bluuebunny/crossref_metadata_2025_split huggingface dataset:
Etomidate produces similar allosteric modulation in α1β3δ and α1β3γ2L GABAA receptors
Authors: Feng H‐J , Jounaidi Y , Haburcak M , Yang X , Forman S A 
Published: November 2013

Background and PurposeNeuronal GABAA receptors are pentameric chloride ion channels, which include synaptic αβγ and extrasynaptic αβδ isoforms, mediating phasic and tonic inhibition respectively. Although the subunit arrangement of αβγ receptors is established as β‐α‐γ‐β‐α, that of αβδ receptors is uncertain and possibly variable. We compared receptors formed from free α1, β3 and δ or γ2L subunits and concatenated β3‐α1‐δ and β3‐α1 subunit assemblies (placing δ in the established γ position) by investigating the effects of R‐(+)‐etomidate (ETO), an allosteric modulator that selectively binds to transmembrane interfacial sites between β3 and α1.Experimental ApproachGABA‐activated receptor‐mediated currents in Xenopus oocytes were measured electrophysiologically, and ETO‐induced allosteric shifts were quantified using an established model.Key ResultsETO (3.2 μM) similarly enhanced maximal GABA (1 mM)‐evoked currents in oocytes injected with 5 ng total mRNA and varying subunit ratios, for α1β3(1:1), α1β3δ(1:1:1) and α1β3δ(1:1:3), but this potentiation by ETO was significantly greater for β3‐α1‐δ/β3‐α1(1:1) receptors. Reducing the amount of α1β3δ(1:1:3) mRNA mixture injected (0.5 ng) increased the modulatory effect of ETO, matching that seen with β3‐α1‐δ/β3‐α1(1:1, 1 ng). ETO similarly reduced EC50s and enhanced maxima of GABA concentration‐response curves for both α1β3δ and β3‐α1‐δ/β3‐α1 receptors. Allosteric shift parameters derived from these data depended on estimates of maximal GABA efficacy, and the calculated ranges overlap with allosteric shift values for α1β3γ2L receptors.Conclusion and ImplicationsReducing total mRNA unexpectedly increased δ subunit incorporation into receptors on oocyte plasma membranes. Our results favour homologous locations for δ and γ2L subunits in α1β3γ2/δ GABAA receptors.
ADN‐1184 a monoaminergic ligand with 5‐HT6/7 receptor antagonist activity: pharmacological profile and potential therapeutic utility
Authors: Kołaczkowski M , Mierzejewski P , Bieńkowski P , Wesołowska A , Newman‐Tancredi A 
Published: November 2013

Background and PurposeMany dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side effects, which are problematic in elderly patients. A need therefore exists for drugs that are better suited for the treatment of BPSD.Experimental ApproachWe used in vitro cellular and in vivo behavioural tests to characterize ADN‐1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD.Key ResultsADN‐1184 exhibits substantial 5‐HT6/5‐HT7/5‐HT2A/D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic‐like activity, it reversed MK‐801‐induced hyperactivity and stereotypies and inhibited conditioned avoidance response (MED = 3 mg·kg−1 i.p.). Remarkably, ADN‐1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg·kg−1 i.p.; higher doses were not significantly active). Notably, up to 30 mg·kg−1 ADN‐1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg·kg−1 i.p.).Conclusions and ImplicationsADN‐1184 combines antipsychotic‐like with antidepressant‐like properties without interfering with memory function or locomotion. This profile is better than that of commonly used atypical antipsychotics tested under the same conditions and suggests that it is feasible to identify drugs that improve BPSD, without exacerbating cognitive deficit or movement impairment, which are of particular concern in patients with dementia.
Chronic blockade of angiotensin AT1receptors improves cardinal symptoms of metabolic syndrome in diet‐induced obesity in rats
Authors: Müller‐Fielitz Helge , Hübel Nils , Mildner Martin , Vogt Florian M , Barkhausen Jörg , Raasch Walter 
Published: November 2013

