VEGF – role in vascular remodelling), matrix metalloproteinase‐9 (MMP‐9 – essential for normal nephrogenesis) and correlation of renal function in patients with unilateral nephrectomized, agenesis and hypoplasic kidney.Methods:  Thirty patients were included in this study. In group I, there were 10 patients with unilateral nephrectomy, while in group II, there were 10 patients with unilateral agenesis. As for group III, there were 10 patients with unilateral hypoplastic kidney. The serum levels of IGF‐1, IGF‐binding protein‐3 (IGFBP‐3), VEGF and MMP‐9 were studied in all the cases. Clearance of creatinin (Ccr) and protein excretion were examined in the 24 h urine. CRG was determined with ultrasonography and scintigraphy. Twenty‐six control subjects were also studied.Results:  The levels of IGF‐1, IGFBP‐3, VEGF and MMP‐9 were significantly higher in patients than in the control subjects (P < 0·001). Ccr and protein excretion levels were different in study groups than in those of the control group (P < 0·01). There were positive correlations between the serum levels of IGF‐1 with IGFBP‐3; IGF‐1 with MMP‐9; IGFBP‐3 with MMP‐9 (r = 0·825, P = 0·0001; P < 0·001 r = 0·611; P < 0·001 r = 0·585, respectively). There were negative correlations between GFR and the serum levels of IGF‐1, IGFBP‐3 and MMP‐9 (P < 0·01 r = −0·708; P = 0·002 r = −0·803; P < 0·05 r = −0·442, respectively). Furthermore, there were positive correlations between proteinuria and the serum levels of IGF‐1, IGFBP‐3 and MMP‐9 (P = 0·039 r = 0·600; P < 0·05 r = 0·456; P < 0·05 r = 0·424).Conclusions:  Increased IGF‐1, IGFBP‐3, VEGF and MMP‐9 were observed in CRG in the follow‐up period. IGF‐1 and MMP‐9 seemed to have increased in patients with CRG in defiance of the development of fibrosis. Moreover, IGF‐1 and MMP‐9 seem to be associated with reduced renal function and proteinuria.
Subtle changes in ADMA andl‐arginine concentrations in normal pregnancies are unlikely to account for pregnancy‐related increased flow‐mediated dilatation
Authors: Saarelainen Heli , Valtonen Pirjo , Punnonen Kari , Laitinen Tomi , Raitakari Olli T. , Juonala Markus , Heiskanen Nonna , Lyyra‐Laitinen Tiina , Viikari Jorma S. A. , Vanninen Esko , Heinonen Seppo 
Published: February 2008

SummaryBackground: Our objective was to investigate whether serum concentrations of asymmetric dimethylarginine (ADMA) orl‐arginine correlate to hyperlipidemia or endothelial function in normal pregnancy compared with the non‐pregnant subjects.Methods and results: As a part of population‐based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we examined 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. Serum glucose, triglycerides (TG), total cholesterol (TC), low‐density cholesterol (LDL‐C), high‐density cholesterol (HDL‐C) and ADMA, symmetric dimethylarginine (SDMA) andl‐arginine were determined concomitantly with endothelium‐dependent brachial artery flow‐mediated dilation (FMD), measured by ultrasound. All serum lipid concentrations were significantly higher in pregnant women than in non‐pregnant women (P < 0·001 for each). The mean serum ADMA concentration in pregnant women was significantly lower compared with the non‐pregnant controls (0·513 μmol l−1 ± 0·0593 versus 0·577 μmol l−1 ± 0·0710,P < 0·001). Lowered ADMA concentrations did not correlate statistically to FMD in these healthy pregnant women but FMD was enhanced towards the end of pregnancy.Conclusions: ADMA andl‐arginine concentrations fall in normal pregnancy despite marked hypercholesterolemia. Endothelium‐dependent vasodilation is enhanced in normal pregnancy but is not statistically correlated to maternal serum ADMA orl‐arginine concentrations.
Reliability of isokinetic strength imbalance ratios measured using the Cybex NORM dynamometer
Authors: Impellizzeri Franco M. , Bizzini Mario , Rampinini Ermanno , Cereda Ferdinando , Maffiuletti Nicola A. 
Published: February 2008

SummaryThe main aim of this study was to examine the absolute and relative reliability of some commonly used strength imbalance indices such as concentric hamstring‐to‐concentric quadriceps ratio, eccentric hamstring‐to‐concentric quadriceps ratio and bilateral concentric and eccentric strength ratios. An additional aim was to examine the reliability of the peak torque and work of the knee extensor and flexor muscles measured using the Cybex NORM dynamometer. Eighteen physically active healthy subjects (mean ± standard deviation, age 23 ± 3 years, height 176 ± 5 cm, body mass 74 ± 8 kg) were tested three times with 96 h between sessions. Peak torque, average work, unilateral and bilateral ratios were determined at 60, 120, 180 and −60° s−1. Low (0·34) to moderate (0·87) relative reliability (intraclass correlation coefficient, ICC) was found for strength imbalance ratios with eccentric hamstring‐to‐concentric quadriceps ratio showing the greater ICC (>0·80). High ICC values (0·90–0·98) were found for peak torque and average work. Absolute reliability (standard error of measurement) ranged from 3·2% to 8·7% for strength imbalance ratios and from 4·3% to 7·7% for peak torque and average work measurements. This study established the reliability of the most common strength imbalance ratios and of absolute isokinetic muscle strength assessed using the Cybex NORM.
Health‐related aspects of objectively measured daily physical activity in children
Authors: Dencker Magnus , Andersen Lars Bo 
Published: February 2008

SummaryIt is well established that physical inactivity in adults is associated with increased mortality and morbidity. Whether daily physical activity level is related to risk factors for cardiovascular disease (CVD) in children has been debated. Furthermore, objective data on the habitual daily physical activity in children have at large been scarce in the literature. The main reason for this is the fact that daily physical activity is very difficult to measure in children. In recent years, a new device, the accelerometer, has emerged as a frequently used instrument for the measurement of daily physical activity. This review summarizes recently published studies that have used accelerometers to measure daily physical activity in children and related activity data to known risk factors for CVD.