Background and PurposeAT1 receptor antagonists decrease body weight gain in models of murine obesity. However, fewer data are available concerning the anti‐obesity effects of these antagonists, given as a treatment after obesity had been established.Experimental ApproachIn spontaneously hypertensive rats, obesity was established by cafeteria diet (CD) feeding for 19 weeks. Rats were then were treated with telmisartan (8 mg·kg−1·d−1) or amlodipine (10 mg·kg−1·d−1; serving as blood pressure control) or telmisartan + amlodipine (2 + 10 mg·kg−1·d−1; to control for dose‐dependency) for 17 weeks. Rats receiving only chow (Cchow) or CD‐fed rats treated with vehicle (CCD) served as controls.Key ResultsThe CD feeding induced obesity, hyperphagia, hyperlipidaemia, and leptin and insulin resistance. Telmisartan reduced the CD‐induced increase in body weight and abdominal fat mass. Whereas energy intake was higher rather than lower, the respiratory ratio was lower. After telmisartan, leptin‐induced energy intake was reduced and respiratory ratio was increased compared with CCD rats. Telmisartan also decreased plasma levels of triglycerides, free fatty acids and low‐density lipoprotein. Amlodipine alone or the combination telmisartan + amlodipine did not affect body weight and eating behaviour. Telmisartan, but not amlodipine and telmisartan + amlodipine, improved glucose utilization. The decrease in BP reduction was almost the same in all treatment groups.Conclusions and ImplicationsTelmisartan exerted anti‐obesity effects and restored leptin sensitivity, given as a treatment to rats with obesity. Such effects required high doses of telmisartan and were independent of the decrease in blood pressure.
Use of the Measure of Processes of Care (MPOC‐20) to evaluate health service delivery for children with cerebral palsy and their families in Jordan: validation of Arabic‐translated version (AR‐MPOC‐20)
Authors: Saleh M. , Almasri N. A. 
Published: November 2013

AbstractBackgroundFamily‐centred service (FCS) is widely accepted now as best practice in paediatric rehabilitation. The Measure of Processes of Care‐20 items set (MPOC‐20) is a valid and reliable self‐report measure of parents' perceptions of the extent to which health services are family‐centred. Arabic‐translated and validated version of the MPOC‐20 (AR‐MPOC‐20) is used to examine Jordanian families' perception of service providers' caregiving behaviours as they receive rehabilitation services for their children with cerebral palsy (CP).MethodsParents of 114 children with CP who are receiving services at different settings in Jordan were interviewed using the AR‐MPOC‐20. Participating children aged 4.1 ± 4.4 years, 53.5% were males. Children varied across gross motor functional classification system (GMFCS). Parents were mostly mothers (76.3%), with at least high school education (71.9%).ResultsFactor analyses of the AR‐MPOC‐20 yielded a five‐factor solution with items loaded differently from the original measure. All items correlated best and significantly with their own Arabic scale score (rs: 0.91–0.26, P < 0.01). Internal consistency values of AR‐MPOC‐20 scales were acceptable (Cronbach's α: 0.69–0.82). Scale ‘Providing Written Information’ has the lowest average score (1.9 ± 1.6), while scale ‘Respectful & Coordinated Care’ has the highest average score (5.2 ± 1.5).ConclusionThe AR‐MPOC‐20 is found to be a valid and reliable measure for use with Arabic‐Jordanian families of children with CP. FCS is not yet well implemented in Jordan, with parents reporting more need for information about their children's health and available services. Service providers are encouraged to apply FCS in paediatric rehabilitation, and giving more attention to effective communication and information exchange with families. AR‐MPOC‐20 is recommended for use for program evaluation.
Is Insecure Parent–Child Attachment a Risk Factor for the Development of Anxiety in Childhood or Adolescence?
Authors: Kerns Kathryn A. , Brumariu Laura E. 
Published: November 2013

AbstractIn this article, we address how and why parent–child attachment is related to anxiety in children. Children who do not form secure attachments to caregivers risk developing anxiety or other internalizing problems. While meta‐analyses yield different findings regarding which insecurely attached children are at greatest risk, our recent studies suggest that disorganized children may be most at risk. Insecure attachment itself may contribute to anxiety, but insecurely attached children also are more likely to have difficulties regulating emotions and interacting competently with peers, which may further contribute to anxiety. Clinical disorders occur primarily when insecure attachment combines with other risk factors. In this article, we present a model of factors related to developing anxiety.
Children's Social Self‐Concept and Internalizing Problems: The Influence of Peers and Teachers
Authors: Spilt Jantine L. , van Lier Pol A. C. , Leflot Geertje , Onghena Patrick , Colpin Hilde 
Published: November 2013

This study aimed to understand how relationships with peers and teachers contribute to the development of internalizing problems via children's social self‐concept. The sample included 570 children aged 7 years 5 months (SD = 4.6 months). Peer nominations of peer rejection, child‐reported social self‐concept, and teacher‐reported internalizing problems were assessed longitudinally in the fall and spring of Grades 2 and 3. Teacher reports of support to the child were assessed in Grade 2. Results showed that peer rejection impeded children's social self‐concept, which in turn affected the development of internalizing problems. Partial support was found for individual (but not classroom‐level) teacher support to buffer the adverse effects of peer problems on children's self‐concept, thereby mitigating its indirect effects on internalizing problems.
Pancreas transplantation with portal venous drainage with an emphasis on technical aspects
Authors: Rogers Jeffrey , Farney Alan C. , Orlando Giuseppe , Farooq Umar , Al‐Shraideh Yousef , Stratta Robert J. 
Published: November 2013

AbstractAdvances in surgical techniques and clinical immunosuppression have led to improving results in vascularized pancreas transplantation. Most pancreas transplants are performed with enteric exocrine drainage and systemic venous delivery of insulin (systemic‐enteric technique) although bladder drainage (systemic‐bladder technique) remains a viable option. To improve the physiology of pancreas transplantation, an innovative technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal‐enteric technique) was developed and refined over the past 27 yr. However, the potential of portal‐enteric pancreas transplantation has never been fully realized as it is currently performed in only 18% of simultaneous pancreas‐kidney/sequential pancreas after kidney and 10% of pancreas‐alone transplants with enteric drainage. A number of studies have demonstrated no major or consistent differences in outcomes for bladder‐drained or enteric‐drained pancreas transplants with either portal or systemic venous drainage although some studies suggest purported metabolic and immunologic advantages associated with portal venous delivery of insulin. The purpose of this study is to review the existing literature on portal‐enteric pancreas transplantation with an emphasis on surgical aspects and technical modifications/nuances that have been introduced with time and experience.
Neuronal activity‐dependent STAT3 localization to nucleus is dependent on Tyr‐705 and Ser‐727 phosphorylation in rat hippocampal neurons
Authors: Murase Sachiko , McKay Ronald D. 
Published: November 2013

AbstractSignal transducer and activator of transcription 3 (STAT3) dramatically increases during the first post‐natal week, and supports the survival of mature hippocampal neurons. Recently, we reported that chronic elevation of excitability leads to a loss of STAT3 signal, inducing vulnerability in neurons. The loss of STAT3 signal was due to impaired Erk1/2 activation. While overnight elevation of activity attenuated STAT3 signal, brief low‐frequency stimuli, which induce long‐term depression, have been shown to activate STAT3. Here we investigated how STAT3 responds to depolarization in mature neurons. A brief depolarization results in the transient activation of STAT3: it induces calcium influx through L‐type voltage‐gated calcium channels, which triggers activation of Src family kinases. Src family kinases are required for phosphorylation of STAT3 at Tyr‐705 and Ser‐727. PTyr‐705 is Janus kinase (JAK)‐dependent, while PSer‐727 is dependent on Akt, the Ser/Thr kinase. Both PTyr‐705 and PSer‐727 are necessary for nuclear translocation of STAT3 in these neurons. Chronic elevation of spontaneous activity by an A‐type potassium blocker, 4‐aminopyridine (4‐AP), also induced the transient phosphorylation of STAT3, which after 4 h fell to basal levels despite the presence of 4‐AP. These results suggest that phasic and chronic neuronal activation induce distinct molecular pathways, resulting in opposing regulation of STAT3 signal.
Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients
Authors: Sairanen T. , Koivisto A. , Koivusalo A.‐M. , Rantanen K. , Mustanoja S. , Meretoja A. , Putaala J. , Strbian D. , Kaste M. , Isoniemi H. , Tatlisumak T. 
Published: November 2013

Background and purposeIntracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation.MethodsA chart review was carried out by a multi‐professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010.ResultsIn all, 955 patients had follow‐up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non‐existent and do‐not‐resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm3 (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012.ConclusionsA considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end‐of‐life care.
Simple clinical predictors of stroke outcome based on National Institutes of Health Stroke Scale score during 1‐h recombinant tissue‐type plasminogen activator infusion
Authors: Osaki M. , Miyashita F. , Koga M. , Fukuda M. , Shigehatake Y. , Nagatsuka K. , Minematsu K. , Toyoda K. 
Published: November 2013

Background and purposeAn index for predictors of stroke outcome was determined based on the National Institutes of Health Stroke Scale (NIHSS) scores during 1‐h intravenous administration of recombinant tissue‐type plasminogen activator (rt‐PA).MethodsStroke patients with baseline NIHSS score ≥8 and occlusion at the internal carotid or middle cerebral arteries (ICA, MCA) were retrospectively studied from a prospective single‐center registry. NIHSS scores and inverse change from baseline scores (ΔNIHSS) were assessed at 30 min and 1 h after rt‐PA infusion. Patients were divided into two groups according to arterial occlusion sites: group P, ICA or proximal M1; and group D, distal M1 or M2. A modified Rankin Scale score of 2–6 at 3 months was defined as an unfavorable outcome.ResultsIn all 108 patients, the cutoff NIHSS score predicting unfavorable outcome was ≥12 and cutoff ΔNIHSS scores were ≤2 at both 30 min and 1 h. In group P (n = 36), the cutoff NIHSS score was ≥14 at both 30 min and 1 h and cutoff ΔNIHSS scores were ≤1 at 30 min and ≤2 at 1 h. Unfavorable outcome was seen in all patients with NIHSS1 h ≥ 14, ΔNIHSS30 min ≤ 1 and ΔNIHSS1 h ≤ 2. In group D (n = 72), the cutoff NIHSS scores were ≥12 at both 30 min and 1 h, and cutoff ΔNIHSS scores were ≤2 at 30 min and ≤7 at 1 h; 90% of patients with unfavorable outcome showed ΔNIHSS1 h ≤ 7.ConclusionNIHSS and ΔNIHSS during 1‐h rt‐PA infusion seemed predictive of 3‐month outcome when the site of arterial occlusion was identified prior to rt‐PA.
Periplasmic glucose‐binding protein from Pseudomonas putida CSV86 – identification of the glucose‐binding pocket by homology‐model‐guided site‐specific mutagenesis
Authors: Modak Arnab , Bhaumik Prasenjit , Phale Prashant S. 
Published: November 2013

Glucose transport in Pseudomonas putida CSV86 is mediated via a periplasmic glucose‐binding protein (GBP)‐dependent putative glucose ABC transporter. Here we describe a homology model and functional characterization of GBP from CSV86 (ppGBP). A whole‐cell [14C]‐glucose uptake study revealed that glucose is transported by the high‐affinity intracellular phosphorylative pathway. ppGBP was cloned, over‐expressed in Escherichia coli and purified to apparent homogeneity. The purified ppGBPs from both E. coli and CSV86 were found to be specific for glucose. A homology model of ppGBP was constructed that resembles the class II family of periplasmic binding proteins. The model showed highest structural similarity to GBP of Thermus thermophilus (ttGBP, rmsd 0.64 Å). Structural analysis and molecular docking studies predicted W35, W36, E41, K92, K339 and H379 of ppGBP as putative glucose‐binding residues. Alanine substitution of these residues resulted in significantly reduced [14C]‐glucose binding activity. Analysis of the operonic arrangement and structural comparative studies suggested that ppGBP and ttGBP probably originated from a common ancestor. Structural adaptations that inhibit binding of di‐ or trisaccharides at the glucose‐binding pocket of ppGBP were also identified.
From projected species distribution to food‐web structure under climate change
Authors: Albouy Camille , Velez Laure , Coll Marta , Colloca Francesco , Le Loc'h François , Mouillot David , Gravel Dominique 
Published: November 2013

AbstractClimate change is inducing deep modifications in species geographic ranges worldwide. However, the consequences of such changes on community structure are still poorly understood, particularly the impacts on food‐web properties. Here, we propose a new framework, coupling species distribution and trophic models, to predict climate change impacts on food‐web structure across the Mediterranean Sea. Sea surface temperature was used to determine the fish climate niches and their future distributions. Body size was used to infer trophic interactions between fish species. Our projections reveal that 54 fish species of 256 endemic and native species included in our analysis would disappear by 2080–2099 from the Mediterranean continental shelf. The number of feeding links between fish species would decrease on 73.4% of the continental shelf. However, the connectance of the overall fish web would increase on average, from 0.26 to 0.29, mainly due to a differential loss rate of feeding links and species richness. This result masks a systematic decrease in predator generality, estimated here as the number of prey species, from 30.0 to 25.4. Therefore, our study highlights large‐scale impacts of climate change on marine food‐web structure with potential deep consequences on ecosystem functioning. However, these impacts will likely be highly heterogeneous in space, challenging our current understanding of climate change impact on local marine ecosystems.
Increased cardiovascular risk in patients with severe mental illness
Authors: Gladigau E. L. , Fazio T. N. , Hannam J. P. , Dawson L. M. , Jones S. G. 
Published: November 2013

AbstractBackgroundPeople with severe mental illness (SMI) have a reduced life expectancy. A major cause of mortality is cardiovascular disease.AimsThe aims of this study were to document the prevalence of cardiovascular risk factors in people with SMI engaged in community psychiatric rehabilitation and compare prevalence rates to the general, and Aboriginal and Torres Strait Islander (ATSI) populations of Australia.MethodA cross‐sectional audit was conducted on patients receiving care from Melbourne's Inner‐West Area Mental Health Service. Profiles were collected on: smoking status, body mass index, waist circumference, blood pressure, diabetic status and fasting lipid profiles. These were compared with the general and ATSI Australian populations.ResultsComplete data were available for 60 patients. Most were involuntary patients with a diagnosis of schizophrenia or schizoaffective disorder. Patients were more likely to smoke, be obese, have dyslipidaemia and the metabolic syndrome compared with the general and ATSI populations of Australia. Patients were more likely to have diabetes than the general population but had similar rates to the ATSI population. Patients had similar rates of hypertension to the general population but were less likely to be hypertensive compared with the ATSI population.ConclusionAustralians living with SMI have very high rates of cardiovascular risk factors, far in excess of the general Australian population and comparable with the ATSI population.
Functional polymorphisms of TLR8 are associated with hepatitis C virus infection
Authors: Wang Chiou‐Huey , Eng Hock‐Liew , Lin Kuei‐Hsiang , Liu Hsiang‐Chun , Chang Cheng‐Hsien , Lin Tsun‐Mei 
Published: November 2013

SummaryChronic hepatitis C virus (HCV) infection is a worldwide threat to public health. Toll‐like receptor 8 (TLR8) is critical for eliminating RNA viruses, and variation within the TLR8 gene may alter the function of TLR8 in response to HCV infection. Our previous study demonstrated that the TLR8‐129G>C (rs3764879) and TLR8+1G>A (rs3764880) variants were in complete linkage disequilibrium, and that the frequency of TLR8‐129C/+1A was significantly higher in male patients with HCV infection compared with the healthy controls. In the present study, we found that the promoter activity of TLR8‐129G was higher than that of TLR8‐129C in THP‐1 cells. Moreover, TLR8‐129G mRNA stability and competitive DNA‐binding ability were significantly lower than that of TLR8‐129C. To investigate the functional effects of TLR8 polymorphisms, we compared the nuclear factor‐κB (NF‐κB)‐driven luciferase activity in HEK293 cells transfected with the TLR8 variants. TLR8+1A plasmids induced less NF‐κB signalling than did those transfected with TLR8+1G after 20 μm CL075 (P = 0·011) stimulation. We also analysed the mRNA expression and cytokine production in whole blood and monocytes from people of various genotypes stimulated ex vivo by the interferon‐γ and TLR7/8 agonist CL075, R848. TLR8 expression in CD14+ cells derived from volunteers with TLR8‐129G/+1G was significantly higher than that derived from TLR8‐129C/+1A, and interleukin‐12p40 production was higher in volunteers with TLR8‐129G/+1G after stimulation. The data indicate that variations in TLR8 genes may modulate immune responses during HCV infection.